Molecular Docking-Aided Identification of Natural Bioactive Molecules as Potential Cancer Cell Proliferation Inhibitors

Molecular Docking as Cancer Cell Inhibitors

Abstract

Cancer is the second leading cause of death worldwide. Uncontrolled proliferation of cells is a hallmark of cancer development and progression. Ki-67 (a marker of proliferation Kiel-67) and Proliferating Cell Nuclear Antigen (PCNA) are two major proliferations, diagnostic and prognostic biomarkers as these are over expressed in cancerous cells. Pharmacological inhibition of Ki-67 and PCNA could effectively inhibit the growth of cancer cells. Objective: To identify Sesquiterpene Lactones (SLs) as potential inhibitors of Ki-67 and PCNA to reduce cancer burden. Methods: The inhibitory potential of SLs, namely sulfocostunolide A, sulfocostunolide B, ilicol, eucalyptone, and ascleposide E, were investigated using Molecular Docking (MD) analysis. MD analysis and visualization of ligand-protein complexes were performed using softwares such as MGL tools, BIOVIA Discovery Studio visualizer and LigPlot plus. Additionally, drug likeness and pharmacokinetic properties of SLs were assessed via pkCSM and ADMET analysis. Results: Results showed that eucalyptone with binding energy of -8.1 kcal/mol with Ki-67 while sulfocostunolide B with -6.4 kcal/mol binding energy with PCNA are the most potent proliferative inhibitors of Ki-67 and PCNA. ADMET properties, MD studies and toxicity prediction shows that current investigated ligands bind effectively with Ki-67 and PCNA without showing any toxicity. Conclusions: Current study concludes that eucalyptone with Ki-67 and sulfocostunolide B with PCNA made stable complexes and can be considered as novel inhibitors. In addition to that, these suggested ligands have also shown effective drug likeness and ADMET profile. Further, in-vitro and in-vivo studies are required to validate these findings.