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Planta Med 2004; 70(9): 808-812
DOI: 10.1055/s-2004-827227
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Anti-HIV-1 Activity of the Iboga Alkaloid Congener 18-Methoxycoronaridine

Edinete M. Silva1 , Claudio C. Cirne-Santos2 , 6 , Izabel C. P. P. Frugulhetti2 , Bernardo Galvão-Castro1 , 3 , Elvira M. B. Saraiva4 , Martin E. Kuehne5 , Dumith Chequer Bou-Habib6
  • 1Laboratório Avançado de Saúde Pública, Centro de Pesquisas Gonçalo Moniz, Salvador, BA, Brazil
  • 2Laboratório de Virologia Molecular, Departamento de Biologia Celular e Molecular, Universidade Federal Fluminense, Niterói, RJ, Brazil
  • 3Escola Bahiana de Medicina e Saúde Pública, Fundação para o Desenvolvimento das Ciências, Salvador, BA. Brazil
  • 4Departamento de Imunologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, RJ, Brazil,
  • 5Department of Chemistry, University of Vermont, Burlington, VT, USA
  • 6Laboratório de Imunologia Clínica, Departamento de Imunologia, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
Further Information

Publication History

Received: February 11, 2004

Accepted: May 15, 2004

Publication Date:
23 September 2004 (online)

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Abstract

The Iboga alkaloid congener 18-methoxycoronaridine (18-MC) exhibits in vitro leishmanicidal and in vivo anti-addiction properties. In this paper, we describe that 18-MC inhibits HIV-1 infection in human peripheral blood mononuclear cells (PBMCs) and monocyte-derived macrophages. We found that 18-MC inhibits the replication of primary isolates of HIV-1 in a dose-dependent manner, regardless of the preferential chemokine receptor usage of the isolates, at non-cell-toxic concentrations. The antiretroviral activity of 18-MC resulted in EC50 values of 22.5 ± 4.7 μM and 23 ± 4.5 μM for R5 and X4 isolates, respectively, in PBMCs, and a therapeutic index (TI) of 14.5. Similar findings were observed for inhibition of HIV-1 replication in macrophages: EC50 equal to 12.8 ± 5 μM and 9.5 ± 3 μM for an R5 virus after 14 and 21 days of infection, respectively, with TI equal to 25.6 and 34.5. 18-MC moderately inhibits the HIV-1 enzyme reverse transcriptase (IC50 = 69.4 μM), which at least partially explains its antiretroviral activity.

Key words

HIV-1 - AIDS - 18-methoxycoronaridine - Iboga alkaloid - reverse transcriptase

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Dr. Dumith Chequer Bou-Habib

Departamento de Imunologia

Instituto Oswaldo Cruz

Av. Brasil 4365 - Manguinhos

Pavilhão Leonidas Deane/409

21045.900 Rio de Janeiro

RJ

Brazil

Phone: +55-21-3865-8128

Fax: +55-21-2209-4110

Email: dumith@ioc.fiocruz.br