Screening of antimicrobial phytochemicals from Allium sativum against bacterial and fungal drug targets: Insights from molecular docking and ADMET analysis

Antimicrobial resistance (AMR) continues to erode the effectiveness of established antibacterial and antifungal therapies, underscoring the need for new antimicrobial agents from natural sources with improved safety profiles. This study aims to computationally screen and evaluate three organosulfur phytochemicals of Allium sativum (garlic): Allicin, ajoene, and diallyl trisulfide, as potential inhibitors of bacterial and fungal drug targets. The three phytochemicals were docked against DNA gyrase and lanosterol 14α-demethylase (CYP51) using Molegro Virtual Docker, with binding affinity assessed via MolDock and Rerank scores and protein-ligand interactions visualised in BIOVIA Discovery Studio. Binding affinities were compared with those of the reference drugs ciprofloxacin and ketoconazole, docked under identical conditions, and drug-likeness and ADMET properties were predicted using SwissADME and pkCSM. All three phytochemicals formed stable, energetically favourable complexes with both targets. Ajoene consistently returned the strongest binding affinity (MolDock: -84.20 kcal/mol against DNA gyrase; - 83.55 kcal/mol against CYP51). It retained 62.0% - 78.0% of the binding strength of each reference drug and shared the active-site residue Asp-73 with ciprofloxacin. ADMET evaluation showed high intestinal absorption (92.6% - 100%) and no predicted hERG inhibition or hepatotoxicity for any compound, although ajoene was Ames-positive (mutagenic) and allicin and diallyl trisulfide were flagged for skin sensitisation. These findings identify ajoene as a promising broad-spectrum natural lead compound for antimicrobial drug development, warranting further in vitro validation together with explicit investigation of its predicted mutagenicity.