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dc.contributor.authorPatterson, Laurence H.*
dc.contributor.authorPors, Klaus*
dc.contributor.authorShnyder, Steven*
dc.contributor.authorTeesdale-Spittle, P.H.*
dc.contributor.authorHartley, J.A.*
dc.contributor.authorSearcey, M.*
dc.contributor.authorZloh, M.*
dc.date.accessioned2009-07-20T10:58:59Z
dc.date.available2009-07-20T10:58:59Z
dc.date.issued2006
dc.identifier.citationPors K, Shnyder SD, Teesdale-Spittle PH et al (2006) Synthesis of DNA-Directed Pyrrolidinyl and Piperidinyl Confined Alkylating Chloroalkylaminoanthraquinones: Potential for Development of Tumor-Selective N-Oxides. Journal of Medicinal Chemistry. 49(24): 7013-7023.en
dc.identifier.urihttp://hdl.handle.net/10454/3060
dc.descriptionNoen
dc.description.abstractA 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 ¿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: ¿40 nM) in human ovarian cancer A2780 cells. Two agents (compounds 18 and 19) exhibited mean GI50 values of 96 nM and 182 nM, respectively, in the NCI human tumor cell line panel. Derivatization of the potent DNA cross-linking agent 15 to an N-oxide resulted in loss of the DNA unwinding, DNA interstrand cross-linking and cytotoxic activity of the parent molecule.en
dc.language.isoenen
dc.subjectDNA intercalating topoisomerase inhibitorsen
dc.subjectAntitumor agentsen
dc.subjectAnticancer drugsen
dc.subjectCanceren
dc.titleSynthesis of DNA-Directed Pyrrolidinyl and Piperidinyl Confined Alkylating Chloroalkylaminoanthraquinones: Potential for Development of Tumor-Selective N-Oxidesen
dc.status.refereedYesen
dc.typeArticleen
dc.type.versionNo full-text in the repositoryen
dc.identifier.doihttps://doi.org/10.1021/jm0608154


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