2-Phenyl-2H-1,2,3-triazole-oxime: oral anti-hyperglycemic effect and in vitro DMPK properties

Digestive glucosidases are targets of anti-hyperglycemic agents used in the treatment of diabetes. Previously, our group synthetized a novel 2-phenyl-2H-1,2,3-triazole-oxime (compound 7) with α-amylase inhibitory activity. Here, we report the acute in vivo antihyperglycemic effect of compound 7 in a murine model and evaluate its drug metabolism and pharmacokinetic (DMPK) properties. At 10 mg/kg, compound 7 reduced peak blood glucose levels by 29% following oral administration of 4 g/kg maltose, with a response comparable to acarbose (38.2%), a clinically approved α-glucosidase inhibitor widely used as a reference compound. In contrast, a significant 22.1% decrease in blood glucose was observed only 120 min after starch administration (4 g/kg). The compound exhibits significant cellular permeability in the MDCK cell assay, good aqueous solubility, and undergoes rapid microsomal hepatic metabolism. In summary, we have further characterized the biological properties of an easily synthesizable non-glycosidic compound and discussed its potential as a lead compound for the treatment of diabetes considering its unconventional DMPK profile. Further studies are needed to better characterize the antihyperglycemic activity of compound 7.