Salim Angela A, Chai Hee-Byung, Rachman Ismail, Riswan Soedarsono, Kardono Leonardus B S, Farnsworth Norman R, Carcache-Blanco Esperanza J, Kinghorn A Douglas
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210.
Tetrahedron. 2007 Aug 13;63(33):7926-7934. doi: 10.1016/j.tet.2007.05.074.
The previously known potent cytotoxic agent silvestrol (1) (0.002% w/w yield) and five new flavagline derivatives (2-6) were isolated from the leaves of Aglaia foveolata collected in Indonesia. The new compound 5 has an unprecedented cyclic amide moiety in its cyclopenta[b]benzopyran skeleton, while compound 6 is a novel benzo[b]oxepine derivative in which the oxepine ring is cleaved. Pyramidatine (7), a biogenetic precursor of the new flavaglines 2-6, was isolated from the leaf extract investigated. Silvestrol was also isolated from the stem bark of A. foveolata (yield of 0.02% w/w) along with a new baccharane-type triterpenoid (8). The structures of the new compounds were elucidated on the basis of their NMR and mass spectrometric data. All new compounds isolated were tested against a panel of cancer cell lines, but only compound 2 was cytotoxic (IC(50) range = 1.4-1.8 muM), and is the first member of the cyclopenta[b]benzopyran class found to exhibit this type of activity. Compound 2 also showed significant NF-kappaB inhibitory activity in an Elisa assay (IC(50) = 0.37 muM).
从印度尼西亚采集的小叶米仔兰叶片中分离出了之前已知的强效细胞毒性剂silvestrol（1）（产率0.002% w/w）和五种新的黄烷类衍生物（2 - 6）。新化合物5在其环戊并[b]苯并吡喃骨架中具有前所未有的环状酰胺部分，而化合物6是一种新型苯并[b]氧杂䓬衍生物，其中氧杂䓬环被裂解。从所研究的叶提取物中分离出了新黄烷类化合物2 - 6的生源前体金字塔碱（7）。还从小叶米仔兰的茎皮中分离出了silvestrol（产率0.02% w/w）以及一种新的羽扇烷型三萜（8）。根据它们的核磁共振和质谱数据阐明了新化合物的结构。对所有分离出的新化合物进行了一组癌细胞系测试，但只有化合物2具有细胞毒性（IC50范围 = 1.4 - 1.8 μM），并且是环戊并[b]苯并吡喃类中首个被发现具有这种活性类型的成员。在酶联免疫吸附测定中，化合物2还表现出显著的核因子κB抑制活性（IC50 = 0.37 μM）。
