Cytotoxic Impact of Fluorinated Ligands in Equatorial Position of Trans-Configured Diam(m)inetetracarboxylatoplatinum(IV) Complexes

Author(s): Yvonne Lerchbammer-Kreith, Michaela Hejl, Dominik Wenisch, Michael A. Jakupec, Mathea S. Galanski, Bernhard K. Keppler
Abstract: A series of thirty novel tetracarboxylatoplatinum(IV) complexes in trans-configuration featuring combinations of mixed ammine, methylamine, dimethylamine, and cyclopentylamine ligands as well as acetato/propanoato and trifluoropropanoato ligands was synthesised. The platinum(IV) complexes were characterised by one- and two-dimensional multinuclear NMR spectroscopy (¹H, ¹³C, ¹⁵N, ¹⁹F, ¹⁹⁵Pt), ESI-MS, elemental analysis, and X-ray diffraction. Additional parameters such as reduction behaviour and lipophilicity were measured via NMR spectroscopy and RP-HPLC, revealing slow reduction and a broad spectrum of log k_w values in line with the respective ligand combination. In order to determine structure–activity relationships, cytotoxic activity was evaluated via the MTT assay in three human cancer cell lines (CH1/PA-1, ovarian teratocarcinoma, SW480, colon adenocarcinoma, A549, non-small-cell lung carcinoma). The induction of apoptosis and necrosis was determined in SW480 cells via the flow-cytometric annexin V/PI assay. In general, a tendency of higher lipophilicity leading to higher cytotoxicity was noticed. In contrast, lipophilicity alone plays a subordinate role for the induction of apoptosis, which strongly depends on the combination of am(m)ine and trifluoropropanoato ligands.
Organisation(s): Department of Inorganic Chemistry, NMR Centre
External organisation(s): Research Cluster Translational Cancer Therapy Research
Journal: Inorganics
Volume: 11
ISSN: 2304-6740
DOI: https://doi.org/10.3390/inorganics11100411
Publication date: 10-2023
Peer reviewed: Yes
Austrian Fields of Science 2012: 104003 Inorganic chemistry
Keywords
ASJC Scopus subject areas: Inorganic Chemistry
Sustainable Development Goals: SDG 3 - Good Health and Well-being
Portal url: https://ucrisportal.univie.ac.at/en/publications/392c0b94-9b0e-443a-b47a-6391d8330c1f