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

被引：33

作者：

Notaro, Anna ^{[1
]}

Frei, Angelo ^{[2
]}

Rubbiani, Riccardo ^{[2
]}

Jakubaszek, Marta ^{[1
,3
]}

Basu, Uttara ^{[1
]}

Koch, Severin ^{[2
]}

Mari, Cristina ^{[2
]}

Dotou, Mazzarine ^{[1
]}

Blacque, Olivier ^{[2
]}

Gouyon, Jeremie ^{[4
]}

Bedioui, Fethi ^{[4
]}

Rotthowe, Nils ^{[5
]}

Winter, Rainer F. ^{[5
]}

Goud, Bruno ^{[3
]}

Ferrari, Stefano ^{[6
,7
]}

Tharaud, Mickael ^{[8
]}

Rezacova, Martina ^{[9
]}

Humajova, Jana ^{[10
]}

Tomsik, Pavel ^{[9
]}

Gasser, Gilles ^{[1
]}

机构：

[1] PSL Univ, Inst Chem Life & Hlth Sci, Lab Inorgan Chem Biol, CNRS,Chim ParisTech, F-75005 Paris, France

[2] Univ Zurich, Dept Chem, CH-8057 Zurich, Switzerland

[3] PSL Univ, Inst Curie, CNRS UMR 144, F-75005 Paris, France

[4] PSL Univ, Inst Chem Life & Hlth Sci, Chim ParisTech,CNRS, Team Synth Electrochim Imagerie & Syst Analyt Dia, F-75005 Paris, France

[5] Univ Konstanz, Dept Chem, D-78457 Constance, Germany

[6] Univ Zurich, Inst Mol Canc Res, CH-8057 Zurich, Switzerland

[7] Czech Acad Sci, Inst Mol Genet, Prague 14300, Czech Republic

[8] Univ Paris, Inst Phys Globe Paris, CNRS, F-75005 Paris, France

[9] Charles Univ Prague, Fac Med Hradec Kralove, Dept Med Biochem, Hradec Kralove 50003, Czech Republic

[10] Charles Univ Prague, Fac Med 1, Inst Biophys & Informat, Prague 15006, Czech Republic

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2020年 / 63卷 / 10期

基金：

瑞士国家科学基金会;

关键词：

MULTICELLULAR TUMOR SPHEROIDS; ANTICANCER DRUG; CELLULAR UPTAKE; POLYPYRIDYL COMPLEXES; METAL-COMPLEXES; CANCER-THERAPY; DNA-BINDING; PHOTODYNAMIC THERAPY; CLINICAL DEVELOPMENT; CHARGE-DISTRIBUTION;

D O I：

10.1021/acs.jmedchem.0c00431

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：5568 / 5584

页数：17

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