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    Alchemix: a novel alkylating anthraquinone with potent activity against anthracycline- and cisplatin-resistant ovarian cancer.

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    Publication date
    2003
    Author
    Pors, Klaus
    Paniwnyk, Z.
    Teesdale-Spittle, P.H.
    Plumb, J.A.
    Willmore, E.
    Austin, C.A.
    Patterson, Laurence H.
    Keyword
    Ovarian Cancer
    Alkylating anthraquinone
    Hydroxyethylaminoanthraquinones
    Alchemix
    Peer-Reviewed
    Yes
    
    Metadata
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    Abstract
    Chloroethylaminoanthraquinones are described with intercalating and alkylating capacity that potentially covalently cross-link topoisomerase II (topo II) to DNA. These compounds have potent cytotoxic activity (IC(50) = 0.9-7.6 nM) against the A2780 human ovarian carcinoma cell line. Hydroxyethylaminoanthraquinones also reported in this paper have similar IC(50) values (0.7-1.7 nM) in the same cell line. Alchemix (ZP281M, 1-(2-[N,N-bis(2-chloroethyl)amino]ethylamino)-4-(2-[N,N-(dimethyl)amino]ethylamino)-5,8-dihydroxy-9,10-anthracenedione), an alkylating anthraquinone, retains excellent antitumor activity in Adriamycin-resistant (2780AD) and cisplatin-resistant (2780/cp70) cell lines in vitro and in vivo. This indicates that Alchemix can evade both P-glycoprotein efflux pump and DNA mismatch repair-mediated resistance. In treated cells, Alchemix was shown to preferentially induce drug-stabilized covalent bound topo IIalpha-DNA complexes over topo IIbeta-DNA complexes.
    URI
    http://hdl.handle.net/10454/3705
    Version
    No full-text available in the repository
    Citation
    Pors, K., Paniwnyk, Z., Teesdale-Spittle, P., Plumb, J.A. and Patterson, L.H. (2003). Alchemix: a novel alkylating anthraquinone with potent activity against anthracycline- and cisplatin-resistant ovarian cancer. Molecular Cancer Therapeutics. Vol 2, No. 7, pp. 607-610.
    Link to publisher’s version
    http://www.ncbi.nlm.nih.gov/pubmed/12883032
    Type
    Article
    Collections
    Life Sciences Publications

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