Ruthenium complexes; Cancer; Drug; NMR; HRMAS; Structural studies; ruthenium-based anticancer drugs; NMR Spectroscopy
Giannini F, Furrer J, Ibao AF, Suss-Fink G, Therrien B, Zava O, Baquie M, Dyson PJ, Stepnicka P (2012), Highly cytotoxic trithiophenolatodiruthenium complexes of the type [(eta(6)-p-MeC6H4Pr (i) )(2)Ru-2(SC6H4-p-X)(3)](+): synthesis, molecular structure, electrochemistry, cytotoxicity, and glutathione oxidation potential, in JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
, 17(6), 951-960.
Giannini F, Paul LEH, Furrer J (2012), Insights into the Mechanism of Action and Cellular Targets of Ruthenium Complexes from NMR Spectroscopy, in CHIMIA
, 66(10), 775-780.
Giannini F, Suss-Fink G, Furrer J (2011), Efficient Oxidation of Cysteine and Glutathione Catalyzed by a Dinuclear Areneruthenium Trithiolato Anticancer Complex, in INORGANIC CHEMISTRY
, 50(21), 10552-10554.
Furrer M. A., Garci A., Denoyelle-di-Muro E., Trouillas P., Giannini F., Furrer J., Clavel C. M., Dyson P. J., Süss-Fink G., Therrien B., Synthesis, Characterisation, and in vitro Anticancer Activity of Hexanuclear Thiolato-Bridged Arene Ruthenium Metalla-Prisms, in Chem Eur J
Giannini F, Furrer J, Ibao A F, Süss-Fink G, Clavel C M, Dyson P J, Synthesis, characterization and in vitro anticancer activity of highly cytotoxic trithiolato diruthenium complexes of the type [(η6-Me¬C6H4-Pri)2Ru2(μ2-SR1)2(μ2-SR2)]+ contai¬ning different thiolato b, in J. Organomet Chem
Unless platinum drugs which are long known to be also toxic to normal tissues, ruthenium-based drugs possess several favorable chemical properties indicating that some of them may be strong candidates to supplant those platinum-based drugs.1 Currently, two ruthenium-based anticancer drugs, NAMI-A2 and KP10193 have successfully completed phase I clinical trials and have entered phase II. NAMI-A appeared to be effective against lung metastases, whereas KP1019 showed activity against colon carcinomas and their metastases.4 Thus, ruthenium-based complexes form a basis for rational anticancer drug design. Several studies have revealed that most arene ruthenium complexes bind covalently to DNA via the N atom of purines and cause cytoxicity by inhibiting cellular DNA synthesis.5 Moreover, ruthenium complexes have a strong affinity to cancer tissues because some of them were shown to bind readily to transferrin molecules.6 The ruthenium-transferrin complex is thought to be carried to tumor cells through transferrin receptors which are abundantly expressed on the surface of highly proliferative cells such as cancer cells.In recent years, colleagues in Neuchâtel as well as others have developed a series of ruthenium-based organometallic compounds offering efficacy toward cancer cells and giving the possibility to be activated by light.7-21 However, in these systems, the mode of action, uptake and the biological processes remain poorly understood. As such, our aims in this project are to define cellular targets of the compounds and elucidate some of their mechanistic profiles.We postulate that the uptake by cells of ruthenium compounds is mediated after binding to extracellular proteins, such as the transferrin or albumin.22 It is also known that DNA and cellular proteins are standard targets for ruthenium drugs. Thus, the detoxifying enzyme GST-?, the lysosomal hydrolases, the ubiquitin pathway and mitochondrial respiratory chain are also involved.10,23-25These possibilities will form the basis of our initial working hypotheses. On the long term our goals are to further improve the efficacy of these compounds by designing new structures based on the information acquired in the proposed research project.The success of this project requires a collaborative approach between the group of Julien Furrer, Georg Süss-Fink (UNINE), Paul J. Dyson (EPFL), and Karim Elbayed, Martial Piotto, Izzie Jacques Namer (University of Strasbourg and CHU Hautepierre). A PhD candidate is requested to perform over a two year period this research project at the UNINE and for several short stays at the University of Strasbourg.