Molecular Docking Of Annonaceous Acetogenins As Akt Inhibitors Against Oral Cancer

Abstract

Annona muricata Linn., is gaining popularity as a significant medicinal plant today. An activePhytochemical found in this plant is annonaceousacetogenin, which has a very potent anticancer effect. To investigate their effectiveness against oral cancer through molecular docking studies, we have chosen fifty compounds from the Annona muricata Linn and protein kinase B (Akt) as the target protein. In oral cancer tissues, it is known that protein kinase B (Akt), particularly Akt1 and Akt2, is overexpressed. All fifty compounds were docked into the active sites of the proteins Akt1 and Akt2 using the docking tool Glide. The docking results were analyzed and predicted binding modes of acetogenins in the active site cavity of Akt1 and Ak2 were examined. The six compounds Annonamuricin A, Annonamuricin E, Annonahexocin, Murihexocin C, Corossolone, and Muricataclicin showed good Glide Score compared to the native ligand, -8.11 kcal/mol, -8.99 kcal/mol, -8.44 kcal/mol, -8.74 kcal/mol, and -8.72 kcal/mol, respectively, in Akt1.Whereas in Akt2, two compounds anonahexocin and murihexocin C, with Glide score of -8.52 kcal/mol and -9.53 kcal/mol, respectively.As a result, the acetogenins indicated above could beconsidered as potential Akt inhibitors for the oral cancer drug development.