In vitro antiplasmodial activity of indole alkaloids from the stem bark of Geissospermum vellosii

Ethnopharmacological relevance: The stem bark of Geissospermum vellosii has been traditionally used by the native population of northern South America to treat malaria. Indole alkaloids have been previously isolated from this plant, but the antiplasmodial constituents have not yet been described. As part of our ongoing investigations of new bioactive compounds with activity against malaria parasites, we tested the in vitro antiplasmodial activity of isolated fractions and purified alkaloids from Geissospermum vellosii. Materials and methods: Indole alkaloids were isolated and identified from a methanolic crude extract of Geissospermum vellosii bark using a combination of high performance counter current chromatography, mass spectrometry and nuclear magnetic resonance technologies. The methanolic extract, the crude alkaloid fractions and the purified compounds were tested for in vitro antiplasmodial activity against the chloroquine-sensitive strain of Plasmodium falciparum (D10). Results: An indole alkaloid (4) along with four known indole alkaloids, geissolosimine (1), geissospermine (2). geissoschizoline (3), and vellosiminol (5) were isolated and structure elucidated. The antiplasmodial activity (IC50) of the methanolic crude extract was 2.22 mu g/mL, while for the isolated compounds it ranged from 0.96 mu M to 13.96 mu M except for (5) which showed a low activity (157 mu M). Geissolosimine (1) showed the highest antiplasmodial activity (0.96 mu M). Conclusions: This study provides evidence to support the use of Geissospermum vellosii as an antimalarial agent, as used by the native populations. Geissolosimine (1) is a lead molecular structure for possible antimalarial drug development. (C) 2011 Elsevier Ireland Ltd. All rights reserved.