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α-Glucosidase is responsible for glucose release of oligosaccharides and disaccharides in the intestine and increase postprandial hyperglycemia. Inhibition of this enzyme is a beneficial therapeutic method for glycemic control in diabetes. This study deals with the design and synthesis of 4,5-diphenylimidazole-N-phenylacetamide derivatives 7a–l and the screen of these compounds for their potential for α-glucosidase inhibition. All the synthesized compounds exhibited superior α-glucosidase inhibition (IC50 = 90.0–598.5 µM) as compared to standard inhibitor acarbose (IC50 = 750.0 µM). In contrast, these compounds were inactive against α-amylase. Among the synthesized compounds, compound 7h was the most potent inhibitor of this library and was a competitive inhibitor into α-glucosidase with Ki value = 86.3 μM. Docking study of the most potent compounds was performed to evaluate the binding interactions of these compounds with the active site of enzyme and to determine of binding energies of ligand–enzyme complexes. The results of this in silico study are in complete agreement with the results obtained from in vitro α-glucosidase inhibition assay. Docking study of the most potent compound demonstrated that it interacted with important residues in the active site of α-glucosidase. In vitro cytotoxic activity of the most potent compounds and in silico druglikeness/ADME/toxicity study of these compounds were evaluated.

A new series of phthalimide-benzamide-1,2,3-triazole hybrids 8a–k as α-glucosidase inhibitors was designed and synthesized. The biological evaluation of compounds 8a–k against yeast α-glucosidase demonstrated that all they have excellent inhibitory activity in comparison with standard inhibitor acarbose. Among them, the most potent compound was compound 8d with inhibitory activity 18.5-fold more than acarbose. Kinetic study revealed that α-glucosidase inhibition of compound 8d was the competitive type. Furthermore, docking study suggested that compound 8d is more stable than acarbose in the active site of α-glucosidase.