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%, 84.6%, and 93.5%, 82.0%, 89.0% at 200 µg/mL. Twenty-three undescribed guaiane-type sesquiterpene lactones, artemisacrolides A‒W, were isolated from A. sacrorum under the guidance of antihepatoma activity. Their structures were elucidated by spectral data (HRESIMS, IR, UV, 1D and 2D NMR), ECD calculations, and a single-crystal X-ray diffraction. Artemisacrolides A‒U were guaiane-type sesquiterpene lactones possessing α-methylene-γ-lactone and containing acetoxyl groups at C-8, and artemisacrolides V and W represented the first report from the genus Artemisia with a 1,10-rearranged guaiane-type sesquiterpene lactone. Antihepatoma assay suggested that artemisacrolides A‒U demonstrated better inhibitory activity in Huh7 and SK-Hep-1 cells than those of HepG2 cells. Among them, nine compounds exhibited significant inhibitory activity against Huh7 cells with IC50 values of 8.2-14.3 µM, superior or equal to that of sorafenib; seven compounds demonstrated obvious activity against SK-Hep-1 cells with IC50 values of 13.5-19.2 µM, which were equivalent to that of sorafenib. Artemisacrolides B and E were the most active ones in three human hepatoma cell lines with IC50 values of 21.9, 8.2, 16.9 and 22.6, 9.0, 17.3 µM.

[Research progress on natural guaiane-type sesquiterpenoids and their biological activities].

Guaiane-type sesquiterpenoids are a class of terpenoids with [5,7] ring-fused system as the basic skeletal structure composed of three isoprene units, which are substituted by 4,10-dimethyl-7-isopropyl. According to the difference in functional groups and degree of polymerization, they can be divided into simple guaiane-type sesquiterpenoids, sesquiterpene lactones, sesquiterpene dimers, and sesquiterpene trimers. Natural guaiane-type sesquiterpenoids are widely distributed in plants, fungi, and marine organisms, especially in families such as Compositae, Zingiberaceae, Thymelaeaceae, Lamiaceae, and Alismataceae. Guaiane-type sesquiterpenoids have good antibacterial, anti-inflammatory, anticancer, and neuroprotective effects. In this paper, the novel guaiane-type sesquiterpenoids isolated and identified in recent 10 years(2013-2022) and their biological activities were reviewed in order to provide refe-rences for the research and development of guaiane-type sesquiterpenoids.

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. 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 IC50 values ranging from 14.0 to 95.2 µM. Of them, compounds 2, 6, and 13 displayed significant cytotoxicity against HSC-LX2 with IC50 values of 22.1, 24.3 and 14.0 µM, which were 6 to 10 times more active than the positive drug silybin (IC50, 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 IC50 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.

Chamaejasnoids A-E, a 2,3-seco-guaiane sesquiterpenoid with a 5/6/7 bridged ring system and related metabolites from Stellera chamaejasme L.

Sixteen guaiane-type sesquiterpenoids were isolated from Stellera chamaejasme L. Among them, chamaejasnoids A-F (1-5) are new compounds. 1 represents the first example of 2,3-seco-guaiane sesquiterpenoid with a 5/6/7 bridged ring system. 2 is a unique 2-nor-guaiane sesquiterpenoid. A plausible biosynthetic pathway for 1 was proposed, involving a Baeyer-Villiger oxidation and a non-enzymatic intramolecular transesterification. 5 exhibited a selective cytotoxicity against HCT8 cell line with an IC50 of 11.82 ± 2.89 µM.

Specialised metabolites as chemotaxonomic markers of Coptosapelta diffusa, supporting its delimitation as sisterhood phylogenetic relationships with Rubioideae.

From the aerial extracts of Coptosapelta diffusa (Champ. ex Benth.) Steenis, twenty-one compounds were isolated and identified by means of column chromatography and NMR and MS techniques, respectively. Amongst, ten ones were determined to be undescribed compounds including six seco-iridoid glucosides (1-6), 2-(hydroxymethyl)-1,2,3,4-tetrahydroanthracene-9,10-dione (7) and three guaiane-type sesquiterpenes (15-17). Compounds 7, 8 and 9 exhibited inhibitory activities against Staphylococcus aureus ATCC25923 with MIC of 8, 4 and 8 µg/mL. The use of 1-6 (iridoids), 7-14 (anthraquinones) and 15-17 (sesquiterpenes) as chemotaxonomic markers for this species was evidenced. Structurally, 7-14 are similar to those anthraquinones isolated from other species of the family Rubiaceae, confirming their close phylogenetic relationship. Whereas, these iridoids and sesquiterpenes with unique structures provided chemotaxonomic evidence to support the genus Coptosapelta (the tribe Coptosapelteae) as a sister of the subfamily Rubioideae. These results contrast with the general producing tendency of indole alkaloids by the species of the subfamily Cinchonoideae, and merit chemotaxonomic significance for the delimitation of Coptosapelta.

Artematrovirenins A-P, guaiane-type sesquiterpenoids with cytotoxicities against two hepatoma cell lines from Artemisia atrovirens.

Random screening revealed that the EtOH extract of Artemisia atrovirens showed significant cytotoxicity against two human hepatoma cell lines (HepG2 and Huh7) with the inhibitory ratio of 98.9% and 99.7% at the concentration of 100 µg/mL. Further bioactivity-guided isolation of active fraction led to 16 new guaiane-type sesquiterpenoids, artematrovirenins A-P (1-16). Their structures were elucidated by extensive spectroscopic data. The absolute stereochemistry of compounds 1 and 14 was determined by single-crystal X-ray diffraction analyses. Pharmacological evaluation suggested that five compounds (3, 5, 8, 10, and 15) exhibited cytotoxicity, compounds 3 and 5 displayed cytotoxicity against HepG2 cell line with an IC50 values of 8.0 and 16.0 µM, as well as against Huh7 cell line with values of 18.2 and 32.2 µM.

Guaiane type of sesquiterpene with NO inhibitory activity from the root of Wikstroemia indica.

Roots of Wikstroemia indica is widely used in China as a folk medicine in treatment of many diseases. However, active compounds of guaiane type of sesquiterpene remain largely unknown. In the present work, five new guaiane of type sesquiterpene compounds wikstronone A-E, along with one known guaiane type of sesquiterpene compound were isolated from the petroleum and CH2Cl2 fraction of roots of Wikstroemia indica. Structures of these compounds including absolute configuration were determined by extensive NMR and CD spectroscopic analysis. The inhibitory activity of all isolated compounds were assayed against LPS-induced NO production in RAW 264.7 macrophages by Griess reagent. Among all compounds, wikstronone A (1) showed remarkable NO inhibitory activity comparable to that of positive control Indometacin. Wikstronone D and E (4 and 5) showed weak NO inhibitory activity. The isolated guaiane type of sesquiterpene may be potent NO synthetase inhibitors.

[A new sesquiterpene from Acorus calamus (â ¡)].

A new quaiane-tgpe sesquiterpene was isolated from the 95% ethanol extract of the rhizomes of Acorus calamus by silica gel and sephadex LH-20 column chromatographic methods. Structure and absolute configuration of the sesquiterpene were elucidated by spectroscopic data and X-ray crystallographic analysis, and named as 1R,5R,7S-guaiane-4R,10R-diol-6-one.

Two new guaiane-type sesquiterpenoids from Valeriana hardwickii and their cytotoxicity.

Two new guaiane-type sesquiterpenoids, named 4α,5α-epoxy-8ß-hydroxy-1α-hydro-α-guaiene (1) and 4α,5α-epoxy-1-hydroxy-α-guaiene (2), were isolated from the whole plants of Valeriana hardwickii. Their structures were elucidated on the basis of spectroscopic analysis. Compounds 1 and 2 showed weak cytotoxicity against the lung adenocarcinoma (A549) and hepatoma (Bel7402) cell lines with IC50 values of 9.2 and 8.5 µM, respectively.

[Sesquiterpenes from stems of Schisandra henryi var. henryi].

The dried stems of Schisandra henryi var. henryi were extracted with 95% ethanol and the extracts were further subjected to partition, affording the ethyl acetate extracts(EtOAc Extrs.).The EtOAc Extrs.were separated and purified with silica gel and octadecyl-silylated silica gel column chromatography, preparative HPLC and preparative TLC. Thirteen known compounds were obtained and identified by spectral methods including MS and NMR, all of which were elucidated as t-cadinol(1), cadinane-4ß,5α,10ß-triol(2), cadinane-5α, 10α-diol-2-ene(3), oxyphyllenodiols A(4), 1ß, 4ß-dihydroxyeudesman-11-ene(5), cyperusol C(6), (7R)-opposit-4(15)-ene-1ß,7-diol(7), dysodensiol E(8), epi-guaidiol A(9), aromadendrane-4ß,10ß-diol(10), tricyclohumuladiol(11), caryolane-1,9ß-diol(12), and guaidiol A(13). Compounds 3, 5-10, and 13 were separated from the genus for the first time, while compounds 1-13 were separated from this species for the first time.