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, IC 50 ) 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 −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 IC 50 value of 3.31 × 10 −4 M.

Research progress on the inhibition of enzymes by polyoxometalates

“…Among them, inhibiting the activity of α-glucosidase is a practical and effective method. α-glucosidase is a membrane-binding enzyme in small intestinal epithelial cells, 20 which is responsible for converting a glycosidic bond into oligosaccharides and finally into monosaccharides, 21 which participates in the digestion and absorption of carbohydrates such as starch and sucrose. α-glucosidase is a key enzyme that affects human metabolism, so α-glucosidase is considered to be an important target for the treatment of non-insulin dependent diabetes.…”

“…24 α-Glucosidase inhibitors widely used in clinic, such as acarbose, misoglitol, and voglibose are all derived from natural products. 25 However, these commonly used clinical α-glucosidase inhibitors have high cost and cause serious side effects on the gastrointestinal tract, 20 which limit their application. Therefore, the design of cheap, safe and efficient enzyme inhibitors has become the focus of research.POMs has many biological activities due to their unique structural and functional properties, including the inhibition of α-glucosidase.…”