In silico pharmacokinetics, molecular docking and dynamic simulation studies of endolichenic fungi secondary metabolites: An implication in identifying novel kinase inhibitors as potential anticancer agents

Abstract

Herein, seventy three (73) anticancer metabolites from different endolichenic fungi which are reported previously, were analyzed for drug likeliness and pharmacokinetic properties using SwissADME, ADMETlab, and admetSAR. The desirable compounds were studied using molecular docking against three clinically important human kinases: pyruvate kinase isoform 2, hexokinase II, and phosphoglycerate kinase. The results displayed a significant binding affinity of the test ligands against the kinases compared to 3-bromopyruvic acid, a reference glycolytic inhibitor. Pharmacokinetics and binding interactions of three compounds including talaromycin A, pyridoxatin, and terricollene A were predicted to be substantial. Terricollene A bound complexes were found to have the most considerable binding free energies and therefore were investigated for their conformational stability and compactness under explicit water conditions using molecular dynamics simulation up to 100 ns. The residual decomposition of binding energies for each of the complexes was calculated using Molecular Mechanics Poisson–Boltzmann Surface Area (MM-PBSA) method. The results demonstrated substantial stability and compactness of terricollene A-kinase complexes. The findings will facilitate the development of potential glycolytic inhibitors for treating and controlling several forms of cancer; however, supplementary experimental investigations to evaluate the efficacy of the test ligand are warranted.