Bioorganic & Medicinal Chemistry 2014-12-15

Synthesis and evaluation of N-acyl-substituted 1,2-benzisothiazol-3-one derivatives as caspase-3 inhibitors.

Zhenghui Li, Yang Pan, Weilong Zhong, Yunpeng Zhu, Yongle Zhao, Lixin Li, Wei Liu, Honggang Zhou, Cheng Yang

Index: Bioorg. Med. Chem. 22(24) , 6735-45, (2015)

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Abstract

A small molecule library of N-acyl-substituted 1,2-benzisothiazol-3-one derivatives has been synthesized and evaluated as inhibitors of caspase-3 and -7, in which some of them showed nanomolar potency against caspase-3 and -7 in vitro. Meanwhile, in 10 lM concentration, both compounds 24 and 25 showed significant protection against apoptosis in camptothecin-induced Jurkat T cells system. The docking studies predicted the interactions and binding modes of the synthesized inhibitors in the caspase-3 active site.