Inorganica Chimica Acta, 79 (1983) tumors of 0.17 cm' (P<O.OOl) and the PCPH-Cu treated group was free from detectable tumors. Treatment was ceased at this point. Tumors in PCPH-Cu and SBH-CU treated mice remained quiescent for an additional three weeks after which their growth resumed. However, 5 of 1.5 tumor-bearing mice (from three separate experiments) treated with PCPH-Cu have remained free of the tumor for four months post-treatment. Administration of free PCPH and SBH did not significantly reduce tumor growth. Treatment of non-tumor bearing mice with similar dosages of SBH-Cu and PCPH-Cu produced a thickening of the skin at the area of injection. No other effects have been observed in these mice in the subsequent four months.
In acute toxicity studies, the dosage of inhibitor that killed 50% of normal mice within 24 hours was 1.9 g/kg for SBH, 60 mg/kg for SBH-Cu, 1 .O g/kg for PCPH and 18 mg/kg for PCPH-Cu. Thus, chelation to copper potentiated both the antitumor and acute toxicity of these chelators.
These results demonstrate that two hydrazonecopper complexes, PCPH-Cu and SBH-Cu are potent mitotic inhibitors. The antineoplastic activity of these two hydrazone-copper analogs of GHL-Cu may reside either in their general cytotoxicity or might possibly be due to an interference with the mechanisms which concentrate the copper ions required for tumor angiogenesis.