Bisabolane-type Sesquiterpenes Research Articles

Sesquiterpenes from the fruits of Piper longum L. and their anti-inflammatory activity

The fruits of Piper longum are called long pepper, which are well-known culinary spice as well as traditional medicine. In present work, thirteen sesquiterpenes including four undescribed compounds were isolated from P. longum fruits. Compound 1 was a rare methylated bisabolane-type sesquiterpene. Compounds (−)-3 and (+)-3 were a pair of enantiomers of an uncommon humulane which were separated by chiral HPLC. The absolute configurations of compounds 1–3 were confirmed through the means of spectroscopic data analyses, 13C NMR calculations employing DP4+ probability analyses, and ECD calculations. Compounds 2 and 11 presented moderated inhibitory effect on the NO release in LPS-induced RAW264.7 cells with IC50 values of 30.65 ± 0.90 and 38.48 ± 2.42 μM, respectively. Above results enriched the chemical information of P. longum fruits, and meanwhile provided scientific evidences for the anti-inflammatory function of P. longum fruits.

Fusarium foetens AQF6 Isolated from Amentotaxus ynnanensis H.L.Li as a Prolific Source of Antioxidant Compounds

Amentotaxus yunnanensis H.L.Li is a threatened conifer distributed only in China, Laos, and Vietnam, whose fungal endophytes have not been exploited yet. The aims of this study were to screen and characterize antioxidant metabolites from endophytic fungi obtained from A. yunnanensis. Using the surface sterilization method, sixteen endophytic fungi were isolated from A. yunnanensis and classified into seven genera including Fusarium, Penicillium, Aspergillus, Diaporthe, Neopestalotiopsis, Purpureocillium, and Simplicillium through the analysis of Internal Transcribed Spacer (ITS) gene sequences. Among the ethyl acetate crude extracts, Fusarium foetens AQF6 contained the highest amount of polyphenol (117.76 ± 0.94 mg gallic acid equivalent/g) and flavonoid (169.01 ± 2.09 mg quercetin equivalent/g). Importantly, 400 µg/mL AQF6 extract exhibited 95.75 ± 1.1% and 85.66 ± 1.91% of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical-scavenging activities, respectively. Chemical investigation led to the isolation and identification of a new bisabolane-type sesquiterpene fusafoetriol (FUS) and 14 known compounds, among which six pure compounds showed free-radical scavenging activity against DPPH and hydroxyl radicals. Under H2O2 stress, the yeast model Saccharomyces cerevisiae treated with 4 mM FUS showed 43.31% increase in viability. FUS has the potential to be applied in nutraceutical, pharmaceutical and food technological applications. Thus, this is the first report demonstrating the presence of endophytic fungi inhabiting A. yunnanensis and their potential as a prolific source of antioxidant metabolites.

Bisabolane-type sesquiterpenes from Vernonia amygdalina: Absolute configuration and anti-inflammatory activity

The phytochemical assessment of Vernonia amygdalina resulted in the isolation and identification of seven undescribed bisabolane-type sesquiterpenes designated amygdanoids A–G and one known analogue. This is the first report of this type of sesquiterpene from V. amygdalina. Their structures, including the absolute configurations, were elucidated by comprehensive analysis with HRESIMS, 1D and 2D NMR, quantum chemical calculations of NMR and electronic circular dichroism (ECD), modified Mosher's method, and the in situ dimolybdenum CD method. The anti-inflammatory activity of the isolates was evaluated. All the isolated compounds clearly inhibited the production of NO and the expression of the iNOS protein. Secretion of the COX-2 protein was constrained by amygdanoids A–F. Further investigation suggested that amygdanoids E exhibited anti-inflammatory activity by suppressing the expression of iNOS and COX-2 as well as the PI3K/AKT/NF-κB signaling pathway.

Bisabolane Sesquiterpenes with Anti-Inflammatory Activities from the Endophytic Fungus Penicillium citrinum DF47.

Seven new bisabolane-type sesquiterpenes (1-7), namely penicibisabolanes A-G, together with eight known analogs (8-15) were obtained from the AcOEt extract of the millet fermentation broth of the endophytic fungus Penicillium citrinum DF47, which was isolated from the fresh root of Codonopsis pilosula (Franch.) Nannf. The gross structures of new metabolites were determined on the basis of the spectroscopic data (HR-ESI-MS, 1D and 2D NMR spectra), while their absolute configurations were resolved by comparison of the experimental and calculated ECD spectra, in association with specific rotation data. Compound 1 is a rare seco-trinor-bisabolane sesquiterpene found in nature, while 3 is the first example of phenolic bisabolanes bearing a methoxy group at C-1. All the isolates were evaluated their inhibitory effects against NO production in lipopolysaccharides (LPS) stimulated RAW264.7 cells. Among them, compounds 7 and 13 showed moderately anti-inflammatory effects with the inhibitory rate more than 50 % at the concentration of 20 μM.

Seasonal variations during two years in the essential oil of Lippia dulcis Trevir., an exotic aromatic of the Amazon

ABSTRACT Lippia dulcis Trevir. (Verbenaceae) is an aromatic plant occurring in the Amazon that has leaves and flowers with a sweet taste. The objective of this study was to evaluate the influence of seasonal variation during two consecutive years on the content and chemical composition of the essential oil (EO) of L. dulcis leaves. The EO content and chemical composition were influenced by precipitation, temperature, and plant age. The EO content ranged from .1 to .5%. The chemical profile of the EO did not vary significantly among seasons. The main constituents identified were the oxygenated bisabolane-type sesquiterpenes epi-α-bisabolol and hernandulcin. The highest concentration of hernandulcin was observed in the dry period, characterized by mild temperatures and the juvenile stage of plant growth. The highest concentrations of epi-α-bisabolol were observed in the hottest and wettest season of each year.

Structure-Based Molecular Networking for the Discovery of Anti-HBV Compounds from Saussurea lappa (Decne.) C.B Clarke.

It is a crucial to find target compounds in natural product research. This study presents a concept of structure-guided isolation to find candidate active molecules from herbs. We establish a process of anti-viral sesquiterpene networking. An analysis of the networking suggested that new anti-HBV sesquiterpene may be attributable to eudesmane-, guaiane-, cadinane-, germacane- and bisabolane-type sesquiterpenes. In order to evaluate the efficiency of the structure-based molecular networking, ethanol extract of Saussurea lappa (Decne.) C.B Clarke was investigated, which led to the isolation of two guaiane-type (1 and 14), ten eudesmane-type (2–5 and 8–13), two chain (6 and 7) and one germacrane-type (15) sesquiterpenes, including seven new ones, lappaterpenes A–G (1–7), which are reported on herein. The absolute configurations of the new compounds were established by coupling constants, calculated ECD and ROESY correlations, as well as comparisons of optical rotation values with those of known compounds. The absolute configuration of compound 2 was further confirmed by X-ray diffraction. Compounds 1–15 were evaluated for their potency against hepatitis B virus. Compounds 4, 6, 7 and 9 showed effect on HBsAg with inhibition ratios of more than 40% at 30 μM concentrations. Compounds 14 and 15 inhibited HBsAg secretion with the values of IC50 0.73 ± 0.18 and 1.43 ± 0.54 μM, respectively. Structure-based molecular networking inspired the discovery of target compounds.

Secondary Metabolites from Annulohypoxylon sp. and Structural Revision of Emericellins A and B.

Seven previously undescribed compounds were isolated from the endophytic fungus Annulohypoxylon sp. KYG-19 (family Xylariaceae), including three gymnomitrane-type sesquiterpenes xylariacinols A, B, and D (1, 2, and 4), one bisabolane-type sesquiterpene annulnol F (6), one phenol derivative lariacinol G (7), and two polyhydroxy compounds hypoxylonols H and I (8 and 9), together with two known gymnomitrane-type sesquiterpenes emericellin A (3) and 3-gymnomitren-15-ol (5). The assignments of their structures was determined by extensive spectroscopic and spectrometric analysis, acetonide analysis, Mosher's method, and X-ray crystallography. In addition, the structures of emericellins A and B, which were reported to possess an unprecedented tricyclo[4, 4, 2, 1]hendecane scaffold, were revised by comparing their spectroscopic data with those of 1 and 3. Compounds 1 and 4 exhibited antibacterial activity against Escherichia coli with minimum inhibitory concentrations of 4 and 2 μg/mL, respectively.

New quinoline alkaloid and bisabolane-type sesquiterpenoid derivatives from the deep-sea-derived fungus Aspergillus sp. SCSIO06786

One new quinoline alkaloid (1), two new bisabolane-type sesquiterpene derivatives (2 and 3), and a new natural product (4) along with ten known compounds (514) were isolated from the deep sea-derived fungus Aspergillus sp. SCSIO06786 which cultured on solid rice medium. Three new structures were elucidated by analysis of 1D/2D NMR data and HR-ESI-MS. The absolute configurations of 2 and 3 were established by comparison of the experimental and reported ECD values. Compounds 11–13 exhibited moderate selective inhibitory activities against the tested pathogenic bacteria with MIC values among 3.13–12.5 μg/mL.

Sesquiterpenes produced by Pestalotiopsis microspora HF 12440 isolated from Artocarpus heterophyllus

A drimane-type sesquiterpene, (+)-dendocarbin L (1) together with two bisabolane-type sesquiterpenes, (+)-sydonic acid (2) and (+)-sydowic acid (3) were isolated from the mycelium of Pestalotiopsis microspora HF 12440, an endophytic fungus from the stem of Artocarpus heterophyllus. The structures of all compounds were elucidated using spectroscopic methods and by comparison with the literature. Compound 1 was isolated from the fungi for the first time, compounds 2 and 3 were firstly obtained from this endophytic fungus. Compound 3 showed cytotoxicity (IC50 2.56 μg/mL) against murine leukemia P-388 cells.

Antioxidant constituents of chrysanthemum ‘jinsidaju’ cultivated in Kaifeng

Dendranthema morifolium cv. ‘jinsidaju’, cultivated only in Kaifeng, has been eaten for more than 1000 years. During the antioxidant-activity-guided studies on its chemistry and health care function, two new bisabolane-type sesquiterpenes, (6R,7R)-7-hydroxybisabol-2,9E,11-triene-4-one (jinsidajuol A, 1) and (6R,7R)-7-hydroxy-11-methoxybisabol-2,9E-diene-4-one (jinsidajuol B, 2), and thirteen known compounds (3–15) were isolated from the flowers. Their structures were elucidated by 1D and 2D NMR spectroscopy and HRMS. 1 and 2 are the first example of bisabolane-type sesquiterpenes isolated from the genus Dendranthema. Compounds 6–8, 12 and 13 exhibited strong scavenging activities on the ABTS radical cation with IC50 3.33, 5.67, 2.00, 2.50, 5.33 μg/mL, respectively. The IC50 values of all compounds on HepG2 human hepatoma tumor cell line were higher than 50 μM.

Three bisabolane-type sesquiterpenes from edible mushroom Pleurotus eryngii

Three bisabolane-type sesquiterpenes (1–3) were isolated from the fruiting bodies of king trumpet mushrooms (Pleurotus eryngii), together with a known compound (4). All isolated compounds were evaluated for their inhibitory effects on nitric oxide (NO) production. Among these, 2 exhibited a moderate inhibitory effect on NO production with an IC50 of 90.9 μM.

Aspergoterpenins A⁻D: Four New Antimicrobial Bisabolane Sesquiterpenoid Derivatives from an Endophytic Fungus Aspergillus versicolor.

Aspergoterpenins A–D (1–4), four new bisabolane sesquiterpenoid derivatives, were obtained from the endophytic fungus, Aspergillus versicolor, together with eight known compounds (5–12), and their structures were elucidated by a comprehensive analysis of their NMR (Nuclear Magnetic Resonance), MS (Mass Spectrum) and CD (Circular Dichroism) spectra. Aspergoterpenin A (1) was the first example with a characteristic ketal bridged-ring part in the degraded natural bisabolane-type sesquiterpene structures. The compounds 1–12 displayed no significant activities against four cancer cell lines (A549, Caski, HepG2 and MCF-7). Further, the antimicrobial activities to Erwinia carotovora sub sp. Carotovora were evaluated, and the results showed that compounds 1–12 displayed antimicrobial activities with MIC values ranging from 15.2 to 85.2 μg/mL.

Four novel bisabolane-type sesquiterpenes from Curcuma longa

Four novel bisabolane sesquiterpenes, turmerone A (1), turmerone B (2), turmerone C (3), and turmerone D (4), were isolated from the rhizomes of Curcuma longa. Their structures were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses and HRESIMS.

Induced production of a new dipeptide with a disulfide bridge by long-term fermentation of marine-derived Trichoderma cf. brevicompactum

The marine-derived fungus Trichoderma sp. TPU199 (cf. T. brevicompactum), originally isolated from a Palauan red alga, was found to produce unprecedented epipolythiodiketopiperazines, such as gliovirin and pretrichodermamide A. Long-term static fermentation of the strain induced the production of a new dipeptide, dithioaspergillazine A (1), together with aspergillazine A (2) and three anthraquinones (3–5). The structure of 1 was identified as a modified dipeptide possessing a disulfide bridge based on spectroscopic data for 1 and comparisons with those for 2. On the other hand, long-term agitating fermentation of the strain led to the production of the known bisabolane-type sesquiterpene, (+)-12-hydroxysydonic acid (6), which formed the cyclic derivative 7 during HPLC purification under acidic conditions. Compound 1 exhibited cytotoxicity against HCT-15 and Jurkat cells with IC50 values of 13 and 1.3μM, respectively. Compound 2 did not affect the proliferation of these cancer cells up to a concentration of 22μM.

Xanthones and sesquiterpene derivatives from a marine-derived fungus Scopulariopsis sp.

Two new xanthone derivatives, 12-dimethoxypinselin (1) and 12-O-acetyl-AGI-B4 (2), as well as two new phenolic bisabolane-type sesquiterpenes, 11,12-dihydroxysydonic acid (15) and 1-hydroxyboivinianic acid (16), together with one new alkaloid, scopulamide (21) and one new α-pyrone derivative, scopupyrone (26), in addition to twenty-three known compounds (3–14, 17–20, 22–25, 27–29) were isolated from solid rice cultures of the marine-derived fungus Scopulariopsis sp. obtained from the Red Sea hard coral Stylophora sp. All compounds were unambiguously identified through extensive NMR spectroscopic analyses, and by comparison with the literature. Marfey's reaction was performed to determine the absolute configuration of scopulamide (21) and TDDFT-ECD calculations were used to assign the configuration of AGI-B4 (3) and scopupyrone (26). All isolated compounds were evaluated for their cytotoxicity against L5178Y mouse lymphoma cells and the structure-activity relationships were discussed.

A seco-laurane sesquiterpene and related laurane derivatives from the red alga Laurencia okamurai Yamada

A ring-cleaved sesquiterpene, named seco-laurokamurone, four laurane-type sesquiterpenes, laurepoxyene, 3β-hydroperoxyaplysin, 3α-hydroperoxy-3-epiaplysin, and 8,10-dibromoisoaplysin, one laurokamurane-type sesquiterpene, laurokamurene D, and one bisabolane-type sesquiterpene, (5S)-5-acetoxy-β-bisabolene, have been isolated from a re-collection of the red alga Laurencia okamurai Yamada, together with six other known sesquiterpenes. Their structures, including relative configuration, were elucidated by detailed analysis of spectroscopic data, and by comparison with data for related known compounds. In addition, on the basis of chemical conversions, degradation results, and biogenetic considerations, the absolute configurations of several of these compounds were also tentatively proposed. seco-Laurokamurone possesses an unprecedented carbon skeleton, formed from an oxidative cleavage of the laurokamurane skeleton, and laurokamurene D represents the fourth example of a laurokamurane-type sesquiterpene from a natural source. The in vitro antifungal activity of many of these compounds was evaluated against four fungi (Cryptococcus neoformans, Candida glabrata, Trichophyton rubrum, and Aspergillus fumigatus), as well as assessing cytotoxicity against HL-60 and A-549 human cancer cell lines. The compounds studied displayed moderate activities, relative to controls.

A new sesquiterpene from the medicinal fungus Inonotus vaninii

A novel sesquiterpene, named inonolane A (1), was isolated from the EtOAc extract of the medicinal fungus Inonotus vaninii, together with two known compounds, phellilane D (2) and N-[2-(1H-indol-3-yl)-2-oxo-ethyl]acetamide (3). Their structures were elucidated by means of extensive NMR and MS spectroscopic analysis. Compound 1 represents the first bisabolane type sesquiterpene from the genus Inonotus.

Four New Bisabolane-type Sesquiterpenes from Ligularia Lankongensis

The chemical constituents of the roots of two Ligularia lankongensis samples collected in Yunnan and Sichuan Provinces, China, were investigated, together with the DNA sequence of the atpB-rbcL and ITS regions. Four new highly oxygenated bisabolane-type sesquiterpenes (1 - 4) were obtained. Intraspecific diversity in the DNA sequence was found to be limited.

Bisabocurcumin, a new skeleton curcuminoid from the rhizomes of Curcuma longa L.

A new skeleton bisabolane-type sesquiterpene curcuminoid, bisabocurcumin (1), along with 5 known compounds, curcumin (2), demethoxycurcumin (3), bidemethoxycurcumin (4), (1E,4E)-1,5-bis(4-hydroxy-3-methoxyphenyl)-penta-1,4-dien-3-one (5), and (1E,4E)-1-(4-hydroxy-3-methoxyphenyl)-5-(4-hydroxy phenyl-)-penta-1,4-dien-3-one (6) were isolated from the rhizomes of Curcuma longa L. Their structures were determined on the basis of spectroscopic analysis. Bisabocurcumin (1) is firstly obtained from nature with a new skeleton combined by a bisabolane-type sesquiterpene and a 1,7-diphenylheptanoid through a C–C bond.

Sesquiterpenoids from the Endophytic Fungus Trichoderma sp. PR‐35 of Paeonia delavayi

A new bisabolane-type sesquiterpene, trichoderic acid (1), and a new acorane-type sesquiterpene, 2β-hydroxytrichoacorenol (2), along with three known compounds, cyclonerodiol (3), cyclonerodiol oxide (4), and sorbicillin (5), were isolated from the culture broth of Trichoderma sp. PR-35, an endophytic fungus isolated from Paeonia delavayi. Their structures were elucidated on the basis of their IR, MS, and 1D- and 2D-NMR analyses. The antibacterial and antifungal activities of 1-5 towards various types of bacteria and fungi were tested. Most of the compounds showed moderate or weak antimicrobial activities in an agar-diffusion assay.