View : 20 Download: 0

5,5′-substituted indirubin-3′-oxime derivatives as potent cyclin-dependent kinase inhibitors with anticancer activity

Title
5,5′-substituted indirubin-3′-oxime derivatives as potent cyclin-dependent kinase inhibitors with anticancer activity
Authors
Choi S.-J.Lee J.-E.Jeong S.-Y.Im I.Lee S.-D.Lee E.-J.Lee S.K.Kwon S.-M.Ahn S.-G.Yoon J.-H.Han S.-Y.Kim J.-I.Kim Y.-C.
Ewha Authors
이상국
Issue Date
2010
Journal Title
Journal of Medicinal Chemistry
ISSN
0022-2623JCR Link
Citation
vol. 53, no. 9, pp. 3696 - 3706
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
To enhance the ability of indirubin derivatives to inhibit CDK2/cyclin E, a target of anticancer agents, we designed and synthesized a new series of indirubin-3′-oxime derivatives with combined substitutions at the 5 and 5′ positions. A molecular docking study predicted the binding of derivatives with OH or halogen substitutions at the 5′ position to the ATP binding site of CDK2, revealing the critical interactions that may explain the improved CDK2 inhibitory activity of these derivatives. Among the synthesized derivatives, the 5-nitro-5′-hydroxy analogue 3a and the 5-nitro-5′-fluoro analogue 5a displayed potent inhibitory activity against CDK2, with IC50 values of 1.9 and 1.7 nM, respectively. These derivatives also showed antiproliferative activity against several human cancer cell lines, with IC50 values of 0.2-3.3 μM. A representative analogue, 3a, showed greater than 500-fold selectivity for CDK relative to selected kinase panel and potent in vivo anticancer activity. © 2010 American Chemical Society.
DOI
10.1021/jm100080z
Appears in Collections:
약학대학 > 약학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE