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Anti-HIV-1 activity of the Iboga alkaloid congener 18-methoxycoronaridine.

By Edinete Melo da Silva, Claudio Cesar Cirne Santos, Izabel C. P. P Frugulhetti, Bernardo Galvão Castro Filho, Elvira Maria B Saraiva, Martin E Keuhne and Dumith Chequer Bou-Habib


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 EC (50) values of 22.5 +/- 4.7 microM and 23 +/- 4.5 microM 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: EC (50) equal to 12.8 +/- 5 microM and 9.5 +/- 3 microM 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 (IC (50) = 69.4 microM), which at least partially explains its antiretroviral activity

Topics: HIV-1, Aids, 18-methoxycoronaridine, Iboga alkaloid, Reverse transcriptase, Fármacos Anti-HIV/farmacologia, HIV-1/efeitos de drogas, Ibogaína/análogos & derivados, Ibogaína/farmacologia, Fitoterapia, Tabernaemontana, Fármacos Anti-HIV/administração & dosagem, Fármacos Anti-HIV/uso terapêutico, Relação Dose-Resposta a Droga, Humanos, Ibogaína/administração & dosagem, Ibogaína/uso terapêutico, Leucócitos Mononucleares/virologia, Extratos Vegetais/administração & dosagem, Extratos Vegetais/farmacologia
Publisher: Georg Thieme Verlag KG Stuttgart
Year: 2004
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