Identification of Indole Derivatives as Selective Cyclooxygenase-2 Inhibitors by Virtual Screening and Molecular Dynamic Simulation

Abstract

Selective COX-2 inhibitors present a promising strategy in pain management due to their reduced adverse effects compared to non-selective COX inhibitors targeting COX-1. This study focuses on the design and virtual exploration of 8 indole derivatives using molecular docking, ADMET, and molecular dynamics (MD) simulations. Molecular docking highlighted the significance of hydrophobic and hydrophilic amino acid residues for ligand stability, with compounds 4 and 5 exhibiting notably strong in silico affinities to COX-2 (docking scores of -11.349 kcal/mol and -10.872 kcal/mol, respectively). Molecular dynamics simulations confirmed the stability of the COX-2-compound 4 complex over 50 ns, revealing consistent ligand-protein interactions through Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), and ligand binding analysis. ADMET analysis of the active compounds showed favorable drug-like profiles and desirable pharmacokinetic properties. This comprehensive computational approach sheds light on the structural dynamics and pharmacological characteristics of these indole derivatives, underscoring their potential as selective COX-2 inhibitors for pain management and paving the way for further experimental validation and clinical exploration.