New AMD3100 derivatives for CXCR4 chemokine receptor targeted molecular imaging studies: synthesis, anti-HIV-1 evaluation and binding affinities.
Fiche publication
Date publication
mars 2015
Journal
Dalton transactions (Cambridge, England : 2003)
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DENAT Franck
Tous les auteurs :
Poty S, Désogère P, Goze C, Boschetti F, D'huys T, Schols D, Cawthorne C, Archibald SJ, Maëcke HR, Denat F
Lien Pubmed
Résumé
CXCR4 is a target of growing interest for the development of new therapeutic drugs and imaging agents as its role in multiple disease states has been demonstrated. AMD3100, a CXCR4 chemokine receptor antagonist that is in current clinical use as a haematopoietic stem cell mobilising drug, has been widely studied for its anti-HIV properties, potential to inhibit metastatic spread of certain cancers and, more recently, its ability to chelate radiometals for nuclear imaging. In this study, AMD3100 is functionalised on the phenyl moiety to investigate the influence of the structural modification on the anti-HIV-1 properties and receptor affinity in competition with anti-CXCR4 monoclonal antibodies and the natural ligand for CXCR4, CXCL12. The effect of complexation of nickel(II) in the cyclam cavities has been investigated. Two amino derivatives were obtained and are suitable intermediates for conjugation reactions to obtain CXCR4 molecular imaging agents. A fluorescent probe (BODIPY) and a precursor for (18)F (positron emitting isotope) radiolabelling were conjugated to validate this route to new CXCR4 imaging agents.
Mots clés
Anti-HIV Agents, chemistry, Boron Compounds, chemistry, Calcium Signaling, drug effects, Chemistry Techniques, Synthetic, Drug Design, HIV-1, drug effects, Halogenation, Heterocyclic Compounds, chemistry, Humans, Jurkat Cells, Positron-Emission Tomography, Receptors, CXCR4, metabolism
Référence
Dalton Trans. 2015 Mar;44(11):5004-16