Molecular Docking of the Cardenolides of Asclepias subulata in the Human p53 Protein Reveals an Interaction in the Cleft of the Y220C Mutant

Abstract

Background and Objective: The objective of the present study is to use docking and ADME analysis to determine if the cardenolides of Asclepias subulata are potential stabilizing drugs of the p53-Y220C mutant. Materials and Methods: Two different receptors, wild-type p53, and the mutant p53-Y220C, were used for docking. Three independent stochastic series were performed, with 60,000 poses considered, and the 30 best poses were selected. ADME analysis was performed using SwissADME. Results: Docking experiments revealed that corotoxigenin 3-O-glucopyranoside and calotropin interact with the cleft, so they were considered potential stabilizers of the p53-Y220C mutant comparable to the control drug 9H5, which was able to predict a position very similar to that already reported in the crystallographic structure. The ADME predicted that calotropin and desglucouzarin have more favorable pharmacokinetic parameters. Both molecules are predicted to be absorbed from the GIT. Conclusion: Calotropin of A. subulata is predicted to be a potential drug for p53-Y220C, because it binds to the cleft of the mutant and has favorable pharmacokinetic parameters. Corotoxigenin 3- O-glucopyranoside also binds to the Y220C cleft, but had less favorable pharmacokinetic parameters. These results have a future impact since calotropin could be used for the treatment of some types of cancer.