Design and Synthesis of Heptadecane-Linked 1,2,4-Triazoles as Antimicrobial Agents

Abstract

Superbugs, as bacterial resistance species, resist known antibiotics. In this study, 20 novel 1,2,4-triazole-functionalized piperazine-stearic acid derivatives 6a–p were designed, synthesized, and characterized via spectroscopic analyses, evaluating their antimicrobial potential against clinically relevant bacterial and fungal strains. Notably, five derivatives (6a, 6c, 6m, 6n, and 6o) demonstrated superior antimicrobial efficacy compared to the gentamicin standard, with compound 6n showing the most potent activity (minimal inhibitory concentration = 3.125 µg/mL against Staphylococcus aureus). Molecular docking simulations further revealed strong binding affinities of these compounds to microbial target proteins (ΔG = -8.2 to -9.7 kcal/mol). These findings present promising antimicrobial candidates of 1,2,4-triazole-appended piperazine-stearic moiety derivatives.