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- W1997091517 abstract "The relationship between cytotoxic activity of platinum dinuclear complexes toward cancer cells and their intrinsic properties (electrophilicity and hydrophobicity) have been examined. It is shown that the reactivity with chloride anion is a good index of the electrophilicity of the platinum complexes. By assuming a cell kill pharmacodynamic model, the relation between IC50 value and the electrophilicity is obtained. It is concluded that inside cells the reactivity of the platinum complexes having imide ligands is higher than that of CDDP. The other important factor which affects the cytotoxic activity is hydrophobicity. The log k′ values (k′: capacity factor) are found useful to estimate the hydrophobicity of platinum complexes. The accumulation of platinum into cells is dominated by the hydrophobicity and the charge of platinum complexes. Highly hydrophobic complexes are thought to be adsorbed in cell membranes, resulting in low cytotoxic activity since they cannot reach DNA. A schematic model of the interaction between platinum complexes and serum proteins reveals that more hydrophobic complexes tend to bind to serum proteins more stably. At least three possible paths of the cellular platinum accumulation are suggested: direct accumulation of the platinum complexes, incorporation in the form of CDDP produced from the complexes, and incorporation through protein–platinum complexes, although the contribution of the third one may be small." @default.
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- W1997091517 date "1998-12-01" @default.
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- W1997091517 title "Physicochemical factors for cytotoxic activity in platinum dinuclear complexes with pyrimidine and imide ligands" @default.
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- W1997091517 doi "https://doi.org/10.1016/s0301-4622(98)00213-0" @default.
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