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dc.contributor.advisorWalsh, John
dc.contributor.authorMcCormack, Emmet Martin
dc.date.accessioned2016-12-01T12:32:35Z
dc.date.available2016-12-01T12:32:35Z
dc.date.issued2003
dc.identifier.citationEmmet Martin McCormack, 'Design, synthesis and in vitro evaluation of novel anti-cancer compounds', [thesis], Trinity College (Dublin, Ireland). School of Pharmacy & Pharmaceutical Sciences, 2003, pp 340
dc.identifier.otherTHESIS 7335
dc.identifier.urihttp://hdl.handle.net/2262/78081
dc.description.abstractThe purpose of this thesis was the design, synthesis and in vitro appraisal of a novel class of ITP/APN dual inhibitory compounds. Additionally, a class of novel biaryls, which were synthesised within the research group, were assayed to evaluate their ability to inhibit tubulin polymerisation (ITP). The introductory chapter commences with brief overview of the history of cancer and role of natural products in conventional chemotherapeutic regimes and adjuvant immunotherapies. Subsequently, the biological mechanisms of mitosis and metastasis are discussed with special emphasis on the importance of tubulin and the spindle apparatus, and the proteolytic degradation of the extracellular matrix by the angiogenic marker, aminopeptidase N (APN). Following, a review of the structural activity requisites of particular aminopeptidase N and antimitotic compounds, a discussion on the novel development of a novel class of dual ITP/APN inhibitory compoimds ensues. The chapter concludes with the rationalisation of the proposed synthetic strategies, and the obligatory development of tubulin extraction, purification and assay procedures. Chapter 2 proceeds with the synthesis a series of investigational compounds coupling colchicbe to several dicarboxylic amino acids and (2S.3R)-2-hydroxy-3-amino-4- phenylbutanoic acid (AHPA), probing the optimum chain length compulsory to fulfil both requirements of minimal disruption to ITP whilst maintaining fianctionality necessary for APN/CD13 inhibition. Consequent ITP in vitro assay results are analysed and the importance of Aspartic acid (Asp) as a linker molecule discussed.
dc.format1 volume
dc.language.isoen
dc.publisherTrinity College (Dublin, Ireland). School of Pharmacy & Pharmaceutical Sciences
dc.relation.isversionofhttp://stella.catalogue.tcd.ie/iii/encore/record/C__Rb12409010
dc.subjectPharmacognosy, Ph.D.
dc.subjectPh.D. Trinity College Dublin
dc.titleDesign, synthesis and in vitro evaluation of novel anti-cancer compounds
dc.typethesis
dc.type.supercollectionthesis_dissertations
dc.type.supercollectionrefereed_publications
dc.type.qualificationlevelDoctoral
dc.type.qualificationnameDoctor of Philosophy (Ph.D.)
dc.rights.ecaccessrightsopenAccess
dc.format.extentpaginationpp 340
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