Synthesis of DNA-directed pyrrolidinyl and piperidinyl confined alkylating chloroalkylaminoanthraquinones: Potential for development of tumor-selective N-oxides

Klaus Pors, Steven D. Shnyder, Paul H. Teesdale-Spittle, John A. Hartley, Mire Zloh, Mark Searcey, Laurence H. Patterson

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A novel series of 1,4-disubstituted chloroethylaminoanthraquinones, containing alkylating chloroethylamino functionalities as part of a rigid piperidinyl or pyrrolidinyl ring-system, have been prepared. The target compounds were prepared by ipso-displacement of halides of various anthraquinone chromophores by either hydroxylated or chlorinated piperidinyl- or pyrrolidinyl-alkylamino side chains. The chloroethylaminoanthraquinones were shown to alkylate guanine residues of linearized pBR322 (1-20 mu M), and two symmetrically 1,4-disubstituted anthraquinones (compounds 14 and 15) were shown to interstrand cross-link DNA in the low nM range. Several 1,4-disubstituted chloroethylaminoanthraquinones were potently cytotoxic (IC50 values:
Original languageEnglish
Pages (from-to)7013-7023
Number of pages11
JournalJournal of Medicinal Chemistry
Issue number24
Publication statusPublished - 2006

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