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dc.contributor.authorTeesdale-Spittle, P.H.*
dc.contributor.authorPors, Klaus*
dc.contributor.authorBrown, R.*
dc.contributor.authorPatterson, Laurence H.*
dc.contributor.authorPlumb, J.A.*
dc.date.accessioned2009-07-29T08:49:33Z
dc.date.available2009-07-29T08:49:33Z
dc.date.issued2005
dc.identifier.citationPors, K., Plumb, J.A., Brown, R., Teesdale-Spittle, P., Searcey, M., Smith, P.J. and Patterson, L.H. (2005). Development of nonsymmetrical 1,4-disubstituted anthraquinones that are potently active against cisplatin-resistant ovarian cancer cells. Journal of Medicinal Chemistry. Vol. 48, No. 21, pp. 6690-6695.en
dc.identifier.urihttp://hdl.handle.net/10454/3191
dc.descriptionNoen
dc.description.abstractA novel series of 1,4-disubstituted aminoanthraquinones were prepared by ipso-displacement of 1,4-difluoro-5,8-dihydroxyanthraquinones by hydroxylated piperidinyl- or pyrrolidinylalkyl-amino side chains. One aminoanthraquinone (13) was further derivatized to a chloropropyl-amino analogue by treatment with triphenylphosphine-carbon tetrachloride. The compounds were evaluated in the A2780 ovarian cancer cell line and its cisplatin-resistant variants (A2780/ cp70 and A2780/MCP1). The novel anthraquinones were shown to possess up to 5-fold increased potency against the cisplatin-resistant cells compared to the wild-type cells. Growth curve analysis of the hydroxyethylaminoanthraquinone 8 in the osteosarcoma cell line U-2 OS showed that the cell cycle is not frozen, rather there is a late cell cycle arrest consistent with the action of a DNA-damaging topoisomerase II inhibitor. Accumulative apoptotic events, using time lapse photography, indicate that 8 is capable of fully engaging cell cycle arrest pathways in G2 in the absence of early apoptotic commitment. 8 and its chloropropyl analogue 13 retained significant activity against human A2780/cp70 xenografted tumors in mice.en
dc.language.isoenen
dc.relation.isreferencedbyhttp://dx.doi.org/10.1021/jm050438fen
dc.subjectTreatment resistanceen
dc.subjectTransition metal Complexesen
dc.subjectDivalent metal Complexesen
dc.subjectPlatinum II Complexesen
dc.subjectMalignant tumouren
dc.subjectAlkylating agenten
dc.subjectVertebrataen
dc.subjectMammaliaen
dc.subjectRodentiaen
dc.subjectCell lineen
dc.subjectChlorine Organic compoundsen
dc.subjectAnimalen
dc.subjectOvaryen
dc.subjectTumour cellen
dc.subjectHumanen
dc.subjectAlcoholen
dc.subjectAntineoplastic agenten
dc.subjectMechanism of actionen
dc.subjectAntimitoticen
dc.subjectIntraperitoneal administrationen
dc.subjectChemotherapyen
dc.subjectCytotoxicityen
dc.subjectIn vivoen
dc.subjectPyrrolidine derivativesen
dc.subjectPiperidine derivativesen
dc.subjectTricyclic compounden
dc.subjectCondensed benzenic compounden
dc.subjectStructure activity relationen
dc.subjectDiphenolsen
dc.subjectAromatic amineen
dc.subjectOvarian canceren
dc.subjectIn vitroen
dc.subjectChemical synthesisen
dc.subjectCisplatinen
dc.titleDevelopment of nonsymmetrical 1,4-disubstituted anthraquinones that are potently active against cisplatin-resistant ovarian cancer cellsen
dc.status.refereedYesen
dc.typeArticleen
dc.type.versionNo full-text available in the repositoryen


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