Antileishmanial constituents of the Panamanian endophytic fungus Edenia sp.
Bioassay-directed fractionation of extracts from the fermentation broth and mycelium of the fungus Edenia sp. led tothe 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 microM, respectively. Compounds 1-5 were inactive when tested against Plasmodium falciparum or Trypanasoma cruzi at a concentration of 10 microg/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 microM, 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.
Martínez-Luis
Sergio
S
Smithsonian Tropical Research Institute, Unit 0948, APO AA 34002-0948, Panama, Republic of Panama.
Della-Togna
Gina
G
Coley
Phyllis D
PD
Kursar
Thomas A
TA
Gerwick
William H
WH
Cubilla-Rios
Luis
L
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001203:Ascomycota / Q000737:chemistry*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D007893:Leishmania donovani / Q000187:drug effects*; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010176:Panama; D010963:Plasmodium falciparum / Q000187:drug effects; D013141:Spiro Compounds / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
D000981:Antiprotozoal Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D009281:Naphthalenes; D013141:Spiro Compounds; C462859:palmarumycin CP2