A SAR Study of Novel Antiproliferative Ruthenium and Osmium Complexes with Quinoxalinone Ligands in Human Cancer Cell Lines
- Author(s)
- Werner Ginzinger, Gerhard Mühlgassner, Vladimir Arion, Michael Jakupec, Alexander Roller, Mathea Sophia Galanski, Michael Reithofer, Walter Berger, Bernhard Keppler
- Abstract
A series of ruthenium(II) arene complexes with 3-(1H-berairnidazol-2-yl)-1H-quinoxalin-2-one, bearing pharmacophoric groups of known protein kinase inhibitors, and related benzoxazole and benzothiazole derivatives have been synthesized. In addition, the corresponding osmium complexes of the unsubstituted ligands have also been prepared. The compounds have been characterized by NMR, UV-vis, and IR spectroscopy, ESI mass spectrometry, elemental analysis, and by X-ray crystallography. Antiproliferative activity in three human cancer cell lines (AS49, CH1, SW480) was determined by MTT assays, yielding IC50 values of 6-60 mu M for three unsubstituted metal-free ligands, whereas values for the metal complexes vary in a broad range from 0.3 to 140 mu M. Complexation with osmium of quinoxalinone derivatives with benzimidazole or benzothiazole results in a more consistent increase in cytotoxicity than complexation with ruthenium. For selected compounds, the capacity to induce apoptosis was confirmed by fluorescence microscopy and flow-cytometric analysis, whereas cell cycle effects are only moderate.
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Medizinische Universität Wien
- Journal
- Journal of Medicinal Chemistry
- Volume
- 55
- Pages
- 3398-3413
- No. of pages
- 16
- ISSN
- 0022-2623
- DOI
- https://doi.org/10.1021/jm3000906
- Publication date
- 2012
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 301305 Medical chemistry
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/2352324e-48fb-454b-be9c-26eb56954d5b