A Structure-Activity Relationship Study of Dihydroajoenes as Anti-Cancer Agents

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dc.contributor.advisorHunter, Rogeren_ZA
dc.contributor.advisorKaschula, Catherine Harten_ZA
dc.contributor.authorBiwi, James Tapiwaen_ZA
dc.date.accessioned2015-05-18T14:24:49Z
dc.date.available2015-05-18T14:24:49Z
dc.date.issued2014en_ZA
dc.descriptionIncludes bibliographical references.en_ZA
dc.description.abstractAjoene (( E-/Z )-4,5,9-trithiadodeca-1,6,11-triene-9-oxide), a constituent of garlic is known to possess in vitro and in vivo anticancer activity based on the presence of a vinyl disulfide as its pharmacophore. This thesis reports on the synthesis of dihydroajoenes, a novel set of ajoene analogues, containing a saturated double bond, in which the intention was to study the influence of removing the double bond on biological activity and metabolic stability, since ajoenes are unstable in blood. A divergent synthetic route to 6 new dihydroajoene analogues has been developed in which a phenolic hydroxyl group at the disulfide end served as a platform for modulating aqueous solubility. The dihydroajoene analogues synthesized retained good in vitro anti-proliferation activity against a WHCO1 oesophageal cancer cell line, with the phenol derivative showing the greatest activity, with an IC 50 of 4.1 μM as about 7-times more active than the parent ajoene. In addition the dihydroajoenes were found to be significantly more stable in the red blood cell fraction of mouse blood, when compared with ajoene analogues retaining the double bond. This opens up the possibility of exploring them as anti-cancer agents in an in vivo setting. This thesis also describes a preliminary study towards the synthesis of an ajoene-drug (fludarabine) conjugate for chemosensitization studies, in which an advanced synthetic intermediate was secured.en_ZA
dc.identifier.apacitationBiwi, J. T. (2014). <i>A Structure-Activity Relationship Study of Dihydroajoenes as Anti-Cancer Agents</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/12826en_ZA
dc.identifier.chicagocitationBiwi, James Tapiwa. <i>"A Structure-Activity Relationship Study of Dihydroajoenes as Anti-Cancer Agents."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Chemistry, 2014. http://hdl.handle.net/11427/12826en_ZA
dc.identifier.citationBiwi, J. 2014. A Structure-Activity Relationship Study of Dihydroajoenes as Anti-Cancer Agents. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Biwi, James Tapiwa AB - Ajoene (( E-/Z )-4,5,9-trithiadodeca-1,6,11-triene-9-oxide), a constituent of garlic is known to possess in vitro and in vivo anticancer activity based on the presence of a vinyl disulfide as its pharmacophore. This thesis reports on the synthesis of dihydroajoenes, a novel set of ajoene analogues, containing a saturated double bond, in which the intention was to study the influence of removing the double bond on biological activity and metabolic stability, since ajoenes are unstable in blood. A divergent synthetic route to 6 new dihydroajoene analogues has been developed in which a phenolic hydroxyl group at the disulfide end served as a platform for modulating aqueous solubility. The dihydroajoene analogues synthesized retained good in vitro anti-proliferation activity against a WHCO1 oesophageal cancer cell line, with the phenol derivative showing the greatest activity, with an IC 50 of 4.1 &#956;M as about 7-times more active than the parent ajoene. In addition the dihydroajoenes were found to be significantly more stable in the red blood cell fraction of mouse blood, when compared with ajoene analogues retaining the double bond. This opens up the possibility of exploring them as anti-cancer agents in an in vivo setting. This thesis also describes a preliminary study towards the synthesis of an ajoene-drug (fludarabine) conjugate for chemosensitization studies, in which an advanced synthetic intermediate was secured. DA - 2014 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - A Structure-Activity Relationship Study of Dihydroajoenes as Anti-Cancer Agents TI - A Structure-Activity Relationship Study of Dihydroajoenes as Anti-Cancer Agents UR - http://hdl.handle.net/11427/12826 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/12826
dc.identifier.vancouvercitationBiwi JT. A Structure-Activity Relationship Study of Dihydroajoenes as Anti-Cancer Agents. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Chemistry, 2014 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/12826en_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.titleA Structure-Activity Relationship Study of Dihydroajoenes as Anti-Cancer Agentsen_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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