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- W2040294032 abstract "Oxazole-bridged combretastatin A-4 analogues bind to tubulin and exert anti-vascular and anti-angiogenic effects. When linked to Ru(η(6)-arene) complex fragments, conjugates with additional cytotoxic activity result which can ruthenate bionucleophiles such as DNA and proteins. For instance, the Ru(II)(p-cymene)(isonicotinate)Cl(2) complex 6a of the known 4-(3,4,5-trimethoxyphenyl)-5-(3-hydroxy-4-methoxyphenyl)-oxazole 4a was far more active than the latter against cells of the p53-competent wild-type form of HCT-116 colon carcinoma at low 0.01 μM concentrations. A fast reaction of 6a with nucleophilic N-acetyl-L-cysteine was observed in NMR studies. The Ru(arene) complexes 6a-c were also more efficacious against combretastatin-refractory p53(+) cells of human HT-29 colon carcinoma when compared to their parent 4-(3,4-dimethoxy-5-methoxy/halo-phenyl)-5-(3-hydroxy-4-methoxyphenyl)-oxazoles 4a-c. These cells are rich in ABC-transporters which are responsible for their multi-drug resistance and for which conjugates 6 are less good substrates than the phenols 4. Unlike 4a, its complex 6a also diminished the motility of human 518A2 melanoma cells in a wound-healing assay which is indicative of anti-metastatic activity in solid tumors. Overall, the Ru(arene) complex conjugates 6 broaden the anti-tumoral spectrum of the combretastatin A-4 analogues 4 considerably." @default.
- W2040294032 created "2016-06-24" @default.
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- W2040294032 date "2010-11-01" @default.
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- W2040294032 title "Ru(η6-arene) complexes of combretastatin-analogous oxazoles with enhanced anti-tumoral impact" @default.
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- W2040294032 doi "https://doi.org/10.1016/j.ejmech.2010.07.061" @default.
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