Ligand-based drug design, molecular docking and pharmacokinetic studies of some series of 1,4 - dihydropyridines derivatives as human intestinal maltase-glucoamylase inhibitor

Abstract

Quantitative Structure Activity Relationship (QSAR) was employed to predict the inhibitory activities of some series of 1,4–dihydropyridines derivatives as potent C-terminal human intestinal maltase-glucoamylase inhibitor (MGAM-C). The Density Functional Theory utilizing B3LYP/6–31G* as the basis set was employed to optimize the chemical structure of 1,4–dihydropyridines derivatives. four models were generated using Genetic Function Approximation with model three having internal validation parameters of R 2 (trng set) = 0.899, R 2 adj = 0.869, Q 2 cv = 0.769, LOF = 0.0129 selected as the best since it has the highest external validation parameter of R 2 (test set) = 0.885. Five potent compounds designed using the ligand-based approach were found to be more enhanced than the template. furthermore, binding interactions of the designed compounds within the active site of (MGAM-C) showed a fascinating MolDock scores with good pharmacokinetic profiles. This study, provide a useful information for the design of new α-glucosidase inhibitors.