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Anti-cancer ytterbium porphyrin and iron polypyridyl complexes: synthesis, cytotoxicity and bioinformaticsstudiesKwong, Wai-lun., 鄺偉倫. January 2012 (has links)
Discovery of anti-cancer cisplatin was a great success in anti-cancer chemotherapy. Numerous analogues of cisplatin such as carboplatin and oxaliplatin, were developed to improve the clinical effectiveness. Nevertheless, the clinical uses of these platinum-based drugs are limited by the occurrence of drug-resistance, narrow range of susceptible cancer types and severe toxicity. These drawbacks have stimulated the development of other metal-based compounds with distinct mechanisms of anti-cancer action. In this study, a series of ytterbium(III) porphyrin and iron(II) polypyridyl complexes were synthesized. Their anti-cancer activities were examined. With the aid of gene expression profiling and bioinformatics analysis, the mechanisms of these anti-cancer active complexes have been examined.
A series of ytterbium(III) porphyrin complexes have been prepared and structurally characterized. An ytterbium(III) octaethylporphyrin complex (1) was found to exhibit potent anti-cancer activities with cytotoxic IC50 values down to sub-micromolar range. Complex (1) was shown to exist as a dimeric hydroxyl-bridged complex [Yb2(OEP)2(μ-OH)2] (where H2OEP = octylethylporphyrin) in CH2Cl2 and in solid state, and as monomeric [Yb(OEP)(DMSO)(OH)(OH2)] in DMSO/aqueous solution. Unlike various anti-cancer lanthanide complexes which are commonly proposed to target cellular DNA, our transcriptomics data, bioinformatics connectivity map analysis and cellular experiments altogether indicate that (1) exerts its anticancer effect through apoptosis which is highly associated with endoplasmic reticulum stress pathway.
Two iron(II) polypyridyl complexes [Fe(qpy)(CH3CN)2](ClO4)2 (Fe-1a) (qpy =2,2’:6’,2”:6”,2’”:6”’,2””-quinquepyridine) and [Fe(Py5-OH)(CH3CN)](ClO4)2 (Fe-2a) (Py5-OH = 2,6-bis[hydroxybis(2-pyridyl)methyl]pyridine) were found to display selective cytotoxicity towards cancer cell lines over a normal lung fibroblast cell line. Affymetrix oligonucleotide microarray and bioinformatics analysis suggested that the anti-cancer mechanisms of Fe-1a and Fe-2a involve apoptosis, cell cycle arrest, activation of p53 and mitogen activated protein kinase (MAPK). Complex Fe-1a induced the formation of reactive oxygen species (ROS) in a concentration-dependent manner. Both iron complexes could cleave supercoiled plasmid DNA. The cellular DNA damage induced by both complexes was confirmed by comet assay and phospho-histone protein ( -H2AX) immunofluorescence assay. Cell cycle progression analysis revealed that Fe-1a induced both S- and G2/M-phase cell cycle arrests, whereas Fe-2a induced a G0/G1-phase arrest. Apoptosis induced by both complexes was confirmed by annexin-V/SYTOX green flow cytometry analysis and western blotting. Moreover, p53 and MAPK activation were found to be associated with the induced apoptosis.
By employing the cationic porphyrin ligand, 5-(p-N-methylpyridyl)triphenylporphyrin [H2(5-MePyTPP)]+, a series of cationic metalloporphyrin complexes formulated as [M(porphyrinato)]n+ (where M = PtII, RuII, CoII or AuIII, n = 1 or 2) were prepared. The cytotoxicities of these complexes were examined. The platinum(II) and ruthenium(II) complexes were relatively non-cytotoxic towards the examined cancer cell lines with IC50 >24 μM. [CoII(5-MePyTPP)]Cl displayed a more pronounced anti-cancer activity with IC50 values between 7.48 – 17.7 μM. However, this Co(II) complex displayed poor selectivity towards the cancer cell lines compared to the normal cell line. The gold(III) porphyrin complex [AuIII(5-MePyTPP)]Cl2 showed a much higher potency (IC50 =3.01 -10.7μM) than the other [M(5-MePyTPP)]n+ prepared. By means of flow cytometry and fluorescence microscopy, [AuIII(5-MePyTPP)]Cl2 was found to induce G2/M-phase cell cycle arrest and necrotic cell death in HeLa cells. / published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy
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The preparation and structure determination of some copper, cobalt, iron and manganese complexes and the study of their properties尹業高, Yin, Yegao. January 1996 (has links)
published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy
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Synthesis and thermal decomposition of alkyl-olefin chelate complexes of iron and rutheniumSteiger, George Edward 08 1900 (has links)
No description available.
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Transition metal chelates with Schiff bases derived from salicylaldehyde and diamo ethane / Transition metal complexesSummerton, Alvin Paul January 1979 (has links)
Title on spine: Transition metal complexes / 173 leaves : ill., tables, graphs ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.1979) from the Dept. of Physical and Inorganic Chemistry, University of Adelaide
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A study of crystallization from water of compounds in the system Fe²⁺ - Cu²⁺ - So₄²⁻.Walton, Wayne J. A. January 1968 (has links) (PDF)
Thesis (M.S. - Geology)--University of Arizona, 1968. / Includes bibliographical references (leaves p.28).
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Iron-platinum granular films for ultra-high density recordingWan, Jun. January 2009 (has links)
Thesis (Ph.D.)--University of Delaware, 2009. / Principal faculty advisor: George C. Hadjipanayis, Dept. of Physics & Astronomy. Includes bibliographical references.
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The preparation and structure determination of some copper, cobalt, iron and manganese complexes and the study of their properties /Yin, Yegao. January 1996 (has links)
Thesis (Ph. D.)--University of Hong Kong, 1996. / Includes bibliographical references (leaf 184-194).
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Die interaksie van yster en ysteroksiedes met korrosiewe gasse : 'n Mossbauerspektroskopiese studieSwanepoel, Stephanie 13 May 2014 (has links)
M.Sc. (Physics) / Please refer to full text to view abstract
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Asymmetric synthesis via iron acyl complexesWalker, Jonathan Charles January 1986 (has links)
No description available.
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Synthesis and reactivity of carbene complexes of iron, ruthenium and osmium porphyrinsLi, Yan, 李艷 January 2004 (has links)
published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy
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