title: Anticancer Agents: Does a Phosphonium Behave Like a Gold(I) Phosphine Complex? Let a "Smart" Probe Answer!
abstract: Gold phosphine complexes, such as auranofin, have been recognized for decades as antirheumatic agents. Clinical trials are now underway to validate their use in anticancer or anti-HIV treatments. However, their mechanisms of action remain unclear. A challenging question is whether the gold phosphine complex is a prodrug that is administered in an inactive precursor form or rather that the gold atom remains attached to the phosphine ligand during treatment. In this study, we present two novel gold complexes, which we compared to auranofin and to their phosphonium analogue. The chosen ligand is a phosphine-based smart probe, whose strong fluorescence depends on the presence of the gold atom. The in vitro biological action of the gold complexes and the phosphonium derivative were investigated, and a preliminary in vivo study in healthy zebrafish larvae allowed us to evaluate gold complex biodistribution and toxicity. The different analyses carried out showed that these gold complexes were stable and behaved differently from phosphonium and auranofin, both in vitro and in vivo. Two-photon microscopy experiments demonstrated that the cellular targets of these gold complexes are not the same as those of the phosphonium analogue. Moreover, despite similar IC50 values in some cancer cell lines, gold complexes displayed a low toxicity in vivo, in contrast to the phosphonium salt. They are therefore suitable for future in vivo investigations.
authors.affiliation: †Institut de Chimie Moléculaire de l'Université de Bourgogne, ICMUB UMR CNRS 6302, 9 Avenue Alain Savary, BP 47870, Dijon Cedex, 21078, France.
authors.forename: Moussa
authors.initials: M
authors.lastname: Ali
authors.affiliation: ‡École Pratique des Hautes Études, Paris, F-75014, France.|§EA7269 EPHE-University of Burgundy, University of Burgundy, Dijon, F-21000, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Dondaine
authors.affiliation: ‡École Pratique des Hautes Études, Paris, F-75014, France.|§EA7269 EPHE-University of Burgundy, University of Burgundy, Dijon, F-21000, France.
authors.forename: Anais
authors.initials: A
authors.lastname: Adolle
authors.affiliation: ‡École Pratique des Hautes Études, Paris, F-75014, France.|§EA7269 EPHE-University of Burgundy, University of Burgundy, Dijon, F-21000, France.
authors.forename: Carla
authors.initials: C
authors.lastname: Sampaio
authors.affiliation: †Institut de Chimie Moléculaire de l'Université de Bourgogne, ICMUB UMR CNRS 6302, 9 Avenue Alain Savary, BP 47870, Dijon Cedex, 21078, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Chotard
authors.affiliation: †Institut de Chimie Moléculaire de l'Université de Bourgogne, ICMUB UMR CNRS 6302, 9 Avenue Alain Savary, BP 47870, Dijon Cedex, 21078, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Richard
authors.affiliation: †Institut de Chimie Moléculaire de l'Université de Bourgogne, ICMUB UMR CNRS 6302, 9 Avenue Alain Savary, BP 47870, Dijon Cedex, 21078, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Denat
authors.affiliation: ‡École Pratique des Hautes Études, Paris, F-75014, France.|§EA7269 EPHE-University of Burgundy, University of Burgundy, Dijon, F-21000, France.
authors.forename: Ali
authors.initials: A
authors.lastname: Bettaieb
authors.affiliation: †Institut de Chimie Moléculaire de l'Université de Bourgogne, ICMUB UMR CNRS 6302, 9 Avenue Alain Savary, BP 47870, Dijon Cedex, 21078, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Le Gendre
authors.affiliation: ‡École Pratique des Hautes Études, Paris, F-75014, France.|§EA7269 EPHE-University of Burgundy, University of Burgundy, Dijon, F-21000, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Laurens
authors.affiliation: †Institut de Chimie Moléculaire de l'Université de Bourgogne, ICMUB UMR CNRS 6302, 9 Avenue Alain Savary, BP 47870, Dijon Cedex, 21078, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Goze
authors.affiliation: ‡École Pratique des Hautes Études, Paris, F-75014, France.|§EA7269 EPHE-University of Burgundy, University of Burgundy, Dijon, F-21000, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Paul
authors.affiliation: †Institut de Chimie Moléculaire de l'Université de Bourgogne, ICMUB UMR CNRS 6302, 9 Avenue Alain Savary, BP 47870, Dijon Cedex, 21078, France.
authors.forename: Ewen
authors.initials: E
authors.lastname: Bodio
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001310:Auranofin / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D007814:Larva / Q000187:drug effects* / Q000254:growth & development; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010720:Phosphines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D015027:Zebrafish / Q000254:growth & development
chemical_list: D000970:Antineoplastic Agents; D018501:Antirheumatic Agents; D008024:Ligands; D010720:Phosphines; D001310:Auranofin; D006046:Gold; C044646:phosphine