N (α)-arylsulfonyl histamines as selective β-glucosidase inhibitors

N (α)-benzenesulfonylhistamine, a new semi-synthetic β-glucosidase inhibitor, was obtained by bioactivity-guided isolation from a chemically engineered extract of Urtica urens L. prepared by reaction with benzenesulfonyl chloride. In order to identify better β-glucosidase inhibitors, a new series of N (α),N (τ)-di-arylsulfonyl and N (α)-arylsulfonyl histamine derivatives was prepared. Biological studies revealed that the β-glucosidase inhibition was in a micromolar range for several N (α)-arylsulfonyl histamine compounds of the series, N (α)-4-fluorobenzenesulfonyl histamine being the most powerful compound. Besides, this reversible and competitive inhibitor presented a good selectivity for β-glucosidase with respect to other target enzymes including α-glucosidase.