Platinum(IV) Complexes Featuring Axial Michael Acceptor Ligands - Synthesis, Characterization, and Cytotoxicity
- Author(s)
- Nadine S. Sommerfeld, Daniel Strohhofer, Klaudia Cseh, Sarah Theiner, Michael A. Jakupec, Gunda Koellensperger, Mathea Sophia Galanski, Bernhard K. Keppler
- Abstract
A series of four new (1R,2R)-cyclohexane-1,2-diamineplatinum(IV) complexes featuring axial Michael acceptor ligands on the basis of the thiol-affine maleimide moiety is presented. The complexes vary in their equatorial ligand sphere (bearing additionally one bidentate oxalate ligand or two monodentate acetate ligands) as well as in their axial Michael acceptor unit (pyrroledione, methylenedioxopyrrolidine, methyldioxodihydropyrrole). Hydrolysis, reaction behavior towards cysteine in water and phosphate buffered saline, and towards human serum albumin was monitored using HPLC,
1H NMR spectroscopy and size exclusion chromatography coupled to ICP-MS, respectively. Reaction with cysteine at pH = 7 was instant and complete within three minutes. In contrast, derivatization of the maleimide moiety resulted in decreased binding kinetics of the complex, especially within the first hour of incubation with human serum. In stability studies using analytical HPLC and
1H NMR spectroscopic measurements, we observed a concentration-dependent stability for the maleimide-containing complex 3 and the methyl derivatized compound 4. A significant increase in hydrolysis rate (up to 100 %) was found at 0.01 mm in comparison to a solution of 1 mm. In contrast, the exocyclic derivatization (5, 6) led to an overall stability in water. The antiproliferative behavior revealed IC
50 values mainly in the low micromolar range for all complexes.
- Organisation(s)
- Department of Inorganic Chemistry, Department of Analytical Chemistry, Mass Spectrometry Centre, NMR Centre
- Journal
- European Journal of Inorganic Chemistry
- Volume
- 2017
- Pages
- 4049-4054
- No. of pages
- 6
- ISSN
- 1434-1948
- DOI
- https://doi.org/10.1002/ejic.201700753
- Publication date
- 09-2017
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry
- Keywords
- 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/954f732d-1f61-4832-8cd4-24102b76f2b4