A series of novel E-ring modified evodiamine derivatives were designed and synthesized as antitumor agents. Their capacity to interfere with the catalytic activity of topoisomerase Ⅰ and Ⅱ was evaluated by the relax...A series of novel E-ring modified evodiamine derivatives were designed and synthesized as antitumor agents. Their capacity to interfere with the catalytic activity of topoisomerase Ⅰ and Ⅱ was evaluated by the relaxation assay. In vitro antitumor activity results revealed that compound 12 showed good antitumor activity with a broad spectrum. Its binding modes with topoisomerase Ⅰ and Ⅱ were clarified by molecular docking.展开更多
Evodiamine and its derivatives have an asymmetric center at the C13 b position.Herein,isomers of evodiamine derivatives 2 and 3 were obtained by straightforward asymmetric total synthesis.Their inhibitory activities t...Evodiamine and its derivatives have an asymmetric center at the C13 b position.Herein,isomers of evodiamine derivatives 2 and 3 were obtained by straightforward asymmetric total synthesis.Their inhibitory activities toward topoisomerases Ⅰ and Ⅱ and their cytotoxicities in cancer cell lines were evaluated.All the four isomers exhibited good to excellent antitumor potency and the（S）-isomers were generally more active than the（R）-isomers.The binding modes of（S）-2 with topoisomerases Ⅰ and Ⅱ were also clarified by molecular docking.展开更多
基金supported by National Natural Science Foundation of China(Nos.81222044,81373278)Key Project of Science and Technology of Shanghai(No.11431920402)+2 种基金the National Basic Research Program of China(No.2014CB541800)Shanghai Rising Star Program(No.12QH1402600)Shanghai Municipal Health Bureau(No.XYQ2011038)
文摘A series of novel E-ring modified evodiamine derivatives were designed and synthesized as antitumor agents. Their capacity to interfere with the catalytic activity of topoisomerase Ⅰ and Ⅱ was evaluated by the relaxation assay. In vitro antitumor activity results revealed that compound 12 showed good antitumor activity with a broad spectrum. Its binding modes with topoisomerase Ⅰ and Ⅱ were clarified by molecular docking.
基金supported by National Natural Science Foundation of China (Nos.81222044,81373278)Key Project of Science and Technology of Shanghai (Nos.11431920402,14YF1405400)
文摘Evodiamine and its derivatives have an asymmetric center at the C13 b position.Herein,isomers of evodiamine derivatives 2 and 3 were obtained by straightforward asymmetric total synthesis.Their inhibitory activities toward topoisomerases Ⅰ and Ⅱ and their cytotoxicities in cancer cell lines were evaluated.All the four isomers exhibited good to excellent antitumor potency and the（S）-isomers were generally more active than the（R）-isomers.The binding modes of（S）-2 with topoisomerases Ⅰ and Ⅱ were also clarified by molecular docking.
