Sesquiterpene Lactones from Centaurea zuccariniana and Their Antimicrobial Activity

Twenty‐nine compounds were isolated from the aerial parts of the Greek plant C. zuccariniana DC. The structures of the isolated compounds were established by means of NMR‐ (¹H,¹H‐COSY, ¹H,¹³C‐HSQC, HMBC, NOESY, and ROESY) and mass‐spectral analyses. These compounds comprise 13 sesquiterpene lactones, 14 flavonoids, two lignans, and one simple lactone. Among the isolated sesquiterpene lactones, three are new, namely one heliangolide, (1E,4Z)‐15‐hydroxy‐8α‐O‐(4′‐acetoxy‐3′‐hydroxy‐2′‐methylidenebutanoyl)‐6βH,7αH‐germacra‐1,4,11(13)‐trien‐6,12‐olide; and two eudesmanolides, 8α‐(4′,5′‐diacetoxyangeloyl)sonchucarpolide and one unusual eudesmanolide with an oxygenated bridge linking C(1) and C(4), named zuccarinin. The main sesquiterpene lactones were malacitenolide, cnicin, and 4′‐O‐acetylcnicin. These results are in agreement with those obtained from the previously studied Greek Centaurea sp. belonging to the section Acrolophus (Cass .) DC.; this finding could be of chemotaxonomic significance for the genus Centaurea. The in vitro antimicrobial activities of the isolated new sesquiterpene lactones were against eight bacteria and eight fungal species. A 96‐well microbioassay procedure for fast and easy evaluation of antibacterial and antifungal activities was applied to compare these compounds with commercial antibiotic and fungicide standards, and with previously isolated analogous sesquiterpene lactones tested by the same bioassay. All of the compounds tested showed moderate antibacterial, but significant antifungal activities; the present results corroborate with previous data, indicating that these types of compounds exhibit low or moderate antibacterial, but potent antifungal activities. The unusual eudesmanolide zuccarinin proved to be the most potent among the present tested sesquiterpene lactones, as well as among all previously tested eudesmanolides isolated from Greek Centaurea sp.     

Further Amphoricarpolides from the Surface Extracts of Amphoricarpos Complex from Montenegro

Analysis of composition of sesquiterpene lactone fraction of leaf cuticular neutral lipids of Amphoricarpos complex from two different localities in north Montenegro, i.e., canyon of river Tara (A. autariatus ssp. autariatus) and mountain Zeletin (A. autariatus ssp. bertisceus) afforded sesquiterpene lactones with guaianolide skeletons (17 compounds), so called amphoricarpolides, typical for this genus. Nine of them, 9 – 17 , were new compounds, and their structures were elucidated by detailed analyses of IR, NMR, and MS data.     

Two New Sesquiterpene Derivatives from the Tunisian Endemic Ferula tunetana Pom.

A new sesquiterpene ester, tunetanin A ( 1 ), a new sesquiterpene coumarin, tunetacoumarin A ( 2 ), together with eight known compounds, i.e., coladin ( 3 ), coladonin ( 4 ), isosmarcandin ( 5 ), 13‐hydroxyfeselol ( 6 ), umbelliprenin ( 7 ) propiophenone ( 8 ), β‐sitosterol ( 9 ), and stigmasterol ( 10 ), were isolated from the roots of Ferula tunetana. Their structures were elucidated on the basis of extensive spectroscopic methods, including 1D‐ and 2D‐NMR experiments and MS analysis, as well as by comparison with published data. The cytotoxicity of compounds 1 – 7 towards two human colon cancer cell lines, HT‐29 and HCT 116, was evaluated. Compounds 3, 4 , and 6 showed weak cytotoxic activities.     

Sesquiterpenoids and Diterpenoids from Chloranthus anhuiensis

A phytochemical investigation of the roots of Chloranthus anhuiensis afforded three new sesquiterpene lactones, chloraniolide A ( 1 ), (3R)‐3‐hydroxyatractylenolide III ( 2 ), and 8β‐hydroxy‐1‐oxoeudesma‐3,7(11)‐dien‐12,8α‐olide ( 3 ), and two new diterpenoids, (12R,13E)‐15‐(acetoxy)‐12‐hydroxylabda‐8(20),13‐dien‐19‐oic acid ( 4 ) and (12S,13E)‐15‐(acetoxy)‐12‐dihydroxylabda‐8(20),13‐dien‐19‐oic acid ( 5 ), as well as 17 known sesquiterpenoid and diterpenoid compounds. Their structures were established on the basis of 1D‐ and 2D‐NMR, and other spectroscopic analyses.     

A new acorane sesquiterpenes of Lysionotus pauciflorus maxim. Form Guizhou province,China

A new acorane sesquiterpene (1), together with fourteen known compounds were isolated from the whole plant of Lysionotus pauciflorus Maxim. The chemical structures of the compounds were identified by physio-chemical properties and 1D-NMR, 2D-NMR, ESI-MS, IR and ECD spectra. Among them, six compounds (1, 4, 6, 7, 13, 15) were first found in the genus Lysionotus. The chemotaxonomic significance of the isolated compounds in the genus Lysionotus and family Gesneriaceae were discussed.     

Anti-Inflammatory Activities of Monoterpene and Sesquiterpene Glycosides from the Aqueous Extract of Artemisia annua L.

Artemisia annua L. is a Chinese medicinal herb, but the origin of its pharmacological properties, including its anti-inflammatory activity, remain unknown. In this study, five new monoterpene glycosides ( 1 – 5 ) and two new sesquiterpene glycosides ( 6 and 7 ) were isolated from the aqueous extract of the aerial parts of A. annua. The structures of these glycosides were determined using high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopy, electronic circular dichroism calculations, and chemical hydrolysis methods. The anti-inflammatory activities of the isolated compounds were evaluated by down-regulating interleukin-6 (IL-6) in lipopolysaccharide-stimulated RAW 264.7 macrophages. Notably, all the new compounds significantly inhibited the expression of IL-6 in a dose-dependent manner.     

New Guaiane-Type Sesquiterpene and Norsesquiterpene from Alisma plantago-aquatica and Their Xanthine Oxidase Inhibitory Activity

A new sesquiterpene ( 1 ) and a new norsesquiterpene ( 2 ) belonging guaiane-type skeleton together with six known compounds ( 3 – 8 ) were isolated from the rhizomes of Alisma plantago-aquatica. Their structures were determined by HR-ESI-MS, 1D and 2D NMR spectroscopic methods. Absolute configurations of new compounds were established by experimental and TD-DFT computational ECD spectra. Compounds 1 – 8 exhibited xanthine oxidase inhibitory activity with their IC₅₀ values in range of 9.4–66.7 μM. The sesquiterpenoids 1 – 5 displayed the inhibitory activity and hence they could be potential xanthine oxidase inhibitors from A. plantago-aquatica.     

Sesquiterpene Lactones with COX‐2 Inhibition Activity from Artemisia lavandulaefolia

Two new sesquiterpene lactones, artelavanolides A ( 1 ) and B ( 2 ), and four known sesquiterpene lactones ( 3 – 6 ) were isolated from the leaves of Artemisia lavandulaefolia. Their structures were elucidated based on the analysis of spectroscopic data (1D, 2D‐NMR and HR‐ESI‐MS). The absolute configuration of 1 was determined by the analysis of single‐crystal X‐ray diffraction data. Artelavanolide A ( 1 ) is a rare sesquiterpene lactone possessing an unusual skeleton with the linkage of Me(14)–C(1) that is probably formed through a rearrangement of the guaiane‐type sesquiterpenoids. Artelavanolide B ( 2 ) is a new highly unsaturated guaianolide. Compounds 1 – 6 were tested for activities on the inhibition of COX‐2 enzyme in vitro. All of compounds exhibited inhibitory activity against COX‐2 with IC₅₀ values ranging from 43.29 to 287.07 μm compared with the positive control, celecoxib (IC₅₀ = 18.10 μm ). Among them, 3 showed the best COX‐2 inhibitory activity with an IC₅₀ value of 43.29 μm .     

牛樟芝倍半萜合酶基因克隆及在不同培养基中的表达

牛樟芝(Antrodia camphorata)是一种珍稀食药用菌,能产生具有抗癌活性的倍半萜类化合物。对牛樟芝基因组进行分析,获得倍半萜合酶基因序列并设计特异引物,提取在Glu培养基(麦芽浸粉6 g/L,酵母提取物3 g/L,葡萄糖40 g/L)上生长的牛樟芝菌丝体的RNA,利用RT-PCR技术克隆得到倍半萜合酶基因AcTPS1。AcTPS1基因c DNA全长为969 bp,编码323个氨基酸,根据系统进化树可知AcTPS1氨基酸序列与其他9种真菌倍半萜合酶聚为一类。AcTPS1拥有典型倍半萜合酶的结构域(RRSRSATAEAYACFIW),之后检测AcTPS1在不同培养基上的菌丝中的表达结果显示不同碳源中,只有葡萄糖作为碳源时该基因表达,不同氮源中,以番茄浸粉和酪蛋白胨为氮源时该基因表达。说明AcTPS1是一类诱导型表达的基因。为利用发酵培养以及异源表达手段获得牛樟芝活性化合物提供参考。     

Systematic implications of sesquiterpene lactones in Lactuca species

A chemosystematic study of eleven species from the genus Lactuca (Asteraceae) was performed, based on the distributional data for eight sesquiterpene lactones as diagnostic characters. The lactones were identified in leaf and root extracts by comparison of their HPLC retention times and on-line UV spectra with those of reference compounds. Our results support the status of the section Lactuca, subsection Lactuca as a recognizable group within the genus, although Lactuca aculeata is a distinct species. Moreover, sesquiterpene lactone patterns of Lactuca perennis, Lactuca tatarica, Lactuca indica and Lactuca capensis are also given. It is worth noting that the sesquiterpene lactones are absent from Lactuca tenerrima. The chemosystematic impact of lactucin-type guaianolides and the germacranolide lactuside A is discussed briefly.     

Analysis of sesquiterpene lactones in Eupatorium lindleyanum by HPLC‐PDA‐ESI‐MS/MS

Introduction – The aerial part Eupatorium lindleyanum is commonly used as an antipyretic and detoxicant clinically in traditional Chinese medicine. Our previous research showed that germacrane sesquiterpene lactones were its main active constituents, so the development of rapid and accurate methods for the identification of the sesquiterpene lactones is of great significance. Objective – To develop an HPLC‐PDA‐ESI‐MS/MS method capable for simple and rapid analysis of germacrane sesquiterpene lactones in the aerial part E. lindleyanum. Methodology – High‐performance liquid chromatography‐photodiode array detection‐electrospray ionization‐tandem mass spectrometry was used to analyze germacrane sesquiterpene lactones of Eupatorium lindleyanum. The fragmentation behavior of germacrane sesquiterpene lactones in a Micromass Q/TOF Mass Spectrometer was discussed, and 9 germacrane sesquiterpene lactones were identified by comparison of their characteristic data of HPLC and MS analyses with those obtained from reference compounds. Results – The investigated germacrane sesquiterpene lactones were identified as eupalinolides C (1), 3β‐acetoxy‐8β‐(4′‐hydroxy‐tigloyloxy)‐14‐hydroxy‐costunolide (2), eupalinolides A (3), eupalinolides B (4), eupalinolides E (5), 3β‐acetoxy‐8β‐(4′‐oxo‐tigloyloxy)‐14‐hydroxy‐heliangolide (6), 3β‐acetoxy‐8β‐(4′‐oxo‐ tigloyloxy)‐14‐hydroxy‐costunolide (7), hiyodorilactone B (8), and 3β‐acetoxy‐8β‐(4′‐hydroxy‐tigloyloxy)‐ costunolide (9). Compounds 6, 7 and 9 were reported for the first time. Conclusion – HPLC‐PDA‐ESI‐MS/MS provides a new powerful approach to identify germacrane sesquiterpene lactones in E. lindleyanum rapidly and accurately. Copyright © 2009 John Wiley & Sons, Ltd.     

Five new germacrane sesquiterpenes with anti-inflammatory activity from Salvia petrophila

Five new germacrane sesquiterpene lactones, petrophins A–E (1–5), were isolated from the whole herbs of Salvia petrophila. The structures were established using spectroscopic analysis (1D and 2D NMR, HR-ESI-MS) and compatible with values in the literature. These sesquiterpenes are unusual with an endocyclic double bond in the γ-lactone ring. All the isolated compounds were evaluated for their inhibitory effects on the LPS-induced nitric oxide production using murine macro-phage RAW264.7 cells.     

Structures of Novel Sesquiterpene Ketones from Chloranthus serratus (Chloranthaceae)

Two naturally occurring new sesquiterpene ketones, neoacolamone (1) and 7α-hydroxyneoacolamone (2), were isolated from the roots of Chloranthus serratus (Thunb.) Roem. et Schult. (Japanese name: Futari-shizuka, Chloranthaceae). The structures were elucidated on the basis of their physicochemical properties and chemical reactions. Three sesquiterpene ketones, acoragermacrone (3), acolamone (4) and zederone (5), and four additional sesquiterpenes including lindenanolides were also found in the same source. The relationships of these isolates to the constituents of C. japonicus and to the sesquiterpene biogenesis in the Chloranthus species are discussed.     

Sesquiterpene Glucosides from Chloranthus japonicus Sieb

A new lindenane sesquiterpene glucoside named yinxiancaoside A (1), a new, rare bidesmosidic megastigmane sesquiterpene glucoside named yinxiancaoside B (5), and three known sesquiterpene glucosides, chloranoside A (2), pisumionoside (3), and sarcaglaboside A (4), were isolated from the whole plant of Chloranthus japonicus Sieb. The structures of the new compounds were established by an extensive study of their spectral data, especially 1D- and 2D-NMR. The cytotoxic activity of the isolated compounds against human hepatoma (Hepg-2), human ovarian carcinoma (OV420), and human breast cancer (MCF-7) cells was investigated.     

Koanolides B-D,new sesquiterpene lactones from Koanophyllon gibbosum

Three new germacrane-type sesquiterpene lactones, koanolides B–D (1-3) have been isolated from the aerial parts of Koanophyllon gibbosum (Asteraceae), along with the previously reported sesquiterpene lactone koanolide A and the flavonoid eupatorin. The structures of the new compounds were elucidated using spectroscopic and spectrometric data analyses, including 1D and 2D NMR, and by comparison with known spectral data. The antiproliferative activities of the new compounds were evaluated in a panel of six representative human solid tumor cell lines and showed GI₅₀ values ranging from 1.3 to 16 μM for the new molecules.     

Five mikanolide derivatives from mikania cynanchifolia and their biogenetic relationships

The investigation of the aerial parts of Mikania cynanchifolia afforded, in addition to miscandenin, five new sesquiterpene lactones, miscandenin-1,2-epoxide, an isomiscandenin and three further dilactones related to mikanolide. The structures of these new compounds were elucidated by high field ¹H NMR spectroscopy. The biogenetic relationships of the sesquiterpene lactones are briefly discussed.     

The chemical constituents of Piper kadsura and their cytotoxic and anti-neuroinflammtaory activities

The n-hexane and CHCl₃ soluble fractions of the MeOH extract of the aerial parts of Piper kadsura were found to potently inhibit nitric oxide (NO) production in LPS-activated BV-2 cells, a microglial cell line. From the active fractions, a new stereoisomer of guaiane sesquiterpene, 1α,5β-guai-4(15)-ene-6β,10β-diol, kadsuguain A (1) and a new cyclohexadienone, kadsuketanone A (2), together with twelve known compounds (3–14) were isolated. The structures of these compounds were elucidated by extensive NMR spectral studies. The absolute configuration of 2 was determined by circular dichroism (CD) spectra. Compounds 2, 6, and 11–14 significantly inhibited both nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in the LPS-activated microglia cells. In addition, compounds 4, 6, and 11–14 exhibited cytotoxicity against the A549, SK-OV-3, SK-MEL-2, and HCT15 human tumour cells.     

Nitric Oxide Production Inhibitory Eudesmane‐Type Sesquiterpenoids from Artemisia argyi

Six new eudesmane‐type sesquiterpene derivatives, artemargyinins A–F were isolated from the leaves of Artemisia argyi. Their structures were elucidated based on the extensive analysis of spectroscopic data. Artemargyinins A–F feature a lactone ring‐opening eudesmane‐type sesquiterpene with an isoprenoid group at C(8). All compounds were tested for their inhibitory effects on lipopolysaccharide‐induced nitric oxide (NO) production in RAW264.7 macrophages. Artemargyinins A–F showed more potent NO production inhibitory activity with IC₅₀ values ranging from 7.66±0.53 to 61.19±2.54 μM than the positive control quercetin (IC₅₀=74.34±1.39 μM). Among them, artemargyinins C and D exhibited strong inhibitory activity with IC₅₀ values of 8.08±0.21 and 7.66±0.53 μM, respectively.     

Harzianoic acids A and B,new natural scaffolds with inhibitory effects against hepatitis C virus

Two new sesquiterpene-based analogues, namely harzianoic acids A (1) and B (2), were isolated from a sponge-associated fungus Trichoderma harzianum. Their structures were determined on the basis of the extensive spectroscopic analyses in association with the ECD data for the configurational assignment. Harzianoic acids A and B were structurally characterized as a sesquiterpene and a norsesquiterpene with a cyclobutane nucleus, which is uncommonly found from nature. Both compounds exhibited the inhibitory activity to reduce the HCV RNA levels with low cytotoxicity. The preliminary investigation of the mode of action revealed that the compounds blocked the entry step in the HCV life cycle, while the viral E1/E2 and the host cell CD81 were the potential target proteins.     

Cadinenes and other metabolites from Verbesina sphaerocephala A. Gray

The phytochemical study of the aerial parts of Verbesina sphaerocephala A. Gray afforded six sesquiterpene lactones of cadinene type, five of them described for the first time, along with known phenyl propanoids, terpenoids, and phenolic compounds. Structures on new compounds were elucidated by spectroscopic techniques including CD and X-ray analyses, and known compounds were identified by comparing their spectral data with those previously reported. Cadinene-like sesquiterpene lactones could be characteristic metabolites of V. sphaerocephala.