Design, synthesis and biological evaluation of E-ring modified evodiamine derivatives as novel antitumor agents  

作　　者：Kun Fang Guo-Qiang Dong Hai Gong Na Liu Zhen-Gang Li Shi-Ping Zhu Zhen-Yuan Miao Jian-Zhong Yao Wan-Nian Zhang Chun-Quan Sheng 

机构地区：[1]School of Pharmacy, Second Military Medical University [2]Department of Radiation Oncology,Ji’nan Military General Hospital

出　　处：《Chinese Chemical Letters》2014年第7期978-982,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(No.11431920402);the National Basic Research Program of China(No.2014CB541800);Shanghai Rising Star Program(No.12QH1402600);Shanghai Municipal Health Bureau(No.XYQ2011038)

摘　　要：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.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.

关 键 词：Evodiamine derivatives Topoisomerase Ⅰ Topoisomerase Ⅱ Antitumor activity 

分 类 号：TQ457.2[化学工程—农药化工]