Histidines, histamines and imidazoles as glycosidase inhibitors.
This present study reports the ability of a range of derivatives of L-histidine, histamine and imidazole to act as inhibitors of sweet-almond beta-glucosidase, yeast alpha-glucosidase and Escherichia coli beta-galactosidase. The addition of a hydrophobic group to the basic imidazole nucleus greatly enhances binding to both the alpha- and beta-glucosidases. L-Histidine (beta-naphthylamide (Ki 17 microM) is a potent competitive inhibitor of sweet-almond beta-glucosidase as is omega-N-acetylhistamine (K1 35 microM), which inhibits the sweet-almond beta-glucosidase at least 700 times more strongly than either yeast alpha-glucosidase or Escherichia coli beta-galactosidase, and suggests potential for the development of selective reversible beta-glucosidase inhibitors. A range of hydrophobic omega-N-acylhistamines were synthesized and shown to be among the most potent inhibitors of sweet-almond beta-glucosidase reported to date.
Field
R A
RA
School of Chemical Sciences, University of East Anglia, Norwich, U.K.
Haines
A H
AH
Chrystal
E J
EJ
Luszniak
M C
MC
D001665:Binding Sites; D001667:Binding, Competitive; D002384:Catalysis; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D006632:Histamine / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry*
D007093:Imidazoles; D006639:Histidine; D006632:Histamine; D006026:Glycoside Hydrolases