Show simple item record

dc.contributor.authorPors, Klaus
dc.contributor.authorShnyder, Steven D.
dc.contributor.authorTeesdale-Spittle, Paul H.
dc.contributor.authorHartley, John A.
dc.contributor.authorZloh, Mire
dc.contributor.authorSearcey, Mark
dc.contributor.authorPatterson, Laurence H.
dc.date.accessioned2013-08-22T12:45:05Z
dc.date.available2013-08-22T12:45:05Z
dc.date.issued2006
dc.identifier.citationPors , K , Shnyder , S D , Teesdale-Spittle , P H , Hartley , J A , Zloh , M , Searcey , M & Patterson , L H 2006 , ' Synthesis of DNA-directed pyrrolidinyl and piperidinyl confined alkylating chloroalkylaminoanthraquinones : potential for development of tumor-selective N-oxides ' , Journal of Medicinal Chemistry , vol. 49 , no. 24 , pp. 7013-23 . https://doi.org/10.1021/jm0608154
dc.identifier.issn0022-2623
dc.identifier.otherPURE: 1457962
dc.identifier.otherPURE UUID: 0a2dddc4-080e-4102-bc75-473cdc512fe8
dc.identifier.otherPubMed: 17125254
dc.identifier.otherScopus: 33845355611
dc.identifier.urihttp://hdl.handle.net/2299/11457
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 microM), 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 moleculeen
dc.format.extent11
dc.language.isoeng
dc.relation.ispartofJournal of Medicinal Chemistry
dc.titleSynthesis of DNA-directed pyrrolidinyl and piperidinyl confined alkylating chloroalkylaminoanthraquinones : potential for development of tumor-selective N-oxidesen
dc.contributor.institutionDepartment of Pharmacy
dc.contributor.institutionMedicinal and Analytical Chemistry
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Life and Medical Sciences
rioxxterms.versionofrecordhttps://doi.org/10.1021/jm0608154
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.rights.accesstyperestrictedAccess


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record