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...

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Veröffentlicht in:Anti-cancer drugs 1993-04, Vol.4 (2), p.241-250
Hauptverfasser: West, Douglas X, Liberia, Anthony E, Rajendran, K G, Hall, Iris H
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Sprache:eng
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Zusammenfassung: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.
ISSN:0959-4973
1473-5741
DOI:10.1097/00001813-199304000-00017