The Center for Research on Redox Processes in Biomedicine

CEPID Redoxoma

Patents

Support:

The Research Center of Redox Processes in Biomedicine, the CEPID Redoxoma, is a network involving 24 researchers from the State of São Paulo and several collaborators, including international researchers. Its headquarters is the Instituto de Química, Universidade de São Paulo and it has 19 other member Institutions. The network is funded by São Paulo Research Foundation, FAPESP, through CEPID program (Research, Innovation and Dissemination Centers).

Mission: To investigate the mechanisms by which oxidants and radicals act as mediators of physiological and pathophysiological networks attempting to transfer the research results to commercially and/or socially relevant applications, as well as to education and dissemination of knowledge.

Oxidants and free radicals are produced in organisms by oxidation and reduction processes (redox).

The health depends on perfect regulation of redox processes.

Deregulation of redox processes lead to diseases, including chronic diseases.

The study of redox processes can elucidate disease mechanisms and reveal new therapeutic targets. In practical terms can lead to the design of novel therapeutic, nutritional and environmental strategies and to the development/improvement of industrialized products.

Metal complexes with indole or oxindole and Metal complexes with indole or oxindole and respective oxindolimine derivatives as potential respective oxindolimine derivatives as potential antiparasite agentsantiparasite agentsPatent protected under code BR 10 2013 026558-6, INPI/SP, 15/10/2013.

Inventors: Ana Maria da Costa Ferreira, Gustavo L. Sabino, Ricardo A. Couto, Queite A. de Paula, Bruno S. Dario (IQ-USP, São Paulo); Grazielle A. Ribeiro and Leda Q. Vieira (UFMG, Belo Horizonte).

Selectivity Index

24h 48h

[Cu(isapn)](ClO4)2 4.8 11.6

[Cu(isaepy)2](ClO4)2 3.7 5.4

[Zn(isapn)]ClO4 5.6 12.4

[Zn(isaepy)Cl2] 2.0 3.2

24 hours

Am

asti

go

tes/

Tota

l Mac

rop

hag

es

1.0

0.8

0.6

0.4

0.2

0.0

1 2 3 4 5 6 7 8 9

10 11 12

Control [Cu(isapn)]

2+ (12.6μmol.L

-1)

[Cu(isapn)]2+

(25.2μmol.L-1

) [Cu(isaepy)2]

2+ (9.8μmol.L

-1)

[Cu(isaepy)2]2+

(19.6μmol.L-1

) [Zn(isapn)]

+ (60.5μmol.L

-1)

[Zn(isapn)]+ (80.6μmol.L

-1)

[Zn(isapn)]+ (120.9μmol.L

-1)

[Zn(isaepy)Cl2] (77.4μmol.L-1

) [Zn(isaepy)Cl2] (103.2μmol.L

-1)

[Zn(isaepy)Cl2] (154.8μmol.L-1

) Benznidazole (192.1μmol.L

-1)

Tropical diseases as Chagas, and Leishmaniose have been neglected for many years, regarding the development of new, more efficient and less toxic therapeutic drugs. Studies with the aim of preparing and characterizing metallodrugs showing remarkable activity against parasites that cause such diseases were developed, combining the inhibitory capacity of indole derivative ligands towards specific proteins (kinases and topoisomerases) and the redox properties of essential metals (as copper). Our goal was to get metallodrugs more efficient and less toxic then presently used drugs; and verify possible mechanisms of action of such metallodrugs.

CEPID Redoxoma - 1

Basic studies

Development step

Applications and targets

tests in vitro: against different forms of parasite (trypomastigotes and amastigotes)

tests in vitro: against different forms of parasite (trypomastigotes and amastigotes)

Antiparasite metallodrugs, alternative do usual drugsAnti-chagasic agents (T. cruzi)Anti-leishmaniose agents (L. amazonensis)

Antiparasite metallodrugs, alternative do usual drugsAnti-chagasic agents (T. cruzi)Anti-leishmaniose agents (L. amazonensis)

Antitumor compounds, processes for its production Antitumor compounds, processes for its production and usesand usesPatent protected under code BR 10 2015 001045-1, INPI/SP, 16/01/2015.

Inventors: Esther Escribano Aranda, Ana Maria da Costa Ferreira, Koiti Araki, Tiago Araújo Matias (IQ-USP, São Paulo); Carolina Portela Luz and Fábio Luiz Navarro Marques (FM-USP, São Paulo).

Alternative metallodrugs containing copper and platinum ions, coordinated to an adequate ligand, were isolated by a novel process, with the aim of combine the redox properties of copper ions, and the strong binding of platinum ions to DNA to obtain better antitumor agents. As ligands, multifunctional derivatives of oxindolimine were used, capable of inhibiting topoisomerases and quinases (as CDK1/CyclinB), and consequently induce apoptosis. The citotoxicity of these new compounds against tumor cells were similar or higher than that of cisplatin, a traditional metallodrug with high toxicity, colateral effects and developed resistance.

CEPID Redoxoma - 2

Antiviral against Foot-and-mouth diseaseAntiviral against Foot-and-mouth diseasePatent protected under code BR 10 2015 006561-2, INPI/SP, 24/03/2015,“Método de identificação de compostos antivirais, compostos antivirais, método de avaliação da funcionalidade dos compostos antivirais, uso dos compostos antivirais composição farmacêutica antiviral”.

Inventors: Antonia Tavares do Amaral, Erika Piccirillo (IQ-USP, São Paulo); Maria Aparecida Juliano and Marcia Yuri Kondo (UNIFESP, São Paulo).

Foot-and-mouth disease (FMD) is a highly contagious viral infection of cloven-hoofed animals, such as cattle, sheep, goats, deer and pig. This infection leads to the slaughter of thousand of infected and in-contact animals, causing a significant economic impact in the infected areas. In Brazil, the prophylactic treatment is made through mandatory animal vaccination, applied every six months, from three months old animals.

Goals: The hereby invention consists on a method of identification of compounds which have inhibitory activity evaluated against FMD virus leader protease (Lbpro), bearing at least one electrophilic center, particularly a nitrile group. It is a pharmaceutical composition which contains a small and non-peptide inhibitor of leader protease (Lbpro), withpotential application against FMD infection.

CEPID Redoxoma - 3

DockingSet of

Compounds

Activity against

Lbpro

Inhibitors

O

O

H NH

N

N

Leu143 Ala149Glu147His148

Asn46

QSAR approaches applied to rational design of QSAR approaches applied to rational design of antibacterials, evaluated against antibacterials, evaluated against Saccharomyces Saccharomyces cerevisiaecerevisiae (BY4741) and (BY4741) and Escherichia coliEscherichia coli (DH5α) (DH5α)Patent protected under code PI 1000927-2 A2, INPI/SP, 11/03/2010,“Composição antimicrobiana, método de inibição de microorganismos, uso de cloretos de N,N[(dimetilamino)etil] benzoatos substituídos e método de avaliação da funcionalidade de antimicrobianos”.

Inventors: Antonia Tavares do Amaral, Elba Vieira Mustafa dos Santos (IQ-USP, São Paulo); Luis Eduardo Soares Netto and Gisele Monteiro de Souza (IB-USP, São Paulo).

R1

R1

R2

R3

(CH2)n

R5

R4

R6-

+H

N

Set of procain analogs, synthesized in the group, showingantimicrobial activities evaluated against Saccaromycescerevisiae (BY4741) and Escherichia coli (DH5α), design by QSARapproaches.

Problem : The spread of multi-resistant infections represents a continuously growing problem to public health. Nowadays, search of novel compounds, showing activity against Multidrug-resistant microorganims becomes a real need. Literature studies indicated that compounds having local anesthetics structure showed also antimicrobial activity, against a wide spectrum of microorganisms.

Solution: QSAR approaches applied to rational design of antibacterials, evaluated against Saccharomyces cerevisiae (BY4741) and Escherichia coli (DH5α).

CEPID Redoxoma - 4

Screening method for modulators of cysteine Screening method for modulators of cysteine proteases activity and related pharmaceutical proteases activity and related pharmaceutical compositioncompositionPatent protected under code PI 0805492-4A2, INPI/SP, 02/12/2008,“Método para triagem de moduladores da atividade de cisteíno-proteases e composição farmacêutica compreendendo os mesmos”.

Inventors: Antonia Tavares do Amaral, Alberto Malvezzi and Leandro de Rezende (IQ-USP, São Paulo).

Virtual Screening: pharmacophoreflter physico-chemical flter → →docking-flter visual inspection→

purchase Enzymatic Assay→ →

NN

O

O

OOO

-

H

H H

H

Br

Chemical structure of the com-pound ZINC01794422 identifed ascruzain inhibitor by virtual screen-ing.

Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of the most serious amongst the so-called neglected diseases in Latin America, specially in Brazil. So far there has been no effective treatment for the chronic phase of this disease. Cruzain is a major cysteine proteaseof T. cruzi and it is recognized as a valid target for Chagas disease chemotherapy. The mechanism of cruzain action is associated with the nucleophilic attack of an activated sulfur atom towards electrophilic groups. In this report, features of a putative pharmacophore model of the enzyme, developed as a virtual screening tool for the selection of potential cruzain inhibitors, are described. The final proposed model wasapplied to the ZINC v.7 database and afterwards experimentally validated by an enzymatic inhibition assay. One of the compounds selected by the model showed cruzain inhibition in the low micromolar range.

CEPID Redoxoma - 5

Porphyrin derivatives, procedure for obtaining them Porphyrin derivatives, procedure for obtaining them and the pharmaceutical composition containing and the pharmaceutical composition containing themthemPatent deposited in INPI at 19/08/2008, under code PI 0802649-1 A2. Today patent is under technical evaluation and technology is ready for transfer.

Inventors: Mauricio da Silva Baptista and Adjaci Uchoa Fernandes.

The present invention belongs to the field of compounds derived from porphyrins. Specifically, the derivatives of the present invention are photochromic compounds and may be used in Photodynamic Therapy. The preparation process of the compounds of the present invention comprises a final methylation step and optionally comprises using as the starting compound a chlorophyllin, specifically a chlorophyllin which is previously subjected to a metal/copper removing step. The invention further comprises pharmaceutical compositions containing such compounds that can be used in treating diseases like cancer, rheumatoid arthritis, psoriasis, among other possible ones.

CEPID Redoxoma - 6

Composition of a surface collector agent and the Composition of a surface collector agent and the procedure for obtaining itprocedure for obtaining itPatent deposited in INPI at 06/10/2009, under code PI 0905673-4 A2. Today patent is under technical evaluation and technology is ready for transfer.

Inventors: Marcos Eduardo Sedra Gugliotti, Vinicius Curcino Carvalho Vieira, Mauricio da Silva Baptista and Divinomar Severino.

The present invention concerns a surface collector agent composition

capable of confining and contract oil slicks and its derivatives scattered

on the surface of the water. The composition of this invention consists

solely of one or more surfactants belonging to the group of fatty acids

containing from 7 to 14 carbon atoms in their molecules. The

composition of this invention does not use organic solvents or other

substances harmful to the environment and has low toxicity. In one of its

preferred forms, the composition of this invention generates a

monomolecular film with a surface pressure of 70 mN/m, which spreads

rapidly over the water and is able to confine oil slicks in the form of

lenses with more than 0.5 cm thick for about 48 hours.

CEPID Redoxoma - 7

Polymer formulations for the treatment of skin Polymer formulations for the treatment of skin tumors by photodynamic therapytumors by photodynamic therapy

Patent was deposited in INPI at 16/04/2010, under code PI 1001299-0 A2. Today patent isunder technical evaluation and technology is ready for transfer.

Inventors: Mauricio da Silva Baptista, Eduardo Caritá, Henrique Eisi Toma, Daiana Kotra Deda and Koiti Araki.

The present invention relates to the preparation of polymeric

compositions for treatment of skin tumors using photodynamic therapy,

consisting of nano/micro capsules containing encapsulated photoactive

agents. This invention seeks to treat skin cancer by photodynamic

therapy based on the injection "in situ" of the polymeric formulations. In

this regard, the results obtained to date indicate the potential

application of these formulations in the therapeutic procedure aiming

beyond the treatment of tumors, also other skin diseases such as

psoriasis, vitiligo and leishmaniasis, as well as for applications with

cosmetic purposes.

CEPID Redoxoma - 8

Methods for obtaining porphyrin derivatives, chlorin Methods for obtaining porphyrin derivatives, chlorin compounds, their pharmaceutical composition and compounds, their pharmaceutical composition and their use in photodynamic therapytheir use in photodynamic therapyPatent was deposited in INPI at 11/02/2011, under code PI 1100371-5 A2. Today patent isunder technical evaluation and technology is ready for transfer.

Inventors: Mauricio da Silva Baptista, Osvaldo Antonio Serra, Yassuko Iamamoto, Adjaci Uchoa Fernandes and Kleber Thiago de Oliveira.

The present invention describes a new method for obtaining porphyrin

and chlorin derivatives, which are sterically hindered avoiding the

formation of aggregation states and pharmaceutical composition

containing these compounds. Additionally, the present application

provides the use of these compounds in the preparation of

pharmaceutical compositions indicated for the Photodynamic Therapy

(PDT), particularly, cancer, inflammatory processes, such as, rheumatoid

arthritis, psoriasis, among others.

CEPID Redoxoma - 9

CEPID Redoxoma – CONTACT

Instituto de Química, Universidade de São Paulo

Av. Prof. Lineu Prestes, 748, Bloco 5 inferior, Sala 500

Butantan – São Paulo, SP – Brazil – 05508-000

Phone: +55-11-2648-0855

Email: admcepid@iq.usp.br

CEPID Redoxoma homepage

http://redoxoma.iq.usp.br

Redoxoma Newsletter

http://redoxomanewsletter.iq.usp.br

Support: Proc. FAPESP 2013/07937-8

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