Improved cellular inhibitors for glycoprotein processing alpha-glucosidases: biological characterisation of alkyl- and arylalkyl-N-substituted deoxynojirimycins

Journal article

A series of N-alkyl- and N-arylalkyl-DNJ compounds have been evaluated for their efficacy for inhibition of endoplasmic reticulum resident α-glucosidases in cells. A recently developed free oligosaccharide (FOS) assay allowed the products of glucosidase inhibition to be quantified and compounds compared for relative inhibitory activity. A N-alkyl chain of one to six carbon atoms provided a flexible linker between deoxynojirimycin (DNJ) and a phenyl, cyclohexyl or cyclopentyl group to explore the requirements for glucosidase inhibition. The most effective compounds were those in which the linker contained four to six carbon atoms and a phenyl group. These compounds all significantly inhibited α-glucosidase I at concentrations of 100 μM following addition to cells for 24 h whereas DNJ was without effect. Inhibition of α-glucosidase II was evident by all inhibitors, consistent with a previously identified mechanism of action of imino sugar inhibitors in cells. © 2009 Elsevier Ltd. All rights reserved.

Authors: Alonzi, D; Dwek, R; Butters, T

• Publication status: Published
• Journal: TETRAHEDRON-ASYMMETRY
• Volume: 20
• Issue: 6-8
• Pages: 897-901
• Publication date: 2009-05-07
• DOI: 10.1016/j.tetasy.2009.03.007
• EISSN: 1362-511X
• ISSN: 0957-4166
• Language: English