Development of nonsymmetrical 1,4-disubstituted anthraquinones that are potently active against cisplatin-resistant ovarian cancer cells
dc.contributor.author | Teesdale-Spittle, P.H. | * |
dc.contributor.author | Pors, Klaus | * |
dc.contributor.author | Brown, R. | * |
dc.contributor.author | Patterson, Laurence H. | * |
dc.contributor.author | Plumb, J.A. | * |
dc.date.accessioned | 2009-07-29T08:49:33Z | |
dc.date.available | 2009-07-29T08:49:33Z | |
dc.date.issued | 2005 | |
dc.identifier.citation | Pors, 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.uri | http://hdl.handle.net/10454/3191 | |
dc.description | No | |
dc.description.abstract | A 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.iso | en | |
dc.subject | Treatment resistance | |
dc.subject | Transition metal Complexes | |
dc.subject | Divalent metal Complexes | |
dc.subject | Platinum II Complexes | |
dc.subject | Malignant tumour | |
dc.subject | Alkylating agent | |
dc.subject | Vertebrata | |
dc.subject | Mammalia | |
dc.subject | Rodentia | |
dc.subject | Cell line | |
dc.subject | Chlorine Organic compounds | |
dc.subject | Animal | |
dc.subject | Ovary | |
dc.subject | Tumour cell | |
dc.subject | Human | |
dc.subject | Alcohol | |
dc.subject | Antineoplastic agent | |
dc.subject | Mechanism of action | |
dc.subject | Antimitotic | |
dc.subject | Intraperitoneal administration | |
dc.subject | Chemotherapy | |
dc.subject | Cytotoxicity | |
dc.subject | In vivo | |
dc.subject | Pyrrolidine derivatives | |
dc.subject | Piperidine derivatives | |
dc.subject | Tricyclic compound | |
dc.subject | Condensed benzenic compound | |
dc.subject | Structure activity relation | |
dc.subject | Diphenols | |
dc.subject | Aromatic amine | |
dc.subject | Ovarian cancer | |
dc.subject | In vitro | |
dc.subject | Chemical synthesis | |
dc.subject | Cisplatin | |
dc.title | Development of nonsymmetrical 1,4-disubstituted anthraquinones that are potently active against cisplatin-resistant ovarian cancer cells | |
dc.status.refereed | Yes | |
dc.type | Article | |
dc.type.version | No full-text in the repository | |
dc.identifier.doi | https://doi.org/10.1021/jm050438f | |
dc.openaccess.status | closedAccess |