Structure-based design of rhodanine-based acylsulfonamide derivatives as antagonists of the anti-apoptotic Bcl-2 protein
Structure-based design of rhodanine-based acylsulfonamide derivatives as antagonists of the anti-apoptotic Bcl-2 protein
复制标题
基于绕丹宁的酰基磺酰胺衍生物作为抗凋亡 Bcl-2 蛋白拮抗剂的结构设计
DOI：
10.1016/j.bmc.2012.05.079
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发表时间：
2012-07-15
影响因子：
3.5
通讯作者：
Qiao, Chunhua
中科院分区：
文献类型：
--
作者：
Li, Huan-qiu;Yang, Jing;Qiao, Chunhua
设计、合成了一系列基于罗丹宁的新型酰基磺酰胺类化合物，并将其作为抗细胞凋亡蛋白的小分子抑制剂进行了评价。这些化合物在三种人肿瘤细胞系(Hep G2、PC-3和B16-F10)中显示出很强的抗增殖活性。其中，最有效的化合物10和11分别与Bcl2结合，K-I分别为20和25 nm。对接研究表明，这两个化合物在Bcl2结合部位具有相似的取向，计算的结合亲和力(Glide XP Score)比化合物11更负。分析了高结合亲和力化合物与Bcl2蛋白的结合作用。(C)2012爱思唯尔有限公司。保留所有权利。
A series of novel rhodanine-based acylsulfonamide derivatives were designed, synthesized, and evaluated as small-molecule inhibitors of anti-apoptotic Bcl-2 protein. These compounds exhibit potent antiproliferative activity in three human tumor cell lines (Hep G2, PC-3 and B16-F10). Among them, the most potent compounds 10 and 11 bind to Bcl-2 with a K-i of 20 and 25 nM, respectively. Docking studies demonstrated that these two compounds orient similarly at the binding site of Bcl-2, and the calculated binding affinities (Glide XP score) of compound 10 is more negative than that of compound 11. The binding interactions of compounds with high binding affinity to Bcl-2 protein were analyzed. (C) 2012 Elsevier Ltd. All rights reserved.