Computational Insights into the Antidiabetic Potential of Young Fronds of Diplazium esculentum (Retz.) Sw.: In silico Analysis of α-Amylase and α-Glucosidase Inhibition

Abstract Objective: Diplazium esculentum (Retz.) Sw. is a dietary plant and possesses diverse biological properties, including potential antidiabetic effects. However, the antidiabetic potential of its young fronds remains unexplored. To bridge this gap, we conducted a computational analysis to assess their anti-diabetic activity by targeting key enzymes, α-amylase and α-glucosidase, which perform a fundamental role in the development of diabetes mellitus (DM). Materials and Methods: The ligands and target proteins associated with DM were obtained from PubChem and the Protein Data Bank, respectively. Drug-likeness and absorption, distribution, metabolism, excretion, and toxicity properties were assessed using MolSoft and the pkCSM repository for predictive modeling. This study investigated their interaction with key carbohydrate-hydrolysing enzymes involved in DM pathogenesis. Molecular docking was executed to appraise the binding energy of selected bioactive compounds. Results: Among the 11 docked phytochemicals, quercetin exhibited the highest binding energy (−294.64 kcal/mol) with α-amylase, forming three hydrogen bonds with key amino acid units. In addition, α-glucosidase docking results showed strong binding interaction with quercetin (−121.471 kcal/mol), forming three hydrogen bonds with two amino acids. Further investigation of quercetin, which exhibited the highest binding energy with α-amylase, was conducted using Schrödinger Maestro for molecular dynamics simulation at 500 ns. The results demonstrated improved stability, as indicated by root-mean-square fluctuation, root-mean-square deviation, and protein-ligand contact analyses, reinforcing its potential as a promising inhibitor of α-amylase. Conclusions: Bioactive compounds from D. esculentum , like quercetin, show promise as natural inhibitors for managing type 2 diabetes, warranting further research and development.