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 β-glucosidase, yeast α-glucosidase, and Escherichia coli β-galactosidase. The addition of a hydrophobic group to the basic imidazole nucleus greatly enhances binding to both the α- and β-glucosidases. L-Histidine β-naphthylamide (K(i) 17 μM) is a potent competitive inhibitor of sweet-almond β-glucosidase as is ω-N-acetylhistamine (K(i) 35 μM), which inhibits the sweet-almond β-glucosidase at least 700 times more strongly than either yeast α-glucosidase or Escherichia coli β-galactosidase, and suggests potential for the development of selective reversible β-glucosidase inhibitors. A range of hydrophobic ω-N-acylhistamines were synthesized and shown to be among the most potent inhibitors of sweet-almond β-glucosidase reported to date.