Synthesis of Anionic Carbosilane Dendrimers via Click Chemistry and Their Antiviral Properties Against HIV

The synthesis and characterization of four families of anionic carbosilane dendrimers bearing carboxylate, phosphonate, naphthylsulfonate, and sulfate terminal groups prepared by cycloaddition of azide-alkyne catalyzed by copper (CuAAC) are presented here. For the preparation of these anionic carbosilane dendrimers, two strategies starting from azide-terminated carbosilane dendrimers were followed: (i) click coupling of neutral alkynes followed by derivatization into anionic moieties or (ii) click coupling of anionic alkynes. Both strategies require different reaction conditions in order to accommodate the different substrate polarities. These anionic dendrimers, in general, do not present cell toxicity in vitro until concentration up to 20 mu M. Therefore, they can be used in inhibition experiments in concentrations below this limit. We have observed that dendrimers bearing phosphonate groups possess poor anti-HIV capabilities in vitro in PBMCs, while carboxylate dendrimers can reduce HIV infection levels moderately. On the other hand, sulfate and naphthylsulfonate dendrimers are powerful anti-HIV agents and their antiviral activity is generation and concentration dependent. (c) 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 1099-1112