Computational investigation of the antibacterial and antioxidant potential of Rosa damascena essential oil from Morocco: Molecular docking and ADMET analysis of fourteen volatile compounds

Abstract

The emergence of multidrug-resistant bacterial strains has intensified the search for novel plant-derived antimicrobial agents. The present study reports the first comprehensive in silico investigation of the major volatile constituents of Rosa damascena Mill. essential oil (RDEO) from the Kelaat M′Gouna region of Morocco, integrating drug-likeness evaluation, ADMET profiling, and molecular docking simulations. Fourteen compounds identified by GC/MS-MS were docked against five biologically relevant protein targets: human tyrosinase (5M8O), Escherichia coli DNA gyrase B (6F86), Staphylococcus aureus DNA gyrase (3G7B), Bacillus subtilis enzyme (4OZ5), and Micrococcus luteus glutaminase (3GAD), using AutoDock Vina software, validated by redocking (RMSD ≈ 1.0 Å). SwissADME-based drug-likeness assessment confirmed that the majority of the selected compounds comply with Lipinski's Rule of 5 and display favorable ADMET profiles. All 14 compounds exhibited significant binding affinities across the five targets. Farnesol consistently ranked as the top-performing ligand, recording binding free energies of - 5.5, - 6.4, - 6.3, - 6.9, and - 6.6 kcal/mol against 5M8O, 6F86, 3G7B, 4OZ5, and 3GAD, respectively. Germacrene D achieved the highest individual binding energies of - 7.0 kcal/mol against B. subtilis and - 6.5 kcal/mol against S. aureus DNA gyrase. Binding was predominantly mediated through alkyl, π-alkyl, and π-σ hydrophobic interactions, supplemented by stabilizing hydrogen bonds. The multi-target engagement profile of Farnesol and Germacrene-D against DNA gyrase, glutaminase, and tyrosinase active sites suggests complementary antibacterial and antioxidant mechanisms that may reduce the likelihood of resistance development. These findings provide a rational molecular basis for the previously documented bioactivities of Moroccan RDEO and identify Farnesol and Germacrene-D as priority candidates for future experimental validation.