Thesis (MSc)--Stellenbosch University, 2013. / Aminoquinolines 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.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/79827 |
| Date | 03 1900 |
| Creators | Taleli, Lebusetsa |
| Contributors | Van Otterlo, William A. L., Blackie, Margaret, Pelly, Stephen, Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science. |
| Publisher | Stellenbosch : Stellenbosch University |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | English |
| Type | Thesis |
| Format | 240 p. : ill. |
| Rights | Stellenbosch University |
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