2. Academic Validation
  3. New bicyclam-GalCer analogue conjugates: synthesis and in vitro anti-HIV activity

New bicyclam-GalCer analogue conjugates: synthesis and in vitro anti-HIV activity

  • Bioorg Med Chem Lett. 2004 Jan 19;14(2):495-8. doi: 10.1016/j.bmcl.2003.10.036.
Jean-Michel Daoudi 1,  Jacques Greiner,  Anne-Marie Aubertin,  Pierre Vierling
Affiliations

Affiliation

  • 1 Laboratoire de Chimie Bioorganique UMR-CNRS 6001, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Cédex 2, Nice, France.
PMID: 14698189 DOI: 10.1016/j.bmcl.2003.10.036
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.

Figures