New aminoquinoline antimalarial cysteine protease inhibitors based on the isatin natural product scaffold

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dc.contributor.advisorChibale, Kellyen_ZA
dc.contributor.authorNtuli, Nelson Axeen_ZA
dc.date.accessioned2014-08-13T14:28:54Z
dc.date.available2014-08-13T14:28:54Z
dc.date.issued2005en_ZA
dc.descriptionIncludes bibliographical references (leaves 120-125).en_ZA
dc.description.abstractMany antimalarial drugs including chloroquine are no longer effective against the disease, as their efficacy has been decreased by the spread of drug resistant strains. This loss has been a major barrier to the effective treatment of malaria and has necessitated an urgent need to discover new antimalarial drugs. New 4-aminoquinoline isatin derivatives have been designed and synthesised. Isatin was used as a biologically validated starting point for the design of chemical libraries directed at the intended target due to its privileged nature. Included in the design of these isatin derivatives is the thiosemicarbazone moiety previously demonstrated to inhibit cysteine proteases from mUltiple protozoan parasites. Synthesized compounds were tested against the enzyme falcipain-2 (Rec-FP-2) as well as the parasite source of this protease, Plasmodium Jalciparum (P.f. W2). The results of structure activity relationship studies demonstrate the influence of substituents at position 5 of the isatin scaffold. With respect to the chain length, a two carbon methylene spacer between the aminoquinoline and isatin moieties, was found optimum. A 5-bromo isatin derivative with this spacer, compound 79b, was found to be the most active with an IC₅₀ value of 163.5 nM against the W2 parasite strain and second most active against the enzyme (lC₅₀ = 3.65 μM).en_ZA
dc.identifier.apacitationNtuli, N. A. (2005). <i>New aminoquinoline antimalarial cysteine protease inhibitors based on the isatin natural product scaffold</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/6352en_ZA
dc.identifier.chicagocitationNtuli, Nelson Axe. <i>"New aminoquinoline antimalarial cysteine protease inhibitors based on the isatin natural product scaffold."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Chemistry, 2005. http://hdl.handle.net/11427/6352en_ZA
dc.identifier.citationNtuli, N. 2005. New aminoquinoline antimalarial cysteine protease inhibitors based on the isatin natural product scaffold. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Ntuli, Nelson Axe AB - Many antimalarial drugs including chloroquine are no longer effective against the disease, as their efficacy has been decreased by the spread of drug resistant strains. This loss has been a major barrier to the effective treatment of malaria and has necessitated an urgent need to discover new antimalarial drugs. New 4-aminoquinoline isatin derivatives have been designed and synthesised. Isatin was used as a biologically validated starting point for the design of chemical libraries directed at the intended target due to its privileged nature. Included in the design of these isatin derivatives is the thiosemicarbazone moiety previously demonstrated to inhibit cysteine proteases from mUltiple protozoan parasites. Synthesized compounds were tested against the enzyme falcipain-2 (Rec-FP-2) as well as the parasite source of this protease, Plasmodium Jalciparum (P.f. W2). The results of structure activity relationship studies demonstrate the influence of substituents at position 5 of the isatin scaffold. With respect to the chain length, a two carbon methylene spacer between the aminoquinoline and isatin moieties, was found optimum. A 5-bromo isatin derivative with this spacer, compound 79b, was found to be the most active with an IC₅₀ value of 163.5 nM against the W2 parasite strain and second most active against the enzyme (lC₅₀ = 3.65 μM). DA - 2005 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2005 T1 - New aminoquinoline antimalarial cysteine protease inhibitors based on the isatin natural product scaffold TI - New aminoquinoline antimalarial cysteine protease inhibitors based on the isatin natural product scaffold UR - http://hdl.handle.net/11427/6352 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/6352
dc.identifier.vancouvercitationNtuli NA. New aminoquinoline antimalarial cysteine protease inhibitors based on the isatin natural product scaffold. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Chemistry, 2005 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/6352en_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.titleNew aminoquinoline antimalarial cysteine protease inhibitors based on the isatin natural product 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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