1. Anticancer Agents: Does a Phosphonium Behave Likea Gold(I) Phosphine Complex? Let a “Smart” Probe Answer!
- Author
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Moussa Ali, Lucile Dondaine, Anais Adolle, Carla Sampaio, Florian Chotard, Philippe Richard, Franck Denat, Ali Bettaieb, Pierre Le Gendre, Véronique Laurens, Christine Goze, Catherine Paul, and Ewen Bodio
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ANTINEOPLASTIC agents , *PHOSPHONIUM compounds , *GOLD compounds , *MOLECULAR probes , *ANTIRHEUMATIC agents , *DRUG administration - Abstract
Gold phosphine complexes, such asauranofin, have been recognizedfor decades as antirheumatic agents. Clinical trials are now underwayto validate their use in anticancer or anti-HIV treatments. However,their mechanisms of action remain unclear. A challenging questionis whether the gold phosphine complex is a prodrug that is administeredin an inactive precursor form or rather that the gold atom remainsattached to the phosphine ligand during treatment. In this study,we present two novel gold complexes, which we compared to auranofinand to their phosphonium analogue. The chosen ligand is a phosphine-basedsmart probe, whose strong fluorescence depends on the presence ofthe gold atom. The in vitro biologicalaction of the gold complexes and the phosphonium derivative were investigated,and a preliminary in vivo study in healthy zebrafish larvae allowedus to evaluate gold complex biodistribution and toxicity. The differentanalyses carried out showed that these gold complexes were stableand behaved differently from phosphonium and auranofin, both in vitroand in vivo. Two-photon microscopy experiments demonstrated that thecellular targets of these gold complexes are not the same as thoseof the phosphonium analogue. Moreover, despite similar IC50values in some cancer cell lines, gold complexes displayed a lowtoxicity in vivo, in contrast to the phosphonium salt. They are thereforesuitable for future in vivo investigations. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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