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dc.contributor.advisorO'Hagan, David
dc.contributor.advisorBotting, Nigel P.
dc.contributor.authorNortcliffe, Andrew
dc.coverage.spatial403en_US
dc.date.accessioned2013-10-29T13:48:12Z
dc.date.available2013-10-29T13:48:12Z
dc.date.issued2013-11-29
dc.identifieruk.bl.ethos.581839 
dc.identifier.urihttp://hdl.handle.net/10023/4124
dc.description.abstractChapter 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.en_US
dc.language.isoenen_US
dc.publisherUniversity of St Andrews
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subjectMedicinal chemistryen_US
dc.subjectNitric oxideen_US
dc.subjectCytotoxicityen_US
dc.subjectProstate canceren_US
dc.subjectRGDen_US
dc.subject.lccQP535.N1N7
dc.subject.lccQP535.N1N7
dc.subject.lcshNitric oxideen_US
dc.subject.lcshPharmaceutical chemistryen_US
dc.subject.lcshProstate--Cancer--Treatmenten_US
dc.subject.lcshNitric oxideen_US
dc.subject.lcshPharmaceutical chemistryen_US
dc.subject.lcshProstate--Cancer--Treatmenten_US
dc.titleNitric oxide donors for the treatment of prostate canceren_US
dc.typeThesisen_US
dc.contributor.sponsorCancer Research UKen_US
dc.type.qualificationlevelDoctoralen_US
dc.type.qualificationnamePhD Doctor of Philosophyen_US
dc.publisher.institutionThe University of St Andrewsen_US


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