Planta Med 2006; 72(4): 295-299
DOI: 10.1055/s-2005-916209
Original Paper
Pharmacology
© 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

Claudio Cesar Cirne-Santos1 , 3 , 4 , Valéria L. Teixeira2 , Luiz Roberto Castello-Branco4 , Izabel C. P. P. Frugulhetti1 , Dumith Chequer Bou-Habib4
  • 1Laboratório de Virologia Molecular, Departamento de Biologia Celular e Molecular, Universidade Federal Fluminense, Niterói, RJ, Brazil
  • 2Laboratório de Biologia Marinha, Departamento de Biologia Marinha, Universidade Federal Fluminense, Niterói, RJ, Brazil
  • 3Instituto de Microbiologia Prof. Paulo de Góes, Universidade Federal do Rio de Janeiro, RJ, Brazil
  • 4Laboratório de Imunologia Clínica, Departamento de Imunologia, Instituto Oswaldo Cruz/Fiocruz, Rio de Janeiro, RJ, Brazil
Further Information

Publication History

Received: June 22, 2005

Accepted: August 30, 2005

Publication Date:
05 January 2006 (online)

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.

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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

Phone: +55-21-3865-8128

Fax: +55-21-2209-4110

Email: dumith@ioc.fiocruz.br