Arylsulfonyl histamine derivatives as powerful and selective α-glucosidase inhibitors

Abstract

A series of simple N-arylbenzenesulfonyl histamine derivatives were prepared and screened against alpha-glucosidase. Inhibition was in the micromolar range for several Nalpha,Nt-di-arylsulfonyl compounds, with Nalpha,Nt-di-4-trifluorobenzenesulfonyl histamine (IId) being the best inhibitor. Compound IId is a reversible and competitive alpha-glucosidase inhibitor, and presented good selectivity with respect to other target enzymes, including beta-glucosidase and alpha-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.