Computational design of new drugs for binding ⍺-amylase as candidates for treating diabetes

Type-2 diabetes is a pandemic metabolic disorder affecting almost 200 million people globally, and this figure is expected to rise gradually to 642 million by 2040. α-amylase is a digestive enzyme that causes postprandial hyperglycemia and blood glucose levels rise. Inhibiting the α-amylase enzyme, it could help to reduce hyperglycemia, obesity, and overweight conditions by reducing postprandial levels of glucose. In the present study, the identification of potential α-amylase inhibitors is explored as a potential strategy for treating type-2 diabetes mellitus. A new computationally driven approach aimed at identifying novel α-amylase inhibitors based on molecular docking was carried out. The interactions of potential drugs with the enzyme’s active site were investigated and compared with the contacts established by acarbose (a reference drug for α-amylase inhibition) in the crystallographic structure 1B2Y. For this active site characterization, both molecular docking and molecular dynamics simulations were performed, and the residues involved in the α-amylase–acarbose complex were considered to analyse the potential drug's interaction with the enzyme. Two potential α-amylase inhibitors (AN-153I105594 and AN-153I104845) have been selected following this computational strategy. Both compounds established a large number of interactions with key binding site α-amylase amino acids and obtained a comparable docking score with respect to the reference drug (acarbose).