A Search for Novel Antidiabetic Agents Using Ligand-Based Drug Design and Molecular Docking Studies Employing Human Intestinal Maltase-Glucoamylase as Model Enzyme
نویسندگان
1 Department of Chemistry, Ahmadu Bello University, Zaria, Nigeria
2 Department of Chemistry, Ahmadu Bello University, Zaria, Nigeria
3 Department of Pure and Industrial Chemistry, Bayero University, Kano, Nigeria
4 Department of Chemistry, Ahmadu Bello University, Zaria, Nigeria
5 Department of Chemistry, Ahmadu Bello University, Zaria, Nigeria
doi
10.22034/ajca.2023.387041.1355چکیده
This study employed quantitative structure-activity relationship (QSAR) to predict the inhibitory activities of N-(alkyl/aryl)-2-chloro-4-nitro-5-[(4-nitrophenyl) sulfamoyl] benzamide derivatives as potent inhibitors of C-terminal human intestinal maltase-glucoamylase (MGAM-C). Density Functional Theory with B3LYP/6-31G* 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 R2int= 0.989, R2adj = 0.984, Q2cv = 0.974, and LOF = 0.0056 being selected as the best due to it highest external validation parameter of R2ext = 0.722. 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.
