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Synthesis and Biological Evaluation of Novel Chloroethylaminoanthraquinones with Potent Cytotoxic Activity against Cisplatin-Resistant Tumor Cells

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journal contribution
posted on 25.03.2004, 00:00 by Klaus Pors, Zennia Paniwnyk, Ketan C. Ruparelia, Paul H. Teesdale-Spittle, John A. Hartley, Lloyd R. Kelland, Laurence H. Patterson
Novel 1- and 1,4-substituted chloroethylaminoanthraquinones with DNA binding and alkylating properties along with their respective hydroxyethylaminoanthraquinone intermediates were synthesized. Selected chloroethylaminoanthraquinones were shown to cross-link DNA and alkylate guanines (at low nM concentration) with a preference for reaction sites containing 5‘-PyG. A compound (Alchemix) with the bis-chloroethyl functionality confined to one side chain alkylated but did not cross-link DNA. All the 1,4-disubstituted chloroethylaminoanthraquinones were potently cytotoxic (nM IC50s) against cisplatin-resistant ovarian cancer cell lines.