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Arylsulfonyl histamine derivatives as powerful and selective ?-glucosidase inhibitors.

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

SUBMITTER: Osella MI

PROVIDER: S-EPMC7489258 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Arylsulfonyl histamine derivatives as powerful and selective α-glucosidase inhibitors.

Osella M I MI Salazar M O MO Gamarra M D MD Moreno D M DM Lambertucci F F Frances D E DE Furlan R L E RLE

RSC medicinal chemistry 20200312 4

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 ...[more]

PMID: 33479653

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Nα-arylsulfonyl histamines as selective β-glucosidase inhibitors† † Electronic supplementary information (ESI) available. See DOI: 10.1039/c8ra06625f

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