Synthesis, characterization, cytotoxic activity, and 19F NMR spectroscopic investigations of (OC-6-33)-diacetato(ethane-1,2-diamine)bis(3,3,3-trifluoropropanoato)platinum(IV) and its platinum(II) counterpart

Publication date: 1 May 2019Source: Inorganica Chimica Acta, Volume 490Author(s): Doris Höfer, Klaudia Cseh, Michaela Hejl, Alexander Roller, Michael A. Jakupec, Markus Galanski, Bernhard K. KepplerAbstractTetracarboxylatoplatinum(IV) complexes are interesting representatives of potential anticancer active platinum(IV) drugs. Revealing higher kinetic inertness in comparison to their cytotoxic platinum(II) counterparts, they offer an opportunity to reduce toxic and deactivating side reactions. Platinum(IV) complexes are generally considered as prodrugs, which have to be reduced in order to exert their anticancer activity. Two model complexes, a platinum(II) and platinum(IV) complex featuring two equatorial 3,3,3-trifluoropropanoato (tfpa) and in the case of the latter two axial acetato ligands, were synthesized and characterized in detail by multinuclear (1H, 13C, 15N, 19F, 195Pt) one- and two-dimensional NMR spectroscopy, high-resolution electrospray ionization mass spectrometry, elemental analysis and X-ray diffraction analysis. Cytotoxicity was evaluated in three human cancer cell lines (A549, SW480 and CH1/PA-1) by the MTT colorimetric assay, exhibiting IC50 values down to the low micromolar range. The fluorinated ligands in equatorial positions allowed detailed and highly sensitive 19F NMR spectroscopic investigations. Besides reaction studies in the presence of small molecules, e.g. ascorbic acid and 5′-GMP, the reduction of the platinum(IV) complex was additionally i...
Source: Inorganica Chimica Acta - Category: Chemistry Source Type: research