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

doi:10.1016/j.bmc.2014.11.005

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

Bioorg Med Chem. 2014 Dec 15;22(24):6735-45. doi: 10.1016/j.bmc.2014.11.005.

Authors

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

PMID: 25468037
DOI: 10.1016/j.bmc.2014.11.005

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / drug effects
Binding Sites
Camptothecin / toxicity
Caspase 3 / chemistry
Caspase 3 / metabolism*
Caspase 7 / chemistry
Caspase 7 / metabolism
Caspase Inhibitors / chemical synthesis*
Caspase Inhibitors / chemistry
Caspase Inhibitors / pharmacology
Catalytic Domain
Humans
Jurkat Cells
Molecular Docking Simulation
Protein Binding
Structure-Activity Relationship
Thiazoles / chemical synthesis
Thiazoles / chemistry*
Thiazoles / pharmacology

Substances

Caspase Inhibitors
Thiazoles
Caspase 3
Caspase 7
Camptothecin