title: New bicyclam-GalCer analogue conjugates: synthesis and in vitro anti-HIV activity.
abstract: The synthesis of bipharmacophore anti-HIV compounds which, in a single molecule, combine two ligands, that is, the bicyclam AMD3100 and a GalCer analogue, that might inhibit several steps of the complex virus/cell cascade interactions has been performed. The 'double-drug' Gal-AMD3100 conjugates elicited inhibitory effects on T (or X4)-tropic HIV-1 replication in all CXCR4 expressing cell lines with EC(50) values ranging from 0.25 to 6.0 microM which were however approximately 40- to 125-fold lower than that of AMD3100. Concerning the mechanism of inhibition of the Gal-AMD3100 conjugates, experiments performed with X4 or R5HIV-1 strains and GHOST cells genetically modified to express CD4 and CXCR4 or CCR5 indicated clearly that the conjugates interact with CXCR4 and not with CCR5.
authors.affiliation: Laboratoire de Chimie Bioorganique UMR-CNRS 6001, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Cédex 2, Nice, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Daoudi
authors.forename: Jacques
authors.initials: J
authors.lastname: Greiner
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Aubertin
authors.forename: Pierre
authors.initials: P
authors.lastname: Vierling
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology; D001596:Benzylamines; D002460:Cell Line; D045744:Cell Line, Tumor; D000080027:Cyclams; D005699:Galactosylceramides / Q000737:chemistry* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans
chemical_list: D019380:Anti-HIV Agents; D001596:Benzylamines; D000080027:Cyclams; D005699:Galactosylceramides; D006571:Heterocyclic Compounds; C088327:plerixafor