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Organoruthenium Complexes with CN Ligands are Highly Potent Cytotoxic Agents that Act by a New Mechanism of Action
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SYSNO ASEP 0486061 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Organoruthenium Complexes with CN Ligands are Highly Potent Cytotoxic Agents that Act by a New Mechanism of Action Author(s) Novohradský, Vojtěch (BFU-R) ORCID
Yellol, J. (ES)
Stuchlíková, O. (CZ)
Santana, M.D. (ES)
Kostrhunová, Hana (BFU-R) RID, ORCID
Yellol, G. (ES)
Kašpárková, Jana (BFU-R) RID, ORCID
Bautista, D. (ES)
Ruiz, J. (ES)
Brabec, Viktor (BFU-R) RID, ORCIDNumber of authors 10 Source Title Chemistry - A European Journal. - : Wiley - ISSN 0947-6539
Roč. 23, č. 61 (2017), s. 15294-15299Number of pages 5 s. Publication form Print - P Language eng - English Country DE - Germany Keywords chemotherapeutic-agents ; ruthenium(ii) complexes ; iridium(iii) complexes Subject RIV CE - Biochemistry OECD category Biochemistry and molecular biology R&D Projects GA17-05302S GA ČR - Czech Science Foundation (CSF) Institutional support BFU-R - RVO:68081707 UT WOS 000414351400006 DOI https://doi.org/10.1002/chem.201703581 Annotation Our study demonstrates that four novel kinetically inert C,N-cyclometalated Ru-II 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. Workplace Institute of Biophysics Contact Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Year of Publishing 2018
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