Artemselenoids A-H, eight guaiane-type sesquiterpenoid dimers from and their antihepatoma activities.

Eight undescribed guaiane-type sesquiterpenoid dimers (GSDs), artemselenoids A-H (1-8), together with nine known GSDs (9-17), were isolated from . Their structures and absolute configurations were determined through comprehensive spectral analyses, theoretical ECD calculations, and NMR computations. Chemically, compound 1 represented the first example of two guaianolide lactone units dimerizing through unprecedented C-3-C-11' and C-4-C-13' bonds a [2 + 2] cycloaddition reaction and producing a structurally unique 5,4 spirocyclic system; compounds 2-8 were biogenetically formed through a [4 + 2] cycloaddition reaction.

Artemyriantholidimers A-G, undescribed guaiane-type sesquiterpenoid dimers from Artemisia myriantha and their antihepatoma activities.

Artemyriantholidimers A-G (1-7), seven undescribed guaiane-type sesquiterpenoid dimers (GSDs), and 27 known compounds (8-34) were isolated from Artemisia myriantha (Asteraceae). Their structures and relative configurations were elucidated based on the comprehensive analyses of UV, IR, MS, NMR data, quantum chemical NMR calculations with DP4+ probability analyses, and the absolute configurations were elucidated by ECD calculations. The undescribed GSDs (1-7) were presumably formed via Diels-Alder reactions, and compounds 5-7 were rare GSDs with α-configuration of H-6'.

Artemordosins A-L, cadinane-monoterpene heterodimers and sesquiterpenoids with antihepatoma activity from Artemisia ordosica.

Two unprecedented sesquiterpene and monoterpene heterodimers and ten previously undescribed sesquiterpenoids, artemordosins A-L (1-12), as well as ten known sesquiterpenoids (13-22), were obtained from Artemisia ordosica. Their structures were elucidated based on comprehensive analyses of NMR, IR, HRESIMS, GIAO NMR calculations with DP4+ probability analysis, and ECD calculations. Notably, artemordosins A and B (1 and 2) were the first examples of cadinane-monoterpene dimers, and artemordosin A (1) was a cadinane-myrceane heterodimer with a 6/6/6/6 ring system formed by [4 + 2] cycloaddition, while artemordosin B (2) was a 4,5-seco-cadinane-artemisane dimer connected through a C-5-O-C-4' linkage.

Compound-protein interaction prediction based on heterogeneous network reveals potential antihepatoma agents.

Despite the development of an increasing number of multi-kinase and immune checkpoint inhibitors for hepatocellular carcinoma (HCC), improvement in cancer survival remains limited due to their similar structures and targets. Natural products (NPs) maintain diverse structures and activities and are important sources of drug discovery. Currently, most of active NPs exhibit ambiguous binding targets and mechanisms.

Unusual cadinane-involved sesquiterpenoid dimers from Artemisia annua and their antihepatoma effect.

Artemisia annua L. ("Qinghao" in Chinese) is a famous traditional Chinese medicinal herb and has been used to treat malaria and various tumors. Our preliminary screening indicated that the EtOAc extract of A.

Artemyriantholides A-K, guaiane-type sesquiterpenoid dimers from Artemisia myriantha var. pleiocephala and their antihepatoma activity.

Artemyriantholides A-K (1-11) as well as 14 known compounds (12-25) were isolated from Artemisia myriantha var. pleiocephala (Asteraceae). The structures and absolute configuration of compounds 2 and 8-9 were confirmed by the single crystal X-ray diffraction analyses, and the others were elucidated by MS, NMR spectral data and electronic circular dichroism calculations.

Artemdubosides A-G, seven unusual polyacetylenes from Artemisia dubia var. subdigitata and their antihepatoma activity.

Artemdubosides A-E (1-5), the first examples of natural polyacetylenes substituted by 6'-O-crotonyl β-glucopyranoside, and artemdubosides F-G (6-7) that were two unusual polyacetylenes featuring a 6'-O-acetyl β-glucopyranoside moiety, were isolated from Artemisia dubia var. subdigitata. Their structures were elucidated based on the spectral data including HRESIMS, UV, IR, 1D and 2D NMR, and ECD calculations.

Highly oxygenated guaiane-type sesquiterpene lactones from Artemisia sacrorum and their antihepatoma activity.

The ethanol and EtOAc extracts of Artemisia sacrorum exhibited inhibitory effect against HepG2, Huh7, and SK-Hep-1 cell lines with inhibitory ratios of 65.5%, 28.1%, 84.

Artemongolins A-K, undescribed germacrane-guaiane sesquiterpenoid dimers from Artemisia mongolica and their antihepatoma activities.

Artemongolins A-K (1-11), which are undescribed sesquiterpenoid dimers, were obtained from Artemisia mongolica and characterized through comprehensive spectral data, including HRESIMS, IR, 1D and 2D NMR, and ECD calculations. The absolute configurations of compounds 1, 4, and 7 were undoubtedly determined by a single-crystal X-ray crystallography. Artemongolins A-K (1-11) featured a rare 5/7/5/5/5/10 hexacyclic system composed of a germacrene and a guaianolide by a fused 2-oxaspiro[4,4]nonane-1-one ring system.

Artemeriosides A-F, the first examples of natural sesquiterpenoids substituted by a 6'-O-crontonyl β-glucopyranoside from Artemisia annua.

Artemeriosides A-F (1-6), six novel sesquiterpenoids containing a 6'-O-crontonyl β-glucopyranoside, were isolated from Artemisia annua L. Their structures were determined by spectral data including HRESIMS, IR, UV, 1D and 2D NMR, and ECD calculations. Compounds 1-6 represented the first examples of natural sesquiterpenoid substituted by 6'-O-crontonyl β-glucopyranoside.

Design and synthesis of guaianolide-germacranolide heterodimers as novel anticancer agents against hepatocellular carcinoma.

Inspired by our previous finding that disesquiterpenoids showed more potent antihepatoma cytotoxicity than their corresponding parent monomers, natural product-like guaianolide-germacranolide heterodimers were designed and synthesized from guaianolide diene and germacranolides via a biomimetic Diels-Alder reaction to provide three antihepatoma active dimers with novel scaffolds. To explore the structure-activity relationship, 31 derivatives containing ester, carbamate, ether, urea, amide, and triazole functional groups at C-14' were synthesized and evaluated for their cytotoxic activities against HepG2, Huh7, and SK-Hep-1 cell lines. Among them, 25 compounds were more potent than sorafenib against HepG2 cells, 15 compounds were stronger than sorafenib against Huh7 cells, and 17 compounds were stronger than sorafenib against SK-Hep-1 cells.

Artemannuols A-C, novel sesquiterpenoid-flavonol hybrids with antihepatoma activity from .

, also known as "Qinghao" in Chinese, is a famous traditional Chinese medicine and has been used for the treatment of malaria and various tumors. In this study, three novel sesquiterpenoid-flavonol hybrids, artemannuols A-C (1-3), were isolated and elucidated by extensive spectral data and ECD calculations. Structurally, artemannuols A-C (1-3) are the first examples of sesquiterpenoid-flavonol hybrids fused by an ether bond, among which artemannuols A and B (1 and 2) are composed of bisabolane-type sesquiterpenoid and flavonol moieties, and artemannuol C (3) is composed of humulane-type sesquiterpenoid and flavonol moieties.

Rubiginosin B selectively inhibits Treg cell differentiation and enhances anti-tumor immune responses by targeting calcineurin-NFAT signaling pathway.

Background: The accumulation of CD4Foxp3 regulatory T cells (Tregs) in the tumor microenvironment (TME) dampens anti-tumor immune responses and promotes tumor progression. Therefore, the elimination of Tregs has become a strategy to enhance the efficacy of tumor immunotherapy, although it is still a daunting challenge. Rhododendron brachypodum (R.

New eudesmanolides from Artemisia verlotorum and their potential targets of hepatocellular carcinoma by network pharmacology.

Fractionation of the ethanol extract of Artemisia verlotorum led to the identification of eight undescribed eudesmane-type sesquiterpenoids, artemverlolides A-H (1-8). Their structures were determined by spectral analyses (HRESIMS, 1D and 2D NMR, IR, and ECD). Network pharmacology predicted that compounds 1-8 might be target on AURKA, CCNA2, CYP2C19, and EPHX2 with possibly antihepatoma effect from Swiss TargetPrediction and Gene Expression Omnibus database.

Artemongolides A-F, undescribed sesquiterpenoid dimers from and their antihepatic fibrosis activities.

Artemongolides A-E (1-5), an unusual class of diseco-guaianolides featuring a rare fused 7-methylbicyclo[2.2.1]-2-ene-7-heptanol ring system, and artemongolide F (6), the first example of [4 + 2] Diels-Alder type adducts presumably incorporating a chain farnesane sesquiterpene and a guaianolide diene, were isolated from the whole plant of Their structures were elucidated based on the spectroscopic analyses of UV, IR, MS, and 1D and 2D NMR spectra.

Artemleucolides A-L, eudesmane-type sesquiterpenoids from Artemisia leucophylla and their antihepatoma cytotoxicity.

Twelve undescribed and 13 known eudesmane-type sesquiterpenoids were obtained from Artemisia leucophylla, and structurally elucidated based on comprehensive analyses of spectral data, including HRESIMS, IR, 1D and 2D NMR, and ECD calculation. The absolute configuration of compound 1 was determined by a single X-ray single crystal diffraction. Chemically, compounds 1-5 featured unprecedented 1,2-seco-1-nor-eudesmane-type skeleton with a cis-fused 6/5 bicyclic system.

Synthesis and biological evaluation of paeoveitol D derivatives as new melatonin receptor agonists with antidepressant activities.

Our previous study demonstrated that paeoveitol D, a benzofuran compound isolated from , displayed activity on MT and MT receptors with agonistic ratios of 57.5% and 51.6% at a concentration of 1 mM.

Distepharinamide, a novel dimeric proaporphine alkaloid from Diploclisia glaucescens, inhibits the differentiation and proliferative expansion of CD4Foxp3 regulatory T cells.

Background: CD4Foxp3 regulatory T cells (Tregs) represent the primary cellular mechanism of tumor immune evasion. Elimination of Treg activity by the pharmacological agent may enhance anti-tumor immune responses. However, Treg-eliminating agents, especially those with small molecules, are rarely reported.

Synthesis and biological evaluation of (+)-paeoveitol derivatives as novel antidepressants.

The antidepressant activity of (+) and (-)-paeoveitol was first evaluated using the forced swimming test (FST), and (+)-paeoveitol showed potential antidepressant activity by decreasing immobility time of mice (by approximately 26.4%) in the FST at a dose of 20 mg/kg. To explore the structure-activity relationships (SARs) and obtain more potent compounds, twenty derivatives of (+)-paeoveitol were synthesized and evaluated for their agonistic activities on melatonin type I (MT) and type II (MT) receptors.

Artemzhongdianolides A1-A21, antihepatic fibrosis guaiane-type sesquiterpenoid dimers from 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.

Design and synthesis of ludartin derivatives as potential anticancer agents against hepatocellular carcinoma.

Our previous study demonstrated that guaiane-type sesquiterpenoid ludartin showed potent antihepatoma activity against two human hepatocellular carcinoma cell lines, HepG2 and Huh7, with IC values of 32.7 and 34.3 μM, respectively.