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Structure-Function Correlations in the Reaction of Bis(thiosemicarbazonato) Copper(II) Complexes with Ehrlich Ascites Tumor Cells¹

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

Examination of a series of substituted bis(thiosemicarbazonato) copper(II) complexes shows that their reaction with Ehrlich ascites tumor cells can be understood in terms of the relative reactivity of the complexes with sulfhydryl groups. In general, the order of reactivity of the complexes correlates directly with their respective degrees of cytotoxicity and ability to inhibit DNA synthesis and cellular respiration. The parent complex, 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazonato) copper(II), leads to widespread cellular effects with the suppression of DNA synthesis particularly sensitive to the complex. The appearent reversible inhibition of DNA synthesis and thymidine uptake by 3-ethoxy-2-oxobutyraldehyde bis(N⁴-dimethylthiosemicarbazonato) copper(II) and its lack of cytotoxicity are explained in terms of the chemical properties of this complex.

¹ This research has been generously supported by Grants CA 13099 and CA 16156 from the National Cancer Institute, NIH.

Received 9/ 3/76. Accepted 10/14/77.