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dc.contributor.authorL. Hickey, Jamesen_US
dc.contributor.authorA. Ruhayel, Rashaen_US
dc.contributor.authorJ. Barnard, Peteren_US
dc.contributor.authorV. Baker, Murrayen_US
dc.contributor.authorJ. Berners-Price, Susanen_US
dc.contributor.authorFilipovska, Aleksandraen_US
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.en_US
dc.publisherAmerican Chemical Societyen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofjournalJournal of the American Chemical Societyen_US
dc.subject.fieldofresearchBioinorganic Chemistryen_US
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 thiolsen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.rights.copyrightCopyright 2008 American Chemical Society. Self-archiving of the author-manuscript version is not yet supported by this publisher. Please refer to the journal link for access to the definitive, published version or contact the authors for more information.en_AU
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