Mechanisms of action and structure-activity relationships of cytotoxic flavokawain derivatives.
作者： Charlotte Thieury , Nicolas Lebouvier , Rémy Le Guével , Yann Barguil , Gaëtan Herbette
DOI: 10.1016/J.BMC.2017.01.049
关键词: Protein kinase B 、 PI3K/AKT/mTOR pathway 、 Chemistry 、 Cell cycle 、 Cell culture 、 Cyclin B1 、 Cytotoxicity 、 Cytotoxic T cell 、 Pharmacology 、 Apoptosis
摘要: 22 Flavokawain derivatives (FKd) were obtained by one step syntheses in order to conduct a SAR study understand the structural requirements for optimum and selective cytotoxicity. FKd natural flavokawains A B found into kava, South Pacific traditional beverage, evaluated against nine cancer healthy cell lines. The targeted cycle phases as well effects on induction of apoptosis protein levels investigated. Therapeutic improvements (more activity selectivity) achieved with compared notably 2',3,4',6'-tetramethoxychalcone (FKd 19). induced G1/S arrest p53 wild-type cells an M mutant-type, via up-regulation p21 cyclin B1 proteins, followed apoptosis. Moreover, exhibited 24h-effect Akt/mTor normal versus 48h-effect up-regulated cells. resulted conclusion that trimethoxy A-ring allowed best compromise between cytotoxicity selectivity, substitution meta position B-ring use halogens substituents.
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