Platinum(II) Complexes with O,S Bidentate Ligands: Biophysical Characterization, Antiproliferative Activity, and Crystallographic Evidence of Protein Binding.

We recently characterized a series of novel platinum(II) compounds bearing a conserved O,S binding moiety as a bifunctional ligand and evaluated their solution behavior and antiproliferative properties in vitro against a representative cancer cell line. On the whole, those platinum compounds showed an appreciable stability in mixed dimethyl sulfoxide–aqueous buffers and promising in vitro cytotoxic effects; yet they manifested a rather limited solubility in aqueous media making them poorly suitable for further pharmaceutical development. To overcome this drawback, four new derivatives of this series were prepared and characterized based on a careful choice of substituents on the O,S bidentate ligand. The solubility and stability profile of these novel compounds in a reference buffer was determined, as well as the ligands’ log Po/w value (Po/w = n-octanol–water partition coefficient) as an indirect measure for the complexes’ lipophilicity. The antiproliferative properties were comparatively evaluated in a ...