Bisphosphonate sequestering agents. Synthesis and preliminary evaluation for in vitro and in vivo uranium(VI) chelation.

Marcin Sawicki , Delphine Lecerclé , Gérard Grillon , Béatrice Le Gall , Anne-Laure Sérandour , Jean-Luc Poncy , Théodorine Bailly , Ramon Burgada , Marc Lecouvey , Vincent Chaleix (1) , Antoine Leydier , S Pellet-Rostaing (2) , Eric Ansoborlo , Frédéric Taran (3)

1 LCSN - Laboratoire de Chimie des Substances Naturelles
2 ICBMS - Institut de Chimie et Biochimie Moléculaires et Supramoléculaires
3 SCBM - Service de Chimie Bio-Organique et de Marquage

A library of bisphosphonate-based ligands was prepared using solution-phase parallel synthesis and tested for its uranium-binding properties. With the help of a screening method, based on a chromophoric complex displacement procedure, 23 dipodal and tripodal chelates bearing bisphosphonate chelating functions were found to display very high affinity for the uranyl ion and were selected for evaluation of their in vivo uranyl-removal efficacy. Among them, 11 ligands induced a huge modification of the uranyl biodistribution by deviating the metal from kidney and bones to liver. Among the other ligands, the most potent was the dipodal bisphosphonate 3C which reduced the retention of uranyl and increased its excretion by around 10% of the injected metal.

Domaines: Chimie; Chimie organique

Marcin Sawicki, Delphine Lecerclé, Gérard Grillon, Béatrice Le Gall, Anne-Laure Sérandour, et al.. Bisphosphonate sequestering agents. Synthesis and preliminary evaluation for in vitro and in vivo uranium(VI) chelation.. European Journal of Medicinal Chemistry, 2008, 43 (12), pp.2768-77. ⟨10.1016/j.ejmech.2008.01.018⟩. ⟨hal-00687055⟩