The synthesis and biological activity of cyclometalated goldIII complexes

Williams, Morwen (2018) The synthesis and biological activity of cyclometalated goldIII complexes. Doctoral thesis, University of East Anglia.

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Abstract

The discovery of cisplatin revolutionised the treatment of cancer and opened the door to investigations into the discovery and use of other metallodrugs as chemotherapeutic agents. Both goldI and goldIII complexes have demonstrated promising anticancer properties both in vitro and in vivo.
The following work will focus on the synthesis and anticancer activity of cyclometalated goldIII complexes with both tridentate (C^Npz^C) pincer ligands and bidentate (C^N) cyclometalated ligands to improve their physiological stability. Biologically relevant ligands were then incorporated into the complexes via the free coordination sites. These were selected to enhance the cytotoxicity of the complexes towards human cancer cell lines as well as improving the selectivity towards cancer cell lines over healthy cells.
Chapter 1 explores the use of goldIII compounds as anticancer agents and their typical cellular and molecular targets. Chapter 2 introduces the synthesis and anticancer activity of the first (C^Npz^C)AuIII complexes of acyclic carbene ligands, decorated with amine and amino ester functional groups. Chapter 3 introduces the synthesis and anticancer properties of cyclometalated goldIII complexes with acridine-decorated functional groups, chosen to promote DNA binding. Chapter 4 discusses the synthesis and biological activity of cyclometalated goldIII complexes with dithiocarbamate ligands.
The complexes were all tested for their anticancer activity in vitro towards a panel of human cancer cell lines, including some cell lines that typically show a reduced sensitivity towards cisplatin. Investigations into the possible mechanism of action of these complexes were also undertaken, including DNA binding assays, GSH reactivity and the production of ROS.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Chemistry
Depositing User: Chris White
Date Deposited: 19 Jul 2018 11:59
Last Modified: 19 Jul 2018 11:59
URI: https://ueaeprints.uea.ac.uk/id/eprint/67658
DOI:

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