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...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.展开更多
Nineteen new cadinane-involving sesquiterpenoid dimers,artemordins A-S(1-—19),together with 13 known SDs(20-32)were isolated from Artemisia ordosica.Their structures and absolute configurations were established by co...Nineteen new cadinane-involving sesquiterpenoid dimers,artemordins A-S(1-—19),together with 13 known SDs(20-32)were isolated from Artemisia ordosica.Their structures and absolute configurations were established by comprehensive spectral analyses,X-ray single crystal diffraction,theoretical ECD,and NMR calculations.Chemically,artemordins A-F(1—6)were the first examples of two cadinane units constructed by unprecedented C-3−C-15′or C-3−C-13′single bond with an oxido-rearranged 6/5/6/6 fused ring system;artemordins G-K(7-11)were biogenetically connected by[4+2]cycloaddition reaction and artemordins G-J(7-10)possessed a novel 5/6/6/6/6/6/5-heptacyclic fused ring system.Artemordins L-S(12-19)were formed by esterification,which involved three different types of sesquiterpenoids.Antihepatoma assay suggested that the most active compounds,artemordins B and H(2 and 8),exhibited inhibitory activities on three hepatoma cell lines with IC50 values of 26.9 and 25.1μmol/L(HepG2),29.5 and 18.3μmol/L(Huh7),19.7 and 15.7μmol/L(SK-Hep-1).展开更多
基金supported by the Key Program of National Natural Science Foundation of China(22137008)the Xingdian Yingcai Project(YNWR-KJLJ-2019-002)+1 种基金the Youth Innovation Promotion Association,CAS(2020386)the Reserve Talents of Young and Middle-aged Academic and Technical Leaders in Yunnan Province(202105AC160021).
文摘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.
基金This work was financially supported by the Key Program of National Natural Science Foundation of China(22137008)the Xingdian Yingcai Project(YNWR-KJLJ-2019-002)+4 种基金the Youth Innovation Promotion Association,CAS(2020386)the Reserve Talents of Young and Middle-aged Academic and Technical Leaders in Yunnan Province(202105AC160021)the High-Level Talent Program of Yunnan Province(YNQR-QNRC-2020-125)the Science and Technology Plan Projects in Yunnan Province(202201AT070143)State Key Laboratory of Phytochemistry and Plant Resources in West China(P2021-ZZ06).
文摘Nineteen new cadinane-involving sesquiterpenoid dimers,artemordins A-S(1-—19),together with 13 known SDs(20-32)were isolated from Artemisia ordosica.Their structures and absolute configurations were established by comprehensive spectral analyses,X-ray single crystal diffraction,theoretical ECD,and NMR calculations.Chemically,artemordins A-F(1—6)were the first examples of two cadinane units constructed by unprecedented C-3−C-15′or C-3−C-13′single bond with an oxido-rearranged 6/5/6/6 fused ring system;artemordins G-K(7-11)were biogenetically connected by[4+2]cycloaddition reaction and artemordins G-J(7-10)possessed a novel 5/6/6/6/6/6/5-heptacyclic fused ring system.Artemordins L-S(12-19)were formed by esterification,which involved three different types of sesquiterpenoids.Antihepatoma assay suggested that the most active compounds,artemordins B and H(2 and 8),exhibited inhibitory activities on three hepatoma cell lines with IC50 values of 26.9 and 25.1μmol/L(HepG2),29.5 and 18.3μmol/L(Huh7),19.7 and 15.7μmol/L(SK-Hep-1).
