essp06

BRINGING 

PHARMACY 

KNOWLEDGE 

AND STUDENTS 

TOGETHER 

Volume 3 | Edition 1 | October 2015 

www.epsa-online.org

EPSA Students' Science Publication 

Dear friends, 

INTRODUCTION 

Another year has passed and it is time for the first edition of the EPSA Students' 

Science Publication (ESSP) of this academic year. The ESSP is a project that 

allows pharmacy students from around the Europe to publish their scientific 

research and outcomes. All of their abstracts are professionally reviewed by the 

European Federation for Pharmaceutical Sciences (EUFEPS). The project thus 

allows the students insight in the process of writing and publishing abstracts 

and, by extension, scientific articles. Every student also has the opportunity to 

present themselves and their motivation for conducting the research. Hopefully 

reading this edition inspires more students to firstly, try your hand at research 

and secondly, write and submit an abstract. 

This edition contains four different abstract, covering various topics. You will 

learn more about 'Biomedical Potential of Stevia - Stevia rebaudiana (Bert.) 

Bertoni', 'Celebrating One Century and Thinking About the Future: Preliminary 

Findings for a New MPharm Syllabus at Lisbon Faculty of Pharmacy', 'Synthesis 

of a Novel 14-membered Oxo-thia-aza Macrocyclic Compound' and 'The 

Influence of Acute Pain on Osmotic Pressure and Cortisol Concentration in 

Tears'. 

I would like to thank EUFEPS and the EPSA Public Relations Department for 

their hard work on this edition and all the students who collaborated on it. This 

would not have been possible without all of you. 

Looking forward to the future editions! 

Eva Shannon Schiffrer, Science Coordinator 2015-2016 

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TABLE OF CONTENT 


Synthesis of a novel 14-membered oxo-thia-aza macrocyclic compound 

Abstract ........................................................................................................... 4 

Q&A of the author ............................................................................................ 5 

Biomedical potential of Stevia - Stevia rebaudiana (Bert.) Bertoni 

Abstract ........................................................................................................... 6 


Celebrating one century and thinking about the future: preliminary 

findings for a new MPharm syllabus at Lisbon Faculty of Pharmacy 

Abstract ........................................................................................................... 8 


The influence of acute pain on osmotic pressure and cortisol 

concentration in tears 

Abstract ......................................................................................................... 10 

Q&A of the author .......................................................................................... 11 

European Federation for Pharmaceutical Sciences (EUFEPS) 

Information .................................................................................................... 12 

Upcoming conferences ................................................................................. 13 

3


SYNTHESIS OF A NOVEL 14-MEMBERED OXO-THIA-AZA 

MACROCYCLIC COMPOUND 

João Franco Machado, Judite Costa, Maria F. Cabral 

Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade 

de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisbon – Portugal 

Background: Macrocyclic compounds have been targets of a widespread 

interest in the last decade due to their similarity to the countless analogue 

scaffolds found in a variety of biological systems. The unique structural, kinetic 

and thermodynamic features of macrocycles, as well as their favourable druglike 

properties, have provided a motivation for further study and has had an 

enormous impact on the fields of medicine, pharmacy, chemistry and biology. 

However, this type of molecule is yet under-exploited as new, effective drugs 

and research continues to be fairly limited. 

Objective: Following our previous studies, we report the design, synthesis and 

structural characterization of a novel oxo-thia-aza macrocyclic compound, the 

dioxo-[14]aneN 3 

S (1-thia-4,8,12-triazacyclotetradecane-3,13-dione). 

Materials and Methods: Dioxo-[14]aneN 3 

S was synthesised by reacting 

dimethyl thiodiglycolate, previously obtained by Fischer-Speier esterification 

technique (η = 89.6 %), with dipropylenetriamine in a large excess of dry 

methanol at 40 ºC, under nitrogen atmosphere for 9 days. This procedure 

was based on the Tabushi methodology for macrocyclization, which consists 

of the condensation of the dimethyl ester of an α,ω-dicarboxylic acid with 

a commercially available polyethylenepolyamine. The pure product was 

then structurally characterized by infrared and nuclear magnetic resonance 

(1H, 13C, COSY, NOESY, HSQC, HMBC) spectroscopies and also by mass 

spectrometry. 

Results and Conclusion: The improvements in the reaction conditions 

introduced to the Tabushi general method (controlled temperature, N 2 

atmosphere, increased reaction time, and use of a dry solvent in a large excess) 

contributed to achieving - after purification by column chromatography - the 

desired macrocycle with a very high yield (η = 76.8 %), compared to the related 

compounds synthesised by Tabushi methodology reported in literature (η = 10 

~ 20 %). The spectroscopic and spectrometric analyses of dioxo-[14]aneN 3 

S 

allowed to confirm its chemical structure as well prove its high level of purity. 

4

Q&A OF THE AUTHOR 

General information about João Franco Machado 

22 years old, Sintra, Portugal, Faculty of Pharmacy, 

University of Lisbon, joaomachado@campus.ul.pt 


Why did you select this topic for your research? 

I am a trainee volunteer at the Research Institute for 

Medicines, where I have been developing a research 

work in the field of coordination chemistry of macrocyclic 

compounds through three years. During this time, I found 

out that macrocyclic ligands have a great potential to be 

developed as very promising therapeutic agents due to 

their unique physicochemical proprieties and also to their range on medical 

applications, which had motivated me to design and study novel and effective 

macrocycles. 

How do you feel about having coped with the challenges that research brings? 

When I started the research project that I am now reporting, I already had a 

considerable amount of experience which turned out to facilitate my research 

work. However, each project is a completely new challenge, because when 

we are designing a novel macrocycle, it is possible to figure out that we can’t 

properly synthesise it or that it doesn´t show the proprieties we are expecting. 

But at the end, and despite all difficulties we can face, the feeling of getting a 

novel and promising pharmaceutical compound is very enthusiastic! 

What skills did you develop as a researcher during your research period? 

During my research period I have not only improved my knowledge in the 

different fields of chemistry, but I also developed a set of valuable skills, 

such as patience, perseverance, dedication, hardworking, time management, 

adaptability, improvising, and critical thinking. 

Would you like to share anything else with the students in Europe? Any 

recommendations? 

The most important advice I can give is to never give up, even if some of 

your objectives seem to be quite unlikely to accomplish. Remember that the 

dedication leads to the success and at the end, you will experience the most 

rewarding feeling you can’t even imagine! 

5


BIOMEDICAL POTENTIAL OF STEVIA - STEVIA 

REBAUDIANA (BERT.) BERTONI 

Ana Begić and Josip Barilar, 

Faculty of Pharmacy and Biochemistry, Zagreb, Croatia 

Introduction: Stevia rebaudiana (Bert.) Bertoni (stevia) is a native plant to South 

America that is spread worldwide by cultivation due to its use as a natural 

sweetener, which is linked to the content of steviol glycoside. In this study, 

for the first time in Croatia, pharmacobotanical, phytochemical and biological 

studies of stevia were conducted, in order to evaluate its potential biomedical 

application possibilities in prevention and treatment. 

Aim: The aim of this study was to evaluate micromorphological and anatomical 

characteristics of the leaves and young stems, phytochemical composition, 

antioxidant effect, reducing power and total antioxidant capacity, ability to 

inhibit acetylcholinesterase and inhibitory effect on Src tyrosine kinase. 

Materials and Methods: The plant material - Stevia rebaudiana (Bert.) Bertoni 

was cultivated in Croatia and collected in August 2012, just before flowering, 

and air-dried at room temperature. Identification of plant material was 

carried out at the Department of Pharmacognosy, Faculty of Pharmacy and 

Biochemistry. The presence of flavonoids, phenolic acids, tannins, saponins, 

triterpenoids, sterols and essential oils were detected in methanolic leaf extract 

by thin layer chromatography. Contents of total polyphenols, tannins, flavonoids 

and phenolic acids in stevia leaves were determined spectrophotometrically. 

Antioxidant activities of ethanolic leaf extract were examined by different 

spectrophotometric methods in comparison with polyphenolic components and 

trolox as a reference. Effect of stevia and its individual bioactive components 

on Src tyrosine kinase was investigated by appropriate in vitro assay and 

compared with staurosporine. 

Results and Conclusion: Our results showed strong antioxidant potential 

of stevia, mostly attributed to the phenolic compounds contained. 

Acetylcholinesterase (AChE) inhibitory activity of ethanolic leaf extract was 

evaluated in comparison with chlorogenic acid and galantamine as a reference. 

Stevia showed ability to inhibit AChE exceeding a 50% effect at 1000 μg/mL. It 

was also found that chlorogenic acid contributes significantly to its anti-AChE 

activity. This research showed that stevia leaves contain a significant amount of 

various bioactive components which demonstrated strong antioxidant activity 

and ability to inhibit acetylcholinesterase and Src tyrosine kinase. Obtained 

results suggested a great potential of stevia in prevention and treatment of 

various diseases and that is not just a plant that serves as means of sweetening 

food and pharmaceutical products. 

6


General information about Ana Begić and Josip 

Barilar 

Both 25 years, Zagreb, Croatia, ana. 

begich@gmail.com, josip.barilar@gmail.com, 

University of Zagreb, Faculty of Pharmacy and 

Biochemistry 



The stevia plant caught our attention when we 

realized that it has other beneficial biomedical 

properties besides being only a natural 

sweetener. As the population was using it more in the food industry, we wanted 

to prove that stevia also has a potential of prevention and treatment of various 

diseases. 


During a student research, confrontation with different challenges and problems 

are fairly common. 

One should always try to approach difficulties rationally and try to use different 

methods and procedures to minimize the risk of getting bad results. Critical 

thinking in the process of research is crucial. 


During our research period we've learned to be more tolerant and more 

respective of people who dedicate their lives to science. We've also learned 

that a round bottom flask should not be placed on a flat surface, because you 

will lose the material you've been working on for weeks. 



We'd like to advise them not to stick their heads in books and blindly believe 

what is written. In order to become a successful scientist it is of great importance 

to develop creativity because creativity is, along with knowledge, a core to 

scientific endeavour. 

7


CELEBRATING ONE CENTURY AND THINKING ABOUT THE 

FUTURE: PRELIMINARY FINDINGS FOR A NEW MPHARM 

SYLLABUS AT LISBON FACULTY OF PHARMACY 

Madalena Plácido, Joana Catarino, Diogo Raimundo and Diana Ferreira 

Faculty of Pharmacy of the University of Lisbon, Lisbon, Portugal 

Supervisors: Afonso Cavaco, Maria Henriques and Andreia Bruno 

Others that contributed to the abstract: Diogo Simões and Francisca Lopes 

Introduction: The current curriculum of the Master degree in Pharmacy 

(MPharm) of the University of Lisbon is under an accreditation process during 

2015. Induced by this evaluation, the Committee for the Centennial Celebrations 

of the Students’ Association (CENTAEFFUL) aimed to collect input from 

several parties involved in pharmacy education that could contribute to the 

improvement of the syllabus towards pharmacy labour opportunities. 

Methodology: The research project was divided into three phases. Phase 

one consisted of two focus groups, with six pharmaceutical professionals in 

each. The second phase was an online survey answered by a national sample 

of pharmacy students and pharmacists. The answers were collected through 

open and closed questions, including Likert scales to measure the agreement 

with sentences stated by professionals from the focus groups. The third 

phase was comprised of the presentation and discussion of the survey results 

at an Educational Forum (EF). The EF consisted of a two day debate using 

an amplification of survey results fed by live presentations of five experts in 

educational matters. The actual EF conclusions were accomplished through 

small group discussions between pharmacists, students and professors, 

complemented by a plenary session opened to the public. 

Results: The need to include internships within the first four years of the degree 

was mentioned in the focus groups. It was mentioned that having practitioners 

outside the university teaching some classes would be beneficial for students. 

Concerning the online survey, there were 473 answers. The majority of the 

respondents (51.8%) either ‘agreed’ or ‘strongly agreed’ that the current 

MPharm curriculum is not completely adapted to practice. Moreover, 77.8% 

strongly ‘agreed’ that students would benefit from internships within the first 

four years of the degree. EF conclusions supported the opinions previously 

mentioned and reinforced the need to introduce new mandatory subjects, such 

as non-prescription medicines pharmacotherapy, clinical trials and seminars 

about soft-skills. Introducing one more optional subject and increasing the use 

of real case studies during classes was also suggested. 

Conclusions: Most participants agreed with the need to adapt MPharm to 

the competencies required in the pharmaceutical labour market. Throughout 

the project several suggestions were able to be collected, which then were 

submitted to the Scientific Council, in order to support the changes that needed 

to be reflected for the proposal to be submitted for accreditation. 

Acknowledges: We would like to acknowledge the Pedagogical Council, 

the local and national Students’ Association (AEFFUL and APEF) and all 

professionals and students that contributed to this project. We are also grateful 

for the support of Merck Sharp & Dohme Portugal.

General information about Madalena 

Plácido 

During 2014 a Committee for the 

Centennial Celebrations of the 

Students’ Association (CENTAEFFUL) 

was formed. This Committee aimed 

to analyse all Students’ Association 

journey: its past, present and future 

challenges. Focused on a more 

educational and scientific aspect, a 

Bureau for Education was born. 




The current curriculum of the Master degree in Pharmacy (MPharm) of 

the University of Lisbon is under an accreditation process during 2015. As 

members of Bureau for Education we wanted to take this opportunity to analyze 

the adequacy of the MPharm syllabus to the labor market through pharmacy 

students and professionals’ eyes. 


The main challenge was to define the right modus operandi for our research. 

Luckily we benefited from the help of professionals and faculty professors, to 

whom we are deeply grateful. Another challenge was the gap between academy 

and practice, which we tried to shorten through this investigation work. 


This kind of research allowed us to develop our critical thinking and data 

analysis abilities. We also improved our communication and organizational 

skills. Moreover, our awareness about the current MPharm syllabus and the 

labor market needs also increased. 



Research is not only discovering new drugs or a cure for a disease. If you 

believe that you can make a difference in your own university, go ahead! 

Understand the opinion of professionals from different areas, professors and 

your colleagues. Certainly you will learn something new and contribute to 

improve your university. 

9


THE INFLUENCE OF ACUTE PAIN ON OSMOTIC PRESSURE 

AND CORTISOL CONCENTRATION IN TEARS 

Maja Lukić and Matea Ćurčić, 

Faculty of Pharmacy and Medical Biochemistry, University of Zagreb, Croatia 

Introduction: Tears are far more than just a fluid on the surface of our eyes. 

Consisting of three distinct layers, they are essential for eye protection, 

lubrication and nourishment as well as maintaining health of the eyes and 

optical function of their surface and for providing clear vision. Furthermore, tears 

prevent eye infections by continually removing foreign matter thus, keeping the 

surface of the eyes smooth and clear. Tear production is controlled both by the 

central and autonomic nervous system. While basal tears’ production is under 

control of the accessory lacrimal glands, reflex lacrimation is mediated by the 

neural reflex arc that stimulates the secretion of the main lacrimal glands. Pain 

causes stress to the organism and therefore, production of stress mediators 

is stimulated. Cortisol is, along with DHEA, adrenalin and noradrenalin, one of 

the four main stress mediators. Although the origin of cortisol in tears is not 

known yet, it is assumed it might derive from the lacrimal gland. The final result 

of the dynamic changes of the lacrimal fluid is determined by measuring the 

osmolarity of the lacrimal fluid. 

Aim: In this study, the applicability of tears in the diagnostics of acute stress 

was evaluated. The main objectives of the study were to evaluate cortisol values 

and osmotic concentration in tears before and after stimulus and whether a 

consistent answer to stress could be diagnosed in tears. 

Materials and Methods: The study included 18 volunteers (10 women and 8 

men) whose tears were collected and analysed at the Clinical Hospital Center 

'Sestre Milosrdnice'. The tear samples were collected before and after nasal 

hair trimming. The concentration of cortisol was measured using ELISA whilst 

osmometry was used as a method to determine the osmolar concentration. 

Results and Conclusion: Basal cortisol values in men showed good correlation 

with osmolarity in tears. After acute stress, this correlation was lost, which 

can be due to the higher sensitivity to pain in males. After stimulus, cortisol 

and osmolar concentration decreased due to the dilution caused by tear 

production. Osmolarity and cortisol showed a moderate correlation before the 

painful stimulus, which is completely lost after the stimulus. Pain stimulus at 

the root hairs activates the sympathetic nervous system and its possible effect 

on the secretion of glands. 

10


General information about Maja Lukić 

27 years old, Osijek, Republic of Croatia 

E-mail: maja__lukic@hotmail.com 

The faculty of Pharmacy and Medical Biochemistry 

(Graduated 2015), University of Zagreb 


The idea of the topic came spontaneously but from the 

very beginning Matea and I knew we wanted to conduct 

an investigation on tears, as they as a sample are rarely 

used in clinical practice. 



From the very beginning, there were a lot of challenging aspects of our 

investigation. Firstly, tears collection and limited sample volume, as well as 

analyte measurement in a low concentration range. Moreover, there was no 

available literature on studies of human tears. Despite all, we did not give up 

and succedeed in obtaining our results. 


Above all, patience, organizational skills, accuracy and punctuality. 



I strongly recommend conducting an investigation during their studies. In 

this way, you can gain great experience in the field of your study and through 

cooperation with your colleagues, gain new friends. 

11


EUROPEAN FEDERATION FOR PHARMACEUTICAL 

SCIENCES (EUFEPS) 

The European Federation for Pharmaceutical Sciences is a voluntary federation 

of national associations and societies 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 mission 

is to advance sciences for better medicines and health and serving the 

pharmaceutical sciences and innovative drug research in Europe. Spearheading 

a number of initiatives, EUFEPS works with its membership, throughout many 

nations in 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. 

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. 

12


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. 

UPCOMING CONFERENCES ORGANISED OR CO- 

ORGANISED BY EUFEPS 

8 th International Symposium on Microdialysis 

Preclinical, Clinical, Analytical 

25-27 May 2016, Uppsala, Sweden 

EUFEPS Annual Meeting 2016 

Clinical Outcome and Regulation of Advanced Drug Delivery Products 

13-15 June 2016, Istanbul, Turkey 

8 th Pan-European Science Conference on QbD and PAT Sciences 

Inventing Tomorrow’s Development and Manufacturing 

3-4 October 2016, Cork, Ireland 

2 nd Conference on the Global Bioequivalence Harmonisation Initiative 

Autumn 2016, Washington DC, United States of America 

For more information see conferences at: www.eufeps.org 

13

EPSA Students' Science Publication


WHAT DOES EPSA OFFER IN THE FIELD OF SCIENCE? 

Next to the EPSA Students' Science Publication (ESSP) that you are reading 

now, EPSA also offers two other projects in the field of Science: the Science 

Day and the Science Excursion. 

Science Day 

The Science Day is an annual 

educational event that takes place 

during the EPSA Annual Congress 

and is dedicated to students’ 

scientific work. Participants are 

given the opportunity to present 

the scientific research they have 

conducted orally and through a 

poster exhibition. This year fourteen students in total participated in one or two 

parts of the event. A jury, consisting of the European Federation for Pharmaceutical 

Sciences, EUFEPS representative, a Pierre Fabre Lab. Representative 

and the EPSA Science Coordinator Successor, assessed the presentations. 

Since the competition this year was extremely tough, the jury agreed on two 

winners for the oral presentation. 

Science Excursion 

The idea of the Science 

Excursion is to bring students 

closer to science and to broaden 

the Congress experience to an 

interactive and local surrounding. 

It is a project that is planned to 

be held at all major EPSA events. 

The upcoming excursion will 

be held during the Autumn 

Assembly in the restored oldest pharmacy in the Santo Spirito Hospital in 

Malta. Participants will visit the pharmacy museum and witness a compounding 

demonstration. 

15

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