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Z. Naturforsch. 2013,
68b, 383 – 390
doi:10.5560/ZNB.2013-2318
Synthesis and Biological Activity of Novel Deoxynojirimycin Derivatives as Potent α-Glucosidase Inhibitors
1 School of Life Sciences, Fudan University, Handan Road 220, Shanghai 200433, P. R. China
2 Department of Chemistry, Tongji University, Siping Road 1239, Shanghai 200092, P. R. China
Reprint requests to Dr. Qing Yang. Fax: +86-21-6564-3446. E-mail:
yangqing68@fudan.edu.cn
Received December 1, 2012 / published online April 19, 2013
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 × 10−4 m and an IC50 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.
Key words: 1-Deoxynojirimycin, α-Glucosidase Inhibitor, Diabetes Mellitus