Molecular docking and drug-likeness for the identification of inhibitory action of acetogenins from annona muricata as potential anticancer against hypoxia inducible factor 1 alpha

Abstract

Hypoxia inducible factor 1 alpha (HIF-1α) regulates cell growth and differentiation which is implicated in human cancers. HIF-1a activates its cascade carcinogenesis mechanism in cancer cells. It is well-understood that signaling is initiated by HIF-1± receptor. Overexpression of HIF-1α is associated with several different human cancers, including breast cancer, lung cancer and colon cancer. Thus, HIF-1α becomes potential target of therapeutic approach in developing HIF-1α inhibitors. The aim of this research is to investigate potential inhibitors which are known as Acetogenins (AGEs) isolated from Annona muricata against HIF-1α. In order to achieve this goal, chemical structures of all compounds were retrieved from PubChem database. Molecular docking was performed by AutoDock Vina program and the resulting binding modes were analyzed with AutoDock Tools program. Among all the compounds, murihexocin A showed the best binding modes compared to other two inhibitors based on the lowest binding energies (LBE = -7.9 kcal/mol) as high as gefitinib. This was indicating that murihexocin A has favorable interaction with the essential amino acid residues at catalytic site of HIF-1α. Drug-likeness calculation of AGEs were also performed. These in silico results could be beneficial as a compound model for further studies in-vitro and in-vivo.