dc.contributor.advisor |
Egan, Timothy J |
en_ZA |
dc.contributor.advisor |
Hunter, Roger |
en_ZA |
dc.contributor.author |
Wicht, Kathryn Jean
|
en_ZA |
dc.date.accessioned |
2016-02-09T12:20:12Z |
|
dc.date.available |
2016-02-09T12:20:12Z |
|
dc.date.issued |
2015 |
en_ZA |
dc.identifier.citation |
Wicht, K. 2015. Discovery of benzamides and triarylimidazoles active against Plasmodium falciparum via haemozoin inhibition : high throughput screening, synthesis and structure-activity relationships. University of Cape Town. |
en_ZA |
dc.identifier.uri |
http://hdl.handle.net/11427/16939
|
|
dc.description |
Includes bibliographical references |
en_ZA |
dc.description.abstract |
New antimalarials are desperately needed to overcome growing P. falciparum resistance to the current drugs. Successful quinoline-based drugs target haemozoin formation causing a cytotoxic accumulation of free haem (Fe(III)PPIX) in the parasite, a target which remains promising for future treatments. Much research has been undertaken on the quinoline antimalarials, which has led to several hypotheses of haemozoin inhibition and drug accumulation mechanisms, however, relatively few studies have been carried out for haemozoin antimalarials with alternate chemotypes. High throughput screening (HTS) can be used to identify novel scaffolds that inhibit β-haematin (βH - synthetic haemozoin) formation and which have favourable P. falciparum activities. In this project, HTS has been carried out on 43,520 small, organic, drug-like compounds as part of a larger screen of 144,330 Vanderbilt University Institute of Chemical Biology (VU) chemical library compounds and 530 were found to be good inhibitors of βH relative to the chloroquine (CQ) and amodiaquine (AQ) controls. A further 171 compounds were found to inhibit parasite growth, showing improved hit rates from previous HTS efforts. Two scaffolds (A=benzamides and B=triarylimidazoles) were selected for further analysis, whereupon analogues were synthesised. |
en_ZA |
dc.language.iso |
eng |
en_ZA |
dc.subject.other |
Chemistry |
en_ZA |
dc.title |
Discovery of benzamides and triarylimidazoles active against Plasmodium falciparum via haemozoin inhibition : high throughput screening, synthesis and structure-activity relationships |
en_ZA |
dc.type |
Doctoral Thesis |
|
uct.type.publication |
Research |
en_ZA |
uct.type.resource |
Thesis
|
en_ZA |
dc.publisher.institution |
University of Cape Town |
|
dc.publisher.faculty |
Faculty of Science |
en_ZA |
dc.publisher.department |
Department of Chemistry |
en_ZA |
dc.type.qualificationlevel |
Doctoral |
|
dc.type.qualificationname |
PhD |
en_ZA |
uct.type.filetype |
Text |
|
uct.type.filetype |
Image |
|
dc.identifier.apacitation |
Wicht, K. J. (2015). <i>Discovery of benzamides and triarylimidazoles active against Plasmodium falciparum via haemozoin inhibition : high throughput screening, synthesis and structure-activity relationships</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/16939 |
en_ZA |
dc.identifier.chicagocitation |
Wicht, Kathryn Jean. <i>"Discovery of benzamides and triarylimidazoles active against Plasmodium falciparum via haemozoin inhibition : high throughput screening, synthesis and structure-activity relationships."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Chemistry, 2015. http://hdl.handle.net/11427/16939 |
en_ZA |
dc.identifier.vancouvercitation |
Wicht KJ. Discovery of benzamides and triarylimidazoles active against Plasmodium falciparum via haemozoin inhibition : high throughput screening, synthesis and structure-activity relationships. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Chemistry, 2015 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/16939 |
en_ZA |
dc.identifier.ris |
TY - Thesis / Dissertation
AU - Wicht, Kathryn Jean
AB - New antimalarials are desperately needed to overcome growing P. falciparum resistance to the current drugs. Successful quinoline-based drugs target haemozoin formation causing a cytotoxic accumulation of free haem (Fe(III)PPIX) in the parasite, a target which remains promising for future treatments. Much research has been undertaken on the quinoline antimalarials, which has led to several hypotheses of haemozoin inhibition and drug accumulation mechanisms, however, relatively few studies have been carried out for haemozoin antimalarials with alternate chemotypes. High throughput screening (HTS) can be used to identify novel scaffolds that inhibit β-haematin (βH - synthetic haemozoin) formation and which have favourable P. falciparum activities. In this project, HTS has been carried out on 43,520 small, organic, drug-like compounds as part of a larger screen of 144,330 Vanderbilt University Institute of Chemical Biology (VU) chemical library compounds and 530 were found to be good inhibitors of βH relative to the chloroquine (CQ) and amodiaquine (AQ) controls. A further 171 compounds were found to inhibit parasite growth, showing improved hit rates from previous HTS efforts. Two scaffolds (A=benzamides and B=triarylimidazoles) were selected for further analysis, whereupon analogues were synthesised.
DA - 2015
DB - OpenUCT
DP - University of Cape Town
LK - https://open.uct.ac.za
PB - University of Cape Town
PY - 2015
T1 - Discovery of benzamides and triarylimidazoles active against Plasmodium falciparum via haemozoin inhibition : high throughput screening, synthesis and structure-activity relationships
TI - Discovery of benzamides and triarylimidazoles active against Plasmodium falciparum via haemozoin inhibition : high throughput screening, synthesis and structure-activity relationships
UR - http://hdl.handle.net/11427/16939
ER -
|
en_ZA |