Synthesis and inhibition potency of novel ureido benzenesulfonamides incorporating GABA as tumor-associated carbonic anhydrase IX and XII inhibitors

Journal of Enzyme Inhibition and Medicinal Chemistry
Mariangela CerusoClaudiu T Supuran

Abstract

New ureido benzenesulfonamides incorporating a GABA moiety as a linker between the ureido and the sulfonamide functionalities were synthesized and their inhibition potency determined against both the predominant cytosolic (hCA I and II) and the transmembrane tumor-associated (hCA IX and XII) isoforms of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The majority of these compounds were medium potency inhibitors of the cytosolic isoform hCA I and effective hCA II inhibitors, whereas they showed strong inhibition of the two transmembrane tumor-associated isoforms hCA IX and XII, with KIs in nanomolar range. Only one derivative had a good selectivity for inhibition of the tumor-associated hCA IX target isoform over the cytosolic and physiologically dominant off-target hCA I and II, being thus a potential tool to develop new anticancer agents.

References

May 9, 2006·Respiratory Physiology & Neurobiology·A J Esbaugh, B L Tufts
Jan 3, 2008·Nature Reviews. Drug Discovery·Claudiu T Supuran
May 3, 2008·Cancer Research·Daniel H BarnettBenita S Katzenellenbogen
Jul 21, 2009·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Ludwig DuboisPhilippe Lambin
Aug 15, 2009·Biochimica Et Biophysica Acta·Giuseppina De Simone, Claudiu T Supuran
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Vincenzo AlterioGiuseppina De Simone
Jun 10, 2010·Bioorganic & Medicinal Chemistry Letters·Claudiu T Supuran
Aug 3, 2011·Future Medicinal Chemistry·Claudiu T Supuran
Sep 17, 2011·Nature Reviews. Drug Discovery·Dario Neri, Claudiu T Supuran
Apr 4, 2012·Journal of Enzyme Inhibition and Medicinal Chemistry·Claudiu T Supuran
Apr 14, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alan McIntyreAdrian L Harris
Jun 16, 2012·Expert Opinion on Therapeutic Patents·Fabrizio CartaClaudiu T Supuran
Oct 18, 2012·Neuro-oncology·Martin A ProescholdtAlexander Brawanski
Mar 5, 2013·Bioorganic & Medicinal Chemistry·Claudiu T Supuran
May 1, 2013·Expert Opinion on Drug Discovery·Giuseppina De SimoneClaudiu T Supuran
Jul 23, 2014·ACS Medicinal Chemistry Letters·Mariangela CerusoClaudiu T Supuran
Aug 5, 2014·Journal of Enzyme Inhibition and Medicinal Chemistry·Mariangela CerusoClaudiu T Supuran

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Citations

Jul 21, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Elif UnluerClaudiu T Supuran
Jul 25, 2019·Bioorganic Chemistry·Immo SerbianRené Csuk

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