Discovery of novel indirubin-3'-monoxime derivatives as potent inhibitors against CDK2 and CDK9.
Discovery of novel indirubin-3'-monoxime derivatives as potent inhibitors against CDK2 and CDK9.
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DOI：
10.1016/j.bmcl.2015.03.066
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发表时间：
2015-06
影响因子：
2.7
通讯作者：
Lei Yan;Fangfang Lai;Xiaoguang Chen;Zhiyan Xiao
中科院分区：
文献类型：
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作者：
Lei Yan;Fangfang Lai;Xiaoguang Chen;Zhiyan Xiao
Indirubin-3′-monoxime (IM) 是一种有效的细胞周期蛋白依赖性激酶 (CDK) 抑制剂。制备了 20 种新型 IM 衍生物来研究此类化合物的构效关系 (SAR)。六种化合物对 CDK2/细胞周期蛋白 E1 和 CDK9/细胞周期蛋白 T1 均表现出显着抑制作用。最有效的化合物7 表现出亚微摩尔水平的IC50 值。提出了初步的 SAR 趋势并研究了这些化合物的细胞毒性。化合物7和7t的分子对接研究为进一步结构优化提供了有利线索。
Indirubin-3′-monoxime (IM) is a potent cyclin-dependent kinase (CDK) inhibitor. Twenty novel IM derivatives were prepared to investigate the structure–activity relationships (SAR) of this compound class. Six compounds showed significant inhibition against both CDK2/cyclin E1 and CDK9/cyclin T1. The most potent compound7texhibited IC50values at submicromolar level. Preliminary SAR trends were suggested and cytotoxicity of these compounds was investigated. Molecular docking studies on compounds7land7tprovided conducive clues for further structural optimization.