Dendritic catanionic assemblies: in vitro anti-HIV activity of phosphorus-containing dendrimers bearing galbeta1cer analogues.
Two series of water-soluble dendritic catanionic assemblies, acting as multisite analogues of galactosylceramide (Galbeta1cer), have been prepared with the goal of blocking HIV infection prior to the entry of the virus into human cells. Trifunctional and hexafunctional cinnamic acid-terminated dendrimers have been synthesized from phosphorus-containing dendrimers bearing aldehyde end groups. A classical acid-base reaction performed in water between acid-terminated dendrimers and stoichiometric amounts of N-hexadecylamino-1-deoxylactitol provided the expected catanionic assemblies. Antiviral assays on these supramolecular entities confirmed the crucial roles both of multivalency effects and of lipophilicity on the biological activity of Galbeta1cer analogues. Moreover, correlation between in vitro tests and molecular modeling highlights the specific influence of the assembly shape on the anti-HIV efficiency, with the tri- and hexafunctional cored dendrimers, both decorated with 12 sugar moieties, exhibiting IC50 values of 1.1 and 0.12 microM, respectively.
Blanzat
Muriel
M
Laboratoire des Interactions Moléculaires et Réactivité Chimique et Photochimique, CNRS UMR 5623 Université Paul Sabatier, 118 Route de Narbonne, 31062 Toulouse Cedex, France. blanzat@chimie.ups-tlse.fr
Turrin
Cédric-Olivier
CO
Aubertin
Anne-Marie
AM
Couturier-Vidal
Christiane
C
Caminade
Anne-Marie
AM
Majoral
Jean-Pierre
JP
Rico-Lattes
Isabelle
I
Lattes
Armand
A
D019380:Anti-HIV Agents / Q000138:chemical synthesis*; D002412:Cations; D002460:Cell Line; D050091:Dendrimers / Q000138:chemical synthesis* / Q000494:pharmacology; D005699:Galactosylceramides / Q000737:chemistry* / Q000494:pharmacology; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D010758:Phosphorus; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D002412:Cations; D050091:Dendrimers; D005699:Galactosylceramides; D010758:Phosphorus