Structure Based Docking of Secondary Metabolites against Alpha-amylase and Alpha-glucosidase Activities in Treating Diabetes

Diabetes mellitus (DM) is a long term disorder of metabolism characterized by high level of blood sugar (hyperglycemia) due to insufficient secretion of insulin, insulin resistance, or both, as well as poor lipid, protein and carbohydrate metabolism. These complications occur as a result of derangement in glucose storage for the regulatory system and metabolic fuel mobilization, including carbohydrate, protein and lipid anabolism and catabolism emanating from impaired action of insulin, secretion of insulin, or both. The in silico study was conducted with the help of molecular docking to treat diabetes to inhibit the activities of α-amylase and α-glucosidase by drug molecule. All the studies were based on docking with molecules. The docking was done using a docking software between all the ligands and the target protein receptors. Natural compounds, such as Conduritol A, Catechin and Quercetin were picked, and protein targets as α-amylase and α-glucosidase. Ligands were imported for visual screening into PyRx software while Biovia Discovery Studio Visualizer was used for protein preparation. Analysis of the properties of drug likeliness of the ligands was done via SwissADME online server according to Lipinski’s Rule of Five. Final docking analysis was done through AutoDockVina and Biovia Discovery Studio client 2020. Molecular docking analysis of the ligands Conduritol A, Catechin and Quercetin showed strong binding interaction with both α-amylase and α-glucosidase. The test revealed different binding affinities, hydrogen bond interactions, hydrophobicity, solvent accessibility surface (SAS), root mean square deviation lower bound (RMSD LB) and root mean square deviation upper bound (RMSD UB). Conduritol A was the strongest compound against the protein targets, with its low binding strength, according to the PyRx test and Lipinski 's Rule of Five. The same molecules were further docked, and the interactions were visualized under PyMol Via Biovia Discovery Studio. According to the in silico study, we have found that these natural compounds can inhibit the activities of α-amylase and α-glucosidase which can be promising drugs for the treatment of diabetes after subjecting them to in vitro and in vivo studies.