Multiple mechanisms for cytotoxicity induced by copper(II) complexes of 2-acetylpyrazine-N-substituted thiosemicarbazones

Abstract

The purpose of this study was to evaluate the mechanism by which 2-acetylpyrazine-4N-substituted thiosemicarbazone copper II complexes mediate their cytotoxicity. These compounds were shown to be cytotoxic to a variety of human and rodent tumors in cell culture and are potent cytocidal agents as determined by dilute agar colony assays. They demonstrated the ability to inhibit several enzymes in vitro including DNA topoisomerase II activity. The data presented suggest that cytotoxicity may be mediated by the cumulative effect of several enzymes being inhibited by the agents. Copyright © 1999 John Wiley & Sons, Ltd.