Sesquiterpene lactone dimers from the fruit of Carpesium abrotanoides L.

Seven undescribed sesquiterpene lactone dimers (SLDs) (carpeabrodilactones A-G), one known SLD, and six known sesquiterpenes were isolated from the fruit of Carpesium abrotanoides L. Carpeabrodilactone A was a dimeric carabrane featuring a rare C-13-C-13' linkage. Carpeabrodilactones B and C are the first two SLDs to be described possessing a carabranolide unit and a guaianolide unit connected by an O-ether linkage. The structures of the SLDs were assigned based on HRESIMS, NMR analysis, 13C NMR calculation, ECD calculation, and modified Mosher's method. Four SLDs showed potent cytotoxicity against K562 and/or A549 cells, with IC50 values below 10 µM, but none inhibited protein tyrosine phosphatases at 40 µM, including PTP1B, SHP1, CD45, and TCPTP.

Aspergichromones A-E, Five Chromone Derivatives with Complicated Polycyclic Architecture from Aspergillus deflectus.

Five unprecedented chromone derivatives involving a 6/6/5/5/5/6 hexacyclic scaffold (1, 2), 6/6/5/6/6/6/6 heptacyclic scaffold (3), and 6/6/6/5/5/6 hexacyclic scaffold (4, 5) were obtained from the fungus Aspergillus deflectus NCC0415. Their structures were identified using comprehensive spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Except for 3, the other compounds, especially the 6/6/6/5/5/6 hexacyclic derivatives (4 and 5), exhibited potent inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitory activities.

Naphthacemycins from a Streptomyces sp. as Protein-Tyrosine Phosphatase Inhibitors.

Nine new naphthacemycins (1-9), along with one known naphthacemycin (10) were isolated from the culture of Streptomyces sp. N12W1565. Their structures were elucidated on the basis of spectroscopic analysis, including UV, NMR, and HRESIMS. All the compounds showed significant activity, with IC50 values less than 10 µM against protein-tyrosine phosphatase 1B (PTP1B). The anti-PTP1B structure-activity relationship of naphthacemycins (1-10) is discussed. These findings provide a promising starting point for the development of naphthacemycins as potential anti-PTP1B agents.

Azaphilones with protein tyrosine phosphatase inhibitory activity isolated from the fungus Aspergillus deflectus.

Six undescribed azaphilones, deflectins C1-C3, deflectins D1-D2, and deflectin E, along with five known azaphilones were obtained from a solid culture of the wild fungus Aspergillus deflectus NCC0415. Their structures were determined by HRESIMS, NMR and ECD analyses, together with the GIAO 13C NMR calculation method. All compounds displayed strong or moderate inhibitory activity against protein tyrosine phosphatases SHP2 and PTP1B. Structure-activity relationship analysis of these azaphilones suggested that the length of the ketone aliphatic side chain would affect their SHP2 and PTP1B inhibitory activity. In addition, the presence of a Δ8(12) double bond on γ-lactone ring and the presence of CH3-2' in fatty chains may increase their inhibitory activity.

Comparison of triterpene compounds of four botanical parts from Poria cocos (Schw.) wolf using simultaneous qualitative and quantitative method and metabolomics approach.

Poria cocos (Schw.) Wolf (PCW) is a widely used traditional Chinese medicine and dietary supplement. Its four parts including Poriae Cutis (PC), Rubra Poria (RP), White Poria (WP) and Poria cum Radix Pini (PRP) have different pharmacological effects and clinical applications. It is necessary to establish analytical platforms for differentiating the chemical composition of four botanical parts for the rational utilization. We established a simultaneous qualitative and quantitative method based on UHPLC-MS combined metabolomics approach to give an explanation of the distribution of triterpene compounds in four parts. Eight triterpene compounds were determined absolutely and a total of 51 triterpene compounds were tentatively identified in PCW. PC and PRP showed a quite clear discrimination by the principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) and twelve differential compounds were found. Four compounds including poricoic acid D, 16α-hydroxydehydrotrametenolic acid, 3-epidehydrotumulosic acid, 25-hydroxypolyporenic acid C were speculated to be related to diuretic effects.

A chemometric-assisted LC-MS/MS method for the simultaneous determination of 17 limonoids from different parts of Xylocarpus granatum fruit.

The marine mangrove Xylocarpus granatum is used as a folk medicine and is rich in bioactive limonoids. The quantitative determination of the chemical composition and distribution of limonoids in different parts of X. granatum fruit (fruit peel, seed coat, seed kernels, seed, and fruit) is significant for authentication and quality control purposes. However, the quantitative determination of limonoids in X. granatum has not yet been reported. In this study, a chemometric-assisted liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of 17 limonoids to reveal the chemical composition and distribution in different parts of X. granatum fruit. Ultrasonic-assisted extraction, optimized by response surface methodology (RSM), was more accurate than the general one-variable-at-a-time method. The overall distribution of 17 limonoids in different parts of X. granatum fruit had the following order: seed kernels > seed > fruit, and 13 limonoids showed a rank order of seed kernels > seed > fruit > fruit peel > seed coat. Furthermore, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to analyze the LC-MS/MS data and provide a chemometric model for easy visualization and interpretation to classify the different parts of X. granatum fruit. In addition, the study indicated that the chemometric-assisted strategy, consisting of RSM, PCA, and OPLS-DA for the development, optimization, and data analysis of multicomponent quantitation by LC-MS/MS, is effective and feasible. This study provided the chemical composition and distribution evidence for the authentication and quality control of X. granatum fruit.

Study on the metabolites of isoalantolactone in vivo and in vitro by ultra performance liquid chromatography combined with Triple TOF mass spectrometry.

Isoalantolactone (IAL) is an active sesquiterpene naturally present in many vegetables, condiments and medicinal plants. In this study, an efficient strategy was developed for the identification of metabolites following the in vivo metabolism and in vitro biotransformation of IAL with rat intestinal bacteria utilizing ultra performance liquid chromatography combined with Triple TOF mass spectrometry (UPLC-Triple TOF-MS/MS). As a result, 46 metabolites including 34 novel sulfur-containing products were identified. The results demonstrated that IAL could undergo general metabolic reactions, including oxidation, hydration, hydrogenation, demethylation, cysteine conjugation and N-acetylcysteine conjugation, but the most noticeable characteristic of IAL metabolism was the H2S addition to the double bond between C-11 and C-13 and subsequent reactions to produce a series of novel sulfur-containing dimers. This is the first study of IAL metabolism in vivo, whose results provide novel and useful data for a better understanding of the safety and efficacy of IAL.

Identification of in vitro and in vivo metabolites of alantolactone by UPLC-TOF-MS/MS.

Alantolactone (AL), an active sesquiterpene originating from Inula helenium, is a potential anticancer and anti-inflammatory agent. However so far, studies on AL metabolism have not been reported. In the present study, we have investigated for the first time the in vivo and in vitro metabolites of AL using ultra performance liquid chromatography combined with time of flight mass spectrometry (UPLC-TOF-MS/MS). A unique on-line information-dependent acquisition (IDA) method multiple mass defect filter (MMDF) combined with dynamic background subtraction (DBS) was applied to trace all of the probable metabolites of AL. Five MMDF templates were set according to the core structure of AL and the general metabolite biotransformation patterns, and other five sulfur-containing dimer filter templates were first established on the basis of structural elucidation of AL metabolites obtained from rat intestinal bacteria biotransformation. As a result, 44 metabolites were characterized: 41 metabolites from rat urine, bile and feces after oral administration of AL, and 13 metabolites from AL biotransformation by rat intestinal bacteria. Particularly, 26 metabolites were identified as novel sulfur-containing products. The results indicated that addition of double bond at Δ((11,13)) and oxidization were the main metabolic reactions of AL. A new metabolism pathway to produce addition products of H2S to AL and further generate a series of sulfur-containing dimers of AL was revealed. This study significantly enriched our knowledge about AL metabolism, which will lead to a better understanding of the safety and efficacy of AL. At the same time, the established methodology can be widely applied for the structural determination of the metabolites of other sesquiterpene containing α-methylene-γ-lactone moiety.

Polyhydroxytriterpenoids and Phenolic Constituents from Forsythia suspensa (Thunb.) Vahl Leaves.

Forsythia suspensa (Thunb.) Vahl leaves have been consumed in China as a health-promoting functional tea for centuries. Three new polyhydroxytriterpenoid glycosides named suspensanosides A-C (1-3), seven known polyhydroxytriterpenoids (4-10), and 12 known phenolics (11-22) were identified from F. suspensa leaves. Compounds 1-10, 15-17, and 22 have not been found in the Forsythia genus previously, whereas compound 14 was first reported to be isolated from the leaves of F. suspensa. All isolates were tested for their antiproliferative activities on BGC-823 and MCF-7 human tumor cell lines, whereas all phenolics were further investigated for their antioxidant activities by a DPPH assay. The results clearly demonstrate that triterpenoids, especially ursane-type triterpenoids, and the diverse phenolic components are crucial for the beneficial effects of F. suspensa leaves.

Xylomexicanins C and D, new mexicanolide-type limonoids from Xylocarpus granatum.

Two new limonoids, named xylomexicanins C and D, were isolated from a dichloromethane extract of the seeds of Xylocarpus granatum cultivated in Hainan, China, and their structures were elucidated on the basis of one- and two-dimensional NMR (including 1H, 13C-NMR, DEPT, 1H-1H COSY, HSQC, HMBC, and NOESY) and confirmed by high-resolution mass spectrometry. Xylomexicanin C exhibited antiproliferative activity against human breast carcinoma cells (KT).

[Non-taxoid chemical constituents from needles of Taxus cuspidata].

OBJECTIVE: To study the chemical constituents in the needles of Taxus cuspidata collected from Japan. METHODS: Chemical constituents were isolated by column chromatography, TLC and preparative HPLC. The structures were identified on the basis of NMR spectral analysis. RESULTS: Six non-taxoids were isolated and identified as: 4-[(1E)-3-hydroxy-1-buten-1-yl]-3,5,5-trimethyl-2-cyclohexen-1-one (1), megastigm-5-ene-3, 9-diol (2), 6alpha-epoxy-7-megastigmen-9-one (3), 4-(4-hydroxyphenyl)-2-butanone (4), 12-hydroxy-alpha-cyperone (5), scutellarein-7-O-alpha-L-rhamnoside (6). CONCLUSION: Compounds 2 - 6 are isolated from Taxus genus for the first time. Compound 1 is obtained from Taxus cuspidata for the first time.

PPARγ agonist from Chromolaena odorata.

A phytochemical investigation of Chromolaena odorata resulted in the isolation of five new compounds, 5aα,6,9,9aß,10-pentahydro-10ß-hydroxy-7-methylanthra[1,2-d][1,3]dioxol-5-one (1), 1,2-methylenedioxy-6-methylanthraquinone (2), 3-hydroxy-1,2,4-trimethoxy-6-methylanthraquinone (3), 3-hydroxy-1,2-dimethoxy-6-methylanthraquinone (4), and 7-methoxy-7-epi-medioresinol (5), together with 12 known compounds, odoratin (6), 3ß-acetyloleanolic acid (7), ursolic acid (8), ombuin (9), 4,2'-dihydroxy-4',5',6'-trimethoxychalcone (10), (-)-pinoresinol (11), austrocortinin (12), tianshic acid (13), cleomiscosin D (14), (-)-medioresinol (15), (-)-syringaresinol (16), and cleomiscosin A (17). All the compounds were evaluated for their PPARγ transactivation activity, and compound 6 showed moderate activity with an EC(50) value of 3.10 µM.

Antitumour activities of sesquiterpene lactones from Inula helenium and Inula japonica.

Eight sesquiterpene lactones were isolated from the roots of Inula helenium and flowers of I. japonica. Among them, isoalantolactone (3) and santamarine (6) exhibited significant growth inhibitory activities against gynecologic cancer cell lines, while others weakly inhibited the growth of the cell lines (IC50 < or = 100 microM). In addition, 3 significantly inhibited the tumour growth of S180 tumour-bearing mice. Compounds 3 and 6 were not toxic to human embryonic lung fibroblast cells in vitro. These results demonstrated that the antitumour activities are closely related to the structures of the compounds, that is, an alpha-exomethylene-gamma-lactone ring is necessary for these activities.

Novel taxa-4(20),12-diene and 2(3→20)abeotaxane from needles of Taxus canadensis.

A novel 6/8/6-membered taxane with a rare C-12(13)-double bond and rare 2(3→20)abeotaxane were isolated from the needles of Taxus canadensis. Their structures were characterized as 7ß,9α,10ß-triacetoxytaxa-4(20),12-diene-2α,5α,11ß-triol (1) and 2α,7ß,10ß-triacetoxy-5α-hydroxy-2(3→20)abeotaxa-4(20),11-diene-9,13-dione (2) on the basis of 1D and 2D spectroscopic data. 1 is the first example of a natural taxane without substitution at both C-13 and C-14.

Achillinin A, a cytotoxic guaianolide from the flower of Yarrow, Achillea millefolium.

Achillinin A (2ß,3ß-epoxy-1α,4ß,10α-trihydroxyguai-11(13)-en-12,6α-olide, 1), a new guaianolide isolated from the flower of Achillea millefolium, exhibited potential antiproliferative activity to A549, RERF-LC-kj and QG-90 cells with 50% inhibitory concentration (IC(50)) values of 5.8, 10 and 0.31 µM, respectively.

A novel taxane 13-glucoside and other taxanes from the leaves of Taxus cuspidata.

Three new taxanes, 2 α,9 α,10 ß-triacetoxy-13 α-( ß-D-glucopyranosyloxy)taxa-4(20),11-dien-5 α-ol, 5 α,10 ß,13 α-triacetoxytax-11-ene-2 α,7 ß,9 α,20-tetraol, and 5 α,10 ß,13 ß-triacetoxy-2 α,7 ß-dihydroxy-2(3→20) abeotaxa-4(20),11-dien-9-one, were isolated from the leaves of the Japanese yew, Taxus cuspidata. Compound 1 is the first example of a taxane with 13-glycosidic linkage.

[Microbiological transformation of paeoniflorin and albiflorin].

OBJECTIVE: To investigate the microbiological transformation of paeoniflorin and albiflorin. METHOD: The bacteria strains able to transform paeoniflorin and albiflorin were screened from 18 strains of microorganisms. The products were isolated by chromatography method and their structures were elucidated by spectral technology. RESULT: It was found that Cunninghamella blakesleana (AS 3.970) and Syncephalastrum racemosum (AS 3.264) could convert paeoniflorin and albiflorin efficiently, respectively. C. blakesleana could convert paeoniflorin to produce albiflorin, while S. racemosum could convert albiflorin to produce paeoniflorin. CONCLUSION: Paeoniflorin and albiflorin could be converted each other in definited condition.