Tetrahydroisoquinolines as novel histone deacetylase inhibitors for treatment of cancer

作     者：Danqi Chen Aijun Shen Guanghua Fang Hongchun Liu Minmin Zhang Shuai Tang Bing Xiong Lanping Ma Meiyu Geng Jingkang Shen 

作者机构：Department of Medicinal ChemistryState Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of Science Division of Anti-tumor PharmacologyState Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of Sciences 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2016年第6卷第1期

页      面：93-99页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

基　　金：supported financially by the National Science & Technology Major Project ‘Key New Drug Creation and Manufacturing Program’ of China(Grant No.2014ZX09507002) the National Marine ‘863’ Project(No.2013AA092902) 

主　　题：Histone deacetylases inhibitor Anticancer Tetrahydroisoquinoline Structure–activity relationship 

摘      要：Histone acetylation is a critical process in the regulation of chromatin structure and gene *** deacetylases(HDACs)remove the acetyl group,leading to chromatin condensation and transcriptional *** inhibitors are considered a new class of anticancer agents and have been shown to alter gene transcription and exert antitumor *** paper describes our work on the structural determination and structure-activity relationship(SAR)optimization of tetrahydroisoquinoline compounds as HDAC *** compounds were tested for their ability to inhibit HDAC 1,3,6 and for their ability to inhibit the proliferation of a panel of cancer cell *** these,compound 82 showed the greatest inhibitory activity toward HDAC 1,3,6 and strongly inhibited growth of the cancer cell lines,with results clearly superior to those of the reference compound,vorinostat(SAHA).Compound 82 increased the acetylation of histones H3,H4 and tubulin in a concentration-dependent manner,suggesting that it is a broad inhibitor of HDACs.