may 27-29, 2011 wow topkapı palace antalya-tÜrkİye · 2011-05-17 · scientific programme 6 drd...

Organized byHacettepe University

Medicinal Chemistry ResearchDevelopment & Application Center

May 27-29, 2011WOW Topkapı PalaceAntalya-TÜRKİYE

www.drd.hacettepe.edu.trABSTRACTS

Dear Colleagues,

I would like to invite you to attend and contribute to the International Symposium on Drug Research and Development “From Chemistry to Medicine” DRD 2011 and New Horizons and Job Opportunities for Young Scientists which is organized by Hacettepe University, Medicinal Chemistry Research, Development and Application Center (MAGUM).

MAGUM, a subunit of Hacettepe University, was established in 1996 for the purpose of realization of the drug design, structure-activity relationships, synthesis, analysis and molecular quality control of synthetic and natural drugs and drug raw materials in medicinal chemistry area with cooperation of departments of Faculty of Pharmacy, Faculty of Medicine and other facul-ties to improve outputs of drug research, development and application by multidisciplinary collaboration approaches.

The high quality performed scientific International Symposium on Drug Research and Development “From Chemistry to Medicine” organized by MAGUM every two years. In addition to DRD 2011 symposium, which will be held on May 27-29, 2011, New Horizons and Job Opportunities for Young Scientists” was also planned to conduct by MAGUM.

The mission of “International Symposium DRD 2011 and New Hori-zons and Job Opportunities for Young Scientists” will be to provide a sci-entific forum by the invitation of distinguished scientists having national / international reputation in their areas, so the most recent advances will be discussed and evaluated interactively and the exchange of interdisciplinary knowledge from chemistry to medicine. The format of the scientific program will also include oral and poster presentations on the concerning scientific topics in addition to the invited lectures.

Members of the organizing committee and I cordially invite you to join us at DRD 2011 in Antalya, May 27-29, 2011. It is important to note that symposium venue Antalya is very famous with its archaeological and natural riches and known as one of the most popular region of Turkish Riviera.

We are looking forward to see you in Antalya,Turkey.With our kind regards,

Prof. Dr. Ünsal ÇALIŞChair

Honorary ChairProf. Uğur ERDENER, M.D.

President of Hacettepe University

Organizing CommitteeÜnsal ÇALIŞ, Ph.D. (Chair)

Selma SARAÇ, Ph.D.Sedef KIR, Ph.D.

Gülberk UÇAR, Ph.D.Funda Nuray YALÇIN, Ph.D.

S. Kutay DEMİRKAN, Pharm.D.

Prof. Melih ALTAN, Ph.D. (Ankara University, Türkiye) Prof. Metin BALCI, Ph.D. (Middle East Technical University, Türkiye)

Prof. Erden BANOĞLU, Ph.D. (Gazi University, Türkiye)Prof. A. Ahmet BAŞARAN, Ph.D. (Hacettepe University, Türkiye)Prof. Erdem BÜYÜKBİNGÖL, Ph.D. (Ankara University, Türkiye)

Prof. Sevim DALKARA, M.D. (Hacettepe University, Türkiye) Prof. Katerina GORACINOVA, Ph.D. (University of Sts Cyrill and Methodius, Macedonia)

Prof. Arzum Erdem GÜRSAN, Ph.D. (Ege University, Türkiye) Prof. Selçuk GEÇİM, Ph.D. (Hacettepe University, Türkiye)Prof. Emin KANSU, M.D. (Hacettepe University, Türkiye)Prof. Hakan ORER, M.D. (Hacettepe University, Türkiye) Prof. Seçkin ÖZDEN, Ph.D. (Ankara University, Türkiye) Prof. Yekta ÖZER, M.D. (Hacettepe University, Türkiye)

Prof. Serhat ÜNAL, M.D. (Hacettepe University, Türkiye)Prof. Metin TÜLÜ, Ph.D. (Yıldız Technical University, Türkiye) Prof. Kemal YELEKÇİ, Ph.D. (Kadir Has University, Türkiye)Prof. Nurşen ÜNLÜ, Ph.D. (Hacettepe University, Türkiye)

ORGANIZING COMMITTEE

ADVISORY BOARD

SCIENTIFIC SECRETERIATProf. Selma SARAÇ, Ph. D.

Hacettepe University, Faculty of PharmacyDepartment of Pharmaceutical Chemistry

06100 Ankara-TÜRKİYEPhone (Fax) : +90 312 305 30 15

[email protected]

Prof. Sedef KIR, Ph. D.Hacettepe University, Faculty of Pharmacy

Department of Analytical Chemistry06100 Ankara-TÜRKİYE

Phone : +90 312 305 21 [email protected]

OFFICIAL SYMPOSIUM AGENCYDMR Congress Organization Services Tourism Inc.

Hollanda Cad. 696. sok. 22/9-1006550 Yıldız Çankaya - Ankara, TURKEY

Phone : +90 312 442 01 50Fax : +90 312 442 04 10www.dmrturizm.com.tr

[email protected]

CON

TENTS

5International Symposium on Drug Research & Development 2011

DRD 2011

SCIENTIFIC PROGRAMME 6

SPONSORS 10

EXHIBITION 11

LECTURES 13

ORAL PRESENTATIONS 39

POSTER PRESENTATIONS 53

INDEX 166

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International Symposium on Drug Research & Development 2011

MAY 27, 201114.30-16.00 OPENING CEREMONY Opening Lectures Engineering Versatile Nano-carriers for Therapeutic Delivery Woei Ping Cheng, University of Hertfordshire, United Kingdom The Use of Novel Enabling Techniques to Overcome Drug Solubility Issues Firas El-Saleh, ISP-International Specialty Products, Germany16.00-16.30 Coffee Break16.00-16.30 Coffee Break

16.30-18.00 SESSION I New Trends and Methods in Drug Research and

Development (All presentations will be in English)

Chairpersons : Rümeysa Demirdamar, Near East University, Turkish Republic of Northern

Cyprus Nur Onar, Ondokuz Mayıs University, Türkiye

New Trends in Pharma: The Growth of Generics Farhad Farshi, Abdi İbrahim Pharmaceutical R&D Center, Türkiye In Silico Design of Novel and Highly Selective Monoamine Oxidase A and B

Inhibitors: Evaluation of Computational and Experimental Inhibition Values Kemal Yelekçi, Kadir Has University, Türkiye Nanomaterial Based Sensor Technology for Electrochemical Monitoring Drug-

DNA Interactions Arzum Erdem Gürsan, Ege University, Türkiye18.00-20.00 WELCOME RECEPTION Sponsored by

MAY 28, 201109.00-10.30 SESSION II Current Approaches for Development of Novel Drug

Delivery Systems (All presentations will be in English)

Chairpersons : Nurşen Ünlü, Hacettepe University, Türkiye Sema Çalış, Hacettepe University, Türkiye

Novel Excipients from Scratch to Launch Nils Rottmann, BASF - The Chemical Company, Germany

Colloidal Carriers for Anticancer Drug Delivery – Formulation Approaches Katerina Goracinova, University of Sts Cyrill and Methodius, Macedonia Novel Nano-carriers Based on Self-assembling Polymers: A New Opportunity for

Improving Treatment of Diseases Woei Ping Cheng, University of Hertfordshire, United Kingdom

10.30-11.00 Coffee Break

Sponsored by

Sponsored by

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11.00-12.30 SESSION III-A Experiences and Expectations of Clinicians: Diabetic Agents (All presentations will be in Turkish) Chairperson: Gülberk Uçar, Hacettepe University, Türkiye Insulin Therapy & Routes of Administration Ercan Tuncel, Uludağ University, Türkiye Oral Diabetic Therapy Nilgün Güvener Demirağ, Başkent University, Türkiye New Antidiabetic Agents Bülent Okan Yıldız, Hacettepe University, Türkiye12.30-14.00 LUNCH11.00-12.30 SESSION III-B Selected Oral Presentations on Research and Development in Pharmaceutical

Sciences (All presentations will be in English) Chairpersons : Arzum Erdem Gürsan, Ege University, Türkiye Katerina Goracinova, University of Sts Cyrill and Methodius, Macedonia

Monitoring Reovirus Entry and Endosomal Trafficking in Live Non-polarized and Polarized Cells by Single Viral Particle Tracking

Cömert Kural, Harvard Medical School, USA Computational Study of the Conformational Interconversion of 4,5-Dimethyl-1,3,4,5-

tetrahydro-2H-1,5-benzodiazepin-2-one Sajid Jahangir, Karl Franzens University, Austria Determination of Antioxidant Activity of Some Biologically Important Samples through

Cyclic Voltammetry Haji Muhammad, Federal Urdu University of Arts, Science and Technology,

Pakistan Synthesis of Folate-PEG-Doxorubicin Conjugate, Radiolabelling with Technetium-

99m and Research into its Applications as an Imaging Agent in Cancer Güliz Ak, Ege University, Türkiye Bioengineering Technique Used to Study the Effects of Grapefruit Extract

Containing Emulsion on Human Skin Mechanical Parameters Naveed Akhtar, The Islamia University of Bahawalpur, Pakistan Study on a Commercial Anthelmentic Combination Efficacy against Fasciola Spp,

Dicrocoelium Dendriticum and Moniezia Spp in Small Ruminants in Urmia, Iran Sohrab Rasouli, Islamic Azad University, Iran Heavy Metals Toxicity in Root Vegetables Irrigated by Industrial Waste Water

Karachi Kousar Yasmeen, Federal Urdu University of Arts, Pakistan Formulation and Characterization of Two Bleach Creams of Mulberry Extract and

Comparison of their Effects on Human Skin Melanin and Erythema Fatima Rasool, The University of the Punjab, Pakistan

12.30-14.00 Lunch

14.00-14.30 Poster Discussion & Exhibition

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14.30-16.00 SESSION IV Interview Fear in Job Applications (All presentations will be in Turkish) Chairperson : Buket Aksu, Santa Farma Pharmaceutical Company, Türkiye

Getting Ready for Interview and Get Over Your Fear Nesrin Dilbaz, Ankara Numune Research And Training Hospital, Türkiye Personal Behaviors During Job Interview Aykut Bora, Bilim Pharmaceutical Company, Türkiye Requirements of Scientific Background for Job Applications in Drug Research and

Development A. Atilla Hıncal, İDE Pharmaceutical Consultancy, Türkiye

16.00-16.30 Coffee Break & Exhibition

16.30-18.00 PANEL New Horizons and Job Opportunities for Young Scientists (All presentations will be in Turkish) Moderator : Selçuk Geçim, Hacettepe University, Türkiye

Tarık Çelik, The Turkish Academy of Sciences TÜBA, Türkiye Tayfun Öner, Small & Medium Enterprises Development Organization

KOSGEB, Türkiye Murat Yıldız, Republic of Turkey Ministry of Industry and Trade, Türkiye Rıza Alagöz, Republic of Turkey Ministry of Industry and Trade, Türkiye Tuğba Arslan Kantarcıoğlu, The Scientific & Technological Research

Council of Türkiye- TÜBİTAK Emel Önder Fırat

The Scientific & Technological Research Council of Türkiye- TÜBİTAK A.Tuncay Teksöz, Pfizer Inc. Pharmaceutical Company, Türkiye Farhad Farshi, Abdi İbrahim Pharmaceutical R&D Center, Türkiye Sami Türkoğlu, Ulkar Holding, Türkiye

20:00-24:00 Gala Dinner

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MAY 29, 2011 09.00-10.30 SESSION V Recent Biochemical Approaches to Drug Development (All presentations will be in English) Chairpersons : Zeliha Büyükbingöl, Ankara University, Türkiye Filiz Hıncal, Hacettepe University, Türkiye

How to Change an Enzyme into a Cytotoxic Agent: Mechanisms of Targeting Top2 in Cancer

John L. Nitiss, St. Jude Children’s Research Hospital, Memphis-USA Enhanced Survival and Paracrine Activity of Bone Marrow Mesenchimal Stem Cells: Impact on Cell Therapy of Ischemic Syndromes

Angelo Parini, Inserm Institut, France Serotonergic Control of Cardiovascular Function Nathalie Pizzinat, University of Toulouse, France

10.30-11.00 Coffee Break

11.00-12.30 SESSION VI Organic Synthesis and Analysis of Pharmaceutical

Molecules (All presentations will be in English)

Chairpersons : Tuncel Özden, Gazi University, Türkiye Erdem Büyükbingöl, Ankara University, Türkiye

Bisacylazides: A New Milestone for the Synthesis of Various Heterocycles Metin Balcı, Middle East Technical University, Türkiye Dendrimers as Potential Drug Carriers: Microwave-Assisted Synthesis of Pamam

Type Dendrimers Metin Tülü, Yıldız Technical University, Türkiye A Novel Polymorph of Zoledronic Acid and Process for its Preparation Bekir Karlığa, Deva Holding API R&D, Türkiye Synthesis of Ezetimibe: A Selective Cholesterol Absorption Inhibitor Esen Bellur Atıcı, Deva Holding API R&D, Türkiye

12.30-14.00 Lunch

14.00-16.00 SEARCH CONFERENCE Visualising the Future of Drug R & D:

Policies, Priorities and Strategies (All presentations will be in Turkish) Moderator: İsmail Üstel, Consultant, Türkiye

16.00-16.30 Closing Remarks

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DRD 2011

STAND AREA

MEETING HALL A

ANAMEDİNCEKARA

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BAS-F REDOKS

MEDSANTEK

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LABOR İLDAM

MEETING HALL B

POSTERAREA

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Today with the advancement of biotechnology, a plethora of new therapeutic macromolecules such as proteins/peptides and siRNA have been discovered to treat a variety of diseases ranging from cancer, autoim-mune diseases to metabolic diseases. Albeit their huge potentials, one of the major hurdles has yet to overcome is drug delivery problem. Unlike small drug molecules, these drugs cannot be given orally because they are destroyed extensively by enzymes in the gastrointestinal tract (GIT). In addition, the large size and water soluble nature of these drugs prevent them from being absorbed through the GIT. For siRNA based therapeutics, another challenge to overcome is the inability of these negatively charge mol-ecules to cross the cell membrane and reach its target site, which is the cytoplasm. We have designed a range of nov-el self-assembled polymers based on water soluble poly-allylamine (PAA) for therapeutic delivery of proteins and peptides. These self-assembled polymers formed nano-complexes spontaneously with model proteins such as in-sulin1 and calcitonin (sCT)2 with the size ranging from 100-250nm. The complexation took place due to electrostatic and hydrophobic interaction between the polymer and proteins. As a result, the fabrication of these complexes is mild and unlike other conventional nanoparticles where the use of organic solvents and high temperature might degrade the labile proteins. Through grafting different types of hydrophobic pendant groups such as cetyl, cho-lesteryl and palmitoyl chains onto PAA, we were able to engineer different types of nano-complexes (i.e. vesicles, nanoparticles) with different complexation efficiencies1,3.

Addition of quaternary ammonium moieties onto these self-assembled polymers have protected insulin and sCT against in vitro enzymatic degradation1,2 and enhanced the uptake of these complexes by CaCO2 cells via trans-cellular and paracellular pathways4. In vivo study using je-junal instillation has demonstrated the feasibility of using these nano-complexes in oral protein delivery2. We have also successfully designed pH triggered self-assembled polymers based on poly-L-lysine (PLL) for siRNA delivery in cancer therapy. Using a benzoic linker which is cleaved in acidic pH, we were able to attach polyethylene glycol (PEG) on PLL grafted with cholate hydrophobic pendant groups. It is expected that PEG will maintain siRNA-poly-mer nanocomplexes’ long circulation in the blood. How-ever, when these complexes are endocytosed by cancer cells, the benzoic linker will be hydrolysed in the acidic en-dolysosomal compartment to detach PEG from the com-plexes. This will promote endosomal escape of siRNA into the cytoplasm before it is being degraded in the endolysosome. Using a confocal microscopy, we were able to demonstrate the cellular uptake of these complexes by human prostate cancer cells (PC-3) and endosomal escape of siRNA, which led to in vitro reporter gene knockdown. In vivo result using tumour bearing mice showed significant tumour suppression was achieved us-ing VEGF siRNA-PEGylated complexes without marked toxicity and undesirable immunological response5. In conclusion, by tailoring the polymer architecture, we are able to design and engineer a range of versatile nanocarriers based on self-assem-bled polymers which showed promising potential in the deliv-ery of therapeutic macromolecules.

ENGINEERING VERSATILE NANO-CARRIERS FOR THERAPEUTIC DELIVERYWoei Ping CHENG

School of Pharmacy, University of Hertfordshire, College Lane, Hatfield, UK AL10 9AB [email protected]

REFERENCES1. Thompson C, et. al. International Journal of Pharmaceu-

tics 376: 46-55, 2009. 2. Cheng WP, et. al. Journal of Controlled Release 147: 289-297, 2010.3. Thompson C, et. al. International Journal of Pharmaceu-

tics 383: 216-227, 2010.4. Thompson C, et. al. Pharmaceutical Research, in press,

2011.5. Guo J, et. al. manuscript in preparation, 2011.

mailto:[email protected]

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Solubility of drugs has become a major issue in the last few years. It has been estimated that 40–60% of drugs in development have poor bioavailability due to low aqueous solubility. This trend has driven increas-ing interest in technologies that help increase drug solubility and / or drug dissolution rate and thus move the drugs from BCS Class 2 (good permeability, poor solubility) into BCS Class 1 (good permeability, good solubility), and thus over-come bioavailability issues, interpatient differences, food ef-fects, etc.

Based on the physicochemical properties of APIs, differ-ent formulation techniques and process technologies are necessary to enhance drug solubility in vivo.

This paper provides an overview of different excipients and techniques necessary to serve this purpose. However, the main focus is put on the technologies used in preparing solid dispersions, namely Spray Drying and Hot Melt Extru-sion (HME). Practical considerations and the main factors in-fluencing the formation of solid dispersions supported with examples are discussed as follows:

Polymers and API miscibility Solubility in solventsInfluence of formulation on process technologyThermal behavior, instabilityThermoreological characteristics Process parameters and machine set-upFactors influencing physical stability

THE USE OF NOVEL ENABLING TECHNIQUES TO OVERCOME DRUG SOLUBILITY ISSUES

Mohammed RAHMAN1, Firas EL-SALEH2,*, Tim BEE31ISP Pharma Systems LLC, Columbia, Maryland, USA

2ISP Global Technologies Deutschland GmbH, Cologne Germany 3ISP, Wayne, New Jersey, USA

*[email protected]

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Pharma landscape is changing due to demographic, epidemiological and economic shifts. Growing and aging population, diseases and medical needs has been offering some huge opportunities for Pharma. The markets of the developing world are changing even more radically than those of the developed world. While there are significant opportunities in the developing world due to health care awareness both of governments and individuals, in case of developed countries, political compulsions to re-duce health care budgets has a direct impact on profitability of pharma sector.

The complex structure of current pharma R&D proces-ses and studies needed to meet expectations of regulatory agencies have made the big pharma less productive. Big pharma started to lose their market share, growth and pro-fitability in the markets they are strong for many years. Drug pricing and reimbursement policies or legislations favoring growth of generics have a major impact on profitability of in-novator companies. They have been forced to change their

traditional business models and look for the opportunities to compensate their loss in those markets.

How does this new pharmaceutical environment look like?Multinational pharma companies have been challanged

for variety of issues in emerging, mature and developed mar-kets. First, they strengthened their presence in those markets with acquisitions and mergers. Since 1999, 60% of the top 25 generic companies from all around the world acquired. Second, outsourcing some of their activities to different in-stitutes, companies from all around the world. It is predicted that 50% of Big Pharma R&D is outsourced to more capable firms in order to maintain a strong pipeline for future drugs. This will result in greater profitability and increased share-holder value for the early adopters of Big Pharma.

This presentation analyses the global pharmaceuticals mar-ket with respect to growing generics and emerging markets. It is also aimed to show the challanges and the opportunities for multinational companies along with big generic players.

NEW TRENDS IN PHARMA: THE GROWTH OF GENERICSFarhad FARSHI

Abdi İbrahim İlaç San. ve Tic. A.Ş. Sanayi Mah. Tunç Cad. No:3 Esenyurt İstanbul, Türkiye

[email protected]


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Monoamine oxidases are flavoenzymes bound to the mitochondrial outer membrane. There are two isozymes named as MAO-A and MAO-B. The basic difference in these two isozymes is in their se-lectivity for the oxidation of the various substrates and in-hibitors. MAO-A oxidizes serotonin and norepinephrine and any compound selectively inhibits this isozyme possesses antidepressant activity. On the other hand, dopamine is the substrate for MAO-B and selective inhibition of MAO-B shows potent anti-Parkinson and plays important role in the therapy of neurodegererative disorders. That is why, they are the well known target for antidepressant, Parkinson’s dis-ease and neuroprotective drugs. Recently published crystal-lographic structures of MAO-A and MAO-B paved the way for computational modeling studies.

In the present work, starting from pyrazoline scaffolds, and generating thousands of structures from these, poten-tial inhibitors are obtained with their structural and physi-cochemical properties in order to increase both selectivity and potency toward MAO-A and MAO-B isozymes. De novo design software is used to generate the diverse structures and, three docking tools, CDOCKER, Libdock and AutoDock, are used to find the most probable potential inhibitor based

on its binding affinity. The dispositions of the candidate mol-ecules within the organism are checked by ADMET_PSA_2D (Polar Surface Area) versus ADMET_AlogP98 and their suit-ability is discussed. The MAO inhibition activities of the candidates are compared with the properties of selegiline and moclobemide, which are the two known inhibitors of MAO-A and MAO-B respectively. Interaction of these can-didate compounds in the active site of the isozyme will be presented in detail.

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This research was supported by The Scientific and Tech-nological Research Council of Turkey with a grand number 108T232.

IN SILICO DESIGN OF NOVEL AND HIGHLY SELECTIVE MONOAMINE OXIDASE A AND B INHIBITORS: EVALUATION OF COMPUTATIONAL AND

EXPERIMENTAL INHIBITION VALUESKemal YELEKÇİ

Kadir Has University, Faculty of Arts and Sciences,Computational Biology and Bioinformatics Program 34083 Fatih- İstanbul, Türkiye

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After the discovery of electroactivity in nucleic ac-ids1, many electrochemical approaches have been developed for analyzing, or quantification of nucleic acids and its interactions with drugs, toxins and pro-teins2-12. Various type of advanced DNA biosensors have been rapidly developed using different nanomaterials towards the goal of simple and low-cost point-of-care detection of specific biorecognition process using nucleic acids4, 9-12.

In the last decade, there has been an increasing atten-tion on the binding of small molecules to nucleic acids. Such studies have a key importance for the rational design

of more-efficient gene-targeted agents3. The investigations at chemistry side based on drug-DNA and protein-DNA in-teractions would provide novel compounds to be tested for an effect on a biochemical target, or would provide new approaches for the design of more effective DNA hybridiza-tion biosensors based on nanomaterials, which will further become DNA microchip systems.

Acknowledgements: A.E would like to express her gra-titude to the Turkish Academy of Sciences (TUBA) as the as-sociate member of TUBA for their support.

NANOMATERIAL BASED SENSOR TECHNOLOGY FOR ELECTROCHEMICAL MONITORING DRUG-DNA INTERACTIONS

Arzum ERDEMEge University, Faculty of Pharmacy, Analytical Chemistry Department, İzmir, Türkiye

[email protected]

REFERENCES1. Palecek E. Oscillographic Polarography of Highly Polym-

erized Deoxyribonucleic Acid. Nature 188: 656-657, 1960.2. Wang J. From DNA biosensors to gene chips. Nucl. Acids

Res. 28: 3011-3016,2000.3. Palecek E, Fojta M. Detecting DNA hybridization and

damage. Analytical Chemistry 73:74A-83A, 2001.4. Erdem A. Nanometarial based electrochemical DNA sens-

ing strategies. Talanta 74: 318-325, 2007. 5. Wang J, Kawde A-K, Erdem A., Salazar M. Magnetic bead-

based label-free electrochemical detection of DNA Hy-bridization. Analyst 126: 2020-2024,2001.

6. Erdem A, Pividori MI, Lermo A, Bonanni A, del Vale M, Alegret S. Genomagnetic assay based on label-free elec-trochemical detection using magneto-composite Elec-trodes. Sensors and Actuators B: Chem. 114: 591-598, 2006.

7. Wang J, Xu D, Erdem A, Polsky R, Salazar M. Genomagnet-ic electrochemical assays of DNA Hybridization. Talanta 56: 931-938, 2002.

8. Karadeniz H, Erdem A, Kuralay F, Jelen F. Indicator-based

and indicator-free magnetic assays connected with dis-posable electrochemical nucleic acid sensor system. Ta-lanta 78: 187-192, 2009.

9. Erdem A, Papakonstantinou P, Murphy H. Direct DNA Hy-bridization at Disposable Graphite Electrodes Modified with Carbon Nanotubes. Analytical Chemistry 78: 6656-6659, 2006.

10. Karadeniz H, Erdem A, Çalışkan A, Pereira CM, Pereira EM, Ribeiro JA. Electrochemical sensing of silver tags labelled DNA immobilized onto disposable graphite Electrodes. Electrochem. Commun, 9: 2167-2173, 2007.

11. Erdem A, Karadeniz H, Çalışkan A. Single walled carbon nanotubes modified graphite electrodes for electro-chemical monitoring of nucleic acids and biomoleculer interactions. Electroanalysis 21: 464-471, 2009.

12. Yapasan E, Çalışkan A, Karadeniz H, Erdem A. Electro-chemical investigation of biomolecular interactions between platinum derivatives and DNA by carbon nanotubes modified sensors. Materials Science and Engi-neering B 169: 169-173, 2010


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The impact of excipients on modern pharmaceuti-cal formulations has increased rapidly during the past years. Reasons for this trend in the pharma-ceutical industry are manifold: Due to numerous of patents expiring in the next few years and at the same time a declin-ing number of New Chemical Entities (NCE), life-cycle man-agement and re-formulation of the existing products with innovative excipients have gained a new importance.

For the development of new drug delivery systems and the re-formulation of existing actives (API), innovative excipi-ents and novel applications are required. Since many years, BASF follows a strategy of developing novel and innovative performance excipients to serve the markets needs.

A strict time-line has to be followed, when a new project is started in the development laboratories. Basically such a development is structured in the phases:

• Market evaluation• Definition of project goal

• Screening of suitable monomers• Screening of suitable polymerization techniques• Optimization of copolymer composition• Optimization of polymerization process• Scale up into pilot plant (1l to 4 m³)• Transfer into production ( > 4 m³ ).

During these phases, application experts keep on test-ing the performance and quality of the new products, try-ing to improve its characteristics constantly. Regulatory and toxicology experts are involved in the projects from the very beginning as well.

Developing a novel excipient for innovative formulations

has a similarity to the development of a new drug product. Therefore, many parties are involved in the excipient devel-opment, within the raw material supplier as well as custom-ers, universities and several authorities.

After launching a novel excipient, a lot of resources have to be invested to facilitate an easy introduction and an easy registration with the new excipient.

NOVEL EXCIPIENTS – FROM SCRATCH TO LAUNCHNils Wilhelm ROTTMANN

BASF SE, Pharma Ingredients and Services, 67056 Ludwigshafen, Germany [email protected]

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Chemotherapy has an important place in clinical management of cancer and the molecular com-plexities associated with the drugs as well as inac-cessibility of most physiological targets have resulted with the development of alternative therapies as an approach to medical intervention (Wang et al., 2009). On one hand, genomics and proteomics research are identifying new tu-mor-specific molecular targets, and on the other, innovative drug-delivery systems are being designed to guide drugs more precisely to tumor cells, away from sites of toxicity and to maintain drugs at therapeutic concentration over pro-longed time periods1. The overall benefit of these improve-ments in disease treatment would be an increase in patient compliance and quality of life. Nanoparticle (NP) delivery of anticancer drugs to tumor tissue can be achieved by either passive or active targeting. Passive targeting takes the ad-vantage of inherent size, physico-chemical properties of NPs and exploits the unique anatomical and patophysiological abnormalities of tumor vasculature, which is regarded as a gold standard in the design of new anticancer delivery sys-tems1-3. It is hypothesized that phenomenon equivalent to EPR (enhanced permeability and retention) effect for drug targeting due to increased endothelial permeability, i.e. epi-thelial EPR effect, might be used as potential strategy that enables inflamed tissue in GI tract to be targeted. Morpho-metric analysis of mucocellular layer overlying colorectal cancer point that inflammatory cells are predominant in the hypercellular mucocellular layer of colorectal cancer closely resembling the abundance of monocytes, macrophages, dendritic cells and T cells at the site of inflamation. This means that epithelial EPR effect strategy and improved ac-cumulation of specially designed nano/microparticles at the site of inflammation might be useful for targeting GI cancer as well.

The influence of different factors on the endothelial and epithelial EPR mediated uptake of the colloidal particles is however not fully understood. For the extravasation of the drug loaded carrier more selectively at tumor tissues, at least some properties of the nannocarriers are particulary impor-tant. To successfully take advantage of NP for drug deliv-ery, a number of significant parameters, including stability, drug loading capacity, size, size distribution, zeta potential, surface hydrophilicity and/or hydrophobicity, and particle decoration with specific and nonspecific ligands in order to improve cell/tissue NP interaction and internalization have to be carefully considered and optimized for each applica-tion. Also, introduction of in vivo biodistribution studies and in vitro cell culture internalization and efficacy experi-ments, as early optimization tool for the design of targeted colloidal drug carriers will properly evaluate the efficacy and potential of surface modification for active targeting and improved drug concentration and localization at the site of action4. Following the principles of passive and nonspe-cific active targeting we have designed polyelectrolyte drug delivery systems with pH dependent swelling and muco/bioadhesivity. In vitro cell culture studies of micro/nanopar-ticulated 5-FU loaded and WGA functionalized bioadhesive carriers designed using principles of epithelial EPR targeting plus nonspecific ligand functionalizatioin point to increased intracellular localization of the anticancer agent, which is the major component for increased anticancer efficacy of the drug delivery system5. In vivo biodistribution studies for these carriers were in favor of increased localization and concentration at the site of patophysiological abnormalities. However, the primary concerns of any targeted drug delivery system still stands for the abilities to successfully load and deliver a desired therapeutic cargo to its target, and drug loading can vary greatly with different carrier materials and fabrication methods. Appropriate drug loading goes hand-

COLLODAL CARRIERS FOR ANTICANCER DRUG DELIVERY – FORMULATION ASPECTS

Marija GLAVAŠ-DODOV1, Sema ÇALIŞ2, Maja SIMONOSKA1,Nikola GESKOVSKI1,Katerina GORAČINOVA1*

1Faculty of Pharmacy, University of Sts Cyril and Methodius, Skopje, Macedonia 2Faculty of Pharmacy, University of Hacettepe, Ankara, Türkiye

*[email protected]

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in-hand with drug release kinetics and, hence, the overall ef-fectiveness of the targeted therapy. Nanoparticles formulat-ed using biodegradable PLGA:Poloxamer blends are among the most intensively investigated drug delivery systems. Available strategies for surface modification by adsorption or covalent binding further increase the potential of these systems for anticancer drug delivery. However, commonly utilized techniques for nanoparticle preparation (emulsifi-cation solvent evaporation, emulsification solvent diffusion, double emulsion solvent evaporation and nanoprecipitation or solvent displacement) usually do not provide conditions for good encapsulation efficiency of hydrophilic anticancer drugs because of the rapid partitioning of the drug into the external aqueous phase. However, there are only few at-tempts through the literature to establish modification of nanoprecipitation method for production of hydrophilic drug loaded particles, but with even less success compared to the emulsification diffusion methods. Formation of sub-microne particles during the nanoprecipitation method de-pends on the differences in the surface tension between the solvents, which leads to interfacial turbulence resulting with breaking up the organic phase and dispersing it as a drops in the aqueous phase6. These droplets continuously brake down into smaller submicrone droplets due to the interfa-cial convective flow which contributes to renewing the in-terfacial surface increasing the mass-exchange rate between the phases. During the diffusion of the organic solvent into the water dissolved polymer chains are also dragged into the water medium which is followed by aggregation and NP formation. In the standard procedure the organic phase containing the polymer that will form the nanoparticles is poured into the aqueous phase under slight magnetic stir-ring. Logical approach to improve hydrophilic drug loading

might be rapid micromixing to induce faster supersatura-tion, polymer agregation and particle formation. Also we hypothesized that dispersing the drug water solution into the organic polymer solution (nonsolvent for the drug sub-stance) prior nanoprecipitation, might delay the hydrophilic drug partitioning into the outer water phase during nanopri-cipitation. Including these principles we developed modified nanoprecipitation method for Irinotechan HCl loading into amphiphilic PLGA nanocarriers. First Irinotechan HCl was dis-solved in small quantity of water and dispersed in polymeric (PLGA/amphiphillc polymers) acetone solution (ultraturax, 6500 rpm, Irinotechan is practically insoluble in water) which was consequently mixed in water to induce nanoprecipita-tion (ultraturax 6500 rpm). The method was highly repro-ducible with nanoparticle size of d(0.5) 100 nm and efficacy of loading ranging from 52 – 67% depending on the concen-tration of Irinotecan HCl solution dispersed within polymeric acetone solution. Application of other solvents like ethanol and acetonitrile resulted with very poor incorporation effi-cacy compared to water probably because of the difference in surface tension, mixing and diffusion among water (71.99 mN/m) and aceton (22.73 mN/m), compared to acetonitrile (28.34 mN/m) and ethanol (21.80 mN/m) (Irinotechan HCL is sparingly soluble in water, ethanol and slightly in aceto-nitrile).

Increased plasma residence time and targeting due to endothelial EPR effect is well documented in literature, and was confirmed for these systems through our experiments. Further comparative studies will be done for comparison of localization of nanoparticles due to EPR effect and due to active targeting after attachment of specific ligand at the nanopaticle surface.

REFERENCES1. Acharya S, Sahoo SK. PLGA nanoparticles containing vari-

ous anticancer agents and tumour delivery by EPR effect. Adv Drug Deliv Rev doi:10.1016/j.addr.2010.10.008, 2010.

2. Muggia FM. Doxorubicin-polymer conjugates: further demonstration of the concept of enhanced permeability and retention. Clin Cancer Res 5: 7–8, 1999.

3. Maeda H. SMANCS and polymer-conjugated macromo-lecular drugs: advantages in cancer chemotherapy. Adv Drug Deliv Rev 46: 169–185, 2001.

4. imonoska-Crcarevska M, Glavas-Dodov M, Petrusevska G, Gjorgoski I, Goracinova K. Bioefficacy of budesonide loaded crosslinked polyeletrolyte microparticles in rat

model of induced colitis. J Drug Target 17 (10): 788-802, 2009.

5. Glavas-Dodov M, Calis S, Simonoska-Crcarevska M, Geskovski N, Petrovska V, Goracinova K. Wheat germ agglutinin-conjugated chitosan-Ca-alginate micropartic-les for local colon delivery of 5-FU: Development and in vitro characterization. Int J Pharm 381: 166-175, 2009.

6. Mora-Huertas CE, Fessi H, Elaissari A. Influence of process and formulation parameters on the formation of submi-cronparticles by solvent displacement and emulsification diffusion methods. Critical comparison. Adv Colloid In-terface Sci doi:10.1016/j.cis.2011.02.005, 2011.

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It has been estimated that 40% of the current drug candidates in development and marketed drugs con-sist of hydrophobic drugs1. Poorly water-soluble drugs present a major challenge to the pharmaceutical industry as it can hinder or even prevent the progress of the drug into clinical use. Self-assembling polymers consisting of hy-drophilic and hydrophobic segments are being explored as potential drug delivery systems for hydrophobic drugs since 1990s. They form different types of nano-size self-assemblies such as polymeric micelles, vesicles, nanoparticles, disc-like structures in aqueous environment upon the aggregations of hydrophobic moieties. The hydrophobic core can be used to encapsulate hydrophobic drugs for improving drug solu-bility and stability. Today the most widely explored self-as-sembled polymer architecture is block copolymer while graft polymer is less reported in the literature. Our work focus on the design of novel graft polymers consisting of water solu-ble polymer backbone, polyallylamine (PAA) grafted with hy-drophobic pendant groups2. Generally, nano-carriers formed by self-assembling polymers are mainly investigated for in-travenous delivery. Here, we investigate their potential as hydrophobic drug solubilisers for oral, ocular as well as par-

enteral delivery. PAA grafted with aromatic pendant groups and cholestryl pendant groups enhanced the encapsulation of a range of hydrophobic drugs such as etoposide, griseo-fulvin, prednisolone, triamcinolone acetonide, propofol and estradiol. The drug water solubility increased from 13 to 557-fold depending on the type of the drug or the hydrophobic pendant group attached to PAA. In vivo study showed the ability of these nano-carriers in promoting oral absorption of griseofulvin in rats3. We also investigated the potential of these nano-carriers in pancreatic cancer therapy. Our re-sult showed that cholesteryl- PAA was able to encapsulate a novel hydrophobic anticancer drug and enhanced the drug cytotoxic effect on human pancreatic carcinoma cells at a non-cytotoxic concentration. In vivo result demonstrated the ability of this formulation to impede tumour growth on xenograft mice with results comparable to gemcitabine, the gold standard therapy for pancreatic cancer when admin-istered peritoneally4. In conclusion, nano-carriers based on self-assembling polymers show promising potential in en-hancing hydrophobic drug solubility and provide a new op-portunity to improve the treatment of diseases.

NOVEL NANO-CARRIERS BASED ON SELF-ASSEMBLING POLYMERS: A NEW OPPORTUNITY FOR IMPROVING TREATMENT OF DISEASES

Woei Ping CHENGSchool of Pharmacy, University of Hertfordshire, College Lane, Hatfield, UK AL10 9AB

[email protected]

REFERENCES1. Kilpatrick P. Nature Reviews Drug Discovery 2, 337, 2003.2. Hoskins C, et. al. Polymers for Advanced Technologies, in

press, 2011.

3. Hoskins C, et. al. manuscript in preparation, 2011.4. Hoskins C, et. al. Pharmaceutical Research 27, 2694-2703,

2010.

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Insulin and insulin treatment, in general, the problems of production, oscillation and the effect can be exami-ned on the topic. 1. Production2. Coordination with other cells of the islet3. Oscillation dynamics4. Delivery to the circulation5. Impact the formation and termination of the effect

Forms of insulin therapy applied today, the first in the beta cell insulin production and stored in vesicles outside the cell to be synchronized with other cells is not provided. Insulin molecule in vitro conditions applied to the original molecule imitation by parenteral route. Pulsatile release of insulin and other hormones levels in a situation according to the balance of construction-oscillation. Therefore, the ef-

fect of parenteral insulin at cellular level is decreasing, and in particular according to the circadian rhythm can not be an adaptation. Today, the most important problem of applied insulin therapy which insülin normally reach to the liver from the portal vein, these effects of insulin provided by giving the caval system. In parenteral treatment, hepatic physiolog-ical insulin levels more than 5-10 times the amount of insulin but can pose with the effect. In other case, half life of venous insulin is around 5 minutes, the effect of treatment, subcu-taneous and intramuscular applications, such as watches on going and life-threatening complications of hypoglyce-mia is important issue. New treatment methods (pancreas transplantation, islet replacement, intraperitoneal injection pumps, subcutaneous pump systems with glucose sensor, insulin molecule changes) is to resolve all the problems men-tioned above as intense. Today, however, at this point is still not obtained complete success.

INSULIN THERAPY & ROUTES OF ADMINISTRATIONErcan TUNCEL

Uludağ University, School of Medicine, Department of Endocrinology and Metabolism, Bursa, Türkiye

REFERENCES1. Rhodes CJ, Shoelson S, Halban P. Insulin biosynthesis,

processing and chemistry. In: Kahn RC (editor), Joslin’s Di-abetes Mellitus. 14th ed. Lippincott Williams and Wilkins Co, Philadelphia, 2005, p. 65-82

2. Manesso E, Toffolo GM, Saisho Y, Butler AE, Matveyenko AV, Cobelli C, Butler PC. Dynamics of beta-cellturnover: Evidence for beta-cell turn over and regeneration from sources of beta-cells other than beta-cell replication in the HIP rat. Am J Physiol Endocrinol Metab 297 (2): 323-30, 2009.

3. Farmer TG, Edgar TF, Peppas NA. Effectiveness of intrave-nous infusion algorithms for glucose control in diabetic

patients using different simulation models. Ind Eng Chem Res 48 (9): 4402-4414, 2009.

4. Hanley SC, Austin E, Assouline-Thomas B, Kapeluto J, Bla-ichman J, Moosavi M, Petropavlovskaia M, Rosenberg L. {beta}-Cell mass dynamics and islet cell plasticity in hu-man type 2 diabetes. Endocrinology 151 (4): 1462-72, 2010.

5. Monte SV, Schentag JJ, Adelman MH, Paladino JA. Glu-cose supply and insulin demand dynamics of antidiabetic agents. J Diabetes Sci Technol 4 (2): 365-81, 2010.

http://www.ncbi.nlm.nih.gov/pubmed/19470833http://www.ncbi.nlm.nih.gov/pubmed/19470833http://www.ncbi.nlm.nih.gov/pubmed/19470833http://www.ncbi.nlm.nih.gov/pubmed/19470833http://www.ncbi.nlm.nih.gov/pubmed/20161147http://www.ncbi.nlm.nih.gov/pubmed/20161147http://www.ncbi.nlm.nih.gov/pubmed/20161147http://www.ncbi.nlm.nih.gov/pubmed/20176718http://www.ncbi.nlm.nih.gov/pubmed/20176718http://www.ncbi.nlm.nih.gov/pubmed/20307399http://www.ncbi.nlm.nih.gov/pubmed/20307399http://www.ncbi.nlm.nih.gov/pubmed/20307399

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The incidence of type 2 diabetes is epidemically in-creasing worldwide. Developments of appropriate strategies to prevent and to treat the diabetes be-come more important and challenging. Main goal of our treat-ment is to have the best glycemic control. While achieving this goal, side effects, weight changes, hypoglycemic symptoms should be in acceptable range. In addition to these, we also expect these drugs to reserve or even increase the pancreatic b cell functions and provide advantages such as prevention or control of hypertension, hyperlipidemia, cardiovascular dis-eases which are commonly seen in diabetics and should be cost effective. Characteristics of currently used antidiabetic medications are summarized in the table below.

Although the large number of therapeutic choices now available, it has been shown that HbA1c level still above 7% for many diabetic patients. Oral antidiabetic therapy is the main treatment of choice for diabetic patients regardless of duration of disease, metabolic control, complications and presence of cardiovascular risk factors and intensification of treatment is usually not good enough.

Type 2 diabetes is a progressive disease therefore; preser-vation of b cell function must be the one of the main treat-ment goals while developing new treatment strategies. As we understand the pathogenesis of diabetes, we would be able to develop new treatment goals and alternatives.

ORAL ANTIDIABETIC DRUGSNilgün Güvener DEMİRAĞ

Başkent University, Department of Internal Medicine, Divison of Endocrinology and Metabolism, Ankara, Tü[email protected]

Interventions Expected decrease in HbA1c Advantages Disadvantages

Lifestyle modifications 1-2 Low cost, many benefits Most patients fail within 1 year

Metformin 1-1.5 Weight neutral, inexpensive GI distress, lactic acidosis

Sulfonylureas 0.8-1.5 Inexpensive

Hypoglycemia, weight gain, insufficient effect on

preservation of β cell function, adverse effects on ischemic

remodelling?

Thiazolidinediones (glitazones) 0.8-1.0 Improved lipid profile

Weight gain, edema, anemia, osteoporosis, possible CV risks,

expensive

GLP-1 analogs 0.8-1.2 Weight loss GI side effects, injection, expensive

DPP-4 inhibitors 0.5-0.9No need for dose adjustment, high

tolerability, weight neutral

Expensive, short duration of experience

Alpha-glucosidase inhibitors 0.5-0.8 Weight neutral

Frequent GI side effects, three-times daily dosing

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Increasing realization of the need for optimal glycemic control and the shortcomings of available therapeutic options in diabetes have led to active search for new-er and improved therapeutic modalities. Physicians have high expectations for the efficacy and safety of new drugs. New antidiabetic agents should offer clear advantages over available agents, lowering glucose via mechanisms ideally associated with beneficial cardiovascular effects. Over the

past decade, increased understanding of the broader patho-physiology of type 2 diabetes has led to the development of new agents. Incretin-based therapies represent one such group of drugs in the pharmacotherapy of diabetes. Several novel classes of drugs with different mechanism of action are under development. Potential molecular targets in adipose tissue and kidney receive particular attention.

NEW ANTIDIABETIC AGENTSBülent Okan YILDIZ

Hacettepe University, School of Medicine, Department of Internal Medicine, Endocrinology and Metabolism Unit, 06100 Sıhhiye, Ankara, Türkiye

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Preparing for job interview can be stresful. The fear of negative evaluation can be basic emotion dur-ing interview. The ways to overcome fear during job interview, To avoid nervousness during interview, How to feel prepared for job interview are the most frequent pro-grams that are prepared for succesful interview.

Dialectical Behavior Therapy (DBT) is built by modifying components of Cognitive Behavior Therapy and adding Zen and mindfullness. According to DBT some people react ab-normally to emotional stimulation due to environments dur-ing upbringing and due to biological factors. Their arousal

level goes up and make a peak and takes more time to return base. This is why some people are experiencing more crises than others. They dont have enough methods for coping with these emotions. DBT is a method for teaching coping and social effectiveness that will be helpful for improving the lifes of these individuals.

The aim of this presentation is teaching individuals to cope with negative evaluation anxiety and fear and also training them about social effectiveness and social skills that will help these individuals to improve their lives.

TO OVERCOME THE FEAR OF JOB INTERVIEW: APPROACHES WITH SOCIAL EFFECTIVENESS AND DIALECTICAL BEHAVIOR

Nesrin DİLBAZAnkara Numune Research and Training Hospital, Türkiye

REFERENCES1. McKay et al. Dialectical Behavior Therapy Skills Work-

book: Practical DBT Exercises for Learning Mindfulness, Interpersonal Effectiveness, Emotion Regulation, & Dis-tress Tolerance (2007).

2. Samuel MT, Deborah CB, Michele RC. Social effectiveness therapy: A program for overcoming social anxiety and so-cial phobia: A therapist guide (1997).

3. Blonna R. Maximize Your Coaching Effectiveness with Ac-ceptance and Commitment Therapy (2011).

http://www.amazon.com/Social-effectiveness-therapy-overcoming-therapist/dp/B0006QW6DM/ref=sr_1_8?s=books&ie=UTF8&qid=1303937381&sr=1-8http://www.amazon.com/Social-effectiveness-therapy-overcoming-therapist/dp/B0006QW6DM/ref=sr_1_8?s=books&ie=UTF8&qid=1303937381&sr=1-8http://www.amazon.com/Social-effectiveness-therapy-overcoming-therapist/dp/B0006QW6DM/ref=sr_1_8?s=books&ie=UTF8&qid=1303937381&sr=1-8http://www.amazon.com/Maximize-Effectiveness-Accpetance-Commitment-Professional/dp/1572249315/ref=sr_1_2?s=books&ie=UTF8&qid=1303937381&sr=1-2http://www.amazon.com/Maximize-Effectiveness-Accpetance-Commitment-Professional/dp/1572249315/ref=sr_1_2?s=books&ie=UTF8&qid=1303937381&sr=1-2

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The range of tasks in a pharmaceutical company spans a wide area of different job descriptions and expert knowledge, from the development of med-icines to their production, the application for the necessary permits, their marketing and communication, to the evalu-ation and reporting on the effects of new pharmaceuticals.

When a new product is defined a team needs to be es-tablished to design it and a process for its cost-efficient manufacture for a large customer group. When setting up such teams, successful and leading companies that are the preferred choice of employees also successfully apply com-petency management. At Bilim İlaç one of our HR priorities is competency management. Our competency management process, which has been designed in line with our company’s strategies and objectives, is based not only on the principle of identifying the best employees and leadership personnel of the future, but also on the principles of defining, acquiring

and retaining the competencies the company needs in order to realise its future goals.

Our competency management process comprises the ac-tivities of recruitment of candidates with the defined skill and qualifications, of monitoring their performances, of personal development, motivation and retention in the company.

With the various practical implementations at our com-pany, we pursue the objective of developing the skills of new team members and of our present staff. With this approach we support in particular university students with an inter-est in our trainee programme. Every year, our company ac-cepts trainees from different university departments. Once we have reached the employment stage, those among them who stand out in terms of performance and potential are subject to our selection and recruitment process which en-sures that their current potential is fully appreciated.

PERSONAL BEHAVIORS DURING JOB INTERVIEWAykut BORA

Bilim Pharmaceutical Company, Türkiye

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Obviously, educational background is among top factors that impact on how successfully a candi-date can perform at an R&D position. However, several other parameters also factor in, including work per-formance, attitudes, image, achievements and efficiency of the candidate in the school and thereafter, if applicable, in the workplace, albeit short. An indispensable point that must not be overlooked is the quality of the education received, and whether the person in question will be able to apply his or her attributes in the most appropriate and effective way to perform in a manner that will best respond to the expecta-tions of both himself and the company/establishment that intends to employ him or her.

What we all know, or should now, that at the end of the day the success and the returns on such success belongs primarily to the individual. In fact, achievements of success-ful individuals that a county is able to generate are a major driver of growth and development for countries. A candidate to a position should therefore carefully weigh whether he or she is possessing the necessary competencies; more so in pharmaceutical R&D, which is highly versatile and where it carries much more relevance. Main expectations from those who intend to get into R&D include the ability to instill trust in others, and possessing the essential characteristics of a person of science. And for newcomers this means not letting the years in school go to waste, and learning, and under-standing that learning is the most important gain and that success, not only in sciences but in every aspect of life, will come only if learnings can be put to appropriate use, and in the benefit of society.

Persons considering getting into R&D should, before anything else, know themselves very well. They should be

well positioned to accurately weigh their own potential for success in a given field. It should be never overlooked that wanting something and achieving it successfully are not the same thing. A person’s success is proportional to the degree by which such person is able to accurately identify the areas and issues in which he or she will be able to perform research tasks or any other job as best as he or she can, while loving it dearly and when circumstances warrant it, by making a sacri-fice. And for persons intending to pursue a career in R&D, this means performing a seriously thorough and down-to-earth analysis of both themselves and of the job they are seek-ing to get, weighing it physically, mentally, and financially to decide whether they are in fact up to it. They must know that scientific research and development is a marathon of an undertaking that requires sacrifice, constantly working, ob-serving, performing new analyses and syntheses using all of these inputs, while building and showcasing a creative side. Scientific methodology requires a knowledge of past work in the field and of comparables before embarking on a re-search undertaking in a specific field. Nevertheless, it must be understood, absorbed, acknowledged and never forgot-ten that science cannot be constructed on replicates, errors, and false findings.

What do we do, think, want to do, can do and what should be look out for in this speech, when applying for a job/a position at a science institute, in the school, during youth, mid-life and maturity? Had it been possible to know all of these before applying for a job, surely we would be living in a vastly different world than what we have now. And what have we done, what are we doing, and what will we do to learn of these? We will address these issues using examples from actual events and experiences.

ABOUT THE REQUIREMENTS OF SCIENTIFIC BACKGROUND FOR JOB APPLICATION IN DRUG RESEARCH AND DEVELOPMENT

A. Atilla HINCALDean of Hacettepe University Faculty of Pharmacy (1981-94); Head of Institute of Health Sciences (1994-97)

İDE Drug Information Consultancy and Education Ltd. Co., Ankara, Türkiye İDE Pharmaceutical Consultancy Ltd. Co., Kavaklıdere, Ankara, Türkiye

[email protected], [email protected]

mailto:[email protected]:[email protected]

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DNA topoisomerases are ubiquitous enzymes that are required for replication, transcription, and many other chromosomal processes1. DNA topoi-somerases make transient breaks in DNA using a unique mechanism that includes the creation of a transient enzyme/DNA covalent intermediate. Many small molecules target-ing these enzymes have been identified that exploit this enzymatic mechanism and increase the level of enzyme co-valently bound to DNA. The generation of elevated levels of enzyme/DNA covalent complexes is the key event in cell kill-ing by drugs targeting DNA topoisomerases, and agents that enhance levels of topoisomerase/DNA covalent complexes are termed topoisomerase poisons. Topoisomerase poisons are important anti-cancer drugs, and include the camptoth-ecins (targeting topoisomerase I) and agents such as etopo-side and doxorubicin (targeting topoisomerase II)2. While topoisomerase poisons are active anti-cancer drugs, there are only limited tools available to predict which patients will respond to this class of agents.

Most topoisomerase poisons are a class of inhibitors termed interstitial inhibitors3. This mode of inhibition depends on both the enzyme and DNA to form a drug binding site. There is limited information about how topoisomerase II and DNA combine to form a drug binding site for agents such as etoposide and doxoru-bicin. We have combined genetic and structural ap-proaches to identify regions of topoisomerase II that are important for drug action. We identified sites near the active site tyrosine that contribute to drug sensitiv-ity. Interestingly, we also identified a domain near the C-terminal dimerization domain that also controls DNA cleavage. This result suggests that it may be possible to identify potent allosteric inhibitors of topoisomerase II that may have unique therapeutic potential.

Since topoisomerase II poisons kill cells by the gen-eration of DNA damage, we hypothesized that under-standing mechanisms for repairing or tolerating this type of enzyme mediated DNA damage would increase our ability to predict which tumors might be sensitive to topoisomerase poisons, and to design safer rational combinations of topoisomerase poison with other anti-cancer drugs. We were particularly interested in genes that were important for repair of protein/DNA adducts, Therefore, we concentrated on proteins that may be in-volved in nucleolytic repair of this unique adduct. We demonstrated that yeast and human Tdp1 could hydro-lyze 5’ as well as 3’ phosphotyrosyl linkages, and play a functional role in repairing topoisomerase II medi-ated DNA damage4. Genetic and biochemical analysis of the MRN complex (Mre11/Rad50/Nbs1) implicated this protein in the removal of the topoisomerase–like protein Spo11 from the ends of DNA during meiotic re-combination. The Mre11 protein carries both endonu-clease and exonuclease activities. We used an assay for quantitating topoisomerase II/DNA covalent complex-es in mammalian cells, and showed that in the absence of the MRN complex, levels of topoisomerase II/DNA covalent complexes were substantially elevated. These results show at least two pathways that are involved in nucleolytic repair of topoisomerase II mediated DNA damage. Our studies with Tdp1 and the MRN complex provide a strong validation for the use of genome wide screens in model organisms to study anti-cancer drug action, coupled with the development of specific bio-chemical assays that can be used to functionally assess the importance of specific proteins in drug effects.

HOW TO CHANGE AN ENZYME INTO A CYTOTOXIC AGENT: MECHANISMS OF TARGETING TOP2 IN CANCER

John L. NITISS*, Anna ROGOJINA, Karthik SHANMUGANATHAM, Karin C. NITISSMolecular Pharmacology Department, St. Jude Children’s Research Hospital, Memphis, TN 38105 USA

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REFERENCES1. Nitiss JL. DNA topoisomerase II and its growing reper-

toire of biological functions.DNA topoisomerase II and its growing repertoire of biological functions. Nat Rev Can-cer 9: 327-337, 2009.

2. Nitiss JL. Targeting DNA topoisomerase II in cancer che-motherapy. Nat Rev Cancer 9: 338-350, 2009.

3. Pommier Y, Cherfils J. Interfacial inhibition of macromo-lecular interactions: nature’s paradigm for drug discovery. Trends in Pharmacological Sciences 26: 138-145, 2005.

4. Nitiss KC, Malik M, He X, White SW, Nitiss JL. Tyrosyl-DNA phosphodiesterase (Tdp1) participates in the repair of Top2-mediated DNA damage. Proc Natl Acad Sci USA 103: 8953-8958, 2006.

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Several studies have shown that Bone Marrow Mes-enchymal Stem Cells (BMMSCs) administration enhances structural and functional recovery of in-jured organs. The beneficial effects of injected BMMSCs have been related, in part, to their transdifferentiation in the cell phenotype of host organs. More recently, it has been sug-gested that BMMSCs improve tissue regeneration through secretion of a variety of paracrine factors. Approaches to im-prove the ability of grafted BMMSCs to survive and secrete paracrine factors represent one of the challenges for the further development of these novel therapies. In our labora-tory, we designed a strategy of ex-vivo pretreatment with the pineal hormone melatonin to improve survival, paracrine ac-tivity and efficiency of BMMSCs.

Experiments in vitro showed that, through stimulation of specific MT receptors, melatonin induced an overexpres-sion of the antioxidant enzyme catalase and superoxyde dismutase-1 and increased the resistance of BMMSCs to hy-

drogen peroxide-dependent apoptosis. Using rat models of ischemic heart or renal failure, we showed that melatonin pretreatment in vitro strongly increased survival of BMMSCs after intraparenchymal injection. This effect was concomitant to increased angiogenesis, decreased fibrosis and improved recovery of cardiac and renal functions. In order to deter-mine whether the effects observed in vivo where related to the secretion of paracrine factors, we tested conditioned culture media from melatonin-treated MSCs on endothe-lial progenitor cells and fibroblasts. Our results showed that conditioned media from melatonin-treated MSCs stimulate tube formation by endothelial progenitor cells and decrease extracellular matrix accumulation by fibroblasts.

In conclusion, our results show that melatonin behaves as a preconditioning agent increasing survival, paracrine ac-tivity and efficiency of BMMSCs. The use of this molecule for pretreatment of BMMSCs may represent a novel and safe ap-proach for improving the beneficial effects of cell therapy of solid organs.

ENHANCED SURVIVAL AND PARACRINE ACTIVITY OF BONE MARROW MESENCHIMAL STEM CELLS: IMPACT ON CELL THERAPY OF ISCHEMIC

SYNDROMESAngelo PARINI1,*, Céline MIAS1, Chiara ALFARANO1, Philippe BOURIN2, Jérôme RONCALLI1,

Daniel CUSSAC11Inserm UMR U 1048 – Institute of Metabolic and Cardiovascular Diseases Toulouse

2Laboratoire de Thérapie Cellulaire EFS, Pyrénées-Méditerranée, Toulouse*[email protected]

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Serotonin, or 5-hydroxytryptamine (5-HT), is a nat-urally-occurring vasoactive substance synthetised from L-tryptophan, primarily by central and periph-eral monoaminergic neurons and the gastro -enterochro-maffin cells. Serotonin released from gastrointestinal tract is avidly taken up and stored by circulating platelets. The car-diovascular system is mostly exposed to free serotonin, the level of which is largely controlled by platelets.

Numerous studies have demonstrated the implication of serotoninnergic receptors in the control of vascular tone and cardiac function. Serotonin produces complex responses on blood pressure including vasoconstrictive and vasodilatory ef-fects. The vasopressor response is a consequence of vasocon-striction mainly mediated by 5-HT2a receptors located on vas-cular smooth muscle cells. The vasodepressor response may involve different mechanisms: vasodilatation by endothelium release of nitric oxide and inhibition of the vasopressor sym-pathetic outflow by sympatho-inhibitory 5HT1 receptors.

Serotonin regulates cardiac function by inducing chro-notropic and inotropic effects mediated by 5HT4 or 5HT2A receptors. This ventricular positive inotropic responsiveness to serotonin exacerbates in conditions of heart failure both in rat and human ventricles. We have also underlined the relevance of platelet derived serotonin on cardiac fibroblast phenotype. Serotonin released by platelets, occuring princi-pally during thrombotic events, promotes cardiac fibroblast activation through stimulation of 5-HT2A receptors. These effects of platelet derived serotonin may have particular rel-evance in acute events following ischemic injury and in the early ventricular remodeling.

Recently, an up regulation of circulating serotonin has been described in patients with cardiopathy and heart fail-

ure. The same observation has been made in rat submitted to cardiac hypertrophy by pressure overload suggesting a targeted effect of serotonin during cardiovascular patholo-gies. In order to address the question of serotonin function during pathological heart remodeling, we used KO mice for the limiting enzyme of serotonin biosynthesis (tryptophan hydroxylase 1) TPH1. This enzyme converts L-Tryptophan to 5-hydroxy-L-tryptophan (5-HTP) which is then transformed into 5HT by the L-aromatic amino acid decarboxylase (LAAD). The KO TPH1 mice exhibited low level of circulating and car-diac serotonin. We submitted KO TPH1 mice and their WT lit-termates to a mild transverse aortic constriction (TAC). Echo-cardiographic analysis revealed in banded KO compared to WT mice an exacerbated left ventricular dilatation and a de-crease in fractional shortening indicating a decompensated cardiac function. In this model of pressure overload hyper-trophy induced by TAC, it appears that low level of serotonin worsen progression to cardiac failure.

To further investigate this hypothesis, we restored 5HT level in KO TPH1 mice by supplementation with the sero-tonin precursor 5-HTP. Preliminary analysis have shown that treatment with 5-HTP induced a significant decrease in ven-tricular dilatation without affecting hypertrophy, measured by echocardiography. Moreover fibrosis was decreased in ventricle indicating a beneficial effect of 5-HTP treatment. Fractional shortening was fully preserved in the KO TPH1 mice treated group. These data indicate that in vivo, normal serotonin concentrations are required to prevent transition from hypertrophy to heart failure.

These findings underline the role of serotonin in regula-tion of cardiovascular function and offer new prospects for the use of serotoninergic drugs in therapies for cardiovascu-lar diseases.

SEROTONERGIC CONTROL OF CARDIOVASCULAR FUNCTIONNathalie PIzzINAT

Institute of Metabolic and Cardiovascular Diseases (I2MC), INSERM, Toulouse, France

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Isocoumarins, indoles, benzoazepines represent an im-portant class of naturally occurring compounds that display a wide range of biological activities. Our inves-tigation began with an attempted synthesis of the diazide derived from the homophthalic acid1. Homophthalic acid 1 was reacted with thionyl chloride, dimethy formamide and sodium azide in the presence of tetrabutyl ammonium bro-mide as a catalyst. Only, 6H-dibenzo[c,h]chromen-6-one (2) was formed in 41% yield 1,2.

COOH

COOHO

O

SOCl2, DMF

Bu4NBr, NaN3

1

N

COOMe

OH

H3CO

O

NHN

O

4 5

COOCH3

COOH

32

The azide derived from the half ester 3 was synthesized. Conversion of the formed azide into the corresponding ure-thane in methanol followed by cyclization and acetylation gave the indol derivative4. On the other hand, the reaction of homophthalic anhydride with hydrazine in dimethyl for-mamide resulted in the formation of a new pyrazole deriva-tive5.

NH

O

NR

RN O

O NR

RN O

ONH

O

ON

O

C

O

NO

O

Furthermore, the synthesis of benzodiazepinone and dihydrofuropyrimidinone3, isoquinolinone and furopyrrol starting from the corresponding diacids will be discussed4-7.

BISACYLAZIDES: A NEW MILESTONE FOR THE SYNTHESIS OF VARIOUS HETEROCYCLES

Metin BALCIDepartment of Chemistry, Middle East Technical University, 06531 Ankara, Türkiye

[email protected]

REFERENCES1. Özcan S, Şahin E, Balcı M. The synthesis of unusual isoco-

umarin derivatives: the chemistry of homophthalic acid. Tetrahedron Lett 48: 2151-2154, 2007.

2. Özcan S, Balci M. The Chemistry of Homophthalic Acid: A New Synthetic Strategy for Construction of Substitut-ed Isocoumarine and Indole Skeletons. Tetrahedron 64: 5531-5540, 2008.

3. Koza G, Özcan S, Şahin E, Balci M. Regioselective Synthe-sis of Dihydrofuro[3,2-d]pyrimidin-2(1H)-one Skeleton: A New Class of Compounds. Tetrahedron 65: 5973-5976, 2009.

4. Dengiz Ç, Özcan S, Şahin E, Balcı M. A new synthetic Methodology for the construction of 1,3,4,5-tetrahydro-2H-1,3-benzodiazepin-2-one skeleton. Synthesis: 1365-1370, 2010.

5. Deliömeroglu MK, Özcan S, Balci M. A short and efficient construction of the dibenzo[c,h]chromen-6-one skel-etone. Arkivoc 148-160, 2010.

6. Koza G, Karahan E, Balci M. Helv Chim Acta 93: 1698-1704, 2010.

7. Özcan S, Çağatay D, Deliömeroğlu KM, Şahin E, Balci M. A novel one-pot three component reaction: Synthesis of isocoumarin-condensed pyrazols. Tetrahedron Lett 52: 1495-1497, 2011.


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Poly(amido amine) (PAMAM) type dendritic macromolecules have become significant im-pact in the field of material sciences and are one of the major starting points for nanotechnology as a result of the numerous modifications that can be conducted, either on the surface or within their mo-lecular infrastructure, thus taking advantage of their unimolecular micelle properties1. These host cavities, maintained by the dendritic branches, allow for the in-corporation of nanoparticles as well as metal particles, which make these attractive in catalysis and imaging studies. Especially Dendritic hosts with hydrogen bon-ding receptors have been made by Newkome et al.2 The poly(amidoether) dendrimers contain (2,6-diacyla-mino)pyridine moieties that serve as donor-acceptor-donor (DAD) H-bonding units. Barbituric acid, a guest that contains two ADA arrays, is bound to the dendri-mer, as evidenced by 1H NMR measurements. For the higher generation dendrimers, intramolecular self-association competes with guest binding. The solubility of these fractal constructs can be tailored depending on their surface modifications. Highly water-soluble, neutral dendrimers appended with, grown from, or ac-ting as hosts to specific molecules give rise to a wide variety of biomedical applications such as drug deli-very systems and MRI imaging agent3. The inherent supramolecular or supramacromolecular chemistry has been exploited but the design and construction of uni-quely tailored macrostructures have just begun. Laser dyes, as well as electron and energy donor and accep-tor functionality, have also been paired with these frac-tal constructs in order to probe their uses in the field

of molecular electronics. With their synthetic control, appearently unlimited modifications and wide variety of potential applications, as well as their commercial4,5 availability, these 1à 2 or 1à 3 branched dendrimers have become an important nanostructured tools for diverse pratical applications. Present study6 mainly co-vers 1 à 3 branched non-chiral dendrimers prepared by a divergent process but selected functional surfaces having antibacterial or antimicrobial properties. As a synthetic method Microwave Assisted Technique has been applied. More detailed; ethylenetriamine (ETA) or trimethylolpropane tris[poly(propylene glycol), amine terminated] ether were selected as cores and methy-acrylate (MA) and ethylenediamine (EDA) were alterna-tively used as building blocks. Novel PAMAM type den-drimers were synthesized up to the 4th. generations. In order to make the molecules water soluble, surface groups were modified by 2-amino-2-(hydroxymethyl) propane-1, 3-diol (AT). The syntheses were carried out mostly by applying microwave irradiation technique and correlated with conventional methods. The prod-ucts were characterized via Elementary Analysis (EA), Fourier Transform Infra Red (FT-IR) and 1H NMR-13C NMR spectroscopy. Since all dendrimer/substrate complexes were completely miscible with water in all proportions. When the bound substrates are drug moieties, then the resulting complexes could be considered as potential drug delivery systems. In the similiar studies (Scheme 1),7 flow calorimetry demonstrates that dendrimers were able to release their hydrophobic guests when in contact with a biological cell.

DENDRIMERS AS POTENTIAL DRUG CARRIERS; MICROWAVE-ASSISTED SYNTHESIS OF PAMAM TYPE DENDRIMERS

Cemil DIZMAN1, Tezcan PARALI1, Ali Serol ERTÜRK1, Metin TÜLÜ1,2,* 1Department of Chemistry, Fatih University, 34500 İstanbul, Türkiye

2Department of Chemistry, Yıldız Technical University, 34210 İstanbul, Türkiye*[email protected], [email protected]

http://www.google.com.tr/url?sa=t&source=web&cd=1&ved=0CBcQFjAA&url=http%3A%2F%2Fwww.yildiz.edu.tr%2F&ei=726UTdPnCs3Dswby6uS6CA&usg=AFQjCNHnfGAW5wNsnN8hnRIOUmFKUzUktA&sig2=Dmnle2Nvc1ZpF47EVwLBYg

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REFERENCES1. Yang H, Lopina ST. Penicillin V-conjugated PEG-PAMAM

star polymers. J Biomater Sci Polymer Edn 14(10), 1043–1056, 2003.

2. Newkome GR, Woosley BD, He E, Moorefield CN, Guther R, Baker GR, Escamilla GH, Merril J, Luftmann H. Cascade Polymers: Synthesis and characterization of one direc-tional arborols based on adamantane. Chem Commun 2737-2738, 1996.

3. Newkome GR, Shreiner CD. Poly(amidoamine), polypro-pylenimine, and related dendrimers and dendrons pos-sessing different 1 à2 branching motifs: An overview of the divergent procedures. Polymer 49, 1-173, 2008.

4. http://www.dendritech.com/5. http://www.frontiersci.com/6. Tulu M, Aghatabay NM, Senel M, Dızman C, Paralı T, Dül-

ger B. Synthesis, characterization and antimicrobial activ-ity of water soluble dendritic macromolecules, European Journal of Medicinal Chemistry 44, 1093-1099, 2009.

7. Beezer AE, King ASH, Martin IK, Mitchel JC, Twyman LJ, Wain CF. Dendrimers as potential drug carriers; encap-sulation of acidic hydrophobes within water soluble PAMAM derivatives. Tetrahedron 59, 3873-3880, 2003.

N

O

HN

O

NH

N

N

O NH

O

NH

N

OHN

O

NH

NN

N

N

N

N

HN O

O

NH

O NH

O

HN

O

O NH

HN

O

HNONH

OHN

O

NH

ONH

O

HN

OHOH

OH

OH

OHOH

OHHO

HO

HO

HOHO

OH

OHOH

HO

HOHO

HO

HOHO

OH

OHOH

OH

OHOHHO

HOHOOHHOHO

OHHOHO

O-O

O

O-

N

O

HN

O

NH

N

N

O NH

O

NH

N

OHN

O

NH

NN

N

N

N

N

HN O

O

NH

O NH

O

HN

O

O NH

HN

O

HNONH

OHN

O

NH

ONH

O

HN

OHOH

OH

OH

OHOH

OHHO

HO

HO

HOHO

OH

OHOH

HO

HOHO

HO

HOHO

OH

OHOH

OH

OHOHHO

HOHOOHHOHO

OHHOHO

OOH

O OH

A B

Scheme 1. Possible interactions: Unlikely hydrogen

http://www.dendritech.com/http://www.frontiersci.com/

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Oncolytic viruses infect and kill cancer cells pref-erentially; either by direct lysis of the tumour cells or by serving vectors for delivery of genes encoding enzymes that convert non-toxic pro-drugs into cytotoxins, e.g., ganciclovir. Recently, reoviridae family viri-ons have been shown to have oncolytic properties and pro-posed as a possible tumor-killing therapy for cancer treat-ment. However, generation of tumour selectivity is a critical factor for constraining the oncolytic activity to cancerous cells without affecting the healthy tissue. Here we employed high-resolution fluorescence microscopy to study inter-nalization and trafficking of reovirus particles in polarized epithelium and non-polarized cells. We controlled the viral

entry routes by drugs such as amiloride and dynasore in or-der to repress macropinocytosis or clathrin-mediated endo-cytosis, respectively. Our results indicate that virions entered non-polarized cells very inefficiently both by clathrin-medi-ated endocytosis and by macropinocytosis-like mechanism. In contrast, efficient entry of virions at the apical surface of polarized cells was strictly mediated by clathrin-mediated endocytosis. Our data provide the first real-time analysis of virus entry into polarized cells and define the entry mecha-nism of reovirus. More generally, our observations empha-size the importance of studying virus entry in relevant cell types, especially for pathogens that invade hosts through the polarized epithelium.

MONITORING REOVIRUS ENTRY AND ENDOSOMAL TRAFFICKING IN LIVE NON-POLARIZED AND POLARIZED CELLS BY SINGLE VIRAL PARTICLE

TRACKINGCömert KURAL1, Steeve BULANT1, Tomas KIRCHHAUSEN1,2

1Immune Disease Institute, Harvard Medical School, Boston, MA.2Department of Cell Biology, Harvard Medical School, Boston, MA.

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Interconversion barriers between different conforma-tions of R and S enantiomer of 4,5-DIMETHYL-1,3,4,5-TETRAHYDRO-2H-1,5-BENZODIAZEPIN-2-ONE were calculated. Starting structures of (R) and (S) enantiomer of 4,5-DIMETHYL-1,3,4,5-TETRAHYDRO-2H-1,5-BENZODIAZ-EPIN-2-ONE were created with the Sybyl molecular model-ing package. Ten conformations of each compound were obtained by Sybyl simulated annealing using the force field MMFF94s followed by B3LYP/6-31G(d) optimization. After optimization, four unique conformations (Figure 1) of each analogue were selected for further calculations. The ground state structure and the transition state geometries were fully optimized, and each stationary point found was character-ized by a frequency calculation followed by IRC calculations. Transition state structures were characterized by one imagi-nary frequency. The interconversion barrier was calculated by the difference between the total energies, including the zero-point and thermal corrections, of the minimum and the transition state (Figure 2). The minimum calculated intercon-version barrier, DG≠ = 1.77 kcal/mol, was observed for inter-conversion of 3rd conformation of 1S to 4th conformation of 1S whereas the maximum interconversion barrier, DG≠ = 7.48 kcal/mol, for corresponding conformation of 1R. These results are unexpected and more investigations are required to get in depth information about interconversion barriers of these types of compounds.

Figure 1

Figure 2

COMPUTATIONAL STUDY OF THE CONFORMATIONAL INTERCONVERSION OF 4,5-DIMETHYL-1,3,4,5-TETRAHYDRO-2H-1,5-BENZODIAZEPIN-2-ONE

Sajid JAHANGIR1,2,* , Walter M. F. FABIAN11Institute of Chemistry, Karl Franzens University, Graz, Heinrichstrasse 28, A-8010 Graz, Austria,

2Department of Chemistry, Federal Urdu University of Arts, Science and Technology, Gulshan-e-Iqbal Science Campus, Karachi, Sindh, Pakistan

*[email protected]


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Traditional herb medicines are an important part of the health care system of Subcontinent of South Asia. Ayurveda, supposed to be the oldest medi-cal system in the world, provides potential leads to find ac-tive and therapeutically useful compounds from plants. In the present work eleven natural samples (Turmeric, Orange juice, Almond, Pistachio, Tea, Ginsing, Green Tea, Olive oil, Vinegar, Narrium indicum Extract, Glucose) were selected to explore their antioxidant activities through cyclic voltam-metry (CV). Although most of them are already known for their antioxidant activities but this is the first time that their antioxidant properties have been investigated through CV.

Superoxide free radical was generated by the run of CV of 0.1M tetrabutylammonium perchlorate (TBAClO4) in acetoni-trile at 100mV scan rate, where Glassy Carbon (GC) was used as working electrode. In the presence of natural samples the oxidation peaks of superoxide were obtained in decreased anodic current. The decreased or diminished oxidation peak current is a clear indication of antioxidant activity of the studied samples. Out of eleven sample, eight samples (Gins-ing, Turmeric, Orange juice, Almond, Pistachio, Tea, Green Tea, Olive oil) have shown high antioxidant activity where-as three sample (Vinegar, N. indicum Extract, Glucose) have shown low antioxidant activity.

DETERMINATION OF ANTIOXIDANT ACTIVITY OF SOME BIOLOGICALLY IMPOR

may 27-29, 2011 wow topkapı palace antalya-tÜrkİye · 2011-05-17 · scientific programme 6 drd...

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