Optical evodiamine derivatives:Asymmetric synthesis and antitumor activity  

作　　者：Zhen-Gang Li Guo-Qiang Dong Sheng-Zheng Wang Zhen-Yuan Miao Jian-Zhong Yao Wan-Nian Zhang Chun-Quan Sheng 

机构地区：[1]School of Pharmacy,Second Military Medical University

出　　处：《Chinese Chemical Letters》2015年第3期267-271,共5页中国化学快报（英文版）

基　　金：supported by National Natural Science Foundation of China (Nos.81222044,81373278);Key Project of Science and Technology of Shanghai (Nos.11431920402,14YF1405400)

摘　　要：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.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.

关 键 词：isomers asymmetric antitumor clarified toward hydrogenation hexane potent relaxation dissolved 

分 类 号：O621.3[理学—有机化学] TQ460.1[理学—化学]