Synthesis and biological evaluation of novel 1,2,4-triazine derivatives bearing carbazole moiety as potent α-glucosidase inhibitors

Abstract

A new series of 1,2,4-triazine derivatives bearing carbazole moiety 7a-7p were designed, synthesized, and evaluated for their α-glucosidase inhibitory activity. The majority of the screened compounds displayed potent α-glucosidase inhibitory activity, with IC50 values in the range of 4.27±0.07-47.75±0.25μM as compared to the standard drug acarbose. Among the series, compound 7k represented the most potent α-glucosidase inhibitory activity with IC50 values of 4.27±0.07μM. Kinetic analysis revealed that compound 7k is a non-competitive inhibitor with a Ki of 4.43μM. Furthermore, the binding interactions of compound 7k with α-glucosidase was confirmed through molecular docking. This study showed these 1,2,4-triazine derivatives bearing carbazole moiety as a new class of α-glucosidase inhibitors.

Keywords: 1,2,4-Triazine; Carbazole; Enzyme kinetic study; Molecular docking; α-Glucosidase inhibitor.