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