Ferrocenic metal chelators : synthesis, biological and electrochemical studies

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dc.contributor.advisorChibale, Kellyen_ZA
dc.contributor.advisorHutton, Allan Ten_ZA
dc.contributor.authorMuganza, Freddy Munyololoen_ZA
dc.date.accessioned2014-08-13T14:27:30Z
dc.date.available2014-08-13T14:27:30Z
dc.date.issued2006en_ZA
dc.descriptionIncludes bibliographical references.en_ZA
dc.description.abstractResistance of Plasmodium falciparum (P. falciparum) to well-established drugs throughout the world has necessitated urgent alternative treatment for malaria. Iron chelation therapy was considered as a possible approach since iron has been found crucial in the metabolic pathways of P. falciparum. A series of novel iron chelators were designed and synthesized based on thiosemicarbazone and/or ferrocenyl moieties. The novel compounds were characterized by NMR, infrared (IR) and mass spectroscopy as well as microanalysis and subjected to biological evaluation. All the N-substituted ferrocenic thiosemicarbazones were evaluated against a chloroquine resistant W2 strain of the malaria parasite P. falciparum and enzymes (falcipains 2 & 3) derived from the same parasite. The intermediate thiosemicarbazone thioesters were also tested against different malaria parasite including chloroquine resistant (K1) and chloroquine sensitive (307) strains as well as against the causative agent of African trypanosomiasis, Trypanosoma brucei (T. brucei). Of the intermediate thiosemicarbazone thioesters, compound 44y a bipyridyl compound was the most active against both K1 and 307 strains with ED50 values of 0.18 /lg/ml (0.625 /lM) and 0.021 /lg/ml (0.072 /lM), respectively. However, this compound 44y also showed similar toxicity to mammalian cells. A number of thiosemicarbazone thioesters displaying preferential potency against a chloroquine resistant (K1) strain were noted. For example, compounds 44a-h, 44k-m, 445, 44u-v were found to be more active against K1 than against the chloroquine sensitive (307) strain.en_ZA
dc.identifier.apacitationMuganza, F. M. (2006). <i>Ferrocenic metal chelators : synthesis, biological and electrochemical studies</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/6345en_ZA
dc.identifier.chicagocitationMuganza, Freddy Munyololo. <i>"Ferrocenic metal chelators : synthesis, biological and electrochemical studies."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Chemistry, 2006. http://hdl.handle.net/11427/6345en_ZA
dc.identifier.citationMuganza, F. 2006. Ferrocenic metal chelators : synthesis, biological and electrochemical studies. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Muganza, Freddy Munyololo AB - Resistance of Plasmodium falciparum (P. falciparum) to well-established drugs throughout the world has necessitated urgent alternative treatment for malaria. Iron chelation therapy was considered as a possible approach since iron has been found crucial in the metabolic pathways of P. falciparum. A series of novel iron chelators were designed and synthesized based on thiosemicarbazone and/or ferrocenyl moieties. The novel compounds were characterized by NMR, infrared (IR) and mass spectroscopy as well as microanalysis and subjected to biological evaluation. All the N-substituted ferrocenic thiosemicarbazones were evaluated against a chloroquine resistant W2 strain of the malaria parasite P. falciparum and enzymes (falcipains 2 & 3) derived from the same parasite. The intermediate thiosemicarbazone thioesters were also tested against different malaria parasite including chloroquine resistant (K1) and chloroquine sensitive (307) strains as well as against the causative agent of African trypanosomiasis, Trypanosoma brucei (T. brucei). Of the intermediate thiosemicarbazone thioesters, compound 44y a bipyridyl compound was the most active against both K1 and 307 strains with ED50 values of 0.18 /lg/ml (0.625 /lM) and 0.021 /lg/ml (0.072 /lM), respectively. However, this compound 44y also showed similar toxicity to mammalian cells. A number of thiosemicarbazone thioesters displaying preferential potency against a chloroquine resistant (K1) strain were noted. For example, compounds 44a-h, 44k-m, 445, 44u-v were found to be more active against K1 than against the chloroquine sensitive (307) strain. DA - 2006 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2006 T1 - Ferrocenic metal chelators : synthesis, biological and electrochemical studies TI - Ferrocenic metal chelators : synthesis, biological and electrochemical studies UR - http://hdl.handle.net/11427/6345 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/6345
dc.identifier.vancouvercitationMuganza FM. Ferrocenic metal chelators : synthesis, biological and electrochemical studies. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Chemistry, 2006 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/6345en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDepartment of Chemistryen_ZA
dc.publisher.facultyFaculty of Scienceen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherChemistryen_ZA
dc.titleFerrocenic metal chelators : synthesis, biological and electrochemical studiesen_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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