Abstract
Hyperglycemia is a condition known for the impairment of insulin secretion and is responsible for diabetes mellitus. Various small molecule inhibitors have been discovered as glucokinase activators. Recent studies on benzamide derivatives showed their importance in the treatment of diabetes as glucokinase activator. The present manuscript showed a computation study on benzamide derivatives to help in the production of potent glucokinase activators. In the present study, pharmacophore development, 3D-QSAR, and docking studies were performed on benzamide derivatives to find out the important features required for the development of a potential glucokinase activator. The generated pharmacophore hypothesis ADRR_1 consisted of essential features required for the activity. The resultant statistical data showed high significant values with R2 > 0.99; 0.98 for the training set and Q2 > 0.52; 0.71 for test set based on atom-based and field-based models, respectively. The potent compound 15b of the series showed a good docking score via binding with different amino acid residues such as (NH…ARG63), (SO2…ARG250, THR65), and π-π staking with (phenyl……TYR214). The virtual screening study used 3563 compounds from ZINC database and screened hit compound ZINC08974524, binds with similar amino acids as shown by compound 15b and crystal ligand with docking scores SP (-11.17 kcal/mol) and XP (-8.43 kcal/mol). Compounds were further evaluated by ADME and MMGBSA parameters. Ligands and ZINC hits showed no violation of Lipinski rules. All the screened compounds showed good synthetic accessibility. The present study may be used by researchers for the development of novel benzamide derivatives as glucokinase activator.