Quinazolinone-1,2,3-triazole-acetamide conjugates as potent α-glucosidase inhibitors: synthesis, enzyme inhibition, kinetic analysis, and molecular docking study

In this study, new hybrids of quinazolinone-1,2,3-triazole-acetamide were designed, synthesized, and screened for their alpha-glucosidase inhibitory activity. The results obtained from the in vitro screening indicated that all analogs exhibited significant inhibitory activity against alpha-glucosidase (IC50 values ranging from 4.8-140.2 mu M) in comparison to acarbose (IC50 = 750.0 mu M). The limited structure-activity relationships suggested the variation in the inhibitory activities of the compounds affected by different substitutions on the aryl moiety. The enzyme kinetic studies of the most potent compound 9c, revealed that it inhibited alpha-glucosidase in a competitive mode with a K-i value of 4.8 mu M. In addition, molecular docking studies investigated the structural perturbation and behavior of all derivatives inside the alpha-glucosidase active site. Next, molecular dynamic simulations of the most potent compound 9c, were performed to study the behavior of the 9c-complex during the time. The results showed that these compounds can be considered as potential antidiabetic agents.

Automated summary

New hybrids of quinazolinone-1,2,3-triazole-acetamide were synthesized and found to have significant inhibitory activity against alpha-glucosidase. The most potent compound 9c showed competitive inhibition with a K-i value of 4.8 mu M. Molecular docking and molecular dynamic simulations suggested that these compounds have the potential to be used as antidiabetic agents.