The cytotoxicity of copper(II) complexes of heterocyclic thiosemicarbazones and 2-substituted pyridine N-oxides.
Thiosemicarbazone complexes of copper(II) were shown to be potent cytotoxic/antineoplastic agents against the growth of murine and human tumor cells. Selectivity of some agents was demonstrated against specific solid tumor growth. In L1210 lymphoid leukemia cells the copper complexes preferentially inhibited DNA synthesis with their major effects on the purine de novo pathway at PRPP amido transferase, IMP dehydrogenase and dihydrofolate reductase. The reductions of purines correlated positively with inhibition of DNA synthesis and cytotoxicity of the agents tested. DNA itself was fragmented after incubation with the drug; however, no binding of the agent to nucleotide bases or intercalation between base pairs was evident.
West
D X
DX
Department of Chemistry, Illinois State University, Normal 61761.
Liberta
A E
AE
Rajendran
K G
KG
Hall
I H
IH
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005493:Folic Acid Antagonists; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D012268:Ribose-Phosphate Pyrophosphokinase / Q000037:antagonists & inhibitors; D013882:Thiosemicarbazones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D005493:Folic Acid Antagonists; D009363:Neoplasm Proteins; D011725:Pyridines; D013882:Thiosemicarbazones; D003300:Copper; D007168:IMP Dehydrogenase; D012268:Ribose-Phosphate Pyrophosphokinase