Bringing pharmacy knowledge and students togetherantibacterial, antifungal, anti-inflammatory...

Bringing pharmacy

knowledge and students

together

Volume 1 | Edition 2 | April 2014www.epsa-online.org

EPSA Students' Science Publication

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INTRODUCTION

Dear friends,

Not long ago, the Education and Public Relations departments presented the first edition of the EPSA Students’ Science Publication (ESSP) during the Autumn Assembly held in Valencia (Spain). The response, since then, has been very good. Students from across Europe have contacted us and expressed interest in sharing their research with others through the publication. It is our great pleasure to present you with the second edition of the ESSP!Since the last edition, some modifications to the publication have been made. A stepping stone was our partnership with the European Federation for Pharmaceutical Sciences (EUFEPS). They have carefully reviewed the abstracts and given feedback to the students. Their role is vital in ensuring that this publication consists of good quality and well-written abstracts.For this edition, we have tried to include a broad spectrum of topics. From pharmacy practice and pharmaceutical sciences, you can read about: services provided by community pharmacies, patent law, modification of the phenothiazine structure, breast cancer metastasis, and polyplexes as a form of delivery system.Hopefully you will find this interesting and inspiring for your future research. In which case, we would like to know all about your project for our next edition in July. Once again, a big thanks for all the authors and the EUFEPS for their hard work. Good luck for your studies, we hope to hear from you soon!

Yours in EPSA,

Rebwar Saleh, Science Coordinator 2013-2014Maria Pace, Publications Coordinator 2013-2014Svenja Laarhuis, Design Coordinator 2013-2014

EPSA Students' Science Publication Volume 1 | Edition 2 | April 2014

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TAblE Of CONTENT

What factors may influence success of Community Pharmacy Stop Smoking Services? K. Mortensen, M. Kinnear, A Muir .... 4

Q&A of the authors ........................................................................ 5

The propargyl dericatives of quinobenzo- and quinonaphthothiazines. M. Małowska, K. Maciusiak, M. Jeleń, K. Pluta, B. Morak-Młodawska, K. Suwińska ........................... 6

Q&A of the authors ........................................................................ 7

Crosstalk between integrin-beta1 and TGF-beta signalling in breast cancer cells. P. Akhavan ................................................ 8

Q&A of the authors ........................................................................ 9

Characterization of nanosystems - polyplexes - for the specific delivery of siRNA targeting HDAC7. D. Barreira .................... 10Q&A of the authors ................................................................. 11

EUFEPS information .................................................................... 13


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What factors may influence success of community Pharmacy stoP smoking services?Mortensen K, Kinnear M, Muir, A NHS Lothian pharmacy service, Western General Hospital, Edinburgh, United Kingdom and Universities of Tromso, Norway and Strathclyde, Glasgow, United Kingdom

Background and objective: To obtain an understanding of the factors which may impact on the varying success rates of NHS Community Pharmacy Stop Smoking Services.Setting and method: A questionnaire survey of 182 pharmacies and a national database of success rates and client demographics within one health board area were used to identify factors.Main outcome measures: Questionnaire parameters included client recruitment methods; staff training; number, type and continuity of staff; use of consultation room; approach used; use of appointments; use of carbon monoxide monitoring and perceived outcomes from repeated quit attempts. Database parameters included gender, age and employment status. Arbitrary pharmacy categories based on their success rates were used to identify potential predictors of success.Results: During 2012, a median (interquartile range (IQR)) of 19 (6 – 45) quit attempts per pharmacy was recorded and the IQR for quit rates (self-reported at 4 weeks) was 25.8% to 55.1%. Questionnaire responses (n = 81), suggested the consulting room was used commonly for initial consultations but less frequently for follow-up consultations. Not all pharmacy staff accessed the NHS smoking cessation training, some utilised sponsored training and employment training, some had only one-off training. A higher proportion (p < 0.001) of responders with a success rate ≥ 41% and with client quit attempts ≥ 10 had clients over 45 years of age compared to responders with a success rate < 41% and with client quit attempts ≥ 10. Using the same arbitrary groups there were differences in the proportions of males and females (p = 0.045) and employed clients and non-employed clients (p < 0.001) having a successful quit attempt. Responses did not suggest other potentially influencing factors on success rates. Respondents requested to receive feedback on their success rates.Conclusions: Gender, age, employment status of clients and use of the consultation room in community pharmacies are potential factors to test for association with successful smoking cessation outcomes. Feedback of success rates may motivate pharmacies. Defining levels of competence to deliver the service may inform training needs and improve consistency in standard of service delivery.


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Q&A Of ThE AUThORs

General information about Mr Kristian MortensenAge: 26City/country: Tromso, NorwayE-mail address: [email protected]: University of Strathclyde.

Why did you select this topic for your research?I developed a great interest for clinical pharmacy throughout my years as a pharmacy student, and Scotland is among the leading nations in clinical pharmacy. Therefore, I decided to complete my master's thesis in Scotland. I also chose Scotland to meet new people and learn about different customs and culture to further develop myself both professionally and personally. As for the topic, smoking cessation services, it was assigned to me. At first, I thought smoking cessation sounded really dull and uninteresting, but as I got deeper into the subject, I found I had developed a true passion for it. The complexity of quitting smoking successfully, is truly fascinating.

How do you feel you have coped with the challenges that research can bring?Very good question. Before starting my thesis, I did not know that there were so many challenges with research. As pharmacists, we have a tendency to want everything to be perfect, but with research there are many bumps in the road that you cannot anticipate. Throughout the project period, I often gave myself a hard time, thinking that I could have done things better. But my supervisor always calmed me down by reminding me that a master's thesis is a learning process. The learning curve has been incredibly steep!

What personal skills did you develop as a researcher during your research period?I have developed a lot more trust in myself with regards to decision making, and discussing academic and professional matters with superiors and other medical professionals. As pharmacists, we encounter quite a few 'know-it-all' physicians; I think the skills I have learned during my time on the project will be really helpful when it comes to discussing patient-orientated matters with these professionals.

Anything else you want to share with the students in Europe? recommendations?To students working on similar projects: do not give yourself a hard time if everything does not go exactly as planned. Prepare, adapt and improvise!


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the ProPargyl Derivatives of QuinoBenZo- anD QuinonaPhthothiaZinesM. Małowska1, K. Maciusiak1, M. Jeleń1, K. Pluta1, B. Morak-Młodawska1, K. Suwińska2

Students Scientific Group and Department of Organic Chemistry, The Medical University of Silesia1; Institute of Physical Chemistry of the Polish Academy of Sciences, Poland2

Classical tricyclic phenothiazines, representing the dibenzo-1,4-thiazine ring system, attract attention because of their significant biological activities and interesting chemical features. Those with aminoalkyl substituents at the nitrogen atom in position 10 are valuable drugs exhibiting neuroleptic, antihistaminic, antitussive and antiemetic activities. Recently the phenothiazine structure has been modified by introduction of new substituents and by substitution of the benzene rings with homoaromatic and heteroaromatic rings. The substitution with an azine ring leads to azaphenothiazines. Such structure modifications changed type of biological properties to show very promising anticancer, antibacterial, antifungal, anti-inflammatory activities, reversal of multidrug resistance and potential benefit in treatment of Alzheimer’s, Creutzfeldt-Jakob’s and AIDS-associated diseases.The aim of this study was to elaborate the synthesis of new type of tetra- and pentacyclic azaphenothiazines, quinobenzothiazines and quinonaphthothiazines, possessing the quinoline and naphthalene rings instead of the benzene rings.The synthesis of those azaphenothiazines was based on the reactions of diquinodithiin and diquinolinyl disulfide with substituted anilines, and naphthylamines. The obtained NH-quinobenzothiazines and quinonaphthothiazines were transformed into derivatives containing a pharmacophoric propargyl substituent in the reaction with propargyl bromide. As the synthesis can proceed through the Smiles rearrangement, the crucial problem was the proper identification of the product structures. The identification of the product structures was based on the spectroscopic NMR (1H, 13C, 2D experiments), MS and X-ray analysis of their derivatives. The analysis excluded the rearrangement products.Most compounds exhibited significant activities as glycosylphosphatidylinositol phospholipase D inhibitor, anaphylatoxin receptor antagonist, antiparkinsonian and muscular dystrophy treatment in silico screening. The new azaphenothiazines will be tested for their anticancer and antioxidant activities.In conclusion, the efficient synthesis of new azaphenothiazines containing the quinoline and naphthalene moieties was elaborated.

References: K. Pluta, B. Morak-Młodawska, M. Jeleń, Eur. J. Med. Chem., 46, (2011) 3179, M. Jeleń, K. Pluta, Heterocycles, 78 (2009) 2325, PASS-http//www.pharmaexpert.ru/PASSOnline/

index.php.


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Q&A Of ThE AUThORs

General information about Ms Monika MalowskaCity and Country: Katowice, PolandYear of Study: 5th.E-mail: [email protected]

Why did you select this topic for your research?I have always been interested in the preparation of medicines. During my studies I have found out how the formation and identification of new compound is difficult. Anyone who takes pills, expects biological effect. The most often active substance in drugs is organic compound. Phenothiazines belong to the oldest, synthetic, antipsychotic drugs. The structural modifications to phenothiazines change the biological properties, for example: anticancer, antibacterial, antifungal, anti-inflammatory activities, reversal of multidrug resistance and potential benefit in treatment of Alzheimer’s, Creutzfeldt-Jakob’s and AIDS-associated diseases. The relationship between chemical structure and biological activity is very interesting.

How do you feel you have coped with the challenges that research can bring?I took part in real scientific research and chemical synthesis based on the theoretical and practical knowledge. I synthesized new derivatives of phenothiazines which were examined for their anticancer and antioxidant activity. I hope that the obtained compounds will be a medicine of the future.

What personal skills did you develop as a researcher during your research period?I found out that synthesis of new compounds require a lot of time and patience. Chemical synthesis leads to the formation of variety products; that’s why the desired product is difficult to separate out. The new products’ structures were deduced using spectroscopic NMR analysis (1H, 13C, two-dimensional experiment), mass spectrometry and X-ray analysis. As a researcher I got to know new methods of product identification and how to synthesise new compounds.

Anything else you want to share with the students in Europe? Recommendations?The aim of this study was to synthesize a new derivatives of phenothiazines, which exhibit other than neuroleptic activity. It was very valuable experience for me. I would like to encourage you to deepen your knowledge. Participate in the scientific group, student’s exchange or oral presentation may improve your ability. If you are reading this text I believe that you are on the right way to achieve it.


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crosstalk BetWeen integrin-Beta1 anD tgf-Beta signalling in Breast cancer cellsMs. Parand AkhavanUniversity of Leiden, the department of toxicology at the Leiden Academic Centre for Drug Research (LACDR)

As the incidence levels of breast cancer continues to increase, the development and discovery of novel treatments are an ongoing priority to researchers. Adhesion receptors of the integrin family allow cells to interact with their environment. These receptors play a crucial role in cell survival and growth which make integrins potential drug targets in oncology. Some integrin antagonists are currently tested in clinical trials. Our group has found that such strategies can decrease the tumour size but actually increase metastatic spreading of triple negative breast cancer cells. This involves the activation of the TGF-beta signalling network leading to a loss of the E-cadherin cell-cell adhesion receptor.In this research project the aim lies in further unravelling the relation between beta1-integrin, the TGF-beta/BMP pathway, and E-cadherin expression in the modulation of breast cancer metastasis. We do this using the triple negative human breast cancer cell lines: BT20, HCC 1806, 70, 1596 & MDA-MB-468. Effects of TGF-beta stimulation and beta1 integrin knockdown are analysed using qPCR and western blot. qPCR results show a difference in regulation of TGF-beta/BMP pathway factors between the BT20 and the HCC 1806 &MDA-MB-468 and their respective knockdowns. Further validation is needed to make an accurate distinction. In parallel, we investigate whether the changes observed in vitro can also be seen in vivo in the tumours generated with these cell lines in mice. Immunohistochemistry is used to detect differences in E-cadherin and components, such as pSMAD2, of the TGF-beta signalling pathway in tumours derived from wild type or beta-1-integrin knockdown breast cancer cells.Together, this study will further unravel how integrins control signalling pathways regulating cell migration and metastasis. This will shed light on the reasons why integrin antagonists can inhibit breast cancer growth but also cause enhanced metastatic spread.


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Q&A Of ThE AUThORs

General information about Ms. Parand AkhavanAge: 22City and country: Leiden, The NetherlandsEmail address: [email protected]: University of Leiden

Why did you select this topic for your research?It was partly a personal reason but also because the research into cancer and its metastasis is always ongoing. It is so amazing to see how, even if it is in vitro, cells change their behaviour.

How do you feel you have coped with the challenges that research can bring?In the beginning it sometimes really drove me mad if something didn’t work for the 20th time or if the cells I work with didn’t grow or there weren’t enough to perform an experiment. Along the way you learn to let go of that and anticipate certain challenges. The thing that also changes is that you learn who to turn to for help.

What personal skills did you develop as a researcher during your research period?I think the most important thing you learn in research is patience. In my case I am dependent on different factors which I can’t control such as cell growth. If the cells don’t have the confluency needed for an experiment you need to wait.

Anything else you want to share with the students in Europe? Recommendations?Try to see every aspect of your studies. It can amaze you what you finally end up enjoying the most.


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characteriZation of nanosystems - PolyPleXes - for the sPecific Delivery of sirna targeting hDac7Daniel António Esperança Faustino Monteiro Barreira. Faculdade de Farmácia, Universidade de Lisboa

Cancer is one of the most deadly pathologies in the world; therefore, it is important to have as many and different approaches as possible when it comes to its treatment. As it is a complex and highly heterogeneous pathology, classic treatments are often lacking efficiency and are insufficient, which makes even more important the development of new strategies, such as gene targeting therapy.Concerning different delivery system-based approaches, there are both viral and non-viral vectors. The non-viral vectors, which are here under discussion, are resultant from the complexation of siRNA molecules with cationic polymers.Preliminary formulation studies have been performed using several polymers – C93, C122, C145, C172 and C173 - in which several tests were performed. These tests included determination of polyplexes capacity to release siRNA into the cytoplasm in the presence of heparin, polyplexes stability and diameter variation depending on pH modulation, and polyplexes capacity to protect siRNA from serum nuclease RNase A.Regarding the heparin destabilization, the developed polyplexes proved to effectively release siRNA in the presence of heparin, being the amount released dependent on the quantity of heparin used (1 UI being the minimum quantity to effectively promote the release of siRNA).About the pH, the polyplexes proved to be stable at pH values varying from 7.5 to 5 (pH 6.0–6.5 in early endosomes to pH 4.5–5.5 in late endosomes and lysosomal compartment) and to have no significant variation in particle size diameter at lower pH values.Concerning the complexes resistance to RNase A, all proved to be resistant to this enzyme.The polymers used for siRNA complexation lead to complexes that have shown to have promising parameters being thus promising candidates for further in vitro studies, as cellular uptake and viability studies, assessment of topographical profiles and complexes’ biological effect by inferring their ability to reduce the level of the HDAC7 protein and thus inhibit its biological function.Keywords: Cancer therapies, Angiogenesis, Polyplexes, Heparin, HDAC7 and siRNA


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Q&A Of ThE AUThORs

General information about Mr Daniel BarreiraAge: 24 years oldFrom: Lisboa, [email protected],Université de Liège (Belgium)

Why did you select this topic for your research?Oncology is a hot topic in health sciences and a challenging area to any pharmacist or student interested in research. So, cancer - and particularly gene therapy applied to tumors - is a whole new world to explore, therefore I was curious to go deeper into that subject.

How do you feel you have coped with the challenges that research can bring?As I was doing research in a foreign country first I had to adapt to different methodologies. After I found my comfort zone, I think I became up to the challenge and enthusiastic about knowing more and being able to self-instruct about the topic.

What personal skills did you develop as a researcher during your research period?I think time management and perseverance are of the utmost importance. Also, it is important to find the motivation (be it in your research work or in other tasks) when the results don’t match what you expect or when the research work is going in a wrong/unexpected direction.

Anything else you want to share with the students in Europe? Recommendations?I would really encourage any of you to try research work as it is one of the most rewarding experiences that I’ve had so far academically. Also, independent of the career path you choose you will develop some transitional skills to an upper level. Definitely try it!


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The european FederaTion For pharmaceuTical ScienceS (euFepS)

The European Federation for Pharmaceutical Sciences is a voluntary association of pharmaceutical scientists, established in 1991 to advance research in the pharmaceutical sciences in Europe. This can be achieved by promoting cooperation between national, regional and European societies or associations which aim at the advancement of pharmaceutical sciences, and by promoting cooperation between and with other pharmaceutical organisations and between individual pharmaceutical scientists.

The mission

EUFEPS exists to help to meet the challenges and seize the opportunities created by the consolidations occurring both within Europe and globally, driven on by a combination of rapid advances in science and technology, economic pressures, and by political will. Within this frame, EUFEPS’s role and contributions are amply expressed in its mission statement “EUFEPS serves and advances excellence in the pharmaceutical sciences and innovative drug research in Europe”. Spearheading a number of initiatives, EUFEPS works with its membership, throughout the nations of Europe.

european dimension

EUFEPS is unique being the only pan-European organisation that represents, under one umbrella, all the pharmaceutical sciences and pharmaceutical scientists engaged in drug research and development, drug regulation and drug policy making. The existence of such an umbrella platform facilitates the highly innovative, integrative and interdisciplinary approaches that are essential if we, in Europe, are to deliver to our citizens safe, effective, economic and timely medicines. The ultimate benefits are an improving health, quality of life, and wealth of our continent.


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EUFEPS is recognised by the European Commission, as representing the integrative pharmaceutical sciences within Europe. EUEFPS is also recognised by the EMEA as a neutral scientific resource for independent opinions on draft regulatory guidelines, while EUFEPS works with other European organisations, such as EFPIA, to help identify and promote training to meet industrial needs.EUFEPS has the ambition to provide a forum for policy development in the pharmaceutical sciences, particularly in relations to the discovery and development of new drugs and their introduction into the market, but also as to medicines usage. This includes policies on and leadership development as to: research, education & training, profiling and regulatory affairs.

In addition, EUFEPS plays an active and influential role also in the global arena. It is recognised by the USA FDA and it works actively with its sister organisation AAPS to develop co-sponsored meetings and workshops that run alternatively in Europe and the USA, and is developing links with Asian scientists. Through involvement with its Board of Pharmaceutical Sciences, EUFEPS is also working with FIP to advance the pharmaceutical sciences globally.


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conferences and Workshops organised by euFepS:

euFepS and BaBp network conferenceDate: May 6-7, 2014Place: Berlin, Germany

euFepS annual meeting 2014: medicines for the Future – System approaches to shape pharmaceutical ScienceDate: June 16-18, 2014Place: Uppsala, Sweden

In addition to these events that is organised, EUFEPS also is listed as co-sponsors to several events during the year. For More information see: http://www.eufeps.org/conferences

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