dc.contributor.author | Moeker, Janina | |
dc.contributor.author | Teruya, Kanae | |
dc.contributor.author | Rossit, Sabine | |
dc.contributor.author | Wilkinson, Brendan L | |
dc.contributor.author | Lopez, Marie | |
dc.contributor.author | Bornaghi, Laurent F | |
dc.contributor.author | Innocenti, Alessio | |
dc.contributor.author | Supuran, Claudiu T | |
dc.contributor.author | Poulsen, Sally-Ann | |
dc.date.accessioned | 2017-05-03T11:45:41Z | |
dc.date.available | 2017-05-03T11:45:41Z | |
dc.date.issued | 2012 | |
dc.date.modified | 2013-06-06T23:49:22Z | |
dc.identifier.issn | 0968-0896 | |
dc.identifier.doi | 10.1016/j.bmc.2012.01.052 | |
dc.identifier.uri | http://hdl.handle.net/10072/47984 | |
dc.description.abstract | A library of 32 novel glycoconjugate thiourea-bridged benzene sulfonamides have been synthesized from the reaction of glycosyl isothiocyanates with a panel of simple benzene sulfonamides comprising either a free amine or hydrazide. All compounds were investigated for their ability to inhibit the enzymatic activity of five human carbonic anhydrase (hCA) isozymes: hCA I, II and membrane-associated isozymes IX, XII and XIV. A physicochemical feature of the free sugar thioureido glycoconjugates was high water solubility (> 20 mg/mL), as well many of these compounds exhibited a desirable potency and CA isozyme selectivity profile. From this library several inhibitors displayed excellent potency-selectivity profiles for transmembrane anchored CAs over off-target CA I and II. These molecules provide potential dual-acting candidates for the development of inhibitors that target the extracellular CAs (IX, XII and XIV) - either directly as free sugars (membrane impermeable) or indirectly as acetylated prodrugs, becoming free sugars upon esterase hydrolysis. | |
dc.description.peerreviewed | Yes | |
dc.description.publicationstatus | Yes | |
dc.format.extent | 885901 bytes | |
dc.format.mimetype | application/pdf | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Elsevier | |
dc.publisher.place | United Kingdom | |
dc.relation.ispartofstudentpublication | N | |
dc.relation.ispartofpagefrom | 2392 | |
dc.relation.ispartofpageto | 2404 | |
dc.relation.ispartofissue | 7 | |
dc.relation.ispartofjournal | Bioorganic & Medicinal Chemistry | |
dc.relation.ispartofvolume | 20 | |
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 | Design and synthesis of thiourea compounds that inhibit transmembrane anchored carbonic anhydrases | |
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 | © 2012 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. | |
gro.date.issued | 2012 | |
gro.hasfulltext | Full Text | |
gro.griffith.author | Poulsen, Sally-Ann | |