Synthesis of 1H-1,2,3-triazole derivatives as new alpha-glucosidase inhibitors and their molecular docking studies

Inhibition of alpha-glucosidase is an effective strategy for controlling the post-prandial hyperglycemia in diabetic patients. For the identification of new inhibitors of this enzyme, a series of new (R)-1-(2-(4-bromo-2-methoxyphenoxy) propyl)-4-(4-(trifluoromethyl) phenyl)-1H-1,2,3-triazole derivatives were synthesized (8a-d and 10a-e). The structures were confirmed by NMR, mass spectrometry and, in case of compound 8a, by single crystal X-ray crystallography. The alpha-glucosidase inhibitory activities were investigated in vitro. Most derivatives exhibited significant inhibitory activity against alpha-glucosidase enzyme. Their structure-activity relationship and molecular docking studies were performed to elucidate the active pharmacophore against this enzyme. Compound 1 0b was the most active analogue with IC50 value of 14.2 mu M, while compound 6 was found to be the least active having 218.1 mu M. A preliminary structure-activity relationship suggested that the presence of 1H1,2,3-triazole ring in 1H-1,2,3-triazole derivatives is responsible for this activity and can be used as anti-diabetic drugs. The molecular docking studies of all active compounds were performed, in order to understand the mode of binding interaction and the energy of this class of compounds.