In-silico evaluation of triazole derivatives as antimicrobial agents against <i>Pseudomonas aeruginosa</i>

Abstract The continuous resistance of Pseudomonas aeruginosa to conventional antibiotics due to biofilm formation necessitates the development of potent alternatives. In this study, the antibacterial activity of 21 triazole derivatives was evaluated through molecular docking against the lasR protein of P. aeruginosa (PDB ID: 3JPU). Among them, compounds G, N, and U exhibited high binding affinity. Further ADMET analysis identified compound N as the most promising candidate due to its favorable pharmacokinetic and pharmacodynamic properties, as well as its compliance with Lipinski’s rule. Molecular dynamics simulations confirmed its stability within the active site, while density functional theory (DFT) calculations, including molecular electrostatic potential (MEP), highlighted the triazole ring and amine group as key interaction sites. Additionally, the frontier molecular orbital (FMO) analysis supported the stability of compound N. These findings suggest that compound N is a strong candidate for further development as an antibacterial drug.