新型小分子Bcl-2蛋白抑制剂的设计、合成及体外活性研究  

Design,synthesis and in vitro activity study of a novel Bcl-2 protein inhibitors

作　　者：李河川[1] 万剑飞[1] 何谷 范举正[1] 

机构地区：[1]四川大学华西药学院,四川成都610041 [2]华西医院生物治疗国家重点实验室,四川成都610041

出　　处：《华西药学杂志》2016年第4期332-338,共7页West China Journal of Pharmaceutical Sciences

摘　　要：目的设计并合成新型小分子Bcl-2蛋白抑制剂。方法基于已报道的活性小分子,运用Autodock4.2研究其与Bcl-2蛋白的作用模式,并以此设计、合成一系列新型小分子抑制剂,采用MTT法对人肝癌细胞Hep G-2进行体外抗肿瘤活性实验。结果设计合成了11个全新小分子化合物,其结构经~1HNMR和^(13)CNMR确定。结论化合物Ⅱ、Ⅴ、Ⅹ、Ⅺ有明显的体外抗肿瘤活性,化合物Ⅵ显示出比较好的体外抗肿瘤活性,高于阳性对照。OBJECTIVE To design and synthesize new small Bcl -2 protein inhibitors. METHODS Based on the active molecules which had been reported,the mode of action with the Bcl - 2 protein was researched by Autodock4.2, a series of new molecule inhibitors were designed and synthesized. The anti - tumor activities of diosgenin derivatives were studied using HepG - 2 in vitro by M3T assay. RESULTS The 11 compounds had been determined by lHNMR and ^13CNMR. CONCLUSION Among these compounds, II , V, X and XI exhibit good activity in vitro, and compound VI shows significant anti - tumor activity in vitro, which is better than the positive control drug.

关 键 词：新型小分子抑制剂 BCL-2 抗肿瘤活性 人肝癌细胞HEPG-2 活性小分子 蛋白抑制剂 

分 类 号：R914[医药卫生—药物化学]