Computational Identification of Natural Phytochemical Inhibitors Against α-Glucosidase for Type 2 Diabetes Mellitus Control

Abstract

Introduction
Type 2 Diabetes Mellitus is a major metabolic disorder characterised by persistent hyperglycemia and impaired glucose metabolism. α-glucosidase is a key enzyme involved in the final stage of carbohydrate digestion, making it an important therapeutic target for controlling postprandial blood glucose levels. Natural phytocompounds have gained increasing attention as safer alternatives to synthetic anti-diabetic drugs.
Materials and Methods
In the present study, Feruperine and Quercetin were evaluated as potential α-glucosidase inhibitors using computational approaches. Virtual screening was performed using Dr. Duke’s Phytochemical and Ethnobotanical Databases. Molecular docking analyses were conducted using PyRx and SwissDock, while binding pocket and interaction analyses were performed using PyMOL and UCSF Chimaera. Molecular dynamics simulation and Normal Mode Analysis were performed using the iMODS server. ADMET prediction was performed using ADMETlab 3.0 to evaluate pharmacokinetic and toxicity profiles.
Results
The selected phytocompounds demonstrated favourable binding affinity and stable interaction profiles against α-glucosidase. Important catalytic residues including GLU196, GLU579, TYR609, and ARG608 contributed to ligand stabilization within the active site Molecular dynamics analyses indicated acceptable conformational stability and flexibility of the docked complexes. ADMET prediction further suggested favourable drug-likeness, pharmacokinetic suitability, and acceptable toxicity profiles of the compounds.
Conclusion
The present study suggests that Feruperine and Quercetin possess promising potential as natural α-glucosidase inhibitors for the management of Type 2 Diabetes Mellitus. Their favourable binding affinity, interaction stability, and pharmacokinetic properties support their possible therapeutic application. However, further experimental validation through in vitro and in vivo studies is required to confirm their anti-diabetic efficacy.