2,4-Dioxochroman Moiety Linked to 1,2,3-triazole Derivatives as Novel α-glucosidase Inhibitors: Synthesis, In vitro Biological Evaluation, and Docking Study

In this study, a novel series of 2,4-dioxochroman-1,2,3-triazole hybrids 8a-1 was synthesized by click reaction. These compounds were screened against alpha-glucosidase through in vitro and in silico evaluations. All the synthesized hybrids exhibited excellent alpha-glucosidase inhibition in comparison to standard drug acarbose. Representatively, 3-((((1-(3,4-dichlorobenzyl)-1H-1,2,3-triazol-4-yl)methypamino)methylene)chroman-2,4-dione 8h with IC50 = 20.1 +/- 1.5 mu M against alpha-glucosidase, was 37-times more potent than acarbose. Enzyme kinetic study revealed that compound 8h was a competitive inhibitor against alpha-glucosidase. In silica docking study on chloro derivatives 8h, 8g, and 8i were also performed in the active site of alpha-glucosidase. Evaluations on obtained interaction modes and binding energies of these compounds confirmed the results obtained through in vitro alpha-glucosidase inhibition.