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Summary
The new rhodium(II) complex Rh2(Form) (02CCF3)2(H20)2 (Form = N, N’ — di-p-tolyl formamidinate) was evaluated for its toxicity on the rat and for its efficacy against two tumors of this animal: the Yoshida ascites sarcoma and the T8 sarcoma of Guérin.
The rhodium(II) formamidinate shows very low toxicity: in fact 150 mg/kg (the highest quantity of drug soluble in 4 ml of dimenthyl sulfoxide) is not toxic for rats. We were unable to establish the lethal dose or the highest nontoxic dose since larger mounts of complex require a dose of dimethyl sulfoxide (DMSO) that is itself toxic and the compound is insoluble in other solvents such as water or Tween.
Doses of rhodium(II) formamidinate, varying from 3 to 30 mg/kg, were administered once by i.p., i.v., i.m. and intratumor (i.t.) route from 1 to 7 days after i.p. injection of 106 Yoshida ascites sarcoma cells and subcutaneous (s.c.) implantation of ˜ 300 mg (corresponding to 2-3 × 107 living tumor cells) of T8 sarcoma of Guérin. The compound is active when administered i.p. 24 hours after Yoshida ascites sarcoma at the smallest dose tested (3 mg/Kg), increasing the average life span of 62.3% and allowing the survival of 50% of the rats. It is also active when administered i.p. at the highest dose tested (30 mg/Kg) 7 days after tumor cell challenge, increasing the average life span in 43.8% and allowing survival in 20% of the rats; it is not active after i.v. or i.m administration. The title complex exhibits anticancer activity against T8 sarcoma of Guérin, increasing significantly the average life span of 17% and 25.9% of rats if administered by i.v. and i.m. routes respectively at the dose of 30 mg/Kg the day following implantation of the neoplasia, and of 12.2% of rats by i.t. route at the dose of 10 mg/Kg five days after tumor challenge.
A comparison between the therapeutic properties of the title complex with those of the complexes Rh2(O2CCH3)4 and cis-Pt(NH3)2Cl2(CDDP) reveals that the rhodium(II) formamidinate derivative exhibits the same antitumor activity associated with considerably reduced toxicity.
