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Pors K, Paniwnyk Z, Teesdale-Spittle P, Plumb JA, Willmore E, Austin CA, Patterson LH: Alchemix: a novel alkylating anthraquinone with potent activity against anthracycline- and cisplatin-resistant ovarian cancer. Mol Cancer Ther. 2003 Jul;2(7):607-10.
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] et hylamino)-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. |
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