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dc.contributor.authorHickey, James L
dc.contributor.authorRuhayel, Rasha A
dc.contributor.authorBarnard, Peter J
dc.contributor.authorBaker, Murray V
dc.contributor.authorBerners-Price, Susan J
dc.contributor.authorFilipovska, Aleksandra
dc.date.accessioned2018-02-13T03:38:19Z
dc.date.available2018-02-13T03:38:19Z
dc.date.issued2008
dc.date.modified2010-11-04T07:07:08Z
dc.identifier.issn0002-7863
dc.identifier.doi10.1021/ja804027j
dc.identifier.urihttp://hdl.handle.net/10072/33124
dc.description.abstractA family of lipophilic, cationic Au(I) complexes of N-heterocyclic carbenes (NHCs) have been designed as new mitochondria-targeted antitumor agents that combine both selective mitochondrial accumulation and selective thioredoxin reductase inhibition properties within a single molecule. Two-step ligand exchange reactions with cysteine (Cys) and selenocysteine (Sec) occur with release of the NHC ligands. At physiological pH the rate constants for the reactions with Sec are 20- to 80-fold higher than those with Cys. The complexes are selectively toxic to two highly tumorigenic breast cancer cell lines and not to normal breast cells, and the degree of selectivity and potency are optimized by modification of the substituent on the simple imidazolium salt precursor. The lead compound is shown to accumulate in mitochondria of cancer cells, to cause cell death through a mitochondrial apoptotic pathway and to inhibit the activity of thioredoxin reductase (TrxR) but not the closely related and Se-free enzyme glutathione reductase.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Chemical Society
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom12570
dc.relation.ispartofpageto12571
dc.relation.ispartofissue38
dc.relation.ispartofjournalJournal of the American Chemical Society
dc.relation.ispartofvolume130
dc.relation.urihttp://purl.org/au-research/grants/ARC/DP0452327
dc.relation.grantIDDP0452327
dc.relation.fundersARC
dc.rights.retentionY
dc.subject.fieldofresearchBioinorganic Chemistry
dc.subject.fieldofresearchChemical Sciences
dc.subject.fieldofresearchcode030201
dc.subject.fieldofresearchcode03
dc.titleMitochondria-targeted chemotherapeutics: the rational design of gold(I) N-heterocyclic carbene complexes that are selectively toxic to cancer cells and target protein selenols in preference to thiols
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2008
gro.hasfulltextNo Full Text
gro.griffith.authorBerners-Price, Sue J.


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