Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.581839
Title: Nitric oxide donors for the treatment of prostate cancer
Author: Nortcliffe, Andrew
Awarding Body: University of St Andrews
Current Institution: University of St Andrews
Date of Award: 2013
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Abstract:
Chapter One provides a general introduction into the biology and chemistry of nitric oxide, with particular focus on the role of nitric oxide in cardiovascular disease, cancer and hypoxia. It also details the types of organic functional groups used as nitric oxide donors, with detailed discussion of nitrate esters, furoxans and sydnonimines. Chapter Two discusses prostate cancer. It provides an overview into the development of prostate cancer, prostate cancer staging, and treatment. The key molecular aspects of prostate cancer are detailed, and the types of treatment available outlined. Chapter Three details the synthesis and activity of NCX-1102, a nitric oxide-donating analogue of the non-steroidal anti-inflammatory drug sulindac, and the synthetic work in the preparation of analogues of NCX-1102, using nitrate esters, furoxans and sydnonimines as nitric oxide-donating functional groups. The compounds prepared were tested against a prostate cancer cell line (PC3) and the cytotoxicity results are presented. Chapter Four describes the synthesis of nitric-oxide donating analogues of abiraterone, a CYP17 inhibitor for the treatment of prostate cancer. The results of cytotoxicity assays against PC3 cells are detailed. Chapter Five discusses the application of nitric oxide-donating functional groups in tandem with biologically active motifs. The synthesis of nitric oxide-donating amino acids, and their application to the preparation of nitric oxide-donating RGD peptides and prostate-specific membrane antigen inhibitors is presented, along with representative biological evaluation. Chapter Six introduces possible future work for the continuation of the project, suggesting the synthesis of fluorinated sydnonimines, prostate-specific membrane antigen inhibitors combined with for prostate cancer imaging and a “tool-box” of nitric oxide-donating bioconjugation reagents.
Supervisor: O'Hagan, David; Botting, Nigel P. Sponsor: Cancer Research UK
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.581839  DOI: Not available
Keywords: Medicinal chemistry ; Nitric oxide ; Cytotoxicity ; Prostate cancer ; RGD ; QP535.N1N7 ; QP535.N1N7 ; Nitric oxide ; Pharmaceutical chemistry ; Prostate--Cancer--Treatment ; Nitric oxide ; Pharmaceutical chemistry ; Prostate--Cancer--Treatment
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