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Six new sesquiterpenes, including four eremophilane derivatives fureremophilanes A-D ( 1 - 4 ) and two acorane analogues furacoranes A and B ( 5 and 6 ), were characterized from the culture extract of the cold-seep derived fungus Furcasterigmium furcatum CS-280 co-cultured with autoclaved Pseudomonas aeruginosa QDIO-4. All the six compounds were highly oxygenated especially 2 and 3 with infrequent epoxyethane and tetrahydrofuran ring systems. The structures of 1 - 6 were established on the basis of detailed interpretation of 1D and 2D NMR and MS data. Their relative and absolute configurations were assigned by a combination of NOESY and single crystal X-ray crystallographic analysis, and by time-dependent density functional (TDDFT) ECD calculations as well. All compounds were tested the anti-inflammatory activity against human COX-2 protein, among which, compounds 2 and 3 displayed activities with IC 50 values 123.00 µM and 93.45 µM, respectively. The interaction mechanism was interpreted by molecular docking.

A new drimane sesquiterpene ester, designated insuetusolate (1), and four reported ones (2-5) were isolated from a culture broth of Aspergillus insuetus BF-1613. The chemical structure of 1 was elucidated by extensive spectroscopic analyses, including MS and NMR. Compound 1 has a drimane-type sesquiterpene core with a 2'E,4'E,6'E-octatrienoate side chain. All these drimane sesquiterpene esters inhibited both sterol O-acyl transferase 1 (SOAT1) and 2 (SOAT2), but exhibited slightly potent inhibition against SOAT1 than SOAT2 with selectivity index (SI) [log (IC 50 for SOAT1/ IC 50 for SOAT2)] values ranging from -0.24 to -0.94., Competing Interests: Compliance with ethical standards. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

As a part of systematic research, an ongoing phytochemical investigation of the sesquiterpenoid-containing fraction led to the isolation of five new sesquiterpenoids from the peeled stems of Syringa pinnatifolia, including two pairs of enantiomeric humulane-type (±)-alashanoids A 1 and B 1 (1 and 2) and one eremophilane-type alashanoid C 1 (3). These structures were elucidated by the analysis of extensive spectroscopic data, including ESI-MS and 1D and 2D NMR, and the absolute configuration was determined by comparing its experimental and calculated electronic circular dichroism and calculated NMR. These isolates exhibited moderate in vitro cardioprotective effects against oxidative injuries in H9c2 cells., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

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. annua manifested activity against HepG2, Huh7, and SK-Hep-1 cell lines with inhibitory ratios of 53.2%, 52.1%, and 59.6% at 200 μg/mL, respectively. Bioassay-guided isolation of A. annua afforded 14 unusual cadinane-involved sesquiterpenoid dimers, artemannuins A‒N (1-14), of which the structures were elucidated by extensive spectral analyses, ECD calculations, and single-crystal X-ray diffraction. Structurally, these compounds were classified into five different types based on the coupled modes of two monomeric sesquiterpenoids. Among them, compounds 1-9 represented the first examples of sesquiterpenoid dimers formed via the C-3‒C-3' single bond of two 5(4 → 3)-abeo-cadinane sesquiterpenoid monomers, while compounds 13 and 14 were dimers fused by cadinane and humulane sesquiterpenoids via an ester bond. Methylated derivatives of 1, 4, 6, and 8 showed antihepatoma activity against HepG2, Huh7, and SK-Hep-1 cell lines with IC 50 values ranging from 30.5 to 57.2 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Eleven new highly oxygenated eremophilane-type sesquiterpenoids were isolated from the whole plant of Synotis solidaginea, including two pairs of C-8 S/R epimers. The structures of the new compounds were elucidated on the basis of detailed spectroscopic analysis and the absolute configurations of 1 and 9 were confirmed by single-crystal X-ray crystallography using Cu Kα radiation. All the isolates were tested for the inhibition of LPS-stimulated NO production in macrophage-like mouse monocytic leukemia RAW264.7 cells. Compound 1 exhibited weak inhibitory effects with an IC 50 of 71.2 μM., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interest in this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Five undescribed eremophilane-type sesquiterpenes, remophilanetriols E-I (1-5), along with seven known compounds (6-12) were isolated from the fresh roots of Rehmannia glutinosa. Their structures were characterized by extensive spectroscopic data analysis and their absolute configurations were determined by comparing their calculated electronic circular dichroism (ECD) spectra and experimental ECD spectra. The anti-pulmonary fibrosis activities of all compounds were evaluated in vitro by MTT methods, and compounds 2, 8, 10, and 12 exhibited excellent anti-pulmonary fibrosis activities. In addition, compound 2 can reduce the levels of ROS and apoptosis in TGF-β1-induced BEAS-2B cells., Competing Interests: Declaration of competing interest No other potential conflict of interest relevant to this article was reported., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Eight new cadinane sesquiterpenoids ( 1 - 8 ), along with two known compounds ( 9 and 10 ), were isolated from infected stems of the semi-mangrove plant, Hibiscus tiliaceus . The structures of compounds 1 - 8 were elucidated through the analysis of their 1D and 2D NMR and MS data, and their absolute configurations were determined by comparing their experimental and calculated ECD spectra and by single-crystal X-ray diffraction. The two confused known compounds ( 9 and 10 ) were resolved using single-crystal X-ray crystallography. Compounds 1 - 3 have novel norsesquiterpene carbon skeletons arising from a ring contraction rearrangement. All obtained isolates were evaluated against the HepG2 and Huh7 cell lines, and compounds 1b , 2b , 4 , 6 , and 8 showed cytotoxic activity toward both cell lines, with IC 50 values ranging from 3.5 to 6.8 μM.

Six new cadinane-type sesquiterpenoids, named Chimnitensin A-F (1-6) were isolated from the leaves of Chimonanthus nitens Oliv. Their structures were elucidated by comprehensive spectroscopic analyses and comparison with structurally related known analogues. In vitro MTT assay showed that all six compounds had cytotoxicity against two selected human breast cancer cell lines (MDA-MB-468 and MDA-MB-231), which indicate their potential of developing into anticancer drugs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ten new bisabolane derivatives, trichobisabolins Q-Z (1-10), one new cadinane derivative, cadin-4-en-11-ol (11), and three new cyclonerane derivatives, cycloner-3-en-7,11-diol (12), isoepicyclonerodiol oxide (13), and norepicyclonerodiol oxide (14), were isolated from the endophytic fungal strain RR-dl-6-11 of Trichoderma asperelloides that was obtained from a marine alga. Their structures along with relative configurations were established mainly by NMR and IR as well as MS techniques, and the absolute configurations of 10 and 11 were assigned by ECD and X-ray diffraction data, respectively. Sesquiterpenes from the fungus T. asperelloides are reported for the first time. It is interesting that half of the bisabolane derivatives are demethylated. Compound 12 represents the first the occurrence of cyclopentenyl-bearing cycloneranes, and 14 seems a cyclopentyl-degrading cyclonerane derivative. Several isolates feature potent inhibition of marine phytoplankton species., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Fifteen new highly oxygenated eremophilane sesquiterpenoids, parasubolides A-O (1-15), were obtained from the whole plant of Parasenecio albus. The structures of 1-15 were elucidated based on the interpretation of NMR and HRESIMS data, along with experimental electronic circular dichroism (ECD) and single-crystal X-ray diffraction analysis. Compounds 1-6, and 9-14 represent the first class of 1,2,10-trioxygenated eremophilane lactones. Selected isolates were evaluated for their immunosuppressive activities. Compounds 4, 5, and 12 exhibited moderate inhibition against LPS-induced B-cell proliferation with IC 50 values of 23.1, 33.8, and 26.6 μM, respectively., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Croton ferrugineus Kunth is an endemic species of Ecuador used in traditional medicine both for wound healing and as an antiseptic. In this study, fresh Croton ferrugineus leaves were collected and subjected to hydrodistillation for extraction of the essential oil. The chemical composition of the essential oil was determined by gas chromatography equipped with a flame ionization detector and gas chromatography coupled to a mass spectrometer using a non-polar and a polar chromatographic column. The antibacterial activity was assayed against three Gram-positive bacteria, one Gram-negative bacterium and one dermatophyte fungus. The radical scavenging properties of the essential oil was evaluated by means of DPPH and ABTS assays. The chemical analysis allowed us to identify thirty-five compounds representing more than 99.95% of the total composition. Aliphatic sesquiterpene hydrocarbon trans-caryophyllene was the main constituent with 20.47 ± 1.25%. Other main compounds were myrcene (11.47 ± 1.56%), β-phellandrene (10.55 ± 0.02%), germacrene D (7.60 ± 0.60%), and α-humulene (5.49 ± 0.38%). The essential oil from Croton ferrugineus presented moderate activity against Candida albicans (ATCC 10231) with an MIC of 1000 μg/mL, a scavenging capacity SC 50 of 901 ± 20 µg/mL with the ABTS method, and very strong antiglucosidase activity with an IC 50 of 146 ± 20 µg/mL.

Two new meroterpenoids, aspermeroterpenes D and E ( 1 and 2 ), two new ophiobolin-type sesterterpenoids, the C-18 epimers of 18,19-dihydro-18-methoxy-19-hydroxyophiobolin P ( 6 and 7 ), and two new drimane-type sesquiterpenoids, 3 S -hydroxystrobilactone A ( 8 ) and 6- epi -strobilactone A ( 9 ), along with 11 known terpenoids ( 3 - 5 and 10 - 17 ) were isolated from the cultures of the algicolous fungus Aspergillus sp. RR-YLW-12, derived from the red alga Rhodomela confervoides . The structures and relative configurations of new compounds were established by detailed spectroscopic analysis of NMR and HRMS experiments, and the absolute configurations were assigned by X-ray diffraction experiments and comparison of their experimental and calculated ECD spectra. Compound 1 features a rare 6/6/6/6/5 pentacyclic system with a meroterpenoid skeleton, and the structure of terretonin E ( 3 ) was revised in this study. Compound 4 showed significant inhibitory activities against three microalgae, Prorocentrum donghaiense , Heterosigma akashiwo , and Chattonella marina , with IC 50 values of 10.5, 5.2, and 3.1 μg/mL, respectively.

Three new eremophilane sesquiterpenes phomadecalins G-I (1-3) and two new benzene derivatives microdiplzenes A and B (12 and 13), together with nine known eremophilane sesquiterpenes (4-11 and 14) were isolated from an endophytic fungus, Microdiplodia sp. WGHS5. Their structures were elucidated by the interpretation of HR-ESI-MS and NMR data; meanwhile, the absolute configurations of new compounds were determined on the base of ECD calculations. All compounds were evaluated for the antimicrobial activities and antiproliferative effect on human gastric cancer cell lines (BGC-823)., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

Biological species collections are critical for natural product drug discovery programs. However, prioritization of target species in massive collections remains difficult. Here, we introduce an untargeted metabolomics-based prioritization workflow that uses MS/MS molecular networking to estimate scaffold-level distribution. As a demonstration, we applied the workflow to 40 polyporoid fungal species. Nine species were prioritized as candidates based on the chemical structural and compositional similarity (CSCS) metric. Most of the selected species showed relatively higher richness and uniqueness of metabolites than those of the others. Cryptoporus volvatus , one of the prioritized species, was investigated further. The chemical profiles of the extracts of C. volvatus culture and fruiting bodies were compared, and it was shown that derivative-level diversity was higher in the fruiting bodies; meanwhile, scaffold-level diversity was similar. This showed that the compounds found from a cultured fungus can also be isolated in wild mushrooms. Targeted isolation of the fruiting body extract yielded three unknown ( 1 - 3 ) and six known ( 4 - 9 ) cryptoporic acid derivatives, which are drimane-type sesquiterpenes with isocitric acid moieties that have been reported in this species. Cryptoporic acid T ( 1 ) is a trimeric cryptoporic acid reported for the first time. Compounds 2 and 5 exhibited cytotoxicity against HCT-116 cell lines with IC 50 values of 4.3 and 3.6 μM, respectively.

Bioactivity-guided isolation of Aspergillus ustus led to the discovery of five new drimane sesquiterpenes, named ustusal A, ustusolate F and G, and ustusoic acid A and B, 1 - 5 respectively. Structural elucidation of these fungal terpenes relied on 1D and 2D NMR techniques, high-resolution mass spectrometry, and chiroptical properties. Their relative configurations were determined by NMR methods, while the absolute configurations were established using comparative analyses of computed and experimental NMR chemical shifts and ECD spectra. The sesquiterpenes exhibited weak activity against the clinically relevant pathogens vancomycin-resistant Enterococcus faecium and multidrug-resistant Staphylococcus aureus ; however, the activity of 5 was drastically enhanced when equal amounts of stromemycin ( 6 ), a known metabolite coisolated from the same fraction from A. ustus , was added.

Cadinanes are typical plant sesquiterpenes with a broad range of biological functions. We report the isolation of three cadinanes (1-3) from a bacterial endophyte (Streptomyces sp.) of the mangrove plant Bruguiera gymnorrhiza. The structures of two new cadinenes, (+)-11-hydroxy-epicubenol (1) and (+)-12-hydroxy-epicubenol (2) were elucidated by nuclear magnetic resonance (NMR) and mass spectrometry. The bacterial product (+)-11-hydroxy-epicubenol was elucidated to be an enantiomer of the plant product pubinernoid C. (+)-12-Hydroxy-epicubenol was established as a diastereomer of the basidiomycete product trichapargin A. In addition, a crystal structure analysis corroborated the structure and configuration of 5,11-epoxy-10-cadinanol (3), a cadinane cycloether initially described as a natural product from liverwort. The discovery of oxygenated cadinanes from a bacterial endophyte may set the basis for the production of cadinanes by bacterial fermentation., (© 2020 John Wiley & Sons, Ltd.)

This report illustrated isolation and identification of 42 compounds comprising five (spicatainoids A-E) undescribed eremophilanolide type sesquiterpenoids and one undescribed nor-eremophilane (spicatainoid F) from Ligularia subspicata.. Among all the isolated new compounds, 4 is reported as the first enantiomeric form of novel eremophilanolide type sesquiterpenoid. Comprehensive analysis of HRESIMS, 1D/2D NMR, experimental circular dichroism (CD), calculated ECD analysis, and X-ray crystallographic (XRD) analysis validated the complete configuration and confirmation of these isolated compounds. All the isolated compounds were tested for the anti-inflammatory potential by measuring the amount of nitric oxide production. Among the tested compounds, 4 was the most effective with 90% NO-inhibition activity. Compounds 1, 2, 3, 9, 10 18, 29, 34, 35 exhibited moderate inhibitory effects against the production of NO, while other compounds displayed no activity even at the concentration of 50 μM. Additionally, compounds 1, 3 and 4 presented moderate anti-inflammatory activity by inhibiting the release of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in LPS-stimulated N9 cells. The IC 50 values of compounds 1, 3 and 4 were calculated 39.6 ± 2.7, 42.5 ± 3.8 and 27.60 ± 1.9 μΜ., (Copyright © 2020. Published by Elsevier B.V.)

The present study aimed to evaluate the antileishmanial effect, the mechanisms of action and the association with miltefosine of Vernonia brasiliana essential oil against Leishmania infantum promastigotes. This essential oil was obtained by hydrodistillation and its chemical composition was determined by gas chromatography-mass spectrometry (GC-MS). The antileishmanial activity against L. infantum promastigotes and cytotoxicity on DH82 cells were evaluated by MTT colorimetric assay. Ultrastructural alterations were evaluated by transmission electron microscopy. Changes in mitochondrial membrane potential, in the production of reactive oxygen species, and analysis of apoptotic events were determined by flow cytometry. The association between the essential oil and miltefosine was evaluated using the modified isobologram method. The most abundant component of the essential oil was β-caryophyllene (21.47 %). Anti-Leishmania assays indicated an IC 50 of 39.01 ± 1.080 μg/mL for promastigote forms after 72 h of treatment. The cytotoxic concentration for DH82 cells was 63.13 ± 1.211 μg/mL after 24 h of treatment. The effect against L. infantum was proven through the ultrastructural changes caused by the oil, such as kinetoplast and mitochondrial swelling, vesicles in the flagellar pocket, discontinuity of the nuclear membrane, nuclear fragmentation and condensation, and loss of organelles. It was observed that the oil leads to a decrease in the mitochondrial membrane potential (35.10 %, p = 0.0031), increased reactive oxygen species production, and cell death by late apoptosis (17.60 %, p = 0.020). The combination of the essential oil and miltefosine exhibited an antagonistic effect. This study evidences the antileishmanial action of V. brasiliana essential oil against L. infantum promastigotes., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

The vascular endothelium is a continuous monolayer of endothelial cells that are in direct contact with the blood and its dysfunction is the starting process in the development of many pathological inflammatory disorders, such as atherosclerosis, which can result in death. The expression of adhesion molecules such as vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM1) is a key stage in modulating vascular inflammation, where the adhesion of monocytes and their transmigration into the intima starting a cascade of inflammatory reactions. Looking for natural compounds with inhibitory activity of VCAM1 and ICAM1, we isolated drimenol, isodrimeninol and polygodial as the main secondary metabolites from barks of Drimys winteri (Dw) and evaluated their effects in the adhesion response of monocytes cells (THP1) to a monolayer of human umbilical vein endothelial cells (HUVEC) in coculture assays. The results showed that the molecules and total extract Dw decrease the adhesion of THP1 to HUVECs, at 10 μg/mL. The adhesion activity is explained due to the inhibition of VCAM1 and ICAM1 evidenced by qRT-PCR and Western-blot assays. In conclusion, drimane sesquiterpenoids could be used as a molecular scaffold in the development of drugs for inflammatory vascular diseases., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Antimicrobial resistance is increasing around the world and the search for effective treatment options, such as new antibiotics and combination therapy is urgently needed. The present study evaluates oregano essential oil (OEO) antibacterial activities against reference and multidrug-resistant clinical isolates of Acinetobacter baumannii (Ab-MDR). Additionally, the combination of the OEO and polymyxin B was evaluated against Ab-MDR. Ten clinical isolates were characterized at the species level through multiplex polymerase chain reaction (PCR) for the gyrB and bla OXA-51-like genes. The isolates were resistant to at least four different classes of antimicrobial agents, namely, aminoglycosides, cephems, carbapenems, and fluoroquinolones. All isolates were metallo-β-lactamase (MβL) and carbapenemase producers. The major component of OEO was found to be carvacrol (71.0%) followed by β-caryophyllene (4.0%), γ-terpinene (4.5%), p-cymene (3,5%), and thymol (3.0%). OEO showed antibacterial effect against all Ab-MDR tested, with minimum inhibitory concentrations (MIC) ranging from 1.75 to 3.50 mg mL -1 . Flow cytometry demonstrated that the OEO causes destabilization and rupture of the bacterial cell membrane resulting in apoptosis of A. baumannii cells (p < 0.05). Synergic interaction between OEO and polymyxin B (FICI: 0.18 to 0.37) was observed, using a checkerboard assay. When combined, OEO presented until 16-fold reduction of the polymyxin B MIC. The results presented here indicate that the OEO used alone or in combination with polymyxin B in the treatment of Ab-MDR infections is promising. To the best of our knowledge, this is the first report of OEO and polymyxin B association against Ab-MDR clinical isolates.

This study was aimed to investigate the chemical compositions of the essential oils from Goniothalamus macrophyllus and Goniothalamus malayanus growing in Malaysia. The essential oils were obtained by hydrodistillation and fully characterized by gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS). Analyses of the essential oils from G. macrophyllus and G. malayanus resulted in 93.6 and 95.4% of the total oils, respectively. The major components of G. macrophyllus oil were germacrene D (25.1%), bicyclogermacrene (11.6%), α-copaene (6.9%) and δ-cadinene (6.4%), whereas in G. malayanus oil bicyclogermacrene (43.9%), germacrene D (21.1%) and β-elemene (8.4%) were the most abundant components.

Two previously undescribed caryophyllane-related sesquiterpenoids, antipacids A ( 1 ) and B ( 2 ), with a novel bicyclo[5.2.0] core skeleton, and known compound clovane-2β,9α-diol ( 3 ), along with rumphellolide L ( 4 ), an esterified product of 1 and 3 , were isolated from the organic extract of octocoral Rumphella antipathes . Their structures, including the absolute configurations were elucidated by spectroscopic and chemical experiments. In vivo anti-inflammatory activity analysis indicated that antipacid B ( 2 ) inhibited the generation of superoxide anions and the release of elastase by human neutrophils, with IC 50 values of 11.22 and 23.53 μM, respectively, while rumphellolide L ( 4 ) suppressed the release of elastase with an IC 50 value of 7.63 μM.

Nowadays, the discovery and development of α-glucosidase inhibitors from natural products or their derivatives represents an attractive approach. Here we reported studies on a series of novel N-acyl-2-aminothiazoles fused (+)-nootkatone and evaluation for their α-glucosidase inhibitory activities. Most of (+)-nootkatone derivatives exhibited more potent α-glucosidase inhibitory ability than the positive drug acarbose. In particular, compounds II7 and II14 showed the most promising α-glucosidase inhibitory ability with IC 50 values of 13.2 and 13.8 µM. II7 and II14 also exhibited relatively low cytotoxicities towards normal LO2 cells. Kinetic study indicated that compounds II7 and II14 inhibited the α-glucosidase in a noncompetitive manner, and molecular docking results were in line with the noncompetitive characteristics that II7 and II14 did not bind to the known active sites (Asp214, Glu276 and Asp349). Based on our findings, these (+)-nootkatone derivatives could be used as antidiabetic candidates., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The pure Soqotri resin of Dracaena cinnabari Balf.f. (Dracaenaceae) has no volatile smell due to its low content of volatile constituents. Although it is insoluble in n -Hexane, we found that the resin, when suspended in n -Hexane within five days at 5 °C, led to the extraction of a small portion of a single volatile liquid constituent, which was identified by GC-MS as sesquiterpene β-caryophyllene. This method of extracting the volatile constituents using hexane under cooling is very suitable for resins of the Dracaena species because these resins usually contain very few volatile terpenes and/or non-terpenes, and they may contain only one volatile terpene per resin as this study result. β-Caryophyllene was identified and separated for the first time from the Soqotri standard resin of Dracaena cinnabari . Therefore, β-caryophyllene, as a new chemical property, can support to evaluate the purity of the Soqotri resin. Moreover, a big mass of D. cinnabari resin can yield concentrated β-caryophyllene as a liquid extract for further pharmaceutical and nutraceutical applications.

Recently, it has been shown that drimane-type sesquiterpenoids isolated from Zygogynum pancheri, a species native to New Caledonia, possessed significant α-amylase inhibitory activities. To further explore their antidiabetic potential, we investigated the effect of 1β-O-(E-cinnamoyl)-6α-hydroxy-9epi-polygodial (D) and 1β-E-O-p-methoxycinnamoyl-bemadienolide (L), two of the most active compounds of the series, on diabetic model rats. Compounds D and L (2 mg kg/day) were daily and orally administrated for 30 days to streptozotocin (STZ) (150 mg/kg) induced male diabetic Wistar rats. Animals were allocated into five groups of six rats. Comparatively to diabetic rats, treatments with D and L compounds were able to significantly (P < 0.05) decrease Fasting Blood Glucose (FBG) (70.15%, 71.02%), serum total cholesterol (46.27% and 39.38%), triglycerides (56.60% and 58.15%), creatinine (37.31% and 36.49%) and uric acid levels (67.76% and 69.68%), respectively. Compounds D and L also restored the altered plasma enzyme (aspartate aminotransferase, AST (47.83% and 43.20%), alanine aminotransferase, ALT (49.76% and 48.35%, alkaline phosphatase, ALP (72.78% and 73.21%)) and lactate dehydrogenase, LDH (47.95% and 53.93%) levels to near normal, respectively. Administration of Glymepiride, significantly (p < 0.05) reduced FBG (73.94%) in STZ induced diabetic rats. Additionally, the compounds D and L exhibited inhibitory effects in vivo on lipase activity of diabetic rats (54.83% and 52.25%), respectively. The outcomes of this study suggested that these two drimanes could be considered as efficient hypoglycemic, hypolipidemic and antiobesity agents for diabetes management and its complications., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Eight cadinane derivatives, trichocadinins H - N (1-7) and methylhydroheptelidate (8), and two carotane derivatives, 14-O-methyltrichocarotin G (9) and 14-O-methyl CAF-603 (10), including eight new ones (1-6, 9, and 10), were isolated from the culture of Trichoderma virens RR-dl-6-8 obtained from the organohalogen-enriched marine red alga Rhodomela confervoides. Their structures and relative configurations were established by analysis of NMR and mass spectroscopic data, and the absolute configurations were assigned on the basis of ECD curves, highlighted by the ECD diversity of carboxylic acid derivatives. Among the isolates, 1 with a halogen atom and 8, a new naturally occurring compound, are 2,3-seco-cadinane sesquiterpenes, and the epimeric 2 and 3 feature a 2-nor-cadinane skeleton. A commercially-sourced compound with the same planar structure as that of 7 has been reported in a patent, but its configuration was not given. Compounds 1-10 exhibited growth inhibition of some marine phytoplankton species., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Chemical investigation of the aerial parts of Mikania micrantha led to the isolation of eight sesquiterpenoids and ten diterpenoids, including five cadinane sesquiterpenoids ( 1 - 5 ), three bisabolene sesquiterpenoids ( 6 - 8 ), nine ent -kaurane diterpenoids ( 9 - 17 ), and an abietane diterpenoid ( 18 ). Among them, 1 - 3 are new and feature a rare lactone or furan ring derived from C-6 isopropyl group side chain. Compound 18 was isolated from genus Mikania for the first time, and was also the first example of abietane-type diterpenoids from this plant. Their structures were elucidated on the basis of extensive spectroscopic analyses (1D and 2D NMR, HRESIMS, and ECD). All compounds were examined for their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophage cells, and compound 18 exhibited pronounced inhibition on NO production (IC 50 = 11.04  µ M), being comparable to the positive control, quercetin (IC 50 = 11.15  µ M).

Background: A. oxyphylla extract is known to possess a wide range of pharmacological activites. However, the molecular mechanism of A. oxyphylla and its bioactive compound nootkatone in colorectal cancer is unknown., Methods: Our study aims to examine the role of A. oxyphylla and its bioactive compound nootkatone, in tumor suppression using several in vitro assays., Results: Both A. oxyphylla extract and nootkatone exhibited antiproliferative activity in colorectal cancer cells. A. oxyphylla displayed antioxidant activity in colorectal cancer cells, likely mediated via induction of HO-1. Furthermore, expression of pro-apoptotic protein NAG-1 and cell proliferative protein cyclin D1 were increased and decreased respectively in the presence of A. oxyphylla. When examined for anticancer activity, nootkatone treatment resulted in the reduction of colony and spheroid formation. Correspondingly, nootkatone also led to increased NAG-1 expression and decreased cyclin D1 expression. The mechanism by which nootkatone suppresses cyclin D1 involves protein level regulation, whereas nootkatone increases NAG-1 expression at the transcriptional level. In addition to having PPARγ binding activity, nootkatone also increases EGR-1 expression which ultimately results in enhanced NAG-1 promoter activity., Conclusion: In summary, our findings suggest that nootkatone is an anti-tumorigenic compound harboring antiproliferative and pro-apoptotic activity.

Trapping multiple dual mode (trapping MDM) is a preparative liquid-liquid chromatography (LLC) technique well-suited to difficult separations of intermediately-eluting components from similarly structured impurities. In this demonstrative study, a design approach for high process throughput is applied for the trapping MDM separation of a target component, nootkatone (NK), initially comprising 16.7% of an industrial side stream mixture with over 90 impurities. This design approach, previously developed and validated using ternary mixtures of model solutes, is applied to a complex real mixture for the first time. The approach consists of five steps: (1) determination of the maximum starting mixture concentration for feed preparation; (2) determination of the maximum flow rate for maintenance of the pre-set stationary phase fraction; (3) determination of the partition coefficients of the target and main impurities; (4) selection of step durations and number of cycles using an established short-cut method; (5) execution of the trapping MDM separation. The target, NK, was obtained along with a co-eluting component at 78.7% purity and 84.6% yield, demonstrating the effectiveness of trapping MDM for the separation of intermediately-eluting natural product target components from complex starting mixtures., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The volatile components emitted from two scale insects, Ceroplastes japonicus and Ceroplastes rubens , were identified using GC-MS analysis. The major volatile components of the solvent extract from C. japonicus were α-humulene (35.8%) and δ-cadinene (17.0%), while those of C. rubens were β-selinene (10.3%) and β-elemene (5.1%). In GC/olfactometry, linalool, butyric acid, 3-methylbutyric acid, 2-methylbutyric acid, and vanillin were identified as the odor-active components of the extract from C. japonicus , in addition to trace amounts of trans -4,5-epoxy-(2 E )-decenal, 4-methyl-(3 E )-hexenoic acid, and phenylacetic acid. With regard to C. rubens, trans -4,5-epoxy-(2 E )-decenal, 3-methylbutyric acid, and phenylacetic acid were identified as the odor-active components. Besides, decan-1,4-olide (γ-decalactone) with milky cherry-like note and 3-hydroxy-4,5-dimethylfuran-2(5 H )-one (sotolone) with brown sugar-like note were also detected as the characteristic cherry-like sweet-and-sour note of these two scale insects., Abbreviations: GC: Gas chromatography; GC/O: gas chromatography/olfactometry.

Chemical screening of culture medium from the soil fungus Stachybotrys sp. resulted in the isolation of the three new phenylspirodrimanes MBJ-0030 ( 1 ), MBJ-0031 ( 2 ) and MBJ-0032 ( 3 ). Their structures were determined by detailed analysis of spectroscopic data. The absolute configurations of 1 - 3 were determined by modified Mosher's and Marfey's methods. In addition, cytotoxic and antimicrobial evaluations of the compounds were conducted.

Ferulago nodosa (L.) Boiss. (Apiaceae) is a species occurring in the Balkan-Tyrrhenian area. The object of the present study is Sicilian F. nodosa subsp. geniculata (Guss.) Troia & Raimondo, classified as an endemic F. nodosa subspecies. Aerial parts of this plant species were subjected to hydrodistillation to obtain an essential oil. A total of 93 compounds were identified with 2,3,6-trimethyl benzaldehyde (19.0%), spathulenol (9.0%), ( E )-caryophyllene (5.4%), and caryophyllene oxide (5.4%) as the main components. The biological activities of F. nodosa essential oil were also investigated. This oil showed an interesting antioxidant potential in a 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) test (IC 50 of 14.05 μg/mL). Additionally, hypoglycemic and antilipidemic effects were evaluated. Lipase enzyme was inhibited with an IC 50 value of 41.99 μg/mL. Obtained data demonstrated that F. nodosa could be considered a promising source of bioactive compounds useful for the treatment and management of obesity.

The volatile components produced by Leptolejeunea elliptica (Lejeuneaceae), which is a liverwort grown on the leaves of tea (Camellia sinensis), were collected and analyzed using headspace solid-phase microextraction-gas chromatography/mass spectrometry (HS-SPME-GC/MS). 1-Ethyl-4-methoxybenzene (1), 1-ethyl-4-hydroxybenzene (2), and 1-acetoxy-4-ethylbenzene (3) were identified as the major components together with several other phenolic compounds, including 1,2-dimethoxy-4-ethylbenzene, and 4-ethylguaiacol in addition to sesquiterpene hydrocarbons, such as α-selinene, β-selinene, β-elemene, and β-caryophyllene. GC/Olfactometry showed the presence of linalool, acetic acid, isovaleric acid, trans-methyl cinnamate, and trans-4,5-epoxy-(2E)-decenal, as the volatile components produced by L. elliptica.

Xanthoxylin was the main compound (content 44.92% of total volatiles) in the leaves of Luodian B. balsamifera, which might be the key cause of failure in collecting essential oil (EO) of the leaves using general hydrodistillation in Clevenger apparatus. A modified hydrodistillation equipped with Clevenger apparatus was designed for isolating EO from the leaves. Six EOs of Luodian B. balsamifera harvested once a month from September to next February were collected successfully. The main components of EOs were δ-elemene, α-cubenene, caryophyllene, caryophyllene epoxide, γ-eudesmol, xanthoxylin, and α-eudesmol. The EOs of Luodian B. balsamifera collected from October to December had higher antioxidant activities (ACs). Combining the principal component analysis of chemical components with the results of ACs and the yields of six EOs, the leaves of Luodian B. balsamifera were suitable to be harvested in November and December to obtain EO with high quality., Competing Interests: The authors collected leaves of Luodian Blumea balsamifera from the Ai Yuan planting base. Ai Yuan received the support of the local government and the support of Chinese Innovation Fund for Technology Based Firms and Guizhou’s Innovation Fund for Technology Based Firms. The authors have a confidential cooperative relationship with Ai Yuan. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products to declare.

Four new phenylspirodrimane-type dimers, namely chartarlactams Q-T, along with stachyin B were isolated from the fermentation broth of a sponge-derived fungus Stachybotrys chartarum WGC-25 C-6. Chartarlactams Q-T were structurally featured by the dimerization of two units of phenylspirodrimane linked by a C-N bond. Their structures were determined on the basis of extensive spectroscopic analysis, while quantum ECD calculation and modified Mosher's method were used for the assignment of absolute configurations. Chartarlactams Q-S and stachyin B showed moderate inhibition against bacterial pathogen Staphylococcus aureus with MIC values ranging from 4 μg/mL to 16 μg/mL, and chartarlactam T exhibited significant inhibition toward ZIKV virus., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

The chemical composition of the volatile fraction from Galium verum L. (leaves and flowers) and Cruciata laevipes Opiz (whole plant), Rubiaceae , was investigated. Samples from these two plant species were collected at full bloom in Val di Susa (Western Alps, Turin, Italy), distilled in a Clevenger-type apparatus, and analyzed by GC/FID and GC/MS. A total of more than 70 compounds were identified, making up 92%-98% of the total oil. Chemical investigation of their essential oils indicated a quite different composition between G. verum and C. laevipes, both in terms of the major constituents and the dominant chemical classes of the specialized metabolites. The most abundant compounds identified in the essential oils from G. verum were 2-methylbenzaldheyde (26.27%, corresponding to 11.59 μg/g of fresh plant material) in the leaves and germacrene D (27.70%; 61.63 μg/g) in the flowers. C. laevipes essential oils were instead characterized by two sesquiterpenes, namely β-caryophyllene (19.90%; 15.68 μg/g) and trans -muurola-4(15),5-diene (7.60%; 5.99 μg/g); two phenylpropanoids, benzyl alcohol (8.30%; 6.71 μg/g), and phenylacetaldehyde (7.74%; 6.26 μg/g); and the green-leaf alcohol cis -3-hexen-1-ol (9.69%; 7.84 μg/g). The ecological significance of the presence of such compounds is discussed.

Ethnopharmacological Relevance: Cedrus libani A. Rich (C. libani) is majestic evergreen Mediterranean conifer growing in the mountains of Lebanon. The ethnobotanical and traditional uses of cedar wood oil traces back to ancient times for the treatment of various ailments including cancer. Previous work in our laboratories revealed that himachalol (7-HC), a major sesquiterpene isolated from C. libani, possesses potent cytotoxic activity against various human cancer cell lines as well as promising anti-inflammatory effect in isolated rat monocytes., Aim of the Study: The present study aims to elucidate the mechanism of action behind the cytotoxic activity of 7-HC against murine melanoma cells (B16F-10) and evaluates its chemopreventive effect against chemically-induced skin carcinogenesis in mice., Materials and Methods: 7-HC was extracted and purified from Cedrus libani wood. Cell viability was evaluated using WST-1 kit. Cell cycle analysis and apoptosis were assessed by Flow cytometry using propidium iodide (PI) and fluorescein Isothiocyanate (FITC)-conjugated Annexin V/PI staining respectively. Apoptosis related protein were quantified using western blot. The chemopreventive activity of 7-HC was evaluated for 20 weeks using a DMBA/TPA induced skin carcinogenesis model in Balb/c mice., Results: 7-HC displayed a potent anti-proliferative activity against the melanoma cells with an IC50 of 8.8 μg/ml and 7.3 μg/ml at 24 and 48 h, respectively. Co-treatment with Cisplatin did not show any synergistic or additive effect on cell viability. Flow cytometry analysis using PI revealed that 7-HC treatment (5 and 10 μg/ml) induces the accumulation of cells in the sub-G1 phase and causes a decline in cell populations in the S and G2/M phases. Annexin/PI staining also reveals that 7-HC treatment significantly increases the percentage of cells undergoing early and late apoptosis. Western blot analysis shows that 7-HC treatment decreases the level of the anti-apoptotic protein Bcl-2 and increases the level of the pro-apoptotic protein Bax. A reduction in the level of phosphorylated Erk and Akt was also observed. 7-HC via topical (2.5%), intraperitoneal (10, 25 and 50 mg/kg) or gavage (50 mg/kg) treatment revealed a significant decrease in papilloma volume with no adverse effect on liver and kidney function., Conclusions: The present study demonstrates that 7-HC treatment protects against chemically-induced skin carcinogenesis, promotes cell cycle arrest and induces apoptosis partially through an inhibition of both the MAPK/Erk and PI3K/Akt pathways., Competing Interests: Declaration of competing interest I, Costantine F. Daher, declare that all authors have no competing interests, financial or otherwise., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Alternarin A ( 1 ), a rearranged drimane meroterpenoid characterized by a thioglycerate moiety, was isolated together with two known analogues from the coral-associated fungi Alternaria sp. ZH-15. Its structure was determined based on spectroscopic analysis, modified Mosher's method, and TDDFT/ECD calculations. In a primary cultured cortical neuronal network, compound 1 effectively inhibited the activity of spontaneous synchronous Ca 2+ oscillations and 4-aminopyridine induced epileptic discharges in the low micromolar concentration range.

Two new caryophyllene-type sesquiterpenoids, pestathenols A (1) and B (2) and one new α-furanone, pestatheranone A (6), along with five known compounds (3-5, 7 and 8) have been isolated from the crude extract of the plant endophytic fungus Pestalotiopsis theae. Their structures were unambiguously established by extensive spectroscopic analyses. The absolute configuration of the 5,6-diol moiety in 1 was assigned using Snatzke's method. Compounds 1 and 2 showed weak cytotoxicity against HeLa cell line., (Copyright © 2020 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Commiphoins A-C (1-3), three new cadinane-type sesquiterpenes, together with two known cadinane-type sesquiterpenes (4 and 5) were isolated from the resinous exudates of Commiphora myrrha. Their structures and relative configurations were established on the basis of comprehensive spectroscopic methods, including HRESIMS, 1D and 2D NMR analyses. Compounds 1 and 3-5 were screened for anti-Alzheimer's disease (AD) activities using the AD pathological model in Caenorhabditis elegans. The results showed that they all had significant anti-AD activities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

An investigation of a co-culture of the Armillaria sp. and endophytic fungus Epicoccum sp. YUD17002 associated with Gastrodia elata led to the isolation of eight new compounds, including five protoilludane-type sesquiterpenes (1-5) and three aryl esters (6-8), together with six known analogues (9-14). The assignments of their structures were conducted via extensive analyses of the spectroscopic data and comparison of experimental and calculatedelectronic circular dichroism(ECD)data. Notably, these new compounds were not present in the pure culture controls and were only detected in the co-cultures. Compound 4 is the first example of an ent-protoilludane sesquiterpenoid scaffold bearing a five-membered lactone. Compound 6 exhibited moderate in vitro cytotoxic activities against five human cancer cell lines (HL-60, A549, MCF-7, SMMC-7721, and SW480) with IC 50 values ranging from 15.80 to 23.03 μM. Moreover, 6 showed weak acetylcholinesterase inhibitory activity (IC 50 value of 23.85 μM)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Paraconiothins A-J ( 1 - 10 ), 10 new sesquiterpenoids, as well as five known sesquiterpenoids, were isolated from the cultures of the endophytic fungus Paraconiothyrium brasiliense ECN-258. The structures of the sesquiterpenoids were elucidated by extensive spectroscopic analysis. Furthermore, the absolute structures of 7 and 8 were determined by comparing their experimental and computed electronic circular dichroism data. Paraconiothins A-G ( 1 - 7 ) were eremophilane sesquiterpenoids, while paraconiothins H-J ( 8 - 10 ) had new or rare carbon frameworks that are possibly biosynthesized by a pathway involving the rearrangement of eremophilane sesquiterpenoids. Paraconiothins C ( 3 ) and I ( 9 ) exhibited an inhibitory effect on the liver X receptor α at a concentration of 50 μM.

The chemical composition and the phytotoxicity potential of the essential oil from leaves of Unonopsis guatterioides (A.DC.) R.E.Fr. (Annonaceae) was investigated. Gas chromatography/mass spectrometry analyses revealed 16 constituents representing 99.50% of the total essential oil, composed mainly of sesquiterpenes. α-copaene, bicyclogermacrene and trans -caryophyllene were the major components (15.7% each), followed by α-humullene, allo -aromadendrene and (+)-spathulenol (9.0, 8.4 and 7.3%, respectively). The essential oil inhibited seed germination and growth in both monocotyledon ( Allium cepa ) and dicotyledon ( Lactuca sativa ) models, pointing to a promising application of this oil obtained from the leaves of U. guatterioides as a new bioherbicide.

The presence of excessive osteoclasts is a major factor in skeletal diseases. The present study aimed to discover osteoclast differentiation inhibitors from the basidiomycete Xylodon flaviporus . Seven new drimane sesquiterpenoids ( 1 - 7 ) and 7-ketoisodrimenin-5-ene ( 8 ) were obtained and characterized by various spectroscopic methods. The isolated compounds were evaluated for their inhibitory effects against receptor activator of nuclear factor-kappa-B ligand-induced osteoclastogenesis in mouse bone marrow macrophages. Compounds 1 , 3 , and 6 showed potent activities with IC 50 values of 1.6, 0.9, and 2.1 μM, respectively, while 4 , 5 , and 7 exhibited relatively weak activities with IC 50 values of 10.7, 10.1, and 8.5 μM, respectively.

Sensitizing activities exerted by 3,4-dihydro-7-hydroxycadalene (1), rac-3,7-dihydroxy-3(4H)-isocadalen-4-one (4) and (1R,4R)-4H-1,2,3,4-tetrahydro-1-hydroxycadalen-15-oic acid (9), the major cadinanes isolated from Heterotheca inuloides, towards multidrug-resistant MES-SA/MX2 and parental MES-SA epithelial human uterine sarcoma cell lines were evaluated. We also evaluated the in silico interactions (expressed as ΔG binding in kcal/mol) of cadinanes 1, 4 and 9 in an in vitro assay, and also tested several structurally related natural compounds with the multidrug resistance protein (MDR1, P-glycoprotein), human multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP) structures as pharmacological targets using AutoDock and AutoDock Vina. Compound 1 potentiated the cytotoxicity of doxorubicin and mitoxantrone drugs in resistant MES-SA/MX2 cells, compared to cells treated with each drug alone. Compound 1 could reverse the resistance to doxorubicin 12.44 fold at a concentration of 5 μM. It also re-sensitized cells to mitoxantrone 3.94 fold. Hence, compound 1 may be considered as a potential chemosensitizing agent to overcome multidrug resistance in cancer. The docking analysis suggested that there are interactions between cadinanes from H. inuloides and MDR1, MRP1, and BCRP proteins mainly through π-π interactions and hydrogen bonds., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The sesquiterpene (+)-zizaene is the direct precursor of khusimol, the main fragrant compound of the vetiver essential oil from Chrysopogon zizanioides and used in nearly 20% of men's fine perfumery. The biotechnological production of such fragrant sesquiterpenes is a promising alternative towards sustainability; nevertheless, product recovery from fermentation is one of the main constraints. In an effort to improve the (+)-zizaene recovery from a metabolically-engineered Escherichia coli , we developed an integrated bioprocess by coupling fermentation and (+)-zizaene recovery using adsorber extractants. Initially, (+)-zizaene volatilization was confirmed from cultivations with no extractants but application of liquid-liquid phase partitioning cultivation (LLPPC) improved (+)-zizaene recovery nearly 4-fold. Furthermore, solid-liquid phase partitioning cultivation (SLPPC) was evaluated by screening polymeric adsorbers, where Diaion HP20 reached the highest recovery. Bioprocess was scaled up to 2 L bioreactors and in situ recovery configurations integrated to fermentation were evaluated. External recovery configuration was performed with an expanded bed adsorption column and improved (+)-zizaene titers 2.5-fold higher than LLPPC. Moreover, internal recovery configuration (IRC) further enhanced the (+)-zizaene titers 2.2-fold, whereas adsorption velocity was determined as critical parameter for recovery efficiency. Consequently, IRC improved the (+)-zizaene titer 8.4-fold and productivity 3-fold from our last report, achieving a (+)-zizaene titer of 211.13 mg L -1 and productivity of 3.2 mg L -1 h -1 . This study provides further knowledge for integration of terpene bioprocesses by in situ product recovery, which could be applied for many terpene studies towards the industrialization of fragrant molecules.

Illudin S from mushroom, such as Omphalotus japonicus and illudens, is a natural sesquiterpene analog with strong anti-tumor and antiviral activities. These illudins compounds are highly effective against various drug-resistant cancers that show extreme cytotoxicity an in vitro assay. However, it is difficult to obtain a sufficient amount of highly pure illudin S from a natural product by simple, efficient and low-cost purification techniques. Here, we offer to apply the high-speed countercurrent chromatography for the preparative purification of illudin S from mushroom extract. For a two-solvent system, the optimal condition of hexane/ethyl acetate/methanol/water (1/5/1/5, v/v/v/v) was optimized to obtain pure illudin S from a crude extract. This purified component was evaluated by liquid chromatography (high-purity >99%) and tandem mass spectrometry. The yield amounts of illudin S (1.3 mg/about 10 g Omphalotus japonicus) at one running are determined by liquid chromatographic calibration. It is concluded that by requiring a natural material and cost-effectiveness, our method represents a significant improvement over complicated techniques for the purification of illudin S from natural materials.

Two novel sesquiterpenoids, curcumanes A (1) and B (2), possessing unprecedented skeletons with a dicyclo[3.2.1]octane and a dicyclo[3.3.1]nonane moiety, respectively, were isolated from Curcuma longa. Both of them had remarkable vasorelaxant activity on rat aorta via blocking extracellular Ca 2+ influx through VDCCs and ROCCs. The activity of 1 was endothelium-independent, while that of 2 was endothelium-dependent. Compound 2 also prolonged APTT and TT to inhibit blood coagulation.