Biological properties of novel ruthenium- and osmium-nitrosyl complexes with azole heterocycles
Online Publication Date2016-03-09
Print Publication Date2016-06
Permanent link to this recordhttp://hdl.handle.net/10754/601317
MetadataShow full item record
AbstractSince the discovery that nitric oxide (NO) is a physiologically relevant molecule, there has been great interest in the use of metal nitrosyl compounds as antitumor pharmaceuticals. Particularly interesting are those complexes which can deliver NO to biological targets. Ruthenium- and osmium-based compounds offer lower toxicity compared to other metals and show different mechanisms of action as well as different spectra of activity compared to platinum-based drugs. Novel ruthenium- and osmium-nitrosyl complexes with azole heterocycles were studied to elucidate their cytotoxicity and possible interactions with DNA. Apoptosis induction, changes of mitochondrial transmembrane potential and possible formation of reactive oxygen species were investigated as indicators of NO-mediated damage by flow cytometry. Results suggest that ruthenium- and osmium-nitrosyl complexes with the general formula (indazolium)[cis/trans-MCl4(NO)(1H-indazole)] have pronounced cytotoxic potency in cancer cell lines. Especially the more potent ruthenium complexes strongly induce apoptosis associated with depolarization of mitochondrial membranes, and elevated reactive oxygen species levels. Furthermore, a slight yet not unequivocal trend to accumulation of intracellular cyclic guanosine monophosphate attributable to NO-mediated effects was observed.
CitationBiological properties of novel ruthenium- and osmium-nitrosyl complexes with azole heterocycles 2016 JBIC Journal of Biological Inorganic Chemistry
SponsorsAustrian Science Fund (FWF). We are deeply grateful to Prof. Dr. Vladimir Arion for overall support and collaborations. Authors wish to thank Anatolie Gavriluta (Université Claude Bernard Lyon 1, France) for cooperation. This work was performed as part of an Austrian-French joint project supported in France by ANR (Agence Nationale de la Recherche) through the project VILYGRu (No. ANR-09-BLAN-0420-01) and in Austria by the Austrian Science Fund (FWF) through the project I374-N19. Partial support by the Austrian Science Fund through the project P-22339-N19 is also acknowledged.
- Striking difference in antiproliferative activity of ruthenium- and osmium-nitrosyl complexes with azole heterocycles.
- Authors: Büchel GE, Gavriluta A, Novak M, Meier SM, Jakupec MA, Cuzan O, Turta C, Tommasino JB, Jeanneau E, Novitchi G, Luneau D, Arion VB
- Issue date: 2013 Jun 3
- Introducing the 4-Phenyl-1,2,3-Triazole Moiety as a Versatile Scaffold for the Development of Cytotoxic Ruthenium(II) and Osmium(II) Arene Cyclometalates.
- Authors: Riedl CA, Flocke LS, Hejl M, Roller A, Klose MH, Jakupec MA, Kandioller W, Keppler BK
- Issue date: 2017 Jan 3
- cis-Tetrachlorido-bis(indazole)osmium(iv) and its osmium(iii) analogues: paving the way towards the cis-isomer of the ruthenium anticancer drugs KP1019 and/or NKP1339.
- Authors: Büchel GE, Kossatz S, Sadique A, Rapta P, Zalibera M, Bucinsky L, Komorovsky S, Telser J, Eppinger J, Reiner T, Arion VB
- Issue date: 2017 Sep 12
- Highly potent half-sandwich iridium and ruthenium complexes as lysosome-targeted imaging and anticancer agents.
- Authors: Li J, Tian Z, Xu Z, Zhang S, Feng Y, Zhang L, Liu Z
- Issue date: 2018 Nov 13
- Half-sandwich Os(ii) and Ru(ii) bathophenanthroline complexes: anticancer drug candidates with unusual potency and a cellular activity profile in highly invasive triple-negative breast cancer cells.
- Authors: Pracharova J, Novohradsky V, Kostrhunova H, Štarha P, Trávníček Z, Kasparkova J, Brabec V
- Issue date: 2018 Sep 11