A Maltol-Containing Ruthenium Polypyridyl Complex as a Potential Anticancer Agent
Language English Country Germany Media print-electronic
Document type Journal Article
Grant support
ANR-10-IDEX-0001-02 PSL
Agence Nationale de la Recherche
PP00P2_133568
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
PP00P2_157545
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Universität Zürich
Novartis Jubilee Foundation
Forschungskredit of the University of Zurich
UBS Promedica Stiftung
Ile de France Region
GINOP-2.3.2-15-2016-00038, FK 124240
National Research, Development and Innovation Office-NKFIA
17-02080S
Czech Science Foundation
GA 681679
European Research Council - International
- Keywords
- DNA, bioinorganic chemistry, cancer, medicinal inorganic chemistry, ruthenium,
- MeSH
- Cisplatin chemistry pharmacology MeSH
- HeLa Cells MeSH
- Coordination Complexes chemistry pharmacology MeSH
- Humans MeSH
- Ligands MeSH
- Molecular Structure MeSH
- Antineoplastic Agents chemistry pharmacology MeSH
- Pyrones chemistry pharmacology MeSH
- Ruthenium chemistry pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Cisplatin MeSH
- Coordination Complexes MeSH
- Ligands MeSH
- maltol MeSH Browser
- Antineoplastic Agents MeSH
- Pyrones MeSH
- Ruthenium MeSH
Cancer is one of the main causes of death worldwide. Chemotherapy, despite its severe side effects, is to date one of the leading strategies against cancer. Metal-based drugs present several potential advantages when compared to organic compounds and they have gained trust from the scientific community after the approval on the market of the drug cisplatin. Recently, we reported the ruthenium complex ([Ru(DIP)2 (sq)](PF6 ) (where DIP is 4,7-diphenyl-1,10-phenantroline and sq is semiquinonate) with a remarkable potential as chemotherapeutic agent against cancer, both in vitro and in vivo. In this work, we analyse a structurally similar compound, namely [Ru(DIP)2 (mal)](PF6 ), carrying the flavour-enhancing agent approved by the FDA, maltol (mal). To possess an FDA approved ligand is crucial for a complex, whose mechanism of action might include ligand exchange. Herein, we describe the synthesis and characterisation of [Ru(DIP)2 (mal)](PF6 ), its stability in solutions and under conditions that resemble the physiological ones, and its in-depth biological investigation. Cytotoxicity tests on different cell lines in 2D model and on HeLa MultiCellular Tumour Spheroids (MCTS) demonstrated that our compound has higher activity than cisplatin, inspiring further tests. [Ru(DIP)2 (mal)](PF6 ) was efficiently internalised by HeLa cells through a passive transport mechanism and severely affected the mitochondrial metabolism.
Department of Chemistry University of Zurich Winterthurerstrasse 190 8057 Zurich Switzerland
Institut Curie PSL University CNRS UMR 144 75248 Paris France
Institute of Molecular Cancer Research University of Zurich 8057 Zurich Switzerland
Institute of Molecular Genetics Czech Academy of Sciences Videnska 1083 14300 Prague Czech Republic
Université de Paris Institut de physique du globe de Paris CNRS 75005 Paris France
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