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[Display omitted] • 51 artemyrianolide H derivatives were synthesized and evaluated for cytotoxicity against human hepatoma cells. • 34 compounds were more active than artemyrianolide H and sorafenib. • Compound 25 induced G2/M phase arrest, apoptosis and bound to PDGFRA and MAP2K2. Artemyrianolide H (AH) is a germacrene-type sesquiterpenolid isolated from Artemisia myriantha , and showed potent cytotoxicity against three human hepatocellular carcinoma cell lines HepG2, Huh7, and SK-Hep-1 with IC 50 values of 10.9, 7.2, and 11.9 µM, respectively. To reveal structure−activity relationship, 51 artemyrianolide H derivatives including 19 dimeric analogs were designed, synthesized, and assayed for their cytotoxicity against three human hepatoma cell lines. Among them, 34 compounds were more active than artemyrianolide H and sorafenib on the three cell lines. Especially, compound 25 exhibited the most promising activity with IC 50 values of 0.7 (HepG2), 0.6 (Huh7), and 1.3 µM (SK-Hep-1), which were 15.5, 12.0, and 9.2-fold higher than that of AH and 16.4, 16.3 and 17.5-fold higher than that of sorafenib. Cytotoxicity evaluation on normal human liver cell lines (THLE-2) demonstrated good safety profile of compound 25 with SI of 1.9 (HepG2), 2.2 (Huh 7) and 1.0 (SK-Hep1). Further studies revealed that compound 25 dose-dependently arrested cells at G2/M phase which was correlated with the up-regulation of both cyclin B1 and p-CDK1, and induced apoptosis through the activation of mitochondrial pathways in HepG2 cells. In addition, the migratory and invasive abilities in HepG2 cells after treatment with 1.5 μM of compound 25 were decreased by 89% and 86% with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, vimentin expression. Bioinformatics analysis based on machine learning predicted that PDGFRA and MAP2K2 might be acting targets of compound 25 , and SPR assays demonstrated compound 25 were bound with PDGFRA and MAP2K2 with K D value of 0.168 nM, and 8.49 µM, respectively. This investigation proposed that compound 25 might be considered as a promising lead compound for the development of antihepatoma candidate. [ABSTRACT FROM AUTHOR]

[Display omitted] • Twenty-one new guaianolide dimers were isolated from Artemisia zhongdianensis. • Nine compounds exhibited cytotoxicity against HSC-LX2. • Compounds 2, 6 and 13 displayed inhibitory activity on the deposition of Col Ⅰ, HA and HL. • This study provides more evidence for understanding of antihepatic fibrosis potency of Artemisia zhongdianensis. In the search for new antihepatic fibrosis candidates, it was observed that the EtOH extract of Artemisia zhongdianensis and EtOAc fraction had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with the inhibitory ratios of 85.7 % and 83.9 % at 400 μg/mL. 21 new guaianolide dimers, artemzhongdianolides A1 − A21 (1 – 21) were isolated from the active fractions under the guidance of bioassay, and elucidated by spectral analyses (HRESIMS, 1D and 2D NMR, IR, ECD). The absolute stereochemistry of compounds 1 , 13 , and 14 was determined by single-crystal X-ray diffraction analyses. Cytotoxicity evaluation suggested that nine compounds exhibited activity against HSC-LX2 with IC 50 values ranging from 14.0 to 95.2 μM. Of them, compounds 2 , 6 , and 13 displayed significant cytotoxicity against HSC-LX2 with IC 50 values of 22.1, 24.3 and 14.0 μM, which were 6 to 10 times more active than the positive drug silybin (IC 50 , 148.6 μM). Preliminary mechanism study revealed that compounds 2 , 6 , and 13 could markedly inhibited the deposition of human collagen type Ⅰ (Col Ⅰ), human hyaluronic acid (HA), and human laminin (HL) with IC 50 values of 37.9, 54.8, and 28.0 μM (Col Ⅰ), 29.5, 25.3, and 42.9 μM (HL), 31.2, 94.6, and 12.4 μM (HA), which were 1.5 to 13-fold more potent than silybin. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fourteen new coumaric acid analogues were isolated from Artemisia capillaris. • Twelve compounds exhibited cytotoxicity against HSC-LX2. • Compound 2 displayed potent inhibitory activity on the deposition of Col Ⅰ, HL and HA. • This study provides more evidence for the traditional use of Artemisia capillaris against hepatic fibrosis. Under the guidance of bioassay against HSC-LX2, the EtOH extract and the EtOAc fraction of Artemisia capillaris (Yin-Chen) exhibited cytotoxic activity against HSC-LX2 with inhibitory ratios of 39.7% and 68.7% at the concentration of 400.0 μg/mL. Bioassay-guided investigation of Fr. D (the active fraction) yielded 14 new coumaric acid analogues, artemicapillasins A–N (1 – 14). The structures of the isolates were elucidated by spectroscopic analyses involving UV, IR, MS, 1D and 2D NMR spectra and ECD calculations. Cytotoxic activity against HSC-LX2 cells of these isolates was performed to reveal that 12 compounds demonstrated cytotoxicity with inhibitory ratios more than 50% at 400 μM. The most active artemicapillasin B (2) gave an IC 50 value of 24.5 μM, which was about 7 times more toxic than the positive drug silybin (IC 50 , 162.3 μM). Importantly, artemicapillasin B (2) showed significant inhibition on the deposition of human collagen type I (Col I), human laminin (HL) and human hyaluronic acid (HA) with IC 50 values of 11.0, 14.4 and 13.8 μM, which was about 7, 11 and 5 times more active than silybin. Artemicapillasin B (2) as an interesting antihepatic fibrosis candidate is worth in-depth study. [ABSTRACT FROM AUTHOR]

• Eleven new sesquiterpenoids were isolated from A. lavandulaefolia. • Fourteen compounds exhibited cytotoxicity against HSC-LX2 with IC 50 values ranging from 16.5 to 337.2 μM. • Compounds 14 , 15 and 18 displayed inhibitory activity on the deposition of Col I and HL. The preliminary assay suggested that the EtOH extract of Artemisia lavandulaefolia had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with an inhibitory ratio of 94.1% at 400 μg/mL. Bioassay-guided investigation led to eleven new sesquiterpenoids, artemilavanolides C–F (1 – 4) and artemlavandulolides A–G (5 – 11), as well as thirteen known compounds (12 – 24). Their structures were elucidated by extensive spectroscopic data and X-ray crystallographic analysis. Cytotoxicity evaluation suggested that fourteen compounds exhibited activity against HSC-LX2; compounds 22 , 23 and 24 were comparable to the positive control, silybin (IC 50 , 162.3 μM); compounds 6 , 9 and 16 showed moderate activity with IC 50 values of 109.3, 114.0 and 124.2 μM. Importantly, compounds 14 , 15 and 18 displayed significant cytotoxicity against HSC-LX2 with IC 50 values of 52.1, 16.5 and 21.3 μM, and inhibitory activity on the deposition of human collagen type I (Col I) and human laminin (HL) with IC 50 values ranging from 7.3 to 71.6 μM and from 18.6 to 72.9 μM. [ABSTRACT FROM AUTHOR]