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组蛋白去乙酰化酶是抗肿瘤作用的新靶点,基于该酶复合物的三维结构,首先对具有分子多样性的数据库进行了虚拟筛选;然后根据已知HDAC抑制剂的结构特征和筛选的结果,以及与生物大分子互补性,选择合理的构建单元,组建靶向的虚拟组合库;最后进行数据库虚拟筛选,对分子对接的结果进行评分,选择出理论上与HDAC有较好结合能力的化合物,设计了酰胺类、脲类和酰肼类全新结构类型的HDAC抑制剂,初步生物活性评价结果表明,预期有生物活性的化合物显示出一定的HDAC酶抑制活性。
Histone deacetylase is a new target of anti-tumor effect. Based on the three-dimensional structure of the enzyme complex, firstly, a database of molecular diversity was selected by virtual screening. Based on the structural characteristics of known HDAC inhibitors and screening As well as the complementarity with the biological macromolecules and the selection of rational building blocks to set up the targeted virtual combinatorial library. Finally, the database virtual screening was performed to score the results of the molecular docking and select the theoretical binding ability with HDAC Compounds, a new structural class of HDAC inhibitors for amides, ureas and hydrazides were designed. The preliminary bioassay results indicated that the expected biological activity of the compounds showed some HDAC inhibitory activity.