Influence of Structural Variation on the Anticancer Activity of RAPTA-Type Complexes: ptn versus pta

Author(s)
Anna K. Renfrew, Andrew Phillips, Alexander Egger, Christian Hartinger, Sylvain S. Bosquain, Alexey Nazarov, Bernhard Keppler, Luca Gonsalvi, Maurizio Peruzzini, Paul J. Dyson
Abstract

A series of compounds of the general formula [M(?6-arene) (ptn)Cl]X (M = Ru, Os; arene = p-cymene, benzene, toluene, hexamethylbenzene; ptn = 3,7-dimethyl-7-phospha-l,3,5-triazabicyclo[3.3.1]nonane; X = Cl -, BF4-) have been prepared and characterized spectroscopically. X-ray diffraction was additionally used to characterize four of the complexes in the solid state. The hydrolysis of the compounds was studied, and their cytotoxicity was evaluated in A2780 ovarian cancer cells and found to be comparable to that of known RAPTA complexes based on 7-phospha-l,3,5-triazatricyclo[3.3.1.1]decane (pta). The reactivity of the complexes toward double-stranded oligonucleotides and the model protein ubiquitin was investigated using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and gel electrophoresis, demonstrating a strong preference for the formation of covalent adducts with the protein. Correlations among compound structure, hydrolysis, biomolecular interactions, and cytotoxicity are established.

Organisation(s)
Department of Inorganic Chemistry
External organisation(s)
École polytechnique fédérale de Lausanne, Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", CNR
Journal
Organometallics
Volume
28
Pages
1165-1172
No. of pages
8
ISSN
0276-7333
DOI
https://doi.org/10.1021/om800899e
Publication date
2009
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/5f2c23b7-7b66-4449-a1ab-679b1fde8f99