Chemical constituents from the rhizomes of Polygonatum sibiricum Red. and anti-inflammatory activity in RAW264.7 macrophage cells

Chemical investigation of the rhizomes of Polygonatum sibiricum Red. led to the identification of 27 constituents. Among them, a total of 16 compounds were obtained from Polygonatum for the first time, in which, 3 and 4 were also firstly isolated as natural products. Anti-inflammatory activity studies on 13 isolated compounds showed that β-carboline constituents, especially compounds 1 and 2, significantly inhibited the expression of NO, TNF-α, IL-6 and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells. Moreover, western blotting analysis demonstrated that compound 1 significantly inhibited the expression of COX-2, iNOS and the activation of NF-κB, suggesting that β-carboline structures may play an important role in inhibition of NF-κB signaling pathway, which thereby inhibits the production of inflammatory factors. The present research may not only help further elucidation of the anti-inflammatory mechanism of P. sibiricum Red., but also provide the potential bioactive molecules for inflammatory diseases research.     

Isolation of a new natural kingiside aglucone derivative and other anti-inflammatory constituents from Syringa reticulata

Abstract

A new secoiridoid, (1R,5S,8S,9R)-1-methyl-kingiside aglucone (1), along with nine known compounds (2–10), were isolated from the ethanol extract of the stem bark of Syringa reticulata (Bl.) Hara. The structure of compound 1 was elucidated using HR-ESI-MS, 1D and 2D NMR spectroscopy. Compounds 1–10 were evaluated for their inhibitory activity against NO, TNF-α and IL-6 production. Compounds 1, 3, 5 and 7–10 significantly inhibited the levels of NO, TNF-α and IL-6 in LPS-induced RAW264.7 cells from concentrations of 3 to 30?μM.     

Three new secoiridoid glycosides from the rhizomes and roots of Gentiana scabra and their anti-inflammatory activities

Three new (1–3) and 17 known (4–20) iridoid and secoiridoid glycosides were isolated from a methanol extract of the rhizomes and roots of Gentiana scabra. Their chemical structures were elucidated from 1D and 2D NMR, IR absorption, and HR-ESI-MS spectra, as well as comparisons of these data with reported values. The effects of the isolated compounds on lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells were investigated. Compounds 6, 10 and 20 exhibited significant inhibitory effects on LPS-induced IL-12 p40 and IL-6 production with IC₅₀ values of 1.62–14.29 μM. Compound 10 also showed a strong inhibitory effect on the LPS-stimulated production of TNF-α with an IC₅₀ value of 10.45 μM.     

A new diarylheptanoid and a new diarylheptanoid glycoside isolated from the roots of Juglans mandshurica and their anti-inflammatory activities

A new diarylheptanoid, (2S,3S,5S)-2,3,5-trihydroxy-1,7-bis(4-hydroxy- 3-methoxyphenyl)heptane (1), and a new diarylheptanoid glycoside, (2S,3S,5S)-2,3-dihydroxy-5-O-β-d-xylopyranosyl-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)heptane (2), together with three known compounds, rhoiptelol C (3), rhoiptelol B (4) and 3′,4″-epoxy-2-O-β-d-glucopyanosyl-1-(4-hydroxyphenyl)- 7-(3-methoxyphenyl)heptan-3-one (5) were isolated from the roots of Juglans mandshurica (Juglandaceae). The structures of compounds 1 and 2 were identified based on HR-ESI-MS, 1D and 2D NMR spectroscopic methods. Compounds 1–5 were assayed for their inhibitory effects on the production of NO, TNF-α and IL-6 in LPS-stimulated RAW264.7 cells.     

Chemical constituents and biological activities of Dianthus elegans var. elegans

Chemical investigation of the aerial parts of Dianthus elegans var. elegans afforded two previously undescribed saponins, named dianosides M-N (1–2), together with four oleanane-type triterpenoid glycosides (3–6). Their structures were elucidated as 3-O-α-L-arabinofuranosyl-16α-hydroxyolean-12-ene-23α, 28β-dioic acid (1) and 3-O-α-L-arabinofuranosyl-(1 → 3)-β-D-glucopyranosyl 16α-hydroxyolean-12-ene-23α-oic acid, 28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glycosyl ester (2) by chemical and extensive spectroscopic methods including IR, 1D, 2D NMR and HRESIMS. Both of the saponins were evaluated for their cytotoxicities against HEK-293, A-549 and HeLa human cancer cells using the MTT method. All compounds showed no substantial cytotoxic activity against tested cell lines. However, dianosides M-N and the n-butanol fraction exhibited considerable haemolysis in human erythrocyte cells. The immunomodulatory properties of dianosides M-N were also evaluated in activated whole blood cells by PMA plus ionomycin. Dianosides M-N increased IL-1β concentration significantly whereas the n-butanol fraction slightly augmented IL-1β secretion. All compounds did not change IL-2 and IFN-γ levels considerably.     

Chemical constituents from Gueldenstaedtia verna and their anti-inflammatory activity

A new triterpenoid glycoside (1) and 15 known compounds (2–16) were isolated from the whole plants of Gueldenstaedtia verna. The new compound (1) was identified as complogenin 22-O-β-d-glucopyranoside by extensive spectroscopic techniques including 1D (¹H and ¹³C) and 2D NMR experiments (HSQC, HMBC and NOESY), HR-DART-MS and chemical methods. Most of the isolates were evaluated for their inhibitory activities on LPS-induced NO production in RAW 264.7 cells. The inhibitory effects of the active compounds, sulphuretin (8) and (22E,24S)-5α,8α-epidioxy-24-methyl-cholesta-6,9(11),22-trien-3β-ol (13), on the production of pro-inflammatory mediators (including IL-6, IL1β and PGE₂) were further estimated in vitro by ELISA in RAW 264.7 macrophages.     

Crystal structure and protective effect in osteoarthritis of Co(II)-mediated pyridinium-bearing coordination polymer

Abstract

By using a mixed-ligand approach, a new Co(II)-mediated pyridinium-bearing coordination polymer, {[Co(BCbpe)(ipa)]·3H₂O}_n (1), has been prepared by reaction of Co(NO₃)₂·6H₂O) and isophthalic acid (H₂ipa) in the presence of pyridinium chloride 1-(4-carboxybenzyl)4-[2-(4-pyridyl)-vinyl] (HBCbpeCl) in EtOH/H₂O (V:V?=?1:1). Furthermore, a green hand grinding technique has been implemented to reduce the particle size of 1 to generate nanosheets of 1 with good water dispersivity. The post-traumatic osteoarthritis (OA) model was constructed and the in vivo protective effect of nano 1 was evaluated. First, the inflammatory level of OA rats was measured by ELISA detection. Second, for further detection, the real-time RT-PCR was carried out to measure the relative expression of caspase-1, nlrp3 as well as il-1β inflammatory factors. Finally, molecular docking analysis of the complex indicated that all of the proposed drug candidates showed desirable drug-like criteria.     

Anti-inflammatory bibenzyls from the stems of Dendrobium huoshanense via bioassay guided isolation

Abstract

The stems of Dendrobium huoshanense have long been used to prevent various diseases, including inflammatory diseases. This study was aimed to explain the anti-inflammatory effect of D. huoshanense stems in LPS-induced RAW 264.7 macrophages and to discover potential anti-inflammatory compounds. Results exhibited that D. huoshanense stems ethanol extract could significantly inhibit LPS-induced production of NO, TNF-α and IL-1β. Based on bioassay guided strategy, four bibenzyls (1–4) were isolated from D. huoshanense stems for the first time. Anti-inflammatory assay showed 1–4 could remarkably inhibit the production of NO in LPS-induced macrophages. Moreover, quantitative RT-PCR analysis displayed that the mRNA levels of iNOs, TNF-α and IL-1β could also be significantly reduced by 1–4. These results suggested that D. huoshanense stems ethanol extract and bibenzyls 1–4 might be well developed as therapeutic agent to prevent inflammatory diseases.     

Crystal and molecular structures of binuclear caesium complexes with 1,3-calix[4]-bis-crown-6 and 1,3-calix[4]-bis-benzo-crown-6

The crystal structures of two binuclear complexes between caesium and 1,3-calix[4]-bis-crowns have been determined. Cs₂ Bis-benzoC6(NO₃)₂. 3CHCl₃ (1) in whichBis-benzoC6 is 1,3-calix[4]-bis-benzo-crown-6, crystallizes in the orthorhombic system: space groupPca2 ₁ a=19.513(10),b=15.382(5),c=23.708(9) Å,V=7116(5) ų,Z=4. Refinement led to a final conventionalR value of 0.065 for 2321 reflections. The structure of (1) is analogous to those already reported withBis-C6, (in whichBis-C6 is, 1,3-calix[4]-bis-crown-6) and NO ₃ ^– as a counter-ion. Cs₂ Bis-C6(NCS)₂ (2) crystallizes in the monoclinic system: space, groupC2 a=36.57(2),b=11.47(1),c=13.65(1) Å, =109.03(5)°.,V=5415(6) ų,Z=4. Refinement led to a final conventionalR value of 0.063 for 2227 reflections. Compound (2) is made of dimers bridged by a disordered NCS^– ion. The crown ether chain conformations are discussed. Supplementary data relating to this article (atomic coordinates, anisotropic displacement parameters, bond distances and angles and observed and calculated structure factors) are deposited with the British Library as Supplementary Publication No. SUP 82199 (52 pages).     

The reaction of 4-methoxycoumarins with prenyl bromide: Synthesis of 4′,4′,5′-trimethyl-dihydrofurano-coumarins and 2,2-dimethyl-chromenopyrans

The reaction of 7-hydroxy-4-methoxy- (1a), 7-hydroxy-4,5-dimethoxy-(1b) and 5-hydroxy-4,7-dimethoxy (1c) -2H-1-benzopyran-2-ones with prenyl bromide in acetone in the presence of anhydrous potassium carbonate gave the corresponding prenyloxycoumarins1d,1e, and1f. The prenyloxy coumarins1d,1e,1f onClaisen migration by refluxing inN,N-dimethyl aniline gave the corresponding 4,4,5-trimethyl-dihydrofuranocoumarins2a,2b, and3. However, the reaction of1a,1b, and1c with 3-chloro-3-methyl-but-1-yne in acetone in presence of potassium carbonate and potassium iodide gave the corresponding propargyl ethers1g,1h,1i, which on refluxing inN,N-dimethyl aniline gave the corresponding 2,2-dimethylchromenopyrans4a,4b, and5. These can also be obtained directly if the reaction is carried out in the presence of dioxan.

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Die Reaktion von 4-Methoxycumarinen mit Prenylbromid: Synthese von 4,4,5-Trimethyl-dihydro-furanocumarinen und 2,2-Dimethylchromenopyranen

Zusammenfassung Die Reaktion von 7-Hydroxy-4-methoxy-(1a), 7-Hydroxy-4,5-dimethoxy-(1b) und 5-Hydroxy-4,7-dimethoxy-2H-1-benzopyran-2-onen (1c) mit Prenylbromid in Aceton in der Gegenwart von wasserfreiem Kaliumcarbonat ergab die entsprechenden Prenylcumarine1d,1e und1f. Diese ergaben durchClaisen-Wanderung bei Rückfluß inN,N-Dimethylanilin die entsprechenden 4,4,5-Trimethyldihydrofuranocumarine2a,2b und3. Die Reaktion von1a,1b und1c mit 3-Chlor-3-methyl-1-butin in Aceton in Gegenwart von wasserfreiem Kaliumcarbonat und Kaliumjodid ergab die entsprechenden Propargylether1g,1h und1i, die ihrerseits bei Rückfluß inN,N-Dimethylanilin die jeweiligen 2,2-Dimethylchromenopyrane4a,4b und5 ergaben. Letztere können auch direkt erhalten werden, wenn die Reaktion in Gegenwart von Dioxan durchgeführt wird.

     

Three new sesquiterpenes from Ainsliaea glabra

Three new sesquiterpenes: 4-acrylic-6-methyl-α-tetralone (1), ainsliaea acid A (2) and ainsliaea acid B (3), together with 8 known compounds (4-11) were isolated from the whole herb of Ainsliaea glabra and their structures were established by means of 1D and 2D NMR spectroscopy and HR-ESIMS. Compounds 1–6 were tested for the inhibition of nuclear factor kappa B (NF-κB) in the 293-NF-κB-luciferase reporter cell line induced by lipopolysaccharide (LPS), and compound 2 was further tested for the production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-10 in RAW264.7 macrophages induced by LPS. The isolated compound 2 exhibited significant anti-inflammatory activity.     

嘧啶并呋咱核苷衍生物的制备及其活性初探

4H,6H-[1,2,5]噁二唑并[3,4-d]嘧啶-5,7-二酮1-氧化物(1)和6-甲基-4H,6H-[1,2,5]噁二唑并[3,4-d]嘧啶-5,7-二酮1-氧化物(2)是一氧化氮(NO)供体, 将它们分别在无溶剂条件下与高温熔融的全乙酰基保护的核糖、木糖、葡萄糖进行糖基化反应, 分别得到相应的噁二唑并[3, 4-d]嘧啶核苷类化合物7, 9～12, 化合物7经NH₃-MeOH处理, 去O-乙酰基制得8, 这些新型核苷化合物可作为潜在的NO供体. 部分此类化合物的生物活性研究表明, 嘧啶并呋咱核苷衍生物具有抗病毒、抗肿瘤活性, 为研究抗病毒、抗肿瘤药物提供了新结构类型的候选化合物.     

A new macrocyclic diterpenoid from Anisomeles indica

Abstract

A new macrocyclic diterpenoid, 4β,5β-dihydroxyovatodiolide (1), together with twenty-two known compounds (2-23) were isolated from the MeOH extract of the dried aerial parts of Anisomeles indica (L.) O. Kuntze (Labiatae). The structure of 1 was established on the basis of spectral evidence. Phenylethanoids, acteoside (5) and isoacteoside (6) showed significant inhibitory to IL-2 secretion of with respect to phorbol myristate acetate and anti-CD28 monoclonal antibody co-stimulated activation of human peripheral blood T cells.     

New chemical constituents from the fruits of Zanthoxylum armatum and its in vitro anti-inflammatory profile

Chemical investigations on the fruits of Zanthoxylum armatum Roxb. (Rutaceae) led to the isolation of two new constituents characterised as 2α-methyl-2β-ethylene-3β-isopropyl-cyclohexan-1β, 3α-diol (1) and phenol-O-β-D-arabinopyranosyl-4′-(3″, 7″, 11″, 15″-tetramethyl)-hexadecan-1″-oate (2) along with known compounds m-methoxy palmityloxy benzene (3), acetyl phenyl acetate (4), linoleiyl-O-α-D-xylopyranoside (5), m-hydroxyphenoxy benzene (6) and palmitic acid (7). The chemical structures were established with the help of physical, chemical and spectroscopic methods. The anti-inflammatory potential of isolated compounds 1 and 2 was evaluated using in vitro target-based anti-inflammatory activity in LPS-stimulated primary peritoneal macrophages isolated from mice. Production of pro-inflammatory cytokines (TNF-α and IL-6) was significantly inhibited by the treatment of isolated compounds 1 and 2 in a dose-dependent manner.     

Cytotoxic constituents of Lasiosphaera fenzlii on different cell lines and the synergistic effects with paclitaxel

The fruit body of Lasiosphaera fenzlii was found to show cytotoxicity on cancer cells during a preliminary screening. Repeated column chromatography of the fungal methanol extract resulted in the isolation of six compounds identified as 5α,8α-epidioxy-ergosta-6,22-dien-3β-ol (1), 5α,8α-epidioxy-ergosta-6,9(11),22-trien-3β-ol (2), 5α-ergosta-7,22-dien-3β-ol (3), 5α-ergosta-7,22-dien-3-one (4), ergosta-7,22-dien-3β,5α,6β-triol (5) and 6-dihydroxy-2,3-dihydro-1H-isoindol-1-one (6). The two peroxide compounds, 1 and 2, showed cytotoxic activity and compound 1 was selectively cytotoxic to cancer cells. Furthermore, compound 1 synergised the cytotoxicity of paclitaxel on Hela cells by increasing intracellular accumulation of paclitaxel in cancer cells but not in normal cells.     

Über 4-Alkylamino-bzw. 4-Arylamino-5,6-dihydro-2(1H)-pyridinthione

Heating 1-alkyl- or 1-aryldihydro-6-methyl-2(1H)-pyrimidinethiones5, 6 in an inert medium causes rearrangement to 4-alkylamino-(4-arylamino-)-5,6-dihydro-2(1H)-pyridinethiones11, 12, probably via the methylene form29, by thermal heterolysis of the N₁/C₂ bond and exchange of the alkylamino (arylamino) group 1 through the carbon atom of the methylene group 6. The aminodihydropyridinethiones11, which can be regarded as cyclic derivatives of 3-aminothiocrotonamide, react with bistrichlorophenylmalonate under diacylation, and with formaldehyde and primary amines to yield aminodialkylation products of the enamine system, tetrahydro-4-hydroxy-7,7-dimethyl-5-thioxopyrido[4,3-b]pyridine-2(1H)-ones13, 14 and hexahydro-7,7-dimethylpyrido[4,3-d]pyrimidine-5(6H)-thiones18, 19, 21 respectively. H₂O₂ converts11 to the corresponding 4-aminodihydro-2(1H)-pyridones22, which can be reconverted into11 with P₄S₁₀.11 reacts with alkyl halides to 2-alkylthiodihydropyridines23, 24, 25. The mechanism of the methylpyrimidine-pyridine rearrangement is discussed.     

Preparation,Isolation and Characterization of all of the Regioisomeric 61, 6N-Bis-O-(Monomethoxytrityl) and-(Dimethoxytrityl) Derivatives of Cyclomalto-Olgosaccharides

Abstract

Regioisomeric 6¹, 6ⁿ-bis-O-(monomethoxytrityl) or 6¹, 6ⁿ-bis-O-(dimethoxytrityl) cyclomaltohexaose, -cyclomaltoheptaose (n = 2-4), and -cyclomaltooctaose derivatives (n = 2-5) were prepared by the reaction of cyclomaltohexaose (1, cG₆, αCD), cyclomaltoheptaose (11, cG₇, βCD) or cyclomaltooctaose (21, cG₈, γCD) and 4-monomethoxytrityl chloride or 4,4′-dimethoxytrityl chloride in pyridine. Products were isolated by HPLC. The regiochemical determination of these positional isomers was done by converting these compounds to the respective 6¹, 6ⁿ-bis-O-(tert-butyldimethylsilyl) derivatives¹ whose structures have been already established.     

哒嗪酮类α1-肾上腺素受体拮抗剂的合成和生物活性研究

将苯(氧)乙胺和苯氧烷胺类α₁-肾上腺素受体拮抗剂中的苯(氧)乙胺、苯氧烷胺片段引入哒嗪酮类化合物中, 设计、合成了30个新的含哒嗪酮环的α₁-肾上腺素受体拮抗剂. 所有新化合物的结构均经¹H NMR, IR, HRMS确证. 生物活性测试表明28个目标物对α₁-肾上腺素受体有较好的拮抗作用(pA₂＞6.00), 化合物6o, 6p, 6q, 6v, 6x, 6y, 10c, 10d的pA₂值＞7.00.     

Four- and Eight-Carbon Homologation of Benzaldehyde by (1Z,3Z)-Butyltelluro-1,3-Butadiene: Synthesis of Navenone B: Alarm Pheromone of the Mollusk Navanax inermis

Four- and eight-carbon homologation of benzaldehydes is described. The hydrotelluration of (Z)-1-methoxy-but-1-en-3-ynes 1 afforded (1Z,3Z)-1-butyltelluro-4-methoxy-1,3-butadiene 2, this compound 2 underwent a Te/Li exchange reaction, and the butadienyllithium 3 obtained reacted with benzaldehyde to form the corresponding allylic alcohol 4 with total retention of configuration. The allylic alcohol 4a formed underwent acidic hydrolysis, resulting in 5-phenyl-(2E,4E)-dienal 5 (four-carbon homologation of benzaldehyde). Product 5 reacted with the butadienyllithium 3, affording the alcohol 9-phenyl-(1Z,3Z,6E,8E)-1-methoxy-5-hydroxy-nonatetraene 6, which was hydrolyzed or spontaneously transformed into 9-phenyl-(2E,4E,6E,8E)-tetraenal 7, completing the eight-carbon homologation of benzaldehyde. Reaction of 9-phenyl-nona-(2E,4E,6E,8E)-tetraenal 7 with methyllithium in tetrahydrofuran afforded (3E,5E,7E,9E)-10-phenyl-deca-3,5,7,9-tetraen-2-ol 8. The product of the reaction described was employed in the synthesis of (3E,5E,7E,9E)-10-phenyl-deca-3,5,7,9-tetraen-2-one 9, which is known as navenone B, an alarm pheromone of the mollusk Navanax inermis.