Novel Di- and Tetracarboxylatoplatinum(IV) Complexes. Synthesis, Characterization, Cytotoxic Activity, and DNA Platination

Octahedrally configured diaminedichloro- and diamineoxalatoplatinum(IV)
complexes with axial hydroxo ligands were carboxylated with succinic
or glutaric anhydride. The free, uncoordinated carboxylic acid groups
were further derivatized with amines and alcohols to the respective
amides and esters and characterized in detail by elemental analysis,
mass spectrometry, and multinuclear (1H, 13C, 15N, and 195Pt) NMR spectroscopy. Cytotoxicity of
the complexes was studied in four human cancer cell lines derived
from ovarian carcinoma (CH1, SK-OV-3), cervical carcinoma (HeLa),
and colon carcinoma (SW480) by means of the MTT assay. Structure–activity
relationships revealed a low activity for platinum complexes with
underivatized carboxylic acid moieties and amide derivatives displaying
the hydroxyethylamino residue. Within the series of amides, cyclopentylamino
analogues were equipped with the highest cytotoxic potential. However,
ester derivatives yielded IC50 values mostly in the low
micromolar range and comparable to those of cisplatin. DNA platination
studies of selected complexes revealed a high DNA platination capacity
in parallel to a high cytotoxic potential and vice versa.