α-1-C-Alkyl-1-deoxynojirimycin derivatives as potent and selective inhibitors of intestinal isomaltase: remarkable effect of the alkyl chain length on glycosidase inhibitory profile

A series of α- and β-1-C-alkyl-1-deoxynojirimycin derivatives was prepared and evaluated as glycosidase inhibitors. Biological assays showed a marked dependence of the selectivity and potency of the inhibitors upon the position of the alkyl chain (α-1-C-, β-1-C- or N-alkyl derivatives). In addition, the efficiency of α-1-C-alkyl-1-deoxynojirimycin derivatives as intestinal isomaltase inhibitors increases with the length of the alkyl chain. The strongest inhibition was found for α-1-C -nonyl-1-deoxynojirimycin with an IC50 = 3.5 nM (25× more potent inhibitor than the shorter chain homologue carrying a C8 chain). These results demonstrate that subtle changes in the aglycon fragment may result in remarkable enzyme specificity.