Dendritic Catanionic Assemblies:In vitro Anti-HIV Activity of Phosphorus-Containing Dendrimers Bearing Gal beta_1 cer Analogues

摘要

Two series of water-soluble dendritic catanionic assemblies,acting as multisite analogues of galactosylceramide (Gal beta_1cer),have been prepared with the goal of blocking HIV infection prior to the entry of the virus into human cells.Trifunctional and hexa-functional 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 (3) provided the expected catanionic assemblies.Antiviral assays on these supra-molecular entities confirmed the crucial roles both of multivalen-cy effects and of lipophilicity on the biological activity of Gal beta_1cer 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 IC_(50) values of 1.1 and 0.12 mum,respectively.