Sesquiterpenes

Three brominated bisabolene-type sesquiterpene derivatives, aldingenin B, C and D, together with cholesterol and palmitic acid, have been isolated from the red alga Laurencia aldingensis (Ceramiales, Rodophyta) and their structures elucidated by spectroscopic methods including NMR analysis.

The chromatographic separation of a methylene chloride extract of Artemisia rubripes led to the isolation of a new sesquiterpene lactone (3), together with four known compounds, a coumarin (2) and three terpenes (1, 4, and 5). Their structures were characterized to be 1beta,6alpha-dihydroxy-4(15)-eudesmene (1), scopoletin (2), 1alpha,4beta-dihydroxy-8alpha-acetoxy-guaia-2,10(14), 11(13)-triene-6,12-olide (3), 1alpha,4beta-dihydroxy-8alpha-acetoxy-guaia-2,9,11(13)-triene-6,12-olide (4), and beta-sitosterol-3-O-beta-D-glycoside (5) by spectroscopic means.

The n-hexane extract of Lovage root was found to significantly inhibit the growth of both Mycobacterium smegmatis mc 2 155 and Mycobacterium bovis BCG, and therefore a bioassay-guided isolation strategy was undertaken. (Z)-Ligustilide, (Z)-3-butylidenephthalide, (E)-3-butylidenephthalide, 3-butylphthalide, a-prethapsenol, falcarindiol, levistolide A, psoralen and bergapten were isolated by chromatographic techniques, characterized by NMR spectroscopy and MS, and evaluated for their growth inhibition activity against Mycobacterium tuberculosis H 37 Rv using the whole-cell phenotypic spot culture growth inhibition assay (SPOTi). Cytotoxicity against RAW 264.7 murine macrophage cells was employed for assessing their degree of selectivity. Falcarindiol was the most potent compound with a minimum inhibitory concentration (MIC) value of 20 mg/L against the virulent H 37 Rv strain; however, it was found to be cytotoxic with a half-growth inhibitory concentration (GIC 50) in the same order of magnitude (SI < 1). Interestingly the sesquiterpene alcohol a-prethapsenol was found to inhibit the growth of the pathogenic mycobacteria with an MIC value of 60 mg/L, being more specific towards mycobacteria than mammalian cells (SI~2). Colony forming unit analysis at different concentrations of this phytochemical showed mycobacteriostatic mode of action.

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Osteoarthritis is a progressive joint disease and a major cause of disability for which no curative therapies are yet available. To identify compounds with potential anti-osteoarthritic properties, in this study, we screened one sesquiterpene, E-caryophyllene, and two monoterpene, myrcene and limonene, hydrocarbon compounds for anti-inflammatory, anti-catabolic and pro-anabolic activities in human chondrocytes. At non-cytotoxic concentrations, myrcene and limonene inhibited IL-1β-induced nitric oxide production (IC50=37.3μg/ml and 85.3µg/ml, respectively), but E-caryophyllene was inactive. Myrcene, and limonene to a lesser extent, also decreased IL-1β-induced NF-κB, JNK and p38 activation and the expression of inflammatory (iNOS) and catabolic (MMP-1 and MMP-13) genes, while increasing the expression of anti-catabolic genes (TIMP-1 and -3 by myrcene and TIMP-1 by limonene). Limonene increased ERK1/2 activation by 30%, while myrcene decreased it by 26%, relative to IL-1β-treated cell...

The antiviral effect against hepatitis B virus (HBV) of artemisinin, its derivative artesunate and other compounds highly purified from traditional Chinese medicine remedies, were investigated. HBV production by permanently transfected HepG2 2.2.15 cells was determined by measuring the release of surface protein (HBsAg) and HBV-DNA after drug exposure (0.01-100 M) for 21 days. The forms of HBV-DNA released were investigated by Southern-blotting. Neutral Red retention test was used to evaluate drug-induced toxicity on host cells. The compounds were classified according to their potential interest as follows: (i) none: they had no effect on viral production (daidzein, daidzin, isonardosinon, nardofuran, nardosinon, tetrahydronardosinon and quercetin); (ii) low: they were able to markedly reduce viral production, but also induced toxicity on host cells (berberine and tannic acid) or they had no toxic effect on host cells but only had a moderate ability to reduce viral production (curcumin, baicalein, baicalin, bufalin, diallyl disulphide, glycyrrhizic acid and puerarin); (iii) high: they induced strong inhibition of viral production at concentrations at which host cell viability was not affected (artemisinin and artesunate). Moreover, artesunate in conjunction with lamivudine had synergic anti-HBV effects, which warrants further evaluation of artemisinin/artesunate as antiviral agents against HBV infection.

The acaricidal activity of Eugenia caryophyllata essential oil was evaluated in vitro and in vivo on Psoroptes cuniculi, a mange mite. In vitro, diVerent concentrations of the oil were tested and the observed mites mortality was compared with that observed in untreated and treated (Acacerulen R ® ) controls. In vivo, six P. cuniculi infected rabbits were topically treated with the oil diluted at 2.5% and compared with untreated and treated control groups of six rabbits each. In vitro, up to the concentration of 0.10% the oil gave highly signiWcant (P < 0.01) percentages of mite mortality respect to the untreated controls, but only up to 0.16% it showed the same eYcacy of Acacerulen R ® . In vivo, the treatment with the essential oil cured all infested rabbits and no statistical diVerences were observed respect to the treated control group. The untreated rabbits remained infested.

A variety of labdane-related diterpenoids, including phytocassanes, oryzalexins and momilactones, were identified as phytoalexins in rice (Oryza sativa L.). Momilactone B was also isolated as an allelochemical exuded from rice roots. The biosynthetic genes of these phytoalexins have been identified, including six labdane-related diterpene cyclase genes such as OsCPS2, OsCPS4, OsKSL4, OsKSL7, OsKSL8 and OsKSL10. Here we identified an OsCPS4 knockdown mutant, cps4-tos, by screening Tos17 mutant lines using polymerase chain reaction. OsCPS4 encodes a syn-copalyl diphosphate synthase responsible for momilactones and oryzalexin S biosynthesis. Because Tos17 was inserted into the third intron of OsCPS4, the mature OsCPS4 mRNA was detected in the cps4-tos mutant as well as the wild type. Nevertheless, mature OsCPS4 transcript levels in the cps4-tos mutant were about one sixth those in the wild type. The cps4-tos mutant was more susceptible to rice blast fungus than the wild type, possibly due to lower levels of momilactones and oryzalexin S in the mutant. Moreover, co-cultivation experiments suggested that the allelopathic effect of cps4-tos against some kinds of lowland weeds was significantly lower than that of the wild type, probably because of lower momilactone content exuded from cps4-tos roots. A reverse-genetic strategy using the cps4-tos mutant showed the possible roles of momilactones not only as phytoalexins but also as allelopathic substances.

Fungi (Ascomycota and Basidiomycota) are prolific producers of structurally diverse terpenoid compounds.
Classes of terpenoids identified in fungi include the sesqui-, di- and triterpenoids. Biosynthetic pathways and
enzymes to terpenoids from each of these classes have been described. These typically involve the scaffold
generating terpene synthases and cyclases, and scaffold tailoring enzymes such as e.g. cytochrome P450
monoxygenases, NAD(P)+ and flavin dependent oxidoreductases, and various group transferases that generate
the final bioactive structures. The biosynthesis of several sesquiterpenoid mycotoxins and bioactive diterpenoids
has been well-studied in Ascomycota (e.g. filamentous fungi). Little is known about the terpenoid biosynthetic
pathways in Basidiomycota (e.g. mushroom forming fungi), although they produce a huge diversity of
terpenoid natural products. Specifically, many trans-humulyl cation derived sesquiterpenoid natural products
with potent bioactivities have been isolated. Biosynthetic gene clusters responsible for the production of transhumulyl
cation derived protoilludanes, and other sesquiterpenoids, can be rapidly identified by genome
sequencing and bioinformatic methods. Genome mining combined with heterologous biosynthetic pathway
refactoring has the potential to facilitate discovery and production of pharmaceutically relevant fungal terpenoids.

In this study, a-bisabolol, a sesquiterpene alcohol present in natural essential oil, was found to have a strong time-and dosedependent cytotoxic effect on human and rat glioma cells. After 24 h of treatment with 2.5-3.5 lM a-bisabolol, the viability of these cells was reduced by 50% with respect to untreated cells. Furthermore, the viability of normal rat glial cells was not affected by treatment with a-bisabolol at the same concentrations as above. Glioma cells treated with high concentration of a-bisabolol (10 lM) resulted in a 100% cell death. Judging from hypo-G1 accumulation, poly(ADP-ribose) polymerase cleavage, and DNA ladder formation, the cytotoxicity triggered by a-bisabolol resulted from apoptosis induction. Moreover, the dissipation of mitochondrialinner transmembrane potential and the release of cytochrome c from mitochondria indicated that, in these glioma cells, apoptosis occurred through an intrinsic pathway. As pointed out by the experimental results, a-bisabolol may be considered a novel compound able to inhibit glioma cell growth and survival.

A new isodaucane sesquiterpenoid, 6,7,10-trihydoxyisodaucane, was isolated from the fruits of Reneilmia cincinnata, together with the known sesquiterpenoids oplodiol, oplopanone, 5E,10(14)-germacradien-1b,4b-diol, 1(10)E,5E-germacradien-4a-ol and eudesman-1,4,7-triol. A large amount of 5-hydroxy-3,7,4 '-trimethoxy¯avone was also isolated. Their structures were established by NMR techniques using 1D and 2D experiments. Three of the known sesquirernenoids exhibited noteworthy anti-plasmodial activity against Plasmodium falciparum strains.

Four new sesquiterpenes, chlorajapolides F-I (1-4), along with nine known terpenoids (5-13) were isolated from the aerial part of Chloranthus japonicus. Their structures were elucidated on the basis of spectroscopic analysis, and a lindenane sesquiterpene, named 9-hydroxy-heterogorgiolide, previously isolated from the C. japonicus, was revised as its 8-epimer (1a). Moreover, methanol extract (ME), EtOAc fraction (EF), water fraction (WF), and all isolates (1a, 1-13) were evaluated for their cytotoxicities using two human cancer cell lines.

Introduction ! Abies georgei Orr (Pinaceae) is a tall tree distributing exclusively in China, especially in the northwest of Yunnan and southwest of Sichuan provinces [1]. Bioevaluation studies indicated that the CHCl 3 -soluble fraction of its EtOH extract had strong antitumor effects, while the EtOAc-soluable fraction exhibited potent anti-inflammatory properties . Therefore, a systematic investigation was carried out in order to isolate and characterize the specific bioactive components of A. georgei. Over 100 potential bioactive compounds have already been isolated from this plant, including biflavanols, norditerpenoids, diterpenoids, and triterpenoids . In this study, we described the isolation and structural elucidation of the nine new compounds. In addition, we tested all bioactivities for antiproliferative activity against tumors and for inhibitory activity against lipopolysaccharide-evoked NO production in RAW 264.7 macrophages.

In a two-microelectrode voltage clamp with Xenopus laevis oocytes, a petroleum ether extract of Acorus calamus rhizomes enhanced the GABA-induced chloride current through GABA A receptors of the α 1 β 2 γ 2S subtype by 277% ± 9.7% (100 μg/mL). β-Asarone (1), (+)dioxosarcoguaiacol (2), (+)-shyobunone (3), and (+)-preisocalamenediol (4) were subsequently identified as main active principles through HPLC-based activity profiling and targeted isolation. The compounds induced maximum potentiation of the chloride current ranging from 588% ± 126% (EC 50 : 65.3 ± 21.6 μM) (2) to 1200% ± 163% (EC 50 : 171.5 ± 34.6 μM) (1), whereas (−)isoshyobunone (5) and (−)-acorenone (6) exhibited weak GABA A modulating properties (5: 164% ± 42.9%; EC 50 : 109.4 ± 46.6 μM and 6: 241% ± 23.1%; EC 50 : 34.0 ± 6.7 μM). The relative configuration of 2 was established as 4R*8S*10R* by NOESY experiments and conformational analysis.

The fixed oil of Laurus novocanariensis (previously L. azorica) contains mostly glycerides together with minor non-saponifiable compounds. The direct identification and quantitative determination of costunolide and dehydrocostuslactone, two sesquiterpene lactones components of the oil that exhibit biological activities, is described. The analysis was carried out using 13 C-NMR spectroscopy (signal acquisition with inverse gated decoupling of protons; diglyme as internal standard) without separation, derivatisation or any sample preparation.

Patch test positivity to parthenolide was observed less often than expected in strongly suspected cases of parthenium dermatitis after Chemotechnique Diagnostics (Sweden) replaced parthenium extract with parthenolide (0.5% pet.) by itself while marketing its Indian baseline series for patch testing. The study was performed to find whether parthenolide detects parthenium contact sensitivity more effectively than parthenium extract in patients clinically presenting with classic parthenium dermatitis. One hundred consecutive patients with suspected parthenium dermatitis were patch tested prospectively with the Indian baseline series, parthenium extract (1% aq.) and parthenolide (0.5% pet.) between July 2011 and April 2012. Only 37 of 100 patients with suspected parthenium dermatitis (male/female ratio of 20:17) reacted to parthenium extract (32 patients), parthenolide (17 patients), or both (12 patients). Reactions to parthenium extract were generally stronger than reactions to parthen...

Saussurea costus (Falc.) Lipschitz, syn Saussurea lappa C.B. Clarke is a well known and important medicinal plant widely used in several indigenous systems of medicine for the treatment of various ailments, viz. asthma, inflammatory diseases, ulcer and stomach problems. Sesquiterpene lactones have been reported as the major phytoconstituents of this species. Different pharmacological experiments in a number of in vitro and in vivo models have convincingly demonstrated the ability of Saussurea costus to exhibit anti-inflammatory, anti-ulcer, anticancer and hepatoprotective activities, lending support to the rationale behind several of its traditional uses. Costunolide, dehydrocostus lactone and cynaropicrin, isolated from this plant, have been identified to have potential to be developed as bioactive molecules. Due to the remarkable biological activity of Saussurea costus and its constituents it will be appropriate to develop them as a medicine. The present review is an up-to-date and comprehensive analysis of the botany, chemistry, pharmacology and traditional and folkloric uses of Saussurea costus.

From the dichloromethane extract of aerial parts of Ferula vesceritensis (Apiaceae), 11 sesquiterpene derivatives were isolated. Among them five were compounds designated as 10-hydroxylancerodiol-6anisate, 2,10-diacetyl-8-hydroxyferutriol-6-anisate, 10-hydroxylancerodiol-6-benzoate, vesceritenone and epoxy-vesceritenol. The six known compounds were identified as feselol, farnesiferol A, lapidol, 2-acetyl-jaeschkeanadiol-6-anisate, lasidiol-10-anisate and 10-oxo-jaesckeanadiol-6-anisate. All the structures were determined by extensive spectroscopic studies including 1D and 2D NMR experiments and mass spectroscopy analysis. Two of the compounds, the sesquiterpene coumarins farnesiferol A and feselol, bound to the model recombinant nucleotide-binding site of an MDR-like efflux pump from the enteropathogenic protozoan Cryptosporidium parvum.

Aedes albopictus (Diptera: Culicidae) has been one of the fastest spreading insects over the past 20 years. Its medical importance is due to the aggressive daytime human-biting behavior and the ability to vector many viruses, including dengue, LaCrosse, Eastern Equine encephalitis and West Nile viruses. In this research, the essential oils (EOs) extracted from fresh air dried leaves of Salvia dorisiana, S. longifolia, and S. sclarea (Lamiaceae) were evaluated for their repellent activity against A. albopictus by using the ...

We determined the cytotoxicity of some artemisinin derivatives against EN2 tumor cells using the MTT assay. Artemisinin (1) was clearly more cytotoxic than deoxyartemisinin (2), which lacks the endoperoxide bridge. Ether-linked dimers of dihydroartemisinin with defined stereochemistry were found to differ in the extent of cytotoxic effect on EN2 cells. The nonsymmetrical dimer (3) was more cytotoxic than the symmetrical dimer (4). The nonsymmetrical dimer of dihydrodeoxyartemisinin (5) lacking the endoperoxide bridges was also effective in the MTT assay, although less cytotoxic than 3 and 4. Similarly, the symmetrical dimer (6) was less effective than 5. Epoxides of artemisitene also showed that stereochemistry was an important factor for cytotoxicity. The results suggested that the endoperoxide bridge was not crucial for cytotoxicity to the tumor cells, but contributed to the cytotoxic effect apparently exerted by the ether linkage of the dimers. Flow cytometry data indicated that the dimers 3 and 4 caused an accumulation of the cells in the G 1 -phase of the cell cycle. In contrast, artemisinin (1) caused a slight increase of S-phase cells.

Ethnopharmacological relevance: In Russian traditional medicine, an extract from the mushroom Inonotus obliquus (Fr.) Pil´at is used as an anti-tumor medicine and diuretic. It has been reported that Inonotus obliquus has therapeutic effects, such as anti-inflammatory, immuno-modulatory and hepatoprotective effects. This study was designed to investigate the chemical composition and biological properties of aqueous and ethanolic extracts of Inonotus obliquus from Finland, Russia, and Thailand. Their antioxidative, antimicrobial, and antiquorum properties were tested as well as the cytotoxicity on various tumor cell lines.

Chemical investigation of rhizomes of Homalomena occulta (Lours) resulted in isolation and identification of two sesquiterpenoids (6,7), and one daucane ester 8, together with five known sesquiterpenoids, oplodiol, oplopanone, homalomenol C, bullatantriol, and 1b,4b,7a-trihydroxyeudesmane. Their structures were elucidated using 1D and 2D NMR spectroscopic and X-ray analyses. The chloroform extract of this plant and compounds 1-7 were tested in vitro for their activities in stimulating osteoblast (OB) proliferation, differentiation and mineralization. Compounds 1-4 had a stimulative effect on significantly proliferation and differentiation of culture osteoblasts, while the chloroform extract and 1 significantly stimulated mineralization of cultured osteoblasts in vitro.

Vetiver is the only grass cultivated worldwide for the root essential oil, which is a mixture of sesquiterpene alcohols and hydrocarbons, used extensively in perfumery and cosmetics. Light and transmission electron microscopy demonstrated the presence of bacteria in the cortical parenchymatous essential oilproducing cells and in the lysigen lacunae in close association with the essential oil. This finding and the evidence that axenic Vetiver produces in vitro only trace amounts of oil with a strikingly different composition compared with the oils from in vivo Vetiver plants stimulated the hypothesis of an involvement of these bacteria in the oil metabolism. We used culture-based and culture-independent approaches to analyse the microbial community of the Vetiver root. Results demonstrate a broad phylogenetic spectrum of bacteria, including a-, band g-Proteobacteria, high-G+C-content Gram-positive bacteria, and microbes belonging to the Fibrobacteres/Acidobacteria group. We isolated root-associated bacteria and showed that most of them are able to grow by using oil sesquiterpenes as a carbon source and to metabolize them releasing into the medium a large number of compounds typically found in commercial Vetiver oils. Several bacteria were also able to induce gene expression of a Vetiver sesquiterpene synthase. These results support the intriguing hypothesis that bacteria may have a role in essential oil biosynthesis opening the possibility to use them to manoeuvre the Vetiver oil molecular structure.

Silylated ethanolic extract of two propolis samples from Kazan and Marmaris regions in Turkey were investigated by capillary GC-MS. The compounds were characterized by comparison with library searches. Twenty four compounds from Kazan samples were identified, eight of them were new for propolis. Eighteen compounds from Marmaris samples were identified, two of them were new for propolis.

Agarwood, one of the valuable non-timber products in tropical forest, is a fragrant wood, whose ethereal fragrance has been prized in Asia for incense in ceremony, as well as sedatives in traditional medicine. We separated the 70% EtOH extract of Vietnamese agarwood, which showed significant induction effect on brain-derived neurotrophic factor (BDNF) mRNA expression in rat cultured neuronal cells, to isolate a new compound and a 2-(2-phenylethyl)chromone derivative. The new compound was determined to be a spirovetivane-type sesquiterpene, (4R,5R,7R)-1(10)-spirovetiven-11-ol-2-one, by spectroscopic data and showed induction effect of BDNF mRNA.The new sesquiterpenoid, (4R,5R,7R)-1(10)-spirovetiven-11-ol-2-one, isolated from agarwood significantly induced brain-derived neurotrophic factor (BDNF) exon III–V mRNA expression.

This article reports the compounds identified in the leaf oils of five Clauseana species growing in Vietnam. The hydrodistilled oils were analysed for their chemical constituents by using gas chromatography -flame ionisation detector and gas chromatography coupled with mass spectrometry. The major compounds identified in Clausena dentata (Willd.) M. Roem. were a-pinene (21.7%), sabinene (18.3%) and b-myrcene (14.3%). Clausena dimidiata Tanaka comprised mainly of safrole (56.9%) and a-terpinolene (22.1%). However, 1-menthone (70.6%) and b-phellandrene (13.0%) were the most abundant compounds of Clausena indica (Dalz.) Oliver. Sesquiterpene compounds represented mainly by b-caryophyllene (16.7%), spathulenol (11.9%) and bicyclogermacrene (7.5%) were the major constituents of Clausena excavata Burm. f., while those of Clausena engleri Tanaka include bicycloelemene (12.1%), bicyclogermacrene (11.0%) and (E)-nerolidol (6.6%). This is the first report on the chemical analysis of essential oils of C. dimidiata and C. engleri.

Russian knapweed is a perennial weed found in many parts of the world, including southern California. Chronic ingestion of this plant by horses has been reported to cause equine nigropallidal encephalomalacia (ENE), which is associated with a movement disorder simulating Parkinson's disease (PD). Repin, a principal ingredient purified from Russian knapweed, is a sesquiterpene lactone containing an ␣-methylenebutyrolactone moiety and epoxides and is a highly reactive electrophile that can readily undergo conjugation with various biological nucleophiles, such as proteins, DNA, and glutathione (GSH). We show in this study that repin is highly toxic to C57BL/6J mice and Sprague-Dawley rats and acutely induces uncoordinated locomotion associated with postural tremors, hypothermia, and inability to respond to sonic and tactile stimuli. We also show that repin intoxication reduces striatal and hippocampal GSH and increases total striatal dopamine (DA) levels in mice. Striatal microdialysis in rats, however, has demonstrated a significant reduction of extracellular DA levels. These findings, coupled with the absence of any demonstrable change in striatal DOPAC levels, suggest that repin acts by inhibiting DA release, a hypothesis that is further supported by our demonstration that, in cultured PC12 cells, repin inhibits the release of DA without affecting its uptake. We believe, therefore, that inhibition of DA release represents one of the earliest pathogenetic events in ENE, leading eventually to striatal extracellular DA denervation, oxidative stress, and degeneration of nigrostriatal pathways. Since the neurotoxic effects of repin appear to be mediated via oxidative stress, and since repin is a natural product isolated from a plant in our environment that can cause a movement disorder associated with degeneration of nigrostriatal pathways, clarification of the mechanism of repin neurotoxicity may provide new insights into our understanding of the pathogenesis of PD. 1998

Leaves, shoots and flowers from two different economy-relevant grape cultivars, Merlot and Cabernet Sauvignon, were examined to assess the distribution of phytoalexins upon inoculation with Botrytis cinerea at pre-bloom, bloom, and post-bloom stages.

Diabetes mellitus is the most common and serious metabolic disorder among people all over the world. Many plants have successfully been used to overcome this problem. Costus speciosus is widely used in Indian medicine to treat various diseases including diabetes. Bioassay guided fractionation was followed to isolate costunolide from the hexane extract of C. speciosus root. The structure was elucidated using X-ray crystallography. Costunolide was administered to streptozotocin (STZ) (50 mg/kg bw)-induced diabetic male wistar rats at different doses (5, 10, 20 mg/kg bw) for 30 days to assess its effect on fasting plasma glucose and cholesterol levels. It was found that plasma glucose was significantly (p < 0.05) reduced in a dose-dependent manner when compared to the control. In addition, oral administration of costunolide (20 mg/kg bw) significantly decreased glycosylated hemoglobin (HbA 1c ), serum total cholesterol, triglyceride, LDL cholesterol and at the same time markedly increased plasma insulin, tissue glycogen, HDL cholesterol and serum protein. Also costunolide restored the altered plasma enzyme (aspartate aminotransferase, alanine aminotrasferase, lactate dehydrogenase, alkaline phosphatase and acid phosphatase) levels to near normal. Costunolide might have stimulated the beta islets to secrete insulin by inhibiting the expression of nitric oxide synthase. The results of this experimental study indicated that costunolide possessed normo-glycemic and hypolipidemic activity and hence it could be used as a drug for treating diabetes.

The presence of the phytotoxic sesquiterpene (-)-hamanasic acid A {(-)HAA; 7-carboxy-8-hydroxy-1(2), 12(13)-dien-bisabolene} isolated from Flourensia campestris (FC), was investigated in the South American species of the genus, together with the evaluation of the phytotoxic activity of their leaf aqueous extracts. (-)HAA was identified and isolated from F. fiebrigii (FF) and F. oolepis (FO), being chemically (GC-MS, NMR, [a]) and biologically (bioassayed on lettuce) indistinguishable from that of FC, while no (-)HAA was found in F. hirta (FH), F. riparia (FR) and F. niederleinii (FN). Its leaf content in FF was similar to that found in FC (ca. 15 mg g-1 WT) and significantly higher than in FO (0.8 mg g-1 WT). The screening for the presence of (-)HAA in other species of Flourensia communities showed that its natural occurrence is restricted only to Flourensia species. No (-)HAA could be detected in any of the 37 -most representative- species of these communities (26 natives, 11 exoti...

Phenolic compounds exist widely in the influents and effluents of sewage treatment plants (STPs) and most are un-regulated. In this study, a gas chromatography-mass spectrometry (GC-MS) method for the simultaneous analysis of 50 phenolic compounds in wastewater was developed. Deconvolution technology was used to identify contaminants that are covered by co-extracted materials. A mass spectral library containing all 50 silylated phenolic compounds was first established and used for deconvolution. Twelve typical phenolic compounds were selected to optimize the sample preparation procedures. Solid-phase extraction using a C18 cartridge coupled with an HLB cartridge was used for pre-concentration and dichloromethane was used for elution. The solutes were derivatized and analyzed by GC-MS. The blank and matrix spike recoveries ranged from 57.46% to 136.4% and 47.87% to 114.8%, respectively. Method detection limits ranged from 3.64 to 97.64 ng L -1 . The relative standard deviations of all the recovery experiments were lower than 13.6%. The instrument limits of quantification ranged from 0.7 to 87.7 pg. The method has been applied to analyze the influents and effluents of 5 Chinese STPs. Except for regulated phenolic compounds (phenol and 2,4,6-trichlorophenol), three un-regulated phenolic compounds, including 2-chlorophenol, 2,5-dichlorophenol and 2,4-dichloro-3-ethyl-6-nitrophenol were identified in the effluent wastewater. The detected concentrations of un-regulated phenolic compounds could possibly cause environmental effects, indicating that immediate attention is required to prevent complications. identify, quantify, phenolic compounds, deconvolution, wastewater Citation:

Seventeen daucane esters have been isolated from the seeds of Ferula hermonis Boiss (Apiaceae). Three of these sesquiterpenes, 4b-hydroxy-6a-benzoyl-7-daucen-9-one (1), 4b, 8b-dihydroxy-6a-benzoyl-dauc-9-ene (2), and 4b, 9a-dihydroxy-6a-benzoyl-dauc-7-ene (4), named feruhermonins A-C, respectively, are novel natural products. The structures of these compounds were elucidated unequivocally by a series of 1D and 2D NMR analyses. Although 4b, 8b-dihydroxy-6a-(4-hydroxy-3-methoxybenzoyl)-dauc-9-ene (3) was reported previously, the complete spectroscopic data for this compound are presented here for the first time.

Two novel eudesmane-type sesquiterpenes, dictyophorines A and B, and a known compound, teucrenone, were isolated from the mushroom Dictyophora indusinta. Dictyophorines A and B promoted nerve growth factor (NGF)-synthesis by astroglial cells. Q

The chemical constituents of essential oils from the leaf, stem bark and resins of Canarium parvum Leen., and Canarium tramdenanum Dai et Yakovl. (Burseracea) grown in Vietnam are being reported. The hydrodistilled oils were analysed for their chemical constituents by means of gas chromatography-flame ionisation detector and gas chromatography coupled with mass spectrometry. The main compounds of C. parvum were b-caryophyllene (18.7%), (E)-b-ocimene (12.9%), (Z)-b-ocimene (11.9%), germacrene D (8.8%) and a-humulene (8.4%) in the leaf; b-caryophyllene (30.4%), a-copaene (20.5%) and (E)-b-ocimene (7.7%) in the stem. However, germacrene D (23.2%), a-amorphene (14.9%), a-copaene (9.8%) and b-elemene (8.6%) were present in the resin. The leaf of C. tramdenanum comprises b-caryophyllene (16.8%), a-phellandrene (15.9%), g-elemene (13.1%) and limonene (11.8%), while limonene (25.7%), a-phellandrene (21.7%), a-pinene (12.3%) and b-caryophyllene (10.9%) were present in the stem. However, d-elemene (14.6%) and bulnesol (16.0%) are the main constituents in the resin.

Huperzine A (HupA), extracted from a club moss (Huperzia serrata), is a sesquiterpene alkaloid and a powerful and reversible inhibitor of acetylcholinesterase (AChE). It has been used in China for centuries for the treatment of swelling, fever and blood disorders. It has demonstrated both memory enhancement in animal and clinical trials and neuroprotective effects. Recently it has undergone double-blind, placebo-controlled clinical trials in patients with Alzheimer's disease (AD), with significant improvements both to cognitive function and the quality of life. Most of the clinical trials are from China, but HupA and derivatives are attracting considerable interest in the West, where AD is a major and growing concern. Furthermore, both animal and human safety evaluations have demonstrated that HupA is devoid of unexpected toxicity. Other interesting aspects of HupA pharmacological profile relate to its neuroprotective properties: it has been shown in animal studies that HupA can be used as a protective agent against organophosphate (OP) intoxication and that it reduces glutamate-induced cell death. D

Sesquiterpenic compounds are natural chemicals present in organisms from different Phylae or Divisions, which have proved to be important bioactive products, namely in potentiating the action of antibiotics. In the first step, the mutagenicity of nine sesquiterpenic compounds (hydrocarbons and alcohols) was screened in a Salmonella typhimurium his(-)-reversion test with strains TA98 and TA100, in the presence or absence of in vitro metabolic activation. Under the test conditions, none of the compounds showed mutagenicity up to a concentration of 222μg/plate. trans-Farnesol, nerolidol, and α-bisabolol displayed cytotoxicity when tested at concentrations ranging from 14 to 222μg/plate. Then, the combined effect of antibiotic-sesquiterpenic compounds was evaluated on two clinically relevant pathogens, Escherichia coli and Staphylococcus aureus, with well-defined resistance-sensitive profiles. The agar-disc diffusion assay revealed that all the combinations of antibiotic-sesquiterpenic compounds increased the antibacterial activity of the antibiotics tested against S. aureus. For E. coli, an antagonistic effect was observed for various combinations on the growth of this bacterium.

A small library of amino acid-linked 1,4disubstituted 1,2,3-bistriazole conjugates has been synthesized from the N-protected L-amino acids propargyl esters through one-pot click reaction. All the newly synthesized compounds were tested in vitro for antimicrobial activity against Gram-positive (Staphylococcus aureus, Bacillus subtilis), Gram-negative (Escherichia coli) bacteria and fungi (Candida albicans, Aspergillus niger). The antibacterial evaluation data indicated that compounds 3c, 3h, 5a, 5b, 5c, 5d, 5e, 5g, and 5h exhibited comparable activity to standard ciprofloxacin. However, the bistriazoles 3b, 3c, 3e, 3f, and 3g showed good antifungal activity than others against both fungi. Further, docking simulation of the two most active compounds 5c against S. aureus tyrosyl tRNA synthetase and 5h into E. coli topoisomerase II DNA Gyrase B, respectively, was also performed.

Tomato plants respond to herbivory by emitting volatile organic compounds (VOCs), which are released into the surrounding atmosphere. We analyzed the tomato herbivore-induced VOCs and tested the ability of tomato receiver plants to detect tomato donor volatiles by analyzing early responses, including plasma membrane potential (V m ) variations and cytosolic calcium ([Ca 2+ ] cyt ) fluxes. Receiver tomato plants responded within seconds to herbivore-induced VOCs with a strong V m depolarization, which was only partly recovered by fluxing receiver plants with clean air. Among emitted volatiles, we identified by GC-MS some green leaf volatiles (GLVs) such as (E)-2-hexenal, (Z)-3-hexenal, (Z)-3-hexenyl acetate, the monoterpene ␣-pinene, and the sesquiterpene ␤-caryophyllene. GLVs were found to exert the stronger V m depolarization, when compared to ␣-pinene and ␤-caryophyllene. Furthermore, V m depolarization was found to increase with increasing GLVs concentration. GLVs were also found to induce a strong [Ca 2+ ] cyt increase, particularly when (Z)-3-hexenyl acetate was tested both in solution and with a gas. On the other hand, ␣-pinene and ␤-caryophyllene, which also induced a significant V m depolarization with respect to controls, did not exert any significant effect on [Ca 2+ ] cyt homeostasis. Our results show for the first time that plant perception of volatile cues (especially GLVs) from the surrounding environment is mediated by early events, occurring within seconds and involving the alteration of the plasma membrane potential and the [Ca 2+ ] cyt flux.

This review summarizes all reports on sesquiterpene lactones and their immediate precursors from the Cichorieae (Lactuceae) tribe of the Asteraceae. A total of 360 compounds have been reported from this tribe. The reported substances belong to three classes of sesquiterpenoids: guaianolides (243 compounds), eudesmanolides (73 compounds), and germacranolides (44 compounds). Sources of these compounds encompass 139 taxa from 31 different genera. The distribution of these lactones within the tribe Cichorieae is discussed in a chemosystematic context. Moreover, some general ideas about the interpretation of chemosystematic data are discussed.

Investigation of extracts from the plant Athroisma proteiforme (Humbert) Mattf. (Asteraceae) for antimalarial activity led to the isolation of the five new sesquiterpene lactones 1−5 together with centaureidin (6). The structures of the new compounds were deduced from analyses of physical and spectroscopic data, and the absolute configuration of compound 1 was confirmed by an X-ray crystallographic study. Athrolides C (3) and D (4) both showed antiplasmodial activities with IC 50 values of 6.6 (3) and 7.2 μM (4) against the HB3 strain and 5.5 (3) and 4.2 μM (4) against the Dd2 strain of the malarial parasite Plasmodium falciparum. The isolates 1−6 also showed antiproliferative activity against A2780 human ovarian cancer cells, with IC 50 values ranging from 0.4 to 2.5 μM.

Flowers and leaves of Disynaphia multicrenulata from Argentina afforded a large number of known germacradienolides and heliangolides, a new germacradienolide, a known melampolide, a new parthenolide derivative, one known and seven new cronquistiolides, a new 4Zmelampolide, three known and five new eudesmanolides, a new elemadienolide, a known grazielolide, an isoguaiagrazielolide, two diepoxygermacran-8,12-olides, three common kauranoic acids, pinoresinol, jaceosidin and the sesquiterpene oplopanone. Structures were elucidated by high-field 1 H NMR spectrometry. The relationship to the known chemistry of other members of the Disynaphiinae is discussed. # : S 0 3 0 5 -1 9 7 8 ( 0 0 ) 0 0 0 9 2 -2