Bioactivity-Guided Isolation of Cytotoxic Sesquiterpenes and Flavonoids from Anthemis ruthenica

A new eudesmanolide sesquiterpene, sivasinolide 6-O-angelate (1), was isolated from the aerial parts of Anthemis ruthenica together with the known compounds chrysanin (2), tanacin (3), 3 beta-hydroxycostunolide (4), centauridin (5), and centaureidin (6). The compounds were obtained by means of bioactivity-guided fractionation from the CHCl3 extract of the herb, which displayed high cytotoxic activity. The structures were determined by UV, HR-ESI-MS, and high-field 1D and 2D NMR spectral analyses, affording complete H-1- and C-13-NMR assignments for all compounds. The cytotoxic activities of the isolated sesquiterpenes and flavonoids were assessed against cervical adenocarcinoma HeLa, breast adenocarcinoma MCF7, and skin epidermoid carcinoma A431 cells using the MTT assay. It was found that, apart from centaureidin (6), which is extremely active (IC50 0.082, 0.13, and 0.35 mu M on the HeLa, MCF7, and A431 cell lines, respectively), all these compounds exert high or moderate tumor cell-growth inhibitory activity (IC50 3.42-58.15 mu M).