Antileishmanial Constituents of the Panamanian Endophytic Fungus Edenia sp.

Abstract

Bioassay-directed fractionation of extracts from the fermentation broth and mycelium of the fungus Edenia sp. led to the isolation of five antileishmanial compounds, preussomerin EG1 (1), palmarumycin CP₂ (2), palmarumycin CP₁₇ (3), palmarumycin CP₁₈ (4), and CJ-12,371 (5). Compounds 3 and 4 are new natural products, and this is only the second report of compound 1. The structures of compounds 1−5 were established by spectroscopic analyses (HRMS and NMR). All metabolites caused significant inhibition of the growth of Leishmania donovani in the amastigote form, with IC₅₀ values of 0.12, 3.93, 1.34, 0.62, and 8.40 μM, respectively. Compounds 1−5 were inactive when tested against Plasmodium falciparum or Trypanasoma cruzi at a concentration of 10 μg/mL, indicating that they have selective activity against Leishmania parasites. Compounds 1−5 showed weak cytotoxicity to Vero cells (IC₅₀ of 9, 162, 174, 152, and 150 μM, respectively); however, the therapeutic window of these compounds is quite significant with 75, 41, 130, 245, and 18 times (respectively) more antileishmanial activity than cytotoxicity.