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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.
dc.identifier.urihttp://hdl.handle.net/10454/3191
dc.descriptionNo
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.
dc.language.isoen
dc.subjectTreatment resistance
dc.subjectTransition metal Complexes
dc.subjectDivalent metal Complexes
dc.subjectPlatinum II Complexes
dc.subjectMalignant tumour
dc.subjectAlkylating agent
dc.subjectVertebrata
dc.subjectMammalia
dc.subjectRodentia
dc.subjectCell line
dc.subjectChlorine Organic compounds
dc.subjectAnimal
dc.subjectOvary
dc.subjectTumour cell
dc.subjectHuman
dc.subjectAlcohol
dc.subjectAntineoplastic agent
dc.subjectMechanism of action
dc.subjectAntimitotic
dc.subjectIntraperitoneal administration
dc.subjectChemotherapy
dc.subjectCytotoxicity
dc.subjectIn vivo
dc.subjectPyrrolidine derivatives
dc.subjectPiperidine derivatives
dc.subjectTricyclic compound
dc.subjectCondensed benzenic compound
dc.subjectStructure activity relation
dc.subjectDiphenols
dc.subjectAromatic amine
dc.subjectOvarian cancer
dc.subjectIn vitro
dc.subjectChemical synthesis
dc.subjectCisplatin
dc.titleDevelopment of nonsymmetrical 1,4-disubstituted anthraquinones that are potently active against cisplatin-resistant ovarian cancer cells
dc.status.refereedYes
dc.typeArticle
dc.type.versionNo full-text in the repository
dc.identifier.doihttps://doi.org/10.1021/jm050438f
dc.openaccess.statusclosedAccess


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