Organometallic indolo[3,2-c]quinolines versus indolo[3,2-d]benzazepines: synthesis, structural and spectroscopic characterization, and biological efficacy
- Author(s)
- Lukas Filak, Gerhard Mühlgassner, Michael Jakupec, Petra Heffeter, Walter Berger, Vladimir Arion, Bernhard Keppler
- Abstract
The synthesis of ruthenium(II) and osmium(II) arene complexes with the closely related indolo[3,2-c]quinolines N-(11 H-indolo[3,2-c]quinolin-6-yl)-ethane-1,2-diamine (L1) and N?-(11 H-indolo[3,2-c]quinolin-6-yl)-N, N-dimethylethane-1,2-diamine (L2) and indolo[3,2-d]benzazepines N-(7,12-dihydroindolo-[3,2-d][1]benzazepin-6-yl)-ethane-1,2-diamine (L3) and N?-(7,12-dihydroindolo-[3,2-d][1]benzazepin-6-yl)-N, N-dimethylethane-1,2-diamine (L4) of the general formulas [(?6-p-cymene)MII(L1)Cl]Cl, where M is Ru (4) and Os (6), [(?6-p-cymene)MII(L2)Cl]Cl, where M is Ru (5) and Os (7), [(?6-p-cymene)MII(L3)Cl]Cl, where M is Ru (8) and Os (10), and [(?6-p-cymene)MII(L4)Cl]Cl, where M is Ru (9) and Os (11), is reported. The compounds have been comprehensively characterized by elemental analysis, electrospray ionization mass spectrometry, spectroscopy (IR, UV-vis, and NMR), and X-ray crystallography (L1·HCl, 4·H2O, 5, and 9·2.5H2O). Structure-activity relationships with regard to cytotoxicity and cell cycle effects in human cancer cells as well as cyclin-dependent kinase (cdk) inhibition and DNA intercalation in cell-free settings have been established. The metal-free indolo[3,2-c]quinolines inhibit cancer cell growth in vitro, with IC50 values in the high nanomolar range, whereas those of the related indolo[3,2-d]benzazepines are in the low micromolar range. In cell-free experiments, these classes of compounds inhibit the activity of cdk2/cyclin E, but the much higher cytotoxicity and stronger cell cycle effects of indoloquinolines L1 and 7 are not paralleled by a substantially higher kinase inhibition compared with indolobenzazepines L4 and 11, arguing for additional targets and molecular effects, such as intercalation into DNA.
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Medizinische Universität Wien
- Journal
- Journal of Biological Inorganic Chemistry
- Volume
- 15
- Pages
- 903-918
- No. of pages
- 16
- ISSN
- 0949-8257
- DOI
- https://doi.org/10.1007/s00775-010-0653-y
- Publication date
- 2010
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/7966c958-7bd4-45d8-8ad1-e9615e7aebc6