Review Article Analgesic, Anti-Inflammatory, and...
8
Hindawi Publishing Corporation Journal of Applied Chemistry Volume 2013, Article ID 247203, 7 pages http://dx.doi.org/10.1155/2013/247203 Review Article Analgesic, Anti-Inflammatory, and Antiplatelet Profile of Hydrazones Containing Synthetic Molecules Mohammad Asif 1 and Asif Husain 2 1 Department of Pharmacy, GRD (PG) Institute of Management and Technology, Dehradun 248009, India 2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard University, New Delhi 110062, India Correspondence should be addressed to Mohammad Asif; [email protected] Received 24 May 2013; Revised 22 September 2013; Accepted 6 October 2013 Academic Editor: Guang-Fu Yang Copyright © 2013 M. Asif and A. Husain. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Hydrazones are present in many of the bioactive compounds with wide interest because of their diverse pharmacological applica- tions. Hydrazones possess wide variety of biological activities such as anticonvulsant, antidepressant, analgesic, anti-inflammatory, antiplatelet, antimicrobial, anticancer, antihypertensive, anthelmintic, antidiabetic, antiparasitic, and other anticipated activities. is created an interest for researchers towards synthesized variety of hydrazone derivatives for different biological activities. erefore many researchers have synthesized hydrazone derivatives as target structures for their biological activities. is is paper focuses on the analgesic, anti-inflammatory, and antiplatelet activities of hydrazones. 1. Introduction Hydrazones constitute an important class of biologically active drug molecules which has attracted the attention of medicinal chemists due to their wide range of pharmaco- logical properties. ese compounds are being synthesized as drugs by many researchers in order to combat diseases with minimal toxicity and maximal effects. ese predictions have provided a therapeutic pathway to develop new effec- tive biologically active hydrazones. A number of hydrazone derivatives have been reported to exert notably biological activities [1, 2]. Hydrazones possess an azomethine –NHN=CH group which are considered as derivatives of aldehydes and ketones in which the oxygen atom has been replaced by the =NNH 2 group. Hydrazones are of wide interest because of their diverse biological applications such as anticonvulsant, antidepressant, analgesic, anti-inflammatory, antiplatelet, antimalarial, antimicrobial, antimycobacterial, anticancer, vasodilator, antiviral, anti-HIV, anthelmintic, antidiabetic, and trypanocidal activities [2–10]. e hydrazones are used as hole transporting agents in organic layer photoconductors, as quantitative analytical reagents, especially in colorimetric and fluorometric determi- nation of metal ions [11–13]. Furthermore, some hydrazones have also been used as herbicides, insecticides, nematocides, rodenticides, and plant growth regulators as well as plas- ticizers and stabilizers for polymers. e metal complexes of hydrazones have potential applications as catalysts, lumi- nescent probes, and molecular sensors [1, 14, 15]. A class of N-arylsulfonyl hydrazones has been developed as novel inhibitors of IMP-1, a metallo--lactamase. As a requirement for bulky aromatic substituents on each side of the sulfonyl hydrazone backbone, these compounds may serve as effi- cient inhibitors of IMP-1. Molecular modeling has provided structural basis for the anti-metallo--lactamase activity of hydrazonone compounds [16]. A series of hydrazones were evaluated as potential inhibitors of anthrax lethal factor. ere were significant differences in the types of inhibition observed with the different assays [17]. Kinetic analysis of the dipeptidyl disulfides and dipeptidyl benzoylhydrazones indicated that these inhibitors act as irreversible inhibitors of Cathepsin S, and benzoylhydrazones were shown to be potent inhibitors of Cathepsin S [18]. Hydrazones and phenyl hydrazones of different aryl aldehydes showed an effect on endogenous proteolysis in liver. It was observed
Transcript of Review Article Analgesic, Anti-Inflammatory, and...
Hindawi Publishing CorporationJournal of Applied ChemistryVolume 2013 Article ID 247203 7 pageshttpdxdoiorg1011552013247203
Review ArticleAnalgesic Anti-Inflammatory and Antiplatelet Profile ofHydrazones Containing Synthetic Molecules
Mohammad Asif1 and Asif Husain2
1 Department of Pharmacy GRD (PG) Institute of Management and Technology Dehradun 248009 India2Department of Pharmaceutical Chemistry Faculty of Pharmacy Jamia Hamdard University New Delhi 110062 India
Correspondence should be addressed to Mohammad Asif aasif321gmailcom
Received 24 May 2013 Revised 22 September 2013 Accepted 6 October 2013
Academic Editor Guang-Fu Yang
Copyright copy 2013 M Asif and A Husain This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited
Hydrazones are present in many of the bioactive compounds with wide interest because of their diverse pharmacological applica-tions Hydrazones possess wide variety of biological activities such as anticonvulsant antidepressant analgesic anti-inflammatoryantiplatelet antimicrobial anticancer antihypertensive anthelmintic antidiabetic antiparasitic and other anticipated activitiesThis created an interest for researchers towards synthesized variety of hydrazone derivatives for different biological activitiesTherefore many researchers have synthesized hydrazone derivatives as target structures for their biological activities This is paperfocuses on the analgesic anti-inflammatory and antiplatelet activities of hydrazones
1 Introduction
Hydrazones constitute an important class of biologicallyactive drug molecules which has attracted the attention ofmedicinal chemists due to their wide range of pharmaco-logical properties These compounds are being synthesizedas drugs by many researchers in order to combat diseaseswith minimal toxicity andmaximal effectsThese predictionshave provided a therapeutic pathway to develop new effec-tive biologically active hydrazones A number of hydrazonederivatives have been reported to exert notably biologicalactivities [1 2]
Hydrazones possess an azomethine ndashNHN=CH groupwhich are considered as derivatives of aldehydes and ketonesin which the oxygen atom has been replaced by the=NNH
2group Hydrazones are of wide interest because of
their diverse biological applications such as anticonvulsantantidepressant analgesic anti-inflammatory antiplateletantimalarial antimicrobial antimycobacterial anticancervasodilator antiviral anti-HIV anthelmintic antidiabeticand trypanocidal activities [2ndash10]
The hydrazones are used as hole transporting agentsin organic layer photoconductors as quantitative analytical
reagents especially in colorimetric and fluorometric determi-nation of metal ions [11ndash13] Furthermore some hydrazoneshave also been used as herbicides insecticides nematocidesrodenticides and plant growth regulators as well as plas-ticizers and stabilizers for polymers The metal complexesof hydrazones have potential applications as catalysts lumi-nescent probes and molecular sensors [1 14 15] A classof N-arylsulfonyl hydrazones has been developed as novelinhibitors of IMP-1 ametallo-120573-lactamase As a requirementfor bulky aromatic substituents on each side of the sulfonylhydrazone backbone these compounds may serve as effi-cient inhibitors of IMP-1 Molecular modeling has providedstructural basis for the anti-metallo-120573-lactamase activity ofhydrazonone compounds [16] A series of hydrazones wereevaluated as potential inhibitors of anthrax lethal factorThere were significant differences in the types of inhibitionobserved with the different assays [17] Kinetic analysis ofthe dipeptidyl disulfides and dipeptidyl benzoylhydrazonesindicated that these inhibitors act as irreversible inhibitorsof Cathepsin S and benzoylhydrazones were shown tobe potent inhibitors of Cathepsin S [18] Hydrazones andphenyl hydrazones of different aryl aldehydes showed aneffect on endogenous proteolysis in liver It was observed
2 Journal of Applied Chemistry
that p-nitro benzaldehyde hydrazone exhibited maximuminhibitory effect [19] The effect of hydrazones and phenylhydrazones of simple aryl aldehydes along with their semi-carbazones and thiosemicarbazones on the activity of liveralkaline and acid phosphatase [20 21]
Hydrazones are an important class of compounds for newdrug development This created an interest to researcherswho have synthesized variety of hydrazone derivatives andscreened them for their various biological activities In thepresent study we have made an attempt to collect analgesicanti-inflammatory and antiplatelet properties of hydrazonederivatives Hydrazones are not only intermediates but alsovery effective organic compounds when they are used asintermediates and coupling products that can be synthesizedby using the active hydrozen component of ndashCONHN=CHndashazomethine group Many effective compounds such as ipro-niazid and isocarboxazid are synthesized by the reductionof hydrazide-hydrazones Iproniazid like INH is used in thetreatment of tuberculosis It has also displayed an antide-pressant effect and patients appear to have a better moodduring the treatment Another clinically effective hydrazide-hydrazones is nifuroxazide which is used as an intestinalantiseptic [22ndash25] Hydrazones are a class of organic com-pounds which possess the structure R
1R2C=NNH
2 They are
related to ketone and aldehyde in which oxygen has beenreplaced with NNH
2group These azometine ndashNHN=CHndash
protons constitute an important class of compounds for drugdevelopment Hydrazones are formed by the reaction ofhydrazine or hydrazide with aldehydes and ketones Hydra-zones are widely used in organic synthesis Many effectivecompounds such as iproniazide and isocarboxazid are syn-thesized by the reduction of hydrazide-hydrazones Anothereffective hydrazide-hydrazone is nifuroxazide which is usedas an intestinal antiseptic [26ndash30] This review highlightsanalgesic anti-inflammatory antipyretic and antiplateletsactivities shown by hydrazones
2 Analgesic and Anti-Inflammatory Activites
Nonsteroidal anti-inflammatory drugs (NSAIDs) are largelyused in the treatment of pain and inflammation Hydrazonesthat are dual inhibitors of both cyclooxygenase (COX)and 5-lipoxygenase (5-LO) are being studied as potentialanalgesic and anti-inflammatory agents in comparisonto NSAIDs [31] Nonsteroidal anti-inflammatory drugs(NSAIDs) have a wide clinical use for the treatment ofinflammation pain rheumatoid arthritis soft tissue and oralcavity lesions respiratory tract infections and fever The twoisoforms of COX are poorly distinguishable by most of theclassical NSAIDs and these agents actually inhibit COX-1extensively besides COX-2 leading to gastrointestinal(GI) injury suppression of TXA2 formation and plateletaggregation The combination of these interactions isprobably the reason for GI bleeding which is themost seriouscomplication of these drugs Some evidence suggests that thehydrazone moiety present in some compounds possesses apharmacophoric character for the inhibition of COX In factsome evidence suggests that the hydrazone moiety presentin derivative possesses a pharmacophoric character for the
inhibition of COX [32]The results showed that pyridine ringat the aryl moiety of the arylhydrazone is having good anal-gesic activity in comparison to mefenamic acid Compoundspossessing the 4-tolyl or 4-fluorophenyl moiety are moreactive than 4-bromophenyl and 4-NN-dimethylaminophe-nyl The anti-inflammatory evaluation showed that thereplacement of carboxylic acid group of mefenamic acid withN-arylhydrazone moiety cannot produce any advantage inthe anti-inflammatory property [33] Analgesic activity ofsome (4Z)-3-methyl-1-[(2-oxo-2Hchromene-4-yl)carbonyl]-1H-pyrazole-45-dione4-(4-substitutedphenyl)hydrazonesome of them showed significant analgesic activity Pharmac-ological evaluation was done by using acetic acid-inducedwrithing model in mice which showed that the presenceof 4-chloro 4-bromo 34-dichloro 34-dibromo and 4-methyl group in the aromatic ring of 4-position of thepyrazole-hydrazono nucleus gave rise to increased analgesicactivities [34] Hydrazone derivatives of quinoxalinoneand evaluated for anti-inflammatory activity showed thatcompounds having methoxy group at the para-positionshowed comparatively good percentage of inhibition ofedema than the other compounds [35] Treatment of 3-cyanoacetylindole with diazonium salts of 3-phenyl-5-aminopyrazole and 2-amino pyrazole gave the correspondinghydrazones Compound 3-(1H-Indol-3-yl)-3-oxo-2-[(5-phe-nyl-2H-pyrazol-3-yl)-hydrazono]-propionitrile was found topossess appreciable analgesic and anti-inflammatory activity[36] The anti-inflammatory derivative 2-(2-formylfuryl)pyridylhydrazone (1) presented a 79 inhibition of pleurisyat a dose of 801 120583molkg The results concerning themechanism of the action of these series of N-heterocyclicderivatives in platelet aggregation suggest a Ca2+ scavengermechanism Compound 2 was able to complex Ca2+ inin vitro experiments at 100 120583M concentration indicatingthat these series of compounds can act as Ca2+ scavengerdepending on the nature of the aryl moiety present at theimine subunit [37] A series of analgesic compounds thatbelong to the N-acylarylhydrazone class were synthesizedfrom natural safrole [(41015840-NN-Dimethylaminobenzylidene-3-(3101584041015840methylenedioxyphenyl)propionyl hydrazine] (2)was more potent than dipyrone and indomethacin [38]Analgesic and anti-inflammatory activity of furoxanyl-N-acylhydrazones (3 4) [39] The anti-inflammatory activityof some aryl hydrazones (5) got good results [40] Varioushydrazone derivatives (6) reported them to have promising invivo anti-inflammatory activity [41] Hydrazone derivatives(7) with selective COX-2 inhibition The compound isreported to have an ED
50value of 02mmolKg [42]
Benzothiophene derivatives (8) with inhibition of 502have been developed [43] see Figure 1
Fifteen different isatin[N-(2-alkylbenzoxazole-5-car-bonyl)] hydrazones (9) were screened for analgesic anti-depressant andH1-antihistaminic activities [44]These com-pounds were also studied for their effect on pentobarbitone-induced narcosisThree compounds bearing amethyl substit-uent at 7-position of the benzoxazole system exhibit goodanalgesic activity Schiff bases and phenyl hydrazone of isa-tins prepared from isatin and appropriate aromatic primary
Journal of Applied Chemistry 3
N NH
NO
O
O
NH
O
N
N
NO
N
N
HN
ONH
N
N ON
O NHN
OH
Br
NHN
O
O
NS
O
N NH
O
N S
Cl
O
NHN
ONH
N
NN
O
BT
O
H3C
H3C
H3C
H3CH3C
H3C
H3C
CH3
CH3
OH2
NO2
CF3
CF3
H3CO
F3C
1 2 3 4
8765
Figure 1
aminehydrazines were screened for analgesic anti-inflam-matory and antipyretic activity [45] 1-Diphenylamino-methyl-3-(1-naphthylimino)-13-dihydroindol-3-one 3-(1-naphthylimino)-5-bromo-13-dihydroindol-2-one (10) and1-diphenylaminomethyl-3-(4-methylphenylimino)-13-dihy-droindol-3-one exhibited the highest analgesic anti-inflammatory and antipyretic activity respectively Few 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(p-substitutedbenzal)hydrazone derivatives exhibited analgesic and anti-inflammatory agents None of the compounds was found toshow gastric ulcerogenic effect in comparison with referenceNSAIDs [46] 2-(2-Formylfuryl)pyridylhydrazone possessedanti-inflammatory activity and showed 79 inhibition ofpleurisy at a dose of 801 120583molkg The results indicated thatthese series of compounds can act as Ca2+ scavenger andplatelet aggregation [37] see Figure 2
21 Antiplatelet Activity The antiplatelet activity of tricyclicacylhydrazone derivatives (11) was evaluated by their abilityto inhibit platelet aggregation of rabbit platelet-rich plasmainduced by platelet activating factor (PAF) at 50 nMBenzylidene-41015840-bromobenzylidene 3-OH-8-CH
3-6-phenyl-
pyrazolo[34-b]thieno-[23-d]pyridine-2-carbohydrazidewasevaluated at 10 120583M presenting respectively 104 and 136
of inhibition of the PAF-induced platelet aggregation [37]The evaluation of platelet antiaggregating profile let to theidentification of a new potent prototype of antiplateletderivative that is benzylidene 10H-phenothiazine-1-carbo-hydrazide (IC
50= 23 120583M) which acts in the AA pathway
probably by the inhibition of platelet COX-1 enzymeAdditionally the change in para-substituent group ofacylhydrazone framework permitted to identify a hydrophiliccarboxylate derivative and a hydrophobic bromo derivativeas two new analgesics that are more potent than dipyronepossessing selective peripheral or central mechanism ofaction [47] The evaluation of platelet antiaggregatingprofile let to the identification of a new potent prototypethat is benzylidene 10H-phenothiazine-1-carbohydrazide(IC50
= 23 120583M) (12) which acts in the arachidonic acid(AA) pathway probably by the inhibition of platelet COX-1enzyme Change in para-substituent group of acylhydrazoneframework permitted to identify a hydrophilic carboxylatederivative and a hydrophobic bromo derivative as twoanalgesics that are more potent than dipyrone possessingselective peripheral or central mechanism of action [48]Hydrazones containing 5-methyl-2-benzoxazoline the anal-gesic effects of 2-[2-(5-methyl-2-benzoxazoline-3-yl)acetyl]-4-chloro-4-methyl benzylidene hydrazine (13a) and (13b)
4 Journal of Applied Chemistry
NH
O
N
HN
O
O
N
R
NHO
Br
N
9 10
Figure 2
NN N
H
S
NH
N
O
H3C
OH
Ar
S
HN
NH
O
N Ar
O
NO
NH
O
N Cl
O
NO
NH
O
NO
O
NH
O
N
OH
NN N
O
HN N
Ar
Me
NH
X
Ar = Ph X = HAr = Pyrid-4-yl X = HAr = 2-Nitrofuryl X = 4-Cl
11 12
13b 14 15 16 17
13a
CH3
Figure 3
were found to be higher than morphine and aspirin Inaddition 2-[2-(5-methyl-2-benzoxazoline-3-yl)acetyl]-4-methoxy benzylidene hydrazine at 200mgkg dose possessedthe anti-inflammatory activity [49] N1015840-(35-Di-tert-butyl-4-hydroxybenzylidene)-6-nitro-13-benzodioxole-5-carbo-hydrazine (14) as an anti-inflammatory compound [50]Antiplatelets decrease platelet aggregation and prevent theformation of thrombus Hydrazone derivatives (15 16 17)exhibited an in vitro antiplatelet activity see Figure 3
3 Synthetic Approach for the NovelHydrzonone and Its Biological Activity
A number of organic compounds obtained by chemicalsynthesis as model compounds have useful analgesic anti-inflammatory antipyretic and antiplatelets activities Manyof hydrazonones its derivatives possess interesting biological
activities such as analgesic anti-inflammatory antimicro-bial and antitumor activitesThe biological activity of synthe-sized hydrazonone derivatives was characterized and detailedstudy is in progress to modify the synthetic route structuralactivity and toxicological barriers for the enhanced pharma-cological efficiency of synthetic hydrazones [37 45ndash49]
4 Development of New NSAIDs
The NSAIDs preparations are among the most commonlyprescribed drugs NSAIDs are sometimes known as theaspirin-like drugs because they have an activity profile thatis broadly similar to that of aspirin that is they all possessanalgesic anti-inflammatory and antipyretic properties tosomedegree and produce characteristic side effects includinggastric intolerance and depression of blood clotting throughinhibitory action on platelet function Two closely related
Journal of Applied Chemistry 5
forms of the cyclooxygenase have been identified whichare now known as COX-1 and COX-2 Both isoenzymestransform arachidonic acid (AA) to prostaglandins (PGs)but differ in their distribution and their physiological rolesMeanwhile the responsible genes and their regulation havebeen clarified COX-1 the predominantly constitutive formofthe enzyme is expressed throughout the body and performsa number of homeostatic functions such as maintainingnormal gastric mucosa and influencing renal blood flowSimmons also recently codiscovered COX-3 in 2002 andanalyzed this new isozymersquos relation which acetaminophen(paracetamol) arguably the most widely used analgesic drugin the world The clinical ramifications and knowledge ofCOX isozymes are therefore rapidly expanding and couldperhaps offer significant hope for future treatments of paininflammation and fever [37 45ndash49]
5 Discussion
Hydrazones possessing an azomethine ndashNHN=CHndash groupconstitute an important class of compounds as target struc-tures for their biological activities These observations guideus for the development of new hydrazones that possess variedbiological activitiesThe literature studies on hydrazones haveshown that these derivatives possess a wide variety of biolog-ical activities such as antitumor antibacterial antiviral anti-hypertensive anticonvulsant anti-inflammatory analgesicantipyretic antiplatelets vasorelaxant anticoagulant andantiprotozoal activities There has been considerable interestin the development of novel compounds with wide varietiesof biological activities These molecules are easily preparedand have diverse pharmacological potential This encouragesto the researchers to synthesize different new compoundsbearing hydrazones with low toxicity Differently substitutedhydrazones have been developed and found to be activeagainst different pharmacological targetsThese observationshave been guiding the development of new hydrazones thatpossess varied biological activities Hydrazone derivativesof carbonyl compounds constitute an important class ofbiologically active compounds [50ndash57]
6 Conclusion
Hydrazonone nucleus exhibited immense pharmacologicalactivities The simple hydrazonone nucleus is present incompounds are evaluating for new products that possesssome remarkable pharmacological activities such as anal-gesic anti-inflammatory antipyretic antiplatelet aggrega-tion cardiotonic antihypertensive analgesic vasodilatoryantidiabetic and anticonvulsant activites The present reviewfocuses on hydrazonone which possesses potential analgesicanti-inflammatory antipyretic and anti-platelet aggregationactivities that are new in development
References
[1] M Singh and N Raghav ldquoBiological activities of hydrazones areviewrdquo International Journal of Pharmacy and PharmaceuticalSciences vol 3 no 4 pp 26ndash32 2011
[2] H S Seleem G A El-Inany B A El-Shetary andM AMousaldquoThe ligational behavior of a phenolic quinolyl hydrazonetowards copper(II)-ionsrdquo Chemistry Central Journal vol 5article 2 2011
[3] B F Abdel-Wahab G E A Awad and F A Badria ldquoSynthesisantimicrobial antioxidant anti-hemolytic and cytotoxic evalu-ation of new imidazole-based heterocyclesrdquo European Journalof Medicinal Chemistry vol 46 no 5 pp 1505ndash1511 2011
[4] A S Abu-Surrah K A Abu Safieh I M Ahmad et al ldquoNewpalladium(II) complexes bearing pyrazole-based Schiff baseligands synthesis characterization and cytotoxicityrdquo EuropeanJournal of Medicinal Chemistry vol 45 no 2 pp 471ndash475 2010
[5] O O Ajani C A Obafemi O C Nwinyi and D A AkinpeluldquoMicrowave assisted synthesis and antimicrobial activity of 2-quinoxalinone-3-hydrazone derivativesrdquoBioorganic andMedic-inal Chemistry vol 18 no 1 pp 214ndash221 2010
[6] M S Al-Said M S Bashandy S I Al-Qasoumi and MM Ghorab ldquoAnti-breast cancer activity of some novel 12-dihydropyridine thiophene and thiazole derivativesrdquo EuropeanJournal of Medicinal Chemistry vol 46 no 1 pp 137ndash141 2011
[7] M A S Aslam S-U Mahmood M Shahid A Saeed andJ Iqbal ldquoSynthesis biological assay in vitro and moleculardocking studies of new Schiff base derivatives as potentialurease inhibitorsrdquoEuropean Journal ofMedicinal Chemistry vol46 no 11 pp 5473ndash5479 2011
[8] Z Cui Y Li Y Ling et al ldquoNew class of potent antitumoracylhydrazone derivatives containing furanrdquo European Journalof Medicinal Chemistry vol 45 no 12 pp 5576ndash5584 2010
[9] D Kaushik S A Khan G Chawla and S Kumar ldquoN1015840-[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene] 24-substituted hydrazides synthesis and anticonvulsant activityrdquoEuropean Journal of Medicinal Chemistry vol 45 no 9 pp3943ndash3949 2010
[10] M M Edrees T A Farghaly F A A El-Hag and M MAbdalla ldquoAntimicrobial antitumor and 5120572-reductase inhibitoractivities of some hydrazonoyl substituted pyrimidinonesrdquoEuropean Journal of Medicinal Chemistry vol 45 no 12 pp5702ndash5707 2010
[11] A A El-Sherif ldquoSynthesis spectroscopic characterizationand biological activity on newly synthesized copper(II) andnickel(II) complexes incorporating bidentate oxygen-nitrogenhydrazone ligandsrdquo Inorganica Chimica Acta vol 362 no 14pp 4991ndash5000 2009
[12] G A Al-Hazmi and A A El-Asmy ldquoSynthesis spectroscopyand thermal analysis of copper(II) hydrazone complexesrdquoJournal of Coordination Chemistry vol 62 no 2 pp 337ndash3452009
[13] Y-L Sang and X-S Lin ldquoSyntheses and crystal structuresof two Schiff-base copper(II) complexes with antibacterialactivitiesrdquo Journal of Coordination Chemistry vol 63 no 2 pp315ndash322 2010
[14] O Pouralimardan A-C Chamayou C Janiak and HHosseini-Monfared ldquoHydrazone Schiff base-manganese(II)complexes synthesis crystal structure and catalytic reactivityrdquoInorganica Chimica Acta vol 360 no 5 pp 1599ndash1608 2007
[15] C Basu S Chowdhury R Banerjee H Stoeckli Evans andS Mukherjee ldquoA novel blue luminescent high-spin iron(III)complex with interlayer O-H Cl bridging synthesis structureand spectroscopic studiesrdquo Polyhedron vol 26 no 14 pp 3617ndash3624 2007
[16] S Siemann D P Evanoff L Marrone A J Clarke TViswanatha and G I Dmitrienko ldquoN-arylsulfonyl hydrazones
6 Journal of Applied Chemistry
as inhibitors of IMP-1 metallo-120573-lactamaserdquo AntimicrobialAgents and Chemotherapy vol 46 no 8 pp 2450ndash2457 2002
[17] M L Hanna T M Tarasow and J Perkins ldquoMechanisticdifferences between in vitro assays for hydrazone-based smallmolecule inhibitors of anthrax lethal factorrdquo Bioorganic Chem-istry vol 35 no 1 pp 50ndash58 2007
[18] C L Cywi R A Firestone D W McNeil C A Grygon K MCrane D M White et al ldquoThe design of potent hydrazonesand disulfides as cathepsin S inhibitorsrdquo Journal of MolecularStructure vol 34 pp 9ndash22 2009
[19] N Raghav M Singh R Kaur S Suman and P Priyanka ldquoPro-teolytic studies in liver homogenate in presence of substitutedaryl hydrazonesrdquo Asian Journal of Chemistry vol 23 no 3 pp1409ndash1410 2011
[20] N RaghavM Singh S Jangra A Rohilla R Kaur and PMalikldquoIn-Vitro studies of various carbonyl derivatives on liver alkalinephosphataserdquo Journal of Chemical and Pharmaceutical Researchvol 2 no 4 pp 801ndash807 2010
[21] N Raghav M Singh S Jangra A Rohilla R Kaur and PMalik ldquoIn-Vitro studies of various carbonyl derivatives on liveracid phosphataserdquo International Journal of Applied Biology andPharmaceutical Technology vol 1 no 3 pp 1011ndash1015 2010
[22] S Eswaran A V Adhikari I H Chowdhury N K Paland K D Thomas ldquoNew quinoline derivatives synthesis andinvestigation of antibacterial and antituberculosis propertiesrdquoEuropean Journal of Medicinal Chemistry vol 45 no 8 pp3374ndash3383 2010
[23] S Kumar S Bawai S Drabu R Kumar and L MachwalldquoChloroquinolinylhydrazone derivative as anticonvulsantrdquoActaPoloniae Pharmaceutica vol 67 pp 567ndash563 2010
[24] J-Y Lee K-W Jeong S Shin J-U Lee and Y Kim ldquoDiscoveryof novel selective inhibitors of Staphylococcus aureus 120573-ketoacylacyl carrier protein synthase IIIrdquo European Journal of MedicinalChemistry vol 47 no 1 pp 261ndash269 2012
[25] G M Maguene J Jakhlal M Ladyman et al ldquoSynthesis andantimycobacterial activity of a series of ferrocenyl derivativesrdquoEuropean Journal of Medicinal Chemistry vol 46 no 1 pp 31ndash38 2011
[26] R M Mohareb K A El-Sharkawy M M Hussein and HM El-Sehrawi ldquoSynthesis of hydrazide-hydrazone derivativesand their evaluation of antidepressant sedative and analgesicagentsrdquo Journal of Pharmaceutical Sciences and Research vol 2no 4 pp 185ndash196 2010
[27] A Ozdemir G Turan-Zitouni Z Asim Kaplancikli G IscanS Khan and F Demirci ldquoSynthesis and the selective antifun-gal activity of 5678-tetrahydroimidazo[12-a]pyridine deriva-tivesrdquo European Journal of Medicinal Chemistry vol 45 no 5pp 2080ndash2084 2010
[28] R N Sharma K P Sharma and S N Dikshit ldquoSynthe-sis characterization and biological activities of some newhypophosphorousadducts of acid hydrazones derived from 2-[(N-benzoyl) 2 3-dichloroanilido] acetohydraziderdquo Archives ofApplied Science Research vol 3 pp 415ndash424 2011
[29] S M Siddiqui A Salahuddin and A Azam ldquoSynthesischaracterization and antiamoebic activity of some hydrazoneand azole derivatives bearing pyridyl moiety as a promisingheterocyclic scaffoldrdquo European Journal ofMedicinal Chemistryvol 49 pp 411ndash416 2012
[30] E A Musad R Mohamed B Ali Saeed B S Vishwanathand K M Lokanatha Rai ldquoSynthesis and evaluation of antiox-idant and antibacterial activities of new substituted bis(134-oxadiazoles) 35-bis(substituted) pyrazoles and isoxazolesrdquo
Bioorganic and Medicinal Chemistry Letters vol 21 no 12 pp3536ndash3540 2011
[31] A Almasirad M Tajik D Bakhtiari et al ldquoSynthesis andanalgesic activity of N-arylhydrazone derivatives of mefenamicacidrdquo Journal of Pharmacy and Pharmaceutical Sciences vol 8no 3 pp 419ndash425 2005
[32] R Kalsi M Shrimali T N Bhalla and J P Barthwal ldquoSynthesisand anti-inflammatory activity of indolyl azetidinonesrdquo IndianJournal of Pharmaceutical Sciences vol 41 pp 353ndash359 2006
[33] A Almasirad M Tajik D Bakhtiari et al ldquoSynthesis andanalgesic activity of N-aryl hydrazone derivatives of mefenmicacidrdquo Journal of Pharmaceutical Sciences vol 8 no 3 pp 419ndash425 2005
[34] K K Sivakumar A Rajasekaran I Ponnilavarasan ASomasundaram R Sivasakthi and S Kamalaveni ldquoAntimi-crobial and analgesic activity of some (4Z)-3-methyl-1-[(2-oxo-2H-chromen-4-yl)carbonyl]-1H-pyrzole-4 5-dione 4-[(4-substitutedphenyl) hydrazone]rdquo Scholars Research Library vol2 no 1 pp 211ndash219 2010
[35] S A Khan P Mullick S Pandit and D Kaushik ldquoSynthesis ofhydrazones derivatives of quinoxalinonemdashprospective antimi-crobial and antiinflammatory agentsrdquo Acta Poloniae Pharma-ceutica vol 66 no 2 pp 169ndash172 2009
[36] M A A Radwan E A Ragab N M Sabry and S MEl-Shenawy ldquoSynthesis and biological evaluation of new 3-substituted indole derivatives as potential anti-inflammatoryand analgesic agentsrdquo Bioorganic and Medicinal Chemistry vol15 no 11 pp 3832ndash3841 2007
[37] A R Todeschini A L P De Miranda K C M Da SilvaS C Parrini and E J Barreiro ldquoSynthesis and evaluationof analgesic antiinflammatory and antiplatelet properties ofnew 2-pyridylarylhydrazone derivativesrdquo European Journal ofMedicinal Chemistry vol 33 no 3 pp 189ndash199 1998
[38] P C Lima L M Lima K C M Da Silva et al ldquoSynthesis andanalgesic activity of novel N-acylarylhydrazones and isostersderived from natural safrolerdquo European Journal of MedicinalChemistry vol 35 no 2 pp 187ndash203 2000
[39] P Hernandez M Cabrera M L Lavaggi et al ldquoDiscoveryof new orally effective analgesic and anti-inflammatory hybridfuroxanyl N-acylhydrazone derivativesrdquo Bioorganic and Medic-inal Chemistry vol 20 no 6 pp 2158ndash2171 2012
[40] G Rajitha N Saideepa and P Praneetha ldquoSynthesis andevaluation of N-(120572-benzamido cinnamoyl) aryl hydrazonederivatives for anti-inflammatory and antioxidant activitiesrdquoIndian Journal of Chemistry B vol 50 no 5 pp 729ndash733 2011
[41] C M Moldovan O Oniga A Parvu et al ldquoSynthesis and anti-inflammatory evaluation of some new acyl-hydrazones bearing2-aryl-thiazolerdquo European Journal of Medicinal Chemistry vol46 no 2 pp 526ndash534 2011
[42] M A-A El-Sayed N I Abdel-Aziz A A-M Abdel-Aziz AS El-Azab Y A Asiri and K E H Eltahir ldquoDesign synthesisand biological evaluation of substituted hydrazone and pyrazolederivatives as selective COX-2 inhibitors molecular dockingstudyrdquo Bioorganic and Medicinal Chemistry vol 19 no 11 pp3416ndash3424 2011
[43] A M Isloor B Kalluraya and K Sridhar Pai ldquoSynthe-sis characterization and biological activities of some newbenzo[b]thiophene derivativesrdquo European Journal of MedicinalChemistry vol 45 no 2 pp 825ndash830 2010
[44] M Sarangapani and V M Reddy ldquoPharmacological screen-ing of isatin-[N-(2-alkylbenzoxazole-5-carbonyl)] hydrazonesrdquo
Journal of Applied Chemistry 7
Indian Journal of Pharmaceutical Sciences vol 59 no 3 pp 105ndash109 1997
[45] S K Sridhar and A Ramesh ldquoSynthesis and pharmacologicalactivities of hydrazones schiff and mannich bases of isatinderivativesrdquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1149ndash1152 2001
[46] M Gokce S Utku and E Kupeli ldquoSynthesis and analgesicand anti-inflammatory activities 6-substituted-3(2H)-py-ridazinone-2-acetyl-2-(p-substitutednonsubstituted benzal)hydrazone derivativesrdquo European Journal of MedicinalChemistry vol 44 no 9 pp 3760ndash3764 2009
[47] A G M Fraga C R Rodrigues A L P De Miranda E JBarreiro and C A M Fraga ldquoSynthesis and pharmacologicalevaluation of novel heterotricyclic acylhydrazone derivativesdesigned as PAF antagonistsrdquo European Journal of Pharmaceu-tical Sciences vol 11 no 4 pp 285ndash290 2000
[48] G A Silva L M M Costa F C F Brito A L P Miranda EJ Barreiro and C A M Fraga ldquoNew class of potent antinoci-ceptive and antiplatelet 10H-phenothiazine-1-acylhydrazonederivativesrdquo Bioorganic andMedicinal Chemistry vol 12 no 12pp 3149ndash3158 2004
[49] U Salgin-Goksen N Gokhan-Kelekci O Goktas et al ldquo1-Acylthiosemicarbazides 124-triazole-5(4H)-thiones 134-thi-adiazoles andhydrazones containing 5-methyl-2-benzoxazolin-ones synthesis analgesic-anti-inflammatory and antimicrobialactivitiesrdquo Bioorganic and Medicinal Chemistry vol 15 no 17pp 5738ndash5751 2007
[50] C D Duarte J L M Tributino D I Lacerda et al ldquoSyn-thesis pharmacological evaluation and electrochemical studiesof novel 6-nitro-34-methylenedioxyphenyl-N-acylhydrazonederivatives discovery of LASSBio-881 a new ligand of cannabi-noid receptorsrdquo Bioorganic andMedicinal Chemistry vol 15 no6 pp 2421ndash2433 2007
[51] A Deep S Jain P C Sharma P Verma M Kumar andC P Dora ldquoDesign and biological evaluation of biphenyl-4-carboxylic acid hydrazide-hydrazone for antimicrobial activityrdquoActa Poloniae Pharmaceutica vol 67 no 3 pp 255ndash259 2010
[52] B Durgun G Capan N Ergenc and S Rollas ldquoSynthesischaracterization and biological evaluation of new benzyli-denebenzohydrazides and 25-disubstituted-23-dihydro-134-oxadiazolesrdquo Pharmazie vol 48 no 12 pp 942ndash943 1993
[53] O I El-Sabbagh M A Shabaan H H Kadry and E SAl-Din ldquoNew octahydroquinazoline derivatives synthesis andhypotensive activityrdquo European Journal of Medicinal Chemistryvol 45 no 11 pp 5390ndash5396 2010
[54] J L Gage R Onrust D Johnston et al ldquoN-Acylhydrazonesas inhibitors of PDE10Ardquo Bioorganic and Medicinal ChemistryLetters vol 21 no 14 pp 4155ndash4159 2011
[55] F Hayat A Salahuddin J Zargan and A Azam ldquoSynthe-sis characterization antiamoebic activity and cytotoxicity ofnovel 2-(quinolin-8-yloxy) acetohydrazones and their cyclizedproducts (123-thiadiazole and 123-selenadiazole derivatives)rdquoEuropean Journal of Medicinal Chemistry vol 45 no 12 pp6127ndash6134 2010
[56] Y Jin Z Tan M He et al ldquoSAR and molecular mechanismstudy of novel acylhydrazone compounds targeting HIV-1 CArdquoBioorganic and Medicinal Chemistry vol 18 no 6 pp 2135ndash2140 2010
[57] S Rollas and S G Kucukguzel ldquoBiological activities of hydra-zone derivativesrdquoMolecules vol 12 no 8 pp 1910ndash1939 2007
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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2 Journal of Applied Chemistry
that p-nitro benzaldehyde hydrazone exhibited maximuminhibitory effect [19] The effect of hydrazones and phenylhydrazones of simple aryl aldehydes along with their semi-carbazones and thiosemicarbazones on the activity of liveralkaline and acid phosphatase [20 21]
Hydrazones are an important class of compounds for newdrug development This created an interest to researcherswho have synthesized variety of hydrazone derivatives andscreened them for their various biological activities In thepresent study we have made an attempt to collect analgesicanti-inflammatory and antiplatelet properties of hydrazonederivatives Hydrazones are not only intermediates but alsovery effective organic compounds when they are used asintermediates and coupling products that can be synthesizedby using the active hydrozen component of ndashCONHN=CHndashazomethine group Many effective compounds such as ipro-niazid and isocarboxazid are synthesized by the reductionof hydrazide-hydrazones Iproniazid like INH is used in thetreatment of tuberculosis It has also displayed an antide-pressant effect and patients appear to have a better moodduring the treatment Another clinically effective hydrazide-hydrazones is nifuroxazide which is used as an intestinalantiseptic [22ndash25] Hydrazones are a class of organic com-pounds which possess the structure R
1R2C=NNH
2 They are
related to ketone and aldehyde in which oxygen has beenreplaced with NNH
2group These azometine ndashNHN=CHndash
protons constitute an important class of compounds for drugdevelopment Hydrazones are formed by the reaction ofhydrazine or hydrazide with aldehydes and ketones Hydra-zones are widely used in organic synthesis Many effectivecompounds such as iproniazide and isocarboxazid are syn-thesized by the reduction of hydrazide-hydrazones Anothereffective hydrazide-hydrazone is nifuroxazide which is usedas an intestinal antiseptic [26ndash30] This review highlightsanalgesic anti-inflammatory antipyretic and antiplateletsactivities shown by hydrazones
2 Analgesic and Anti-Inflammatory Activites
Nonsteroidal anti-inflammatory drugs (NSAIDs) are largelyused in the treatment of pain and inflammation Hydrazonesthat are dual inhibitors of both cyclooxygenase (COX)and 5-lipoxygenase (5-LO) are being studied as potentialanalgesic and anti-inflammatory agents in comparisonto NSAIDs [31] Nonsteroidal anti-inflammatory drugs(NSAIDs) have a wide clinical use for the treatment ofinflammation pain rheumatoid arthritis soft tissue and oralcavity lesions respiratory tract infections and fever The twoisoforms of COX are poorly distinguishable by most of theclassical NSAIDs and these agents actually inhibit COX-1extensively besides COX-2 leading to gastrointestinal(GI) injury suppression of TXA2 formation and plateletaggregation The combination of these interactions isprobably the reason for GI bleeding which is themost seriouscomplication of these drugs Some evidence suggests that thehydrazone moiety present in some compounds possesses apharmacophoric character for the inhibition of COX In factsome evidence suggests that the hydrazone moiety presentin derivative possesses a pharmacophoric character for the
inhibition of COX [32]The results showed that pyridine ringat the aryl moiety of the arylhydrazone is having good anal-gesic activity in comparison to mefenamic acid Compoundspossessing the 4-tolyl or 4-fluorophenyl moiety are moreactive than 4-bromophenyl and 4-NN-dimethylaminophe-nyl The anti-inflammatory evaluation showed that thereplacement of carboxylic acid group of mefenamic acid withN-arylhydrazone moiety cannot produce any advantage inthe anti-inflammatory property [33] Analgesic activity ofsome (4Z)-3-methyl-1-[(2-oxo-2Hchromene-4-yl)carbonyl]-1H-pyrazole-45-dione4-(4-substitutedphenyl)hydrazonesome of them showed significant analgesic activity Pharmac-ological evaluation was done by using acetic acid-inducedwrithing model in mice which showed that the presenceof 4-chloro 4-bromo 34-dichloro 34-dibromo and 4-methyl group in the aromatic ring of 4-position of thepyrazole-hydrazono nucleus gave rise to increased analgesicactivities [34] Hydrazone derivatives of quinoxalinoneand evaluated for anti-inflammatory activity showed thatcompounds having methoxy group at the para-positionshowed comparatively good percentage of inhibition ofedema than the other compounds [35] Treatment of 3-cyanoacetylindole with diazonium salts of 3-phenyl-5-aminopyrazole and 2-amino pyrazole gave the correspondinghydrazones Compound 3-(1H-Indol-3-yl)-3-oxo-2-[(5-phe-nyl-2H-pyrazol-3-yl)-hydrazono]-propionitrile was found topossess appreciable analgesic and anti-inflammatory activity[36] The anti-inflammatory derivative 2-(2-formylfuryl)pyridylhydrazone (1) presented a 79 inhibition of pleurisyat a dose of 801 120583molkg The results concerning themechanism of the action of these series of N-heterocyclicderivatives in platelet aggregation suggest a Ca2+ scavengermechanism Compound 2 was able to complex Ca2+ inin vitro experiments at 100 120583M concentration indicatingthat these series of compounds can act as Ca2+ scavengerdepending on the nature of the aryl moiety present at theimine subunit [37] A series of analgesic compounds thatbelong to the N-acylarylhydrazone class were synthesizedfrom natural safrole [(41015840-NN-Dimethylaminobenzylidene-3-(3101584041015840methylenedioxyphenyl)propionyl hydrazine] (2)was more potent than dipyrone and indomethacin [38]Analgesic and anti-inflammatory activity of furoxanyl-N-acylhydrazones (3 4) [39] The anti-inflammatory activityof some aryl hydrazones (5) got good results [40] Varioushydrazone derivatives (6) reported them to have promising invivo anti-inflammatory activity [41] Hydrazone derivatives(7) with selective COX-2 inhibition The compound isreported to have an ED
50value of 02mmolKg [42]
Benzothiophene derivatives (8) with inhibition of 502have been developed [43] see Figure 1
Fifteen different isatin[N-(2-alkylbenzoxazole-5-car-bonyl)] hydrazones (9) were screened for analgesic anti-depressant andH1-antihistaminic activities [44]These com-pounds were also studied for their effect on pentobarbitone-induced narcosisThree compounds bearing amethyl substit-uent at 7-position of the benzoxazole system exhibit goodanalgesic activity Schiff bases and phenyl hydrazone of isa-tins prepared from isatin and appropriate aromatic primary
Journal of Applied Chemistry 3
N NH
NO
O
O
NH
O
N
N
NO
N
N
HN
ONH
N
N ON
O NHN
OH
Br
NHN
O
O
NS
O
N NH
O
N S
Cl
O
NHN
ONH
N
NN
O
BT
O
H3C
H3C
H3C
H3CH3C
H3C
H3C
CH3
CH3
OH2
NO2
CF3
CF3
H3CO
F3C
1 2 3 4
8765
Figure 1
aminehydrazines were screened for analgesic anti-inflam-matory and antipyretic activity [45] 1-Diphenylamino-methyl-3-(1-naphthylimino)-13-dihydroindol-3-one 3-(1-naphthylimino)-5-bromo-13-dihydroindol-2-one (10) and1-diphenylaminomethyl-3-(4-methylphenylimino)-13-dihy-droindol-3-one exhibited the highest analgesic anti-inflammatory and antipyretic activity respectively Few 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(p-substitutedbenzal)hydrazone derivatives exhibited analgesic and anti-inflammatory agents None of the compounds was found toshow gastric ulcerogenic effect in comparison with referenceNSAIDs [46] 2-(2-Formylfuryl)pyridylhydrazone possessedanti-inflammatory activity and showed 79 inhibition ofpleurisy at a dose of 801 120583molkg The results indicated thatthese series of compounds can act as Ca2+ scavenger andplatelet aggregation [37] see Figure 2
21 Antiplatelet Activity The antiplatelet activity of tricyclicacylhydrazone derivatives (11) was evaluated by their abilityto inhibit platelet aggregation of rabbit platelet-rich plasmainduced by platelet activating factor (PAF) at 50 nMBenzylidene-41015840-bromobenzylidene 3-OH-8-CH
3-6-phenyl-
pyrazolo[34-b]thieno-[23-d]pyridine-2-carbohydrazidewasevaluated at 10 120583M presenting respectively 104 and 136
of inhibition of the PAF-induced platelet aggregation [37]The evaluation of platelet antiaggregating profile let to theidentification of a new potent prototype of antiplateletderivative that is benzylidene 10H-phenothiazine-1-carbo-hydrazide (IC
50= 23 120583M) which acts in the AA pathway
probably by the inhibition of platelet COX-1 enzymeAdditionally the change in para-substituent group ofacylhydrazone framework permitted to identify a hydrophiliccarboxylate derivative and a hydrophobic bromo derivativeas two new analgesics that are more potent than dipyronepossessing selective peripheral or central mechanism ofaction [47] The evaluation of platelet antiaggregatingprofile let to the identification of a new potent prototypethat is benzylidene 10H-phenothiazine-1-carbohydrazide(IC50
= 23 120583M) (12) which acts in the arachidonic acid(AA) pathway probably by the inhibition of platelet COX-1enzyme Change in para-substituent group of acylhydrazoneframework permitted to identify a hydrophilic carboxylatederivative and a hydrophobic bromo derivative as twoanalgesics that are more potent than dipyrone possessingselective peripheral or central mechanism of action [48]Hydrazones containing 5-methyl-2-benzoxazoline the anal-gesic effects of 2-[2-(5-methyl-2-benzoxazoline-3-yl)acetyl]-4-chloro-4-methyl benzylidene hydrazine (13a) and (13b)
4 Journal of Applied Chemistry
NH
O
N
HN
O
O
N
R
NHO
Br
N
9 10
Figure 2
NN N
H
S
NH
N
O
H3C
OH
Ar
S
HN
NH
O
N Ar
O
NO
NH
O
N Cl
O
NO
NH
O
NO
O
NH
O
N
OH
NN N
O
HN N
Ar
Me
NH
X
Ar = Ph X = HAr = Pyrid-4-yl X = HAr = 2-Nitrofuryl X = 4-Cl
11 12
13b 14 15 16 17
13a
CH3
Figure 3
were found to be higher than morphine and aspirin Inaddition 2-[2-(5-methyl-2-benzoxazoline-3-yl)acetyl]-4-methoxy benzylidene hydrazine at 200mgkg dose possessedthe anti-inflammatory activity [49] N1015840-(35-Di-tert-butyl-4-hydroxybenzylidene)-6-nitro-13-benzodioxole-5-carbo-hydrazine (14) as an anti-inflammatory compound [50]Antiplatelets decrease platelet aggregation and prevent theformation of thrombus Hydrazone derivatives (15 16 17)exhibited an in vitro antiplatelet activity see Figure 3
3 Synthetic Approach for the NovelHydrzonone and Its Biological Activity
A number of organic compounds obtained by chemicalsynthesis as model compounds have useful analgesic anti-inflammatory antipyretic and antiplatelets activities Manyof hydrazonones its derivatives possess interesting biological
activities such as analgesic anti-inflammatory antimicro-bial and antitumor activitesThe biological activity of synthe-sized hydrazonone derivatives was characterized and detailedstudy is in progress to modify the synthetic route structuralactivity and toxicological barriers for the enhanced pharma-cological efficiency of synthetic hydrazones [37 45ndash49]
4 Development of New NSAIDs
The NSAIDs preparations are among the most commonlyprescribed drugs NSAIDs are sometimes known as theaspirin-like drugs because they have an activity profile thatis broadly similar to that of aspirin that is they all possessanalgesic anti-inflammatory and antipyretic properties tosomedegree and produce characteristic side effects includinggastric intolerance and depression of blood clotting throughinhibitory action on platelet function Two closely related
Journal of Applied Chemistry 5
forms of the cyclooxygenase have been identified whichare now known as COX-1 and COX-2 Both isoenzymestransform arachidonic acid (AA) to prostaglandins (PGs)but differ in their distribution and their physiological rolesMeanwhile the responsible genes and their regulation havebeen clarified COX-1 the predominantly constitutive formofthe enzyme is expressed throughout the body and performsa number of homeostatic functions such as maintainingnormal gastric mucosa and influencing renal blood flowSimmons also recently codiscovered COX-3 in 2002 andanalyzed this new isozymersquos relation which acetaminophen(paracetamol) arguably the most widely used analgesic drugin the world The clinical ramifications and knowledge ofCOX isozymes are therefore rapidly expanding and couldperhaps offer significant hope for future treatments of paininflammation and fever [37 45ndash49]
5 Discussion
Hydrazones possessing an azomethine ndashNHN=CHndash groupconstitute an important class of compounds as target struc-tures for their biological activities These observations guideus for the development of new hydrazones that possess variedbiological activitiesThe literature studies on hydrazones haveshown that these derivatives possess a wide variety of biolog-ical activities such as antitumor antibacterial antiviral anti-hypertensive anticonvulsant anti-inflammatory analgesicantipyretic antiplatelets vasorelaxant anticoagulant andantiprotozoal activities There has been considerable interestin the development of novel compounds with wide varietiesof biological activities These molecules are easily preparedand have diverse pharmacological potential This encouragesto the researchers to synthesize different new compoundsbearing hydrazones with low toxicity Differently substitutedhydrazones have been developed and found to be activeagainst different pharmacological targetsThese observationshave been guiding the development of new hydrazones thatpossess varied biological activities Hydrazone derivativesof carbonyl compounds constitute an important class ofbiologically active compounds [50ndash57]
6 Conclusion
Hydrazonone nucleus exhibited immense pharmacologicalactivities The simple hydrazonone nucleus is present incompounds are evaluating for new products that possesssome remarkable pharmacological activities such as anal-gesic anti-inflammatory antipyretic antiplatelet aggrega-tion cardiotonic antihypertensive analgesic vasodilatoryantidiabetic and anticonvulsant activites The present reviewfocuses on hydrazonone which possesses potential analgesicanti-inflammatory antipyretic and anti-platelet aggregationactivities that are new in development
References
[1] M Singh and N Raghav ldquoBiological activities of hydrazones areviewrdquo International Journal of Pharmacy and PharmaceuticalSciences vol 3 no 4 pp 26ndash32 2011
[2] H S Seleem G A El-Inany B A El-Shetary andM AMousaldquoThe ligational behavior of a phenolic quinolyl hydrazonetowards copper(II)-ionsrdquo Chemistry Central Journal vol 5article 2 2011
[3] B F Abdel-Wahab G E A Awad and F A Badria ldquoSynthesisantimicrobial antioxidant anti-hemolytic and cytotoxic evalu-ation of new imidazole-based heterocyclesrdquo European Journalof Medicinal Chemistry vol 46 no 5 pp 1505ndash1511 2011
[4] A S Abu-Surrah K A Abu Safieh I M Ahmad et al ldquoNewpalladium(II) complexes bearing pyrazole-based Schiff baseligands synthesis characterization and cytotoxicityrdquo EuropeanJournal of Medicinal Chemistry vol 45 no 2 pp 471ndash475 2010
[5] O O Ajani C A Obafemi O C Nwinyi and D A AkinpeluldquoMicrowave assisted synthesis and antimicrobial activity of 2-quinoxalinone-3-hydrazone derivativesrdquoBioorganic andMedic-inal Chemistry vol 18 no 1 pp 214ndash221 2010
[6] M S Al-Said M S Bashandy S I Al-Qasoumi and MM Ghorab ldquoAnti-breast cancer activity of some novel 12-dihydropyridine thiophene and thiazole derivativesrdquo EuropeanJournal of Medicinal Chemistry vol 46 no 1 pp 137ndash141 2011
[7] M A S Aslam S-U Mahmood M Shahid A Saeed andJ Iqbal ldquoSynthesis biological assay in vitro and moleculardocking studies of new Schiff base derivatives as potentialurease inhibitorsrdquoEuropean Journal ofMedicinal Chemistry vol46 no 11 pp 5473ndash5479 2011
[8] Z Cui Y Li Y Ling et al ldquoNew class of potent antitumoracylhydrazone derivatives containing furanrdquo European Journalof Medicinal Chemistry vol 45 no 12 pp 5576ndash5584 2010
[9] D Kaushik S A Khan G Chawla and S Kumar ldquoN1015840-[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene] 24-substituted hydrazides synthesis and anticonvulsant activityrdquoEuropean Journal of Medicinal Chemistry vol 45 no 9 pp3943ndash3949 2010
[10] M M Edrees T A Farghaly F A A El-Hag and M MAbdalla ldquoAntimicrobial antitumor and 5120572-reductase inhibitoractivities of some hydrazonoyl substituted pyrimidinonesrdquoEuropean Journal of Medicinal Chemistry vol 45 no 12 pp5702ndash5707 2010
[11] A A El-Sherif ldquoSynthesis spectroscopic characterizationand biological activity on newly synthesized copper(II) andnickel(II) complexes incorporating bidentate oxygen-nitrogenhydrazone ligandsrdquo Inorganica Chimica Acta vol 362 no 14pp 4991ndash5000 2009
[12] G A Al-Hazmi and A A El-Asmy ldquoSynthesis spectroscopyand thermal analysis of copper(II) hydrazone complexesrdquoJournal of Coordination Chemistry vol 62 no 2 pp 337ndash3452009
[13] Y-L Sang and X-S Lin ldquoSyntheses and crystal structuresof two Schiff-base copper(II) complexes with antibacterialactivitiesrdquo Journal of Coordination Chemistry vol 63 no 2 pp315ndash322 2010
[14] O Pouralimardan A-C Chamayou C Janiak and HHosseini-Monfared ldquoHydrazone Schiff base-manganese(II)complexes synthesis crystal structure and catalytic reactivityrdquoInorganica Chimica Acta vol 360 no 5 pp 1599ndash1608 2007
[15] C Basu S Chowdhury R Banerjee H Stoeckli Evans andS Mukherjee ldquoA novel blue luminescent high-spin iron(III)complex with interlayer O-H Cl bridging synthesis structureand spectroscopic studiesrdquo Polyhedron vol 26 no 14 pp 3617ndash3624 2007
[16] S Siemann D P Evanoff L Marrone A J Clarke TViswanatha and G I Dmitrienko ldquoN-arylsulfonyl hydrazones
6 Journal of Applied Chemistry
as inhibitors of IMP-1 metallo-120573-lactamaserdquo AntimicrobialAgents and Chemotherapy vol 46 no 8 pp 2450ndash2457 2002
[17] M L Hanna T M Tarasow and J Perkins ldquoMechanisticdifferences between in vitro assays for hydrazone-based smallmolecule inhibitors of anthrax lethal factorrdquo Bioorganic Chem-istry vol 35 no 1 pp 50ndash58 2007
[18] C L Cywi R A Firestone D W McNeil C A Grygon K MCrane D M White et al ldquoThe design of potent hydrazonesand disulfides as cathepsin S inhibitorsrdquo Journal of MolecularStructure vol 34 pp 9ndash22 2009
[19] N Raghav M Singh R Kaur S Suman and P Priyanka ldquoPro-teolytic studies in liver homogenate in presence of substitutedaryl hydrazonesrdquo Asian Journal of Chemistry vol 23 no 3 pp1409ndash1410 2011
[20] N RaghavM Singh S Jangra A Rohilla R Kaur and PMalikldquoIn-Vitro studies of various carbonyl derivatives on liver alkalinephosphataserdquo Journal of Chemical and Pharmaceutical Researchvol 2 no 4 pp 801ndash807 2010
[21] N Raghav M Singh S Jangra A Rohilla R Kaur and PMalik ldquoIn-Vitro studies of various carbonyl derivatives on liveracid phosphataserdquo International Journal of Applied Biology andPharmaceutical Technology vol 1 no 3 pp 1011ndash1015 2010
[22] S Eswaran A V Adhikari I H Chowdhury N K Paland K D Thomas ldquoNew quinoline derivatives synthesis andinvestigation of antibacterial and antituberculosis propertiesrdquoEuropean Journal of Medicinal Chemistry vol 45 no 8 pp3374ndash3383 2010
[23] S Kumar S Bawai S Drabu R Kumar and L MachwalldquoChloroquinolinylhydrazone derivative as anticonvulsantrdquoActaPoloniae Pharmaceutica vol 67 pp 567ndash563 2010
[24] J-Y Lee K-W Jeong S Shin J-U Lee and Y Kim ldquoDiscoveryof novel selective inhibitors of Staphylococcus aureus 120573-ketoacylacyl carrier protein synthase IIIrdquo European Journal of MedicinalChemistry vol 47 no 1 pp 261ndash269 2012
[25] G M Maguene J Jakhlal M Ladyman et al ldquoSynthesis andantimycobacterial activity of a series of ferrocenyl derivativesrdquoEuropean Journal of Medicinal Chemistry vol 46 no 1 pp 31ndash38 2011
[26] R M Mohareb K A El-Sharkawy M M Hussein and HM El-Sehrawi ldquoSynthesis of hydrazide-hydrazone derivativesand their evaluation of antidepressant sedative and analgesicagentsrdquo Journal of Pharmaceutical Sciences and Research vol 2no 4 pp 185ndash196 2010
[27] A Ozdemir G Turan-Zitouni Z Asim Kaplancikli G IscanS Khan and F Demirci ldquoSynthesis and the selective antifun-gal activity of 5678-tetrahydroimidazo[12-a]pyridine deriva-tivesrdquo European Journal of Medicinal Chemistry vol 45 no 5pp 2080ndash2084 2010
[28] R N Sharma K P Sharma and S N Dikshit ldquoSynthe-sis characterization and biological activities of some newhypophosphorousadducts of acid hydrazones derived from 2-[(N-benzoyl) 2 3-dichloroanilido] acetohydraziderdquo Archives ofApplied Science Research vol 3 pp 415ndash424 2011
[29] S M Siddiqui A Salahuddin and A Azam ldquoSynthesischaracterization and antiamoebic activity of some hydrazoneand azole derivatives bearing pyridyl moiety as a promisingheterocyclic scaffoldrdquo European Journal ofMedicinal Chemistryvol 49 pp 411ndash416 2012
[30] E A Musad R Mohamed B Ali Saeed B S Vishwanathand K M Lokanatha Rai ldquoSynthesis and evaluation of antiox-idant and antibacterial activities of new substituted bis(134-oxadiazoles) 35-bis(substituted) pyrazoles and isoxazolesrdquo
Bioorganic and Medicinal Chemistry Letters vol 21 no 12 pp3536ndash3540 2011
[31] A Almasirad M Tajik D Bakhtiari et al ldquoSynthesis andanalgesic activity of N-arylhydrazone derivatives of mefenamicacidrdquo Journal of Pharmacy and Pharmaceutical Sciences vol 8no 3 pp 419ndash425 2005
[32] R Kalsi M Shrimali T N Bhalla and J P Barthwal ldquoSynthesisand anti-inflammatory activity of indolyl azetidinonesrdquo IndianJournal of Pharmaceutical Sciences vol 41 pp 353ndash359 2006
[33] A Almasirad M Tajik D Bakhtiari et al ldquoSynthesis andanalgesic activity of N-aryl hydrazone derivatives of mefenmicacidrdquo Journal of Pharmaceutical Sciences vol 8 no 3 pp 419ndash425 2005
[34] K K Sivakumar A Rajasekaran I Ponnilavarasan ASomasundaram R Sivasakthi and S Kamalaveni ldquoAntimi-crobial and analgesic activity of some (4Z)-3-methyl-1-[(2-oxo-2H-chromen-4-yl)carbonyl]-1H-pyrzole-4 5-dione 4-[(4-substitutedphenyl) hydrazone]rdquo Scholars Research Library vol2 no 1 pp 211ndash219 2010
[35] S A Khan P Mullick S Pandit and D Kaushik ldquoSynthesis ofhydrazones derivatives of quinoxalinonemdashprospective antimi-crobial and antiinflammatory agentsrdquo Acta Poloniae Pharma-ceutica vol 66 no 2 pp 169ndash172 2009
[36] M A A Radwan E A Ragab N M Sabry and S MEl-Shenawy ldquoSynthesis and biological evaluation of new 3-substituted indole derivatives as potential anti-inflammatoryand analgesic agentsrdquo Bioorganic and Medicinal Chemistry vol15 no 11 pp 3832ndash3841 2007
[37] A R Todeschini A L P De Miranda K C M Da SilvaS C Parrini and E J Barreiro ldquoSynthesis and evaluationof analgesic antiinflammatory and antiplatelet properties ofnew 2-pyridylarylhydrazone derivativesrdquo European Journal ofMedicinal Chemistry vol 33 no 3 pp 189ndash199 1998
[38] P C Lima L M Lima K C M Da Silva et al ldquoSynthesis andanalgesic activity of novel N-acylarylhydrazones and isostersderived from natural safrolerdquo European Journal of MedicinalChemistry vol 35 no 2 pp 187ndash203 2000
[39] P Hernandez M Cabrera M L Lavaggi et al ldquoDiscoveryof new orally effective analgesic and anti-inflammatory hybridfuroxanyl N-acylhydrazone derivativesrdquo Bioorganic and Medic-inal Chemistry vol 20 no 6 pp 2158ndash2171 2012
[40] G Rajitha N Saideepa and P Praneetha ldquoSynthesis andevaluation of N-(120572-benzamido cinnamoyl) aryl hydrazonederivatives for anti-inflammatory and antioxidant activitiesrdquoIndian Journal of Chemistry B vol 50 no 5 pp 729ndash733 2011
[41] C M Moldovan O Oniga A Parvu et al ldquoSynthesis and anti-inflammatory evaluation of some new acyl-hydrazones bearing2-aryl-thiazolerdquo European Journal of Medicinal Chemistry vol46 no 2 pp 526ndash534 2011
[42] M A-A El-Sayed N I Abdel-Aziz A A-M Abdel-Aziz AS El-Azab Y A Asiri and K E H Eltahir ldquoDesign synthesisand biological evaluation of substituted hydrazone and pyrazolederivatives as selective COX-2 inhibitors molecular dockingstudyrdquo Bioorganic and Medicinal Chemistry vol 19 no 11 pp3416ndash3424 2011
[43] A M Isloor B Kalluraya and K Sridhar Pai ldquoSynthe-sis characterization and biological activities of some newbenzo[b]thiophene derivativesrdquo European Journal of MedicinalChemistry vol 45 no 2 pp 825ndash830 2010
[44] M Sarangapani and V M Reddy ldquoPharmacological screen-ing of isatin-[N-(2-alkylbenzoxazole-5-carbonyl)] hydrazonesrdquo
Journal of Applied Chemistry 7
Indian Journal of Pharmaceutical Sciences vol 59 no 3 pp 105ndash109 1997
[45] S K Sridhar and A Ramesh ldquoSynthesis and pharmacologicalactivities of hydrazones schiff and mannich bases of isatinderivativesrdquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1149ndash1152 2001
[46] M Gokce S Utku and E Kupeli ldquoSynthesis and analgesicand anti-inflammatory activities 6-substituted-3(2H)-py-ridazinone-2-acetyl-2-(p-substitutednonsubstituted benzal)hydrazone derivativesrdquo European Journal of MedicinalChemistry vol 44 no 9 pp 3760ndash3764 2009
[47] A G M Fraga C R Rodrigues A L P De Miranda E JBarreiro and C A M Fraga ldquoSynthesis and pharmacologicalevaluation of novel heterotricyclic acylhydrazone derivativesdesigned as PAF antagonistsrdquo European Journal of Pharmaceu-tical Sciences vol 11 no 4 pp 285ndash290 2000
[48] G A Silva L M M Costa F C F Brito A L P Miranda EJ Barreiro and C A M Fraga ldquoNew class of potent antinoci-ceptive and antiplatelet 10H-phenothiazine-1-acylhydrazonederivativesrdquo Bioorganic andMedicinal Chemistry vol 12 no 12pp 3149ndash3158 2004
[49] U Salgin-Goksen N Gokhan-Kelekci O Goktas et al ldquo1-Acylthiosemicarbazides 124-triazole-5(4H)-thiones 134-thi-adiazoles andhydrazones containing 5-methyl-2-benzoxazolin-ones synthesis analgesic-anti-inflammatory and antimicrobialactivitiesrdquo Bioorganic and Medicinal Chemistry vol 15 no 17pp 5738ndash5751 2007
[50] C D Duarte J L M Tributino D I Lacerda et al ldquoSyn-thesis pharmacological evaluation and electrochemical studiesof novel 6-nitro-34-methylenedioxyphenyl-N-acylhydrazonederivatives discovery of LASSBio-881 a new ligand of cannabi-noid receptorsrdquo Bioorganic andMedicinal Chemistry vol 15 no6 pp 2421ndash2433 2007
[51] A Deep S Jain P C Sharma P Verma M Kumar andC P Dora ldquoDesign and biological evaluation of biphenyl-4-carboxylic acid hydrazide-hydrazone for antimicrobial activityrdquoActa Poloniae Pharmaceutica vol 67 no 3 pp 255ndash259 2010
[52] B Durgun G Capan N Ergenc and S Rollas ldquoSynthesischaracterization and biological evaluation of new benzyli-denebenzohydrazides and 25-disubstituted-23-dihydro-134-oxadiazolesrdquo Pharmazie vol 48 no 12 pp 942ndash943 1993
[53] O I El-Sabbagh M A Shabaan H H Kadry and E SAl-Din ldquoNew octahydroquinazoline derivatives synthesis andhypotensive activityrdquo European Journal of Medicinal Chemistryvol 45 no 11 pp 5390ndash5396 2010
[54] J L Gage R Onrust D Johnston et al ldquoN-Acylhydrazonesas inhibitors of PDE10Ardquo Bioorganic and Medicinal ChemistryLetters vol 21 no 14 pp 4155ndash4159 2011
[55] F Hayat A Salahuddin J Zargan and A Azam ldquoSynthe-sis characterization antiamoebic activity and cytotoxicity ofnovel 2-(quinolin-8-yloxy) acetohydrazones and their cyclizedproducts (123-thiadiazole and 123-selenadiazole derivatives)rdquoEuropean Journal of Medicinal Chemistry vol 45 no 12 pp6127ndash6134 2010
[56] Y Jin Z Tan M He et al ldquoSAR and molecular mechanismstudy of novel acylhydrazone compounds targeting HIV-1 CArdquoBioorganic and Medicinal Chemistry vol 18 no 6 pp 2135ndash2140 2010
[57] S Rollas and S G Kucukguzel ldquoBiological activities of hydra-zone derivativesrdquoMolecules vol 12 no 8 pp 1910ndash1939 2007
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
Journal of Applied Chemistry 3
N NH
NO
O
O
NH
O
N
N
NO
N
N
HN
ONH
N
N ON
O NHN
OH
Br
NHN
O
O
NS
O
N NH
O
N S
Cl
O
NHN
ONH
N
NN
O
BT
O
H3C
H3C
H3C
H3CH3C
H3C
H3C
CH3
CH3
OH2
NO2
CF3
CF3
H3CO
F3C
1 2 3 4
8765
Figure 1
aminehydrazines were screened for analgesic anti-inflam-matory and antipyretic activity [45] 1-Diphenylamino-methyl-3-(1-naphthylimino)-13-dihydroindol-3-one 3-(1-naphthylimino)-5-bromo-13-dihydroindol-2-one (10) and1-diphenylaminomethyl-3-(4-methylphenylimino)-13-dihy-droindol-3-one exhibited the highest analgesic anti-inflammatory and antipyretic activity respectively Few 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(p-substitutedbenzal)hydrazone derivatives exhibited analgesic and anti-inflammatory agents None of the compounds was found toshow gastric ulcerogenic effect in comparison with referenceNSAIDs [46] 2-(2-Formylfuryl)pyridylhydrazone possessedanti-inflammatory activity and showed 79 inhibition ofpleurisy at a dose of 801 120583molkg The results indicated thatthese series of compounds can act as Ca2+ scavenger andplatelet aggregation [37] see Figure 2
21 Antiplatelet Activity The antiplatelet activity of tricyclicacylhydrazone derivatives (11) was evaluated by their abilityto inhibit platelet aggregation of rabbit platelet-rich plasmainduced by platelet activating factor (PAF) at 50 nMBenzylidene-41015840-bromobenzylidene 3-OH-8-CH
3-6-phenyl-
pyrazolo[34-b]thieno-[23-d]pyridine-2-carbohydrazidewasevaluated at 10 120583M presenting respectively 104 and 136
of inhibition of the PAF-induced platelet aggregation [37]The evaluation of platelet antiaggregating profile let to theidentification of a new potent prototype of antiplateletderivative that is benzylidene 10H-phenothiazine-1-carbo-hydrazide (IC
50= 23 120583M) which acts in the AA pathway
probably by the inhibition of platelet COX-1 enzymeAdditionally the change in para-substituent group ofacylhydrazone framework permitted to identify a hydrophiliccarboxylate derivative and a hydrophobic bromo derivativeas two new analgesics that are more potent than dipyronepossessing selective peripheral or central mechanism ofaction [47] The evaluation of platelet antiaggregatingprofile let to the identification of a new potent prototypethat is benzylidene 10H-phenothiazine-1-carbohydrazide(IC50
= 23 120583M) (12) which acts in the arachidonic acid(AA) pathway probably by the inhibition of platelet COX-1enzyme Change in para-substituent group of acylhydrazoneframework permitted to identify a hydrophilic carboxylatederivative and a hydrophobic bromo derivative as twoanalgesics that are more potent than dipyrone possessingselective peripheral or central mechanism of action [48]Hydrazones containing 5-methyl-2-benzoxazoline the anal-gesic effects of 2-[2-(5-methyl-2-benzoxazoline-3-yl)acetyl]-4-chloro-4-methyl benzylidene hydrazine (13a) and (13b)
4 Journal of Applied Chemistry
NH
O
N
HN
O
O
N
R
NHO
Br
N
9 10
Figure 2
NN N
H
S
NH
N
O
H3C
OH
Ar
S
HN
NH
O
N Ar
O
NO
NH
O
N Cl
O
NO
NH
O
NO
O
NH
O
N
OH
NN N
O
HN N
Ar
Me
NH
X
Ar = Ph X = HAr = Pyrid-4-yl X = HAr = 2-Nitrofuryl X = 4-Cl
11 12
13b 14 15 16 17
13a
CH3
Figure 3
were found to be higher than morphine and aspirin Inaddition 2-[2-(5-methyl-2-benzoxazoline-3-yl)acetyl]-4-methoxy benzylidene hydrazine at 200mgkg dose possessedthe anti-inflammatory activity [49] N1015840-(35-Di-tert-butyl-4-hydroxybenzylidene)-6-nitro-13-benzodioxole-5-carbo-hydrazine (14) as an anti-inflammatory compound [50]Antiplatelets decrease platelet aggregation and prevent theformation of thrombus Hydrazone derivatives (15 16 17)exhibited an in vitro antiplatelet activity see Figure 3
3 Synthetic Approach for the NovelHydrzonone and Its Biological Activity
A number of organic compounds obtained by chemicalsynthesis as model compounds have useful analgesic anti-inflammatory antipyretic and antiplatelets activities Manyof hydrazonones its derivatives possess interesting biological
activities such as analgesic anti-inflammatory antimicro-bial and antitumor activitesThe biological activity of synthe-sized hydrazonone derivatives was characterized and detailedstudy is in progress to modify the synthetic route structuralactivity and toxicological barriers for the enhanced pharma-cological efficiency of synthetic hydrazones [37 45ndash49]
4 Development of New NSAIDs
The NSAIDs preparations are among the most commonlyprescribed drugs NSAIDs are sometimes known as theaspirin-like drugs because they have an activity profile thatis broadly similar to that of aspirin that is they all possessanalgesic anti-inflammatory and antipyretic properties tosomedegree and produce characteristic side effects includinggastric intolerance and depression of blood clotting throughinhibitory action on platelet function Two closely related
Journal of Applied Chemistry 5
forms of the cyclooxygenase have been identified whichare now known as COX-1 and COX-2 Both isoenzymestransform arachidonic acid (AA) to prostaglandins (PGs)but differ in their distribution and their physiological rolesMeanwhile the responsible genes and their regulation havebeen clarified COX-1 the predominantly constitutive formofthe enzyme is expressed throughout the body and performsa number of homeostatic functions such as maintainingnormal gastric mucosa and influencing renal blood flowSimmons also recently codiscovered COX-3 in 2002 andanalyzed this new isozymersquos relation which acetaminophen(paracetamol) arguably the most widely used analgesic drugin the world The clinical ramifications and knowledge ofCOX isozymes are therefore rapidly expanding and couldperhaps offer significant hope for future treatments of paininflammation and fever [37 45ndash49]
5 Discussion
Hydrazones possessing an azomethine ndashNHN=CHndash groupconstitute an important class of compounds as target struc-tures for their biological activities These observations guideus for the development of new hydrazones that possess variedbiological activitiesThe literature studies on hydrazones haveshown that these derivatives possess a wide variety of biolog-ical activities such as antitumor antibacterial antiviral anti-hypertensive anticonvulsant anti-inflammatory analgesicantipyretic antiplatelets vasorelaxant anticoagulant andantiprotozoal activities There has been considerable interestin the development of novel compounds with wide varietiesof biological activities These molecules are easily preparedand have diverse pharmacological potential This encouragesto the researchers to synthesize different new compoundsbearing hydrazones with low toxicity Differently substitutedhydrazones have been developed and found to be activeagainst different pharmacological targetsThese observationshave been guiding the development of new hydrazones thatpossess varied biological activities Hydrazone derivativesof carbonyl compounds constitute an important class ofbiologically active compounds [50ndash57]
6 Conclusion
Hydrazonone nucleus exhibited immense pharmacologicalactivities The simple hydrazonone nucleus is present incompounds are evaluating for new products that possesssome remarkable pharmacological activities such as anal-gesic anti-inflammatory antipyretic antiplatelet aggrega-tion cardiotonic antihypertensive analgesic vasodilatoryantidiabetic and anticonvulsant activites The present reviewfocuses on hydrazonone which possesses potential analgesicanti-inflammatory antipyretic and anti-platelet aggregationactivities that are new in development
References
[1] M Singh and N Raghav ldquoBiological activities of hydrazones areviewrdquo International Journal of Pharmacy and PharmaceuticalSciences vol 3 no 4 pp 26ndash32 2011
[2] H S Seleem G A El-Inany B A El-Shetary andM AMousaldquoThe ligational behavior of a phenolic quinolyl hydrazonetowards copper(II)-ionsrdquo Chemistry Central Journal vol 5article 2 2011
[3] B F Abdel-Wahab G E A Awad and F A Badria ldquoSynthesisantimicrobial antioxidant anti-hemolytic and cytotoxic evalu-ation of new imidazole-based heterocyclesrdquo European Journalof Medicinal Chemistry vol 46 no 5 pp 1505ndash1511 2011
[4] A S Abu-Surrah K A Abu Safieh I M Ahmad et al ldquoNewpalladium(II) complexes bearing pyrazole-based Schiff baseligands synthesis characterization and cytotoxicityrdquo EuropeanJournal of Medicinal Chemistry vol 45 no 2 pp 471ndash475 2010
[5] O O Ajani C A Obafemi O C Nwinyi and D A AkinpeluldquoMicrowave assisted synthesis and antimicrobial activity of 2-quinoxalinone-3-hydrazone derivativesrdquoBioorganic andMedic-inal Chemistry vol 18 no 1 pp 214ndash221 2010
[6] M S Al-Said M S Bashandy S I Al-Qasoumi and MM Ghorab ldquoAnti-breast cancer activity of some novel 12-dihydropyridine thiophene and thiazole derivativesrdquo EuropeanJournal of Medicinal Chemistry vol 46 no 1 pp 137ndash141 2011
[7] M A S Aslam S-U Mahmood M Shahid A Saeed andJ Iqbal ldquoSynthesis biological assay in vitro and moleculardocking studies of new Schiff base derivatives as potentialurease inhibitorsrdquoEuropean Journal ofMedicinal Chemistry vol46 no 11 pp 5473ndash5479 2011
[8] Z Cui Y Li Y Ling et al ldquoNew class of potent antitumoracylhydrazone derivatives containing furanrdquo European Journalof Medicinal Chemistry vol 45 no 12 pp 5576ndash5584 2010
[9] D Kaushik S A Khan G Chawla and S Kumar ldquoN1015840-[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene] 24-substituted hydrazides synthesis and anticonvulsant activityrdquoEuropean Journal of Medicinal Chemistry vol 45 no 9 pp3943ndash3949 2010
[10] M M Edrees T A Farghaly F A A El-Hag and M MAbdalla ldquoAntimicrobial antitumor and 5120572-reductase inhibitoractivities of some hydrazonoyl substituted pyrimidinonesrdquoEuropean Journal of Medicinal Chemistry vol 45 no 12 pp5702ndash5707 2010
[11] A A El-Sherif ldquoSynthesis spectroscopic characterizationand biological activity on newly synthesized copper(II) andnickel(II) complexes incorporating bidentate oxygen-nitrogenhydrazone ligandsrdquo Inorganica Chimica Acta vol 362 no 14pp 4991ndash5000 2009
[12] G A Al-Hazmi and A A El-Asmy ldquoSynthesis spectroscopyand thermal analysis of copper(II) hydrazone complexesrdquoJournal of Coordination Chemistry vol 62 no 2 pp 337ndash3452009
[13] Y-L Sang and X-S Lin ldquoSyntheses and crystal structuresof two Schiff-base copper(II) complexes with antibacterialactivitiesrdquo Journal of Coordination Chemistry vol 63 no 2 pp315ndash322 2010
[14] O Pouralimardan A-C Chamayou C Janiak and HHosseini-Monfared ldquoHydrazone Schiff base-manganese(II)complexes synthesis crystal structure and catalytic reactivityrdquoInorganica Chimica Acta vol 360 no 5 pp 1599ndash1608 2007
[15] C Basu S Chowdhury R Banerjee H Stoeckli Evans andS Mukherjee ldquoA novel blue luminescent high-spin iron(III)complex with interlayer O-H Cl bridging synthesis structureand spectroscopic studiesrdquo Polyhedron vol 26 no 14 pp 3617ndash3624 2007
[16] S Siemann D P Evanoff L Marrone A J Clarke TViswanatha and G I Dmitrienko ldquoN-arylsulfonyl hydrazones
6 Journal of Applied Chemistry
as inhibitors of IMP-1 metallo-120573-lactamaserdquo AntimicrobialAgents and Chemotherapy vol 46 no 8 pp 2450ndash2457 2002
[17] M L Hanna T M Tarasow and J Perkins ldquoMechanisticdifferences between in vitro assays for hydrazone-based smallmolecule inhibitors of anthrax lethal factorrdquo Bioorganic Chem-istry vol 35 no 1 pp 50ndash58 2007
[18] C L Cywi R A Firestone D W McNeil C A Grygon K MCrane D M White et al ldquoThe design of potent hydrazonesand disulfides as cathepsin S inhibitorsrdquo Journal of MolecularStructure vol 34 pp 9ndash22 2009
[19] N Raghav M Singh R Kaur S Suman and P Priyanka ldquoPro-teolytic studies in liver homogenate in presence of substitutedaryl hydrazonesrdquo Asian Journal of Chemistry vol 23 no 3 pp1409ndash1410 2011
[20] N RaghavM Singh S Jangra A Rohilla R Kaur and PMalikldquoIn-Vitro studies of various carbonyl derivatives on liver alkalinephosphataserdquo Journal of Chemical and Pharmaceutical Researchvol 2 no 4 pp 801ndash807 2010
[21] N Raghav M Singh S Jangra A Rohilla R Kaur and PMalik ldquoIn-Vitro studies of various carbonyl derivatives on liveracid phosphataserdquo International Journal of Applied Biology andPharmaceutical Technology vol 1 no 3 pp 1011ndash1015 2010
[22] S Eswaran A V Adhikari I H Chowdhury N K Paland K D Thomas ldquoNew quinoline derivatives synthesis andinvestigation of antibacterial and antituberculosis propertiesrdquoEuropean Journal of Medicinal Chemistry vol 45 no 8 pp3374ndash3383 2010
[23] S Kumar S Bawai S Drabu R Kumar and L MachwalldquoChloroquinolinylhydrazone derivative as anticonvulsantrdquoActaPoloniae Pharmaceutica vol 67 pp 567ndash563 2010
[24] J-Y Lee K-W Jeong S Shin J-U Lee and Y Kim ldquoDiscoveryof novel selective inhibitors of Staphylococcus aureus 120573-ketoacylacyl carrier protein synthase IIIrdquo European Journal of MedicinalChemistry vol 47 no 1 pp 261ndash269 2012
[25] G M Maguene J Jakhlal M Ladyman et al ldquoSynthesis andantimycobacterial activity of a series of ferrocenyl derivativesrdquoEuropean Journal of Medicinal Chemistry vol 46 no 1 pp 31ndash38 2011
[26] R M Mohareb K A El-Sharkawy M M Hussein and HM El-Sehrawi ldquoSynthesis of hydrazide-hydrazone derivativesand their evaluation of antidepressant sedative and analgesicagentsrdquo Journal of Pharmaceutical Sciences and Research vol 2no 4 pp 185ndash196 2010
[27] A Ozdemir G Turan-Zitouni Z Asim Kaplancikli G IscanS Khan and F Demirci ldquoSynthesis and the selective antifun-gal activity of 5678-tetrahydroimidazo[12-a]pyridine deriva-tivesrdquo European Journal of Medicinal Chemistry vol 45 no 5pp 2080ndash2084 2010
[28] R N Sharma K P Sharma and S N Dikshit ldquoSynthe-sis characterization and biological activities of some newhypophosphorousadducts of acid hydrazones derived from 2-[(N-benzoyl) 2 3-dichloroanilido] acetohydraziderdquo Archives ofApplied Science Research vol 3 pp 415ndash424 2011
[29] S M Siddiqui A Salahuddin and A Azam ldquoSynthesischaracterization and antiamoebic activity of some hydrazoneand azole derivatives bearing pyridyl moiety as a promisingheterocyclic scaffoldrdquo European Journal ofMedicinal Chemistryvol 49 pp 411ndash416 2012
[30] E A Musad R Mohamed B Ali Saeed B S Vishwanathand K M Lokanatha Rai ldquoSynthesis and evaluation of antiox-idant and antibacterial activities of new substituted bis(134-oxadiazoles) 35-bis(substituted) pyrazoles and isoxazolesrdquo
Bioorganic and Medicinal Chemistry Letters vol 21 no 12 pp3536ndash3540 2011
[31] A Almasirad M Tajik D Bakhtiari et al ldquoSynthesis andanalgesic activity of N-arylhydrazone derivatives of mefenamicacidrdquo Journal of Pharmacy and Pharmaceutical Sciences vol 8no 3 pp 419ndash425 2005
[32] R Kalsi M Shrimali T N Bhalla and J P Barthwal ldquoSynthesisand anti-inflammatory activity of indolyl azetidinonesrdquo IndianJournal of Pharmaceutical Sciences vol 41 pp 353ndash359 2006
[33] A Almasirad M Tajik D Bakhtiari et al ldquoSynthesis andanalgesic activity of N-aryl hydrazone derivatives of mefenmicacidrdquo Journal of Pharmaceutical Sciences vol 8 no 3 pp 419ndash425 2005
[34] K K Sivakumar A Rajasekaran I Ponnilavarasan ASomasundaram R Sivasakthi and S Kamalaveni ldquoAntimi-crobial and analgesic activity of some (4Z)-3-methyl-1-[(2-oxo-2H-chromen-4-yl)carbonyl]-1H-pyrzole-4 5-dione 4-[(4-substitutedphenyl) hydrazone]rdquo Scholars Research Library vol2 no 1 pp 211ndash219 2010
[35] S A Khan P Mullick S Pandit and D Kaushik ldquoSynthesis ofhydrazones derivatives of quinoxalinonemdashprospective antimi-crobial and antiinflammatory agentsrdquo Acta Poloniae Pharma-ceutica vol 66 no 2 pp 169ndash172 2009
[36] M A A Radwan E A Ragab N M Sabry and S MEl-Shenawy ldquoSynthesis and biological evaluation of new 3-substituted indole derivatives as potential anti-inflammatoryand analgesic agentsrdquo Bioorganic and Medicinal Chemistry vol15 no 11 pp 3832ndash3841 2007
[37] A R Todeschini A L P De Miranda K C M Da SilvaS C Parrini and E J Barreiro ldquoSynthesis and evaluationof analgesic antiinflammatory and antiplatelet properties ofnew 2-pyridylarylhydrazone derivativesrdquo European Journal ofMedicinal Chemistry vol 33 no 3 pp 189ndash199 1998
[38] P C Lima L M Lima K C M Da Silva et al ldquoSynthesis andanalgesic activity of novel N-acylarylhydrazones and isostersderived from natural safrolerdquo European Journal of MedicinalChemistry vol 35 no 2 pp 187ndash203 2000
[39] P Hernandez M Cabrera M L Lavaggi et al ldquoDiscoveryof new orally effective analgesic and anti-inflammatory hybridfuroxanyl N-acylhydrazone derivativesrdquo Bioorganic and Medic-inal Chemistry vol 20 no 6 pp 2158ndash2171 2012
[40] G Rajitha N Saideepa and P Praneetha ldquoSynthesis andevaluation of N-(120572-benzamido cinnamoyl) aryl hydrazonederivatives for anti-inflammatory and antioxidant activitiesrdquoIndian Journal of Chemistry B vol 50 no 5 pp 729ndash733 2011
[41] C M Moldovan O Oniga A Parvu et al ldquoSynthesis and anti-inflammatory evaluation of some new acyl-hydrazones bearing2-aryl-thiazolerdquo European Journal of Medicinal Chemistry vol46 no 2 pp 526ndash534 2011
[42] M A-A El-Sayed N I Abdel-Aziz A A-M Abdel-Aziz AS El-Azab Y A Asiri and K E H Eltahir ldquoDesign synthesisand biological evaluation of substituted hydrazone and pyrazolederivatives as selective COX-2 inhibitors molecular dockingstudyrdquo Bioorganic and Medicinal Chemistry vol 19 no 11 pp3416ndash3424 2011
[43] A M Isloor B Kalluraya and K Sridhar Pai ldquoSynthe-sis characterization and biological activities of some newbenzo[b]thiophene derivativesrdquo European Journal of MedicinalChemistry vol 45 no 2 pp 825ndash830 2010
[44] M Sarangapani and V M Reddy ldquoPharmacological screen-ing of isatin-[N-(2-alkylbenzoxazole-5-carbonyl)] hydrazonesrdquo
Journal of Applied Chemistry 7
Indian Journal of Pharmaceutical Sciences vol 59 no 3 pp 105ndash109 1997
[45] S K Sridhar and A Ramesh ldquoSynthesis and pharmacologicalactivities of hydrazones schiff and mannich bases of isatinderivativesrdquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1149ndash1152 2001
[46] M Gokce S Utku and E Kupeli ldquoSynthesis and analgesicand anti-inflammatory activities 6-substituted-3(2H)-py-ridazinone-2-acetyl-2-(p-substitutednonsubstituted benzal)hydrazone derivativesrdquo European Journal of MedicinalChemistry vol 44 no 9 pp 3760ndash3764 2009
[47] A G M Fraga C R Rodrigues A L P De Miranda E JBarreiro and C A M Fraga ldquoSynthesis and pharmacologicalevaluation of novel heterotricyclic acylhydrazone derivativesdesigned as PAF antagonistsrdquo European Journal of Pharmaceu-tical Sciences vol 11 no 4 pp 285ndash290 2000
[48] G A Silva L M M Costa F C F Brito A L P Miranda EJ Barreiro and C A M Fraga ldquoNew class of potent antinoci-ceptive and antiplatelet 10H-phenothiazine-1-acylhydrazonederivativesrdquo Bioorganic andMedicinal Chemistry vol 12 no 12pp 3149ndash3158 2004
[49] U Salgin-Goksen N Gokhan-Kelekci O Goktas et al ldquo1-Acylthiosemicarbazides 124-triazole-5(4H)-thiones 134-thi-adiazoles andhydrazones containing 5-methyl-2-benzoxazolin-ones synthesis analgesic-anti-inflammatory and antimicrobialactivitiesrdquo Bioorganic and Medicinal Chemistry vol 15 no 17pp 5738ndash5751 2007
[50] C D Duarte J L M Tributino D I Lacerda et al ldquoSyn-thesis pharmacological evaluation and electrochemical studiesof novel 6-nitro-34-methylenedioxyphenyl-N-acylhydrazonederivatives discovery of LASSBio-881 a new ligand of cannabi-noid receptorsrdquo Bioorganic andMedicinal Chemistry vol 15 no6 pp 2421ndash2433 2007
[51] A Deep S Jain P C Sharma P Verma M Kumar andC P Dora ldquoDesign and biological evaluation of biphenyl-4-carboxylic acid hydrazide-hydrazone for antimicrobial activityrdquoActa Poloniae Pharmaceutica vol 67 no 3 pp 255ndash259 2010
[52] B Durgun G Capan N Ergenc and S Rollas ldquoSynthesischaracterization and biological evaluation of new benzyli-denebenzohydrazides and 25-disubstituted-23-dihydro-134-oxadiazolesrdquo Pharmazie vol 48 no 12 pp 942ndash943 1993
[53] O I El-Sabbagh M A Shabaan H H Kadry and E SAl-Din ldquoNew octahydroquinazoline derivatives synthesis andhypotensive activityrdquo European Journal of Medicinal Chemistryvol 45 no 11 pp 5390ndash5396 2010
[54] J L Gage R Onrust D Johnston et al ldquoN-Acylhydrazonesas inhibitors of PDE10Ardquo Bioorganic and Medicinal ChemistryLetters vol 21 no 14 pp 4155ndash4159 2011
[55] F Hayat A Salahuddin J Zargan and A Azam ldquoSynthe-sis characterization antiamoebic activity and cytotoxicity ofnovel 2-(quinolin-8-yloxy) acetohydrazones and their cyclizedproducts (123-thiadiazole and 123-selenadiazole derivatives)rdquoEuropean Journal of Medicinal Chemistry vol 45 no 12 pp6127ndash6134 2010
[56] Y Jin Z Tan M He et al ldquoSAR and molecular mechanismstudy of novel acylhydrazone compounds targeting HIV-1 CArdquoBioorganic and Medicinal Chemistry vol 18 no 6 pp 2135ndash2140 2010
[57] S Rollas and S G Kucukguzel ldquoBiological activities of hydra-zone derivativesrdquoMolecules vol 12 no 8 pp 1910ndash1939 2007
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
4 Journal of Applied Chemistry
NH
O
N
HN
O
O
N
R
NHO
Br
N
9 10
Figure 2
NN N
H
S
NH
N
O
H3C
OH
Ar
S
HN
NH
O
N Ar
O
NO
NH
O
N Cl
O
NO
NH
O
NO
O
NH
O
N
OH
NN N
O
HN N
Ar
Me
NH
X
Ar = Ph X = HAr = Pyrid-4-yl X = HAr = 2-Nitrofuryl X = 4-Cl
11 12
13b 14 15 16 17
13a
CH3
Figure 3
were found to be higher than morphine and aspirin Inaddition 2-[2-(5-methyl-2-benzoxazoline-3-yl)acetyl]-4-methoxy benzylidene hydrazine at 200mgkg dose possessedthe anti-inflammatory activity [49] N1015840-(35-Di-tert-butyl-4-hydroxybenzylidene)-6-nitro-13-benzodioxole-5-carbo-hydrazine (14) as an anti-inflammatory compound [50]Antiplatelets decrease platelet aggregation and prevent theformation of thrombus Hydrazone derivatives (15 16 17)exhibited an in vitro antiplatelet activity see Figure 3
3 Synthetic Approach for the NovelHydrzonone and Its Biological Activity
A number of organic compounds obtained by chemicalsynthesis as model compounds have useful analgesic anti-inflammatory antipyretic and antiplatelets activities Manyof hydrazonones its derivatives possess interesting biological
activities such as analgesic anti-inflammatory antimicro-bial and antitumor activitesThe biological activity of synthe-sized hydrazonone derivatives was characterized and detailedstudy is in progress to modify the synthetic route structuralactivity and toxicological barriers for the enhanced pharma-cological efficiency of synthetic hydrazones [37 45ndash49]
4 Development of New NSAIDs
The NSAIDs preparations are among the most commonlyprescribed drugs NSAIDs are sometimes known as theaspirin-like drugs because they have an activity profile thatis broadly similar to that of aspirin that is they all possessanalgesic anti-inflammatory and antipyretic properties tosomedegree and produce characteristic side effects includinggastric intolerance and depression of blood clotting throughinhibitory action on platelet function Two closely related
Journal of Applied Chemistry 5
forms of the cyclooxygenase have been identified whichare now known as COX-1 and COX-2 Both isoenzymestransform arachidonic acid (AA) to prostaglandins (PGs)but differ in their distribution and their physiological rolesMeanwhile the responsible genes and their regulation havebeen clarified COX-1 the predominantly constitutive formofthe enzyme is expressed throughout the body and performsa number of homeostatic functions such as maintainingnormal gastric mucosa and influencing renal blood flowSimmons also recently codiscovered COX-3 in 2002 andanalyzed this new isozymersquos relation which acetaminophen(paracetamol) arguably the most widely used analgesic drugin the world The clinical ramifications and knowledge ofCOX isozymes are therefore rapidly expanding and couldperhaps offer significant hope for future treatments of paininflammation and fever [37 45ndash49]
5 Discussion
Hydrazones possessing an azomethine ndashNHN=CHndash groupconstitute an important class of compounds as target struc-tures for their biological activities These observations guideus for the development of new hydrazones that possess variedbiological activitiesThe literature studies on hydrazones haveshown that these derivatives possess a wide variety of biolog-ical activities such as antitumor antibacterial antiviral anti-hypertensive anticonvulsant anti-inflammatory analgesicantipyretic antiplatelets vasorelaxant anticoagulant andantiprotozoal activities There has been considerable interestin the development of novel compounds with wide varietiesof biological activities These molecules are easily preparedand have diverse pharmacological potential This encouragesto the researchers to synthesize different new compoundsbearing hydrazones with low toxicity Differently substitutedhydrazones have been developed and found to be activeagainst different pharmacological targetsThese observationshave been guiding the development of new hydrazones thatpossess varied biological activities Hydrazone derivativesof carbonyl compounds constitute an important class ofbiologically active compounds [50ndash57]
6 Conclusion
Hydrazonone nucleus exhibited immense pharmacologicalactivities The simple hydrazonone nucleus is present incompounds are evaluating for new products that possesssome remarkable pharmacological activities such as anal-gesic anti-inflammatory antipyretic antiplatelet aggrega-tion cardiotonic antihypertensive analgesic vasodilatoryantidiabetic and anticonvulsant activites The present reviewfocuses on hydrazonone which possesses potential analgesicanti-inflammatory antipyretic and anti-platelet aggregationactivities that are new in development
References
[1] M Singh and N Raghav ldquoBiological activities of hydrazones areviewrdquo International Journal of Pharmacy and PharmaceuticalSciences vol 3 no 4 pp 26ndash32 2011
[2] H S Seleem G A El-Inany B A El-Shetary andM AMousaldquoThe ligational behavior of a phenolic quinolyl hydrazonetowards copper(II)-ionsrdquo Chemistry Central Journal vol 5article 2 2011
[3] B F Abdel-Wahab G E A Awad and F A Badria ldquoSynthesisantimicrobial antioxidant anti-hemolytic and cytotoxic evalu-ation of new imidazole-based heterocyclesrdquo European Journalof Medicinal Chemistry vol 46 no 5 pp 1505ndash1511 2011
[4] A S Abu-Surrah K A Abu Safieh I M Ahmad et al ldquoNewpalladium(II) complexes bearing pyrazole-based Schiff baseligands synthesis characterization and cytotoxicityrdquo EuropeanJournal of Medicinal Chemistry vol 45 no 2 pp 471ndash475 2010
[5] O O Ajani C A Obafemi O C Nwinyi and D A AkinpeluldquoMicrowave assisted synthesis and antimicrobial activity of 2-quinoxalinone-3-hydrazone derivativesrdquoBioorganic andMedic-inal Chemistry vol 18 no 1 pp 214ndash221 2010
[6] M S Al-Said M S Bashandy S I Al-Qasoumi and MM Ghorab ldquoAnti-breast cancer activity of some novel 12-dihydropyridine thiophene and thiazole derivativesrdquo EuropeanJournal of Medicinal Chemistry vol 46 no 1 pp 137ndash141 2011
[7] M A S Aslam S-U Mahmood M Shahid A Saeed andJ Iqbal ldquoSynthesis biological assay in vitro and moleculardocking studies of new Schiff base derivatives as potentialurease inhibitorsrdquoEuropean Journal ofMedicinal Chemistry vol46 no 11 pp 5473ndash5479 2011
[8] Z Cui Y Li Y Ling et al ldquoNew class of potent antitumoracylhydrazone derivatives containing furanrdquo European Journalof Medicinal Chemistry vol 45 no 12 pp 5576ndash5584 2010
[9] D Kaushik S A Khan G Chawla and S Kumar ldquoN1015840-[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene] 24-substituted hydrazides synthesis and anticonvulsant activityrdquoEuropean Journal of Medicinal Chemistry vol 45 no 9 pp3943ndash3949 2010
[10] M M Edrees T A Farghaly F A A El-Hag and M MAbdalla ldquoAntimicrobial antitumor and 5120572-reductase inhibitoractivities of some hydrazonoyl substituted pyrimidinonesrdquoEuropean Journal of Medicinal Chemistry vol 45 no 12 pp5702ndash5707 2010
[11] A A El-Sherif ldquoSynthesis spectroscopic characterizationand biological activity on newly synthesized copper(II) andnickel(II) complexes incorporating bidentate oxygen-nitrogenhydrazone ligandsrdquo Inorganica Chimica Acta vol 362 no 14pp 4991ndash5000 2009
[12] G A Al-Hazmi and A A El-Asmy ldquoSynthesis spectroscopyand thermal analysis of copper(II) hydrazone complexesrdquoJournal of Coordination Chemistry vol 62 no 2 pp 337ndash3452009
[13] Y-L Sang and X-S Lin ldquoSyntheses and crystal structuresof two Schiff-base copper(II) complexes with antibacterialactivitiesrdquo Journal of Coordination Chemistry vol 63 no 2 pp315ndash322 2010
[14] O Pouralimardan A-C Chamayou C Janiak and HHosseini-Monfared ldquoHydrazone Schiff base-manganese(II)complexes synthesis crystal structure and catalytic reactivityrdquoInorganica Chimica Acta vol 360 no 5 pp 1599ndash1608 2007
[15] C Basu S Chowdhury R Banerjee H Stoeckli Evans andS Mukherjee ldquoA novel blue luminescent high-spin iron(III)complex with interlayer O-H Cl bridging synthesis structureand spectroscopic studiesrdquo Polyhedron vol 26 no 14 pp 3617ndash3624 2007
[16] S Siemann D P Evanoff L Marrone A J Clarke TViswanatha and G I Dmitrienko ldquoN-arylsulfonyl hydrazones
6 Journal of Applied Chemistry
as inhibitors of IMP-1 metallo-120573-lactamaserdquo AntimicrobialAgents and Chemotherapy vol 46 no 8 pp 2450ndash2457 2002
[17] M L Hanna T M Tarasow and J Perkins ldquoMechanisticdifferences between in vitro assays for hydrazone-based smallmolecule inhibitors of anthrax lethal factorrdquo Bioorganic Chem-istry vol 35 no 1 pp 50ndash58 2007
[18] C L Cywi R A Firestone D W McNeil C A Grygon K MCrane D M White et al ldquoThe design of potent hydrazonesand disulfides as cathepsin S inhibitorsrdquo Journal of MolecularStructure vol 34 pp 9ndash22 2009
[19] N Raghav M Singh R Kaur S Suman and P Priyanka ldquoPro-teolytic studies in liver homogenate in presence of substitutedaryl hydrazonesrdquo Asian Journal of Chemistry vol 23 no 3 pp1409ndash1410 2011
[20] N RaghavM Singh S Jangra A Rohilla R Kaur and PMalikldquoIn-Vitro studies of various carbonyl derivatives on liver alkalinephosphataserdquo Journal of Chemical and Pharmaceutical Researchvol 2 no 4 pp 801ndash807 2010
[21] N Raghav M Singh S Jangra A Rohilla R Kaur and PMalik ldquoIn-Vitro studies of various carbonyl derivatives on liveracid phosphataserdquo International Journal of Applied Biology andPharmaceutical Technology vol 1 no 3 pp 1011ndash1015 2010
[22] S Eswaran A V Adhikari I H Chowdhury N K Paland K D Thomas ldquoNew quinoline derivatives synthesis andinvestigation of antibacterial and antituberculosis propertiesrdquoEuropean Journal of Medicinal Chemistry vol 45 no 8 pp3374ndash3383 2010
[23] S Kumar S Bawai S Drabu R Kumar and L MachwalldquoChloroquinolinylhydrazone derivative as anticonvulsantrdquoActaPoloniae Pharmaceutica vol 67 pp 567ndash563 2010
[24] J-Y Lee K-W Jeong S Shin J-U Lee and Y Kim ldquoDiscoveryof novel selective inhibitors of Staphylococcus aureus 120573-ketoacylacyl carrier protein synthase IIIrdquo European Journal of MedicinalChemistry vol 47 no 1 pp 261ndash269 2012
[25] G M Maguene J Jakhlal M Ladyman et al ldquoSynthesis andantimycobacterial activity of a series of ferrocenyl derivativesrdquoEuropean Journal of Medicinal Chemistry vol 46 no 1 pp 31ndash38 2011
[26] R M Mohareb K A El-Sharkawy M M Hussein and HM El-Sehrawi ldquoSynthesis of hydrazide-hydrazone derivativesand their evaluation of antidepressant sedative and analgesicagentsrdquo Journal of Pharmaceutical Sciences and Research vol 2no 4 pp 185ndash196 2010
[27] A Ozdemir G Turan-Zitouni Z Asim Kaplancikli G IscanS Khan and F Demirci ldquoSynthesis and the selective antifun-gal activity of 5678-tetrahydroimidazo[12-a]pyridine deriva-tivesrdquo European Journal of Medicinal Chemistry vol 45 no 5pp 2080ndash2084 2010
[28] R N Sharma K P Sharma and S N Dikshit ldquoSynthe-sis characterization and biological activities of some newhypophosphorousadducts of acid hydrazones derived from 2-[(N-benzoyl) 2 3-dichloroanilido] acetohydraziderdquo Archives ofApplied Science Research vol 3 pp 415ndash424 2011
[29] S M Siddiqui A Salahuddin and A Azam ldquoSynthesischaracterization and antiamoebic activity of some hydrazoneand azole derivatives bearing pyridyl moiety as a promisingheterocyclic scaffoldrdquo European Journal ofMedicinal Chemistryvol 49 pp 411ndash416 2012
[30] E A Musad R Mohamed B Ali Saeed B S Vishwanathand K M Lokanatha Rai ldquoSynthesis and evaluation of antiox-idant and antibacterial activities of new substituted bis(134-oxadiazoles) 35-bis(substituted) pyrazoles and isoxazolesrdquo
Bioorganic and Medicinal Chemistry Letters vol 21 no 12 pp3536ndash3540 2011
[31] A Almasirad M Tajik D Bakhtiari et al ldquoSynthesis andanalgesic activity of N-arylhydrazone derivatives of mefenamicacidrdquo Journal of Pharmacy and Pharmaceutical Sciences vol 8no 3 pp 419ndash425 2005
[32] R Kalsi M Shrimali T N Bhalla and J P Barthwal ldquoSynthesisand anti-inflammatory activity of indolyl azetidinonesrdquo IndianJournal of Pharmaceutical Sciences vol 41 pp 353ndash359 2006
[33] A Almasirad M Tajik D Bakhtiari et al ldquoSynthesis andanalgesic activity of N-aryl hydrazone derivatives of mefenmicacidrdquo Journal of Pharmaceutical Sciences vol 8 no 3 pp 419ndash425 2005
[34] K K Sivakumar A Rajasekaran I Ponnilavarasan ASomasundaram R Sivasakthi and S Kamalaveni ldquoAntimi-crobial and analgesic activity of some (4Z)-3-methyl-1-[(2-oxo-2H-chromen-4-yl)carbonyl]-1H-pyrzole-4 5-dione 4-[(4-substitutedphenyl) hydrazone]rdquo Scholars Research Library vol2 no 1 pp 211ndash219 2010
[35] S A Khan P Mullick S Pandit and D Kaushik ldquoSynthesis ofhydrazones derivatives of quinoxalinonemdashprospective antimi-crobial and antiinflammatory agentsrdquo Acta Poloniae Pharma-ceutica vol 66 no 2 pp 169ndash172 2009
[36] M A A Radwan E A Ragab N M Sabry and S MEl-Shenawy ldquoSynthesis and biological evaluation of new 3-substituted indole derivatives as potential anti-inflammatoryand analgesic agentsrdquo Bioorganic and Medicinal Chemistry vol15 no 11 pp 3832ndash3841 2007
[37] A R Todeschini A L P De Miranda K C M Da SilvaS C Parrini and E J Barreiro ldquoSynthesis and evaluationof analgesic antiinflammatory and antiplatelet properties ofnew 2-pyridylarylhydrazone derivativesrdquo European Journal ofMedicinal Chemistry vol 33 no 3 pp 189ndash199 1998
[38] P C Lima L M Lima K C M Da Silva et al ldquoSynthesis andanalgesic activity of novel N-acylarylhydrazones and isostersderived from natural safrolerdquo European Journal of MedicinalChemistry vol 35 no 2 pp 187ndash203 2000
[39] P Hernandez M Cabrera M L Lavaggi et al ldquoDiscoveryof new orally effective analgesic and anti-inflammatory hybridfuroxanyl N-acylhydrazone derivativesrdquo Bioorganic and Medic-inal Chemistry vol 20 no 6 pp 2158ndash2171 2012
[40] G Rajitha N Saideepa and P Praneetha ldquoSynthesis andevaluation of N-(120572-benzamido cinnamoyl) aryl hydrazonederivatives for anti-inflammatory and antioxidant activitiesrdquoIndian Journal of Chemistry B vol 50 no 5 pp 729ndash733 2011
[41] C M Moldovan O Oniga A Parvu et al ldquoSynthesis and anti-inflammatory evaluation of some new acyl-hydrazones bearing2-aryl-thiazolerdquo European Journal of Medicinal Chemistry vol46 no 2 pp 526ndash534 2011
[42] M A-A El-Sayed N I Abdel-Aziz A A-M Abdel-Aziz AS El-Azab Y A Asiri and K E H Eltahir ldquoDesign synthesisand biological evaluation of substituted hydrazone and pyrazolederivatives as selective COX-2 inhibitors molecular dockingstudyrdquo Bioorganic and Medicinal Chemistry vol 19 no 11 pp3416ndash3424 2011
[43] A M Isloor B Kalluraya and K Sridhar Pai ldquoSynthe-sis characterization and biological activities of some newbenzo[b]thiophene derivativesrdquo European Journal of MedicinalChemistry vol 45 no 2 pp 825ndash830 2010
[44] M Sarangapani and V M Reddy ldquoPharmacological screen-ing of isatin-[N-(2-alkylbenzoxazole-5-carbonyl)] hydrazonesrdquo
Journal of Applied Chemistry 7
Indian Journal of Pharmaceutical Sciences vol 59 no 3 pp 105ndash109 1997
[45] S K Sridhar and A Ramesh ldquoSynthesis and pharmacologicalactivities of hydrazones schiff and mannich bases of isatinderivativesrdquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1149ndash1152 2001
[46] M Gokce S Utku and E Kupeli ldquoSynthesis and analgesicand anti-inflammatory activities 6-substituted-3(2H)-py-ridazinone-2-acetyl-2-(p-substitutednonsubstituted benzal)hydrazone derivativesrdquo European Journal of MedicinalChemistry vol 44 no 9 pp 3760ndash3764 2009
[47] A G M Fraga C R Rodrigues A L P De Miranda E JBarreiro and C A M Fraga ldquoSynthesis and pharmacologicalevaluation of novel heterotricyclic acylhydrazone derivativesdesigned as PAF antagonistsrdquo European Journal of Pharmaceu-tical Sciences vol 11 no 4 pp 285ndash290 2000
[48] G A Silva L M M Costa F C F Brito A L P Miranda EJ Barreiro and C A M Fraga ldquoNew class of potent antinoci-ceptive and antiplatelet 10H-phenothiazine-1-acylhydrazonederivativesrdquo Bioorganic andMedicinal Chemistry vol 12 no 12pp 3149ndash3158 2004
[49] U Salgin-Goksen N Gokhan-Kelekci O Goktas et al ldquo1-Acylthiosemicarbazides 124-triazole-5(4H)-thiones 134-thi-adiazoles andhydrazones containing 5-methyl-2-benzoxazolin-ones synthesis analgesic-anti-inflammatory and antimicrobialactivitiesrdquo Bioorganic and Medicinal Chemistry vol 15 no 17pp 5738ndash5751 2007
[50] C D Duarte J L M Tributino D I Lacerda et al ldquoSyn-thesis pharmacological evaluation and electrochemical studiesof novel 6-nitro-34-methylenedioxyphenyl-N-acylhydrazonederivatives discovery of LASSBio-881 a new ligand of cannabi-noid receptorsrdquo Bioorganic andMedicinal Chemistry vol 15 no6 pp 2421ndash2433 2007
[51] A Deep S Jain P C Sharma P Verma M Kumar andC P Dora ldquoDesign and biological evaluation of biphenyl-4-carboxylic acid hydrazide-hydrazone for antimicrobial activityrdquoActa Poloniae Pharmaceutica vol 67 no 3 pp 255ndash259 2010
[52] B Durgun G Capan N Ergenc and S Rollas ldquoSynthesischaracterization and biological evaluation of new benzyli-denebenzohydrazides and 25-disubstituted-23-dihydro-134-oxadiazolesrdquo Pharmazie vol 48 no 12 pp 942ndash943 1993
[53] O I El-Sabbagh M A Shabaan H H Kadry and E SAl-Din ldquoNew octahydroquinazoline derivatives synthesis andhypotensive activityrdquo European Journal of Medicinal Chemistryvol 45 no 11 pp 5390ndash5396 2010
[54] J L Gage R Onrust D Johnston et al ldquoN-Acylhydrazonesas inhibitors of PDE10Ardquo Bioorganic and Medicinal ChemistryLetters vol 21 no 14 pp 4155ndash4159 2011
[55] F Hayat A Salahuddin J Zargan and A Azam ldquoSynthe-sis characterization antiamoebic activity and cytotoxicity ofnovel 2-(quinolin-8-yloxy) acetohydrazones and their cyclizedproducts (123-thiadiazole and 123-selenadiazole derivatives)rdquoEuropean Journal of Medicinal Chemistry vol 45 no 12 pp6127ndash6134 2010
[56] Y Jin Z Tan M He et al ldquoSAR and molecular mechanismstudy of novel acylhydrazone compounds targeting HIV-1 CArdquoBioorganic and Medicinal Chemistry vol 18 no 6 pp 2135ndash2140 2010
[57] S Rollas and S G Kucukguzel ldquoBiological activities of hydra-zone derivativesrdquoMolecules vol 12 no 8 pp 1910ndash1939 2007
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
Journal of Applied Chemistry 5
forms of the cyclooxygenase have been identified whichare now known as COX-1 and COX-2 Both isoenzymestransform arachidonic acid (AA) to prostaglandins (PGs)but differ in their distribution and their physiological rolesMeanwhile the responsible genes and their regulation havebeen clarified COX-1 the predominantly constitutive formofthe enzyme is expressed throughout the body and performsa number of homeostatic functions such as maintainingnormal gastric mucosa and influencing renal blood flowSimmons also recently codiscovered COX-3 in 2002 andanalyzed this new isozymersquos relation which acetaminophen(paracetamol) arguably the most widely used analgesic drugin the world The clinical ramifications and knowledge ofCOX isozymes are therefore rapidly expanding and couldperhaps offer significant hope for future treatments of paininflammation and fever [37 45ndash49]
5 Discussion
Hydrazones possessing an azomethine ndashNHN=CHndash groupconstitute an important class of compounds as target struc-tures for their biological activities These observations guideus for the development of new hydrazones that possess variedbiological activitiesThe literature studies on hydrazones haveshown that these derivatives possess a wide variety of biolog-ical activities such as antitumor antibacterial antiviral anti-hypertensive anticonvulsant anti-inflammatory analgesicantipyretic antiplatelets vasorelaxant anticoagulant andantiprotozoal activities There has been considerable interestin the development of novel compounds with wide varietiesof biological activities These molecules are easily preparedand have diverse pharmacological potential This encouragesto the researchers to synthesize different new compoundsbearing hydrazones with low toxicity Differently substitutedhydrazones have been developed and found to be activeagainst different pharmacological targetsThese observationshave been guiding the development of new hydrazones thatpossess varied biological activities Hydrazone derivativesof carbonyl compounds constitute an important class ofbiologically active compounds [50ndash57]
6 Conclusion
Hydrazonone nucleus exhibited immense pharmacologicalactivities The simple hydrazonone nucleus is present incompounds are evaluating for new products that possesssome remarkable pharmacological activities such as anal-gesic anti-inflammatory antipyretic antiplatelet aggrega-tion cardiotonic antihypertensive analgesic vasodilatoryantidiabetic and anticonvulsant activites The present reviewfocuses on hydrazonone which possesses potential analgesicanti-inflammatory antipyretic and anti-platelet aggregationactivities that are new in development
References
[1] M Singh and N Raghav ldquoBiological activities of hydrazones areviewrdquo International Journal of Pharmacy and PharmaceuticalSciences vol 3 no 4 pp 26ndash32 2011
[2] H S Seleem G A El-Inany B A El-Shetary andM AMousaldquoThe ligational behavior of a phenolic quinolyl hydrazonetowards copper(II)-ionsrdquo Chemistry Central Journal vol 5article 2 2011
[3] B F Abdel-Wahab G E A Awad and F A Badria ldquoSynthesisantimicrobial antioxidant anti-hemolytic and cytotoxic evalu-ation of new imidazole-based heterocyclesrdquo European Journalof Medicinal Chemistry vol 46 no 5 pp 1505ndash1511 2011
[4] A S Abu-Surrah K A Abu Safieh I M Ahmad et al ldquoNewpalladium(II) complexes bearing pyrazole-based Schiff baseligands synthesis characterization and cytotoxicityrdquo EuropeanJournal of Medicinal Chemistry vol 45 no 2 pp 471ndash475 2010
[5] O O Ajani C A Obafemi O C Nwinyi and D A AkinpeluldquoMicrowave assisted synthesis and antimicrobial activity of 2-quinoxalinone-3-hydrazone derivativesrdquoBioorganic andMedic-inal Chemistry vol 18 no 1 pp 214ndash221 2010
[6] M S Al-Said M S Bashandy S I Al-Qasoumi and MM Ghorab ldquoAnti-breast cancer activity of some novel 12-dihydropyridine thiophene and thiazole derivativesrdquo EuropeanJournal of Medicinal Chemistry vol 46 no 1 pp 137ndash141 2011
[7] M A S Aslam S-U Mahmood M Shahid A Saeed andJ Iqbal ldquoSynthesis biological assay in vitro and moleculardocking studies of new Schiff base derivatives as potentialurease inhibitorsrdquoEuropean Journal ofMedicinal Chemistry vol46 no 11 pp 5473ndash5479 2011
[8] Z Cui Y Li Y Ling et al ldquoNew class of potent antitumoracylhydrazone derivatives containing furanrdquo European Journalof Medicinal Chemistry vol 45 no 12 pp 5576ndash5584 2010
[9] D Kaushik S A Khan G Chawla and S Kumar ldquoN1015840-[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene] 24-substituted hydrazides synthesis and anticonvulsant activityrdquoEuropean Journal of Medicinal Chemistry vol 45 no 9 pp3943ndash3949 2010
[10] M M Edrees T A Farghaly F A A El-Hag and M MAbdalla ldquoAntimicrobial antitumor and 5120572-reductase inhibitoractivities of some hydrazonoyl substituted pyrimidinonesrdquoEuropean Journal of Medicinal Chemistry vol 45 no 12 pp5702ndash5707 2010
[11] A A El-Sherif ldquoSynthesis spectroscopic characterizationand biological activity on newly synthesized copper(II) andnickel(II) complexes incorporating bidentate oxygen-nitrogenhydrazone ligandsrdquo Inorganica Chimica Acta vol 362 no 14pp 4991ndash5000 2009
[12] G A Al-Hazmi and A A El-Asmy ldquoSynthesis spectroscopyand thermal analysis of copper(II) hydrazone complexesrdquoJournal of Coordination Chemistry vol 62 no 2 pp 337ndash3452009
[13] Y-L Sang and X-S Lin ldquoSyntheses and crystal structuresof two Schiff-base copper(II) complexes with antibacterialactivitiesrdquo Journal of Coordination Chemistry vol 63 no 2 pp315ndash322 2010
[14] O Pouralimardan A-C Chamayou C Janiak and HHosseini-Monfared ldquoHydrazone Schiff base-manganese(II)complexes synthesis crystal structure and catalytic reactivityrdquoInorganica Chimica Acta vol 360 no 5 pp 1599ndash1608 2007
[15] C Basu S Chowdhury R Banerjee H Stoeckli Evans andS Mukherjee ldquoA novel blue luminescent high-spin iron(III)complex with interlayer O-H Cl bridging synthesis structureand spectroscopic studiesrdquo Polyhedron vol 26 no 14 pp 3617ndash3624 2007
[16] S Siemann D P Evanoff L Marrone A J Clarke TViswanatha and G I Dmitrienko ldquoN-arylsulfonyl hydrazones
6 Journal of Applied Chemistry
as inhibitors of IMP-1 metallo-120573-lactamaserdquo AntimicrobialAgents and Chemotherapy vol 46 no 8 pp 2450ndash2457 2002
[17] M L Hanna T M Tarasow and J Perkins ldquoMechanisticdifferences between in vitro assays for hydrazone-based smallmolecule inhibitors of anthrax lethal factorrdquo Bioorganic Chem-istry vol 35 no 1 pp 50ndash58 2007
[18] C L Cywi R A Firestone D W McNeil C A Grygon K MCrane D M White et al ldquoThe design of potent hydrazonesand disulfides as cathepsin S inhibitorsrdquo Journal of MolecularStructure vol 34 pp 9ndash22 2009
[19] N Raghav M Singh R Kaur S Suman and P Priyanka ldquoPro-teolytic studies in liver homogenate in presence of substitutedaryl hydrazonesrdquo Asian Journal of Chemistry vol 23 no 3 pp1409ndash1410 2011
[20] N RaghavM Singh S Jangra A Rohilla R Kaur and PMalikldquoIn-Vitro studies of various carbonyl derivatives on liver alkalinephosphataserdquo Journal of Chemical and Pharmaceutical Researchvol 2 no 4 pp 801ndash807 2010
[21] N Raghav M Singh S Jangra A Rohilla R Kaur and PMalik ldquoIn-Vitro studies of various carbonyl derivatives on liveracid phosphataserdquo International Journal of Applied Biology andPharmaceutical Technology vol 1 no 3 pp 1011ndash1015 2010
[22] S Eswaran A V Adhikari I H Chowdhury N K Paland K D Thomas ldquoNew quinoline derivatives synthesis andinvestigation of antibacterial and antituberculosis propertiesrdquoEuropean Journal of Medicinal Chemistry vol 45 no 8 pp3374ndash3383 2010
[23] S Kumar S Bawai S Drabu R Kumar and L MachwalldquoChloroquinolinylhydrazone derivative as anticonvulsantrdquoActaPoloniae Pharmaceutica vol 67 pp 567ndash563 2010
[24] J-Y Lee K-W Jeong S Shin J-U Lee and Y Kim ldquoDiscoveryof novel selective inhibitors of Staphylococcus aureus 120573-ketoacylacyl carrier protein synthase IIIrdquo European Journal of MedicinalChemistry vol 47 no 1 pp 261ndash269 2012
[25] G M Maguene J Jakhlal M Ladyman et al ldquoSynthesis andantimycobacterial activity of a series of ferrocenyl derivativesrdquoEuropean Journal of Medicinal Chemistry vol 46 no 1 pp 31ndash38 2011
[26] R M Mohareb K A El-Sharkawy M M Hussein and HM El-Sehrawi ldquoSynthesis of hydrazide-hydrazone derivativesand their evaluation of antidepressant sedative and analgesicagentsrdquo Journal of Pharmaceutical Sciences and Research vol 2no 4 pp 185ndash196 2010
[27] A Ozdemir G Turan-Zitouni Z Asim Kaplancikli G IscanS Khan and F Demirci ldquoSynthesis and the selective antifun-gal activity of 5678-tetrahydroimidazo[12-a]pyridine deriva-tivesrdquo European Journal of Medicinal Chemistry vol 45 no 5pp 2080ndash2084 2010
[28] R N Sharma K P Sharma and S N Dikshit ldquoSynthe-sis characterization and biological activities of some newhypophosphorousadducts of acid hydrazones derived from 2-[(N-benzoyl) 2 3-dichloroanilido] acetohydraziderdquo Archives ofApplied Science Research vol 3 pp 415ndash424 2011
[29] S M Siddiqui A Salahuddin and A Azam ldquoSynthesischaracterization and antiamoebic activity of some hydrazoneand azole derivatives bearing pyridyl moiety as a promisingheterocyclic scaffoldrdquo European Journal ofMedicinal Chemistryvol 49 pp 411ndash416 2012
[30] E A Musad R Mohamed B Ali Saeed B S Vishwanathand K M Lokanatha Rai ldquoSynthesis and evaluation of antiox-idant and antibacterial activities of new substituted bis(134-oxadiazoles) 35-bis(substituted) pyrazoles and isoxazolesrdquo
Bioorganic and Medicinal Chemistry Letters vol 21 no 12 pp3536ndash3540 2011
[31] A Almasirad M Tajik D Bakhtiari et al ldquoSynthesis andanalgesic activity of N-arylhydrazone derivatives of mefenamicacidrdquo Journal of Pharmacy and Pharmaceutical Sciences vol 8no 3 pp 419ndash425 2005
[32] R Kalsi M Shrimali T N Bhalla and J P Barthwal ldquoSynthesisand anti-inflammatory activity of indolyl azetidinonesrdquo IndianJournal of Pharmaceutical Sciences vol 41 pp 353ndash359 2006
[33] A Almasirad M Tajik D Bakhtiari et al ldquoSynthesis andanalgesic activity of N-aryl hydrazone derivatives of mefenmicacidrdquo Journal of Pharmaceutical Sciences vol 8 no 3 pp 419ndash425 2005
[34] K K Sivakumar A Rajasekaran I Ponnilavarasan ASomasundaram R Sivasakthi and S Kamalaveni ldquoAntimi-crobial and analgesic activity of some (4Z)-3-methyl-1-[(2-oxo-2H-chromen-4-yl)carbonyl]-1H-pyrzole-4 5-dione 4-[(4-substitutedphenyl) hydrazone]rdquo Scholars Research Library vol2 no 1 pp 211ndash219 2010
[35] S A Khan P Mullick S Pandit and D Kaushik ldquoSynthesis ofhydrazones derivatives of quinoxalinonemdashprospective antimi-crobial and antiinflammatory agentsrdquo Acta Poloniae Pharma-ceutica vol 66 no 2 pp 169ndash172 2009
[36] M A A Radwan E A Ragab N M Sabry and S MEl-Shenawy ldquoSynthesis and biological evaluation of new 3-substituted indole derivatives as potential anti-inflammatoryand analgesic agentsrdquo Bioorganic and Medicinal Chemistry vol15 no 11 pp 3832ndash3841 2007
[37] A R Todeschini A L P De Miranda K C M Da SilvaS C Parrini and E J Barreiro ldquoSynthesis and evaluationof analgesic antiinflammatory and antiplatelet properties ofnew 2-pyridylarylhydrazone derivativesrdquo European Journal ofMedicinal Chemistry vol 33 no 3 pp 189ndash199 1998
[38] P C Lima L M Lima K C M Da Silva et al ldquoSynthesis andanalgesic activity of novel N-acylarylhydrazones and isostersderived from natural safrolerdquo European Journal of MedicinalChemistry vol 35 no 2 pp 187ndash203 2000
[39] P Hernandez M Cabrera M L Lavaggi et al ldquoDiscoveryof new orally effective analgesic and anti-inflammatory hybridfuroxanyl N-acylhydrazone derivativesrdquo Bioorganic and Medic-inal Chemistry vol 20 no 6 pp 2158ndash2171 2012
[40] G Rajitha N Saideepa and P Praneetha ldquoSynthesis andevaluation of N-(120572-benzamido cinnamoyl) aryl hydrazonederivatives for anti-inflammatory and antioxidant activitiesrdquoIndian Journal of Chemistry B vol 50 no 5 pp 729ndash733 2011
[41] C M Moldovan O Oniga A Parvu et al ldquoSynthesis and anti-inflammatory evaluation of some new acyl-hydrazones bearing2-aryl-thiazolerdquo European Journal of Medicinal Chemistry vol46 no 2 pp 526ndash534 2011
[42] M A-A El-Sayed N I Abdel-Aziz A A-M Abdel-Aziz AS El-Azab Y A Asiri and K E H Eltahir ldquoDesign synthesisand biological evaluation of substituted hydrazone and pyrazolederivatives as selective COX-2 inhibitors molecular dockingstudyrdquo Bioorganic and Medicinal Chemistry vol 19 no 11 pp3416ndash3424 2011
[43] A M Isloor B Kalluraya and K Sridhar Pai ldquoSynthe-sis characterization and biological activities of some newbenzo[b]thiophene derivativesrdquo European Journal of MedicinalChemistry vol 45 no 2 pp 825ndash830 2010
[44] M Sarangapani and V M Reddy ldquoPharmacological screen-ing of isatin-[N-(2-alkylbenzoxazole-5-carbonyl)] hydrazonesrdquo
Journal of Applied Chemistry 7
Indian Journal of Pharmaceutical Sciences vol 59 no 3 pp 105ndash109 1997
[45] S K Sridhar and A Ramesh ldquoSynthesis and pharmacologicalactivities of hydrazones schiff and mannich bases of isatinderivativesrdquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1149ndash1152 2001
[46] M Gokce S Utku and E Kupeli ldquoSynthesis and analgesicand anti-inflammatory activities 6-substituted-3(2H)-py-ridazinone-2-acetyl-2-(p-substitutednonsubstituted benzal)hydrazone derivativesrdquo European Journal of MedicinalChemistry vol 44 no 9 pp 3760ndash3764 2009
[47] A G M Fraga C R Rodrigues A L P De Miranda E JBarreiro and C A M Fraga ldquoSynthesis and pharmacologicalevaluation of novel heterotricyclic acylhydrazone derivativesdesigned as PAF antagonistsrdquo European Journal of Pharmaceu-tical Sciences vol 11 no 4 pp 285ndash290 2000
[48] G A Silva L M M Costa F C F Brito A L P Miranda EJ Barreiro and C A M Fraga ldquoNew class of potent antinoci-ceptive and antiplatelet 10H-phenothiazine-1-acylhydrazonederivativesrdquo Bioorganic andMedicinal Chemistry vol 12 no 12pp 3149ndash3158 2004
[49] U Salgin-Goksen N Gokhan-Kelekci O Goktas et al ldquo1-Acylthiosemicarbazides 124-triazole-5(4H)-thiones 134-thi-adiazoles andhydrazones containing 5-methyl-2-benzoxazolin-ones synthesis analgesic-anti-inflammatory and antimicrobialactivitiesrdquo Bioorganic and Medicinal Chemistry vol 15 no 17pp 5738ndash5751 2007
[50] C D Duarte J L M Tributino D I Lacerda et al ldquoSyn-thesis pharmacological evaluation and electrochemical studiesof novel 6-nitro-34-methylenedioxyphenyl-N-acylhydrazonederivatives discovery of LASSBio-881 a new ligand of cannabi-noid receptorsrdquo Bioorganic andMedicinal Chemistry vol 15 no6 pp 2421ndash2433 2007
[51] A Deep S Jain P C Sharma P Verma M Kumar andC P Dora ldquoDesign and biological evaluation of biphenyl-4-carboxylic acid hydrazide-hydrazone for antimicrobial activityrdquoActa Poloniae Pharmaceutica vol 67 no 3 pp 255ndash259 2010
[52] B Durgun G Capan N Ergenc and S Rollas ldquoSynthesischaracterization and biological evaluation of new benzyli-denebenzohydrazides and 25-disubstituted-23-dihydro-134-oxadiazolesrdquo Pharmazie vol 48 no 12 pp 942ndash943 1993
[53] O I El-Sabbagh M A Shabaan H H Kadry and E SAl-Din ldquoNew octahydroquinazoline derivatives synthesis andhypotensive activityrdquo European Journal of Medicinal Chemistryvol 45 no 11 pp 5390ndash5396 2010
[54] J L Gage R Onrust D Johnston et al ldquoN-Acylhydrazonesas inhibitors of PDE10Ardquo Bioorganic and Medicinal ChemistryLetters vol 21 no 14 pp 4155ndash4159 2011
[55] F Hayat A Salahuddin J Zargan and A Azam ldquoSynthe-sis characterization antiamoebic activity and cytotoxicity ofnovel 2-(quinolin-8-yloxy) acetohydrazones and their cyclizedproducts (123-thiadiazole and 123-selenadiazole derivatives)rdquoEuropean Journal of Medicinal Chemistry vol 45 no 12 pp6127ndash6134 2010
[56] Y Jin Z Tan M He et al ldquoSAR and molecular mechanismstudy of novel acylhydrazone compounds targeting HIV-1 CArdquoBioorganic and Medicinal Chemistry vol 18 no 6 pp 2135ndash2140 2010
[57] S Rollas and S G Kucukguzel ldquoBiological activities of hydra-zone derivativesrdquoMolecules vol 12 no 8 pp 1910ndash1939 2007
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
6 Journal of Applied Chemistry
as inhibitors of IMP-1 metallo-120573-lactamaserdquo AntimicrobialAgents and Chemotherapy vol 46 no 8 pp 2450ndash2457 2002
[17] M L Hanna T M Tarasow and J Perkins ldquoMechanisticdifferences between in vitro assays for hydrazone-based smallmolecule inhibitors of anthrax lethal factorrdquo Bioorganic Chem-istry vol 35 no 1 pp 50ndash58 2007
[18] C L Cywi R A Firestone D W McNeil C A Grygon K MCrane D M White et al ldquoThe design of potent hydrazonesand disulfides as cathepsin S inhibitorsrdquo Journal of MolecularStructure vol 34 pp 9ndash22 2009
[19] N Raghav M Singh R Kaur S Suman and P Priyanka ldquoPro-teolytic studies in liver homogenate in presence of substitutedaryl hydrazonesrdquo Asian Journal of Chemistry vol 23 no 3 pp1409ndash1410 2011
[20] N RaghavM Singh S Jangra A Rohilla R Kaur and PMalikldquoIn-Vitro studies of various carbonyl derivatives on liver alkalinephosphataserdquo Journal of Chemical and Pharmaceutical Researchvol 2 no 4 pp 801ndash807 2010
[21] N Raghav M Singh S Jangra A Rohilla R Kaur and PMalik ldquoIn-Vitro studies of various carbonyl derivatives on liveracid phosphataserdquo International Journal of Applied Biology andPharmaceutical Technology vol 1 no 3 pp 1011ndash1015 2010
[22] S Eswaran A V Adhikari I H Chowdhury N K Paland K D Thomas ldquoNew quinoline derivatives synthesis andinvestigation of antibacterial and antituberculosis propertiesrdquoEuropean Journal of Medicinal Chemistry vol 45 no 8 pp3374ndash3383 2010
[23] S Kumar S Bawai S Drabu R Kumar and L MachwalldquoChloroquinolinylhydrazone derivative as anticonvulsantrdquoActaPoloniae Pharmaceutica vol 67 pp 567ndash563 2010
[24] J-Y Lee K-W Jeong S Shin J-U Lee and Y Kim ldquoDiscoveryof novel selective inhibitors of Staphylococcus aureus 120573-ketoacylacyl carrier protein synthase IIIrdquo European Journal of MedicinalChemistry vol 47 no 1 pp 261ndash269 2012
[25] G M Maguene J Jakhlal M Ladyman et al ldquoSynthesis andantimycobacterial activity of a series of ferrocenyl derivativesrdquoEuropean Journal of Medicinal Chemistry vol 46 no 1 pp 31ndash38 2011
[26] R M Mohareb K A El-Sharkawy M M Hussein and HM El-Sehrawi ldquoSynthesis of hydrazide-hydrazone derivativesand their evaluation of antidepressant sedative and analgesicagentsrdquo Journal of Pharmaceutical Sciences and Research vol 2no 4 pp 185ndash196 2010
[27] A Ozdemir G Turan-Zitouni Z Asim Kaplancikli G IscanS Khan and F Demirci ldquoSynthesis and the selective antifun-gal activity of 5678-tetrahydroimidazo[12-a]pyridine deriva-tivesrdquo European Journal of Medicinal Chemistry vol 45 no 5pp 2080ndash2084 2010
[28] R N Sharma K P Sharma and S N Dikshit ldquoSynthe-sis characterization and biological activities of some newhypophosphorousadducts of acid hydrazones derived from 2-[(N-benzoyl) 2 3-dichloroanilido] acetohydraziderdquo Archives ofApplied Science Research vol 3 pp 415ndash424 2011
[29] S M Siddiqui A Salahuddin and A Azam ldquoSynthesischaracterization and antiamoebic activity of some hydrazoneand azole derivatives bearing pyridyl moiety as a promisingheterocyclic scaffoldrdquo European Journal ofMedicinal Chemistryvol 49 pp 411ndash416 2012
[30] E A Musad R Mohamed B Ali Saeed B S Vishwanathand K M Lokanatha Rai ldquoSynthesis and evaluation of antiox-idant and antibacterial activities of new substituted bis(134-oxadiazoles) 35-bis(substituted) pyrazoles and isoxazolesrdquo
Bioorganic and Medicinal Chemistry Letters vol 21 no 12 pp3536ndash3540 2011
[31] A Almasirad M Tajik D Bakhtiari et al ldquoSynthesis andanalgesic activity of N-arylhydrazone derivatives of mefenamicacidrdquo Journal of Pharmacy and Pharmaceutical Sciences vol 8no 3 pp 419ndash425 2005
[32] R Kalsi M Shrimali T N Bhalla and J P Barthwal ldquoSynthesisand anti-inflammatory activity of indolyl azetidinonesrdquo IndianJournal of Pharmaceutical Sciences vol 41 pp 353ndash359 2006
[33] A Almasirad M Tajik D Bakhtiari et al ldquoSynthesis andanalgesic activity of N-aryl hydrazone derivatives of mefenmicacidrdquo Journal of Pharmaceutical Sciences vol 8 no 3 pp 419ndash425 2005
[34] K K Sivakumar A Rajasekaran I Ponnilavarasan ASomasundaram R Sivasakthi and S Kamalaveni ldquoAntimi-crobial and analgesic activity of some (4Z)-3-methyl-1-[(2-oxo-2H-chromen-4-yl)carbonyl]-1H-pyrzole-4 5-dione 4-[(4-substitutedphenyl) hydrazone]rdquo Scholars Research Library vol2 no 1 pp 211ndash219 2010
[35] S A Khan P Mullick S Pandit and D Kaushik ldquoSynthesis ofhydrazones derivatives of quinoxalinonemdashprospective antimi-crobial and antiinflammatory agentsrdquo Acta Poloniae Pharma-ceutica vol 66 no 2 pp 169ndash172 2009
[36] M A A Radwan E A Ragab N M Sabry and S MEl-Shenawy ldquoSynthesis and biological evaluation of new 3-substituted indole derivatives as potential anti-inflammatoryand analgesic agentsrdquo Bioorganic and Medicinal Chemistry vol15 no 11 pp 3832ndash3841 2007
[37] A R Todeschini A L P De Miranda K C M Da SilvaS C Parrini and E J Barreiro ldquoSynthesis and evaluationof analgesic antiinflammatory and antiplatelet properties ofnew 2-pyridylarylhydrazone derivativesrdquo European Journal ofMedicinal Chemistry vol 33 no 3 pp 189ndash199 1998
[38] P C Lima L M Lima K C M Da Silva et al ldquoSynthesis andanalgesic activity of novel N-acylarylhydrazones and isostersderived from natural safrolerdquo European Journal of MedicinalChemistry vol 35 no 2 pp 187ndash203 2000
[39] P Hernandez M Cabrera M L Lavaggi et al ldquoDiscoveryof new orally effective analgesic and anti-inflammatory hybridfuroxanyl N-acylhydrazone derivativesrdquo Bioorganic and Medic-inal Chemistry vol 20 no 6 pp 2158ndash2171 2012
[40] G Rajitha N Saideepa and P Praneetha ldquoSynthesis andevaluation of N-(120572-benzamido cinnamoyl) aryl hydrazonederivatives for anti-inflammatory and antioxidant activitiesrdquoIndian Journal of Chemistry B vol 50 no 5 pp 729ndash733 2011
[41] C M Moldovan O Oniga A Parvu et al ldquoSynthesis and anti-inflammatory evaluation of some new acyl-hydrazones bearing2-aryl-thiazolerdquo European Journal of Medicinal Chemistry vol46 no 2 pp 526ndash534 2011
[42] M A-A El-Sayed N I Abdel-Aziz A A-M Abdel-Aziz AS El-Azab Y A Asiri and K E H Eltahir ldquoDesign synthesisand biological evaluation of substituted hydrazone and pyrazolederivatives as selective COX-2 inhibitors molecular dockingstudyrdquo Bioorganic and Medicinal Chemistry vol 19 no 11 pp3416ndash3424 2011
[43] A M Isloor B Kalluraya and K Sridhar Pai ldquoSynthe-sis characterization and biological activities of some newbenzo[b]thiophene derivativesrdquo European Journal of MedicinalChemistry vol 45 no 2 pp 825ndash830 2010
[44] M Sarangapani and V M Reddy ldquoPharmacological screen-ing of isatin-[N-(2-alkylbenzoxazole-5-carbonyl)] hydrazonesrdquo
Journal of Applied Chemistry 7
Indian Journal of Pharmaceutical Sciences vol 59 no 3 pp 105ndash109 1997
[45] S K Sridhar and A Ramesh ldquoSynthesis and pharmacologicalactivities of hydrazones schiff and mannich bases of isatinderivativesrdquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1149ndash1152 2001
[46] M Gokce S Utku and E Kupeli ldquoSynthesis and analgesicand anti-inflammatory activities 6-substituted-3(2H)-py-ridazinone-2-acetyl-2-(p-substitutednonsubstituted benzal)hydrazone derivativesrdquo European Journal of MedicinalChemistry vol 44 no 9 pp 3760ndash3764 2009
[47] A G M Fraga C R Rodrigues A L P De Miranda E JBarreiro and C A M Fraga ldquoSynthesis and pharmacologicalevaluation of novel heterotricyclic acylhydrazone derivativesdesigned as PAF antagonistsrdquo European Journal of Pharmaceu-tical Sciences vol 11 no 4 pp 285ndash290 2000
[48] G A Silva L M M Costa F C F Brito A L P Miranda EJ Barreiro and C A M Fraga ldquoNew class of potent antinoci-ceptive and antiplatelet 10H-phenothiazine-1-acylhydrazonederivativesrdquo Bioorganic andMedicinal Chemistry vol 12 no 12pp 3149ndash3158 2004
[49] U Salgin-Goksen N Gokhan-Kelekci O Goktas et al ldquo1-Acylthiosemicarbazides 124-triazole-5(4H)-thiones 134-thi-adiazoles andhydrazones containing 5-methyl-2-benzoxazolin-ones synthesis analgesic-anti-inflammatory and antimicrobialactivitiesrdquo Bioorganic and Medicinal Chemistry vol 15 no 17pp 5738ndash5751 2007
[50] C D Duarte J L M Tributino D I Lacerda et al ldquoSyn-thesis pharmacological evaluation and electrochemical studiesof novel 6-nitro-34-methylenedioxyphenyl-N-acylhydrazonederivatives discovery of LASSBio-881 a new ligand of cannabi-noid receptorsrdquo Bioorganic andMedicinal Chemistry vol 15 no6 pp 2421ndash2433 2007
[51] A Deep S Jain P C Sharma P Verma M Kumar andC P Dora ldquoDesign and biological evaluation of biphenyl-4-carboxylic acid hydrazide-hydrazone for antimicrobial activityrdquoActa Poloniae Pharmaceutica vol 67 no 3 pp 255ndash259 2010
[52] B Durgun G Capan N Ergenc and S Rollas ldquoSynthesischaracterization and biological evaluation of new benzyli-denebenzohydrazides and 25-disubstituted-23-dihydro-134-oxadiazolesrdquo Pharmazie vol 48 no 12 pp 942ndash943 1993
[53] O I El-Sabbagh M A Shabaan H H Kadry and E SAl-Din ldquoNew octahydroquinazoline derivatives synthesis andhypotensive activityrdquo European Journal of Medicinal Chemistryvol 45 no 11 pp 5390ndash5396 2010
[54] J L Gage R Onrust D Johnston et al ldquoN-Acylhydrazonesas inhibitors of PDE10Ardquo Bioorganic and Medicinal ChemistryLetters vol 21 no 14 pp 4155ndash4159 2011
[55] F Hayat A Salahuddin J Zargan and A Azam ldquoSynthe-sis characterization antiamoebic activity and cytotoxicity ofnovel 2-(quinolin-8-yloxy) acetohydrazones and their cyclizedproducts (123-thiadiazole and 123-selenadiazole derivatives)rdquoEuropean Journal of Medicinal Chemistry vol 45 no 12 pp6127ndash6134 2010
[56] Y Jin Z Tan M He et al ldquoSAR and molecular mechanismstudy of novel acylhydrazone compounds targeting HIV-1 CArdquoBioorganic and Medicinal Chemistry vol 18 no 6 pp 2135ndash2140 2010
[57] S Rollas and S G Kucukguzel ldquoBiological activities of hydra-zone derivativesrdquoMolecules vol 12 no 8 pp 1910ndash1939 2007
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
Journal of Applied Chemistry 7
Indian Journal of Pharmaceutical Sciences vol 59 no 3 pp 105ndash109 1997
[45] S K Sridhar and A Ramesh ldquoSynthesis and pharmacologicalactivities of hydrazones schiff and mannich bases of isatinderivativesrdquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1149ndash1152 2001
[46] M Gokce S Utku and E Kupeli ldquoSynthesis and analgesicand anti-inflammatory activities 6-substituted-3(2H)-py-ridazinone-2-acetyl-2-(p-substitutednonsubstituted benzal)hydrazone derivativesrdquo European Journal of MedicinalChemistry vol 44 no 9 pp 3760ndash3764 2009
[47] A G M Fraga C R Rodrigues A L P De Miranda E JBarreiro and C A M Fraga ldquoSynthesis and pharmacologicalevaluation of novel heterotricyclic acylhydrazone derivativesdesigned as PAF antagonistsrdquo European Journal of Pharmaceu-tical Sciences vol 11 no 4 pp 285ndash290 2000
[48] G A Silva L M M Costa F C F Brito A L P Miranda EJ Barreiro and C A M Fraga ldquoNew class of potent antinoci-ceptive and antiplatelet 10H-phenothiazine-1-acylhydrazonederivativesrdquo Bioorganic andMedicinal Chemistry vol 12 no 12pp 3149ndash3158 2004
[49] U Salgin-Goksen N Gokhan-Kelekci O Goktas et al ldquo1-Acylthiosemicarbazides 124-triazole-5(4H)-thiones 134-thi-adiazoles andhydrazones containing 5-methyl-2-benzoxazolin-ones synthesis analgesic-anti-inflammatory and antimicrobialactivitiesrdquo Bioorganic and Medicinal Chemistry vol 15 no 17pp 5738ndash5751 2007
[50] C D Duarte J L M Tributino D I Lacerda et al ldquoSyn-thesis pharmacological evaluation and electrochemical studiesof novel 6-nitro-34-methylenedioxyphenyl-N-acylhydrazonederivatives discovery of LASSBio-881 a new ligand of cannabi-noid receptorsrdquo Bioorganic andMedicinal Chemistry vol 15 no6 pp 2421ndash2433 2007
[51] A Deep S Jain P C Sharma P Verma M Kumar andC P Dora ldquoDesign and biological evaluation of biphenyl-4-carboxylic acid hydrazide-hydrazone for antimicrobial activityrdquoActa Poloniae Pharmaceutica vol 67 no 3 pp 255ndash259 2010
[52] B Durgun G Capan N Ergenc and S Rollas ldquoSynthesischaracterization and biological evaluation of new benzyli-denebenzohydrazides and 25-disubstituted-23-dihydro-134-oxadiazolesrdquo Pharmazie vol 48 no 12 pp 942ndash943 1993
[53] O I El-Sabbagh M A Shabaan H H Kadry and E SAl-Din ldquoNew octahydroquinazoline derivatives synthesis andhypotensive activityrdquo European Journal of Medicinal Chemistryvol 45 no 11 pp 5390ndash5396 2010
[54] J L Gage R Onrust D Johnston et al ldquoN-Acylhydrazonesas inhibitors of PDE10Ardquo Bioorganic and Medicinal ChemistryLetters vol 21 no 14 pp 4155ndash4159 2011
[55] F Hayat A Salahuddin J Zargan and A Azam ldquoSynthe-sis characterization antiamoebic activity and cytotoxicity ofnovel 2-(quinolin-8-yloxy) acetohydrazones and their cyclizedproducts (123-thiadiazole and 123-selenadiazole derivatives)rdquoEuropean Journal of Medicinal Chemistry vol 45 no 12 pp6127ndash6134 2010
[56] Y Jin Z Tan M He et al ldquoSAR and molecular mechanismstudy of novel acylhydrazone compounds targeting HIV-1 CArdquoBioorganic and Medicinal Chemistry vol 18 no 6 pp 2135ndash2140 2010
[57] S Rollas and S G Kucukguzel ldquoBiological activities of hydra-zone derivativesrdquoMolecules vol 12 no 8 pp 1910ndash1939 2007
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
![ANALGESIC AND ANTI-INFLAMMATORY ACTIVITY OF ......tive activity [6]. Myrtenol is a mono-oxidized isomer of pinene, which also exhibits anti-inflammatory properties combined with analgesic](https://static.fdocuments.us/doc/165x107/609d2bf24dd87504107fcf19/analgesic-and-anti-inflammatory-activity-of-tive-activity-6-myrtenol.jpg)
