Supramolecular derivatisation of new anti-tubercular and antimalarial drug leads

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dc.contributor.advisorCaira, Mino Ren_ZA
dc.contributor.advisorChibale, Kellyen_ZA
dc.contributor.authorJoseph, Laurelle Margauxen_ZA
dc.date.accessioned2016-06-09T11:19:59Z
dc.date.available2016-06-09T11:19:59Z
dc.date.issued2015en_ZA
dc.description.abstractThe UCT Drug Discovery and Design Centre, H3D, provided anti-tubercular and antimalarial drug leads that display potent in vitro and in vivo activity, but with unfavourable physicochemical properties. The primary objective of this study was to prepare supramolecular derivatives of the drug leads in an attempt to improve their physicochemical properties. Any new solid forms were to be characterized by a variety of analytical techniques, including X-ray analysis, spectroscopic and thermal techniques. Where possible, such derivatives would be tested for any enhancement in the aqueous solubility or biological activity of the drug lead. The second objective of this study was to employ supramolecular intervention in the early stages of the drug discovery and development process to help streamline the process by distinguishing between compounds that might be amenable to beneficiation via supramolecular modification and those that might not. The crystal structure of a novel anti-tubercular drug lead, DL2, was solved and the compound was fully characterized using thermal and X-ray techniques. This compound displayed very poor solubility in both aqueous and organic media. Phase solubility studies were performed with anti-tubercular drug lead DL3 and selected cyclodextrins (CDs). The apparent solubility of DL3 increased by a factor of more than 300 at the highest concentration of hydroxypropyl-β-CD (HPβCD) and β-CD investigated. Three salts of antimalarial drug lead DL4 and carboxylic acids were prepared. The salts were characterized by X-ray and thermal techniques. A salt of citric acid and DL4 could be prepared by the liquid-assisted grinding method. The equilibrium solubility of this salt was 48 times greater than that of DL4.en_ZA
dc.identifier.apacitationJoseph, L. M. (2015). <i>Supramolecular derivatisation of new anti-tubercular and antimalarial drug leads</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/19974en_ZA
dc.identifier.chicagocitationJoseph, Laurelle Margaux. <i>"Supramolecular derivatisation of new anti-tubercular and antimalarial drug leads."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Chemistry, 2015. http://hdl.handle.net/11427/19974en_ZA
dc.identifier.citationJoseph, L. 2015. Supramolecular derivatisation of new anti-tubercular and antimalarial drug leads. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Joseph, Laurelle Margaux AB - The UCT Drug Discovery and Design Centre, H3D, provided anti-tubercular and antimalarial drug leads that display potent in vitro and in vivo activity, but with unfavourable physicochemical properties. The primary objective of this study was to prepare supramolecular derivatives of the drug leads in an attempt to improve their physicochemical properties. Any new solid forms were to be characterized by a variety of analytical techniques, including X-ray analysis, spectroscopic and thermal techniques. Where possible, such derivatives would be tested for any enhancement in the aqueous solubility or biological activity of the drug lead. The second objective of this study was to employ supramolecular intervention in the early stages of the drug discovery and development process to help streamline the process by distinguishing between compounds that might be amenable to beneficiation via supramolecular modification and those that might not. The crystal structure of a novel anti-tubercular drug lead, DL2, was solved and the compound was fully characterized using thermal and X-ray techniques. This compound displayed very poor solubility in both aqueous and organic media. Phase solubility studies were performed with anti-tubercular drug lead DL3 and selected cyclodextrins (CDs). The apparent solubility of DL3 increased by a factor of more than 300 at the highest concentration of hydroxypropyl-β-CD (HPβCD) and β-CD investigated. Three salts of antimalarial drug lead DL4 and carboxylic acids were prepared. The salts were characterized by X-ray and thermal techniques. A salt of citric acid and DL4 could be prepared by the liquid-assisted grinding method. The equilibrium solubility of this salt was 48 times greater than that of DL4. DA - 2015 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - Supramolecular derivatisation of new anti-tubercular and antimalarial drug leads TI - Supramolecular derivatisation of new anti-tubercular and antimalarial drug leads UR - http://hdl.handle.net/11427/19974 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/19974
dc.identifier.vancouvercitationJoseph LM. Supramolecular derivatisation of new anti-tubercular and antimalarial drug leads. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Chemistry, 2015 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/19974en_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.titleSupramolecular derivatisation of new anti-tubercular and antimalarial drug leadsen_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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