New 5,6-diphenyl-1,2,4-triazine-hydrazineylidene-phenoxy-1,2,3-triazole-acetamide derivatives as potent synthetic α-glucosidase inhibitors

Abstract

The current work aims to introduce 5,6-diphenyl-1,2,4-triazine-hydrazineylidene-phenoxy-1,2,3-triazole-acetamide derivatives 13a–n as a new class of potent α-glucosidase inhibitors. These compounds were synthesized through well-known and effective chemical reactions in good yields. All title derivatives 13a–n showed high α-glucosidase inhibition in comparison to the standard inhibitor (acarbose). In this regard, the most potent compounds, compounds 13j and 13h, were approximately 6250- and 3947-fold more potent than acarbose, respectively. An in vitro kinetics study revealed that compound 13j is an uncompetitive α-glucosidase inhibitor. Molecular docking and molecular dynamics studies on compound 13j revealed highly favorable results, confirming stable binding interactions and robust complex formation of this compound with the enzyme's active site. Furthermore, in silico studies indicated that compound 13j possesses favorable and comparable drug-likeness, ADME, and toxicity profiles relative to acarbose, highlighting its potential as a promising lead.