Antibacterial mechanisms of Mentha longifolia L. essential oil from AlUla (Saudi Arabia) using in silico molecular docking tools as an innovative approach to developing sustainable antibiotics

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Antibiotic-resistant bacteria are a significant global challenge. In Saudi Arabia, 7,592 antibiotic-resistant strains were documented from 2003 to 2023. We investigated the antibacterial efficacy and mechanisms of action of Mentha longifolia L. essential oil (EO). GC–MS and GC-FID analyses identified 73 constituents, with piperitone epoxide (37.96%), 1,8-cineole (16.37%), and menthone (10.01%). In vitro assays (agar well diffusion and minimum inhibitory concentration, MIC) showed substantial activity: inhibition zones were 28.5 ± 0.57 mm for Escherichia coli, 24.7 ± 1.5 mm for Staphylococcus aureus, and 22.5 ± 2.5 mm for Bacillus subtilis, with MICs of 0.003, 0.005, and 0.007 μg/mL, respectively. Molecular docking revealed strong ligand–receptor affinities (−13.40 kcal/mol for 2W9S, −12.50 for 4QM9, −14.70 for 4JX7), with 4JX7 showing the most favorable interactions, consistent with the experimental potency and suggesting synergistic effects among the major monoterpenes. This is the first comprehensive examination of M. longifolia from the AlUla region, integrating complete GC–MS chemotyping, solvent-controlled antibacterial assays with statistical analysis, and multi-ligand docking across three bacterial targets to relate the composition and mechanism. These findings underscore the antibacterial potential of M. longifolia EO and its synergistic effects, offering a promising basis for sustainable antibiotics against drug-resistant bacteria.