Computational Assessment of Substituted 2-Mercaptobenzimidazole Schiff Bases Derivatives Targeting α-Amylase, α-Glucosidase, and PPAR-γ Receptor in Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder marked by elevated blood glucose levels due to insulin resistance and impaired insulin secretion. Current therapeutic strategies often focus on inhibiting carbohydrate-hydrolyzing enzymes such as α-amylase and α-glucosidase to reduce postprandial hyperglycemia. Additionally, increasing insulin sensitivity is mostly dependent on PPAR-γ receptor activity. In this study, a computational docking approach was employed to assess the antidiabetic potential of fifteen substituted 2-mercaptobenzimidazole Schiff base derivatives targeting α-amylase, α-glucosidase, and PPAR-γ receptor. Molecular docking was conducted using AutoDock Tools version 1.5.7 to evaluate binding affinity and interaction profiles. As the standard reference medication, acarbose was employed. Among the designed compounds, five derivatives showing the highest binding affinity were selected for detailed comparative analysis. The docking results revealed that several compounds exhibited stronger binding energies and stable interactions within the active sites of the target proteins compared to Acarbose. Key interactions included hydrogen bonds and hydrophobic contacts with catalytically important amino acids. These findings suggest that substituted 2-mercaptobenzimidazole Schiff bases hold promise as multi-target antidiabetic agents. The study provides valuable insight for further in vitro validation and potential lead optimization in the development of novel antidiabetic therapies.