We analyzed the apoptosis and anti-tumour activities of several Mn(III)-salen and -salphen complexes (1-14) towards three different cultured human cancer and non-cancer cells. We demonstrated that most of the Mn(III)-salen and -salphen complexes affect cell viability and induce apoptosis in MCF7 cells. Biochemically active Mn(III)-salen and -salphen complexes induced nuclear fragmentation and release of cytochrome c from the mitochondria to cytosol indicating involvement of mitochondrial pathway of apoptosis. The nature and position of the substituents and the bridging group on the salen ligands play crucial roles in determining the apoptotic activities of Mn(III)-salen and -salphen complexes. The IC50 values for the active Mn(III)-salen complexes ranged between 12 and 55 microM. For Mn(III)-salen complexes with ethylenediamine bridges, methoxy substituted complexes were more active than the corresponding hydroxy derivatives. However, this correlation does not hold when the bridging group was changed from ethylenediamine to o-phenylenediamine. Importantly, several Mn(III)-salen and -salphen complexes showed about 2-3 fold selectivity toward cancer cells such as MCF7 (breast cancer), and CCL228 (colon cancer) over a normal non-malignant cell MCF10 (breast epithelial cells) indicating their potential application towards novel anti-tumour therapy.