The effects of the diterpenes isolated from the Brazilian brown algae Dictyota pfaffii and Dictyota menstrualis against the herpes simplex type-1 replicative cycle.
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.
Abrantes
Juliana L
JL
Laboratório de Estrutura e Regulação de Proteínas, Programa de Pós-Graduação em Química Biológica, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil. abrantes@bioqmed.ufrj.br
Barbosa
Jussara
J
Cavalcanti
Diana
D
Pereira
Renato C
RC
Frederico Fontes
Carlos L
CL
Teixeira
Valeria L
VL
Moreno Souza
Thiago L
TL
Paixão
Izabel C P
IC
D000818:Animals; D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D001938:Brazil; D002522:Chlorocebus aethiops; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006561:Herpes Simplex / Q000188:drug therapy* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000472:pathogenicity; D000459:Phaeophyceae / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D014709:Vero Cells; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
C551639:6-hydroxydichotoma-4,14-diene-1,17-dial; C551638:8,10,18-trihydroxy-2,6-dolabelladiene; D000998:Antiviral Agents; D004224:Diterpenes; D010936:Plant Extracts; D014764:Viral Proteins