Synthesis of triazole-linked chloroquinoline derivatives as novel antimalarial agents

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dc.contributor.advisorVan Otterlo, William A. L.en_ZA
dc.contributor.advisorBlackie, Margaret A. L.en_ZA
dc.contributor.advisorPelly, Stephenen_ZA
dc.contributor.authorTaleli, Lebusetsaen_ZA
dc.contributor.otherStellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.en_ZA
dc.date.accessioned2013-02-20T11:15:37Zen_ZA
dc.date.accessioned2013-03-15T07:20:46Z
dc.date.available2013-02-20T11:15:37Zen_ZA
dc.date.available2013-03-15T07:20:46Z
dc.date.issued2013-03en_ZA
dc.descriptionThesis (MSc)--Stellenbosch University, 2013.en_ZA
dc.description.abstractAminoquinolines are important class of drugs that have been used for malaria chemotherapy for centuries. However, long-term exposure to these drugs leads to extensive spread of drug resistance. As such, modified chloroquinoline derivatives are being studied as alternative antimalarial agents with the possibility to overcome drug resistance associated with chloroquine analogues. In this study, 15 aminoquinoline derivatives that are linked by a 1,4-disubstituted 1,2,3-triazole ring to an ethyl and propyl carbon spacer with a distal amine motif were designed and synthesized as novel antimalarial agents using the Cu(I)-promoted Huisgen reaction. The compounds have been synthesized from the 7-chloro-N-(prop-2-yn-1-yl)quinolin-4-amine alkyne precursor and the azides of ethyl and propyl amino moieties using a 1,3-dipolar cycloadditioncoupling in the presence of CuI catalyst to obtain moderate to good yields (53 – 85%). These compounds have been characterized by the combination of NMR, ESI+ HRMS and IR spectroscopic methods. The antiplasmodial activity of the compounds was investigated in vitro against P. falciparum strain NF54 using chloroquine as a reference drug together with a standard antimalarial drug artesunate. Of the 15 novel chloroquinoline derivatives, 11 have demonstrated to possess promising potency by way of the inhibition concentrations less than 250 nM with the lowest being 28 nM. The observed activities have been ascribed to the overall modifications such as the introduction of a triazole linker and changing of carbon chain length as these were the variables. The compounds are accordingly under further biological investigations and only the chloroquine sensitive results are reported in this work.en_ZA
dc.format.extent240 p. : ill.
dc.identifier.urihttp://hdl.handle.net/10019.1/79827en_ZA
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch Universityen_ZA
dc.rightsStellenbosch Universityen_ZA
dc.subjectAntimalarial agentsen_ZA
dc.subjectAminoquinoline derivativesen_ZA
dc.subjectMalaria -- Drug therapyen_ZA
dc.subjectDissertations -- Chemistryen_ZA
dc.subjectTheses -- Chemistryen_ZA
dc.subject.otherChemistry & Polymer Scienceen_ZA
dc.titleSynthesis of triazole-linked chloroquinoline derivatives as novel antimalarial agentsen_ZA
dc.typeThesisen_ZA
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