Metal-Arene Complexes with Indolo[3,2-c]-quinolines: Effects of Ruthenium vs Osmium and Modifications of the Lactam Unit on Intermolecular Interactions, Anticancer Activity, Cell Cycle, and Cellular Accumulation

Author(s)
Lukas Filak, Simone Göschl, Petra Heffeter, Alexander Egger, Michael Jakupec, Bernhard Keppler, Walter Berger, Vladimir Arion
Abstract

Six novel ruthenium(II)- and osmium(II)- arene complexes with three modified indolo[3,2-c]quinolines have been synthesized in situ starting from 2-amino-indoloquinolines and 2-pyridinecarboxaldehyde in the presence of [M(p-cymene)Cl-2](2) (M = Ru, Os) in ethanol. All complexes have been characterized by elemental analysis, spectroscopic techniques (H-1, C-13 NMR, IR, UV vis), and ESI mass spectrometry, while four complexes were investigated by X-ray diffraction. The complexes have been tested for antiproliferative activity in vitro in A549 (non-small cell lung), 5W480 (colon), and CHI (ovarian) human cancer cell lines and showed IC50 values between 1.3 and >80 mu M. The effects of Ru vs Os and modifications of the lactam unit on intermolecular interactions, antiproliferative activity, and cell cycle are reported. One ruthenium complex and its osmium analogue have been studied for anticancer activity in vivo applied both intraperitoneally and orally against the murine colon carcinoma model CT-26. Interestingly, the osmium(II) complex displayed significant growth-inhibitory activity in contrast to its ruthenium counterpart, providing stimuli for further investigation of this class of compounds as potential antitumor drugs.

Organisation(s)
Department of Inorganic Chemistry
External organisation(s)
Medizinische Universität Wien
Journal
Organometallics
Volume
32
Pages
903-914
No. of pages
12
ISSN
0276-7333
DOI
https://doi.org/10.1021/om3012272
Publication date
2013
Peer reviewed
Yes
Austrian Fields of Science 2012
104003 Inorganic chemistry, 301 Medical-Theoretical Sciences, Pharmacy
Sustainable Development Goals
SDG 3 - Good Health and Well-being
Portal url
https://ucrisportal.univie.ac.at/en/publications/428634cb-c677-41a0-a576-a9613f6efdcc