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

Year 2025, Volume: 9 Issue: 2, 19 - 32

Mohammed Abdulaali Sahib , Monther Faisal Mahdi

https://doi.org/10.33435/tcandtc.1442939

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.

Keywords

Indole Derivatives, Molecular dynamic simulation, Compound 4, molecular docking, 4-Imidazolidinone, COX-2

Ethical Statement

Ethical considerations for computational research were meticulously addressed throughout this study. All simulations, data analysis, and modeling techniques were conducted in adherence to established computational biology and bioinformatics protocols. No human or animal subjects were involved in the study, and all data used were obtained from publicly available databases or generated through computational algorithms. Any potential biases or limitations in the computational methodologies employed were carefully considered and disclosed to ensure the integrity and reliability of the research findings.

Supporting Institution

Our research was supported by Mustansiriyah University

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