title: Gold(I) NHC-based homo- and heterobimetallic complexes: synthesis, characterization and evaluation as potential anticancer agents.
abstract: While N-heterocyclic carbenes (NHC) are ubiquitous ligands in catalysis for organic or industrial syntheses, their potential to form transition metal complexes for medicinal applications has still to be exploited. Within this frame, we synthesized new homo- and heterobimetallic complexes based on the Au(I)-NHC scaffold. The compounds were synthesized via a microwave-assisted method developed in our laboratories using Au(I)-NHC complexes carrying a pentafluorophenol ester moiety and another Au(I) phosphane complex or a bipyridine ligand bearing a pendant amine function. Thus, we developed two different methods to prepare homo- and heterobimetallic complexes (Au(I)/Au(I) or Au(I)/Cu(II), Au(I)/Ru(II), respectively). All the compounds were fully characterized by several spectroscopic techniques including far infrared, and were tested for their antiproliferative effects in a series of human cancer cells. They showed moderate anticancer properties. Their toxic effects were also studied ex vivo using the precision-cut tissue slices (PCTS) technique and initial results concerning their reactivity with the seleno-enzyme thioredoxin reductase were obtained.
authors.affiliation: Institut de Chimie Moléculaire, UMR 6302 CNRS Université de Bourgogne Franche Comté, 9 Avenue A. Savary, 21078, Dijon, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Bertrand
authors.forename: Anna
authors.initials: A
authors.lastname: Citta
authors.forename: Inge L
authors.initials: IL
authors.lastname: Franken
authors.forename: Michel
authors.initials: M
authors.lastname: Picquet
authors.forename: Alessandra
authors.initials: A
authors.lastname: Folda
authors.forename: Valeria
authors.initials: V
authors.lastname: Scalcon
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Rigobello
authors.forename: Pierre
authors.initials: P
authors.lastname: Le Gendre
authors.forename: Angela
authors.initials: A
authors.lastname: Casini
authors.forename: Ewen
authors.initials: E
authors.lastname: Bodio
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003300:Copper; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000627:therapeutic use*; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors; D006801:Humans; D050607:Organogold Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use; D051381:Rats; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013863:Thioglucosides / Q000138:chemical synthesis* / Q000627:therapeutic use*; D054481:Thioredoxin Reductase 1 / Q000037:antagonists & inhibitors; D054482:Thioredoxin Reductase 2 / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D050607:Organogold Compounds; D029701:Saccharomyces cerevisiae Proteins; D013863:Thioglucosides; D003300:Copper; D005980:Glutathione Reductase; D054481:Thioredoxin Reductase 1; D054482:Thioredoxin Reductase 2; C516126:Txnrd1 protein, rat; C516129:Txnrd2 protein, rat