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

By Klaus Pors, Z. Paniwnyk, P.H. Teesdale-Spittle, J.A. Plumb, E. Willmore, C.A. Austin and Laurence H. Patterson

Abstract

NoChloroethylaminoanthraquinones 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

Topics: Ovarian Cancer, Alkylating anthraquinone, Hydroxyethylaminoanthraquinones, Alchemix
Year: 2003
OAI identifier: oai:bradscholars.brad.ac.uk:10454/3705
Provided by: Bradford Scholars
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