Synthesis and biological evaluation of antiparasitic Cysteine protease inhibitors based on the Isatin Scaffold

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dc.contributor.advisorChibale, Kellyen_ZA
dc.contributor.authorChiyanzu, Idanen_ZA
dc.date.accessioned2014-08-13T14:26:03Z
dc.date.available2014-08-13T14:26:03Z
dc.date.issued2004en_ZA
dc.descriptionIncludes bibliographical references.en_ZA
dc.description.abstractWidespread drug resistance, loss of efficacy and toxicity has limited the full utilization of the current available drugs against malaria and other parasitic diseases. This necessitates the development of new drugs. Meanwhile, the cysteine protease family of enzymes has been identified as potential targets for new modes of chemotherapy due to the numerous critical roles they play in the disease-causing agents. In this project, a non-peptidic and low molecular weight isatin (indole-2, 3-dione) possessing a wide range of pharmacological properties was used as a scaffold to which different moeities were appended. Potential inhibitors of parasitic cysteine proteases and three strains of P. falciparum were identified from synthesized libraries of compounds. Various N-substituted isatin derivatives were synthesized by KF/Ah03-mediated reaction of isatins with an alkyl, acyl or sulfonyl halide. A series of isatin-3-thiosemicarbazones were prepared by condensation of isatin I substituted isatins with thiosemicarbazide, and also a series of isatin-based Schiff and Mannich bases were prepared by reacting selected isatin-3-thiosemicarbazones with formaldehyde and appropriate secondary amines. To compare the effects of replacing the Mannich bases, a similar series of aminoquinolineethylene isatin-based derivatives were then synthesized. The synthesis was accomplished by condensation of quinoline-ethylene ketone forms with thiosemicarbazide. All synthesized compound were obtained in reasonable to excellent yields and characterized by spectroscopic and analytical techniques.en_ZA
dc.identifier.apacitationChiyanzu, I. (2004). <i>Synthesis and biological evaluation of antiparasitic Cysteine protease inhibitors based on the Isatin Scaffold</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/6300en_ZA
dc.identifier.chicagocitationChiyanzu, Idan. <i>"Synthesis and biological evaluation of antiparasitic Cysteine protease inhibitors based on the Isatin Scaffold."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Chemistry, 2004. http://hdl.handle.net/11427/6300en_ZA
dc.identifier.citationChiyanzu, I. 2004. Synthesis and biological evaluation of antiparasitic Cysteine protease inhibitors based on the Isatin Scaffold. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Chiyanzu, Idan AB - Widespread drug resistance, loss of efficacy and toxicity has limited the full utilization of the current available drugs against malaria and other parasitic diseases. This necessitates the development of new drugs. Meanwhile, the cysteine protease family of enzymes has been identified as potential targets for new modes of chemotherapy due to the numerous critical roles they play in the disease-causing agents. In this project, a non-peptidic and low molecular weight isatin (indole-2, 3-dione) possessing a wide range of pharmacological properties was used as a scaffold to which different moeities were appended. Potential inhibitors of parasitic cysteine proteases and three strains of P. falciparum were identified from synthesized libraries of compounds. Various N-substituted isatin derivatives were synthesized by KF/Ah03-mediated reaction of isatins with an alkyl, acyl or sulfonyl halide. A series of isatin-3-thiosemicarbazones were prepared by condensation of isatin I substituted isatins with thiosemicarbazide, and also a series of isatin-based Schiff and Mannich bases were prepared by reacting selected isatin-3-thiosemicarbazones with formaldehyde and appropriate secondary amines. To compare the effects of replacing the Mannich bases, a similar series of aminoquinolineethylene isatin-based derivatives were then synthesized. The synthesis was accomplished by condensation of quinoline-ethylene ketone forms with thiosemicarbazide. All synthesized compound were obtained in reasonable to excellent yields and characterized by spectroscopic and analytical techniques. DA - 2004 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2004 T1 - Synthesis and biological evaluation of antiparasitic Cysteine protease inhibitors based on the Isatin Scaffold TI - Synthesis and biological evaluation of antiparasitic Cysteine protease inhibitors based on the Isatin Scaffold UR - http://hdl.handle.net/11427/6300 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/6300
dc.identifier.vancouvercitationChiyanzu I. Synthesis and biological evaluation of antiparasitic Cysteine protease inhibitors based on the Isatin Scaffold. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Chemistry, 2004 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/6300en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDepartment of Chemistryen_ZA
dc.publisher.facultyFaculty of Scienceen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherChemistryen_ZA
dc.titleSynthesis and biological evaluation of antiparasitic Cysteine protease inhibitors based on the Isatin Scaffolden_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMScen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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