Cytotoxic Sesquiterpene Lactones from the Root of Saussurea lappa

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 μg/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 α-methylene-γ-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 1β,6α-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.