Discovery of novel indirubin-3′-monoxime derivatives as potent inhibitors against CDK2 and CDK9. Issue 11 (1st June 2015)

• Record Type: Journal Article
• Authors: Yan, Lei; Lai, Fangfang; Chen, Xiaoguang; Xiao, Zhiyan
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 11(2015)
• Page Start: 2447
• Page End: 2451
• Publication Date: 2015-06-01
• Subjects: Indirubin-3′-oxime derivatives -- Cyclin-dependent kinase 2 -- Cyclin-dependent kinase 9 -- Structure–activity relationship; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.03.066
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 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 compound7t exhibited IC50 values at submicromolar level. Preliminary SAR trends were suggested and cytotoxicity of these compounds was investigated. Molecular docking studies on compounds7l and7t provided conducive clues for further structural optimization.