Discovery of potent inhibitors from traditional rice varieties targeting α-amylase: A computational approach and in vitro validation.

Diabetes involves complex metabolic dysregulation and necessitates approaches such as α-amylase inhibition to moderate postprandial glucose spikes and hyperglycemia. Thus, this study scrutinizes the α-amylase inhibitory potential of selected traditional rice varieties (Athur Kichili Samba, Poonkar, Karuppu Kavuni) as well as a modern variety (CO 43) in the cooked condition, using computational approaches alongside in vitro validation. The 156 metabolites obtained from gas chromatography-mass spectrometry analysis, docked with human pancreatic α-amylase (HPA), and based on the binding energies top-five-ranked metabolites were shortlisted (PubChem IDs: 91714169, 13821354, 167795, 2756016, and 3075922). In addition, molecular dynamics simulation was carried out for a timescale of 200 ns to assess protein-ligand complex stability, with parameters such as root mean square deviation, root mean square fluctuation, radius of gyration, solventaccessible surface area, H-bond, and interaction energy. Furthermore, molecular mechanics Poisson- Boltzmann surface area (MM/PBSA) and molecular mechanics generalized Born surface area (MM/GBSA) analyses were performed to validate the selected inhibitors. In vitro studies corroborated inhibitory effectiveness, with Athur Kichili Samba having the highest potency (IC50=4.48 mg/mL), followed by CO 43, Poonkar, and Karuppu Kavuni (IC50=5.12, 6.29, and 11.35 mg/mL). The consistent ranking of antidiabetic functionality observed across both computational and experimental approaches highlights the potential of these traditional rice varieties, suggesting additional clinical investigations to endorse their global consumption.