Reyes-Chilpa Ricardo, Estrada-Muñiz Elizabeth, Vega-Avila Elisa, Abe Fumiko, Kinjo Junei, Hernández-Ortega Simón
Instituto de Química, Universidad Nacional Autónoma de México, México, DF, México.
Mem Inst Oswaldo Cruz. 2008 Aug;103(5):431-6. doi: 10.1590/s0074-02762008000500004.
Calophyllum brasiliense and Mammea americana (Clusiaceae) are two trees from the tropical rain forests of the American continent. A previous screening showed high trypanocidal activity in the extracts of these species. Several mammea-type coumarins, triterpenoids and biflavonoids were isolated from the leaves of C. brasiliense. Mammea A/AA was obtained from the fruit peels of M. americana. These compounds were tested in vitro against epimastigotes and trypomastigotes of Trypanosoma cruzi, the etiologic agent of Chagas disease. The most potent compounds were mammea A/BA, A/BB, A/AA, A/BD and B/BA, with MC100 values in the range of 15 to 90 microg/ml. Coumarins with a cyclized gamma,gamma-dimethylallyl substituent on C-6, such as mammea B/BA, cyclo F + B/BB cyclo F, and isomammeigin, showed MC100 values > 200 microg/ml. Several active coumarins were also tested against normal human lymphocytes in vitro, which showed that mammea A/AA and A/BA were not toxic. Other compounds from C. brasiliense, such as the triterpenoids, friedelin, canophyllol, the biflavonoid amentoflavone, and protocatechuic and shikimic acids, were inactive against the epimastigotes. The isopropylidenedioxy derivative of shikimic acid was inactive, and its structure was confirmed by X-ray diffraction. Our results suggest that mammea-type coumarins could be a valuable source of trypanocidal compounds.
巴西红厚壳和美国山竹子（藤黄科）是原产于美洲大陆热带雨林的两种树木。先前的筛选显示，这些物种的提取物具有较高的杀锥虫活性。从巴西红厚壳的叶子中分离出了几种山竹子型香豆素、三萜类化合物和双黄酮类化合物。美国山竹子的果皮中提取出了山竹子A/AA。这些化合物在体外针对恰加斯病的病原体克氏锥虫的无鞭毛体和锥鞭毛体进行了测试。最有效的化合物是山竹子A/BA、A/BB、A/AA、A/BD和B/BA，其MC100值在15至90微克/毫升范围内。在C-6位带有环化γ,γ-二甲基烯丙基取代基的香豆素，如山竹子B/BA、环F + B/BB环F和异山竹子素，其MC100值>200微克/毫升。几种活性香豆素也在体外针对正常人淋巴细胞进行了测试，结果表明山竹子A/AA和A/BA无毒。巴西红厚壳的其他化合物，如三萜类化合物、木栓酮、红厚壳醇、双黄酮类化合物穗花杉双黄酮以及原儿茶酸和莽草酸，对无鞭毛体无活性。莽草酸的异亚丙基二氧基衍生物无活性，其结构通过X射线衍射得以证实。我们的研究结果表明，山竹子型香豆素可能是一种有价值的杀锥虫化合物来源。
