Cytotoxicity of copper and cobalt complexes of furfural semicarbazone and thiosemicarbazone derivatives in murine and human tumor cell lines

The 2-furfural semicarbazone and thiosemicarbazone copper and cobalt comple xes demonstrated potent cytotoxicity against the growth of suspended leukem ias and lymphomas as well as human lung MB9812, colon SW480, ovary 1-A9 and HeLa-S-3 uterine carcinoma. In L1210 lymphoid leukemia cell the complexes inhibited preferentially DNA synthesis over 60 min at 25 to 100 muM. The co pper and cobalt complexes functioned by multiple mechanisms to suppress syn thetic steps in nucleic acid metabolism to reduce deoxynucleotide pools for incorporation into DNA. At high concentrations the complexes suppressed hu man DNA topoisomerase II activity with DNA nicks and DNA fragmentation but they did not alkylate the bases of DNA, cause intercalation between base pa irs or cause cross-linking of DNA strands.