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dc.contributor.authorCoverdale, J.P.C.*
dc.contributor.authorBridgewater, H.E.*
dc.contributor.authorSong, J-I.*
dc.contributor.authorSmith, N.A.*
dc.contributor.authorBarry, Nicolas P.E.*
dc.contributor.authorBagley, I.*
dc.contributor.authorSadler, P.J.*
dc.contributor.authorRomero-Canelon, I.*
dc.date.accessioned2018-10-30T15:21:16Z
dc.date.available2018-10-30T15:21:16Z
dc.date.issued2018-10
dc.identifier.citationCoverdale JPC, Bridgewater HE, Song J-I et al (2018) In vivo selectivity and localization of reactive oxygen species (ROS) induction by osmium anticancer complexes that circumvent platinum resistance. Journal of Medicinal Chemistry. 61(20): 9246-9255.en_US
dc.identifier.urihttp://hdl.handle.net/10454/16636
dc.descriptionYesen_US
dc.description.abstractPlatinum drugs are widely used for cancer treatment. Other precious metals are promising, but their clinical progress depends on achieving different mechanisms of action to overcome Pt-resistance. Here, we evaluate 13 organo-Os complexes: 16-electron sulfonyl-diamine catalysts [(η6-arene)Os(N,N′)], and 18-electron phenylazopyridine complexes [(η6-arene)Os(N,N’)Cl/I]+ (arene = p-cymene, biphenyl, or terphenyl). Their antiproliferative activity does not depend on p21 or p53 status, unlike cisplatin, and their selective potency toward cancer cells involves the generation of reactive oxygen species. Evidence of such a mechanism of action has been found both in vitro and in vivo. This work appears to provide the first study of osmium complexes in the zebrafish model, which has been shown to closely model toxicity in humans. A fluorescent osmium complex, derived from a lead compound, was employed to confirm internalization of the complex, visualize in vivo distribution, and confirm colocalization with reactive oxygen species generated in zebrafish.en_US
dc.description.sponsorshipWellcome Trust (grant no. 107691/Z/15/Z), ERC (grant nos. 247450, 324594), Science City (AWM and ERDF), WCPRS and Bruker Daltonics (Studentship for JPCC), Mike and Enfys Bagguley, and EPSRC (Studentship for HEB, and grant no. EP/F034210/1).en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1021/acs.jmedchem.8b00958en_US
dc.rights© 2018 American Chemical Society. ACS AuthorChoice - This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.en_US
dc.subjectOrgano-osmium complexesen_US
dc.subjectAnticanceren_US
dc.subjectFluorescent labellingen_US
dc.subjectReactive oxygen speciesen_US
dc.subjectIn vivo zebrafishen_US
dc.titleIn vivo selectivity and localization of reactive oxygen species (ROS) induction by osmium anticancer complexes that circumvent platinum resistanceen_US
dc.status.refereedYesen_US
dc.date.Accepted2018-09-19
dc.date.application2018-09-19
dc.typeArticleen_US
dc.type.versionpublished version paperen_US
refterms.dateFOA2018-10-30T15:21:16Z


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