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Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
Novel di- and tetracarboxylatoplatinum(IV) complexes. Synthesis, characterization, cytotoxic activity, and DNA
Michael R Reithofer1, Seied M Valiahdi, Michael A Jakupec
1Institute of Inorganic Chemistry, University of Vienna, Austria.
Abstract:
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.
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