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

The copper complexes of 2-furaldehyde and furan oximes have previously demonstrated potent cytotoxicity, L1210 DNA synthesis inhibition, DNA topoisomerase II inhibition and DNA fragmentation. Currently a series of cobalt metal complexes of 2-furaldehyde oximes were compared with copper complexes of furan oximes to determine whether the type of metal is important to the cytotoxicity and mode of action of the complexes. The cobalt complexes of furan oximes, like the copper complexes, were shown to be cytotoxic to suspended tumor cell lines, e.g. leukemias, lymphomas, acute monocytic leukemia and HeLa-S3 uterine carcinoma. The cobalt complexes did not demonstrate dramatic cytotoxicity against the growth of tumors derived from solid human tumor lines. The cobalt complexes preferentially inhibited L1210 DNA synthesis, followed by inhibition of RNA and protein synthesis from 25 to 100 µM over 60 min. These agents, like the copper complexes of 2-furaldehyde and furan oximes, were inhibitors of DNA polymerase α activity and de novo purine synthesis with marginal inhibition of ribonucleoside reductase and dihydrofolate reductase activities with DNA fragmentation. Unlike the copper complexes, the cobalt complexes did not inhibit L1210 DNA topoisomerase II activity but did reduce thymidylate synthetase activity. Thus, varying the type of metal within the complexes of 2-furaldehyde and furan oximes produces differences in both cytotoxicity and mode of action. Copyright © 1999 John Wiley & Sons, Ltd.