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Title: Towards metal based anti-cancer agents : synthesis, structure, and biological studies
Author: Miller-Shakesby, David M.
ISNI:       0000 0004 6420 8951
Awarding Body: University of Hull
Current Institution: University of Hull
Date of Award: 2016
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The most successful metal currently utilized in anti-cancer therapeutics is platinum. Despite its success though, cisplatin and other platinum derivatives have major limitations including high rates of drug resistance, a variety of side effects and a propensity to only work against cancers that have other, cheaper, treatments. For these reasons a considerable interest has emerged in developing other metal based anti-cancer therapeutics. In this work calixarenes are utilized for their metal co-ordination ability and low inherent toxicity to synthesise a number of metal complexes that are then put forward for initial anti-cancer activity. The first set of complexes are based on lanthanide ions (Eu, Gd, Tb) and p-sulfonatocalix[4]arene. Each complex consists of lanthanide ions bridging multiple calixarene molecules forming coordination polymers. The biological studies reveal low toxicity, suggesting that these complexes are suitable for optical imaging techniques rather than therapeutic use. The second set of complexes are based on simple endo rim functionalised calix[4]arenes forming complexes with titanium. There are similar systems in the literature however they have only been exploited for the catalytic potential in α-olefin polymerisation or ring opening polymerisation of cyclic esters. Initial studies of a calix[8]arene titanium complex is also presented. Biological studies reveal low toxicity for human brain glioblastoma cells. The final set are vanadium complexes of a range of linear phenolic ligands. Vanadium is a metal that is currently enjoying a resurgence in research around anti-cancer therapeutics having initially been designated as inactive. Biological studies again reveal low toxicity against human brain glioblastoma cells. All compounds synthesised for this work have been fully characterised with a number of crystal structures being presented.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Chemistry