Molecular docking study on anticancer activity of plant-derived natural products

摘要

A variety of compounds from plant sources have been reported to possess substantial anticancer properties; however, their modes of action have not been clearly defined. Selected plant-derived compounds that exhibit anticancer activity were subjected to docking simulations using AutoDock 3.0.5. To preliminarily investigate the potential molecular targets and to confirm the experimental activity testing for these anticancer compounds, the docking was performed using different enzymes and receptor proteins involved with 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 lupeol exhibited better binding interaction to CDK-2 and Bcl-2 than the known CDK-2 and Bcl-2 inhibitors. Epigallocatechin gallate (EGCG) was found to bind to CDK-6 with tighter interaction than several reported CDK-6 inhibitors. Flavopiridol, a synthetic flavonoid, was best bound to DNA topoisomerase I. Green tea catechin was best docked with topoisomerase II and VEGFR-2 and quercetin showed very good binding interaction with telomere: G-quadruplex. The experimental-derived inhibition constant (Ki) against Bcl-2 and Ki calculated from docking energy were well correlated. Therefore, the calculated Ki could be used as a preliminary tool for screening of Bcl-2 inhibitors before performing experimental activity assay.