Synthesis of anionic carbosilane dendrimers via “click chemistry” and their antiviral properties against HIV

Abstract

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 µM. 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. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 1099–1112

Structures and Synthesis of Zwitterionic Polymers

“…Still, it must be kept in mind that responsiveness implies reversibility of the changes induced after applying a counter-stimulus. Many chemical "switching" processes, as e.g., the hydrolysis or photo-deprotection of ester groups that convert polycations into polycarboxybetaines (see Figure 10) [398,403,438,439], or polyzwitterions into polyanions [151][152][153]440], are not reversible, at least not under aqueous conditions.…”

Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides

“…53 A new water-soluble dendrimers with carbosilane structure, which are characterized by the easy availability of reagents, short reaction times, high reproducibility and quantitative yields of reaction, have been synthesized. [15][16][17] These polyanionic carbosilane dendrimers are stable compounds and their microbicide capacity against HIV-1 has been previously reported. 22,54 However, the potential microbicide capacity against HIV-2 infection is still unknown.…”

Polymeric Anti‐HIV Therapeutics

“…[92] Arnaiz et al demonstrated that these dendrimers showed little cytotoxicity up to 20 Â 10 À6 M as judged by MTT assays on PBMC and efficacy was shown to correlate with an increase in dendrimer generation. Dendrimers with terminal phosphonate groups did not exhibit any anti-HIV-1 activity.…”