Naphthoquinone-derived tridentate Ru(ii) and Os(ii) organometallics with exceptional cytotoxicity: synthesis, characterization, stability in aqueous solution and biological <i>in vitro</i> evaluation
- Author(s)
- Alexander Rosner, Heiko Geisler, Michaela Hejl, Mathias Gradl, Anton A. Legin, Alexander Prado-Roller, Michael A. Jakupec, Petra Heffeter, Walter Berger, Bernhard K. Keppler, Wolfgang Kandioller
- Abstract
In this work, a panel of twelve ruthenium(ii) and osmium(ii) derived N,O,O-tridentate complexes (1a–2f) with a variation of longer, branched and unbranched alkyl substituents was synthesized and characterized via NMR, HRMS, elemental analysis and X-ray diffraction analysis. Resilience to dissociation in biologically relevant solution was determined over 72 hours, revealing most stable complexes to derive from naphthoquinones bearing tert-butyl- and neopentyl-substituents. Osmium derived complexes were found to be generally more inert than their ruthenium counterparts. Cytotoxicity was examined, revealing IC50 values in the nanomolar to lower micromolar range for derivatives 1a–2f in three human cancer lines and a typical pattern of selectivity for SW480 cells. Cellular accumulation correlated with in vitro cytotoxicity; however, longer and branched substituents did not improve the cellular accumulation. Cell cycle experiments showed consistent cell cycle inhibition in both SW480 and CH1/PA-1 cells for ruthenium-based compounds only. Indolamin-2,3-dioxygenase 1 (IDO1) inhibition assays in SKOV3 cells revealed significant inhibitory potential of Ru-Ethyl, in clear distinction to other ruthenium and osmium complexes.
- Organisation(s)
- Department of Inorganic Chemistry, Core Facility Crystal Structure Analysis
- External organisation(s)
- Vienna Doctoral School in Chemistry (DoSChem), Research Cluster Translational Cancer Therapy Research, Medizinische Universität Wien
- Journal
- Dalton Transactions
- Volume
- 55
- Pages
- 2254-2268
- No. of pages
- 15
- ISSN
- 1477-9226
- DOI
- https://doi.org/10.1039/d5dt01649e
- Publication date
- 02-2026
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 104002 Analytical chemistry, 104004 Chemical biology, 301904 Cancer research
- ASJC Scopus subject areas
- Inorganic Chemistry
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/79a5c230-5e2a-4631-a0f4-9097f5f3e239