X-ray crystallographic and kinetic investigations of 6-sulfamoyl-saccharin as a carbonic anhydrase inhibitor

Organic & Biomolecular Chemistry
Vincenzo AlterioClaudiu T Supuran

Abstract

6-Sulfamoyl-saccharin was investigated as an inhibitor of 11 α-carbonic anhydrase (CA, EC 4.2.1.1) isoforms of human (h) origin, hCA I-XIV, and X-ray crystallographic data were obtained for its adduct with hCA II, the physiologically dominant isoform. This compound possesses two potential zinc-binding groups, the primary sulfamoyl one and the secondary, acylatedsulfonamide. Saccharin itself binds to the Zn(II) ion from the CA active site coordinating with this last group, in deprotonated (SO2N(-)CO) form. Here we explain why 6-sulfamoyl-saccharin, unlike saccharin, binds to the metal ion from the hCA II active site by its primary sulfonamide moiety and not the secondary one as saccharin itself. Our study is useful for shedding new light to the structure-based drug design of isoform-selective CA inhibitors of the sulfonamide type.

References

Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Jan 1, 1984·Annals of the New York Academy of Sciences·K K KannanT A Jones
Nov 21, 1995·Proceedings of the National Academy of Sciences of the United States of America·P A Boriack-SjodinD W Christianson
Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·T StamsD W Christianson
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Aug 9, 2001·Proceedings of the National Academy of Sciences of the United States of America·D A WhittingtonD W Christianson
May 31, 2002·Acta Crystallographica. Section B, Structural Science·Frank H Allen
Dec 25, 2002·Medicinal Research Reviews·Claudiu T SupuranAngela Casini
Jan 3, 2008·Nature Reviews. Drug Discovery·Claudiu T Supuran
Mar 14, 2008·Current Pharmaceutical Design·Claudiu T Supuran
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Vincenzo AlterioGiuseppina De Simone
Aug 7, 2010·Bioorganic & Medicinal Chemistry Letters·Anna Di FioreGiuseppina De Simone
Sep 8, 2010·Current Pharmaceutical Design·Claudiu T SupuranGiuseppina De Simone
Sep 17, 2011·Nature Reviews. Drug Discovery·Dario Neri, Claudiu T Supuran
Dec 8, 2011·Journal of Enzyme Inhibition and Medicinal Chemistry·Elif Akin KazancioğluClaudiu T Supuran
Dec 16, 2011·Journal of Enzyme Inhibition and Medicinal Chemistry·Fei LiuClaudiu T Supuran
Dec 24, 2011·Expert Opinion on Therapeutic Patents·Fabrizio CartaAndrea Scozzafava
Feb 1, 2012·Oncotarget·Paul C McDonaldShoukat Dedhar
Feb 4, 2012·Journal of Enzyme Inhibition and Medicinal Chemistry·Alfonso MarescaClaudiu T Supuran
Feb 18, 2012·Expert Opinion on Emerging Drugs·Claudiu T Supuran
Jun 16, 2012·Expert Opinion on Therapeutic Patents·Fabrizio CartaClaudiu T Supuran
Nov 10, 2012·Journal of Enzyme Inhibition and Medicinal Chemistry·Mayank AggarwalRobert McKenna
Feb 6, 2013·Journal of Enzyme Inhibition and Medicinal Chemistry·Claudiu T Supuran
Mar 5, 2013·Bioorganic & Medicinal Chemistry·Claudiu T Supuran
Mar 8, 2013·Journal of Enzyme Inhibition and Medicinal Chemistry·Jinhe PanKuo-Shyan Lin
Mar 16, 2013·Expert Opinion on Therapeutic Patents·Fabrizio Carta, Claudiu T Supuran
Mar 22, 2013·Expert Opinion on Therapeutic Patents·Mayank AggarwalRobert McKenna
Apr 24, 2013·Expert Opinion on Therapeutic Patents·Andrea ScozzafavaFabrizio Carta
May 1, 2013·Expert Opinion on Drug Discovery·Giuseppina De SimoneClaudiu T Supuran
May 1, 2013·Expert Opinion on Therapeutic Patents·Emanuela MasiniClaudiu T Supuran
Aug 7, 2013·Journal of Enzyme Inhibition and Medicinal Chemistry·Sonia Del PreteClemente Capasso
Jan 25, 2014·Journal of Enzyme Inhibition and Medicinal Chemistry·Sonia Del PreteClemente Capasso
Apr 3, 2014·Journal of Medicinal Chemistry·Janina MoekerSally-Ann Poulsen

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Citations

Mar 31, 2015·Chemical Communications : Chem Comm·Jekaterina IvanovaKaspars Tars
Apr 17, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Aleksandrs PustenkoClaudiu T Supuran
May 2, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Srishti SinghRobert McKenna

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