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 1â 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 1â 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 1â 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.
