组蛋白去乙酰化酶抑制剂研究进展  

Structure-activity relationships of histone deacetylase inhibitors

作　　者：谭玉梅[1] 黄文渊[1] 余聂芳[1] 

机构地区：[1]中南大学药学院分子设计与药物发现研究所,湖南长沙410013

出　　处：《药学学报》2009年第10期1072-1083,共12页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30772645;30873137)

摘　　要：组蛋白去乙酰化酶(histone deacetylases,HDACs)作为调控基因的关键蛋白酶,其功能异常被证实与肿瘤的发生和发展有直接关系。通过对HDAC功能的抑制调节,可以达到治疗肿瘤的目的。组蛋白去乙酰化酶抑制剂的作用机制已得到广泛研究,已开发出各种组蛋白去乙酰化酶抑制剂。按结构类型,组蛋白去乙酰化酶抑制剂大致可以分为:异羟肟酸类化合物(hydroxamic acid)、环状四肽类化合物、脂肪酸盐类化合物、苯甲酰胺类化合物和亲电酮类化合物等。本文对组蛋白去乙酰化酶抑制剂的各类结构及构效关系作一综述。Among those enzymes that regulate gene expression, histone deacetylases （HDACs） play important roles in cell cycles. Extensive studies were carded out in the field of HDACs and the applications of HDAC inhibitors （HDACIs） as chemotherapeutic interventions for diverse diseases. HDACIs have moved from laboratories to clinic uses. Huge bodies of related research results were well documented and dispersed in literature. According to our understanding, HDACIs can be broadly classified as hydroxamic acids, cyclic tetrapeptides, short chain fatty acids, benzamides and electrophilic ketones. Herein, we are going to review the design and their structure-activity relationships of HDACIs and according to their structural catalogs.

关 键 词：组蛋白 HDAC抑制剂 构效关系 

分 类 号：R916[医药卫生—药学]