Synthesis and Biological Activity of Novel Deoxynojirimycin Derivatives as Potent α-Glucosidase Inhibitors

Thirteen 1-deoxynojirimycin (DNJ) derivatives of five different skeletal structures were designed and synthesized. The newly synthesized compounds were evaluated using an in vitro alpha-glucosidase assay, and kinetic parameters (Ki, IC50) were measured. Some DNJ derivatives showed weak alpha-glucosidase inhibitory activities, and the compounds 1-(3-benzyloxy-2-hydroxypropy1)2-hydroxymethyl-piperidine-3,4,5-triol (2a) and 1-{3[1-(4-fluoropheny1)-1H-[1,2,3]triazol-4-ylmethoxy]-2-hydroxypropyl}-2-hydroxymethyl-piperidine-3,4,5-triol (13d) showed activities comparable to that of DNJ. While 2a was found to be a reversible, non-competitive inhibitor of alpha-glucosidase with a Ki value of 1.56 x 10(-4) M and an IC50 value of 3.07 x 10(-4) M, 13d was a reversible, competitive inhibitor of alpha-glucosidase with a Ki value of 2.08 x 10(-4) M and an IC50 value of 3.31 x 10(-4) M.