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.