Martínez-Luis Sergio, Della-Togna Gina, Coley Phyllis D, Kursar Thomas A, Gerwick William H, Cubilla-Rios Luis
Smithsonian Tropical Research Institute, Unit 0948, APO AA 34002-0948, Panama, Republic of Panama.
J Nat Prod. 2008 Dec;71(12):2011-4. doi: 10.1021/np800472q.
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.
对真菌Edenia sp.发酵液和菌丝体提取物进行生物测定导向的分级分离，得到了五种抗利什曼原虫化合物，即普雷索菌素EG1（1）、棕榈霉素CP2（2）、棕榈霉素CP17（3）、棕榈霉素CP18（4）和CJ-12,371（5）。化合物3和4是新的天然产物，这是化合物1的第二篇报道。通过光谱分析（高分辨质谱和核磁共振）确定了化合物1-5的结构。所有代谢产物对杜氏利什曼原虫无鞭毛体形式的生长均有显著抑制作用，IC50值分别为0.12、3.93、1.34、0.62和8.40微摩尔。化合物1-5在浓度为10微克/毫升时对恶性疟原虫或克氏锥虫进行测试时无活性，表明它们对利什曼原虫具有选择性活性。化合物1-5对Vero细胞显示出较弱的细胞毒性（IC50分别为9、162、174、152和150微摩尔）；然而，这些化合物的治疗窗口相当显著，其抗利什曼原虫活性分别比细胞毒性高75、41、130、245和18倍。
