Synthesis of 1,2,3,triazole modified analogues of hydrochlorothiazide via click chemistry approach and in‑vitro α‑glucosidase enzyme inhibition studies

Abstract

The current study was aimed to discover potent inhibitors of the α-glucosidase enzyme. A 25 membered library of new 1,2,3-triazole derivatives of hydrochlorothiazide (1) (HCTZ, a diuretic drug also being used for the treatment of high blood pressure) was synthesized through the click chemistry approach. The structures of all derivatives 2–26 were deduced by MS, IR, 1 H NMR, and 13C-NMR spectroscopic techniques. All the compounds were found to be new. Compounds 1–26 were evaluated for α-glucosidase enzyme inhibition activity. Among them, 18 compounds showed potent inhibitory activity against α-glucosidase with IC50 values between 24 and 379 µM. α-Glucosidase inhibitor drug acarbose (IC50=875.75±2.08 μM) was used as the standard. Kinetics studies of compounds 6, 9, 11, 12, 15, 20, 23, and 24 revealed that only compound 15 was a mixed-type of inhibitor, while others were non-competitive inhibitors of the α-glucosidase enzyme. All the compounds were found to be non-cytotoxic when checked against the mouse fibroblast 3T3 cell line.