Cytotoxicity of Metallic Complexes of Furan Oximes in Murine and Human Tissue Cultured Cell Lines

The copper complexes of furan oxime derivatives were found to be potent cytotoxic agents in both murine and human tissue cultured cell lines which were suspended as well as solid tumors, Mode of action studies in murine L1210 lymphoid leukemia cells showed that the compounds suppressed DNA, RNA and protein synthesis after 60 min at 100 mu M. Inhibition of purine and pyrimidine de novo syntheses, as well as inhibition of ribonucleoside reductase and nucleoside kinase activities with DNA strand scission occurred, All of these effects of the drug probably added to its ability to cause cell death but most important was the inhibition of DNA topoisomerase II activity with IC50 values lower than those afforded by VP-16, the standard, which should cause apoptosis. (C) 1997 by John Wiley & Sons, Ltd.