Coordination compounds from simple transition metals are robust substitutes for platinum-based complexes due to their remarkable anticancer properties. In a quest to find new metal complexes that could substitute or augment the platinum based chemotherapy we synthesized three transition metal complexes C1-C3 with Cu(ii), Ni(ii), and Co(ii) as the central metal ions, respectively, and evaluated them for their anticancer activity against the human keratinocyte (HaCaT) cell line and human cervical cancer (HeLa) cell lines. These complexes showed different activity profiles with the square planar copper complex C1 being the most active with IC50 values lower than those of the widely used anticancer drug cisplatin. Assessment of the morphological changes by DAPI staining and ROS generation by DCFH-DA assay exposed that the cell death occurred by caspase-3 mediated apoptosis. C1 displayed interesting interactions with Ct-DNA, evidenced by absorption spectroscopy and validated by docking studies. Together, our results suggest that binding of the ligand to the DNA-binding domain of the p53 tumor suppressor (p53DBD) protein and the induction of the apoptotic hallmark protein, caspase-3, upon treatment with the metal complex could be positively attributed to a higher level of ROS and the subsequent DNA damage (oxidation), generated by the complex C1, that could well explain the interesting anticancer activity observed for this complex.
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