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dc.contributor.advisorMeegan, Mary Jane
dc.contributor.authorO'Boyle, Niamh
dc.date.accessioned2016-12-01T14:48:15Z
dc.date.available2016-12-01T14:48:15Z
dc.date.issued2010
dc.identifier.citationNiamh O'Boyle, 'Synthesis, biochemical evaluation and structural studies of novel antiproliferative βeta-lactams', [thesis], Trinity College (Dublin, Ireland). School of Pharmacy & Pharmaceutical Sciences, 2010, pp 499
dc.identifier.otherTHESIS 9398
dc.identifier.urihttp://hdl.handle.net/2262/78133
dc.description.abstractThe synthesis and antiproliferative evaluation of anti-cancer β-lactams targeting tubulin, heat shock protein 90 and the estrogen receptor is described. Compounds were planned to include relevant substituents known to confer target selectivity and included a diverse range in order to discern meaningful structure-activity relationships. The core β-lactam heterocycle was formed using established chemistry - the Staudinger and Reformatsky reactions. The Staudinger reaction was employed for the majority of analogues as the necessary synthetic precursors were readily available. All products were fully characterised. A library of over 100 combretastatin A-4 analogues containing the β-lactam core scaffold were prepared and evaluated for antiproliferative activity. Phenolic compound 181 was particularly potent, with activity in the picomolar range for a variety of cell types. Combretastatin A-4 is a known tubulin-targeting agent that binds at the colchicine-binding site, and selected β-lactam analogues including 181 inhibited the polymerisation of tubulin at low micromolar concentrations.
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__Rb14880818
dc.subjectPharmaceutical Chemistry, Ph.D.
dc.subjectPh.D. Trinity College Dublin
dc.titleSynthesis, biochemical evaluation and structural studies of novel antiproliferative βeta-lactams
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 499
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