Tuning the hydrophobicity of ruthenium(II)-arene (RAPTA) drugs to modify uptake, biomolecular interactions and efficacy
Scolaro, Claudine; Chaplin, Adrian B.; Hartinger, Christian G.; Bergamo, Alberta; Cocchietto, Moreno; Keppler, Bernhard K.; Sava, Gianni; Dyson, Paul J.
2007

Abstract

The antitumor activity of the organometallic ruthenium(II)-arene mixed phosphine complexes, [Ru(h6-p-cymene)Cl(PTA)(PPh3)]BF4 1b and [Ru(h6-C6H5CH2CH2OH)Cl(PTA)(PPh3)]BF4 2b (PTA = 1,3,5-triaza-7-phosphaadamantane), have been evaluated in vitro and compared to their RAPTA analogs, [Ru(h6-p-cymene)Cl2(PTA)] 1a and [Ru(h6-C6H5CH2CH2OH)Cl2(PTA)] 2a. The results show that the addn. of the PPh3 ligand to 2a increases the cytotoxicity towards the TS/A adenocarcinoma cancer cells, which correlates with increased uptake, but also increases cytotoxicity to non-tumorigenic HBL-100 cells, thus decreasing selectivity. The decrease in selectivity has been correlated to increased DNA interactions relative to proteins, demonstrated by reactivity of the compds. with a 14-mer oligonucleotide and the model proteins ubiquitin and cytochrome-c.

Details

Title Tuning the hydrophobicity of ruthenium(II)-arene (RAPTA) drugs to modify uptake, biomolecular interactions and efficacy
Author(s) Scolaro, Claudine ; Chaplin, Adrian B. ; Hartinger, Christian G. ; Bergamo, Alberta ; Cocchietto, Moreno ; Keppler, Bernhard K. ; Sava, Gianni ; Dyson, Paul J.
Published in Dalton Transactions
Volume 43
Pages 5065-5072
Date 2007
DOI https://doi.org/10.1039/b705449a
Other identifier(s) DAR: 11500
View record in Web of Science
Laboratories LCOM
Record Appears in Scientific production and competences > SB - School of Basic Sciences > ISIC - Institute of Chemical Sciences and Engineering > LCOM - Laboratory of Organometallic and Medicinal Chemistry
Peer-reviewed publications
Work produced at EPFL
Journal Articles
Published
Record creation date 2007-12-13

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