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Ruthenium(II) Complex Containing a Redox-Active Semiquinonate Ligand as a Potential Chemotherapeutic Agent: From Synthesis to In Vivo Studies.
Notaro, Anna; Frei, Angelo; Rubbiani, Riccardo; Jakubaszek, Marta; Basu, Uttara; Koch, Severin; Mari, Cristina; Dotou, Mazzarine; Blacque, Olivier; Gouyon, Jérémie; Bedioui, Fethi; Rotthowe, Nils; Winter, Rainer F; Goud, Bruno; Ferrari, Stefano; Tharaud, Mickaël; Rezácová, Martina; Humajová, Jana; Tomsík, Pavel; Gasser, Gilles.
Afiliação
  • Notaro A; Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology, F-75005 Paris, France.
  • Frei A; Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
  • Rubbiani R; Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
  • Jakubaszek M; Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology, F-75005 Paris, France.
  • Basu U; Institut Curie, PSL University, CNRS UMR 144, F-75005 Paris, France.
  • Koch S; Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology, F-75005 Paris, France.
  • Mari C; Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
  • Dotou M; Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
  • Blacque O; Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology, F-75005 Paris, France.
  • Gouyon J; Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
  • Bedioui F; Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Team Synthèse, Electrochimie, Imagerie et Systèmes Analytiques pour le Diagnostic, F-75005 Paris, France.
  • Rotthowe N; Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Team Synthèse, Electrochimie, Imagerie et Systèmes Analytiques pour le Diagnostic, F-75005 Paris, France.
  • Winter RF; Department of Chemistry, University of Konstanz, Universitätsstrasse 10, D-78457 Konstanz, Germany.
  • Goud B; Department of Chemistry, University of Konstanz, Universitätsstrasse 10, D-78457 Konstanz, Germany.
  • Ferrari S; Institut Curie, PSL University, CNRS UMR 144, F-75005 Paris, France.
  • Tharaud M; Institute of Molecular Cancer Research, University of Zurich, CH-8057 Zurich, Switzerland.
  • Rezácová M; Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, 143 00 Prague, Czech Republic.
  • Humajová J; Université de Paris, Institut de physique du Globe de Paris, CNRS, F-75005 Paris, France.
  • Tomsík P; Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, 500 03 Hradec Kralove, Czech Republic.
  • Gasser G; Institute of Biophysics and Informatics, First Faculty of Medicine, Charles University in Prague, 150 06 Prague, Czech Republic.
J Med Chem ; 63(10): 5568-5584, 2020 05 28.
Article em En | MEDLINE | ID: mdl-32319768
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Quinonas / Rutênio / Antineoplásicos Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Quinonas / Rutênio / Antineoplásicos Idioma: En Ano de publicação: 2020 Tipo de documento: Article