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Morier-Teissier, Elisabeth; Boitte, Nezha; Helbecque, Nicole; Bernier, Jean Luc; Pommery, Nicole; Duvalet, Jean Loup; Fournier, Charles; Hecquet, Bernard; Catteau, Jean Pierre; Henichart, Jean Pierre
Journal of medicinal chemistry, 07/1993, Letnik: 36, Številka: 15Journal Article
A new molecule 4 (GGH-DAE)2DHQ associating the 1,4,5,8-tetrahydroxyanthraquinone ring (DHQ) of the antitumor drug mitoxantrone (2), two diaminoethylene chains (DAE), and the metal-chelating peptide Gly-Gly-His (GGH) has been synthesized. Such a molecule presents characteristics able to induce antitumor activity: compound 4 intercalates into DNA as measured by delta Tm, fluorescence quenching, and viscometry; ESR studies demonstrate that several types of Cu complexes are formed depending on pH; and the production of free radicals, as evidenced by spin-trapping, is enhanced by 4. In vitro, in leukemia cells L1210 and mammary cells MCF7, 4 is slightly less cytostatic than mitoxantrone, but substantially less toxic. In vivo, in leukemia P388 on mice, a T/C value of 230 is obtained at 25 mg/kg, higher than the one of mitoxantrone, which is toxic at the same dose.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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