Identification of putative inhibitors of human pancreatic ?-amylase from phytochemicals using molecular docking and computational analysis

Background: Diabetes mellitus is a global chronic metabolic disorder characterized by elevated blood glucose levels, primarily due to impaired insulin activity or secretion. ?-amylase, a key enzyme in carbohydrate digestion, is a validated molecular target for controlling postprandial hyperglycemia in type 2 diabetes. Objectives: This study aimed to identify potential ?-amylase inhibitors from phytochemicals derived from Bauhinia forficata, Citrus spp. and Echinops ritro using an in-silico approach. Methods: A total of 55 phytochemicals were virtually screened against human pancreatic ?-amylase (PDB ID: 3BAJ) using molecular docking via Schrödinger Maestro (version 12.5). The top-ranked ligands were further assessed for pharmacokinetic and toxicity profiles using SwissADME, ProTox-II and StopTox platforms. Electronic reactivity was evaluated using Density Functional Theory (DFT) with Gaussian 09. Results: Among the screened compounds, kaempferitrin (-10.3 kcal/mol), Rutin (-10.1 kcal/mol), Naringin (-9.7 kcal/mol) and Hyperoside (-9.6 kcal/mol) demonstrated strong binding affinities, favorable pharmacokinetic properties and compliance with drug-likeness criteria. DFT analysis supported their chemical reactivity and stability, indicating potential for biological activity. Conclusion: The results suggest that these phytochemicals could serve as promising lead molecules for the development of plant-based antidiabetic drugs targeting ?-amylase. However, further experimental validation and mechanistic studies are recommended to confirm these findings.