Date of Award

6-2016

Document type

Thesis

Degree Name

PhD (Doctor of Philosophy)

First Supervisor

Professor Celine Marmion

Second Supervisor

Dr. Andrew Kellett

Funder/Sponsor

Higher Education Authority

Keywords

Anticancer Agents, Copper (11)

Abstract

The development of metal complexes as therapeutic agents remains a focal point of modern medicinal inorganic chemistry. While platinum drugs are well established therapeutic agents, recent progress has shown that some copper complexes possess enhanced cytotoxic activity and in vivo cytotoxic tolerance owing to their DNA binding and DNA scission capabilities. In parallel, the design, synthesis and evaluation of enzyme inhibitors rationally chosen for their potential in suppressing tumour cell proliferation as well as possessing selective toxicity towards tumour over normal cells is another area receiving considerable attention of late.

To date, we have successfully synthesized a library of novel copper(II) drug conjugates for potential use as anti-cancer agents. We have characterised these complexes using a variety of analytical chemistry techniques and we have also carried out a preliminary speciation study of these complexes. These complexes have been shown to possess low μM and even nM in vitro cytotoxic activity in human cancerous cell lines as well as potent enzyme inhibitory properties. Metallodrug-DNA interaction studies also suggest DNA binding and efficient chemical nuclease activities. Our recent results suggest that these complexes may possess a different mechanism of action to classical platinum drugs such as cisplatin and thus may overcome some of the drawbacks associated with these platinum-based therapies.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

File Size

4.59MB

Comments

A thesis submitted for the degree of Doctor of Philosophy from the Royal College of Surgeons in Ireland in 2016.

Available for download on Thursday, May 30, 2019

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