Synthesis and Evaluation of Phenyltriazole-Deoxynojirimycin Hybrids as Potent α-Glucosidase Inhibitors

1-deoxynojirimycin (DNJ) is a well-known α-glucosidase inhibitor. A series of phenyltriazole-deoxynojirimycin hybrids containing C and C (4 and 6 methylenes, respectively) linkers were synthesized. These novel compounds were assessed for preliminary glucosidase inhibition and cytotoxicity tests in vitro. Among them, compounds - and - (IC : 105 ± 9-11 ± 1 μM) were more active than deoxynojirimycin (DNJ, IC = 155 ± 15 μM). The kinetics of enzyme inhibition measured by using Lineweaver-Burk plots indicated that compounds and were competitive inhibitors. In addition, a molecular docking study of α-glucosidase revealed that the interaction modes and the orientations of compound and DNJ were clearly different. Furthermore, in tissue culture, HL60 cell compounds showed no cytotoxicity at low concentrations. When the concentration reached 50 µM, only compound exhibited cytotoxicity. The structure-activity relationships exhibit that the length of the linker and the nature of 4-position substituents on the phenyl have a significant effect on the inhibitory potency of glucosidases and cytotoxicity.