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

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.

• Authors: Klaus Pors, Zennia Paniwnyk, Paul Teesdale-Spittle, Jane A Plumb, Elaine Willmore, Caroline A Austin, Laurence H Patterson
• Journal: Molecular cancer therapeutics (Mol Cancer Ther) Vol. 2 Issue 7 Pg. 607-10 (Jul 2003) ISSN: 1535-7163 [Print] United States
• PMID: 12883032 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Alchemix
• Anthracyclines
• Anthraquinones
• Antigens, Neoplasm
• Antineoplastic Agents, Alkylating
• DNA-Binding Proteins
• DNA
• DNA Topoisomerases, Type II
• Cisplatin

Topics

• Animals
• Anthracyclines (pharmacology)
• Anthraquinones (therapeutic use)
• Antigens, Neoplasm
• Antineoplastic Agents, Alkylating (therapeutic use)
• Cisplatin (pharmacology)
• DNA (metabolism)
• DNA Repair
• DNA Topoisomerases, Type II (metabolism)
• DNA-Binding Proteins
• Drug Resistance, Neoplasm
• Female
• Humans
• In Vitro Techniques
• Mice
• Mice, Nude
• Ovarian Neoplasms (drug therapy, metabolism)
• Tumor Cells, Cultured