Design, synthesis, and antiproliferative and CDK2-cyclin a inhibitory activity of novel flavopiridol analogues

Bioorg Med Chem. 2007 Jan 15;15(2):702-13. doi: 10.1016/j.bmc.2006.10.063.

Yu Mi Ahn ¹, Lakshminarayana Vogeti, Chun-Jing Liu, Hari K R Santhapuram, Jonathan M White, Veena Vasandani, Lester A Mitscher, Gerald H Lushington, Paul R Hanson, Douglas R Powell, Richard H Himes, Katherine F Roby, Qizhuang Ye, Gunda I Georg

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Affiliation

1 Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, University of Kansas, Lawrence, KS 66045-7582, USA.

PMID: 17123821 DOI: 10.1016/j.bmc.2006.10.063

Abstract

The design and synthesis of a small library of 8-amidoflavone, 8-sulfonamidoflavone, 8-amido-7-hydroxyflavone, and heterocyclic analogues of flavopiridol is reported. The potential activity of these compounds as kinase inhibitors was evaluated by cytotoxicity studies in MCF-7 and ID-8 Cancer cell lines and inhibition of CDK2-Cyclin A enzyme activity in vitro. The antiproliferative and CDK2-Cyclin A inhibitory activity of these analogues was significantly lower than the activity of flavopiridol. Molecular docking simulations were carried out and these studies suggested a different binding orientation inside the CDK2 binding pocket for these analogues compared to flavopiridol.

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