Please use this identifier to cite or link to this item: https://hdl.handle.net/1959.11/22912
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dc.contributor.authorWilkinson, Brendanen
dc.contributor.authorBornaghi, Laurent Fen
dc.contributor.authorHouston, Todd Aen
dc.contributor.authorInnocenti, Alessioen
dc.contributor.authorVullo, Danielaen
dc.contributor.authorSupuran, Claudiu Ten
dc.contributor.authorPoulsen, Sally-Annen
dc.date.accessioned2018-04-27T14:34:00Z-
dc.date.issued2007-
dc.identifier.citationBioorganic & Medicinal Chemistry Letters, 17(4), p. 987-992en
dc.identifier.issn1464-3405en
dc.identifier.issn0960-894Xen
dc.identifier.urihttps://hdl.handle.net/1959.11/22912-
dc.description.abstractA library of glycoconjugate benzenesulfonamides that contain diverse carbohydrate-triazole tails were investigated for their ability to inhibit the enzymatic activity of the three human transmembrane carbonic anhydrase (CA) isozymes hCA IX, hCA XII and hCA XIV. These isozymes have their CA domains located extracellularly, unlike the physiologically dominant hCA II, and are of immense current interest as druggable targets. Elevated expression of isozymes IX and XII is a marker for a broad spectrum of hypoxic tumors-this physiology may facilitate a novel approach to discriminate between healthy cells and cancerous cells. Many of these glycoconjugates were potent inhibitors (low nM), but importantly exhibited different isozyme selectivity profiles. The most potent hCA IX inhibitor was the glucuronic acid derivative 20 (Kᵢ = 23 nM). This compound was uniquely hCA IX selective cf. all other isozymes (16.4-, 16.8- and 4.6-fold selective against hCA II, XII, and XIV, respectively). At hCA XII there were many inhibitors with Kᵢs < 10 nM that also demonstrated excellent selectivity (up to 344-fold) against other isozymes. Potent hCA XIV inhibitors were also identified, several with Kᵢs ~ 10 nM, however no hCA XIV-selective derivatives were evidenced from this library. The sugar tails of this study have shown promise as a valuable approach to both solubilize the aromatic sulfonamide CA recognition pharmacophore and to deliver potent inhibition and isozyme differentiation of the transmembrane CAs.en
dc.languageenen
dc.publisherPergamon Pressen
dc.relation.ispartofBioorganic & Medicinal Chemistry Lettersen
dc.titleInhibition of membrane-associated carbonic anhydrase isozymes IX, XII and XIV with a library of glycoconjugate benzenesulfonamidesen
dc.typeJournal Articleen
dc.identifier.doi10.1016/j.bmcl.2006.11.046en
dc.subject.keywordsOrganic Chemical Synthesisen
dc.subject.keywordsMedicinal and Biomolecular Chemistryen
dc.subject.keywordsBiologically Active Moleculesen
local.contributor.firstnameBrendanen
local.contributor.firstnameLaurent Fen
local.contributor.firstnameTodd Aen
local.contributor.firstnameAlessioen
local.contributor.firstnameDanielaen
local.contributor.firstnameClaudiu Ten
local.contributor.firstnameSally-Annen
local.subject.for2008030499 Medicinal and Biomolecular Chemistry not elsewhere classifieden
local.subject.for2008030401 Biologically Active Moleculesen
local.subject.for2008030503 Organic Chemical Synthesisen
local.subject.seo2008970106 Expanding Knowledge in the Biological Sciencesen
local.subject.seo2008970103 Expanding Knowledge in the Chemical Sciencesen
local.subject.seo2008929999 Health not elsewhere classifieden
local.profile.schoolSchool of Science and Technologyen
local.profile.emailbwilkin7@une.edu.auen
local.output.categoryC1en
local.record.placeauen
local.record.institutionUniversity of New Englanden
local.identifier.epublicationsrecordune-20180425-101510en
local.publisher.placeUnited Kingdomen
local.format.startpage987en
local.format.endpage992en
local.identifier.scopusid33846575753en
local.peerreviewedYesen
local.identifier.volume17en
local.identifier.issue4en
local.contributor.lastnameWilkinsonen
local.contributor.lastnameBornaghien
local.contributor.lastnameHoustonen
local.contributor.lastnameInnocentien
local.contributor.lastnameVulloen
local.contributor.lastnameSupuranen
local.contributor.lastnamePoulsenen
dc.identifier.staffune-id:bwilkin7en
local.profile.orcid0000-0003-1866-6540en
local.profile.roleauthoren
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local.identifier.unepublicationidune:23097en
local.identifier.handlehttps://hdl.handle.net/1959.11/22912en
dc.identifier.academiclevelAcademicen
local.title.maintitleInhibition of membrane-associated carbonic anhydrase isozymes IX, XII and XIV with a library of glycoconjugate benzenesulfonamidesen
local.output.categorydescriptionC1 Refereed Article in a Scholarly Journalen
local.search.authorWilkinson, Brendanen
local.search.authorBornaghi, Laurent Fen
local.search.authorHouston, Todd Aen
local.search.authorInnocenti, Alessioen
local.search.authorVullo, Danielaen
local.search.authorSupuran, Claudiu Ten
local.search.authorPoulsen, Sally-Annen
local.uneassociationUnknownen
local.year.published2007en
local.subject.for2020340499 Medicinal and biomolecular chemistry not elsewhere classifieden
local.subject.for2020340401 Biologically active moleculesen
local.subject.for2020340503 Organic chemical synthesisen
local.subject.seo2020280102 Expanding knowledge in the biological sciencesen
local.subject.seo2020200199 Clinical health not elsewhere classifieden
local.subject.seo2020280105 Expanding knowledge in the chemical sciencesen
local.codeupdate.date2022-02-13T17:09:59.738en
local.codeupdate.epersonbwilkin7@une.edu.auen
local.codeupdate.finalisedtrueen
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