Guaiane-type Sesquiterpenoid Dimers from Artemisia zhongdianensis and Antihepatoma Carcinoma Activity via the p38MAPK Pathway  

作　　者：Wei Dong Wen-Jing Ma Yun-Bao Ma Feng-Jiao Li Tian-Ze Li Yong-Cui Wang Xiao-Feng He Chang-An Geng Xue-Mei Zhang Ji-Jun Chen 

机构地区：[1]State Key Laboratory of Phytochemistry and Plant Resources in West China,Kunming Institute of Botany,Chinese Academy of Sciences,Kunming,Yunnan,650201 China [2]University of Chinese Academy of Sciences,Beijing,100049 China

出　　处：《Chinese Journal of Chemistry》2023年第19期2453-2468,共16页中国化学（英文版）

基　　金：supported by the Key Program of National Natural Science Foundation of China(22137008);the Xingdian Yingcai Project(YNWR-KJLJ-2019-002);the Youth Innovation Promotion Association,CAS(2020386);the Reserve Talents of Young and Middle-aged Academic and Technical Leaders in Yunnan Province(202105AC160021).

摘　　要：17 new guaiane-type sesquiterpenoid dimers(GSDs),artemzhongdianolides B1—B17(1—17),were isolated from Artemisia zhongdianensis under the guidance of bioassay,and elucidated by spectral analyses(HRESIMS,1D and 2D NMR,IR,ECD).The absolute configuration of compounds 1,3,7,9,10,and 13 was determined by single-crystal X-ray diffraction analyses.Structurally,artemzhongdianolides B1(1)and B2(2)were the first example of the GSDs fused via a C-13/C-13'single bond,and artemzhongdianolides B3—B17 were[4+2]Diels–Alder adducts of two monomeric guaianolides.Most of the compounds showed antihepatoma cytotoxicity with IC_(50) values ranging from 9.9 to 170.1μmol/L.Importantly,artemzhongdianolide B9(9)was the most active one against three hepatoma cell lines with IC_(50) values of 13.1μmol/L(HepG2),19.5μmol/L(Huh7),and 19.5μmol/L(SK-Hep-1),and dose-dependently inhibited cell migration and invasion,induced G1 cell cycle arrest and cell apoptosis in HepG2 cells.Compound 9 might suppress HepG2 cells via affecting the p38MAPK signaling pathway suggested by machine learning approach,and significantly upregulated expression of phosphorylated p38 validated by Western blot assay.

关 键 词：Artemzhongdianolides B1-B17 Artemisia zhongdianensis Guaiane-type sesquiter penoid dimers Antihepatoma activity p38MAPK pathway Cancer NMR spectroscopy X-ray diffraction 

分 类 号：R285[医药卫生—中药学]