Day 3 :
Keynote Forum
Laurent Désaubry
Tianjin University of Science and Technology, China
Keynote: Anticancer agents used in traditional Chinese medicine that target prohibitins and the translation initiation factor eIF4a
Time : 9:30 AM
Biography:
Laurent Désaubry is a CNRS Research Director in the University of Strasbourg in France and Professor at Tianjin University of Science and Technology (TUST) in China. He is currently Editor and Board Member of Frontiers in Chemistry, Medicinal Chemistry and Advances in Oncology Research and Treatments. In 1992, he received a PhD degree in Medicinal Chemistry from Strasbourg University. From 1992 to 1996, he worked as a Post-doctoral fellow at SUNY at Stony Brook, USA. He made another Post-doctoral internship in Prof. Pierre Chambon’s laboratory before to get a CNRS Research Senior Scientist at the University of Strasbourg-CNRS. He was promoted to the position of CNRS Research Director (corresponds to Full Professor) in 2014, and became Professor at TUST in 2015.
Abstract:
Flavaglines are a family of anticancer natural products that relieve the resistance to cancer chemotherapies and display a strong cytotoxicity that is specific to cancer cells in a low nanomolar range. Not only flavaglines are not toxic to non-cancer cells, but they protect normal cells from various stresses. Thus, we demonstrated for the first time that these compounds protect the heart and neurons from the adverse effects of cancer chemotherapies involving anthracyclines and cisplatin. We also identified the scaffold proteins prohibitins-1 and -2 (PHB1/2) as the molecular targets of flavaglines. The binding of flavaglines to PHBs prevents their interaction with C-Raf and, thereby, inhibits C-Raf activation, which is critical to the survival and proliferation of cancer cells. Flavaglines also directly inhibit another emerging target in oncology, the translation initiation factor eIF4a. In vivo data indicate that flavaglines could greatly improve the treatment of chemoresistant metastatic melanoma.
Keynote Forum
Miguel Ãngel López Zavala
Water Center for Latinamerica and the Caribbean, México
Keynote: Simultaneous extraction and determination of four different groups of pharmaceuticals in compost using optimized ultrasonic extraction and ultrahigh pressure liquid chromatography–mass spectrometry
Time : 10:10AM
Biography:
Miguel Ángel López Zavala has completed his PhD and Post-doctoral studies at the Hokkaido University, Japan, in the field of Urban and Environmental Engineering. He is Professor at the Tecnológico de Monterrey, Mexico. He is member and evaluator of the National Research System of the National Council of Science and Technology. He was researcher of the Japan Science and Technology Agency at Hokkaido University, Japan. He is the author of more than 55 scientific papers published in international journals and proceedings of international conferences and congresses. He is active member of the International Water Association and Treasurer of IWA-Mexico from 2010-2011.
Abstract:
The simultaneous extraction and determination of different groups of pharmaceuticals in complex environmental matrices such as compost is particularly challenging because of the low detection limits required, the complex nature of the samples, the different chemical characteristics of the pharmaceuticals, and the difficulty in extracting and separating these compounds from interference. Thus, the aim of this study was to develop and validate a reliable and affordable analytical method for the simultaneous extraction and determination of four different groups of pharmaceuticals in compost obtained from the thermophilic aerobic treatment of placenta. The pharmaceuticals were two non-steroidal anti-inflammatory drugs, ketorolac and naproxen, usually administered to humans; two fluoroquinolones, ofloxacin and ciprofloxacin (which are among the most commonly prescribed class of antibiotics in Mexico); two anti-cancer (antineoplastic or cytotoxic) chemotherapy drugs, ifosfamide and cyclophosphamide; and two b-blockers, atenolol and propranolol, also called b-adrenergic blocking agents, which treat a variety of conditions, such as high blood pressure, glaucoma and migraines. The pharmaceuticals of each group were selected because they are commonly used in Mexico and environmental and health impacts has been reported. The clustering was based on the use of the drug and not on the similarity of thestructure. Recovery values of the ultrasonic extraction for all compounds were on the order of 87% to 113%. The limits of detection and quantification for the eight pharmaceuticals were on the order of 0.66 ng g−1 and 2 ng g−1 respectively for all the pharmaceuticals analyzed. These values are lower than those valuesreported in the literature.
- Technologies in Natural Products | Pharmacology Studies | Modern Analytical Techniques
Session Introduction
Anna Maria Waszkielewicz
Jagiellonian University Medical College, Poland
Title: Activity of some phenoxyalkyl- and phenoxyethoxyethylamine derivatives on the central nervous system
Biography:
Anna Maria Waszkielewicz defended her PhD in 2008 in Medicinal Chemistry. She has published more than 35 papers in reputed journals (overall IF>60) and has been serving as an Editorial Board Member of repute Organic Chemistry – Current Research as well as Jacobs Journal of Organic Chemistry. She was granted patents for new drug candidates in US, EPO, Russia, Japan, Canada, Korea, and Poland. She has coordinated cooperation between National Cancer Institute and Jagiellonian University Medical College in discovery of anticancer agents. She is an Assistant Professor at Department of Bioorganic Chemistry, Chair of Organic Chemistry, Jagiellonian University Medical College, Poland.
Abstract:
The aim of the study was determination of correlation between activities: anticonvulsant, analgesic, antidepressant and anxiolytic, among novel compounds, as well as finding mechanism of action of these compounds. Premise for the above aim constitutes coexistence and common etiology of these disorders, such as trauma, intoxication, or neurodegeneration. Among epilepsy patients, morbidity in migraine is 2.4 times as high as between patients who have no seizures. 20-50% of epilepsy patients suffer from depression. Special situation is observed for patients such as children or pregnant women, as well as those who suffer from drug-resistant epilepsy. It is known that anticonvulsants such as carbamazepine, valproates, or gabapentin improve mood and that tianeptine may cause depression. On the other hand, epilepsy can be caused by maprotyline and klomipramine. Drugs such as venlafaxine and selective serotonin reuptake inhibitors are considered relatively safe. Based on our experience regarding aroxyalkyl- and aroxyethoxyethylaminoalkanols and their anticonvulsant and analgesic activity, new phenoxyalkyl and phenoxyethoxyethyl derivatives of piperazine have been designed and synthesized for in vivo screening for epilepsy (maximal electroshock, MES), neurotoxicity (rotarod), antidepressant-like activity (Porsolt test), as well as anxiolytic activity (four-plate test) have been examined. Receptor profile for the compounds has been determined. As an additional assay, mutagenic activity was excluded. Moreover, metabolic stability was determined with use of murine liver microsomes for the most active compounds.
Sahar Ahmed
Assiut University, Egypt
Title: Design, synthesis and validation of an in vitro platform peptide-whole cell screening assay using MTT reagent
Biography:
Sahar Ahmed is an Assistant Professor at the Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, KSA. She received her BSc from the Faculty of Pharmacy, Assiut University, Egypt and then her MSc from the same faculty. She subsequently obtained her PhD from the Faculty of Pharmacy, University of Alberta, Canada in 2010 under the supervision of Dr. K Kaur followed by one year of a Post-doc at the same faculty. She has participated in many international conferences and published 15 publications in international journals and one chapter book.
Abstract:
An in-vitro platform to perform a peptide screening against different cancer cell lines was designed. The strategy for this screening relied on detection of high affinity cancer targeting peptides based on the sequence of NGR and P160. Evaluation of the best binding peptides was done through incubation of the cellulose membrane-bounded cells with MTT reagent which is reduced to purple formazan in living cells, further quantified using Elispot and Kodak imager. For a proof of concept, a peptide library (132 spot, 66 different peptides) was designed, synthesized, and screened against different cancer cell lines. Current screening process assist in the identification of positive, negative peptide, and the relative binding between positive ones. Better binding peptides of NGR sequence were pointed out to show up to 2.6 fold increase to CD13 positive cell lines with insignificant binding to CD13 negative ones. Comparable results were observed for P160 sequences where different peptides showed higher binding up to 3 fold increase relative to the native P160 peptide. Based on our results, an alternative colour approach to identify new peptides for cancer targeting was developed and applied for two different peptide libraries.
Flavio S P Cardoso
Libbs Pharmaceuticals, Brazil
Title: Application of in situ FTIR for the preparation of 17-α-estradiol via Mitsunobu reaction
Biography:
Flavio S P Cardoso obtained a BS degree in Chemistry in 2009 at the State University of Campinas (UNICAMP), Brazil. He performed undergraduate research under the supervision of Prof. Carlos Roque Duarte Correia for a period of nearly three years. His research at UNICAMP focused on the palladium-catalyzed Heck-Matsuda reaction. Next, he started his graduate studies at the University of Florida, USA. Under the guidance of Prof. Aaron Aponick, his PhD studies involved the development of a new class of atropisomers which was ultimately applied in asymmetric catalysis. Upon graduation in 2014, he moved back to Brazil to work at Libbs Pharmaceuticals as a Chemical Development Scientist.
Abstract:
An efficient synthesis of 17-α-estradiol 1 is described. Utilization of in situ IR allowed for an online monitoring of the key Mitsunobu reaction and development of a safe and reliable synthesis of 17-α-estradiol 1 in 78% overall yield over three steps. Benzoylation of 17-β-estradiol 2 is conducted at high regioselectivity under phase-transfer catalysis (PTC) conditions, followed by a Mitsunobu reaction to invert the chiral center at C-17 and provide intermediate 5, containing the core structure of 17-α-estradiol 1. Finally, the desired active pharmaceutical ingredient (API) is prepared by saponification of the remaining esters.
Nafiz Oncu Can
Anadolu University, Turkey
Title: A novel stability-indicating LC method for determination of avanafil
Biography:
Nafiz Oncu Can has completed his PhD from Anadolu University under the supervision of Prof. Dr. Goksel ARLI. He has published 15 papers in reputed journals and has an H-index value of 7. He is working as a full-time Associate Professor at the Department of Analytical Chemistry, Faculty of Pharmacy, Anadolu University, Turkey.
Abstract:
Avanafil (AVA) is a phosphodiesterase type 5 inhibitor compound, prescribed to treat erectile dysfunction. Up to date, due to recent introduction of AVA to the market, chemical analysis of its degradation products and possible process impurities were not published anywhere. A novel reversed-phase high-performance liquid chromatography method was developed and validated for the determination of avanafil, in the presence of its degradation products. Forced degradation studies were performed employing acidic, alkaline, neutral, oxidative, thermal and photolytic stress conditions and retention characteristics of AVA was assessed by the evaluation of common chromatographic and system suitability parameters. Identification of compounds was realized using LCMS-IT-TOF instrument and an additional LC-MS/MS system was utilized for precise quantitation of AVA. The developed method was validated as per International Conference on Harmonization (ICH) guidelines with respect to specificity, accuracy, precision, linearity, limit of detection and quantification, and robustness. The applicability of the proposed method for the determination of avanafil was demonstrated.
Karem H Alzoubi
Jordan University of Science & Technology, Jordan
Title: The antimutagenic activity of selected medicinal plants from Jordan
Biography:
Karem H Alzoubi, PhD, Professor of Pharmacology, Dean of the Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan. He has published over 160 peer-reviewed research articles and review article in well-respected international journals, and a number of book chapters. He presented his work in over 50 international conferences all over the world. His scientific work has been highly cited. He has a current, Scopus h index of 24, which is the highest among researchers in Jordan and among the highest in the Arab world in the fields of pharmacy/pharmacology. He was awarded Khalifah Award for Education (an international award) distinguished University Professor in the Field of Scientific Research from Government of United Arab Emirates (UAE) (2014-2015). He also won the Abdul-Hameed Shoman Young Arab investigators Award for Medical Sciences for 2012 from the Shoman forum. He was also awarded the Distinguished Researcher Award in the fields of Medicine and Pharmacy from the Ministry of Higher Education and Scientific Research, Amman, Jordan (2013).
Abstract:
Herbal medicinal products represent a major focus for drug development and industry and it holds a significant share in drug-market all over the globe. Recently, a number of medicinal plant extracts from Jordan with high antioxidative capacity were shown for their protective effect against DNA damage, which correlates future likelihood of cancer development or birth defects. In this study, we evaluated plant extract with high antioxidative DNA damage properties for anti-mutagenic effect using sister chromatid exchange assay in cultured human lymphocytes. As per our screening results, plant extracts with antioxidative DNA damage properties were the hexane fraction of Silybum marianum L. (aerial parts), the chloroform fractions of Pistacia palaestina Boiss (Fruits), the ethanolic fractions of Salvia triloba L. (leaves), Ziziphus spina-christi L. Desf. (Fruits/leaves) and Eucalyptus camaldulensis Dehnh (leaves). These plant extract fractions were further analyzed using sister chromatid exchange assay in cultured human lymphocytes. Results showed that the ethanolic fractions of spina-christi L. Desf. (Fruits/leaves), and Eucalyptus camaldulensis Dehnh (leaves) significantly reduced the rate of sister chromatid exchanges in cultured human lymphocytes at doses of 100 ug/ml, 500 ug/ml. Additionally, the hexane fraction of Silybum marianum L. (aerial parts) significantly reduced the rate of sister chromatid exchanges in cultured human lymphocytes at a dose of 500 ug/ml. These results indicate the antimutagenic activity of the ethanolic fractions of spina-christi L. Desf. (Fruits/leaves), Eucalyptus camaldulensis Dehnh (leaves) and hexane fraction of Silybum marianum L. (aerial parts); and thus, their increased potential as cancer protective agents.
Biography:
Gary Gellerman has completed his PhD from Tel Aviv University in 1994 and joined Compugen Ltd. In 2000, he accepted the position of Vice-president, Molecular Diversity in Compugen where he was responsible for developing drug discovery platform. In 2005, he moved to Ariel University, currently holding Deanship of Faculty of Natural Sciences. He has published more than 50 articles in reputed journals.
Abstract:
Resistance to drugs that cancer cells develop and the inherent capability of these cells to survive the drug treatment, produces a great motivation to look for new techniques of chemotherapeutic cure and search for novel anti-proliferative agents. In the present report, we demonstrate a facile synthetic strategy towards the discovery of new anti-cancer substances. This strategy is based on simple covalent coupling between known anti-cancer drugs, which results in novel 'chimeric' small molecules. One of the novel compounds presented here, CM358, is a result of amide bond formation between known Topo II inhibitor amonafide (AM) and DNA mustard alkylator chlorambucil (CLB). It demonstrates a significant cytotoxic predominance over the equimolar mixture of AM and CLB in various cancer cell lines and in xenograft model of human metastatic melanoma. Modeling studies and FACS analysis of CM358 will also be presented.
Wen-Nee Tan
Universiti Sains Malaysia, Malaysia
Title: Phytochemical constituents from Garcinia atroviridis
Biography:
Garcinia atroviridis is a medium-sized fruit tree found wild in the forest of Peninsular Malaysia, Thailand, Myanmar, India and sometimes in a half-cultivated state in villages. It is commonly known as ‘Asam Gelugor’ in Malaysia or ‘Som-Khaek’ in Thailand. G. atroviridis has been used as a postpartum medication agent in folkloric medicine. The fruit is used in a lotion made with vinegar, which is rubbed upon the abdomen of a woman after confinement and the juice from the leaves is given to a woman after childbirth in one of those numerous protective preparations. In the investigation on the chemical constituents of the stem bark of G. atroviridis, eleven compounds have been isolated and purified using column chromatography. These compounds were characterized using various spectroscopic techniques and were assayed for antioxidant and cholinesterase enzyme inhibitory activities.
Abstract:
Wen-Nee Tan has completed her PhD in Natural Products Chemistry from Universiti Sains Malaysia and is currently a Lecturer in Universiti Sains Malaysia. Her research interests focus on natural products isolation and their structural characterization, as well as bioassay on the isolated pure compounds.