Anti-HIV-1 activity of the Iboga alkaloid congener 18-methoxycoronaridine.
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.
Silva
Edinete M
EM
Laboratório Avançado de Saúde Pública, Centro de Pesquisas Gonçalo Moniz, Salvador, BA, Brazil.
Cirne-Santos
Claudio C
CC
Frugulhetti
Izabel C
IC
Galvão-Castro
Bernardo
B
Saraiva
Elvira M
EM
Kuehne
Martin E
ME
Bou-Habib
Dumith Chequer
DC
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007050:Ibogaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000821:virology; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D030014:Tabernaemontana
D019380:Anti-HIV Agents; D010936:Plant Extracts; D007050:Ibogaine; C103345:18-methoxycoronaridine