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    In vivo selectivity and localization of reactive oxygen species (ROS) induction by osmium anticancer complexes that circumvent platinum resistance

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    Publication date
    2018-10
    Author
    Coverdale, J.P.C.
    Bridgewater, H.E.
    Song, J-I.
    Smith, N.A.
    Barry, Nicolas P.E.
    Bagley, I.
    Sadler, P.J.
    Romero-Canelon, I.
    Keyword
    Organo-osmium complexes
    Anticancer
    Fluorescent labelling
    Reactive oxygen species
    In vivo zebrafish
    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.
    Peer-Reviewed
    Yes
    
    Metadata
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    Abstract
    Platinum 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.
    URI
    http://hdl.handle.net/10454/16636
    Version
    published version paper
    Citation
    Coverdale 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.
    Link to publisher’s version
    http://dx.doi.org/10.1021/acs.jmedchem.8b00958
    Type
    Article
    Collections
    Life Sciences Publications

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