Docking studies of a Triazole-based Chalcone on Various Matrix Metalloproteinases

Abstract

Docking is a powerful tool that has been validated for lead optimization. Cancer research has been always concerned with matrix metalloproteinases (MMPs) inhibition being a validated druggable target that is implicated in almost all stages of carcinogenesis. Therefore, optimization of lead inhibitors is of utmost importance. The present study explores the possible binding modes of a novel triazole-based chalcone into various MMPs catalytic domains in attempt to explore its potential as possible MMP inhibitors, identify its isoform selectivity and deduce the structural determinants of activity within the scaffold. The investigated chalcone, referred to as compound 3, demonstrated preferential binding to MMP-9 and MMP-13 in terms of favorable binding energies (-11.92 and -11.25 kcal/mol), inhibition constants (1.82 and 5.65 nM), electrostatic (-0.38 and -0.14 Kcal/mol) and vdW (-13.63 and -13.32 Kcal/mol, respectively) interactions referring to its potential utility for targeted selective tumor-associated MMPs inhibition. These results encourage further research to evaluate the compound’s in vitro potency of the studied compound against MMP-9 and MMP-13 and sensitive cancer cell lines.