Pre-clinical development as microbicide of zinc tetra-ascorbo-camphorate, a novel terpenoid derivative: Potent in vitro inhibitory activity against both R5- and X4-tropic HIV-1 strains without significant in vivo mucosal toxicity

Abstract

BackgroundTerpenoid derivatives originating from many plants species, are interesting compounds with numerous biological effects, such as anti-HIV-1 activity. The zinc tetra-ascorbo-camphorate complex (or "C14"), a new monoterpenoid derivative was evaluated in vitro for its anti-HIV-1 activity on both R5- and X4-HIV-1 infection of primary target cells (macrophages, dendritic cells and T cells) and on HIV-1 transfer from dendritic cells to T cells.ResultsThe toxicity study was carried out in vitro and also with the New Zealand White rabbit vaginal irritation model. C14 was found to be no cytotoxic at high concentrations (CC50 > 10 μM) and showed to be a potential HIV-1 inhibitor of infection of all the primary cells tested (EC50 = 1 μM). No significant changes could be observed in cervicovaginal tissue of rabbit exposed during 10 consecutive days to formulations containing up to 20 μM of C14.ConclusionOverall, these preclinical studies suggest that zinc tetra-ascorbo-camphorate derivative is suitable for further testing as a candidate microbicide to prevent male-to-female heterosexual acquisition of HIV-1.

Adaptive HIV-Specific B Cell-Derived Humoral Immune Defenses of the Intestinal Mucosa in Children Exposed to HIV via Breast-Feeding

“…Half of the medium, including all supplements, was replaced every 3 days. After 7 days of culture, adherent cells corresponding to the macrophages-enriched fraction were harvested, washed, and used for subsequent experiments [41], [42]. At the time of collection, MDM were more than 90% pure, expressing by flow cytometry analysis (CellQuest software, Becton Dickinson) CD4 + , CXCR4 low , CCR5 high+ , CD14 (73%) and CD11b (70%) (data not shown).…”

“…Adherent monocytes were incubated in RPMI medium with 10% FCS, glutamine, and antibiotics in the presence of 10 ng/ml rhM-CSF (10 ng/ml) to differentiate to macrophages, as previously described [41]. The relative concentration of rhM-CSF improve cell viability and maintained a neutral environment with respect to activation marker quantitative expression (HLA-DR, CD14, CD16), which remained similar to that of MDM cultured in medium alone [41]. Half of the medium, including all supplements, was replaced every 3 days.…”

Current and future microbicide approaches aimed at preventing HIV infection in women

“…This is the case for glycerol monolaurate [63], which is supposed to inhibit the inflammatory response generated by HIV-exposed epithelial cells, Praneem polyherbal [64], developed in India and containing several vegetal extracts, and zinc salts [65], including zinc tetra-ascorbo-camphorate [66], a terpen derivative.…”

The Potential of Sub-Saharan African Plants in the Management of Human Immunodeficiency Virus Infections: A Review

“…Cough suppressant, respiratory problems (Hutchings et al, 1996a(Hutchings et al, , 1996b Whole plant, leaves Gallic, tannic and quinic acids, terpenoids, glycosides (Hutchings et al, 1996a(Hutchings et al, , 1996b) Gallic acid inhibits HIV-1 reverse transcriptase activity (Kratz et al, 2008;Nutan et al, 2013) Tannic acid represses 12-o-tetra-decanoyl phorbol-13-acetate-induced HIV promoter activity (Uchiumi et al, 2003) Dicaffeoylquinic acids inhibit HIV integrase activity Terpenoids inhibit HIV-1, (IC50: 0.1-3.11 μg/ mL) (Bruno et al, 2002;Saidi et al, 2008;Shahidul Alam et al, 2000) Agavaceae Agave L. sp.…”