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Platinum complexes as potential photochemotherapeutic agentsFarley, Sarah J. January 2010 (has links)
A major challenge of platinum anticancer therapy lies in overcoming the severe side-effects associated with treatment. Photoactivatable PtIV azido complexes, which are stable in the dark and reduced to cytotoxic PtII species upon irradiation, have recently emerged as a potential site-specific treatment. This thesis is concerned with the investigation of PtII and PtIV azido complexes as potential cytotoxic and photochemotherapeutic agents. PtII azido complexes such as [Pt(en)(N3)2] were shown to bind to both 5'-guanosine monophosphate (5'-GMP) and glutathione, at a much reduced rate compared with their PtII chlorido analogues. Interestingly, and unexpectedly, these PtII azido complexes showed moderate cytotoxicity towards the A2780 cancer cell line (IC50 21–47 μM). Binding to 5'-GMP was observed to occur more rapidly upon irradiation with UVA light, although the extent of binding was low and the complexes did not demonstrate phototoxicity towards HaCaT keratinocytes. The pendant hydroxyl group of a PtII azido complex was functionalised with a fluorescent probe; conjugation to one axial hydroxyl ligand of a PtIV azido complex was also achieved. The latter conjugate showed a rapid increase in fluorescence intensity upon irradiation, resulting from loss of the axial ligands upon photoreduction. The functionalisation of quantum dots with PtII complexes was also investigated. Water soluble CdSe-ZnS quantum dots were synthesised and derivatised with an amine ligand to which platinum was bound. Conjugation of apo-transferrin to quantum dots was also achieved, with subsequent platinum binding yielding a conjugate with improved aqueous solubility and fluorescence properties. However, the conjugate was inactive towards the A2780 cancer cell line, likely due to surface modifications preventing cellular internalisation. PtII chlorido and azido conjugates with a porphyrin were synthesised and found to show differing behaviour upon irradiation with visible light; evidence of hydrogen peroxide generation from the chlorido complex was much reduced in the case of the azido complex; it is suggested this may result from quenching of reactive oxygen species by the azide anion released upon irradiation. PtII chlorido and azido complexes of highly coloured azo ligands were synthesised in an attempt to shift the wavelength of activation into the visible region. TD-DFT calculations allowed frontier orbital analysis and assignment of the transitions in the absorption spectra. Irradiation of the PtII azido complexes with UVA or broadband visible light led to their decomposition; one water-soluble complex was found to show moderate cytotoxicity and phototoxicity; in addition, its intense blue colour allowed for visual monitoring of this complex inside cells.
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Insights into the mode of action of cisplatinOrton, David Michael January 1992 (has links)
No description available.
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Kinetic and mechanistic studies of Cisplatin derivatives with nucleic acid fragmentsGarner, Mark January 1992 (has links)
No description available.
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An investigation of the induction of vincristine and multidrug resistance in Chinese hamster ovary cells following exposure to hydroxyurea or adriamycinSwingler, Lisa G. January 1991 (has links)
No description available.
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Polysialylated liposomes : preparation, characterisation and stability studies in vitro and in vivoZhang, Xiaoqin January 1999 (has links)
No description available.
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Pharmacokinetics of 5-fluorouracil in cancer patientsWattanatorn, Wiboon January 1998 (has links)
No description available.
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Design, synthesis and evaluation of a scaffold and capping units based on the pyrrolo[2,1-c][1,4]benzodiazepines for combinatorial chemistryGonzaliez, Laura Maritza Calderon January 2000 (has links)
No description available.
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Evaluation of novel compounds to modulate the cytotoxicity of anticancer agents in mammalian cellsBowman, Karen Julia January 1999 (has links)
No description available.
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Structure/activity relationships of antitumour diazridinylquinonesShahbakhti, Hassan January 1996 (has links)
No description available.
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Drug interactions with the anticancer drug aminoglutethimide and related compounds : A study of aminoglutethimide and pyridoglutethimide as inducers and inhibitors of hepatic metabolismDamanhouri, Z. A. January 1987 (has links)
No description available.
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