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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) is a kind of zinc ion-dependent metalloproteinase widely distributed in various eukaryotic cells and plays an important biological function. HDAC inhibitors have emerged as a new class of non-cytotoxic anti-tumor drugs that have a good selective inhibitory effect on the growth, maturation, metastasis and invasion of various solid tumors, lymphoma and leukemia cells. Most of the inhibitors exert their inhibitory activity by chelating the zinc ions of the catalytic active center, whereas the benzamide HDAC inhibitors differ from the conventional hydroxamic acid inhibitors in that their molecules contain unique N - (2 - aminophenyl) benzamide pharmacophore structure so that it has good oral bioactivity and anti-tumor activity. This review summarizes recent progress in the structure-activity relationship of these inhibitors.