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.
BACKGROUND
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.


RESULTS
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 muM) and showed to be a potential HIV-1 inhibitor of infection of all the primary cells tested (EC50 = 1 muM). No significant changes could be observed in cervicovaginal tissue of rabbit exposed during 10 consecutive days to formulations containing up to 20 muM of C14.


CONCLUSIONS
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.
Laboratoire de Virologie, Hôpital Européen Georges Pompidou, and Université Paris Descartes (Paris V), Paris, France.
Héla
H
Saïdi
Laboratoire de Virologie, Hôpital Européen Georges Pompidou, and Université Paris Descartes (Paris V), Paris, France.
Mohammad-Ali
MA
Jenabian
MGB Pharma, Nîmes, France.
Bernard
B
Gombert
Laboratoire de Virologie, Hôpital Européen Georges Pompidou, and Université Paris Descartes (Paris V), Paris, France.
Charlotte
C
Charpentier
MGB Pharma, Nîmes, France.
Aurèle
A
Mannarini
Laboratoire de Virologie, Hôpital Européen Georges Pompidou, and Université Paris Descartes (Paris V), Paris, France.
Laurent
L
Bélec