Background: 1,2,3-Triazoles and imidazole are important five-membered heterocyclic
scaffolds due to their extensive biological activities. These products have been an area of growing
interest to many researchers around the world because of their enormous pharmaceutical scope.
Methods: The in vivo and in vitro enzyme inhibition of some thioglycosides encompassing 1,2,4-
triazole N1, N2, and N3 and/or imidazole moieties N4, N5, and N6. The effect on the antioxidant
enzymes (superoxide dismutase, glutathione S-transferase, glutathione peroxidase and catalase) was
investigated as well as their effect on α-glucosidase and β-glucuronidase. Molecular docking studies
were carried out to investigate the mode of the binding interaction of the compounds with α-
glucosidase and β-glucuronidase. In addition, quantitative structure-activity relationship (QSAR)
investigation was applied to find out the correlation between toxicity and physicochemical properties.
Results: The decrease of the antioxidant status was revealed by the in vivo effect of the tested compounds.
Furthermore, the in vivo and in vitro inhibitory effects of the tested compounds were clearly
pronounced on α-glucosidase, but not β-glucuronidase. The IC50 and Ki values revealed that the thioglycoside
- based 1,2,4-triazole N3 possesses a high inhibitory action. In addition, the in vitro studies
demonstrated that the whole tested 1,2,4-triazole are potent inhibitors with a Ki magnitude of 10-6
and exhibited a competitive type inhibition. On the other hand, the thioglycosides - based imidazole
ring showed an antioxidant activity and exerted a slight in vivo stimulation of α-glucosidase and β-
glucuronidase. Molecular docking proved that the compounds exhibited binding affinity with the
active sites of α-glucosidase and β-glucuronidase (docking score ranged from -2.320 to -4.370
kcal/mol). Furthermore, QSAR study revealed that the HBD and RB were found to have an overall
significant correlation with the toxicity.
Conclusion: These data suggest that the inhibition of α-glucosidase is accompanied by an oxidative