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

Article abstract of DOI:10.5560/ZNB.2013-2318

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 a-glucosidase with a Ki value of 1.56×10^-4 M and an IC ₅₀ value of 3.07×10^-4 M, 13d was a reversible, competitive inhibitor of α-glucosidase with a Ki value of 2.08×10^-4 M and an IC₅₀ value of 3.31×10 ^-4 M.