New mono and bimetallic chloroquine derivatives : synthesis and evaluation as antiparasitic agents

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dc.contributor.advisorMoss, John Ren_ZA
dc.contributor.advisorChibale, Kellyen_ZA
dc.contributor.authorBlackie, Margaret Anne Lilliasen_ZA
dc.date.accessioned2014-09-08T09:57:49Z
dc.date.available2014-09-08T09:57:49Z
dc.date.issued2002en_ZA
dc.descriptionIncludes bibliographical references.en_ZA
dc.description.abstractSeveral series of new ferrocenyl-quinoline antimalarial agents have been synthesised and fully characterised using standard spectroscopic and analytical techniques. The molecular structure of N-(7-Chloro-quinolin-4-yl)-N'-[2 -( N”,N""-dimethylaminomethyl)ferrocenylmethyl]-ethane-1.2-diamine has been determined by x-ray crystallography. N-(7-Chloro-quinolin-4-yl)-N'-[2-( N”, N""-dimethylaminomethyl)ferrocenylmethyl]-alkyl-1 ,n-diamine compounds were made where n = 2-6. These compounds contain a reactive secondary amine centre through which derivatisation to form aryl urea and aryl sulfonamide compounds was achieved. Complexes of the types: triphenylphosphine(L)gold(l) nitrate, pentafluorophenyl(L)gold(l) and chloro(cyclooctadiene)(L)rhodium(l) have been synthesised (where L = chloroquine, ferroquine, N-(7-chloro-quinolin-4-yl)-N'-[2-( N”, N""-dimethylaminomethyl)ferrocenyl methyl]-ethane-1 ,2-diamine, 3-benzyl-1-[2-(7-chloro-quinolin-4-ylamino)-ethyl]-1-[2-(N"",N""-dimethylaminomethyl)-ferrocenylmethyl]urea). All compounds have been evaluated against chloroquine sensitive and chloroquine resistant strains of Plasmodium falciparum. In most cases good activity was found in both strains of the parasite. N-(7-Chloro-quinol in-4-yl)-N'-[2 -( N”, N""-dimethylaminomethyl)ferrocenyl methyl]-alkyl-1, n-diamine compounds have been made where n = 2-6. It was found that in vitro efficacy against P. falciparum diminished with increasing spacer length. The introduction of the aryl urea moiety served to influence efficacy towards P. falciparum and toxicity towards mammalian cells. In some cases the toxicity was significantly reduced accompanied by an improvement in efficacy. The coordination complexes where L = chloroquine showed improved efficacy in the chloroquine resistant K1 strain of P. falciparum. In the heterobimetallic complexes, the ligand L showed equivalent or better in vitro efficacy than the coordination complexes of L against both chloroquine sensitive D10 and chloroquine resistant K1 strains of P. falciparum. Preliminary structure-activity studies were carried out on some of the prepared compounds. Phenylene analogues of some of the ferrocenyl compounds have been synthesized and it was found that the analogues show similar in vitro efficacy to each other in both chloroquine sensitive 3D7 and chloroquine resistant K1 strains of P. falciparum. The presence of a ferrocenyl moiety in the side chain of chloroquine analogues appears to have a synergistic or additive effect on in vitro efficacy.en_ZA
dc.identifier.apacitationBlackie, M. A. L. (2002). <i>New mono and bimetallic chloroquine derivatives : synthesis and evaluation as antiparasitic agents</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/6975en_ZA
dc.identifier.chicagocitationBlackie, Margaret Anne Lillias. <i>"New mono and bimetallic chloroquine derivatives : synthesis and evaluation as antiparasitic agents."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Chemistry, 2002. http://hdl.handle.net/11427/6975en_ZA
dc.identifier.citationBlackie, M. 2002. New mono and bimetallic chloroquine derivatives : synthesis and evaluation as antiparasitic agents. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Blackie, Margaret Anne Lillias AB - Several series of new ferrocenyl-quinoline antimalarial agents have been synthesised and fully characterised using standard spectroscopic and analytical techniques. The molecular structure of N-(7-Chloro-quinolin-4-yl)-N'-[2 -( N”,N""-dimethylaminomethyl)ferrocenylmethyl]-ethane-1.2-diamine has been determined by x-ray crystallography. N-(7-Chloro-quinolin-4-yl)-N'-[2-( N”, N""-dimethylaminomethyl)ferrocenylmethyl]-alkyl-1 ,n-diamine compounds were made where n = 2-6. These compounds contain a reactive secondary amine centre through which derivatisation to form aryl urea and aryl sulfonamide compounds was achieved. Complexes of the types: triphenylphosphine(L)gold(l) nitrate, pentafluorophenyl(L)gold(l) and chloro(cyclooctadiene)(L)rhodium(l) have been synthesised (where L = chloroquine, ferroquine, N-(7-chloro-quinolin-4-yl)-N'-[2-( N”, N""-dimethylaminomethyl)ferrocenyl methyl]-ethane-1 ,2-diamine, 3-benzyl-1-[2-(7-chloro-quinolin-4-ylamino)-ethyl]-1-[2-(N"",N""-dimethylaminomethyl)-ferrocenylmethyl]urea). All compounds have been evaluated against chloroquine sensitive and chloroquine resistant strains of Plasmodium falciparum. In most cases good activity was found in both strains of the parasite. N-(7-Chloro-quinol in-4-yl)-N'-[2 -( N”, N""-dimethylaminomethyl)ferrocenyl methyl]-alkyl-1, n-diamine compounds have been made where n = 2-6. It was found that in vitro efficacy against P. falciparum diminished with increasing spacer length. The introduction of the aryl urea moiety served to influence efficacy towards P. falciparum and toxicity towards mammalian cells. In some cases the toxicity was significantly reduced accompanied by an improvement in efficacy. The coordination complexes where L = chloroquine showed improved efficacy in the chloroquine resistant K1 strain of P. falciparum. In the heterobimetallic complexes, the ligand L showed equivalent or better in vitro efficacy than the coordination complexes of L against both chloroquine sensitive D10 and chloroquine resistant K1 strains of P. falciparum. Preliminary structure-activity studies were carried out on some of the prepared compounds. Phenylene analogues of some of the ferrocenyl compounds have been synthesized and it was found that the analogues show similar in vitro efficacy to each other in both chloroquine sensitive 3D7 and chloroquine resistant K1 strains of P. falciparum. The presence of a ferrocenyl moiety in the side chain of chloroquine analogues appears to have a synergistic or additive effect on in vitro efficacy. DA - 2002 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2002 T1 - New mono and bimetallic chloroquine derivatives : synthesis and evaluation as antiparasitic agents TI - New mono and bimetallic chloroquine derivatives : synthesis and evaluation as antiparasitic agents UR - http://hdl.handle.net/11427/6975 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/6975
dc.identifier.vancouvercitationBlackie MAL. New mono and bimetallic chloroquine derivatives : synthesis and evaluation as antiparasitic agents. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Chemistry, 2002 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/6975en_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.titleNew mono and bimetallic chloroquine derivatives : synthesis and evaluation as antiparasitic agentsen_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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