New 4,5-diphenylimidazole-acetamide-1,2,3-triazole hybrids as potent α-glucosidase inhibitors: synthesis, in vitro and in silico enzymatic and toxicity evaluations

Herein, a new series of 4,5-diphenylimidazole-acetamide-1,2,3-triazole hybrids as potent α-glucosidase inhibitors was designed and synthesized. All the synthesized compounds exhibited excellent inhibition potencies (IC50 values = 55.6�149.2 μM) against α-glucosidase when compared with the standard inhibitor acarbose (IC50 = 750.0 μM). Among the newly synthesized compounds, 4-methyl, 4-methoxy, and 2,3-dichloro derivatives exhibited the highest anti-α-glucosidase activities and were also non-cytotoxic against human normal dermal fibroblast cells. In silico druglikeness, ADME, and toxicity studies of these compounds were performed and obtained results were compared with acarbose. All the synthesized compounds were also inactive against α-amylase in comparison to acarbose. Kinetic study of the most potent compound, 4-methyl derivative, against α-glucosidase demonstrated that this compound is a competitive inhibitor. Furthermore, in silicoinduced fit docking and molecular dynamic studies were performed to further investigate the interaction, orientation, and conformation of these compounds over the active site of α-glycosidase. Graphic abstract: Figure not available: see fulltext. © 2021, Springer-Verlag GmbH Austria, part of Springer Nature