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

Abstract

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.

Molecular docking of the anticancer bioactive compound proceraside with macromolecules involved in the cell cycle and DNA replication

“…However, with topoisomerase II, its binding energy (-1.09 kcal/mol) and inhibition constant (7.40 nM) values were comparable to those of the cocrystal ligand. DNA topoisomerases I and II have both been implicated in cell survival and they play critical roles in DNA metabolism and structure (Phosrithong and Ungwitayatorn, 2010). Proceraside A showed the best interaction with topoisomerases I, which involved six hydrogen bonds formed via the following: the backbone N atom of Glu356, the backbone O atom of Tyr426; the backbone N atom of Met428; the side chain N atoms of Asn722 and Lys751 and the hydrophobic interactions via Ala351, Asn352, Trp416, Ile427, Leu429, Pro431, Lys436, and Leu721.…”

Target fishing of glycopentalone using integrated inverse docking and reverse pharmacophore mapping approach

“…Both DNA Topoisomerases I and II have implicated functions in cell survival and play critical roles in DNA metabolism and structure (Phosrithong and Ungwitayatorn, 2010). Glycopentalone showed fine interaction with Topoisomerase I, which involved five hydrogen bonds of distances 3.30, 2.97, 2.40, 2.98, and 3.05Å formed via backbone N atom and O atom of Asn352, backbone O atom of Tyr426, backbone N atom of Met428 and side chain NZ atom of Lys436 respectively, and hydrophobic interactions via Ala351, Ala356 and Ile.…”

In Vitro and Computational Assessment of Genotoxic Potential of Active Constituents Present in Three Medicinally Important Plant Extracts

“…Effects of these molecules are now subjected to computational analysis through molecular docking like use of AUTODOCK in order to investigate their anticancer and other properties with accuracy at molecular level. This also helps to identify the nature of formed complexes with receptor proteins present in cell cycle and other biological processes (Phosrithong, 2010).…”