Cytotoxic sesquiterpene lactones from aerial parts of Xanthium sibiricum.

Chemical investigation of the aerial parts of Xanthium sibiricum led to the isolation of four new xanthanolide-type sesquiterpene lactones, including two xanthanolide dimers, pungiolide D (1) and pungiolide E (2), and two xanthanolide monomers, 8-epi-xanthatin-1α,5α-epoxide (3) and 1β-hydroxyl-5α-chloro-8-epi-xanthatin (4), together with four known compounds, pungiolide A (5), 8-epi-xanthatin-1β,5β-epoxide (6), xanthatin (7), and 11α,13-dihydro-8-epi-xanthatin (8). The structures of these compounds were elucidated on the basis of spectroscopic data analysis. Pungiolide D (1) displayed an unusual structure featuring a 5/5/6-fused tricyclic system in the unit B. Compound 4 was shown to be a rare sesquiterpene lactone containing halogen, and its absolute configuration was determined by X-ray crystallographic analysis. The evaluation of the cytotoxic activities of the isolated new compounds against the SNU387 liver and A-549 lung human cancer cell lines showed that compound 4 possessed significant in vitro cytotoxicity with an IC50 value of 5.1 µM against SNU387 liver cells. Georg Thieme Verlag KG Stuttgart · New York.