Compréhension du mécanisme d’interaction alpha-glucosidase - inhibiteurs par modélisation moléculaire

Abstract

Type 2 diabetes is a metabolic disorder characterized by chronic postprandial hyperglycemia. Alpha-glucosidase contributes to the rise in postprandial blood glucose levels by facilitating the breakdown of carbohydrates into glucose in the intestine. Its inhibition represents an important therapeutic approach for diabetes management. In this context, our work focused on the study of α-glucosidase inhibition using in silico analysis methods, particularly molecular docking using the Surflex-dock program. The latter demonstrated a good ability to reproduce experimental structures, with 67% of the protein-ligand complexes showing an RMSD ≤ 2 Å. The visual analysis also confirmed this performance by a satisfactory superposition of the simulated ligands with the experimental structures, while a significant correlation (r=0.8410) was observed between the calculated affinities and the biological activities. Subsequently, a ligand-based virtual screening was conducted using the reference inhibitor, which is voglibose .This approach allowed the identification of four compounds with higher binding affinity for α-glucosidase, namely: CID44328007, CID44327991, CID44327637 and CID68230303, with respective affinity scores of 9.33 M⁻¹, 8.69 M⁻¹, 8.44 M⁻¹ and 8.36 M⁻¹. Finally, the in silico evaluation of the physicochemical, pharmacokinetic, and toxicological properties of these drug candidates confirmed their compliance with oral bioavailability standards, allowing them to be considered as potential new therapeutic agents against type 2 diabetes.