Artemiprincepsolides A—F, Novel Germacrane‐guaiane and Eudesmane‐guaiane Sesquiterpenoid Dimers from <i>Artemisia princeps</i> and Their Antihepatoma Activity
Li‐Hua Su, Wenjing Ma, Yun‐Bao Ma, Tian‐Ze Li, Chang‐An Geng, Wei Dong, Xiaofeng He, Xue‐Mei Zhang, Ji‐Jun Chen
Abstract
Comprehensive Summary Artemiprincepsolides A—F ( 1 — 6 ) were isolated from Artemisia princeps guided by bioactivity and elucidated by comprehensive spectral data and ECD calculation. Compounds 1 — 3 represented the first connecting model of germacrane‐guaiane hetero‐dimeric adducts, and compounds 4 — 6 were eudesmane‐guaiane hetero‐coupled sesquiterpenoid dimers, meanwhile, all these were presumably formed by Diels‐Alder cycloaddition. Compounds 1 — 6 were evaluated for their hepatomatic cytotoxicity on three hepatoma cell lines, and demonstrated cytotoxicity with IC 50 values in the range of 5.0—67.3 μmol/L. Interestingly, compound 1 manifested significant cytotoxicity against HepG2, Huh7, and SK‐Hep‐1 cells with IC 50 values of 9.9, 9.2, and 5.0 μmol/L, which were almost equivalent to the positive control, sorafenib. Flow cytometry data and Western blot assays revealed the most active compound 1 dose‐dependently inhibited cell migration and invasion, and significantly induced HepG2 cells arrest in G2/M phase by downregulating proteins pcdc2 and upregulating the level of protein CyclinB1; and induced apoptosis by downregulating of Bcl‐2 expression and upregulating Bax level.