Cytotoxic and NF-κB inhibitory sesquiterpene lactones from Piptocoma rufescens

Six new (1-6) and eight known germacranolide-type sesquiterpene lactones, along with several known phenylpropanol coumarates and methylated flavonoids, were isolated from the leaves of Piptocoma rufescens, collected in the Dominican Republic. The new compounds were identified by analysis of their spectroscopic data, with the molecular structure of 3 being established by single-crystal X-ray diffraction. The absolute configurations of the sesquiterpene lactones isolated were determined from their CD and NOESY NMR spectra, together with the analysis of Mosher ester reactions. Bioassay screening results showed the majority of the sesquiterpene lactones isolated (1-13) to be highly cytotoxic toward the HT-29 human colon cancer cell line, with the most potent compound being 15-deoxygoyazensolide (10, IC(50), 0.26 μM). In addition, several of the sesquiterpene lactones exhibited NF-κB (p65) inhibitory activity.     

Complete NMR spectral assignments of two lactucin-type sesquiterpene lactone glycosides from Picris conyzoides

Complete (1)H and (13)C NMR signal assignments of two lactucin-type sesquiterpene lactone glycosides, derivatives of 11β,13-dihydrolactucin, isolated from roots of Picris conyzoides, were achieved by one- and two-dimensional NMR experiments, allowing the correction of previously published data for cichorioside B and the structure elucidation of its new ester with 3-hydroxy-2-methylpropanoic acid. In addition, seven known sesquiterpene lactones and three phenolic compounds were isolated from the plant material.     

Three new eudesmane sesquiterpenes from Artemisia vestita

Three eudesmane sesquiterpene lactones,namely artemivestinolides A–C(1–3),along with three known 11-epimeric lactones(4–6),were isolated from the aerial parts of Artemisia vestita.Their structures were elucidated on the basis of extensive spectroscopic analyses(IR,HR-ESIMS,1D NMR and 2D NMR),and the absolute confgurations were determined by single-crystal X-ray diffraction(with copper radiation).Furthermore,in an in vitro assay,the three new compounds exhibited a moderate inhibition of the lipopolysaccharide(LPS)-induced nitric oxide(NO)production in BV-2 microglial cells.     

New sesquiterpene lactones from the aerial parts of Pseudoelephantopus spicatus

Two new sesquiterpene lactones, spicatolide C (1) and spicatocadinanolide A (2), have been isolated along with the known piptocarphol isomers (3, 4) and one eudismane type sesquiterpene (5) from the EtOAc extract of the aerial parts of Pseudoelephantopus spicatus. The structures and the relative stereochemistries of the new metabolites were determined by spectroscopic methods.     

Ligustolide A and B, two novel sesquiterpenes with rare skeletons and three 1,10-seco-guaianolide derivatives from Achillea ligustica

Achillea ligustica afforded two novel sesquiterpene lactones with rare 5/6/5 skeletons, three 1,10-seco-guaianolides and a chlorine-containing sesquiterpene lactone as well as six known compounds, including two monoterpenes, two guaianolides, one eudesmane and one secocaryophyllene derivative. The structures of the compounds were elucidated by extensive application of one- and two-dimensional NMR spectroscopy.     

The first guaian-12-oic acid glucopyranosyl ester and other constituents from Picris rhagadioloides (L.) Desf. (Asteraceae)

The first guaian-12-oic acid glucopyranosyl ester was isolated from the roots of Picris rhagadioloides (L.) Desf. (Asteraceae), in addition to five costuslactone-type guaianolides, four germacranolides and three phenolic compounds. This is the first time that the known phenolics syringaldehyde and syringaresinol, as well as the known sesquiterpene lactones glucozaluzanin C, cichorioside C and hypochoeroside A have been described from a Picris species. The compounds were characterized on the basis of physicochemical, 1D- and 2D-NMR spectroscopic, and mass spectrometric data.     

The isolation and structure elucidation of a new sesquiterpene lactone from the poisonous plant Coriaria japonica (Coriariaceae)

A new sesquiterpene lactone named coriarin was isolated from achenes (seeds) of Coriaria japonica (Coriariaceae) along with known constituents tutin, dihydrotutin and corianin, and its structure was deduced on a spectroscopic basis. The structure of coriarin was finally confirmed by the base-catalized chemical conversion of tutin into coriarin, in which the lactone ring linkage was transposed from C-3 to C-2. Chemical investigation of sarcocarps was also undertaken in parallel, but neither sesquiterpene lactones nor related constituents were obtained. The results indicate that sesquiterpene lactones occur only in achenes of C. japonica berry, as is the case in other Coriaria species.     

Sesquiterpene Lactones from Daucus glaber

Six new sesquiterpene lactone esters, daucoguaianolactones A–F ( 1 – 6 ), and one new sesquiterpene lactone, daucoeudesmanolactone A ( 7 ) were isolated from the leaves and stems of Daucus glaber (Forssk .) Thell ., along with the known sesquiterpene lactones talasins A and B and badkhysin. The structures of 1 – 6 were established on the basis of extensive 1D‐ and 2D‐NMR spectroscopic studies and that of 7 by X‐ray crystallography. Compounds 4, 7 , and talasins A and B showed moderate cytotoxicity against P‐388 leukemia cells.     

Chemical Constituents from Notoseris Species

The genus Notoseris (Asteraceae) comprising of 14 species is endemic in China^[1]. Two new sesquiterpene lactones,notoserolides A and B,along with 12 known compounds were isolated from the aerial parts of N. Porphyrolepis^[2], but nothing is known about secondary metabolites of other N species.     

Chemical Constituents from the Roots of Neolitsea hiiranensis

One triterpenoid, taraxerone ( 1 ); four germacrane-type sesquiterpene lactones, linderane ( 2 ), linderalactone ( 6 ), pseudoneolinderane ( 7 ), (+)-linderadine ( 8 ); one sesquiterpene dilactone, pseudoneoliacine ( 10 ); three elemane-type sesquiterpenes, isolinderalactone ( 3 ), compound 4 and sericealactone ( 9 ); one eudesmane type sesquiterpene, cryptomeridol ( 11 ); one glucoside, β-sitosterol-β-D-glucoside ( 12 ) along with β-sitosterol (5) were isolated from the roots of Neolitsea hiiranensis. The structures of these compounds were identified on the basis of spectral properties.     

Simultaneous quantitative determination of 11 sesquiterpene lactones in Jerusalem artichoke (Helianthus tuberosus L.) leaves by ultra high performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry

A method of ultra high performance liquid chromatography coupled to quadrupole time‐of‐flight mass spectrometry was developed for the simultaneous quantification of 11 sesquiterpene lactones in 11 Jerusalem artichoke leaf samples harvested in a number of areas at different periods. The optimal chromatographic conditions were achieved on a ZORBAX Eclipse Plus C₁₈ column (3.0 × 150 mm, 1.8 μm) with linear gradient elution of methanol and water in 8 min. Quantitative analysis was carried out under selective ion monitoring mode. All of the sesquiterpene lactones showed good linearity (R ² ≥ 0.9949), repeatability (relative standard deviations < 4.66%), and intra‐ and interday precisions (relative standard deviations < 4.52%) with an accuracy of 95.24–104.84%. The recoveries measured at three concentration levels varied from 95.07 to 104.87% with relative standard deviations less than 4.9%. The limit of detection and limit of quantitation for this method were 0.89–5.05 and 1.12–44.33 ng/mL, respectively. The results showed that the contents of sesquiterpene lactones varied significantly in the Jerusalem artichoke leaf samples from different areas. Among them, the content of sesquiterpene lactones in the sample collected from Dalian, Liaoning province was the highest and the early flowering period was considered to be the optimal harvest time.     

Sesquiterpene Lactones from Notoseris Porphyrolepis

Two new sesquiterpene lactones, notoserolides A and B, along with 12 known compounds were isolated from the aerial parts of Notoseris porphyrolepis.By means of spectral methods including MS, NMR (1H NMR, 13C NMR, DEPT, HMQC, HMBC) and X-ray diffraction, as well as chemical reactions, the structures of notoserolides A and B were established as austricin 8-O-β-D-glucopyranoside and 8-O-senecioylaustricin, respectively.     

Isolation of three sesquiterpene lactones from the roots of Cichorium glandulosum Boiss. et Huet. by high-speed counter-current chromatography

Because of the skeletal complexity and similarity of the polarity, little research was reported on the isolation of sesquiterpene lactones by high-speed counter-current chromatography (HSCCC). Herein, three sesquiterpene lactones were successfully purified from the ethyl acetate extract of the roots of the traditional Uyghur medicinal plant Cichorium glandulosum Boiss. et Huet. by HSCCC. The separation was performed in two steps with two solvent systems: n-hexane-ethyl acetate-methanol-water (1.5:5:2.75:5, v/v/v/v) and ethyl acetate-methanol-water (20:1:20, v/v/v). From 166 mg of the ethyl acetate extract, 19 mg of lactucopicrin was isolated with the first solvent system and 10 mg of 11beta,13-dihydrolactucin and 16 mg of lactucin were obtained with the second solvent system. All purified compounds were over 94% purity as determined by HPLC analysis, and these chemical structures were confirmed by (1)H NMR and (13)C NMR.     

Cytotoxic germacrane-type sesquiterpene lactones from the whole plant of Inula cappa

Phytochemical investigation on the whole plant of Inula cappa led to the isolation of two new germacrane-type sesquiterpene lactones,ineupatolides D and E(1 and 2),together with three known analogs.The structures of the new compounds were established by extensive analysis of 1Dand 2DNMR spectra,as well as MS data.Their absolute configurations were determined by CD spectra.All compounds showed moderate inhibitory effects on A431,A549,BGC-823,HL-60,HT-29,and MCF-7 cancer cell lines with IC_(50) values ranging from 2.1 to 36.3 μM.     

Further cytotoxic sesquiterpene lactones from Elephantopus mollis KUNTH

Three new sesquiterpene lactones, (4betaH)-5alpha-hydroxy-8alpha-(2-methylbut-2-enoyloxy)-2-oxo-1(10),11(13)-guaiadien-12,6alpha-olide (1), (4betaH)-8alpha-(2-methylbut-2-enoyloxy)-2-oxo-1(5),10(14),11(13)-guaiatrien-12,6alpha-olide (2) and 2,5-epoxy-2beta-hydroxy-4alpha-methoxy-8alpha-(2-methylbut-2-enoyloxy)-4(15),10(14),11(13)-germacratrien-12,6alpha-olide (3), have been isolated from roots and stems of Elephantopus mollis together with two known sesquiterpene lactones (4, 5). The identification of the isolates was accomplished by spectroscopic methods. Compounds (1-5) exhibited significant cytotoxic activities against mouse neuroblastoma B104 cells.     

Terpenoids and bibenzyls from three Argentine liverworts

A new rosane diterpenoid, 3a-hydroxy-5,15-rosadien-11-one (3), was isolated, together with a known rosane diterpenoid, 5,15-rosadiene-3,11-dione (4), and an aromadendrane sesquiterpenoid, ent-cyclocolorenone (5), from the Et(2)O extract of an unidentified Argentine liverwort Anastrophyllum species. Moreover, four known sesquiterpene lactones 6-9 and two known bibenzyls 10, 11 were isolated from the Et(2)O extracts of Argentine Frullania brasiliensis and Radula voluta, respectively. The structures of compounds 3-11 were determined by the use of NMR techniques.     

Effects of plant lactones on the production of biofilm of Pseudomonas aeruginosa

Sixteen plant sesquiterpene lactones, thirteen from four species of the Family Asteraceae, and three from a species of Hepaticae, as well as seven annonaceous acetogenins isolated from the seeds of the tropical tree Annona cherimolia (Family Annonaceae), were evaluated for their ability to inhibit or stimulate the production of biofilm by a strain of Pseudomonas aeruginosa. The tested compounds carry a gamma-lactone moiety in their structures. This structural feature is similar to the lactone moiety present in N-acyl homoserine lactones, compounds that play the important role of "quorum sensors" in the mechanisms of biofilm formation observed in many gram-negative bacteria. A special assay was employed to evaluate the influence of the tested plant compounds to inhibit or stimulate the production of biofilm in a P. aeruginosa wild strain. Most of the tested compounds affected the biofilm formation mechanism. Six sesquiterpene lactones isolated from Acanthospermum hispidum and one from Enydra anagallis as well as an acetogenin from Annona cherimolia strongly inhibited (69-77%) the biofilm formation when incorporated to a bacterial culture at a concentration of 2.5 microg/ml. However, one of the acetogenins, squamocin, stimulated the biofilm formation even at a concentration of 0.25 microg/ml. The study of substances affecting the biofilm formation can lead to the design of new strategies to control P. aeruginosa infections.     

Wedelolides A and B: novel sesquiterpene delta-lactones, (9R)-eudesman-9,12-olides, from Wedelia trilobata

Two new sesquiterpene lactones, wedelolides A (1) and B (2), were isolated by bioassay-guided fractionation from the leaves of Wedelia trilobata, together with known trilobolides 6-O-isobutyrate (3) and 6-O-methacrylate (4). The compounds 1 and 2 were the first examples of an unprecedented framework: a novel sesquiterpene delta-lactone, (9R)-eudesman-9,12-olide. The structures of the antimalarial wedelolides A (1) and B (2) were determined on the basis of MS and 2D NMR spectral analysis. The absolute configuration of eight carbon stereocenters of compounds 1 and 2 was determined to be 1S,4S,5S,6R,7S,8S,9R,10S by mean of auxiliary chiral MTPA derivatives.     

Anti-Inflammatory and Immunoregulatory Action of Sesquiterpene Lactones

Sesquiterpene lactones (SL), characterized by their high prevalence in the Asteraceae family, are one of the major groups of secondary metabolites found in plants. Researchers from distinct research fields, including pharmacology, medicine, and agriculture, are interested in their biological potential. With new SL discovered in the last years, new biological activities have been tested, different action mechanisms (synergistic and/or antagonistic effects), as well as molecular structure–activity relationships described. The review identifies the main sesquiterpene lactones with interconnections between immune responses and anti-inflammatory actions, within different cellular models as well in in vivo studies. Bioaccessibility and bioavailability, as well as molecular structure–activity relationships are addressed. Additionally, plant metabolic engineering, and the impact of sesquiterpene lactone extraction methodologies are presented, with the perspective of biological activity enhancement. Sesquiterpene lactones derivatives are also addressed. This review summarizes the current knowledge regarding the therapeutic potential of sesquiterpene lactones within immune and inflammatory activities, highlighting trends and opportunities for their pharmaceutical/clinical use.     

Antibacterial and cytotoxic activities of the sesquiterpene lactones cnicin and onopordopicrin

The antimicrobial and cytotoxic activities of chloroform extracts from the weeds Centaurea tweediei and C. diffusa, and the main sesquiterpene lactones isolated from these species, onopordopicrin and cnicin, respectively, were assayed. Results show that the chloroform extracts from both Centaurea species possess antibacterial activities against a panel of Gram-positive and Gram-negative bacteria. Remarkable antibacterial activity against methicillin-resistant Staphylococcus aureus was also measured. Both the extracts and the purified sesquiterpene lactones show high cytotoxicity against human-derived macrophages. Despite this cytotoxicity, C. diffusa chloroform extract and cnicin are attractive candidates for evaluation as antibiotics in topical preparations against skin-associated pathogens.