Antimalarial activity of quinoline thiosemicarbazones: synthesis and antiplasmodial evaluation
- Authors: Nqeno, Lukhanyiso Khanyisile
- Date: 2022-04-06
- Subjects: Antimalarials , Quinoline , Thiosemicarbazones , Malaria Chemotherapy , Plasmodium falciparum , Malaria Africa, Sub-Saharan , Iron chelates Therapeutic use
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/291292 , vital:56841
- Description: Africa is one of the regions that is most affected by malaria, as 90% of all malaria deaths occur in sub-saharan Africa. Malaria is a life threatening disease responsible for an estimated 800000 deaths each year, the majority of these deaths occurred in children under the age of five. The disease is a mosquito-borne, and it is transmitted to humans by the female Anopheles mosquito. The parasite responsible for this disease belong to the Plasmodium genus with Plasmodium falciparum causing the most severe cases of the disease in humans. The most widely available anti-malarials were designed to specifically target the pathogenic blood stage in humans, however, in order to completely eradicate malaria there is a need for the development of medicines that not only target the pathogenic blood stage of the parasite but also block parasite transmission and eliminate asymptomatic and cryptic hepatic forms of the parasite. Iron chelators have recently gained importance as potent antimalarials, to cause infection nearly all protozoa obtain growth essential iron from their hosts. Iron is required for the development of the parasite. Deprivation of utilizable iron by chelation is a proficient approach to arrest parasite growth and associated infection. Thiosemicarbazones are known iron chelating agents by bonding through the sulfur and azomethine nitrogen atoms. This study is aimed at the identification of thiosemicarbazone based derivatives as possible antimalarial agents. Due to their iron chelation abilities there has been increasing interest in the investigation of thiosemicarbazones as possible antimalarials. During the course of this project, several thiosemicarbazone derivatives were synthesized and their structure confirmed using routine analytical techniques (NMR, FTIR, and HRMS). The synthesized compounds were evaluated in vitro against the chloroquine sensitive strain (3D7) of P. falciparum for antimarial activity. The compounds were also evaluated agsinst Hela cells for overt cytotoxicity. The compounds generally showed poor antimalarial activity. One compound (LKN11) was identified to possess intrinsic and moderate antimalarial activity of 6.6 μM. The compounds were generally not cytotoxic against Hela cell at concentrations of up to 20 μM, with only compound LKN10 showing modest cytotoxic activity of 9.5 μM. This research went on to identify two thiosemicarbazone based derivatives which had a significant effect on HeLa and pLDH cells. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
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- Date Issued: 2022-04-06
The use of the cochineal insect, Dactylopius tomentosus Lamarck, as a biological control agent for the invasive alien thistle cholla, Cylindropuntia pallida (Rose) F.M. Knuth in South Africa
- Authors: Zozo, Ekhona
- Date: 2022-04-06
- Subjects: Cochineal insect , Thistles Biological control South Africa , Alien plants South Africa , Invasive plants South Africa , Cactus South Africa , Biological assay
- Language: English
- Type: Master's thesis , text
- Identifier: http://hdl.handle.net/10962/233823 , vital:50131
- Description: Cylindropuntia pallida (Rose) F.M. Knuth (Cactaceae) is an invasive alien plant in South Africa indigenous in the southern U.S.A. and Mexico. Large infestations of this species can be found in the Kalahari and arid Karoo regions of South Africa, which is also present in Namibia. Because it is a very spiny cactus, dense infestations have a negative impact on agriculture and natural ecosystems. This cactus has become naturalised to the extent that eradication is impossible and the negative impacts are steadily increasing due to its increasing distribution and density. The cochineal insect, Dactylopius tomentosus Lamarck (Dactylopiidae), is native in Mexico and parts of North America, such as Texas, Arizona, and New Mexico in the U.S.A. This cochineal species is highly specialized and associated only with Cylindropuntia species, a group of cacti that are primarily restricted to the same areas. It has been introduced into Australia and South Africa as a biological control agent to control various invasive alien Cylindropuntia species. This cochineal species has several biotypes specific to certain Cylindropuntia species hosts. A biotype is a clade that cannot be differentiated morphologically from others but has different host ranges and impacts depending on the host plant species. Included amongst biotypes that have been released in South Africa are D. tomentosus ‘imbricata’ and D. tomentosus ‘cholla’ for the biological control of Cylindropuntia imbricata (Haw.) F.M. Knuth (Cactaceae) and Cylindropuntia fulgida (Engelmann) F.M. Knuth var. mamillata (Schott ex Engelmann) Backeb. (Cactaceae), respectively. These biotypes have resulted in both host plants being under substantial control in South Africa. The first part of this thesis evaluated which of the two D. tomentosus biotypes already in use in South Africa could be an effective biological control agent for C. pallida. This was done by assessing the fitness of the cochineals on the three cactus species and assessing the impact that each of the cochineals has on each of the target weed species. Should these biotypes prove ineffective, there is a third biotype, namely D. tomentosus ‘californica var. parkerii’, which researchers in Australia have worked on and have found to be suitably host-specific for release in Australia and suitably damaging to C. pallida in that country. Therefore, this new biotype could be released in South Africa if it is required. Sexually compatible biological control agents, especially those closely related and occurring in close spatial proximity to one another, may interbreed and the impacts of this hybridisation are difficult to predict. It is important to understand the outcomes of the hybridisation of cochineal because it can affect the impact of the biological control agents and thus the control of the target weed. The second part of this thesis investigated the impacts of the hybridisation of the two cochineal biotypes by assessing the damage the agents would have on the target weed, and on C. imbricata and C. fulgida var. mamillata, in the presence of one or both cochineal biotypes. The ‘cholla’ biotype performed better on C. pallida than the ‘imbricata’ biotype, but neither biotype could control C. pallida to an extent similar to the control they provide for their respective target weeds, C. imbricata and C. fulgida var. mamillata. Both the ‘cholla’ biotype and hybrids of the two biotypes of cochineal were effective at killing C. pallida when both C. imbricata and C. fulgida var. mamillata were also present. This suggests that the ‘cholla’ or hybrids may be effective at controlling C. pallida when either C. imbricata or C. fulgida var. mamillata are also present in the field due to the high population density of cochineal that results under these circumstances. There are, however, many C. pallida infestations in South Africa where the plant is problematic and is isolated from other Cylindropuntia species, and these populations are unlikely to be controlled by the ‘cholla’ biotype or the hybrids. Neither of the cochineal biotypes that are used for biological control in South Africa are suitably damaging to C. pallida to warrant their use as biological control agents for this species. Dactylopius tomentosus ‘californica var. parkerii’ is therefore recommended for release based on its host-specificity and impact to C. pallida in Australia. , Thesis (PhD) -- Faculty of Science, Zoology and Entomology, 2022
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- Date Issued: 2022-04-06