Three Types of Isocoumarins with Unusual Carbon Skeletons from Artemisia dubia var. subdigitata and Their Antihepatoma Activity  

作　　者：Ke-Xin Yang Tian-Ze Li Yun-Bao Ma Yong-Cui Wang Feng-Jiao Li 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》2024年第16期1901-1912,共12页中国化学（英文版）

基　　金：financially supported by the Key Program of the 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：Ten novel isocoumarins,including four pairs of enantiomers,were isolated from Artemisia dubia var.subdigitata(Asteraceae).Compounds 1,2 and 3a/3b possessed a unique 6/6/6-tricyclic system comprising an unusual 1-(2-methylcyclohexyl)propan-1-one moiety fused with isocoumarin core skeleton.Compounds 4a/4b were characterized as an unexpected 2,5-dimethylcyclohexan-1-one scaffold,and compounds 5a/5b and 6a/6b were rare 1,2-seco-isocoumarin.Their structures and absolute configurations were elucidated through spectroscopic data,X-ray crystallography,ECD and NMR calculations with DP4+analyses.Plausible biosynthetic pathways were proposed from the naturally occurring isocoumarin.Network pharmacological analysis suggested that the targets of compound 1 were significantly enriched in the cell cycle and Pl3K-Akt signaling pathway.The molecular docking revealed that compound 1 had high binding affinity with CDK2(total score:6.8717).Furthermore,compounds 1 and 2 exhibited inhibitory activity on three human hepatoma cell lines,with inhibitory ratios of 85.1% and 84.5%(HepG2),88.2% and 87.3%(Huh7),and 69.2% and 69.1%(SK-Hep-1)at 200μmol·L^(-1),respectively.

关 键 词：Artemisia dubia var.subdigitata ISOCOUMARINS Antihepatoma activity Cancer Natural products X-ray diffraction 

分 类 号：R285[医药卫生—中药学]