In vitro cytotoxic activity of tri-n-butyltin(IV)lupinylsulfide hydrogen fumarate (IST-FS 35) and preliminary antitumor activity in vivo.
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 microM. 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.
Alama
Angela
A
Tumor Genetic, Lung Cancer Unit, National Institute for Cancer Research, Largo R. Benzi 10, 16132, Genoa, Italy. angela.alama@istge.it
Viale
Maurizio
M
Cilli
Michele
M
Bruzzo
Cristina
C
Novelli
Federica
F
Tasso
Bruno
B
Sparatore
Fabio
F
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D007941:Leukemia P388; D020714:Maximum Tolerated Dose; D008546:Melanoma, Experimental; D051379:Mice; D009947:Organotin Compounds / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D014267:Triethyltin Compounds / Q000737:chemistry / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; C408503:IST-FS 29; C541255:IST-FS 35; D009947:Organotin Compounds; D014267:Triethyltin Compounds