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Organoruthenium Complexes with C^N Ligands are Highly Potent Cytotoxic Agents that Act by a New Mechanism of Action
Author(s) -
Novohradsky Vojtech,
Yellol Jyoti,
Stuchlikova Olga,
Santana María Dolores,
Kostrhunova Hana,
Yellol Gorakh,
Kasparkova Jana,
Bautista Delia,
Ruiz José,
Brabec Viktor
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201703581
Subject(s) - ruthenium , cisplatin , chemistry , cytotoxic t cell , cytotoxicity , mechanism of action , internalization , stereochemistry , cancer cell , combinatorial chemistry , in vitro , biochemistry , cell , cancer , biology , chemotherapy , genetics , catalysis
Our study demonstrates that four novel kinetically inert C, N ‐cyclometalated Ru II complexes of the type [Ru(C^N)(N^N) 2 ][PF 6 ] 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.