Platinum(II) Complexes with 1,10-Phenanthroline and Hydrophilic Alkoxyacetate Ligands as Potential Antitumor Agents.

Four platinum complexes, formulated as [Pt(phen)(OCOCH2 OR)2 ] (phen=1,10-phenanthroline, R=Me, Et, i Pr, or t Bu), have been synthesized and well characterized by elemental analysis, IR, 1 H-NMR, 13 C-NMR and ESI-MS spectroscopy. Replacing chloride groups of the precursor Pt(phen)Cl2 with alkoxyacetate anions greatly improved the aqueous solubility and cytotoxicity of the resulting platinum complexes. The in vitro cytotoxicity study revealed that complexes 1-3 were active in vitro towards four human tumor cell lines, especially complex 1 which exhibited prominent in vitro cytotoxic activity against HCT-116 cell lines comparable to cisplatin and oxaliplatin. Flow cytometry assay indicated that representative complexes 1 and 2 exerted cytotoxicity on HCT-116 cell lines through inducing cell apoptosis and blocking cell cycle progression in the S or G2/M phases. The interaction of representative complexes with pET28a plasmid DNA was tested by agarose gel electrophoresis, which demonstrated that complexes 1 and 2 were capable of distorting plasmid DNA mainly by covalent binding and degradation effect.