Iron(III)-salen complexes with less DNA cleavage activity exhibit more efficient apoptosis in MCF7 cells.

To understand the relationship between DNA damage potential and biochemical activities, we synthesized nine different Fe(III)-salen derivatives with varying substituents, and analyzed their in vitro DNA cleavage properties and biochemical effects on cultured human cells. Our results demonstrated that Fe(III)-salen complexes affect cell viability, induce nuclear fragmentation, and activate caspases and apoptosis in cultured human cells. The nature and the position of the substituents in the Fe(III)-salen complexes play critical roles in determining their apoptotic efficiencies. Most importantly, our results demonstrated that the in vitro DNA cleavage activities of Fe(III)-salen complexes are not essential for their apoptotic activities in human cells. Instead, the lesser their DNA cleavage activity the greater is their apoptotic efficiency.