title: Bisphosphonate sequestering agents. Synthesis and preliminary evaluation for in vitro and in vivo uranium(VI) chelation.
abstract: 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.
authors.affiliation: Service de Chimie Bio-organique et de Marquage, iBiTec-S, CEA-Saclay, 91191 Gif sur Yvette, France.
authors.forename: Marcin
authors.initials: M
authors.lastname: Sawicki
authors.forename: Delphine
authors.initials: D
authors.lastname: Lecerclé
authors.forename: Gérard
authors.initials: G
authors.lastname: Grillon
authors.forename: Béatrice
authors.initials: B
authors.lastname: Le Gall
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Sérandour
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Poncy
authors.forename: Théodorine
authors.initials: T
authors.lastname: Bailly
authors.forename: Ramon
authors.initials: R
authors.lastname: Burgada
authors.forename: Marc
authors.initials: M
authors.lastname: Lecouvey
authors.forename: Vincent
authors.initials: V
authors.lastname: Challeix
authors.forename: Antoine
authors.initials: A
authors.lastname: Leydier
authors.forename: Stephane
authors.initials: S
authors.lastname: Pellet-Rostaing
authors.forename: Eric
authors.initials: E
authors.lastname: Ansoborlo
authors.forename: Frédéric
authors.initials: F
authors.lastname: Taran
mesh_terms: D000818:Animals; D001665:Binding Sites; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004164:Diphosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D014018:Tissue Distribution / Q000187:drug effects; D014501:Uranium / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D002614:Chelating Agents; D004164:Diphosphonates; D008024:Ligands; D054852:Small Molecule Libraries; D014501:Uranium