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

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• 作者：Ye Zhong^&dagger ; ; Mengzhu Xue^&dagger ; ; Xue Zhao^&dagger ; ; Jun Yuan ; Xiaofeng Liu ; Jin Huang ; Zhenjiang Zhao ; ^{zhjzhao@ecust.edu.cn} ; Honglin Li ; ^{hlli@ecust.edu.cn} ; Yufang Xu ; ^{yfxu@ecust.edu.cn}
• 关键词：RSK2 ; Kinase inhibitor ; Molecular docking
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2013
• 出版时间：1 April, 2013
• 年：2013
• 卷：21
• 期：7
• 页码：1724-1734
• 全文大小：2768 K

文摘

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 ¦ÌM 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.