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组蛋白去乙酰化酶抑制剂是一类以组蛋白去乙酰化酶为靶点的新型靶向抗肿瘤药物,在抗增殖、促凋亡、促分化、阻滞细胞生长周期、抗血管生成等方面有很好的作用。组蛋白去乙酰化酶抑制剂以其独特的抗肿瘤作用机理,在研发肿瘤治疗药物中占有重要地位。在组蛋白去乙酰化酶抑制剂分类中,环肽类抑制剂结构最为复杂,对多种类型的实体瘤及血液学癌细胞均具有良好的对抗作用。本文针对天然和化学合成的环肽类组蛋白去乙酰化酶抑制剂中金属结合区、表面识别区以及连接区的结构特点进行了综述,并描述了各类抑制剂对酶的抑制活性和抗肿瘤增殖活性。对抑制剂不同结构区的修饰、改造可以使抑制剂对不同肿瘤细胞具有高效性和特异性作用,通过构效关系研究寻找具有高效低毒、靶向性环肽类抑制剂的结构规律,可为研究开发抗肿瘤药物提供帮助。
Histone deacetylase inhibitors are a new class of targeted anti-tumor drugs targeting histone deacetylase. They are widely used in antiproliferation, proapoptosis, differentiation, cell cycle arrest, anti-angiogenesis, etc. Have a good role. Histone deacetylase inhibitors with its unique anti-tumor mechanism of action in the development of cancer treatment drugs occupy an important position. Among the histone deacetylase inhibitor classes, cyclopeptide inhibitors are the most complex and have good antagonism against many types of solid tumors and hematological cancers. In this paper, the structural characteristics of the metal-binding region, the surface recognition region and the junction region of natural and chemically synthesized cyclopeptide histone deacetylase inhibitors are summarized, and the inhibitory activity and anti-enzyme activity of various inhibitors on the enzyme Tumor proliferation activity. The modification and modification of different structural regions of inhibitors can make the inhibitors have high efficiency and specificity for different tumor cells, and the structural rules of high, low toxicity and targeted cyclic peptide inhibitors can be searched through the structure-activity relationship study To research and development of anticancer drugs to help.