Artematrovirenolides A-D and Artematrolides S-Z,Sesquiterpenoid Dimers with Cytotoxicity against Thr

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Inspired by the intriguing structures and remarkable activities of sesquiterpenoid dimers,12 new sesquiterpenoid dimers,arte-matrovirenolides A-D (1-4) and artematrolides S-Z (8-12),were isolated from the EtOAc fraction of Artemisia atrovirens through a bioactivity-guided approach.Their structures were elucidated by comprehensive spectroscopic data and absolute config-uration was assigned based on single crystal X-ray diffraction data and ECD calculations.Structurally,all compounds are presumably formed via[4+2]cycloaddition involving three connecting model.Compounds 1-4 are four novel hetero-dimeric[4+2]Diels-Alder adducts dimerized from a rotundane-type unit and a guaiane-type monomer,and compounds 5-12 are eight new homo-dimeric[4+2]adducts derived from two guaianolide moieties.A putative biosynthetic pathway for compounds 1-4 was also proposed.Compounds 4,6,7,and 10 demonstrated moderate cytotoxicity against HepG2,SMMC-7721,and Huh7 cell lines with ICs0 values ranging from 9.3 to 62.3 μmol/L.Interestingly,compounds 5 and 11 manifested cytotoxicity with IC50 values of 13.6 and 12.8(HepG2),18.5 and 13.1 (SMMC-7721),and 16.5 and 19.4 μmol/L (Huh7),respectively,which were equivalent to the positive control,sorafenib.This investigation suggests that compounds 5 and 11 might be considered as potent antihepatoma candidates and de-serve further structural modification and mechanism study.
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