Synthesis of novel methyl jasmonate derivatives and evaluation of their biological activity in various cancer cell lines
Autor: | Bilgesu Onur Sucu, Sukran Ozdatli Kurtulus, Busra Emine Yazici, Nihal Karakaş, Ozgecan Savlug Ipek, Mustafa Guzel |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Novel Drug Discovery and Development
Aerobic Glycolysis Antineoplastic Agents Cyclopentanes Acetates 01 natural sciences Biochemistry Hexokinase-II Inhibition chemistry.chemical_compound Methyl Jasmonate Hexokinase Neoplasms Drug Discovery Tumor Cells Cultured Humans Glycolysis Oxylipins Viability assay Phosphorylation Molecular Biology chemistry.chemical_classification Methyl jasmonate 010405 organic chemistry Chemistry Voltage-Dependent Anion Channel 1 Organic Chemistry Biological activity Warburg effect Mitochondria 0104 chemical sciences 010404 medicinal & biomolecular chemistry Glucose Enzyme Anaerobic glycolysis Cancer cell Cancer Therapy Warburg Effect |
Popis: | 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. Türkiye Bilimsel ve Teknolojik Araştırma Kurumu (TÜBİTAK) |
Databáze: | OpenAIRE |
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