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
Affiliations
  • 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.