Synthesis and evaluation of novel quinolines and quinazolinediones as potential anti-cancer agents

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dc.check.embargoformatE-thesis on CORA onlyen
dc.check.opt-outNoen
dc.check.reasonThis thesis is due for publication or the author is actively seeking to publish this materialen
dc.contributor.advisorMcCarthy, Florence O.en
dc.contributor.authorGreaney, Kieran
dc.contributor.funderHigher Education Authorityen
dc.date.accessioned2015-11-06T12:28:56Z
dc.date.issued2014
dc.date.submitted2014
dc.description.abstractThis thesis outlines the design and effectuation of novel chemical routes towards a nascent class of functionalised quinoline-5,8-diones and the expansion of a series of contemporary quinazolinediones towards an innovative family of pyridinoquinazolinetetrone derivatives. This fragment based approach is envisaged to lead to advancements in the three scaffolds, expanding the SAR pool of both quinolines and quinazolinediones with subsequent evaluation of chemotherapeutic potential as well as furnishing a new class of tricycle for biological investigation. Development of novel quinoline-5,8-diones is provided for by expanding on existing methodology. Using a variety of nucleophiles on a critical intermediate, a broad range of novel compounds was afforded allowing chemotherapeutic potential to be assessed, while also serving as intermediates for accomplishing novel pyridinoquinazolinetetrone congeners. In order to incorporate functionality into our quinazolinedione template, an efficient synthetic strategy was constructed which provided a robust route to effectuate a highly derivatised pyrimidinedione ring. As derivatisation of this template is unreported our chief priority was to synthesise a range of diverse quinazolinediones. The application of annulation methodology using functionalised precursors provided a library of N-3 derivatised quinazolinedione analogues. These, along with their N-1 functionalised derivatives provide a wide scope from which to construct a series of pyridinoquinazolinetetrone derivatives while also serving as a unique class of molecules whose biological potential is uncharted. Although the actualisation of the pyridinoquinazolinetetrone was ultimately unsuccessful, our work has led to the development of novel quinoline-5,8-diones which were found to possess excellent anti-cancer activity when assessed by the NCI screen. Of the quinazolinediones synthesised eight compounds were accepted for screening by the NCI. Results from the single-dose tests however indicated that these compounds possessed little cytotoxic activity at 10 μM. The development of this novel template in conjunction with the highly active quinolinediones serves as an excellent rostrum for future synthetic endeavours.en
dc.description.sponsorshipHigher Education Authority (Programme for Research in Third-Level Institutions (PRTLI))en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationGreaney, K. 2014. Synthesis and evaluation of novel quinolines and quinazolinediones as potential anti-cancer agents. PhD Thesis, University College Cork.en
dc.identifier.endpage276
dc.identifier.urihttps://hdl.handle.net/10468/2042
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2014, Kieran Greaney.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectQuinolineen
dc.subjectQuinazolinedioneen
dc.subjectAnti-canceren
dc.subjectChemotherapyen
dc.thesis.opt-outfalse
dc.titleSynthesis and evaluation of novel quinolines and quinazolinediones as potential anti-cancer agentsen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoral Degree (Structured)en
dc.type.qualificationnamePhD (Science)en
ucc.workflow.supervisorf.mccarthy@ucc.ie
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