Loading…

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. Compoun...

Full description

Saved in:
Bibliographic Details
Published in:MedChemComm 2020-04, Vol.11 (4), p.518-527
Main Authors: Osella, M. I, Salazar, M. O, Gamarra, M. D, Moreno, D. M, Lambertucci, F, Frances, D. E, Furlan, R. L. E
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2632-8682
2040-2503
2632-8682
2040-2511
DOI:10.1039/c9md00559e