Molecular Docking Study of Mangiferonic Acid as a Potential Anti-Hypercholesterolemic Agent

Abstract

Introduction: Hypercholesterolemia is a major risk factor for cardiovascular disease. Mangiferonic Acid, a bioactive compound isolated from Mangifera indica L., has attracted attention as a potential natural inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. This study aimed to evaluate the anti-hypercholesterolemic potential of Mangiferonic Acid using an in-silico approach.

Methods: Biological activity was predicted using PASS Online based on the Probability of Activity (Pa) and Probability of Inactivity (Pi). Drug-likeness was evaluated according to Lipinski's Rule of Five. Molecular docking was performed using AutoDock Vina on the PyRx platform with the HMG-CoA reductase structure obtained from the Protein Data Bank (PDB), while the ligand structure was retrieved from the PubChem database. Binding affinity and ligand–protein interactions were analyzed, followed by pharmacokinetic and toxicity prediction through ADMET analysis.

Results: Mangiferonic Acid demonstrated a high predicted biological activity (Pa = 0.938) and satisfied most Lipinski criteria. Molecular docking revealed a binding affinity of −6.5 kcal/mol toward HMG-CoA reductase, with hydrogen bond interactions involving MET655 and VAL805 residues. ADMET analysis indicated high intestinal absorption (97.96%), favorable permeability, high plasma protein binding, and non-mutagenic and non-carcinogenic properties.

Conclusion: Mangiferonic Acid exhibits promising in silico anti-hypercholesterolemic potential through favorable binding interactions and pharmacokinetic characteristics. Nevertheless, further in vitro and in vivo studies are required to validate its efficacy and safety before therapeutic application.