西达本胺衍生物的设计合成及抗肿瘤活性评价（英文）  

Design, Synthesis and Evaluation of Anti-tumor Activities of Chidamide Derivatives

作　　者：张祥娜 何峰 张秋琼 吕佳徽 徐阿娜 虞成功 曲颖 吴敬德[1] Zhang Xiangna;He Feng;Zhang Qiuqiong;Lü Jiahui;Xu A-na;Yu Chenggong;Qu Ying;Wu Jingde(Key Laboratory of Chemical Biology(Ministry of Education),School of Pharmaceutical Science,Shandong University,Jinan 250012)

机构地区：[1]山东大学药学院化学生物学教育部重点实验室

出　　处：《有机化学》2019年第7期1983-1989,共7页Chinese Journal of Organic Chemistry

基　　金：Project supported by the Key Research and Development Plan of Shandong Province(No.2017CXGC1401)~~

摘　　要：以西达本胺为基础设计合成了一系列新型组蛋白去乙酰化酶(HDACs)抑制剂,以提高与Zn^2+的螯合作用和亚型选择性.大部分化合物表现出一定的抗肿瘤增殖活性.其中,(E)-N-(4-氨基-6-氟-[1,1'联苯]3-基)-4-((3-(吡啶-3-基)丙烯酰氨基)甲基)苯甲酰胺(7i)和(E)-N-(2-氨基-4-氟-5-(噻吩-2-基)苯基)-4-((3-(吡啶-3-基)丙烯酰胺基)甲基)苯甲酰胺(7j)抗肿瘤增殖活性最佳,对Jurkat细胞的IC50分别为3.29和12.59μmol/L,并且这两个化合物表现出一定的HDAC抑制活性,为更有潜力的西达本胺衍生物的设计合成提供了新思路.A series of novel chidamide based histone deacetylases(HDACs)inhibitors were rationally designed and synthesized to increase the Zn2+chelating and selectivity.Biological characterization established that most of the compounds showed moderate antiproliferative activitites in cancer cell lines.Among the tested analogs,(E)-N-(4-amino-6-fluoro-[1,1'-biphenyl]-3-yl)-4-((3-(pyridin-3-yl)acrylamido)methyl)benzamide(7i)and(E)-N-(2-amino-4-fluoro-5-(thiophen-2-yl)phenyl)-4-((3-(pyridin-3-yl)acrylamido)methyl)benzamide(7j)exhibit the most potent antiproliferative activity with IC50 of 3.29 and 2.59μmol/L in Jurkat cells,respectively.Furthermore,these two compounds have a certain HDAC inhibitory activity.Collectively,the results partly encourage further development of more potential analogs based on chidamide.

关 键 词：西达本胺 HDACS 抗肿瘤活性 苯甲酰胺 

分 类 号：TQ460.1[化学工程—制药化工]