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DOI: 10.1055/s-2005-916209
© Georg Thieme Verlag KG Stuttgart · New York
Inhibition of HIV-1 Replication in Human Primary Cells by a Dolabellane Diterpene Isolated from the Marine Algae Dictyota pfaffii
Publikationsverlauf
Received: June 22, 2005
Accepted: August 30, 2005
Publikationsdatum:
05. Januar 2006 (online)
![](https://www.thieme-connect.de/media/plantamedica/200604/lookinside/thumbnails/10.1055-s-2005-916209-1.jpg)
Abstract
We describe in this paper that the dolabellane diterpene 8,10,18-trihydroxy-2,6-dolabelladiene (3), isolated from the marine algae Dictyota pfaffii, inhibits the HIV-1 infection in human primary cells and tumor cell lines. We initially observed that compound 3 inhibited the activity of a purified HIV-1 enzyme reverse transcriptase (RT) in a dose-dependent manner, with an IC50 value of 16.5 ± 4.3 μM. Next, we found that compound 3 inhibited HIV-1 infection by an R5-tropic isolate in peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner with an EC50 value of 8.4 ± 2.8 μM. The replication of HIV-1 isolates presenting distinct tropism for chemokine receptors was also inhibited, as analyzed in PBMCs or U87 cells infected with R5-, X4- or R5X4-tropic isolates. Likewise, compound 3 blocked HIV-1 infection in macrophages by R5 and R5X4 viruses in a dose-dependent manner with EC50 values of 1.7 ± 0.6 μM and 1.85 ± 0.75 μM, respectively. Compound 3 sustained antiretroviral activity even when added to HIV-1-infected Sup-T1 cells at 12 h after infection, suggesting that, as well as inhibiting HIV-1 RT, it also blocks HIV-1 replication at a post transcriptional step. Our results support further investigations on compound 3 pharmacokinetics and we propose that this diterpene could be considered as a potential compound for HIV-1 therapy.
Key words
Dictyota pfaffii - HIV-1 - AIDS - diterpenes - dolabellane
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Dr. Dumith Chequer Bou-Habib
Departamento de Imunologia
Instituto Oswaldo Cruz/FIOCRUZ
Av. Brasil, 4365
Manguinhos
Pavilhão Leônidas Deane/409
Rio de Janeiro
RJ 21045-900
Brazil
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