We describe in this paper that the diterpenes 8,10,18-trihydroxy-2,6-dolabelladiene ( 1) and (6 R)-6-hydroxydichotoma-4,14-diene-1,17-dial ( 2), isolated from the marine algae DICTYOTA PFAFFII and D. MENSTRUALIS, respectively, inhibited HSV-1 infection in Vero cells. We initially observed that compounds 1 and 2 inhibited HSV-1 replication in a dose-dependent manner, resulting in EC (50) values of 5.10 and 5.90 microM, respectively, for a multiplicity of infection (MOI) of 5. Moreover, the concentration required to inhibit HSV-1 replication was not cytotoxic, resulting in good selective index (SI) values. Next, we found that compound 1 sustained its anti-herpetic activity even when added to HSV-1-infected cells at 6 h after infection, while compound 2 sustained its activity for up to 3 h after infection, suggesting that these compounds inhibit initial events during HSV-1 replication. We also observed that both compounds were incapable of impairing HSV-1 adsorption and penetration. In addition, the tested molecules could decrease the contents of some HSV-1 early proteins, such as UL-8, RL-1, UL-12, UL-30 and UL-9. Our results suggest that the structures of compounds 1 and 2, Brazilian brown algae diterpenes, might be promising for future antiviral design.
Copyright Georg Thieme Verlag KG Stuttgart New York.