Synthesis of water soluble polymer-bound antiproliferative agents

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dc.contributor.author Johnson, Mark Trevor
dc.date.accessioned 2006-10-31T08:13:59Z
dc.date.available 2006-10-31T08:13:59Z
dc.date.issued 2006-10-31T08:13:59Z
dc.identifier.uri http://hdl.handle.net/10539/1511
dc.description Student Number : 9903022H MSc Dissertation School of Chemistry Faculty of Science en
dc.description.abstract Cancer is characterised by the unconstrained growth of cancerous cells, which damages the healthy cells and ultimately the tissue of the host. Chemotherapy forms an essential component in the treatment of this disease, however most anti-tumour drugs suffer from various deficiencies, e.g. increased toxicity, reduced serum half life and poor water solubility. The focus of this project was to address some of these deficiencies by conjugating selected drugs to a water-soluble polymeric carrier. Selected water-soluble biodegradable carriers were synthesized. Copolyaspartamides, polyamidoamines and polyamides were obtained by condensation polymerisation, Michéal–type addition polymerisation and ester amine base-catalysed polymerisation. The nascent water soluble polymers were used to conjugate platinum, ferrocene and tetramethylmelamine derivative, respectively. The percentage drug in each polymer drug conjugate was determined by considering the mass of the drug in the conjugate as a percentage of the total mass of the drug-polymer conjugate. Platinum was linked to the carrier via polymer attached amine, carboxyl and hydroxyl ligands. Platinum content of the conjugates ranged from 7 to 11 % by mass. The ferrocenylation agent, 4-ferrocenylbutanoic acid, and the tetramethylmelamine derivative, 3-(4,6-bis(N,N-dimethylamino)-1,3,5-triazacyclohexatrien-2-yl) propanoic acid was polymer-bound by amidation reactions. Iron content of the ferrocence conjugated ranged from 2 to 12 % by mass. While the drug content based on tetramethylmelamine in the 3-(4,6-bis[N,N-dimethylamino]-1,3,5-triazacyclohexatrien-2-yl) propanoic acid polymer conjugate ranged from 8.4 to 8.6 % by mass. There was a preliminary attempt to coconjugate both, 4-ferrocenylbutanoic acid and 3-(4,6-bis[N,N-dimethylamino]-1,3,5- triazacyclohexatrien-2-yl) propanoic acid to the same polymer. This co-conjugate contained 2.9 % iron and 3.4 % tetramethylmelamine by mass. en
dc.format.extent 727554 bytes
dc.format.mimetype application/pdf
dc.language.iso en en
dc.subject water soluble polymers en
dc.subject macromolecular carriers en
dc.subject drug conjugates en
dc.title Synthesis of water soluble polymer-bound antiproliferative agents en
dc.type Thesis en


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    Thesis (Ph.D.)--University of the Witwatersrand, 1972.

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