Water-Soluble Co(III) Complexes of Substituted Phenanthrolines with Cell Selective Anticancer Activity

Transition
metal complexes with substituted phenanthrolines as ligands represent
potential anticancer products without the drawbacks of platinum complexes
that are currently marketed. Here, we report the synthesis and cell
selective anticancer activity of five new water-soluble Co­(III) complexes
with methyl substituted phenanthroline ligands. The complexes were
characterized by elemental analysis, NMR, FAB-mass spectrometry, FTIR,
electronic spectroscopy, and single crystal X-ray diffraction. Possible
interaction of these complexes with DNA was assessed by a combination
of circular dichroism, UV–vis spectroscopy titration, and ethidium
bromide displacement assay, and the results indicated that DNA interaction
is weak for these complexes. Cellular uptake and cytotoxicity of complexes
at low concentrations were assessed by flow cytometry on PC-3 cells,
while their effect on intracellular mitochondrial function was measured
by MTS assay on HeLa and PC-3 cell lines. These complexes showed selective
cytotoxicity with a significantly higher effect on intracellular mitochondrial
function in PC-3 cells than in HeLa cells. At low concentrations,
complex 2 had the highest cytotoxic effect on PC-3 cells,
inducing around 38% cell death, and the correlation of cytotoxicity
of these complexes to their hydrophobicity indicates that an appropriate
value of the hydrophobicity is essential for high antitumor activity.