A Search for Novel Antidiabetic Agents Using Ligand-Based Drug Design and Molecular Docking Studies Employing Human Intestinal Maltase-Glucoamylase as Model Enzyme

This study employed quantitative structure-activity relationship (QSAR) to predict the inhibitory activities of N-(alkyl/aryl)-۲-chloro-۴-nitro-۵-[(۴-nitrophenyl) sulfamoyl] benzamide derivatives as potent inhibitors of C-terminal human intestinal maltase-glucoamylase (MGAM-C). Density Functional Theory with B۳LYP/۶-۳۱G* as the basis set was used to optimize the chemical structures of the derivatives. Genetic function approximation generated three models, with model one having validation keys of R۲int= ۰.۹۸۹, R۲adj = ۰.۹۸۴, Q۲cv = ۰.۹۷۴, and LOF = ۰.۰۰۵۶ being selected as the best due to it highest external validation parameter of R۲ext = ۰.۷۲۲. The ligand-based approach designed four compounds with higher activities than the lead compound. The binding interactions of the designed compounds within the active site of (MGAM-C) revealed interesting MolDock scores. This research concluded that the designed compounds from the derivatives could serve as potent inhibitors of MGAM-C, offering valuable insight into developing novel medications to treat diabetes mellitus.

کلیدواژه ها:

Quantitative structure activity relationship ، Antidiabetic agents ، Molecular docking ، Molegro virtual docker ، Density functional theory