Exploring the Potential of Avenanthramides and their Analogues as α-Glucosidase Inhibitors for Type 2 Diabetes Treatment Utilizing Virtual Screening, Molecular Dynamics, and Drug-likeness Predictions

Abstract

Background: Optimal glycemic control is crucial in type 2 diabetes treatment, with αglucosidase inhibitors emerging as promising candidates. Avenanthramides, compounds found in oats, exhibit therapeutic potential, but their efficacy as α-glucosidase inhibitors requires thorough evaluation. Objective: This study investigates the potential of avenanthramides and their derivatives as inhibitors of α-glucosidase for the treatment of type 2 diabetes through comprehensive computational analysis. Methods: Structure-Based Virtual Screening of 3543 avenanthramides and their analog compounds was conducted using FlexX. The top 30 ranked compounds were subjected to visual inspection of their binding mode within the α-glucosidase binding site to eliminate false positives. The top-ranked molecule was subjected to dynamic simulation and ADMET prediction. Results: The results revealed that 1634 compounds were found to exhibit a greater α-glucosidase inhibitory potency than miglitol, the reference molecule. Compound S1 exhibited superior αglucosidase inhibitory potency with a binding energy of -45.7786 kJ/mol compared to miglitol, which had a binding energy of -26.5186 kJ/mol. S1 was predicted to occupy the entire binding site with an optimized number of hydrogen bonds and hydrophobic interactions. Molecular dynamics simulations demonstrated that S1 had a lower average RMSD (0.15 ± 0.01 nm) compared to miglitol (0.16 ± 0.01 nm), indicating superior stability within the α-glucosidase binding site. S1 exhibited favorable drug-like properties, suggesting its potential as a lead compound for further development in type 2 diabetes treatment. Conclusion: These findings highlight S1's potential for diabetes treatment and pave the way for future experimental investigations. The computational approach utilized offers valuable insights into the inhibitory potential of avenanthramides, providing a foundation for further drug development for type 2 diabetes.