Indexed by:
期刊论文
First Author:
Zhang, Zhichao
Correspondence Author:
Zhang, ZC (reprint author), Dalian Univ Technol, Sch Chem, Dalian 116012, Peoples R China.
Co-author:
Wu, Guiye,Xie, Feibo,Song, Ting,Chang, Xilong
Date of Publication:
2011-02-24
Journal:
JOURNAL OF MEDICINAL CHEMISTRY
Included Journals:
Scopus、SCIE、PubMed
Document Type:
J
Volume:
54
Issue:
4
Page Number:
1101-1105
ISSN No.:
0022-2623
Abstract:
We recently described the discovery of a dual inhibitor of Bcl-2 and Mcl-1, 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (3, S1). Here we report a structure-guided design in combination with structure activity relationship studies to exploit the difference in the p2 binding pocket of Bcl-2 and Mcl-1, from which a novel dual inhibitor 3-(4-aminophenylthio)-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (6h) was obtained, which showed significant enhanced IC(50) value against Mcl-1 (5 nM), greater Mcl-1/Bak disruption potential, and accordingly a 10-fold increased cytotoxicity over 3.
Translation or Not:
no
