Comparative cytotoxic and biochemical effects of ligands and metal complexes of .alpha.-N-heterocyclic carboxaldehyde thiosemicarbazones

Abstract

Several .alpha.-N-heterocyclic carboxaldehyde thiosemicarbazones and their Fe and Cu complexes were tested for their cytotoxicity and inhibiting activity against DNA synthesis under controlled metal conditions. No ligands showed cytotoxicity against Ehrlich [ascites carcinoma] cells at the concentrations tested, while some Fe and Cu complexes were active. The ligands inhibited DNA synthesis at much lower concentrations than used above. The metal complexes were effective inhibitors at concentrations much below those necessary to demonstrate cytotoxicity. The Fe complexes of 1-formylisoquinoline thiosemicarbazone, 2-formylpyridine thiosemicarbazone and 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone were 3-6 times more active than their free ligands as inhibitors of partially purified ribonucleotide reductase to which no Fe had been added. The Cu complex of 2-formylpyridine thiosemicarbazone was slightly more active than the free ligand against the reductase.