Planta Med 2005; 71(11): 1019-1024
DOI: 10.1055/s-2005-873113
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Effects of Diterpenes Isolated from the Brazilian Marine Alga Dictyota menstrualis on HIV-1 Reverse Transcriptase

Helena de Souza Pereira1 , Luiz Roberto Leão-Ferreira1 , Nissin Moussatché3 , Valéria Laneuville Teixeira2 , Diana Negrão Cavalcanti2 , Luciana Jesus da Costa4 , Ricardo Diaz4 , Izabel Christina de Palmer Paixão Frugulhetti1
  • 1Departamento de Biologia Celular e Molecular/Programa de Neuroimunologia, Instituto de Biologia, Universidade Federal Fluminense, Niterói - RJ, Brasil
  • 2Departamento de Biologia Marinha, Instituto de Biologia, Universidade Federal Fluminense, Niterói - RJ, Brasil
  • 3Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro - RJ, Brasil
  • 4UNIFESP-EPM, Universidade Federal de São Paulo, São Paulo - SP, Brasil
Further Information

Publication History

Received: February 3, 2005

Accepted: May 23, 2005

Publication Date:
18 October 2005 (online)

Abstract

It has been recently demonstrated that HIV-1 reverse transcriptase is the target of two diterpenes, (6R)-6-hydroxydichotoma-3,14-diene-1,17-dial (compound 1) and (6R)-6-acetoxydichotoma-3,14-diene-1,17-dial (compound 2), that inhibit HIV-1 replication in vitro. In this work, the effects of both diterpenes on the kinetic properties of the recombinant HIV-1 reverse transcriptase (RT) enzyme were evaluated. RNA-dependent DNA-polymerase (RDDP) activity assays demonstrated that both diterpenes behave as non-competitive inhibitors with respect to dTTP and uncompetitive inhibitors with respect to poly(rA)·oligo(dT) template primers. The K i values obtained for compounds 1 and 2 were 10 and 35 μM, respectively. Neither of these diterpenes affected the DNA-dependent DNA-polymerase (DDDP) activity of the HIV-1 RT. The RDDP activities of AMV-RT and MMLV-RT enzymes were also inhibited by compounds 1 and 2. In contrast to the HIV-1 enzyme, the DDDP activities of AMV-RT and MMLV-RT enzymes were significantly reduced by compound 1. Taken together, our results demonstrate that compound 1 is a more effective inhibitor of the viral reverse transcriptases from HIV-1, AMV and MMLV than compound 2. The kinetic behavior analyses of the HIV-1 RT demonstrate that both diterpenes have similar mechanisms of inhibition of RDDP activity.

Abbreviations

Compound 1:(6R)-6-hydroxydichotoma-3,14-diene-1,17-dial

Compound 2:(6R)-6-acetoxydichotoma-3,14-diene-1,17-dial

HIV-1 RT:human immunodeficiency virus type-1 reversetranscriptase

AMV:avian myeloblastosis virus

MMLV:Moloney murine leukemia virus

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Helena de Souza Pereira, PhD

Universidade Federal do Rio de Janeiro

Instituto de Biologia

Bloco A - 2 andar - sala 121

Lab. de Virologia Molecular - CCS

21941-570 - Cidade Universitária

Rio de Janeiro

Brazil

Phone: /Fax: +55-21-2629-2268

Email: helena@biologia.ufrj.br