Essential oil from <i>Acacia nilotica</i> leaves: Integrated GC–MS/NMR profiling, antibacterial and antibiofilm assays, and computational evaluation of key constituents

Abstract

The rising prevalence of antibiotic-resistant infections underscores the urgent need for new natural antimicrobial agents. <i>Acacia nilotica</i>, a medicinally important species in African and Asian ethnobotany, was investigated for its leaf essential oil (EO) composition, antibacterial, antibiofilm, and <i>in silico</i> pharmacological properties. GC-MS and multidimensional NMR analyses identified 42 constituents dominated by cumin aldehyde (12.26%), eucalyptol (7.42%), α-pinene (7.06%), eugenol (5.73%), and β-caryophyllene (9.18%). The EO exhibited broad-spectrum antibacterial activity, producing inhibition zones of 20–40 mm and minimum inhibitory concentrations (MICs) between 0.375 and 1.5 mg/mL. Notably, it inhibited <i>Klebsiella ozaenae</i> (40 ± 3 mm) and <i>Escherichia coli</i> (35 ± 2 mm) more effectively than gentamicin (24 ± 1.8 mm and 22 ± 1.5 mm, respectively), though the antibiotic had lower MICs (0.03–0.06 mg/mL). The EO also suppressed <i>Pseudomonas aeruginosa</i> biofilm formation by 78% at 0.5×MIC and 69% at 0.25×MIC, and reduced <i>Staphylococcus aureus</i> biofilms by 48% and 36% at the same concentrations. Molecular docking revealed strong interactions of eugenol with <i>S. aureus</i> Sortase A (−10.93 kcal/mol) and <i>P. aeruginosa</i> LasR (−9.23 kcal/mol), supported by stable molecular dynamics simulations with low RMSD values (1.13–1.72 Å) and sustained hydrogen bonding (average 133–135 bonds). ADMET predictions indicated good oral bioavailability, compliance with Lipinski's and Veber's rules, and no cytochrome P450 inhibition or predicted toxicity. Overall, the findings demonstrate that <i>A. nilotica</i> leaf EO, rich in oxygenated monoterpenes such as eugenol and cumin aldehyde, exhibits potent antibacterial and antibiofilm properties supported by favorable pharmacokinetics. These results position <i>A. nilotica</i> EO as a promising natural candidate or adjuvant in the development of alternative therapeutics against multidrug-resistant bacterial infections.