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

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

Bioorganic & medicinal chemistry (2014-12-04)
Zhenghui Li, Yang Pan, Weilong Zhong, Yunpeng Zhu, Yongle Zhao, Lixin Li, Wei Liu, Honggang Zhou, Cheng Yang
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.

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