Synthesis and biological activity of novel deoxynojirimycin derivatives as potent α-glucosidase inhibitors

Abstract

Thirteen 1-deoxynojirimycin (DNJ) derivatives of five different skeletal structures were designed and synthesized. The newly synthesized compounds were evaluated using an in vitro α-glucosidase assay, and kinetic parameters (Ki, IC50) were measured. Some DNJ derivatives showed weak α-glucosidase inhibitory activities, and the compounds 1-(3-benzyloxy-2-hydroxypropyl)-2-hydroxymethyl-piperidine-3,4,5-triol (2a) and 1-{3-[1-(4-fluorophenyl)-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 α-glucosidase with a Ki value of 1.56×10-4m and an IC50 value of 3.07×10-4m, 13d was a reversible, competitive inhibitor of α-glucosidase with a Ki value of 2.08×10-4m and an IC50 value of 3.31×10-4m. © 2013 Verlag der Zeitschrift für Naturforschung, Tübingen.