New guaiane-type sesquiterpenoid dimers from Artemisia atrovirens and their antihepatoma activity

• 作者: Lihua Su Xintian Zhang Yunbao Ma Changan Geng Xiaoyan Huang Jing Hu Tianze Li Shuang Tang Cheng Shen Zhen Gao Xuemei Zhang Ji-Jun Chen
• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2021,（6）
• 所属期刊栏目: Original articles
• 页码范围: 1648-1666
• 页数: 19页
• 语种: 英文

摘要

Leading by cytotoxicity against HepG2 cells,bioactivity-guided fractionation of the EtOAc fraction from Artemisia atrovirens led to the isolation of 18 new guaianolide dimers,artematrolides A--R and lavandiolides A,B,C,H,and J.Eight compounds (1,4,10,12,13,and 19-21) were unambiguously confirmed by the single-crystal X-ray diffraction analyses,and the others were elucidated based on IR,UV,HRESIMS,1D and 2D NMR experiments,and comparison of the experimental and calculated ECD data.Structurally,all of them were[4 + 2]Diels--Alder adducts of two monomeric guaianolides.The isolates were evaluated for their cytotoxicity against three human hepatoma cell lines,and 19 com-pounds demonstrated cytotoxicity against HepG2,SMMC-7721,and Huh7 cell lines.Especially,com-pounds 1,12,14,and 15 exhibited cytotoxicity with IC50 values of 4.4,3.8,7.6,and 6.7 μmol/L(HepG2),9.6,4.6,6.6,and 6.0 μmol/L (SMMC-7721),and 7.6,4.5,6.9,and 5.6 μmol/L (Huh7),respec-tively.Notably,compound 12 showed the most promising activity against three human hepatoma cell lines and dose-dependently inhibited cell migration and invasion,induced G2/M cell cycle arrest and cell apoptosis in HepG2 cells,down-regulated the expression of BCL-2 and PARP-1,and activated PARP-1 to up-regulate the expression of cleaved-PARP-1.