Cytotoxic and antitumor properties of bleomycin and several of its metal complexes

Journal of Medicinal Chemistry
1980.0

Abstract

This study examines the concentration-dependent cytotoxicity and antitumor activity of bleomycin (Blm) and Cu-, Zn-, Fe(III)-, and CoBlm using Ehrlich cells in culture and the Ehrlich ascites tumor. The order of activity in culture under several conditions is CuBlm approximately equal to Blm approximately equal to ZnBlm > Fe(III)Blm > CoBlm approximately equal to control. Short exposures of cells to drugs in the presence or absence of serum produced effects on cell proliferation similar to 48-h incubations. With Blm and CuBlm there was no obvious relationship between cytotoxicity and the modest short-term inhibition of DNA synthesis by the drugs. The antitumor experiments produced qualitatively similar results with the order of antitumor potency being CuBlm > Blm > ZnBlm approximately equal to FeBlm > CoBlm approximately equal to control tumor. The host toxicity produced by these drugs as measured by weight loss had the opposite ordering: CoBlm < FeBlm < ZnBlm < Blm < CuBlm. At therapeutically effective concentrations, FeFlm was significantly less toxic relative to ther other active agents.

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