Quinoline-thiosemicarbazone-1,2,3-triazole-acetamide derivatives as new potent α-glucosidase inhibitors.

In this work, a novel series of quinoline-thiosemicarbazone-1,2,3-triazole-aceamide derivatives 10a-n as new potent α-glucosidase inhibitors was designed, synthesized, and evaluated. All the synthesized derivatives 10a-n were more potent than acarbose (positive control). Representatively, (E)-2-(4-(((3-((2-Carbamothioylhydrazineylidene)methyl)quinolin-2-yl)thio)methyl)-1H-1,2,3-triazol-1-yl)-N-phenethylacetamide (10n), as the most potent entry, with IC = 48.4 µM was 15.5-times more potent than acarbose. According to kinetic study, compound 10n was a competitive inhibitor against α-glucosidase. This compound formed the desired interactions with important residues of the binding pocket of α-glucosidase with favorable binding energy in the molecular docking and molecular dynamics. Compounds 10n, 10e, and 10 g as the most potent compounds among the synthesized compounds were evaluated in term of pharmacokinetics and toxicity via online servers. These evaluations predicted that compounds 10n, 10e, and 10 g had good pharmacokinetic properties and toxicity profile.