摘要/Abstract

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Zn²⁺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12.59 μmol/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.
关键词: 西达本胺, HDACs, 抗肿瘤活性, 苯甲酰胺
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 2.59 μmol/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.
Key words: chidamide, HDACs, anti-tumor activity, benzamide


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