A collection of novel mono- and three-tailed derivatives based on a sugar (glucose) or an iminosugar (trihydroxy piperidine) featuring a terminal benzenesulfonamide were synthesized to investigate the so-called “sugar” and “azasugar” approach with the aim of exploring the activity and selectivity towards the inhibition of human carbonic anhydrases (hCAs). The synthetic approach relies on a general copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction followed by an amine–isothiocyanate coupling. Biological assays were used to collect subtle information on the role of these single or multiple hydrophilic chains. Among the sugar based inhibitors, the single-tailed compound 10 was identified as a better inhibitor than the reference compound (AAZ) towards three different hCAs, while, among the three sugar tailed derivatives, potent and selective inhibition was found for compounds 25 and 26. A promising and selective inhibitory activity was discovered for the iminosugar single-tailed compound 31 towards hCAVII (Ki = 9.7 nM).

Mono- and three-tailed sugar and iminosugar decorated benzenesulfonamide carbonic anhydrase inhibitors / Maria Giulia Davighi, Camilla Matassini, Andrea Goti, Marta Ferraroni, Andrea Angeli, Claudiu T. Supuran, Francesca Cardona. - In: ORGANIC & BIOMOLECULAR CHEMISTRY. - ISSN 1477-0520. - STAMPA. - 2023:(2023), pp. 1-13. [10.1039/d3ob00529a]

Mono- and three-tailed sugar and iminosugar decorated benzenesulfonamide carbonic anhydrase inhibitors

Maria Giulia Davighi
Membro del Collaboration Group
;
Camilla Matassini
Membro del Collaboration Group
;
Andrea Goti
Membro del Collaboration Group
;
Marta Ferraroni
Membro del Collaboration Group
;
Andrea Angeli
Membro del Collaboration Group
;
Claudiu T. Supuran
Membro del Collaboration Group
;
Francesca Cardona
Membro del Collaboration Group
2023

Abstract

A collection of novel mono- and three-tailed derivatives based on a sugar (glucose) or an iminosugar (trihydroxy piperidine) featuring a terminal benzenesulfonamide were synthesized to investigate the so-called “sugar” and “azasugar” approach with the aim of exploring the activity and selectivity towards the inhibition of human carbonic anhydrases (hCAs). The synthetic approach relies on a general copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction followed by an amine–isothiocyanate coupling. Biological assays were used to collect subtle information on the role of these single or multiple hydrophilic chains. Among the sugar based inhibitors, the single-tailed compound 10 was identified as a better inhibitor than the reference compound (AAZ) towards three different hCAs, while, among the three sugar tailed derivatives, potent and selective inhibition was found for compounds 25 and 26. A promising and selective inhibitory activity was discovered for the iminosugar single-tailed compound 31 towards hCAVII (Ki = 9.7 nM).
2023
2023
1
13
Maria Giulia Davighi, Camilla Matassini, Andrea Goti, Marta Ferraroni, Andrea Angeli, Claudiu T. Supuran, Francesca Cardona
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1311422
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