In silico evaluation of Ocimum sanctum phytochemicals for diabetic foot ulcer therapy through docking, ADMET, DFT, and molecular dynamics

Due to poorly managed diabetes, diabetic foot ulcers (DFUs) often have elevated MMP-9 levels that slow wound healing. High levels of matrix metalloproteinases (MMPs), notably MMP-9, which are necessary for inflammation and wound repair, slow DFU recovery. This study investigates phytocompounds from Ocimum sanctum as MMP-9 inhibitors for diabetic foot ulcers to promote wound healing and develop effective treatments. Phytocompounds from Ocimum sanctum were compared to (R)-ND-336 for MMP-9 inhibition via molecular docking. Toxicology, ADME, and drug-likeness were assessed. MMP-9 interactions and compound stability were analyzed by molecular dynamics simulations, whereas reactivity was tested using density functional theory calculations. The binding stability was determined using structural and energetic studies. Docking experiments discovered nine phytochemicals with higher binding affinities than (R)-ND-336. Seven compounds met Lipinski’s rule of five and demonstrated drug-like properties. Cytotoxicity, hepatotoxicity, and neurotoxicity were absent in most substances, while chlorogenic acid and rosmarinic acid showed immunotoxicity. Docking research revealed strong binding affinities between MMP-9 and cianidanol, luteolin, rosmarinic acid, apigenin, and quercetin (-9.1 to -9.8 kcal/mol). Thermal study demonstrated spontaneous binding of rosmarinic acid and quercetin. In HOMO-LUMO analysis, smaller energy gaps suggested greater reactivity and metabolic stability. Molecular electrostatic potential research showed lutein was most polar. Molecular dynamics simulations validated apigenin’s stability, negligible RMSD variations, optimal SASA, and robust receptor binding. This study investigates apigenin, a phytochemical found in Ocimum sanctum, as a prospective inhibitor of MMP-9 for the healing of diabetic foot ulcers.