Sulfamide derivatives with selective carbonic anhydrase VII inhibitory action

Bioorganic & Medicinal Chemistry
Maria Luisa VillalbaLuciana Gavernet

Abstract

A set of N,N'-disubstituted sulfamides and sodium cyclamate have been tested for their inhibitory action against six isoforms of carbonic anhydrase (CA, EC 4.2.1.1) found in the brain, that is, CA I, CA II, CA VII, CA IX, CA XII and CA XIV, some of which are involved in epileptogenesis. The biological data showed interesting results for CA VII inhibition, the isozyme thought to be a novel antiepileptic target. Strong CA VII inhibitors, with Ki values in the low nanomolar-subnanomolar range were identified. Some of these derivatives showed selectivity for inhibition of CA VII versus the ubiquitous isoform CA II, for which the Ki values were in the micromolar range. Molecular modeling approaches were employed to understand the binding interactions between these compounds and the two CA isoforms, since the mechanism of action of such disubstituted sulfamides was not yet investigated by means of X-ray crystallography.

References

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Jan 3, 2008·Nature Reviews. Drug Discovery·Claudiu T Supuran
Dec 8, 2011·Journal of Enzyme Inhibition and Medicinal Chemistry·Ramazan DemirdağClaudiu T Supuran
Apr 4, 2012·Journal of Enzyme Inhibition and Medicinal Chemistry·Claudiu T Supuran
Feb 6, 2013·Journal of Enzyme Inhibition and Medicinal Chemistry·Claudiu T Supuran
May 1, 2013·Expert Opinion on Drug Discovery·Giuseppina De SimoneClaudiu T Supuran
May 1, 2013·Journal of Enzyme Inhibition and Medicinal Chemistry·Clemente Capasso, Claudiu T Supuran
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Dec 2, 2015·Journal of Enzyme Inhibition and Medicinal Chemistry·Claudiu T Supuran

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Citations

Jul 28, 2016·Expert Opinion on Drug Discovery·Alan Talevi
Dec 3, 2016·Bioorganic & Medicinal Chemistry Letters·Carole-Anne LefebvreJean-François Paquin
May 11, 2019·Expert Opinion on Drug Discovery·Carolina L Bellera, Alan Talevi
Oct 18, 2019·Journal of Enzyme Inhibition and Medicinal Chemistry·Manuel A LlanosLuciana Gavernet
Nov 19, 2020·International Journal of Molecular Sciences·Cecilia Zavala-TecuapetlaHiram Luna-Munguia
Mar 23, 2021·Organic Letters·Hai-Ming WangDong-Yu Wang

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