Identification of effective natural compounds as HIF-1Alpha mimetics for diabetic wound healing; A systematic in-silico study

Esakkimuthukumar Mariappan; Akey Krishna Swaroop; Preeya Negi; Saranya RajanBabu; Dhinesh Kumar Murugesan; Nadimpalli Prudhvi Varma; Jubie Selvaraj

doi:10.7324/JAPS.2023.135162

Abstract

The Von Hippel-Lindau (VHL) E3 ubiquitin ligase is responsible for the degradation of hypoxia-inducible factor 1α (HIF-1α) under hydroxylation. Computer-aided drug design leads to the discovery of HIF-1α mimetics for the stabilization of hydroxylated α subunit of HIF-1α from subsequent proteasomal degradation to improve diabetic wound healing. The protein-protein interaction (PPI) networking confirms the interaction between the VHL—HIF-1α proteins. So, VHL is the potential target to stabilize the HIF-1α. A set of natural compounds as an inhibitor of PPI between VHL—HIF-1α is identified by structure-based virtual screening. The free HIF-1α leads to accelerates wound closure in both normal and diabetic conditions, with a more significant effect being observed in the diabetic condition. The natural products were designed as HIF-1α mimetics through in-silico Pharmacophore modeling followed by structure-based virtual screening and molecular simulation. In the pharmacophore modeling, 2 acceptors and 1 donor pharmacophore are generated. In the virtual screening process, generated pharmacophore gives a data set of natural compounds that have the same pharmacophoric feature. Based on the docking and absorption, distribution, metabolism, elimination, toxicity studies, the potential inhibitor (ZINC ID: ZINC15959407, ZINC12884117) of PPI is identified.

Keyword: Natural compounds HIF-1α diabetic wound pharmacophore virtual screening impaired wound healing

Citation:

Mariappan E, Swaroop AK, Negi P, RajanBabu S, Murugesan DK, Varma NP, Selvaraj J. Identification of effective natural compounds as HIF-1Alpha mimetics for diabetic wound healing; A systematic in-silico study. J Appl Pharm Sci, 2023; 13(Suppl 1):041–050. https://doi.org/10.7324/JAPS.2023.135162

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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