Show simple item record

dc.contributor.advisorBarry, Nicolas P.E.
dc.contributor.advisorPitto-Barry, Anaïs
dc.contributor.advisorPicksley, Stephen M.
dc.contributor.advisorShnyder, Steven
dc.contributor.advisorMartin, William H.C.
dc.contributor.authorAzmanova, Maria T.
dc.date.accessioned2024-09-10T17:29:45Z
dc.date.available2024-09-10T17:29:45Z
dc.date.issued2022
dc.identifier.urihttp://hdl.handle.net/10454/19994
dc.description.abstractThere is an urgent need to find novel anticancer therapeutics with different mechanisms of action than platinum-containing drugs, particularly for patients who relapse after having been initially treated with a platinum-containing chemotherapy regimen. This chemoresistance phenomena, along with the serious side effects observed with cisplatin, have led research in Medicinal Inorganic Chemistry to using other precious metals for the design of novel anticancer therapeutics. This work reports on the synthesis and characterisation of a series of organometallic drug candidates based on ruthenium, osmium, rhodium, and iridium, followed by investigation of their cancer-inhibiting properties via in vitro and in vivo studies. The cytotoxicity of these complexes against various human cancer cell lines is presented, as well as preliminary studies on their possible modes of action, determined via gene expression studies, cell cycle and apoptosis analysis, reactive oxygen species detection and mitochondrial-membrane potential assays. In addition, to confirm the surprising absence of in vitro toxicity against normal cells exhibited by some compounds, studies on ex vivo/in vitro isolated human lymphocytes from healthy individuals, have been conducted. One lead molecule has been progressed to in vivo studies in mice and toxicity and efficacy were assessed with a series of assays including determination of the maximum tolerated dose and pharmacodynamic studies. Structural modifications of the lead molecule with water-soluble phosphines were subsequently undertaken, with the aim to improve the stability and solubility of the parent 16-electron specie, and evaluations of the biological activity of these novel complexes are presented.en_US
dc.language.isoenen_US
dc.rights<a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>.eng
dc.subjectHalf-sandwich metal complexesen_US
dc.subjectElectron-deficient organometallicsen_US
dc.subjectBioinorganic chemistryen_US
dc.subjectAnticancer metallodrugsen_US
dc.subjectAnticancer therapeuticsen_US
dc.titleDevelopment and Evaluation of Organometallic Anticancer Drug Candidatesen_US
dc.type.qualificationleveldoctoralen_US
dc.publisher.institutionUniversity of Bradfordeng
dc.publisher.departmentFaculty of Life Sciences. School of Chemistry and Biosciencesen_US
dc.typeThesiseng
dc.type.qualificationnamePhDen_US
dc.date.awarded2022
refterms.dateFOA2024-09-10T17:29:45Z


Item file(s)

Thumbnail
Name:
14006069 Maria Azmanova Final ...
Size:
22.13Mb
Format:
PDF
Description:
PhD Thesis

This item appears in the following Collection(s)

Show simple item record