Docking Study for Assessment of Wound Healing Potential of Quercetin in the Treatment of Diabetic Foot Ulcers

Introduction: Diabetes mellitus (DM) is a complex disease affecting almost all the vital organs in the body. Up to ۲۵% of DM patients suffer from diabetic foot ulcers (DFU), which are associated with infection, amputation, and death. A group of important endopeptidases that play a vital role in the repair of damaged skin are matrix metalloproteinases (MMPs). This group of enzymes in the normal range, accelerates the wound healing mechanism by helping angiogenesis and vasodilation, but elevated MMPs are believed to be responsible for poor wound healing. Oxidative stress and High glucose in diabetic patients, increase matrix metalloproteinase expression. Quercetin is a flavonoid that is found in many plants and foods such as grapes, onions, and broccoli. In this article, we focus on quercetin's function as a MMP inhibitor for the assessment of wound healing in the treatment of diabetic foot ulcers.Methods: In this study, HyperChem Professional application is used to draw Quercetin compound. Then Matrix Metalloproteinase enzyme is extracted from the PDB site with ۱G۴۹ pdb ID. In addition, Discovery Studio ۳.۵ Client application is used to delete the water molecules and co-crystal structure from the MMP۳ to be prepared for docking with Quercetin. We did molecular docking in Autodock vina. After docking Hydrogen bonds and involved aminoacids are marked by Discovery Studio ۳.۵ Client. To compare with the control ligand, Hbonds of the co-crystal and the MMP۳ were determined.Results: According to Autodock vina results, the affinity between the enzyme and studied ligand was -۸.۳۲۱ kcal/mol and it was linked with amino acids ASN۶۰۳, HIS۶۵۱, PHE۶۴۶ of B chain, and GLU۱۵۰ in the A chain. According to Discovery Studio ۳.۵ Client application, the involved amino acids in the Hydrogen bond between MMP۳ and co-crystal were LEU۶۶۴, ALA۶۶۵, HIS۷۰۱, HIS۷۱۱, and GLU۷۰۲ of the B chain. One pi interaction between HIS۷۰۱ and the co-crystal was detected.Conclusion: Based on the results of this in silico study, Quercetin showed inhibitory potential towards the enzyme, and a good affinity was established between ligand and target protein, but laboratory confirmation will complement these results.