COMPARATIVE CYTOTOXIC AND BIOCHEMICAL EFFECTS OF LIGANDS AND METAL-COMPLEXES OF ALPHA-N-HETEROCYCLIC CARBOXALDEHYDE THIOSEMICARBAZONES

Several α-N-heterocyclic carboxaldehyde thiosemicarbazones and their iron and copper complexes have been tested for their cytotoxicity and inhibiting activity against DNA synthesis under controlled metal conditions. No ligands show cytotoxicity against Ehrlich cells at the concentrations tested, while some iron and copper complexes are active.In contrast, the ligands inhibit DNA synthesis at much lower concentrations than used above. Similarly, the metal complexes are effective inhibitors at concentrations much below those necessary to demonstrate cytotoxicity. In addition, the iron complexes of 1-formylisoquinoline thiosemicarbazone, 2-formylpyridine thiosemicarbazone, and 4-methyl-5-amino-l-formylisoquinoline thiosemicarbazone were shown to be three-to sixfold more active than their free ligands as inhibitors of partially purified ribonucleotide reductase to which no iron has been added. The copper complex of 2-formylpyridine thiosemicarbazone was slightly more active than the free ligand against the reductase. © 1979, American Chemical Society. All rights reserved.