Arylsulfonyl histamine derivatives as powerful and selective alpha-glucosidase inhibitors

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

RSC Medicinal Chemistry

Royal Society of Chemistry

Año: 2020 p. 518 - 527

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, being Nα,Nτ-di 4 trifluorobenzenesulfonyl histamine (IId) 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 the dose of it.