Synthesis, structure and molecular modelling of anionic carbosilane dendrimers

Abstract

Anionic carbosilane dendrimers of generations 1-3 have been synthesized containing carboxylate G(n)X(C(2)H(4)CO(2)Na)(m) and sulfonate G(n)X(C(2)H(4)SO(3)Na)(m) peripheral groups and derived from two different cores, 1,3,5-(HO)(3)C(6)H(3) (X = O(3)) and Si(C(3)H(5))(4) (X = Si). The peripheral anionic groups make these dendrimers water soluble, despite their highly hydrophobic framework. These dendrimers present a net negative charge in water, which was influenced by the pH of the medium. This characteristic was studied by pH titration. Also molecular modeling calculations have been performed to study differences in an aqueous medium between carboxylate and sulfonate dendrimers of different cores. The results obtained were also compared with those obtained from DOSY NMR experiments and zeta-potential measurements.

Efficacy of HIV antiviral polyanionic carbosilane dendrimer G2-S16 in the presence of semen

“…G2-S16 does neither alter semen motility nor affect other functions of the semen. 16,19,28 No irritation or vaginal lesions were detected in rabbits after 2 weeks of intravaginal G2-S16 application 19 or in CD1(ICR) mice after G2-S16 vaginal administration. 19 The application of one dose of 1.5%, 3%, and 4.5% of G2-S16 to hydroxyethylcellulose (HEC) gel-treated BALB/c at various consecutive time periods does not cause disruption of the epithelial cells or produce damage in the vaginal mucosa.…”

Antiviral mechanism of polyanionic carbosilane dendrimers against HIV-1

“…30 HeLa MAGI P4.R5 and TZM.bl cell lines were cultured as described. 24,28 The Ethical Committee of Clinical Research of the Health Institute of Gregorio Maranon Hospital deemed that no approval was required for this set of experiments because the experiments were performed on commercially available cell lines. Raji-DC-SIGN, a B lymphoblastic cell line expressing high levels of DC-SIGN surface marker, 31 8E5/LAV, containing a single integrated copy of proviral DNA, 32 and Jurkat E6-1 cell lines were cultured in RPMI complete medium (Thermo Fisher Scientific, Waltham, MA, USA) supplemented with 5% fetal bovine serum.…”

“…23 A relative recent group of dendrimers with carbosilane structure has also demonstrated its potential as topical microbicides against HIV and other pathogens. 12,13,[24][25][26][27][28][29] These nanosystems present a C-and Si-based skeleton, and they distinguish from other dendrimers in the high apolarity of their central core and the high mobility of their peripheral branches.…”

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

“…These dendrimers are particularly suitable for this application due to the simplicity of their synthesis, which allows for large amounts of the polymer to be generated; the ability to obtain a polymer with a defined molecular weight and number of terminal functions; chemical and biochemical stability; biologically inertness; and the low polarity of the C-Si bond, which imparts hydrophobicity to the carbosilane scaffold. [15][16][17] One of the most promising targets of the HIV cycle is the viral entry/fusion process, which is divided into three steps: (i) attachment of gp120 to CD4, (ii) binding to CCR5 and/or CXCR4, and (iii) fusion of the envelope with the cell membrane and releasing of the viral capsid into the cytoplasm of the host cell. 18 Dendrimers containing functionalized groups at their periphery can bind to their target in a multivalent manner, providing a strategy for the development of potent viral entry inhibitors.…”