reynosin and Ovarian-Neoplasms

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.

Topics: Antineoplastic Agents, Phytogenic; Carcinoma, Hepatocellular; Crystallography, X-Ray; Drug Screening Assays, Antitumor; Drugs, Chinese Herbal; Female; HeLa Cells; Humans; Lactones; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Ovarian Neoplasms; Plant Roots; Plants, Medicinal; Saussurea; Sesquiterpenes; Structure-Activity Relationship; Tumor Cells, Cultured