Undescribed Sesquiterpene Research Articles

Sesquiterpene lactones from Artemisia porrecta Krasch.ex Poljakov and their anti-inflammatory, cytotoxic and anti-vitiligo activities.

This experiment focused on investigating the chemical constituents of the plant Artemisia porrecta Krasch.ex Poljakov, resulting in the isolation and characterization of twenty-seven sesquiterpene lactones belonging to the eudesmanolides, germacronolides, melampolides, and heliangolide types. These compounds include ten undescribed sesquiterpene lactones, Porrectolide A-I, 11-epi-Deacetylherbolide D and seventeen known ones. All known compounds were isolated from this plant for the first time. Their structures were established by 1D, 2D NMR spectroscopic and HR-ESI-MS data, electronic circular dichroism, and single crystal X-ray diffraction analysis. Evaluations of the anti-inflammatory activity revealed that 6 had moderate anti-inflammatory activity on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells with the IC50 value of 14.57±0.24 μM.

HDAC inhibitor SAHA triggers the production of previously undescribed sesquiterpenes and undergoes biotransformation by the fungus Robillarda sessilis from Verbena officinalis L.

Cultivation of the endophytic fungus Robillarda sessilis XL-308 with SAHA resulted in the discovery of two previously undescribed cyclonerane sesquiterpenes (1 and 2), one previously unreported norcadinane type sesquiterpene (3), and seven suberanilohydroxamic acid (SAHA) derivatives (4-10). The identification of previously undescribed compounds was confirmed through NMR spectroscopic analyses, quantum chemistry calculations, and single-crystal X-ray crystallography. Among them, compounds 1 and 2 were products of the silenced genome in XL-308 that activated by SAHA. Concurrently, SAHA underwent biotransformation because of its moderate toxicity towards this fungus. It was hypothesized that the hydroxamic acid group in SAHA triggering the self-defense mechanism of XL-308 and converting SAHA into a less toxic derivative 5.

Sesquiterpene Monomers and Dimers From the Flower of Inula japonica Thunb. With Selective Antiproliferation Against Breast Cancer Cells.

A total of 34 sesquiterpene derivates were obtained from the flower of Inula japonica Thunb. Compounds 2, 14-34 were identified as sesquiterpene monomers, whereas the other 12 isolates (1, 3-13) were characterized as sesquiterpene dimers. Among them, japonicone Z (1), a present undescribed sesquiterpene dimer, and another undescribed monomer, japonicol A (2), were discovered. Their structures were determined through extensive spectroscopic techniques. Structurally, these dimers shared a common guaiane moiety that fused with either 1,10-seco-eudesmanes or germacrenes by a [4+2] biogenetic pathway. The antiproliferative activity of these isolates was assayed on triple negative breast cancer cell line (MDA-MB-231), breast cancer cell line (MCF-7), and normal human mammary epithelial cells (MCF-10A). As a result, most of these compounds exhibited significant effects toward cancer cell lines. More importantly, they possessed promising selectivity toward TNBC cell line with a dramatically increased selectivity index, as they showed similar or superior IC50 values compared to paclitaxel and exhibited minimal or weak inhibitory effects on normal cells. These findings provided valuable insight for natural anti-TNBC sources.

Sesquiterpene lactones from Seriphidium transiliense and their anti-inflammation activity.

Six undescribed sesquiterpene lactones (1-6) and fifteen known compounds (7-21) were isolated from Seriphidium transiliense. The chemical structures were determined by extensive NMR spectroscopic data, HRESIMS, ECD and X-ray diffraction. Among the known compounds, twelve known compounds were isolated for the first time from this plant, including taurine (9), 11-epitaurin (10), α-santonin (11), artesin (13), 11-epiartesin (14), 1α-hydroxy-3β-acetoxyeudesm-4-en-6β, 7α, 11βH-12, 6-olide (15), 1α-hydroxy-3β-acetoxyeudesm-4-en-6β, 7α, 11αH-12, 6-olide (16), artegallin (17), 8α-hydroxytaurin (18), 8α-acetoxytaurine (19), methyl-4α-hydroxy-11(13)-eudesmen-12-oatesaniculamoid D (20), and saniculamoid D (21). The absolute configuration of 2 was determined by X-ray. The X-ray crystal structures of 15 and 16 were reported for the first time. At a concentration of 20 μM, all compounds (1-21) showed significant inhibition of NO production in LPS- stimulated BV2 cells. Among them, compounds 3 and 4 inhibited NO release with IC50 values of 19.30 and 22.05 μM, respectively. Based on the present results, these compounds may be potential anti-inflammatory agents.

Isolation and Characterization of Sesquiterpene Lactones From Syneilesis aconitifolia and Evaluation of Their Anti-Breast Cancer Activity.

Two undescribed sesquiterpene lactones (1 and 2), along with two known analogs (3 and 4), were isolated from Syneilesis aconitifolia. Their structures and absolute configurations were elucidated using spectroscopic analysis, ECD calculations, and single crystal x-ray diffraction. Compound 3 exhibited the highest cytotoxic activity against 4T1 cells, with an IC50 value of 10.89µM. In addition, compound 3 significantly induced the apoptosis of 4T1 cells at the concentration of 20µM. Further anticancer study showed that compound 3 distinctly increased the production of intracellular reactive oxygen species.

Curcumaones A-N, sesquiterpenes from the secondary rhizomes of Curcuma wenyujin.

Fourteen undescribed sesquiterpenes, named curcumaones A-N (1-14), as well as forty-four (15-58) known ones, were isolated from the secondary rhizomes of Curcuma wenyujin. The structures and absolute configurations of 1-14 were elucidated based on NMR spectroscopic analyses, high resolution electrospray ionization mass spectroscopy (HRESIMS) data and electronic circular dichroism (ECD) spectral analysis. Among these, five sesquiterpenes with the peroxide linkage (1-5) were obtained and the change of chemical shift between the α-C connecting the peroxide linkage and the oxygen atom has been discussed. In addition, all the isolated compounds were evaluated for their agonistic effect on farnesoid X receptors (FXR) situated with human embryonic kidney (HEK) 293T cells and the results showed that compounds 12 and 14 exhibited a significant agonistic effect dose-dependently at 20, 50 and 100μM, while 8, 32, 17 and 34 possessed moderate to weak agonistic effects.

Three New Sesquiterpenes from the Leaves of Aglaia elaeagnoidea with NO Inhibitory Activity.

Aglanoideas A-C (1-3), three undescribed sesquiterpenes and eleven known compounds (4-14) were isolated from the leaves of Aglaia elaeagnoidea. Their structures including absolute configurations were characterized by using IR, HR-ESI-MS, NMR, and experimental and calculating ECD methods. Compounds 3-5, and 7 showed moderate nitric oxide inhibitory activity with IC50 values ranging from 53.7 to 72.5 μM.

Sesquiterpenes from the aerial parts of Artemisia vachanica krasch. ex poljakov and their anti-inflammatory and anti-diabetic activities

Eleven undescribed sesquiterpenes, vachanins A−K covering types of germacrane, eudesmane, guaiacane, and cadinane, along with fifteen known analogs were isolated from the aerial parts of Artemisia vachanica Krasch. ex Poljakov. Their structures were established on the basis of HRMS and NMR data, and their absolute configurations were successfully determined by single-crystal X-ray diffraction analysis, 13C-NMR calculations and DP4+ probability analysis, and ECD data in corporation with quantum chemical calculations. Vachanin A is the first example of germacrane bearing an uncommon C5, C10-oxygen bridge. All isolated compounds were assayed for anti-inflammatory and anti-diabetic activities. Compounds 15 and 22 presented weak anti-inflammatory activity by inhibiting the release of NO in RAW 264.7 cells induced by LPS with IC50 values of 42.82 ± 1.43, and 63.37 ± 3.28 μM.

Five Undescribed Sesquiterpenes with Anti-Inflammasome Activity Isolated from Saussurea Laniceps.

Five previously undescribed guaialactone-type sesquiterpenes (1-5), called Lanicepsmines A-E, along with eleven know compounds (6-16), were isolated from the whole plant of Saussurea laniceps. NMR spectroscopic data analysis and MASS permitted the definition of their structures. The stereochemistry of the compounds was confirmed by ECD calculations. It is worth noting that compound 1 and 2 contain amino groups. Part of compounds were tested the anti-inflammasome activity, and compound 14 exhibited potent activity and decreased LDH level in a dose-dependent manner, with IC50 values of 0.698 μM.

Sesquiterpenes from the seeds of Cichorium glandulosum and their anti- neuroinflammation activities

Three previously undescribed sesquiterpenes, along with three known ones were isolated from the seeds of Cichorium glandulosum. The structures of them were elucidated by the analysis of spectroscopic data. The isolated compounds were tested for their neuroprotective effects against LPS-induced neuroinflammation in BV-2 cells. Santamarine (5) exhibited inhibitory activity on LPS-induced NO production in BV-2 cells with IC50 of 0.89 ± 0.12 μM. The mechanism of the compound 5 was related to activating the NF-κB, MAPK and cGAS/STING pathways.

One Undescribed Sesquiterpene from Streptomyces sp.

One Undescribed Sesquiterpene from Streptomyces sp.

Anti-inflammatory Lindenane Sesquiterpene Dimers from the Roots of Chloranthus fortunei.

In this study, eight lindenane-type sesquiterpene dimers, including five previously undescribed sesquiterpene dimers (1-5), were isolated from the roots of Chloranthus fortunei, and their structures were elucidated using 1D/2D NMR, HRESIMS, and ECD calculations. Compound 1 presents the second example of a type of novel 8,9-seco lindenane-type sesquiterpene dimer, considered a product of 8/9-diketone oxidation. Compounds 2 and 3 represent the third and fourth examples, respectively, of this kind of C-11 methine dimer. Furthermore, compound 4 was considered as an artifact generated from the radical reaction of a known compound chlojaponilide F (6), which was explained by the density functional theory quantum calculation. All isolates were evaluated for their protective activity against the LPS-induced pulmonary epithelial cell line with compound 7 exhibiting the most potent bioactivity. Further in vitro biological evaluation demonstrated that 7 reduced the production of reactive oxygen species and interleukin-1β, further regulated by the expression of the NLRP3. These results show that compound 7 exhibits therapeutic potential for lung inflammatory diseases.

Sesquiterpene lactones from Tithonia diversifolia with ferroptosis-inducing activities

Eight previously undescribed sesquiterpene lactones (1–8), together with six known ones (9–14) were isolated from the aerial parts of Tithonia diversifolia (Hemsl.) A. Gray. The absolute configurations of these compounds were elucidated using HRMS, NMR spectroscopy, optical rotation measurements, X-ray crystallography, and ECD. Among them, sesquiterpene lactones 2–4 share a unique carbon skeleton with a rare C-3/C-4 ring-opened structure. Compounds 1 and 8 showed moderate inhibitory effects toward CT26 murine colon carcinoma cells by promoting lipid ROS production, highlighting their potential as ferroptosis inducers.

Four undescribed sesquiterpenes from Artemisia mongolica and their anti-inflammatory activity

Four undescribed sesquiterpene compounds (1–4) and six known compounds (5–10) were isolated from A. mongolica. Furthermore, compound 5 was a new natural product previously synthesized. The LPS-stimulated BV2 cells were used as a model to evaluate the anti-inflammatory activity of the isolated compounds, among them, compounds 2, 3 and 4 showed significant inhibition of NO levels with IC50 values of 27.48, 27.39 and 24.96 μM, respectively.

Atramacrolodes A-D (1-4), Four Undescribed Eudesmane-Type Sesquiterpenes from the Rhizome of Atractylodes macrocephala.

Four undescribed sesquiterpenes, atramacrolodes A-D (1-4), along with six known compounds 5-10 were isolated from the rhizome of Atractylodes macrocephala. Compound 3 possessed a new skeleton based on an unprecedented carton-carton connection. Their structures were determined by UV, IR, HRESIMS, NMR spectra, 13C NMR calculation with DP4+ analysis, and the comparison of experimental and calculated ECD spectra. Compounds 5 and 8 showed protective effects against paracetamol-induced liver cell injury.

Chemical Composition of Artemisia Scoparia and Their Bioactivities.

Three undescribed sesquiterpenes (1-3), two enantiomeric pairs of monoterpenes (4a/4b-5a/5b), one alkyne (6), two known alkynes (7-8) and eight known coumarins (9-16) were isolated from the aerial parts extracts of Artemisia scoparia. The structures of these compounds were fully elucidated by their 1D and 2D NMR, HRESIMS spectral data analyses, and comparison with literature. The absolute configurations of compounds were determined by single-crystal X-ray crystallography (1), a comparison of experimental and calculated electronic circular dichroism (ECD) data (2-6). 15 showed moderate inhibitory activity with the NO release in LPS-induced RAW264.7 cells. 9-16 showed varying degrees of promoting melanogenesis and tyrosinase activity in B16 cells.

Sesquiterpene coumarins with anti-vitiligo and cytotoxic activities from Ferula samarkandica

Two undescribed sesquiterpene coumarins (1–2) and eight known analogues (3–10) were isolated from the roots of Ferula samarkandica Korovin, growing in Uzbekistan. Their structures were established by comprehensive spectroscopic analysis including NMR, HRESIMS, UV and IR data. The absolute configurations were determined based on ECD calculations and confirmed by single-crystal X-ray diffraction analysis. Six compounds carrying 7′-carbonyl, 3′-carbonyl and 3′-acetoxy (4, 5, 6, 7, 9, 10) demonstrated anti-vitiligo potentials, in addition to five (4, 7, 8, 9, 10) with cytotoxic effects. Evaluation of anti-vitiligo activity in B16 cells revealed that compounds 4–7 and 9 exhibited promotion effects on melanin synthesis in B16 cells more potent than the positive control 8-methoxypsoralen (8-MOP), while 5, 7, 9 and 10 could also stimulate the tyrosinase activity superior to 8-MOP. Besides, compounds 4 and 7–10 also presented certain cytotoxic activities against HeLa, HT-29 and A549 cell lines, wherein 8 displayed a significant cytotoxicity against HT-29 cells with an IC50 value of 8.33 ± 0.34 μM.

New sesquiterpenoids with neuroprotective effects in vitro and in vivo from the Picrasma chinensis

Three undescribed sesquiterpenes, designed as pichinenoid A-C (1–3), along with nine known ones (4–12) were isolated from the stems and leaves of Picrasma chinensis. The new isolates including their absolute configurations were elucidated based on extensive spectroscopic methods, single crystal X-ray diffraction, and electronic circular dichroism (ECD) experiments, as well as comparison with literature data. Structurally, compounds 1 and 2 are descending sesquiterpenes, while pichinenoid C (3) is a rare sesquiterpene bearing a 2-methylenebut-3-enoic acid moiety at the C-6 side chain. All the isolated compounds were tested for their neuroprotective effects against the H2O2-induced damage on human neuroblastoma SH-SY5Y cells, and most of them showed moderate neuroprotective activity. Especially, compounds 1, 3–5, and 7 showed a potent neuroprotective effect at 25 or 50 μM. Moreover, the neuroprotective effects of compounds 1 and 4 were tested on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Results of western blot and immunofluorescence indicated that compound 4 significantly counteract the toxicity of MPTP, and reversed the expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum (ST) of the mouse brain. Interestingly, western blot data suggested compound 4 also enhanced B-cell lymphoma-2 (Bcl-2) and heme oxygenase 1 (HO-1) expressions in the brain tissues from MPTP damaged mouse.

Anti-Inflammatory Sesquiterpenes from Fruiting Bodies of Schizophyllum commune.

Schizophyllum commune, a fleshy fungus, is an important medicinal and food-homologous mushroom in China. In this work, eight undescribed sesquiterpenes schizomycins A-H (1-8) and one new meroterpenoid schizomycin I (9) together with three known analogues (10-12) were isolated from fruiting bodies of S. commune. Their planar structures were established by extensive spectroscopic and mass spectrometric data. The absolute configurations of compounds 1, 2, and 4 were determined by single crystal X-ray diffraction, and compounds 3 and 5-9 were confirmed by electronic circular dichroism calculations. Anti-inflammatory activities of all isolated compounds were evaluated for their inhibitory effects on IL-6 and IL-1β production in RAW 264.7 cells. Among them, compound 7 exhibited significant IL-6 inhibitory activity with an IC50 value of 3.6 μM. The results of molecular docking showed that compound 7 interacts with amino acid residues (Gly117, Lys118, Asp120, Thr166, and Try168) of the IL-6 receptor protein through hydrogen bonding.

Discovery of sesquiterpene from Youngia japonica with antitumor effect

Fourteen sesquiterpenes, including one undescribed sesquiterpene lactone, were isolated from Youngia japonica, and their structures were identified by NMR, HRESIMS, ECD and calculated ECD. Cytotoxic activities of all isolates against A549, HeLa, and 4 T1 cell lines were detected by CCK8 assay. Among them, 2 showed obvious cytotoxic activity against A549 cells. Subsequently, the production of ROS, and apoptosis of A549 cells treated with 2 were evaluated. The result showed that 2 distinctly increased the ROS level, and induced the apoptosis of A549 cells. Further anticancer mechanism studies showed that 2 increased the expression of cleaved caspase 3. Taken together, our results demonstrated that 2 might become potential leading compounds for the treatment of lung cancer.