dc.contributor.author | Carroux, Cindy J | |
dc.contributor.author | Rankin, Gregory M | |
dc.contributor.author | Moeker, Janina | |
dc.contributor.author | Bornaghi, Laurent F | |
dc.contributor.author | Katneni, Kasiram | |
dc.contributor.author | Morizzi, Julia | |
dc.contributor.author | Charman, Susan A | |
dc.contributor.author | Vullo, Daniela | |
dc.contributor.author | Supuran, Claudiu T | |
dc.contributor.author | Poulsen, Sally-Ann | |
dc.date.accessioned | 2017-05-03T11:45:44Z | |
dc.date.available | 2017-05-03T11:45:44Z | |
dc.date.issued | 2013 | |
dc.identifier.issn | 0022-2623 | |
dc.identifier.doi | 10.1021/jm401163e | |
dc.identifier.uri | http://hdl.handle.net/10072/57021 | |
dc.description.abstract | The selective inhibition of cancer-associated human carbonic anhydrase (CA) enzymes, specifically CA IX and XII, has been validated as a mechanistically novel approach toward personalized cancer management. Herein we report the design and synthesis of a panel of 24 novel glycoconjugate primary sulfonamides that bind to the extracellular catalytic domain of CA IX and XII. These compounds were synthesized from variably acylated glycopyranosyl azides and either 3- or 4-ethynyl benzene sulfonamide using Cu(I)-catalyzed azide alkyne cycloaddition (CuAAC). The CA enzyme inhibition profile for all compounds was determined, while in vitro metabolic stability, plasma stability, and plasma protein binding for a representative set of compounds was measured. Our findings demonstrate the influence of the differing acyl groups on these key biopharmaceutical properties, confirming that acyl group protected carbohydrate-based sulfonamides have potential as prodrugs for selectively targeting the extracellular cancer-associated CA enzymes. | |
dc.description.peerreviewed | Yes | |
dc.description.publicationstatus | Yes | |
dc.format.extent | 400838 bytes | |
dc.format.mimetype | application/pdf | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | American Chemical Society | |
dc.publisher.place | United States | |
dc.relation.ispartofstudentpublication | Y | |
dc.relation.ispartofpagefrom | 9623 | |
dc.relation.ispartofpageto | 9634 | |
dc.relation.ispartofissue | 23 | |
dc.relation.ispartofjournal | Journal of Medicinal Chemistry | |
dc.relation.ispartofvolume | 56 | |
dc.rights.retention | Y | |
dc.subject.fieldofresearch | Medicinal and biomolecular chemistry | |
dc.subject.fieldofresearch | Biologically active molecules | |
dc.subject.fieldofresearch | Organic chemistry | |
dc.subject.fieldofresearch | Pharmacology and pharmaceutical sciences | |
dc.subject.fieldofresearchcode | 3404 | |
dc.subject.fieldofresearchcode | 340401 | |
dc.subject.fieldofresearchcode | 3405 | |
dc.subject.fieldofresearchcode | 3214 | |
dc.title | A prodrug approach toward cancer-related carbonic anhydrase inhibition | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
gro.faculty | Griffith Sciences, Griffith Institute for Drug Discovery | |
gro.rights.copyright | This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Medicinal Chemistry, copyright 2012 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/jm401163e. | |
gro.date.issued | 2015-07-30T23:12:48Z | |
gro.hasfulltext | Full Text | |
gro.griffith.author | Poulsen, Sally-Ann | |