Synthesis and the intestinal glucosidase inhibitory activity of 2-aminoresorcinol derivatives toward an investigation of its binding site.
2-Aminoresorcinol is a potent and selective intestinal glucosidase inhibitor. Unlike the majority of glucosidase inhibitors, it shows an uncompetitive mode of inhibition. In this study, we tested the intestinal glucosidase inhibitory activity of various 2-aminoresorcinol derivatives. We found that structural changes, in amino and two phenolic hydroxyl groups had a negative impact on inhibitory activity, but methylation of the phenolic hydroxyl group was found to maintain its activity and replacement of the aromatic ring with an acyl or alkoxy carbonyl group at the 4th position also retained its activity. This enable us to design a molecular probe for further study of the inhibition mechanism of 2-aminoresorcinol.
Laboratory of Food Biochemistry, Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Japan.
Eisuke
E
Kato
Kenichi
K
Oikawa
Keisuke
K
Takahashi
Jun
J
Kawabata
D001665:Binding Sites; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis*; D007422:Intestines / Q000201:enzymology; D015335:Molecular Probes / Q000138:chemical synthesis*; D012118:Resorcinols / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship; D013393:Sucrase / Q000037:antagonists & inhibitors / Q000737:chemistry; D000520:alpha-Glucosidases / Q000737:chemistry*
D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D015335:Molecular Probes; D012118:Resorcinols; D000520:alpha-Glucosidases; D013393:Sucrase