Mono- and three-tailed sugar and iminosugar decorated benzenesulfonamide carbonic anhydrase inhibitors
Maria Giulia Davighi1, Camilla Matassini1, Andrea Goti1
1Dipartimento di Chimica "Ugo Schiff" DICUS, Università degli Studi di Firenze, Via della Lastruccia 3-13, 50019 Sesto Fiorentino (FI), Italy. francesca.cardona@unifi.it.
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 hCA VII (Ki = 9.7 nM).
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