Synthesis, characterisation and evaluation of benzoxaborole-based hybrids as antiplasmodial agents
- Authors: Gumbo, Maureen
- Date: 2017
- Subjects: Malaria Chemotherapy , Antimalarials , Boron compounds , Drug resistance , Plasmodium falciparum , Drug development
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/59193 , vital:27456
- Description: Malaria is a mosquito-borne disease, which continues to pose a threat to the entire humanity. About 40% of the world population is estimated to be at risk of infections by malaria. Despite efforts undertaken by scientific community, government entities and international organizations, malaria is still rampant. The major problem is drug resistance, where the Plasmodium spp have over the past decades developed drug resistance against available drugs. In order to counter this problem, novel antimalarial drugs that are efficacious and with novel mode of action are of great necessity. Benzoxaborole derivatives have been shown to exhibit promising antimalarial activity against Plasmodium falciparum strains. Previous studies reported on the compounds such as 6-(2- (alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles, which showed good antimalarial activity against both W7 and 3D7 strains without significant toxicity. On the other hand, chloroquine (CQ) and cinnamic acids have a wide variety of biological activity including antimalarial activity. Herein, a hybridisation strategy was employed to synthesise new CQ-benzoxaborole and cinnamoyl-benzoxaborole hybrids. CQ-Benzoxaborole 2.12a-c and cinnamoylbenzoxaborole 2.11a-g hydrid molecules were synthesised in low to good yields. Their structural identities were confirmed using conventional spectroscopic techniques (1H and 13C NMR, and mass spectrometry). CQ-benzoxaborole compounds, however, showed instability, and only 2.12b was used for in vitro biological assay and showed activity comparable to CQ. Furthermore, in vitro biological assay revealed that compounds 2.11a-g poorly inhibited the growth of P. falciparum parasites. Interestingly, these compounds, however, exhibited satisfactory activity against Trypanosoma brucei with IC50 = 0.052 μM for compound 2.11g. The cell cytotoxicity assay of all final compounds confirmed that all CQ-benzoxaborole 2.12b and cinnamoyl-benzoxaborole 2.11a-g hybrids were non-toxic against HeLa cell lines. However, efforts to further expand the structure-activity relationship (SAR) of CQbenzoxaborole by increasing the length of the linker with one extra carbon (Scheme 2.10) were not possible as an important precursor 6-formylbenzoxaborole 2.29 could not be synthesized in sufficient yields. , Thesis (MSc) -- Faculty of Faculty of Science, Chemistry, 2017
- Full Text:
- Authors: Gumbo, Maureen
- Date: 2017
- Subjects: Malaria Chemotherapy , Antimalarials , Boron compounds , Drug resistance , Plasmodium falciparum , Drug development
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/59193 , vital:27456
- Description: Malaria is a mosquito-borne disease, which continues to pose a threat to the entire humanity. About 40% of the world population is estimated to be at risk of infections by malaria. Despite efforts undertaken by scientific community, government entities and international organizations, malaria is still rampant. The major problem is drug resistance, where the Plasmodium spp have over the past decades developed drug resistance against available drugs. In order to counter this problem, novel antimalarial drugs that are efficacious and with novel mode of action are of great necessity. Benzoxaborole derivatives have been shown to exhibit promising antimalarial activity against Plasmodium falciparum strains. Previous studies reported on the compounds such as 6-(2- (alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles, which showed good antimalarial activity against both W7 and 3D7 strains without significant toxicity. On the other hand, chloroquine (CQ) and cinnamic acids have a wide variety of biological activity including antimalarial activity. Herein, a hybridisation strategy was employed to synthesise new CQ-benzoxaborole and cinnamoyl-benzoxaborole hybrids. CQ-Benzoxaborole 2.12a-c and cinnamoylbenzoxaborole 2.11a-g hydrid molecules were synthesised in low to good yields. Their structural identities were confirmed using conventional spectroscopic techniques (1H and 13C NMR, and mass spectrometry). CQ-benzoxaborole compounds, however, showed instability, and only 2.12b was used for in vitro biological assay and showed activity comparable to CQ. Furthermore, in vitro biological assay revealed that compounds 2.11a-g poorly inhibited the growth of P. falciparum parasites. Interestingly, these compounds, however, exhibited satisfactory activity against Trypanosoma brucei with IC50 = 0.052 μM for compound 2.11g. The cell cytotoxicity assay of all final compounds confirmed that all CQ-benzoxaborole 2.12b and cinnamoyl-benzoxaborole 2.11a-g hybrids were non-toxic against HeLa cell lines. However, efforts to further expand the structure-activity relationship (SAR) of CQbenzoxaborole by increasing the length of the linker with one extra carbon (Scheme 2.10) were not possible as an important precursor 6-formylbenzoxaborole 2.29 could not be synthesized in sufficient yields. , Thesis (MSc) -- Faculty of Faculty of Science, Chemistry, 2017
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An unsung dialogue: music, society and the history of The Flames
- Authors: Park, Duncan Keith
- Date: 2016
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/193645 , vital:45376
- Description: This research aims to examine the relationship between music and social conditions within the context of apartheid. The focus area is the city of Durban, specifically 1960-1970. A case study of the multi-racial Durban-based band, The Flames (1963 – 1972) will be used to rigorously assess the extent to which social conditions and music can affect each other in both directions. This will also be the first coherent and historical narrative of the band, The Flames. As such, the thesis aims to make an original contribution to this field of music history, while it will provide the very first academic discussion of The Flames. , Thesis (MA) -- Faculty of Humanities, History, 2016
- Full Text:
- Authors: Park, Duncan Keith
- Date: 2016
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/193645 , vital:45376
- Description: This research aims to examine the relationship between music and social conditions within the context of apartheid. The focus area is the city of Durban, specifically 1960-1970. A case study of the multi-racial Durban-based band, The Flames (1963 – 1972) will be used to rigorously assess the extent to which social conditions and music can affect each other in both directions. This will also be the first coherent and historical narrative of the band, The Flames. As such, the thesis aims to make an original contribution to this field of music history, while it will provide the very first academic discussion of The Flames. , Thesis (MA) -- Faculty of Humanities, History, 2016
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Islamic compliant short term insurance: an exploratory study to develop an Islamic compliant insurance model within a South African context
- Authors: Jeeva, Shakir
- Date: 2016
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/193633 , vital:45375
- Description: In a world where there is ever increasing risks to be mitigated, either by choice or due to the law of the country, an insurance instrument is the most popular risk mitigation tool. However, from an Islamic perspective, Muslims have certain parameters to adhere to due to the laws and boundaries as set out in the Quraan, as well as the teachings of the final prophet, Prophet Muhammed (Peace Be Upon Him). This has relevance in this context as, according to Islam, the conventional insurance models are in contravention of certain Islamic laws as they contain elements which are not acceptable in the Muslim faith. Therefore, the Islamic insurance models, or Takaful models, have removed the impermissible elements of usury, speculation, and uncertainty, which are all contained in the current conventional insurance models. By removing these impermissible elements from the insurance model, the Takaful model is acceptable for Muslims to use as a risk mitigation tool. The primary aim of the study sought to propose a short term Islamic compliant insurance model within a South African framework. The secondary aims were to ascertain the Islamic requirements for an Islamic insurance model, how these requirements fit into an insurance model, to then compare and contrast the differences between conventional insurance and Islamic insurance and, lastly, to explore awareness and attitudes towards Islamic insurance. Therefore, from the above, a proposed short term Islamic insurance model was developed within a South African context which conforms to the laws and boundaries of Islam, making this insurance model permissible to use as a Takaful tool. Additionally, semi structured interviews were conducted with certain research participants, using purposive sampling, to examine the attitudes and knowledge of the Muslim community towards the Takaful model within a South African context. It was concluded that while the majority of the research participants understand the Takaful model and the significance of this, they have chosen to use the conventional insurance offerings due to the fact that they were unaware of other Takaful alternatives, or due to the fact that the Takaful alternative was out-priced when compared to the conventional insurance offerings. It was therefore concluded that while there is a need for Takaful offerings within South Africa, this must be done in conjunction with additional marketing, education and competitive pricing for potential clients to consider this as an insurance option. , Thesis (MCom) -- Faculty of Commerce, Accounting, 2016
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- Authors: Jeeva, Shakir
- Date: 2016
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/193633 , vital:45375
- Description: In a world where there is ever increasing risks to be mitigated, either by choice or due to the law of the country, an insurance instrument is the most popular risk mitigation tool. However, from an Islamic perspective, Muslims have certain parameters to adhere to due to the laws and boundaries as set out in the Quraan, as well as the teachings of the final prophet, Prophet Muhammed (Peace Be Upon Him). This has relevance in this context as, according to Islam, the conventional insurance models are in contravention of certain Islamic laws as they contain elements which are not acceptable in the Muslim faith. Therefore, the Islamic insurance models, or Takaful models, have removed the impermissible elements of usury, speculation, and uncertainty, which are all contained in the current conventional insurance models. By removing these impermissible elements from the insurance model, the Takaful model is acceptable for Muslims to use as a risk mitigation tool. The primary aim of the study sought to propose a short term Islamic compliant insurance model within a South African framework. The secondary aims were to ascertain the Islamic requirements for an Islamic insurance model, how these requirements fit into an insurance model, to then compare and contrast the differences between conventional insurance and Islamic insurance and, lastly, to explore awareness and attitudes towards Islamic insurance. Therefore, from the above, a proposed short term Islamic insurance model was developed within a South African context which conforms to the laws and boundaries of Islam, making this insurance model permissible to use as a Takaful tool. Additionally, semi structured interviews were conducted with certain research participants, using purposive sampling, to examine the attitudes and knowledge of the Muslim community towards the Takaful model within a South African context. It was concluded that while the majority of the research participants understand the Takaful model and the significance of this, they have chosen to use the conventional insurance offerings due to the fact that they were unaware of other Takaful alternatives, or due to the fact that the Takaful alternative was out-priced when compared to the conventional insurance offerings. It was therefore concluded that while there is a need for Takaful offerings within South Africa, this must be done in conjunction with additional marketing, education and competitive pricing for potential clients to consider this as an insurance option. , Thesis (MCom) -- Faculty of Commerce, Accounting, 2016
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