Quantum Chemical Analyses of Methylated Derivatives of Gallic Acid and In Silico Evaluations of their Interactions with the Cyclooxygenase-2 Enzyme

Abstract

Structural and electronic features of methylated derivatives of gallic acid were analyzed by performing quantum chemical density functional theory (DFT) calculations. Subsequently, interactions of each stabilized structure of gallic acid (ligand) were evaluated towards the cyclooxygenase-2 (COX-2) enzyme target by performing in silico-based molecular docking simulations to approach a point of exploring new sets of anti-inflammatory agents. The available OH groups of gallic acid were substituted by one, two, three, and four methyl groups to yield the new OMe groups for the derivatives. Accordingly, their electronic features indicated the impacts of such structural modifications on the electronic properties of gallic acid. The results of stabilizations and electronic features evaluations indicated the majority of structural modification of gallic acid for achieving more specific ligand structures. Additionally, the results of molecular docking simulations of interacting ligand-target complexes indicated a benefit of structural modification of gallic acid for approaching a higher strength level of interaction with the COX-2 enzyme target compared with the original gallic acid compound. As a remarkable achievement of this work, the methylation of gallic acid could yield more efficient ligands for interacting with the COX-2 enzyme target. © 2023 by the authors.