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dc.contributor.advisorMaguire, Glen Eamonn Mitchel.
dc.contributor.advisorKruger, Hendrik Gert.
dc.creatorPareskevopoulos, Jason Nicholas.
dc.date.accessioned2010-08-20T10:21:33Z
dc.date.available2010-08-20T10:21:33Z
dc.date.created2008
dc.date.issued2008
dc.identifier.urihttp://hdl.handle.net/10413/432
dc.descriptionThesis (M.Sc.)-University of KwaZulu-Natal, Westville, 2008.en_US
dc.description.abstractMalaria remains one of the greatest problems facing developing nations, especially in sub-Saharan Africa. Part of the problem stems from increased resistance to current treatments hence there is a large drive to develop novel antimalarial compounds. Several chelating compounds, including 8-hydroxyquinoline (8-HQ), 1,10- phenanthroline (1,10-phen) and 2,2.6,2-terpyridine (terpy), have disputed activities (8-HQ and 1,10-phen) or are untested (terpy). Furthermore the mechanism(s) by which these ligands and/or their complexes with metal ions exhibit their toxic effect is unknown. In order to resolve these issues, a study of the antimalarial activities of the free ligands, the ligands complexed with metal ions (Au 3+, Cu 2+, Fe 3+, Pd 2+ and Pt 2+), and the ligands with free metals in solution were measured. The ligands, complexes and metals were also tested for their ability to inhibit β-haematin formation, the mode of action ascribed to the most widely used antimalarial, chloroquine. The background toxicity levels of the various metal ions (previously unreported) were also measured and are reported here. None of the ligands were found to have particularly high activity (all approximately 1μM). In general the metals in were found to have no beneficial effect on activity whether complexed or freely available in solution. None of the ligands were found to inhibit β-haematin formation. The complexes however, with the exception of those of Cu 2+, all inhibited β-haematin formation. Upon further investigation it was found that the each of the metal ions with the exception of Cu 2+ had an innate ability to inhibit β-haematin formation. Thus the mode of action of the ligands and the complexes is likely to be via different mechanisms. In an attempt to enhance the activities of the ligands they were modified by covalently linking them to nutrients essential to the malaria parasite (adenosine and pantothenic acid). These six novel compounds however, showed no improvement in action.
dc.language.isoenen_US
dc.subjectAntimalarials.en_US
dc.subjectLigands (Biochemistry)en_US
dc.subjectTheses--Chemistry.en_US
dc.titleAn investigation into the antimalarial activity of metal chelatorsen_US
dc.typeThesisen_US


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