Sun Chang-Ming, Syu Wan-Jr, Don Ming-Jaw, Lu Jang-Jih, Lee Gum-Hee
National Research Institute of Chinese Medicine, Taipei, Taiwan, Republic of China.
J Nat Prod. 2003 Sep;66(9):1175-80. doi: 10.1021/np030147e.
Bioassay-directed fractionation of Saussurea lappa led to the isolation of a novel lappadilactone (1) and seven sesquiterpene lactones (2-8) as cytotoxic principles against selected human cancer cell lines. Lappadilactone (1), dehydrocostuslactone (2), and costunolide (5) exhibited the most potent cytotoxicity with CD50 values in the range 1.6-3.5 microg/mL in dose- and time-dependent manners. The cytotoxicities were not specific and showed similar activities against HepG2, OVCAR-3 and HeLa cell lines. The structure-activity relationship showed that the alpha-methylene-gamma-lactone moiety is necessary for cytotoxicity, and activity is reduced with the presence of a hydroxyl group. In addition, seven noncytotoxic compounds (9-15) were also isolated, including two novel sesquiterpenes, a guaianolide-type with a C17 skeleton, lappalone (13), and 1beta,6alpha-dihydroxycostic acid ethyl ester (14). The structures of the new compounds were elucidated from spectroscopic and/or X-ray data interpretations. Some representative compounds were also tested for antibacterial activity; however, only marginal activities were observed. Therefore, compounds 1-8 are potential cytotoxic agents but without significant antibacterial effect.
对木香进行生物活性导向的分离，得到了一种新型的木香二内酯（1）和七种倍半萜内酯（2 - 8），它们是针对选定的人类癌细胞系的细胞毒性成分。木香二内酯（1）、脱氢木香内酯（2）和木香烃内酯（5）表现出最强的细胞毒性，其半数细胞毒性浓度（CD50）值在1.6 - 3.5微克/毫升范围内，呈剂量和时间依赖性。细胞毒性不具有特异性，对肝癌细胞系HepG2、卵巢癌细胞系OVCAR - 3和宫颈癌细胞系HeLa表现出相似的活性。构效关系表明，α-亚甲基-γ-内酯部分是细胞毒性所必需的，而羟基的存在会降低活性。此外，还分离出七种无细胞毒性的化合物（9 - 15），包括两种新型倍半萜、一种具有C17骨架的愈创木烷型内酯、木香酮（13）和1β,6α-二羟基木香酸乙酯（14）。通过光谱和/或X射线数据解析确定了新化合物的结构。还对一些代表性化合物进行了抗菌活性测试；然而，仅观察到微弱的活性。因此，化合物1 - 8是潜在的细胞毒性剂，但没有显著的抗菌作用。
