title: New Luminescent Polynuclear Metal Complexes with Anticancer Properties: Toward Structure-Activity Relationships.
abstract: A series of new heterodinuclear luminescent complexes with two different organic ligands have been synthesized and characterized. A luminescent Ru(II)(polypyridine) moiety and a metal-based anticancer fragment (AuCl, (p-cymene)RuCl2, (p-cymene)OsCl2, (Cp*)RhCl2, or Au-thioglucose) are the two general features of these complexes. All of the bimetallic compounds have been evaluated for their antiproliferative properties in vitro in human cancer cell lines. Only the complexes containing an Au(I) fragment exhibit antiproliferative activity in the range of cisplatin or higher. The photophysical and electrochemical properties of the bimetallic species have been investigated, and fluorescence microscopy experiments have been performed successfully. The most promising bimetallic cytotoxic complexes (i.e., with the Au-thioglucose scaffold) have shown to be easily taken up by cancer cells at 37 °C in the cytoplasm or in specific organelles. Interestingly, experiments repeated at 4 °C showed no uptake of the bimetallic species inside cells, which confirms involvement of active transport processes. To evaluate the role of glucose transporters in the cell uptake of the gold complexes, inhibition of the GluT-1 (glucose transporter isoform with high level of expression in cancer cells) was achieved, showing only scarce influence on the compounds' uptake. Finally, the observed absence of interactions with nucleic acid model structures suggests that the gold compounds may have different intracellular targets with respect to cisplatin.
authors: School of Chemistry, Cardiff University , Main Building, Park Place, CF10 3AT Cardiff, United Kingdom.|Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR 6302 CNRS, Université de Bourgogne Franche-Comté , 9 avenue A. Savary, BP47870, 21078 Dijon, France.
authors: Margot
authors: M
authors: Wenzel
authors: Department of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute of Pharmacy, University of Groningen , Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors: Andreia
authors: A
authors: de Almeida
authors: Department of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute of Pharmacy, University of Groningen , Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors: Emilia
authors: E
authors: Bigaeva
authors: School of Chemistry, National University of Ireland Galway , University Road, Galway, Ireland.
authors: Paul
authors: P
authors: Kavanagh
authors: Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR 6302 CNRS, Université de Bourgogne Franche-Comté , 9 avenue A. Savary, BP47870, 21078 Dijon, France.
authors: Michel
authors: M
authors: Picquet
authors: Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR 6302 CNRS, Université de Bourgogne Franche-Comté , 9 avenue A. Savary, BP47870, 21078 Dijon, France.
authors: Pierre
authors: P
authors: Le Gendre
authors: Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR 6302 CNRS, Université de Bourgogne Franche-Comté , 9 avenue A. Savary, BP47870, 21078 Dijon, France.
authors: Ewen
authors: E
authors: Bodio
authors: School of Chemistry, Cardiff University , Main Building, Park Place, CF10 3AT Cardiff, United Kingdom.|Department of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute of Pharmacy, University of Groningen , Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors: Angela
authors: A
authors: Casini
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry*; D004247:DNA / Q000187:drug effects; D006801:Humans; D049449:Luminescence; D009682:Magnetic Resonance Spectroscopy; D008670:Metals / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008670:Metals; D004247:DNA