0486061 - BFÚ 2018 RIV DE eng J - Journal Article
Novohradský, Vojtěch - Yellol, J. - Stuchlíková, O. - Santana, M.D. - Kostrhunová, Hana - Yellol, G. - Kašpárková, Jana - Bautista, D. - Ruiz, J. - Brabec, Viktor
Organoruthenium Complexes with CN Ligands are Highly Potent Cytotoxic Agents that Act by a New Mechanism of Action.
Chemistry - A European Journal. Roč. 23, č. 61 (2017), s. 15294-15299. ISSN 0947-6539. E-ISSN 1521-3765
R&D Projects: GA ČR(CZ) GA17-05302S
Institutional support: RVO:68081707
Keywords : chemotherapeutic-agents * ruthenium(ii) complexes * iridium(iii) complexes
OECD category: Biochemistry and molecular biology
Impact factor: 5.160, year: 2017 ; AIS: 1.26, rok: 2017
DOI: https://doi.org/10.1002/chem.201703581

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.
Permanent Link: http://hdl.handle.net/11104/0280948