Title of article :
Design, synthesis, and antiproliferative and CDK2-cyclin a inhibitory activity of novel flavopiridol analogues Original Research Article
Author/Authors :
Yu Mi Ahn، نويسنده , , Lakshminarayana Vogeti، نويسنده , , Chun-Jing Liu، نويسنده , , Hari K.R. Santhapuram، نويسنده , , Jonathan M. White، نويسنده , , Veena Vasandani، نويسنده , , Lester A. Mitscher، نويسنده , , Gerald H. Lushington، نويسنده , , Paul R. Hanson، نويسنده , , Douglas R. Powell، نويسنده , , Richard H. Himes، نويسنده , , Katherine F. Roby، نويسنده , , Qizhuang Ye، نويسنده , , Gunda I. Georg، نويسنده ,
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.
Keywords :
Docking simulations , Flavopiridol analogues , Synthesis , Cytotoxicity , CDK2-Cyclin A
