Docking study on anticancer activity of chromone derivatives

Several phenyl substituted chromones (also called flavonoids) have been reported to possess substantial anticancer properties; however, their modes of action have not been clearly defined. To preliminarily investigate the potential anticancer activity and mode of action of some synthetic chromone derivatives, the docking was performed using different enzymes and receptor proteins involved with cancer cell cycle, cell growth, and DNA replication, i.e., cyclin-dependent protein kinase-2 (CDK-2), CDK-6, DNA topoisomerases I and II, B-cell lymphoma-2 (Bcl-2), vascular endothelial growth factor receptor-2 (VEGFR-2), and the telomere: G-quadruplexes. The docking results revealed that chromone 32 exhibited better binding interactions to CDK-2 and Bcl-2 than the known CDK-2 and Bcl-2 inhibitors. Chromone 39 was found to bind to CDK-6 with tighter interaction than several reported CDK-6 inhibitors. Chromone 47 was best bound to both DNA topoisomerases I and II. Chromones 24 and 15 showed good binding interaction with VEGFR-2 and telomere: G-quadruplex, respectively. The inhibition constants (Ki) of each chromone compound against each target molecule were calculated. These Ki values could be used as a preliminary tool for screening specific inhibitors before performing experimental activity assay.