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dc.contributor.authorLiu, Johnson J
dc.contributor.authorGalettis, Peter
dc.contributor.authorFarr, Alistair
dc.contributor.authorMaharaj, Lenushka
dc.contributor.authorSamarasinha, Hasitha
dc.contributor.authorMcGechan, Adam C
dc.contributor.authorBaguley, Bruce C
dc.contributor.authorBowen, Richard J
dc.contributor.authorBerners-Price, Susan J
dc.contributor.authorMcKeage, Mark J
dc.contributor.editorDr. J H Dawson (Editor-in-Chief)
dc.date.accessioned2018-02-13T03:37:09Z
dc.date.available2018-02-13T03:37:09Z
dc.date.issued2008
dc.date.modified2012-05-23T22:03:39Z
dc.identifier.issn0162-0134
dc.identifier.doi10.1016/j.jinorgbio.2007.09.003
dc.identifier.urihttp://hdl.handle.net/10072/23449
dc.description.abstractIn this study we characterised the in vitro antitumour and hepatotoxicity profiles of a series of Au(I) and Ag(I) bidentate phenyl and pyridyl complexes in a panel of cisplatin-resistant human ovarian cancer cell-lines, and in isolated rat hepatocytes. The gold and silver compounds overcame cisplatin-resistance in the CH1-cisR, 41M-cisR and SKOV-3 cell-lines, and showed cytotoxic potencies strongly correlated with their lipophilicity. Complexes with phenyl or 2-pyridyl ligands had high antitumour and hepatotoxic potency and low selectivity between different cell-lines. Their cytotoxicity profiles were similar to classic mitochondrial poisons and an example of this type of compound was shown to accumulate preferentially in the mitochondria of cancer cells in a manner that depended upon the mitochondrial membrane potential. In contrast, complexes with 3- or 4-pyridyl ligands had low antitumour and hepatotoxic potency and cytotoxicity profiles similar to 2-deoxy-D-glucose. In addition, they showed high selectivity between different cell-lines that was not attributable to variation in uptake in different cell-types. The in vitro hepatotoxic potency of the series of gold and silver compounds varied by over 61-fold and was closely related to their lipophilicity and hepatocyte uptake. In conclusion, Au(I) and Ag(I) bidendate pyridyl phosphine complexes demonstrate activity against cisplatin-resistant human cancer cells and in vitro cytotoxicity that strongly depends upon their lipophilicity.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom303
dc.relation.ispartofpageto310
dc.relation.ispartofissue2
dc.relation.ispartofjournalJournal of Inorganic Biochemistry
dc.relation.ispartofvolume102
dc.relation.urihttp://purl.org/au-research/grants/ARC/DP0452327
dc.relation.grantIDDP0452327
dc.relation.fundersARC
dc.rights.retentionY
dc.subject.fieldofresearchInorganic chemistry
dc.subject.fieldofresearchTheoretical and computational chemistry
dc.subject.fieldofresearchOther chemical sciences
dc.subject.fieldofresearchBiochemistry and cell biology not elsewhere classified
dc.subject.fieldofresearchcode3402
dc.subject.fieldofresearchcode3407
dc.subject.fieldofresearchcode3499
dc.subject.fieldofresearchcode310199
dc.titleIn vitro antitumour and hepatotoxicity profiles of Au(I) and Ag(I) bidentate pyridyl phosphine complexes and relationships to cellular uptake
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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