Arylsulfonyl histamine derivatives as powerful and selective α-glucosidase inhibitors

OSELLA, M.I.; SALAZAR, M.O.; GAMARRA, M.D.; MORENO, D.M.; LAMBERTUCCI, F.; FRANCES, D.E.; FURLAN, R.L.E.

RSC Medicinal Chemistry

Royal Society of Chemistry

Año: 2020 vol. 11 p. 518 - 527

A series of simple N-arylbenzenesulfonyl histamine derivatives were prepared and screened against α-glucosidase. Inhibition was in the micromolar range for several Nα,Nτ-di-arylsulfonyl compounds, with Nα,Nτ-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 -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.