Organoruthenium Complexes with C^N Ligands are Highly Potent Cytotoxic Agents that Act by a New Mechanism of Action
Language English Country Germany Media print-electronic
Document type Journal Article
- Keywords
- anticancer agents, cell growth, mitochondrial disfunction, protein synthesis, ruthenium,
- MeSH
- Apoptosis drug effects MeSH
- Drug Resistance, Neoplasm drug effects MeSH
- Cisplatin toxicity MeSH
- Nitrogen chemistry MeSH
- Coordination Complexes chemistry metabolism toxicity MeSH
- Microscopy, Confocal MeSH
- Cell Cycle Checkpoints drug effects MeSH
- Humans MeSH
- Ligands MeSH
- Membrane Potential, Mitochondrial drug effects MeSH
- Cell Line, Tumor MeSH
- Antineoplastic Agents chemistry metabolism toxicity MeSH
- Reactive Oxygen Species metabolism MeSH
- Ruthenium chemistry MeSH
- Drug Screening Assays, Antitumor MeSH
- Carbon chemistry MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Cisplatin MeSH
- Nitrogen MeSH
- Coordination Complexes MeSH
- Ligands MeSH
- Antineoplastic Agents MeSH
- Reactive Oxygen Species MeSH
- Ruthenium MeSH
- Carbon MeSH
Our study demonstrates that four novel kinetically inert C,N-cyclometalated RuII complexes of the type [Ru(C^N)(N^N)2 ][PF6 ] containing a handle for functionalization on the C^N ligand are very potent cytotoxic agents against several different human cancer cell lines and are up to 400-fold more potent than clinically used cisplatin. In addition, the investigated ruthenium complexes are less cytotoxic in noncancerous cells, and exhibit higher selectivity for cancer cells than conventional platinum anticancer drugs. The high potency of the investigated ruthenium compounds can be attributed to several factors, including enhanced internalization and their capability to change mitochondrial transmembrane potential in cells. The new ruthenium complexes also interfere with protein synthesis with a markedly higher potency than conventional inhibitors of DNA translation. Notably, the latter mechanism has not been hitherto described for other cytotoxic Ru compounds and cisplatin.
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