Histidines, histamines and imidazoles as glycosidase inhibitors

Abstract

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 alpha-glucosidase and Escherichia coli β-galactosidase. The addition of a hydrophobic group to the basic imidazole nucleus greatly enhances binding to both the alpha- and β-glucosidases. L-Histidine (beta-naphthylamide (Ki 17 microM) is a potent competitive inhibitor of sweet-almond β-glucosidase as is omega-N-acetylhistamine (K1 35 microM), which inhibits the sweet-almond β-glucosidase at least 700 times more strongly than either yeast alpha-glucosidase or Escherichia coli β-galactosidase, and suggests potential for the development of selective reversible β-glucosidase inhibitors. A range of hydrophobic omega-N-acylhistamines were synthesized and shown to be among the most potent inhibitors of sweet-almond β-glucosidase reported to date.