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

Lookup NU author(s): Dr Elaine Willmore, Professor Caroline Austin

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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 (IC50 = 0.9-7.6 nm) against the A2780 human ovarian carcinoma cell line. Hydroxyethylaminoanthraquinones also reported in this paper have similar IC50 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.


Publication metadata

Author(s): Pors, K., Paniwnyk, Z., Teesdale-Spittle, P., Plumb, J. A., Willmore, E., Austin, C. A., Patterson, L. H.

Publication type: Article

Publication status: Published

Journal: Molecular Cancer Therapeutics

Year: 2003

Volume: 2

Issue: 7

Pages: 607-610

ISSN (print): 1535-7163

ISSN (electronic): 1538-8514


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