Arylsulfonyl histamine derivatives as powerful and selective α-glucosidase inhibitors

A series of simple N -arylbenzenesulfonyl histamine derivatives were prepared and screened against α-glucosidase. Inhibition was in the micromolar range for several N α , N τ -di-arylsulfonyl compounds, with N α , N τ -di-4-trifluorobenzenesulfonyl histamine ( IId ) being the best inhibitor. Compound IId is a reversible and competitive α-glucosidase inhibitor, and presented good selectivity with respect to other target enzymes, including β-glucosidase and α-amylase, and interesting predicted physicochemical properties. Docking studies have been run to postulate ligand-enzyme interactions to account for the experimental results. In vivo , compound IId produced a similar hypoglycemic effect to acarbose with half of its dose. N α , N τ -Di-4-trifluorobenzenesulfonyl histamine inhibits α-glucosidase in vitro reversibly and selectively with a K i value of 11.6 μM, and shows an in vivo hypoglycemic effect in mice.