Antileishmanial sesquiterpene lactones from Pseudelephantopus spicatus, a traditional remedy from the Chayahuita Amerindians (Peru). Part III

Ethnopharmacological relevance: The study of traditional remedies used by the Chayahuita, an ethnic group from the Peruvian Amazonia, has prompted us to investigate in detail the ethanolic extract of Pseudelephantopus spicatus (Juss. ex Aubl.) C.F. Baker, which has demonstrated strong biological activity towards Leishmania amazonensis. Our goal was to discover the active compound of this plant-based remedy. Materials and methods: A bioguided fractionation of the crude extract was undertaken based on the biological activity recorded against Leishmania amazonensis axenic amastigotes in in vitro bioassays. Results: Three strongly to moderately active compounds were isolated: two hirsutinolides (the 8,13-diacetyl-piptocarphol and the 8-acetyl-13-O-ethyl-piptocarphol) and ursolic acid. IC₅₀ against Leishmania amazonensis axenic amastigotes are respectively 0.2, 0.37 and 0.99 μM (while IC₅₀ of amphotericin B is 0.41 μM). These compounds have never been isolated from this plant species, and germacranolides have never been identified as potential antileishmanial agents. Conclusions: The compounds isolated from Pseudelephantopus spicatus account for the antileishmanial activity of the plant, thus giving support to its use by the Chayahuita in Peru.