Chapter 1 | Reviews innate host-defence α-helices and their mimetics as potential anticancer chemotherapeutics. Introduces biologically relevant bimetallic triple metallohelices as potential non-peptide mimics, and reviews the known flexicates. Discusses the criteria such compounds would need to satisfy in order to be successful anticancer agents. Chapter 2 | Describes the discovery, synthesis and characterisation of nineteen new class Ib flexicates with varying ligand functionality. These compounds are found to be highly active and selective in cancer, with no observed activity in bacteria. Preliminary modes of action studies indicate that they do not act through DNA interactions, but cause changes to the cell cycle and induce programmed cell death. Chapter 3 | Describes the conception, synthesis and characterisation of a new asymmetric type of architecture, named a triplex metallohelix. A range of these novel complexes are found to be highly active and selective in several cancer cell lines. Possible modes of action found the triplex metallohelices do not bind or damage DNA, but do cause changes to the cell cycle, induce programmed cell death and appear to localise on the cellular membrane of colon cancer cells. Chapter 4 | Summarises the aims and results of this research project and concludes this work by discussing the perspectives of the novel metallohelices described as α-helix mimetics. Final remarks consider some possible directions that this research could take in the future. Chapter 5 | Provides details of the experimental procedures used to carry out the work in this thesis.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:640964 |
| Date | January 2014 |
| Creators | Kaner, Rebecca A. |
| Publisher | University of Warwick |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://wrap.warwick.ac.uk/66673/ |
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