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

被引：9

作者：

Li, Zhenghui ^{[1
]}

Pan, Yang ^{[3
]}

Zhong, Weilong ^{[3
]}

Zhu, Yunpeng ^{[1
]}

Zhao, Yongle ^{[5
]}

Li, Lixin ^{[5
]}

Liu, Wei ^{[2
]}

Zhou, Honggang ^{[4
]}

Yang, Cheng ^{[4
]}

机构：

[1] Tianjin Univ Sci & Technol, Coll Biotechnol, Tianjin 300457, Peoples R China

[2] Tianjin Univ Sci & Technol, Coll Sci, Tianjin 300457, Peoples R China

[3] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China

[4] Nankai Univ, Coll Pharm, Tianjin 300071, Peoples R China

[5] TEDA, Tianjin Int Joint Acad Biotechnol & Med, High Throughput Mol Drug Discovery Ctr, Tianjin 300457, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2014年 / 22卷 / 24期

基金：

中国国家自然科学基金;

关键词：

1,2-Benzisothiazol-3-one; Caspase-3; inhibitors; Apoptosis; Docking; Amides; DESIGN; APOPTOSIS; ACTIVATION; DISEASE;

D O I：

10.1016/j.bmc.2014.11.005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 mu M 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. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：6735 / 6745

页数：11

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