A Ruthenium(II) Complex Containing a Redox-Active Semiquinonate Ligand as Potential Chemotherapeutic Agent: From Synthesis to In Vivo Studies

Anna Notaro (1) , Angelo Frei , Riccardo Rubbiani (2) , Marta Jakubaszek (1) , Uttara Basu (1) , Severin Koch (2) , Cristina Mari (2) , Mazzarine Dotou (1) , Olivier Blacque (2) , Jeremie Gouyon , Fethi Bedioui (3) , Nils Rotthowe , Rainer F Winter , Bruno Goud (4) , Stefano Ferrari , Mickaël Tharaud (5) , Martina Rezácová , Jana Humajová , Pavel Tomšík , Gilles Gasser (1)

1 ENSCP - Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL
2 UZH - Universität Zürich [Zürich] = University of Zurich
3 PSL - Université Paris Sciences et Lettres
4 Mécanismes moléculaires du transport intracellulaire
5 IPGP - Institut de Physique du Globe de Paris

Chemotherapy remains one of the dominant treatments to cure cancer. However, due to the many inherent drawbacks, there is a surge for new chemotherapeutic drugs. Many classes of compounds have been investigated over the years in order to discover new targets and synergistic mechanisms of action including multicellular targets. In this work, we designed a new chemotherapeutic drug candidate against cancer, namely [Ru(DIP)2(sq)]PF6 (Ru-sq) (DIP = 4,7-diphenyl-1,10-phenanthroline; sq = semiquinonate ligand). The aim was to combine the great potential expressed by Ru(II) polypyridyl complexes and the singular redox and biological properties associated to the catecholate moiety. Experimental evidences (e.g. X-ray crystallography, electron paramagnetic resonance, electrochemistry) demonstrate that the semiquinonate is the preferred oxidation state of the dioxo ligand in this complex. The biological activity of Ru-sq was then scrutinised in vitro and in vivo, and the results highlight the auspicious potential of this complex as a chemotherapeutic agent against cancer.

Mots clés: Bioinorganic Chemistry; Cancer; Medicinal Inorganic Chemistry

Domaines: Chimie; Chimie thérapeutique

Anna Notaro, Angelo Frei, Riccardo Rubbiani, Marta Jakubaszek, Uttara Basu, et al.. A Ruthenium(II) Complex Containing a Redox-Active Semiquinonate Ligand as Potential Chemotherapeutic Agent: From Synthesis to In Vivo Studies. Journal of Medicinal Chemistry, 2020, ⟨10.1021/acs.jmedchem.0c00431⟩. ⟨hal-02551981⟩