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ID: ALA2046328

Journal: Bioorg Med Chem

Title: Structure-based design of rhodanine-based acylsulfonamide derivatives as antagonists of the anti-apoptotic Bcl-2 protein.

Authors: Li HQ, Yang J, Ma S, Qiao C.

Abstract: 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.

CiteXplore: 22739087

DOI: 10.1016/j.bmc.2012.05.079