Exploring the potential of imines as antiprotozoan agents with focus on t. Brucei and p. Falciparum
- Authors: Oluwafemi, Kola Augustus
- Date: 2018
- Subjects: Protozoa , Parasites , Imines , Nuclear magnetic resonance , HeLa cells , Plasmodium falciparum , Trypanosoma brucei , Isomerism
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/62235 , vital:28145 , DOI 10.21504/10962/62235
- Description: This work focuses on the design, synthesis and evaluation of imine-containing heterocyclic and acyclic compounds with special focus on their bioactivity against parasitic protozoans (P. falciparum and T. brucei) - given the context of drug resistance in the treatment of malaria and Human African sleeping sickness and the fact that several bioactive organic compounds have been reported to possess the imino group. Starting from 2-aminopyridine, novel #-alkylated-5-bromo-7-azabenzimidazoles and substituted 5-bromo-1-(carbamoylmethy)-7-azabenzimidazole derivatives were prepared, and their bioactivity against parasitic protozoans was assessed. NMR spectra of the substituted 5- bromo-1-(carbamoylmethy)-7-azabenzimidazole derivatives exhibited rotational isomerism, and a dynamic NMR study was used in the estimation of the rate constants and the free- energies of activation for rotation. The free-energy differences between the two rotamers were determined and the more stable conformations were predicted. Novel 2-phenyl-7-azabenzimidazoles were also synthesised from 2-aminopyridine. A convenient method for the regioselective formylation of 2,3-diaminopyridines into 2-amino- 7-(benzylimino)pyridine analogues of 2-phenyl-7-azabenzimidazole was developed, and some of the resulting imino derivatives were hydrogenated to verify the importance of the imino moiety for bioactivity. The 2-phenyl-7-azabenzimidazoles and the 2-amino-7- (benzylimino)pyridine analogues were screened for their anti-protozoal activity and their cytotoxicity level was determined against the HeLa cell line. In order to validate the importance of the pyridine moiety, novel #-(phenyl)-2- hydroxybenzylimines, #-(benzyl)-2-hydroxybenzylimines and (±)-trans-1,2-bis[2- hydroxybenzylimino]cyclohexanes were also synthesized and screened for activity against the parasitic protozoans and for cytotoxicity against the HeLa cell line. The biological assay results indicated that these compounds are not significantly cytotoxic and a good number of them show potential as lead compounds for the development of new malaria and trypanosomiasis drugs. , Thesis (PhD) -- Faculty of Science, Chemistry, 2018
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Comparative study of clan CA cysteine proteases: an insight into the protozoan parasites
- Authors: Moyo, Sipho Dugunye
- Date: 2015
- Subjects: Cysteine proteinases , Proteolytic enzymes , Protozoan diseases , Parasites , Protozoan diseases -- Chemotherapy , Bioinformatics , Plasmodium , Antiprotozoal agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4165 , http://hdl.handle.net/10962/d1020309
- Description: Protozoan infections such as Malaria, Leishmaniasis, Toxoplasmosis, Chaga’s disease and African trypanosomiasis caused by the Plasmodium, Leishmania, Toxoplasma and Trypanosoma genuses respectively; inflict a huge economic, health and social impact in endemic regions particularly tropical and sub-tropical regions. The combined infections are estimated at over a billion annually and approximately 1.1 million deaths annually. The global burden of the protozoan infections is worsened by the increased drug resistance, toxicity and the relatively high cost of treatment and prophylaxis. Therefore there has been a high demand for new drugs and drug targets that play a role in parasite virulence. Cysteine proteases have been validated as viable drug targets due to their role in the infectivity stage of the parasites within the human host. There is a variety of cysteine proteases hence they are subdivided into families and in this study we focus on the clan CA, papain family C1 proteases. The current inhibitors for the protozoan cysteine proteases lack selectivity and specificity which contributes to drug toxicity. Therefore there is a need to identify the differences and similarities between the host, vector and protozoan proteases. This study uses a variety of bioinformatics tools to assess these differences and similarities. The Plasmodium cysteine protease FP-2 is the most characterized protease hence it was used as a reference to all the other proteases and its homologs were retrieved, aligned and the evolutionary relationships established. The homologs were also analysed for common motifs and the physicochemical properties determined which were validated using the Kruskal-Wallis test. These analyses revealed that the host and vector cathepsins share similar properties while the parasite cathepsins differ. At sub-site level sub-site 2 showed greater variations suggesting diverse ligand specificity within the proteases, a revelation that is vital in the design of antiprotozoan inhibitors.
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The parasite complex of the citrus psylla, trioza erytreae (Del Guercio) (Homoptera)
- Authors: McDaniel, J. R.
- Date: 1971
- Subjects: Psylla -- Regulation , Citrus , Biological control systems , Parasites
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5865 , http://hdl.handle.net/10962/d1012866
- Description: 1. Fifteen parasite species comprising the T. erytreae complex in Salisbury are listed. 2. Detailed, illustrated accounts are given of the biology of two primary parasites, Tetrastichus Pradiatus Waterston and Psyllaephagus pulvinatus (Waterston ), and their main hyperparasite, Aphidencyrtus cassatus Annecke. 3. The biology of the remaining twelve less important hyperparasites is briefly described and illustrated. 4. Keys are given to the adults, pupae and pupal remains of the parasites. 5 . The population fluctuations of T. erytreae and its parasites, as determined from field studies in the Salisbury area, are reported . 6. The interrelationships between T. erytreae and its parasites are summarised and discussed. Summary, p. 89.
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A study of the predators and parasites of Planococcus citri (Risso) (Homoptera) on vines in the Western Cape Province, South Africa
- Authors: Whitehead, Vincent Booth
- Date: 1959
- Subjects: Hemiptera , Parasites , Insect pests -- Biological control , Grapes -- Diseases and pests
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5896 , http://hdl.handle.net/10962/d1013425
- Description: [Introduction] In the Western Cape Province the mealybug, Planococcus citri (Risso), was first reported on vines in 1930 by Joubert (1943a). By 1935 this mealybug had spread to the Hex River Valley, and subsequently to all the main table grape producing areas of the Western Cape Province. At present Pl. citri is the most important insect pest of the table grape industry and can, if not effectively controlled, result in a loss of at least five per cent of the export table grape crop (Kriegler, 1954). Some preliminary work on the natural enemies of Pl. citri on vines was carried out by Stubbings in 1948, but no further work of this nature has been undertaken in this area since then. The fact that the natural enemies can be an effective check to this mealybug on vines in the Western Cape Province has been known for a number of years (Potgieter, 1937; Hattingh, 1943; Joubert, 1943a; Myburgh, 1951). The present work is an attempt to obtain some basic knowlege of the population fluctuations of the insects concerned in this biological control. Surveys undertaken have shown that there is a complex of primary, secondary and possibly tertiary Hynenopterous parasites associated with Pl. citri. The presence of hyperparasites reduces the efficiency of the primary parasitic Hymenoptera. The usefulness of these primary parasites is further reduced as they only occur in effective numbers for a short period of the year. On the other hand, although attacked by some parasites, the numerous coccinellids found preying on Pl. citri are of more importance in reducing the mealybug populations, as they are present on the vines in effective numbers for the greater part of the year.
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