The purpose of this study was to evaluate the mechanism by which 2-acetylpyrazine-4 N-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 #

Copper(II) complexes of 6-methyl-2-acetylpyridine N(4)-substituted thiosemicarbazones, coordinated either as a neutral or a monoanionic ligand, have been prepared and characterized. I.r., electronic and e.p.r, spectra of the complexes, as well as ~H-and ~3C-n.m.r. spectra of the thiosemicarbazones, have been recorded. Both the thiosemicarbazones and their copper(lI) complexes show either modest or no growth inhibitory activity against Aspergillus niger, but the N(4)-dialkyl-and 3-azacycloderivatives, and particularly their copper(II) complexes, have considerable activity against Paecilomyces variotii.

The thiosemicarbazones and their related metal complexes were shown to be potent anti-inflammatory agents in rodents at 8 mg kg-*. They were effective in blocking induced edema and endotoxic shock while blocking both local and central pain processes. The ability of the agents to function as anti-inflammatory agents is multifold. First, Tumor Necrosis Factor-alpha (TNFar) and Interleukin-1 (IL-1) release was markedly reduced by the agents. Second, high-affinity receptor binding on fibroblasts of TNFa and IL-1 was significantly inhibited. Third, cellular events, e.g. lysosomal enzymes of specific cells, such as macrophages, were inhibited and prostaglandin cyclo-oxygenase and leukotriene 5'-lipoxygenase enzymic synthetic rates were significantly reduced, which should cause an overall reduction of the inflammatory process.

The synthesis and spectral characterization of a new triangular, trinuclear palladium(II) complex with the dianion of 2-hydroxy-4-methoxyacetophenone N 4 -dimethylthiosemicarbazone, 4MeOAp4Me 2 2-is reported. The X-ray crystal structure determination of [Pd(4MeOAp4Me 2 )] 3 ⋅DMSO shows it