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Investigational New Drugs

, Volume 27, Issue 2, pp 124–130 | Cite as

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

  • Angela AlamaEmail author
  • Maurizio Viale
  • Michele Cilli
  • Cristina Bruzzo
  • Federica Novelli
  • Bruno Tasso
  • Fabio Sparatore
PRECLINICAL STUDIES

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.

Keywords

Organotin Cytotoxicity Antitumor activity Murine tumors In vivo 

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Angela Alama
    • 1
    Email author
  • Maurizio Viale
    • 2
  • Michele Cilli
    • 3
  • Cristina Bruzzo
    • 1
  • Federica Novelli
    • 4
  • Bruno Tasso
    • 4
  • Fabio Sparatore
    • 4
  1. 1.Tumor Genetic, Lung Cancer UnitNational Institute for Cancer ResearchGenoaItaly
  2. 2.Immunological TherapyNational Institute for Cancer ResearchGenoaItaly
  3. 3.Animal FacilityNational Institute for Cancer ResearchGenoaItaly
  4. 4.Department of Pharmaceutical SciencesUniversity of GenoaGenoaItaly

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