Cationic first-row transition metal saccharinate complexes with tris(2-pyridylmethyl)amine: synthesis, structures and anticancer studies

A series of new cationic first-row transition metal complexes of [Mn(sac)(H₂O)(tpma)](sac)·H₂O (Mn), [(μ-O){FeCl(tpma)}₂](sac)₂·3H₂O (Fe), [Co(sac)(H₂O)(tpma)](sac)·H₂O (Co), [Ni(H₂O)₂(tpma)](sac)₂·2H₂O (Ni), [Cu(sac)(tpma)](sac) (Cu) and [Zn(sac)(H₂O)(tpma)](sac) (Zn), where sac = saccharinate and tpma = tris(2-pyridylmethyl)amine, were synthesized and structurally characterized by elemental analysis, UV-Vis, IR, ESI-MS, NMR, X-ray diffraction and conductivity measurements. The cytotoxic activity of the metal complexes was evaluated <i>in vitro</i> against lung carcinoma (A549), breast adenocarcinoma (MCF7), colon (HT29), and normal BEAS-2B cell lines. Mn and Fe displayed potent cytotoxic activity in all cell lines with IC₅₀ values between 1.99 ± 0.33 and 6.65 ± 0.67 μM, while Cu moderately affected the growth of HT29 cells. However the rest of the metal complexes did not demonstrate any growth inhibitory effect. Further studies with Fe treated HT29 cells through cellular imaging analysis indicated that Fe significantly induced intracellular ROS (reactive oxygen species) accumulation, mitochondrial dysfunction and double-strand DNA breaks, and eventually caused apoptotic cell death through the intrinsic pathway.