3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
TABLE OF CONTENT
Table of Contents 1 Welcome 2 Committees 4 Scientific Programme 7 Plenary Lectures 11 Oral Presentations 31 Poster Presentations 48 Short Oral Presentations 181 List of Abstracts 203
October 05-07, 2017, ERZURUM-TÜRKİYE 1
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
WELLCOME
Dear Friends and Colleagues,
It is a great pleasure for me to extend you a cordial invitation to participate in the International Multidisciplinary Symposium on Drug Research and Development 2017(DRD-2017) at the Anatolian Peak. The congress is co-organized by “Society of Researchers in Pharmacy and Medicine (ILARUD)” and Atatürk University. Faculty of Pharmacy, Atatürk University, will host the DRD-2017 on 05–07 October 2017 at the Nenehatun Cultural Center located in the Central Campus of the Ataturk University, Erzurum- Turkey.
The primary goal of the DRD-2017 is to improve the activities on drug research, development and application. Another goal is to promote scientific information interchange between researchers, academicians, students, professionals and institutions working in Turkey and abroad.We expect that “cardiovascular system drugs”,the special theme of DRD-2017, will provide ample flexibility in many directions.
Erzurum is the city located in Eastern Anatolia Region which is situated 1.850 m (6.070 ft) above sea level and has over 320 cultural landmarks. It is a city on the traditional Silk Road and has hosted many ancient civilizations throughout history. There are several historical mosques, churches and historical places in the city. Erzurum is one of the world’s winter tourism centers, known with its special geographical features, convenient for skiing for 5 months, with its high snow quality, long tracks and facilities. Palandöken Mountains is among the skiing areas of first-degree importance with regards to winter sports and winter tourism and carries the feature of being an international station in terms of freestyle skiing and touristic movements in winter.
On behalf of the Organizing Committee, I would like to welcome you to DRD-2017 and I hope you will enjoy the scientific eventsat every level of participation which will facilitate the initiation of friendships, collaborations, and joint projects as well as to experience the traditional culture in Erzurum.
We are looking forward to welcoming you to the DRD-2017 in Erzurum.
Yours sincerely Professor Yucel KADIOĞLU, PhD Dean & Chair of the Organizing Comittee
October 05-07, 2017, ERZURUM-TÜRKİYE 2
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
Dear Colleagues,
"The Society of Researchers in Pharmacy and Medicine" was founded with the aim of improving the activities on drug research, development and application as well as establishing an active networking platform for the academic staff, graduate and undergraduate students from the faculties of pharmacy, medicine and chemistry; professionals who are working in the research & development and quality control departments of drug industry and also the representatives of public institutions.
Our society recently decided to organize a series of international meetings titled as “International Multidisciplinary Symposium on Drug Research and Development” in coordination with the pharmacy faculties in Türkiye every two years. The meetings which were co-organized by Faculty of Pharmacy, Gazi University in 2013, and Faculty of Pharmacy Anadolu University in 2015, with a broad participation.
Faculty of Pharmacy, Atatürk University, will host the “International Multidisciplinary Symposium on Drug Research and Development-2017 (DRD 2017)” on 5-7th of October, 2017 with the contributions of thirty four pharmacy faculties. The Symposium intends to have professionals working on drug research and development; share information, discuss innovations, establish and develop partnerships. All stakeholders of drug research and development are invited to participate and expected to provide their valuable contributions in DRD 2017.
We delighted to invite you to participate in the “International Multidisciplinary Symposium on Drug Research and Development-2017” in Erzurum, Türkiye. Sincerely,
Prof. Sedef Kır, Ph.D
Cochair of the Organizing Committee & President of the Society of Researchers in Pharmacy and Medicine (ILARUD)
October 05-07, 2017, ERZURUM-TÜRKİYE 3
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
COMMITTEES HONORARY CHAIRMAN
Prof. Dr. Ömer ÇOMAKLI Rector of Atatürk University
ORGANIZING COMMITTEE Prof. Yücel KADIOĞLU, Ph.D. (Chair & Dean of the Faculty of Pharmacy, Atatürk University) Prof. Sedef KIR, Ph.D. (Cochair&President of the ILARUD) Prof. Gülberk UÇAR, Ph.D. (Executive Committee Member of ILARUD ) Prof. Mutlu AYTEMİR, Ph.D.(Executive Committee Member of ILARUD) Prof. Selma SARAÇ TARHAN, Ph.D. (Executive Committee Member of ILARUD ) Assoc.Prof. Beyzagül POLAT, Ph.D. (Faculty of Pharmacy, Atatürk University) Assoc.Prof. Fatma DEMİRKAYA MİLOĞLU, Ph.D.(Faculty of Pharmacy, Atatürk University) Assoc.Prof. Buket AKSU, Ph.D.(Executive Committee Member of ILARUD) Assist. Prof. Rukiye Sevinç ÖZAKAR, Ph.D. (Faculty of Pharmacy, Atatürk University) Assist. Prof. Sinan BİLGİNER, Ph.D. (Faculty of Pharmacy, Atatürk University)
LOCAL ORGANIZING COMMITTEE Assit. Prof. Hilal ÖZBEK Department of Pharmacognosy Assit. Prof. Ş. Sezin PALABIYIK Department of Pharmaceutical Toxicology Research Assit. Mehtap TUĞRAK, Ph.D. Department of Pharmaceutical Chemistry Research Assit. Özlem A. BERKTAŞ Department of Biochemistry Research Assit. M. Emrah YAMAN Department of Analytical Chemistry Research Assit. Zerrin KUTLU Department of Biochemistry Research Assit. Hafize YUCA Department of Pharmacognosy Research Assit. Emrah ÖZAKAR Department of Pharmaceutical Technology Research Assit. Afife Büşra UĞUR Department of Pharmaceutical Technology Research Assit. Merve BECİT Department of Pharmacology Research Assit. Büşra SERVER Department of Pharmaceutical Technology Research Assit. Cem YAMALI Department of Pharmaceutical Chemistry Research Assit. Lale DUYSAK Department of Biochemistry
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
MEETING & SCIENTIFIC COMMITIEE
Prof. Mert ÜLGEN, Ph.D. Dean of Faculty of Pharmacy, Acıbadem University Prof. İdris TÜREL, Ph.D. Dean of Faculty of Pharmacy, Adıyaman University Prof. Yücel ÜNAL, Ph.D. Dean of Faculty of Pharmacy, Ağrı İbrahim Çeçen University Prof. Yusuf ÖZTÜRK, Ph.D. Dean of Faculty of Pharmacy, Anadolu University Prof. Gülbin ÖZÇELİKAY, Ph.D. Dean of Faculty of Pharmacy, Ankara University Prof. Yücel KADIOĞLU, Ph.D. Dean of Faculty of Pharmacy, Atatürk University Prof. Gülaçtı TOPÇU, Ph.D. Dean of Faculty of Pharmacy, Bezm-i Alem University Prof. Süreyya ÖLGEN, Ph.D. Dean of Faculty of Pharmacy, Biruni University Prof. Hale SAYAN ÖZAÇMAK, Ph.D. Dean of Faculty of Pharmacy, Bülent Ecevit University Prof. Ali ÇETİN, Ph.D. Dean of Faculty of Pharmacy, Cumhuriyet University Prof. Mehmet KOYUNCU, Ph.D. Dean of Faculty of Pharmacy, Cyprus International University Prof. Nuran ÖĞÜLENER, Ph.D. Dean of Faculty of Pharmacy, Çukurova University Prof. Meral ERDİNÇ, Ph.D. Dean of Faculty of Pharmacy, Dicle University Prof. M. Fethi ŞAHİN, Ph.D. Dean of Faculty of Pharmacy, Eastern Mediterranean University Prof. Hüsniye KAYALAR, Ph.D. Dean of Faculty of Pharmacy, Ege University Prof. İbrahim NARİN, Ph.D. Dean of Faculty of Pharmacy, Erciyes University Prof. Bülent GÜMÜŞEL, Ph.D. Dean of Faculty of Pharmacy, Erzincan University Prof. İlkay ERDOĞAN ORHAN, Ph.D. Dean of Faculty of Pharmacy, Gazi University Prof. K. Turay YARDIMCI, Ph.D. Dean of Faculty of Pharmacy, Girne American University Prof. Terken BAYDAR, Ph.D. Dean of Faculty of Pharmacy, Hacettepe University Prof. Yılmaz ÇİĞREMİŞ, Ph.D. Dean of Faculty of Pharmacy, İnönü University Prof. Emine AKALIN URUŞAK, Ph.D. Dean of Faculty of Pharmacy, İstanbul University Prof. Mehmet TANOL, Ph.D. Dean of Faculty of Pharmacy, İstanbul Kemerburgaz University Prof. Gülden OMURTAG, Ph.D. Dean of Faculty of Pharmacy, İstanbul Medipol University Prof. Feride Sena SEZEN, Ph.D. Dean of Faculty of Pharmacy, Karadeniz Technical University Prof. Ş. Güniz KÜÇÜKGÜZEL, Ph.D. Dean of Faculty of Pharmacy, Marmara University Prof. Rümeysa DEMİRDAMAR Dean of Faculty of Pharmacy, Lefke European University Prof. Serap YALIN, Ph.D. Dean of Faculty of Pharmacy, Mersin University Prof. İhsan ÇALIŞ, Ph.D. Dean of Faculty of Pharmacy, Near East University Prof. Ahmet AKKAYA, Ph.D. Dean of Faculty of Pharmacy, Süleyman Demirel University Prof. Gülay ŞEREN, Ph.D. Dean of Faculty of Pharmacy, Trakya University Prof. Meriç KÖKSAL AKKOÇ, Ph.D. Dean of Faculty of Pharmacy, Yeditepe University Prof. İmer OKAR, Ph.D. Dean of Faculty of Pharmacy, Yeni Yüzyıl University Prof. Ali ASLAN, Ph.D. Dean of Faculty of Pharmacy, Yüzüncü Yıl University Prof. Antony C. CALOKERINOS, Ph.D. National and Kapodistrian University of Athens October 05-07, 2017, ERZURUM-TÜRKİYE 5
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
Prof. Angelo PARİNİ, Ph.D. Director of Unite Inserm 858, Toulouse, France Prof. Abeer Al GHANANEEM, Ph.D. Assoc. Dean, Sullivan University College of Pharmacy Prof. Ahmad HASSAN, Ph.D. Syrian Private University Prof. Bashar ALKHALIDI, Ph.D. The University of Jordan Assoc. Prof. Assoc. Prof. Bijo Department of Pharmaceutical Chemistry, Ahalia School of Pharmacy, India MATHEW, PhD Jalal HANAEE, Ph.D Department of Pharmaceutical Analysis, University of Tabriz, Iran Abolghasem JOUYBAN Tabriz University of Medical Sciences, Tabriz, Iran
LOCAL ADVISORY BOARD
Prof. Dr. Fuat GÜNDOĞDU Vice of Director, Department of Cardiology Prof. H. İnci GÜL, Ph.D. Department of Pharmaceutical Chemistry Prof. Zühal GÜVENALP Department of Pharmacognosy Assoc. Prof. Meltem ÇETİN, Ph.D. Department of Pharmaceutical Technology Assoc. Prof. Mine GÜLAPOĞLU, Ph.D. Department of Biochemistry Assoc. Prof. Elif ÇADIRCI, Ph.D. Department of Pharmacology Assoc. Prof. Yasin BAYIR, Ph.D. Department of Biochemistry Assoc. Prof. Bilal YILMAZ, Ph.D. Department of Analytical Chemistry Assist. Prof. Alptuğ ATİLA, Ph.D. Department of Analytical Chemistry Assist. Prof. Nurcan K.BAYGUTALP, Ph.D. Department of Biochemistry Assist. Prof. Esen S. KARAOĞLAN , Ph.D. Department of Pharmaceutical Botanic Assist. Prof. Ali AŞÇI, Ph.D. Department of Pharmaceutical Toxicology Assist. Prof. Handan G. SEVİNDİK, Ph.D. Department of Pharmacognosy Assist. Prof. Irmak F. OKKAY, Ph.D Department of Pharmacology Assist. Prof. Hayrünisa HANCI, Ph.D Department of Pharmaceutical Microbiology Assist. Prof. Songül KARAKAYA, Ph.D Department of Pharmacognosy Assist. Prof. Mehmet KOCA, Ph.D Department of Pharmaceutical Chemistry
SCIENTIFIC SECRETERIAT
Fatma DEMIRKAYA MILOGLU, Ph.D Onur ŞENOL, Ph.D (CONGRESS SECRETARY) (CONGRESS SECRETARY) Faculty of Pharmacy, Atatürk University Faculty of Pharmacy, Atatürk University [email protected] [email protected]
October 05-07, 2017, ERZURUM-TÜRKİYE 6
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
SCIENTIFIC PROGRAMME
International Multidisciplinary Symposium on Drug Research and Development (DRD-2017) (5-7 October 2017 Erzurum/ TURKEY) CONGRESS PROGRAMME
5 October 2017 Thursday 09.00-10.00 REGISTRATION (Congress Center) 10.00-11.00 Opening Ceremony Prof. Dr. Yücel KADIOĞLU (Dean of Atatürk University Faculty of Pharmacy, Chair of the Organizing Committee) Prof. Dr. Sedef KIR (President of Society of Researchers in Pharmacy and Medicine (İLARUD)- Cochair of the Organizing Committee) Dr. Hakkı GÜRSÖZ (President of Turkish Medicines and Medical Devices Agency (TİTCK), Turkish Ministry of Health) Pharm. M. Kazım DİNÇ (Former Health Minister of Turkey) Prof. Dr. Ömer ÇOMAKLI (Rector of Atatürk University) Prof. Dr. Mustafa ILICALI (Member of the Grand National Assembly) Mr. Mehmet SEKMEN (President of Municipal of Erzurum) Mr. Seyfettin AZİZOĞLU (Governer of Erzurum) 11.00-11.15 Coffee Break 11.15-13.00 Opening Lecturers 11.15-12.15 Invited Lecturer-Prof. Dr. Bingür SÖNMEZ Cholesterol Drugs : Known Truths-Told Wrongs 12.15-13.00 Invited Lecturer-Prof. Dr. Emin KANSU Nobel Prizes and Voyage in Science 13.00-14.30 Lunch Break
HALL A SESSION I (Cardiovascular System Drugs) (English) Session Chairmen: Prof. Dr. Fuat GÜNDOĞDU, Prof. Dr. Kudret AYTEMİR 14.30-15.15 Invited Lecturer - Prof. Dr. Barış KAYA Advances in Treatment of Pulmonary Arterial Hypertension 15.15-16.00 Invited Lecturer - Assoc. Prof. Dr. Hikmet YORGUN Drug Therapy for Arterial Fibrillation; What’s New? 16.00-16.30 Coffee Break
HALL A PANEL SESSION (Turkish) Session Chairmen: Dr. Hakkı GÜRSÖZ, Prof. Dr. Yılmaz ÇAPAN 16.30-18.00 Current Status of Turkey in Drug Research and Development and Future Aspects Dr. Hakkı GÜRSÖZ - President, Turkish Medicines and Medical Devices Agency, Turkish Ministry of Health Prof. Dr. Yılmaz ÇAPAN - İLKO Pharmaceuticals R&D and Regulatory Affairs Director Prof. Dr. Sevim AYDIN - Vice President of Academic Research Founding Program Directorate, The Scientific and Technological Research Council of Turkey (TÜBİTAK) Dr. Ümit DERELİ - General Secretary, Association of Research-Based Pharmaceutical Companies (AİFD) Pharm. Vedat EĞİLMEZ - Public and Academic Affairs Consultant, Pharmaceutical Manufacturers Association of Turkey (İEİS) Chem. Eng. Şirin DEHA – Board member, Association of Health Products (SURDER)
Refreshment Time 19.30-22.30 Welcome Reception
October 05-07, 2017, ERZURUM-TÜRKİYE 7
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
6 October 2017 Friday HALL A SESSION II (Turkish) Session Chairmen: Dr. Ali ALKAN 08.30-10.30 Pharmacovigilance and Drug Registration: Recent Perspective of Turkish Medicines and Medical Devices Agency 08.30-09.10 Invited Lecturer - Dr. Pharm. Nihan BURUL BOZKURT Clinical Trials in the Drug Development Process 09.10-09.50 Invited Lecturer - Dr. Pharm. N. Demet AYDINKARAHALİLOĞLU Pharmacovigilance Activities in Turkey 09.50-10.30 Invited Lecturer - Pharm. Hacer ÇOŞKUN ÇETİNTAŞ Marketing Autorisation of Medicine in Turkey 10.30-11.00 Coffee Break HALL A SESSION III (English) (İLARUD-Prof. Dr. Ünsal ÇALIŞ Session) Session Chairmen: Prof. Dr. Sema CALIŞ, Prof. Dr. Emin KANSU 11.00-12.30 Current Status of Drug Discovery and Development 11.00-11.30 Invited Lecturer - Prof. Katerina GORACİNOVA Biological Efficacy of SN-38 Loaded PLGA-PEG-PLGA Nanoparticles 11.30-12.00 Invited Lecturer - Assist. Prof. Dr. Mert ÇALIŞ Recent Advances in Regenerative Medicine: Plastic Surgery Perspective 12.00- 12.30 Inivited Lecturer - Assoc. Prof. Dr. Hakan EROĞLU Drug Delivery for Neuroprotection: Opportunities and Challenges 13.00-14.00 Lunch Break HALL A SESSION IV (English) Session Chairmen: Prof. Dr. Yusuf ÖZTÜRK, Prof. Abolghasem JOUYBAN 14.00-16.00 Drug Delivery Pharmaceutical Technology, Biopharmaceutics, Radiopharmaceutisc 14.00-14.30 Invited Lecturer - Prof. Dr. Bashar AL KHALIDI The Buccal Drug Delivery of Carvedilol Which is a Cardiovascular Drug 14.30-15.00 Invited Lecturer - Prof. Dr. Tuncer DEĞİM Pros and Cons of Using Tubular Nanostructures and Quantum Dots to Deliver Drug Molecules 15.00-15.20 Assist. Prof. Dr. Mine SİLİNDİR GÜNAY Radiopharmaceutical for Brain Imaging 15.20-15.40 Assist. Prof. Dr. Özge İNAL In vitro Studies on Atenolol Loaded Ion Exchange Resins 15.40-16.00 Dr. Selin Seda TİMUR Design and in vitro Evaluation of Bispecific Complexes and Drug Conjugates of Anticancer Peptide, LyP-1 in Human Breast Cancer HALL B SESSION V (English) Session Chairmen: Prof. Dr. Bülent GÜMÜŞEL, Prof. Dr. Gülbin ÖZÇELİKAY 14.00-16.00 Current Developments in Device Analysis 14.00-14.30 Invited Lecturer – Prof. Dr. Sibel ÖZKAN The Overview of Commonly Used Electrochemical Carbon Nanosensors in Pharmaceutical Assay 14.30-15.00 Invited Lecturer - Prof. Abolghasem JOUYBAN Drug solubility prediction in water + cosolvent mixtures, recent progresses 15.00-15.30 Invited Lecturer - Prof. Dr. Şeref GÜÇER Fundamental Analysis Studies for Pharmacological Analysis: Assesment of Lithium Bioavailability 15.30-15.45 Dr. Nihal ŞİMŞEK OZEK Molecular Analysis of Effects of Chronic Simvastatin in Rat Sciatic Nerve and Liver Microsomal Membrane by FTIR Spectroscopy
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
15.45-16.00 Assist. Prof. Dr. Gülşah GÜNDOĞDU Association of Serum Omentin Levels with ST Segment Elevation and Non-ST Segment Elevation Acute Coronary Syndrome
16.30-18.30 Social Programme (Center Trip)
20.00-22.00 Gala Dinner
7 October 2017 Saturday HALL A SESSION VI (Turkish) Session Chairmen: Prof. Dr. Selma SARAÇ TARHAN, Prof. Dr. Halise İnci GÜL 09.00-10.30 In Memory of Prof. Dr. Tuncel ÖZDEN 09.00-09.30 Invited Lecturer - Prof. Dr. Tijen ÖNKOL My Distinguished Mentor: Prof. Dr. Tuncel Özden 09.30-10.00 Invited Lecturer - Prof. Dr. Yunus KARA Prof.Dr. Tuncel ÖZDEN and R&D Centers 10.00-10.30 Pharm. Fırat NALBANTOĞLU Particular Size Determination of Aerosols Containing Salmeterol and Fluticasone
HALL B SESSION VII (English) Session Chairmen: Prof. Dr. Terken BAYDAR, Prof. Dr. Süreyya ÖLGEN 09.00-10.30 Natural Drugs 09.00-09.30 Invited Lecturer - Prof. Dr. Filiz MERİÇLİ Investigations on some medical plants from Turkey and Northern Cyprus 09.30-09.50 Assist. Prof. Dr. Hilal ÖZBEK Phenolic Compounds from the Leaves of Cotinuscoggygria Scop with Alpha Glucosidase Inhibition 09.50-10.10 Res. Assist. Mert İLHAN Effects of Hyoscyamus niger L. on Myiasis Diseases Caused by Lucilia Sericata 10.10-10.30 Res. Assist. Saime ÖZBEK ŞEBİN The Effects of Tarantula cubensis Extract in Rats with Polymicrobial Sepsis by Cecal Ligation and Puncture Method
10.30-12.00 POSTER SESSION (P1-P132)
HALL A SESSION VIII (English) Session Chairmen: Prof. Dr. Serdar GÜLTEKİN, Prof. Dr. Ahmet HACIMÜFTÜOĞLU 12.00-13.30 Medicinal Chemistry 12.00-12.30 Invited Lecturer - Prof. Dr. Süreyya ÖLGEN Comparison of Predicted Physicochemical Properties and In Vitro Activity of Substituted Indolin-2- one Derivatives 12.30-12.50 Res. Assist. Suat SARI New Azoles in Oxime Ester Structure: Antifungal Susceptibility, Anti-Biofilm Activity and Molecular Modelling Studies 12.50-13.10 Dr. Sülünay PARLAR Lead Compound Optimization Studies on 1H-Benzimidazole Derivatives for Alzheimer Disease 13.10-13.30 Assist. Prof. Dr. Mustafa Kemal GÜMÜŞ Synthesis of Novel Sulphur-Containing Imidazole Derivatives from Glycine Ester
October 05-07, 2017, ERZURUM-TÜRKİYE 9
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
HALL B SESSION IX (English) Session Chairmen: Prof. Dr. İbrahim NARİN, Prof. Dr. Bashar AL KHALIDI 12.00-13.30 Molecular Medicine, Omics 12.00-12.30 Invited Lecturer - Prof. Dr. Tanıl KOCAGÖZ Peptide Antibiotics Inspired from Natural Antimicrobial Peptides 12.30-13.00 Invited Lecturer - Prof. Dr. Bekir SALİH New Advances in Mass Spectrometry-Based Glycoproteomics 13.00-13.20 Assoc. Prof. Dr. Ayşe ERCAN Cytotoxic Effect of Allomaltol Derivative on A375 Human Malignant Melanoma and MCF7 Breast Cancer Cells 13.20-13.40 Dr. Engin KOÇAK MCF-7 Breast Cell Proteome Analysis Determination with New UPLC/MS Method 13.30-14.30 Lunch Break
HALL A SESSION X (English) Session Chairmen: Prof. Dr. Sena SEZEN, Prof. Dr. Nazan BERGİŞADİ 14.30-16.00 Pharmacology and Toxicology 14.30-15.00 Invited Lecturer - Prof. Dr. Ahmet HACIMÜFTÜOĞLU Biocompatible and Second by Second Neurotransmitter Analyzing 15.00-15.20 Assist Prof. Dr. Ayhan TANYELI Possible Protective Effects of Gossypinin on Rats Applied Renal Ischemia Reperfusion Damage 15.20-15.40 Dr. Ferhunde AYSİN Cytotoxic and Antioxidant Activities of a Chitin Derivative on Human Blood Cells 15.40-16.00 Dr. Shemsu Umer HUSSEN Effects Heparin Derivatives on Experimental Pain and Inflammation Models in Rats
HALL B SESSION XI (English) Session Chairmen: Prof. Dr. Mutlu AYTEMİR, Assoc. Prof. Dr. Arzu KARAKURT 14.30-16.00 Short Oral Presentation 14.30-16.00 Short Oral Presentation (OP1-OP21)
16.00-16.45 ORAL POSTER SESSION (OP1-OP21) Session Chair : Prof. Dr. Gülberk UÇAR 16.45- Closing Remarks
8 October 2017 Sunday 09.00- 18.00 Tortum Waterfall Trip
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
Plenary Lectures
October 05-07, 2017, ERZURUM-TÜRKİYE 11
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
PL01 - Advances in Treatment of Pulmonary Arterial Hypertension
Barış Kaya
Department of Cardiology, Faculty of Medicine, Hacettepe University, 06100, Sıhhiye, Ankara, Turkey. E-mail: [email protected]
Pulmonary hyepertension (PH) is a progressive disease of multifactorial etiologies that has poor prognosis and results in right heart failure and eventually death. PH is an hemodynamic and pathophysiologic condition defined as mPAP ≥ 25mmHg at rest measured during right heart catheterisation. Pulmonary arterial hypertension (PAH) is a complex, progressive disease with several pathobiological mechanisms, including the endothelin, nitric oxide and prostacyclin pathways. Together, these complex interactions promote aberrant cellular growth, vasoconstriction, apoptosis, and hemostasis within the pulmonary vascular arteries that result in elevation of pulmonary vascular resistance (PVR) and right ventricular failure. The past decade has witnessed an unsurpassed interest and progress in the field of PAH. Before 1996, PAH was a uniformly fatal disease with no effective treatment. Now, there are different therapeudic options targeting one of these pathways and with several more being actively investigated. As a result, significant improvements have been achieved in helping patients live better and live longer. However, significant morbidity and mortality continue to dominate despite treatment. Significant developments have been made in the management of PAH over the last decade. These include an increased understanding of the need for earlier detection and treatment, changing disease characteristics, the continuing development of new treatment options and an increasing perception of the specific challenges that patients with PAH face at each stage of illness. Furthermore, an updated treatment guidelines on Pulmonary Hypertension has been published. Current management strategies for PAH target one of these pathways and, in more severe cases or instances of disease worsening, may be combined with a view to target multiple pathways in parallel. Treatment combination is performed either by sequentially (as an intensification from initial monotherapy) or upfront (use of two or more therapies in treatment-naive patients). Future is promising in terms of understanding pathobiology, development of new drugs or lung diseases.
Keywords: Pulmonary arterial hypertension, right heart failure, combination therapy.
October 05-07, 2017, ERZURUM-TÜRKİYE 12
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
PL02 - Drug Therapy for Arterial Fibrillation; What’s New?
Hikmet Yorgun
Department of Cardiology, Faculty of Medicine, Hacettepe University, 06100, Sıhhiye, Ankara, Turkey E-mail: [email protected]
Atrial fibrillation is the most significant rhythm disorder in the clinical setting which is associated with increased stroke risk, heart failure, hospitalization and mortality. Management of atrial fibrillation mainly includes rhythm control, anticoagulation therapy and treatment of structural disorders. Rhtyhm control for atrial fibrillation includes antiarrhytmic therapy and catheter ablation methods. Antiarrhythmic drugs affect many ionic channels that are operative in the genesis for atrial fibrillation. Therefore understanding the physiology of ionic channels in the atrial myocardium is paramount for the appropriate use of antiarrhtyhmic drugs in various clinical settings but especially atrial fibrillation. Current antiarrhtyhmic drugs mainly affect various parts of action potential according to their ionic channel selectivity and most often antiarrhytmic drugs affect multiple ion channels. Although these drugs can be used in atrial fibrillation, they are also associated with adverse effects with moderate effectiveness. As a result, novel antiarrhythmic drugs mainly affecting pathophysiologic processes in atrial fibrillation are under investigation. Other than traditional antiarrhythmic drugs, these novel drugs mainly affect specific ion channels that are important in the development of AF. In addition to rhythm control, anticoagulation therapy is also important to decrease the stroke risk and mortality in AF. Other than vitamin K antagonists, novel oral anticoagulants mainly affecting as direct thrombin inhibitors or Factor Xa inhibitors gained wide acceptance in the clinical use in the recent years. These novel agents are not only more effective in preventing stroke but also associated with decreased bleeding risk. Atrial fibrillation treatment also includes management of structural remodelling, which includes modification of risk factors like hypertension, diabetes mellitus, thyroid disorders and weight reduction. These measures are important in both primary and secondary prevention of AF. Finally, apart from drug treatment, cardiac interventional electrophysiologic procedures like catheter ablation are more effective in long term freedom from AF. Although catheter ablation is more effective in the rhythm control of AF, adjunctive antiarrhtyhmic treatment is needed in most cases. Future research is needed aiming development of AF specific medical treatment in terms of rhtyhm control, anticoagulation and structural remodelling.
October 05-07, 2017, ERZURUM-TÜRKİYE 13
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
PL03 - Clinical Trials in the Drug Development Process
Nihal Burul Bozkurt
Head of Department of Clinical Trials, Turkish Medicines and Medical Devices Agency, Turkish Ministry of Health, Ankara, Turkey E-mail: [email protected]
Pharmaceutical R&D is comprised of relevant actors and several factors that constitute the environmental conditions. The main actors are universities, research centers, public institutions, private companies and entrepreneurs. Although whole actors subsist in Turkey, the coordination and cooperation between them is insufficient. Both pre-clinical and clinical research are integral parts of R&D. In Turkey, R&D ecosystem is being supported by the government and it is emphasized in the Tenth Development Plan. The long story of the drug begins with discovery. Story continues with in vitro and in vivo preclinical research and afterwards clinical research. Before the application for regulatory affairs, it should be demonstrated with the early tests, preclinical and clinical research that a drug is safe and effective for its intended use. Preclinical studies must provide detailed information on dosing and toxicity levels. After preclinical testing, it is decided whether the drug might be tested on volunteers. “Clinical research” refers to trials that are performed in volunteers. Generally, clinical trials are designed to answer specific research questions related to a medicinal product. It takes about 15 years from discovery to approval. On average, from more than ten thousand molecules only one is investigated in late stage clinical trials and is finally made available for patients. Probability of success rate from phase 1 to approval is 9.6%. Majority of the clinical trials being conducted in Turkey are Phase 3 studies. Turkey provides related conditions for clinical trials. Legal legislation meets international standards andthe infrastructure such as clinical research centers is appropriate. Unlike clinical trials, the infrastructure for preclinical research is inadequate. For being a major actor in pharmaceutical R&D we need to pay special attention to the pre-clinical research as well as clinical research.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
PL04 - Pharmacovigilance Activities in Turkey
N. Demet Aydın Karahaliloğlu
Head of Pharmacovigilande and Controlled Substances Department, Turkish Medicines and Medical Devices Agency, Ankara, Turkey E-mail:[email protected]
In Turkey, pharmacovigilance activities began with the establishment of ‘‘Turkish Adverse Drug Reaction Monitoring and Evaluation Center’’ (TADMER) in 1985. TADMER joined the WHO Programme for International Drug Monitoring as a 27th member in 1987. First pharmacovigilance regulation known as “Regulation on the Monitoring and Assessment of the Safety of Medicinal Products for Human Use” became effective in June 2005, which was prepared in accordance with the European Union directive. With this regulation, TADMER is renamed as Turkish Pharmacovigilance Center (TUFAM) in order to stress the term “pharmacovigilance”. In addition, three separate guidelines have been issued about the responsibilities of marketing authorizations holders, pharmacovigilance inspections and risk management systems.
In April 2014, the pharmacovigilance legislation was amended and guidelines on good pharmacovigilance practices (GVP) were issued. GVP consists of eight different modules: Module I: Management and reporting of adverse reactions to medicinal products, Module II: Additional monitoring, Module III: Periodic benefit/risk evaluation report, Module IV: Pharmacovigilance quality systems, Module V: Pharmacovigilance system master file, Module VI: Risk management systems, Module VII: Signal management and Annex I: Definitions.
The new regulation allowed patients to report the suspected side effects to the TUFAM or the marketing authorization holders. In this respect, patients who experience side effects themselves, are now the active contributers to the monitoring of drug safety. In addition, information on how and where to report adverse reactions has been added to the summary of product characteristics and patient information leaflets with the new regulation.
Pharmacovigilance mediates the provision of drug safety and therefore the protection of public health. In this respect, our aim is to increase awareness about the adverse drug reactions, to collect and to monitor our national data, and use our national database as a reference to the decision making processes conducted for the medicinal products licensed in Turkey.
Keywords: TUFAM, pharmacovigilance, drug safety
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
PL05 - Marketing Authorısatıon of Medicines in Turkey
Hacer Çoşkun Çetintaş Turkish Medicines and Medical Devices Agency, Ankara, Turkey
Modern developments related to medicine regulations have started in particular since 19th century. These regulations have accelerated due to some unfortunate events like sulfanilamide disaster and thalidomide tragedy. As a result, since 1960s and 1970s, regulations on medicines have been quickly reshaped and the process from the development of medicines to the production, distribution, storage and delivery to patients has begun to be strictly regulated. Therefore, the main task of the medicines regulatory authorities is to examine the safety, efficacy and quality of medicines and make regulations in this direction. The main regulatory activity developed within these regulations to ensure safety, efficacy and quality of medicines is marketing authorisation which includes a comprehensive evaluation process of medicines in scientific and administrative terms. The medicines regulatory authority responsible for the marketing authorisation of human medicines in Turkey is Turkish Medicines and Medical Devices Agency (TMMDA). Marketing authorisation procedures are conducted in line with the legislation of European Medicines Agency in the context of harmonization with the European Union. Marketing authorisation applications accepted under various types of applications are approved by clinical, pharmaceutical technological, pharmacological and administrative evaluation processes according to the characteristics of the drugs and requirements of the application. Monitoring of the safety of medicines after approval is also carried out by TMMDA.
October 05-07, 2017, ERZURUM-TÜRKİYE 16
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
PL06 - Biological efficacy of SN-38 loaded PLGA-PEG-PLGA nanoparticles
S.Dimchevska, N.Geskovski, K.Goracinova
Faculty of Pharmacy, University of SS Cyril and Methodius, Skopje, Macedonia *E-mail: [email protected]
Within the last several decades, nanomedicines has emerged as proficient vessels for targeted drug delivery and diagnostics. However, the limited number of consistent assays and evaluation criteria for these novel t h e r a p e u t i c Aside the physico-chemical characterization for the formulations from the design we evaluated the sprocesses at the nano-bio interface and protein corona formation for particles with different surface yproperties as well as their influence upon the bioreactivity, biodistribution profile, cell internalization rate sand efficacy potential. The copolymer/drug ratio during the nanoparticle preparation using tnanoprecipitation method as well as solvent extraction and solidification rate were extremely important for eavoiding of the premature precipitation, free drug crystallization and low drug loading. BSA adsorption mstudies pointed that thicker and more rigid hydrophilic barrier at the surface of the NPs was an effective ssteric barrier to protein adsorption. During plasma protein adsorption studies, various composition of ,protein corona for each type of NPs was observed especially at the later time periods (1h and 4h). especiallyInternalization in the studies field ofpointed comprehensive to protein analysiscorona influence of the interactions upon the ratewith of the cell biological internalization. environment The MTT and theirtest revealed efficacy, that safety the and viability toxicity, of theis a cellsconstant was drawbacknot altered that in hindersthe tested the NP marketing concentration approval. range. Hence, Different there isgene an expressionevident need profiles for new of SNapproaches-38 solution in theand developmentSN-38 loaded of NPs, the demonstratednanomedicines the an efficacyd evolution potential of new of standardizedthe prepared nanocarrierstests and criteria Accordingly that will shedwe’v moree created light a onpool their of usefulbiological data behaviorthat may andbe employed fate. Therefore, for further our workimprovements is an attempt of the to targeting introduce potential the concept and safetyof quality of the by nanomedicines. design and safety by design in the development of biodegradable self-assembly nanoparticles (NPs) as carriers for extremely hydrophobic anticancer drug (SNKeywords:-38). Thus, SN -a38,long nanoparticles, with the application protein ofcorona, DoE duringgene expression the development studies of the NPs and evaluation of the factors influencing the physico-chemical properties, we employed a battery of assays to study NP interactionsReferences: with the biological environment in an in vitro and in vivo setup in order to select the optimal formulation1. Dimchevska not S, only Geskovski on account N, Koliqi of their R, Matevska physic chemical-Geskovska properties N, Gomez but Vallejo the biological V, Szczupak behavior B, et al. of Efficacy the NP asassessment well (1) . of self-assembled PLGA-PEG-PLGA nanoparticles: Correlation of nano-bio interface interactions, biodistribution, internalization and gene expression studies. Int J Pharm; https://doi.org/10.1016/j.ijpharm.2017.05.054
Acknowledgement This research received support from the Ministry of Education and Science of Republic of Macedonia and the QualityNano Project http://www.qualitynano.eu/ which is financed by European Community Research Infrastructure Action under the FP7 "Capacities" Program.
October 05-07, 2017, ERZURUM-TÜRKİYE 17
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
PL07 - Recent Advances in Regenerative Medicine: Plastic Surgery Perspective
Mert Çalış
Department of Plastic and Reconstructive Surgery, Hacettepe University, Ankara, Türkiye E-mail: [email protected]
Recently, following the discovery of the adipose tissue as a novel source of mesenchymal stem cells, the stem cell research is a growing field of plastic surgery. Mesenchymal stem cells having trophic effect, immunomodulation, homing to injured tissue and ability to differentiate to other cell lineages appears to be promising in application for regenerative purposes. Stromal vascular fraction known to possess high quantity of stem cells obtained by the enzymatic degredation of the adipose tissue is hoped to be promising as well. Besides having a potential benefit in combined application with fat grafting procedures to increase the viability of adipocytes and postmastectomy breast reconstruction, stromal vascular fraction has a potential application field of chronic wound treatment, autoimmune diseases, tissue engineering research and many indications of regenerative medicine. Most striking restriction in their application in the long term period is the oncologic concerns and there is no doubt that it will be an emerging field of research in the upcoming decades. Besides cellular treatment options, other regenerative advances also appears to offer new solutions for healing problems.
October 05-07, 2017, ERZURUM-TÜRKİYE 18
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
PL08 - Drug Delivery for Neuroprotection: Opportunities and Challenges
Hakan Eroğlu1, Alice Gaudin2,3, Sinda Lepetre-Mouelhi2,3, Ömer Faruk Tü rkoğlu4, Mustafa F. Sargon5, Patrick Couvreur2,3, Mohammad Karim Haidar1, Gülen Melike Demirbolat6, Şükrü Öztürk7, Cem Bayram8, Emirhan Nemutlu9, Kezban Ulubayram7,10, Canan Çakır Aktaş11, Ebru Bodur11, Levent Öner1 E-mail: [email protected]
1 Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 06100 Sıhhiye, Ankara, Turkey 2 Institute Galien Paris-Sud, UMR CNRS 8612, Faculty of Pharmacy, University of Paris Sud XI, 92296, Chatenay Malabry, France 3 Labex d’Excellence NanoSaclay, France 4 Ankara Atatü rk Research and Training Hospital, clinics of Neurosurgery, Bilkent, Ankara, Turkey 5 Hacettepe University, Faculty of Medicine, Department of Anatomy, 06100, Sıhhiye, Ankara, Turkey 6 Gazi Üniversity, Faculty of Pharmacy, Department of Pharmaceutical Technology, 06330, Etiler, Ankara, Turkey. 7 Hacettepe University, Institute for Graduate Studies in Science and Engineering, Bioengineering Division, 06100, Beytepe, Ankara, Turkey 8 Hacettepe University, Advanced Technologies Application and Research Center, 06800, Beytepe, Ankara, Turkey 9 Hacettepe University, Faculty of Pharmacy Department of Analytical Chemistry, 06100 Sıhhiye, Ankara, Turkey 10Hacettepe University, Faculty of Pharmacy Department of Basic Pharmaceutical Sciences, 06100 Sıhhiye, Ankara, Turkey 11 Hacettepe University, Faculty of Medicine Department of Biochemistry, 06100, Sıhhiye, Ankara, Turkey
Nerve injury is a clinical situation, which is observed depending on various reasons and affects the life quality of the patients seriously. Traumatic injuries as well as metabolic, toxic and vascular reasons might be the causes for peripheral nerve injury. The major causes of trauma are laceration, focal contusion (armed injuries) traction injuries, compression injuries, drug injection injuries and electrical injuries. Especially, spinal cord injury and peripheral nerve injury affect the daily life of the patients in a higher degree. It is very clearly stated in the classification of peripheral nerve injuries that prognosis includes a time period of starting from weeks up to months. The surgery is almost necessary; however clinical outcomes that do not end positively is observed in most cases with incomplete recovery. Depending on these facts, new formulation perspectives are being explored to improve the efficacy of the treatment in neural injury models. Although some pharmacological agents exert neuroprotective effects in such cases, they still lack of maintenance at the site of action for proper time period, enough elimination half-life to show its effects or stability problems in systemic circulation. Dual delivery of some pharmacological agents may also be a new treatment option in such cases, despite this theory is not novel; but might be a precious one in injury treatment. In this lecture, new formulations like adenosine squalene nanoparticles, PLGA microspheres containing atorvastatin and alpha- lipoic acid for dual effect and nanofiber formulations, in which nanoparticles are embedded for dual delivery of the prior agents will be discussed in details and current experimental results will be outlining the recent improvements. (The authors would like to thank TÜBİTAK for supporting nanofiber part of this study with the project number 115S202)
October 05-07, 2017, ERZURUM-TÜRKİYE 19
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
PL09 - In Vitro Artificial Membrane-Natural Mucosa Correlation of Carvedilol Buccal Delivery
Bashar Alkhalidi
Pharmaceutical Technology (Industrial Pharmacy), Faculty of Pharmacy, University of Jordan, Amman-Jordan E-mail:[email protected]
Development and evaluation of buccal formulations is highly challenging and requires lengthy permeation studies. In vitro studies include preparation of freshly excised mucosa from sacrificed animals that should be immediately employed to test permeation. In addition, inconsistent permeability results arise due to variations in tissue preparation. A simple and rapid method for in vitro evaluation is required to overcome erratic results, save on animals, and accelerate the development process of buccal products. The current work investigated the use of model polymeric membranes; cellulose acetate and cellulose acetate-nitrate, as rapid-screening alternative to the natural mucosa. Permeability coefficient and steady-state flux for carvedilol, a model hydrophobic drug, were determined in natural and artificial membranes. The effect of chemical enhancers on permeability through polymeric membranes was measured and compared against that in porcine and rabbit mucosa. A strong and statistically significant correlation between artificial membranes and buccal mucosa for the delivery of carvedilol was established.
October 05-07, 2017, ERZURUM-TÜRKİYE 20
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
PL10 - Pros and Cons of Using Tubular Nanostructures and Quantum Dots to Deliver Drug Molecules
İsmail Tuncer Değim, Zelihagül Değim Biruni University Faculty Of Pharmacy, Department of Pharmaceutical Technology, 34010 Topkapi, İstanbul; Turkey Nanostructures have been proposing and using to deliver active drug molecules to the body or targeted cells for years in many experiments. Lipid nanotubes, carbon nanotubes, boron nitride nanotubes, fullarens, cochleates and quantum dots have been using and many experimental results showed some successful results but although many of them have been conducting using similar conditions their results were not exactly the same. Tubular nanostructures sometimes deliver active molecules through biological membranes by acting as nano-needles but interestingly many of them have been delivering the same molecules by adsorption/desorption mechanism at the same time. The surface or depot effect plays an important role. Active phagocytosis, entering to lymphatic system can also be possible. Penetrating through pores or vacuoles can also be incorporated. It is important to understand which mechanism can be dominant or what can be the main mechanism when environmental condition is known. The present results in the literature can be used predict when tubular nanostructures act as nano-needles. The other hurdles appeared to be toxicity and unpredictable behavior of these nanostructures. Therefore recent study results will be given using lipid, carbon, boron nitride nanotubes and cochleates as well as quantum dots. Recent interpretations about tubular nanostructures will be given and when and why they can act as nano-needles will be explained. A new type of quantum dots will be introduced to overcome some toxicity issues. The changes on solvent molecules (namely water) behavior will be given, why solvent molecule characteristics are changing and how it can affect the delivery of parent drug molecules will be explained. Finally all results were compared and pros and cons of using tubular nanostructures and quantum dots to deliver drug molecules will be discussed. References 1- Ilbasmis-Tamer S, Unsal H, Tugcu-Demiroz F, Kalaycioglu GD, Degim IT, Aydogan N, Stimuli Responsive Lipid Nanotubes In Gel Formulations For The Delivery Of Doxorubicin, Colloids and Surfaces B: Biointerfaces 143, 406– 414, 2016. 2- Andersen AJ, Windschiegl B, Ilbasmis-Tamer S, Degim IT, Alan Christy Hunter, Thomas L. Andresen, Seyed Moein Moghimi, Complement activation by PEG-functionalized multi-walled carbon nanotubes is independent of PEG molecular mass and surface density, Nanomedicine: Nanotechnology, Biology, and Medicine, 9, 469–473, 2013. 3- Degim IT and Kadioglu D, Cheap, Suitable, Predictable and Manageable Nanoparticles for Drug Delivery: Quantum Dots Current Drug Delivery, 10, 32-38, 2013. 4- Ilbasmiş-Tamer S, Yilmaz S, Banoğlu E, Degim IT, Carbon nanotubes to deliver drug molecules, J Biomed Nanotechnol., 6, 20-7, 2010. 5- Degim IT, Burgess DJ, Papadimitrakopoulos F, Carbon nanotubes for transdermal drug delivery, J Microencapsul. 27, 669-681, 2010. 6- Ilbasmis – Tamer S, Degim IT, A feasible way to use carbon nanotubes to deliver drug molecules: transdermal application, Expert Opinion on Drug Delivery, 9, 991-999, 2012. 7- Konczak L, Narkiewicz-Michalek J, Pastorin G, Panczyk T, Effects of intermolecular interactions on the stability of carbon nanotube–gold nanoparticle conjugates in solution, Dovepress, 11, 5837—5849, 2016. 8- Liu X, Pan X, Zang S, Han X, bao X, Diffusion of water inside carbon nanotubes studied by pulsed field gradient NMR spectroscopy, Langmuir, 30, 8038-8045, 2014. 9- Youn SK, Buchheim J, Park HG, (2014) Confined Water in Carbon Nanotubes and Its Applications. In: Mercury L., Tas N., Zilberbrand M. (eds) Transport and Reactivity of Solutions in Confined Hydrosystems. NATO Science for Peace and Security Series C: Environmental Security. Springer, Dordrecht.
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PL11 - The Overview of Commonly Used Electrochemical Carbon Nanosensors in Pharmaceutical Assay
Sibel A. Özkan
Department of Analytical Chemistry, Faculty of Pharmacy, Ankara University, 06100 Ankara, Turkey E-mail: [email protected]
Electrochemical nanosensors have recently found extensive applications in pharmaceutical and biomedical industries with some advantages such as lower detection limits, wider linear response range, sensitivity, good stability and reproducibility when compared with other sensors and techniques. Nowadays, a lot of different analytical methods are used in environmental, pharmaceutical, or clinical laboratories and also a number of the commercial point-of-care devices work using nanosensors as a whole or a basic part. Nanotechnology has become very popular in the sensor fields.It is thought that the utilization of such technologies, as well as the use of nanosized materials, could well have beneficial effects for the performance of sensors. Nano-sized materials have been shown to have a number of novel and interesting physical and chemical properties. Low-dimensional nanometer-sized materials and systems have defined a new research area in condensed-matter physics within past decades. Apart from the aforesaid categories of materials, there exist various materials of different types for fabricating nanosensors. In recent years, carbon based nanosensors have great use of in pharmaceutical application, further for real sample applications like dosage forms, human body fluids etc. Carbon is called as a unique element, due to its magnificent applications in many areas. It is an astonishing element that can be found many forms including graphite, diamond, fullerenes, and graphene. Today, application of different nanoparticles in construction of sensors as a modifier is quite frequent. The nanoparticles have different effects on response of the nanosensor besides improving their thermal, electrical, and mechanical properties. As the demand for smaller, faster, cheaper, and ultrasensitive qualification and quantification of samples rapidly increases, these methods provide a viable path toward the next generation of electrochemical sensors.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
PL12 - Fundamental Analytical Studies for Pharmacological Analysis: Assessment of Lithium Bioavailability
Umran Seven Erdemir, Seref Gucer *
Uludag University, Faculty of Arts and Sciences, Department of Chemistry, 16059, Bursa, Turkey *E-mail: [email protected]
Li is an ultra-microelement although its essentiality seems controversial (1-3). Various medicinal properties of Li especially its neuroprotective and mood-stabilizing effects stand out since the end of the 1940s (3, 4). There is an interest nowadays in Li-enriched foods (fortified with different Li salts) with its effectiveness to take place in markets depending on the potential roles of dietary Li beside its usage in psychiatric medicine as a drug in the form of carbonate salt of lithium (3). Although inductively coupled plasma-mass spectrometry (ICP-MS) is a powerful analytical technique for ultra-trace analysis, direct analysis of Li could be seen problematic by ICP-MS without elimination of the major type of interferences. Moreover, in vitro bioavailability methodologies are needed for pharmacological interests depending on the importance of Li as a drug and its narrow therapeutic index.
In this study, nutritional characteristic of a tea as a commonly used beverages were detailed which will show the importance of competitive and the complementary effects of macromolecules to Li dosages in terms of bioavailable levels. As unknown mechanisms of Li has been also highlighted, understanding its real pathway as well as any extrinsic factors that may affect its absorption in metabolomics networks will provide a threshold knowledge before prescription of Li drugs.
Keywords: Lithium, Lithium Drug, Nutrition, Bioavailability, ICP-MS
References: 1. Franzaring J, Schlosser S, Damsohn W, Fangmeier A. Regional differences in plant levels and investigations on the phytotoxicity of lithium, Environ. Pollut. 2016; 216:858–865. 2. Maria D, Zaneta K, Jadwiga M. Lithium content in the tea and herbal infusions, Eur. Food Res. Technol. 2015; 241:289–293. 3. Rzymski P, Niedzielski P, Siwulski M et al. [1] Lithium biofortification of medicinal mushrooms Agrocybe cylindracea and Hericium erinaceus. Journal of Food Science and Technology-Mysore. 2017; 54: : 2387–2393. 4. Diniz BS, Machado-Vieira R, Forlenza OV. Lithium and neuroprotection: translational evidence and implications for the treatment ofneuropsychiatric disorders. Neuropsychiatric Disease and Treatment. 2013; 9: 493–500.
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PL13 - Particular Size Determination of Aerosols Containing Salmeterol and Fluticasone
Fırat Nalbantoğlu a*, Tijen Onkol a, Metin Karabulut b, Gürmen Kaynar b, Mahmut Özbek b, S. Tuncel Özden c
a Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University b World Medicine Pharmaceutical Company c Üsküdar University *E-mail: [email protected]
Inhalers are mainly used to treat respiratory diseases and they are applied with respiration while they target the lungs of the patient for local treatment. Inhalers have advantages over conventional drug formulations and some of the advantages can be stated as smaller dosing, faster response time, less side effects. Thus, they are widely used for the treatment of pulmonary disesases.1 Salmeterol is a long acting β2 adrenergic agonist used in inhaler formulations for the treatment of pulmonary diseases like asthma and chronic obstructive pulmonary disease. Fluticasone is a steroid molecule used for its anti-inflammatory effects and it is also used in pulmonary diseases. Both drugs can be used in treatment in separate formulations but combination formulations have advantages over formulations consisting these drugs individually.2 This study is conducted on the pressurized metered dose inhaler (MDI) formulations consisting combination of salmeterol (xinafoate salt) and fluticasone (propionate salt). Particle size attributes of the drugs were simultaneously evaluated using a newly developed and validated analytical method. Andersen Cascade Impactor was used to separate the particles as per their aerodynamic particle size distribution. High performance liquid chromatography (HPLC) is used to determine the assay in the separated particles. The method was validated according to International Conference on Harmonisation (ICH) guidelines. This study is conducted in collaboration of Gazi University and World Medicine Pharmaceutical Company as a part of the San-Tez project (00919.STZ.2011-1) awarded by Turkish Ministry of Science, Industry and Technology.
Keywords: Inhaler, HPLC, Andersen Cascade Impactor
References: 1. McFadden Jr, E. R., Improper patient techniques with metered dose inhalers; Clinical consequences and solutions to misuse, Journal of Allergy and Clinical Immunology, 1995;96(2):278-283 2. Calverley, P., R. Pauwels, J. Vestbo, P. Jones, N. Pride, A. Gulsvik, J. Anderson, and C. Maden., Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial, The Lancet, 2003;361(9356):449-456
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PL14 - Investigations on some medical plants from Turkey and Northern Cyprus
Filiz Meriçli
Near East University, Faculty of Pharmacy, Deparment of Phytotherapy- Phytopharmacy, Nicosia, Turkish Republic of Northern Cyprus E-mail: [email protected]
Turkey and Cyprus are the points of the encounter of several different eco-systems. Flora of Turkey is represented with more than 10.000 plants and about one-third of them are endemic. Cyprus, the third largest island of the Mediterranean Sea, in Northern Cyprus more than 1800 plants are growing wildly and 22 of them are endemic plants. Besides a rich plant diversity, Turkey and Cyprus are also very rich in cultural variation depending on historical and geopraphical situations. The plant and cultural diversities in Turkey and Cyprus, provide very rich traditional treatments and folk medicines. Folk remedies and medicinal plants of Turkey and Cyprus are investigated by Turkish scientists working in Faculty of Pharmacy and related professions. More than 1100 new compounds have been isolated from the plants collected from different areas of Turkey. Some posionus plants such as Aconitum, Delphinium and Consolida species can be evaluated for producing homeopathic medicines(1). The active principles of Silybum marianum, Crataegus, Thymus, Origanum, Salvia species and Dorystoechas hastata which is a monotypic plant endemic to Antalya of Turkey, have been determined and their uses as sources of herbal medicinal products have been also investigated by us(2,3). Ceratonia siliqua, Prunus dulcis and Thymus capitatus are the most important plants used traditionaly in Northern Cyprus(4,5).
In this speech, our researches on some medicinal plants from Turkey and Northern Cyprus and their possibility of herbal medicines production will be summarized.
References: 1. Meriçli. F., Meriçli A.H., et al.“Willipelletierine, a New Diterpenoid Alkaloid from Consolida scleroclada (Boiss.) Schrod.”, Pharmazie, 57. 761-62 (2002). 2. Süzgeç,S., Meriçli, A.H., Houghton, P.J., Çubukçu, B.,Flavonoids of Helichrysum compactum and their Antioxidant and Antibacterial Activity, Fitoterapia, 76, 269-272 (2005). 3. Ulubelen. A., Meriçli A.H., Meriçli, F., ” Diterpenes and norditerpenes from the roots of Dorystoechas hastata”, Pharmazie, 59. 301-303 (2004). 4. Tuncay,B., Özalp,Y. , Başgut,B., Yiğit-Hanaoğlu,D., Meriçli, F. “Herbal Chewing” Tablet Preformulation Studies Using A Mediterranean Plant Ceratonia siliqua For Weight Control And Diabetic Disorders” MESMAP-3(3rd Symposium on Medicinal and Aromatic Plants of Mediterranean, April 13-16, Kyrenia,TRNC (2017). 5. Meriçli, F., Becer, E., Kabadayı, H., Hanoğlu, A., Yiğit Hanoğlu, Özkum Yavuz, D., Özek, T., Vatansever,S. “Fatty Acid Composition and Anticanser Activity in Colon Carcinoma cell Lines Of Prunus dulcis seed Oil”, Pharmaceutical Biology, 55,1,1239-1248 (2017)
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
PL15 - Comparison of Predicted Physicochemical Properties and In Vitro Activity of Substituted Indolin-2-one Derivatives
Süreyya Ölgen
Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, Biruni University, 34010, Topkapı, İstanbul, Turkey. E-mail: [email protected]
Src Family Kinase (SFKs) inhibitors have been designed as anti-cancer agents in past several years and several small molecules were approved by FDA for clinical studies1. The discovery of novel small molecules with potential usefulness and to design a potent, selective and less toxic anticancer agent is still a major challenge for medicinal chemistry researchers. Unwanted pharmacokinetic properties of drugs are major problems for drug development2. Prediction of pharmacokinetic properties is important to adjust dose and to select pharmacotherapy regimen. This is also very important to minimize the potential disadvantages of new drug candidates during the preclinical development phase and it is necessary to fully understand the role of pharmacokinetic properties in clinical studies. In the literature, it was shown that various substituted indolin-2-one derivatives have the ability to inhibit several SFKs3. In this study, the pharmacokinetic data of indole based compounds (Figure 1) were predicted by using internet based medchemstudio program4. Predictions of tyrosine kinase inhibitory properties of compounds were determined by molinspiration program5. The correlation between these data and actual in vitro kinase activity results will be discussed.
Figure 1. Novel 3-(substituted-benzylidene)-5-(4-fluorophenyl)indolin-2-one (1-8), 1-(3-substituted- benzylidene-2-oxoindolin-5-yl)-3-ethylurea (9-16) and 1-benzyl-3-(3-substituted-benzylidene-2- oxoindolin-5-yl)thiourea (17-24) derivatives
Keywords: Src Family Kinase, Prediction, Pharmacokinetic Properties, Anti-Cancer
REFERENCES 1. Roskoski, R. Src protein-tyrosine kinase structure, mechanism, and small molecule inhibitors. Pharmacol. Res., 2015;94:9-25. 2. Hisaka A, Ohno, Y, Yamamoto, T, Suzuki, H. Prediction of pharmacokinetic drug–drug interaction caused by changes in cytochrome P450 activity using in vivo information, Pharmacology & Therapeutics, 2010;125:230- 248. 3. Zhang S, Yu D. Targeting Src family kinases in anti-cancer therapies: turning promise into triumph. Trends in Pharmacological Sciences. 2012;33:122-128. 4. http://www.simulations-plus.com/software/medchem-studio/ 5. http://www.molinspiration.com/
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PL16 - Peptide Antibiotics Inspired from Natural Antimicrobial Peptides
Tanıl Kocagöz M.D., Ph.D. Acıbadem Mehmet Ali Aydınlar University, Faculty of Medicine, Dept. of Medical Microbiology and Medical Biotechnology, İstanbul, Turkey Antimicrobial peptides produced by a wide spectrum of organisms from insects to humans are natural antibiotics, which may be important alternative therapy agents for infections caused by organisms resistant to classical antimicrobials. Inspired from natural antimicrobial peptides, we designed short peptides showing good antibacterial activity. The peptides consisted of repeating hydrophobic and positively charged amino acids, positioned on one side of the alpha helix. Arginine in peptides resulted in better activity compared to lysine. Having positively charged amino acids at both ends, created better activity for Escherichia coli compared to Staphylococcus aureus, and only at one end, created comparable activities for both organisms. Positioning of arginines on one side in zigzag form prominently increased the activity compared to positioning on linear axis. Elongating hydrophobic tail resulted in self-binding and eliminated the antibacterial activity. Molecular dynamic simulations suggested that a single molecule is capable of creating hydrophilic channel in membrane. Electron microscopic examination of staphylococci treated with these peptides revealed that the bacteria split into halves. Docking studies revealed that the peptides strongly bind to the major peptidoglycan synthesizing membrane protein, glycosyltransferase. Once their safety is proven, these peptides may be promising drugs against organisms resistant to other antibiotics. Development of their synthetic similar derivatives resistant to proteases, will increase their clinical usefulness.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
PL17 - New Advances in Mass Spectrometry-Based Glycoproteomics
Bekir Saliha*, Hacı Mehmet Kayılıb
a Hacettepe University, Department of Chemistry, 06800 Ankara-TURKEY b Çankırı Karatekin University, Department of Chemistry, 18100 Çankırı-TURKEY *E-mail: [email protected]
Glycoproteomics and glycomics are important sub-disciplines of proteomics and both are focused on analyzing to glycosylated proteins to understand their role in the living organisms. In order to achieve in- depth site-specific glycosylation analysis, comprehensive bioanalytical methods including high-throughput tools such as mass spectrometry are required. However, mass spectrometry-based glycosylation analysis includes time-consuming sample preparation steps. On the other hand, there are several difficulties observed in the glycosylation analysis by MS. In a peptide mixture, the ion signals of glycopeptides are suppressed by the ordinary peptides due to low amount of them. Besides that, released glycans have low ionization efficiency. To enhance the analysis efficiency of glycosylated species, enrichment and purification methods are required prior to mass spectrometric analysis. Herein, we describe several bioanalytical methods having different strategies to increase the analysis efficiency of glycopeptides and glycans by MS. In addition, we developed some sol-gel based smart materials for the enrichment of glycopeptides and glycans. In-depth site-specific glycosylation analysis of standard glycoproteins such as IgG and fetuin was achieved by MALDI-MS using sol-gel based materials. These strategies were carried out at the glycopeptide and the glycan level. In addition, human plasma and fetuin N-glycans were analyzed with MALDI-MS and HPLC-FLD by the application of being developed bioanalytical methods. Consequently, glycoproteomics and glycomics-based bioanalytical methods were developed and the mass spectrometric analysis efficiency of glycopeptides and glycans are improved. Determination of the glycosylation sites and the glycoside sequences of glycans on Monoclonal Antibodies (mAbs) used for some different cancer as a new generation drug were performed in details. Keywords: Glycoproteomics, glycan, mass spectrometry, sol-gel, mAbs
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PL18 - Biocompatible and Second by Second Neurotransmitter Analyzing
Ahmet Hacımüftüoğlu
Head of the Dep. of Medical Pharmacology, Medical Faculty, Ataturk University, Erzurum, Turkey. E-mail: [email protected]
Neurotransmitters are playing important roles in some disorders including Parkinson’s disease, major depression, epilepsy, schizophrenia, attention deficit hyperactivity disorder and drug abuse. While microdialysis methods have been used extensively over the last decade to investigate minute-by-minute measures of L-glutamate, the rapid time dynamics of neurotransmitter signaling in the CNS has warranted a technique to measure L-glutamate release on a second-by- second basis. In vivo electrochemistry utilizes microelectrodes that can be implanted into the mammalian CNS, which can provide records of chemical signaling of neurons. The microelectrode’s recording surface can oxidize or reduce compounds of interest.
The goal of my studies is to develop a recording technology for recording second-by-second measurements of neurotransmitters with biocompatible brain sensors. The fabrication of our biocompatible sensors, which can detect brain neurotransmitter concentrations, consists of three steps. These are production of the microelectrodes by photolithographic methods, packaging and coating with selective chemical barriers respectively. The produced sensors are cost efficient and biocompatible. Applied new barriers have increased the selectivity and sensitivity values (This study is supported by Tubitak. Project number: 113S083)
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PL19 Drug Solubility Prediction in Water + Cosolvent Mixtures, Recent Progresses
Abolghasem Jouybana
a Pharmaceutical Analysis Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
Drug solubility is an important property in pharmaceutical area from both practical and theoretical viewpoints and ~ 40% of drug candidates fail to proceed further simply due to their poor solubility. Drug solubility is involved in several pharmaceutical procedures like drug purification processes, drug identification, and liquid dosage forms design. It is generally accepted that the more soluble drugs also exhibit higher dissolution rates in the respective solvents. The experimental determination and correlation of the solubility of drugs in mixed solvents has been a rapidly growing area. The solvent composition effects on drug solubility is represented by log-linear model of Yalkowsky and the combined nearly ideal binary solvent/Redlich-Kister model as cosolvency prediction tools. Furthermore, the combined effects of temperature and mixtures composition are analyzed by means of the Jouyban-Acree model. A number of attempts were made to include some physic-chemical properties such as Abraham parameters within the common cosolvency models for providing better predictions. This presentation is focused on recent progresses made on drug solubility prediction methods in water + cosolvent mixtures at various temperatures.
References: Jouyban A. Handbook of Solubility Data for Pharmaceuticals; CRC Press: Boca Raton, FL, 2010. Jouyban A, Acree Jr WE. Int J Pharm, 167 (1998) 177-182.
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Oral Presentations
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O 01 - Possible Protective Effects of Gossypinin on Rats Applied Renal Ischemia Reperfusion Damage
Ayhan Tanyeli a*, Ersen Eraslan a, Mustafa Can Güler a, Nezahat Kurt b, Erdem Toktay c
a Department of Physiology, Faculty of Medicine, Atatürk University, Erzurum, Turkey bDepartment of Biochemistry, Faculty of Medicine, Atatürk University, Erzurum, Turkey cDepartment of Histology and Embryology, Faculty of Medicine, Atatürk University, Erzurum, Turkey *E-mail: [email protected]
The kidney is very sensitive to ischemia reperfusion (IR) damage due to its high metabolism. IR injury is seen in intensive care units as secondary trauma, shock, sepsis, kidney transplantation, cardiovascular and urological surgery [1, 2]. Acute renal failure, which is caused by renal IR injury, causes high mortality and morbidity, but unfortunately today no effective preventive or therapeutic drug has been developed. In this study, the effect of Gossypin on renal ischemia reperfusion injury was investigated. A total of 48 Wistar albino rats have been used in the study. Random 6 groups were formed (8 rats in each group). Group 1: Control; Group 2: Sham control; right nephrectomy was performed. Group 3: I / R; Right nephrectomy was performed and 1 hour ischemia and 24 hours reperfusion were applied to the left kidney. Group 4: I/R + DMSO; Group 5: I/R + low dose Gossypin; Group 6: I/R + high dose Gossypin; Surgical procedures in group 3 were performed on groups 4, 5 and 6. Respectively, DMSO, low dose and high dose Gossypin were administered intraperitoneally to the animals in Group 4, 5 and 6 before the commencement of reperfusion. 24 hours after the renal IR model, the rats were sacrificed and renal tissues were removed and biochemical examinations were performed. Although not statistically significant in the I/R group compared to the control group, the increased TNF-α level decreased in the high-dose gossypin group compared to the I/R group. In the DMSO group, the TNF-α level, which was higher than that of the I/R group, decreased in the low dose gossypin group, even though it was not statistically significant. IL-10 level was decreased in I/R group compared to the control group but increased in gossypin groups, although not statistically significant. Total oxidant level (TOS) was decreased in gossypin groups, although it was not statistically significant compared to I/R group. While total antioxidant level (TAS) decreased statistically in the I/R group compared to the control group, it increased in gossypin groups but not statistically significant compared to the I/R group. Oxidative stress index (OSI) was increased in the I/R group compared to the control, but decreased in the gossypin groups, although it was not statistically significant. Gossypinin, I/R hasarında önemli rol oynayan proinflamatuar sitokin olan TNF-α düzeyini azaltırken, antinflamatuar sitokin olan IL-10 seviyesini arttırdığını saptadık. In this study, it was determined that gossypin increased the antioxidant level and decreased the oxidant level and decreased the oxidative stress. Gossypin reduced the level of TNF-α, a proinflammatory cytokine that plays an important role in I/R injury, it increased IL-10 level, which is an anti-inflammatory cytokine. These results suggest that gossypin reduces I/R damage in the kidney.
References: 1.Ahmadiasl N, Banaei S, Alihemmati A, Baradaran B, Azimian E. The anti-inflammatory effect of erythropoietin and melatonin on renal ischemia reperfusion injury in male rats. Advanced pharmaceutical bulletin. 2014;4(1):49- 54. 2.Sancaktutar AA, Bodakci MN, Hatipoglu NK, Soylemez H, Basarili K, Turkcu G. The protective effects of pomegranate extracts against renal ischemia-reperfusion injury in male rats. Urology annals. 2014;6(1):46-50.
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O 02 - Cytotoxic Effect of Allomaltol Derivative on A375 Human Malignant Melanoma and MCF7 Breast Cancer Cells
Ayşe Ercan.a , Aytemir M.D. b, Karakaya G.b, Öncül S. a
a Hacettepe University, Faculty of Pharmacy, Department of Biochemistry, 06100, Sıhhiye, Ankara, Turkey bHacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 06100, Sıhhiye, Ankara, Turkey *E-mail: [email protected]
Malignant melanoma is the most aggressive and life threatening type of skin cancer and shows an increasing incidence every year. Affecting fair-skinned people mostly, it can be seen at any age and in any region of the skin following excessive sun exposure. Despite improved treatment options, patients with advanced malignant melanoma still have poor prognosis. [1]. Breast cancer is the most prevalent malignancy amongst women worldwide. Despite improved treatments including surgery, radiotherapy, chemotherapy and hormone therapy, poor diagnosis, the risk of metastasis and the possibility to develop multidrug resistance remain to be great obstacles. Treatment of both malignant melanoma and breast cancer cells mostly rely on chemotherapy. Still, less toxic, more effective solutions are needed. In our laboratory, kojic acid derivatives were synthesized and their extensive bioactivities were determined including anticonvulsant, antibacterial, antifungal, anti-mycobacterium and antiviral activities 2-5. In this study, we will present the results of the cytotoxic activity of the “Compound” which is a Mannich base of allomaltol carrying 3,4-dichlorobenzyl piperazine moiety. Viability of A375 malign melanoma, MCF-7 breast cancer cells and HGF1 fibroblast cells exposed to the Compound was assessed by sulforhodamine B (SRB) assay. SRB under mild acidic conditions is an aminoxanthene dye that binds to the basic amino acid residues of cellular proteins. SRB assay is a colorimetric method based on measurement of cellular protein content and used for the determination of cytotoxic cells [6]. Vemurafenib, dacarbazine, temozolomide, lenalidomide and fotemustine currently used in the treatment of malign melanoma and doxorubicin used in the treatment of breast cancer cells were designated as control agents. In our findings, we have discovered that “Compound” was proven to be more effective on malignant melanoma cells compared the standard drugs, except for Vemurafenib. In HGF1 cells the Compound has shown no cytotoxic activity and in breast cancer cells apoptosis was shown to be the preferred cell death mechanism upon administration. Therefore “Compound” is a promising molecule which needs further investigation to enlighten the complex carcinogenesis machinery.
Keywords: A375, MCF7, HGF1, allomaltol, cytotoxicity
References:
1. MacKie RM, Hauschild A, Eggermont AMM. Ann Oncol. 2009, 20 (Supplement 6):1. 2. M.D. Aytemir, Ü. Çalış, M. Özal, Arch Pharm Pharm Med Chem, 2004, 337, 281. 3. M.D. Aytemir, B. Özçelik, Med Chem Res, 2011, 20, 443. 4. G. Karakaya, M.D. Aytemir, B. Özçelik, Ü. Çalış, J Enz Inh Med Chem, 2013, 28(3), 627. 5. M.D. Aytemir, B. Özçelik, G. Karakaya, Bioorg. & Med Chem Lett, 2013, 23(12), 3646. 6. V. Vichai, K. Kirtikara. Nat Protoc 2006, 1,1112
Acknowledgements: This research is funded as a project by TÜBİTAK. Project no: SBAG-315S067.
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O 03 - Cytotoxic and Antioxidant Activities of a Chitin Derivate on Human Blood Cells
Salim Cerig a, Fatime Geyikoglu a, Kübra Koc a, Nihal Simsek Ozek a,b, Ferhunde Aysin a,b*
aAtatürk University, Faculty of Science, Department of Biology, 25240, Erzurum, Turkey bEast Anatolian High Technology Research and Application Center (DAYTAM), Atatürk University, 25240, Erzurum, Turkey *E-mail: [email protected]
Chitin is the second most abundant available biopolymer after cellulose in the world. Chitosan is derived from a natural product, chitin, quite abundant in Crustaseanse and it is widely used in biomedical and pharmaceutical fields. In the current research, cytotoxic and antioxidant effects of chitosan (0-500 mg/L) on human blood lymphocyte (hBL) cultures were investigated. Total antioxidant capacity (TAC) and total oxidative status (TOS) were analyzed to evaluate the changes in oxidant/antioxidant levels of chitosan in cultured cells and also XTT cytotoxicity test was used to determine cell viability. Consequently, 0-150 mg/L doses of chitosan increased the antioxidant capacity while reducing oxidative damage. Morever, 500 mg/L dose of chitosan caused oxidative stress. It was determined that 0-250 mg/L doses of chitosan did not cause any damage in cell viability but 500 mg/L dose of chitosan decreased cell viability when the cytotoxic damage was assessed by XTT assay. In conclusion, this abundant biopolymer has dose-dependent effects for human blood cells by inducing oxidative damage and cytotoxicity.
Keywords: Chitosan, cytotoxicity, antioxidant capacity, human blood cells
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O 04 - Association of Serum Omentin Levels with ST Segment Elevation and Non-ST Segment Elevation Acute Coronary Syndrome
Gülşah Gündoğdua, Yavuzer Kozab, Betül Çiçeka, Fatma Demirkaya-Miloğluc, Fuat Gündoğdub
aDepartment of Physiology, Faculty of Medicine, Atatürk University, Erzurum, Turkey bDepartment of Cardiology, Faculty of Medicine, Atatürk University, Erzurum, Turkey cDepartment of Analytical Chemistry, Faculty of Pharmacy, Atatürk University, Erzurum, Turkey *E-mail:[email protected]
Acute coronary syndrome (ACS) is the dominant cause of death and disability in both developed and developing countries. Adipokines are protein/peptides with hormone-like properties released from the adipose tissue and are involved in different stages of atherosclerosis as well as endothelial dysfunction, plaque destabilization and rupture. Omentin is an adipocytokine with antiinflammatory properties. It has been reported to play a role in the pathogenesis of atherosclerosis and coronary disease [1,2].
The aim of study to determine the serum levels of omentin levels before and after percutaneous coronary intervention (PCI) in patients with ST segment elevation (STEMI) and non-ST segment elevation (NSTEMI) ACS and its relationship with ACS. Eighty patients with the diagnosis of ACS (40 STEMI and 40 NSTEMI) between the ages of 45-75 who were admitted to the Cardiology Clinic of Faculty of Medicine of Atatürk University (have not been diagnosed with MI in the last 6 months, severe valve disease, chronic heart failure, coronary artery disease, atrial fibrillation, coronary bypass, malignancy and chronic renal failure) and 30 healthy controls were included in the study. Patients and control groups were questioned about active smoking, drugs used, diabetes mellitus, hypertension, hyperlipidemia and chronic illness. Patients were assessed by using gessini score. Blood samples were taken before and after PCI in the patient group and in the control group during the admission to the hospital. The serum levels of omentin was measured by using ELISA method in patient and healthy groups. At the same time, routine hemogram and biochemical parameters were also measured. The obtained data were evaluated statistically.
The omentin levels of the patient groups were significantly lower than the control group (P<0.001). While there was a statistically significant increase (P <0.01) in the omentin levels after PCI compared to before PCI in the NSTEMI group, was not statistically significant increase in the STEMI group (p>0.05). Omentin levels of the patient groups were determined statistically significant positive correletions between before PCI and after PCI, and also there was statistically significant negative corelated between omentin levels and gessini score in the NSTEMI group, but there was not statistically significant in the STEMI group. In this study; determination of serum omentin levels in patients with ACS can be used by clinicians as new parameters in the diagnosis and treatment of ACS.
Keywords: Acute Coronary syndrom, Omentin, Gessini score References: 1. Chen Q, Shang X, Yuan M, Liang L, Zhong X. Effect of atorvastatin on serum omentin-1 in patients with coronary artery disease. Coronary artery disease, 2017, 28: 44-51. 2. Stejskal D, Vaclavik J, Smekal A, Svobodova G, Richterova R, Svestak M. Omentin-1 levels in patients with premature coronary artery disease, metabolic syndrome and healthy controls. Short communication. Biomedical Papers of the Medical Faculty of Palacky University in Olomouc, 2016,160.
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O 05 - Phenolic compounds from the leaves of Cotinus coggygria Scop. with alpha glucosidase inhibition
Hilal Özbeka, Hafize Yucaa, Sefa Gözcüb, Benan Dursunoğlua, Nadire Özenverc, Cavit Kazazd, Mehmet Önale, L. Ömür Demirezerc, Zühal Güvenalpa
a Department of Pharmacognosy, Faculty of Pharmacy, Atatürk University, Erzurum 25240, Turkey b Department of Pharmacognosy, Faculty of Pharmacy, Erzincan University, Erzincan 24100, Turkey c Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey d Department of Chemistry, Faculty of Science, Atatürk University, Erzurum 25240, Turkey e Non-wood Products Chief Engineering, Regional Directorate of Forestry, Erzurum, 25050, Turkey E-mail: [email protected] Cotinus genus is represented in Turkey with one species [1]. Cotinus coggygria Scop. (Anacardiaceae), commonly known as “smoke tree”, is generally seen as small trees or large shrubs [2] and grows mainly in South and Central Europe, South Russia, Crimea, Caucasia, Latakia and Turkey [1].
In Turkish folk medicine, the decoction of C. coggygria leaves are used against Diabetes mellitus [3] which rises the risk of cardiovascular, renal and neurologic diseases [4]. Several parts like shoots, flowers, leaves and stem of C. coggygria contain biologically active constituents which are mainly polyphenols, flavonoids and tannins [2].
The current study describes the bioguided fractionation and isolation assay for C. coggygria. The ethyl acetate extract, due to its significant α-glucosidase inhibitory effect (IC50 = 0.0082 ± 0.01 mg/mL), was selected for isolation. As a result of this study five phenolic compounds: gallocatechin (1), methyl gallate (2), myricetin-3-O-α- L-rhamnoside (3), myricetin-3-O-β-D-galactoside (4) and 1,2,3,4,6-penta-O-galloyl-β-D-glucose (5) were isolated from this active fraction. The structures of these compounds were determined by extensive spectroscopic analyses. Compound 5 showed significant α-glucosidase inhibitory activity with 0.0015 mg/mL IC50 value among the tested compounds, when compared to the reference standard compound acarbose (3.3642 ± 0.12 mg/mL). The present study has given supporting evidence to verify the ethnomedical use of C. coggygria Scop. against Diabetes mellitus.
Keywords: Cotinus coggygria Scop., Anacardiaceae, α-glucosidase inhibition
References:
1. Davis PH, Coode MJE, Cullen J. Cotinus Adans. In: Davis PH (ed.) Flora of Turkey and the East Aegean Islands Vol. 2. University Press, Edinburgh, 1982. 2. Matic S, Stanic S, Mihailovic M, Bogojevic D. Cotinus coggygria Scop.: An overview of its chemical constituents, pharmacological and toxicological potential. Saudi Journal of Biological Sciences. 2016; 23:452- 461. 3. Baytop T. Türkiye’de Bitkiler ile Tedavi: Geçmişte ve Bugün. Nobel Tıp Kitabevleri, İstanbul, 1999. 4. Shan W, Wu Z, Pang W, Ma L, Ying Y, Zhan Z. α-Glucosidase inhibitors from the fungus Aspergillus terreus 3.05358. Chem Biodivers. 2015; 12: 1718-1724.
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O 06 - Effects of Hyoscyamus niger L. on myiasis disease caused by Lucilia sericata
Mert Ilhan a, Esma Kozan b, Fatma Tuğçe Gürağaç a, Mustafa Sak a, Esra Küpeli Akkol b,*
a Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Etiler 6330, Ankara, Turkey b Department of Parasitology, Faculty of Veterinary Medicine, Afyon Kocatepe University, Afyon, Turkey *E-mail: [email protected]
Hyoscyamus niger L. (Solanaceae) commonly known as herbane is widely distributed in Europe and Asia [1]. The plant has been used treatment of stomach cramps, heavy coughs, neuralgia, manic psychosis, pain and inflammation in Europe. In Turkey, seeds of the plant has been used to eradicate worms on the eyes in folk medicine [2]. The usage of maggot debridement therapy in the world has gained interest in the past decade. Lucilia sericata is a common visitor to carrion, feces and garbage. It plays important role in forensic, medical and veterinary science. Medical treatment using maggot therapy can help to heal infections that are otherwise incurable. In the field of veterinary medicine, feeding by larval L. sericata can cause substantial loses in animals and production. For this purpose we aimed to evaluate the larvicidal activity of H. niger seeds that have been shown earlier to have biological activity against the pathogens causing complicated various larvicidal infections as wild growing in Turkey. Alkaloid extract prepared from seeds of this plant displayed significant activity. So this extract further led to recognition of some alkaloids, mainly hyoscyamine and scopolamine by capillary gas chromatography-mass spectrometry (GC-MS). These results confirmed the folkloric use of the plant. It was suggested that the alkaloid content of the plant could be responsible from the larvicidal activity.
Keywords: Hyoscyamus niger, GC-MS, myiasis
References: 1. Alizadeh A, Moshiri M, Alizadeh J, Balali-Mood M. Black Henbane and Its Toxicity–A Descriptive Review. Avicenna Journal of Phytomedicine. 2014;4(5):297-311. 2. Yeşilada E, Honda G, Sezik E, Tabata M, Fujita T, Tanaka T, Takeda Y, Takaishi Y. Traditional Medicine in Turkey. V. Folk Medicine in The Inner Taurus Mountains. Journal of Ethnopharmacology. 1995;46(3):133-152.
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O 07 - Radiopharmaceuticals for Brain Imaging
Mine Silindir-Gunay a, A. Yekta Ozer a*
Hacettepe University, Faculty of Pharmacy, Department of Radiopharmacy, 06100, Sıhhiye, Ankara. *E-mail: [email protected]
The brain is one of the most complex organs within the human body. It is made up of more than 100 billion nerves communicating lots of connections with synapses. The main problem standing in front of effective imaging and therapy of central nervous system (CNS) disorders is the very limited penetration of imaging agents and drug molecules due to the physical barriers like blood brain barrier (BBB) and brain microvascular endothelial cells (BMVEC) composed of tight junctions between endothelial cells by the absence of fenestrations [1, 2]. They limit and prevent the penetration and entry of compounds from blood to the brain. These barriers can be spoiled and getting leaky in some conditions and diseases such as brain tumors, inflammation, infection etc. [3]. Formulation of new, effective and BBB penetrating nanosized delivery systems is crutial for brain delivery and by this way effective imaging and therapy depending on the existance of barriers. Although conventional radiopharmaceuticals like 99mTc-HMPAO, 99mTc-ECD for brain perfusion and 99mTc-DTPA, 99mTc- pertechnetate for brain death imaging studies can be frequently and practically used in Nuclear Medicine Clinics, novel radiolabeled nanosized nanocarriers are getting important and mostly researched approaches nowadays. Researchers who are expert in brain drug-discovery and brain drug-targeting should work together to formulate more effective formulations to enable BBB transport. One of the most commonly researched approach is the formulation of radiolabeled or contrast agent modified effective drug delivery systems which can deliver to the brain in a large amount. Researchers work on improving radiolabeled drug delivery strategies to the brain to obtain an effective clinical outcome in the diagnosis and imaging of brain disorders such as Parkinson’s disease, Alzheimer’s disease, dementia, glioma etc. Nanocarriers have important advantages in this issue. The essential reasons of choice of directing these formulations are their ability for radiolabeling, ability for BBB penetration by surface modification, improved pharmacokinetic and pharmacodinamic properties, enhanced blood circulation, effective and specific targeting potential, biocompatibility, biodegradability and nontoxicity. By using these approaches target specific radiopharmaceuticals can be successfully formulated in order to specifically and defenselessly diagnose and image several CNS disorders.
Keywords: Brain imaging, blood-brain penetration, radiopharmaceuticals
References: 1. Brightman, M. W., Reese, T.S. (1969). Junctions between intimately apposed cell membranes in the vertebrate brain. The Journal of Cell Biology, 40, 648-677. 2. Pardridge, W. M. (1997). Drug delivery to the brain. Journal of Cerebral Blood Flow Metabolism, 17, 713- 731. 3. Provenzale, J. M., Mukundan, S., Dewhirst, M. (2005). The role of blood-brain barrier permeability in brain tumor imaging and therapeutics. American Journal of Roentgenology, 185 (3), 763-767.
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O 08 - Synthesis of Novel Sulfur-Containing Imidazolone Derivatives from Glycine Ester Mustafa Kemal Gümüş a*, Yiannis Elemes b
a Science-Technology Research and Application Center, Artvin Coruh University, Artvin, Turkey, bDepartment of Chemistry, University of Ioannina, 45110 Ioannina, Greece *E-mail: [email protected]
In the past thirty years, hydantoin or thiohydantoin type imidazolone derivatives have been the point of interest for the synthetic and pharmaceutical industry due to their biological properties, including anticonvulsant, [1] antidepressant, [2] antiinflammatory, [3] antiviral, [4] antitumor [5] activities. Another important characteristic is that they are also effective precursors for the slow release of bioactive volatile compounds [6] and some derivatives have been used with success in crop protection. Imidazolinone herbicides, for example imazapyr imazapic, imazethapyr, imazamox, imazamethabenz, and imazaquin are distinguished selective herbicides that act by inhibiting the enzyme acetohydroxyacid synthase (AHAS), also known as acetolactate synthase (ALS), which is a critical enzyme for the biosynthesis of branched-chain amino acids in plants [7]. Some imidazolinones also have been found to possess fungicidal activities, for example 5-methyl-2-methylthio-5-phenyl-3-phenylamine-3,5-dihydro imidazolin-4-one (Fenamidone) shows high fungicidal activities. The most common synthetic approach to obtain imidazolone skeleton requires the condensation of α-aminoamides, with ketones or aldehydes. Although such procedures do exist, novel methods for imidazole synthesis are still in demand. In our new method methyl-2- [bis(alkyl)sulfanylmethylenamino]acetates (3a-d) were prepared from methyl glycinate by the known procedure and then they reacted with several amines under microwave irradiation without solvent that gave glycine amides (4a-l). Than by the one-component cyclocondensation the amides (4a-l) were transformed into cyclic imidazole-4-ones (5a- l) using solvent-free microwave irradiation as well.
H O O H O 1 R1X CS 1 R S N HClH N 2 S N R X OMe 2 OMe K2CO3 OMe S 2a-d Et3N, CHCl3 acetone 1 S 1 1 S 1 R S O R N R S O 2 MW, 150 °C R NH2 2 N N R solvent free N OMe 1 N 2 R1S MW, 100 °C R S H R 3a-d solvent free O 2 4a-l 5a-l R1: Me, Et, Pr, Bu R : Bn, Bu, Pentyl
Keywords: Imidazolone, thiohydantoin, glycine ester, solvent-free, microwave irradiation
References: 1. Mehta, N.; Risiger, C. A.; Soroko, F. E. J. Med. Chem. 1981, 24, 465. 2. Wessels, F. L.; Sehwan, T. J.; Pong, S. F. J. Pharmacol. Sci. 1980, 69, 1102. 3. Chazeau, V.; Cussac, M.; Boucherle, A. Eur. J. Med. Chem. 1992, 27, 615. 4. El-Barbary, A. A.; Khodair, A. I.; Pedersen, E. B.; Nielsen, C. J. Med. Chem. 1994, 37, 73. 5. Ai-Obaid, A. M.; El-Subagh, H. I.; Khodair, A. I.; Eimaxar, M. M. A. Anti-Cancer Drugs 1996, 7, 873. 6. Trachsel, A.; Buchs, B.; Guillaume, G.; Crochet, A.; From, K. M.; Herrmann, A. Eur. J. Org. Chem. 2012, 14, 2837. 7. Shaner, D. L.; Anderson, P. C.; Stidham, M. A. Plant Physiol. 1984, 76, 545.
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O 09 - Molecular Analysis of Effects of Chronic Simvastatin in Rat Sciatic Nerve and Liver Microsomal Membrane by FTIR Spectroscopy
Nihal Simsek Ozek a,b*, Kumsal Ozgun b, Feride Severcan b,c
a Department of Biology, Ataturk University, Erzurum, Turkey b Department of Biological Sciences, Middle East Technical University, Ankara, Turkey c Altinbas University, Faculty of Medicine, Department of Biophysics, Istanbul, Turkey *E-mail: [email protected]
Statins, known as HMG-CoA reductase inhibitors, are most widely prescribed cholesterol reducing drugs worldwide. Recent studies reported that they have hepatotoxic and neurotoxic effects. Although these toxic effects of drugs have been studied at molecular and genetic level, the underlying mechanisms behind these toxicities have not been elucidated very well. Therefore, the aim to this study to determine the toxic effects of statins in sciatic nerve and liver microsomal membrane with respect to the changes in the structure, concentration and function of macromolecules and thus to contribute to better understanding of the adverse effects of these drugs. During 30 days, 50mg simvastatin/kg and serum physiologic were given orally to both simvastatin and control groups. Drug induced macromolecular alterations were determined from the band frequency, band area and bandwidth analysis of spectral bands in both groups. Student’s t-test was used to calculate statistical significance of the results. Based on the spectral changes, cluster analysis was performed to differentiate the studied groups. Spectral results indicated that simvastatin treatment led to the decrease in unsaturated lipid contents in sciatic nerve whereas the increase in unsaturated lipid amounts in liver microsomal membrane. These results may be due to simvastatin-induced the increased lipid peroxidation. Moreover, the significant alterations in saturated lipid, protein and membrane fluidity were obtained in the studied tissue and membrane. Based on these alterations both groups were successfully discriminated in all samples. High-dose statin treatment induced the formation of hepatotoxic and neurotoxic effects through the biochemical structural and functional alterations in sciatic nerve and liver microsomal membranes. This study also showed that FTIR spectroscopy is an efficient and non-destructive tool in the characterization of drug-induced toxic effects in biological systems.
Keywords: Simvastatin, sciatic nerve, liver microsomal membrane, FTIR spectroscopy.
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O 10 - In vitro Studies on Atenolol Loaded Ion Exchange Resins Özge İnal a*
a University of Ankara, Faculty of Pharmacy, Department of Pharmaceutical Technology, 06100 Tandoğan- Ankara, Turkey *E-mail: [email protected]
Using ion-exchange mechanism could be an alternative drug delivery method for drugs showing poor gastrointestinal stability or various side effects. In this study, atenolol (ATN), a cationic model drug with pKa: 9.6 was used for the preparation of drug-resin complex with an anionic resin, Dowex 50W (DW). Atenolol resinate (ATN-DW) was prepared by batch method [1] by mixing drug and resin (1:1) in HEPES buffer medium for 90 min. Due to low permeation of atenolol through intestinal barriers, permeation enhancers can be utilized to increase paracellular permeability. Chitosan (CH), a cationic polymer providing controlled release, is known to have paracellular permeation enhancing ability because of its Ca+2 inhibition property [2]. Therefore, low molecular weight chitosan was combined with Dowex resin at 1% acetic acid medium while it is in H+ protonated form. The effect of free drug ions and un-loaded resin as well as the effect of chitosan on release kinetics of ATN-DW was studied by dialysis bag method at increasing pH values (Figure 1) and the ion exchange mechanism was monitored by FTIR and SEM (Figure 2) analyses. Release of atenolol from ATN-DW showed an increase due to pH with fitting to Higuchi kinetics and also Case II non-fickian release according to Korsmeyer-Peppas [3]. According to Boyd kinetics, resin-matrix controlled diffusion was also obtained [1]. Although release was significantly higher in pH 6.8 medium, only the 45% of drug released from ATN-DW in 8 hours. The reason of this sustained release profile is thought to be depending on the re-loading of atenolol detached from the resinate. Chitosan, when complexed with Dowex, did not significantly affect the release rate of resinate. However, when used as free polymer, it reduced the release rate as much as un-loaded Dowex. As a result, ion exchange complexes can be used as drug carriers for oral dosage forms. They can sustain or control the release and can be modified in order to ensure the gastrointestinal stability of drugs.
Figure 1. Release profile of drug from of ATN-DW Figure 2. SEM image of ATN-DW in the presence of ATN, Dowex or Chitosan Keywords: Atenolol, dowex 50w, chitosan, ion-exchange complex, release kinetics References: 1. Jeong SH, Park K. Int. J Pharm. 2008: 361: 26-32. 2. Shaikh MS, Derle ND, Bhamber J. J Applied Pharm. Sci. 2012:02 (06): 34-39. 3. Costa P, Lobo JMS. Eur. J Pharm. Sci. 2001: 13:123-133.
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O 11 - The Effects of Tarantula Cubensis Extract in Rats with Polymicrobial Sepsis by Cecal Ligation and Puncture Method
Ayhan Tanyeli a*, Ersen Eraslan a, Mustafa Can Güler a, Saime Özbek Şebin a, Fatma Betül Özgeriş b, Erdem Toktay c a Department of Physiology, Faculty of Medicine, Atatürk University, Erzurum, Turkey b Department of Biochemistry, Faculty of Medicine, Atatürk University, Erzurum, Turkey c Department of Histology and Embryology, Faculty of Medicine, Atatürk University, Erzurum, Turkey *E-mail:[email protected]
Sepsis is a systemic infection that can cause tissue and organ damage, caused by viruses, fungi or parasites, including mostly bacterial infections [1]. Sepsis, which is difficult to diagnose and treat, can cause fatal septic shock resulting in multiorgan failure, especially in the lungs if early diagnosis and treatment is not possible [2]. In this study, polymicrobial sepsis was induced in rats and the effects of Tarantula Cubensis Extract (TCE) were investigated. Wistar albino male rats weighing 220-250 gr were used in this study. 4 random groups were formed. Group 1 (n=8), Sham control: The rat was closed with a suture without any procedure and reached the peritoneum with a 2 cm incision from the abdominal area of the rat. Group 2 (n=7), CLP: The cecum was isolated by reaching the peritoneum with a 2 cm incision from the abdominal area of the rat and the ileocecal valve was ligated up to 2 cm distal, then it was pierced by 18 gauge (4 holes) needle, the cecum was placed back in the abdomen and abdomen was closed with suture. Group 3 (n=7) and 4 (n=7) were administered the same procedures as group 2 were used, and TCE was administered intraperitoneally in low and high doses, respectively, 30 min before the CLP model. After 18 hours from the CLP model, the rats were sacrificed and lung tissues were removed and histopathological and biochemical examinations were performed. Severe edema and leukocyte infiltration observed in the sepsis group were reduced in the low dose TCE group compared to the sham group. No pathology such as sham group was observed in the high dose TCE group. Increased NF-κB, caspase-3, IL-1β and IL-6 immunoreactivity in the sepsis group were found to be negative in the low and high dose TCE groups. In addition, increased TNF-α levels in the sepsis group decreased significantly in the high dose TCE group (p <0.05). In this study, it was determined that TCE decreased NF-κB level playing a role in the release of proinflammatory cytokines, and caspase-3 level, a marker of cellular damage. Expressions of IL-1β, IL-6 and TNF-α, which play an important role in inflammation, were found to decrease in TCE groups. These findings indicate that TCE may have protective effects against sepsis.
Keywords: Sepsis, tarantula cubensis extract, cecal ligation and puncture
References:
1.Hotchkiss, R.S. and I.E. Karl, The pathophysiology and treatment of sepsis. N Engl J Med, 2003. 348(2): p. 138- 50. 2.Sakaguchi, S., et al., Preventive effects of a biscoclaurine alkaloid, cepharanthine, on endotoxin or tumor necrosis factor-alpha-induced septic shock symptoms: involvement of from cell death in L929 cells and nitric oxide production in raw 264.7 cells. Int Immunopharmacol, 2007. 7(2): p. 191-7.
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O 12 - Design and In Vitro Evaluation of Bispecific Complexes and Drug Conjugates of Anticancer Peptide, LyP-1 in Human Breast Cancer
Selin Seda Timur a, Prashant Bhattarai b, R. Neslihan Gürsoy a, İmran Vural a, Ban-An Khaw b *
a Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Turkey b Northeastern University, School of Pharmacy, Department of Pharmaceutical Sciences, USA *E-mail: [email protected]
LyP-1, a nine-amino-acid tumor homing peptide with anticancer properties, selectively binds to its specific receptor, p32. Overexpression of p32 in certain tumors offers an opportunity to use LyP-1 as a tumor targeting peptide for selective delivery of therapeutic or diagnostic agents. Therefore, the aim of this study was developing conjugates for enhanced pretargeting of MDA-MB-231 breast cancer cells with peptide-antibody bispecific complexes and targeting with multiple drug/-fluorophore-conjugated nanopolymers. LyP-1-anti-DTPA bispecific antibody complexes (LyP-1-bsAbCx) were generated by conjugation of anti-DTPA antibody and LyP-1. LyP-1-Doxorubicin conjugates (LyP-1-Dox) were prepared by modification of the linear LyP- 1 peptide with sulfo-NHS and 1-ethyl- 3-(3-dimethylaminopropyl) carbodiimide (EDC). Then, Dox-HCl in dimethylformamide was added and the conjugates were purified by the Sephadex G-10 column centrifugation. DTPA-Dox-PL-LyP-1 conjugates were prepared by coupling of polylysine (PL) with anhydride of DTPA. DTPA- PL was bromoacetylated and purified prior to addition of LyP-1 for coupling. EDC activated Dox was then added drop wise and the un-bound Dox was separated as described above. DTPA- rhodamine conjugated polylysine (DSPL- RITC) were prepared and used in immunocytochemistry studies to evaluate two step targeting of bispecific complexes. Cytotoxicity studies were conducted in MDA-MB-231 breast cancer cells comparing Dox HCl alone and LyP-1-Dox conjugates. For internalization studies, MDA-MB-231 cells were incubated with LyP-1-Fluorescein conjugates for predetermined time intervals and analyzed with iCyte® Automated Imaging Cytometer (Thorlabs Inc., NJ, USA). Cytotoxicity of Dox-LyP-1conjugates was significantly greater than free doxorubicin hydrochloride (p<0.0001). The fluorescent-labeled LyP-1 was shown to be internalized by the tumor cells after 30 minutes of incubation. Flow cytometric analyses illustrated statistical difference between the fluorescence intensity of cells treated with doxorubicin hydrochloride alone and peptide-drug conjugates (LyP-1-Dox, p=0.002 and DTPA-Dox-PL-LyP-1, p<0.001) in MDA-MB-231 breast cancer cells. Fluorescence intensity of two-step targeted cells showed that pretargeting with LyP-1-bsAbCx, followed by targeting with DSPL-RITC increased cellular uptake when compared to that of non-pretargeted DSPL- RITC (p<0.05)
Keywords: Peptide-antibody bispecific complexes, polymer pro-drug conjugates
References: 1.Timur SS, Bhattarai P, Gursoy RN, Vural I, Khaw BA. Design and In Vitro Evaluation of Bispecific Complexes and Drug Conjugates of Anticancer Peptide, LyP-1 in Human Breast Cancer. Pharmaceutical research. 2017;34(2):352-64. 2. Khaw BA, Gada KS, Patil V, Panwar R, Mandapati S, Hatefi A, et al. European Journal of Nuclear Medicine and Molecular Imaging. 2014;41(8):1603-16.
Acknowledgment: This project was supported by TUBITAK (The Scientific and Technological Research Council of Turkey) 2214/A International Doctoral Research Fellowship Program.
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O 13 – Effects of Heparin Derivatives on Experimental Pain and Inflammation Models in Rats
Shemsu Umer Hussen a*, Günnur Özbakış-Dengiz b, Nilüfer Onak Kandemir c
a Department of Pharmacology, Faculty of Pharmacy, Bülent Ecevit University, Zonguldak, Turkey b Department of Medical Pharmacology, School of Medicine, Bülent Ecevit University, Zonguldak, Turkey c Department of Medical Pathology, Ankara Atatürk Education and Research Hospital, Ankara, Turkey *E-mail: [email protected], [email protected]
Heparin and heparin derivatives are widely used for prevention and treatment of arterial and venous thromboembolic diseases. They are commonly prescribed in any clinical situations, including cardiovascular and orthopaedic surgery, acute coronary syndromes, atrial fibrillation, peripheral occlusive disease, and dialysis [1,2]. Heparin also binds to coagulating and fibrinolysing proteins, many growth factors, and immune response proteins such as cytokines and chemokines. Apart from its anticoagulant effects, there are studies showing it possesses anti-inflammatory and immunomodulatory properties. In our study, we investigated whether different heparin derivatives (heparin, enoxaparin and bemiparin) have acute and chronic anti-inflammatory and analgesic effects in rats. In our study, acute inflammation was evaluated using carrageenan induded paw edema model, chronic inflammation in cotton-pellet granuloma test and analgesic effect by hot-plate pain model. In acute inflammation and pain studies, heparin (100- 500-1000 U/kg), enoxaparin (100-200-400 U/kg) and bemiparin (125-250-500 U/kg) doses were used. In chronic inflammaton study heparin 1000 U/kg, enoxaparin 400 U/kg and bemiparin 125U/kg doses were used In carrageenan induced paw edema model in rats, heparin (100-1000 Ü/kg) showed significant anti-inflammatory effect compared to the control group based on paw volumes, weight differences between the two feet and histopathologic evaluations. Bemiparin reduced inflammation at 2nd and 3rd h only at low doses (125 U / kg), but the weight difference between the two feet and histopathological results did not support this. Enoxaparin did not show significant anti-inflammatory effect. Heparin (1000 U/kg) and bemiparin (125 U / kg) showed significant antiproliferative effects in the coton- pellet granuloma test. In the hot-plate test, enoxaparin (100, 200 and 400 U / kg) showed significant antinociceptive effects in almost all measurements, whereas heparin (at all doses) and bemiparin (125 U / kg) showed significant antinociceptive effect only at the 30th minute. In conclusion, heparin and bemiparin showed acute and chronic antiinflammatory and early phase antinociceptive effects. We think that acute antiinflammatory effects may be due to the inhibition of some neuromediators (serotonin, prostaglandin, etc) and active coagulation factors, while their chronic antiinflammatory effects may be a favorable feature for some chronic inflammatory diseases. Enoxaparin showed only antinociceptive effect and this may be through a different mechanism.
Keywords: Heparin, enoxaparin, bemiparin, hot-plate, carragenin, inflammation, rats
References:
1. Alkindi S, Smith OP, Enright H. Successful use of alternative anticoagulants in the management of heparin-induced thrombocytopenia with thrombotic complications: Report of 5 cases and review of literature. Sultan Qaboos University Mededical Journal 2011;11(3):391-398. 2. Chong BH.Heparin-induced thrombocytopenia. Journal of Thrombosis and Haemostasis 2003;1(7):1471-1478.
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O 14 - New Azoles in Oxime Ester Structure: Antifungal Susceptibility, Anti-Biofilm Activity, and Molecular Modeling Studies
Suat Sarıa*, Didem Kartb, Selma Saraça, Arzu Karakurtc, Sevim Dalkaraa
a Dept. of Pharmaceutical Chemistry, Hacettepe University, Faculty of Pharmacy, Ankara, Turkey b Dept. of Pharmaceutical Microbiology, Hacettepe University, Faculty of Pharmacy, Ankara, Turkey c Dept. of Pharmaceutical Chemistry, İnönü University, Faculty of Pharmacy, Malatya, Turkey *E-mail: [email protected]
Candida albicans is a dangerous pathogen with various virulence factors such as biofilm formation and predominantly isolated in invasive candidiasis. Non-albicans Candida infections associate with high mortality and drug resistance. Azoles, which target fungal lanosterol 14 α-demethylase (CYP51), are first-choice antifungals in Candida infections [1]. The minimum inhibitor concentration (MIC) values of a set of previously reported 1-(4- chlorophenyl)-2-(1H-imidazol-1-yl)/(1H-1,2,4-triazol-1-y)ethanone oxime esters [2] against standard Candida sp. (C. albicans, C. parapsilosis, C. krusei) were determined by Broth microdilution in agreement with the CLSI standards. Promising compounds were further tested against immature C. albicans biofilm formation according to the MBEC AssayTM protocol and their MIC values against a flucytosine resistant clinical C. tropicalis isolate were determined. To get insights into their antifungal mechanism molecular docking molecular dynamics (MD) simulations were performed using AutoDock 4 and NAMD, respectively.
Figure. 9-CACYP51 interactions and RMSD/time plots of 9-CACYP51 complex and the apo system Low MIC values were obtained compared to fluconazole, the positive control. Especially, 9 showed highly potent inhibition against all the tested fungi. The compounds showed promising activity against the clinical C. tropicalis isolate and immature biofilm formation of C. albicans. Molecular docking studies revealed that binding interactions of 9 fulfilled the molecular determinants of CACYP51 inhibition. The 25-CACYP51 complex maintained time- dependent stability regarding conformation and energy compared to the apo system in the MD studies.
Keywords: azole antifungal, Candida tropicalis, MIC, biofilm, molecular modeling References: 1.Wong SSW et al. In pursuit of the ideal antifungal agent for Candida infections: high-throughput screening of small molecules. Drug Discovery Today. 2014;11:1721-1730. 2.Sari S et al. New Anti‐Seizure (Arylalkyl)azole Derivatives: Synthesis, In Vivo and In Silico Studies. Archiv der Pharmazie. 2017;350(6):e1700043.
Acknowledgements: This study was supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) (Grant number: 113S060) and Hacettepe University Scientific Research Projects Coordination Unit (Grant number: 014 D09301 001-703, TPT-2015-6794).
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O 15 - Leader Compound Optimization Studies On 1h-Benzimidazole Derivatives for Alzheimer Disease
Güneş Çoban a, Sülünay Parlar a, Görkem Sarıkaya a, Ayşe Hande Tarikoğulları a, Vildan Alptüzün a, Ayşe Selcen Alpan a
a Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ege University, 35040 Bornova, Izmir, Turkey Email: [email protected]
Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disorder. Currently, one of the effective approaches for enhancing the cholinergic transmission is to use the acetylcholinesterase inhibitors in order to enhance the acetylcholine (ACh) concentration in the brain. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) are two different types of cholinesterase that hydrolyze Ach [1]. It is known that the nitrogen atom plays a crucial role in the enzyme-compound interaction [2]. In addition, benzimidazole scaffold is the ring isoster of indanone pharmacophore of donepezil. Thus, 2-phenylsubstitue-1H-benzimidazole ring was chosen as a core structure and basic amine groups were linked to this scaffold with ethoxy chain. Due to the biological activity results, inhibitor activity of the compounds was found generally stronger against AChE than BuChE. According to molecular modeling results, some chemical modifications on the previous compounds were planned for our next study. They included the following changes: i) Due to BuChE active center being wider than that of AChE, basic amine group attached to the ethoxy side chain was replaced from para to ortho position of the phenyl moiety to increase BuChE inhibitory potency. ii) To investigate the dual binding potential, the side chain was extended in the derivatives. With this study, the results showed that ortho substituted derivatives displayed generally more active inhibitory ability than para analogues against BuChE enzyme. However, para substituted derivatives displayed strong inhibitory activity against AChE enzyme and our molecular modeling study confirmed that these analogues could combine both with the AChE central catalytic site and PAS.
Keywords: Acetylcholinesterase inhibitors, Butyrylcholinesterase inhibitors, 1H-benzimidazole.
References: 1. Luo W, Li YP, He Y, Huang SL, Tan JH, Ou TM, Li D, Gu LQ, Huang ZS. Design, synthesis and evaluation of novel tacrine-multialkoxybenzene hybrids as dual inhibitors for cholinesterases and amyloid beta aggregation. Bioorg Med Chem 2011;19(2):763-770. 2. Refolo LM, Fillit HM. Drug discovery for Alzheimer's disease: the end of the beginning. J Mol Neurosci 2004;24(1):1-8.
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O 16 MCF-7 Breast Cell Proteome Analysis Determination with New UPLC/MS Method
Engin Koçak a*, Selin Öncül b, Ozan Kaplan a, Merve Nenni a, Mustafa Çelebier a, Ayşe Ercan b, İncilay Süslü a, Sacide Altınöz a
a Department of Analytical Chemistry, Faculty of Pharmacy, Hacettepe University Sıhhıye 06100 Ankara b Department of Biochemistry, Faculty of Pharmacy, Hacettepe University Sıhhıye 06100 Ankara *E-mail: [email protected]
Proteomics is the study area that complements genomic studies that enable cellular activities to be studied at the protein level [1,2]. Mass spectroscopy is the main analytical system used in proteomic studies with high sensitivity and precision [3]. Chromatographic systems are frequently used to separate peptides belonging to proteins by order to be able to analyze in more accurate and high sensitivity in mass spectroscopy. For this purpose, although nano-liquid chromatography are frequently used, the robustness and reproducibility problems of the system are difficult to analyze [4]. In this study, an ultra pressure liquid chromatography method, which may be an alternative to nano-liquid chromatography, was developed to analyze the proteins of MCF-7 breast cancer cells. The UPLC flow rate in the study was 0.1 mL / min. Water and acetonitrile were used as the mobile phase. Formic acid was also used to analyze the peptides in positive mode. In studies, MS/MS data belonging to peptides were obtained with Q-TOF-MS system. In qualitative analysis studies, the Maxquant search program was used to compare experimental MS/MS data with theoretical MS / MS spectrum in the Uniprot database. 696 proteins were identified with qualitative analysis in three replicate injection. The obtained proteins were evaluated by gene ontology analysis. The results were evaluated in the Perseus statistical program.
Keywords: Proteomics, UPLC/MS, cell biology, maxquant
References: 1.Mann M, Hendrickson RC, Pandey A. Analysis of proteins and proteomes by mass spectrometry. Annu Rev Biochem. 2001;70:437-73. 2.Phizicky E, Bastiaens PI, Zhu H, Snyder M, Fields S. Protein analysis on a proteomic scale. Nature. 2003;422(6928):208-15. 3.Doerr A. Mass spectrometry-based targeted proteomics. Nat Methods. 2013;10(1):23. 4.Noga M, Sucharski F, Suder P, Silberring J. A practical guide to nano-LC troubleshooting. J Sep Sci. 2007;30(14):2179-89.
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Poster Presentations
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P01 - Inhibition Effect of 4-Methylbenzenesulfonamide Derivatives on Human Carbonic Anhydrase Isoenzymes (hCA I-II)
Asiye Efe a, Emir Alper Türkoğlu b*, Tayfun Arslan c, Murat Şentürk d
a Ağrı İbrahim Çeçen University, Science and Art Faculty, Ağrı, Turkey b University of Health Sciences, Faculty of Pharmacy, İstanbul, Turkey c Giresun University, Science and Art Faculty, Giresun, Turkey d Ağrı İbrahim Çeçen University, Faculty of Pharmacy, Ağrı, Turkey *E-mail: [email protected]
Carbonic anhydrases (CAs, EC 4.2.1.1), essential enzymes at the cellular level for both transport and - metabolic processes, are metalloenzymes catalyzing the hydration of CO2 to HCO3 and protons [1,2]. Carbonic anhydrase inhibitors (CAIs) are carried out therapeutic agents in the treatment or prevention of many diseases. However, since there are many undesirable side effects of the present inhibitors, the development of sulfonamide inhibitors will be very useful for obtaining novel drug types with no side effects as well as for specific physiological studies involving specific inhibitors [3]. Sulfonamides, which represent one of the important classes of CAIs, have been used for many years in the treatment of several diseases in recent times [4,5]. In this study, the effects of the 4- methylbenzenesulfonamides on the isoenzymes of human carbonic anhydrase I and II (hCA I-II) were performed. IC50 values were calculated using the plotted %Activity [Sulfonamide] graphs, and are in the ranges 0,770-5,196, 18,887-56,862 nM for hCA I and hCA II, respectively. As a result of the study, it reported that sulfonamide derivatives can be used as effective inhibitors for hCA I-II. Moreover, the development of sulfonamide inhibitors is believed to be beneficial not only in obtaining novel drug types that have no significant side effects, but also in specific physiological studies in which selective inhibitors are present.
Keywords: Carbonic anhydrase, sulfonamides, inhibition, hCA I-II, enzymes.
References: 1. Hassan MdI, Shajee B, Waheed A, Ahmad F, Sly WS. Structure, Function and Applications of Carbonic Anhydrase Isozymes. Bioorganic & Medicinal Chemistry. 2013;21:1570-1582. 2. Güler OO, Capasso C, Supuran CT. A Magnificent Enzyme Superfamily: Carbonic Anhydrases, Their Purification and Characterization. Journal of Enzyme İnhibition and Medicinal Chemistry. 2016;31(5):689-694. 3. Supuran CT, Scozzafava A, Casini A. Carbonic Anhydrase Inhibitors. Medicinal Research Reviews. 2003;23(2):146-189. 4. De Simone G, Supuran, CT. (In)organic Anions as Carbonic Anhydrase Inhibitors. Journal of Inorganic Biochemistry. 2012;111:117-129. 5. Eldehna WM, Al-Ansary GH, Bua S, Nocentini A, Gratteri P, Altoukhy A, Ghabbour H, Ahmed HY, Supuran CT. Novel Indolin-2-one-based Sulfonamides as Carbonic Anhydrase Inhibitors: Synthesis, in vitro Biological Evaluation Against Carbonic Anhydrases Isoforms I, II, IV and VII and Molecular Docking Studies. Europen Journal of Medicinal Chemistry. 2017;127:521-530.
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P02 - Effects of Probucol on K562 Chronic Myelogenous Leukemia Cell line
Koc A a* Karabay AZ a, Buyukbingol Z a, Aktan F a
a Ankara University, Faculty of Pharmacy, Department of Biochemistry *E-mail: [email protected]
Chronic myeloid leukemia, a hematopoietic stem cell disease, is characterized by an unregulated growth of myeloid cells in the bone marrow, and the Bcr / Abl fusion gene and protein resulting from the presence of the Philadelphia (Ph) t (9; 22) (q34; q11) chromosome has a central role in this disease [1]. This 210 kDa protein product of Bcr / Abl oncogene has constitutively active tyrosine kinase activity, resulting in uncontrolled proliferation of cells and apoptosis resistance [2]. Imatinib, a tyrosine kinase inhibitor, is the first choice in the treatment of CML, but problems such as therapy resistance lead investigators to discover new drug candidates. In this study, probucol, an anti-cholesterolemic drug was tested for its effects on cell proliferation and apoptosis in K562 chronic myeloid leukemia cell line originating from a late stage CML patient of blast crisis [3]. MTT assay, of caspase-3 enzyme activity, PARP fragmentation and apoptotic Bax and Bcl-2 proteins were examined by spectrophotometry, flow cytometry and western blot. Our results showed that probucol significantly reduced K562 leukemia cell viability at 100 micromolar dose at 96 hours of incubation. However, despite the significant reduction in cell viability, this effect was not potent. When the action mechanism of probucol administration at 100 micromolar concentration leading to decreased cell viability was examined, it was determined that the expression of caspase-3 enzyme, Bax and Bcl-2 protein did not change. All these results indicate that caspase-3, bax and bcl-2 proteins do not function in the viability-reducing effects of probucol at 100 micromolar concentration.
Keywords: Probucol, chronic myeloid leukemia, apoptosis
References: 1.Lozzio CB, Lozzio BB. Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood. 1975;45(3):321-34. 2.Kurzrock R, Gutterman JU, Talpaz M. The molecular genetics of Philadelphia chromosome-positive leukemias. N Engl J Med. 1988;319(15):990-8. 3.Woessner DW, Lim CS, Deininger MW. Development of an effective therapy for chronic myelogenous leukemia. Cancer journal (Sudbury, Mass). 2011;17(6):477-86.
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P03 - Effect of Glucagone-Like Peptide-1 on Diminished Corpus Cavernosum Function Induced by Chronic Methylglyoxal Administration in Rats
Selvinaz Dalaklıoğlu a, Arda Taşatargil a, Ayşe Barutcigil a
a Akdeniz University, Medical Faculty, Department of Pharmacology, 07070, Antalya, Turkey E-mail: [email protected]
The aim of this study was to investigate the effect of exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, on diminished corpus cavernosum (CC) function induced by chronic methylglyoxal (MGO) administration. Male rats were divided into four groups as control group rats, MGO (75 mg/kg/day in drinking water for 12 weeks) group rats, low-dose exendin-4 (0.1 µg/kg twice daily subcutaneously for 12 weeks concomitant with MGO) group rats, high-dose exendin-4 (1 µg/kg twice daily subcutaneously for 12 weeks concomitant with MGO) group rats. Nitric oxide (NO)-mediated endothelium-dependent and neurogenic CC relaxation were evaluated by acetylcholine (ACh) and electrical field stimulation (EFS; 2– 32 Hz), respectively. In MGO administrated rats, NO-mediated, both endothelium-dependent and neurogenic CC relaxations, were significantly impaired when compared to control rats. The diminished CC relaxation in response to ACh or EFS in MGO administrated rats were significantly improved by exendin- 4 treatment. These results suggest that exendin-4 improves NO-mediated endothelium-dependent and neurogenic CC relaxations in MGO administrated rats.
Keywords: Corpus cavernosum, methyglyoxal, exendin-4
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P04 - Examination of Inhibition of Anticholinesterase Enzyme of Caliytagia Growing in Two Different Regions
Sıla Ozlem Senera , Merve Badema, Seyda Akkayab, Nuriye Korkmazb, , Ufuk Özgena, Rezzan Aliyazicioglub aKaradeniz Technical University, Faculty of Pharmacy, Department of Pharmacognosy, Trabzon bKaradeniz Technical University, Faculty of Pharmacy, Department of Biochemistry, Trabzon *E-mail: [email protected]
The Convolvulaceae family is represented by 85 genus and about 2800 species on the earth. Calystegia 183, one of the family members of this family, is represented by 8 species of this genus in Turkey. In this study, it was aimed to investigate the anticholinesterase enzyme activity on Calystegia silvatica collected from Trabzon (Bostancı) (CS1) and Ordu (Akkuş) (CS2) regions. Acetylcholinesterase (AChE) predominates in the healthy brain, with butyrylcholinesterase (BuChE) considered to play a minor role in regulating brain acetylcholine (ACh) levels. However, BuChE activity progressively increases in patients with Alzheimer's disease (AD), while AChE activity remains unchanged or declines. Both enzymes therefore represent legitimate therapeutic targets for ameliorating the cholinergic deficit considered to be responsible for the declines in cognitive, behavioral and global functioning characteristic of AD [1]. For these purpose, inhibitory activities of AChE and BuChE of the methanolic extract were evaluated by colorimetric Ellman’s method [2]. As a result of the study, CS1 and CS2 of AChE% inhibition results for concentrations of 25 μg/mL, 50 μg/mL, 100 μg/mL and 200 μg/mL were found as 9.32 ± 0.5; 10.9 ± 0.3; 25.1 ± 0.6; 34.25 ± 0.7 and 11.8 ± 0.2; 24.1 ± 0.4; 38.3 ± 0.9; 62.55 ± 0.6. BuChE inhibition results were found as 16.5 ± 0.5; 26.7 ± 0.7; 32.6 ± 0.8; 36.9 ± 0,7 and 3.8 ± 0.4; 12.3 ± 0.7; 17.3 ± 0.6; 22.0 ± 0,8, respectively. It can be said that the differences observed in the results stem from due to the plant is collected from different regions. These differences may be due to climate, soil structure, altitude of the region.
Keywords: Acetylcholinesterase, butyrylcholinesterase, Calystegia silvatica References: 1. Greig, NH.; Lahiri, DK.; Sambamurti K., Butyrylcholinesterase: an important new target in Alzheimer's disease therapy. Int. Psychogeriatr. 2002;14(1):77-91. 2. Ellman, GL.; Courtney, D.; Andies, V., Featherstone, R.M., A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961;7,88-95.
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P05 - Synthesis of New Benzimidazole Derivatives and Evaluation of Their Anticholinesterase Activity
Begüm Nurpelin Sağlik a,b*, Ulviye ACAR Çevik a,b, Serkan Levent a,b, Yusuf Özkay a,b, Zafer Asım Kaplancikli a
a Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu Universty, Eskişehir, Turkey
b Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu Universty, Eskişehir, Turkey
*E-mail: [email protected]
Alzheimer’s disease (AD) is a progressive and fatal neurodegenerative disorder recognized as memory loss and behavioural disturbance [1]. The cholinergic hypothesis is based upon degraded ACh levels in the brain of AD patients. Thus, cholinesterase inhibitors are the first preference in the treatments of Alzheimer’s disease (AD) that are affirmed by the US Food and Drug Administration (FDA) [2]. Morever, benzimidazole and its isosteric related benzothiazole scaffolds have been reported for their ChE inhibitory activities [3,4]. So, in this study new benzimidazole derivatives were designed and synthesized in order to evaluate their anticholinesterase activity. Structures of gained compounds were characterized by IR, 1H- NMR, 13C-NMR and HRMS spectroscopic methods. Their inhibitory activity against AChE and BChE enzymes was elucidated by using Ellman’s spectroscopic method. The enzyme inhibition assay revealed that compound 3c presented a significant inhibitory activity and selectivity against AChE enzyme. Enzyme kinetic studies were performed to examine the type of inhibition and docking studies were applied for this compound in order to explore the binding modes with enzyme active site.
Keywords: Benzothiazole, hydrazone, MAO enzyme inhibition
References: 1. Kumar A, Seghal N, Padi SV, Naidu PS. Differential effects of cyclooxygenase inhibitors on intracerebroventricular colchicine-induced dysfunction and oxidative stress in rats. Eur J Pharmacol. 2006;551(1- 3):58-66. 2. Anand P, Singh B. A review on cholinesterase inhibitors for Alzheimer’s disease. Arch Pharm Res. 2013;36:375- 399. 3. Alpan AS, Parlar S, Carlino L, Tarikogullari AH, Alptuzun V, Gunes HS. Synthesis, biological activity and molecular modelingstudies on 1H-benzimidazole derivatives as acetylcholinesteraseinhibitors. Bioorg Med Chem. 2013;21:4928-4937. 4. Demir Özkay Ü, Can ÖD, Sağlık BN, Acar Çevik U, Levent S, Özkay Y, Ilgın S, Atlı Ö. Design, synthesis, and AChE inhibitory activity of new benzothiazole-piperazines. Bioorg Med Chem Lett. 2016;26:5387-5394.
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P06 - The Effects of Surface Modifications of Gold Nanoparticles on Cytotoxicity and Intracellular Reactive Oxygen Species in Hepg2 Cells
Gamze Tilbe Sen a,b, Gizem Ozkemahli c,d, Reza Shahbazi b,e, Pınar Erkekogluc, Kezban Ulubayram f, Belma Kocer-Gumusel c,*
a Başkent University, Biomedical Engineering Program, Ankara, Turkey b Hacettepe University, Department of Nanotechnology and Nanomedicine, Ankara, Turkey c Hacettepe University, Faculty of Pharmacy, Department of Toxicology, Ankara, Turkey d ErzincanUniversity, Faculty of Pharmacy, Department of Toxicology, Ankara, Turkey e Fred Hutchinson Cancer Research Center, Seattle, US f Hacettepe University, Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Ankara, Turkey *E-mail: [email protected]
Gold nanoparticles (AuNP) have been widely used in diagnostics, gene or drug delivery system and other biological owing to their easy synthesis, amenable surface modification and bio-conjugation, rational stability and unique optoelectronic properties. Also, gold nanoparticles can be synthesized in different size ranges which facilitates their accumulation in different organs. Despite the great excitement about the potential uses of gold nanoparticles for biomedical applications, their toxicity must be investigated before any in vivo applications. However, depending on size, surface chemistry, gold nanoparticles can be harmful to the cell, which prevents them from being used clinically. The aim of this study was to investigate the effect of different polymeric coating of AuNPs on cytotoxicity and intracellular reactive oxygen species (ROS) production in HepG2 cell line. For this purpose, AuNPs (45 nm) were coated with polyethylene glycol (PEG) and polyethyleneimine (PEI) with low and high molecular weight (2000 and 25000). Cell viability was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and intracellular ROS production was determined by a fluorometric intracellular ROS kit that detects intracellular ROS (especially superoxide and hydroxyl radicals) in live cells after a 1 hour incubation. After incubation of HepG2 cells with different concentrations of AuNPs, the inhibitory concentration 50 (IC50) doses for AuNPs, PEG/AuNPs and PEI2000/AuNPs were 167 µM, 257 µM, and 198 µM, respectively. However, 20% of the cells were alive after incubations with high molecular weight PEI coated AuNPs at 25 µM concentrations. Intracellular ROS levels were significantly higher after exposure to AuNPs, PEG/AuNPs, PEI 2000/AuNPs and PEI25000/AuNPs samples (vs. control, p<0.05, all, at IC70 doses). As a results, while PEG coated AuNPs and PEI2000 coated AuNPs showed higher cell viability and comparable intracellular ROS levels (vs. gold nanoparticles) whereas PEI25000 did not. Thus, PEG/AuNPs and PEI2000/AuNP can be used safely in biomedical applications.
Keywords: Gold nanoparticles, cytotoxicity, reactive oxygen species
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P07 - Preparation and Characterization of GST Inhibitor ETA-Loaded Nanoparticles for Targeting to Chemotherapeutic Resistant Cancer Cells
Burcin Ozcelik a, b, Ipek Baysal c, Ipek Eroglu d, Gulberk Ucar c*
a Hitit University, Faculty of Arts and Sciences, Department of Biology, Corum, Turkey b Hacettepe University, Graduate School of Science and Engineering, Nanotechnology and Nanomedicine Department, Ankara, Turkey c Hacettepe University, Faculty of Pharmacy, Department of Biochemistry, Ankara, Turkey d Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Basic Sciences, Ankara, Turkey *E-mail: [email protected]
Hepatocellular carcinoma (HCC) is a highly fatal cancer. The chemotherapeutic treatment of HCC has been limited by systemic toxicity, poor efficacy, and acquired resistance resulted from a variety of factors including the change in anti-oxidant mechanisms [1]. Glutathione S-transferases (GSTs) is a family which catalyzes the conjugation of the reduced form of glutathione to xenobiotic substrates for detoxification. GSTs serve two distinct roles in the development of drug resistance via direct detoxification as well as acting as an inhibitor of the MAP kinase pathway. Since increase in GSTs levels was previously reported in tumor types, the inhibition of GST is suggested to increase the efficacy of chemotherapeutics which are detoxified by GSTs. Ethacrynic acid (ETA) is a FDA approved GST inhibitor which is clinically used as a diuretic drug. However, free ETA can inhibit the GSTs in somatic cells and destroy the normal oxidative balance [2]. Drug delivery systems (DDS) are engineered approaches transporting pharmaceutical compounds to the body/organs as needed, such as targeted delivery and/or controlled release. In the present study, ETA was encapsulated into poly (D, L-lactic-co-glycolic acid) (PLGA) and poly (D, L-lactic-co- glycolic acid) poly (ethylene glycol) (PLGA-PEG) nanoparticles. Hepatocellular carcinoma cells (HepG2) were exposed to increasing doses of oxaliplatin (OXA) to establish stable cell lines resistant to oxaliplatin. GST-π and µ levels were determined in normal and OXA-resistant cells using ELISA in order to investigate the alterations in GST phenotype levels in HCC. Anti-GST efficacy of free and nanoparticle encapsulated ETA were determined in OXA-resistant HepG2 cells. Oxaliplatin significantly increased the levels of GST- π while GST-µ levels were not alterated. Neither free ETA nor nanoparticulated ETA were able to inhibit the GST-µ activity but there was a significant decrease in GST-π activity after ETA treatment. As a conclusion, GST- π is the key enzyme that detoxified oxaliplatin and ETA acts as a GST- π specific inhibitor. Further in vitro and in vivo studies are needed to improve a novel chemotherapeutic combination including nanoparticulated ETA for overcoming the drug resistance in HCC. Keywords: Hepatocellular cancer, oxaliplatin resistance, GSTs, nanoparticle References: 1. Josiah C, Steven W. Mechanisms of doxorubicin resistance in hepatocellular carcinoma. Hepatic Oncology. 2016; 3(1): 57–59. 2. Arai T, Miyoshi Y, Kim SJ, Akazawa K, Maruyama N, Taguchi T, Tamaki Y, Noguchi S. Association of GSTP1 Expression with Resistance to Docetaxel and Paclitaxel in Human Breast Cancers. Journal of Cancer Surgery. 2008;(34):734-38.
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P08 - 1,5-Bis(4-hydroxy-3-(aminomethyl)phenyl)penta-1,4-dien-3-ones: Bis Mannich Bases as Anticancer Agents
Halise Inci Gul a*, Cem Yamali a, Hiroshi Sakagami b a Department of Pharmaceutical Chemistry, Faculty of Pharmacy,Ataturk University, Turkey. b Meikai University Research Institute of Odontology (M-RIO), Meikai University School of Dentistry, Sakado, Saitama, Japan *E-mail: [email protected] Natural products and their analogues are expected to play a vital role in designing novel chemotherapeutic agents[1]. Curcumin and its analogues shows potential chemopreventive and therapeutic value in a wide range of cancers[1]. Mannich bases were reported with many bioactivities especially with anticancer effects[1-3]. In this research, bis Mannich bases having the chemical structure of 1,5-bis(4-hydroxy-3- (aminomethyl)phenyl)penta-1,4-dien-3-ones were synthesized3 and their cytotoxic activities were evaluated3 towards human squamous carcinoma cell lines, human normal oral mesemchymal cells and human normal epithelial cells. The results of the compounds are shown in Table 1.The compounds have shown anticancer properties towards human squamous cell carcinoma lines in the range of 1 µM-100 µM. The compound J1, 1,5-bis(4-hydroxy-3-((4-methylpiperazin-1-yl)methyl)phenyl)penta-1,4-dien-3-one, was considered as the most cytotoxic compound with the highest tumor-specificity (TS) and a potency selectivity expression (PSE) values to design new anticancer compounds for further investigations. Table 1. Cytotoxicity results of the compounds
TS PSE
J1 4,62 3,53 228,15 174,36
J2 ><1.09 ><1.09 ><1.18 ><1.18
J3 ><1.99 <1.22 ><3.98 <2.44
5-FU ><2.18 <0.17 ><0.49 <0.038
MTX ><1.98 ><1.98 ><0.98 ><0.98
Melphalan >2.86 1,10 >4.26 1,63
TS value was calculated by dividing the mean CC50 value of each compound against three human oral normal cells (HGF, HPLF, HPC) by the mean CC50 value against four human OSCC cell lines. Secondly, TS value was also calculated by dividing the mean CC50 value of each compound against two human normal epithelial cells (HOK, HGEP) by the mean CC50 value against four human OSCC cell lines. PSE was calculated using the following equation: PSE = TS/CC50 against tumor cells × 100. 5-Fluorouracil (5-FU), Methotrexate (MTX) and Melphalan were used as reference compounds in this study.
Keywords: Mannich base, anticancer, curcumin analogue, PSE, TS References: 1. Robles-Escajeda E, Das U, Ortega NM, et al. Cell Oncol (Dordr). Jun 2016;39(3):265-277. 2. Roman G. Eur J Med Chem. Jan 07 2015;89:743-816. 3. Yamali C, Gul HI, Sakagami H, Supuran CT. J Enzyme Inhib Med Chem. 2016;31(sup4):125-131. Acknowledgements: The authours thank to Ataturk University BAP office for the financial support .
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P09 - A LC-MS/MS Method for the Simultaneous Determination of Pronuciferine and Romerine in Some Papaver Species
Cemil Can Eylem a, Omer Bayazeid b, Tuba Reçber a, Emirhan Nemutlu a, Funda Nuray Yalçın b, Sedef Kır a aHacettepe University, Faculty of Pharmacy, Department of Analytical Chemistry bHacettepe University, Faculty of Pharmacy, Department of Pharmacognosy Sıhhiye, Ankara, 06100, Turkey *E-mail: [email protected]
Papaver species well known for their alkaloids have been used for the treatment of several diseases such as inflammation, diarrhea, and sleep disorders, as well as used as anti-depressant in some regions of Anatolia [1-3]. Five Papaver species (P. lacerum, P. syriacum, P. macrostomum, P. glaucum, P. rhoeas) were collected from different localities of Turkey. The methanolic extracts prepared from aerial parts of the plants. In this study, a rapid, sensitive and selective analytical method was developed for the simultaneously quantitative analysis of two alkaloids, which are pronuciferine and romerine using liquid chromatography tandem mass spectrometry (LC-MS/MS). Multiple reaction monitoring (MRM) in the positive ionization mode was used for detection. Pronuciferine and romerine were analyzed on a C18 column (2.1 x 50 mm, 3 µm) with the mobile phase run in gradient mode with % 0.1 formic acid in water (A) and % 0.1 formic acid in acetonitrile at a flow rate of 0.3 mL/min. Precursor to product ion transitions (m/z 312.1/283.1, m/z 280.0/249.0) were used to measure pronuciferine and romerine respectively. The assay was linear a concentration range of 0.01 µg/mL to 1 µg/mL (r2=0.996 for romerine, r2=0.998 for pronuciferine). End of the validation studies, the method was found robust, specific, sensitive and linear [4]. Finally, the developed method was applied to quantify pronuciferine and romerine amount in some Papaver species (P. lacerum, P. syriacum, P. macrostomum, P. glaucum, P. rhoeas). According to the analysis results of these plants, the amount of pronuciferine and romerine were respectively found between 0.004 µg/mL- 4.9 µg/mL and 0.087 µg/mL and 94 µg/mL.
Keywords: Pronuciferine, romerine, papaver species, LC-MS/MS, validation.
References: 1. Sarıyar G. Biodiversity in the alkaloids of Turkish Papaver species. Pure Appl. Chem. 2002 (74),557-574 2. Yildirim B, Terzioglu O.Ethnobotonical and Pharmacological uses of some plants in the districts of Karpuzalan and Adiguzel (Van-Turkey). Journal of animal and veterinary advances 2008 (7), 877. 3. Baytop T. Therapy with medicinal plants in Turkey (Past and Present). 1st ed. Istanbul, Turkey; 1984, 208-209. 4. Food and Drug Administration. FDA Guidance for Industry: Bioanalytical Method Validation. Rockville, MD: US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research; 2013.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P10 - In Vitro Inhibitory Effects of Some Calcium Channel Blockers (CCBs) on Human CA I and CA II Activities
Cüneyt Türkeş a, Yeliz Demir b, Şükrü Beydemir c*
a Erzincan University, Faculty of Pharmacy, Department of Biochemistry, Erzincan, 24100, Turkey b Atatürk University, Faculty of Sciences, Department of Chemistry, Erzurum, 25240, Turkey c Anadolu University, Faculty of Pharmacy, Department of Biochemistry, Eskişehir, 26470, Turkey *E-mail: [email protected] Carbonic anhydrases (EC 4.2.1.1., CAs) are pH regulatory metalloenzymes in prokaryotes and eukaryotes. CAs catalyse the reversible hydration of carbon dioxide to the bicarbonate. Up to now, sixteen CA isozymes have been identified in mammals that exhibit different catalytic activity, subcellular localization and tissue distribution and susceptibility to different classes of inhibitors. CA I and CA II are cytosolic isoenzymes, and CA I is found together with CA II in erythrocytes. The CA reactions are involved in numerous metabolic processes, primarily in the respiration and transport of carbon dioxide (CO2) and bicarbonate (HCO3-). Calcium channel blockers (CCBs) or calcium antagonists, are commonly used for vasodilator activities in the treatment of many cardiovascular conditions, such as hypertension, chest pain and Raynaud's disease. The in vitro effects of some calcium channel blockers such as isradipine, nitrendipine, nilvadipine, amlodipine and nifedipine were investigated on enzyme activities of human erythrocyte CA I and CA II in this study. hCA I and hCA II were purified by affinity chromatography. SDS-PAGE was performed to determine the purity of the enzymes. The inhibitory effects of the drugs on hCA I and hCA II were determined by spectrophotometric method. IC50 values for hCA I were 9.24, 9.90, 11.55, 12.60 and 13.07 µM using isradipine, nitrendipine, nilvadipine, amlodipine and nifedipine, respectively. IC50 values for hCA II of nitrendipine and nilvadipine were 138.60 and 115.50 µM, respectively. For isradipine, nitrendipine, nilvadipine, amlodipine and nifedipine, Ki values from Lineweaver-Burk plots were obtained as 7.949, 7.605, 8.567, 13.100 and 10.862 µM, respectively for hCA I. Ki values for hCA II were calculated as 135.126 and 162.354 μM for nitrendipine and nilvadipine by the Lineweaver-Burk plots, respectively. All calcium channel blockers were noncompetitive inhibitors.
Keywords: Calcium channel blocker, carbonic anhydrase, CA isoenzymes, erythrocyte
References: 1. Ekinci D, Beydemir S, Alim Z. Some drugs inhibit in vitro hydratase and esterase activities of human carbonic anhydrase-I and II. Pharmacological Reports. 2007;59(5):580. 2. Supuran CT. Diuretics: from classical carbonic anhydrase inhibitors to novel applications of the sulfonamides. Current pharmaceutical design. 2008;14(7):641-8. 3. Coban TA, Beydemir Ş, Gücin İ, Ekinci D, Innocenti A, Vullo D, et al. Sildenafil is a strong activator of mammalian carbonic anhydrase isoforms I–XIV. Bioorganic & medicinal chemistry. 2009;17(16):5791-5. 4. Supuran CT. Structure-based drug discovery of carbonic anhydrase inhibitors. Journal of enzyme inhibition and medicinal chemistry. 2012;27(6):759-72.
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P11 - Influence of Calcium Channel Blockers on Sheep Kidney Aldose Reductase Enzyme
Cüneyt Türkeş a, Yeliz Demir b, Şükrü Beydemir c *
a Erzincan University, Faculty of Pharmacy, Department of Biochemistry, Erzincan, 24100, Turkey b Atatürk University, Faculty of Sciences, Department of Chemistry, Erzurum, 25240, Turkey c Anadolu University, Faculty of Pharmacy, Department of Biochemistry, Eskişehir, 26470, Turkey *E-mail: [email protected]
Aldose reductase (EC 1.1.1.21, AR, ALR2) a key enzyme in the polyol pathway, converts D-glucose into D-sorbitol using NADPH as a cofactor. It is the first and rate-limiting enzyme of the polyol pathway. Aldose reductase enzyme inhibitors have vital significant in the treatment and prevention of diabetes mellitus complications. Calcium channel blockers are widely used in the treatment of hypertension. They are obstructed the channel by physically and inhibit the influx of extracellular calcium. In this study, aldose reductase was partially purified from sheep kidney and investigated the in vitro effects of some calcium channel blockers on enzyme activity. IC50 values were found for nilvadipine, amlodipine, nifedipine, cinnarizine, isradipine and nitrendipine as 6.36, 6.60, 8.77, 5.87, 7.22 and 8.35 µM, respectively. Ki constants were calculated as 2.11, 2.45, 2.47, 2.07, 5.42 and 5.62 µM respectively. The inhibition mechanism of nilvadipine, amlodipine, nifedipine and cinnarizine were competitive, and for isradipine and nitrendipine were noncompetitive.
Keywords: Calcium channel blocker, aldose reductase, polyol pathway, sheep kidney
References: 1. Petrash J. All in the family: aldose reductase and closely related aldo-keto reductases. Cellular and molecular life sciences. 2004;61(7):737-49. 2. Türkeş C, Söyüt H, Beydemir Ş. Effect of calcium channel blockers on paraoxonase-1 (PON1) activity and oxidative stress. Pharmacological Reports. 2014;66(1):74-80. 3. Bhadada SV, Vyas VK, Goyal RK. Protective effect of Tephrosia purpurea in diabetic cataract through aldose reductase inhibitory activity. Biomedicine & Pharmacotherapy. 2016;83:221-8. 4. Alim Z, Kilinç N, Şengül B, Beydemir Ş. Inhibition behaviours of some phenolic acids on rat kidney aldose reductase enzyme: an in vitro study. Journal of enzyme inhibition and medicinal chemistry. 2017;32(1):277-84. 5. Aslan HE, Beydemir Ş. Phenolic compounds: The inhibition effect on polyol pathway enzymes. Chemico- Biological Interactions. 2017;266:47-55.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P12 - Antimicrobial Activities of Ferula Caspica and F. halophila Extracts
Cigdem Kahraman a*, Melike Ekizoglu b, Zeliha S. Akdemir a
a Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe University, TR-06100, Ankara, Turkey b Department of Microbiology, Faculty of Pharmacy, Hacettepe University, TR-06100, Ankara, Turkey *E-mail: [email protected]
Ferula L. represented by 23 species, 13 of which are endemic to Turkey is the third largest genus of the Apiaceae family [1,2] and used for several diseases in Traditional Medicine [3]. The aim of this study was to investigate the antimicrobial activities of various extracts from F. caspica M. Bieb. and F. halophila Pesmen. by broth microdilution [4,5] method against the bacteria (Escherichia coli ATCC 25922, Enterococcus faecalis ATCC 29212, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213) and the fungi (Candida albicans ATCC 90028, C. krusei ATCC 6258, C. parapsilosis ATCC 90018). The aerial parts and roots of these plants were extracted with petroleum ether, chloroform, methanol, ethylacetate and n-butanol. The chloroform extracts of the aerial parts and roots from F. caspica showed the highest antimicrobial activity. While the aerial parts exibited the antimicrobial acitivity against the gram pozitive bacteria with the MIC value of 32 and 64 μg/mL, the MIC value of the roots was found to be 64 μg / mL against the gram pozitive bacteria and C. parapsilosis. Through the highest activity, secondary metabolites of the chloroform extract from the aerial parts were isolated and their structures were elucidated by spectroscopic methods (1H-NMR, 13C-NMR, HMQC, HMBC, COSY and Mass Spektrometry) [6].
Keywords: Ferula L., apiaceae, antimicrobial activity
References: 1. Davis PH, Flora of Turkey and the East Aegean Islands, Vol 4. Edinburgh: Edinburgh University Press; 1972: 440-453. 2. Kahraman C. PhD thesis, 2016: 1-8. 3. Altundag E, Ozturk M. Ethnomedicinal Studies on the Plant Resources of East Anatolia, Turkey. Procedia Social and Behavioral Sciences. 2011;19:756-77. 4 Wayne P. Reference method for broth dilution antifungal susceptibility testing of yeasts: Approved standard. 3rd ed., M 27-A3 ed: Clinical and Laboratory Standards Institute; 2008. 5. Wayne P. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: Approved standard. 8th ed., M 07-A8 ed: Clinical and Laboratory Standards Institute; 2008. 6. Kahraman C, Topcu G, Bedir E, Akdemir ZS. A New Sesquiterpene Isolated from The Aerial Parts of Ferula caspica M. Bieb. 65th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA). 2017.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P13 - Cytotoxic and Antioxidant Activities of a Chitin Derivate on Human Blood Cells
Salim Cerig a, Fatime Geyikoglu a, Kübra Koc a, Nihal Simsek Ozek a,b, Ferhunde Aysin a,b*
a Atatürk University, Faculty of Science, Department of Biology, 25240, Erzurum, Turkey b East Anatolian High Technology Research and Application Center (DAYTAM), Atatürk University, 25240, Erzurum, Turkey *E-mail:[email protected]
Chitin is the second most abundant available biopolymer after cellulose in the world. Chitosan is derived from a natural product, chitin, quite abundant in Crustaseanse and it is widely used in biomedical and pharmaceutical fields. In the current research, cytotoxic and antioxidant effects of chitosan (0-500 mg/L) on human blood lymphocyte (hBL) cultures were investigated. Total antioxidant capacity (TAC) and total oxidative status (TOS) were analyzed to evaluate the changes in oxidant/antioxidant levels of chitosan in cultured cells and also XTT cytotoxicity test was used to determine cell viability. Consequently, 0-150 mg/L doses of chitosan increased the antioxidant capacity while reducing oxidative damage. Morever, 500 mg/L dose of chitosan caused oxidative stress. It was determined that 0-250 mg/L doses of chitosan did not cause any damage in cell viability but 500 mg/L dose of chitosan decreased cell viability when the cytotoxic damage was assessed by XTT assay. In conclusion, this abundant biopolymer has dose-dependent effects for human blood cells by inducing oxidative damage and cytotoxicity.
Keywords: Chitosan, cytotoxicity, antioxidant capacity, human blood cells
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P14 - The Role of Potassium Channels in The Relaxation Response of Intermedin/Adrenomedullin2 (IMD/AM2) in The Rat Pulmonary Artery
Gokcen Telli a*, H.Burak Kandilci b, Banu C. Tel a, Bulent Gumusel a,c a Hacettepe University, Faculty of Pharmacy, Department of Pharmacology, Ankara-Turkey b Ankara University, Faculty of Medicine, Department of Biophysics, Ankara-Turkey c Erzincan University, Faculty of Pharmacy, Department of Pharmacology, Erzincan-Turkey *E-mail:[email protected]
Calcitonin gene related peptide (CGRP) family has important effects on the cardiovascular system. It is well known that especially two peptides of this family, CGRP and adrenomedullin (AM), have vasorelaxant effect in aorta, pulmonary artery (PA) and mesenteric artery. Effects of these peptides are mostly endothelium-dependent and nitric oxide (NO) mediated (1). Potassium channels (K+ channels) are another important factors that play roles in the mechanisms of action of these peptides (2). Intermedin/Adrenomedullin2 (IMD/AM2) is the last isolated member of this family. IMD/AM2 which is particularly effective in the pulmonary vascular bed, has structural and physiological similarities with CGRP and AM. It was demonstrated that IMD/AM2 provides endothelium-dependent and NO-mediated + relaxation however studies investigating the role of K channels in the relaxation response of IMD/AM2 are + limited (1). In our study, the role of various K channels in IMD/AM2 responses was assessed using the isolated organ bath. Isolated PAs were cleaned and cut into rings 3 to 4 mm in length and mounted in organ baths. PA rings were initially stretched to produce a preload of 1,5 g of force and allowed to equilibrate for 90 minutes. Next, the rings were pre-contracted with phenlyephrine (3x10-6M). Once a stable contraction -9 -7 was obtained, cumulative concentration of IMD/AM2 (10 -3x10 M) was added to the bath, and changes in relaxation was assessed. After incubation with non-specific K+ channels inhibitor tetraethylammonium -2 + -5 (TEA, 10 M), ATP sensitive K channels (KATP) inhibitor glibenclamide (10 M), voltage-gated potassium -5 2+ + channels (Kv) inhibitor 4-aminopyridine (10 M), small-conductance Ca activated K channels (SKCa) -5 2+ + inhibitor apamine (10 M), intermediate-conductance Ca activated K channels inhibitor (IKCa) TRAM34 -5 2+ + -7 (10 M) and large-conductance Ca activated K channels (BKCa) inhibitor iberotoxin (3x10 M) for 30 -9 -7 + minutes, concentration-response curves of IMD/AM2 (10 -3x10 M) were repeated. The role of K channels was also assessed in PAs that were pre-contracted with 60 mM KCl. In the presence of TEA and in the PAs that pre-contracted with 60 mM KCl, IMD/AM2 responses were significantly inhibited. Iberiotoxin also significantly inhibited to IMD/AM2 vasorelaxant effects. However there were no changes in the responses with KATP, Kv, SKCa and IKCa channels inhibitors. Our results demonstrated that BKCa channels has an important role in IMD/AM2 responses. However, although the relaxation response was inhibited almost completely in the presence of non-specific inhibitor TEA, the responses were partially inhibited with BKca inhibitor.
+ Keywords: Intermedin/Adrenomedullin2, K channels, BKCa channels, pulmonary artery References: 1. Born W, Fischer JA. The Calcitonin Peptide Family: What Can We Learn from Receptor Knock Out and Transgenic Mice. In: Hay DL, Dickerson IM, editors. The Calcitonin Gene-related Peptide Family Form, Function and Future Perspectives. Springer Dordrecht Heidelberg London New York: Springer; 2010. p. 75-86. 2. Ghatta S, Nimmagadda D. Calcitonin gene-related peptide: Understanding its role. Indian J Pharmacol. 2004;36:277–83.3:19. This study was supported by Hacettepe University Scientific Research Projects Coordination Unit (Project numbers: THD-2016-9281).
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P15 - Differential Pulse Voltammetric Determination of Terbinafine in Pharmaceuticals using Bromocresol Purple Modified Glassy Carbon Electrode
Gokce Ozturk a *, Dilek Kul a a Karadeniz Technical University, Faculty of Pharmacy, Department of Analytical Chemistry, 61080, Ortahisar, Trabzon, TURKEY *E-mail: [email protected] Terbinafine (TRB) is a synthetic antifungal agent, used in treatment of mycosis of the skin, hair, or nails caused by Saccharomycetes or dermatophytes, and classified among allylamines from the naftifine group. Terbinafine is well-tolerated and demonstrates high effectiveness in general and local treatment [1]. Bromocresol purple (BCP), 5,5-dibromo-o-cresolsulfophthalein, is a pH indicator. It is also used as dye to measure albumin in medical laboratories [2]. In this work, bromocresol purple was selected to prepare a polymer film on the surface of glassy carbon electrode by electrochemical method. Three-electrode system, the bromocresol purple modified glassy carbon electrode as working electrode, an Ag/AgCl reference electrode, and platinum wire counter electrode, were used in the experiments. Stock solutions of TRB (1.0x10-3 M) were prepared with deionized water. Three different supporting electrolytes at different pH values, phosphate buffer (PB), Britton Robinson buffer (BRB), and acetate buffer (AB) solutions were used. The electrochemical study of TRB was investigated at bromocresol purple modified glassy carbon electrode (BCP/GCE) on the anodic direction using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). CV results showed that TRB had an irreversible redox process. The effect of pH on the peak current and the peak potential was examined in the range of pH 2.0-12.0. According to the peak current vs pH graphs, supporting electrolyte was selected as AB at pH 3.5 for DPV technique. Scan rate studies were carried out and found that the process of TRB was diffusion controlled. Quantitative determination of TRB was studied with DPV technique. The peak current of TRB had a linear dependence with the concentration of TRB in the range of 0.08-20 µM for DPV. The detection limit was calculated as 4.60 nM. The proposed method was successfully applied for the determination of terbinafine from its pharmaceutical dosage form. The electrochemical determination of TRB was achieved with wide linear range and good detection limit at bromocresol purple modified glassy carbon electrode using DPV technique.
Keywords: Bromocresol purple, voltammetry, glassy carbon electrode, terbinafine
References 1. Mielech-Łukasiewicz K, Dabrowska A. Comparison of Boron-Doped Diamond and Glassy Carbon Electrodes for Determination of Terbinafine in Pharmaceuticals using Differential Pulse and Square Wave Voltammetry. Electrochemistry. 2014;47:1697-1711. 2. Wang Y, Tong L. Electrochemical Sensor for Simultaneous Determination of Uric Acid, Xanthine and Hypoxanthine Based on Poly (Bromocresol Purple) Modified Glassy Carbon Electrode. Sensors and Actuators B: Chemical. 2010;150:43-49.
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P16 - Anticandidal Activity Screening of Novel Triazole Derivatives
Harun Uslu a*, Derya Osmaniye b, Ulviye Acar Çevik b, Yusuf Özkay b, Kadriye Benkli c, Zafer Asım Kaplancıklı b a İnönü University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Malatya, Turkey b Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Eskişehir, Turkey c Bezmialem University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, İstanbul, Turkey *E-mail: [email protected]
Azole type antifungal drugs has been divided into two groups namely triazoles and imidazoles [1]. 1,2,4- triazole and its derivatives represent an interesting class of compounds, which have been explored for their wide spectrum of pharmacological properties. Prompted by biological importance of triazole derivatives, in the present study some novel triazole compounds bearing piperazine moiety were synthesized in order to investigate their anticandidal activitiy. Structure eluciaditions of the synthesized compounds were confirmed by spectral analyses. Anticandidal activity test was performed according to CLSI reference M7- A7 broth microdilution method [2] as described in our previously [3]. Synthesized compounds (5a-5h) displayed anticandidal activity to different extends, which are comparable to reference agent ketoconazole.
Keywords: Triazole, piperazine, anticandida
References: 1. Stefanska J, Szulczyk D, Koziol AE, Miroslaw B, Kedzierska E, Fidecka S, et al. Disubstituted thiourea derivatives and their activity on CNS: Synthesis and biological evaluation. Eur J Med Chem. 2012;55:205-13. 2. Clinical and Laboratory Standards Institute. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved Standard-Ninth Edition. Pennsylvania, USA: CLSI document M07-A9. 3. Gencer HK, Cevik UA, Cavusoglu BK, Saglik BN, Levent S, Atli O, et al. Design, synthesis, and evaluation of novel 2-phenylpropionic acid derivatives as dual COX inhibitory-antibacterial agents. J Enzym Inhib Med Ch. 2017;32(1):732-45.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P17 - Synthesis and Anticholinesterase Activity of Novel Oxadiazole-Piperazine Derivatives
Harun Uslu a*, Serkan Levent b, Begüm Nurpelin Sağlık b, Yusuf Özkay b, Kadriye Benkli c, Zafer Asım Kaplancıklı b a İnönü University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Malatya, Turkey b Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Eskişehir, Turkey c Bezmialem University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, İstanbul, Turkey *E-mail: [email protected]
The cholinesterase inhibitors have reached a great deal of interest Alzheimer's disease (AD) in recent years due to their enhancer effect on levels of acetylcholine (ACh) in cholinergic neurons of patient with AD. Enhancement of ACh neurotransmission in the remaining cholinergic neurons would be expected to stabilize the disease symptomatically [1]. In recent studies, anticholinesterase importance of piperazine ring system has been emphasised [2]. In addtion oxadiazole is another pharmacophore group in medicinal chemistry as acetylcholinesterase inhibitor agent [3] From this point of view, in the present study a novel series of piperazine-oxadiazole derivatives was designed, synthesized, characterized. BuChE and AChE inhibitory activities of the compounds were investigated in order to acquire new biologically active compounds. Compound 4c and 4h was found the be most active derivatives in the series.
Keywords: Oxadiazole, Piperazine, BuChE, AChE, Alzheimer's disease
References: 1. Yue CM, Jing NH. The promise of stem cells in the therapy of Alzheimer's disease. Transl Neurodegener. 2015;4. 2. Sadashiva CT, Chandra JNNS, Ponnappa KC, Gowda TV, Rangappa KS. Synthesis and efficacy of 1-[bis(4- fluorophenyl)-methyl]piperazine derivatives for acetylcholinesterase inhibition, as a stimulant of central cholinergic neurotransmission in Alzheimer's disease. Bioorg Med Chem Lett. 2006;16(15):3932-6. 3. Mohammadi-Khanaposhtani M, Mahdavi M, Saeedi M, Sabourian R, Safavi M, Khanavi M, et al. Design, Synthesis, Biological Evaluation, and Docking Study of Acetylcholinesterase Inhibitors: New Acridone-1,2,4- oxadiazole-1,2,3-triazole Hybrids. Chem Biol Drug Des. 2015;86(6):1425-32.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P18 - Phenolic Compounds from Pedicularis atropurpurea Nordm.
Hilal Özbek a*, Bilge Akcıl b, Cavit Kazaz c, Zühal Güvenalp a a Department of Pharmacognosy, Faculty of Pharmacy, Atatürk University, 25240, Erzurum, Turkey b Department of Pharmacognosy, Faculty of Pharmacy, Erzincan University, 24100, Erzincan, Turkey c Department of Chemistry, Faculty of Science, Atatürk University, 25240, Erzurum, Turkey
E-mail: [email protected]
The genus Pedicularis (Scrophulariaceae) has eleven species growing in Turkey and two of them are endemic [1,2]. Many Pedicularis species have been used in the Traditional Chinese Medicine for the treatment of exhaustion, collapse, senility, uneasiness of body and mind, malignant sores, digestive problems and as cardiotonic [3]. According to phytochemical studies; iridoids, phenylpropanoids, lignans, flavonoids and alkaloids have been isolated and identified from the genus Pedicularis. The biological activity studies of this species indicated antitumor, hepatoprotective, antioxidant, antihaemolysis, antibacterial, skeletal muscle relaxant and nootropic activities [4].
In this study, methanol extract of Pedicularis atropurpurea was dissolved in water and partitioned with n- hexane, chloroform, ethyl acetate and n-butanol, respectively. Ethyl acetate extract was subjected to column chromatography on silica gel followed by sephadex LH-20 and reversed phase silica gel to give two flavonoids (apigenin, luteolin) and two phenylethanoid glycosides (verbascoside, leucosceptoside A). The structures of these compounds were determined by extensive spectroscopic analyses.
Keywords: Pedicularis atropurpurea, Scrophulariaceae, isolation, phenolic compounds
References:
1. Hedge IC. Pedicularis L. In: Davis PH (ed). Flora of Turkey and the East Aegan Islands. Edinburg University Press, Edinburg, 1978.
2. Güner A, Aslan S, Ekim T, Vural M, Babaç MT. (eds). Türkiye Bitkiler Listesi (Damarlı Bitkiler). Nezahat Gökyiğit Botanik Bahçesi ve Flora Araştırmaları Derneği Yayını. İstanbul, 2012.
3. Khodaie L, Delazar A, Lotfipour F, Nazemiyeh H, Asnaashari S, Moghadam SB, Nahar L, Sarker SD. Phytochemistry and Bioactivity of Pedicularis sibthorpii Growing in Iran. Brazilian Journal of Pharmacognosy. 2012; 22(6):1268-1275.
4. Li MX, He XR, Tao R, Cao X. Phytochemistry and Pharmacology of the Genus Pedicularis used in traditional Chinese medicine. The American Journal of Chinese Medicine. 2014; 42(5):1071-1098.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P19 - Investigation of Reaction of Some Ester Ethoxycarbonyl Hydrazones with 1- Adamantyl Amine
İnci Selin Doğan a*, Bahittin Kahveci b
a Karadeniz Technical Uni., Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Trabzon, Turkey b Karadeniz Technical Uni., Faculty of Health Sciences, Department of Nutrition and Dietetics, Trabzon, Turkey *E-mail: [email protected], [email protected]
The 1-adamantyl amine, which has been used in the synthesis of heterocyclic compounds since 1967, has been a highly studied substance due to the important pharmacological activities of its derivatives in the following years [1]. Compounds carrying the adamantan ring are known for their antiviral activity [2]. Ester ethoxycarbonyl hydrazones have long been used in the synthesis of heterocyclic compounds containing the triazole ring [3, 4]. It is known that compounds carrying triazole ring have antibacterial, antifungal, antitumoral and antiepileptic activities. In this study, we have studied the reaction of the 1- adamantyl amine compound with 6 different ester ethoxycarbonyl hydrazone derivatives. First, we synthesized iminoester hydrochloride derivatives according to the Pinner method. Then, ester ethoxycarbonyl hydrazone derivative compounds were synthesized by reacting iminoester hydrochlorides with ethylcarbazate at 0-5 °C in ethanol (3, 4). In the last step, the ester ethoxycarbonyl hydrazone derivative compounds were heated in oil bath with 1-adamantyl amine and we synthesized the 3- substituted-4-adamantyl-1,2,4-triazol-5-one derivative as an original compounds (3, 4). But we have seen that triazole ring can’t closed by this reaction conditions, Ethyl N- (adamantylcarbamoyl)alkylcarbohydrazonoate derivative was synthesized as stabile and original compound. The structure of the synthesized compounds, were elucidated by spectroscopic methods using IR, 1H –NMR, 13C-NMR spectra and Mass analysis. The activities of the 6 new Ethyl N- (adamantylcarbamoyl)alkylcarbohydrazonoate derivative compounds will be examined.
R: -CH₃, -C₂H₅, -C₆H₅, -CH₂-C₆H₅, -CH₂-C₆H₄(p-Cl), -CH₂-C₆H₄(p-Me)
Keywords: 1-adamantyl amine, 3-substituted-4-adamantyl-1,2,4-triazol-5-one, ethyl carbazate
References: 1. Daniker, H.U. 1-Hydrazinoadamantane. Helvetica Chimica Acta. 1967; 50(7): 2008-10. 2. Akgün, H., Balkan, A., Bilgin, A., A., Çalış, Ü., Dalkara, S., Erol, D. v.d. Farmasötik Kimya, 4. Baskı, Hacettepe Üniversitesi Hastaneleri Basımevi, Ankara, 2016. 3. İkizler, A., Demirbas, N., Demirbas A. and İkizler A.A. The reaction of Ester Etohoxycarbonyl hydrazones with carboxylic acid hydrazides. Polish J. Chem. 1996; 70: 1114-1120. 4. Kahveci, B. Synthesis of 4-amino- 4,5-dihydro-1H,1,2,4-triazole-5-ones and their Isatin-3-imine Derivatives. Molecules. 2005;10: 376-382.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P20 - The Effect of Cetuximab on the Total Oxidative Status of HT-29 Cell Line
Fatma Betul Ozgerisa, Nezahat Kurta, Omer Faruk Kocakb, Mehmet Ali Gula, Mevlut Sait Kelesa
a Ataturk Universty,Medical Faculty Depertmant of Medical Biochemistry, Erzurum b Ataturk Universty,Erzurum Vocational School Department of Chemical Technology *E-mail: [email protected]
Cetuximab (CTX), an epidermal growth factor antagonist monoclonal antibody, is widely used in the treatment of corectal cancer (CRC)(1). Oxidative stress is defined as the imbalance between free radical production of cells and antioxidant defense of the body(2). The aim of the current study is to investigate the relationship between total antioxidant capacity (TAS), total oxidant capacity (TOS) and oxidative stress index (OSI) of CTX used in the treatment of CRC. 10 different experimental groups were formed by applying CTX at different doses to CRC cell lines and all groups were left for incubation for 24 and 48 hours. TAS, TOS and OSI values were determined from the cell lysates in all groups. There was a significant decrease in TOS levels in the group treated with 10 μM CTX compared to the control group after 24 h of incubation (p <0,05). In the same way, the decrease in OSI has been a factor. A significant decrease in TOS levels was observed in the 1 μM CTX group compared to the 48 h incubation control group. When all the CTX groups were evaluated, a significant difference was found in TAS values and a significant decrease was seen in OSI values (p <0,05). In HT-29 KRK cells, when CTX stops cell growth, it may result in decreased oxidative stress. Keywords: Cetuximab, Total Oxidative Status, Colorectal Cancer. References: 1.Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. New England journal of medicine. 2004;351(4):337-45. 2.Davies KJ. Oxidative stress, antioxidant defenses, and damage removal, repair, and replacement systems. IUBMB life. 2000;50(4‐5):279-89.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P21 - Synthetic Protocol for Imidazo-1,4-Oxazines and Evaluation of Their Cytotoxicity and Genotoxicity with SAR
Mehmet Taşpınar a*, Burak Kuzu b, Meltem Tan b, Nurettin Mengeş b
a Van Yüzüncü Yil University, Faculty of Medicine,Deparmten of Medical Biology, 65080, Van, Turkey b Van Yüzüncü Yil University, Faculty of Pharmacy, 65080, Van, Turkey *E-mail: [email protected]
The design and synthesis of desired and tolerable methods to attain the complex molecules from appropriate starting materials is still challenging work for a lots of scientific areas such as modern synthetic and medicinal chemistry.
MTT assay was used to determine the drug sensitivity of the LN405 glioma cell line. Single cell gel electrophoresis (COMET) DNA damage was determined by COMET assay after LN405 cells were treated with compounds.
Imidazo-1,5-alkynyl alcohols derivatives were synthesized and they were cyclized to imidazo-1,4-oxazines by means of Cesium carbonate. Propargyl-allene isomerization which was base-supported was examined and the reaction mechanism was proposed. Moreover, cytotoxicity of synthesized molecules on the cells were investigated using structure activity relationship (SAR). With SAR study, toxicities of some functional groups have been shown. In addition, two lead compounds were tested for DNA damaging.
With SAR study, we have uncovered that phenyl ring at exact orientation is responsible for higher toxicity on the cells. Furthermore, flour atom at para position of phenyl ring exhibited also important toxicity which might be due to specific interactions with guanidine which are unique for flour atom resulting in DNA damaging
Keywords: Imidazooxazine, SAR, DNA damaging, cytotoxicity, NMR
Acknowledgements: This Project has been funded by Scientific and Technological Research Agency of Turkey (TUBİTAK) with grand nıumber 115Z894
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P22 - Synthesis and Carbonic Anhydrase Inhibitory Activities of Some Novel Azafluorenone Derıvatıves
Halise Inci Gul a*, Mehtap Tugrak a, Ilhami Gulcin b
a Ataturk University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 25240 Erzurum, Turkey, b Department of Chemistry, Faculty of Science, AtaturkUniversity, Erzurum, Turkey *E-mail: [email protected]
Carbonic anhydrases (CAs, EC 4.2.1.1) belong to the family of zinc metallo enzymes and primarily responsible for catalyzing simple fundamental reaction, i.e CO2 hydration to bicarbonate and protons [1]. Carbonic anhydrase inhibitors (CAIs) have several bioactivities and also many clinical uses such as diuretics, anti-glaucoma, anti-ulcers, and anti-epileptic [2,3]. CA inhibitors (CAIs) have generally sulfonamide moiety in their chemical structure. However, some phenolic compounds and coumarin derivatives were also reported with inhibitory profiles on CAs in the literatures [4]. The 4-azafluorenone alkaloids from Annonaceae species comprise a small but biologically intriguing group of alkaloids. 4- Azafluorenone derivatives were also reported as phosphodiesterase inhibitors, which is useful in te treatment of neurodegenerative disorders and inflammation related diseases [5]. In this study, it was aimed to synthesize new azafluorenone derivatives (H1-H8, Figure 1,) to evaluate their inhibitory effects on hCA I and II isoenzymes (Table 1). As a conclusion, H7 and H5 seemed the leader compounds of this study towards hCAI and hCAII, respectively, according to IC50 value.
Keywords: Azafluorenone, carbonic anhydrase
Figure 1. Structures of azafluorenone Table 1: Carbonic Anhyrase Inhibitory Profiles of H1-H8 on hCAI and hCAII derivatives, H1-H8.
OH IC50 (nM) KI (nM)
Compound hCA I r2 hCA II r2 hCA I hCA II H1 61.875 0.9688 67.281 0.9450 6.8316±2.022 3.5280±1.135 O
H2 70.020 0.9292 71.443 0.9792 4.6577±1.022 6.7563±1.535
H3 58.728 0.9495 74.516 0.9455 7.2645±3.140 5.6070±1.671 Ar N H4 68.613 0.9646 73.723 0.9626 8.4757±2.554 7.9153±2.016 H5 59.230 0.9689 59.741 0.9705 5.1777±1.463 3.8242±0.874 H1-H8 H6 61.327 0.9791 67.281 0.9725 5.0125±1.258 7.2065±1.740 H7 54.140 0.9103 68.613 0.9832 7.5103±3.442 3.5061±0.911 Ar: C6H5 (H1), 4-CH3C6H4 (H2), H8 73.723 0.9399 76.153 0.9880 6.6933±1.386 6.1730±1.155 4-CH3OC6H4 (H3), 4-FC6H4 (H4), 4- AZA 197.304 0.9889 115.50 0.9719 183.390±19.71 104.60±27.60 BrC6H4 (H5), 4-ClC6H4 (H6), 3-HOC6H4 (H7), 4-HOC 6H4 (H8) AZA: Acetazolamide
Ref erences: 1.SupuranKey words: CT. Structure and Function of Carbonic Anhydrase. Biochemistry Journal. 2016; 473: 2023-2032. 2.Scozzafava A, Supuran CT, et al. Antiobesity Carbonic Anhydrase Inhibitors. Expert Opinion Ther. Patent. 2013; 23: 725–35. 3.Carta F, Supuran CT. Diuretics with carbonic anhydrase inhibitory action: a patent and literature review. Expert Opinion Ther. Patent. 2013; 23: 681–91. 4.Maresca A, Temperini C, et al. Deciphering the mechanism of carbonic anhydrase inhibition with coumarins and thiocoumarins. Journal of Medicinal Chemistry. 2010; 53: 335–44. 5.Heintzelman GR, Averill KM, et al. Preparation of 5-oxo and 5-thio derivatives of 5H-indeno[1,2-b]pyridine with adenosine A2a receptor binding and phosphodiesterase inhibiting activity for the treatment of neurodegenerative disorders and inflammation related diseases Int. Appl.WO 2003088963, 2003.
Acknowledgements: The authors thank to Ataturk University BAP office for the financial support.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P23 - Discovery of Novel Indeno-Pyridine Derivatives as Anticancer Agents
Halise Inci Gul a*, Mehtap Tugrak a, Hiroshi Sakagamib
a Ataturk University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 25240 Erzurum, Turkey, b Division of Pharmacology, Meikai University School of Dentistry, Sakado, Saitama, Japan *E-mail: [email protected]
Cancer is the second leading cause of mortality and morbidity after heart diseases across the world which affected 14.1 million in 2012 [1]. Although enormous efforts and developments in chemotherapeutic strategies, the available drugs in clinical use available drugs have various problems such as low selectivity, cross resistance, and low stability [2]. So, there is urgent need to develop more safe, potent and selective anticancer agents. Neidle and co-workers have shown that fluorenones not only performed anticancer activity but also low cytotoxicity towards normal human cells in their study.The anticancer activities of these fluorenone-based compounds may be achieved by their property on DNA strand intercalation [3]. In the present study, it was aimed to evaluate the cytotoxicities of new azafluorenone derivatives (I1-I8, Figure 1). Compounds were synthesized according to literatures. The cytotoxicities were tested via MTT test as reported. As conclusion, according to Table 1, the compound I5 is the leader compound of this study with the highest PSE value.
Figure 1. Structures of azafluorenone derivatives synthesized I1-I8. Ar: C6H5 (I1), 4-CH3C6H4 (I2), 4-CH3OC6H4 (I3), 4- FC6H4 (I4), 4-ClC6H4 (I5), 4-BrC6H4 (I6), 4-NO2C6H4 (I7), C4H3S (2-yl) (I8) Table 1. Cytotoxicity of the compounds (I1-I8)
Tumour cell line CC50 (μM) Non-tumour cell lineCC50 (μM) TS PSIx100
Compound Ca9-22 (A) SI HSC-2 (B) SI HSC-4 (C) SI D J HGF (E) HPLF (F) G (G/D) (E/A) J/D I 23 1.8 15 2.8 26 1.6 21 2.1 43 41 42 2.0 1.9 10.0 F I1 >1000 <0.8 994 0.8 >1000 <0.8 >998 <0.8 861 820 841 <0.8 <0.9 <0.08
I2 7.2 4.0 15 1.9 194 0.1 72 2.0 26 31 29 0.4 3.6 2.8
I3 6.5 1.2 11 0.7 <3.9 ˃1.9 7.1 ˃1.3 9 6.3 7.7 1.1 1.4 ˃18.3
I4 4.3 1.1 13 0.4 <3.9 ˃1.2 7.1 ˃0.9 4.6 4,9 4.8 0.7 1.1 ˃12.7
I5* 7.5 16.8 17 7.4 7.2 17.5 11 13.9 125 127 126 11.5 16.7 126.4 O
I6 7.1 3.5 7.8 3.2 146 0.2 54 2.3 36 14 25 0.5 5.1 4.3
I7 <3.9 ˃3.1 <3.9 ˃3.1 56 0.2 <21 ˃2.1 21 <3.9 12 <0.6 >5.4 ˃10.0
I8 10 4.8 12 4.0 7.8 6.2 9.9 5.0 49 47 48 4.8 4.9 50.5 Ar N Average 118.83 4.12 120.97 2.7 160.53 3.3 133.46 3.38 130.51 116.98 126.17 2.49 4.56 26.1
Melphalan 22.6 7.1 8.5 18.8 11.9 13.4 14.3 13.1 140.0 179.0 159.5 11.1 6.2 91.6 5-FU 29 ˃34.5 13 ˃77.0 13 ˃77.0 18.3 ˃62.8 ˃1000 ˃1000 ˃1000 ˃54.6 ˃34.5 ˃343.2 I1-I8 [Gingival carcinoma (Ca9-22), oral squamous cell carcinoma (HSC-2, HSC-4)] [gingival fibroblasts (HGF), periodontal ligament fibroblasts (HPLF)] PSI (potency selectivity expression): It is the product of the reciprocal of the average CC50figure towards Ca9–22, HSC-2, HSC-3 and HSC-4 cell lines and the average SI value towards these neoplasms expressed as a percentage. Keywords: Cancer, fluorenone, cytotoxicity
References: 1.Mahapatra DK, Bharti SK et al. Anti-cancer chalcones: Structural and molecular target perspectives. Europen Journal of Medicinal Chemistry. 2015; 98: 69-114. 2.Bisi A, Meli M, et al. Multidrug Resistance Reverting Activity and Antitumor Profile of New Phenothiazine Derivatives. Bioorganic Medicinal Chemistry. 2008; 16: 6474-6482. 3.Alcaro S, Artese A, et al. Rational design, synthesis, biophysical and antiproliferative evaluation of fluorenone derivatives with DNA G-quadruplex binding properties. Chemial Medicinal Chemistry. 2010; 5: 575-583. Acknowledgements: The authors thank to Ataturk University BAP office for the financial support.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P24 - Effect of Sample Preparation Techniques for 2D Applications
Merve Nenni a, b*, Mustafa Çelebier a, Selin Öncül c, Ayşe Ercan c, Sacide Altınöz a a Hacettepe University, Faculty of Pharmacy, Department of Analytical Chemistry, 06100, Sıhhiye, Ankara, Turkey b Çukurova University, Faculty of Pharmacy, Department of Analytical Chemistry, 01330, Sarıçam, Adana, Turkey
c Hacettepe University, Faculty of Pharmacy, Department of Biochemistry, 06100, Sıhhiye, Ankara, Turkey *E-mail: [email protected]
Two-dimensional gel electrophoresis (2-D) is the first step in the classical proteomics strategy to resolve the complex nature of cellular part. The procedure combines two types of 2-D: pI based protein separation by isoelectric focusing (IEF), and molecular weight separation by SDS-PAGE (poliacrylamide gel electrophoresis) [1,2]. Because of the outstanding separating capabilities of 2-D for complete proteins, it would be advantageous to be able to apply it to all types of proteins. Unfortunately, severe solubility problems hamper the analysis of many classes of proteins. Sample preparation is a fundamental step in the proteomics workflow. Many techniques are available for cell lysis. The method must be compatible with the amount of material to be processed and the analytical procedures that are going to be used: electrophoresis, chromatography or mass spectrometry. Although physical lysis has been the method of choice, in the last years procedures using detergents have become very popular due to their ease of use, low cost and new protocols with proven efficiency [3]. The purpose of this study was to investigate the effects of physical methods and detergent methods used to prepare cell fractions on 2-D results. In this study, MCF-7 cell line was used in proteomic study. Protein precipitation was carried out with 10% (v/v) TCA and 20 mM DTT in acetone at -20 C. Protein pellets were dissolved sample buffer to a final protein concentration of 1.5 mg/mL. Each 11-cm long IPG pH 5-8 strip was rehydrated with 280 L of protein solution for 5 hrs. After IEF, the IPG strips were equilibrated for 10 min in equilibration buffer 1 and 10 min in equilibration buffer 2 under shaking. After equilibration, the IPG strips were laid on a 4-12% (m/v) Bis-Tris Criterion XT Precast Gel from Bio-Rad. SYPRO Ruby was used for gel staining. The 2-D gels were scanned and the relative gel images were analyzed by using PDQuest software. According to the results, it was seen that lysis technique using detergent was not suitable for 2D applications. Keywords: Proteomic, 2-D gel electrophoresis, isoelectric focusing, detergent, cell lysis References: 1.Liu H, Luo Y, Han J, Wu J, Wu Z, Feng D, et al. Proteome reference map of Haloarcula hispanica and comparative proteomic and transcriptomic analysis of polyhydroxyalkanoate biosynthesis under genetic and environmental perturbations. Journal of proteome research. 2013;12(3):1300-15. 2.Rabilloud T, Luche S, Santoni V, Chevallet M. Detergents and chaotropes for protein solubilization before two- dimensional electrophoresis. Plant proteomics: methods and protocols. 2007:111-9. 3.Van Broekhoven A, Peeters M-C, Debeer LJ, Mannaerts GP. Subcellular distribution of coenzyme A: evidence for a separate coenzyme A pool in peroxisomes. Biochemical and biophysical research communications. 1981;100(1):305-12
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P25 - Comparison of HPLC and Spectrophotometric Methods on Determination of the pKa of Drugs
Mustafa Çelebier a,*, Merve Nenni a,b, Ozan Kaplana, Emrah Akgeyikc, Mustafa Sinan Kaynak c, Sacide Altınöz a, Selma Şahind a Hacettepe University, Faculty of Pharmacy, Department of Analytical Chemistry, 06100, Sıhhiye, Ankara, Turkey. b Çukurova University, Faculty of Pharmacy, Department of Analytical Chemistry, 01330, Sarıçam, Adana, Turkey c Inonü University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 44210, Malatya, Turkey. d Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 06100, Ankara, Turkey. *E-mail: [email protected]
It is important to know the lipophilicity and pKa of drugs to understand their behavior in gastrointestinal system. In this study, pKa value of piroxicam was determined using HPLC and UV-VIS Spectrophotometry. Piroxicam was used as a model drug in this study to compare the ability of Spectrophotometric and HPLC method on pKa determination. Piroxicam belongs to a long-acting class of nonsteroidal anti-inflammatory drugs (NSAIDs) which displays potent anti-inflammatory and analgesic activity [1]. On UV-VIS Spectrophotometric pKa determination, the spectra of piroxicam in the phosphate buffers at different pH values from 2.70 to 10.00 were recorded by UV-VIS Spectrophotometry. The sigmoidal curve was constructed at 285 nm wavelength and pKa value of piroxicam was found to be 5.7 optimum conditions at various pH values (pH 3.09 – 7.48). For chromatographic detection, piroxicam was eluted at 7.44 min in acidic pH (pH 3.64) and eluted at 4.34 min in relatively basic pH (pH 5.94) values. When the pH of mobile phase was plotted against k’ values, a sigmoidal relationship was obtained between pH and capacity factor. The pKa value of piroxicam was calculated as 5.3 from this relationship by HPLC. All these results indicate that different experimental approaches used for pKa determination could provide different values. Due to the fact that not all of the drugs have chromophore group, UV Spectrophotometric method is not possible to apply for wide range of drugs. HPLC is an unique technique to determine for pKa values of active pharmaceutical ingredients.
Keywords: Piroxicam, pKa, HPLC, UV-VIS Spectrophotometry
References: 1.Sweetman, S. C. (Ed.), Martindale, The Complete Drug Reference, 35th ed., Pharmaceutical Press, London 2007.
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P26 - A New HPLC Method for Determination of Naproxen in Human Plasma Samples
Merve Nenni a,b*, Mustafa Çelebier a, İncilay Süslü a, Sacide Altınöz a a Hacettepe University, Faculty of Pharmacy, Department of Analytical Chemistry, 06100, Sıhhiye, Ankara, Turkey b Çukurova University, Faculty of Pharmacy, Department of Analytical Chemistry, 01330, Sarıçam, Adana, Turkey *E-mail: [email protected].
Naproxen sodium (NS) is a well-known and widely used member of the aryl acetic acid group of Nonsteroidal anti-inflammatory drugs (NSAIDs) [1]. NSAIDs are anti-inflammatory, analgesic, and antipyretic properties. They chronically use to reduce pain, decrease stiff ness, and improve function in patients with osteoarthritis, rheumatoid arthritis, and other forms of arthritis [2]. The aim of this study is to develop a rapid and simple analysis technique for determination of NS in spiked human plasma samples. The described method is simple and rapid for the analysis of naproxen sodium from biological samples since no extraction is needed and direct injection to the HPLC is achieved after simply precipitation of plasma protein. The naproxen sodium samples were precipitated by methanol and then filtrated. The supernatant was injected into the HPLC system where an ACE 5 µm C18 100 Å LC Column (150 x 4.6 mm) was used. The optimum conditions for reverse phase HPLC analyses were found by initial experiments and the mobile phase was an acetonitrile:phosphate buffer (55:45 v/v) (pH 3.0, 20 mM) mixture. The injection volume was 20 μL and UV detection was set at 240 nm. Plasma samples including spiked NS were successfully analysed by the validated HPLC method. Under these conditions, NS was eluted at 3.2 min. Run time was thus kept shorter than 5 min. The optimized HPLC method was validated according to the FDA definition [3] and found that the limits of detection (LOD) was 2 ng mL-1 and the limits of quantitation (LOQ) was 10 ng mL-1 for NS. The recoveries were 96.69 ±1.21, 102.94 ± 0.64 and 94.41 ± 1.35 (n=6) for the plasma samples containing 10.0, 30.0 and 50.0 µg mL-1 of NS, respectively. All the parameters were validated for accuracy, precision, linearity, sensitivity, reproductivity and stability. The method was successfully applied for the quantification of the naproxen sodium in human plasma. Therefore, the method was found to be accurate, reproducible, sensitive, cost effective, less time consuming and can be successfully applied on routine analysis of naproxen sodium in human plasma. Keywords: Naproxen sodium, human plasma, HPLC, validation
References: 1. Brogden R, Heel R, Speight T, Avery G. Naproxen up to date: a review of its pharmacological properties and therapeutic efficacy and use in rheumatic diseases and pain states. Drugs, 18: 241-277, 1979. 2. Crofford L.J., Arthritis Res. Ther., 15(3), S2 1-10, 2013 3. FDA, Bioanalytical Method Validation, http://www.fda.gov (Accessed 02.08.2017).
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P27 - Inhibition Effects of 2-Amino-3-Cyanoquinolin Derivatives on Carbonic Anhydrase I and II Aliye Altundas a, Berna Gül a, Murat Çankaya b*, Ali Atasever c, İlhami Gülçin d,
a Department of Chemistry, Faculty of Science and Arts, Gazi University, Ankara, Turkey b Department of Biology, Faculty of Science and Arts, Erzincan University, Erzincan, Turkey* c Department of Food Science, Ispir H. Polat Vocational School, Atatürk University, Erzurum, Turkey d Department of Chemistry, Faculty of Science, Atatürk University, Erzurum, Turkey E-mail: [email protected]
Pyridine derivatives have an important role in medicinal chemistry. Naturally occurring or synthetically produced pyridine scaffolds have different pharmacological properties [1]. Carbonic anhydrases (EC4.2.1.1, carbonate dehydratase) commonly found in all organisms and are zinc-containing - metaloenzymes. For metabolism, the conversion of CO2 and HCO3 to each other is very important [2]. The aim of this study was to investigate the in vitro effects of 2-amino-3-cyanoquinolin derivatives on human carbonic anhydrases I and II isoenzymes. CA I and II have been purified from human blood erythrocytes using by Sepharose-4B-l tyrosine-sulfanilamide affinity gel chromatography. The inhibitory effects of 2- amino-3-cyanoquinolin derivatives on two isoenzymes were checked using IC50 and Ki values. Chemicals have vitally role for continuation of life and activity of some of enzymes. Therefore, we recommend that you pay attention to the use of chemicals substances.
CH 3 CN NH 4 O A c , Y H2 C 2 Be n z e n e, O CN Y CN X H C 3 X K2 CO 3 H3 C X CH O CN H CN 6 X= S or O 3a , b n X N NH 2 Y= C or N X 1a , b X= C, O o r S n 7 a- f n = 1 ,2 Scheme. Synthesis of 2-amino-3-cyanoquinolin derivatives (7a-f)
IC50 (µM) KI (µM) Compounds hCA I r2 hCA II r2 hCA I hCA II
7b 138.66 0.9848 6.19 0.9970 53.9122.25 2.560.74
7d 5.63 0.9992 5.68 0.9989 2.842.23 4.561.39
7f 46.22 0.9942 - - 12.980.78 - Keywords: Amino-3-cyanoquinolin, inhibition, affinity, carbonic anhydrase. References: 1. Baumann M, Baxendale IR. An overview of the synthetic routes to the best selling drugs containing 6- membered heterocycles. Beilstein Journal of Organic Chemistry. 2013;9:2265-2319. 2. Ayvaz S, Çankaya M, Atasever A, Altuntas A. 2-Amino-3-cyanopyridine derivatives as carbonic anhydrase inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry. 2013;28:305-310.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P28 - Investigation of Cholinergic Effects of Some Methanesulfonates
Murat Şentürk a, Nashia Zilbeyaz a, Murat Güney b, Kani Zilbeyaz b
a Ağrı İbrahim Çeçen University, Faculty of Pharmacy, Ağrı, Turkey b Ağrı İbrahim Çeçen University, Science and Art Faculty, Ağrı, Turkey
*E-mail: [email protected]
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by intellectual decline and abnormal behaviors and has become one of the main public health problems, especially in the western world due to the increasing number of elderly population [1,2]. Although pathogenesis of AD has not been clarified as yet, one of the most accepted theories has been ‘‘cholinergic hypothesis”. A deficiency in levels of the neuromediators called acetylcholine (ACh) and butyrylcholine (BCh) has been observed in the brains of AD patients. Inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), the key enzymes which hydrolyze ACh and BCh, respectively, has become a major treatment option towards AD [3]. Therefore, we initiated a study to screen their acetylcholinesterase (AChE, EC 3.1.1.7) inhibitory activities, which are the key enzymes taking place in pathogenesis of Alzheimer’s disease. Simple methanesulfonates (1-6) showed IC50 values in the range of 0.660-7.487 µM for AChE and BChE.
Keyword: Methanesulfonate, acetylcholinesterase, butyrylcholinesterase, inhibitors.
References: 1. Bachman DL, Wolf PA, Linn RT, Knoefel JE, Cobb JL, Belanger AJ, D’Agnostino RB, White IR. Prevalence of dementia and problem senile dementia of the Alzheimer type in the Framingham study. Neurology. 1992;42:115- 119. 2. Diehl J, Kurz A. Die vaskulären Demenzen. Fortschr Neurol Psychiatrie. 2002;70:145-154. 3. Schneider LS. Training of Alzheimer's disease with cholinesterase inhibitors. Clinics in Geriatric Medicine. 2001;17:337-358.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P29 - Acetylcholinesterase In Vitro Inhibitory Effects of Tryptophan Based Natural Compounds
Esra Şentürka,b, Hilal Urçarb,c, Murat Şentürkd
a Agri Ibrahim Cecen University, School of Health Services, Agri, Turkey
b Ataturk University, Faculty of Medicine, Department of phsyology, Erzurum, Turkey
c Artvin Coruh University, Department of Nursing, Artvin, Turkey
d Agri Ibrahim Cecen University, Faculty of Pharmacy, Agri, Turkey *E-mail: [email protected]
Tryptophan is an essential amino acid which is the precursor of serotonin and melatonin. Therapeutic melatonin is a therapeutic chemically synthesized form of the pineal indole melatonin with antioxidant properties. The pineal synthesis and secretion of melatonin, a serotonin-derived neurohormone, is dependent on beta-adrenergic receptor function. Melatonin is involved in numerous biological functions including circadian rhythm, sleep, the stress response, aging, and immunity [1]. Acetylcholinesterase (AChE) enzyme is situated in the group of ChEs and hydrolyses the neurotransmitter acetylcholine (ACh) to choline and acetic acid. AChE is found in high concentrations in erythrocytes and brain. AChE is a necessary enzyme for the nervous system. AChE inhibitors are used in treatment of several neuromuscular diseases and were studied for treatment of Alzheimer’s disease [2]. In the present study, inhibition of AChE with tryptophan, melatonin and serotonin were investigated. IC50 value these natural compounds were calculated submicromolar levels. The IC50 value was obtained from activity (%) vs. these compounds concentration plots. These compounds investigated here are promising agents which may be used as lead molecules in order to derivative novel AChE inhibitors that might be useful in medical applications.
Keyword: Melatonine, acetylcholinesterase, inhibitors.
References: 1. https://pubchem.ncbi.nlm.nih.gov 2. Greenblatt HM, Dvir H, Silman I, Sussman JL. Acetylcholinesterase: a multifaceted target for structure-based drug design of anticholinesterase agents for the treatment of Alzheimer's disease. Journal of Molecular Neuroscience. 2003:20;369-383.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P30 - White Root Basidiomycete Trametes versicolor: Safety, Antioxidant and Cytotoxic Activities
Salim Cerig a, Fatime Geyikoglu a, Murat Ozdal a, Kübra Koc a, Özlem Gülmez a,Ömer Faruk Algur a, Nihal Simsek Ozek a,b*, Ferhunde Aysin a,b
a Atatürk University, Faculty of Science, Department of Biology, 25240, Erzurum, Turkey b East Anatolian High Technology Research and Application Center (DAYTAM), Atatürk University, 25240, Erzurum, Turkey *Corresponding Author:[email protected]
Trametes versicolor (TV) known as “turkey tail” is an extremely common polypore mushroom which can be commonly found throughout the world. The purpose of this study was to investigate the antioxidant activity and cytotoxic effects of mycelium extracts of the TV (0 - 500 µg/ml) on human blood cells (hBCs). Total antioxidant capacity (TAC) and total oxidant status (TOS) were performed to determine the oxidant/antioxidant levels. Cytotoxic effect was determined by 3-(4,5 dimetylthiazol-2–yl)–2,5 diphenltetrazolium bromide (MTT) assay. TAC was found to be significantly increased with TV (0-100 µg/ml) treatment. However, a significant increase in TOS was obtained with 250 and 500 µg/ml doses of TV treatment. Moreover, no cytotoxic effect was observed in 0-100 µg/ml dose of TV treated cells. On the other hand, significant decreased in cell viability was found in hBCs treated with 250 and 500 µg/ml doses of TV. The results of the present study indicated that TV treatment induces cytotoxicity and oxidative damage on human blood cells in a dose dependent manner. Therefore, the overconsumption of TV can be harmful for human health.
Keywords: Trametes versicolor, oxidative stress, MTT, human health
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P31 - Synthesis of Sensiline and its Aromatic Derivatives
Nurhan Kishali a, Özlem Gündoğdu b, Yunus Kara a
a Department of Chemistry, Faculty of Sciences, Atatürk University, TR-25240, Erzurum
b Department of Food, Kaman Vocational Training School, Ahi Evran University-TR-40100-Kırşehir
*E-mail: [email protected]
Uncontrolled platelets aggregation is critical in arterial thrombosis. Therefore, the regulation of platelet function can be a promising approach for the treatment of thrombosis. Anti-thrombotic agent development from medicinal plants with little side effect has attracted much interest [1]. In China, the fruits of Acanthopanax sessiliflorus have been developed into a series of products for food therapy, since they are proven to be non-toxic with significant therapeutic effects on the cardiovascular and cerebrovascular diseases. The antiplatelet activity of Acanthopanax sessiliflorus is mainly investigated in the in vitro studies of individual components [2]. Sessiline (1) was isolated from the fruits of Acanthopanax sessiliflorus3. In this study, Sessiline derivatives were synthesized to investigate thrombosis effects in vitro.
Keywords: Acanthopanax sessiliflorus, sessiline
References: 1. Davies, M. J., Thomas, A. C. Plaque fissuring--the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angına. Br Heart J. 1985; 53(4); 363-373. 2. Yang S., Chun-Juan Y., Kai Y., Fa-Mei L. Studies on the Chemical Constituents of the Fruit of Acanthopanax sessiliflorus. Chinese Journal of Natural Medicines. 2011; 9(2): 0141−0145. 3. Ilkei, V., Faragó, K., Sánta, Z., Dékány, M., Hazai, L., Szántay, Jr. C., Szántay, C., Kalaus, G. The First Synthesis of Sessiline. International Journal of Organic Chemistry. 2014; 4; 309-313.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P32 - Synthesis of Isoindole-1,3-Dion derivatives
Özlem Gündoğdu a, Nurhan Kishali b* a Department of Food, Kaman Vocational Training School, Ahi Evran University-TR-40100-Kırşehir
b Department of Chemistry, Faculty of Sciences, Atatürk University, TR-25240, Erzurum
*E-mail: [email protected]
Isoindole-1,3-diones, are key structural units in a variety of biologically important compounds. Several fungicides, metabolic drugs, and functional materials contain alkyl-substituted İsoindole-1,3-dion as key structural elements [1]. Furthermore the cyclic imido group is a common protecting group for amines and is widely used in carbohydrate chemistry [2]. Recently it is reported that some Isoindole-1,3-diones derivatives directly inhibits COX-1/COX-2 with efficacy comparable to that of the representative drug, aspirin. Photoluminescence and anti-cancer activity of some isoindole-1,3-diones derivatives has been previously determined by our group. These compounds have also been used in protein markers. In this study, isoindole- 1,3-dione derivatives containing carboxylic acid and its derivatives were synthesized to investigate anti- cancer properties.
Keywords: Isoindole-1,3-dion, anti-cancer, photoluminescence
References: 1. Brown, A. D., Bunnage, M. E., Lane, C. A. L., Lewthwaite, R. A., Glossop, P. A., James, K., Price, D. A. US 20,050,215,590, 2005; Chem. Abstr. 2005; 143; 346910. 2. A.A.-M. Abdel-Aziz. Novel and versatile methodology for synthesis of cyclic imides and evaluation of their cytotoxic, DNA binding, apoptotic inducing activities and molecular modeling study. Eur. J. Med. Chem. 2007; 42; 614-626. 3. Sano H., Noguchi T., Tanatani A., Hashimoto Y., Miyachi H. Design and synthesis of subtype-selective cyclooxygenase (COX) inhibitors derived from thalidomide. Bioorg. Med. Chem. 2005; 13; 3079-3091.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P33 - Heterogeneous Fenton Process by Magnetite Nanostructures Prepared by High Energy Planetary Ball Mill for Ciprofloxacin Removal from Aqueous Solutions
Melike Karaca a, Aydin Hassani a, Özkan Açışlı b, Semra Karaca a∗, Bilal Yılmazc a Department of Chemistry, Faculty of Science, Atatürk University, 25240 Erzurum, Turkey b Department of Petroleum and Natural Gas Engineering, Oltu Faculty of Earth Sciences, Atatürk University, 25240 Erzurum, Turkey c Department of Analytical Chemistry, Faculty of Pharmacy, Atatürk University 25240, Erzurum, Turkey *E-mail:[email protected] Recently, scientists have been focused to find effective ways in removing of the pharmaceutical compounds, due to their ubiquitous distribution in the environment, fate, effects and their potential toxic risk on the ecosystems and living organisms [1]. Advanced oxidation processes as green technologies, are a good option to degrade most of the organic pollutants [2]. Among them, Fenton process which is produced 2+ highly reactive hydroxyl radicals through the catalytic decomposition of H2O2 by Fe is commonly used for the degradation of organic pollutants because it is cheap, simple and effective to the resistant compounds [2]. Fe3O4 is a very appealing catalyst for remediation of organic compounds [3]. In this study, nano-sized magnetite particles (Fe3O4) were used as a catalyst and ciprofloxacin (CIP) was choosed as a target recalcitrant contaminant. The obtained results clearly indicated that the Fe3O4 in nano-sized catalyzed heterogeneous Fenton reaction can be successfully applied for the degradation of CIP from the aqueous solutions. The characterization results of magnetite catalyst in nano-sized was prepared from natural magnetite using high energy planetary ball milling process confirmed that magnetite was formed at the nanoscale. The catalytic activity of the ball milled magnetite sample increased in parallel with the improvement in the its physicochemical properties. It was determined that the optimum conditions for the parameters such as pH, catalyst dosage, hydrogen peroxide amount and initial CIP concentration affecting CIP removal efficiency by heterogeneous Fenton process are 3, 1.75 g/L, 12 mM and 10 mg/L, respectively. In the optimum conditions, CIP removal was 88.92%. The addition of scavengers caused a reduction in CIP degradation. From the results obtained from all experiments, it was concluded that CIP degradation over Fe3O4 nanocatalyst by heterogeneous process occurs from the steps of adsorption and oxidation and OH radicals has predominantly role in degradation. The results of GC–MS analysis verified efficient degradation of CIP molecules. Keywords: Ball milling process, magnetite nanoparticles, ciprofloxacin, wastewater treatment References: 1.Xiong J-Q, Kurade MB, Kim JR, Roh H-S, Jeon B-H. Ciprofloxacin toxicity and its co-metabolic removal by a freshwater microalga Chlamydomonas mexicana. Journal of Hazardous Materials. 2017;323,PartA:212-9. 2.Acisli O, Khataee A, Karaca S, Karimi A, Dogan E. Combination of ultrasonic and Fenton processes in the presence of magnetite nanostructures prepared by high energy planetary ball mill. UltrasonicsSonochemistry.2017;34:754-62. 3.Hou L, Wang L, Royer S, Zhang H. Ultrasound-assisted heterogeneous Fenton-like degradation of tetracycline over a magnetite catalyst. Journal of Hazardous Materials. 2016;302:458-67.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P34 - Application of Dispersive Liquid-Liquid Microextraction for the Determination of Donepezil in Urine by HPLC Using a Core-Shell Column
Sercan Yıldırım a, Nevin Ulaş Çolak a, Ahmet Yaşar a
a Department of Analytical Chemistry, Faculty of Pharmacy, Karadeniz Technical University, Trabzon, Turkey *E-mail: [email protected]
Alzheimer’s disease is a neurodegenerative disorder characterized by the decline in cognitive skills as well as complete dementia and a significant subject in health sciences owing to its frequent occurrence in older people. Two main classes of drugs, cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists, are currently used in the treatment of Alzheimer's disease. Donepezil is a second-generation cholinesterase inhibitor, which exerts its action by enhancing cholinergic function through inhibition of acetylcholinesterase, thus decreasing the breakdown of acetylcholine [1,2]. A rapid and novel method combining dispersive liquid-liquid microextraction and high-performance liquid chromatography coupled with fluorescence detection was developed for the determination of donepezil in human urine. Parameters affecting extraction efficiency and chromatographic determination, such as the type and volume of the extraction and disperser solvent, and pH of sample for dispersive liquid-liquid microextraction, and mobile phase composition, pH, column oven temperature, and flow rate for chromatographic determination, were evaluated and optimized. Using a C18 core-shell column (7.5 × 4.6 mm, 2.7 µm), the determination of donepezil was accomplished within 5 min. For the assessment of the suitability of the technique for the determination of donepezil in urine the developed method was validated according to recommendations of the Food and Drug Administration [3]. Under optimum conditions, developed method was linear in the range of 0.5-25 ng mL-1 with the correlation coefficient >0.99. Limit of detection was 0.15 ng mL-1. The relative standard deviation at three concentration levels (2, 12.5 and 20 ng mL-1) was less than 11% with accuracy in the range of 96.9-102.8%. The results of this study demonstrate that the use of dispersive liquid- liquid microextraction and core-shell column can be considered as a desirable alternative for the analysis of donepezil in human urine.
Keywords: Core-shell column, donepezil, high-performance liquid chromatography, urine
References: 1. Anand R, Gill KD, Mahdi AA. Therapeutics of Alzheimer’s Disease: Past, Present and Future. Neuropharmacology. 2014;76:27-50. 2. Barnes DE, Yaffe K. The Projected Effect of Risk Factor Reduction on Alzheimer’s Disease Prevalence. Lancet Neurology. 2011;10:819-828. 3. Food and Drug Administration Guidance for Industry, Bioanalytical Method Validation, 2001.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P35 - Anticancer Effect of Ethanolic Extract and Isolated Coumarins from the Roots of Ferulago trachycarpa Boiss. (Apiaceae) on Cancer Cell Proliferation Songül Karakaya a, Filiz Bakar b, Ceyda Sibel Kılıç c
a Department of Pharmacognosy, Faculty of Pharmacy, Atatürk University, Erzurum 25240, Turkey; b Department of Biochemistry, Faculty of Pharmacy, Ankara University, Ankara 06100, Turkey c Department of Pharmaceutical Botany, Faculty of Pharmacy, Ankara University, Ankara 06100, Turkey *E-mail: [email protected]
Ferulago species have been used since ancient times for the treatment of intestinal worms, hemorrhoids and as tonic, digestive, aphrodisiac and sedative. Apart from its medicinal uses, they have been used as salad or spice due to their special odors. However recent reports that various Ferulago species have anticancer activity, as well [1-2]. This study reports the in vitro anticancer activity of the ethanol extract and bioactive compounds isolated from the roots obtained from F. trachycarpa were investigated on cancer cell proliferation. The structures of isolated compounds from the roots of F. trachycarpa were elucidated by detailed analyses of 1D and 2D NMR and ESI-MS data. Human breast adenocarcinoma cells (MCF-7) and human prostate (PC-3) cells were used and measurements were performed via MTT test. Five known coumarins such as osthol (1), prantschimgin (2), xanthotoxin (3), felamidin (4), umbelliferone (5) and a known flavonoid such as rutin (6) were isolated from the roots of F. trachycarpa. Ethanolic extract of roots from F. trachycarpa and prantschimgin showed significant anticancer activity on MCF-7 cells with 0.378 and 0.472 mg/mL IC50 values, respectively. Also, ethanolic extract of roots from F. trachycarpa and osthol showed significant anticancer activity on PC-3 cells with 0.026 and 1.711 mg/mL IC50 values, respectively. The present study demonstrated that among the compounds isolated from CH2Cl2 fraction of F. trachycarpa roots coumarins were determined the main chemical constituents of this fraction. This study aims to give first report on isolation and characterization of the bioactive compounds from root extracts of F. trachycarpa and to report anticancer activity on MCF-7 and PC-3 cells of this species.
Keywords: Apiaceae anticancer, coumarin, Ferulago trachycarpa
References: 1.Demetzos C, Perdetzoglou D, Gazouli M, Tan K, Economakis C. Chemical analysis and antimicrobial studies on three species of Ferulago from Greece. Planta Med. 2000; 66 (6), 560-563. 2.Erdurak CS. Investigations on Ferulago isaurica Peşmen and F. syriaca Boiss. (Umbelliferae) species. 2003; Ankara University Doctorate Thesis, Ankara.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P36 - Anticancer Effect of Aqueous Extract of Ferulago trachycarpa Boiss. (Apiaceae) on Cancer Cell Proliferation
Songül Karakaya a, Filiz Bakar b, Ceyda Sibel Kılıç c
a Department of Pharmacognosy, Faculty of Pharmacy, Atatürk University, Erzurum 25240, Turkey; b Department of Biochemistry, Faculty of Pharmacy, Ankara University, Ankara 06100, Turkey c Department of Pharmaceutical Botany, Faculty of Pharmacy, Ankara University, Ankara 06100, Turkey *E-mail: [email protected]
Ferulago W. Koch., belonging to Apiaceae family, is represented by approximately 50 taxa throughout the world and 35 taxa in Turkey 18 of which are endemic. Therefore Anatolia is considered to be the gene center of this genus. F. trachycarpa Boiss is a perennial species, growing in Southeastern Anatolia, Turkey. Ferulago species have been used since ancient times for the treatment of intestinal worms, hemorrhoids and as tonic, digestive, aphrodisiac and sedative. Apart from its medicinal uses, they have been used as salad or spice due to their special odors. However recent reports that various Ferulago species have anticancer activity, as well [1-5]. This study reports the in vitro anticancer activity of the aqueous extract from F. trachycarpa were investigated on cancer cell proliferation. Human prostate (PC-3) cells were used and measurements were performed via MTT test. The aqueous extracts had significant effects on inhibition of cell proliferation on PC-3 cells. Aqueous extract of roots has shown the highest cytotoxic effect on PC-3 cells with IC50 value of 1.272 mg/mL. This study aims to give first report on anticancer activity on PC-3 cells of extracts from F. trachycarpa. Therefore we can conclude that this species can be used in anticancer diseases and may represent a herbal alternative to synthetic drugs.
Keywords: Apiaceae anticancer, coumarin, ferulago trachycarpa
References: 1. Güner A, Aslan S, Ekim T, Vural M, Babaç MT. 2012. Türkiye Bitkileri Listesi (Damarlı Bitkiler), Nezahat Gökyiğit Botanik Bahçesi ve Flora Araştırmaları Derneği Yayını, İstanbul. 2.Peşmen H. 1972. Ferulago W. Koch, in: Davis, P.H. (Ed.), Flora of Turkey and the East Aegean Islands, Edinburgh University Press, Edinburgh, pp. 4: 469-471. 3.Troia A, Raimondo FM, Castellan, G, Spadaro V. Morphological, karyological and taxonomic remarks on Ferulago nodosa (L.) Boiss. (Apiaceae). Plant Biosystems. 2012; 146 (1), 330-337. 4.Demetzos C, Perdetzoglou D, Gazouli M, Tan K, Economakis C. Chemical analysis and antimicrobial studies on three species of Ferulago from Greece. Planta Med. 2000; 66 (6), 560-563. 5.Erdurak CS. Investigations on Ferulago isaurica Peşmen and F. syriaca Boiss. (Umbelliferae) species. 2003; Ankara University Doctorate Thesis, Ankara.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P37 - Investigation of Cholinesterase Enzyme Inhibition Activity of 3 Barbarea Species
Merve Badem a, Sıla Ozlem Sener a, Nuriye Korkmaz b, Seyda Akkaya b, Rezzan Aliyazicioglu b, Ufuk Özgen a
a Karadeniz Technical University, Faculty of Pharmacy, Department of Pharmacognosy, Trabzon b Karadeniz Technical University, Faculty of Pharmacy, Department of Biochemistry, Trabzon *E-mail:[email protected]
Barbarea genus belongs to Brassicaceae family has been presented about 20 species in Europe and Asia, 15 taxon, 9 taxon are endemic, in Turkey. Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. Alzheimer's disease (AD) is a chronic neurodegenerative disease and enzyme inhibitors are frequently used in the treatment of Alzheimer's disease [1]. With this study, methanolic extracts from the aerial parts the dried and powdered 3 Barbarea species (B. auriculata, B. integrifolia, and B. plantaginea) growing in Turkey and 2 of which are endemic (B. auriculata ve B. integrifolia) were prepared and investigated inhibitory activities of AChE and BuChE of the plant by colorimetric Ellman’s method with some modifications. As a result of the study, the IC50 values for inhibitory activities of AChE assay of B. auriculata, B. integrifolia, and B. plantaginea have been found as 150,95 ± 2,65; 206,90 ± 4,48 and 243,26 ± 4,18 µg/mL, for inhibitory activities of BuChE 679,04 ± 9,36; 247,68 ± 3,89 and 308,14 ± 5,21 have been found, respectively. Inhibitory activities of AChE and BuChE of the plants were found significiant compared with reference compound. The plants can be an alternative native drug source in the treatment of Alzheimer's disease.
Keywords: Alzheimer, barbarea, cholinesterase
References: 1. Colovic M, Danijela Z, Tamara D, et al. Acetylcholinesterase inhibitors: pharmacology and toxicology. Current neuropharmacology. 2013;11(3): 315-335.
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P38 - A GC-MS Based Metabolomic Profiling of the Mouse Lung in Airway Inflammation
Tuba Reçber a, Reshed Abohalaka b, Emirhan Nemutlu a, Turgut Emrah Bozkurt b, İnci Şahin Erdemli b, Sedef Kır a a Hacettepe University, Faculty of Pharmacy, Department of Analytical Chemistry, Sıhhiye, Ankara, Türkiye b Hacettepe University, Faculty of Pharmacy, Department of Pharmacology, Sıhhiye, Ankara, Türkiye *E-mail: [email protected] Airway inflammation is an important feature of chronic airway diseases like asthma and chronic obstructive pulmonary disease (COPD). Therefore anti-inflammatory treatment is one of the main therapeutic approaches for these diseases. In the present study we aimed to perform a metabolomic analysis in the mouse airways in a model of airway inflammation. Lipopolysaccharide (LPS) was used in order to induce experimental airway inflammation. For this purpose, LPS was applied intranasally (60 µL; 0.1 mg/mL in PBS) to mice. The control group received vehicle (60 µL PBS) by the same route. 48 hours after LPS/vehicle application mice were sacrificed by cervical dislocation, the lungs were removed and the blood was collected by cardiac puncture. Isolated lungs were frozen by liquid nitrogen and stored at -80°C until the analysis. In metabolomics, the purpose is to identify and quantify as much as metabolites in a biological system. Analytes in a metabolomic sample comprise highly complex mixture. Combined gas chromatography with mass spectrometry (GC-MS) is one of the most powerful techniques and commonly used in metabolomics studies [1]. Metabolomic profiling of lung homogenate samples were performed using GC-MS (Shimadzu). The derivatized sample was injected split (1:10) by an auto sampler into a gas chromatograph equipped with a 30 m (+10 m duraguard)×0.25 mm i.d. fused-silica capillary column with a chemically bonded 0.25-µm DB-5MS stationary phase. The injector temperature was 250°C, the purge flow was 5 mL min-1, and the purge was turned on after 60 s. The gas flow rate through the column was 2.8 mL min-1, and the column temperature was held at 60°C for 1 min, then increased to 325°C, and held there for 10 min. The interface and the ion source temperatures were 230 and 290°C, respectively. Ions were generated by a 70-eV electron beam at an ionization current of 2.0 mA, and 30 spectra s-1 were recorded in the mass range 50-600 m/z. The lung homogenate samples were compared with control group. As a result of the data evaluation, metabolites differing between the control group and the study group were identified.
Keywords: Metabolomic, GC-MS, profiling, mouse lung, lipopolysaccharide
References: 1. Nemutlu E, Zhang S, Xu YZ, Terzic A, Zhong L, Dzeja PD, Cha YM, Cardiac resynchronization therapy induces adaptive metabolic transitions in the metabolomic profile of heart failure. Journal of cardiac failure. 2015;21(6),460– 469.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P39 - The Role of Pharmacists in Rational Drug Use of Elderly Patients Who Apply to Community
Yağmur Kılıçdağı a, Gülbin Özçelikay b
a Ankara University of Pharmacy Faculty of Department of pharmacy management b Ankara University of Pharmacy Faculty of Department of pharmacy management *E-mail: [email protected]
Just as it is in the whole world, Turkey's population is getting older as a result of the developments in the field of health and decreasing birth rates. Along with aging, changes in perception and creative abilities, such as carelessness, slowing in thinking speed, and weak memory are affecting the life cycle. These changes also affect the use of medicines, especially in the treatment of chronic diseases. As a result, rational drug use work is accelerating in the elderly, and the pharmacist plays a critical role in these studies. This research is a pretest-posttest semi-experimental research of people aged 65 years and over who apply to a pharmacy in the city centre of Ankara. The aim of this research is to measure the effect of education given by the pharmacist on drug use of elderly patients. A three- part questionnaire consisting of demographic information, health status and information on the drugs used, and the role of the pharmacist in drug use was prepared by reviewing the relevant literatures on this subject. After the pre-test, the pharmacist gave education to the patient. The education was about proper drug using, dosage forms, what to do when adverse reactions are seen, adverse effects, drug-drug interactions, drug-food interactions, importance of controlling the expiration date of the drug, storage conditions, herbal products, and importance of drug use in pharmacist counselling. After 3 months from pretest and education, the elderly who came to the pharmacy were post- tested and their scores were determined. Evaluation of the data was performed on the computer using the Statistical Package for the Social Sciences (SPSS)ver.23.0 package program. T-test analysis was performed fort he evaluation of the data samples associated. As a result of the t test, there was a significant difference in pre-education drug knowledge levels and post- education drug knowledge levels. This research shows that the pharmacist who forms the last step between patient and treatment has an important role in providing and devoloping rational drug use.
Keywords: Rational drug use, pharmacist, pharmacy, elderly, older people
References: 1. LeSage J. Polypharmacy in Geriatric Patients. The Nursing Clinics of North America. 1991;26(2):273-290. 2. Wyles H, Rehman H. Inappropriate polypharmacy in the elderly. European Journal of Internal Medicine.2005;16(5):311-313. 3. Borman, P. The principles of rational drug use in the elderly/Yaslilarda akilci ilac kullanimi ilkeleri. Turkish Journal of Physical Medicine and Rehabilitation.2009;72-75. 4. Monette J. Gurwitz J. H, Avorn J. Epidemiology of adverse drug events in the nursing home setting. Drugs & Aging. 1995;7(3), 203-211.
October 05-07, 2017, ERZURUM-TÜRKİYE 87
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P40 - Elevated Glutathione S-Transferase- π (GST- π) Activity in Mesenchymal Phenotype of Human Colorectal Adenocarcinoma Cells (HT-29)
Burcin Ozcelik a b, Acelya Erikci c, Alper Bektas İskit d, Gulberk Ucar c *
a Hitit University, Faculty of Arts and Science, Department of Biology, Corum, Turkey b Hacettepe University, Graduate School of Science and Engineering, Nanotechnology and Nanomedicine Department, Ankara, Turkey c Hacettepe University, Faculty of Pharmacy, Department of Biochemistry, Ankara, Turkey d Hacettepe University, Faculty of Medicine, Department of Pharmacology, Ankara, Turkey *E-mail: [email protected]
Colorectal cancer (CRC) is the most common type of malignancy in the gastrointestinal tract. Widely used chemotherapeutic regiments in CRC such as standard neoadjuvant based and adjuvant therapies have remarkable limitations (serious adverse side effects, recurrency, drug-resistance, etc). Epithelial- mesenchymal transition (EMT) has been found to play a critical role in cancer drug resistance and apoptosis, but the nature of these intrinsic links remains unclear [1]. It has been suggested that EMT causes resistance to oxidative stress and also chemotherapeutic regime based on the creating oxidative stress to become self- advocates. The π and µ classes of GSTs play a regulatory role in cell survival and cancer development. GSTs have been implicated in the development of resistance toward chemotherapy agents via direct detoxification as well as acting as an inhibitor of the MAP kinase pathway. High levels of GSTs have been reported in some tumor types [2]. Although there are some studies suggesting the role of EMT in drug resistance, the relationship between the resistance profile of epithelial and mesenchymal forms and GST in CRC is not yet been elucidated. The aim of the present preliminary study is to induce EMT in the HT-29 cell line and to compare the GST- π and µ levels for both epithelial and mesenchymal phenotypes in order to investigate the role of GST in the progress of drug resistance in CRC. For EMT induction, HT-29 cells were treated with 10 ng/ml of TGF-β1 for 12 to 60 hours. The expression of the mesenchymal markers α-SMA, vimentin, and the epithelial marker E-cadherin as a function of time was analyzed by qRT-PCR. The GST-π and µ isozyme levels of epithelial and mesenchymal forms were quantified by ELISA. As a result, vimentin and α-SMA expression increased in a time dependent manner whereas E-cadherin expression decreased. The levels of GST-π in mesenchymal cells were significantly higher than in epithelial cells but no significant changes in GST-µ levels were observed after TGF-β1 treatment. The data demonstrated that GST-π had a functional importance in drug resistance of mesenchymal cells in CRC. Further in vitro and in vivo studies based on the inhibition of GST-π in mesenchymal phenotype are needed for the development of new chemotherapeutic systems in order to overcome the drug resistance in cancer-associated EMT. Keywords: Colorectal cancer, drug resistance, epithelial-mesenchymal transition (EMT), GSTs. References: 1. Cao H, Xua E, Liu H, Wan L. Lai M. Epithelial–Mesenchymal Transition in Colorectal Cancer Metastasis: A System Review. Pathology Research and Practice. 2015; 211(8):557-69. 2. Arai T, Miyoshi Y, Kim SJ, Akazawa K, Maruyama N, Taguchi T, Tamaki Y, Noguchi S. Association of GSTP1 Expression with Resistance to Docetaxel and Paclitaxel in Human Breast Cancers. Journal of Cancer Surgery. 2008;(34):734-38.
October 05-07, 2017, ERZURUM-TÜRKİYE 88
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P41 - Use of Electronic Impedance Spectroscopy to Monitor Inhibition of Biofilm Formation in Pseudomonas Aeruginosa
Seyit Ahmet Conker a, Erkan Rayaman b, Turgut Şekerler c, Gülgün Boşgelmez Tinaz a*
a Department of Pharmaceutical Basic Sciences, Faculty of Pharmacy, Marmara University, 34668, İstanbul, Turkey b Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Marmara University, 34668, İstanbul, Turkey c Department of Biochemistry, Faculty of Pharmacy, Marmara University, 34668, İstanbul, Turkey *E-mail: [email protected]
Biofilm-associated infections are very difficult to treat with traditional antibiotics as bacteria are embedded in an extracellular matrix composed of exopolysaccharides and proteins that reduces the contact between bacteria and antibacterial agent. Pseudomonas aeruginosa is a opportunistic Gram-negative pathogen that causes chronic biofilm-associated infections in cystic fibrosis and wound patients. Biofilms formed within the human body may increase the resistance of pathogens to drug therapies a thousand-fold. The formation of bacterial biofilms poses serious challenges not only for antibiotic resistance, but also for implants and sterilizing surfaces. For the analysis of biofilms, different methods are available. But most of these methods are time-consuming and - like crystal violet staining - suffer from a high standard deviation. Recently, an impedance-based spectroscopy, initially developed for the study of adherent eukaryotic cells, has been used to monitor the formation of prokaryotic biofilms. This method allows monitoring biofilm formation very precisely with only little standard deviation. Since this is a very new technology, there is very little work available on the formation of P. aeruginosa biofilms using electronic impedance. In the present study, inhibition of biofilm formation upon treatment of P. aeruginosa PA01 cultures with tobramycin and cinnamaldehyde was investigated in real time using impedance spectroscopy (xCELLigence Real Time Cell Analyzer). Our results demonstrated that sub-MIC concentrations of tobramycin and cinnamaldehyde inhibited biofilm formation by P. aeruginosa PA01 strain. Therefore, we suggest that impedance spectroscopy can be succesfully used for the searching of compounds that interfere with the biofilm formation by P. aeruginosa and other clinically important bacteria.
Keywords: Quorum sensing, biofilm inhibition, pseudomonas aeruginosa, RTCA.
References: 1 Hentzer M, Givskov M. Pharmacological inhibition of quorum sensing for the treatment of chronic bacterial infections. J Clin Invest. 2003;(112): 1300-1307. 2 Rasmussen TB, Givskov M. Quorum-sensing inhibitors as antipathogenic drugs. Int J Med Microbiol. 2006; (296):149-161. 3. Van Duuren, JBJH, Müseken M, Karge B, Tomasch J, Wittmann C, Häussler S, Brönstrup M. Use of single- frequency impedance spectroscopy to characterize the growth dynamics of biofilm formation in Pseudomonas aeruginosa. Scientific Reports. 2017; 7 (5223):1-11.
October 05-07, 2017, ERZURUM-TÜRKİYE 89
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P42 - The Investigation of Potential Protective Effects Of Curcumin Against Hearth Toxicity Induced by Irinotecan in Rats
Neşe Başak Türkmen a, Osman Çiftçi b, Aslı Taşlıdere c, Şükrü Gürbüz d a Department of Pharmaceutical Toxicology,Faculty of Pharmacy, University of Inonu, Malatya, Turkey b Department of Medical Pharmacology,Faculty of Medicine, University of Inonu, Malatya, Turkey. c Department of Histology and Embryology, Faculty of Medicine, University of Inonu, Malatya, Turkey. d Department of Emergency, Faculty of Medicine,University of Inonu, Malatya
*E-mail:[email protected] This study was planned to investigation of potential protective effects of curcumin on oxidative and histological damage with cardiac toxicity induced by irinotecan in male rats. Animals were randomly divided into 4 groups: (1) Control, (2) IRN, (3) CRC and 4) IRN + CRC. The control group received 0.1% carboxymethyl cellulose vehicle. In the IRN group, IRN was given once a week at a dose of 10 mg / kg. CRC (50 mg / kg) was dissolved in 0.1% CMC and given for 14 days. CRC + IR group was treated with curcumin for 14 days in the same manner as IRN. As a result, IRN caused oxidative damage (increased TBARS, decreased antioxidant parameters). Curcumin treatment increased GSH, GPx, CAT, SOD activities while reducing TBARS level. In addition, IRN increased histopathologic damage in the heart tissue, but these cardiodegenerative effects were eliminated with curcumin treatment. This study has shown that curcumin efficiently reduces IRN-induced oxidative and histological damage in the heart. Curcumin has beneficial effects, potent antioxidants and radical scavenging properties. This study showed that curcumin administration induced IRN-induced oxidative and histological damage in heart tissue.
Keywords: Irinotekan, curcumin, oxidative and histological damage
References: 1. Alvarenga EM, Souza LK, Araújo TS, Nogueira KM, Sousa FB, Araújo AR, Martins CS, Pacífico DM, de C Brito GA, Souza EP, Sousa DP, Medeiros JV 2. Carvacrol reduces irinotecan-induced intestinal mucositis through inhibition of inflammation and oxidative damage via TRPA1 receptor activation. Chem Biol Interact. 2016; 25;260:129-140. doi: 10.1016/j.cbi.2016.11.009. Epub 2016 Nov 9
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P43 - A Facile Synthesis of Enamines with 1,4-Dimethoxy-2-butyne Mediated by Titanium Tetrachloride
Mustafa Kemal Gümüş a Nesimi Uludağ b*
a Artvin Coruh University Science-Technology Research and Application Center, Artvin, Turkey b Namık Kemal University, Department of Chemistry, Organic Chemistry Division, Tekirdag, Turkey *E-mail: [email protected], [email protected]
Enamines are a versatile functional group capable of alkylations, acylations, cycloadditions and annulation cascade and are also involved in a range of heterocycle forming processes [1]. The broad applicability of heterocyclic secondary enamines and related structures in heterocyclic synthesis has been demonstrated in the past two decades [2-4]. The reaction conditions, yield and nature of enamine ring-opening have received great attention in the literature. We have previously reported the [2+2] cyloaddition reactions for enamines from cyclic ketones with electron-deficient acetylenes such as diethyl acetylenedicarboxylate (DEAD) [5] as well as methyl acetyelencarboxylate [6]. A wide variety of products can be obtained by changing the type of cyclic enamine and acetylene, but the polarity of the solvent used can also influence the route of the reaction. Acetylenedicarboxylate derivatives have found a broad range of applications in the synthetic organic chemistry [7] and our aim was to seek an alternative to the [2+2] cycloaddition of enamines and electron- deficient acetylenes. In this study, we investigated the reaction between cyclic enamines (1a-c) and electrons transferred group substituted acetylene: 1,4-dimethoxy-2-butyne (2). One of the reasons we chose this acetylene was that its electrophilicity is lower than DEAD and other electron-deficient acetylenes.
1 2 1 2 1 2 a) R + R = -CH2CH2OCH2CH2 b) R + R = -(CH2)5- c) R + R = -(CH2)4- i) TiCl4, ˂ 0 °C, Toluene, ii) Reflux, Toluene Scheme Formation of the products 3a-c via [2+2] cycloaddition and 4a-c by cycloisomerization
Keywords: Enamines, [2+2] cycloaddion, acetylenedicarboxylate (DEAD), ring-opening
References: 1. A. G. Cook, Enamines: Synthesis, Structure, and Reactions, Marcel Dekker Inc., New York and Basel (1988). 2. B. Stanovnik and J. Svete, Synlett, 8, 1077 (2000). 3. B. Stanovnik and J. Svete, Chemical Reviews, 104(5), 2433 (2004). 4. J. Svete, J. Heterocycl. Chem., 2(3), 361 (2005). 5. N. Tunoglu and N. Uludag, Org. Prep. Proc. Int., 29(5), 541 (1997). 6. N. Uludag, O, Asutay and M. Yakup, Asian J. Chemistry, 26(4), 971 (2014). 7. B. Stanovnik, Org. Prep. Proc. Int., 46, 24 (2014).
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P44 - New Chromane-Thiazoles as Potent Anticancer Agents
Leyla Yurttaş a*, Şeyma Aydınlık b, Elif İlkay Armutak c
a Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Eskişehir b Uludağ University, Faculty of Science, Department of Molecular Biology, Bursa c İstanbul University, Faculty of Veterinary Medicine, Department of Histology and Embryology, İstanbul *E-mail: [email protected]
Chromanone ring is an important pharmacophore and its derivatives are privileged structures in medicinal chemistry especially with anticancer potential [1]. There are many reported literatures about cytotoxic properties of benzopyran-4-one against various cell lines [2,3]. Thiazole heterocyle is also another significant ring system which is found both in biologically active molecules and clinically used synthetic drugs [4]. Interest in the antineoplastic activity of thiazoles has increased after discovery of the thiazole based cytotoxic agents tiazofurin, distamycin, bleomycin, netropsin and thia-netropsin. New 2-[2- (chroman-4-ylidene)hydrazinyl]-4/5-substituted thiazole derivatives (2a-i) were synthesized in this work. The structures of the compounds were elucidated using 1H, 13C NMR and HRMS spectroscopic techniques. Nine compounds will be tested against MCF7 human breast adenocarcinoma cell line according to Sulforhodamine B colorimetric assay for cytotoxicity screening.
Figure 1. The synthesized compounds (2a-i)
Keywords: Chromane, thiazole, anticancer, MCF-7 cell line.
References: 1. Demirayak S, Yurttas L, Gündoğdu-Karaburun N, Karaburun AC, Kayagil İ. New Chroman-4-one/thiochroman- 4-one Derivatives As Potential Anticancer Agents. Saudi Pharmaceutical Journal. in press, 2017. 2. Keri RS, Budagumpi S, Pai RK, Balakrishna RG. Chromones As a Privileged Scaffold in Drug Discovery: A Review. European Journal of Medicinal Chemistry. 2014;78:340-374. 3. Emami S, Ghanbarimasir Z. Recent Advances of Chroman-4-one Derivatives: Synthetic Approaches and Bioactivities. European Journal of Medicinal Chemistry. 2015;26:539-563. 4. Lu Y, Li CM., Wang Z, Ross CR, Chen J, Dalton J, Li W, Miller DD. Discovery of 4-Substituted Methoxybenzoyl- aryl-thiazole As Novel Anticancer Agents: Synthesis, Biological Evaluation and Structure-activity Relationships. Journal of Medicinal Chemistry. 2009;52:1701-1711.
October 05-07, 2017, ERZURUM-TÜRKİYE 92
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P45 - In vitro Antidiabetic Activity of Elaeagnus angustifolia L. and Its Active Compounds
Hafize Yuca a*, Hilal Özbek a, Cavit Kazaz b, Zühal Güvenalp a
a Department of Pharmacognosy, Faculty of Pharmacy, Atatürk University, 25240 Erzurum, Turkey b Department of Chemistry, Faculty of Science, Atatürk University, 25240 Erzurum, Turkey *E-mail: [email protected]
Elaeagnus angustifolia L. (Elaeagnaceae) is known as “Kuş İğdesi” in Turkey [1]. Its leaves are used as antidiabetic as well as flowers and leaves as diuretic and antipyretic in Turkish folk medicine [2,3]. According to previous studies, its extracts were found to have β-carboline alkaloids, polysaccharides, esters, flavonoids, phenols, phenolic acids, ketones, phenyl ethers, steroids, terpenes; and possessed antimicrobial, insecticidal, antioxidant, anti-arthritic, wound healing, cardioprotective, hypolipidemic, antinociceptive, anti-inflammatory, antimutagenic, gastroprotective and antitumor activities in vivo and in vitro [4]. In the present study, the methanol extract and its different polarity fractions (n-hexane, dichloromethane, ethyl acetate, n-butanol) prepared from leaves of E. angustifolia were evaluated for in vitro α-glucosidase and α- amylase inhibitory activities [5]. The ethyl acetate fraction showed the best α-glucosidase inhibitory activity with 90.1% (IC50=0.0912 mg/mL) when compared with the standard compound acarbose that displayed 7.0% inhibitory activity (IC50=4.2839 mg/mL) at 200 µg/mL concentration. For isolation of compound(s) responsible for activity, the fractions of ethyl acetate extract were evaluated and showed 30-50% inhibitory activity at the same concentration. A known flavonoid: trans-tiliroside (EAE-1) with a new one: isorhamnetin-3-O-β-D-glucopyranosyl-7-O-[2,6-dimethyl-6-hydroxy-2,7-octadienoyl-(1→4)]-α-L- rhamnopyranoside (EAE-2) were isolated from these fractions which were identified by means of spectral methods. Also, EAE-1 showed 41.7% (IC50=0.2382 mg/mL) and EAE-2 showed 25.9% (IC50=0.4400 mg/mL) inhibitory activities at the same concentration. However, the extracts showed no inhibition against α-amylase.
Keywords: Elaeagnus angustifolia, antidiabetic, in vitro, isolation, NMR
References: 1. McKean DR, Davis PH (ed). Elaeagnus L. Flora of Turkey and the East Aegean Island, Edinburg University Press, UK, 1982;7:533-534. 2. Arıtuluk ZC, Ezer N. Halk arasında diyabete karşı kullanılan bitkiler (Türkiye)-II. Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi. 2012;32(2):179-208. 3. Baytop T. Türkiye’de Bitkiler ile Tedavi- Geçişte ve Bugün, Nobel Tıp Kitabevleri, İstanbul. 1999;244. 4. Farzaei MH, Bahramsoltani R, Abbasabadi Z, Rahimi R. A comprehensive review on phytochemical and pharmacological aspects of Elaeagnus angustifolia L. Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology. 2015;67:1467-1480. 5. Tao Y, Zhang Y, Cheng Y, Wang Y. Rapid screening and identification of α-glucosidase inhibitors from mulberry leaves using enzyme-immobilized magnetic beads coupled with HPLC/MS and NMR. Biomedical Chromatography. 2013;27:148-155.
October 05-07, 2017, ERZURUM-TÜRKİYE 93
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P46 - Nesfatin-1 Has a Protective Effect against Isoproterenol-Induced Myocardial Infarction in Rats
Arda Tasatargil a, Selvinaz Dalaklioglu a, Sebahat Ozdem b, Ayse Barutcigil a, Sadi Ozdem a
a Akdeniz University, Medical Faculty, Department of Pharmacology, 07070, Antalya, Turkey
b Akdeniz University, Medical Faculty, Department Of Biochemistry, 07070, Antalya, Turkey E-mail: [email protected]
The present study was designed to evaluate the cardioprotective effects of nesfatin-1, a novel peptide with anorexigenic properties, in rats with isoproterenol (ISO)-induced myocardial infarction (MI). Rats were randomly divided into four groups. First group that served as control (C group, n = 8) received only intraperitoneal (i.p.) physiological saline of 1ml/kg for 9 days. Second group (MI group, n = 8) received i.p. physiological saline of 1ml/kg for 1 week and then ISO was injected subcutaneously (s.c.) for two consecutive days at a dosage of 85 mg/kg/day. Third group (MI-treatment group, n = 8) received i.p. physiological saline of 1ml/kg for 1 week and then ISO was injected s.c. for two consecutive days at a dosage of 85 mg/kg/day, concomitant with 10 µg/kg/day i.p. nesfatin-1. Fourth group (MI-pretreatment group, n = 8) received 10 µg/kg/day i.p. nesfatin-1 for 1 week and then ISO was injected s.c. for two consecutive days at a dosage of 85 mg/kg/day. Left ventricle weight/whole body weight ratio increased significantly in rats with ISO-induced MI compared to control rats ISO-induced myocardial damage was indicated by elevated levels of cardiac specific troponin-T and enhanced myocardial expression of proinflammatory cytokines (interleukin-1β, interleukin-6 and tumor necrosis factor-α). However, nesfatin- 1 administration either as pretreatment or treatment resulted in significant reductions in cardiac troponin- T, interleukin-1β and interleukin-6 levels of rats with ISO-induced MI. Although there were substantial reductions in tumor necrosis factor-α levels both in nesfatin-1 pretreated and nesfatin-1-treated rats, tumor necrosis factor-α levels decreased down to control levels only in nesfatin-1 pretreated but not in nesfatin-1 treated rats. The results of the present study showed that nesfatin-1, which appears to possess anti- inflammatory properties, may confer protection against ISO-induced MI.
Keywords: Nesfatin-1, myocardial infarction, cardioprotective effects
October 05-07, 2017, ERZURUM-TÜRKİYE 94
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P47 - Screening for Cytotoxic Effects of Chlorokojic Acid Derivatives
Aytemir M.D.a*, Karakaya G.a, Ercan A.b, Öncül S. b
a Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100, Sıhhiye, Ankara, Turkey. b Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, 06100, Sıhhiye, Ankara, Turkey. * E-mail: [email protected]
Malignant melanoma is an aggressive form of cancer caused by malignantly transformed melanocytes. It has an increasing incidence and mortality, and represents a major public health issue. Numerous agents are currently under development to provide alternative therapeutic options [1]. Previously, some Mannich bases of chlorokojic acid derivatives were synthesized in our laboratory and their extensive bioactivities were determined including anticonvulsant, antimicrobial, antiviral, antioxidant, anti-mycobacterium, anti-aging and anti-tyrosinase activities, additionally cytotoxicity evaluation 2-6. In this study, Mannich bases of chlorokojic acid derivatives were synthesized and evaluated for cytotoxic effect on A375 human malignant melanoma, HGF-1 fibroblast and MRC-5 lung cells. Chlorination of the 2-hydroxymethyl moiety of kojic acid using thionyl chloride at room temperature produced chlorokojic acid, with the ring hydroxyl being unaffected. Mannich bases were prepared by the reaction of appropriate substituted benzylpiperazine derivatives with chlorokojic acid and formaline at room temperature with quite significant yield. Viability of A375 malign melanoma, HGF-1 fibroblast and MRC-5 lung cells exposed to the compound was assessed by sulforhodamine B (SRB) assay. SRB is an aminoxanthene dye that binds to the basic amino acid residues of cellular proteins under mild acidic conditions. SRB assay is a colorimetric method based on measurement of cellular protein content and used for the determination of cytotoxicity [7]. Vemurafenib, dacarbazine, temozolomide, lenalidomide and fotemustine currently used in the treatment of malign melanoma were utilized as control agents. It was found that the cytotoxicity effect of the Compounds 1-9 was higher when compared to all of the control agents, except vemurafenib. This research was funded as a project by TÜBİTAK. Project No: SBAG-315S067.
Keywords: Chlorokojic acid, mannich base, cytotoxicity
References: 1. Lacy KE, Karagiannis SN, Nestle FO. Advances in the treatment of melanoma. Clinical Medicine. 2012;12(2):168- 71. 2. Aytemir MD, Özçelik B. A study of cytotoxicity of novel chlorokojic acid derivatives with their antimicrobial and antiviral activities. European Journal of Medicinal Chemistry. 2010;45(9):4089-95. 3. Aytemir MD, Özçelik B. Synthesis and biological activities of new mannich bases of chlorokojic acid derivatives. Medicinal Chemistry Research. 2011;20(4):443-52. 4. Karakaya G, Aytemir MD, Özçelik B, Çalış Ü. Design, synthesis and in vivo/in vitro screening of novel chlorokojic acid derivatives. Journal of Enzyme Inhibition and Medicinal Chemistry. 2013;28(3):627-38. 5. Aytemir MD, Özçelik B, Karakaya G. Evaluation of bioactivities of chlorokojic acid derivatives against dermatophytes couplet with cytotoxicity. Bioorganic & Medicinal Chemistry Letters. 2013;23(12):3646-9. 6. Aytemir MD, Özçelik B. Erdoğan Orhan I., Karakaya G, Şenol FS. Turkish Patent 23.06.2015 TR2015/07653 (WO2016/209180) International Patent 17.05.2016 (PCT/TR2016/000070). 7. Vichai V, Kirtikara K. Sulforhodamine B colorimetric assay for cytotoxicity screening. Nature Protocols. 2006;1(3):1112-6.
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P48 - Simultaneous Determination of Arbutin and Hydroquinone in Different Herbal Slimming Products by Gas Chromatography-Mass Spectrometry
Benan Dursunoğlu a*, Hafize Yuca a, Sefa Gözcü b, Bilal Yılmaz c, Zühal Güvenalp a a Department of Pharmacognosy, Faculty of Pharmacy, Atatürk University, 25240, Erzurum, Turkey b Department of Pharmacognosy, Faculty of Pharmacy, Erzincan University, 24100, Erzincan, Turkey c Department of Analytical Chemistry, Faculty of Pharmacy, Atatürk University, 25240, Erzurum, Turkey
E-mail: [email protected]
Arbutin (4-hydroxyphenyl-β-D-glucopyranoside) is a phenolic glucoside that is found mainly in Ericaceae and Saxifragaceae species [1]. Hydroquinone is 1,4-dihydroxybenzene and the metabolite of arbutin [2]. In this study, a simple, precise, sensitive and specific method has been developed for the simultaneous determination of arbutin and hydroquinone in different herbal slimming products containing Calluna vulgaris by gas chromatography-mass spectrometry (GC-MS). The retention times of arbutin and hydroquinone were found 11.32 and 5.44 min, respectively. The linear range in this developed method was 5-500 ng/mL for arbutin and hydroquinone. The intra- and inter-day precisions, expressed as the relative standard deviation, were less than 1.94 and 2.73%, determined from quality control samples for arbutin and hydroquinone, and accuracy was within 1.13 and 2.56% in terms of relative error, respectively. Limit of detection and quantification for arbutin were 0.555 and 1.665 ng/mL, for hydroquinone 0.031 and 0.093 ng/mL, respectively. The developed method can be used for routine quality control analysis of arbutin and hydroquinone in different herbal slimming products.
Keywords: Arbutin, hydroquinone, GC-MS, herbal slimming product, calluna vulgaris
References:
1. Migas P, Krauze-Baranowska M. The Significance of Arbutin and Its Derivatives in Therapy and Cosmetics. Phytochemistry Letters. 2015; 13:35-40.
2. Jurica K, Karaconji IB, Segan S, Opsenica DM, Kremer D. Quantitative Analysis of Arbutin and Hydroquinone in Strawberry Tree (Arbutus unedo L., Ericaceae) Leaves by Gas Chromatography-Mass Spectrometry. Archives of Industrial Hygiene and Toxicology. 2015; 66:197-202.
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P49 - Synthesis and Evaluation of Antidepressant Activity of Some Novel Naphtyl Etanone Oxime Ester Derivatives Bearing Pyrazole Moiety
İrem Bozbey a*, Harun Uslu a, Zeynep Özdemir a, Arzu Karakurt a
a Inonu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Malatya, Turkey *[email protected] Pyrazole derivatives have diverse biological activities such as antimicrobial, anticancer, cytotoxic, analgesic, anti-inflammatory, antihypertensive, CNS activity like antiepileptic, antidepressant, etc. Several pyrazole derivatives possess important pharmacological activities and they have been proven as useful materials in drug research [1]. From this point of view, in this present study some novel naphtyl etanone oxime ester derivatives bearing pyrazole moiety were designed, synthesized, characterized and antidepressant activity was evaluated. The antidepressant effect of these compounds was evaluated by the forced-swimming test on mice. The behavioural parameter observed in this test is a reduction in the immobility time, which is indicative of antidepressant activity also known as described in the Porsolt test [2]. Novel naphtyl etanone oxime ester derivatives bearing pyrazole moiety have been synthesized according to the reaction pathways given below. The structures of oxime compounds were confirmed by 13C-NMR, 1H-NMR and Mass spectra.
Keywords: Antidepressant, Oxime Ester, Pyrazole
References: 1. Küçükgüzel ŞG, Şenkardeş S. Recent advances in bioactive pyrazoles. Eur J Med Chem. 2015;97:786-815. 2. Porsolt RD, Bertin A, Blavet N, Deniel M, Jalfre M. Immobilityinducedbyforcedswimming in rats: effects ofagentswhichmodifycentralcatecholamineandserotoninactivity. Eur J Pharmacol 1979;57:201-10.
October 05-07, 2017, ERZURUM-TÜRKİYE 97
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P50 - New Chromane-Thiazoles as Potent Anticancer Agents
Leyla Yurttaş a*, Şeyma Aydınlık b, Elif İlkay Armutak c
a Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Eskişehir b Uludağ University, Faculty of Science, Department of Molecular Biology, Bursa c İstanbul University, Faculty of Veterinary Medicine, Department of Histology and Embryology, İstanbul *E-mail: [email protected]
Chromanone ring is an important pharmacophore and its derivatives are privileged structures in medicinal chemistry especially with anticancer potential [1]. There are many reported literatures about cytotoxic properties of benzopyran-4-one against various cell lines [2,3]. Thiazole heterocyle is also another significant ring system which is found both in biologically active molecules and clinically used synthetic drugs [4]. Interest in the antineoplastic activity of thiazoles has increased after discovery of the thiazole based cytotoxic agents tiazofurin, distamycin, bleomycin, netropsin and thia-netropsin. New 2-[2- (chroman-4-ylidene)hydrazinyl]-4/5-substituted thiazole derivatives (2a-i) were synthesized in this work. The structures of the compounds were elucidated using 1H, 13C NMR and HRMS spectroscopic techniques. Nine compounds will be tested against MCF7 human breast adenocarcinoma cell line according to Sulforhodamine B colorimetric assay for cytotoxicity screening.
Figure 1. The synthesized compounds (2a-i)
Keywords: Chromane, thiazole, anticancer, MCF-7 cell line.
References: 1. Demirayak S, Yurttas L, Gündoğdu-Karaburun N, Karaburun AC, Kayagil İ. New Chroman-4-one/thiochroman- 4-one Derivatives As Potential Anticancer Agents. Saudi Pharmaceutical Journal. in press, 2017. 2. Keri RS, Budagumpi S, Pai RK, Balakrishna RG. Chromones As a Privileged Scaffold in Drug Discovery: A Review. European Journal of Medicinal Chemistry. 2014;78:340-374. 3. Emami S, Ghanbarimasir Z. Recent Advances of Chroman-4-one Derivatives: Synthetic Approaches and Bioactivities. European Journal of Medicinal Chemistry. 2015;26:539-563. 4. Lu Y, Li CM., Wang Z, Ross CR, Chen J, Dalton J, Li W, Miller DD. Discovery of 4-Substituted Methoxybenzoyl- aryl-thiazole As Novel Anticancer Agents: Synthesis, Biological Evaluation and Structure-activity Relationships. Journal of Medicinal Chemistry. 2009;52:1701-1711.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P51 - Determination of Antioxidant Capacity of Ether Extract of Myrtus communis L. Leaf via DPPH and ABTS/TEAC Methods
Zerrin Kutlua, Lale Duysaka, Mine Gulaboglua*
aAtatürk University, Faculty of Pharmacy, Department of Biochemistry, 25240, Erzurum E-mail: [email protected] Myrtus communis L. is an endemic plant in the Mediterranean region, which is widely grown and used in west and south Anatolia. Various parts of Myrtus communis L. are used in folk medicine [1]. Leaves of Myrtus communis L.contain small amounts of phenolic acids (caffeic, ellagic and gallic acids) and quercetin derivatives, whereas catechin derivatives and myricetin derivatives are present in large amounts [2]. In this study, ether extract of Myrtus communis L. leaf were analyzed with different antioxidant activity methods as DPPH and ABTS/TEAC which are the most common and cited antioxidant capacity measurement method. In procedure, Myrtus communis L. leaf ether extract were prepared in 40 ug/mL and then the samples were analyzed with DPPH and ABTS/TEAC methods. In order to compare and calculate the equivalant antioxidant capacity of each sample, different concentration of reference samples were prepared in between 1-40 ug/mL. All measurements were performed in Biotek Elisa Reader and results were evaluated with Microsoft Excel 2010 software [3,4]. According to the results, Myrtus communis L. leaf ether extract exhibit antioxidant capacity in terms of DPPH and ABTS/TEAC.
Key words: Antioxidants capacity, ABTS/TEAC, DPPH, Myrtus Communis L.
References:
1. Alipour G, Dashti S, Hosseinzadeh H. Review of pharmacological effects of Myrtus communis L. and its active constituents. Phytotherapy Research. 2014;28(8): 1125-36. 2. Romani A, Pinelli P, Mulinacci N, Vincieri FF, Tattini M. Identification and quantitation of polyphenols in leaves of Myrtus communis L. Chromatographia. 1999;49:17-20. 3. Huang DJ, Ou BX, RL. P. The chemistry behind antioxidant capacity assays. Journal of Agricultural and Food Chemistry,. 2005;53:1841-56. 4. Sanchez-Moreno C, Larrauri JA, Saura-Calixto F. A procedure to measure the antiradical efficiency of polyphenols. Journal of the Science of Food and Agriculture. 1998;76:270-6.
October 05-07, 2017, ERZURUM-TÜRKİYE 99
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P52 - Synthesis, Molecular Modeling and Biological Evaluation of
4-[5-aryl-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl] benzenesulfonamides
Cem Yamali a, Halise Inci Gul a*, Abdulilah Ece b, İlhami Gulcin c a Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University,Erzurum Turkey. b Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Biruni University, Istanbul, Turkey c Department of Chemistry, Faculty of Arts and Sciences, Ataturk University, Erzurum, Turkey. *E-mail: [email protected]
Carbonic anhydrase (CAs, EC 4.2.1.1), a zinc-containing enzyme, catalyzes a reversible reaction between - CO2 and HCO3 . CAs are present in many organism and have an essential role in pathological and physiological events [1]. Pharmacophore hybrid approach is one of the most effective method in medicinal chemistry to produce new drug candidates [2]. On the basis of this rational, it was planned to combine two pharmacophores as sulfonamide and pyrazoline in a single molecule to obtain potent and selective CA inhibitors. Pyrazolines TP1-10 (Figure 1) were synthesized according to literatüre [3] and chemical structures of them were confirmed by 1H NMR and 13C NMR and HRMS. Enzyme inhibition studies and molecular docking experiments [4] were carried out (Figure 2). Ki values of the compounds towards hCA I were in the range of 24.2±4.6 - 49.8±12.8 nM while they were in the range of 37.3±9.0 - 65.3±16.7 nM towards hCA II. Ki values of the Acetazolamide were 282.1±19.7 nM and 103.60±27.6 nM towards both isoenzymes, respectively. According to the interactions of the compounds with enzyme active side, sulfonamide groups in the most active compound TP8, adopts similar orientation with Acetazolamide, making the key interactions with the Thr199 and zinc ion in the catalytic binding site of CAI (Fig. 2a). Same key interactions exist in the TP1-CAII complex too (Fig. 2b). The experimental and computational findings obtained in the present study might be useful in the design of novel inhibitors against hCA I and hCA II isoenzymes.
Ar: C6H5, TP1; 4-CH3C6H4, TP2; 4-CH3OC6H4, TP3; 4- FC6H4, TP4; 4-ClC6H4, TP5; 4-BrC6H4, TP6; 4-CF3C6H4, TP7; C4H3S(2-yl), TP8; 2,4- (CH3O)2C6H3, TP9; 3,4- (CH 3O)2C6H3, TP10.
Figure 1. General chemical structures of pyrazolines TP1-10 Figure 2. 2D ligand interaction diagrams of CA I-TP8 (a) and CA II-TP1 (b) Figure 2. 2D ligand interaction diagrams of CA I-TP8 (a) and CA II-TP1 (b) Keywords: Doking, pyrazoline, CA inhibitors
References: 1. Supuran CT. Bioorg Med Chem Lett. 2010;20(12):3467-3474. 2. De Oliveira Pedrosa M et al. Curr Top Med Chem. 2017;17(9):1044-1079. 3. Gul HI et al. J Enzyme Inhib Med Chem. 2017;32(1):169-175. 4. Ece A et al. J Enzyme Inhib Med Chem. 2015;30(4):528-532.
Acknowledgements: The authours thank to Ataturk University BAP office for the financial support.
October 05-07, 2017, ERZURUM-TÜRKİYE 100
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P53 - Monoamine Oxidase Inhibitory Potential of New Chalcone Derivatives Containing Piperazine Ring
Betül Kaya Çavuşoğlu a*, Serkan Levent a, Begüm Nurpelin Sağlık a, Abdullah Burak Karaduman b, Özlem Atlı b, Yusuf Özkay a, Zafer Asım Kaplancıklı a
a Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470 Eskişehir, Turkey b Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, 26470 Eskişehir, Turkey *E-mail: [email protected]
The flavin adenine dinucleotide (FAD)-containing enzyme monoamine oxidase (MAO) catalyzes the oxidation of monoamines and exists as two isoforms, MAO-A and MAO-B [1]. MAO-A inhibitors can be employed in the cases of depression while MAO-B inhibitors can be used for the symptomatic treatment of Parkinson’s and Alzheimer’s diseases [2]. Chalcones (1,3-diphenyl-2-propen-1-ones) are open chain flavonoids that are an important class of natural compounds and have various biological activities. Compounds bearing chalcone scaffold can act on the central nervous system (CNS) owing to its low polar surface area. Many of the studies clearly revealed that chalcone compounds showed selective and potent MAO inhibition [3]. In addition, compounds bearing piperazine ring have also MAO inhibitory effect [4]. Based on these observations, we have synthesized nine compounds and examined their MAO inhibitory activities by an in vitro fluorometric method. The structures of the synthesized compounds have been determined by using FT-IR, 1H NMR, 13C NMR, MS spectral data and elemental analyses results. Compounds have found more selective against MAO-B than MAO-A. Among them, compounds 4, 5, 7, 9 showed the highest inhibitory activity.
Keywords: Chalcone, MAO inhibition, piperazine.
References:
1. Yamada M, Yasuhara H. Clinical Pharmacology of MAO Inhibitors: Safety and Future. Neurotoxicology.2004;25(1-2):215-221. 2. Pacher P, Kohegyi E, Keckemeti V, Furst S. Current Trends in the Development of New Antidepressants. Current Medicinal Chemistry.2001;8(2):89–100. 3. Chimenti F, Fioravanti R, Bolasco A, Chimenti P, Secci D, Rossi F, Yáñez M, Orallo F, Ortuso F, Alcaro S. Chalcones: A Valid Scaffold for Monoamine Oxidases Inhibitors. Journal of Medicinal Chemistry.2009;52(9):2818- 2824. 4. Kaya B, Yurttaş L, Sağlık BN, Levent S, Özkay Y, Kaplancıklı ZA. Novel 1-(2-Pyrimidin-2-yl)piperazine Derivatives as Selective Monoamine Oxidase (MAO)-A Inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry.2017;32(1):193-202.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P54 - Novel Mannich Bases Derived From 1,2,4-Triazole-5-thione Containing Naproxen Moiety as Analgesic/Anti-inflammatory Compounds
Hayrünnisa Taşci a, Birsen Tozkoparan a, Nesrin Gökhan Kelekçi a*
a Hacettepe University, Faculty of Pharmacy, Dept of Pharmaceutical Chemistry, 06100 Ankara-Turkey
Non-steroidal anti-inflammatory drugs (NSAIDs) are a heterogeneous group of substances that share similar therapeutic effects and side‐effects. They are currently one of the most frequently used drugs worldwide for the treatment of pain, inflammation and inflammation-related disorders. Unfortunately, all NSAID treatment carries some side effects including gastrointestinal perforation, ulceration, bleeding (PUB) and renal toxicity which are mainly observed in cases of chronic NSAID usage. Therefore, although these drugs have a big market share, it is still very challenging to develop novel safe, selective and efficient chemical entities for treating inflammation. Over the past 15 years we have been interested in the development of novel compounds with analgesic/anti-inflammatory activity. In this respect, the chemistry and the synthesis of mercapto-1,2,4-triazoles, their various derivatives have been attracted our widespread attention [1-5]. Mannich bases of various mercapto-1,2,4-triazoles with primary and/or secondary amines also studied as anti-inflammatory/and analgesic compounds. In present investigation, to develop novel anti- inflammatory/analgesic agents with improved safety profile, a new series of Mannich derivatives of 1,2,4- triazole-5-thione containing naproxen moiety, with possible analgesic anti-inflammatory activity, was designed and synthesized as naproxen analogues. Firstly, 3-[1-(6-methoxy-2-naphthyl)ethyl]-1,2,4- triazole-5-thione prepared via dicyclohexyl_ carbodiimide (DCC)-promoted amide formation reaction, starting from naproxen according to the reported procedure [2]. This compound was then submitted to Mannich reaction by the treatment with formaldehyde and secondary amines in ethanol. The structures of the isolated compounds were confirmed by spectroscopic and elemental analysis.
References: 1. B. Tozkoparan, G. Ayhan Kılcıgil, R. Ertan, M. Ertan, P. Kelicen, R. Demirdamar, Synthesis and Evaluation of Antiinflammatory Activity of the Thiazolo3,2-b-1,2,4-triazole-5(6H)-ones and Their Michael Addition Products, Arzneim.-Forsch./Drug Res. 49, 1006 (1999). 2. B. Tozkoparan, N. Gökhan, G. Aktay, E. Yeşilada, M. Ertan, 6-Benzylidenethiazolo3,2-b-1,2,4-triazole-5(6H)- ones Substituted with Ibuprofen: Synthesis, Characterization and Evaluation of Antiinflammatory Activity, Eur. J. Med. Chem. 35, 743 (2000). 3. B. Tozkoparan, G. Aktay, E. Yeşilada, Synthesis of some 1,2,4-triazolo[3,2-b]-1,3-thiazine-7-ones with potential analgesic and antiinflammatory activities, Il Farmaco 57, 145 (2002). 4. P.S. Aytaç, B. Tozkoparan, B.F. Kaynak, G. Aktay, Ö. Göktaş, S. Ünüvar, Synthesis of 3,6-disubstituted 7H-1,2,4- triazolo[3,4-b]-1,3,4-thiadiazines as novel analgesic/anti-inflammatory compounds, Eur. J. Med. Chem. 44, 4528 (2009). 5. D. Sarigol, A. Uzgoren-Baran, B. C. Tel, E. I. Somuncuoglu, I. Kazkayasi, K. Ozadali-Sari, O. Unsal-Tan, G. Okay, M. Ertan, B. Tozkoparan, Novel thiazolo[3,2-b]-1,2,4-triazoles derived from naproxen with analgesic/anti- inflammatory properties: Synthesis, biological evaluation and molecular modeling studies, Bioorg. Med. Chem. 23, 2518 (2015).
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P55 - Bioactivities of Isatin Mannich Bases
Dilan Ozmen Ozgun a, Halise Inci Gul b*, Cem Yamali b a Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Agri Ibrahim Cecen University, Agri, Turkey b Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey *E-posta: [email protected]
Isatin (1H-Indole-2,3-dion) and its derivatives are biologically active compounds and have significant importance in medicinal chemistry. Isatin moiety has many biological activities, such as anticonvulsant, MAO-A and MAO-B inhibitory, antianxiety, antimicrobial, anti-inflammatory, analgesic, antioxidant, anticancer, and cholinesterase inhibitory activities [1]. In this study it was aimed to investigate carbonic anhydrase, acetylcholinesterase and butyrylcholinesterase inhibitory activities of some isatin Mannich bases to make a contribution to the Mannich bases literature library on which limited information is available.
Scheme 1. Synthesis of isatin Mannich bases, P1-P3.
i = Paraformaldehyde, amine (P1=Piperidine; P2=Morfoline; P3=N-Methylpiperazine), ethanol, reflux. Mannich derivatives of isatin were synthesized and then evaluated their bioactivities according to literatüre [2]. This pilot study suggests that P1–P3 demonstrated impressive inhibition profiles against AChE and BChE and also inhibited both CAs at nanomolar level. These inhibitory effects were more powerful in all cases than the reference compounds used for all these enzymes. This study suggests that isatin Mannich bases P1–P3 are good candidate compounds especially for the development of new cholinesterase inhibitors since they were 2.2–5.9 times better inhibitors than clinically used drug Tacrine.
Keywords: Mannich bases, isatin, carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase References: 1.Bhrigu B, Pathak D, Siddiqui N, et al. Search for biological active isatins: a short review. Inter J Pharm Sci Drug Res 2010;2:229–35. 2. Ozgun DO, Yamali C, Gul HI, et al. Inhibitory effects of isatin Mannich bases on carbonic anhydrases, acetylcholinesterase, and butyrylcholinesterase. J Enzyme Inhib Med Chem, 2016; 31(6): 1498–1501.
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P56 - Design, Synthesis and Bioevaluation of Pyrazoline Derivatives
Bearing Primary Sulfonamide As Carbonic Anhydrase Inhibitors
Halise Inci Gul a*, Cem Yamali a, Dilan Ozmen Ozgun b, Ilhami Gulcin c
a Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey b Department of Pharmaceutical Chemistry,Faculty of Pharmacy,Ibrahım Cecen University, Agri, Turkey c Department of Chemistry, Faculty of Arts and Sciences, Ataturk University, Erzurum, Turkey *E-posta: [email protected]
Aromatic or heterocyclic compounds containing primary sulfonamide group have been extensively studied as important scaffolds for the development of new and selective carbonic anhydrase inhibitors (CAIs) [1]. Sulfonamide derivatives such as acetazolamide (AZA), methazolamide (MZA), ethoxzolamide (EZA) etc. are widely used as CAIs in clinical trials [2]. Our group recently focused on the synthesis of the compounds having both pyrazoline and primary sulfonamide pharmacophores in a molecule to search for several bioactivities [3,4]. The present study aims to synthesize 4-[3-(difluorophenyl)-5-(dimethoxyphenyl)-4,5- dihydro-1H-pyrazol-1-yl]benzenesulfonamides to investigate their inhibitory effects on CA isoenzymes, expecting to find out new candidate compounds for further studies. The compounds designed (Figure 1) were synthesized according to literature3,4 and their chemical structures were elucidated by 1H NMR, 13C NMR, and HRMS spectra. The compounds were tested in terms of CA inhibition profile on hCA I and II isoenzymes based on the reported literatures3,4.
Table 1. CA inhibition results of the compounds
Figure 1. General Chemical Structure of the Compounds
The compounds tested were found 31-61 times more potent towards hCA I and 17-25 times more potent towards hCA II than Acetazolamide (AZA). All compounds can be considered as leader compounds to design new CA inhibitors.
Keywords: Pyrazoline, carbonic anhydrase, primary sulfonamide
References: 1. Shewach DS et al. Chem Rev. 2009;109:2859-61. 2.Rogez-Florent T et al. Bioorg Med Chem 2013;21:1451-64 3.Gul HI et al. J Enzyme Inhib Med Chem. 2017;32(1):169-175. 4.Gul HI et al. J Enzyme Inhib Med Chem. 2017;32(1):189-192.
Acknowledgements: The authours thank to Ataturk University BAP office for the financial support (PN:2015/078).
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P57 - Synthesis of Novel Pyrazolines and Their Inhibitory Effects
on hCA IX and XII Isoenzymes
Halise Inci Gul a*, Cem Yamali a, Claudiu T. Supuran b a Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University,Erzurum,Turkey. b Laboratorio di Chimica Bioinorganica, Universita degli Studi di Firenze, Sesto Fiorentino, Italy *E-posta: [email protected]
Carbonic anhydrase (CA) isozymes are important therapeutic targets for the treatment of several disorders such as edema, glaucoma, obesity, cancer, epilepsy, diuretics, antiepileptics, and osteoporosis [1]. New tumor cell targets have been identified which led to the emergence of CA isozymes as promising target [2]. The selective inhibition of CA IX and XII provide significant anticancer effects. Unfortunately, classical CA inhibitors do not selectively target CA IX and XII. They also inhibit other types of CA isoenzymes which have physiological relevance such as CA I and II. There is an urgent need to development new and more selective CA inhibitors. This work focused on synthesises of new 4-[5-(polymethoxyphenyl)-3-(aryl)- 4,5-dihydro-1H-pyrazol-1-yl] benzenesulfonamides (1-6) and evaluation of their inhibition effects on CA IX and XII. The compounds designed (1-6) were synthesized [3] and their chemical structures were elucidated by 1H NMR, 13C NMR and HRMS. The compounds were tested in terms of CA inhibition profile on hCA IX and XII isoenzymes according to literatüre [1]. The core structures synthesized were Table 1. CA inhibition of the compounds 1-6 shown in Figure 1. Inhibition constants Ki (µM) (Ki) of the compounds 1-6 were in the Compound hCA IX hCA XII range of 0.009 - >50 µM towards hCA 1 0.44 0.37 IX and XII isoenzymes (Table 1). 2 1.43 0.64 >50 >50 3 The compound 4 (4-[5-(2,3,4- 4 0.044 0.009 trimethoxyphenyl)-3-(thiophen-2-yl)- 5 0.061 0.054 4,5-dihydro-1H-pyrazol-1-yl] 6 5.85 0.040 benzenesulfonamide) can be considered Acetazolamide 0.025 0.005 as a leader compound to develop new
and selective CA inhibitors.
The authours thank to TUBITAK for the financial support (Project Number: 1002/115S694).
Figure 1. General Chemical Structure of Pyrazolines 1-6
Keywords: hCA IX, hCA XII, pyrazoline, anticancer, sulfonamide
References: 1. Supuran CT. J Enzyme Inhib Med Chem 2012;27:759–72. 2. Winum JY et al. Med Res Rev 2008;28:445–63. 3. Gul HI et al. J Enzyme Inhib Med Chem. 2017;32(1):169-175. October 05-07, 2017, ERZURUM-TÜRKİYE 105
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P58 - Association of Platelet to Lymphocyte Ratio and Neutrophil to Monocyte Ratio with Serum Adropin Level in Knee Osteoarthritis
Gülşah Gündoğdu1, Köksal Gündoğdu2
1Department of Physiology, Faculty of Medicine, Atatürk University, Erzurum, Turkey 2Department of Orthopedics and Traumatology, Erzurum Regional Training and Research Hospital, Erzurum, Turkey E-mail:[email protected]
Osteoarthritis (OA) most commonly seen in the knee joint, progressive joint cartilage loss and joint pain characterized. The most common risk factors for knee OA are the aging, obesity, trauma and inflammation. In addition this, inflammation plays a critical role in the pathogenesis of OA. Recently, platelet to lymphocyte Ratio (PLR) and neutrophil to monocyte ratio (NMR) are considered as a biomarker to determine inflammation. Adropin, mainly in liver and brain, is relatively newly discovered a peptid hormone and implicated in the regulation of insulin sensitivity and energy homeostasis. The aim of the present study to determine the association of PLR and NMR with serum adropin level in knee osteoarthritis. This study was enrolled 60 patients with knee OA and 30 healthy controls aged 45-75 years old for routine checkup attending the department of orthopedics and traumatology policlinic of Erzurum Regional Training and Research Hospital. Blood samples were taken during the admission to the hospital in both groups and radiography of the knee was obtained. The serum levels of adropin was measured by using ELISA method in patient and healthy control groups. At the same time, routine hemogram parameters were also measured. The obtained data were evaluated statistically. Knee OA patients had an increased PLR compared with the healthy control (p<0.05), but NMR did not differ significantly between in both groups (p>0.05). There were statistically significant negative correlations between serum adropin level and PLR in the patients group (p<0.05). However, there were no significantly negative correlations between serum adropin level and NMR in the patients group (p>0.05). In our study, we determined the relationship between serum adiponin level and PLR and NMR in knee OA. This may have important implications for the patogenesis of knee OA. Keywords: Knee OA, Adropin, Platelet to Lymphocyte Ratio, Neutrophil to Monocyte Ratio
Referances: 1. Shi J, Zhao W, Ying H, Du J, Chen J, Chen S, Shen B. The relationship of platelet to lymphocyte ratio and neutrophil to monocyte ratio to radiographic grades of knee osteoarthritis. Z Rheumatol. 2017 Jul 5. doi: 10.1007/s00393-017-0348-7. 2. Kume T, Calan M, Yilmaz O, Kocabas GU, Yesil P, Temur M, Bicer M, Calan OG. A possible connection between tumor necrosis factor alpha and adropin levels in polycystic ovary syndrome. J Endocrinol Invest. 2016 Jul;39(7):747-54.
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P59 - Inhibitory Properties of Chalcone and Pyrazole Derivatives on Human Carbonic Anhydrases
Tayfun Arslan a*, Yazgı Dizdaroğlu a, Canan Albay a, Emir Alper Türkoğlu b, Asiye Efe3, Murat Şentürk d
a Giresun University, Science and Art Faculty, Giresun, Turkey b University of Health Sciences, Faculty of Pharmacy, İstanbul, Turkey c Ağrı İbrahim Çeçen University, Science and Art Faculty, Ağrı, Turkey d Ağrı İbrahim Çeçen University, Faculty of Pharmacy, Ağrı, Turkey *E-mail: [email protected]
This study has focused on the inhibitory characteristics of chalcone and pyrazole derivatives on human carbonic anhydrase I and II (hCA I-II). Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes - catalyzing the hydration dehydration process of CO2 / HCO3 and are found in vertebrates, invertebrates, high plants and bacteria [1,2]. CAs, which plays some roles in biosynthetic, physiological and pathological processes, is inhibited by CA inhibitors [3,4]. A new series of chalcones and pyrozoles compounds showed important inhibitory profiles for these human CA isoforms, with Ki values in the range of 5.13 to 67.39 nM. These data demonstrate that chalcone and pyrazole derivatives are carbonic anhydrase inhibitors with further investigational potency. In addition, the nanomolar inhibitory properties of these isoform-selective against human CAs have demonstrated great potential in the discipline of medicinal chemistry, and may provide descriptive details regarding the design and development of various biomedical applications.
Keyword: Chalcones, pyrazoles, carbonic anhydrases, inhibitors.
References: 1. Arslan T, Türkoğlu EA, Şentürk M, Supuran CT. Synthesis and Carbonic Anhydrase Inhibitory Properties of Novel Chalcone Substituted Benzenesulfonamides. Bioorganic & Medicinal Chemistry Letters. 2016;26:5867-5870. 2. Khameneh HP, Bolouri TG, Nemati F, Rezvani F, Attar F, Saboury AA, Falahati M. A Spectroscopic Study on the Absorption of Carbonic Anhydrase onto the Nanoporous Silica Nanoparticle. International Journal of Biologicial Macromolecules. 2017;99:739-745. 3. Bayrak Ç, Taslimi P, Gülçin İ, Menzek A. The first synthesis of 4-Phenylbutenone Derivative Bromophenols Including Natural Products and Their Inhibition Profiles for Carbonic Anhydrase, Acetylcholinesterase and Butyrylcholinesterase Enzymes. Bioorganic Chemistry. 2017;72:359–366. 4. Ferraroni M, Cornelibo B, Sapi J, Supuran CT, Scozzafava A. Sulfonamide Carbonic Anhydrase Inhibitors: Zinc Coordination and Tail Effects Influence Inhibitory Efficacy and Selectivity for Different Isoforms. Inorganica Chimica Acta. In Press. 2017.
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P60 - Determination of Antimicrobial Activity of some Probiotic Preparations and A. muciniphila against Enteric Pathogens
Ceren Ozkul a, Meral Sağıroğlu a a Hacettepe University Faculty of Pharmacy, Department of Phamaceutical Microbiology, Ankara *E-mail: [email protected]
The purpose of the present study is to determine antimicrobial activity of some of the commercial probiotic preparations and A. muciniphila, which is a novel next generation probiotic bacteria in some clinical enteric isolates. E.coli ATCC 25922, K.pneumoniae ATCC 700603 standard bacteria and total of 15 enteric bacteria including (8 E. coli, 7 K. pneumonia) was used as indicator strains in order to determine in-vitro antimicrobial activity by using agar spot test. The antimicrobial activity of probiotic preparations containing Bifidobacterium animalis subsp. lactis and standard strain of Akkermansia muciniphila BAA-835 was tested. Briefly, spot culture of A. muciniphila was prepared from prec-culture on BHI broth and incubated for 4-5 days anaerobically. Probiotic preparations were dissolved in 500 uL PBS solution and their spot cultures were prepared on MRS Agar. Indicator strains containing standart bacteria and clinical isolates were inoculated on 9 mL soft TSA and overlayed on spot cultures. The inhibiton zones were evaluated 2 days after anaerobic incubation. All the probiotic preparations were found effective against all strains used in the study with a mean zone of 29 mm, as expected. A novel probiotic strain A. muciniphila found effective against 4 of the clinical isoaltes and standard strains of E. coli and K. pneumonia with a mean zone of (18 mm). The present results indicate that A. muciniphila, which is a recently reported intestinal bacterium and a promosing next generation probiotic strain has an antimicrobial effect on enteric bacteria tested in the present study.
Keywords: A. muciniphila, probiotics, enteric bacteria
References: 1. Derrien M, Vaughan EE, Plugge CM, de Vos WM. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol. 2004 Sep;54(Pt 5):1469-76. 2. Shim YH1, Lee SJ1, Lee JW2. Antimicrobial activity of lactobacillus strains against uropathogens. Pediatr Int. 2016 Oct;58(10):1009-1013.
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P61 - Qualitative and Quantitative Determination of Epigallocatechin Gallate, Epigallocatechin, Epicatechin Gallate and Catechin in Different Herbal Slimming Products Containing Camellia sinensis by HPLC
Benan Dursunoğlu a*, Hafize Yuca a, Sefa Gözcü b, Bilal Yılmaz c, Zühal Güvenalp a a Department of Pharmacognosy, Faculty of Pharmacy, Atatürk University, 25240, Erzurum, Turkey b Department of Pharmacognosy, Faculty of Pharmacy, Erzincan University, 24100, Erzincan, Turkey c Department of Analytical Chemistry, Faculty of Pharmacy, Atatürk University, 25240, Erzurum, Turkey
E-mail: [email protected]
Camellia sinensis (L.) Kuntze (green tea) is an evergreen shrub which is grown in China, India, Sri Lanka, Japan, Indonesia, Kenya, Turkey, Pakistan and Argentina [1]. It is a member of Theaceae family. The leaves of C. sinensis contain caffeine and various phenolic compounds (e.g. epicatechin, epicatechin gallate, epigallocatechin, epigallocatechin gallate, quercetin, myricetin) [2]. C. sinensis is presented in herbal slimming products due to its diuretic and promoting of lipolysis effects [1]. In the present study, new, simple and sensitive high performance liquid chromatography (HPLC) methods have been developed for qualitative and quantitative determination of epigallocatechin gallate, epigallocatechin, epicatechin gallate and catechin in seven herbal slimming products containing Camellia sinensis in Turkey. The developed methods can be used for routine quality control analysis of epigallocatechin gallate, epigallocatechin, epicatechin gallate and catechin in different herbal slimming products.
Keywords: Catechin, HPLC, herbal slimming product, camellia sinensis
References:
1. Gruenwald J, Brendler T, Jaenicke C. (eds). PDR for Herbal Medicines. Medical Economics Co., Inc., Montvale, NJ. 2007; 383-384.
2. Aslan M, Orhan N. Obezite Tedavisine Yardımcı Olarak Kullanılan Doğal Ürünler. MİSED. 2010; 23-24:96-97.
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P62 - Determination of Antioxidant Capacity of Ether Extract of Myrtus communis L. Leaf via CUPRAC and FRAP Methods
Zerrin Kutlua, Lale Duysaka, Mine Gulaboglua*
aAtatürk University, Faculty of Pharmacy, Department of Biochemistry, 25240, Erzurum *E-mail: [email protected] All leaves, fruits, brunches, flowersand volatile oil of Myrtus communis L. have been traditionally widely used for the treatment of various diseases in Mediterranean region and Turkey. The leaf often contain organic acids such as essential oils, tannins, sugars, flavonoids and citric and malic acid [1]. In this study, ether extract of Myrtus communis L. leaf were analyzed with different antioxidant activity methods as CUPRAC and FRAP which are the most common and cited antioxidant capacity measurement method. In procedure, Myrtus communis L. leaf ether extract were prepared in 40 ug/mL and then the samples were analyzed with FRAP and CUPRAC, methods. In order to compare and calculate the equivalant antioxidant capacity of each sample, different concentration of reference samples were prepared in between 1-40 ug/mL. All measurements were performed in Biotek Elisa Reader and results were evaluated with Microsoft Excel 2010 software [2,3]. According to the results, Myrtus communis L. leaf ether extract exhibit antioxidant capacity in terms of FRAP and CUPRAC.
Key words: Antioxidants capacity, CUPRAC, FRAP, Myrtus Communis L.
References:
1. Romani A, Pinelli P, Mulinacci N, Vincieri FF, Tattini M. Identification and quantitation of polyphenols in leaves of Myrtus communis L. Chromatographia. 1999;49:17-20. 2. Apak R, Guclu K, Ozyurek M, Karademir SE. Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, using their cupric ion reducing capability in the presence of neocuproine: CUPRAC method. Journal of Agricultural and Food Chemistry,. 2004;52:7970-81. 3. Sanchez-Moreno C, Larrauri JA, Saura-Calixto F. A procedure to measure the antiradical efficiency of polyphenols. Journal of the Science of Food and Agriculture. 1998;76:270-6.
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P63 - The Restoring Efficacy of Oleuropein Against Non-Steroidal Anti- inflammatory Drug Toxicity in Rat Kidney
Fatime Geyikoglu a, Mehmet Yılmaz a, Kubra Koc a , Salim Cerig a, Nihal Simsek Ozek a,b* Ferhunde Aysin a,b
a Atatürk University, Faculty of Science, Department of Biology, 25240, Erzurum, Turkey b East Anatolian High Technology Research and Application Center (DAYTAM), Atatürk University, 25240, Erzurum, Turkey E-mail: [email protected]
Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) which has gastro toxic and nephrotoxic effects. These adverse effects are associated with this drug-caused oxidative stress. Moreover, the reducing role of oleuropein, as a antioxidant, in the oxidative stress has been commonly demonstrated in recent studies. Therefore, in the present study, we explored the protective effects of oral oleuropein against renal injury in indomethacin-induced gastric ulcer model. Rats were treated as follows: normal control (group I); indomethacin (35 mg/kg) treated rats (group II); indomethacin-induced rats treated with reference standard (50 mg/kg rantidine hydrochloride) (group III); indomethacin-induced rats treated with oleuropein (75, 150 and 300 mg/kg), respectively (group IV, V and VI). Enzyme-linked immunosorbent assay (ELISA) method was used to analyze the protein expression of prostaglandin E2, TNF-α, eNOS and caspase-3. The oxidant/antioxidant status (TOS/TAS) were measured in the blood and kidney tissue homogenates of the rats. In addition, the level of 8-Oxo-2'-deoxyguanosine (8-OHdG) was assessed to determine oxidative damages in DNA. Evaluation of kidney histology and pathological scores were also performed. The biochemical and histopathological findings clearly indicated the toxic effects of indomethacin in kidney. The high dose of oleuropein treatment reduced such these toxic effects by restoring the inflammation, oxidant/antioxidant imbalance, 8-OHdG levels and also apoptotic activities. Our study demonstrates the renal protective role of oleuropein treatment in the indomethacin-treated rats.
Keywords: Oleuropein, indomethacin, nephrotoxicity, TNF-α, oxidative stress.
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P64 - GC-MS Based Metabolomic Profile of Caco 2 Cell Lines
Gürkan Özen a, İpek Baysal b, Cemil Can Eylem a, Samiye Yabanoğlu Çiftçi b, Sedef Kır a, Emirhan Nemutlu a a Hacettepe University, Faculty of Pharmacy, Department of Analytical Chemistry b Hacettepe University, Faculty of Pharmacy, Department of Biochemistry Sıhhiye, Ankara, 06100, TURKEY *E-mail: [email protected]
In the treatment of gastrointestinal malignancies, the major problem is the frequent occurrence of resistance to drugs. Knowing the mechanism leading to drug resistance could be beneficial in terms of overcoming the problem. In the search for the mechanism of anticancer drug resistance in colon tumors; human colon adenocarcinoma cell line, Caco-2, has been widely used. The omic studies (metabolomics, proteomics, fluxomics…etc) are currently used tools to elucidate the biochemical mechanism of drug resistance. In the present study as a first step the basal metabolomics profile of untreated Caco-2 cells was investigated. The metabolomic profile of Caco-2 cell line was compared with Fetal Human Cell (FHC) in order to find altered metabolites. The Caco-2 cell lines were grown in T- 25 cm2 cell culture flasks at 37 °C in incubator. The cells were quickly washed with 5 ml of phosphate-buffered saline. The metabolism was quenched by addition of 1 ml of methanol-water mix (9:1 vol:vol) and then the flask was soak into liquid nitrogen to freeze the cells. The frozen cells were scraped off into 2 mL ependorf tube and centrifuged. A 200 µL of the Caco-2 cell extracts was evaporated to dryness in a vacuum dryer concentrator and methoxyamineted and derivatized MSTFA with 1% TMCS. After derivatization, the samples were transferred into GC-MS vials. Metabolomic profiling was performed using GC-MS (Shimadzu GCMS-QP2010 Ultra) with DB-5MS stationary phase column (30 m +10 m duraguard × 0.25 mm i.d. and 0.25-µm film thickness). Once analysis completed the complex chromatograms were deconvoluted using AMDIS and the retention time correction and data matrixes creation were done using SpectConnect software. Results: The Caco-2 (n=6) and FHC (n = 6) cell lines extracts were run on the GC-MS. After deconvolution and aligned of the chromatograms, 336 mass spectral features have been detected and 106 of them were annotated using retention index libraries. These identified metabolites belong to Krebs cycle, amino acid and fatty acid metabolism. The multivariate analysis shows clear separation between Caco-2 and FHC cell lines (Figure 1).
FHC
Caco-2
Figure 1: GC-MS metabolomic profile of Caco-2 and FHC cell lines. PCA score plots showing distinct metabolomic profiles between cell lines This study was supported by TUBITAK. (Project no: 116Z292) Keywords: Caco-2, GC-MS, metabolomics.
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P65 - Identification of Polychlorinated Biphenyls (PCBs) in Spiked Human Plasma Samples by GC-MS
Merve Nenni a,b*, Özge Cansın Zeki a, İncilay Süslü a, Mustafa Çelebier a, Sacide Altınöz a a Hacettepe University, Faculty of Pharmacy, Department of Analytical Chemistry, 06100, Sıhhiye, Ankara, Turkey b Çukurova University, Faculty of Pharmacy, Department of Analytical Chemistry, 01330, Sarıçam, Adana, Turkey
*E-mail: [email protected]
Polychlorinated biphenyls (PCBs) and many chlorinated pesticides are widely used and they are found in various parts of the environment in quite small concentrations, but they accumulate and thus become a threat to human health and life [1]. Metabolized in the organism these compounds cause many cases of acute accidental or suicidal poisonings. Because PCBs inhibits cholinesterase activity via phosphorylation by the oxygen analogue. A rapid identification of the pesticide would provide very useful information to clinicians for making treatment decisions in emergencies. For the pesticide monitoring, both gas chromatography (GC) and liquid chromatography (LC) with mass spectrometry (MS) have been extensively used. While there are many different extraction techniques associated with analyzing pesticides, they can typically be classified as either solid or liquid phase or supercritical fluid extraction methods. Liquid-liquid extraction is one of the fundamental techniques for the separation of a chemical species from a different medium. This most widely used procedure is extraction from an aqueous medium into a properly chosen organic solvent, particularly for partial purification of a biological fluid such as blood containing toxic chemicals and has been used in human body fluids . The aim of this study is to develop an analysis technique for identification of 5 different PCBs (PCB 52, 101, 138, 153 and 180) in spiked human plasma samples by GC-MS method. Human plasma samples were extracted by using liquid-liquid extraction. After extraction, supernatant was dried with vacuum centrifuged and dissolved by adding hexane. Then samples were injected into GC-MS system where an Agilent J&W DB-35MS UI 20 m×0.18 mm, 0.18 µm column was used. The injector temperature was 280 oC, the purge flow was 10 mLmin-1, and the column temperature was held at 90 oC for 1 min, then the increased to 320 oC and held there for 10 min. The interface and the ion source temperatures were 230 and 290 oC, respectively. Ions were generated by a 70- eV electron beam. The proposed procedure combining liquid-liquid extraction technique with GC-MS was applied for the qualitative analysis of PCBs pesticides in human blood sample.
Keywords: Pesticides, PCBs, GC - MS, Liquid - liquid extraction References: 1.Banerjee K, Utture S, Dasgupta S, Kandaswamy C, Pradhan S, Kul- karni S, Adsule P. Multiresidue determination of 375 organic contaminants including pesticides, polychlorinated biphenyls and poly- aromatic hydrocarbons in fruits and vegetables by gas chromatography-triple quadrupole mass spectrometry with introduction of semi- quantification approach. J Chromatogr A, 2012,1270:283–295.
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P66 - Determination of Log P Value of Kojic Acid Derivative by Using UV-Visible Spectroscopy
Ozan Kaplan a, Engin Koçak a, Sacide Altınöz a , Mutlu Dilsiz Aytemir b*
a Department of Analytical Chemistry, Faculty of Pharmacy, Hacettepe University Sıhhıye 06100 Ankara b Department Of Pharmaceutical Chemistry, Faculty Of Pharmacy, Hacettepe University Sıhhıye 06100 Ankara *E-mail: [email protected]
Partition co-efficient (Log P) is defining as a ratio of non-ionised drugs of distribution between the organic (oil phase) and aqueous phase [1]. Log P value is one of the most important parameter to determine drug metabolism in body. When an excess amount of solid or liquid is added to a mixture of two immiscible liquids while this substance is slightly soluble in both immiscible liquid. It will distribute itself between the two phases until separation of mixture by shaking vigorously the ratio of the concentration of the solute in the two immiscible solvent is found to be constant [2]. Several analytical methods like HPLC and potentiometry have been developed to determine Log P but UV-Visible Spectroscopy that is simple, robust and reliable system is the main tool [3]. In this study we used UV-Visible Spectroscopy to determine Log P value of kojic acid derivative. Kojic acid derivative was solved in chloroform then added to water and n- octanol mixture that contained 2 mL water and 8 mL n-octanol. The mixture was shaken for 30 minutes and water and n-octaol phases were separated. To calculate amount of drug in n-octanol phase calibration curve studies were made between 10-70 ppm at 275 nm. Concentration of drug in two different phase was used to calculate Log P value. Log P value of kojic acid derivative was calculated as 1.88. The calculated result was compared with literature and observed very good correlation.
Keywords: Log P, Spectroscopy, Octanol-Water
References 1.Xu L, Li L, Huang J, Yu S, Wang J, Li N. Determination of the lipophilicity (log P o/w) of organic compounds by microemulsion liquid chromatography. J Pharm Biomed Anal. 2015;102:409-16. 2.Wahbi AA, Hassan E, Barary M, Khamis E, Hamdi D. Derivative spectrophotometry in the visible region using absorbance versus log wavelength or wavenumber determination of cyanocobalamin in injection solutions. Pak J Pharm Sci. 2007;20(2):93-9. 3.Takacs-Novak K, Avdeef A. Interlaboratory study of log P determination by shake-flask and potentiometric methods. J Pharm Biomed Anal. 1996;14(11):1405-13
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P67 - Synthetic Protocol for Imidazo-1,4-Oxazines and Evaluation of Their Cytotoxicity and Genotoxicity with SAR
Mehmet Taşpınar a, Burak Kuzu b, Meltem Tan b, Nurettin Mengeş b
a Van Yüzüncü Yil University, Faculty of Medicine,Deparmten of Medical Biology, 65080, Van, Turkey b Van Yüzüncü Yil University, Faculty of Pharmacy, 65080, Van, Turkey *E-mail: [email protected]
The design and synthesis of desired and tolerable methods to attain the complex molecules from appropriate starting materials is still challenging work for a lots of scientific areas such as modern synthetic and medicinal chemistry.
MTT assay was used to determine the drug sensitivity of the LN405 glioma cell line. Single cell gel electrophoresis (COMET) DNA damage was determined by COMET assay after LN405 cells were treated with compounds.
Imidazo-1,5-alkynyl alcohols derivatives were synthesized and they were cyclized to imidazo-1,4-oxazines by means of Cesium carbonate. Propargyl-allene isomerization which was base-supported was examined and the reaction mechanism was proposed. Moreover, cytotoxicity of synthesized molecules on the cells were investigated using structure activity relationship (SAR). With SAR study, toxicities of some functional groups have been shown. In addition, two lead compounds were tested for DNA damaging.
With SAR study, we have uncovered that phenyl ring at exact orientation is responsible for higher toxicity on the cells. Furthermore, flour atom at para position of phenyl ring exhibited also important toxicity which might be due to specific interactions with guanidine which are unique for flour atom resulting in DNA damaging
Keywords: Imidazooxazine, SAR, DNA damaging, cytotoxicity, NMR
Acknowledgements: This Project has been funded by Scientific and Technological Research Agency of Turkey (TUBİTAK) with grand nıumber 115Z894
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P68 - Evaluation of Antimicrobial Activities of 1,3,5-Trisubstituted-pyrazolines
Ebru Mete a*, Halise Inci Gul b, Ahmet Adiguzel c
a Department of Chemistry, Faculty of Sciences, Ataturk University, Erzurum, Turkey b Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey c Department of Molecular Biology and Genetics, Faculty of Science, Ataturk University, Erzurum, Turkey *E-mail: [email protected]
In this study, the sulfonamide compounds shown at Scheme 1 (2a-h) were synthesized [1] and the antimicrobial activities of them were investigated. Sulfonamide moiety is an important pharmacophore in antimicrobial activity. The antimicrobial activities of the compounds (2a-h) were tested according to literature procedure by disc diffusion method and the results were presented at Table 1.
Scheme 1: Synthesis of sulfonamide compounds 2a-h (i) NaOH 10% aq, EtOH, 0-5 °C, 12 h; (ii) 4-Hydrazinobenzenesulfonamide hydrochloride, EtOH/glacial acetic acid, reflux 12 h. R: H for 1a, 2a; CH3 for 1b, 2b; CH3O for 1c, 2c; Cl for 1d, 2d; F for 1e, 2e; Br for 1f, 2f; NO2 for 1g, 2g; OH for 1h, 2h.
Table 1: Antimicrobial activities of the compounds (2a-h) by disc diffusion (diameter of zone) Compounds (2a-h) inhibited zones at 100 mg/ml only towards E. Coli 5157:H7. So the compounds are not good candidates to develop new antimicrobial compounds according to results of Table 1. Keywords: Antimicrobial activity, pyrazoline, sulfonamide. References: 1.Sharma PK, Kumar S, Kumar P, Kaushik P, Sharma C, Kaushik D, Aneja KR. Synthesis of 1-(4- aminosulfonylphenyl)-3,5-diarylpyrazoline derivatives as potent antiinflammatory and antimicrobial agents. Medicinal Chemistry Research. 2012, 21, 2945-2954.
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P69 - Inhibition of Cellular Proliferation and Induction of Apoptosis by Halofuginone in Human Mesothelioma Cell Lines
Hurmuz Ceylan a, Halime Topal a, Gulseren Turhal a, Asuman Demiroglu-Zergeroglu a a Gebze Technical University, Molecular Biology & Genetics *E-mail: [email protected]
Malignant Mesothelioma is an aggressive and deadly tumour of pleura peritoneum and pericardium. The main causative factor for Malignant Mesothelioma is an inhalation of asbestos fibers. This disease is an epidemic in Turkey, especially in a region of Central Anatolia due to long time exposure to erionite, an asbestos-like mineral. Although several drug treatments have been proposed for Malignant Mesotheliomas, no curative therapy has been reported yet. It has been well known that natural products play critical roles in current cancer drug development. Halofuginone or {7-bromo-6-chloro-3-[3-(3-hydroxy-2-piperidinyl)-2-oxopropyl]-4(3H)-quinazolinone is isolated from Dichroa febrifuga can suppress SMAD pathway in osteosarcoma and AKT/mTORC1 pathway in colon cancers. It has also shown that Halaofuginone inhibits progression of melanoma bone metastases, prevents invasion and metastasis in hepatocellular carcinoma and causes cell cycle arrest in myeloma cells. In this study, inhibitory effect of Halofuginone on cellular proliferation and induction of apoptosis were investigated in human Malignant Mesothelioma and human mesothelial cell lines. Viability of cells after treatment with Halofuginone was examined using Acid phosphatase assay. The induction of apoptosis by Halofuginone was detected with AO/EB staining and PARP cleavage. We found that viability of Malignant Mesothelioma cells was reduced in a dose-dependent manner. Apoptotic morphology and PARP cleavage were observed in human Malignant Mesothelioma cells. However, only high doses of Halofuginone reduced viability and induced apoptosis in human mesothelial control cells, which may suggest that Halofuginone is more selective to kill cancer cells. To our best knowledge, this is the first time anti-carcinogenic effects of Halofuginone on Malignant Mesothelioma cells have been investigated. Our results propose that plant derived Halofuginone might be a good candidate for the management of Malignant Mesothelioma through its anti-proliferative and pro-apoptotic activities.
Keywords: Malignant mesothelioma, halofuginone, viability, apoptosis
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P70 - Synthesis, Biological Activity, and Molecular Modelling Studies on New Oxime Ether Compounds Bearing Imidazole Ring
Irem Bozbey a*, Zeynep Özdemir a, Suat Sarı b, Didem Kart c, Arzu Karakurt a, Selma Saraç b, Sevim Dalkara b
a Inonu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Malatya, Turkey b Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ankara, Turkey c Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Microbiology, Ankara, Turkey *E-mail: [email protected]
Mycoses are infections caused by fungi and mostly Candida albicans, an opportunistic species. In recent years rise in immune-suppressive conditions (AIDS, cancer, resistant bacterial infections) and use of devices such as prosthetics and stents has led to an increase in morbidity and mortality of systemic mycoses, which are hard to cure. Some non-albicans candida species, which are less sensitive to current medications and have high mortality, have increasingly been isolated in mycoses. Azole antifungals are the most common antifungal class thanks to their wide spectra, systemic efficacies, low side effect profiles, oral availability, and slow metabolism. They block synthesis of ergosterol, a crucial component of fungus membrane, by inhibiting lanosterol 14 α-demethylase (CYP51), which leads to disruption of membrane permeability [1,2]. 1-(4-trifluoromethylphenyl)-2-(2H-imidazol-1-yl)ethyl oxime ethers synthesized according to the reaction pathways given below. Their structures were confirmed by IR, NMR, LC-MS and the elemental analysis. Moleculer docking method was utilized via virtual screening.
Keywords: oxime ester, antifungal, lanosterol 14 α-demethylase, virtual screening
References: 1. Romani L. Cell-mediated immunity to fungi: a reassessment. Medical Mycology. 2008; 46:515-29. 2. Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009; 48(5):503-35.
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P71 - Synergy of Coupling Ultrasound and Heterogeneous Fenton Processes using Magnetite Nanoparticles Prepared by High Energy Planetary Ball Mill in the Degradation of Basic Violet 10 from Aqueous Solutions
Canan Karaca a, Aydin Hassani a, Özkan Açışlı b, Semra Karaca a∗, Bilal Yılmaz c a Department of onur şenolChemistry, Faculty of Science, Atatürk University, 25240 Erzurum, Turkey b Department of Petroleum and Natural Gas Engineering, Oltu Faculty of Earth Sciences, Atatürk University, 25240 Erzurum, Turkey c Department of Analytical Chemistry, Faculty of Pharmacy, Atatürk University 25240, Erzurum, Turkey *E-mail:[email protected] Industrial wastewaters include a variety of resistant organic compounds with variable toxicity, carcinogenic and mutagenic properties [1]. The removal of these compounds from wastewater is of great importance [2]. Sono-Fenton processes are regarded as a promising technology for the removal of pollutant compounds from waste water at room temperature and pressure. In this study, the removal of Basic Violet 10, a cationic dye, from aqueous solutions by heterogeneous sono-Fenton process over the nano-sized magnetite(Fe3O4) nanocatalyst prepared by the milling of magnetite mineral using high energy planetary ball milling process was studied. The magnetite samples after and before ball milling operation were characterized by means of the various analytical techniques. The catalytic activity of the ball milled magnetite sample enhanced in parallel with the improvement in the its physicochemical properties and ball milled magnetite of 6 h demonstrated the highest catalytic activity in BV10 degradation by heterogeneous sono-Fenton process. Effect of operational parameters involving pH, catalyst dosage, hydrogen peroxide concentration, ultrasonic power and initial BV10 concentration on the decolorization efficiency of BV10 were investigated. The optimum conditions for the BV10 removal efficiency was found to be pH value of 3, catalyst dosage of 1.5 g/L, hydrogen peroxide concentration of 36 mM, ultrasonic power of 450W and initial BV10 concentration of 30 mg/L. The removal efficiency of BV10 was 75.94% at this conditions after reaction time of 120 min.The trapping experiments revealed that hydroxyl radicals are the dominant oxidative species, but radicals have also a partly role in BV10 degradation. The results of GC–MS analysis confirmed efficient degradation of BV10 molecules in aqueous solution during the process.
Keywords: Ball milling process; magnetite nanostructures; wastewater treatment
References: 1.Pang YL, Abdullah AZ, Bhatia S. Review on sonochemical methods in the presence of catalysts and chemical additives for treatment of organic pollutants in wastewater. Desalination. 2011;277(1–3):1-14. 2.Cai M, Su J, Lian G, Wei X, Dong C, Zhang H, et al. Sono-advanced Fenton decolorization of azo dye Orange G: Analysis of synergistic effect and mechanisms. Ultrasonics Sonochemistry. 2016;31:193-200.
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P72 - Effects of Nesfatin-1 on Atrial Contractility in Male Rats
Ayşe Barutcigil a*, Selvinaz Dalaklioglu a, Arda Taşatargil a
a Akdeniz University, Medical Faculty, Department of Pharmacology, 07070, Antalya, Turkey
*E-mail: [email protected]
Nesfatin-1, one of the new adipokine, exerted pleiotropic actions at the cardiovascular system as well as playing a role in stress response. However, there have been few reports about the in vitro effects of nesfatin- 1 on cardiovascular functions. This study was aimed to investigate the acute inotropic and chronotropic effects of the nesfatin-1 on spontaneous contractions of the isolated rat atria. For isometric tension studies, isolated right atria were used in organ baths. The effects of nesfatin-1 on spontaneous contractions of the rat atria were examined. After the propranolol incubation (10-6 M, 30 min), contractile responses to nesfatin- 1 were repeated. In addition, norepinephrine-induced contractions (10-10 M-10-5 M) were obtained in isolated right atria in the presence and absence of 10 ng/ml nesfatin-1. Nesfatin-1 in the concentration 0.1- 100 ng/ml increased the intensity of atrial contractions. Also, this adipokine significantly altered the frequency of atrial contractions. On the other hand, norepinephrine-induced atrial contractions were not significantly augmented by nesfatin-1 incubation. In the presence of propranolol, a non-specific β- adrenergic receptor blocking agent, the increase in atrial contraction to nesfatin-1 was not inhibited significantly. These results demonstrated that short-term exposure to nesfatin-1 produced a concentration- dependent positive inotropic and chronotropic effects on rat atria.
Keywords: Adipokine, nesfatin-1, contractile responses
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P73 - Simultaneous Determination of Thiocolchicoside and Diclofenac Diethyl Ammonium in Topical Gel Formulation by Square-Wave Voltammetric Method
Nuran Özaltın a*, Sevilay Erdoğan Kablan a Hacettepe University, Faculty of Pharmacy, Department of Analytical Chemisty *E-mail: [email protected] A rapid, simple, sensitive, precise and specific square wave voltammetric method was developed for the simultaneous determination of Thiocolchicoside (THIO) and Diclofenac diethyl ammonium (DIC) in topical gel formulation which has synergetic action. The effect of supporting electrolyte pH and voltammetric parameters were investigated. The optimum conditions were obtained in Britton-Robinson buffer pH 3.0 for electroreduction at hanging mercury drop electrode. A well-defined peak was observed for THIO at −0.85 V, and for DIC at -1.18 V vs. Ag/AgCl/4.6 M KCl. Under optimum conditions, the linear response ranges for determination of THIO and DIC were 1.07 – 24.2 µM and 5.64 – 45.8 µM, with detection limits of 0.54 µM and 3.25 µM, respectively using square wave voltammetric method (Figure 1). Current type and reversibility of the electrode reaction were investigated by using cyclic voltammetry. The proposed method was validated for accuracy, precision, sensitivity and specificity according to the International Conference on Harmonization (ICH) guidelines [1]. The developed method was applied for the simultaneous determination of THIO and DIC in topical gel formulation including binary mixtures. Keywords: Simultaneous determination of Thiocolchicoside and Diclofenac diethyl ammonium, topical gel, square wave voltammetry, validation.
Figure 1. Square wave voltammograms of A) Increasing THIO concentrations:1)1.07, 2) 2.12, 3) 6.22, 4)11.1, 5)15.7, 6) 20.0 and 7) 24.2 µM in presence of 16.1 µM DIC. Inset shows calibration curve of THIO. B) Increasing DIC concentrations: 1) 5.64, 2) 9.53, 3)13.3, 4)17.24, 5) 30.7, 6) 37.0, 7) 42.9 and 8) 45.8 µM in presence of 16.1 µM THIO. Inset shows calibration curve of DIC.
References: 1. Guideline IHT. Validation of analytical procedures: text and methodology. Q2 (R1). 2005;1.
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P74 - Cytotoxic Effects of Nanoemulsion and Nanoemulsion Based Gel Containing Daidzein on SK-MEL30/An1 Cells
Afife Büşra Uğura, Dilara Örgülb, Süeda Hekimoğlub, Meltem Çetina aAtatürk University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Erzurum bHacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Ankara * E-mail: [email protected]
Daidzein (DZ), a water-insoluble isoflavone, has antioxidant and anti-inflammatory activities and it also has dose-dependent inhibition effect on several cancer cells [1,2]. The aim of this study is to evaluate the cytotoxic effects of nanoemulsion (DZ-NE), nanoemulsion based gel (DZ-NEG) and conventional emulsion (DZ-CE) containing daidzein and base formulations (B-NE, B-NEG and B-CE) on melanoma cell lines (SK-MEL30/An1 cell line). The conventional emulsion was prepared using the oil phase [ethyl oleate (10%)], DMSO (5%), ultrapure water and surfactant [Tween 80 (10%) and Lipoid S100 (5%)]. The nanoemulsion formulation was prepared by passing the conventional emulsion through high-pressure homogenizer. Protosan G213 (1% w/w) was added to NE formulation to prepare NEG formulation. Droplet size values were 151.12±2.70 nm and 149.80±3.52 nm for B-NE and DZ-NE, 191.48±5.26 nm and 200.25 ±11.09 nm for B-NEG and DZ-NEG, 2.830±0.011 μm and 4.420±0.017 μm for B-CE and DZ-CE, respectively. The cytotoxic effects of the all formulations were determined using MTT method. Control cells were treated with only culture medium (C1) or culture medium containing 2% of DMSO (C2). Pure DZ and the formulations (equivalent to 90,180 and 270 M of DZ) had significant cytotoxic effects on the melanoma cells compared to the controls (p<0.05), (Figure 1a and 1b). All formulations maintained the cytotoxic effect of DZ against the melanoma cells for 24 and 48 hours of incubation periods. For 24 hours of incubation time, there was a significant difference only between the cytotoxic effects of DZ-NE formulation (equivalent to 270 μM of DZ) and pure DZ (270 M) (p<0.05).Cell viability assay also revealed that DZ-NE formulation (equivalent to 270 μM of DZ) induced significant cell death compared to pure DZ (270 M), DZ-NEG (equivalent to 270 μM of DZ) and DZ-CE (equivalent to 270 μM of DZ) (p<0.05) for 48 hours of incubation period. As a result of this study, we can conclude that NE and NEG formulations may be useful for the topical application of DZ and treatment of skin cancer.
Figure 1. Cytotoxic effects of pure drug and formulations on SK-MEL30/An1 cells a) after 24 hours incubation b) after 48 hours incubation.
Keywords: Daidzein, nanoemulsion, cytotoxicity, melanoma cell line.
References:
1. Zhao X, Shen Q, Ma Y. An HPLC Method for The Pharmacokinetic Study of Daidzein-Loaded Nanoparticle Formulations After İnjection to Rats. Journal of Chromatography B. 2011;879:113-116. 2. Zhang Y, Xie L, Wang H, Wang F, Yu X, Chen C, Zhang R. Effects of Genistein and Daidzein on The Proliferation, Invasion, Migration and Adhesion of Melanoma Cells. Tsinghua Science and Technology. 2002;7(4):398-403. This study was supported by Ataturk University Research Foundation (Project Number: 2015-079). October 05-07, 2017, ERZURUM-TÜRKİYE 122
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P75 - Studies on QSAR of Some Antibacterial 1-(2-Naphthyl)-2-(Imidazole-1 yl)Ethanone Oxime and Oxime Ether Derivatives
Mehmet Abdullah Alagöz, a Arzu Karakurt a
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Inonu University, Turkey *E-mail: [email protected] The compounds had been evaluated in vitro against Staphylococcus aureus (ATCC 25923) and Enterococcus faecalis (ATCC 29212) by using broth microdilution method. Amikacine, an antibacterial drug, was used as the reference compound. Most of the compounds (2, 3-A, 3-B, 4, 6, 7, 8, 9) had been found to be active against Gr (+) bacteria especially S. aureus in low MIC values. The difference between the activity of 3A and 3B may indicate that the antibacterial activity against S. aureus was stereoselective [1]. HOMO, LUMO, band gap, dipole moment, length, log P, molecular refractivity and polar surface area values estimated to be related to activity for physicochemical parameters of the molecules, have been theoretically calculated. As a result of the QSAR study, equations were created to calculate theoretical MIK (µg/mL) values of novel compounds.
Figure 1. Structure of compounds studied on QSAR
Keywords: Oxime Ethers, antibacterial activity, QSAR
References: 1. Karakurt A, Dalkara S, Ozalp M, Ozbey S, Kendi E, Stablesd JP. Synthesis of some 1-(2-naphthyl)-2-(imidazole- 1-yl)ethanone oxime and oxime ether derivatives and their anticonvulsant and antimicrobial activities. Eur. J. Med. Chem. 36 (2001) 421- 433.
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P76 - Effects of Nesfatin-1 On Thoracic Aorta Reactivity in Male Rats
Ayşe Barutcigil a*, Arda Taşatargil a a Akdeniz University, Medical Faculty, Department of Pharmacology, 07070, Antalya, TURKEY *E-mail: [email protected]
This study was aimed to examine the effects of nesfatin-1, one of the new identified adipokine, on the rat thoracic aorta vasoreactivity. For isometric tension studies, isolated thoracic aorta rings were used in organ baths. The reactivity of thoracic aorta was evaluated by concentration-response curves to potassium chloride (KCl), phenylephrine (Phe), acetylcholine (ACh, an endothelium-dependent vasodilator), and sodium nitroprusside (SNP, an endothelium-independent vasodilator). Nesfatin-1 (0.1-100 ng/ml) produced concentration-dependent relaxation response in rat thoracic aorta precontracted by Phe. The relaxant responses to nesfatin-1 significantly inhibited by removal of endothelium, NO synthase (NOS) blocker N- nitro-L-arginine methyl ester (L-NAME, 10−4 M), and soluble guanylate cyclase inhibitor 1H- [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10-5 M). While Nesfatin-1 (10 ng/ml, 30 min) significantly increased the relaxation responses to either ACh or SNP, the contractile response to both Phe and KCl was not significantly changed in arteries that were incubated with nesfatin-1 (10 ng/ml) for 30 min, compared with controls. Moreover, thoracic aorta contractions induced by stepwise addition to Ca2+ to high KCl solution with no Ca2+ were not significantly changed by nesfatin-1 incubation. Under calcium- free conditions, contractions of thoracic aorta rings incubated with nesfatin-1 (10 ng/ml, 30 min) in response to Phe were not significantly lower than those of rings from control rats. These results demonstrated that short-term exposure to nesfatin-1 significantly changed vascular responsiveness in rat thoracic aorta. The vasodilator effect of nesfatin-1 is concentration dependent, and thought to be mediated primarily through endothelium-dependent mechanisms. Keywords: Nesfatin-1, adipokine, aorta reactivity
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P77 - Evaluation of Analgesic and Anti-inflammatory Activities of a Novel Arylalkyl Azole Compound in Mice
Seçkin Engin a*, Elif Nur Barut a, Yeşim Kaya Yaşar a, İnci Selin Doğan b, F. Sena Sezen a, Hilal Zaimoğlu c, Kübra Nur Sarıca c
a Department of Pharmacology, bDepartment of Pharmaceutical Chemistry, cFaculty of Pharmacy Karadeniz Technical University Trabzon/TURKEY *E-mail: [email protected] Despite great advances in understanding the processes of analgesia and inflammation, there is still a challenge to treat persistant pain and chronic inflammatory diseases. Current analgesic drugs mainly classified as opioids or non-opioid analgesics such as non-steroidal anti-inflammatory drugs, antidepressants, anticonvulsants are frequently associated with undesired effects and/or lack of efficacy in clinical use [1,2]. Therefore, newer analgesic/anti-inflammatory drugs with improved efficacy and tolerability have been under intense investigation. Anticonvulsants are effective in the treatment of neuropathic pain via modulating the neurotransmitters and ion channels in the central nervous system [3]. We have recently synthesized 1-phenyl/4-chlorophenyl-2-(1H-imidazol-1-yl) ethanol ester derivative compounds that were found to have significant anticonvulsant and antifungal activities [4]. In this study, 1-Phenyl-2-(1H-imidazol-1-yl) ethyl 2-propyl pentanoate hydrochloride (C1) having “phenyl” ring instead of “naphthalene ring” in Nafimidone which is the representative of the (arylalkyl) imidazole anticonvulsant compounds was synthesized and analgesic and anti-inflammatory activity of C1 were evaluated by hot plate test and formalin-induced paw edema method in male balb/c mice, respectively. C1 was administered intraperitoneally (i.p) at doses of 3, 30 and 50 mg/kg. Morphine hydrochloride (10 mg/kg, i.p) and Diclofenac sodium (10 mg/kg, i.p) were used as reference drugs for analgesic and anti-inflammatory activity, respectively. Our results showed that 60 minutes after the administration of 30 and 50 mg/kg of C1, reaction time was significantly increased (p<0.01) in the hot plate test indicating the analgesic activity of the compound (n=7-8/groups). Morever, in the formalin-induced paw edema test, C1 caused a significant (p<0.05) reduction in edema compared with the control at all doses tested indicating an anti-inflammatory activity of the compound (n=7-9/groups). Our findings suggest that C1 is a promosing candidate in the development of new analgesic and anti-inflammatory compounds. Further pharmacological studies are needed to clarify the mechanism(s) of its action. Keywords: Arylalkyl azoles, analgesic activity, anti-inflammatory activity, formalin test, hot plate test References: 1. Botz B, Bölcskei K , Helyes Z. Challenges to develop novel anti-inflammatory and analgesic drugs. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 2017; 9 (3). doi: 10.1002. 2. Wolkerstorfer A, Handler N, Buschmann H. New approaches to treating pain. Biorganic&Medicinal Chemistry Letters 2016; 26: 1103-1119. 3. Maizels M, McCarberg B. Antidepressants and antiepileptic drugs for chronic non-cancer pain. American Family Physician 2005; 71 (3): 483-490. 4. Doğan İ.S , Saraç S , Sarı S , Kart D, Gokhan ŞE, Vural İ , Dalkara S. New azole derivatives showing antimicrobial effects and their mechanism of antifungal activity by molecular modeling studies. European Journal of Medicinal Chemistry 2017; 130: 124-138. Acknowledgement: This work was supported by a grant from The Scientific and Technological Research Council of Turkey (TUBITAK-2209/A,No.1919B011603759)
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P78 - Synthesis and Evaluation of Novel Hydrazone Derivatives as
Monoamin Oxidase Inhibitors
Hayrünnisa Taşci a, Begüm Nurpelin Sağlık b, Yusuf Özkay b, Birsen Tozkoparan a, Nesrin GökhanKelekçi a* a Hacettepe University Faculty of Pharmacy Dept of Pharmaceutical Chemistry, 06100 Ankara-Turkey b Anadolu University Faculty of Pharmacy Dept of Pharmaceutical Chemistry, 44280 Eskişehir-Turkey *E-mail: [email protected] Monoamine oxidase (MAO) plays a key role in the regulation of various monoamine neurotransmitters such as serotonin (5HT), norepinephrine (NE), and dopamine (DA)1. In mammals MAO exists in two isoforms, MAO-A and MAO-B, which are encoded by two different genes1. Both enzymes are tightly bound to the mitochondrial outer membrane. They share about 70% amino acid identity and differ with respect to substrate specificity, sensitivity to inhibitors, and tissue distribution [1]. MAO-A preferentially metabolizes 5-HT, NE, and DA and is selectively inhibited by low concentrations of the acetylenic inhibitor clorgyline, whereas MAO-B has higher affinity toward â-phenylethylamine (PEA) and benzylamine and is selectively and irreversibly inhibited by selegiline (L-deprenyl). Selective and reversible MAO-A inhibitors (MAO-A Is) are used in the treatment of depression and anxiety disorders [2], whereas MAO-B inhibitors (MAO-B Is) are used as adjuncts in the treatment of Parkinson’s disease (PD) [3]. In the recent years, the discovery of reversible and selective inhibitors has renewed the interest toward MAO enzymes as drug targets [4]. Different chemical structures have been designed and evaluated in terms of MAO inhibition. Hydrazones are one of the these structures and there have been many reports on the antidepresant / MAO- inhibition activity of hydrazones derived from substituted hydrazides and their reduction products9. For pursuing more potent and less toxic MAO inhibitors we have designed a series of hydrazones containing substituted-2-benzoxazolinone derivatives. Theoretically designed compounds were docked computationally to the active site of the MAO-A and MAO-B isoenzyme. The compounds were synthesized and investigated for their ability to inhibit hMAO isoforms by in-vitro tests. All the compounds were found to inhibit MAO isoenzymes.
Keywords: Hydrazone, 2-benzoxazolinone, MAO inhibition. References: 1. Wouters, J. Structural aspects of monoamine oxidase and its reversible inhibition. Curr. Med. Chem. 1998, 5, 137- 162. (2) Yamada, M.; Yasuhara, H. Clinical pharmacology of MAO inhibitors: safety and future. Neurotoxicology 2004, 25, 215-221. (3) Palhagen, S.; Heinonen, E.; Ha¨gglund, J.; Kaugesaar, T.; Ma¨ki-Ikola, O.; Palm, R. Selegiline slows the progression of symptoms of Parkinson disease. Neurology 2006, 66, 1200-1206. (4) Riederer, P.; Lachenmayer, L.; Laux, G. Clinical applications of MAO-inhibitors. Curr. Med. Chem. 2004, 11, 2033-2043. (5) Salgin-Gökşen, U., et al., Synthesis, molecular modeling and in vitro screening of monoamine oxidase inhibitory activities of some novel hydrazone derivatives. J. Neural Transm., 2013. 120(6): p. 883-891.
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P79 - The Role of Potassium Channels in The Relaxation Response of Intermedin/Adrenomedullin2 (IMD/AM2) in The Rat Pulmonary Artery
Gokcen Telli a*, H. Burak Kandilci b, Banu C. Tel a, Bulent Gumusel a,c a Hacettepe University, Faculty of Pharmacy, Department of Pharmacology, Ankara-Turkey b Ankara University, Faculty of Medicine, Department of Biophysics, Ankara-Turkey c Erzincan University, Faculty of Pharmacy, Department of Pharmacology, Erzincan-Turkey *E-mail: [email protected]
Calcitonin gene related peptide (CGRP) family has important effects on the cardiovascular system. It is well known that especially two peptides of this family, CGRP and adrenomedullin (AM), have vasorelaxant effect in aorta, pulmonary artery (PA) and mesenteric artery. Effects of these peptides are mostly endothelium-dependent and nitric oxide (NO) mediated [1]. Potassium channels (K+ channels) are another important factors that play roles in the mechanisms of action of these peptides. Intermedin/Adrenomedullin2 (IMD/AM2) is the last isolated member of this family. IMD/AM2 which is particularly effective in the pulmonary vascular bed, has structural and physiological similarities with CGRP and AM. It was demonstrated that IMD/AM2 provides endothelium-dependent and NO-mediated relaxation however + studies investigating the role of K channels in the relaxation response of IMD/AM2 are limited [2]. In our + study, the role of various K channels in IMD/AM2 responses was assessed using the isolated organ bath. Isolated PAs were cleaned and cut into rings 3 to 4 mm in length and mounted in organ baths. PA rings were initially stretched to produce a preload of 1,5 g of force and allowed to equilibrate for 90 minutes. Next, the rings were pre-contracted with phenlyephrine (3x10-6M). Once a stable contraction was obtained, -9 -7 cumulative concentration of IMD/AM2 (10 -3x10 M) was added to the bath, and changes in relaxation was assessed. After incubation with non-specific K+ channels inhibitor tetraethylammonium (TEA, 10-2M), + -5 ATP sensitive K channels (KATP) inhibitor glibenclamide (10 M), voltage-gated potassium channels (Kv) -5 2+ + inhibitor 4-aminopyridine (10 M), small-conductance Ca activated K channels (SKCa) inhibitor apamine -5 2+ + -5 (10 M), intermediate-conductance Ca activated K channels inhibitor (IKCa) TRAM34 (10 M) and large- 2+ + -7 conductance Ca activated K channels (BKCa) inhibitor iberotoxin (3x10 M) for 30 minutes, -9 -7 + concentration-response curves of IMD/AM2 (10 -3x10 M) were repeated. The role of K channels was also assessed in PAs that were pre-contracted with 60 mM KCl. In the presence of TEA and in the PAs that pre-contracted with 60 mM KCl, IMD/AM2 responses were significantly inhibited. Iberiotoxin also significantly inhibited to IMD/AM2 vasorelaxant effects. However there were no changes in the responses with KATP, Kv, SKCa and IKCa channels inhibitors. Our results demonstrated that BKCa channels has an important role in IMD/AM2 responses. However, although the relaxation response was inhibited almost completely in the presence of non-specific inhibitor TEA, the responses were partially inhibited with BKca inhibitor.
+ Keywords: Intermedin/Adrenomedullin2, K channels, BKCa channels, pulmonary artery References: 1. Born W, Fischer JA. The Calcitonin Peptide Family: What Can We Learn from Receptor Knock Out and Transgenic Mice. In: Hay DL, Dickerson IM, editors. The Calcitonin Gene-related Peptide Family Form, Function and Future Perspectives. Springer Dordrecht Heidelberg London New York: Springer; 2010. p. 75-86. Acknowledgements: This study was supported by Hacettepe University Scientific Research Projects Coordination Unit (Project numbers: THD-2016-9281).
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P80 - Synthesis, Molecular Docking and Acetylcholinesterase Inhibitory Activity of Some Novel Quinoline Derivatives
Harun Uslu a*, Arif Mermer b, Zeynep Özdemir a, Neslihan Demirbaş b a İnönü University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Malatya, Turkey b Karadeniz Technical University, Department of Chemistry, 61080, Trabzon, Turkey *E-mail: [email protected] Alzheimer’s disease is a complex neurodegenerative disorder characterized by synapse dysfunction, neuronal death, memory loss and learning ability. Cholinesterase inhibitors are used in the treatment of various neuromuscular disorders which occur as a result of reduced cortical and hippocampal levels of ACh such as Alzheimer’s disease [1-2]. In the present study a novel series of quinoline derivatives were designed, synthesized, characterized. Acetylcholinesterase inhibitory activities of the compounds were investigated in order to acquire new biologically active compounds. Using molecular docking approach we tried to get insights into binding interactions of our derivatives in comparison with 5b and 10c in the active site of enzyme and understand the facts that underlie the relationships between structural modifications on these ligands and their efficacies.
Keywords: Acetylcholinesterase, docking, quinoline References: 1. Cacabelos R. Pharmacogenomics in Alzheimer's Disease. In: Yan Q, editor. Pharmacogenomics in Drug Discovery and Development: From Bench to Bedside. Totowa, NJ: Humana Press; 2008. p. 213-357. 2. Strelnik AD, Petukhov AS, Zueva IV, Zobov VV, Petrov KA, Nikolsky EE, et al. Novel potent pyridoxine-based inhibitors of AChE and BChE, structural analogs of pyridostigmine, with improved in vivo safety profile. Bioorg Med Chem Lett. 2016;26(16):4092-4.
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P81 - Oleuropein Restores Chemotherapy Drug-Induced Pancreas Injury in Rats
Kubra Koc a*, Fatime Geyikoglu a, Salim Cerig a, Murat Bakir a, Ferhunde Aysin, Nihal Simsek Ozek
aDepartment of Biology, Faculty of Science, Ataturk University, Erzurum, Turkey
*E-mail: [email protected]
Cisplatin (CIS) is one of the important chemotherapeutic drugs having high level and broad spectrum of antitumor activity commonly used to treat head, neck, lung, testis, ovary, and breast cancers [1,2]. On the other hand, several side effects have been shown, such as nephrotoxicity, infertility, ototoxicity, and neurotoxicity. Oleuropein (OLE) is a natural antioxidant and scavenging free radicals. Here, we first explore the efficacy of OLE in pancreas against to the toxicity of CIS and also analyses its mechanism. Fifty-six Sprague-Dawley rats were equally divided into eight groups including, control, group which received 7 mg/kg/day CIS intraperitoneally (i.p.) for 24 hours, groups treated with doses of 50, 100 and 200 mg/kg OLE i.p. for 3 days, and groups which received same dose of CIS with three doses of OLE. After the treatments, animals were sacrificed. The oxidative DNA damage [(8-hydroxy-2'-deoxyguanosine) (8-OHdG)], total oxidative stress (TOS), total antioxidant status (TAS) and malondialdehyde (MDA) levels were evaluated in the pancreas. The histology of pancreas was examined by using three different staining methods: Hematoxylin-eosin, Periodic acid Schiff, Alcian blue. Serum was provided to assess pancreatic function the lipase and amylase values. The results showed that compared to the control group, CIS significantly increased both the amount of 8-OHdG, the level of TOS and MDA into tissue. Moreover, severe tissue damages were detected in pancreas. Whereas, OLE at high dose significantly decreased the formations of 8-OHdG, the level of MDA, and increased levels of TAS in tissue samples. In the CIS group the levels of amylase and lipase increased compared with the control group. But there were statistically significant differences among the CIS group and the CIS+OLE groups in the values of both amylase and lipase. In addition histopathological findings that observed in CIS group in the pancreatic tissue alleviated in CIS+OLE groups.OLE can decrease CIS-induced pancreas toxicity by inhibiting lipid peroxidation and ROS; and this method has good clinical applicability. This means that OLE combined with CIS may be applied to tumor patients to improve chemotherapy efficiency in the near future. On the basis of long-term experience and extensive clinical data, OLE may represent a candidate for the management of CIS-induced DNA damages, pathological lesions and functional disorders in pancreas.
Keywords: Oleuropein, cisplatin, 8-OHdG, oxidative stress, pancreas.
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P82 – The Effects of Parietin on Wound Healing on the Human Dermal Fibroblast Cell Line
Gülşah Gündoğdu a, Köksal Gündoğdu b, Kemal Alp Nalci c, Ahmet Hacimüftüoğlu c,
aDepartment of Physiology, Faculty of Medicine, Atatürk University, Erzurum, Turkey bDepartment of Orthopedics and Traumatology, Erzurum Regional Training and Research Hospital, Erzurum, Turkey cDepartment of Pharmacology, Faculty of Medicine, Atatürk University, Erzurum, Turkey *E-mail: [email protected]
Parietin isolated from lşgın (Rheum Ribes L.) is anthraquinone structure compunds. Antroquinones are known to have antimicrobial, antiinflammatory and hepatoprotective activities. In this study, it is aimed to investigate the effects of parietin on wound healing on the human dermal fibroblast cell line. Human dermal fibroblast cells were cultured in appropriate culture medium. They were transferred to 6-well plates and were waited until 100% confluence was achieved. The wound model was created by using a pipette tip and then the floating cells and medium were changed. Different concentrations of parietin (final concentrations in the well to be 5-750 µM) were added into the medium. The proliferation-inducing effect on cell viability was determined by using MTT assay and images were taken at cells at 0, 3, 6, 9, 12, 24, 48, 72 and 108 hours. The obtained data were analyzed statistically by using the One-way ANOVA test. The proliferation effect of parietin at a dose range of 5-750 μM were studied on the human dermal fibroblast cell line. With regard to MTT result analysis, it was determined that parietin had significant proliferation-inducing effect on cell viability at 72 hours in a dose range of 5 to 10 μM (p <0.05). In addition this, image of the cell proliferation was shown at the same doses at 72 hours. It was shown that parietin induces cell proliferation in cases of dermal fibroblast loss in a dose-dependent manner in this study and it was found that parietin was the effective at low doses and can be used in wound healing.
Keywords: Rheum ribes, parietin, fibroblast, wound healing
References: 1. Backorová, M., et al., Variable responses of different human cancer cells to the lichen compounds parietin, atranorin, usnic acid and gyrophoric acid, Toxicology in Vitro, 25, 2011, 37–44. 2. Tobar, EL., et al., Detection and aggregation of the antitumoral drug parietin in ethanol/water mixture and on plasmonic metal nanoparticles studied by surface-enhanced optical spectroscopy: Effect of pH and ethanol concentration, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 159, 2016, 134–140.
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P83 - Evaluation of Studies Between 2006-2016 Years Contributions Related To Treatment of Clinical Pharmacists
Aysel Pehlivanlı a, Büşra Akyol a, Gülbin Özçelikay b*
a Ankara University, Department of Clinical Pharmacy, Ankara, Turkey b Ankara University, Department of Pharmacy Management, Ankara, Turkey *E-mail: [email protected]
Clinical pharmacy is a health science discipline. Namely; pharmacists encourage patient care that optimizes medication therapy and promotes health, wellness, and disease prevention [1]. Clinical pharmacy has a significant role in the provision of rational drug treatment and has changed into patient-centered all around the world in last 30-40 years [2]. Many research has been conducted on clinical pharmacy in Turkey [3, 4] and important steps are taken in terms of health system. Namely; besides the institution of clinical pharmacy graduate and doctorate programs in universities, the Ministry of Health has designated ‘‘Clinical Pharmacy ’’as one of the expertise fields in higher pharmacy education. Thus, the clinical pharmacist is a significant component between physician and patient in the patient-oriented health system. In this article, the case reports of clinical pharmacy practices performed by clinical pharmacists are reviewed and the importance of clinical pharmacy which is very popular because of the recent regulations on Clinical Pharmacy Graduate Education will be evaluated. In the current study, disease-specific, pharmacist-based, English-written full- text articles indexed in Pubmed database by the keyword ‘‘ Clinical Pharmacy ’’ were evaluated. As a result of examining the 46 articles obtained in these features; it has been determined cases in which the clinical pharmacist is actively involved are mostly associated with cardiovascular system diseases. The articles which are indexed for current study are mostly prospective, as well as, retrospective and also randomized controlled including both observational and interventional methods. Interestingly, the article on ‘‘clinical pharmacy and ethic’’ was not found. In conclusion it has been determined that the clinical pharmacist has a positive effect in most cases given in this article.
Keywords: Clinical Pharmacy, Clinical Pharmacist, pharmaceutical care
References: 1.American College of Clinical P. The definition of clinical pharmacy. Pharmacotherapy. 2008;28(6):816-7. 2.Rapp RP. A perspective on 45 years in clinical pharmacy education. Ann Pharmacother. 2007;41(6):1047-9. 3.Sancar M, Izzettin FV, Apikoglu-Rabus S, Besisik F, Tozun N, Dulger G. Pharmacoeconomic comparison of Helicobacter pylori eradication regimens. Pharm World Sci. 2006;28(4):207-14. 4.Ekincioglu AB, Demirkan K. Clinical nutrition and drug interactions. Ulus Cerrahi Derg. 2013;29(4):177-86.
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P84 - In vitro toxicity evaluation of mycelium extracts of Lepista nuda
Fatime Geyikoglu a, Salim Cerig a, Murat Ozdal a, Kübra Koc a, Özlem Gür Özdal a, Ömer Faruk Algur a, Nihal Simsek Ozek a,b, Ferhunde Aysin a,b*
a Atatürk University, Faculty of Science, Department of Biology, 25240, Erzurum, Turkey b East Anatolian High Technology Research and Application Center (DAYTAM), Atatürk University, 25240, Erzurum, Turkey *E-mail:[email protected]
Lepista nuda (LN), commonly known as the wood blewit and alternately known as Clitocybe nuda, is an edible mushroom native to Europe and North America. The objective of this study was to explore the cytotoxic and oxidative effects of mycelium of the LN (0-500 µg/ml concentrations) on human blood cells (hBCs). Total antioxidant capacity (TAC) and total oxidant status (TOS) were applied to evaluate the global oxidant/antioxidant levels ın human blood cells. Cytotoxicity was determined by neutral red (NR) assay. 0-200 µg/ml doses of LN treatment increased TAC levels and decreased TOS amounts. However, 250 and 500 µg/ml doses of this mushroom treatment increased the TOS levels in blood cells. In addition, no change in the cell viability was found in the low doses of LN treatment (0- 200 µg/ml) whereas decreased cell viability was obtained in the high dose of LN treatment (500 µg/ml). The findings of the present study showed that high dose of LN induces the oxidative stress and cytotoxicity on hBCs.
Keywords: Lepista nuda, oxidative damage, cytotoxicity, human blood
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P85 - Synthesis of New Benzothiazole- Hydrazone Derivatives as Potential Mao Enzymes Inhibitors
Derya Osmaniye a,b*, Serkan Levent a,b, Ulviye Acar Çevik a,b, Beril İnci c, Sinem Ilgın c, Yusuf Özkay a,b, Zafer Asım Kaplancıklı a
aDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu Universty, Eskişehir, Turkey bDoping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu Universty, Eskişehir, Turkey cDepartment of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu Universty, Eskişehir, Turkey *E-mail: [email protected]
Monoamine oxidase (MAO) including flavin adenine dinucleotide is an outer mitochondrial membrane. This enzyme has an important role in the metabolism of endogenous and exogenous amines [1, 2]. Literature survey displays that the compounds, including benzothiazole, have important MAO enzymes inhibitory activity [3]. Besides, several substituted hydrazones have been reported as MAO inhibitors [4,5]. Prom this point of view, in the present study new benzothiazole-hydrazone derivatives (3a-3n) were synthesized in order to observe MAO enzymes inhibition. The structures of the synthesized compounds were elucidated using FT-IR, 1H-NMR, 13C-NMR, and HRMS spectral data. The inhibitory activity of the compounds 3a-3n against hMAO-A and hMAO-B enzymes was evaluated by using in vitro Amlex Red® reagent based fluorometric method. Genotoxicity and cytotoxicity of the most active compound were also evaluated. The activity results showed that compound 3e is most active derivative in the series.
Keywords: Benzothiazole, hydrazone, MAO enzyme inhibition
References: 1. Weyler W, Hsu YP, Breakefield XO. Biochemistry and genetics of monoamine oxidase. Pharmacol Ther. 1990;47(3):391-417. 2. Shih JC, Chen K, Ridd MJ. Monoamine oxidase: from genes to behavior. Annu Rev Neurosci. 1999;22:197-217. 3. Thull U, Carrupt PA, Testa B. Pargyline analogues as potent, nonselective monoamine oxidase ınhibitors. Pharm Pharmacol Commun. 1998;4:579-581. 4. Tripathi RK, Ayyannan SR. Design, Synthesis, and Evaluation of 2-Amino-6- nitrobenzothiazole-Derived Hydrazones as MAO Inhibitors: Role of the Methylene Spacer Group. ChemMedChem. 2016;11:1551-1567.
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P86 - Investigation of Cholinesterase Enzyme Inhibition Activity of 3 Barbarea Species
Merve Badema, Sıla Ozlem Senera, Nuriye Korkmazb, Seyda Akkayab, Rezzan Aliyazicioglub, Ufuk Özgena
aKaradeniz Technical University, Faculty of Pharmacy, Department of Pharmacognosy, Trabzon bKaradeniz Technical University, Faculty of Pharmacy, Department of Biochemistry, Trabzon E-mail:[email protected]
Barbarea genus belongs to Brassicaceae family has been presented about 20 species in Europe and Asia, 15 taxon, 9 taxon are endemic, in Turkey. Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. Alzheimer's disease (AD) is a chronic neurodegenerative disease and enzyme inhibitors are frequently used in the treatment of Alzheimer's disease [1]. With this study, methanolic extracts from the aerial parts the dried and powdered 3 Barbarea species (B. auriculata, B. integrifolia, and B. plantaginea) growing in Turkey and 2 of which are endemic (B. auriculata ve B. integrifolia) were prepared and investigated inhibitory activities of AChE and BuChE of the plant by colorimetric Ellman’s method with some modifications. As a result of the study, the IC50 values for inhibitory activities of AChE assay of B. auriculata, B. integrifolia, and B. plantaginea have been found as 150,95 ± 2,65; 206,90 ± 4,48 and 243,26 ± 4,18 µg/mL, for inhibitory activities of BuChE 679,04 ± 9,36; 247,68 ± 3,89 and 308,14 ± 5,21 have been found, respectively. Inhibitory activities of AChE and BuChE of the plants were found significiant compared with reference compound. The plants can be an alternative native drug source in the treatment of Alzheimer's disease.
Keywords: Alzheimer, Barbarea, Cholinesterase
References: 1. Colovic M, Danijela Z, Tamara D, et al. Acetylcholinesterase inhibitors: pharmacology and toxicology. Current neuropharmacology. 2013;11(3): 315-335.
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P87 - Plants Traditionally Used for The Treatment Of Kidney Stones in Turkey
Seçil Karahüseyin a,b*, Aynur Sarı a a Istanbul University, Faculty of Pharmacy, Department of Pharmacognosy, 34116, Fatih, Istanbul bCukurova University, Faculty of Pharmacy, Department of Pharmacognosy,01330, Balcali, Adana *Email: [email protected]
Turkey is one of the most floristically rich countries in the world with astonishing plant diversity. Its flora consists of about 10000 vascular plant and approximately one third of its flora (34.4 %) is endemic to the country [1,2]. Recently, numerous ethnobotanical studies have been published and much has been written about medicinal plants in our country [1,2]. During the past three decades, major advances have been made in the field of nephrolithiasis. Today, most urinary stones in patients in most countries are renal stones. The incidence and prevalence rates of kidney stones may be affected by genetic, nutritional, and environmental factors [3]. Kidney stone prevention relies on the 24-hour urine collection to diagnose metabolic abnormalities and direct dietary and pharmacological therapy. While its use is guideline supported for high risk and interested patients, evidence that the test can accurately predict recurrence or treatment response is limited [4]. However, diagnosis and treatment of remediable causes of stones requires testing and drugs that impose a cost; this cost is balanced by the presumed reductions in stone related events and medical encounters [5]. Ethnobotanical studies carried out by traditional methods of treatment are recorded and this information is aimed to contribute to the development of the drug. The information about how to traditionally use these medicinal or wild plants has been transferred from generation to generation. In this study, ethnobotanical studies has been searched and also found a lot of taxa used in traditional treatment for kidney stones in Turkey. It is aimed to give information about scientific and local names of these taxa, families, using parts and used fort he treatment of kidney stones.
Keywords: Medicinal plants, traditional treatment, kidney stones, Turkey
References: 1. Demirci S, Özhatay N. An Ethnobotanical Study in Kahramanmaraş (Turkey); Wild Plants Used for Medicinal Purpose in Andırın, Kahramanmaraş. Turkish Journal of Pharmaceutical Sciences. 2012; 9(1):75-92. 2. Gürdal B, Kültür Ş. An ethnobotanical study of medicinal plants in Marmaris (Muğla, Turkey). Journal of Ethnopharmacology. 2013; 146:113–126. 3. Pak C Y C. Kidney Stones. The Lancet. 1998; 351:1797-801. 4. His R S, Sanford T, Goldfarb D S, Stoller M L. The Role of the 24-Hour Urine Collection in the Prevention of Kidney Stone Recurrence. The Journal of Urology. 2017; 197:1084-1089. 5. Parks J H, Coe F L. The financial Effects of Kidney Stone Prevention. Kidney International. 1996; 50:1706-1712.
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P88 - Design, Synthesis, Biological Evaluation and Molecular Modeling of Novel 5- Arylidene-4-Thiazolidinones as Potential COX-1/COX-2 Inhibitors
Necla Kulabaş a*, Özlem Bingöl Özakpınar b, İlkay Küçükgüzel a*
a Marmara University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Haydarpaşa 34668 İstanbul, Turkey b Marmara University, Faculty of Pharmacy, Department of Biochemistry, Haydarpaşa 34668 İstanbul, Turkey *E-mail: [email protected]
In recent years, studies provided evidence indicating the importance of COX-2 inhibitors in the treatment of cancer chemotherapy and neurological diseases such as Alzheimer's and Parkinson as well as anti-inflammatory effects of these drugs [1]. COX-2 isoenzyme released in inflammatory cells and cancer cells appears to be an ideal drug target for the inhibition of cancer formation and inflammation [2]. The literature findings on 5-arylidene-4-thiazolidinone derivatives with a broad spectrum of biological effects, have led us to design selective inhibitors of COX-2 [3]. In this study, 5-arylidene-2-(heteroarylimino)-1,3-thiazolidin-4-one derivatives were synthesized via Knoevenagel condensation of aryl aldehydes with appropriate 1,3-thiazolidin-4-one derivatives. The synthesized compounds were identified by the help of IR, 1H-NMR, 13C-NMR and mass spectral data while the purities of them were proved with TLC and elemental analysis. Synthesized compounds were evaluated for their COX-1/COX-2 enzyme inhibition to determine their selectivity. In scope of this study, mechanism of binding to COX enzymes for active compounds was evaluated using computer-assisted molecular modeling techniques. The crystal structures of COX-1 (PDB code: 1Q4G) and COX-2 (PDB code: 3LN1) were used for docking after cleaning the enzyme structures from co- crystallized compounds and from water molecules. Three-dimentional structures of the synthesized compounds were optimized with semiempirical PM3 method and used for initial geometry in docking calculation. The resultant docking files were analyzed to explain the mechanism of binding.
Keywords: Anti-inflammatory; COX-2 selectivity; 1,3-thiazolidin-4-one; molecular modeling. References: 1. Dündar Y, Ünlü S, Banoğlu E, Entrena A, Costantino G, Nunez MT, Labeaga L, Sahin MF, Noyanalpan N. Eur J Med Chem 2009; 44: 1830-1837. 2. Sarkar FH, Adsule S, Li Y, Padhye S. Mini-Rev Med Chem 2007; 7: 599-608. 3. Song Y, Connor DT, Doubleday R, Sorenson RJ, Sercel AD, Unangst PC, Roth BD, Gilbertsen RB, Chan K, Schrier DJ, Guglietta A, Bornemeier DA, Dyer RD. J Med Chem 1999; 42: 1151-1160.
Acknowledgements: This study was supported by Scientific Research Project Commision of Marmara University (Project number: SAG-C-DRP-050614-0227), also thanks to the Scientific and Technological Research Council of Turkey (TUBITAK) for Domestic PhD Scholarship intended for Priority Areas (Code: 2211-C).
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P89 - Synthesis and Cytotoxicities of Bis Mannich Bases of Phenolic Chalcones
Fatma Yesilyurt a, Halise Inci Güla*, Hiroshi Sakagami b
aDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy,Ataturk University, Turkey. bMeikai University Research Institute of Odontology (M-RIO), Meikai University School of Dentistry, Sakado, Saitama, Japan *Eposta: [email protected] Cancer is one of the most important diseases of death worldwide. It is fast progressing in twenty-first century and is predicted to affect 22 million people by 2030 [1]. Mannich bases are generally formed by the reaction between a compound containing a reactive hydrogen atom, formaldehyde, and mostly secondary amine [2]. The Mannich bases were reported with their remarkable biological activities such as analgesic, anticonvulsant, cytotoxic, antiinflammatory, and antimicrobial activities [1,3]. In this study, bis Mannich bases of phenolic chalcones FY1-6, 1-[3,5-bis(aminometil)-4-hidroksi-fenil]-3-(aril)-2-propen-1- on, were synthesized and their chemical structures were confirmed by spectral tecniques. Cytotoxities of the compounds were carried out by MTT method1. Results were shown in Table 1.
Table 1. Cytotoxicities of the compounds FY1-6
Malign cell lines, CC50 Nonmalign cells, CC50 PSE
Ca9-22 HSC-2 HSC-3 HSC-4 Mean HGF HPLF HPC Mean J/E Compound (A) SI (B) SI (C) SI (D) SI (E) SI (J) (F) (G) (H) (I) *100 FY-1 12.0 3.55 29.9 1.43 33.1 1.29 38.4 1.11 28.4±11.4 1.85 50.0 48.3 29.6 42.6±11.3 6.51 FY-2 43.2 3.69 70.7 2.25 61.7 2.58 122.4 1.30 74.5±33.9 2.46 236.1 163.9 78.1 159.3±79.0 3.30 FY-3 10.7 3.72 17.6 2.26 22.3 1.78 38.8 1.03 22.4±12.0 2.20 48.0 44.4 27.0 39.8±11.2 9.82 FY-4 8.7 5.15 17.6 2.55 21.1 2.12 16.2 2.77 15.9±5.2 3.15 49.2 62.5 22.8 44.8±20.2 19.81 FY-5 5.4 7.30 14.4 2.74 11.5 3.43 12.9 3.05 11.1±3.9 4.13 47.2 47.7 23.4 39.4±13.9 37.2 FY-6 12.1 2.17 8.7 3.01 11.6 2.26 16.6 1.58 12.3±3.3 2.26 22.0 45.6 10.9 26.2±17.7 18.4 Melfalan 22.6 6.50 8.5 17.29 5.6 26.25 11.9 12.35 12.2±7.4 12.05 140.0 179.0 123.0 147.0±29.0 98.77 5-FU >200.0 ><1 28.3 >7.06 69.0 >2.90 41.7 >4.80 >84.8±78.7 >3.94 >200.0 >200.0 >200.0 >200.0 ><4.65 PSE: Potency-Selectivity Expression. SI: Selectivity Index. 5-FU: 5-Fluorouracil According to Table 1, the compound FY 5, 1-(4-hydroxy-3,5-bis(morpholinomethyl)phenyl)-3- phenylprop-2-en-1-one, with highest PSE value (PSE=37.2) can be considered as a leader compound to design new anticancer compounds for further studies. Keywords: Mannich bases, cytotoxicity, phenolic chalcone, dental cells. References: 1. Yamali C, Gul HI, Sakagami H, Supuran CT. Synthesis And Bioactivities Of Halogen Bearing Phenolic Chalcones And Their Corresponding Bis Mannich Bases. Journal of Enzyme Inhibition and Medicinal Chemistry 2016;31(S4):125-131. 2. Dimmock JR, Kandepu NM, Hetherington M, et al. Cytotoxic Activities Of Mannich Bases Of Chalcones And Related Compounds. J Med Chem 1998;41:1014-26.
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P90 - Examination of Inhibition of Anticholinesterase Enzyme of Caliytagia Growing in Two Different Regions
Sıla Ozlem Sener a, Merve Badem a, Seyda Akkaya b*, Nuriye Korkmaz b, Ufuk Özgen a, Rezzan Aliyazicioglu b aKaradeniz Technical University, Faculty of Pharmacy, Department of Pharmacognosy, Trabzon bKaradeniz Technical University, Faculty of Pharmacy, Department of Biochemistry, Trabzon *E-mail: [email protected]
The Convolvulaceae family is represented by 85 genus and about 2800 species on the earth. Calystegia 183, one of the family members of this family, is represented by 8 species of this genus in Turkey. In this study, it was aimed to investigate the anticholinesterase enzyme activity on Calystegia silvatica collected from Trabzon (Bostancı) (CS1) and Ordu (Akkuş) (CS2) regions. Acetylcholinesterase (AChE) predominates in the healthy brain, with butyrylcholinesterase (BuChE) considered to play a minor role in regulating brain acetylcholine (ACh) levels. However, BuChE activity progressively increases in patients with Alzheimer's disease (AD), while AChE activity remains unchanged or declines. Both enzymes therefore represent legitimate therapeutic targets for ameliorating the cholinergic deficit considered to be responsible for the declines in cognitive, behavioral and global functioning characteristic of AD [1]. For these purpose, inhibitory activities of AChE and BuChE of the methanolic extract were evaluated by colorimetric Ellman’s method [2]. As a result of the study, CS1 and CS2 of AChE% inhibition results for concentrations of 25 μg/mL, 50 μg/mL, 100 μg/mL and 200 μg/mL were found as 9.32 ± 0.5; 10.9 ± 0.3; 25.1 ± 0.6; 34.25 ± 0.7 and 11.8 ± 0.2; 24.1 ± 0.4; 38.3 ± 0.9; 62.55 ± 0.6. BuChE inhibition results were found as 16.5 ± 0.5; 26.7 ± 0.7; 32.6 ± 0.8; 36.9 ± 0,7 and 3.8 ± 0.4; 12.3 ± 0.7; 17.3 ± 0.6; 22.0 ± 0,8, respectively. It can be said that the differences observed in the results stem from due to the plant is collected from different regions. These differences may be due to climate, soil structure, altitude of the region. Keywords: Acetylcholinesterase, butyrylcholinesterase, Calystegia silvatica References: 1. Greig, NH.; Lahiri, DK.; Sambamurti K., Butyrylcholinesterase: an important new target in Alzheimer's disease therapy. Int. Psychogeriatr. 2002;14(1):77-91. 2. Ellman, GL.; Courtney, D.; Andies, V., Featherstone, R.M., A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961;7,88-95.
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P91 - Inhibition effects of 2-amino-3-cyanoquinolin Derivatives on Carbonic Anhydrase I and II
Aliye Altundas a, Berna Gül a, Murat Çankaya b*, Ali Atasever c, İlhami Gülçin d
aDepartment of Chemistry, Faculty of Science and Arts, Gazi University, Ankara, Turkey bDepartment of Biology, Faculty of Science and Arts, Erzincan University, Erzincan, Turkey* cDepartment of Food Science, Ispir H. Polat Vocational School, Atatürk University, Erzurum, Turkey dDepartment of Chemistry, Faculty of Science, Atatürk University, Erzurum, Turkey E-mail: [email protected]
Pyridine derivatives have an important role in medicinal chemistry. Naturally occurring or synthetically produced pyridine scaffolds have different pharmacological properties [1]. Carbonic anhydrases (EC4.2.1.1, carbonate dehydratase) commonly found in all organisms and are zinc-containing - metaloenzymes. For metabolism, the conversion of CO2 and HCO3 to each other is very important [2]. The aim of this study was to investigate the in vitro effects of 2-amino-3-cyanoquinolin derivatives on human carbonic anhydrases I and II isoenzymes. CA I and II have been purified from human blood erythrocytes using by Sepharose-4B-l tyrosine-sulfanilamide affinity gel chromatography. The inhibitory effects of 2- amino-3-cyanoquinolin derivatives on two isoenzymes were checked using IC50 and Ki values. Chemicals have vitally role for continuation of life and activity of some of enzymes. Therefore, we recommend that you pay attention to the use of chemicals substances.
CH 3 CN NH 4 O A c , H C 2 Y 2 Y Be n z e n e, O CN CN X H3 C X H3 C CH O K2 C O 3 X CN H CN 6 3a , b X N NH 2 X= S or O n X Y= C or N 1a , b X= C, O o r S n 7a - f n= 1, 2 Scheme. Synthesis of 2-amino-3-cyanoquinolin derivatives (7a-f)
IC50 (µM) KI (µM) Compounds hCA I r2 hCA II r2 hCA I hCA II
7b 138.66 0.9848 6.19 0.9970 53.9122.25 2.560.74
7d 5.63 0.9992 5.68 0.9989 2.842.23 4.561.39
7f 46.22 0.9942 - - 12.980.78 -
Keywords: Amino-3-cyanoquinolin, inhibition, affinity, carbonic anhydrase. References: 1. Baumann M, Baxendale IR. An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles. Beilstein Journal of Organic Chemistry. 2013;9:2265-2319. 2. Ayvaz S, Çankaya M, Atasever A, Altuntas A. 2-Amino-3-cyanopyridine derivatives as carbonic anhydrase inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry. 2013;28:305-310.
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P92 - Qualitative and Quantitative Determination of Ursolic Acid and Chlorogenic Acid in Different Herbal Slimming Products Containing Ilex paraguariensis by HPLC
Hafize Yuca a*, Benan Dursunoğlu a, Sefa Gözcü b, Bilal Yılmaz c, Zühal Güvenalp a
aDepartment of Pharmacognosy, Faculty of Pharmacy, Atatürk University, 25240, Erzurum, Turkey bDepartment of Pharmacognosy, Faculty of Pharmacy, Erzincan University, 24100, Erzincan, Turkey cDepartment of Analytical Chemistry, Faculty of Pharmacy, Atatürk University, 25240, Erzurum, Turkey E-mail: [email protected]
Ilex paraguariensis A. St. Hil. (mate) is a South America plant and a member of Aquifoliaceae family. The medicinal parts of plant are dried or roasted leaves [1]. Two of the major components of mate are chlorogenic acid and ursolic acid that have anti-obesity and stimulator of lipolysis effects, respectively [2,3]. I. paraguariensis is presented in herbal slimming products due to its diuretic and lipolytic effects1. In the present study, new, simple and sensitive high performance liquid chromatography (HPLC) methods have been developed for qualitative and quantitative determination of ursolic acid and chlorogenic acid in eight herbal slimming products containing Ilex paraguariensis in Turkey. The developed methods can be used for routine quality control analysis of ursolic acid and chlorogenic acid in different herbal slimming products.
Keywords: Ursolic acid, chlorogenic acid, HPLC, herbal slimming product, Ilex paraguariensis
References:
1. Gruenwald J, Brendler T, Jaenicke C. (eds). PDR for Herbal Medicines. Medical Economics Co., Inc., Montvale, NJ. 2007;383-384. 2. Li Y, Kang Z, Li S, Kong T, Liu X, Sun C. Ursolic Acid Stimulates Lipolysis in Primary-Cultured Rat Adipocytes. Molecular Nutrition Food Research. 2010;54:1609-1617. 3. Cho AS, Jeon SM, Kim MJ, Yeo J, Seo KI, Choi MS, Lee MK. Chlorogenic Acid Exhibits Anti-Obesity Property and Improves Lipid Metabolism in High-Fat Diet-Induced-Obese Mice. Food and Chemical Toxicology. 2010;48:937-943.
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P93 - Cytotoxicity and Reactive Oxygen Species Production Induced by Bisphenol A and/or Mono (2-ethylhexyl) Phthalate in Human Hepatoma Cells
Gizem Ozkemahli A,B, Pınar Erkekoglu A, Belma Kocer-Gumusel A*
a Department of Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey b Department of Toxicology, Faculty of Pharmacy, Erzincan University, Erzincan, Turkey *E-mail: [email protected]
Bisphenol A (BPA) and di-(2-ethylhexyl) phthalate (DEHP) are widely used in the production of plastics in industry and they are endocrine disrupting chemicals (EDC). Consumer products can sometimes contain both DEHP and BPA. Today, widespread uses of these products or food contaminated with these EDCs is suggested to be related to different metabolic and hormonal defects and pathological conditions, including hepatotoxicity and carcinogenicity. The present study aimed to evaluate the cytotoxic and reactive oxygen species (ROS)-producing of BPA and/or the main DEHP metabolite, mono (2-ethylhexyl) phthalate (MEHP), in human liver hepatocarcinoma cells (HepG2). BPA and/or MEHP were applied to HepG2 cells for 24 hours. Cytotoxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay while intracellular ROS production was determined by a fluorometric intracellular ROS kit that detects intracellular ROS (especially superoxide and hydroxyl radicals) in live cells after 1hour incubation. Inhibitory concentration 50 (IC50) doses for BPA, MEHP and BPA+MEHP were 614 µM, µM, 17 µM and 500 µM+15 µM, respectively. IC70 doses for BPA, MEHP and BPA+MEHP were 343 µM, 4.5 µM and 400+10 µM, respectively. At IC70 doses, BPA caused an increase of 98%; MEHP caused an increase of 51% and BPA+MEHP caused an increase of 290% in intracellular ROS production vs. control (p<0.05, all). These results indicate that combined exposure to plasticizers cause much higher cytotoxicity and intracellular ROS generation when compared to each substance applied alone. Serious concern should be given particularly to childhood exposure to these plasticizers.
Keywords: Bisphenol A, mono (2-ethylhexyl) phthalate, combined exposure, HepG2 cell, cytotoxicity
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P94 - Development and Validation of an HPLC-UV Method for Simultaneous Determination of Levetiracetam and Carbamazepine in Pharmaceutical Formulations
Büşra Kandilli a, Afife Büşra Uğur a, Meltem Çetin a, Fatma Demirkaya-Miloğlu b aAtatürk University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Erzurum bAtatürk University, Faculty of Pharmacy, Department of Analytical Chemistry, Erzurum * E-mail: [email protected]
A combination of levetiracetam (LEV) and carbamazepine (CBZ) may be used to obtain synergistic effect in treatment of partial seizures [1,2]. The aim of the study is to develop and validate a simple reversed phase (RP) HPLC-UV method to determine both LEV and CBZ in pharmaceutical formulations. Separation was achieved on a C18 column (5 μm, 4.6 mm×250 mm) using a mobile phase consisting of methanol and ultrapure water (50:50, v/v), at a flow rate of 1.0 mL/min and UV detection at 230 nm. The LEV and the CBZ were eluted after 3.4 and 13.1 min, respectively. Calibration (n= 7) and validation samples (n=3) were prepared in mobile phase for analysis and the method was validated for specificity, linearity, range, sensitivity, accuracy and precision. Calibration curves were linear over the concentration range of 0.5-32 μg/mL for both drugs and the coefficient of correlation (r2) for LEV and CBZ were found to be 0.99996 and 0.99997, respectively. LOD and LOQ values were found to be 0.052 and 0.159 μg/mL for LEV and 0.026 and 0.080 μg/mL for CBZ, respectively. The relative error (RE) and the percent relative standard deviation (RSD %) values (<2%; 0.5, 4 and 32 μg/mL for LEV and CBZ; n=6 for each concentration) indicated good accuracy and precision of the developed method. It was concluded that the developed analytical method was linear, sensitive, accurate, precise and selective. It could be useful for simultaneous estimation of of LEV and CBZ in pharmaceutical formulations.
Figure 1. Calibration curve of LEV (a), calibration curve of CBZ (b) and the chromatogram of LEV and CBZ (c).
Keywords: Levetiracetam, carbamazepine, HPLC-UV method, validation
References: 1. Shakya DR, Dutta A, Gautam R. Hallucination in a Seizure Patient Using Levetiracetam: A Case Report. Case Reports in Medicine. 2012; doi:10.1155/2012/706243. 2. Kaminski RM, Matagne A, Patsalos PN, Klitgaard H. Benefit of Combination Therapy in Epilepsy: A Review of The Preclinical Evidence with Levetiracetam. Epilepsia. 2009;50(3):387-397. October 05-07, 2017, ERZURUM-TÜRKİYE 142
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P95 - Cytotoxic Activities of New Sulphonamides on OSCC
Mehtap Tugrak a, Halise Inci Gul a*, Hiroshi Sakagami b
aAtaturk University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 25240 Erzurum, Turkey, bDivision of Pharmacology, Meikai University School of Dentistry, Sakado, Saitama, Japan *E-mail: [email protected]
Cancer is a disease characterized by uncontrolled cell division which spread throughout the body and cause damage to essential organs. Despite several drugs are available in market, they have several problems such as several side effects, stability, selectivity or gained resistance problems. So there is an urgent need to find new drug candidates with high selectivity to the cancer cells [1,2]. Pyrazoles derivatives and sulfonamides possess a broad range of biological activitiy spectrum such as antimicrobial, antihypertensive, antitumor, antiinflammatory, antidepressant and anticonvulsant activities [3,4]. In this study it was aimed to synthesize (Figure 1, [5]) new compounds bearing pyrazoline and sulfonamide pharmacophores to investigate their cytotoxic activities towards four cancer cell lines. The cytotoxic activity of the compounds are presented at Table 1. In conclusion, the compounds 4, which is 3,4,5-trimethoxy derivative, and 6, which is 4-hydroxy derivative, were found candidate cytotoxic compounds for further studies. Figure 1: Structures of benzenesulfonamides synthesized R
R: H (1), 4-OCH3 (2), 2-OCH3 (3), 3,4,5-(OCH ) (4), 4-F (5), 4-OH (6) N 3 3 N
SO2NH2 1-6 Table 1. Cytotoxicity and tumour-specificity of new benzenesulfonamides (1-6) “4-(3-(4-substitutedphenyl)-3a,4-dihydro-3H-indeno[1,2-c]pyrazol-2-yl)”
CC50 (μM) Human oral squamous cell carcinoma cell lines Human normal oral cells mean Compounds Ca9-22 (A) SI HSC-2 SI HSC-3 SI HSC-4 SI mean (B) SI HGF (C) HPLF HPC mean (D) TS(D/B) TS(C/A) 1 19.3±4.7 1.7 37.1±1.3 0.9 8.6±5.2 3.8 4.6±0.6 7.2 17.4 3.4 27.4±24.7 8.1±2.3 63.3±19.8 33 1.9 1.4 2 18.7±4.7 2.5 41.2±1.8 1.1 32.8±1.6 1.4 34.8±7.8 1.3 31.9 1.5 48.7±15.3 38.0±2.0 52.0±10.3 46,2 1.5 2.6 3 14.0±2.0 2.4 25.6±1.1 1.3 23.0±0.7 1.5 17.1±2.2 2.0 19.9 1.8 36.0±1.6 36.0±7.5 30.3±6.0 34,1 1.7 2.6 4 24.7±4.7 2.8 35.2±1.9 1.9 29.4±3.8 2.3 27.8±2.9 2.4 29.3 2.3 97.3±25.1 41.7±3.2 65.3±18.5 68,1 2.3 3.9 5 21.3±0.6 1.9 35.2±2.0 1.2 26.1±7.8 1.6 19.2±3.3 2.2 25.5 1.7 45.0±2.6 38.3±2.3 41.3±4.6 41,6 1.6 2.1 6 58.0±20.8 6.9 >400 <1 >400 <1 >400 <1 314.5 <2.5 >400 >400 >400 400 1.3 ˃6.9 Average 26 3 >95,7 >1.2 >86,6 >1.9 >83,9 >2.7 73.1 2.2 >109,1 >93,7 >108,7 103,8 5-FU 12.1±0.7 72.3 15.2±2.7 57.6 7.2±1.0 121.6 7.3±0.17 119.9 10.5 92.8 >1000 >1000 626.3±87.9 875.4 83.8 83.3 Ca9- (22 Gingival carcinoma), HSC-2, HSC-4 (oral squamous cell carcinoma), HGF (gingival fibroblasts), HPLF (periodontal ligament fibroblasts), SI (selectivity index): the quotient of the average CC50figures towards HGF, HPC and HPLF non-malignant cells divided by the CC50 figure of the compound towards a specific tumour cell line.
Keywords: Pyrazole, sulphonamide, cytotoxicity, OSCC, selectivity index References: 1.Supuran CT. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Natural Review Drug Discovery. 2008;7: 168–81. 2.Neri D, Supuran CT. Interfering with pH regulation in tumours as a therapeutic strategy. Natural Review Drug Discovery. 2011;10: 767–77. 3.Özdemir A,Turan-Zitouni G, et al. Synthesis and antimicrobial activity of 1-(4-aryl-2-thiazolyl)-3-(2-thienyl)-5- aryl-2-pyrazoline derivatives. Europen Journal of Medicinal Chemistry. 2007; 42: 403. 4.Bagheri M, Shekarchi M, et al. Synthesis and Antihypertensive Activity of 1-(2-Thiazolyl)-3,5-disubstituted -2- Pyrazolines. Archive der Pharmazie Medicinal Chemistry. 2004; 337: 25-34. 5.Tugrak M, Synthesis of potential bioactive compounds derived from indanone and indandiones and their bioactivities. Doctora Thesis, 2016. Acknowledgements: The authors thank to Ataturk University BAP office for the financial support. October 05-07, 2017, ERZURUM-TÜRKİYE 143
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P96 - Design, Synthesis and Antibacterial Activitiy of Novel Modified Fluoroquinolone Derivatives
Necla Kulabaş a, Aslı Demirci a, Arif Bozdeveci b, Şengül Alpay Karaoğlu b, İlkay Küçükgüzel a
a Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, Haydarpaşa 34668 İstanbul, Turkey. b Department of Biology, Faculty of Arts and Sciences, Recep Tayyip Erdoğan University, Rize, Turkey
Fluoroquinolones (FQs) are commonly used antibacterial agents that have been shown to possess broad spectrum of antibacterial activity, great potency and good oral bioavailability, besides low side effects [1]. Despite the remarkable success of FQs in clinic, new fluoroquinolone containing medicinal agents are needed immediately owing to increasing resistance against commonly prescribed antibacterial drugs [2], since resistance is a growing problem for treatment [3].
Modifying already known FQ containing agents is a widely used approach for drug discovery. Based on the above mentioned thoughts, new FQ containing compounds were designed.
For this purpose, substituted anilines as starting compounds were converted to 2-chloro-N-arylacetamide derivatives by using α-chloroacetyl chloride. Equimolar amounts of 2-chloro-N-arylacetamide derivatives and selected FQ containing antibacterial agents were reacted to yield the target compounds. Following the isolation process, the crude products were crystallized from appropriate solvents. Purity of the synthesized compounds was checked by HPLC and their structures were confirmed by IR, 1H-NMR, 13C-NMR and mass spectral data besides elemental analysis. Afterwards, antibacterial activity of the synthesized compounds was evaluated in vitro.
Molecular docking studies concerning the synthesized compounds were run to simulate potential inhibition of DNA Gyrase. Studies on calculation of binding energy (Ebind=kcal/mol) between different crystal structures of DNA Gyrase as receptor (and synthesized compounds as ligands were performed. Docked poses of each ligand were visualized while binding energies and conformations were re-evaluated in the light of biological study results.
Further in silico and in vitro studies associated with synthesized compounds will be discussed in detail.
References: 1. Cheng G, Hao H, Dai M, Liu Z, Yuan Z. Eur J Med Chem 2013; 66: 555-562. 2. Hawkey PM. J Antimicrob Chemother 2003; 51(S1): 29–35. 3. Peet NP. J Drug Discov Today 2010; 15: 583-586.
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P97 - Normalization Effects on the Repeatability of Long Term GC-MS Metabolomic Analysis
Gürkan Özen a, Tuba Reçber a*, Cemil Can Eylem a, Sedef Kır a, Emirhan Nemutlu a
Hacettepe University, Faculty of Pharmacy, Department of Analytical Chemistry, Sıhhiye, Ankara, Türkiye *E-mail: [email protected]
Metabolomic refers to the systematic identification and quantification of the small molecule metabolic products of a biological system (cell, tissue, organ, biological fluid, or organism) at a certain time. Metabolite profiling studies have recently been used frequently in biomarker detection, enzyme substrate- related evaluation, drug activity studies, metabolic pathway analyzes, and many others [1]. Combined gas chromatography with mass spectrometry (GC-MS) is one of the most powerful techniques and commonly used in metabolomics profiling. Metabolomics analyzes consist of three main stages: sample preparation, analysis of metabolites and analysis of obtained data [2]. Data analysis is the major challenge in metabolomic studies [3]. In this study, the normalization effect on the precision for long term GC-MS metabolomic profiling was examined.For this purpose, the pooled plasma samples was frozen in aliquots of 100 µL and analyzed on seven different days at the same conditions. For sample preparation: 100 µL of plasma was extracted with 900 µL methanol: water (8:1, v/v) and 300 µL of the extract was evaporated to dryness in a vacuum dryer concentrator. Then, dried samples were methoxamineted and derivatized with MSTFA + 1% TMCS. The derivatized sample was injected split (1:10) by an autosampler into a GC-MS (Shimadzu QPlus) system with DB-5MS stationary phase column (30 m +10 m duraguard×0.25 mm i.d. and 0.25-µm film thickness). Once analysis completed, the complex chromatograms were deconvoluted using AMDIS and the retention time correction and data matrixes creation were done using SpectConnect software. The data matrix was transferred into the Excel file and the file was used for comparison of normalizationeffects on GC-MS data. To find the best fitted normalization technique for long term GC-MS analysis, different sample normalization techniques (normalization by sum, normalization by median, normalization by reference sample, normalization by internal standard, quantile normalization techniques and RobustLOESS Signal Correction) were compared (This study was supported by TUBITAK. (Project no: 116Z292)) Keywords: Metabolomic, GC-MS, normalization, profiling, precision. References: 1. Nemutlu E, Zhang S, Gupta A, Juranic N, Macura SI, Terzic A, Jahangir A, Dzeja P Dynamic phosphormetabolomic profiling of human tissues and transgenic models by 18O-assisted 31P NMR and mass spectrometry. Physiological Genomics (ISI). 2012;44(7),386-402. 2. Nemutlu E, Zhang S, Xu YZ, Terzic A, Zhong L, Dzeja PD, Cha YM, Cardiac resynchronization therapy induces adaptive metabolic transitions in the metabolomic profile of heart failure. Journal of cardiac failure. 2015;21(6),460– 469. 3. Dunn WB, Broadhurst D, Begley P, Zelena E, Francis-McIntyre S, Anderson N & Nicholls AW. Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry. Nature protocols. 2011;6(7),1060.
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P98 - Toxic Proteins of Plants
Ishak Erik a, Can O Yalcin b*
a Karadeniz Technical University, Faculty of Pharmacy, Department of Pharmacognosy, Trabzon, Turkey b Karadeniz Technical University, Faculty of Pharmacy, Department of Toxicology, Trabzon, Turkey *E-mail: [email protected]
Plants contain many biologically active chemicals. Some of these chemicals (such as colchicine, atropine, digoxin) can be used to treat diseases. However, exposure to some components with pharmacologically active may cause to poisoning and even death. Thus there are hundreds of plants poisoning in the world. There are some similarities in the general structure of the substances that cause the toxicity of these plants. These constituents include mainly alkaloids, glycosides, resins and proteins which are low molecular weight toxic compounds. A variety of toxic protein species are synthesized in plants such as lectins, ribosome inactivating proteins, protease inhibitors, α-amylase inhibitors, ureas, arselins, antimicrobial peptides and porcogenic toxins [1]. Although these proteins do not have a basic function in the cell, it was known that they have effects on highly structured animals, arthropods, molluskus, bacterias, viruses as well [2,3]. Therefore the research of toxic plant proteins has been focused on potential applications in pest control and medicine.
Keywords: Poisonous plants, plant poisoning
References: 1. Dang L, Van Damme JM. Toxic proteins in plants. Phytochemistry.2015;117:51-64. 2. Mithöfer A, Boland W. Plant defense against herbivores: chemical aspects. Annu Rev Plant Biol.2012;63:431- 450. 3. Cushnie TT, Cushnie B, Lamb AJ. Alkaloids: an overview of their antibacterial, antibiotic-enhancing and antivirulence activities. Int J Antimicrob Agents.2014;44:377-386.
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P99 - Synthesis of New Mannich Bases
Halise Inci Gul a*, Sertaç Mazlumoglu a, Mehtap Tugrak a
aAtaturk University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 25240 Erzurum, Turkey *E-mail: [email protected]
Mannich bases (MB) 1-8, [2-(4-hydroxy- 3 or 5-methoxy- 5 or 3-((4-substitutedpiperazin-1- yl)methyl)benzylidene)-2,3-dihydroinden-1-one, Scheme 1] were designed as candidate anticancer compounds. The chemical structures contain α,β-unsaturated ketone moiety and hydrogen donor and acceptor substituents on phenyl ring. The logic of the study was: α,β-unsaturated ketone is a very important pharmacophore being responsiple from the anticancer activity of many compounds and making a hydrogen bond/s of a drug with biological target/s is/are very important at their bioactivity. To synthesize the compounds, a solution of the 4-hydroxy-3-methoxybenzaldehyde in ethanol was added into a stirred solution of 1-indanone in aqueous solution of sodiumhydroxide. Stirring was maintained at room temperature overnight. Then, the reaction mixture was poured on water and neutralized with hydrochloric acid. The precipitated solid was filtered, washed with water, and recrystallized from water- ethanol1 to obtaine A (Scheme 1). To synthesize MB 1-8, the mixture of A, paraformaldehyde and a suitable secondary amine [N-methylpiperazine (1), N-phenylpiperazine (2), N-benzylpiperazine (3), 1-(2- methoxyphenyl)piperazine (4), 1-(3-methoxyphenyl)piperazine (5), 1-(2-fluorophenyl)piperazine (6), 1-(4- fluorophenyl)piperazine (7), 1-(3-(trifluoromethyl)phenyl)piperazine (8)] was heated in acetonitrile (120 °C, 200 Watt, 13.8 barr) for sometimes 1. Their chemical structures of 1-8 were confirmed by 1H NMR, 13C NMR and HRMS spectra.
Scheme 1. Synthesis of compounds 1-8.
H3CO OH H3CO OH
H CO 3 O O X + HO + H H + Secondary amine H O O O
A 1-8 X= Suitable amine moiety as stated above
Keywords: Mannich bases, indanone, synthesis, NMR, HRMS
References: 1.Tugrak M, Yamali C, et al. Synthesis of mono Mannich bases of 2-(4-hydroxybenzylidene)-2,3-dihydroinden-1- one and evaluation of their cytotoxicities. Journal of Enzyme Inhibition Medicinal Chemistry. 2015; 31(5): 818-823.
Acknowledgements: The authors thank to Ataturk University BAP office for the financial support.
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P100 - The Effect of Perifosine and Vitamin D Combination on Endometrial Cancer Cell Line (HEC1A)
Karagül Meryem İ lkay a, Aktaş Savaş a, Yetkin Derya a, Kibar Kezban a*, Çelikcan Didem b
a Mersin University, Faculty of Medicine, Department of Histology and Embryology TR33169, Yenisehir, Mersin, Turkey b Mersin University, Faculty of Medicine, Department of Biostatistics and Medical Informatics, TR33169, Yenisehir, Mersin, Turkey *E-mail: [email protected]
Endometrial cancer is the most common cancer of the female reproductive system. Perifosine has shown anti-tumor activity in a variety of cancers by inhibition of AKT phosphorylation [1]. The active metabolite of vitamin D (1,25(OH)2D3) has antiproliferative and proapoptotic properties and is recognized as agent with great potential for cancer intervention [2]. In this study, we aimed to investigate the anti-carcinogenic and anti-proliferative effect of varying concentrations of perifosine and vitamin D on endometrial cancer cell line (HEC1A). In our study, we used xCELLigence RTCA system which measures cell proliferation and drug-mediated cytotoxicity in a time-dependent manner. Cells were seeded in E-plate (2x104 cells/well) with 90 μl of normal culture medium. After 24 h, 10 μl of perifosine (50, 30, 10 μM) or vitamin D (200, 50 nM) and combinations of perifosine and vitamin D were added to each well. Afterwards cell proliferations were evaluated for 96 h in all groups. The difference between control and other groups was statistically significant in all time zones (p<0,05). A decrease in cell proliferation was observed in all other groups when compared to the control group at 30th h. However, compared with the control group, the only statistically significant decrease was observed in the groups of 50μMperifosine+50nMvitaminD and 30 μM perifosine (p<0,05). The decrease in cell proliferation in the 50μMperifosine+50nMvitaminD group was statistically significant compared to the 10μMperifosine+50nMvitaminD, 10μMperifosine+200nMvitaminD, 50 μM perifosine, 50 nM vitamin D and 200 nM vitamin D groups (p<0,05). A statistically significant decrease was found between the 50 μM perifosine and the 30 μM perifosine groups (p<0,05). IC50 value of perifosine was calculated as 30 μM. There was a statistically significant difference between the control and all other groups at measurements taken at 36th h (p<0,05). The decrease in cell proliferation between all perifosine and combination groups was statistically significant when compared with the vitamin D group (p<0,05). After the 48th h, the difference between the mean of all the combination groups was not statistically significant (p>0,05). The results show that perifosine and vitamin D combination produced dose-dependent growth inhibition in endometrial cancer cells, although growth inhibition was less pronounced with vitamin D treatment alone. These results provide attractive data for the possible use of perifosine and vitamin D in the treatment of endometrial tumors. Keywords: Endometrial cancer, perifosine, vitamin D, xCELLigence. References: 1. Engel JB, Honig A, Schönhals T, et al. Perifosine inhibits growth of human experimental endometrial cancers by blockade of AKT phosphorylation. Eur J Obstet Gynecol Reprod Biol. 2008;141(1):64-9. 2. Kasiappan R, Sun Y, Lungchukiet P, et al. Vitamin D suppresses leptin stimulation of cancer growth through microRNA. Cancer Res. 2014;74(21):6194-204.
Acknowledgements: This study was supported by the Research Fund of Mersin University in Turkey with Project Number 2016-2- TP3-1888.
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P101 - Qualitative and Quantitative Determination of Arbutin and Hydroquinone in Different Herbal Slimming Products Containing Calluna vulgaris by HPLC
Hafize Yuca a*, Benan Dursunoğlu a, Sefa Gözcü b, Bilal Yılmaz c, Zühal Güvenalp a aDepartment of Pharmacognosy, Faculty of Pharmacy, Atatürk University, 25240, Erzurum, Turkey bDepartment of Pharmacognosy, Faculty of Pharmacy, Erzincan University, 24100, Erzincan, Turkey cDepartment of Analytical Chemistry, Faculty of Pharmacy, Atatürk University, 25240, Erzurum, Turkey E-mail: [email protected]
Calluna vulgaris (L.) Hull (heather) is a perennial shrub that is a member of Ericaceae family. It is distributed throughout most of Europe, Russia, Asia Minor and Atlantic coast of North America [1,2]. The medicinal parts of C. vulgaris are the complete herb with leaves and flowers. Arbutin and hydroquinone are two of the major components of heather. C. vulgaris is presented in herbal slimming products due to its diuretic and digestive effects2. In the present study, a new, simple and sensitive high performance liquid chromatography (HPLC) method has been developed for qualitative and quantitative determination of arbutin and hydroquinone in nine herbal slimming products containing Calluna vulgaris in Turkey. The developed method can be used for routine quality control analysis of arbutin and hydroquinone in different herbal slimming products.
Keywords: Arbutin, hydroquinone, HPLC, herbal slimming product, Calluna vulgaris References:
1. Monschein M, Neira JI, Kunert O, Bucar F. Phytochemistry of Heather (Calluna vulgaris (L.) Hull) and Its Altitudinal Alteration. Phytochemistry Reviews. 2010;9:205-215. 2. Gruenwald J, Brendler T, Jaenicke C. (eds). PDR for Herbal Medicines. Medical Economics Co., Inc., Montvale, NJ. 2007;383-384.
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P102 - Investigation of the Effects of Alchemilla barbatiflora Methanol Extract on Isolated Rat Detrusor Muscle
Elif Nur Barut a*, Seçkin Engin a, Hatice Demirtaş a, Gülin Rendab, F. Sena Sezen a
aDepartment of Pharmacology, bDepartment of Pharmacognosy, Faculty of Pharmacy, Karadeniz Technical University, Trabzon/TURKEY *E-mail: [email protected]
Alchemilla L. species are traditional medicinal plants represented by nearly 100 species and used for a wide range of disorders due to its astringent, anti-hemorroidal, anti-diarrheal, sedative and antiseptic activity [1]. In addition, Alchemilla L. species are used as a diuretic in Turkish folk medicine, but its mechanism of action is still unknown [2]. In this study, we conducted isolated organ bath study to investigate the effect of three different concentrations (0,03125 mg/mL, 0,0625 mg/mL, 0,125 mg/mL) of Alchemilla barbatiflora methanol extract (ME) on male Sprague-Dawley rats detrusor smooth muscle (DSM) contractility (n=14). ME induced contractions in DSM at all concentrations. Pre-incubation with atropine (10-6 M, a cholinergic antagonist) reduced significantly ME-induced contraction at 0.03125 mg/mL, indicating an action via muscarinic receptors (p<0.05). Morever, ME-induced contraction at 0.03125 mg/mL was also reduced by prior incubation with verapamil (10-6 M, a calcium channel blocker), indicating the role of L-type calcium channels (p<0.05). Higher concentration of ME (0,0625 mg/mL and 0,125 mg/mL)-induced contractions did not change by pre-incubation with atropine and verapamil. Our results suggest that contractile effects of the extract may be acting via stimulating muscarinic receptors and L-type calcium channels. More studies are required to clarify the mechanism(s) of its action on detrusor contractility.
Keywords: Alchemilla barbatiflora, detrusor smooth muscle, detrusor contractility, isolated organ bath, rat References: 1. Neagu E, Paun G, Albu C, Radu G.L. Assessment of acetylcholinesterase and tyrosinase inhibitory and antioxidant activity of Alchemilla vulgaris and Filipendula ulmaria extracts. Journal of the Taiwan Institute of Chemical Engineers. 2015; 52:1–6. 2. Küpeli Akkol E, Demirel M.A, Bahadır Acıkara Ö, Süntar İ, Ergene B, İlhan M, Özbilgin S, Saltan G, Keleş H, Tekin M. Phytochemical analyses and effects of Alchemilla mollis (Buser) Rothm. and Alchemilla persica Rothm. in rat endometriosis model. Arch Gynecol Obstet. 2015; 292(3):619-628.
Acknowledgements: This work was supported by a grant from TUBITAK (to HD, 2209/A, No.1919B011503185)
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P103 - In Vitro Effects of Melatonin on Rat Carbonic Anhydrase
Esra Şentürk a,b, Hilal Urçar b,c, Murat Şentürkd aAgri Ibrahim Cecen University, School of Health Services, Agri, Turkey bAtaturk University, Faculty of Medicine, Department of phsyology, Erzurum, Turkey cArtvin Coruh University, Department of Nursing, Artvin, Turkey dAgri Ibrahim Cecen University, Faculty of Pharmacy, Agri, Turkey *E-mail: [email protected] Melatonin (N-acetyl-5-methoxytryptamine) is the main product of the pineal gland, and remains an intriguing indoleamin. This compound is widely distributed among living organisms and has been detected in all living species [1,2]. Carbonic anhydrases (CAs; EC 4.2.1.1) are ubiquitously distributed zinc containing metalloenzymes with their involvement in diverse pathological conditions, CAs have been the targets of drug developments for the treatments of glaucoma, epilepsy, high altitude sickness, as well as some cancer species [3]. Several CA inhibitors have been utilized as antiglaucoma, anticonvulsant, antiepileptic and anticancer agents, and a few such inhibitors have been approved as drugs [3,4]. We report here the inhibitory capacity of melatonin against rat carbonic ahydrase (rCA) was isolated by means of sepharose 4B-tyrosine sulfanilamide affinity column. The rCA enzyme showed quite diverse inhibition profiles with this compound. Inhibitory capacities of this compound on rCA activity was determined using p-nitrophenilacetate under in vitro conditions. This indolic compound inhibit this isozyme quite effectively. Keyword: Melatonine, carbonic anhydrase, inhibitors. References: 1. Reiter RJ, Tan DX, Rosales-Corral S, Manchester LC. The universal nature, unequal distribution and antioxidant functions of melatonin and its derivatives. Mini Review of Medicinal Chemistry. 2013:13;373-384. 2. Calvo JR, Gonzales-Yanes C, Maldonado MD. The role of melatonin in the cells of the innate immunity: A review. Journal of Pineal Research. 2013:55;103-120. 3. Supuran CT. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat Rev Drug Discovery. 2008:7;168-181. 4. Turkoglu EA, Senturk M, Supuran CT, Ekinci D. Carbonic anhydrase inhibitory properties of some uracil derivatives. Journal of Enzyme Inhibition and Medicinal Chemistry. 2017:32;74-77.
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P104 - Synthesis and Structural Characterization of Naproxen Hydrazide- Hydrazones
M. İhsan Han a, Ş. Güniz Küçükgüzela* aMarmara University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, İstanbul, Turkey *E-mail: [email protected] Non-steroidal antiinflammatory (NSAI) drugs show anticancer activity due to the inhibition of cyclooxygenase-2 enzyme according to recent researchers [1]. It has been observed that inhibition of COX- 2 enzyme results in antiproliferative effec in cancer cells [2]. Naproxen, (R,S)-2-(6-methoxy-2- napthyl)propanoic acid is a non-steroidal anti-inflammatory drug which has analgesic and antipyretic effects. Anticancer effect of naproxen [3], hydrazide-hydrazones [4-7] and 1,2,4-triazole-3-thiones [8,9] has been reported in the literature. In the light of these observations, naproxen was chosen as a starting substance to synthesize hydrazide-hydrazone and 1,2,4-triazole-3-thione compounds. The purity of synthesized compounds was controlled by elemental analysis and thin layer chromatography. Their structures were elucidated with FT-IR and 1H-NMR spectroscopy. Keywords: NSAI drugs, anticancer activity, naproxen, 1,2,4-triazole, hydrazide-hydrazone, References: 1. Dempke W, Rie C, Grothey A, Schmoll HJ. Cyclogenase-2: A novel target for cancer chemotherapy. J. Cancer Res. Clin. Oncol. 2001; 127: 411-417. 2. Kaur J, Vaish V, Sanyal SN. COX-2 as a Molecular Target of Colon Cancer Chemoprevention: Promise and Reality. Biomedicine & Aging Pathology. 2012; 2: 67–72. 3. Kim MS, Kim JE, Lim DY, Huang Z, Chen H, Langfald A, Lubet RA, Grubbs CJ, Dong Z, Bode AM. Naproxen Induces Cell-Cycle Arrest and Apoptosis in Human Urinary Bladder Cancer Cell Lines and Chemically Induced Cancers by Targeting PI3K. Cancer. Prev. Res. 2014; 7(2): 236-245. 4. Rollas S, Küçükgüzel ŞG. Biological Activities of Hydrazone Derivatives. Molecules. 2007; 12: 1910-1939. 5. Aydın S, Basu NK, Arora P, Basu A, Nichols DB, Talele TT, Akkurt M, Çelik İ, Büyükgüngör O, Küçükgüzel ŞG. Microwave assisted synthesis of some novel Flurbiprofen hydrazide-hydrazones as anti-HCV NS5B and anticancer agents. Marmara Pharmaceutical Journal. 2013; 17: 181-189. 6. Çıkla P, Özsavcı D, Özakpınar ÖB, Şener A, Çevik Ö, Turan SÖ, Akbuğa J, Şahin F, Küçükgüzel ŞG. Synthesis, Cytotoxicity, and Pro-Apoptosis Activity of Etodolac Hydrazide Derivatives as Anticancer Agents. 2013; 346: 367– 379. 7. Küçükgüzel ŞG, Koç D, Süzgün PÇ, Özsavcı D, Özakpınar ÖB, Tiber PM, Orun O, Erzincan P, Erdem SS, Şahin F. Synthesis of Tolmetin Hydrazide–Hydrazones and Discovery ofa Potent Apoptosis Inducer in Colon Cancer Cells. 2015; 348: 730-742. 8. Süzgün PÇ, Basu NK, Basu A, Arora P, Talele TT, Durmaz İ, Atalay RÇ, Küçükgüzel ŞG. Anti-cancer and anti- hepatitis C virus NS5B polymerase activity of etodolac 1,2,4-triazoles. J. Enzyme Inhib. Med. Chem. 2015; 30(5): 778–785. 9. Küçükgüzel ŞG, Süzgün PÇ. Recent advances bioactive 1,2,4-triazole-3-thiones. Eur. J. Med. Chem. 2015; 97: 830-870. Acknowledgement: This research was supported by the The Scientific and Technical Research Council of Turkey (TÜBİTAK), Research Fund Project Number: 215S009.
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P105 - Synthesis and DNA Interaction Properties of Novel Water Soluble Zn(II) and Cu(II) Phthalocyanines
Arzu ÖZEL a, Burak BARUT a*, Ümit Demirbaş b, Halit Kantekin b
aKaradeniz Technical University, Faculty of Pharmacy, Department of Biochemistry bKaradeniz Technical University, Faculty of Science, Department of Chemistry *E-mail: [email protected]
Cancer, is the leading cause of mortality in worldwide, caused by uncontrolled division of abnormal cells [1]. To treat this disease, uncontrolled growth of cancer cells must be controlled. Therefore, DNA is a drug target due to its importance in biological system such as replication, transcription, translation etc. Photodynamic therapy (PDT) is a newly non-invasive method for treatment of malignant tumors or macular degeneration with light and photosensitizer. During the photodynamic reaction, photosensitizer generates highly reactive oxygen species (ROS) such as singlet oxygen and destroys tumor cells [2]. Phthalocyanines are used as photosensitizer agents for PDT due to strong absorbtion in the region of biological optical window (600-800 nm), efficiency in generating singlet oxygen and low dark toxicity [3]. In this study, 3- methyl-4-(3-morpholinopropyl)-1H-1,2,4-triazole-5(4H)-one substituted Zn(II) and Cu(II) phthalocyanines and their water soluble derivatives were synthesized. These novel compounds were characterized by a combination of different spectroscopic techniques such as FT-IR, 1H-NMR, UV–vis and mass spectroscopy. DNA binding mode and cleavage mechanism of water soluble compounds were determined using CT-DNA and supercoiled plasmid DNA. The DNA binding mode of water soluble compounds were investigated using electronic absorption titration, competitive ethidium bromide, thermal denaturation and electrophoresis experiments. The DNA-photocleavage activities of compounds were investigated using supercoiled pBR322 plasmid DNA on agarose gel electrophoresis. The DNA binding studies claimed that compounds bind strongly to CT-DNA. In addition, the water soluble compounds cleaved supercoiled pBR322 plasmid DNA via photocleavage mechanism induced by singlet oxygen under irradition. These results suggested that these compounds offer potential as candidate photosensitizers for cancer treatment.
Keywords: Cancer, DNA-binding, photocleavage, phthalocyanine, synthesis. References: 1. Tabassum S, Zaki, M. Afzal M, Arjmand F. Synthesis and characterization of Cu(II)-based anticancer chemotherapeutic agent targeting topoisomerase Iα: In vitro DNA binding, Pbr322 cleavage, molecular docking studies and cytotoxicity against human cancer cell lines. European Journal of Medicinal Chemistry. 2014; 74: 509- 523. 2. Çakır V, Göksel M, Durmuş M, Biyiklioglu Z. Synthesis and photophysicochemical properties of novel water soluble phthalocyanines. Dyes and Pigments. 2016; 125: 414-425. 3. Keleş T, Barut B, Biyiklioglu Z, Özel A. A comparative study on DNA/BSA binding, DNA photocleavage and antioxidant activities of water soluble peripherally and non-peripherally tetra-3-pyridin-3-ylpropoxy-substituted Mn(III), Cu(II) phthalocyanines. Dyes and Pigments. 2017; 139: 575-586.
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P106 - Determination of Antioxidant Capacity of Olive Leaf (Olea europaea L.) Ethanol Extract via DPPH and ABTS/TEAC Methods
Ahmet Gokhan Aggula,B, Mine Gulaboglub, Zerrin Kutlub
aAgrı Ibrahim Cecen University, Faculty of Pharmacy, Department of Biochemistry, 04100, Agri
bAtaturk University, Faculty of Pharmacy, Department of Biochemistry, 25240, Erzurum
E-mail:[email protected] This study was designed to determination of antioxidant capacity of olive leaf (Olea europaea L.) ethanol extract via DPPH and ABTS/TEAC methods. This study dwells on two different methods, 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azino- bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assays. These methods are widely used to assess the effect of free radical scavenging activity of natural products. DPPH method is based on the decrease of the absorbance of the DPPH• solution (when methanol is used as the solvent), at 515 nm, due to its inactivation from antioxidants [1]. ABTS method relies on the ability of antioxidants in the sample to decrease the absorbance of the ABTS+• solution (when ethanol is used as the solvent) at 734 nm [2]. Olive leaf extract is a potential source of bioactive compounds such as oleuropein which have antioxidant activity. In this study, the free radical scavenging capacity of the extract, calculated as the inhibition percentage of ABTS.+ and DPPH•, was equated against a Trolox standart curve prepared with different concentrations. Different concentrations of the sample were prepared in 1, 5, 10, 15, 20, 30 and 40 ug/mL. The concentration of olive leaf ethanol extract in 30 ug/mL was found to be more effective than that of the others. The extract had the ABTS capacity (63.43 %) and the DPPH capacity (68.59 %). The results indicate that olive leaf ethanol extract exhibits antioxidant capacity in terms of DPPH and ABTS/TEAC. Keywords: Antioxidant capacity, ABTS/TEAC, DPPH, Olive leaf
References
1. Huang DJ, Ou BX, RL. P. The chemistry behind antioxidant capacity assays. Journal of Agricultural and Food Chemistry,. 2005;53:1841-56. 2. Sanchez-Moreno C, Larrauri JA, Saura-Calixto F. A procedure to measure the antiradical efficiency of polyphenols. Journal of the Science of Food and Agriculture. 1998;76:270-6.
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P107 - Determination of Antioxidant Capacity of Olive Leaf (Olea europaea L.) Ethanol Extract Via CUPRAC and FRAP Methods
Ahmet Gokhan Aggula,b, Mine Gulaboglub, Zerrin Kutlub
aAgri Ibrahim Cecen University, Faculty of Pharmacy, Department of Biochemistry, 04100, Agri bAtaturk University, Faculty of Pharmacy, Department of Biochemistry, 25240, Erzurum E-mail: [email protected]
This study was designed to determination of antioxidant capacity of olive leaf ethanol extract via FRAP and CUPRAC methods. In this study, the two different antioxidant assays were used to evaluate antioxidant capacity of the extract. These methods measure the reducing power of the extract (ferric reducing antioxidant power (FRAP) and cupric reducing antioxidant power (CUPRAC)). In procedure, olive leaf ethanol extract were prepared in 40 ug/mL and then the samples were analyzed with FRAP and CUPRAC methods [1,2]. In order to compare and calculate the equivalant antioxidant capacity of each sample, different concentration of reference samples were prepared in between 1-40 ug/mL. All measurements were performed in Biotek Elisa Reader and the results were evaluated with Microsoft Excel 2010 software. The concentration of olive leaf ethanol extract in 30 ug/mL was found to be more effective than that of the others. The results indicate that olive leaf ethanol extract exhibits antioxidant capacity in terms of FRAP and CUPRAC methods.
Keywords: Antioxidants capacity, CUPRAC, FRAP, Olive leaf
References: 1. Apak R, Guclu K, Ozyurek M, Karademir SE. Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, using their cupric ion reducing capability in the presence of neocuproine: CUPRAC method. Journal of Agricultural and Food Chemistry,. 2004;52:7970-81. 2. Sanchez-Moreno C, Larrauri JA, Saura-Calixto F. A procedure to measure the antiradical efficiency of polyphenols. Journal of the Science of Food and Agriculture. 1998;76:270-6
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P108 - Phytochemical Screening of Alcea pallida via GC-MS Method
Onur Senola, Esen Sezen Karaoglanb
aDepartment of Analytical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey bDepartment of Botany, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey
Alcea (Malvaceae) species commonly known as mallow flower and mostly used in treatment of cough. Alcea pallida plant is traditionally used in cough, bronchitis, infertility and treatment of any wound in accordance with the ethnobotanical studies 1,2. In this study, it is aimed to perform a phytochemical screening research on volatile extracts (dichloromethane and n-hexane) of Alcea pallida via Gas Chromatography Mass Spectroscopy (GC-MS) method.
In order to perform phytochemical screening studies, two volatile extracts were selected and diluted to 10 µg/mL by their own solvents. After that diluted samples were measured by Shimadzu QP2010 ULTRA instrument. For GC/MS detection, an electron ionization system with ionizing energy of 20 eV was used. Helium gas (99.999%) was used as the carrier gas at constant flow rate 1 ml/min and an injection volume of 2 µl was employed. Split mode is preferred and split ratio arranged to be 1:10. Injector temperature were 250°C while ion-source temperature was 280°C. The oven temperature was programmed from 110°C (isothermal for 2 min) with an increase of 10°C/min to 200°C, then 5°C/min to 280°C, ending with a 9 min isothermal at 280°C. Mass spectra were taken at 20eV; a scan interval of 0.5 seconds and fragments from 50 to 500 Da. Total analysis time were determined to be 36 minutes. Interpretation of mass spectrum of GC-MS was conducted using the database of National Institute Standard and Technology (NIST) having more than 62,000 patterns. The spectrum of the known component was compared with the spectrum of the known components stored in the NIST library.
Keywords: NIST Library, GC-MS, phytochemical screening, Alcea pallida
References
1. Polat R., Cakilcioglu U., Satıl F. 2013. Traditional uses of medicinal plants in Solhan (Bingöl— Turkey). Journal of Ethnopharmacology, 148 (3): 951–963. 2. Başer K.H.C., Tümen G., Malyer H., Kırımer N. 2006. Plants used for common cold in Turkey. Proceedings of the IVth International Congress of Ethnobotany (ICEB 2005), 133-137
Acknowledgement : The study was supported by DAYTAM (East Anatolia High Tech Research Center
October 05-07, 2017, ERZURUM-TÜRKİYE 156
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P109 - Effect of Acute and Chronic Administration of Amitriptyline on Experimental Gastric Ulcer
Shemsu Umer HUSSEN1*, Günnur Özbakış-Dengiz2, Yılmaz Baş3 and Musa Kıran4
1 Department of Pharmacology, Faculty of Pharmacy, Bülent Ecevit University, Zonguldak, Turkey. 2 Department of Medical Pharmacology, School of Medicine, Bülent Ecevit University, Zonguldak, Turkey. 3 Department of Medical Pathology, School of Medicine, Hitit University, Çorum, Turkey. 3 Department of Pharmacy, Zonguldak Atatürk State Hospital, Zonguldak, Turkey * Corresponding author e-mail: [email protected]; [email protected]
Amitriptyline is an antidepressant drug and widely used as an analgesic in the treatment of chronic pain syndromes such as neuropathic pain, lower back pain, fibromyalgia and inflammatory bowel syndrome. Nowadays, amitriptyline is attracting the attention of researchers as an alternative drug for peptic ulcer treatment because it has been shown that most patients with peptic ulcer also suffer from depression. Thus, the present study was conducted to investigate gastroprotective effects of acute (single dose) and chronic (multiple doses) administration of amitriptyline against indomethacin induced gastric injury in rats. The animals were divided into three groups. For 14 days, distilled water was orally administered to group I (control) and group II (acute amitriptyline group) and amitriptyline (10 mg/kg) was administered orally to group III (chronic amitriptyline group). On day 15, amitriptyline (10 mg/kg) was given orally to amitriptyline groups and distilled water to control. Thirty minutes later, indomethacin (25 mg/kg) was administrated to all the groups. Six hours later, animals were sacrificed and stomachs were rapidly removed. The stomachs were macroscopically evaluated and mean ulcer indexes were calculated.Finally,the stomachs were histopathologically evaluated. Ulcer indexes were calculated to be 6.75±0.81, 0.52±0.29 and 0±0.00 for group I, group II and group III, respectively. Acute administration of amitriptyline significantly reduced ulcer indexes and gastric erosions (p<0.05), but its role against necrosis, neutrophil and eosinophil reactions was statistically insignificant. On the contrary, chronic administration of amitriptilyine exerted significant gastroprotective effects macroscopically and histopathologically compared to control (p<0.05). There was also a significant difference between acute and chronic effects of amitriptyline against indomethacin induced gastric damage (p<0.05). Prolonged administration of amitriptyline showed better gastroprotective effects both macroscopically and histopathologically, compared to single dose amitriptyline administration and control group. Hence, based on the results of this study, amitriptyline might be considered as a potential alternative drug for patients with gastric ulcers in the future.
References
1. Egbunike IG, Chaffee BJ. Antidepressants in the management of chronic pain syndromes. Pharmacotherapy. 1990;10(4): 262-270. 2. Sen T, Abdulsalam CA, Pal S, Sen S, Karmakar S, Saravanan KS, Chaudhuri AK. Effect of amitriptyline on gastric ulceration. Fundamentals of Clinical Pharmacolology. (2002) 16: 311–5. Key words: Amitriptyline, gastric ulcer, indomethacin, rats.
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P110 - Determination of Antioxidant Capacity of Water Extract of Myrtus Communis L. Leaf via DPPH and ABTS/TEAC Methods
Zerrin Kutlua, Mine Gulaboğlua
aAtatürk University, Faculty of Pharmacy, Department of Biochemistry, 25240, Erzurum E-mail:[email protected]
Myrtus communis is a typical plant of the Mediterranean area, which is mainly used as animal and human food and, in folk medicine, for treating some disorders. It contains flavonoids (such as cutaneous, catechin, and myrsetine derivatives) that blend the leaves with volatile oil. Myrtus communis L. leaf is rich in phenolic compounds as well as vitamins, minerals, dietary fiber, essential oils and carotenoids [1]. In this study, water extract of Myrtus communis L. leaf were analyzed with different antioxidant activity methods as DPPH and ABTS/TEAC which are the most common and cited antioxidant capacity measurement method. In procedure, Myrtus communis L. leaf water extract were prepared in 40 ug/mL and then the samples were analyzed with DPPH and ABTS/TEAC methods. In order to compare and calculate the equivalant antioxidant capacity of each sample, different concentration of reference samples were prepared in between 1-40 ug/mL. All measurements were performed in Biotek Elisa Reader and results were evaluated with Microsoft Excel 2010 software [2,3]. According to the results, Myrtus communis L. leaf water extracts exhibit antioxidant capacity in terms of DPPH and ABTS/TEAC. Keywords: Antioxidants capacity, ABTS/TEAC, DPPH, Myrtus Communis L References: 1. Romani A, Pinelli P, Mulinacci N, Vincieri FF, Tattini M. Identification and quantitation of polyphenols in leaves of Myrtus communis L. Chromatographia. 1999;49:17-20. 2. Huang DJ, Ou BX, RL. P. The chemistry behind antioxidant capacity assays. Journal of Agricultural and Food Chemistry,. 2005;53:1841-56. 3. Sanchez-Moreno C, Larrauri JA, Saura-Calixto F. A procedure to measure the antiradical efficiency of polyphenols. Journal of the Science of Food and Agriculture. 1998;76:270-6.
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P111 - Determination of Antioxidant Capacity of Methanol Extract of Myrtus Communis L. Leaf Via DPPH and ABTS/TEAC Methods
Zerrin Kutlua, Mine Gülaboğlua
aAtatürk University, Faculty of Pharmacy, Department of Biochemistry, 25240, Erzurum E-mail: [email protected]
The different parts of the plant such as fruids, branches, leaves of Myrtus communis L. have been widely used in folk medicine, food additives and perfume industry for a long time. It contains flavonoids (such as cutaneous, catechin, and myrsetine derivatives) that blend the leaves with volatile oil. Myrtus communis L. leaf is rich in phenolic compounds as well as vitamins, minerals, dietary fiber, essential oils and carotenoids [1]. In this study, methanol extract of Myrtus communis L. leaf were analyzed with different antioxidant activity methods as DPPH and ABTS/TEAC which are the most common and cited antioxidant capacity measurement method. In procedure, Myrtus communis L. leaf methanol extract were prepared in 40 ug/mL and then the samples were analyzed with DPPH and ABTS/TEAC methods. In order to compare and calculate the equivalant antioxidant capacity of each sample, different concentration of reference samples were prepared in between 1-40 ug/mL. All measurements were performed in Biotek Elisa Reader and results were evaluated with Microsoft Excel 2010 software [2, 3]. According to the results, Myrtus communis L. leaf methanol extracts exhibit antioxidant capacity in terms of DPPH and ABTS/TEAC. Keywords: Antioxidants capacity, ABTS/TEAC, DPPH, Myrtus Communis L. References: 1. T. B. Türkiye’de Bitkiler ile Tedavi. Nobel Tıp Kitabevi, İstanbul,2000. 2. Huang DJ, Ou BX, RL. P. The chemistry behind antioxidant capacity assays. Journal of Agricultural and Food Chemistry,. 2005;53:1841-56. 3. Sanchez-Moreno C, Larrauri JA, Saura-Calixto F. A procedure to measure the antiradical efficiency of polyphenols. Journal of the Science of Food and Agriculture. 1998;76:270-6.
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P112 - Determination of Antioxidant Capacity of Methanol Extract of Myrtus Communis L. Leaf Via CUPRAC and FRAP Methods
Zerrin Kutlua, Mine Gülaboğlua
aAtatürk University, Faculty of Pharmacy, Department of Biochemistry, 25240, Erzurum E-mail:[email protected]
It is a perennial, leafless, endemic therapeutic plant that is found in tropical and subtropical regions of South America and Australia, and in the Mediterranean region of our country. The different parts of the plant such as fruids, branches, leaves of Myrtus Communis L. have been widely used in folk medicine, food additives and perfume industry for a long time It contains flavonoids (such as cutin, catechin, myrsetin derivatives) that blend the leaves with volatile oil. The leaf often contain organic acids such as essential oils, tannins, sugars, flavonoids and citric and malic acid [1]. In this study, methanol extract of Myrtus Communis L leaf were analyzed with different antioxidant activity methods as CUPRAC and FRAP which are the most common and cited antioxidant capacity measurement method. In procedure, Myrtus Communis L. leaf methanol extract were prepared in 40 ug/mL and then the samples were analyzed with FRAP and CUPRAC, methods. In order to compare and calculate the equivalant antioxidant capacity of each sample, different concentration of reference samples were prepared in between 1-40 ug/mL. All measurements were performed in Biotek Elisa Reader and results were evaluated with Microsoft Excel 2010 According to the results, Myrtus Communis L. Leaf methanol extracts exhibit antioxidant capacity in terms of FRAP and CUPRAC. Keywords: Antioxidants capacity, CUPRAC, FRAP, Myrtus Communis L. References: 1. Bezanger-Bequese L, Pinkas M, Maloine. TA. Les plantes dans la th´erapeutique moderne,. 1975. 2. Apak R, Guclu K, Ozyurek M, Karademir SE. Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, using their cupric ion reducing capability in the presence of neocuproine: CUPRAC method. Journal of Agricultural and Food Chemistry,. 2004;52:7970-81. 3. Sanchez-Moreno C, Larrauri JA, Saura-Calixto F. A procedure to measure the antiradical efficiency of polyphenols. Journal of the Science of Food and Agriculture. 1998;76:270-6.
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P113 - Determination AChE Inhibition of Some Bischalcone Derivatives
Tayfun Arslana, İmdat Aygülb, Murat Şentürkc
aGiresun University, Science and Art Faculty, Giresun, Turkey bGümüşhane University, Health Science Faculty Gumushane, Turkey cAğrı İbrahim Çeçen University, Faculty of Pharmacy, Ağrı, Turkey
*E-mail: [email protected]
Chalcone and their analogs have many properties with their pharmaceutical and biological properties. Chalcone derivatives have been used to prevent certain types of cancer [1], diabetes [2] and cardiovascular diseases [3]. The pathogenesis of Alzheimer's disease (ADI) has not yet been clarified, but the most important of the accepted theory is the "cholinergic hypothesis". A deficiency in levels of the neuromediators called butyrylcholine (BCh) and acetylcholine (ACh) has been observed in the brains of AD patients. The inhibition of the key enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which hydrolyze ACh and BCh, has become an important option for the treatment of AD [4]. Therefore, we initiated a study to screen their acetylcholinesterase (AChE, EC 3.1.1.7) inhibitory activities, which are the key enzymes taking place in pathogenesis of AD. Some bischalcone derivatives (1-3) showed IC50 values in the range of 0.019-2.615 mM for AChE.
Keywords: Bischalcone, acetylcholinesterase, inhibitors.
References: 1. A. Modzelewska, C. Pettit, G. Achanta, N. E. Davidson, P. Huang, S. R. Khana, Bioorg. Med. Chem. 2006;14:3491-3495. 2. C. T. Hsieh, T. J. Hsieh, M. El-Shazly, D. W. Chuang, Y. H. Tsai, C. T. Yen, S. F. Wu, Y. C. Wu, F. R. Chang, Bioorg. Med. Chem. Lett. 2012;12:3912-3915. 3. C. Furman, J. Lebeau, J. C. Fruchart, J. L. Bernier, P. Duriez, N. Cotelle, E. Teissier, J. Biochem. Mol. Toxic. 2001;15:270-278. 4. Schneider LS. Clinics in Geriatric Medicine. 2001;17:337-358.
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P114 – Protective effect of an L-type calcium channel blocker, amlodipine, on paracetamol- induced hepatotoxicity in rats
Hilal Kayaa; Beyzagul Polatb, Abdulmecit Albayraka*, Tolga Mercantepec, Basak Buyukd
a Ataturk University, Faculty of Medicine, Department of Pharmacology, 25240 Erzurum
b Ataturk University, Faculty of Pharmacy, Department of Pharmacology, 25240 Erzurum
c Recep Tayyip Erdogan University, Faculty of Medicine, Department of Histology and Embryology, 53100 Rize
d Canakkale 18 Mart University, Faculty of Medicine, Department of Histology and Embryology, Canakkale
Paracetamol, one of the most popular and commonly used analgesic and antipyretic agents, can cause hepatotoxicity in overdoses. Amlodipine, an L-type calcium channel blocker, has been shown to have anti-inflammatory activity by reversing the effect of calcium in the inflammation pathogenesis.
In the present study, we evaluated the hepatoprotective activity of amlodipine on paracetamol-induced hepatotoxicity, as well as dose-related effects of amlodipine. Thirty male Albino Wistar rats were divided into five groups as follows, with each group composed of six rats: (1) intact (healthy), (2) 2 g/kg of paracetamol, (3) 2 g/kg of paracetamol+5 mg/kg of amlodipine, (4) 2 g/kg of paracetamol+10 mg/kg of amlodipine, and (5) 10 mg/kg of amlodipine.
Liver and blood samples were analyzed histopathologically and biochemically. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the expression of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) in the liver tissues were significantly increased in the group treated with paracetamol. The superoxide dismutase (SOD) activity and glutathione (GSH) level decreased and malondialdehyde (MDA) levels increased in the livers of the rats treated with paracetamol. All these parameters were improved with both doses of the amlodipine. A histopathological examination of the liver showed that amlodipine administration ameliorated the paracetamol-induced liver damage. In immunohistochemical staining, the expression of TNF-α in the cytoplasm of the hepatocytes was increased in the paracetamol group but not in other treatment groups when compared to the healthy control.
In conclusion, amlodipine treatment appeared to provide significant hepatoprotection against paracetamol-induced hepatotoxicity by increasing the activity of antioxidants and reducing that of the inflammatory cytokines TNF-α and TGF-β.
Keywords: Amlodipine, Hepatotoxicity, Paracetamol, Rat, TNF-α, TGF-β.
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P115 - Examination of Paraoxonase Activity in Smokers and Nonsmokers Male Students Serum Samples in Ağrı İbrahim Çeçen University Department of Nursing
Esra Şentürka, Hilal Urçarb, İmdat Aygülc, Murat Şentürkd
aAgri Ibrahim Cecen University, School of Health Services, Agri, Turkey bArtvin Coruh University, Department of Nursing, Artvin, Turkey cGümüşhane University, Health Science Faculty, Gumushane, Turkey dAgri Ibrahim Cecen University, Faculty of Pharmacy, Agri, Turkey *E-mail: [email protected]
Paraoxonase (PON1; EC 3.1.8.1; formerly EC 3.1.1.2) is a calcium-dependent serum enzyme belonging to the class of A-esterases and it is closely associated with the high-density lipoprotein complex [1]. It is known that cigarette damage both the smoker and the passive smokers. In this study, it was aimed to determine the effects of cigarette smoking on the frequency of smoking and serum PON enzyme levels in nursing students. In our research, we create a group from Agri Ibrahim Cecen University’s 57 male nursing students who accepted to participate in this study in between 2016 and 2017 academic year. We took the blood samples for investigate purposes the level of PON enzyme with questionnaires of demographic characteristics and smoking prevalence under the observation of the students. In this study, 57 were male and the age range was 18-24. The number of non-smoking male students (AE) the number of male students (AE) was 20 (35.09%), 15 (%16,32) passive smoker male students (BE) and 22 (%38,59) smoker male students (CE). Specific activity values were determined for PON enzyme at three different experimental groups. We found that smoking and exposure to cigarette smoke rates were higher in especially male students. PON enzyme activity had a low level in smoker compared to nonsmokers.
Keywords: Paraoxonase, serum, smoking.
References:
1. Mackness MI, Hallam SD, Peard T, Warner S, Walker CH. The separation of sheep and human serum ‘A’- esterase activity into the lipoprotein fraction by ultracentrifugation.Comperative Biochemistry and Physiology. 1985;82:675-677.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P116 - Cytotoxicities of Five New Benzoxazolone Derived Chalcones
Feyza Sena Engina, Sinan Bilginer a, Hiroshi Sakagami b, HaliseInci Gul a a Ataturk University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Erzurum, Turkey, bMeikai University, Faculty of Pharmaceutical Sciences, Tokyo, Japan *E-mail: [email protected] Chalcones and benzoxazolones are known with several bioactivities including anticancer activitiy [1]. In this study, first, 2(3H)-benzoxazolone was acethylated to use in the synthesis of suitable chalchones as suggested at Scheme 1[2]. The chemical structures were confirmed by spectral analysis and compounds were tested towards OSCC cell lines. PSE values of the compounds in cytotoxicity tests were 16, 94, 158, 74, 131, respectively while reference compound doxorubicin had PSE value of >2030.
Scheme 1: Synthetic pathway of the chalcones 1-5.
H H O N i O N O C O H C Cl C 3 O H C 3 O
H H N O N O ii O Ar-CHO O C C H C Ar C 3 O H O
Ar: Phenyl (1), 4-Methylphenyl (2), 3-Bromophenyl (3), 2,4-Dichlorophenyl (4), 2,3,4-trimethoxyphenyl (5). i: AlCl3-DMF ii: EtOH, 10% KOH
References: 1. Ivanova, Y., Momekov, G., Petrov, O. Synthesis of novel substituted 1, 3-diarylpropenone derivatives and their in vitro cytotoxic activity. (2009). Letters in Drug Design & Discovery, 6(5): 353-357. 2. Bilginer S., Gul HI., Mete E., Das U., Sakagami H., Umemura N., Dimmock, JR. 1-(3-aminomethyl-4- hydroxyphenyl)-3-pyridinyl-2-propen-1-ones: A novel group of tumour-selective cytotoxins. (2013). Journal of Enzyme Inhıbıtıon And Medıcınal Chemıstry, 28(5): 974-980.
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P117 - Synthesis of Chalcone Derivatives as Selective MAO-B Inhibitors
Gulsen Gunesacara, Dilan Ozmen Ozgunb, Halise Inci Gulc, Begum Nurpelin Saglikd,e, Derya Osmaniyed,e, Yusuf Ozkayd
aDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Erzincan University, bAğrı İbrahim Çeçen University cAtatürk University, dAnadolu University and eDoping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University. E-mail: [email protected]
In this study, it was aimed to synthesize some chalcone derivatives (according to Scheme 1) and screen them for their inhibitory potencies against hMAO-A and hMAO-B enzymes (Table 1) since the available drugs in market are not sufficient selectivity and some chalcones were reported with MAO inhibitory activit [1]. As conclusion: Non-significant inhibition was noted for synthesized compounds against hMAO-A. Compounds IG-5, IG-6, IG-7 showed significant inhibition against hMAO-B with lower IC50 values than 1 µM. The most active compound IG-7 showed a significant IC50 of 0.016 µM.
Scheme 1. Synthetic pathway of indanone derivatives
Table 1: IC50 (µM) values of the compounds IG1-IG41 against hMAO isoforms.
Compound IC50 (µM) hMAO- IC50 (µM) *SI Selectivity A hMAO-B
IG-1 17.274 3.004 5.751 MAO-B
IG-2 22.172 1.622 13.667
IG-3 6.895 1.569 4.393 MAO-B
IG-4 19.111 2.344 8.152 MAO-B
IG-5 33.180 0.061 542.575 MAO-B
IG-6 19.735 0.685 28.810 MAO-B
IG-7 6.291 0.016 393.188 MAO-B
Clorgiline 0.0058 - - MAO-A
Selegiline - 0.044 - MAO-B
*The selectivity index (SI) was calculated as IC50 (MAO-A) / IC50 (MAO-B). Keywords: Chalcone, MAO-B inhibitors
References:
1. Kaya, B, Saglik, BN, Levent, S, Ozkay, Y, Kaplancikli, ZA. Synthesis of some novel 2-substituted benzothiazole derivatives containing benzylamine moiety as monoamine oxidase inhibitory agents. J Enzyme Inhib Med Chem. 2016; 31: 1654-1661.
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P118 - Use Of A Compaction Simulator To Compare Two Commercial Tablet Presses Nailla Jiwaa, Assist. Prof. Dr.Metin Celika
a Near East University
E-mail: [email protected]
The aim of the study is to use a mechanical Compaction Simulator (Stylecam) to simulate two rotary presses namely, Fette and Kilian.machines to compare the results obtained. A (Design of Experiments framework was used to perform 16 experiments. Tablets of 420 mg were produced on a Stylcam Compaction Simulator using an 11.8 mm flat faced Euro B punch. Two different tablet profiles (Fette 102i and Killian S700) were then used in order to make a comparison between breaking force and friability as measured on a tablet hardness tester and friabilitor, respectively. The breaking force of the tablets was found to be over 120 N in order to produce tablets with acceptable friability. The results show that the Stylcam simulator is capable of mimicking the action of rotary tablet presses and, thus, a compaction simulator can be successfully used to simulate different rotary tablet presses. Keywords: Tablet, Compaction Speed, Compaction Force, Friability, Breaking Force. References: 1. Çelik, M. Overview of Compaction Data Analysis Techniques. Drug Development and Industrial Pharmacy. 1992; 767-810. 2. Çelik, M. Pharmaceutical Powder Compaction Technology Second Edition. 2011. 3. Lachman, L., Lieberman, H., & Kanig , J. The Theory and Practice of Industrial Pharmacy Third Edition. Bombay: Varghese Publishing House. 1987. 4. Michael E. Aulton, K. M. Aultons Pharmaceutics Fourth Edition. 2013. 5. Mohd Cairul Iqbal Mohd Amin, S. M. A Comparative Study of the Compaction Properties of Binary and Bilayer Tablets of Direct Compression Excipients. Tropical Journal of Pharmaceutical Research, 2012; 585-594. 6. Qiu, Y., Chen, Y., & Zhang, G. Developing Solid Oral Dosage Forms: Pharmaceutical Theory and Practice. 2009. 7. T. Higuchi, A. N. The physics of tablet compression. II. The influence of degree of compression on properties of table. Journal of the American Pharmaceutical Association. 2006; 42(4): 194-200.
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P119 – Sensitive Detection of Pemetrexed Disodium from its Pharmaceutical Dosage form by Adsorptive Stripping Differential Pulse Voltammetry
Nurgul K. Bakirhana, Sibel A. Ozkanb
a Hitit University, Faculty of Art&Science, Department of Chemistry, Corum, Turkey
b Ankara University, Faculty of Pharmacy, Department of Analytical Chemistry, Tandogan, Ankara, Turkey
*E-mail: [email protected]
Electrochemical behavior of pemetrexed disodium was investigated on over-oxidized polypyrrole modified glassy carbon electrode (oo-PPy/MWCNTs-COOH/GCE) by cyclic and adsorptive stripping differential pulse voltammetric techniques. The oo-PPy/MWCNTs-COOH/GCE is very sensitive to the oxidation of pemetrexed disodium. The effects of pH, concentrations of MWCNTs and monomer, the number of cycles for the electropolymerization and the scan rate for sensor preparation were optimized. The MWCNTs-COOH and oo-PPy based sensor showed an excellent recognition capacity toward pemetrexed disodium. The linear responses have been obtained in the range from 8.00×10-7 M to 1.00×10-4 M with 2.0×10-7 M detection limit for the bare GCE and from 1.00×10-8 M to 1.00×10-7 M with 3.28×10-9 M detection limit for the modified GCE. The oxidation of pemetrexed disodium was controlled by the adsorption process on both types of electrode surfaces. The developed method was compared with UV spectrophotometric assay that was Show an absorption maximum of 225 nm. As a result, the developed method and nanosensor have been applied for sensitive quantification of antineoplastic drug: pemetrexed disodium from its dosage forms.
Keywords: Pemetrexed disodium, conductive polymers, multi walled carbon nanotubes, stripping voltammetry
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P120 - Preliminary Studies on Optimization of Topical Formulations of Cinnarizine: Physical Characterization and Stability Assessment
Melike Üner*, Şükran Damgalı
Istanbul University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Turkey. *E-mail: [email protected]
Cinnarizine (CN) is a histamine H1-antagonist and a selective calcium channel blocker drug prescribed commonly for peripheral and cerebral disorders, vertigo, tinnitus, nistagmus, motion sickness and Meniere disease. 1 After oral administration of CN, which has a low and variable oral bioavailability, its various side effects have been reported. 2
Topical formulations of CN were aimed to optimize in this study. Therefore, risk of side effects of the drug could be minimized and efficient therapy would be provided by improving drug bioavailability. 3 For this purpose, transdermal patches, O/W emulsions, hydrogels and oleaginous creams of CN were designed. Transcutol®, propylene glycol, glycerol, oleic acid and menthol were used in different proportions as penetration enhancers. Formulations were physically characterized. Drug release profiles from the formulations meeting pharmaceutical quality were obtained using Franz type diffusion cells. Physical and chemical stability of those formulations were also investigated storing them at the room temperature, 4°C ve 40°C in the dark for 6 months.
Physically stable formulations were obtained after evaluation of data. They were also determined to maintain the chemical stability of the active substance during 6 months. Formulations showed the highest chemical stability at 4°C. According to in vitro release study, O/W emulsion formulations were determined to display the highest drug release rate after 6 hours followed by hydrogels, oleaginous creams and transdermal patches in general.
Transdermal dosage forms were designed by providing an alternative to oral administration of CN. As a result of this preliminary study, topical formulations of CN were found to meet pharmaceutical quality expected. As the next step of this study, an ex vivo experince was also employed on topical formulations to ascertain the drug penetration through the skin and to find out effect of penetration enhancers on drug penetration. All the results of the whole study is going to be presented as a full researh article in a near future.
Keywords: Cinnarizine, transdermal patch, topical delivery.
References: 1. Raghuvanshian S, Pathak K. Recent advances in delivery systems and therapeutics of cinnarizine: A poorly water soluble drug with absorption window in stomach. J. Drug Deliv. 2014;Article ID 479246:1-15. 2. Shi S, Chen H, Lin X, Tang X. Pharmacokinetics,tissue distribution and safety of cinnarizine delivered in lipid emulsion. Int. J. Phar. 2010;383(1-2):264-270. 3. Li N, Quan P, Wan X, Liu C, Liu X, Fang L. Mechanistic insights of the enhancement effect of sorbitan monooleate on olanzapine transdermal patch both in release and percutaneous absorption processes. Eur. J. Pharm. Sci. 2017;107:138-147.
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P121 - (Thio)urea Derivatives Enhance Wound Closure by Increasing Cell Proliferation: Synthesis and In Vitro Evaluation
Deryanur KILICa*, Farrokh LAFZIb, Haydar KILICc,d, Ali TAGHIZADEHGHALEHJOUGHIe, Ahmet HACIMUFTUOGLUe, Omer Irfan KUFREVIOGLUb, Nurullah SARACOGLUb
a Faculty of Art and Science, Department of Chemistry, Aksaray University, Aksaray, Turkey b Faculty of Sciences, Department of Chemistry, Atatürk University, Erzurum, Turkey c Oltu Vocational School, Atatürk University, Erzurum, Turkey d East Anatolia High Technology Application and Research Center, Erzurum, Turkey e Department of Veterinary Pharmacology and Toxicology, Atatürk University, Erzurum, Turkey *E-mail: [email protected]
In all time humans try to healing all type of wounds (ex. Burn, diabetic, sharp material injury, animal bite). Wound healing and the management of chronic wounds remain a major challenge. Skin has 3 main structure (epidermis, dermis, and hypodermis). Dermis by having hydro chondroitin sulfate molecule and fibroblast cells play important role in wound healing (1). In this study, a new series of (thio)urea derivatives were synthesized from the reaction of 2- guanidinobenzimidazole, 2-aminobenzimidazole, 2-aminobenzothiazole and 5-aminoindole with chiral (thio)isocyanates. The effects of synthesized these derivatives on the proliferation of fibroblasts were examined in vitro. Human fibroblast cell cultures were obtained from Atatürk University, Department of Pharmacology. In the fibroblast proliferation study, fibroblast cells were seeded in 96 well plate and replicated by culture medium (10% FBS, 1% PBS and 89% DMEM). The compounds were treated with various concentrations on the cells. MTT assay was hired to evaluate skin cells viability and proliferation rate after 24 h chemical exposures (Figure 1). The data were analyzed by SPSS-22.
Figure 1 The most effective compound was determined by evaluating the obtained data. These data demonstrate the potential of the use of these derivatives, particularly in tissue engineering, in the biomedical field.
Keywords: Urea, thiourea, fibroblast cell, wound healing
References: 1. Law JX, Chowdhury SR, Aminuddin BS, Ruszymah BHI. Role of plasma-derived fibrin on keratinocyte and fibroblast wound healing. Cell Tissue Bank. 2017.
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P122 - Determination of Cefpodoxime proxetil in Pure and Pharmaceutical Preparations with spectrophotometer
Elif Özdemir1, Mevlüt Albayrak2, Onur Senol3 1Department of Analytical Chemistry, Faculty of Pharmacy, Istanbul Yeni Yuzyıl University, Istanbul, Turkey 1Department of medical laboratory techniques, Health Services Vocational Training School, Ataturk University, Erzurum, Turkey 3Department of Analytical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey E-mail: [email protected]
Cefpodoxime proxetil is an excellent antibacterial activity against entero bacteriaceae and other gram negative bacilli. Its chemical name RS-1 isopropoxy carbonyloxy)ethyl (+)-(6R,7R)-7-[2-(2-amino-4-thiazolyl)-2-[(Z)-methoxy imino]acetamido-3-methoxy methyl-8-oxo-5-thia-1-azabicyclo[4.2.1]oct-2-ene-2- carboxylate [1]. In this study, a novel, sensitive and selective spectrophotometric method was developed for the determination of cefpodoxime in pharmaceutical preparations. Maximum absorbance of derivative in methanol is measured at 235 nm. The described method was validated and the analytical parameters of linearity, limit of detection, limit of quantification, accuracy, precision, recovery and robustness were evaluated. A linear relationship existed between absorbance and cefpodoxime proxetil concentration over 7.5-25 µg/mL range. The proposed method was successfully applied for the determination of cefpodoxime proxetil in pharmaceutical preparations and the obtained results were in good agreement with those obtained by the reference method.
Keywords: cefpodoxime proxetil, spectrophotometric, determination, validation
References: 1. Subbayama, A.B, Rambabu C. Spectrophotmetric Determination of Cefpodoxime Proxetil in Tablets. 2010; 5: 3345-3348.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P123 - Main Toxic Compounds of Palm Oil
Ishak Erik a, Sezen Yilmaz Sarialtin b, Can O Yalcin c
a Karadeniz Technical University, Faculty of Pharmacy, Department of Pharmacognosy, Trabzon, Turkey b Ankara University, Faculty of Pharmacy, Department of Toxicology, Ankara, Turkey c Karadeniz Technical University, Faculty of Pharmacy, Department of Toxicology, Trabzon, Turkey E-mail: [email protected]
Palm oil is a vegetable oil obtained from red pulp of oil palm fruit. It is produced mainly from American oil palm (Elaeis oleifera) and maripa palm (Attalea maripa) as well as the main African oil palm (Elaeis guineensis). Different derivatives are obtained by subjecting to the refining process. Many processed foods contain palm oil or its derivatives. Due to its low cost it is used in the production of many take-home foods. Numerous chemicals in the food production process; can be infected as depending on the environment, the presence of environmental pollutants, storage and cooking conditions. It is called food contaminants. 3- Chloropropanediol (3-MCPD), 2-chloropropanediol (2-MCPD) and esters and glycidyl fatty acid esteri (GE) in the palm oil are the most important food contaminants during palm oil refining process and use at high temperature. 3-MCPD, 2-MCPD and GE have negative effects on human health.1,2 Due to these adverse effects, 3-MCPD has been identified as Group-2B by the International Agency for Research on Cancer (IARC); the other contaminant, glycidol, free compound of GE, is classified under Group-2A.3 According to the scientific opinion published by the European Food Authority (EFSA) in May 2016 reported taking precautions to reduce exposure to these contaminants as much as possible and should be assessed that the validity of the limits set by new works. Keywords: Palm oil, 3-MCPD, 2-MCPD, Glycidol, Food contaminants
References 1. EFSA Journal (2016). Scientific Opinion: Risk for human health related to the presence of 3- and 2- monochloropropanediol (MCPD), and their fatty acid esters, and glycidyl fatty acid esters in food. EFSA Panel on Contaminants in Food Chain (CONTAM). EFSA Journal 2016;14(5): 4426, 159 pp. doi:10.2903/j.efsa.2016.4426. 2. NTP (National Toxicology Program), (2007). National Toxicology Program, Toxicology and carcinogenesis studies of glycidol (CAS No. 556-52-5) in genetically modified haploinsufficient p16Ink4a/p19Arf mice (gavage study). Technical Report Series No. 13. National Institutes of Health Publication No. 08-5962. Research Triangle Park, NC. 3. Appel, K., Abraham, K., Berger-Preiss, E., Hansen, T., Apel, E., Schuchardt, S., Vogt, C., Bakhiya, N., Creutzenberg, O., Lampen, A. 2013. Relative oral bioavailability of glycidol from glycidyl fatty acid esters in rats, Arch Toxicol 87: 1649-59.
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P124 - New Spectrophotometric Method with Chemometric Design-Optimization Approach for the Simultaneous Determination of Thiamin and Pyridoxin
Fatma Demirkaya-Miloglu1, Elmas Polatdemir1, Alper Kürsat Demirkaya2, Elif Seyma Aslan1, Sule Aydin1, Okan Senturk1
1Department of Analytical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey 2Department of 2Food Processing, Vocational School, Bilecik Seyh Edebali University, Bilecik, Turkey E-mail:[email protected]
Hydophilic B vitamins were accepted to be required catalysts for metabolism of protein, lipid and carbohydrate. Tiamin and pyridoxin are vitamins of group B which play a key role in many biochemical reactions and are indispensable elements of healthy life. They are used together to suppress the transmission of neural stimuli and to act analgesic [1,2].
The aim of study was to develop and validate an UV-Vis spectrophotometric method coupled with different chemometric calibration (PLS (partial least squares), PCR (principal component regression) and CLS (Classical Least Squares) for quantitative analysis of thiamin and pyridoxin without any separation process.
Five-level factorial design was used to prepare the calibration (25 samples) and validation (8 samples) sets containing mixtures thiamine and pyridoxine within their linear ranges (5-25 μg/mL) in 0.1 M HCl. Absorption spectra of obtained mixtures were recorded between wavelengths of 200 nm to 360 nm with the intervals Δλ=1 nm. The calibration models (PLS, PCR and CLS) were generated and their cross validations of calibration sample using leave one out technique to ensure the maximum predictive ability and validation over synthetic and pharmaceutical preparation were performed.
Calibration and validation models for PLS, PCR and CLS were evaluated by both the coefficient of determination (R2) and root mean square error of calibration (RMSEC). According to the obtained results for all three method, R2 for the relationship between actual values and predicted values for both analyte was higher than 0.999 indicating good accuracy. The RMSEC values of PLS, PCR and CLS methods which was shown good precision were relatively low.
These three chemometric techniques, do not require any separation step, were successfully used for analysis of tiamin and pyridoxine in vitamin tablet. The obtained results were compared with each other and good agreement was found.
Keywords: Tiamin, Pyridoxine, PLS, PCR, CLS, Experimental Design References: 1. Marks, John, A guide to the vitamins: their role in health and disease. Springer Science & Business Media. 2012. 2. Lukaski H.C, Vitamin and mineral status: effects on physical performance. Nutrition. 2014; 20.7: 632-644.
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3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P125 - A new Spectrofluorimetric Method for Determination of Zinc by using the Fe3O4-SiO2–NH2 Nanocomposite Functionalized with Zinpyr-1 Ligand in Artificial Saliva
Elmas Polatdemir1, Fatma Demirkaya-Miloglu1, Önder Metin2, Yücel Kadioglu2
1Department of Analytical Chemistry, Faculty of Pharmacy, Ataturk University,Erzurum,TURKEY 2Department of Chemistry, Faculty of Science, Atatürk University, Erzurum, TURKEY E-mail: [email protected]
Zinc is as an essential bioelement for the vital functions of the organism, which plays a vital role in various biological processes, such as gene expression, cell apoptosis, enzyme regulation, and neurotransmission. These important characteristics of Zn2+ occur in a quite narrow concentration range So, Zn2+ concentration in biological fluids might be an auxiliary factor in diagnosis, etiology and development of mentioned diseases. Nowadays, interest in development of composites which have ability to be functionalized with organic molecules in order to create desired features in elemental analysis increases day by day and these methods are very valuable in application of analytical methods [1,2].
The aim of study was to develop and validate a new spectrofluorimetric method based on the magnetic 2+ Fe3O4-SiO2-NH2 nanocomposite functionalized with Zinpyr-1 that form chelates between Zn to determine 2+ the concentration of Zn in artificial saliva. In accordance with this purpose, the magnetic Fe3O4-SiO2- NH2 nanocomposite functionalized with Zinpyr-1 have been synthesized. The structure of the nanocomposite and chemical composition have been confirmed by TEM, XRD and FTIR techniques. Zn2+ in artifical saliva was interacted with Fe3O4-SiO2–NH2-Zn(Zinpyr-1) nanocomposites. A new Fe3O4-SiO2– NH2-Zn(Zinpyr-1) nanocomposites from artifical saliva by the help of a magnet discarded and then spectra of Fe3O4-SiO2-NH2 Zn(Zinpyr-1) was taken with Tris-HCl (pH: 7.2) included 100 mM KCl and 50 µM EDTA. Excitation and emission maxima for this condition were selected 490 and 530 nm, respectively. The developed spectrofluorimetric method was validated by using specificity, accuracy, precision, linearity and sensitivity validation parameters. The method for artifical saliva was determined to be linear between 20-160 ng/mL with a correlation coefficient of 0.9988. The limit of detection (LOD) and limit of quantification (LOQ) were calculated to be 9.7 and 29.5 ng/mL, respectively.
In order to determine by removing of Zn2+ from artificial saliva, an easy and effective way was provided by a new spectrofluorometric method based on the formation of chelate between Fe3O4-SiO2-NH2 (Zinpir- 1) nanocomposite and Zn2+. Moreover, this developed original method can be used in routine analysis of clinical and epidemiological studies (This study was supported by TUBİTAK (Project Number: 214Z153)).
Keywords: Zinc, Zinpyr-1, Fe3O4-SiO2-NH2 nanocomposite, artificial saliva
References: 1. Skalny A.V, Bioelementology as an interdisciplinary integrative approach in life science: terminology, classification, perspectives. Journal of Trace Elements in Medicine and Biology. 2011; 25(1): 3-10. 2. Sarika S., Barick K.C., Bahadur D, Functional Oxide Nanomaterials and Nanocomposites for the Removal of Heavy Metals and Dyes. Nanomaterials and Nanotechnology. 2013; 3(20): 1-20.
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P126 - Involvement of serotonin receptors in low-dose ketamine analgesia in mice
Meral Erdinça, İlker Kellea, Hasan Akkoça, Emre Uyara, Levent Erdinçb aDepartment of Pharmacology, Medical Faculty, Dicle University, Diyarbakır, Turkey bDepartment of Biochemistry, Medical Faculty, Dicle University, Diyarbakır, Turkey *E-mail: [email protected]
Ketamine was introduced nearly half a century ago to serve as a mono anesthetic drug with analgesia, loss of consciousness and immobility (1). However, significant side effects reported led ketamine's role to diminish in anesthesia (2). Studies indicate that low doses of ketamine could produce profound analgesia with fewer side effects (3). Perception of pain is closely associated with serotonin. Changes in serotonin levels lead pain altering effects (4). It is stated that ketamine is tended to increase serotonin transmission (5). Therefore, interactions of ketamine with the serotonergic system may be an important way to explain its effects on pain. The present study was performed to reveal the involvement of serotonergic system in ketamine analgesia and to test acute effects of ketamine on pain. 88 male BALB/c mice were separated into 11 groups and treated intraperitoneally (ip) with fluoxetine (20 mg/kg, 7 days) and p-chlorophenyl alanine (pCPA) (150 mg/kg, 4 days) or %0.9 saline. Methiothepin (0.1 mg/kg), GYKI-52466 (20 mg/kg), metamizole (500 mg/kg); and ketamine (10 mg/kg), were administered 60 mins before the test procedure. Mice were individually placed and kept on the hot plate (HP) test apparatus for 60 secs if no reaction were recorded. The time passes to lick the hind paws, or jumping was considered as the index of pain reaction and test ended afterward. The results were evaluated using the One- way ANOVA followed by post hoc Tukey test. The data are presented as mean values and ±SD. In the HP test, pain reaction latencies were increased with metamizole (p<0.001), ketamine (p<0.01), fluoxetine (p<0.01), fluoxetine-ketamine (p<0.05) compared to control group. Ketamine failed to increase pain reaction latencies when combined with a serotonin receptor antagonist; methiothepin, a serotonin depletion agent; pCPA and an AMPA receptor antagonist; GYKI-52466. These results indicate that ketamine analgesia is closely associated with presence and activity of serotonin and AMPA receptors. In the light of latest findings, indications of ketamine may need to be reviewed. Analgesic properties of ketamine may offer a worthy alternative to traditional drugs, for the practitioner and the patient in the pain management. Keywords: Ketamine, analgesia, anesthesia, serotonin
References: 1. Persson, Jan. Ketamine in pain management. CNS neuroscience & therapeutics, 2013;19.6: 396-402. 2. Niesters, Marieke; MARTINI, Christian; DAHAN, Albert. Ketamine for chronic pain: risks and benefits. British journal of clinical pharmacology, 2014;77.2: 357-367. 3. Finck, A. Donald; NGAI, S. H. Opiate receptor mediation of ketamine analgesia. Anesthesiology, 1982;56.4: 291- 297 4. Pekoe, Gary M.; SMITH, David J. The involvement of opiate and monoaminergic neuronal systems in the analgesic effects of ketamine. Pain, 1982;12.1: 57-73. 5. Øye, L. Ketamine analgesia, NMDA receptors and the gates of perception. Acta anaesthesiologica scandinavica, 1998;42.7: 747-749.
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P127 - Protective Effects of Melatonin and Fluoxetine on Immobilization-Induced Stress in Mice
Meral Erdinça, Merve İnci Çamçia, Emre Uyara, İlker Kellea, Hasan Akkoça, Levent Erdinçb
aDepartment of Pharmacology, Medical Faculty, Dicle University, Diyarbakır, Turkey bDepartment of Biochemistry, Medical Faculty, Dicle University, Diyarbakır, Turkey *E-mail: [email protected]
Exposure to stress produces physiological and psychological problems (1). Studies support that psychiatric disorders caused by stress respond to antidepressant therapy (2). Fluoxetine is a widely used drug in depression treatment, and also is known to have anxiolytic and antioxidant effects (3). Melatonin is known to have anti-depressant like effects and may be beneficial against oxidative damage triggered by stress (4,5). In the present study, therapeutical effects of fluoxetine and melatonin on immobilization-induced stress in mice have been analyzed. An immobilization stress model was used for this experiment. 64 male BALB/c mice were separated into 8 groups and either treated intraperitoneally (ip) with melatonin (10 mg/kg, Mel), fluoxetine (20 mg/kg, Flu) for 7 days or had %0.9 saline injections. Immobilization (IM) groups were placed into individual cages 6 hours for 7 days. Measurements of anxiety were made by an elevated plus maze (EPM) and an open field (OF) test, locomotor activity by an OF test, depression by a forced swimming test (FST) and memory by a passive avoidance (PA) test. The animal behaviors were recorded and analyzed with Ethovision-XT video tracking system. Subsequently, mice were sacrificed to assess malondialdehyde (MDA) levels. The results were evaluated using One-way ANOVA followed by post hoc Tukey test. Data are presented as mean and ±SD. In the PA test, learning was improved in the IM group compared to control group (p<0.01), and learning was declined in IM+Mel and IM+Mel+Flu groups compared to IM group (p<0.05). In the FST, immobility time was higher in the IM group compared to the control group (p<0.05). In the OF test, the time spent in the center was significantly decreased in IM group compared to the control group (p<0.01). MDA levels were higher in the IM group compared to control group (p<0.01). Exposure to stress is common in society, and it has notable effects in our lives. In our experiment, we have demonstrated a stress model with immobilization. As a result, we state that stress may improve emotional learning, yet it may increase depression and anxiety. Furthermore, stress also increases oxidation levels and can be reduced with drugs like fluoxetine and melatonin. Keywords: Immobilisation, Stress, Fluoxetine, Melatonin References: 1. Chrousos, George P. Stress and disorders of the stress system. Nature reviews endocrinology, 2009;5.7: 374-381. 2. Lee, Seung-Yup, et al. Oxidative/nitrosative stress and antidepressants: targets for novel antidepressants. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2013;46: 224-235. 3. Caiaffo, Vitor, et al. Anti‐inflammatory, antiapoptotic, and antioxidant activity of fluoxetine. Pharmacology research & perspectives, 2016;4.3. 4. Hoehn, Richard, et al. Melatonin acts as an antidepressant by inhibition of the acid sphingomyelinase/ceramide system. Neurosignals, 2016;24.1: 48-58. 5. Lopez-Munoz, Francisco, et al. (ed.). Melatonin, Neuroprotective Agents and Antidepressant Therapy. Springer India, 2016.
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P128 - Neuroprotective effects of austricine on differentiated SH-SY5Y neuroblastoma cell line
Mehmet Enes ARSLANa*, Hasan TÜRKEZ a, Recep KÜÇÜKDOĞRUa
aDepartment of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, Erzurum, Turkey *E-mail: [email protected]
Alzheimer's disease (AD) generally covers 60% of mental disorders and is one of the most important neurodegenerative diseases. In our study, the human neuroblastoma cell line (SH-SY5Y) was transformed into neuron-like cells by applying retinoic acid. In the transformed cells, β-amyloid protein (0-200 μM) was applied for 24/48 hours at wide dose intervals to establish the Alzheimer's environment and IC50 values were determined. Next, neuroprotective effect against toxicity generated by administration of austricine sesquiterpene in a wide spectrum doses (0-100 μg/ml) to β-amyloid administered cell culture was examined for 24 and 48 hours. 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release tests were performed to determine cell viability rates in the in vitro Alzheimer model. Subsequently, the Annexin-V/PI study flow cytometry method was used to determine the type of death caused by toxicity in the cells. Apoptosis and nucleus integrities of the cells were examined under the microscope using the Hoechst 33258 fluorescence staining method. Furthermore, austricine effects on acetylcholinesterase (AChE) activity, total antioxidant capacity (TAC) and total oxidative status (TOS) levels were determined. According to the results, the protective effect of austricine concentrations against β-amyloid for 24 hours and 48 hours was determined by cell viability tests and the result of flow- cytometry revealed that austricine cause significant decrease in necrosis deaths in cells. It was further analyzed that the AchE activity, the TOS level and the TAC level decreased after austricine application.
Keywords: Alzheimer's disease, β-amyloid protein, Austricine, Necrosis, Antioxidant
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P129 - The Effects of GLP-1 Analogs and Sitagliptin on Heart Rate in Isolated Diabetic Rat Atrium and Whole Heart Preparations
Esra AKCABAĞ ÇIRA a, Feride ÖNER a, Zeliha BAYRAM b, Sebahat ÖZDEM c, Arda TAŞATARGİL a, Sadi S. ÖZDEM a*
a Akdeniz University Medical Faculty, Department of Medical Pharmacology b Turkish Medicines and Medical Device Agency c Akdeniz University Medical Faculty, Department of Medical Biochemistry
*E-mail: [email protected] We investigated effects of GLP-1 analogs and sitagliptin on heart rate in isolated atrial and whole heart preparations from control and diabetic rats together with mechanisms playing a role in these effects. Experimental diabetes was induced by intraperitoneal injection of 50 mg/kg single dose of istreptozotocin. Twelve-weeks after diabetes induction, the effects of GLP-1 analogs (GLP-1 (7-36), GLP-1 (9-36), Exendin-4 (1-39), 10-12 - 10-7 M for all) and sitagliptin (10-12 - 10-7 M) on heart rate and myocardial function parameters were recorded by isometric transducers in isolated atrial preparations and by a pressure transducer connected to a balloon placed in left ventricle of whole heart preparations perfused isovolumetrically in Langendorff apparatus. Basal heart rate was significantly lower in diabetic compared to control atrial and whole heart preparations. GLP-1 analogs increased heart rate significantly in diabetic and control atrial preparations, whereas sitagliptin produced the same effect only in diabetic group. Effects of GLP-1 analogs occured through specific GLP-1 receptors and were mediated by nitric oxide and prostanoids. Neither GLP-1 analogs nor sitagliptin altered heart rate in whole heart preparations but unfavorable effects of diabetes on left ventricular myocardial contraction and relaxation were partly reversed by GLP-1 analogs. It was determined that the unfavorable effects of the GLP-1 analogs and sitagliptin on heart rate of isolated atrial preparations from rats were not reflected at the level of isolated whole heart level. It was concluded that partial reversal of infavorable effects of diabetes on left ventricular myocardial functions by GLP-1 analogs and sitagliptin together with the above finding supported the favorable effects of these agents on cardiovascular functions in clinical practise1.
This study was supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) with the project number 114S410
Keywords: Diabetes mellitus, Glucogone-like peptide-1, Heart rate, Nitric oxide, Sitagliptin
References: 1. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. New England Journal of Medicine. 2016; 375(4):311-22.
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P130 - Nickel boride nanoparticle toxicity and microarray analysis on human pulmonary alveolar cells
Hasan TÜRKEZa, Mehmet Enes ARSLANa*, Erdal SÖNMEZb, Abdulgani TATARc, Fatime GEYİKOĞLUd aDepartment of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, Erzurum, Turkey bAdvanced Materials Research Laboratory, Department of Nanoscience & Nanoengineering, Graduate School of Natural and Applied Sciences, Ataturk University, Erzurum, Turkey cDepartment of Medical Genetics, Medical Faculty, Atatürk University, Erzurum, Turkey dDepartment of Biology, Faculty of Arts and Sciences, Atatürk University, Erzurum, Turkey
*E-mail: [email protected]
During the recent years, microarray analysis of gene expression has become an inevitable tool for exploring toxicity of drugs and other chemicals on biological systems. In this study, synthesis, characterization and cytotoxicity evaluation of nickel boride (BNi2) nanoparticles were performed on human pulmonary alveolar epithelial cells (HPAEpiC) since, main exposure to nanoparticles would generally happen through lung via inhalation. Chemically synthesized Co2B NPs were characterized by using XRD, TEM, SEM and EDX techniques. MTT, NR and LDH release assays were used to analyse cytotoxicity after NPs exposure. Whole genome microarray analysis was used to find out the effects of NiB2 NPs on gene expressions of HPAEpiC cells. Finally, the database for annotation, visualization and integrated discovery (DAVID) analysis was used to reveal relationships between different cellular pathways and NPs exposure. According to cytotoxicity analysis LC20 value for NiB2 NPs was 24.313 mg/L. Microarray results showed that 705 genes expression change (FC≥2) significantly over 40.000 genes analysis. When the gene pathways were analysed, it was seemed that NiB2 NPs mostly affect centrosome organization, microtubule regulation, nucleus regulation and phosphoprotein synthesis.
Keywords: Nickel boride nanoparticles, In vitro, Toxicogenomics, Human pulmonary alveolar epithelial cells, Microarray
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P131 - Functional Effects Of Visfatin In Small Resistance Arteries Of Rat Isolated Mesenteric Bed
Esra AKCABAĞ ÇIRA a* Zeliha BAYRAM b, Sebahat ÖZDEM c, Sadi S. ÖZDEM a
a Akdeniz University Medical Faculty, Department of Medical Pharmacology b Turkish Medicines and Medical Device Agency cAkdeniz University Medical Faculty, Department of Medical Biochemistry
*E-mail: [email protected]
Visfatin, a new adipocytokine, is expressed in perivascular adipose tissue (PVAT) and exerts effects in vascular system in addition to its relation with various pathological conditions1. It is suggested that visfatin is a potential biomarker for endothelial dysfunction and vascular damage. Although, it is reported that visfatin may play a direct role in deterioration of vascular relaxation, there are conflicting results regarding its functional effects in small resistance arteries. Therefore, the present study aimed to investigate the functional effects and the possible underlying mechanism(s) of visfatin in isolated rat mesenteric small resistance arteries.
The study was conducted in isolated rings of small resistance arteries from mesenteric vascular bed obtained from male Wistar rats aged 10-12 weeks. While visfatin incubation (1, 5, 25, 50 and 100 ng/mL) did not produce significant alterations in contractile responses of mesenteric arterial rings to noradrenaline (NA: 10-10 – 10-5 M), relaxation responses to acetylcholine (ACh: 10-10 – 10-5 M) were significantly reduced in endothelium-intact rings. The inhibitory effect of visfatin was not observed in endothelium-denuded rings. Incubation of tissues with Nampt inhibitor FK866 (10 µM) or superoxide dismutase (SOD: 100 U/ml) reversed the inhibitory effects of visfatin on relaxation responses to ACh. Visfatin incubation did not cause a significant alteration in relaxation responses of rat mesenteric artery rings to sodium nitroprusside (SNP: 10-10 – 10-5 M). Mesenteric PVAT visfatin levels (117.75 ± 12.47 ng/mg) were significantly higher than plasma visfatin levels (8.75 ± 0.81 ng/mL) and there was a significant positive correlation between these two parameters.
Taken together, present results suggested that visfatin inhibited the endothelium-dependent relaxation responses in isolated rat mesenteric resistance arteries probably through NO inhibition and free oxgen radicals. Given that NO is a vasoprotective agent inhibiting endothelial inflammation and thrombosis, the results of our study indicated that increments in local and/or systemic visfatin levels due to various pathological conditions may contribute, at least at the level of small resistance arteries through unfavorable effects on endothelial functions, in these pathologies.
This study was suported by Akdeniz university (Project Number: 2014.02.0122.002)
Keywords: Adipokines, Visfatin, Rat mesenteric artery, Nitric oxide, Vasoprotective
References: 1. Liu SW, Qiao SB, Yuan JS, Liu DQ. Association of plasma visfatin levels with inflammation, atherosclerosis and acute coronary syndromes (ACS) in humans. Clinical endocrinology. 2009;71:202-7.
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P132 - Cloning of Pseudomonas aeruginosa azurin in Lactococcus lactis
Melike YILDIZ and Hakan ASKIN
University of Atatürk, Department of Molecular Biology and Genetics, Erzurum, Turkey *E-mail: [email protected]
Chemotherapeutic agents are widely used as antibiotic or anticancer drugs, but they usually affect normal human cells and cause serious side effects. In addition, cancer cells can develop resistance to traditional chemotherapy agents through multi-mechanisms/cellular changes. Therefore, the development of chemotherapeutic agents that can be used for effective and safe treatment has gained importance (1). Several studies have shown that bacterial cupredoxin (especially azurin) can serve as a source for the development of therapeutic medicines to treat cancer, as well as various infectious agents such as viruses and parasites (2). The aim of this study was to clone azurin gene from Pseudomonas aeruginosa in Lactococcus lactis. The gene was amplified using genomic DNA of P. aeruginosa and ligated into food- grade vector pNZ8149. The ligation product was transformed into L. lactis (3). After colony PCR, the bands of gene were observed on the 1% agarose gel and DNA sequence analysis was performed for the recovered DNA fragments. The cloned gene was 99% similar to P. aeruginosa azurin according to the BLAST result of the DNA sequencing. In our future work, we will carry out food-grade expression of the azurin cloned in L. lactis. It is thought that L. lactis, producing azurin, can be used in pharmacology and food field.
Keywords: Azurin, cloning, food-grade, Lactococcus lactis
References: 1. Arpornsuwan T, Sriwai W, Jaresitthikunchai J, Phaonakrop N, Sritanaudomchai H, Roytrakul S. Anticancer Activities of Antimicrobial BmKn2 Peptides Against Oral and Colon Cancer Cells. Int J Pept Res Ther. 2014;20(4):501-9. 2. Fialho AM, Bernardes N, Chakrabarty AM. Exploring the anticancer potential of the bacterial protein azurin. Aims Microbiol. 2016;2(3):292-303. 3. Villatoro-Hernandez J, Kuipers OP, Saucedo-Cardenas O, Montes-de-Oca-Luna R. Heterologous protein expression by Lactococcus lactis. Methods Mol Biol. 2012;824:155-65.
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Short Oral Presentations
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OP01 - The New Generation Drug Candidate Molecules for Cancer Treatment
Aysegul Gölcü
Istanbul Techinical University, Faculty of Science and Letters, Department of Chemistry, Istanbul, Turkey. *E-mail: [email protected]
Cis-platinum ([Pt(NH3)2Cl2]), developed by Rosenberg in 1969 and used for cancer treatment has led many research group to synthesize metal-based drugs since those years. Pt(II), Zn(II), Ru(III), Cu(II), Mn(III) and Au(I/IV) have mostly used as the metal ion for the drug development studies. In all of those studies, the drug molecules act as ligands and form mostly monodentate or bidentate molecular structures by offering pair of electrons to metal atoms. The studies of this topic over the last forty years have gathered under the roof of “Medicinal Chemistry”. The main objective of Medicinal Chemistry is to identify new anticancer agents and put them into clinical practice procedures. In addition, one of the most important reasons that metal-based drugs (MBD) are used in cancer treatment, is that metal atoms have variable oxidation step and the ability to be bound to nucleic acid molecules through different mechanisms. Metals are endowed with unique characteristics that include redox activity, variable coordination modes, and reactivity towards organic substrates. Due to their reactivity, metals are tightly regulated under normal conditions and aberrant metal ion concentrations are associated with various pathological disorders, including cancer. For these reasons, coordination complexes, either as drugs or prodrugs, become very attractive probes as potential anticancer agents. Especially in the last fifty years, many MBD of biological assays in-vitro and in-vivo have performed.
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OP02 - Green Pharmaceutical Analysis in High Performance Liquid Chromatography by Organic Modifier Replacement in the Mobile Phase
Ayşegül Doğan a*, Nursabah E Başcı a
a Hacettepe University, Faculty of Pharmacy, Department of Analytical Chemistry, 06100, Sihhiye, Ankara,Turkey
*E-mail: [email protected]
Green chromatography techniques are a developing area in the scientific research studies due to their security for environment and human health. Greening procedures in high performance liquid chromatography (HPLC) techniques can be based on reduction of toxic solvent usage and/or the replacement of toxic solvents with less or non-toxic ones which are friendly to the environment [1-3]. The major advantage of green solvent use HPLC is the massive reduction in produced toxic waste and its management in routine quality control analysis in pharmaceutical industry. In this study, green HPLC methods of voriconazole and tadalafil analysis in their tablets were optimized and developed. For this purpose, non-toxic propylene carbonate (PC) and ethanol (EtOH) were used as organic solvents, and low particle sized small columns and microflow HPLC approach were also tested. Shim-Pack XR-ODS (100 x 2.0 mm, 2.2 µm) analytical column was utilized for the analysis of voriconazole and tadalafil in the presence of phenazoprydine as internal standard. Mobile phase was constructed as PC/(% 70 phosphate buffer (50 mM, pH: 3.0) + % 30 EtOH) (10:90, v/v) at a flow rate 0.3 mL min-1. Photodiode array detector was set to 256 nm for voriconazole and 284 nm for tadalafil. Developed pharmaceutical analysis methods in this study were validated in terms International Commission for Harmonization (ICH) regulations. Linearity for voriconazole and tadalafil was in the range of 0.10 - 100.00 g mL-1 and 0.10 - 80.00 g mL-1, respectively. Limit of detection for voriconazole was 0.05 g mL-1 and 0.08 g mL-1 for tadalafil, while limit of quantification was 0.1 g mL-1 for both active substances. The highest relative standard deviation were found to be below 1.31% while the lowest recovery was 99.27 g mL-1. The methods were accurate, precise, specific, sensitive, rugged and robust with acceptable system suitability testing (SST) values. Developed methods were also tested for their applicability and reliability in pharmaceutical analysis and according to the findings the methods were found to be applicable and reliable in long-term use in their tablet analysis.
Keywords: Greening, voriconazole, phenazopyridine, tadalafil, HPLC
References: 1. Gałuszka A, Migaszewski Z, Namieśnik J. The 12 principles of green analytical chemistry and the SIGNIFICANCE mnemonic of green analytical practices. TrAC Trends in Analytical Chemistry, 2013; 50: 78-84. 2. Suvarna B, Varsha N, Pratibha V, Soni M, Ashok, B. Prospective use of propylene carbonate as a mobile phase component in RP-HPLC. International Journal of Research in Pharmaceutical Sciences, 2011; 1:15-28. 3. Tache F, Udrescu S, Albu F, Micăle F, Medvedovici A. Greening pharmaceutical applications of liquid chromatography through using propylene carbonate–ethanol mixtures instead of acetonitrile as organic modifier in the mobile phases. Journal of Pharmaceutical and Biomedical Analysis, 2013; 75: 230-238. Acknowledgement: This study is study is partially supported by Hacettepe University Scientific Research Coordination Unit (TDK-2015-8149)
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OP03 - Tyrosinase Inhibitory Effect of Aerial Parts of Alchemilla caucasica Buser
Esen Sezen Karaoğlana*, Ufuk Özgenb a Department of Pharmaceutical Botany, Faculty of Pharmacy, Atatürk University, Erzurum, Turkey bDepartment of Pharmacognosy, Faculty of Pharmacy, Karadeniz Tecnical University, Trabzon, Turkey * E-mail: [email protected]
Tyrosinase is a copper-containing enzyme which could be found in microorganism, plants, fungi, and animals. This enzyme takes a place in melanin synthesis. Activity of tyrosinase cause production of the melanin on skin, hair, and eye. Hyperpigmentation is brought about due to the abnormal melanin accumulation in human skins and browning of foods. Because of that reason, tyrosinase inhibitors gained importance in medicine, cosmetic and food industries. Some compounds like kojic acid and arbutin are known to be strong tyrosinase inhibitors, whereas these compounds have certain adverse effects as liver damage and gastrointestinal disturbances. Therefore, the development of novel, potent, non toxic and stable tyrosinase inhibitors are quite important in medical, cosmetic, food and agricultural fields [1-4]. Alchemilla species (Rosaceae) are locally known as "aslanpençesi" in Turkey. Alchemilla plants (lady's mantle) are used in traditional medicine for different indications which are minimizing the symptoms of sore throat, promoting wound healing, stopping bleeding, alleviating nausea and vomiting [5]. In this study, the tyrosinase inhibitory activities of the methanol, dichloromethane, ethyl acetate, butanol and aqueous extracts of Alchemilla caucasica have been investigated. Tyrosinase inhibition activity was determined by described study of Masuda et al. with 3,4-dihidroxyl- L-phenylalanin (L-DOPA) as substrate with some modification. Kojic acid were chosen to be positive control [6]. The ethyl acetate extract showed the highest tyrosinase inhibition (52.87 ± 1.52 %) at 500 µg/mL concentration in accordance with the data.
Keywords: Alchemilla caucasica, tyrosinase inhibitory effect, hyperpigmentation
References: 1. Dat LC, Thao NP, Thuy Luyen BT, Tai BH, Jeong BH, Woo MH, Kim YH. Identification of six new lupane-type triterpenoids from Acanthoponax koreanum leaves and their tyrosinase inhibitory activities. Bioorg Med Chem Led. 2016; 26: 1061-1067. 2. Seo SY, Sharma VK, Sharma NJ. Mushroom tyrosinase: Recent prospects. J Agric Food Chem. 2003; 51: 2837- 2853. 3. Hu YH, Chen QX, Cui Y, Gao HJ, Xu L, Yu XY, Wang Y, Yan CL, Wang Q. 4- Hidroxy cinnamic acid as mushroom preservation: Anti-tyrosinase activity kinetics and application. Int J Biol Macromol. 2016; 86: 489-495. 4. Asadzadeh A, Sirous H, Pourfarzam M, Yaghmaei P, Fassihi A. In vitro and in silico studies of the inhibitory effects of some novel kojic acid derivatives on tyrosinase enzyme. Iran J Basic Med Sci. 2016; 19: 131-144. 5. Makau JN, Watanabe K, Kobayashi N. Anti-influenza activity of Alchemilla mollis extract: Possible virucidal activity against influenza virus particles. Drug Discoveries & Therapeutics. 2013; 7(5):189-195. 6. Masuda T, Yamashita D, Tekada Y, Yonemorı S. Screening for Tyrosinase Inhibitors among Extracts of Seashore Plants and Identification of Potent Inhibitors from Garcinia subelliptica. Biosci Biotec Biochem 2005; 69 (1):197- 201.
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OP04 - Enhancement of Disulfiram Cytotoxicity by Sodium Butyrate in Breast Cancer Cells
Ferhunde Aysin a,b*,Nihal Simsek Ozek a,b,Fatime Geyikoglu a, Kübra Koc a, Salim Cerig a
a Department of Biology, Ataturk University, 25240, Erzurum, Turkey b East Anatolian High Technology Research and Application Center (DAYTAM), Atatürk University, 25240, Erzurum, Turkey * E-mail: [email protected]
Histone deacetylase inhibitors (HDACi) have been proposed to enhance the cytotoxic effects of anticancer drugs in recent studies so they can be used in combination cancer therapy. However, the molecular mechanism of their action still remains unclear. Therefore, the present study was established to assess whether sodium butyrate (NaBu), one of the HDACi, enhance the disulfiram-induced cytototoxicity in breast cancer cells or not. Disulfiram was used since it has demonstrated anti-cancer effects in a wide range of cancer types including breast cancers. MCF7 cells were treated with NaBu, disulfiram or both. The inhibition of cell proliferation was monitored by MTT cytotoxicity assay. The macromolecular structural and contextual alterations in cellular molecules such as lipids, proteins and nucleic acids were determined by Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) Spectroscopy and quantitative spectral analysis. Based on the spectral changes, hierarchical cluster (HCA) and principal component analysis (PCA) were performed to differentiate the studied groups. The proliferation of cells treated with both disulfiram and NaBu demonstrated two-fold decrease with respect to the cells treated with disulfiram only. Spectral results indicated the alterations in the concentrations of lipid, protein and nucleic acids and also membrane fluidity in both agents treated cells in comparison to the control and disulfiram treated cells. Moreover, the succesfull clustering of the studied groups were obtained from both HCA and PCA. The results of the present work offers that NaBu can be used as chemotheurapeutic adjuvant in chemotherapy to lower therapeutic doses and reduction of the adverse side effects of the chemotherapeutic agents.
Keywords: Sodium butyrate, disulfiram, breast cancer, ATR-FTIR spectroscopy
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OP05 - In vitro Antidiabetic Activity of Elaeagnus angustifolia L. and Its Active Compounds
Hafize Yuca a, Hilal Özbek a, Cavit Kazaz b, Zühal Güvenalp a
a Department of Pharmacognosy, Faculty of Pharmacy, Atatürk University, 25240 Erzurum, Turkey b Department of Chemistry, Faculty of Science, Atatürk University, 25240 Erzurum, Turkey *E-mail: [email protected]
Elaeagnus angustifolia L. (Elaeagnaceae) is known as “Kuş İğdesi” in Turkey [1]. Its leaves are used as antidiabetic as well as flowers and leaves as diuretic and antipyretic in Turkish folk medicine [2,3]. According to previous studies, its extracts were found to have β-carboline alkaloids, polysaccharides, esters, flavonoids, phenols, phenolic acids, ketones, phenyl ethers, steroids, terpenes; and possessed antimicrobial, insecticidal, antioxidant, anti-arthritic, wound healing, cardioprotective, hypolipidemic, antinociceptive, anti-inflammatory, antimutagenic, gastroprotective and antitumor activities in vivo and in vitro [4]. In the present study, the methanol extract and its different polarity fractions (n-hexane, dichloromethane, ethyl acetate, n-butanol) prepared from leaves of E. angustifolia were evaluated for in vitro α-glucosidase and α- amylase inhibitory activities [5,6]. The ethyl acetate fraction showed the best α-glucosidase inhibitory activity with 90.1% (IC50=0.0912 mg/mL) when compared with the standard compound acarbose that displayed 7.0% inhibitory activity (IC50=4.2839 mg/mL) at 200 µg/mL concentration. For isolation of compound(s) responsible for activity, the fractions of ethyl acetate extract were evaluated and showed 30- 50% inhibitory activity at the same concentration. A known flavonoid: trans-tiliroside (EAE-1) with a new one: isorhamnetin-3-O-β-D-glucopyranosyl-7-O-[2,6-dimethyl-6-hydroxy-2,7-octadienoyl-(1→4)]-α-L- rhamnopyranoside (EAE-2) were isolated from these fractions which were identified by means of spectral methods. Also, EAE-1 showed 41.7% (IC50=0.2382 mg/mL) and EAE-2 showed 25.9% (IC50=0.4400 mg/mL) inhibitory activities at the same concentration. However, the extracts showed no inhibition against α-amylase.
Keywords: Elaeagnus angustifolia, antidiabetic, in vitro, isolation, NMR
References: 1. McKean DR, Davis PH (ed). Elaeagnus L. Flora of Turkey and the East Aegean Island, Edinburg University Press, UK, 1982;7:533-534. 2. Arıtuluk ZC, Ezer N. Halk arasında diyabete karşı kullanılan bitkiler (Türkiye)-II. Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi. 2012;32(2):179-208. 3. Baytop T. Türkiye’de Bitkiler ile Tedavi- Geçişte ve Bugün, Nobel Tıp Kitabevleri, İstanbul. 1999;244. 4. Farzaei MH, Bahramsoltani R, Abbasabadi Z, Rahimi R. A comprehensive review on phytochemical and pharmacological aspects of Elaeagnus angustifolia L. Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology. 2015;67:1467-1480. 5. Tao Y, Zhang Y, Cheng Y, Wang Y. Rapid screening and identification of α-glucosidase inhibitors from mulberry leaves using enzyme-immobilized magnetic beads coupled with HPLC/MS and NMR. Biomedical Chromatography. 2013;27:148-155. 6. Nampoothiri SV, Prathapan A, Cherian OL, Raghu KG, Venugopalan VV, Sundaresan A. In vitro antioxidant and inhibitory potential of Terminalia bellerica and Emblica officinalis fruits against LDL oxidation and key enzymes linked to type 2 diabetes. Food and Chemical Toxicology. 2011;49(1):125-131.
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OP06 - In-vitro Antifungal Activities of Fluconazole, Quince Leaf and Green Tea Extracts Against Candida Species Isolated From Blood Cultures
Hayrunisa Hanci a*, Mehmet Veysel Coskun b, Muhammet Hamidullah Uyanik c, Selma Sezen d, Hakan Igan e
a. Atatürk University, Faculty of Pharmacy, Department of Pharmaceutical Microbiology, 25240, Erzurum, Turkey. b. Gümüshane State Hospital, Department of Microbiology, Gümüshane, Turkey c. Ataturk University, Medical Faculty, Department of Medical Microbiology, Erzurum, Turkey. d. Department of Biology, Faculty Science, Ataturk University, Erzurum, Turkey e. Palandöken State Hospital, Department of Microbiology, Erzurum, Turkey *E-mail:[email protected]
The increased incidence of Candida infections and the emergence of antifungal resistant strains have led to the importance of antifungal studies. There are many plants traditionally used for treatment because of their antimicrobial properties[1]. In this study in- vitro antifungal activities of fluconazole (antifungal agent), green tea and quince leaves were investigated against Candida species isolated from blood cultures. Fifty Candida isolates from Atatürk University Hospital Medical Microbiology Laboratory icluded to this study (37 Candida albicans, 7 Candida parapisilosis and 6 other species). Quince and green tea leaves were collected from Tortum/Erzurum and Rize in their appropriate season. Broth microdilution method was applied using L-glutamine, bicarbonate free, RPMI 1640 according to CLSI M27-A3 recommendations [2]. Fluconazole minimum inhibitory concentration (MIC) values were evaluated according to the CLSI M27- S4 limit values [3]. Since there is no standard MIC values for quince leaf and green tea extracts, MIC values were evaluated like fluconazole. Three Candida strains were resistant to fluconazole (MIC: 16 μg/mL). For all strains, MIC50 and MIC90 values for fluconazole were found to be 0.125 μg / mL, 0.25 μg / mL respectively. In the study with green tea, all strains were found to have MIC50: 0.125 μg/mL, MIC90: 64 μg/mL and MIK50 / MIK90 values of 0.125 μg/mL for quince leaves. MIC50 and MIC90 values for C. albicans strains for green tea were 0.125 μg/mL and 2 μg/mL, respectively; And 0.125 μg/mL and 64 μg/mL for C. parapsilosis, respectively. The MIC50 and MIC90 values for quince leaves in C. albicans strains were 0.125 μg/mL and 0.125 μg/mL, respectively; And 0.125 μg/mL and 64 μg/mL for C. parapsilosis, respectively. Overall results indicate that quince leaf and green tea extracts have antifungal effects. As a result, we believe that studies concerning natural products should be increased in the combat against challenges due to the resistance to antimicrobial agents in the treatment of infections.
Keywords: Antifungal effect, Green tea, Quince leaf
References:
1. Ning Y, Ling J, Wu CD. Synergistic effects of tea catechin epigallocatechin gallate and antimycotics against oral Candida species. Archives of Oral Biology. 2015; 60: 1565–1570. 2. Clinical and Laboratory Standards Institute (CLSI). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard M27-A3. CLSI, Wayne PA, USA. 2008. 3. Clinical and Laboratory Standards Institute (CLSI). Reference Method for Broth Dilution Antifungal Susceptbility Testing of Yeasts; 4th Informational Supplement, M27-S4. CLSI, Wayne PA, USA. 2012.
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OP07 - The Cytotoxic Effects of Parietin on HepG2 Hepatocellular Carcinoma Cells
Alper Kürsat Demirkaya a*, Gülşah Gündoğdu b, Yavuz Dodurga c
aDepartment of Food Processing, Vocational School, Bilecik Seyh Edebali University, Bilecik, Turkey bDepartment of Physiology, Faculty of Medicine, Atatürk University, Erzurum, Turkey cDepartment of Medical Biology, Faculty of Medicine, Pamukkale University, Denizli, Turkey E-mail*: [email protected]
Hepatocellular carcinoma (HCC) originating from liver cells is the fifth most common malignant cancer and the third leading cause of cancer-related death. Parietin has an anthraquinone chemical structure and is isolated from ışkın (Rheum ribes L.). It has various pharmacological activities such as antimicrobial, antiinflammatory, hepatoprotective effect, antioxidant and anticancer properties. Cytotoxicity and genotoxicity tests have an important role in the assessment of heritable and carcinogenic risks. The aim of this study was to investigate the cytotoxic and genotoxic effects of parietin on HepG2 hepatocellular Carcinoma Cells. Hep G2 cells were cultured in appropriate culture medium.They were transferred to 96- well plates and were incubated at 24 hours. Then, different concentrations of parietin (final concentrations in the well to be 25-1000 µM) were added into the medium and the cytotoxic effect on Hep G2 cell line was measured by using XTT method according to time and dose dependent manner. At the same time, its genotoxic effect was determineted by using the comet assay. The obtained data were statistically evaluated by Student's t-test. The IC50 concentration of parietin was detected as 25 µM at the 48 th hour in HepG2 cells. According to the comet assay, there was no statistically significant increase DNA tail lenght, DNA tail intensity and DNA tail moment in parietin treated cell groups with respect to control group (p>0.05). In this study, it has been shown that parietin has cytotoxic at low dose, but has not genotoxic effect in Hep- G2 cells, and as a result parietin was found to be useful in combination with other drugs in the treatment of HepG2 Hepatocellular Carcinoma Cells. However, this effect of parietin should be supported by further studies.
Keywords: Parietin, Hep G2 cell, Comet assay
References: 1. Backorová, M., et al., Variable responses of different human cancer cells to the lichen compounds parietin, atranorin, usnic acid and gyrophoric acid, Toxicology in Vitro, 25, 2011, 37–44. 2. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics. CA Cancer J Clin 55:74–108
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OP08 - Synthesis of Some New 1-Phenyl/1-(4-chlorophenyl)-2-(1H-triazole-1- yl)ethanol Ester Derivatives and Evaluation of Their Anticonvulsant and Antimicrobial Activities
İnci Selin Doğana*, Zeynep Özdemirb, İrem Bozbeyb, Didem Kartc Arzu Karakurtb, Selma Saraç Tarhand
a Karadeniz Technical Uni., Faculty of Pharmacy, Department of Pharmaceutical Chemistry, b Inonu Uni., Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Malatya, c Hacettepe Uni., Faculty of Pharmacy, Department of Pharmaceutical Microbiology, d Hacettepe Uni., Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ankara *E-mail: [email protected], [email protected]
Epilepsy is a common neurological disorder which shows different symptoms depending on the affected different parts of the brain and usually characterized spontaneously seizures (1). Antiepileptic drugs used for the treatment of symptomatic epilepsy, have ureid structure classically, in recent years antiepileptic compounds containing various amide, oxime ether and oxime ester functional groups have been designed (1,2). One of these group is (arylalkyl)azoles; as a prototype, nafimidone and denzimol, have an aryl group, an imidazole ring, and an interface between the two ring chain (1-4). (Arylalkyl)azole group anticonvulsant compounds are structurally similar to antifungal azole drugs, have a wide spectrum of activity, show both topical and systemic effects (3,4). In this study, we prepare new compounds with (arylalkyl) azole structure; ester derivatives of 1-phenyl/4- chlorophenyl-2-(1H-triazol-1-yl)ethanol (28 compounds, 4a1-14 and 4b1-14). 24 of them new compounds and 1 of them (compound 4a1) is represented in the literature (5); 3 of them (compounds 4a9, 4a11, 4a13) have Chem.number but no literature data. The compounds have been synthesized according to the reaction pathways given below (2-4). The structures confirmed through IR, 1H-NMR, 13C-NMR and LC-Ms spectral data analysis. The anticonvulsant activities of the compounds were determined according to National Institute of Health (NIH) Anticonvulsant Drug Development (ADD) program by maximal electroshock seizure (MES) and subcutaneous metrazole seizure (ScM) tests. Rotorod toxicity test was performed for the neurological deficits. Antimicrobial activity of the compounds was determined by microdilution method. O OH O C R' CH N R'-COOH CH N CH2 N CH2 N . HCl R N R N
R: H, 4-Cl Compounds (4a1-14 and 4b1-14)
R' : -CH3, -C2H5, -C3H7, -C4H9, -CH2CH(CH3)2,, -CH2CH2COCH3, -CH=CHCH=CHCH3, -CH2C6H5, - CH2CH2CH2C6H5, -CH2CH2COC6H5, -CH=CH-C6H5,-C6H11, -C6H5, -C6H4-C6H5 Keywords: 1-Phenyl/1-(4-chlorophenyl)-2-(1H-triazole-1-yl)ethanol esters, (arylalkyl)triazole, anticonvulsant activity, antimicrobial activity. References: 1. Malawska, B. New anticonvulsant agents. Curr Top Med Chem. 2005; 5294(1), 69-85. 2. Walker, K.A., Wallach, M.B., Hirschfeld, D.R. 1-(Naphthylalkyl)-1H-imidazole derivatives, a new class of anticonvulsant agents. J Med Chem. 1981; 2445(1), 67-74. 3. Doğan, İ.S., Saraç, S., Sarı, S., Didem Kart, Şebnem Eşsiz Gokhan, İmran Vural, Sevim Dalkara. New azole derivatives showing antimicrobial effects and their mechanism of antifungal activity by molecular modeling studies, Eur. J. of Med. Chem. 130 (2017) 124-138. 4. Karakurt, A., Dalkara, S., Ozalp, M., Ozbey, S., Kendi, E., Stables, J.P. Synthesis of some 1-(2-naphthyl)-2-(imidazole-1- yl)ethanone oxime and oxime ether derivatives and their anticonvulsant and antimicrobial activities. Eur J Med Chem. 2001; 3653(5), 421-433. 5. Balasubramanyan, S., Shephard, M.C. 1,2,4-Triazole-containing compounds and their use as pesticides. US 4086351 A, 25 Nis 1978, Patent. Acknowledgement: This study was supported by TUBITAK Fund (114S862).
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OP09 - Histopathological Effects of Naringenin on Vancomycin-induced Nephrotoxicity in Rats Kezban Kibar a, Zuhal Uçkun b*, Sevda Güzel c, Banu Coşkun Yılmaz a
a Mersin University, Faculty of Medicine, Department of Histology and Embryology TR33169, Yenisehir, Mersin, Turkey bMersin University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, TR33169, Yenisehir, Mersin, Turkey cMersin University, Faculty of Pharmacy, Department of Pharmacognosy, TR33169, Yenisehir, Mersin, Turkey, *E-mail: [email protected]
Vancomycin (VCM), a glycopeptide antibiotic, is widely used for the treatment of infectious diseases caused by methicillin-resistant Staphylococcus aureus (MRSA) [1]. The most common adverse effect of VCM is nephrotoxicity that may limit its dose and duration of administration [2]. Naringenin (NAR), a naturally occurring plant bioflavonoid, has powerful free radical scavenging properties [3]. The purpose of this study was to examine the effects of naringenin (NAR) on vancomycin (VCM)-induced nephrotoxicity in rats histopathologically. Approval for the study was obtained from the Animal Experiments Local Ethics Committee in Mersin University (2016/HADYEK/E.98180). Adult male Wistar rats were randomly divided into seven groups, as follows: (i) Control group: saline was injected intraperitoneally (i.p.) at a dose of 2.0 ml for 8-day, (ii) Carboxymethyl cellulose (0.5% CMC) group: CMC was administered orally at a dose 2.0 ml gavage for 8-day, (iii) VCM group: VCM was injected at a dose of 400 mg/kg i.p. for 7-day, (iv) NAR group: NAR suspended in CMC was administered orally at a dose of 100 mg/kg for 8-day. VCM plus NAR25 (v), NAR50 (vi), and NAR100 (vii) groups: VCM plus NAR administered orally at a dose of 25, 50, and 100 mg/kg for 8-day, respectively. On 9th day, all the rats were sacrificed under anesthesia. The kidneys were fixed in 10% formaldehyde, sampled and embedded in paraffin for light microscopic evaluation. Tissues were stained with hematoxylin and eosin (H&E). During the histopathological examinations, tubular epithelial alterations (dilatation, vacuolization, necrosis, atrophy and casts), interstitial infiltration, and glomerular alterations were detected and scored. All histopathological parameters were graded as follows: (–) no meaningful histopathological damage; (+) mild degree of damage; (++) moderate degree of damage and (+++) severe degree of damage. As a result, VCM administration caused histopathologically pronounced damage in the kidneys.The improvement of these histopathological damages was observed in the VCM plus NAR treated groups.
Keywords: Vancomycin, naringenin, nephrotoxicity, rats.
References: 1. Basarslan F, Yilmaz N, Ates S, Ozgur T, Tutanc M, Motor VK, Arica V, Yilmaz C, Inci M, Buyukbas S. Human and Experiment Toxicology. 2012; 31(7): 726–733. 2. Oktem F, Arslan MK, Ozguner F, Candir O, Yilmaz HR, Ciris M, Uz E. 2005;Toxicology, 215: 227–233. 3. Renugadevi J, Prabu SM. Naringenin protects against cadmium-induced oxidative renal dysfunction in rats. Toxicology. 2009; 256:128–134.
Acknowledgement: This study was supported by the Research Fund of Mersin University in Turkey with Project Number 2016-2-AP3-1906
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OP10 - Determination the Correlation between Serum Adropin Level and Hemorheological Parameters in Knee Osteoarthritis Patients
Köksal Gündogdu a,Gülşah Gündogdub, Fatma Demirkaya –Miloğluc
aDepartment of Orthopedics and Traumatology, Erzurum Regional Training and Research Hospital, Erzurum, Turkey bDepartment of Physiology, Faculty of Medicine, Atatürk University, Erzurum, Turkey
cDepartment of Analytical Chemistry, Faculty of Pharmacy, Atatürk University, Erzurum, Turkey E-mail: [email protected]
Osteoarthritis (OA), most commonly seen in the knee joint, characterized by progressive joint cartilage loss and joint pain. The most common risk factors of the disease are aging, obesity, trauma and inflammation. Recent studies have shown that inflammation plays a critical role in the pathogenesis of OA. Hemorheological parameters are a simple, noninvasive and cost-effective marker of inflammation in various systemic diseases. Adropin, mainly in liver and brain, is relatively newly discovered a peptide hormone [1-3].The aim of the present study was to determine the correlation between serum adropin level and hemorheological parameters in knee OA patients. This study was enrolled 60 patients aged 45-75 years old with knee OA (have not been diagnosed with secondary arthrosis causes the traumatic arthritis, rheumatic diseases such as suppurative and rheumatoid arthritis, hip OA, metabolic disease, knee arthroscopic surgery within the last 6 months, bilateral or unilateral knee replacements, knee joint trauma and histories of glucocorticoid and/or steroid hormones) and 30 healthy controls for routine checkup attending the department of orthopedics and traumatology policlinic of Erzurum Regional Training and Research Hospital. K-L grading was done according to the antero-posterior and lateral radiography. Blood samples were taken in both groups. White blood cell (WBC) and blood neutrophil-lymphocyte ratio (NLR) were recorded and the adropin level was measured by using ELISA method. The obtained data were evaluated statistically. There were no significant differences observed because of age, gender, WBC and NLR in knee OA patients when compared with healthy control. According to the K-L grading scale in the patients group, mean blood NLR of K-L grade 4 was significantly increased compared with the other grades (p<0.05). Serum adropin level was statistically significant negatively correlated with blood WBC and NLR (p<0.05). In present study, determination of negative correlation between blood WBC and NLR with serum adropin levels in knee OA patients and NLR increased in severity knee OA. It can be used by clinicians as new parameters in the pathogenesis and diagnosis of knee OA. Keywords: Knee OA, adropin and blood neutrophil-lymphocyte ratio
Referances: 1. Bondeson J, Bloom AB, Wainwright S, Hughes C, Caterson B, van den Berg WB (2010) The role of synovial macrophages and macrophage produced mediators in driving inflammatory and destructive responses in osteoarthritis. Arthritis Rheum 62(3):647–57 2. Buyukkaya E, Karakas MF, Karakas E, Akcay AB, Tanboga IH, Kurt M, Sen N (2014) Correlation of neutrophil to lymphocyte ratio with the presence and severity of metabolic syndrome. Clin Appl Thromb Hemost 20(2):159–63 3. Ganesh Kumar K, Zhang J, Gao S, et al. (2012) Adropin deficiency is associated with increased adiposity and insulin resistance. Obesity (Silver Spring).20: 1394-1402.
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OP11 - Efficiency of Inula helenium Extracts nn Activity of APEX1 in Human Glioma Cell Lines
Kubra Koca*, Fatime Geyikoglua, Salim Ceriga, Ferhunde Aysina, Nihal Simsek Ozeka
aDepartment of Biology, Faculty of Science, Ataturk University, Erzurum, TURKEY
*E-mail: [email protected]
Inula helenium is the plant species widely used for treatment of various diseases in the form of herbal tea in folk medicine. Although the antioxidant and antiproliferative properties of root extracts and the specific compound from extracts of this plant has been demonstrated in previous studies, anticancer activities of the aerial parts of the plant has not been yet investigated on human brain cancer.Therefore, in this study, antioxidant and anti-proliferative effects of aqueous extract prepared from the aerial parts of I. helenium against human glioblastoma cell line (U-87 MG) were evaluated at in vitro experiment conditions. For this purpose, the aqueous extracts were applied to healthy and cancerous cell lines at varying concentrations of 0-500 mg/L. Cell viability and cell membrane damage were determined using 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) test for 48 hours. TOS (total oxidative status) and TAC (total antioxidant capacity) levels were also measured to determine oxidative stress. Besides, apurinic/apyrimidinic endonuclease 1 (APEX1) test and immunohistochemical 8-hydroxy-2′- deoxyguanosine (8-OHdG) staining were performed to detect DNA damage on samples from cultures. It has been determined for the first time that aqueous extracts of I. helenium in the brain tumor cells show antiproliferative effect depending on the dose given. Moreover, extracts decreased APEX1 levels depending on the increase in concentration on glioma cells. On the other hand, when looking at the effects on healthy cells, it has been found that it increased the level of TAC and that this plant was reliable, but that it should be used with caution in increasing doses. The results of present research is the basis for the use of I. helenium aerial parts as an alternative to chemotherapeutic drugs used in the treatment of brain cancer and having more side effects.
Keywords: Inula helenium, U-87 MG cell line, aqueous extracts, APEX1, oxidative stres.
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OP12 - Synthesis and In Vitro Anticancer Activity of Novel 6,8,9-Trisubstituted Purine Analogs
M. Fatih Polat a, Meral Tuncbilek b*, Irem Durmaz c, Rengul Cetin Atalay d
a Department of Analytical Chemistry, Faculty of Pharmacy, Erzincan University, 24100 Erzincan, Turkey b Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06100 Ankara, Turkey c Department of Molecular Biology and Genetics, Bilkent University, 06800 Ankara, Turkey d Bioinformatics Department, Graduate School of Informatics, Middle East Technical University, 06800 Ankara, Turkey *E-mail: [email protected]
Cancer is one of the most important causes of death in the world with millions of people dying of cancer every year. Therefore, the development of new potent anticancer drugs that enable more selective treatment strategies is very important. Nucleobase and nucleoside analogs are significant drugs used in chemotherapy for the treatment of solid tumors and hematological malignancies1. For more than six decades, drugs in purine structure, 6-mercaptopurine and 6-thioguanine have been used as inhibitors of nucleic acid metabolism in pediatric acute lymphoblastic leukemia. In the present work, we report on the synthesis and in vitro cytotoxic activity of 9-cyclopentyl-8-[4-(methyl/trifluoromethyl)phenyl]-6-(4-phenylpiperazin-1- yl)-9H-purine derivatives against selected human cancer cell lines. The synthesis of the compounds 6-19 were carried out starting from commercially available 4,6-dichloro-5-nitropyrimidine in four steps. The newly obtained compounds were first evaluated for their anti-tumor activities against human liver (Huh7), colon (HCT116) and breast (MCF7) carcinoma cell lines. The IC50 values were in micromolar concentrations with 6,8,9-trisubstituted purine derivatives. Time-dependent IC50 values for each molecule were also calculated in comparison with known cytotoxic agents Camptothecin (CPT), 5-Fluorouracil (5- FU), Cladribine, Fludarabine and Pentostatine. N6-(phenyl)/(4-methoxyphenyl)/(4-fluorophenyl), 8-(4- trifluoromethylphenyl derivatives 13, 16, 17 displayed the best cytotoxic activity with IC50 values of 7.6- 8.6 µM against Huh7 cell line. The N6-(4-trifluoromethylphenyl)/(4-methoxyphenyl)/(3,4- dichlorophenyl), analogs 15, 16, 19 were also very active (IC50= 5.2-7.2 μM) against MCF7 cell line. Furthermore, compound 16 had a better cytotoxic activity than the known cell growth inhibitors 5-FU, Fludarabine and Pentostatine on Huh7 and MCF7 cells.
Keywords: Trisubstituted, purine, synthesis, anticancer, activity
References: 1.Karran, P. Thiopurines, DNA damage, DNA repair and therapy-related cancer. Br. Med. Bull. 2006, 79−80, 153−170.
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OP13 - Synthesis, Structural Characterization, in Vitro Cytotoxicities, and FS-Dsdna Binding Studies of Metal Based Compound of Methotrexate
Mustafa Çeşme a,c*, Ayşegül Gölcü b
a Department of Chemistry, Faculty of Art and Sciences, Kahramanmaras Sutcu Imam University, 46040, Kahramanmaras, Turkey. bDepartment of Chemistry, Faculty of Arts and Sciences, Istanbul Technical University, Maslak, 34469, Istanbul cAfsin Vocational High School, Kahramanmaras Sutcu Imam University, 46500, Kahramanmaras, Turkey. *E-mail: [email protected]
In the present study we aimed to obtain novel metal-based drug molecules as alternatives to the current metal-based anticancer drugs. Therefore, in the context of the work, Cu(II), Zn(II) and Pt(II) metal based compounds of pharmaceutically active compounds, effective antineoplastic Methotrexate (MTX) were synthesised and their structures were elucidated by analytical, spectroscopic and thermal methods. The interaction of the obtained compounds with FS-dsDNA was examined by DPV technique using pencil graphite electrode and uv-vis1. All metal-based compounds synthesized and anticancer activities of MTX active agent were studied on He-La and C6 cell cultures. In all experiments, cell suspensions containing an average of 20000 cells were used and measurements were made at four different concentrations (100, 50, 10, 1 μg / ml) on the xCELLIGENCE system2. Metal-based compounds and anticancer activities of MTX have been compared with compounds such as cisplatin, carboplatin, and oxaliplatin used in cancer treatment. Experimental designs were monitored every half hour over 48 hours and the results were analyzed over anticancer activities of compounds at 12, 24, 36 and 48 hours (Fig.1).
Fig.1. Cell index diagram on He-La cell line
Keywords: Metal based drugs, Methotrexate, Drug-DNA interaction, xCELLigence, anticancer
References: 1. Çeşme M, Gölcü A, Demirtaş I. New metal based drugs: Spectral, electrochemical, DNA-binding, surface morphology and anticancer activity properties. Spectrochim Acta - Part A Mol Biomol Spectrosc 2015; 135: 887–906. 2. Urcan E, Haertel U, Styllou M, et al. Real-time xCELLigence impedance analysis of the cytotoxicity of dental composite components on human gingival fibroblasts. Dent Mater 2010; 26: 51–58.
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OP14 - Synthesis, Structure Elucidation and Biological Activities of Some Novel 4(3H)-Quinazolinones as Anti-Biofilm Agents
Sevgi Karakuşa*, Sevda Türka, Seyhan Ulusoyb, Gülgün Bosgelmez-Tınazc
aDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, İstanbul, Turkey bDepartment of Biology, Faculty of Arts and Sciences, Süleyman Demirel University, Isparta, Turkey cDepartment of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Marmara University, İstanbul, Turkey *E-mail: [email protected]
In this research, a new series of substituted-4(3H)-quinazolinones were synthesized and tested for their quorum sensing inhibitory (QSI) capacity using quorum sensing inhibitor selector 1 (QSIS1) bioassay [1]. QS system has been shown to control production of an array of extracellular virulence factors and the formation of biofilm in a variety of bacterial pathogens including Pseudomonas aeruginosa [2]. In the present study, we investigated anti-biofilm effects of 4(3H)-quinazolinone derivatives. Our results showed that these molecules inhibited biofilm formation by 20-32% at 12,5 µM concentration. The obtained results suggest that the newly synthesized molecules may procure a starting point for the design and development of new drugs that can be used for combatting biofilm associated infection caused by clinically important human pathogens.
Keywords: 4(3H)-Quinazolinones, synthesis, structure elucidation, Pseudomonas aeruginosa, quorum sensing
References: 1. Jatav V, Mishra P, Kashaw S, Stables JP. Synthesis and CNS depresassant activity of some novel 3-[5- substituted-1,3,4-thiadiazole-2-yl]-2-styrylquinazoline-4(3H)-ones. European Journal of Medicinal Chemisty 2008; 43: 135-141. 2.Hentzer M, Givskov M. Pharmacological inhibition of quorum sensing for the treatment of chronic bacterial infections. The Journal of Clinical Investigation. 2003; 112: 1300-1307.
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OP15 - A novel approach to contrast-induced nephrotoxicity: the melatonergic agent agomelatine
Adem Karamana , Busra Diyarbakirb , Irmak Durur-Subasic , Duygu Koseb , Asli Özbek-Bilginb , Atilla Topcud , Cemal Gundogdue , Afak Durur-Karakayaf , Zafer Bayraktutang and Fatih Alpera a Department of Radiology, Faculty of Medicine, Ataturk University, Erzurum, Turkey b Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey c Department of Radiology, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey d Department of Pharmacology, Faculty of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey e Department of Pathology, Faculty of Medicine, Ataturk University, Erzurum, Turkey f Department of Radiology, Istanbul Medipol University, Istanbul, Turkey g Department of Biochemistry, Erzurum Regional Training and Research Hospital, Erzurum, Turkey
To study the potential nephroprotective role of agomelatine in rat renal tissue in cases of contrast- induced nephrotoxicity (CIN). The drug's action on the antioxidant system and proinflammatory cytokines, superoxide dismutase (SOD) activity, levels of glutathione (GSH) and malondialdehyde (MDA) and the gene expression of interleukin-6 (IL-6), tumour necrosis factor (TNF)-α and nuclear factor kappa B (NF- κB) was measured. Tubular necrosis and hyaline and haemorrhagic casts were also histopathologically evaluated.
The institutional ethics and local animal care committees approved the study. Eight groups of six rats were put on the following drug regimens: Group 1: healthy controls, Group 2: GLY (glycerol), Group 3: CM (contrast media—iohexol 10 ml kg−1), Group 4: GLY+CM, Group 5: CM+AGO20 (agomelatine 20 mg kg−1), Group 6: GLY+CM+AGO20, Group 7: CM+AGO40 (agomelatine 40 mg kg−1) and Group 8: GLY+CM+AGO40. The groups were evaluated by one-way analysis of variance and Duncan's multiple comparison test.
Agomelatine administration significantly improved the serum levels of blood urea nitrogen (BUN) and creatinine, SOD activity, GSH and MDA. The use of agomelatine had substantial downregulatory consequences on TNF-α, NF-κB and IL-6 messenger RNA levels. Mild-to-severe hyaline and haemorrhagic casts and tubular necrosis were observed in all groups, except in the healthy group. The histopathological scores were better in the agomelatine treatment groups.
Agomelatine has nephroprotective effects against CIN in rats. This effect can be attributed to its properties of reducing oxidative stress and inhibiting the secretion of proinflammatory cytokines (NF-κB, TNF-α and IL-6).
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OP16 - Increased Antioxidant activity After Exposure of CCI4 in Rat Lungs Toxicity Model
Gulsah Yildiz Deniza, Kubra Kocb, Fatime Geyikoglub, Salim Cerigb
aVocational School of Health Services, Ataturk University, 25240 Erzurum, TURKEY
aDepartment of Biology, Faculty of Science, Ataturk University, Erzurum, TURKEY
Corresponding author: Asst. Associate Professor. Gulsah Yildiz DENIZ, e-mail: [email protected]
Exposure to CCl4 induces oxidative stress and causes tissue damage by the induction of CCl4 free radicals. CCl4 has been shown to cause lung toxicity by intra-alveolar septal ruptures, interstitial cell degenerations, and fibrosis owing to accumulation of exaggerated neutrophils, fibroblasts, and macrophages in blood vessels. The aim of this study was to investigate the effect of Rheum ribes extract (RR) on lungs toxicity in rats. Forty-nine male Sraque dawley rats were divided equally into six groups (Control, CCI4, 150-300 mg/kg RR and CCI4+150 mg/kg RR-CCI4+300 mg/kg RR). The activity of antioxidant enzymes as superoxide dismutase (SOD) and glutathione peroxidase (GPx) was established in the lungs. immunohistochemical changes of lungs tissue were evaluated by using Cysteine-dependent aspartate- directed proteases 3 (Caspase-3) and 8-hydroxydeoxyguanosine (8-OhdG) methods. Administration of CCl4 caused a significant (p<0.01) decrease in the activities of antioxidant enzymes,. The alterations caused by CCl4 were significantly (p<0.01) reversed toward control levels by supplementation of RR. These results suggest that in rats RR could protect the lungs against CCl4-induced oxidative damage, this may be due to its effects of antioxidative results.
Key words: Lungs, Carbon tetrachloride, Rheum ribes, Antioxidant enzyme.
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OP17 - Synthesis and Cytotoxic Activities of Mannich Bases of Heterocyclic Chalcone Analogues
Sinan Bilginera*, Halise Inci Gula aAtaturk University, Faculty of Pharmacy,Erzurum, Turkey *E-mail: [email protected] Cancer is one of reasons of death after cardiovascular diseases [1]. Although several drugs are available in the market, they have several problems such as low selectivity and several side effects or gained resistance [1]. So there is an urgent need for new compounds with high selectivity. In this study, chalcone compounds 1-(4-hydroxyphenyl)-3-pyridin-2-yl-propenone (1, Series 1) and 1-(4-hydroxyphenyl)-3-pyridin-3-yl- propenone (3, Series 3) and their Mannich bases (MBs) (2a-f and 4a-e in Series 2 and Series 4, respectively) were synthesized to find new compounds with cytotoxic activity. Amine groups in MB were changed using different amines (dimethylamine (a), diethylamine (b), pyrrolidine (c), piperidine (d), N-methylpiperazin (e) and morpholin (f)) since different pKa values of the amine used may affect the cytotoxicity. MBs were synthesized by conventional heating (2d, 2f, 4a, 4b, 4c, 4d, 4e) or microwave irradiation (2a, 2b, 2c, 2e) methods with the yield of 15-77 % (Series 2) or 14-39 % (Series 4). The chemical structures of the compounds were confirmed by 1H NMR, 13C NMR and TOF-MS spectra. MBs were reported for the first time by our study. Cytotoxic activity of the compounds were tested against human HL-60 (promyelocytic leukemia cells), human HSC-2, HSC-3 and HSC-4 (oral cell carcinoma cells) cells by MTT method as described [2-4]. In addition, the cytotoxicity of the compounds were also tested against non malignant cells. Melphalan was used as the anticancer, reference drug. In conclusion, as expected, preparation of the MBs of chalcones was a useful modification in terms of cytotoxic activity. Keywords: Chalcone, Mannich bases, cytotoxicity References: 1. Palaska E. Antikanser İlaçlar. 2nd ed. Ankara: Hacettepe Üniversitesi Yayınları; 2004. 2. Bilginer S, Gul HI, Mete E, Das U, Sakagami H, Umemura N, Dimmock JR. 1-(3-aminomethyl-4-hydroxyphenyl)- 3-pyridinyl-2-propen-1-ones: a novel group of tumour-selective cytotoxins. J Enzyme Inh Med Chem. 2013; 28; 974–980. 3. Tugrak M, Gul HI, Sakagami H, Mete E. Synthesis and anticancer properties of mono Mannich bases containing vanillin moiety. Medicinal Chemistry Research. 2017;26;1528-1534. 4. Gul HI, Mete E, Eren SE, et al. Designing, synthesis and bioactivities of 4-[3-(4-hydroxyphenyl)-5-aryl-4,5- dihydro-pyrazol-1-yl] benzenesulfonamides. J Enzyme Inh Med Chem. 2017; 32:169-175.
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OP18 - Synthesis of 4-(2-(5,6-dimethoxy-1H-inden-1- ylidene)hydrazineyl)benzenesulfonamide and Its Structural Elucidation by NMRs
Mehmet Kocaa, Halise Inci Gula a Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey *Email: [email protected] Carbonic anhydrases (CAs, EC 4.2.1.1) are zinc (Zn2+)-containing metalloenzymes that catalyze the reversible 2 - + hydration of carbon dioxide (CO ) to bicarbonate (HCO3 ) and a proton (H ) (1).Carbonic anhydrase inhibitors (CAIs) has been used for the treatment of several diseases such as edema, glaucoma, hypertension, epilepsy, and cancer (2). It was reported that CAIs carring an indane ring and a primary sulfonamide moieties had carbonic anhydrase inhibitory activity at micromolar concentration (3). In this study, a new compound having the chemical structure of 4-(2-(5,6-dimethoxy-1H-inden-1-ylidene)hydrazineyl)benzenesulfonamide was synthesized and and its chemical structure was confirmed by 1H NMR and 13C NMR. A simulation system was built on the crystallographic structures of CA ( pdb: 1H9Q ) for predict binding mode of the compund with CA. The molecular modelling studies were performed via SurflexDock in Sybyl-X 2.0 by Tripos Associates. According to the simulation results, the molecule displayed multiple binding patterns with CA ( pdb: 1H9Q (figure1) which will be discused during the presentation.
Figure 1 : Predicted binding mode of the compund with CA (pdb: 1H9Q) 1. Blasie CA, Berg JM. Structure-based thermodynamic analysis of a coupled metal binding-protein folding reaction involving a zinc finger peptide. Biochemistry. 2002;41(50):15068-73. 2. Supuran CT. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat Rev Drug Discov. 2008;7(2):168-81. 3. Gul HI, Kucukoglu K, Yamali C, Bilginer S, Yuca H, Ozturk I, et al. Synthesis of 4-(2-substituted hydrazinyl)benzenesulfonamides and their carbonic anhydrase inhibitory effects. J Enzym Inhib Med Ch. 2016;31(4):568-73.
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OP19 - Effects of Some Pesticides on Some Carbonic Anhydrase Isoenzymes
İmdat Aygüla, Murat Şentürkb
aGümüşhane University, Health Science Faculty Gumushane, Turkey bAğrı İbrahim Çeçen University, Faculty of Pharmacy, Ağrı, Turkey
*E-mail: [email protected]
Pesticides are may be antimicrobial, disinfectant, biological factor, material or device utilised against pests. Some advantages can be achieved with the use of toxic drugs, but they are disadvantageous for the potential toxicity of many organisms [1]. Metaloenzymes carbonic anhydrase (CA) have been shown to play an important role in ion transport and in pH regulation in living organisms [2]. We report here the inhibitory capacities of some pesticides (Tebuconazole, propoxur, carbaryl, carbofuran, and atrazine) were investigated for the inhibition of human CA I, II and honey bee (Apis mellifera) (hbCA) enzymes were isolated by means of affinity chromatography. Inhibitory capacities of these pesticides on these CA isoenzymes activity were determined using p-nitrophenil acetate under in vitro conditions. These pesticides showed effective inhibition against these CA isoforms with IC50 values in the range of 3 to 42.4 nM. As a result, the inhibitory effects of these pesticides on the enzymatic activity of hCA I, II and hbCA isoenzymes were determined. The results indicate that among the five pesticides used in this study, these pesticides are widely used both at homes and in agricultural fields. This would lead to the increase in food insufficiency for increasing populations and cause disruption of ecological balance. Therefor, the usage of these chemical materials must be well controlled.
Keywords: Pesticides, carbonic anhydrase, inhibition.
References: 1. Ceyhun SB, Senturk M, Erdogan O, Kufrevioglu OI. Pesticide Biochemistry and Physiology. 2010;97:177- 181. 2. Supuran CT. Nature Review Drug Discovery. 2008;7:81-168.
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OP20 - Determination of Antioxidant Capacity PPO Enzyme Purified from Morchella Esculenta by ABTS and DPPH Methods
Fatma Özabacıgil Güra, Zerrin Kutlub, Bahri Gürc, Ayşe Türkhand, Mine Gülaboğlub, Yasemin OĞULe aDepartment of Medical Services and Techniques, Health Services Vocational School, Atatürk University, TR- 25240, Erzurum, Turkey bDepartment of Biochemistry, Faculty of Pharmacy, Atatürk University, TR-25240, Erzurum, Turkey cDepartment of Medical Services and Techniques, Health Services Vocational School, Iğdır University, TR-76000, Iğdır, Turkey dResearch Laboratory and Application and Research Centery, Iğdır University, TR-76000, Iğdır, Turkey eBiochemistry and Clinical Biochemistry Laboratory, Erzurum Regional Training and Research Hospital, TR- 25000, Turkey
The polyphenol oxidase enzyme (PPO, E.C.1.14.18.1) consists of two subunits. It has a copper element in its active center is a metalloenzym, belonging to the oxidoreductase group. It uses the phenolic compounds as substrate (Mayer, A.M., 2006). PPO enzyme catalyzes the conversion of monophenols to o-kines by a series of reactions in the presence of oxygen. Since the quinones that come to the end of the reaction are not stable, these kinons are converted to dark colored pigments as non-enzymatic reactions (Robb et al. 1984). These pigments adversely affect the sensory properties of the foods such as color, taste and odor. In this study, the PPO enzyme was purified from the edible fungus Morchella esculenta by cold acetone precipitation and affinity chromatography. Enzymes were 2.22 to 33.48 fold pure, respectively. Enzyme purity was shown by SDS-PAGE electrophoresis technique. Then, dilute extracts were prepared from stock solution of PPO enzyme and antioxidant capacity was measured by ABTS and DPPH methods. Both ABTS and DPPH methods were used to prepare reference samples at concentrations ranging from 1 to 40 μg / mL to determine the antioxidant capacity of the PPO enzyme. All measurements were performed in the Biotek Elisa Reader and the results were evaluated. The values of capacity to trolox antioxidant capacity at 30 μg / mL concentration of the extract were determined as 47.54% by the ABTS and 54.49% by the DPPH methods. According to the results, the antioxidant activity of the PPO enzyme purified from Morchella esculenta was determined by ABTS and DPPH methods
Keywords: Antioxidant capacity, ABTS, DPPH, Morchella esculenta, Polyphenol oxidase.
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OP21 - Assessment of Lipid Peroxidation and Protein Oxidation Parameters in Obese Children with Metabolic Syndrome
Ali Asci a, Derya Bulus b, Nesibe Andiran c, Belma Kocer-Gumusel d
aAtatürk University, Faculty of Pharmacy, Department of Toxicology, Erzurum, Turkey bMinistry of Health, Keçiören Training and Research Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey cNeorama Trade Center, Yaşam Street, No: 13 A, Ankara, Turkey dHacettepe University, Faculty of Pharmacy, Department of Toxicology, Ankara, Turkey *E-mail: [email protected]
The metabolic syndrome (MS) is a common and complex disorder combining obesity, dyslipidemia, hypertension, and insulin resistance. It is a primary risk factor for diabetes and cardiovascular disease. The prevalence of MS among children and adolescents is increasing in the worldwide. In children, it can be diagnosed with obesity and the presence of two or more other clinical features (ie elevated triglycerides, low HDL-cholesterol, high blood pressure, increased plasma glucose) according to International Diabetes Federation. The pathogenesis of the metabolic syndrome is multiple and still poorly understood. A number of studies indicate that oxidative stress may play an important role in the pathogenesis of metabolic diseases and in the progression of its complications. Oxidative stress occurs when the balance between antioxidants and ROS are disrupted. If cellular antioxidants do not remove free radicals, radicals attack and damage proteins, lipids, and nucleic acids. The objective of this study was to investigate the alterations in protein oxidation and lipid peroxidation parameters in obese children with MS. Thirty-one newly diagnosed obese children who fulfilled the diagnostic criteria for MS were included in the study. The control group (n = 30) was comprised of non-obese healthy individuals without any chronic diseases. Levels of the lipid peroxidation (MDA and F2-Isoprostane) and protein oxidation (protein carbonyl) products were determined. Anthropometric measurements and determinations of lipid and glucose profile parameters were performed. The homeostasis model assessment of insulin resistance (HOMA-IR) index was calculated to assess insulin resistance. Protein oxidation and lipid peroxidation markers were significantly higher in obese children compared to controls. Significant correlations were also found between parameters of lipid peroxidation and MS diagnostic criteria. Obese children with MS had signs of oxidative stress induced damage to lipids and proteins. These results might be indicative of early cardiovascular disease processes. Antioxidant treatment and life style changes are indicated for children with MS, as well as closer observation in order to assess the cardiovascular morbidity symptoms.
Keywords: Obesity, metabolic syndrome, MDA, F2-Isoprostane, protein carbonyl
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LIST OF ABSTRACT Abstract No and Title Page
PL01 - Advances in Treatment of Pulmonary Arterial Hypertension ...... 12 PL02 - Drug Therapy for Arterial Fibrillation; What’s New? ...... 13 PL03 - Clinical Trials in the Drug Development Process ...... 14 PL04 - Pharmacovigilance Activities in Turkey ...... 15 PL05 - Marketing Authorısatıon of Medicines in Turkey ...... 16 PL06 - Biological efficacy of SN-38 loaded PLGA-PEG-PLGA nanoparticles ...... 17 PL07 - Recent Advances in Regenerative Medicine: Plastic Surgery Perspective ...... 18 PL08 - Drug Delivery for Neuroprotection: Opportunities and Challenges ...... 19 PL09 - In Vitro Artificial Membrane-Natural Mucosa Correlation of Carvedilol Buccal Delivery ...... 20 PL10 - Pros and Cons of Using Tubular Nanostructures and Quantum Dots to Deliver Drug Molecules ...... 21 PL11 - The Overview of Commonly Used Electrochemical Carbon Nanosensors in Pharmaceutical Assay ...... 22 PL12 - Fundamental Analytical Studies for Pharmacological Analysis: Assessment of Lithium Bioavailability ...... 23 PL13 - Particular Size Determination of Aerosols Containing Salmeterol and Fluticasone ...... 24 PL14 - Investigations on some medical plants from Turkey and Northern Cyprus ...... 25 PL15 - Comparison of Predicted Physicochemical Properties and In Vitro Activity of Substituted Indolin-2-one Derivatives ...... 26 PL16 - Peptide Antibiotics Inspired from Natural Antimicrobial Peptides ...... 27 PL17 - New Advances in Mass Spectrometry-Based Glycoproteomics ...... 28 PL18 - Biocompatible and Second by Second Neurotransmitter Analyzing ...... 29 PL19 Drug Solubility Prediction in Water + Cosolvent Mixtures, Recent Progresses ...... 30 O 01 - Possible Protective Effects of Gossypinin on Rats Applied Renal Ischemia Reperfusion Damage ...... 32 O 02 - Cytotoxic Effect of Allomaltol Derivative on A375 Human Malignant Melanoma and MCF7 Breast Cancer Cells ...... 33 O 03 - Cytotoxic and Antioxidant Activities of a Chitin Derivate on Human Blood Cells ...... 34 O 04 - Association of Serum Omentin Levels with ST Segment Elevation and Non-ST Segment Elevation Acute Coronary Syndrome ...... 35 O 05 - Phenolic compounds from the leaves of Cotinus coggygria Scop. with alpha glucosidase inhibition ...... 36 O 06 - Effects of Hyoscyamus niger L. on myiasis disease caused by Lucilia sericata ...... 37 O 07 - Radiopharmaceuticals for Brain Imaging ...... 38 O 08 - Synthesis of Novel Sulfur-Containing Imidazolone Derivatives from Glycine Ester ...... 39 O 09 - Molecular Analysis of Effects of Chronic Simvastatin in Rat Sciatic Nerve and Liver Microsomal Membrane by FTIR Spectroscopy ...... 40 O 10 - In vitro Studies on Atenolol Loaded Ion Exchange Resins ...... 41 O 11 - The Effects of Tarantula Cubensis Extract in Rats with Polymicrobial Sepsis by Cecal Ligation and Puncture Method ...... 42
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O 12 - Design and In Vitro Evaluation of Bispecific Complexes and Drug Conjugates of Anticancer Peptide, LyP-1 in Human Breast Cancer ...... 43 O 13 – Effects of Heparin Derivatives on Experimental Pain and Inflammation Models in Rats ...... 44 O 14 - New Azoles in Oxime Ester Structure: Antifungal Susceptibility, ...... 45 Anti-Biofilm Activity, and Molecular Modeling Studies...... 45 O 15 - Leader Compound Optimization Studies On 1h-Benzimidazole Derivatives for Alzheimer Disease ...... 46 O 16 MCF-7 Breast Cell Proteome Analysis Determination with New UPLC/MS Method ...... 47 P01 - Inhibition Effect of 4-Methylbenzenesulfonamide Derivatives on Human Carbonic Anhydrase Isoenzymes (hCA I-II) ...... 49 P02 - Effects of Probucol on K562 Chronic Myelogenous Leukemia Cell line ...... 50 P03 - Effect of Glucagone-Like Peptide-1 on Diminished Corpus Cavernosum Function Induced by Chronic Methylglyoxal Administration in Rats ...... 51 P04 - Examination of Inhibition of Anticholinesterase Enzyme of Caliytagia Growing in Two Different Regions ..... 52 P05 - Synthesis of New Benzimidazole Derivatives and Evaluation of Their Anticholinesterase Activity ...... 53 P06 - The Effects of Surface Modifications of Gold Nanoparticles on Cytotoxicity and Intracellular Reactive Oxygen Species in Hepg2 Cells ...... 54 P07 - Preparation and Characterization of GST Inhibitor ETA-Loaded Nanoparticles for Targeting to Chemotherapeutic Resistant Cancer Cells...... 55 P08 - 1,5-Bis(4-hydroxy-3-(aminomethyl)phenyl)penta-1,4-dien-3-ones: Bis Mannich Bases as Anticancer Agents56 P09 - A LC-MS/MS Method for the Simultaneous Determination of Pronuciferine and Romerine in Some Papaver Species ...... 57 P10 - In Vitro Inhibitory Effects of Some Calcium Channel Blockers (CCBs) on Human CA I and CA II Activities ...... 58 P11 - Influence of Calcium Channel Blockers on Sheep Kidney Aldose Reductase Enzyme ...... 59 P12 - Antimicrobial Activities of Ferula Caspica and F. halophila Extracts ...... 60 P13 - Cytotoxic and Antioxidant Activities of a Chitin Derivate on Human Blood Cells ...... 61
P14 - The Role of Potassium Channels in The Relaxation Response of Intermedin/Adrenomedullin2 (IMD/AM2) in The Rat Pulmonary Artery ...... 62 P15 - Differential Pulse Voltammetric Determination of Terbinafine in Pharmaceuticals using Bromocresol Purple Modified Glassy Carbon Electrode ...... 63 P16 - Anticandidal Activity Screening of Novel Triazole Derivatives ...... 64 P17 - Synthesis and Anticholinesterase Activity of Novel Oxadiazole-Piperazine Derivatives...... 65 P18 - Phenolic Compounds from Pedicularis atropurpurea Nordm...... 66 P19 - Investigation of Reaction of Some Ester Ethoxycarbonyl Hydrazones with 1-Adamantyl Amine ...... 67 P20 - The Effect of Cetuximab on the Total Oxidative Status of HT-29 Cell Line ...... 68 P21 - Synthetic Protocol for Imidazo-1,4-Oxazines and Evaluation of Their Cytotoxicity and Genotoxicity with SAR ...... 69 P22 - Synthesis and Carbonic Anhydrase Inhibitory Activities of Some Novel Azafluorenone Derıvatıves ...... 70 P23 - Discovery of Novel Indeno-Pyridine Derivatives ...... 71 as Anticancer Agents ...... 71 October 05-07, 2017, ERZURUM-TÜRKİYE 204
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P24 - Effect of Sample Preparation Techniques for 2D Applications ...... 72 P25 - Comparison of HPLC and Spectrophotometric Methods on Determination of the pKa of Drugs ...... 73 P26 - A New HPLC Method for Determination of Naproxen in Human Plasma Samples ...... 74 P27 - Inhibition Effects of 2-Amino-3-Cyanoquinolin Derivatives on Carbonic Anhydrase I and II ...... 75 P28 - Investigation of Cholinergic Effects of Some Methanesulfonates ...... 76 P29 - Acetylcholinesterase In Vitro Inhibitory Effects of Tryptophan Based Natural Compounds ...... 77 P30 - White Root Basidiomycete Trametes versicolor: Safety, Antioxidant and Cytotoxic Activities ...... 78 P31 - Synthesis of Sensiline and its Aromatic Derivatives ...... 79 P32 - Synthesis of Isoindole-1,3-Dion derivatives ...... 80 P33 - Heterogeneous Fenton Process by Magnetite Nanostructures Prepared by High Energy Planetary Ball Mill for Ciprofloxacin Removal from Aqueous Solutions ...... 81 P34 - Application of Dispersive Liquid-Liquid Microextraction for the Determination of Donepezil in Urine by HPLC Using a Core-Shell Column ...... 82 P35 - Anticancer Effect of Ethanolic Extract and Isolated Coumarins from the Roots of Ferulago trachycarpa Boiss. (Apiaceae) on Cancer Cell Proliferation ...... 83 P36 - Anticancer Effect of Aqueous Extract of Ferulago trachycarpa Boiss. (Apiaceae) on Cancer Cell Proliferation ...... 84 P37 - Investigation of Cholinesterase Enzyme Inhibition Activity of 3 Barbarea Species ...... 85 P38 - A GC-MS Based Metabolomic Profiling of the Mouse Lung in Airway Inflammation ...... 86 P39 - The Role of Pharmacists in Rational Drug Use of Elderly Patients Who Apply to Community ...... 87 P40 - Elevated Glutathione S-Transferase- π (GST- π) Activity in Mesenchymal Phenotype of Human Colorectal Adenocarcinoma Cells (HT-29) ...... 88 P41 - Use of Electronic Impedance Spectroscopy to Monitor Inhibition of Biofilm Formation in Pseudomonas Aeruginosa ...... 89 P42 - The Investigation of Potential Protective Effects Of Curcumin Against Hearth Toxicity Induced by Irinotecan in Rats ...... 90 P43 - A Facile Synthesis of Enamines with 1,4-Dimethoxy-2-butyne Mediated by Titanium Tetrachloride...... 91 P44 - New Chromane-Thiazoles as Potent Anticancer Agents ...... 92 P45 - In vitro Antidiabetic Activity of Elaeagnus angustifolia L. and Its Active Compounds ...... 93 P46 - Nesfatin-1 Has a Protective Effect against Isoproterenol-Induced Myocardial Infarction in Rats...... 94 P47 - Screening for Cytotoxic Effects of Chlorokojic Acid Derivatives ...... 95 P48 - Simultaneous Determination of Arbutin and Hydroquinone in Different Herbal Slimming Products by Gas Chromatography-Mass Spectrometry ...... 96 P49 - Synthesis and Evaluation of Antidepressant Activity of Some Novel Naphtyl Etanone Oxime Ester Derivatives Bearing Pyrazole Moiety ...... 97 P50 - New Chromane-Thiazoles as Potent Anticancer Agents ...... 98 P51 - Determination of Antioxidant Capacity of Ether Extract of Myrtus communis L. Leaf via DPPH and ABTS/TEAC Methods...... 99 P52 - Synthesis, Molecular Modeling and Biological Evaluation of ...... 100
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4-[5-aryl-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl] benzenesulfonamides ...... 100 P53 - Monoamine Oxidase Inhibitory Potential of New Chalcone Derivatives Containing Piperazine Ring ...... 101 P54 - Novel Mannich Bases Derived From 1,2,4-Triazole-5-thione Containing Naproxen Moiety as Analgesic/Anti- inflammatory Compounds ...... 102 P55 - Bioactivities of Isatin Mannich Bases ...... 103 P56 - Design, Synthesis and Bioevaluation of Pyrazoline Derivatives ...... 104 Bearing Primary Sulfonamide As Carbonic Anhydrase Inhibitors ...... 104 P57 - Synthesis of Novel Pyrazolines and Their Inhibitory Effects ...... 105 on hCA IX and XII Isoenzymes ...... 105 P58 - Association of Platelet to Lymphocyte Ratio and Neutrophil to Monocyte Ratio with Serum Adropin Level in Knee Osteoarthritis ...... 106 P59 - Inhibitory Properties of Chalcone and Pyrazole Derivatives on Human Carbonic Anhydrases ...... 107 P60 - Determination of Antimicrobial Activity of some Probiotic Preparations and A. muciniphila against Enteric Pathogens ...... 108 P61 - Qualitative and Quantitative Determination of Epigallocatechin Gallate, Epigallocatechin, Epicatechin Gallate and Catechin in Different Herbal Slimming Products Containing Camellia sinensis by HPLC ...... 109 P62 - Determination of Antioxidant Capacity of Ether Extract of Myrtus communis L. Leaf via CUPRAC and FRAP Methods...... 110 P63 - The Restoring Efficacy of Oleuropein Against Non-Steroidal Anti-inflammatory Drug Toxicity in Rat Kidney ...... 111 P64 - GC-MS Based Metabolomic Profile of Caco 2 Cell Lines ...... 112 P65 - Identification of Polychlorinated Biphenyls (PCBs) in Spiked Human Plasma Samples by GC-MS ...... 113 P66 - Determination of Log P Value of Kojic Acid Derivative by Using UV-Visible Spectroscopy...... 114 P67 - Synthetic Protocol for Imidazo-1,4-Oxazines and Evaluation of Their Cytotoxicity and Genotoxicity with SAR ...... 115 P68 - Evaluation of Antimicrobial Activities of 1,3,5-Trisubstituted-pyrazolines ...... 116 P69 - Inhibition of Cellular Proliferation and Induction of Apoptosis by Halofuginone in Human Mesothelioma Cell Lines ...... 117 Keywords: Malignant mesothelioma, halofuginone, viability, apoptosis ...... 117 P70 - Synthesis, Biological Activity, and Molecular Modelling Studies on New Oxime Ether Compounds Bearing Imidazole Ring ...... 118 P71 - Synergy of Coupling Ultrasound and Heterogeneous Fenton Processes using Magnetite Nanoparticles Prepared by High Energy Planetary Ball Mill in the Degradation of Basic Violet 10 from Aqueous Solutions ...... 119 P72 - Effects of Nesfatin-1 on Atrial Contractility in Male Rats ...... 120 P73 - Simultaneous Determination of Thiocolchicoside and Diclofenac Diethyl Ammonium in Topical Gel Formulation by Square-Wave Voltammetric Method ...... 121 P74 - Cytotoxic Effects of Nanoemulsion and Nanoemulsion Based Gel Containing Daidzein on SK-MEL30/An1 Cells ...... 122 P75 - Studies on QSAR of Some Antibacterial 1-(2-Naphthyl)-2-(Imidazole-1 yl)Ethanone Oxime and Oxime Ether Derivatives ...... 123 October 05-07, 2017, ERZURUM-TÜRKİYE 206
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P76 - Effects of Nesfatin-1 On Thoracic Aorta Reactivity in Male Rats ...... 124 P77 - Evaluation of Analgesic and Anti-inflammatory Activities of a Novel Arylalkyl Azole Compound in Mice ..... 125 P78 - Synthesis and Evaluation of Novel Hydrazone Derivatives as ...... 126 Monoamin Oxidase Inhibitors ...... 126
P79 - The Role of Potassium Channels in The Relaxation Response of Intermedin/Adrenomedullin2 (IMD/AM2) in The Rat Pulmonary Artery ...... 127 P80 - Synthesis, Molecular Docking and Acetylcholinesterase Inhibitory Activity of Some Novel Quinoline Derivatives ...... 128 P81 - Oleuropein Restores Chemotherapy Drug-Induced Pancreas Injury in Rats ...... 129 P82 – The Effects of Parietin on Wound Healing on the Human Dermal Fibroblast Cell Line ...... 130 P83 - Evaluation of Studies Between 2006-2016 Years Contributions Related To Treatment of Clinical Pharmacists ...... 131 P84 - In vitro toxicity evaluation of mycelium extracts of Lepista nuda ...... 132 P85 - Synthesis of New Benzothiazole- Hydrazone Derivatives as Potential Mao Enzymes Inhibitors ...... 133 P86 - Investigation of Cholinesterase Enzyme Inhibition Activity of 3 Barbarea Species ...... 134 P87 - Plants Traditionally Used for The Treatment Of Kidney Stones in Turkey ...... 135 P88 - Design, Synthesis, Biological Evaluation and Molecular Modeling of Novel 5-Arylidene-4-Thiazolidinones as Potential COX-1/COX-2 Inhibitors ...... 136 P89 - Synthesis and Cytotoxicities of Bis Mannich Bases of Phenolic Chalcones ...... 137 P90 - Examination of Inhibition of Anticholinesterase Enzyme of Caliytagia Growing in Two Different Regions ... 138 P91 - Inhibition effects of 2-amino-3-cyanoquinolin Derivatives on Carbonic Anhydrase I and II ...... 139 P92 - Qualitative and Quantitative Determination of Ursolic Acid and Chlorogenic Acid in Different Herbal Slimming Products Containing Ilex paraguariensis by HPLC ...... 140 P93 - Cytotoxicity and Reactive Oxygen Species Production Induced by Bisphenol A and/or Mono (2-ethylhexyl) Phthalate in Human Hepatoma Cells ...... 141 P94 - Development and Validation of an HPLC-UV Method for Simultaneous Determination of Levetiracetam and Carbamazepine in Pharmaceutical Formulations ...... 142 P95 - Cytotoxic Activities of New Sulphonamides on OSCC ...... 143 P96 - Design, Synthesis and Antibacterial Activitiy of Novel Modified Fluoroquinolone Derivatives ...... 144 P97 - Normalization Effects on the Repeatability of Long Term GC-MS Metabolomic Analysis ...... 145 P98 - Toxic Proteins of Plants ...... 146 P99 - Synthesis of New Mannich Bases ...... 147 P100 - The Effect of Perifosine and Vitamin D Combination on Endometrial Cancer Cell Line (HEC1A) ...... 148 P101 - Qualitative and Quantitative Determination of Arbutin and Hydroquinone in Different Herbal Slimming Products Containing Calluna vulgaris by HPLC ...... 149 P102 - Investigation of the Effects of Alchemilla barbatiflora Methanol Extract on Isolated Rat Detrusor Muscle 150 P103 - In Vitro Effects of Melatonin on Rat Carbonic Anhydrase ...... 151 P104 - Synthesis and Structural Characterization of Naproxen Hydrazide-Hydrazones ...... 152 P105 - Synthesis and DNA Interaction Properties of Novel Water Soluble Zn(II) and Cu(II) Phthalocyanines ...... 153 October 05-07, 2017, ERZURUM-TÜRKİYE 207
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P106 - Determination of Antioxidant Capacity of Olive Leaf (Olea europaea L.) Ethanol Extract via DPPH and ABTS/TEAC Methods...... 154 P107 - Determination of Antioxidant Capacity of Olive Leaf (Olea europaea L.) Ethanol Extract Via CUPRAC and FRAP Methods...... 155 P108 - Phytochemical Screening of Alcea pallida via GC-MS Method ...... 156 P109 - Effect of Acute and Chronic Administration of Amitriptyline on Experimental Gastric Ulcer ...... 157 P110 - Determination of Antioxidant Capacity of Water Extract of Myrtus Communis L. Leaf via DPPH and ABTS/TEAC Methods...... 158 P111 - Determination of Antioxidant Capacity of Methanol Extract of Myrtus Communis L. Leaf Via DPPH and ABTS/TEAC Methods...... 159 P112 - Determination of Antioxidant Capacity of Methanol Extract of Myrtus Communis L. Leaf Via CUPRAC and FRAP Methods ...... 160 P113 - Determination AChE Inhibition of Some Bischalcone Derivatives ...... 161 P114 – Protective effect of an L-type calcium channel blocker, amlodipine, on paracetamol- induced hepatotoxicity in rats ...... 162 P115 - Examination of Paraoxonase Activity in Smokers and Nonsmokers Male Students Serum Samples in Ağrı İbrahim Çeçen University Department of Nursing ...... 163 P116 - Cytotoxicities of Five New Benzoxazolone Derived Chalcones ...... 164 P117 - Synthesis of Chalcone Derivatives as Selective MAO-B Inhibitors ...... 165 P118 - Use Of A Compaction Simulator To Compare Two Commercial Tablet Presses ...... 166 P119 – Sensitive Detection of Pemetrexed Disodium from its Pharmaceutical Dosage form by Adsorptive Stripping Differential Pulse Voltammetry ...... 167 P120 - Preliminary Studies on Optimization of Topical Formulations of Cinnarizine: Physical Characterization and Stability Assessment ...... 168 P121 - (Thio)urea Derivatives Enhance Wound Closure by Increasing Cell Proliferation: Synthesis and In Vitro Evaluation ...... 169 P122 - Determination of Cefpodoxime proxetil in Pure and Pharmaceutical Preparations with spectrophotometer ...... 170 P123 - Main Toxic Compounds of Palm Oil ...... 171 P124 - New Spectrophotometric Method with Chemometric Design-Optimization Approach for the Simultaneous Determination of Thiamin and Pyridoxin ...... 172
P125 - A new Spectrofluorimetric Method for Determination of Zinc by using the Fe3O4-SiO2–NH2 Nanocomposite Functionalized with Zinpyr-1 Ligand in Artificial Saliva ...... 173 P126 - Involvement of serotonin receptors in low-dose ketamine analgesia in mice ...... 174 P127 - Protective Effects of Melatonin and Fluoxetine on Immobilization-Induced Stress in Mice ...... 175 P128 - Neuroprotective effects of austricine on differentiated SH-SY5Y neuroblastoma cell line ...... 176 P129 - The Effects of GLP-1 Analogs and Sitagliptin on Heart Rate in Isolated Diabetic Rat Atrium and Whole Heart Preparations ...... 177 P130 - Nickel boride nanoparticle toxicity and microarray analysis on human pulmonary alveolar cells ...... 178 P131 - Functional Effects Of Visfatin In Small Resistance Arteries Of Rat Isolated Mesenteric Bed...... 179
October 05-07, 2017, ERZURUM-TÜRKİYE 208
3 rd International Multidisciplinary Symposium on Drug Research and Development - DRD 2017
P132 - Cloning of Pseudomonas aeruginosa azurin in Lactococcus lactis ...... 180 OP01 - The New Generation Drug Candidate Molecules for Cancer Treatment ...... 182 OP02 - Green Pharmaceutical Analysis in High Performance Liquid Chromatography by Organic Modifier Replacement in the Mobile Phase ...... 183 OP03 - Tyrosinase Inhibitory Effect of Aerial Parts of Alchemilla caucasica Buser ...... 184 OP04 - Enhancement of Disulfiram Cytotoxicity by Sodium Butyrate in Breast Cancer Cells ...... 185 OP05 - In vitro Antidiabetic Activity of Elaeagnus angustifolia L. and Its Active Compounds ...... 186 OP06 - In-vitro Antifungal Activities of Fluconazole, Quince Leaf and Green Tea Extracts Against Candida Species Isolated From Blood Cultures ...... 187 OP07 - The Cytotoxic Effects of Parietin on HepG2 Hepatocellular Carcinoma Cells ...... 188 OP08 - Synthesis of Some New 1-Phenyl/1-(4-chlorophenyl)-2-(1H-triazole-1-yl)ethanol Ester Derivatives and Evaluation of Their Anticonvulsant and Antimicrobial Activities ...... 189 OP09 - Histopathological Effects of Naringenin on Vancomycin-induced Nephrotoxicity in Rats ...... 190 OP10 - Determination the Correlation between Serum Adropin Level and Hemorheological Parameters in Knee Osteoarthritis Patients...... 191 OP11 - Efficiency of Inula helenium Extracts nn Activity of APEX1 in Human Glioma Cell Lines ...... 192 OP12 - Synthesis and In Vitro Anticancer Activity of Novel 6,8,9-Trisubstituted Purine Analogs ...... 193 OP13 - Synthesis, Structural Characterization, in Vitro Cytotoxicities, and FS-Dsdna Binding Studies of Metal Based Compound of Methotrexate ...... 194 OP14 - Synthesis, Structure Elucidation and Biological Activities of Some Novel 4(3H)-Quinazolinones as Anti-Biofilm Agents ...... 195 OP15 - A novel approach to contrast-induced nephrotoxicity: the melatonergic agent agomelatine ...... 196
OP16 - Increased Antioxidant activity After Exposure of CCI4 in Rat Lungs Toxicity Model ...... 197 OP17 - Synthesis and Cytotoxic Activities of Mannich Bases of Heterocyclic Chalcone Analogues...... 198 OP18 - Synthesis of 4-(2-(5,6-dimethoxy-1H-inden-1-ylidene)hydrazineyl)benzenesulfonamide and Its Structural Elucidation by NMRs ...... 199 OP19 - Effects of Some Pesticides on Some Carbonic Anhydrase Isoenzymes ...... 200 OP20 - Determination of Antioxidant Capacity PPO Enzyme Purified from Morchella Esculenta by ABTS and DPPH Methods...... 201 OP21 - Assessment of Lipid Peroxidation and Protein Oxidation Parameters in Obese Children with Metabolic Syndrome ...... 202
October 05-07, 2017, ERZURUM-TÜRKİYE 209