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- W2465357879 abstract "Malignant glioma are often resistant to cisplatin. Numerous chemical modifications have been made to overcome this limitation. Analyzing such novel compounds, we previously hypothesized, that hydrophobicity improves the cytotoxicity of NH3 substituted platinum agents.Testing this hypothesis, we synthesized further eight novel platinum agents, substituting the NH3 groups with various pyridyl ring systems. The cytotoxicity was measured in MTT tests using the cisplatin resistant human U25 1 malignant glioma cell line as a model. Solubility was measured in water using flameless atomic absorption spectroscopy.Cytotoxicity correlated significantly with low water solubility. The relation of cells surviving 72-hours of 1 OuM drug exposure was best described by a logarithmic formula: Surviving cells (% of control) = 6.4 + 38.4 log (water solubility in mg Pt/L) Adding an oximgroup to the aromatic substitute decreased cytotoxicity.These data confirmed that increased hydophobicity increases cytotoxicity in this group. This might be caused by better cellular penetration, or by shielding of DNA-adducts from repair processes. The data created a further hypothesis: A positive mesomeric effect as characteristic for the oxim-group might decrease DNA binding, a negative mesomeric might improve it." @default.
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- W2465357879 date "2001-02-24" @default.
- W2465357879 modified "2023-09-23" @default.
- W2465357879 title "Rational design of platinum chemotherapeutic drugs: hydrophobicity increases cytotoxicity." @default.
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