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Development of an oxime bond containing Daunorubicin-Gonadotropin-releasing hormone-III conjugate as a potential anticancer drug

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2009

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Szabó, Ildikó
Orbán, Erika
Csámpai, Antal
Bösze, Szilvia
Szabó, Rita
Tejeda, Miguel
Gaál, Dezsõ
Kapuvári, Bence

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Bioconjugate Chemistry. 2009, 20(4), pp. 656-665. Available under: doi: 10.1021/bc800542u

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Here, we report on the synthesis and biological properties of a conjugate in which daunorubicin (Dau) as chemotherapeutic agent was attached through an oxime bond to gonadotropin-releasing hormone-III (GnRH-III) as targeting moiety. In vitro toxicity and the cytostatic effect of the conjugate on MCF-7 human breast and C26 murine colon cancer cell lines were determined, and the results were compared with those obtained for the free daunorubicin, as well as with the doxorubicin containing derivative. In vivo antitumor effect of daunorubicin-GnRH-III was studied on Balb/c female mice transplanted with C26 tumor. Our data indicate that the daunorubicin-GnRH-III conjugate had a lower toxic effect than the free daunorubicin and it was essentially nontoxic up to 15 mg (Dau content)/kg body weight. The treatment of the C26 tumor bearing mice with the conjugate led to tumor growth inhibition and longer survival time in comparison with the controls and with the administration of the free drug. When mice were treated twice with the conjugate (on days 4 and 7 after tumor transplantation), 46% tumor growth inhibition was obtained. In this case, the increase of the median survival time was 38% compared to the controls.

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540 Chemie

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ISO 690SZABÓ, Ildikó, Marilena MANEA, Erika ORBÁN, Antal CSÁMPAI, Szilvia BÖSZE, Rita SZABÓ, Miguel TEJEDA, Dezsõ GAÁL, Bence KAPUVÁRI, Michael PRZYBYLSKI, Ferenc HUDECZ, Gábor MEZÖ, 2009. Development of an oxime bond containing Daunorubicin-Gonadotropin-releasing hormone-III conjugate as a potential anticancer drug. In: Bioconjugate Chemistry. 2009, 20(4), pp. 656-665. Available under: doi: 10.1021/bc800542u
BibTex
@article{Szabo2009Devel-3290,
  year={2009},
  doi={10.1021/bc800542u},
  title={Development of an oxime bond containing Daunorubicin-Gonadotropin-releasing hormone-III conjugate as a potential anticancer drug},
  number={4},
  volume={20},
  journal={Bioconjugate Chemistry},
  pages={656--665},
  author={Szabó, Ildikó and Manea, Marilena and Orbán, Erika and Csámpai, Antal and Bösze, Szilvia and Szabó, Rita and Tejeda, Miguel and Gaál, Dezsõ and Kapuvári, Bence and Przybylski, Michael and Hudecz, Ferenc and Mezö, Gábor}
}
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