Molecular Pharmacology, Vol 12, 1036-1044, Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics

Reactions of 3-Ethoxy-2-oxobutyraldehyde Bis(N⁴-dimethylthiosemicarbazonato)-Zinc(II) with Tumor Cells and Mitochondria

¹ Department of Chemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201

Physicochemical and biological properties of bis(thiosemicarbazonato)-zinc complexes have been investigated. Respiration of Ehrlich ascites cells is inhibited by 3-ethoxy-2-oxobutyraldehyde bis(N⁴-dimethylthiosemicarbazonato)-zinc(II). Zinc ion is much less effective, but the thiosemicarbazone ligand initially stimulates, then depresses, oxygen uptake. State 3 oxygen uptake of tumor cell mitochondria is more sensitive to this zinc complex than is state 4. In bovine heart mitochondria respiratory inhibition occurs almost exclusively in state 3. The insensitivity of the electron transport chain to the complex was confirmed with Keilin-Hartree particles. Formation constants and partition coefficients for several bis(thiosemicarbazonato)-zinc complexes are used to interpret the different behavior of zinc ion, thiosemicarbazone ligand, and zinc complex with tumor cells and mitochondria.