Alpha-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 alpha- and beta-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 (alpha-1-C-, beta-1-C- or N-alkyl derivatives). In addition, the efficiency of alpha-1-C-alkyl-1-deoxynojirimycin derivatives as intestinal isomaltase inhibitors increases with the length of the alkyl chain. The strongest inhibition was found for alpha-1-C -nonyl-1-deoxynojirimycin with an IC50=3.5 nM (25x 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.
Godin
Guillaume
G
Institut de Chimie Organique et Analytique, Université d'Orléans, CNRS UMR 6005, BP 6759, 45067 Orléans, France.
Compain
Philippe
P
Martin
Olivier R
OR
Ikeda
Kyoko
K
Yu
Liang
L
Asano
Naoki
N
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D005069:Evaluation Studies as Topic; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D007421:Intestine, Small / Q000201:enzymology*; D015394:Molecular Structure; D009834:Oligo-1,6-Glucosidase / Q000037:antagonists & inhibitors*; D051381:Rats; D013329:Structure-Activity Relationship
D017485:1-Deoxynojirimycin; D006026:Glycoside Hydrolases; D009834:Oligo-1,6-Glucosidase