TY - JOUR
T1 - Arene Variation of Highly Cytotoxic Tridentate Naphthoquinone-Based Ruthenium(II) Complexes and In-Depth In Vitro Studies
AU - Cseh, Klaudia
AU - Geisler, Heiko
AU - Stanojkovska, Kristina
AU - Westermayr, Julia
AU - Brunmayr, Philipp
AU - Wenisch, Dominik
AU - Gajic, Natalie
AU - Hejl, Michaela
AU - Schaier, Martin
AU - Koellensperger, Gunda
AU - Jakupec, Michael A. A.
AU - Marquetand, Philipp
AU - Kandioller, Wolfgang
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/11
Y1 - 2022/11
N2 - 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
1H-NMR and
13C-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.
AB - 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
1H-NMR and
13C-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.
KW - metal-based drugs
KW - ruthenium
KW - piano-stool complexes
KW - anticancer
KW - DRUG
KW - APOPTOSIS
KW - CHALLENGES
KW - CELLS
UR - http://www.scopus.com/inward/record.url?scp=85146539613&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics14112466
DO - 10.3390/pharmaceutics14112466
M3 - Article
VL - 14
JO - Pharmaceutics
JF - Pharmaceutics
IS - 11
M1 - 2466
ER -
