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dc.contributor.authorWilkinson, Brendanen_US
dc.contributor.authorBornaghi, Laurenten_US
dc.contributor.authorHouston, Todden_US
dc.contributor.authorInnocenti, Alessioen_US
dc.contributor.authorVullo, Danielaen_US
dc.contributor.authorT. Supuran, Claudiuen_US
dc.contributor.authorPoulsen, Sally-Annen_US
dc.contributor.editorD.L. Boger, L. Ghosez and M. Shibasakien_US
dc.date.accessioned2017-05-03T11:45:27Z
dc.date.available2017-05-03T11:45:27Z
dc.date.issued2007en_US
dc.date.modified2009-12-07T07:54:28Z
dc.identifier.issn0960894Xen_US
dc.identifier.doi10.1016/j.bmcl.2006.11.046en_AU
dc.identifier.urihttp://hdl.handle.net/10072/18265
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 anhydrases (CAs) 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-fold, 16.8-fold 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 therefore 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_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.format.extent96086 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherPergamon Pressen_US
dc.publisher.placeOxford, UKen_US
dc.publisher.urihttp://www.elsevier.com/wps/find/journaldescription.cws_home/129/description#descriptionen_AU
dc.relation.ispartofstudentpublicationYen_AU
dc.relation.ispartofpagefrom987en_US
dc.relation.ispartofpageto992en_US
dc.relation.ispartofjournalBioorganic & Medicinal Chemistry Lettersen_US
dc.relation.ispartofvolume17en_US
dc.rights.retentionYen_AU
dc.subject.fieldofresearchcode250302en_US
dc.titleInhibition of membrane-associated carbonic anhydrase isozymes IX, XII and XIV with a library of glycoconjugate benzenesulfonamides.en_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.facultyGriffith Sciences, School of Natural Sciencesen_US
gro.rights.copyrightCopyright 2007 Elsevier. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.en_AU
gro.date.issued2007
gro.hasfulltextFull Text


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