Tuning physicochemical properties and antiproliferative activity of platinum(II) terpyridine complexes through ligand substitution

Three platinum(II) complexes of methoxyphenyl substituted terpyridine ligands, were prepared and characterized by various spectroscopic methods as well as through DFT calculations. The cytotoxic properties of the complexes were evaluated against various cancer cells, including Sw620, MCF7 and HepG2, along with normal human fibroblasts (hFB). The cytotoxicity showed a strong correlation with the lipophilicity of the Pt(II) complexes. Increasing the number of methoxy groups on the phenyl ring of the terpyridine framework provided measurable cytotoxicity against the tested cancer cell lines while keeping harmful effects on normal cells to a minimum and a moderate selectivity index. In comparison to cisplatin, only the complex functionalized with three methoxy groups exhibited substantial cytotoxicity against the examined cell types. The cytotoxic complex showed moderate anticancer activity with respect to cisplatin, with less toxicity in the normal cell line model. Cisplatin and the trimethoxy Pt(II) complex both depolarized the mitochondrial potential, raised oxidative stress, caused DNA fragmentation, started apoptosis, and stopped the cell cycle.