Comprehensive Analysis of Pithecellobium dulce as a Natural Source of α ‐Amylase Inhibitors: Experimental and Computational Approaches

Chronic hyperglycemia is one of the main causes of diabetes mellitus, a common metabolic disorder. α ‐Amylase inhibition, a key enzyme in carbohydrate digestion, is an appealing strategy for the regulation of postprandial blood glucose levels. The current research explored the α ‐amylase inhibitory activity of Pithecellobium dulce (Roxb.) leaf extracts by phytochemical analysis, GC–MS, in vitro enzyme assays, and in silico molecular modeling, including ADME, toxicity predictions, and molecular dynamics (MD) simulations. Among four solvent extracts, the ethyl acetate (EA) extract had the highest total phenolic (131.26 mg GAE/g) and flavonoid (244.78 mg CE/g) contents and exhibited 70.51% α ‐amylase inhibition at 400 μg/mL, approaching the activity of acarbose (82.72%). GC–MS analysis of the EA extract identified several bioactive constituents, with 3,7,11,15‐tetramethyl‐2‐hexadecen‐1‐ol and 2‐hexadecen‐1‐ol acetate exhibiting good docking scores (−5.9 and −5.7 kcal/mol, respectively). Among them, 1‐cyclohexanol, 2‐(2‐ethylbutyl)‐ showed the best drug‐likeness with good oral bioavailability (0.794) and zero predicted toxicity. MD simulations (100 ns) confirmed the stability of ligand–enzyme complexes with minimal RMSD fluctuations and stable hydrogen bonding. The findings suggest that P. dulce EA extract and phytocompounds are potential natural α ‐amylase inhibitors and putative antidiabetic drugs, meriting further in vivo validation.