New precious metal compounds in cancer therapy

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dc.contributor.advisorHendricks, Ten_ZA
dc.contributor.advisorMoss, Ren_ZA
dc.contributor.authorPeters, Dean Douglasen_ZA
dc.date.accessioned2014-07-28T14:55:53Z
dc.date.available2014-07-28T14:55:53Z
dc.date.issued2008en_ZA
dc.descriptionIncludes abstract.
dc.descriptionIncludes bibliographical references (leaves 139-160).
dc.description.abstractCisplatin is one of the most effective cancer medications currently available. However, it is seriously limited by patient toxicity and drug resistance. As such, there is a real need for altemative treatments. Some compounds of gold(l) have been found to be biologically active in various contexts, including in killing cancer cells. The metal centres gold(lIl) and rhodium(lI) are isoelectronic to the platinum(ll) centre in cisplatin, and some of their compounds have been shown to have biological activity. The aims of this work were to prepare pyridinecontaining complexes of the three metal centres gold(I), gold(llI) and rhodium(I), and assess these complexes for in vitro anti-cancer activity. Phenyl pyridine and ferrocenylpyridine complexation was achieved with all three metal centres described above. With gold(I), either a chloride or pentafluorophenyl counter-anion was used. The rhodium(l) complexes contained 1,5-cyclooctadiene moieties linked to the metal centre via diene complexation, and a chloride counter-anion. Phenylpyridine complexes of gold(lIl) were achieved via standard reaction with tetrachloroaurate anion. However, the analogous ferrocenylpyridine complexes display unusually low stability and other unexpected physical properties, and are believed to be highly novel chlorobridged gold dimers. The 4-phenylpyridine complex of rhodium(l) was initially found to be active against cancer cells in vitro. It was, however, demonstrated that this activity was actually due to the breakdown product of this compound in DMSO. It was found that this breakdown product interacts with DNA, implying a similar mechanism of action to cisplatin. This is supported by the fact that a cisplatin-resistant cell line displays hjgh cross-resistance against this product. (4-Phenylpyridine)gold(l) (pentafluorophenyl) was also found to be extremely active against cell lines in vitroen_ZA
dc.identifier.apacitationPeters, D. D. (2008). <i>New precious metal compounds in cancer therapy</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Medical Biochemistry. Retrieved from http://hdl.handle.net/11427/3146en_ZA
dc.identifier.chicagocitationPeters, Dean Douglas. <i>"New precious metal compounds in cancer therapy."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Medical Biochemistry, 2008. http://hdl.handle.net/11427/3146en_ZA
dc.identifier.citationPeters, D. 2008. New precious metal compounds in cancer therapy. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Peters, Dean Douglas AB - Cisplatin is one of the most effective cancer medications currently available. However, it is seriously limited by patient toxicity and drug resistance. As such, there is a real need for altemative treatments. Some compounds of gold(l) have been found to be biologically active in various contexts, including in killing cancer cells. The metal centres gold(lIl) and rhodium(lI) are isoelectronic to the platinum(ll) centre in cisplatin, and some of their compounds have been shown to have biological activity. The aims of this work were to prepare pyridinecontaining complexes of the three metal centres gold(I), gold(llI) and rhodium(I), and assess these complexes for in vitro anti-cancer activity. Phenyl pyridine and ferrocenylpyridine complexation was achieved with all three metal centres described above. With gold(I), either a chloride or pentafluorophenyl counter-anion was used. The rhodium(l) complexes contained 1,5-cyclooctadiene moieties linked to the metal centre via diene complexation, and a chloride counter-anion. Phenylpyridine complexes of gold(lIl) were achieved via standard reaction with tetrachloroaurate anion. However, the analogous ferrocenylpyridine complexes display unusually low stability and other unexpected physical properties, and are believed to be highly novel chlorobridged gold dimers. The 4-phenylpyridine complex of rhodium(l) was initially found to be active against cancer cells in vitro. It was, however, demonstrated that this activity was actually due to the breakdown product of this compound in DMSO. It was found that this breakdown product interacts with DNA, implying a similar mechanism of action to cisplatin. This is supported by the fact that a cisplatin-resistant cell line displays hjgh cross-resistance against this product. (4-Phenylpyridine)gold(l) (pentafluorophenyl) was also found to be extremely active against cell lines in vitro DA - 2008 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2008 T1 - New precious metal compounds in cancer therapy TI - New precious metal compounds in cancer therapy UR - http://hdl.handle.net/11427/3146 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/3146
dc.identifier.vancouvercitationPeters DD. New precious metal compounds in cancer therapy. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Medical Biochemistry, 2008 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/3146en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDivision of Medical Biochemistryen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherMedicineen_ZA
dc.titleNew precious metal compounds in cancer therapyen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMScen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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