Identification of Structurally Similar Phytochemicals to Quercetin with High SIRT1 Binding Affinity and Improving Diabetic Wound Healing by Using In silico Approaches

Diabetes Mellitus is the most prevalent metabolic disorder that is increasing at an alarming rate worldwide. The unregulated glucose level leads to various types of health disorders, and one of the major diabetic complications is delayed wound healing. Due to the more side effects of synthetic drugs, there is a need to explore plants and their phytochemicals for medicinal purposes. It was found that Quercetin, a flavonoid, increases the rate of diabetic wound healing by enhancing the expression of SIRT1. This demands more insight towards Quercetin and its similar compounds, as it is hypothesized that similar compounds may have similar biological properties. Thus similarity searching was done to identify the most similar compounds of Quercetin, and then the molecular docking of the screened compounds was performed using AutoDock Vina. The unique ligands were docked into the active site of SIRT1 protein (PDB ID: 4ZZJ). The binding free energy of the interacting ligand with the protein was estimated. Six compounds were identified which possess the maximum structural similarity with Quercetin, and upon docking, it was found that gossypetin and herbacetin have similar binding modes and binding energy as that of Quercetin (-7.5 kcal/mol). Therefore, the hypothesis has been validated by in silico analysis. Our study identified two phytochemicals, Gossypetin, and Herbacetin which can prove beneficial for improving diabetic wound healing but needs to be validated further by in vitro and in vivo studies.

Automated summary

Diabetes Mellitus is a rapidly increasing metabolic disorder with delayed wound healing as a major complication. Quercetin, a flavonoid, has been found to enhance diabetic wound healing by increasing the expression of SIRT1. In this study, similarity searching and molecular docking were performed to identify compounds similar to Quercetin. Gossypetin and herbacetin were found to have similar binding modes and energy as Quercetin, validating the hypothesis. Further in vitro and in vivo studies are needed to validate the potential of Gossypetin and Herbacetin in improving diabetic wound healing.