Synthesis, in vitro and computational studies of 1,4-disubstituted 1,2,3-triazoles as potential α-glucosidase inhibitors

Abstract

1,4-Disubstituted-1,2,3-triazoles were synthesized by Cu(I) catalyzed click reaction, where the azides, with electron donating and electron withdrawing groups acted as 1,3-dipoles and 1-ethynyl-1-cyclohexanol served as the terminal alkyne. These synthesized triazoles were subjected to enzymatic assay which showed promising activity against α-glucosidase; 1-(2-cyano-4-nitrophenyl)-4-(1-hydroxycyclohexyl)-1H-1,2,3-triazole 3m being the most active members of the library. Molecular docking studies of these triazoles with the homology-modeled α-glucosidase protein were also performed to delineate ligand-protein interactions at molecular level which suggested that Phe157, Arg312 and His279 are the major interacting residues in the biding site of the protein and may have a significant role in the inhibition of enzyme's function.

Keywords: 1,2,3-Triazoles; Click chemistry; Computational studies; Molecular modeling; α-Glucosidase inhibitors.