The Effects of the Diterpenes Isolated from the Brazilian Brown AlgaeDictyota pfaffiiandDictyota menstrualisagainst the Herpes Simplex Type-1 Replicative Cycle

Abstract

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.

Evaluation of the acute toxicity of dolabelladienotriol, a potential antiviral from the brown alga Dictyota pfaffii, in BALB/c mice

“…The screening of natural products derived vitro effects of diterpenes with encouraging results for antiviral activity (Abrantes et al, 2010;Khan et al, 2005;Siamopoulou et al, 2004;Suzuki et al, 2002). Several studies with natural products demonstrate their potential role in inhibiting certain diseases, as well as their good performance during the active stage of viral replication.…”

“…The diterpene, at over 99% purity, was diluted in 100% dimethyl sulfoxide (DMSOMerck) and stored at -20 °C. The resulting DMSO concentrations during the assays were below 0.1%, a level that is not significantly cytotoxic (Abrantes et al, 2010).…”

“…The diterpene 8,10,18-trihydroxy-2,6-dolabelladiene or dolabelladienetriol (1) was obtained by reduction of the major natural product from Dictyota pfaffii (Abrantes et al, 2010;Barbosa et al, 2004;Barbosa et al, 2003;Cirne-Santos et al, 2008;CirneSantos et al, 2006). The diterpene, at over 99% purity, was diluted in 100% dimethyl sulfoxide (DMSOMerck) and stored at -20 °C.…”

“…Studies in vitro have shown that this compound has low cytotoxicity and acts as a potent inhibitor of the HIV-1 replication cycle in primary cell cultures by inhibiting the Reverse Transcriptase (RT) enzyme. It has also been shown to inhibit the initial replication of HSV-1 (Abrantes et al, 2010;Barbosa et al, 2004;Cirne-Santos et al, 2008;.…”

Anti-snake venom effect of secodolastane diterpenes isolated from Brazilian marine brown alga Canistrocarpus cervicornis against Lachesis muta venom

“…These molecules are the products of secondary metabolism and display pharmacological properties (Mayer et al, 2007;Cirne-Santos et al, 2008;Abrantes et al, 2010) as well as ecological functions (Bianco et al, 2009). A previous study demonstrated that L. muta venom displayed phospholipase A 2 (indirect hemolytic activity), hemorrhagic, clotting and proteolytic activities (Fuly et al, 1993).…”