Design, synthesis, and biological evaluation of N-hydroxycinnamamide/salicylic acid hybrids as histone deacetylase inhibitors

作     者：Tao You Ke Chen Fei-Hai Wang Pi-Hong Li Li-Yi Li Zhi-Hao Wu Kong-Hai Ni Zhi-Qiang Zheng 

作者机构：Department of General SurgeryThe Second Affiliated HospitalWenzhou Medical University School of Clinical MedicineWenzhou Medical University 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2014年第25卷第3期

页      码：474-478页

摘      要：Novel histone deacetylase （HDAC） inhibitors 9a-1 were designed and synthesized by coupling the carboxyl group of salicylic acid （SA） with N-hydroxycinnamamides through various alkylol amines, and their in vitro biological activities were evaluated. The N-hydroxycinnamamide/SA hybrids 9b-f and 9h showed good to moderate anti-tumor activities. Notably, compound 9e had a greater potency, comparable to vorinostat （SAHA）, in human colon carcinoma cells, which was probably, or at least partially, attributable to the positive effects of the chain length noted in allojlol amines. Furthermore, the HDAC inhibitory activities of 9e against Hela cell nuclear were also similar to that of vorinostat （SAHA）, while the tested compounds 9c-f did not exhibit any isoform selectivity in the inhibition of HDACs. In addition, compound 9e could selectively inhibit tumor cells, but not inhibit non-tumor cell proliferation in vitro. Our findings suggest that the N-hydroxycinnamamide/SA hybrids may hold significant promise as therapeutic a^ents for the intervention of human cancers.

主 题 词：SynthesisAnti tumor agentsHistone deacetylase inhibitorsN HydroxycinnamamidesSalicylic acid 

学科分类：1007[医学-药学类] 100701[100701] 10[医学] 

核心收录：

D　O　I：10.1016/j.cclet.2013.11.039

馆 藏 号：203227535...