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

<p>Abstract</p> <p>Background</p> <p>Terpenoid 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.</p> <p>Results</p> <p>The 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.</p> <p>Conclusion</p> <p>Overall, 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.</p

Monocyte-derived macrophages (A), monocyte-derived dendritic cells (B) and T cells (C) were incubated with R5 or X4 viruses in the presence of increasing concentrations of C14 or an unique dose of T 20 (5 μM) for 3 hours at 37°C

Cells were then washed and cultured in fresh medium for 3 days. DNA was extracted and the viral DNA was quantified by real time PCR. Means are representative of 3 independent experiments and assays were performed in triplicates. *, ≤ 0.05; **, ≤ 0.01 between untreated and treated cells.<p><b>Copyright information:</b></p><p>Taken from "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"</p><p>http://www.aidsrestherapy.com/content/5/1/10</p><p>AIDS Research and Therapy 2008;5():10-10.</p><p>Published online 3 Jun 2008</p><p>PMCID:PMC2426711.</p><p></p

Monocyte-derived macrophages, monocyte-derived dendritic cells and T cells were incubated with R5 viruses in the presence of increasing concentrations of C14 for 3 hours at 37°C

Cells were then washed and incubated with polyclonal human anti-gp160 antibodies. The staining was revealed with FITC-conjugated mouse anti-human IgG mAbs. Cells were then analysed by confocal microscopy. The experiment was performed 3 times with cells from three different donors. 30 cells were at least analyzed for each donor.<p><b>Copyright information:</b></p><p>Taken from "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"</p><p>http://www.aidsrestherapy.com/content/5/1/10</p><p>AIDS Research and Therapy 2008;5():10-10.</p><p>Published online 3 Jun 2008</p><p>PMCID:PMC2426711.</p><p></p

HIV-1 was adsorbed on poly-L-lysin pre-coated wells (Greiner Bio-One) at 4°C overnight and further incubated with C14 for 1 h

In positive and negative control wells, 1% Triton X-100 and medium were added, respectively. After four washes, activated peripheral blood lymphocytes were incubated with C14 or triton-treated or untreated HIV-1 particles. After 6 days, viral production was assessed by p24 Ag capture ELISA. Means are representative of 3 independent experiments were performed in triplicates. **, ≤ 0.01.<p><b>Copyright information:</b></p><p>Taken from "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"</p><p>http://www.aidsrestherapy.com/content/5/1/10</p><p>AIDS Research and Therapy 2008;5():10-10.</p><p>Published online 3 Jun 2008</p><p>PMCID:PMC2426711.</p><p></p