Pelargonidin-3,5-diglucoside found in Pomegranate aril acts as a potent HIF-1α inhibitor in in-silico study

Abstract

Abstract Hypoxia-inducible factor 1 alpha (HIF-1α) is a transcription factor that regulates the transcription of over 100 genes involved in erythropoiesis, angiogenesis, autophagy, cell survival, and energy metabolism signalling; it appears to be a potential target in cancer therapy. The aim of this study was to identify natural compounds from Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target (NPACT) database with anticancer potential. Molecular docking of 1574 phytochemicals was carried out using Autodock Vina 1.1.2 using the site-specific docking method and the amino acid residue site was near Asn803 of HIF-1α. The protein-ligand complexes considered for molecular dynamics simulation were HIF1α- Bortezomib (as control), HIF 1α- Pelargonidin-3 ,5-diglucoside and HIF1α- (25S)-5-beta-spirostan-3-beta-ol-3-O-alpha-L-rhamnopyranosyl-(1->2)-[alpha-L-rhamnopyranosyl-(1->4)]-beta-D-glucopyranoside. Furthermore, ADMET evaluation for the best ligands was carried out using the pkCSM ADMET server.