Phenolic compounds as α-glucosidase inhibitors: a docking and molecular dynamics simulation study

Area of Science:

• Biochemistry
• Pharmacology
• Computational Chemistry

Background:

• Phenolic compounds exhibit significant biological activities, with notable medicinal importance in managing diabetes.
• Alpha-glucosidase inhibitors are crucial for controlling postprandial hyperglycemia in diabetic patients.

Purpose of the Study:

• To investigate the alpha-glucosidase inhibitory activity of various plant-derived phenolic compounds.
• To identify potent phenolic inhibitors of alpha-glucosidase using computational methods.
• To correlate physicochemical properties with binding affinities for drug discovery.

Main Methods:

• Collection and curation of 155 phenolic compounds from existing literature.
• Molecular docking simulations using AutoDock Vina to assess binding affinities.
• Molecular dynamics simulations to evaluate the stability of docked complexes.
• Analysis of physicochemical properties (e.g., LogP, molecular complexity) and their correlation with binding energy.

Main Results:

• Amentoflavone demonstrated the highest binding affinity to alpha-glucosidase, surpassing the reference drug acarbose.
• Binding energy correlated positively with molecular complexity, hydrogen bonding capacity, and heavy atom count.
• Polar surface area also showed a positive correlation with binding affinity.
• Amentoflavone exhibited stable binding and conformation during molecular dynamics simulations.

Conclusions:

• Amentoflavone is a highly promising therapeutic candidate for an alpha-glucosidase inhibitor.
• The identified phenolic compounds possess favorable drug-likeness and low toxicity profiles.
• This research provides a strong basis for developing novel antidiabetic drugs targeting alpha-glucosidase.