Synthesis of novel methyl jasmonate derivatives and evaluation of their biological activity in various cancer cell lines |
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| Institution: | 1. Istanbul Medipol University, Vocational School of Health Services, Pharmacy Services, Kavacik Campus, Kavacik-Beykoz, Istanbul 34810, Turkey;2. Istanbul Medipol University, Regenerative and Restorative Medicine Research Center (REMER), Kavacik Campus, Kavacik-Beykoz, Istanbul 34810, Turkey;3. Yildiz Technical University, Graduate School of Natural and Applied Sciences, Department of Chemistry, Besiktas, Istanbul 34349, Turkey;4. Istanbul Medipol University, School of Medicine, Department of Medical Biology, Kavacik Campus, Kavacik-Beykoz, Istanbul 34810, Turkey;5. Istanbul Medipol University, International School of Medicine, Department of Medical Pharmacology, Kavacik Campus, Kavacik-Beykoz, Istanbul 34810, Turkey;1. Aix-Marseille Univ, CNRS, EIPL, Marseille, France;2. Aix-Marseille Univ, CNRS, Centrale Marseille, ISM2, France;3. Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 – CNRS – UM – ENSCM, Faculté de Pharmacie, 15 Avenue Charles Flahault, 34093 Montpellier Cedex 5, France;4. ITERG-ENMS, Université de Bordeaux, rue Léo Saignat, 33076 Bordeaux Cedex, France;1. N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47, Leninsky Prosp., 119991 Moscow, Russian Federation;2. A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28, Vavilova Str., 119991 Moscow, Russian Federation;1. Research Center, Boryung Pharmaceuticals Co. Ltd., Republic of Korea;2. New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Republic of Korea;1. College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350116, China;2. Department of Chemistry, Ningde Normal University, Ningde, 352100, China |
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| Abstract: | Warburg hypothesized that the energy consumption of cancer cells is different than the normal cells. When compared to normal conditions, cancer cells do not undergo tricarboxylic acid (TCA) cycle therefore resulting in more lactate in the cells. Glycolysis pathway is a way of cancer cells to provide energy. The first step in glycolysis is the phosphorylation of glucose to glucose-6-phosphate. This reaction is catalyzed by the hexokinase-II enzyme (HK-II) which is known to be overexpressed in tumor cells. The feeding of cancer cells can be prevented by inhibiting the hexokinase-II enzyme in the first step of aerobic glycolysis. In literature, Methyl Jasmonate (MJ) is known as a Hexokinase-II inhibitor since it disposes VDAC and HK-II interaction on mitochondrial membrane. In our study, we aimed to increase the activity by synthesizing the novel MJ analogues with appropriate modifications. Here we report Hexokinase-2 enzyme and cell viability study results in different cancer cells. Based on the three different cancer cell lines we investigated, our novel MJ analogues proved to be more potent than the original molecule. Thus this research may provide more efficacious/novel HK-II inhibitors and may shed light to develop new anti-cancer agents. |
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| Keywords: | Cancer therapy Aerobic glycolysis Warburg effect Hexokinase-II inhibition Methyl jasmonate Novel drug discovery and development |
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