Fruit Bioactive Compounds as P-Glycoprotein Inhibitors - An In-Silico Study

Abstract

Introduction: P-glycoprotein is a crucial efflux transporter whose overexpression contributes to drug resistance, hindering effective treatment of various diseases.

Objective: This study aims to identify the inhibitory bioactive fruit components on p-glycoprotein, which could potentially overcome drug resistance.

Methodology: 150 bioactive components were identified from 40 regional fruits from India. The druggability and pharmacokinetic profiles of the components were examined, revealing 8 potential inhibitors. Molecular docking was performed to identify the most suitable inhibitor, which was then subjected to simulation to validate its interaction with p-glycoprotein.

Result: According to our research, Δ5-Avenasterol (−79.5 kcal/mol) and Phyllanthin (−78.8 kcal/mol) have a comparable binding affinity to the control inhibitor rifampin (−73.6 kcal/mol), making them appropriate inhibitors for p-glycoprotein.

Conclusion: The conformational stability of the most effective inhibitory drugs inside the p-glycoprotein structure was evaluated using molecular dynamics simulations. This research may lead to the development of novel natural p-glycoprotein inhibitors, providing a promising strategy for combating multidrug resistance.