Synthesis and biological evaluation of Complex I inhibitor R419 and its derivatives as anticancer agents in HepG2 cells |
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| Authors: | Yaping Huang Geng Sun Pengfei Wang Rui Shi Yanchun Zhang Xiaoan Wen Hongbin Sun Caiping Chen |
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| Institution: | Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China |
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| Abstract: | In this study, Complex I inhibitor R419 was firstly revealed to have significant anticancer activity against HepG2 cells (IC50?=?5.2?±?0.9?μM). Based on this finding, a series of R419 derivatives were synthesized and biologically evaluated. As results, 9 derivatives were found to have obvious anticancer activity. Among them, H20 exhibited the most potent activity (IC50?=?2.8?±?0.4?μM). Mechanism study revealed that H20 caused severe depletion of cellular ATP, dose-dependently activated AMPK, decreased Bcl-2/Bax ratio and induced necrotic cell death. Most importantly, H20 displayed definite inhibitory activity against Complex I. |
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| Keywords: | Complex I Flavonoids derivatives Human hepatocellular carcinoma |
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