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

Ildikó Szabó, Marilena Manea, Erika Orbán, Antal Csámpai, Szilvia Bó́sze, Rita Szabó, Miguel Tejeda, Dezsó́ Gaál, Bence Kapuvári, Michael Przybylski, Ferenc Hudecz, Gábor Mezó́

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Abstract

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.

Original languageEnglish
Pages (from-to)656-665
Number of pages10
JournalBioconjugate Chemistry
Volume20
Issue number4
DOIs
Publication statusPublished - ápr. 15 2009

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ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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