Cytotoxicity of copper complexes of 2-furaldehyde oxime derivatives 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 either suspended or solid tumors. The ED50 values were frequently improved over the clinically useful antineoplastic agents. These copper complexes of 2-furaldehyde oximes were effective inhibitors of L1210 lymphoid leukemia DNA synthesis followed by RNA synthesis. Purine synthesis regulatory enzyme activities were markedly reduced by the compounds with marginal inhibition of t-RNA polymerase, and nucleoside kinases activities. L1210 DNA topoisomerase II activity was markedly reduced with IC50 values better than the standard VP-16, etoposide. Yet, the copper complexes caused no further protein linked breaks than VP-16 did, but did block phosphorylation activation of the topoisomerase II enzyme.
Hall
I H
IH
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27559-7360, USA.
Taylor
K
K
Miller
M C
MC
Dothan
X
X
Khan
M A
MA
Bouet
F M
FM
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D004273:DNA, Neoplasm / Q000378:metabolism; D005662:Furaldehyde / Q000031:analogs & derivatives / Q000633:toxicity*; D006801:Humans; D007939:Leukemia L1210; D009363:Neoplasm Proteins / Q000378:metabolism; D010091:Oximes / Q000633:toxicity; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D010091:Oximes; D003300:Copper; D005662:Furaldehyde