| Autor: |
Cseh K; Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 42, 1090 Vienna, Austria., Geisler H; Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 42, 1090 Vienna, Austria., Stanojkovska K; Institute of Theoretical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 17, 1090 Vienna, Austria., Westermayr J; Wilhelm-Ostwald-Institute for Physical and Theoretical Chemistry, Faculty of Chemistry and Mineralogy, University of Leipzig, Linnéstr. 2, 04103 Leipzig, Germany., Brunmayr P; Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 42, 1090 Vienna, Austria., Wenisch D; Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 42, 1090 Vienna, Austria., Gajic N; Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 42, 1090 Vienna, Austria., Hejl M; Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 42, 1090 Vienna, Austria., Schaier M; Institute of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 38, 1090 Vienna, Austria.; Vienna Doctoral School in Chemistry (DoSChem), University of Vienna, Waehringer Str. 42, 1090 Vienna, Austria., Koellensperger G; Institute of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 38, 1090 Vienna, Austria., Jakupec MA; Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 42, 1090 Vienna, Austria.; Research Cluster 'Translational Cancer Therapy Research', University of Vienna, 1090 Vienna, Austria., Marquetand P; Institute of Theoretical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 17, 1090 Vienna, Austria.; Vienna Research Platform on Accelerating Photoreaction Discovery, University of Vienna, 1090 Vienna, Austria., Kandioller W; Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 42, 1090 Vienna, Austria.; Research Cluster 'Translational Cancer Therapy Research', University of Vienna, 1090 Vienna, Austria. |
| Abstrakt: |
The main purpose of this study was to synthesize a new set of naphthoquinone-based ruthenium(II) arene complexes and to develop an understanding of their mode of action. This study systematically reviews the steps of synthesis, aiming to provide a simplified approach using microwave irradiation. The chemical structures and the physicochemical properties of this novel group of compounds were examined by 1 H-NMR and 13 C-NMR spectroscopy, X-ray diffractometry, HPLC-MS and supporting DFT calculations. Several aspects of the biological activity were investigated in vitro, including short- and long-term cytotoxicity tests, cellular accumulation studies, detection of reactive oxygen species generation, apoptosis induction and NAD(P)H:quinone oxidoreductase 1 (NQO1) activity as well as cell cycle analysis in A549, CH1/PA-1, and SW480 cancer cells. Furthermore, the DNA interaction ability was studied in a cell-free assay. A positive correlation was found between cytotoxicity, lipophilicity and cellular accumulation of the tested complexes, and the results offer some important insights into the effects of the arene. The most obvious finding to emerge from this study is that the usually very chemosensitive CH1/PA-1 teratocarcinoma cells showed resistance to these phthiocol-based organometallics in comparison to the usually less chemosensitive SW480 colon carcinoma cells, which pilot experiments suggest as being related to NQO1 activity. |
