Studies in molecular modeling, in vitro CDK2 inhibition and antimetastatic activity of some synthetic flavones

Naturally occurring flavonoids have been shown to possess anticancer activity. We have previously shown that certain synthetic flavonoids also exert significant antiproliferative potential in MOLT-4, MCF-7, and HepG2 cell lines. To this end, we evaluated eight synthetic flavones for their CDK2 binding by molecular docking. Most flavones showed interaction with Leu 83. Based on docking and antiproliferative activity, we chose 3'-nitroflavone and 3', 5'-dimethoxyflavone for the molecular dynamics (MD) simulation and CDK2 inhibition studies. MD simulation studies confirmed interactions with CDK2 (as observed in docking). Furthermore, the inhibitory activities of CDK2/cyclin A2 enzyme for 3'-nitroflavone and 3', 5'-dimethoxyflavone were found to be 6.17 and 7.19 mu M, respectively. 3'-nitroflavone and 3', 5'-dimethoxyflavone displayed moderate activity in colony formation assay, wound-scratch assay, and Leighton tube studies. Based on these data, the synthesized flavones might have clinical potential as potential inhibitors of CDK2.