Substituted indolin-2-ones as p90 ribosomal S6 protein kinase 2 (RSK2) inhibitors: Molecular docking simulation and structure-activity relationship analysis

被引：23
|
作者：
Zhong, Ye [1 ]
Xue, Mengzhu [1 ]
Zhao, Xue [1 ]
Yuan, Jun [1 ]
Liu, Xiaofeng [1 ]
Huang, Jin [1 ]
Zhao, Zhenjiang [1 ]
Li, Honglin [1 ]
Xu, Yufang [1 ]
机构：
[1] E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2013年 / 21卷 / 07期
基金：
中国国家自然科学基金;
关键词：
RSK2; Kinase inhibitor; Molecular docking; CRYSTAL-STRUCTURE; HYBRID APPROACH; IDENTIFICATION; ACTIVATION; REGULATOR; DISCOVERY; INSIGHTS; REVEALS; PATHWAY; BIOLOGY;
D O I：
10.1016/j.bmc.2013.01.047
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 series of novel indolin-2-ones inhibitors against p90 ribosomal S6 protein kinase 2 (RSK2) were designed and synthesized and their structure-activity relationship (SAR) was studied. The most potent inhibitor, compound 3s, exhibited potent inhibition against RSK2 with an IC50 value of 0.5 mu M and presented a satisfactory selectivity against 23 kinases. The interactions of these inhibitors with RSK2 were investigated based on the proposed binding poses with molecular, docking simulation. Four compounds and six compounds exhibited moderate anti-proliferation activities against PC 3 cells and MCF-7 cells, respectively. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码：1724 / 1734
页数：11
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