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In vitro cytotoxic activity of tri-n-butyltin(IV)lupinylsulfide hydrogen fumarate (IST-FS 35) and preliminary antitumor activity in vivo

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Summary

The cytotoxicity in vitro and antitumor activity in vivo of the organotin compound tri-n-butyltin(IV)lupinylsulfide hydrogen fumarate (IST-FS 35) have been investigated. The IC50 values obtained in a panel of tumor cell lines were compared to those of the parental compound IST-FS 29 in the same cells. IST-FS 35 resulted significantly more active than IST-FS 29 with IC50 values in the range 0.16–1.8 μM. Toxicity studies in vivo, after intravenous administration of escalating concentrations of IST-FS 35, provided the identification of the maximal tolerated dose (3.5 mg/kg) which was employed as therapeutic dose in the antitumor activity experiments. Preliminary results, in transplanted murine tumor models, revealed that both the P388 myelomonocytic leukaemia and the B16-F10 melanoma, implanted subcutaneously in BDF1 mice, were inhibited about 96% in their tumor volume at day 11, following a single intravenous injection of the compound. Additional studies are mandatory to unravel the mechanism of action for the development of IST-FS 35 as potential antitumor drug.

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Authors and Affiliations

  1. Tumor Genetic, Lung Cancer Unit, National Institute for Cancer Research, Largo R. Benzi 10, 16132, Genoa, Italy

    Angela Alama & Cristina Bruzzo

  2. Immunological Therapy, National Institute for Cancer Research, Genoa, Italy

    Maurizio Viale

  3. Animal Facility, National Institute for Cancer Research, Genoa, Italy

    Michele Cilli

  4. Department of Pharmaceutical Sciences, University of Genoa, Genoa, Italy

    Federica Novelli, Bruno Tasso & Fabio Sparatore

Authors
  1. Angela Alama
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  2. Maurizio Viale
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  3. Michele Cilli
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  4. Cristina Bruzzo
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  5. Federica Novelli
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  6. Bruno Tasso
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  7. Fabio Sparatore
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Correspondence to Angela Alama.

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Alama, A., Viale, M., Cilli, M. et al. In vitro cytotoxic activity of tri-n-butyltin(IV)lupinylsulfide hydrogen fumarate (IST-FS 35) and preliminary antitumor activity in vivo. Invest New Drugs 27, 124–130 (2009). https://doi.org/10.1007/s10637-008-9148-x

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  • DOI: https://doi.org/10.1007/s10637-008-9148-x

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