Molecular Insights into Antimicrobial Triazole Compounds: A Synergistic 2D‐QSAR, DFT, and POM Approach

Abstract A comprehensive study was conducted using DFT quantum calculations, 2D‐QSAR, and POM analysis, to evaluate the potential of triazole derivatives against Mycobacterium tuberculosis (MTB) and Pseudomonas aeruginosa (PA). Twenty‐one compounds were analyzed, with Ciprofloxacin as a reference, and two key protein targets, LasR and LipY, were studied for their interactions. Quantum parameters of the molecules were calculated using the B3LYP/6–311G(d) basis set, focusing on electrostatic and nucleophilic potential. The QSAR models, developed using MLR, and MNLR techniques, demonstrated strong predictive power, with the RNLM model exhibiting high predictive accuracy (R 2 MTB = 0.81 and R 2 PA = 0.91) for both bacterial strains. The most significant descriptors for predicting antibacterial activity included E HOMO , E LUMO , PSA, NHA, and γ. Notably, three compounds (A, S, and T) showed the highest activity against MTB, while compounds M, R, and T exhibited promising efficacy against PA. Additionally, the antimicrobial effects of triazole derivatives were investigated, revealing significant activity for these molecules against both MTB and PA. Pharmacophore site identification using POM analysis further supported the potential of these compounds, offering valuable insights for drug discovery. This integrated approach underscores the importance of understanding the structure‐activity relationships of triazole molecules, demonstrating their potential for the development of novel antibacterial agents.