New AMD3100 derivatives for CXCR4 chemokine receptor targeted molecular imaging studies: Synthesis, anti-HIV-1 evaluation and binding affinities

Sophie Poty; Pauline Désogère; Christine Goze; Frédéric Boschetti; Thomas D'huys; Dominique Schols; Christopher Cawthorne; Stephen J. Archibald; Helmut R. Maëcke; Franck Denat

doi:10.1039/c4dt02972k

New AMD3100 derivatives for CXCR4 chemokine receptor targeted molecular imaging studies: Synthesis, anti-HIV-1 evaluation and binding affinities

Sophie Poty, Pauline Désogère, Christine Goze^*, Frédéric Boschetti, Thomas D'huys, Dominique Schols, Christopher Cawthorne, Stephen J. Archibald, Helmut R. Maëcke, Franck Denat

^*Corresponding author for this work

Imaging Chemistry & Biology

Research output: Contribution to journal › Article › peer-review

33 Citations (Scopus)

Abstract

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 ¹⁸F (positron emitting isotope) radiolabelling were conjugated to validate this route to new CXCR4 imaging agents.

Original language	English
Pages (from-to)	5004-5016
Number of pages	13
Journal	Dalton Transactions
Volume	44
Issue number	11
DOIs	https://doi.org/10.1039/c4dt02972k
Publication status	Published - 21 Mar 2015

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title = "New AMD3100 derivatives for CXCR4 chemokine receptor targeted molecular imaging studies: Synthesis, anti-HIV-1 evaluation and binding affinities",

abstract = "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 18F (positron emitting isotope) radiolabelling were conjugated to validate this route to new CXCR4 imaging agents.",

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AU - Poty, Sophie

AU - Désogère, Pauline

AU - Goze, Christine

AU - Boschetti, Frédéric

AU - D'huys, Thomas

AU - Schols, Dominique

AU - Cawthorne, Christopher

AU - Archibald, Stephen J.

AU - Maëcke, Helmut R.

AU - Denat, Franck

PY - 2015/3/21

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AB - 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 18F (positron emitting isotope) radiolabelling were conjugated to validate this route to new CXCR4 imaging agents.

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New AMD3100 derivatives for CXCR4 chemokine receptor targeted molecular imaging studies: Synthesis, anti-HIV-1 evaluation and binding affinities

Abstract

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