Ruthenium(II) Complex Containing a Redox-Active Semiquinonate Ligand as a Potential Chemotherapeutic Agent: From Synthesis to <i>In Vivo</i> Studies
Anna Notaro, Angelo Frei, Riccardo Rubbiani, Marta Jakubaszek, Uttara Basu, Severin Koch, Cristina Mari, Mazzarine Dotou, Olivier Blacque, Jérémie Gouyon, Fethi Bédioui, Nils Rotthowe, Rainer F. Winter, Bruno Goud, Stefano Ferrari, Mickaël Tharaud, Martina Řezáčová, Jana Humajová, Pavel Tomšík, Gilles Gasser
Abstract
Chemotherapy remains one of the dominant treatments to cure cancer. However, due to the many inherent drawbacks, there is a search for new chemotherapeutic drugs. Many classes of compounds have been investigated over the years 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 with the catecholate moiety. Experimental evidence (e.g., X-ray crystallography, electron paramagnetic resonance, electrochemistry) demonstrates that the semiquinonate is the preferred oxidation state of the dioxo ligand in this complex. The biological activity of Ru-sq was then scrutinized in vitro and in vivo, and the results highlight the promising potential of this complex as a chemotherapeutic agent against cancer.