苯甲酰胺类组蛋白去乙酰化酶抑制剂的构效关系研究进展

Progress in the research of structure-activity relationship of the benzamide class of histone deacetylase inhibitors

组蛋白去乙酰化酶(histone deacetylase,HDAC)是一类锌离子依赖性金属蛋白酶,广泛分布于各种真核细胞内并发挥着重要的生物学功能。HDAC抑制剂已成为一种新型的非细胞毒抗肿瘤药物,其对各种实体瘤、淋巴癌和白血病细胞的生长、成熟、转移和侵袭具有良好的选择性抑制作用。大部分抑制剂是通过螯合酶催化活性中心的锌离子来发挥抑酶活性,而苯甲酰胺类HDAC抑制剂不同于传统的异羟肟酸类抑制剂,其分子中所含有的独特的N-(2-氨基苯基)苯甲酰胺的药效团结构使其具有良好的口服生物活性和抗肿瘤活性。文中主要综述了近年来该类抑制剂的构效关系研究进展。

Histone deacetylase （HDAC） , a class of zinc-dependent metalloprotease existing in all kinds of eukaryotic cells, has important biological function. HDAC inhibitors （HDACi） have emerged as a novel class of noncytotoxic antitumor agents. They are attracting attention of the researchers in the world because they can exhibit exciting inhibitory activity to selectively inhibit proliferation, maturation, migration and diffusion of various solid tumor, lymphoma and leukaemia cells. Most of HDACi exert their enzymatic inhibitory activity by chelating the zinc ion in the catalyticsite of HDAC. The benzamide class of HDACi, characterized by the N-（2-aminophenyl） benzamide, is an active pharmacophore that ensure the potent oral bioactivity and antitumor activity. This review mainly summarizes structure-activity relationship of this class of HDACi in recent years.