Structure-Activity Relationships of Highly Cytotoxic Copper(II) Complexes with Modified Indolo[3,2-c]quinoline Ligands
- Author(s)
- Michael Primik, Simone Göschl, Michael Jakupec, Alexander Roller, Bernhard Keppler, Vladimir Arion
- Abstract
A number of indolo[3,2-c]quinolines were synthesized and modified at the lactam unit to provide a peripheral binding site able to accommodate metal ions. Potentially tridentate ligands HL1a-HL4a and HL1b-HL4b were reacted with copper(II) chloride in isopropanol/methanol to give novel five-coordinate copper(II) complexes [Cu(HL1a-4a)Cl-2] and [Cu(HL1b-4b)Cl-2]. In addition, a new complex [Cu(HL5b)Cl-2] and two previously reported compounds [Cu(HL6a)Cl-2] and [Cu(HL6b)Cl-2] with modified paullone ligands HL5b, HL6a, and HL6b, which can be regarded as close analogues of indoloquinolines HL1b, HL4a, and HL4b, in which the pyridine ring was formally substituted by a seven-membered azepine ring, were synthesized for comparison. The new ligands and copper(II) complexes were characterized by H-1 and C-13 NMR, IR and electronic absorption spectroscopy, ESI mass spectrometry, magnetic susceptibility measurements in solution at 298 K ([Cu(HL1a)Cl-2] and [Cu(HL4b)Cl-2]), and X-ray crystallography ([Cu(HL3b)Cl-2] center dot 3DMF, [Cu(HL4b)Cl-2] center dot 2.4DMF, HL5b and [Cu(HL5b)Cl-2] center dot 0.5CH(3)OH). All complexes were tested for cytotoxicity in the human cancer cell lines CH1 (ovarian carcinoma), A549 (non-small cell lung cancer), and SW480 (colon carcinoma). The compounds are highly cytotoxic, with IC50 values ranging from nanomolar to very low micromolar concentrations. Substitution of the seven-membered azepine ring in paullones by a pyridine ring resulted in a six- to nine-fold increase of cytotoxicity in SW480 cells. Electron-releasing or electron-withdrawing substituents in position 8 of the indoloquinoline backbone do not exert any effect on cytotoxicity of copper(II) complexes, whereas copper(II) compounds with Schiff bases obtained from 2-acetylpyridine and indoloquinoline hydrazines are 10 to 50 times more cytotoxic than those with ligands prepared from 2-formylpyridine and indoloquinoline hydrazines.
- Organisation(s)
- Department of Inorganic Chemistry
- Journal
- Inorganic Chemistry
- Volume
- 49
- Pages
- 11084-11095
- No. of pages
- 12
- ISSN
- 0020-1669
- DOI
- https://doi.org/10.1021/ic101633z
- 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/b31f6e6b-c1c1-40c2-8109-25c845b9628f