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Sample records for cyathane diterpenoid natural

  1. Structure Diversity, Synthesis, and Biological Activity of Cyathane Diterpenoids in Higher Fungi.

    PubMed

    Tang, Hao-Yu; Yin, Xia; Zhang, Cheng-Chen; Jia, Qian; Gao, Jin-Ming

    2015-01-01

    Cyathane diterpenoids, occurring exclusively in higher basidiomycete (mushrooms), represent a structurally diverse class of natural products based on a characteristic 5-6-7 tricyclic carbon scaffold, including 105 members reported to date. These compounds show a diverse range of biological activities, such as antimicrobial, anti-MRSA, agonistic toward the kappa-opioid receptor, antiinflammatory, anti-proliferative and nerve growth factor (NGF)-like properties. The present review focuses on the structure diversity, structure elucidation and biological studies of these compounds, including mechanisms of actions and structure-activity relationships (SARs). In addition, new progress in chemical synthesis of cyathane diterpenoids is discussed. PMID:25994862

  2. Anti-inflammatory and cytotoxic cyathane diterpenoids from the medicinal fungus Cyathus africanus.

    PubMed

    Han, Junjie; Chen, Yuhui; Bao, Li; Yang, Xiaoli; Liu, Dailin; Li, Shaojie; Zhao, Feng; Liu, Hongwei

    2013-01-01

    Five novel cyathane diterpenes, cyathins D-H (1-5), as well as three known diterpenes, neosarcodonin O (6), cyathatriol (7),and 11-O-acetylcyathatriol (8), were isolated from the solid culture of Cyathus africanus. The structures of the new compounds were elucidated by spectroscopic methods. The absolute configurations of compounds 2 and 8 were determined by single-crystal X-ray crystallographic analysis, whereas the absolute configuration of C-14 in 1 was determined via the circular dichroism data of the [Rh(2)(OCOCF(3))(4)] complex. Compounds 3, 5, 6, 8, and 9 showed potent inhibition against nitric oxide production in lipopolysaccaride-activated macrophages with an IC(50) value of 2.57, 1.45, 12.0, 10.73, and 9.45μM, respectively. Compounds 6 and 8 showed strong cytotoxicity against Hela and K562 cell lines with the IC(50) value less than 10μM. PMID:23075884

  3. Ingenane Diterpenoids.

    PubMed

    Appendino, Giovanni

    2016-01-01

    Despite a more recent isolation and chemical characterization when compared to phorbol, along with its chemical instability, limited distribution in Nature, and scarce availability, ingenol is the only Euphorbia diterpenoid that has undergone successful pharmaceutical development, with ingenol 3-angelate (ingenol mebutate, Picato(®)) entering the pharmaceutical market in 2012 for the treatment of actinic keratosis. The phytochemical, chemical, and biological literature on members of the ingenane class of diterpenoids is reviewed from their first isolation in 1968 through 2015, highlighting unresolved issues both common to phorboids (biogenesis, relationship between molecular targets, and in vivo activity) and specific to ingenol derivatives (two-dimensional representation, in-out stereoisomerism, versatility of binding mode to PKC, and inconsistencies in the structural elucidation of some classes of derivatives). The biogenesis of ingenol is discussed in the light of the Jakupovic proposal of a dissection between the formation of the macrocyclic Euphorbia diterpenoids and the phorboids, and the clinical development of ingenol mebutate is chronicled in the light of its "reverse-pharmacology" focus. PMID:27380406

  4. New cytotoxic diterpenylnaphthohydroquinone derivatives obtained from a natural diterpenoid.

    PubMed

    Miguel Del Corral, José M; Castro, M Angeles; Lucena Rodri Guez, M; Chamorro, Pablo; Cuevas, Carmen; San Feliciano, Arturo

    2007-09-01

    Diterpenylquinone/hydroquinone derivatives were prepared through Diels-Alder cycloaddition between natural myrcecommunic acid or its methyl ester and p-benzoquinone (p-BQ), using BF(3).Et(2)O as catalyst or under microwave (Mw) irradiation. Acetyl, methyl and benzyl derivatives of several diterpenylnaphthohydroquinone were prepared from cycloadducts following two basic synthetic strategies, either protection before aromatisation or viceversa. Some of them were further functionalised at the B-ring of the decaline core. Most of the new compounds were evaluated and some of them resulted cytotoxic against several tumour cell lines with IC(50) values under the microM level. PMID:17583515

  5. Laxitextines A and B, Cyathane Xylosides from the Tropical Fungus Laxitextum incrustatum.

    PubMed

    Mudalungu, Cynthia M; Richter, Christian; Wittstein, Kathrin; Abdalla, Muna Ali; Matasyoh, Josphat C; Stadler, Marc; Süssmuth, Roderich D

    2016-04-22

    Bioassay-guided fractionation of the mycelial extract of a basidiomycete culture collected in Kenya led to the isolation of two new cyathane diterpenoids named laxitextines A (1) and B (2). The producer strain was characterized by detailed taxonomic studies based on rDNA using the 5.8S gene region, the internal transcribed spacer 2 (ITS2), and part of the large subunit that identified the fungus as Laxitextum incrustatum. The structures of 1 and 2 were elucidated by NMR spectroscopic and mass spectrometric analyses. Both compounds exhibited moderate activities against Gram-positive bacteria Bacillus subtilis (DSM 10), Staphylococcus aureus (DSM 346), and methicillin-resistant Staph. aureus (DSM 1182). The two compounds also showed variable antiproliferative activities against mouse fibroblast (L929) and selected human cell lines (breast cancer MCF-7, epidermoid carcinoma A431, and umbilical vein endothelial HUVEC). The IC50 values with respect to the MCF-7 cell line for compounds 1 and 2 were 2.3 and 2.0 μM, respectively. PMID:27043217

  6. A natural diterpenoid kamebacetal A with anti-tumor activity: Theoretical and experimental study

    NASA Astrophysics Data System (ADS)

    Wang, Tao; Tang, Fu-ming; Zhang, Yi-Heng; Chen, Zhong

    2010-06-01

    Kamebacetal A ( 1) is an ent-kaurane diterpenoid isolated from Isodon racemosa (Hemsl) Hara. This natural product exhibits significant cytotoxicity against human Bel-7402 and HO-8910 tumor cells. The geometrical conformation of 1 has been optimized at the B3LYP/6-311+G(d) level of theory. The results indicated that the calculated geometric parameters are close to the X-ray crystal structure. The theoretical 13C NMR chemical shifts of 1 were also calculated at the GIAO-B3LYP level of theory with different basis sets. The calculated NMR chemical shifts are in closer agreement with the experimental results. A molecular electrostatic potential (MEP) map was used in an attempt to identify key features of the kamebacetal A to account for its anti-tumor activity. MEP investigations reveal that compound 1, which shows anti-tumor activity, possesses electron-rich regions that extend over the hydroxyl and carbonyl groups of compound 1. The data generated in this study is valuable as it provides an insight into kamebacetal A molecular and structure-activity relationships.

  7. Production of bioactive cyathane diterpenes by a bird's nest fungus Cyathus gansuensis growing on cooked rice.

    PubMed

    Wang, Botao; Han, Junjie; Xu, Wei; Chen, Yuhui; Liu, Hongwei

    2014-01-01

    Cyathane diterpenes are important bioactive substances produced by some edible and medicinal fungi. Seven new cyathane type diterpenes, named as cyathins J-P (1-7), together with two known diterpenes (8 and 9), were isolated from the solid culture of the bird's nest fungus Cyathus gansuensis growing on cooked rice. The structures of the new secondary metabolites were elucidated by NMR experiments. Bioactivity screening indicated that compounds 1, 2, 4, and 8 showed moderate inhibitory activity against NO production in lipopolysaccharide-activated macrophages with an IC50 value of 42, 78, 80, and 16 μM, respectively. The fungus C. gansuensis is a promising source of bioactive secondary metabolites and has application potential in preparing healthy food. PMID:24444922

  8. Diterpenoids from Fagonia mollis.

    PubMed

    Sallam, Amal; Nugroho, Alfarius Eko; Hirasawa, Yusuke; Chin-Piow, Wong; Kaneda, Toshio; Shirota, Osamu; Gedara, Sahar R; Morita, Hiroshi

    2014-09-01

    A new acyclic diterpenoid (1) and a new erythroxan diterpenoid (2), together with 4 erythroxan diterpenoids and 3 triterpenoids, have been isolated from the aerial parts of Fagonia mollis. Their structures were elucidated on the basis of 1D and 2D NMR data. The cytotoxic activity of the isolated compounds was investigated against HL-60 cancer cells. PMID:25918782

  9. New clerodane diterpenoids from Croton crassifolius.

    PubMed

    Qiu, Maosong; Cao, Di; Gao, Youheng; Li, Shuhua; Zhu, Jinping; Yang, Bao; Zhou, Lian; Zhou, Yuan; Jin, Jing; Zhao, Zhongxiang

    2016-01-01

    Two new clerodane diterpenoids (1-2), one new clerodane diterpenoid alkaloid (3), as well as thirteen known compounds were isolated from Croton crassifolius. The structures of new compounds were established by a combination of spectroscopic methods, including HRMS, (1)H NMR, (13)C NMR, (1)H (1)H COSY, HSQC, HMBC, NOESY and X-ray crystallographic analysis. Compound 3 is firstly reported as the clerodane-type diterpenoid alkaloid in natural products. All of the compounds were evaluated for in vitro cytotoxic activities against CT26.WT cell using the MTT method. PMID:26611371

  10. Analysis of cyathane-type diterpenoids from Cyathus striatus and Hericium erinaceus by high-resolution MALDI MS imaging.

    PubMed

    Bhandari, Dhaka Ram; Shen, Tian; Römpp, Andreas; Zorn, Holger; Spengler, Bernhard

    2014-01-01

    Fungal secondary metabolites in both fruiting bodies and pellets from submerged cultures of basidiomycetes were analyzed by atmospheric pressure matrix-assisted laser desorption/ionization-mass spectrometry imaging at a lateral resolution of 15 μm, a mass resolution of 140,000 at m/z 200 and a mass accuracy of better than 2 ppm. The striatals A, B, C, and D, and a number of erinacine type metabolites were detected in the basidiomycetes Cyathus striatus and Hericium erinaceus, respectively. The two fungi were selected as model species, as they are well-known for efficient production of terpenoid secondary metabolites with interesting biological activities, e.g., antibacterial, fungicidal, cytotoxic properties, and stimulating effects on nerve growth factor synthesis. The localization of metabolites revealed a mostly homogeneous distribution of the striatals in the pellets of C. striatus, while a concentration gradient, increasing to the center, was observed in the pellets of H. erinaceus. A mostly homogeneous distribution of metabolites was also found in the fruiting body of H. erinaceus. PMID:24287632

  11. Diterpenoids from Leaves of Rubus chingii.

    PubMed

    Shu, Jicheng; Huang, Yingzheng; Cui, Hangqing; Peng, Caiying; Liu, Jianqun; Huang, Huilian

    2016-03-01

    The leaves of Rubus chingii were examined for their phytochemical composition and anti-yeast activity. In the process, seven diterpenoids (compounds 1-7), including a new natural compound (14β, 16-epoxy-7-pimarene-3α, 15β-diol, 1), were isolated and elucidated. Compound 1 exhibited moderate anti-Candida activity. PMID:27169185

  12. NMR spectroscopicsearch module for Spektraris, an online resource for plant natural product identification – taxane diterpenoids from Taxus × media cell suspension cultures as a case study

    PubMed Central

    Fischedick, Justin T.; Johnson, Sean R.; Ketchum, Raymond E.B.; Croteau, Rodney B.; Lange, B. Markus

    2014-01-01

    Development and testing of Spektraris-NMR an online spectral resource, is reported for the NMR-based structural identification of plant natural products (PNPs). Spektraris-NMRallows users to search with multiple spectra at once and returns a table with alist of hits arranged according to the goodness of fit between query data and database entries. For each hit, a link to a tabulated alignment of 1H-NMR and 13C-NMR spectroscopic peaks (query versus database entry) is provided. Furthermore, full spectroscopic records and experimental meta information about each database entry can be accessed online. To test the utility of Spektraris-NMR for PNP identification, the database was populated with NMR data (total of 466 spectra) for ∼250 taxanes, which are structurally complex diterpenoids (including the anticancer drug taxol) commonly found in the genus Taxus. NMR data generated used was then generated with metabolites purified from Taxus cell suspension cultures to search Spektraris-NMR, and were able to identify eight taxanes with high confidence. A ninth isolated metabolite could be assigned, based on spectral searches, to a taxane skeletal class, but no high confidence hit was produced. Using various spectroscopic methods, this metabolite was characterized as the taxane 2-deacetylbaccatin IV, a novel taxane. These results indicate that Spektraris-NMR is a valuable resource for rapid and reliable identification of known metabolites and has the potential to contribute to de-replication efforts in the search for novel PNPs. PMID:25534952

  13. Functional identification of rice syn-copalyl diphosphate synthase and its role in initiating biosynthesis of diterpenoid phytoalexin/allelopathic natural products.

    PubMed

    Xu, Meimei; Hillwig, Matthew L; Prisic, Sladjana; Coates, Robert M; Peters, Reuben J

    2004-08-01

    Rice produces a number of phytoalexins, and at least one allelopathic agent, from syn-copalyl diphosphate (CPP), representing the only known metabolic fate for this compound. Thus, the class II terpene synthase that converts the universal diterpenoid precursor geranylgeranyl diphosphate to syn-CPP catalyzes the committed step in biosynthesis of these natural products. Here the extensive sequence information available for rice was coupled to recombinant expression and functional analysis to identify syn-copalyl diphosphate synthase (OsCPSsyn). In addition, OsCPSsyn mRNA was found to be specifically induced in leaves by conditions that stimulate phytoalexin biosynthesis. Therefore, transcription of OsCPSsyn seems to be an important regulatory point for controlling the production of these defensive compounds. Finally, alignments carried out with OsCPSsyn revealed that class II terpene synthases exhibit a sequence conservation pattern substantially different from that of the prototypical class I enzymes. One particularly notable feature is the specific conservation of the functionally cryptic 'insertional' sequence element in class II terpene synthases, indicating that this region is important for the corresponding cyclization reaction. PMID:15255861

  14. Diterpenoids of terrestrial origin.

    PubMed

    Hanson, James R

    2015-12-19

    Covering January to December 2014. Previous review, Nat. Prod. Rep., 2015, 32, 76-87 This review covers the isolation and chemistry of diterpenoids from terrestrial as opposed to marine sources and includes, labdanes, clerodanes, abietanes, pimaranes, kauranes, cembranes and their cyclization products. There are 200 references. PMID:26514379

  15. New diterpenoids from euphorbia teheranica

    PubMed

    Ahmad; Jassbi

    1999-07-01

    Two novel pentacyclic diterpenoid esters of the cyclomyrsinane type (1, 2), and one tetracyclic diterpenoid ester of the myrsinane type (3) were isolated from the aerial parts of the plant Euphorbia teheranica. The structures of the novel compounds were determined by spectral data interpretation. PMID:10425130

  16. The isolation and synthesis of neodolastane diterpenoids.

    PubMed

    Marković, Dean; Kolympadi, Maria; Deguin, Brigitte; Porée, François-Hugues; Turks, Māris

    2015-02-01

    The neodolastane diterpenoids comprise a group of 44 compounds including guanacastepenes, heptemerones, plicatilisins, radianspenes, 2,15-epoxy-5,13-dihydroxyneodolast-3-en-14-one and sphaerostanol. These fungal and marine natural products are characterized by a tricyclic neodolastane skeleton that consists of fused five-, seven- and six-membered rings. Their reported antibiotic activities against antibiotic-resistant bacteria together with strong antifungal and anticancer activities and their novel structures render these compounds interesting synthetic targets. The aim of this account is to summarise the progress in the isolation, characterisation and synthesis of these diterpenoids as well as to review their biogenetic origins and diverse biological activities since their discovery in 2000. PMID:25366359

  17. ent-kaurane diterpenoids from Annona glabra.

    PubMed

    Chen, C Y; Chang, F R; Cho, C P; Wu, Y C

    2000-07-01

    Three new kaurane diterpenoids, annoglabasin C (16alpha-acetoxy-ent-kauran-19-oic acid-17-methyl ester) (1), annoglabasin D (16alpha-acetoxy-ent-kauran-19-al-17-methyl ester) (2), and annoglabasin E (16alpha-hydro-19-ol-ent-kauran-17-oic acid) (3), and a new norkaurane diterpenoid, annoglabasin F (16alpha-acetoxy-19-nor-ent-kauran-4alpha-ol-17-methyl ester) (4), along with 13 known kaurane derivatives were isolated from the stems of Annona glabra. 16alpha-Methoxy-ent-kauran-19-oic acid (5) and 16alpha-hydro-ent-kauran-17,19-dimethyl ester (6) were obtained for the first time as natural products. The structures of compounds 1-6 were characterized by spectral analysis. PMID:10924186

  18. Diterpenoids from Isodon sculponeatus.

    PubMed

    Jiang, Hua-Yi; Wang, Wei-Guang; Zhou, Min; Wu, Hai-Yan; Zhan, Rui; Li, Xiao-Nian; Du, Xue; Li, Yan; Pu, Jian-Xin; Sun, Han-Dong

    2014-03-01

    Phytochemical investigation of the aerial parts of Isodon sculponeatus afforded six new 7,20-epoxy-ent-kauranoids, sculponins U-Z (1-6), and 11 known diterpenoids (7-17). The structures of these new compounds were elucidated primarily by means of extensive spectroscopic analysis, and the absolute configuration of 1 was determined by single crystal X-ray diffraction. Compound 5 exhibited weak cytotoxic activity against HL-60, SMMC-7721, MCF-7, and SW-480 cell lines, and it also inhibited NO production in LPS-stimulated RAW264.7 cells, with IC50 value of 13.8 μM. PMID:24418655

  19. Diterpenoid tetracyclic hydrocarbons of petroleum

    SciTech Connect

    Vorob'eva, N.S.; Zemskova, Z.K.; Pekh, T.I.; Petrov, A.A.

    1987-08-01

    Diterpenoid hydrocarbons are fairly widespread in various caustobioliths. However, if petroleums contain mainly acyclic diterpenoids (phytane, pristane and norpristane), cyclic diterpaenes such as fichtelite, pimarane, iosene (kaurane) and hibbane are often found in hydrocarbons isolated from coal and shale. Recent advances in the chemistry of diterpenoids isolated from caustobioliths, are described in a separate paper. Much less is known about petroleum polycyclic diterpenoid hydrocarbons, particularly those with four saturated rings. A series of tetracyclic hydrocarbons C/sub 19/H/sub 32/ (molar mass 260), found in a number of light petroleums and gas condensates from the Jura deposits of Central Kara-Kum (Turkmen S.S.R.), are examined here. These hydrocarbons are present in petroleums and condensates from the Davaly, Erden, Ortakak, Southern Beuideshik deposits, they are always identical and occur in the same ratios. The composition of the tretracyclanes isolated from the Ortakak gas condensates (well 17) will be examined in detail.

  20. Two rings in them all: The labdane-related diterpenoids

    PubMed Central

    Peters, Reuben J.

    2013-01-01

    In his original exposition of the biogenetic isoprenoid rule, L. Ruzicka noted the structural identity between the fused A/B rings of triterpenoids/sterols and certain multicyclic diterpenoids as part of the impetus leading to that profound insight. His prescient hypothesis that this chemical structure relationship reflects similarities in the initial cyclization of these diterpenoids with that occurring in triterpenoid biosynthesis has since been verified. However, this chemical structure relationship does not continue to hold true for the additional rings found in many of these di- and tri- terpenoid natural products. This is now appreciated to arise from differences in their subsequent biogenesis, specifically further cyclization and/or rearrangement of these diterpenoids after formation of an initial bicyclic intermediate in a separately catalyzed reaction. The trivial name for the hydrocarbon skeleton of the most commonly found version of the corresponding unique intermediate forms the basis for a unifying “labdane-related” designation. This defines a large super-family of diterpenoids that contains nearly 7,000 already known natural products. Many of these are found in plants, where the requisite biosynthetic machinery for gibberellin phytohormones, particularly the relevant diterpene cyclases, provides a biosynthetic reservoir that appears to have been repeatedly drawn upon to evolve new labdane-related diterpenoids. The potent biological activity of the “ancestral” gibberellins, which has led to the independent evolution of distinct gibberellin biosynthetic pathways in plants, fungi, and bacteria, is further discussed as an archetypical example of the selective pressure driving the observed diversification of the large super-family of labdane-related diterpenoid natural products. PMID:20890488

  1. Characterization of an orphan diterpenoid biosynthetic operon from Salinispora arenicola.

    PubMed

    Xu, Meimei; Hillwig, Matthew L; Lane, Amy L; Tiernan, Mollie S; Moore, Bradley S; Peters, Reuben J

    2014-09-26

    While more commonly associated with plants than microbes, diterpenoid natural products have been reported to have profound effects in marine microbe-microbe interactions. Intriguingly, the genome of the marine bacterium Salinispora arenicola CNS-205 contains a putative diterpenoid biosynthetic operon, terp1. Here recombinant expression studies are reported, indicating that this three-gene operon leads to the production of isopimara-8,15-dien-19-ol (4). Although 4 is not observed in pure cultures of S. arenicola, it is plausible that the terp1 operon is only expressed under certain physiologically relevant conditions such as in the presence of other marine organisms. PMID:25203741

  2. Characterization of an Orphan Diterpenoid Biosynthetic Operon from Salinispora arenicola

    PubMed Central

    2015-01-01

    While more commonly associated with plants than microbes, diterpenoid natural products have been reported to have profound effects in marine microbe–microbe interactions. Intriguingly, the genome of the marine bacterium Salinispora arenicola CNS-205 contains a putative diterpenoid biosynthetic operon, terp1. Here recombinant expression studies are reported, indicating that this three-gene operon leads to the production of isopimara-8,15-dien-19-ol (4). Although 4 is not observed in pure cultures of S. arenicola, it is plausible that the terp1 operon is only expressed under certain physiologically relevant conditions such as in the presence of other marine organisms. PMID:25203741

  3. Ozonolytic transformations of labdane diterpenoids

    NASA Astrophysics Data System (ADS)

    Vlad, Pavel F.; Aryku, A. N.

    1992-07-01

    Information on the products of ozonolysis of labdane and ent-labdane diterpenoids is correlated. The effects of the ozonolysis conditions, the procedure for treating the products and the location of double bonds and other functional groups on the character of the resulting ozonolysis products are considered. The bibliography includes 91 references.

  4. Crotofolane diterpenoids from Croton caracasanus.

    PubMed

    Chávez, Katiuska; Compagnoneb, Reinaldo S; Riina, Ricarda; Briceño, Alexander; González, Teresa; Squitieri, Emilio; Landaetab, Carlos; Soscrún, Humberto; Suáreza, Alírica I

    2013-12-01

    Four new crotofolane-type diterpenoids, crotocarasin (A-D) (1-4), together with the known crotofolin E, were isolated from a dichloromethane extract of the stems of Croton caracasanus Pittier. The structures of the new compounds were determined by spectroscopic methods, and the structure of 3 was further confirmed by single-crystal X-ray data analyses. PMID:24555271

  5. Marine Diterpenoids as Potential Anti-Inflammatory Agents.

    PubMed

    González, Yisett; Torres-Mendoza, Daniel; Jones, Gillian E; Fernandez, Patricia L

    2015-01-01

    The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules. PMID:26538822

  6. Marine Diterpenoids as Potential Anti-Inflammatory Agents

    PubMed Central

    González, Yisett; Torres-Mendoza, Daniel; Jones, Gillian E.; Fernandez, Patricia L.

    2015-01-01

    The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules. PMID:26538822

  7. Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

    PubMed Central

    2015-01-01

    Summary This review describes strategies for the chemical synthesis of xenicane diterpenoids and structurally related metabolites. Selected members from the four different subclasses of the Xenia diterpenoid family, the xenicins, xeniolides, xeniaphyllanes and xeniaethers, are presented. The synthetic strategies are discussed with an emphasis on the individual key reactions for the construction of the uncommon nine-membered carbocycle which is the characteristic structural feature of these natural products. Additionally, the putative biosynthetic pathway of xenicanes is illustrated. PMID:26734099

  8. Biotransformations of diterpenoids and triterpenoids: a review.

    PubMed

    Bhatti, Haq Nawaz; Khera, Rasheed Ahmad

    2014-01-01

    During the past few years, research has focused on the microbial transformation of a huge variety of organic compounds to obtain compounds of therapeutic and/or industrial interest. Microbial transformation is a useful tool for organic chemists looking for new compounds, as a consequence of the variety of reactions for natural products. Terpenoids are a large family of natural products exhibiting a wide range of biological activities such as antibiotics, anti-inflammatory, anti-HIV and anti-tumor effects; hypotensive agents; sweeteners; insecticides; anti-feedants; phytotoxic agents; perfumery intermediates; and plant growth hormones. This article describes the biotransformation products of diterpenoids and triterpenoids in a variety of biological media. Emphasis is placed on reporting the metabolites that may be of special interest as well as the practical aspects of this work in the field of microbial transformations. This review covers the literature from 1991 to 2012. PMID:24266458

  9. Synthetic Studies on Tricyclic Diterpenoids: Direct Allylic Amination Reaction of Isopimaric Acid Derivatives.

    PubMed

    Timoshenko, Mariya A; Kharitonov, Yurii V; Shakirov, Makhmut M; Bagryanskaya, Irina Yu; Shults, Elvira E

    2016-02-01

    A selective synthesis of 7- or 14-nitrogen containing tricyclic diterpenoids was completed according to a strategy in which the key step was the catalyzed direct allylic amination of methyl 14α-hydroxy-15,16-dihydroisopimarate with a wide variety of nitrogenated nucleophiles. It was revealed that the selectivity of the reaction depends on the nature of nucleophile. The catalyzed reaction of the mentioned diterpenoid allylic alcohol with 3-nitroaniline, 3-(trifluoromethyl)aniline, and 4-(trifluoromethyl)aniline yield the subsequent 7α-, 7β- and 14αnitrogen-containing diterpenoids. The reaction with 2-nitroaniline, 4-nitro-2-chloroaniline, 4-methoxy-2-nitroaniline, phenylsulfamide, or tert-butyl carbamate proceeds with the formation of 7α-nitrogen-substituted diterpenoids as the main products. PMID:27308214

  10. Synthetic Studies on Tricyclic Diterpenoids: Direct Allylic Amination Reaction of Isopimaric Acid Derivatives†

    PubMed Central

    Timoshenko, Mariya A.; Kharitonov, Yurii V.; Shakirov, Makhmut M.; Bagryanskaya, Irina Yu.

    2015-01-01

    Abstract A selective synthesis of 7‐ or 14‐nitrogen containing tricyclic diterpenoids was completed according to a strategy in which the key step was the catalyzed direct allylic amination of methyl 14α‐hydroxy‐15,16‐dihydroisopimarate with a wide variety of nitrogenated nucleophiles. It was revealed that the selectivity of the reaction depends on the nature of nucleophile. The catalyzed reaction of the mentioned diterpenoid allylic alcohol with 3‐nitroaniline, 3‐(trifluoromethyl)aniline, and 4‐(trifluoromethyl)aniline yield the subsequent 7α‐, 7β‐ and 14αnitrogen‐containing diterpenoids. The reaction with 2‐nitroaniline, 4‐nitro‐2‐chloroaniline, 4‐methoxy‐2‐nitroaniline, phenylsulfamide, or tert‐butyl carbamate proceeds with the formation of 7α‐nitrogen‐substituted diterpenoids as the main products. PMID:27308214

  11. Clerodane diterpenoids from Croton crassifolius.

    PubMed

    Wang, Guo-Cai; Li, Jia-Gui; Li, Guo-Qiang; Xu, Jiao-Jiao; Wu, Xia; Ye, Wen-Cai; Li, Yao-Lan

    2012-12-28

    Seven new clerodane diterpenoids (1-7) were isolated from roots of Croton crassifolius, along with six known compounds. The structures were elucidated by extensive spectroscopic methods (IR, UV, HRESIMS, 1D NMR, and 2D NMR), and the structures of 1, 3, 4, and 7 were confirmed by single-crystal X-ray diffraction analyses. Compounds 1-13 were evaluated for in vitro antiviral activity against herpes simplex virus type 1 using the cytopathic effect reduction assay. PMID:23194476

  12. Labdane Diterpenoids from Leonotis leonurus

    PubMed Central

    Wu, Hankui; Li, Jun; Fronczek, Frank R.; Ferreira, Daneel; Burandt, Charles L.; Setola, Vincent; Roth, Bryan L.; Zjawiony, Jordan K.

    2012-01-01

    Three known (leoleorins A-C) and eight new (leoleorins D-J and 16-epi-leoleorin F) labdane diterpenoids, were isolated from leaves of Leonotis leonurus. The absolute configurations of leoleorins A and D were established by X-ray crystallographic analyses. In competitive binding assay all isolated compounds showed inhibition in excess of 50% at various CNS receptors. Leoleorin C showed moderate binding affinity (Ki = 2.9 μM) for the Sigma 1 receptor. PMID:22445074

  13. A Novel Norclerodane Diterpenoid from the Roots of Croton crassifolius.

    PubMed

    Zhang, Zhan-Xin; Li, Hui-Hong; Fan, Gai-Xia; Li, Zheng-Yu; Dong, Le-Le; Li, Hong-Yu; Fei, Dong-Qing

    2015-11-01

    A chemical investigation of Croton crassifolius afforded a novel norclerodane diterpenoid (1) with an unprecedented six-membered oxygen ring between C-1 and C-12, together with three known compounds. The structure of the new compound was elucidated based on spectroscopic (IR, 1D, and 2D NMR) and HR-ESI-MS techniques. This report describes the first example of a natural norclerodane with a 4H-chromene ring system. PMID:26749826

  14. Two New Diterpenoids from Salvia przewarskii.

    PubMed

    Tsukada, Haruka; Kawabe, Hiroshi; Ohtaka, Aya; Saito, Yoshinori; Okamoto, Yasuko; Tori, Motoo; Kagechika, Hiroyuki; Hirota, Hiroshi; Gong, Xun; Kuroda, Chiaki; Ohsaki, Ayumi

    2016-02-01

    One abietane-type and one dinoricetexane-type diterpenoid, salviskin A (1) and salviskin B (2), respectively, together with fourteen known diterpenoids, were isolated from Salvia przewarskii. Structural elucidation of these compounds was performed by spectroscopic methods including 2D NMR. The compounds isolated were evaluated for their cytotoxicity against HeLa and HL-60 cells. PMID:27032190

  15. Asymmetric synthesis and absolute stereochemistry of a labdane-type diterpenoid isolated from the rhizomes of Isodan yuennanensis.

    PubMed

    Deng, Heping; Cao, Wei; Zhang, Zhijiang; Liu, Bo

    2016-07-14

    The first synthesis of a labdane-type diterpenoid isolated from Isodon yuennanensis was achieved in fourteen steps from commercially available starting material, (+)-sclareolide. The synthesis features the Barton nitrite ester reaction to introduce an oxime at the angular methyl group and the Jones oxidation to construct the lactone segment. By comparison of the optical rotation of our synthetic sample and the natural sample, the absolute stereochemistry of the natural diterpenoid has been determined. PMID:27251032

  16. Grindelane diterpenoids from Stevia subpubescens.

    PubMed

    Román, L U; Cambrón, J I; del Río, R E; Hernández, J D; Cerda-García-Rojas, C M; Joseph-Nathan, P

    2000-02-01

    Four new 9R,13R-epoxylabdane diterpenes (1-4) and a known clerodane derivative, 3,4beta-epoxy-5beta,10beta-cis-17alpha, 20alpha-clerod-13(14)-en-15,16-olide, were isolated from the leaves of Stevia subpubescens. The structures, which correspond to the grindelane class of diterpenoids, were elucidated by NMR data, chemical correlation, and single-crystal X-ray diffraction analysis of monoacetate 5. The absolute configuration of 1-4 is based on the optical activity of ketone 3 as compared with data of closely related substances. PMID:10691714

  17. Diterpenoid derivatives of Kenyan Croton sylvaticus.

    PubMed

    Ndunda, Beth; Langat, Moses K; Midiwo, Jacob O; Omosa, Leonidah K

    2015-04-01

    Kenyan Croton sylvaticus Hochst. ex Krauss gave four clerodane diterpenoids, the new ent-3,13E-clerodadiene-15-formate (1), the known 15-acetoxy-ent-3,13E-clerodadiene (2), ent-3,13E-clerodadien-15-ol (3) and hardwickiic acid (4), two known halimane diterpenoids, penduliflaworosin (5) and crotohalimaneic acid (6) and one labdane diterpenoid, labda-13E-ene-8a,15-diol (7). The compounds, when tested for their anti-microbial activities against Bacillus subtilis, Xanthomonas campestris and Candida albicans, were found to be inactive. PMID:25973474

  18. Syntheses of Denudatine Diterpenoid Alkaloids: Cochlearenine, N-Ethyl-1α-hydroxy-17-veratroyldictyzine, and Paniculamine.

    PubMed

    Kou, Kevin G M; Li, Beryl X; Lee, Jack C; Gallego, Gary M; Lebold, Terry P; DiPasquale, Antonio G; Sarpong, Richmond

    2016-08-31

    The denudatine-type diterpenoid alkaloids cochlearenine, N-ethyl-1α-hydroxy-17-veratroyldictyzine, and paniculamine have been synthesized for the first time (25, 26, and 26 steps from 16, respectively). These syntheses take advantage of a common intermediate (8) that we have previously employed in preparing aconitine-type natural products. The syntheses reported herein complete the realization of a unified strategy for the preparation of C20, C19, and C18 diterpenoid alkaloids. PMID:27525345

  19. Antimicrobial Diterpenoids of Wedelia trilobata (L.) Hitchc.

    PubMed

    Li, Shi-Fei; Ding, Jia-Yin; Li, Ya-Ting; Hao, Xiao-Jiang; Li, Shun-Lin

    2016-01-01

    Continued interest in the metabolites of Wedelia trilobata (L.) Hitchc, a notoriously invasive weed in South China, led to the isolation of twenty-six ent-kaurane diterpenoids, including seven new ones 1-7. Their structures and relative configuration were elucidated on the basis of extensive spectroscopic analysis, including 1D- and 2D-NMR experiments. The antimicrobial activities of all isolated diterpenoids were evaluated against a panel of bacteria and fungi. PMID:27070557

  20. Five New Diterpenoids from an Okinawan Soft Coral, Cespitularia sp.

    PubMed Central

    Roy, Prodip K.; Maarisit, Wilmar; Roy, Michael C.; Taira, Junsei; Ueda, Katsuhiro

    2012-01-01

    Five new diterpenoids 1–5 were isolated from an Okinawan soft coral, Cespitularia sp., together with the known diterpenoid, alcyonolide (6). New diterpenoid structures were elucidated by spectroscopic methods and by comparison of their NMR data with those of related compounds. Alcyonolide (6) was cytotoxic against HCT 116 cells (IC50 5.85 μM), while these new diterpenoids 1–5 were much less active (IC50 28.2–91.4 μM). PMID:23201595

  1. Diterpenoid alkaloids from the roots of Aconitum brachypodum Diels.

    PubMed

    Yang, Li-Guo; Zhang, Ying-Jie; Xie, Jia-Ying; Xia, Wei-Jun; Zhang, Hai-Yuan; Tang, Meng-Yun; Mei, Shuang-Xi; Cui, Tao; Wang, Jing-Kun; Zhu, Zhao-Yun

    2016-09-01

    A new diterpenoid alkaloid, named bullatine H (1), along with 10 known diterpenoid alkaloids were isolated from the roots of Aconitum brachypodum Diels (Ranunculaceae). The structure of 1 was elucidated by analysis of its spectroscopic data. It should be noted that compound 1 is the first example with 11, 13-dioxygenated denudatine-type diterpenoid alkaloid isolated from Aconitum brachypodum. PMID:27268073

  2. Cytotoxic diterpenoids from Rabdosia lophanthoides var. gerardianus.

    PubMed

    Lin, Chao-Zhan; Zhao, Wei; Feng, Xiu-Li; Liu, Fang-Le; Zhu, Chen-Chen

    2016-03-01

    Two new abietane diterpenoids, Gerardianin B (1) and Gerardianin C (2), one new lignan glycoside, Gerardianin D (3) and one new lupane-type triterpenoid, Gerardianol A (4), together with seven known abietane diterpenoids were isolated from the aerial parts of Rabdosia lophanthoides var. gerardianus. Their structures were determined by 1D and 2D NMR spectroscopic data. The cytotoxic activities of the nine diterpenoids were evaluated on human cancer cell lines. Compounds 6-11 exhibited significant cytotoxic activities against HepG2 cell lines with IC50 from 4.68 to 9.43μM and HCF-8 cell lines with IC50 from 9.12 to 13.53μM. PMID:26608401

  3. Diterpenoid Biopolymers: New Directions for Renewable Materials Engineering

    PubMed Central

    Hillwig, Matthew L.; Mann, Francis M.; Peters, Reuben J.

    2010-01-01

    Most types of ambers are naturally occurring, relatively hard, durable resinite polymers derived from the exudates of trees. This resource has been coveted for thousands of years due to its numerous useful properties in industrial processes, beauty, and purported medicinal properties. Labdane diterpenoid based ambers represent the most abundant and important resinites on earth. These resinites are a dwindling, non-renewable natural resource, so a new source of such materials needs to be established. Recent advances in sequencing technologies and biochemical engineering are rapidly accelerating the rate of identifying and assigning function to genes involved in terpenoid biosynthesis, as well as producing industrial-scale quantities of desired small-molecules in bacteria and yeast. This has provided new tools for engineering metabolic pathways capable of producing diterpenoid monomers that will enable the production of custom-tailored resinite-like polymers. Furthermore, this biosynthetic toolbox is continuously expanding, providing new possibilities for renewing dwindling stocks of naturally occurring resinite materials and engineering new materials for future applications. PMID:20857504

  4. Diterpenoid biopolymers: new directions for renewable materials engineering.

    PubMed

    Hillwig, Matthew L; Mann, Francis M; Peters, Reuben J

    2011-02-01

    Most types of ambers are naturally occurring, relatively hard, durable resinite polymers derived from the exudates of trees. This resource has been coveted for thousands of years due to its numerous useful properties in industrial processes, beauty, and purported medicinal properties. Labdane diterpenoid-based ambers represent the most abundant and important resinites on earth. These resinites are a dwindling nonrenewable natural resource, so a new source of such materials needs to be established. Recent advances in sequencing technologies and biochemical engineering are rapidly accelerating the rate of identifying and assigning function to genes involved in terpenoid biosynthesis, as well as producing industrial-scale quantities of desired small-molecules in bacteria and yeast. This has provided new tools for engineering metabolic pathways capable of producing diterpenoid monomers that will enable the production of custom-tailored resinite-like polymers. Furthermore, this biosynthetic toolbox is continuously expanding, providing new possibilities for renewing dwindling stocks of naturally occurring resinite materials and engineering new materials for future applications. PMID:20857504

  5. [A diterpenoid quinone from Periploca forrestii].

    PubMed

    Wang, Yan; Sun, Lei; Qiao, Shanyi

    2010-06-01

    Tanshinone II A, which was known unique to the salvia, was separated and purified by silica gel column chromatography and recrystallisation from an ethyl acetate-soluble portion (the anti-inflammatory active portion) of ethanol extract of Periploca forrestii. The diterpenoid quinone was obtained from the Periploca for the first time. PMID:20815227

  6. Identification of a new cyathane diterpene that induces mitochondrial and autophagy-dependent apoptosis and shows a potent in vivo anti-colorectal cancer activity.

    PubMed

    He, Luwei; Han, Junjie; Li, Baowei; Huang, Li; Ma, Ke; Chen, Quan; Liu, Xinzhong; Bao, Li; Liu, Hongwei

    2016-03-23

    Diterpenes has been reported to possess multiple bioactivities consisting of anti-microbial and anti-inflammatory properties. This study reveals a new cyathane-type diterpene (cyathin Q) from the culture of the fungus Cyathus africanus by bioactivity-guided separation. The structure of cyathin Q was determined based on spectroscopic measurements (NMR and MS). The bioactivity evaluation shows that cyathin Q has a strong anticancer activity against HCT116 cells and Bax-deficient HCT116 in vitro and in vivo. This compound induced hallmarks of apoptotic events in HCT116 cells, including caspase activation, cytochrome c release, poly (ADP-ribose) polymerase (PARP) cleavage, and depolarization of the mitochondrial inner transmembrane potential. This process is accompanied with the increased mitochondrial ROS, down-regulation of Bcl-2 protein, and up-regulation of Bim protein. We also observed the cleavage of autophagy-related protein ATG5 in cyathin Q-induced apoptosis. Taken together, our study identified a new fungal diterpene that exhibited anticancer activity via induction of mitochondria and autophagy-dependent apoptosis in HCT116 cells. PMID:26871659

  7. Oridonin, a Promising ent-Kaurane Diterpenoid Lead Compound.

    PubMed

    Li, Dahong; Han, Tong; Liao, Jie; Hu, Xu; Xu, Shengtao; Tian, Kangtao; Gu, Xiaoke; Cheng, Keguang; Li, Zhanlin; Hua, Huiming; Xu, Jinyi

    2016-01-01

    Oridonin belongs to ent-kaurane tetracyclic diterpenoid and was first isolated from Isodon species. It exhibits inhibitory activities against a variety of tumor cells, and pharmacological study shows that oridonin could inhibit cell proliferation, DNA, RNA and protein synthesis of cancer cells, induce apoptosis and exhibit an antimutagenic effect. In addition, the large amount of the commercially-available supply is also very important for the natural lead oridonin. Moreover, the good stability, suitable molecular weight and drug-like property guarantee its further generation of a natural-like compound library. Oridonin has become the hot molecule in recent years, and from the year 2010, more than 200 publications can be found. In this review, we summarize the synthetic medicinal chemistry work of oridonin from the first publication 40 years ago and share our research experience of oridonin for about 10 years, which may provide useful information to those who are interested in this research field. PMID:27563888

  8. Euphorbesulins A-P, Structurally Diverse Diterpenoids from Euphorbia esula.

    PubMed

    Zhou, Bin; Wu, Yan; Dalal, Seema; Cassera, Maria B; Yue, Jian-Min

    2016-08-26

    Aqueous ethanol extracts of powdered twigs of Euphorbia esula afforded 16 new diterpenoids, named euphorbesulins A-P. These euphorbesulins included presegetane (1-3), jatrophane (4-14), paraliane (15), and isopimarane (16) diterpenoids as well as six known analogues. Compounds 1-3 represent a rare type of presegetane diterpenoid. Their structures were determined by analysis of the spectroscopic data, and the absolute configuration of 1 was established by X-ray crystallography. Diterpenoid 7 showed low nanomolar antimalarial activity, while the remaining compounds showed only moderate or no antimalarial activity. PMID:27447736

  9. A new kaurane diterpenoid from Isodon inflexus.

    PubMed

    Xu, Guang-Hua; Cai, Xing-Fu; Jin, Xuejun; Lee, Jung Joon

    2016-01-01

    A new 7,20-epoxy kaurane diterpenoid, 15-acetyldemethylkamebacetal A (1) and six known kaurane diterpenoids (2-7) were isolated from the aerial parts of Isodon inflexus in nuclear transcription factor-κB (NF-κB)-dependent reporter gene assay-guided fractionation. Their chemical structures were determined on the basis of extensive spectroscopic analysis (UV, IR, MS, 1D- and 2D-NMR) and comparison with literature data. The isolated compounds were evaluated for their inhibitory effects on TNF-α-induced NF-κB activation, and all compounds exhibited NF-κB inhibitory activities with IC50 values ranging from 1.91 to 20.15 μM. PMID:26461051

  10. Bis-spirolabdane Diterpenoids from Leonotis nepetaefolia

    PubMed Central

    Li, Jun; Fronczek, Frank R.; Ferreira, Daneel; Burandt, Charles L.; Setola, Vincent; Roth, Bryan L.; Zjawiony, Jordan K.

    2012-01-01

    Ten new bis-spirolabdane diterpenoids, leonepetaefolins A–E (1, 3, 5, 7, 9) and 15-epi-leonepetaefolins A-E (2, 4, 6, 8, 10), together with eight known labdane diterpenoids (11–18) as well as two known flavonoids apigenin and cirsiliol, were isolated from the leaves of Leonotis nepetaefolia. The structures of the new compounds were determined on the basis of 1D-and 2D-NMR experiments including 1H, 13C, DEPT, 1H-1H COSY, HSQC, HMBC, and NOESY. The absolute configuration of an epimeric mixture of 1 and 2 was determined by X-ray crystallographic analysis. The compounds isolated were evaluated for their binding propensity in several CNS G protein-coupled receptor assays in vitro. PMID:22475308

  11. New kaurene diterpenoid glycosides from fenugreek seeds.

    PubMed

    Pang, Xu; Kang, Li-Ping; Yu, He-Shui; Zhao, Yang; Xiong, Cheng-Qi; Zhang, Jie; Ma, Bai-Ping

    2013-01-01

    Two new kaurene diterpenoid glycosides, named Graecumoside A (1) and B (2), were isolated from fenugreek seeds, along with three known flavonoid-C-glycosides, isoorientin (3), isovitexin (4) and vitexin (5). By combined analyses of 1D- and 2D-NMR, and MS spectroscopy, the structures of two new compounds were elucidated as 3-O-β- D-glucopyranosyl kaur-5, 16-dien-3β, 6, 13β-trihydroxy-7-oxo-18-oic acid methyl ester and 3-O-β-neohesperidosyl kaur-5, 16-dien-3β, 6, 13β-trihydroxy-7-oxo-18-oic acid methyl ester, respectively. The kaurene diterpenoid glycosides were first isolated and identified from fenugreek seeds. PMID:22950814

  12. Anti-inflammatory diterpenoids from Croton tonkinensis.

    PubMed

    Kuo, Ping-Chung; Yang, Mei-Lin; Hwang, Tsong-Long; Lai, Yuan-Yu; Li, Yue-Chiun; Thang, Tran Dinh; Wu, Tian-Shung

    2013-02-22

    Phytochemical investigation of the methanolic extract of Croton tonkinensis afforded two known kauranes (1, 2), eight new ent-kauranes (3-10), and 16 known ent-kaurane-type diterpenoids (12-27). In addition, 30 known compounds were identified by comparison of their physical and spectroscopic data with reported data. Among the isolated compounds, ent-18-acetoxykaur-16-en-15-one (20) displayed the most significant inhibition of superoxide anion generation and elastase release. PMID:23347584

  13. New 3,4-seco-Grayanane Diterpenoids from the Flowers of Pieris japonica.

    PubMed

    Cao, Lang; Li, Yanping; Li, Hongmei; Liu, Dan; Li, Rongtao

    2016-01-01

    Three new 3,4-seco-grayanane diterpenoids, neopierisoids D-F (2-4), and a new natural one, neopierisoid C (1), were isolated from the flowers of Pieris japonica. Their structures were elucidated on the basis of extensive spectroscopic analysis, including one and two dimensional (1- and 2D)-NMR, as well as high resolution-electron ionization (HR-EI)-MS. PMID:27477663

  14. A Group of ent-Kaurane Diterpenoids Inhibit Hedgehog Signaling and Induce Cilia Elongation

    PubMed Central

    Jiang, Shiyou; Du, Jiacheng; Kong, Qinghua; Li, Chaocui; Li, Yan; Sun, Handong; Pu, Jianxin; Mao, Bingyu

    2015-01-01

    The Hedgehog (Hh) signaling pathway plays important roles in the tumorigenesis of multiple cancers and is a key target for drug discovery. In a screen of natural products extracted from Chinese herbs, we identified eight ent-Kaurane diterpenoids and two triterpene dilactones as novel Hh pathway antagonists. Epistatic analyses suggest that these compounds likely act at the level or downstream of Smoothened (Smo) and upstream of Suppressor of Fused (Sufu). The ent-Kauranoid-treated cells showed elongated cilia, suppressed Smo trafficking to cilia, and mitotic defects, while the triterpene dilactones had no effect on the cilia and ciliary Smo. These ent-Kaurane diterpenoids provide new prototypes of Hh inhibitors, and are valuable probes for deciphering the mechanisms of Smo ciliary transport and ciliogenesis. PMID:26439749

  15. An unusual mulinane diterpenoid from the Chilean plant Azorella trifurcata (Gaertn) Pers.

    PubMed

    Areche, Carlos; Sepulveda, Beatriz; San Martin, Aurelio; Garcia-Beltrán, Olimpo; Simirgiotis, Mario; Cañete, Alvaro

    2014-09-01

    Four new mulinane-type diterpenoids besides the known compounds mulin-11,13-dien-20-oic acid, 13α-hydroxyazorellane, 13β-hydroxyazorellane, mulinolic acid, azorellanol, and mulin-11,13-dien-18-acetoxy-16,20-dioic acid were isolated from the Chilean plant Azorella trifurcata. One of the new metabolites isolated, 7α-acetoxy-9-epi-13β-hydroxymulinane, possesses a new trans-syn-trans arrangement in a tricyclic ring system not previously encountered in nature. Among the mulinane diterpenoids isolated, mulin-11,13-dien-20-oic acid showed the gastroprotective effect on HCl-EtOH-induced gastric lesions in mice (ED50 = 55 mg kg(-1)). Regarding the mode of gastroprotective action for this active compound, its effect was reduced by pre-treatment of the mice with indomethacin and N-ethylmaleimide, suggesting that prostaglandins and sulfhydryl compounds are positively involved in the gastroprotective activity using this model. PMID:25008488

  16. Leonuketal, a Spiroketal Diterpenoid from Leonurus japonicus.

    PubMed

    Xiong, Liang; Zhou, Qin-Mei; Zou, Yike; Chen, Ming-Hua; Guo, Li; Hu, Guan-Ying; Liu, Zhao-Hua; Peng, Cheng

    2015-12-18

    An architecturally complex spiroketal diterpenoid, leonuketal (1), was isolated from the aerial parts of the plant Leonurus japonicus. This compound possessed an unprecedented tetracyclic skeleton that comprised a bridged spiroketal moiety fused with a ketal-γ-lactone unit. The structure and absolute configuration were determined by spectroscopic analyses, a modified Mosher's method, and ECD (electronic circular dichroism) calculations. Leonuketal (1) showed significant vasorelaxant activity against KCl-induced contraction of rat aorta, with the EC50 value of 2.32 μM. PMID:26634796

  17. New Diterpenoids from Soft Coral Sarcophyton ehrenbergi

    PubMed Central

    Wang, Shang-Kwei; Hsieh, Mu-Keng; Duh, Chang-Yih

    2013-01-01

    Continuing chemical investigation on the acetone extracts of the soft coral Sarcophyton ehrenbergi collected off the coast of San-hsian-tai, Taitong County, Taiwan led to the isolation of two new diterpenoids, ehrenbergol C and acetyl ehrenberoxide B (1 and 2). The structures of these isolated metabolites were elucidated through extensive spectroscopic analyses. Moreover, in vitro tests show that compounds 1 and 2 displayed antiviral activity towards human cytomegalovirus, with EC50 of 20 and 8.0 µg/mL, respectively. PMID:24177676

  18. Two new diterpenoids from Croton crassifolius.

    PubMed

    Hu, Ying; Zhang, Lei; Wen, Xiao-Qiong; Zeng, Xiao-Jun; Rui, Wen; Cen, Ying-Zhou

    2012-01-01

    Two new clerodane-type diterpenoids were isolated from the roots of Croton crassifolius Geisel. The structures of these compounds were elucidated as 9-[2-(2(5H)-furanone-4-yl)ethyl]-4,8,9-trimethyl-1,2,3,4,5,6,7,8-octahydronaphthalene-4-carboxylic acid (1) and methyl 9-[2-(2(5H)-furanone-4-yl)ethyl]-4,8,9-trimethyl-1,2,3,4,5,6,7,8-octahydronaphthalene-4-carboxylic ester (2) by spectroscopic methods. PMID:22694251

  19. New Cytotoxic Tigliane Diterpenoids from Croton caudatus.

    PubMed

    Chen, Ying-Ying; Yang, Kun-Xian; Yang, Xing-Wei; Khan, Afsar; Liu, Lu; Wang, Bei; Zhao, Yun-Li; Liu, Ya-Ping; Li, Yan; Luo, Xiao-Dong

    2016-05-01

    Three new tigliane-type diterpenoids were isolated from the methanolic extract of the twigs and leaves of Croton caudatus, trivially named crotusins A-C (1-3). The structures of compounds 1-3 were elucidated on the basis of extensive spectral methods. These new compounds were highly oxygenated and heavily substituted. Cytotoxic activity against five human tumor cell lines was assessed for compounds 1-3 of which compound 3 showed significant inhibitory activity with IC50 values ranging from 0.49 to 4.19 µM against these cells, while crotusins A and B exhibited moderate activity. PMID:27002392

  20. Antimicrobial abietane diterpenoids from Plectranthus elegans.

    PubMed

    Dellar, J E; Cole, M D; Waterman, P G

    1996-02-01

    Two novel abietane diterpenoids have been isolated from the aerial material of Plectranthus elegans and identified as 11-hydroxy-12-oxo-7,9(11),13-abietatriene and 7 alpha,11-dihydroxy-12-methoxy-8,11,13-abietatriene. Their structures were determined through rigorous use of spectroscopic methods. Both inhibited spore germination of the fungus Cladosporium cucumerinum, in direct bioautography, at a dose of 1 microgram. The new diterpenes also inhibited the growth of Gram-positive bacteria, in the concentration range 10-40 micrograms ml-1 in broth dilution assay. No effect was observed against Gram-negative bacteria. The ecological implications of these findings are discussed. PMID:8835454

  1. New jatrophane diterpenoid esters from Euphorbia turczaninowii.

    PubMed

    Liu, L G; Tan, R X

    2001-08-01

    Five new (1-5) and one known (6) jatrophane diterpenoid esters were isolated from the ethanol extract of the whole herb of Euphorbia turczaninowii. Their structures were established by extensive spectroscopic methods. The absolute stereochemistry of 3 beta,5 alpha,8 alpha,15 beta-tetraacetoxy-7 beta-benzoyloxyjatropha-6(17),11E-dien-9,14-dione (1) was confirmed by a single-crystal X-ray analysis coupled with the exciton chirality circular dichroism method. Compounds 1-6 were inactive when evaluated both in a mouse ear inflammation assay and for cytotoxicity against the B16 mouse melanoma cell line. PMID:11520228

  2. New macrocyclic diterpenoids from Euphorbia esula.

    PubMed

    Liu, L G; Meng, J C; Wu, S X; Li, X Y; Zhao, X C; Tan, R X

    2002-03-01

    The structures of two new macrocyclic jatrophane diterpenoid esters from the whole herb of Euphorbia esula, were established as 11,14-epoxy-3beta,5alpha,7beta,8alpha,9alpha,15beta-hexaacetoxy-12-oxo-13alphaH-jatropha-6(17)-ene (1) and 1alpha,3beta-diacetoxy-5alpha,7beta-dibenzoyloxy-9,14-dioxo-11beta,12alpha-epoxy-2alpha,8alpha,15beta-trihydroxy-13betaH-jatropha-6(17)-ene (2) by a combination of 1D- and 2D-NMR techniques as well as UV, IR and mass spectral data. Bioassay evaluation of all isolates against the human tumor cell lines (B16, KB, SMMC and BGC) indicated that ester 2 was cytotoxic to B16 with the IC50 value being 1.81 microg/ml. In addition, the irritant activity assay indicated that both diterpenoids were inactive (ID(24)50 > 100 microg/ear). PMID:11914962

  3. Nitrogen-Containing Diterpenoids, Sesquiterpenoids, and Nor-Diterpenoids from Cespitularia taeniata

    PubMed Central

    Wang, Shih-Sheng; Cheng, Yuan-Bin; Lin, Yu-Chi; Liaw, Chia-Ching; Chang, Jiun-Yang; Kuo, Yao-Haur; Shen, Ya-Ching

    2015-01-01

    Two new nitrogen-containing verticillene diterpenoids, cespilamides A and B (1 and 2), three new nitrogen-containing sesquiterpenoids, cespilamides C–E (3–5), and five new norverticillene and verticillene diterpenoids, cespitaenins A–E (6–10), were isolated from the Taiwanese soft coral Cespitularia taeniata. Compound 1 possesses an unusual oxazo ring system at C-10 while compound 2 displays an unprecedented C–C bond cleavage between C-10 and C-11 with an N-ethylphenyl group at C-10. Biogenetic pathways of 1 and 2 are proposed. The absolute configuration of 1 was confirmed by Mosher’s method and molecular mechanics calculations (MM2). The cytotoxicities of compounds 1–10 were evaluated against a small panel of human cancer cell lines. PMID:26389921

  4. Bicyclic sesquiterpenoids and diterpenoids in Australian crude oils

    NASA Astrophysics Data System (ADS)

    Paul Philp, R.; Gilbert, Trevor D.; Friedrich, Jane

    1981-07-01

    Bicyclanes previously reported only in heavily biodegraded Texas Gulf Coast crudes have been found to be ubiquitous in Australian crude oils of non-marine origin from four different basins. The compounds are present in oils, thought to be derived from the same or similar sources, that have undergone varying degrees of biodegradation. They are also found to be present in oils of different geological age. In addition a series of tricyclic diterpenoid hydrocarbons was common to four oils from the Gippsland Basin. Four of these compounds had the molecular formula C 20H 34 and mass spectral fragmentation patterns suggested they were mono-unsaturated diterpenoids. The presence of unsaturated diterpenoids in crude oils appears to be a unique observation. It is proposed that the diterpenoids may be the source of the bicyclanes also observed in these oils.

  5. A new cassane diterpenoid from the seeds of Caesalpinia decapetala.

    PubMed

    Wei, Hua; Liu, Xiao-Qian; Zhu, Jing-Jing; Gao, Liang-Liang; Wang, Zhi-Min; Yan, Li-Hua

    2016-04-01

    Phytochemical investigation on the seeds of Caesalpinia decapetala led to the isolation of a new cassane diterpenoid with an unusual O bridge between C-19 and C-20, named phanginin Q (1), together with three known cassane diterpenoids, caesaljapin (2), caesaldekarin A (3), and caesaldekarin B (4). The structure of the new compound was elucidated by spectroscopic methods, including (1)H NMR, (13)C NMR, HSQC, (1)H - (1)H COSY, HMBC, NOESY, and HR-ESI-MS. PMID:26268793

  6. Total synthesis of diterpenoid steenkrotin A.

    PubMed

    Pan, Saiyong; Xuan, Jun; Gao, Beiling; Zhu, An; Ding, Hanfeng

    2015-06-01

    A concise and diastereoselective total synthesis of the diterpenoid (±)-steenkrotin A is described for the first time. The strategy mainly features three key ring formations: 1) a rhodium-catalyzed O-H bond insertion followed by an intramolecular carbonyl-ene reaction to build up the tetrahydrofuran subunit; 2) sequential SmI2 -mediated Ueno-Stork and ketyl-olefin cyclizations to construct the [5,7] spirobicyclic skeleton; and 3) an intramolecular aldol condensation/vinylogous retro-aldol/aldol sequence to form the final six-membered ring with inversion of the relative configuration at the C7 position. PMID:25891977

  7. Bioactive diterpenoid containing a reversible "spring-loaded" (E,Z)-dieneone Michael acceptor.

    PubMed

    Gupta, Prasoon; Sharma, Upasana; Schulz, Thomas C; Sherrer, Eric S; McLean, Amanda B; Robins, Allan J; West, Lyndon M

    2011-08-01

    Three new briarane diterpenoids, briareolate esters L-N (1-3), have been isolated from a gorgonian Briareum asbestinum. Briareolate esters L (1) and M (2) are the first natural products possessing a 10-membered macrocyclic ring with a (E,Z)-dieneone and exhibit growth inhibition activity against both human embryonic stem cells (BG02) and a pancreatic cancer cell line (BxPC-3). Briareolate ester L (1) was found to contain a "spring-loaded" (E,Z)-dieneone Michael acceptor group that can form a reversible covalent bond to model sulfur-based nucleophiles. PMID:21749084

  8. Eight new diterpenoids and two new nor-diterpenoids from the stems of Croton cascarilloides.

    PubMed

    Kawakami, Susumu; Toyoda, Hiroki; Harinantenaina, Liva; Matsunami, Katsuyoshi; Otsuka, Hideaki; Shinzato, Takakazu; Takeda, Yoshio; Kawahata, Masatoshi; Yamaguchi, Kentaro

    2013-01-01

    From the stems of Croton cascarilloides, eight new diterpenoids, named crotocascarins A-H (1-8), having a crotofolane skeleton were isolated along with two new nor-diterpenoids (9 and 10), named crotocascarins α and β, derived through rearrangement of the crotofolane skeleton. The structures of these compounds were elucidated by means of extensive one- and two-dimensional NMR spectroscopic analyses. The absolute structures of the diterpene moiety were determined by application of the circular dichroism (CD) rule for the γ-lactone ring. The relative structures of the two crotofolanes (1 and 2) and one rearranged compound (9) were confirmed by X-ray crystallographic analyses. Compounds 1, 2 and 9 possessed 2-methylbutyric acid in their molecules, the absolute configuration of which was found to be 2S by comparison of its HPLC behavior with that of an authentic sample. Therefore, the absolute structures of these crotocascarins (1, 2 and 9) were unambiguously determined. The absolute structures of crotofolanes are reported for the first time in this paper. PMID:23370306

  9. Diterpenoid glycosyl esters from Phlomis younghusbandii and P. medicinalis roots.

    PubMed

    Katagiri, M; Ohtani, K; Kasai, R; Yamasaki, K; Yang, C R; Tanaka, O

    1994-01-01

    From the roots of Phlomis younghusbandii collected in Tibet, new furanolabdane-type diterpenoid glycosides named phlomisosides III and IV were isolated together with a known sweet furanolabdane-type diterpenoid glycoside, phlomisoside I. The structure of the common aglycone of phlomisosides III and IV, which we have named phlomisoic acid, was established as 15,16-epoxy-8,13(16),14-labdatrien-19-oic acid by MS and NMR spectroscopy. Phlomisosides III and IV are tasteless and the structures of these were determined to be the beta-D-xylopyranosyl(1-->2)-beta-D-glucopyranosyl and the alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl ester of phlomisoic acid by chemical and spectroscopic methods, respectively. The diterpenoid glycoside constituents of the roots of P. medicinalis collected in Tibet were also elucidated, and baiyunoside and phlomisosides II and III were isolated and identified. PMID:7764482

  10. Structure-cardiac activity relationship of C19-diterpenoid alkaloids.

    PubMed

    Jian, Xi-Xian; Tang, Pei; Liu, Xiu-Xiu; Chao, Ruo-Bing; Chen, Qiao-Hong; She, Xue-Ke; Chen, Dong-Lin; Wang, Feng-Peng

    2012-06-01

    Thirty three C19-diterpenoid alkaloids, twenty-two prepared from known C19-diterpenoid alkaloids and eleven isolated from Aconitum and Delphinium spp. were evaluated for their cardiac activity in the isolated bullfrog heart assay. Among them, eleven compounds exhibited cardiac activity, with average rate of amplitude increase in the range of 16-118%. Compound 7, mesaconine (17), hypaconine (25), and beiwutinine (26) exhibited strong cardiac activities relative to the reference drug. The structure-activity relationship data acquired indicated that an alpha-hydroxyl group at C-15, a hydroxyl group at C-8, an alpha-methoxyl or hydroxyl group at C-1, and a secondary amine or N-methyl group in ring A are important structure features necessary for the cardiac activities of the aconitine-type C19-diterpenoid alkaloids without any ester groups. In addition, an alpha-hydroxyl group at C-3 is also helpful for the cardiac activity of these alkaloids. PMID:22816290

  11. Biochemistry and toxicology of the diterpenoid glycoside atractyloside.

    PubMed

    Obatomi, D K; Bach, P H

    1998-04-01

    Atractyloside (Atr) is a diterpenoid glycoside that occurs naturally in plants (many of which are used in ethnomedicines) found in Europe, Africa, South America, Asia and the far East. It is also present in animal grazing forage. Atr (and its analogues) may be present at levels as high as 600 mg/kg dried plant material. Consumption of the plants containing Atr or carboxyatractyloside (carboxyAtr) has caused fatal renal proximal tubule necrosis and/or centrilobular hepatic necrosis in man and farm animals. Although pure Atr and crude plant extracts disrupt carbohydrate homeostasis and induce similar pathophysiological lesions in the kidney and liver, it is also possible that the toxicity of Atr may be confounded by the presence of other natural constituents in plants. Atr competitively inhibits the adenine nucleoside carrier in isolated mitochondria and thus blocks oxidative phosphorylation. This has been assumed to explain changes in carbohydrate metabolism and the toxic effects in liver and kidney. Although the acute toxicity of Atr is well described, many aspects of Atr toxicity (subchronic and chronic toxicity, reproductive toxicity, mutagenicity and carcinogenicity) have not been investigated and pharmacokinetic and metabolism data are limited. In vitro proximal tubular cells are selectively sensitive to Atr, whereas other renal cell types are quite resistant. There are also differences in the response of liver and renal tissue to Atr. Thus, not all of the clinical, biochemical and morphological changes caused by Atr can simply be explained on the basis of inhibition of mitochondrial phosphorylation. The relevance to a wider human risk is shown by the presence of Atr analogues in dried roasted Coffea arabica beans (17.5 32 mg/kg). There are no data to help identify the risk of low dose chronic exposure in human coffee consumers, nor is there information on the levels of Atr or its analogues in other commonly consumed human foodstuffs. PMID:9651051

  12. Diterpenoids from Callicarpa kwangtungensis and their NO inhibitory effects.

    PubMed

    Xu, Jing; Li, Shen; Sun, Xiaocong; Ma, Jun; Liu, Feng; Tong, Ling; Lee, Dongho; Ohizumi, Yasushi; Tuerhong, Muhetaer; Guo, Yuanqiang

    2016-09-01

    A phytochemical investigation of the leaves of Callicarpa kwangtungensis led to the isolation of three new diterpenoids (1-3), callipenes A-C, and eleven known analogues (4-14). Their structures were established on the basis of extensive analysis of NMR spectroscopic data, X-ray diffraction data, and experimental and calculated electronic circular dichroism spectra. Compounds 1 and 2 are rare abietane diterpenoids possessing a peroxide bridge. All of the isolates were found to inhibit LPS-induced NO production in BV-2 cells. PMID:27491749

  13. New Cembrane Diterpenoids from a Hainan Soft Coral Sinularia sp

    PubMed Central

    Yang, Bin; Zhou, Xuefeng; Huang, Hui; Yang, Xian-Wen; Liu, Juan; Lin, Xiuping; Li, Xiubao; Peng, Yan; Liu, Yonghong

    2012-01-01

    Five new cembrane diterpenoids, named sinuflexibilins A–E (1–5), along with nine other known diterpenoids (6–14), have been isolated from the organic extract of a Hainan soft coral Sinularia sp. Their structures were determined on the basis of extensive spectroscopic analyses and by comparison of their spectral data with those of related metabolites. Compound 13, flexibilide, exhibited significant inhibitory activity of NF-κB activation using the cell-based HEK293 NF-κB luciferase reporter gene assay. PMID:23118718

  14. Hepatoprotective diterpenoids from the roots of Salvia grandifolia.

    PubMed

    Kang, Jie; Zhang, Ting; Li, Li; Sun, Hua; Wang, Ding-Ding; Chen, Ruo-Yun

    2016-05-01

    One new diterpenoid, grandifolia G (1), together with a known diterpenoid (6,7,8,8a-tetrahydro-6,6-dimethyl-2-oxonaphtho[1,8-bc]furan-3-yl)-4-methylfuran-3-carboxylic acid (2), was isolated from 70% EtOH extract of root of Salvia grandifolia. Their structures were determined by UV, IR, HRESIMS, NMR spectra. Compounds 1 and 2 (10 μM) exhibited hepatoprotective activities (61 and 55%) against DL-galactosamine-induced cell damage in HL-7702 cells. PMID:27086714

  15. neo-Clerodane diterpenoids from Scutellaria barbata with cytotoxic activities.

    PubMed

    Dai, Sheng-Jun; Tao, Jia-Yi; Liu, Ke; Jiang, Yong-Tao; Shen, Li

    2006-07-01

    Three neo-clerodane diterpenoids, named barbatins A-C (1-3), and the neo-clerodane diterpenoid nicotinyl ester, named scutebarbatine B (4), were isolated from the whole plant of Scutellaria barbata D. Don. Their structures were elucidated by spectroscopic analyses (UV, IR, HRFAB-MS, 1D NMR and 2D NMR). In vitro, compounds 1-4 showed significant cytotoxic activities against three human cancer lines, namely, HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells, with IC50 values in the range 3.5-8.1 microM. PMID:16769097

  16. Fimbriatols A–J, Highly Oxidized ent-Kaurane Diterpenoids from Traditional Chinese Plant Flickingeria fimbriata (B1.) Hawkes

    PubMed Central

    Ding, Gang; Fei, Jiaodong; Wang, Jing; Xie, Yong; Li, Rongtao; Gong, Ningbo; Lv, Yang; Yu, Changyuan; Zou, Zhongmei

    2016-01-01

    Fimbriatols A–J (1–10), ten new ent-kaurane diterpenoids possessing differently highly oxidized sites, were isolated from Flickingeria fimbriata (B1.) Hawkes. The structures of these new compounds were determined by HRESI-MS, NMR, CD spectra and X-ray diffraction analysis. Compound 1 displayed moderately inhibitory ratio (48.5%) compared with the positive compound NSC-87877 (81.6%) at the concentration of 0.022 μg/mL. Compounds 7–10 possess 3, 4-seco-ent-kaurane skeleton containing a disaccharide moiety with an unusual linkage at C-2′ to C-1′′ instead of the common linkage at C-6′ to C-1′′, and this is the first report in 600 more ent-kauranes found in nature, which might be originated from ent-kaurane diterpenoids through post-modified reactions of Baeyer-Villiger oxygenation and glycosylation. PMID:27484744

  17. Fimbriatols A-J, Highly Oxidized ent-Kaurane Diterpenoids from Traditional Chinese Plant Flickingeria fimbriata (B1.) Hawkes.

    PubMed

    Ding, Gang; Fei, Jiaodong; Wang, Jing; Xie, Yong; Li, Rongtao; Gong, Ningbo; Lv, Yang; Yu, Changyuan; Zou, Zhongmei

    2016-01-01

    Fimbriatols A-J (1-10), ten new ent-kaurane diterpenoids possessing differently highly oxidized sites, were isolated from Flickingeria fimbriata (B1.) Hawkes. The structures of these new compounds were determined by HRESI-MS, NMR, CD spectra and X-ray diffraction analysis. Compound 1 displayed moderately inhibitory ratio (48.5%) compared with the positive compound NSC-87877 (81.6%) at the concentration of 0.022 μg/mL. Compounds 7-10 possess 3, 4-seco-ent-kaurane skeleton containing a disaccharide moiety with an unusual linkage at C-2' to C-1'' instead of the common linkage at C-6' to C-1'', and this is the first report in 600 more ent-kauranes found in nature, which might be originated from ent-kaurane diterpenoids through post-modified reactions of Baeyer-Villiger oxygenation and glycosylation. PMID:27484744

  18. The simultaneous analysis of proteins, lipids, and diterpenoid resins found in cultural objects.

    PubMed

    Singer, Brian; McGuigan, Ross

    2007-07-01

    We report a GC-MS method for the simultaneous analysis of proteins oil, and diterpenoid resins found in cultural objects. The method was initially designed for protein analysis of protenaceous paints and adhesives and involves acid hydrolysis as the first step. The amino acids in the protein hydrolysates, thus obtained, are treated with propan-l-ol/ hydrogen chloride and then pentafluoropropionic anhydride. The procedure was found also to yield the propyl esters of fatty acids derived from lipids and diterpenoid acids derived from natural resins, and thus allows the choice of a single method for the analysis of artists media which contain either oil s or proteins or mixtures of both proteins and oils or even resins. Thus natural mixtures such as egg yolk and also mixtures made by the artist such as animal glue/seed oil emulsions can be analysed. Coupled with FTIR analysis of paints and the staining of cross sections, to indicate layer structure the method can help to elucidate the paints and adhesives used by artists. PMID:17867529

  19. New clerodane diterpenoids from the roots of Polyalthia laui.

    PubMed

    Yu, Zhang-Xin; Fu, Yan-Hui; Chen, Guang-Ying; Song, Xiao-Ping; Han, Chang-Ri; Li, Xiao-Bao; Song, Xin-Ming; Wu, Ai-Zhen; Chen, Shi-Chen

    2016-06-01

    Five new clerodane diterpenoids, polylauiester A (1), (4→2)-abeo-2,13-diformyl-cleroda-2,12E-dien-14-oic acid (2) and polylauiamides B-D (3-5), together with 11 known clerodane diterpenoids (6-16), were isolated from the roots of Polyalthia laui. Among them, polylauiester A (1) represents the first example of a novel norclerodane diterpenoid only containing 17 carbon atoms on the carbon skeleton, and polylauiamide B (3) is an unusual diterpenoid with a p-substituted benzene ring as a substituent. Their structures were elucidated by extensive spectroscopic methods, and the relative configuration of polylauiamide B (3) was further confirmed by the single crystal X-ray diffraction method. Biological evaluation of new compounds against human Hela, MCF-7 and A549 human cancer cell lines showed that all compounds displayed weak cytotoxicities against various human cancer cell lines in the range of IC50 at 25.01-39.31μM. PMID:27058277

  20. Maize Kauralexins: inducible diterpenoid phytoalexins protect against fungal pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phytoalexins constitute a broad category of pathogen and insect-inducible biochemicals that locally protect plant tissues. In rice, a complex array of inducible diterpenoid phytoalexins constitute an important component of the plants anti-pathogen defenses. In contrast, despite the demonstration of ...

  1. Prenylbicyclogermacrane diterpenoids from the formosan soft coral Nephthea elongata.

    PubMed

    El-Gamal, Ali Ali Hassan; Wang, Shang-Kwei; Duh, Chang-Yih

    2007-06-01

    Seven new prenylbicyclogermacrane diterpenoids, pacificins K--Q (1--7), were isolated from the methylene chloride solubles of the Formosan soft coral Nephthea elongata. Their structures were elucidated by extensive spectroscopic analysis and their cytotoxicity against selected cancer cells was measured in vitro. PMID:17541187

  2. Two diterpenoids from the roots of gaultheria yunnanensis

    PubMed

    Zhang; Guo; Li; Zheng; Koike; Jia; Nikaido

    1999-02-01

    Two new diterpenoids, gaultheric acid (1) and gaultheronoterpene (2), were isolated from the roots ofGaultheria yunnanensis. Their structures were elucidated as 12-hydroxy-13-acetyl-8,11, 13-podocarpatrien-18-oic acid (1) and 3beta, 12-dihydroxy-13-acetyl-4(18),8,11,13-podocarpatetraene (2) on the basis of spectral analysis. PMID:10075764

  3. Supression of inflammatory responses by labdane-type diterpenoids

    SciTech Connect

    Giron, Natalia; Rodriguez, Benjamin; Lopez-Fontal, Raquel; Bosca, Lisardo; Hortelano, Sonsoles Heras, Beatriz de las

    2008-04-15

    A series of 11 labdane-type diterpenoids (1-11) with various patterns of substitution were tested for potential anti-inflammatory activity. Of these compounds, 4 and 11 were selected to evaluate their influence on targets relevant to the regulation of the inflammatory response. These diterpenoids reduced the production of nitric oxide (NO), prostaglandin E2, and tumor necrosis factor-{alpha} in LPS-activated RAW 264.7 macrophages, with IC50 in the range 1-10 {mu}M. Inhibition of these inflammatory mediators was related to inhibition of the expression of nitric oxide synthase-2 (NOS-2) and cyclooxygenase-2 (COX-2) at the transcriptional level, as determined by western-blot and RT-PCR. Examination of the effects of these diterpenoids on nuclear factor {kappa}B signaling showed that both compounds inhibit the phosphorylation of I{kappa}B{alpha} and I{kappa}B{beta}, preventing their degradation and the nuclear translocation of the NF-{kappa}B p65 subunit. Inhibition of IKK activity was also observed. These derivatives displayed significant anti-inflammatory activity in vivo, suppressing mouse ear edema induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) and inhibiting myeloperoxidase activity, an index of neutrophil infiltration. The anti-inflammatory effects of these labdane diterpenoids, together with their low cell toxicity, suggest potential therapeutic applications in the regulation of the inflammatory response.

  4. Bioactivity-guided isolation of antiproliferative diterpenoids from Euphorbia kansui.

    PubMed

    Wang, Hong-Ying; Wang, Jun-Song; Wei, Dan-Dan; Wang, Xiao-Bing; Luo, Jun; Yang, Ming-Hua; Kong, Ling-Yi

    2012-06-01

    Cytotoxic assay guided multistep separation on the dichloromethane extract of the roots of Euphorbia kansui resulted in the isolation of 10 ingenol-type diterpenoids (1-4 and 7-12), of which, 5-O-(2'E,4'E-decadienoyl)-20-O-acetylingenol (1) is a new compound, and two are jatrophane-type diterpenoids (13-14). Interconversion of two pairs of positional ester isomers (1-4) in aqueous alcoholic solution was observed, the transesterification mechanism of which was speculated and confirmed by acylation of 3 and 4 to 6 and 5, respectively. All the isolates and the two acyl derivatives (5 and 6) were evaluated in vitro for their cytotoxicities in Bel-7402, Bel-7402/5FU, BGC-823 and SGC-7901 cell lines. The 12 ingenol-type diterpenoids exhibited weak to moderate cytotoxicities, whereas the two jatrophane-type diterpenoids displayed no antiproliferative effects, which, however, may increase the antitumour efficacy of those ingenol-type diterpenoids. The structure--activity relationships were investigated by principal component analysis (PCA) of the pIC₅₀ (-logIC₅₀) values of the compounds tested and their calculated molecular descriptors. The pIC₅₀ values were highly correlated with most descriptors, especially the highest occupied molecular orbital energy (E(HOMO)), absolute hardness (η) and positively charged solvent accessible surface areas (P-ASA). As the values of E(HOMO) increase, η and P-ASA decrease, and the antiproliferative effects of these compounds increase. PMID:22095916

  5. Pericolactines A–C, a New Class of Diterpenoid Alkaloids with Unusual Tetracyclic Skeleton

    PubMed Central

    Wu, Yue-Hua; Chen, Guo-Dong; He, Rong-Rong; Wang, Chuan-Xi; Hu, Dan; Wang, Gao-Qian; Guo, Liang-Dong; Yao, Xin-Sheng; Gao, Hao

    2015-01-01

    Fusicoccane diterpenoids usually possess a fused 5-8-5 tricyclic ring system, which are biogenetically generated from geranylgeranyl diphosphate (GGDP). In our report, three novel diterpenoid alkaloids with fusicoccane skeleton, pericolactines A–C (1–3), were isolated from Periconia sp.. Their structures with absolute configurations were determined by spectroscopic analyses and quantum chemical ECD calculation. Pericolactines A–C (1–3) are a new class of diterpenoid alkaloids with an unusual fused 5-5-8-5 tetracyclic ring system, which derive from a geranylgeranyl diphosphate (GGDP) and serine conjugated biosynthesis. They belong to the atypical diterpenoid alkaloids. PMID:26611465

  6. Synthesis and antituberculosis activity of the first macrocyclic glycoterpenoids comprising glucosamine and diterpenoid isosteviol.

    PubMed

    Garifullin, Bulat F; Strobykina, Irina Yu; Sharipova, Radmila R; Kravchenko, Marionella A; Andreeva, Olga V; Bazanova, Olga B; Kataev, Vladimir E

    2016-08-01

    The first macrocyclic glycoterpenoids comprising glucosamine and diterpenoid isosteviol moieties were synthesized and evaluated for inhibition activity against Mycobacterium tuberculosis H37Rv. PMID:27267064

  7. Cytotoxic, apoptotic, and sensitization properties of ent-kaurane-type diterpenoids from Croton tonkinensis Gagnep on human liver cancer HepG2 and Hep3b cell lines.

    PubMed

    Pham, Minh Quan; Iscache, Anne Laure; Pham, Quoc Long; Gairin, Jean Edouard

    2016-04-01

    Human hepatocellular carcinoma (HCC) is the most common type of liver cancer, the second most common cause of death from cancer worldwide. A very poor prognosis and a lack of effective treatments make liver cancer a major public health problem, notably in less developed regions, particularly in eastern Asia. This fully justifies the search of new molecules and therapeutic strategies against HCC. Ent-kaurane diterpenoids are natural compounds displaying a broad spectrum of potential therapeutic effects including anticancer activity. In this study, we analyzed the pharmacological properties of a family of ent-kaurane diterpenoids from Croton tonkinensis Gagnep in human HepG2 and Hep3b cell lines, used as cellular reference models for in vitro evaluation of new molecules active on HCC. A structure-related cytotoxicity was observed against both HCC cell lines, enlighting the role of the 16-en-15-one skeleton of ent-kaurane diterpenoids. Cytotoxicity was closely correlated to apoptosis, evidenced by concentration-dependent subG1 cell accumulation, and increased annexin V expression. In addition, subtoxic concentration of ent-kaurane diterpenoid dramatically enhanced the sensitivity of HCC cells to doxorubicin. All together, our data bring strong support to the potential interest of ent-kaurane diterpenoids, alone or in combination with a cytotoxic agent, in cancer and more precisely against HCC. PMID:26713517

  8. Macrocyclic Diterpenoids from the Latex of Euphorbia helioscopia.

    PubMed

    Hua, Juan; Liu, Yan-Chun; Jing, Shu-Xi; Luo, Shi-Hong; Li, Sheng-Hong

    2015-12-01

    One new jatrophane diterpenoid, 7α,9β,15β-triacetoxy-3β-benzoyloxy-14β-hydroxyjatropha-5E,11E-diene (3), together with four known macrocyclic diterpenoids, euphoheliosnoid A (1), epieuphoscopin B (2), euphohelioscopin A (4) and euphoscopin C (5), were isolated from the stem latex of Euphorbia helioscopia. Their structures were established by spectroscopic analyses. In the anti-inflammatory assay, euphohelioscopin A (4) exhibited moderate inhibitory activity on the release of cytokine TNF-α (IC50 = 23.7 ± 1.7 μM), IL-6 (IC50 = 46.1 ± 1.1 μM) and chemokine MCP-1 (IC50 = 33.7 ± 3.8 μM) in lipopolysaccharide (LPS) induced RAW 264.7 macrophages without notable cytotoxicity (IC50 > 80 μM). PMID:26882659

  9. Cytotoxic diterpenoids from Jatropha curcas cv. nigroviensrugosus CY Yang Roots.

    PubMed

    Liu, JieQing; Yang, YuanFeng; Xia, JianJun; Li, XuYang; Li, ZhongRong; Zhou, Lin; Qiu, MingHua

    2015-09-01

    An investigation of phytochemicals from the roots of Jatropha curcas cv. nigroviensrugosus resulted in the isolation of twenty diterpenoids, including lathyranlactone, an unusual diterpenoid lactone possessing a 5/13/3 tricyclic skeleton, jatrocurcasenones A-E and jatrophodiones B-E, as well as 10 known analogues. All isolates were evaluated for cytotoxicity against the HL-60, SMMC-772, A-549, MCF-7 and SW480 human tumor cell lines using the MTS viability assay. Four of the known analogues showed cytotoxic activity in these cell lines, with IC50 values ranging from 2.0 to 23.0 μM. Moreover, the assessment of their cytotoxic structure-activity relationships showed the epoxy ring between C-5 and C-6 and the hydroxyl group at C-2 were the key functionalities for cytotoxicity. PMID:26209936

  10. ent-Kaurane diterpenoids from Croton tonkinensis stimulate osteoblast differentiation.

    PubMed

    Dao, Trong-Tuan; Lee, Kwang-Youl; Jeong, Hyung-Min; Nguyen, Phi-Hung; Tran, Tien Lam; Thuong, Phuong-Thien; Nguyen, Bich-Thu; Oh, Won-Keun

    2011-12-27

    Four new ent-kaurane diterpenoids (1-4) were isolated from the leaves of Croton tonkinensis by bioactivity-guided fractionation using an in vitro osteoblast differentiation assay. Their structures were identified as ent-11β-acetoxykaur-16-en-18-ol (1), ent-11α-hydroxy-18-acetoxykaur-16-ene (2), ent-14β-hydroxy-18-acetoxykaur-16-ene (3), and ent-7α-hydroxy-18-acetoxykaur-16-ene (4). Compounds 1-4 significantly increased alkaline phosphatase activity and osteoblastic gene promoter activity. Compounds 1-3 also increased the levels of ALP and collagen type I alpha mRNA in C2C12 cells in a dose-dependent manner. These results suggest that ent-kaurane diterpenoids from C. tonkinensis have a direct stimulatory effect on osteoblast differentiation and may be potential therapeutic molecules against bone diseases such as osteoporosis. PMID:22085418

  11. The Chemistry of Perfumes Based on Labdane Diterpenoids

    NASA Astrophysics Data System (ADS)

    Vlad, Pavel F.

    1982-07-01

    The advances in the synthesis of C14-C19 perfumes derived from bicyclic labdane diterpenoids and their enantiomers as well as data concerning the sources of the starting materials are presented. The dependence of the odour of the above compounds on their structure and stereochemistry and the questions arising in the manufacture of some of them and their practical applications are considered. The bibliography includes 242 references

  12. Crystal structure of sepaconitine, a C19-diterpenoid alkaloid from the roots of Aconitum sinomontanum Nakai

    PubMed Central

    Shi, Xin-Wei; Lu, Qiang-Qiang; Zhou, Jun-Hui; Cui, Xin-Ai

    2015-01-01

    The title compound [systematic name: [(1α,14α,16β)-20-ethyl-8,9,10-trihy­droxy-1,14,16-tri­meth­oxy­aconitan-4-yl 2-amino­benzoate], C30H42N2O8, a natural C19-diterpenoid alkaloid, possesses an aconitane carbon skeleton with four six-membered rings and two five-membered rings. The fused ring system contains two chair, one boat, one twist-boat and two envelope conformations. Intra­molecular N—H⋯O hydrogen bonds are observed between the amino and carbonyl groups. The mol­ecules are linked together via O—H⋯O hydrogen bonds, forming a three-dimensional framework. PMID:26396791

  13. Epoxide Opening of a 7,17-Seco-7,8-Epoxy-C19-Diterpenoid Alkaloid.

    PubMed

    Ji, Hong; Wang, Feng-Peng; Chen, Qiao-Hong

    2015-12-01

    A new and effective approach toward epoxide opening of a 7,17-seco-7,8-epoxy-C19-diterpenoid alkaloid is herein described. The starting epoxide was prepared from naturally occurring yunnaconitine via a nine-step transformation. Treatment of this epoxide with trifluoroacetic anhydride in dioxane at 110 degrees C followed by reduction with sodium boron hydride generated two epoxide opening compounds 7 and 8. Each of their structures is characteristic of a Δ8,15 bridgehead double bond and a 7β-oxygen-substituted group. PMID:26882668

  14. Semisynthesis of the antiviral abietane diterpenoid jiadifenoic acid C from callitrisic acid (4-epidehydroabietic acid) isolated from sandarac resin.

    PubMed

    González, Miguel A; Zaragozá, Ramón J

    2014-09-26

    The semisynthesis of the antiviral abietane diterpenoid (+)-jiadifenoic acid C starting from the available methyl ester of callitrisic acid (4-epidehydroabietic acid) isolated from sandarac resin is reported. A protocol for the isolation of methyl callitrisate (methyl 4-epidehydroabietate) in gram quantities from sandarac resin is also described. Allylic C-17 oxygenation was introduced by regioselective dehydrogenation of the isopropyl group of methyl callitrisate with DDQ followed by selenium-catalyzed allylic oxidation. Ester hydrolysis afforded (+)-jiadifenoic acid C in 22% overall yield from methyl callitrisate. This semisynthetic route provides a convenient source of this anti-Coxsackie virus B natural product for further biological studies. PMID:25166492

  15. Clerodane diterpenoids, long chain esters of coumaric acid and other compounds from Baccharis myrsinites.

    PubMed

    Li, C J; Ahmed, A A; Arias, A C; Mabry, T J

    1997-06-01

    A new clerodane diterpenoid and two new long chain esters of trans- and cis-coumaric acid, in addition to known triterpenoids and one known clerodane diterpenoid, have been isolated and characterized from Baccharis myrsinites. The structures were determined by spectroscopic techniques. PMID:9190087

  16. ent-Kaurane-based regio- and stereoselective inverse electron demand hetero-Diels-Alder reactions: synthesis of dihydropyran-fused diterpenoids.

    PubMed

    Ding, Chunyong; Wang, Lili; Chen, Haijun; Wild, Christopher; Ye, Na; Ding, Ye; Wang, Tianzhi; White, Mark A; Shen, Qiang; Zhou, Jia

    2014-11-14

    A mild and concise approach for the construction of a 3,4-dihydro-2H-pyran ring integrated into the A-ring of the natural product oridonin using an optimized inverse electron demand hetero-Diels-Alder (IED HDA) reaction is reported herein. A self-dimerization of the exocyclic enone installed in the A-ring through a homo-HDA reaction was identified to exclusively give a dimeric ent-kaurane diterpenoid with the spirochroman core. Moreover, efficient cross-HDA cycloadditions of this enone with various vinyl ethers or vinyl sulfides, instead of its own homo-HDA dimerization, were achieved in a regio- and stereoselective manner, thus providing access to novel dihydropyran-fused diterpenoids as potential anticancer agents to overcome chemoresistance. PMID:25225052

  17. A new ent-kaurane diterpenoid from Ixora amplexicaulis.

    PubMed

    Chen, Lijun; Zhan, Rui; Jiang, Jinhe; Zhang, Yan; Dong, Yi; Chen, Yegao

    2016-01-01

    A new ent-kaurane diterpenoid, 6α,16α-dihyroxy-ent-kaurane (1), was isolated from the stems of Ixora amplexicaulis, together with (24R)-6β-hydroxy-24-ethyl-cholest-4-en-3-one (2), 7β-hydroxysitosterol (3), maslinic acid (4), 3,3'-bis(3,4-dihydro-4-hydroxy-6-methoxy-2H-1-benzopyran) (5) and protocatechuric acid (6). Their structures were established by extensive spectroscopic analysis, including 2D NMR techniques. Compounds 2-5 were isolated from the genus Ixora for the first time and 6 obtained originally from I. amplexicaulis. PMID:25941744

  18. Cytotoxic ent-kaurane diterpenoids from Isodon nervosus.

    PubMed

    Gao, You-Heng; Wei, Zhi-Xiong; Cheng, Yi; Wang, Teng-Hua; Ni, Lin; Zhou, Xiao-Hong; Zhang, Li-Yuan

    2013-08-01

    Four new ent-kaurane diterpenoids, rabdonervosins G-J (1-4, resp.), were isolated from the leaves and stems of Isodon nervosus. Their structures were elucidated by extensive spectroscopic analyses, including 1D-, 2D-NMR and HR mass spectra. Compound 2 showed potent cytotoxicity against the HepG2 and PC-9/ZD cell lines with IC50 values of 2.36 and 6.07 μM, respectively, and compound 3 exhibited cytotoxicity against the HepG2 and CNE2 cell lines with IC50 values of 8.64 and 9.77 μM, respectively. PMID:23939796

  19. Bioactive ent-kaurane diterpenoids from Isodon rosthornii.

    PubMed

    Zhan, Rui; Li, Xiao-Nian; Du, Xue; Wang, Wei-Guang; Dong, Ke; Su, Jia; Li, Yan; Pu, Jian-Xin; Sun, Han-Dong

    2013-07-26

    Isorosthin A (1), the first 20-nor-enmein-type diterpenoid, and 15 new ent-kauranoids, isorosthins B-P (2-16), along with 22 known analogues were isolated from the aerial parts of Isodon rosthornii. The structures of 1-16 were elucidated by means of spectroscopic analysis. The relative configuration of 2 and the absolute configuration of 3 were determined by single-crystal X-ray diffraction. Cytotoxicity evaluation against five human tumor lines showed inhibitory effects by several of the compounds tested. Furthermore, 12 of the isolates exhibited inhibitory activity against nitric oxide production in LPS-activated RAW264.7 macrophages. PMID:23819871

  20. A new abietane diterpenoid from Salvia xanthocheila Boiss.

    PubMed

    Habibi, Zohreh; Gandomkar, Somayyeh; Yousefi, Maryam; Ghasemi, Sabrieh

    2013-01-01

    From the chloroform extract of aerial part of Salvia xanthocheila Boiss. one new abietane diterpenoid, xantoquinone (5α,6α-dimethoxy-7,11,14-trioxoabieta-8,12-diene) and one known oleanene triterpenoid namely 1β,3β-dihydroxy-12-oleanene were isolated. The structure of the new terpenoid was elucidated by comprehensive spectroscopic analysis including electron ionisation-mass spectra, (1)H NMR, (13)C NMR, distortionless enchancement by polarisation transfer, H,H correlation spectroscopy, heteronuclear multiple-quantum coherence and heteronuclear multiple-bond correlation. PMID:22475036

  1. Four new diterpenoids isolated from the Euphorbia rapulum.

    PubMed

    Liu, Xiao-Xue; Shang, Lei; Huang, Chao; Feng, Xue-Song; Li, Wen; Sha, Yi; Huang, Jian; Wang, Jin-Hui

    2016-09-01

    Four new diterpenoids named 1-epi-9-hydroxydepressin (1), 1-epi-8-hydroxydepressin (2), 2,13,9-trihydroxy-labda-8(17),12(E),14-triene (3) and tagalsin I (4) were isolated from Euphorbia rapulum. The structures of these compounds were elucidated by means of various spectroscopic methods. All the isolated compounds were evaluated for cytotoxic activities against HepG2, MCF-7, and C6 cell lines, and compound 4 showed moderate selective activity against MCF-7 cell line with an IC50 value of 31.8 μM. PMID:27089930

  2. abeo-taxane diterpenoids from the Taiwanese Yew Taxus sumatrana.

    PubMed

    Wang, Shih-Sheng; Abd El-Razek, Mohamed H; Chen, Yi-Cheng; Chien, Ching-Te; Guh, Jih-Hwa; Kuo, Yao-Haur; Shen, Ya-Ching

    2009-12-01

    Chemical investigation of the acetonic extract of the leaves and twigs of Taxus sumatrana (Taxaceae) led to the isolation of four new taxane diterpene esters, taiwantaxins A-D (1-4, resp.). Their structures were determined primarily on the basis of 1D- and 2D-NMR techniques as well as MS. Compound 1 is a rearranged taxane diterpenoid possessing an opened oxetane ring moiety containing C(4), C(5), and C(20). The metabolites 2 and 3 belong to a 5/6/6 taxene system having a rare five-membered gamma-lactone ring comprising C(8), C(9), C(10), and C(19). Compound 4 is an example of a taxane diterpene containing a 6/8/6 ring system with a tetrahydrofuran ring comprising C(2), C(3), C(4), and C(20). The 11(15-->1)abeo-taxane diterpenoids, taiwantaxins A-C (1-3, resp.) are lacking an O-bearing functionality at either C(13) or C(14). Compound 2 showed significant cytotoxic activity against human PC-3 tumor cells. PMID:20020457

  3. Diterpenoids from the twigs and leaves of Croton caudatus var. tomentosus.

    PubMed

    Song, Jin-Tong; Han, Yang; Wang, Xiao-Ling; Shen, Tao; Lou, Hong-Xiang; Wang, Xiao-Ning

    2015-12-01

    One new 9,10-seco-abietane derivative, crotontomentosin A (1), four new abietane-type diterpenoids, crotontomentosins B-E (2-5), one new ent-halimane-type diterpenoid, crotontomentosin F (6), along with five known diterpenoids (7-11) and one known sesquiterpenoid (12) were obtained from the twigs and leaves of Croton caudatus Geisel. var. tomentosus Hook. The structures of the compounds were established on the basis of extensive spectroscopic data. Compounds 1-4 and 11 exhibited moderate to weak inhibitory activity against the proliferation of the Hela, Hep G2, MDA-MB-231, or A549 cell lines selectively. PMID:26475984

  4. An O-to-N intramolecular acyl migration in C₁₉-diterpenoid alkaloids.

    PubMed

    Chen, Qi-Feng; Jian, Xi-Xian; Chen, Qiao-Hong; Wang, Feng-Peng

    2012-01-01

    The O-acyl group at C-1 of two C₁₉-diterpenoid alkaloids 2 and 5 was transferred to the secondary amine nitrogen to form amides 3 and 6 in the basic condition. This kind of O-to-N intramolecular acyl migration could be caused by the near distance between the nucleophilic nitrogen atom and the carbonyl group of the ester at C-1 in the C₁₉-diterpenoid alkaloids, which is consistent with the conformation of rings A and E in the C₁₉-diterpenoid alkaloids. PMID:22568819

  5. New Casbane and Cembrane Diterpenoids from an Okinawan Soft Coral, Lobophytum sp.

    PubMed

    Roy, Prodip K; Ashimine, Runa; Miyazato, Haruna; Taira, Junsei; Ueda, Katsuhiro

    2016-01-01

    A new rare casbane-type diterpenoid 1 and two new cembrane diterpenoids 2, 3 were isolated from an Okinawan soft coral, Lobophytum sp., together with four known cembrane diterpenoids 4-7. Their structures were elucidated by extensive analysis of spectroscopic data (1D and 2D NMR, IR, and MS) and a molecular modeling study. The new isolates showed weak anti-bacterial activity, mild cytotoxicity against HCT116 cells, and anti-inflammatory effect in LPS/IFN-γ-stimulated RAW 264.7 macrophage cells. PMID:27223275

  6. Diterpenoid compounds and other lipids in deep-sea sediments and their geochemical significance

    NASA Technical Reports Server (NTRS)

    Simoneit, B. R. T.

    1977-01-01

    Cyclic diterpenoid compounds have been found by various investigators in the geosphere (e.g., fossil resins, coals, soil, shale, and deep-sea sediments). These compounds occur in significant amounts only in higher plants and are therefore potential markers of terrigenous plant lipids. Diterpenoids with the abietane skeleton (mainly dehydroabietic acid) have been identified in the lipids of sediment samples from the northeast Pacific Ocean, Black Sea, and North Atlantic Ocean. The presence of these resin-derived compounds was correlated with the terrigenous clay components and with the presence of pollen. The presence of polycyclic diterpenoids was also correlated with the distribution patterns and inferred sources of other sediment lipid constituents. Potamic transport, followed by turbidite redistribution, is the probable input mechanism of these resin-derived compounds to the deep-sea sediments. These diterpenoids appear to be excellent biological markers of resinous higher plants.

  7. Diterpenoid alkaloids from the Chinese traditional herbal "Fuzi" and their cytotoxic activity.

    PubMed

    Gao, Feng; Li, Yuan-Yuan; Wang, Dan; Huang, Xing; Liu, Qian

    2012-01-01

    Ten diterpenoid alkaloids, including eight aconitine-type C₁₉-diterpenoid alkaloids and two hetisine-type C₂₀-diterpenoid alkaloids, were isolated from the secondary roots of Aconitum carmichaeli Debx., known as "Fuzi" in Chinese traditional herbal medicine. Their structures were established on the basis of their spectroscopic data and comparison with those of the literature. Among these alkaloids, chasmanine, oxonitine and 15-acetylsongoramine were isolated for the first time from this medicinal plant. The cytotoxic activity of the alkaloids were tested against several cell lines by the MTT method in which aconitine, hypaconitine, mesaconitne and oxonitine were found to strongly inhibit the growth of the HePG2 cell line, which showed that the existence and quantity of the ester groups have a significant influence on the cytotoxicity of the diterpenoid alkaloids. PMID:22628040

  8. Hapmnioides A-C, Rearranged Labdane-Type Diterpenoids from the Chinese Liverwort Haplomitrium mnioides.

    PubMed

    Zhou, Jinchuan; Zhang, Jiaozhen; Li, Ruijuan; Liu, Jun; Fan, Peihong; Li, Yi; Ji, Mei; Dong, Yiwen; Yuan, Huiqing; Lou, Hongxiang

    2016-09-01

    Many exceptional labdane-type diterpenoids have been exclusively found in liverworts, which serve as taxonomic molecules or play important ecological roles in interactions among organisms. Three unprecedented labdane-type diterpenoids hapmnioides A (1), B (2), and C (3) formed through cascade rearrangement from the Chinese liverwort Haplomitrium mnioides are reported. Their structures were established by comprehensive spectroscopic analysis coupled with single-crystal X-ray diffraction, and their anti-inflammatory activities were also preliminarily tested. PMID:27513610

  9. Characterization of New Ent-kaurane Diterpenoids of Yunnan Arabica Coffee Beans.

    PubMed

    Chu, Rui; Wan, Luo-Sheng; Peng, Xing-Rong; Yu, Mu-Yuan; Zhang, Zhi-Run; Zhou, Lin; Li, Zhong-Rong; Qiu, Ming-Hua

    2016-08-01

    Five new ent-kaurane diterpenoids, named mascaroside III-V (1-3), and 20-nor-cofaryloside I-II (4-5), together with seven known diterpenoids, were isolated from methanol extracts of the green coffee beans of Yunnan Arabica Coffee. Their chemical structures were elucidated by extensive spectroscopic analyses. Meanwhile, cytotoxicity assay against HL-60, A-549, SMMC-7721, MCF-7 and SW480 cell lines showed that they have not evident inhibition of cytotoxicity. PMID:27165414

  10. Production of bioactive diterpenoids in the euphorbiaceae depends on evolutionarily conserved gene clusters.

    PubMed

    King, Andrew J; Brown, Geoffrey D; Gilday, Alison D; Larson, Tony R; Graham, Ian A

    2014-08-01

    The Euphorbiaceae produce a diverse range of diterpenoids, many of which have pharmacological activities. These diterpenoids include ingenol mebutate, which is licensed for the treatment of a precancerous skin condition (actinic keratosis), and phorbol derivatives such as resiniferatoxin and prostratin, which are undergoing investigation for the treatment of severe pain and HIV, respectively. Despite the interest in these diterpenoids, their biosynthesis is poorly understood at present, with the only characterized step being the conversion of geranylgeranyl pyrophosphate into casbene. Here, we report a physical cluster of diterpenoid biosynthetic genes from castor (Ricinus communis), including casbene synthases and cytochrome P450s from the CYP726A subfamily. CYP726A14, CYP726A17, and CYP726A18 were able to catalyze 5-oxidation of casbene, a conserved oxidation step in the biosynthesis of this family of medicinally important diterpenoids. CYP726A16 catalyzed 7,8-epoxidation of 5-keto-casbene and CYP726A15 catalyzed 5-oxidation of neocembrene. Evidence of similar gene clustering was also found in two other Euphorbiaceae, including Euphorbia peplus, the source organism of ingenol mebutate. These results demonstrate conservation of gene clusters at the higher taxonomic level of the plant family and that this phenomenon could prove useful in further elucidating diterpenoid biosynthetic pathways. PMID:25172144

  11. Further Studies on Structure-Cardiac Activity Relationships of Diterpenoid Alkaloids.

    PubMed

    Zhang, Zhong-Tang; Jian, Xi-Xian; Ding, Jia-Yu; Deng, Hong-Ying; Chao, Ruo-Bing; Chen, Qiao-Hong; Chen, Dong-Lin; Wang, Feng-Peng

    2015-12-01

    The cardiac effect of thirty-eight diterpenoid alkaloids was evaluated on the isolated bullfrog heart model. Among them, twelve compounds exhibited appreciable cardiac activity, with compounds 3 and 35 being more active than the reference drug lanatoside. The structure-cardiac activity relationships of the diterpenoid alkaloids were summarized based on our present and previous studies [2]: i) 1α-OMe or 1α-OH, 8-OH, 14-OH, and NH (or NMe) are key structural features important for the cardiac effect of the aconitine-type C19-diterpenoid alkaloids without any esters. C18-diterpenoid alkaloids, lycoctonine-type C19-diterpenoid alkaloids, and the veatchine- and denudatine-type C20-diterpenoid alkaloids did not show any cardiac activity; ii) the presence of 3α-OH is beneficial to the cardiac activity; iii) the effect on the cardiac action of 6α-OMe, 13-OH, 15α-OH, and 16-demethoxy or a double bond between C-15 and C-16 depends on the substituent pattern on the nitrogen atom. PMID:26882669

  12. Cytotoxic diterpenoid pseudodimers from the Korean sponge Phorbas gukhulensis.

    PubMed

    Jeon, Ju-eun; Liao, Lijuan; Kim, Heegyu; Sim, Chung J; Oh, Dong-Chan; Oh, Ki-Bong; Shin, Jongheon

    2013-09-27

    Four new cytotoxic diterpenoid pseudodimers (2-5), along with a previously reported one, gukulenin A (1), were isolated from the marine sponge Phorbas gukhulensis collected off the coast of Gagu-do, Korea. These novel compounds, designated gukulenins C-F (2-5), were determined by extensive spectroscopic analyses to be pseudodimers of the gagunins, like gukulenin A. The termini of the tropolone-containing side chains in gukulenins C-E (2-4) were found to have diverse modifications involving acetamides or taurine, whereas gukulenin F (5) was formed from 1 by the ring-opening of a cyclic hemiketal. The relative and absolute configurations were assigned by Murata's and modified Snatzke's methods using a HETLOC experiment and a CD measurement of a dimolybdenum complex, respectively. All of these compounds exhibited significant cytotoxicity against the K562 and A549 cell lines. PMID:24025124

  13. Characterization and Biological Evaluation of Diterpenoids from Casearia graveolens.

    PubMed

    Xu, Jing; Ji, Feifei; Sun, Xiaocong; Cao, Xiangrong; Li, Shen; Ohizumi, Yasushi; Guo, Yuanqiang

    2015-11-25

    Biologically active substances that promote the neurite outgrowth of nerve cells against neuron degeneration may be useful for the treatment of Alzheimer's disease. In a continuing search for bioactive compounds from plants, an ethyl acetate-soluble extract of the twigs of Casearia graveolens showed moderate stimulatory activity of neurite outgrowth from PC12 cells. Further investigation to obtain bioactive compounds led to the isolation of 10 new clerodane diterpenoids, graveopenes A-J (1-10). Their structures including absolute configurations were elucidated based on analysis of their NMR spectroscopic data and experimental and calculated ECD spectra. Compounds 3-6 and 8 were shown to stimulate NGF-mediated neurite outgrowth from PC12 cells. PMID:26474353

  14. Two new labdane diterpenoids from the rhizomes of Isodon yuennanensis.

    PubMed

    Huang, Zhen-Yuan; Huang, Bo; Xiao, Chao-Jiang; Dong, Xiang; Jiang, Bei

    2015-01-01

    Two new labdane diterpenoids, s-trans-8(17),12E,14-labdatrien-20-oic acid (1), s-trans-12E,14-labdadien-20,8β-olide (2), along with 10 known compounds, hinokiol (3), ursonic acid (4), 2α,3α-dihydroxyolean-12-en-28-oic acid (5), 2α,3β,23-trihydroxyolean-12-en-28-oic acid (6), ethyl 3-(3,4-dihydroxyphenyl)lactate (7), ethyl rosmarinate (8), (Z,E)-2-(3,4-dihydroxyphenyl)ethenyl caffeic ester (9), tridecanoic acid (10), β-sitosterol (11) and daucosterol (12), were isolated from the 70% acetone extract of the rhizomes of Isodon yuennanensis. Their structures were elucidated based on the analyses of extensive spectroscopic data and physicochemical properties. PMID:25420949

  15. Cytotoxic ent-kaurane diterpenoids from Isodon wikstroemioides.

    PubMed

    Wu, Hai-Yan; Zhan, Rui; Wang, Wei-Guang; Jiang, Hua-Yi; Du, Xue; Li, Xiao-Nian; Li, Yan; Pu, Jian-Xin; Sun, Han-Dong

    2014-04-25

    Phytochemical investigation of EtOAc extracts of the aerial parts of Isodon wikstroemioides afforded 18 new ent-kaurane diterpenoids (wikstroemioidins E-V, 1-18), along with 17 known analogues (19-35). The absolute configurations of 1 and 16 were confirmed by single-crystal X-ray diffraction analysis. The isolates were screened against five human tumor cell lines; compounds 3, 4, 9, 11-13, 23, 25-28, and 33 exhibited significant cytotoxic activity against all five, with IC50 values ranging from 0.4 to 5.1 μM. In addition, 17 of the isolates strongly inhibited nitric oxide production in LPS-activated RAW264.7 macrophages. PMID:24697496

  16. Minor ent-abietane diterpenoids from Euphorbia guyoniana.

    PubMed

    Haba, Hamada; Marcourt, Laurence; Benkhaled, Mohammed; Long, Christophe

    2013-11-01

    Three new abietane-type diterpenoids: ent-abieta-8,11,13-trien-16-ol (1), ent-abieta-8,11,13-trien-11,16-diol (2) and 11,12-dihydroxy-7-oxo-ent-abieta-8,11,13-trien-16-oic acid methyl ester (3), in addition to three known triterpenoids: euphol (4), 24,25-epoxycycloartanol (5) and beta-sitosterol O-beta-D-glucoside (6) were isolated from the chloroform extract of the roots of Euphorbia guyoniana. Structures of the isolated compounds were established on the basis of spectroscopic analyses, including 1D and 2D homo and heteronuclear NMR experiments and ESIMS, and comparison with literature data. PMID:24427931

  17. Three Minor Diterpenoids with Three Carbon Skeletons from Euphorbia peplus.

    PubMed

    Wan, Luo-Sheng; Nian, Yin; Ye, Chen-Jun; Shao, Li-Dong; Peng, Xing-Rong; Geng, Chang-An; Zuo, Zhi-Li; Li, Xiao-Nian; Yang, Jian; Zhou, Ming; Qiu, Ming-Hua

    2016-05-01

    Euphorbia peplus has been used in traditional medicine to treat asthma and psoriasis. Three highly modified diterpenoids, namely, pepluacetal (1) and pepluanol A-B (2-3), have been isolated and identified from this plant. Compounds 1-3 exhibit unprecedented 5/4/7/3, 5/6/7/3, and 5/5/8/3 ring systems, respectively. Their structures with absolute configurations were determined by spectroscopic analyses, X-ray crystallography, and electronic circular dichroism calculations. Since Kv1.3 is a validated target for the treatment of autoimmune diseases, such as multiple sclerosis, type-1 diabetes, asthma, and psoriasis, Kv1.3 was studied in terms of its response to the new compounds. All three compounds inhibit Kv1.3, with compound 3 being the most effective with an IC50 value of 9.50 μM. PMID:27075046

  18. Diterpenoids from the branch and leaf of Abies fargesii.

    PubMed

    Wu, Wen-Ming; Liu, Ye; Chen, Xu; Jin, An; Zhou, Ming; Tian, Tian; Ruan, Han-Li

    2016-04-01

    Five new abietane diterpenoids, named abifadines A-E (1-5), and nine known ones (6-14), together with two known podocarpenes (15 and 16), were isolated from the branch and leaf of Abies fargesii. Their structures including the relative configurations were established on the basis of extensive spectroscopic analyses. The absolute configuration of 1 was determined through single-crystal X-ray diffraction analysis with Cu Kα irradiation. All the isolates were evaluated for their in vitro cytotoxicities. Only compounds 5 and 12 exhibited weak anti-proliferative effects against three cancer cell lines (B16, MCF7, and HepG2) with IC50 values range from 14.8 to 42.8μM. The antimicrobial activities against Staphylococcus aureus, Escherichia coli and Monilia albicans of all compounds were also tested, but none of them showed significant activities. PMID:26969787

  19. Antileishmanial and Cytotoxic Activity of Some Highly Oxidized Abietane Diterpenoids from the Bald Cypress, Taxodium distichum.

    PubMed

    Naman, C Benjamin; Gromovsky, Anthony D; Vela, Cory M; Fletcher, Joshua N; Gupta, Gaurav; Varikuti, Sanjay; Zhu, Xiaohua; Zywot, Emilia M; Chai, Heebyung; Werbovetz, Karl A; Satoskar, Abhay R; Kinghorn, A Douglas

    2016-03-25

    Two new compounds, namely, a para-benzoquinone ring-containing abietane (1) and a para-benzoquinone ring-containing 7,8-seco-abietane (2), and 14 other known highly oxidized abietane diterpenoids (3-16) were isolated from an extract prepared from the cones of Taxodium distichum, collected in central Ohio. The active subfraction from which all compounds isolated in this study were purified was tested in vivo using Leishmania donovani-infected mice and was found to dose-dependently reduce the parasite burden in the murine livers after iv administration of this crude mixture at 5.6 and 11.1 mg/kg. The structures of 1 and 2 were established by detailed 1D- and 2D-NMR experiments, HRESIMS data, and electronic circular dichroism studies. Compounds 3 and 4 were each fully characterized spectroscopically and also isolated from a natural source for the first time. Compounds 2-16 were tested in vitro against L. donovani promastigotes and L. amazonensis intracellular amastigotes. Compound 2 was the most active against L. amazonensis amastigotes (IC50 = 1.4 μM), and 10 was the most potent against L. donovani promastigotes (IC50 = 1.6 μM). These compounds may be suggested for further studies such as in vivo experimentation either alone or in combination with other Taxodium isolates. PMID:26905523

  20. Antimicrobial and Antiparasitic Abietane Diterpenoids from the Roots of Clerodendrum eriophyllum

    PubMed Central

    Machumi, Francis; Samoylenko, Volodymyr; Yenesew, Abiy; Derese, Solomon; Midiwo, Jacob O.; Wiggers, Frank T.; Jacob, Melissa R.; Tekwani, Babu L.; Khan, Shabana I.; Walker, Larry A.

    2013-01-01

    Chromatographic separation of the roots of a Kenyan medicinal plant, Clerodendrum eriophyllum, led to the isolation of ten abietane diterpenoids (1-10), one of which (1) was isolated for the first time from a natural source. Using spectroscopic data, the structure of 1 was determined to be 12-hydroxy-8,12-abietadiene-3,11,14-trione. Circular dichroism (CD) spectra showed that the stereochemistry of compounds 1, 3, and 6-8 belongs to the normal series of abietane diterpenes, which confirmed the absolute stereochemistry of the isolated compounds. Compounds 2-10 were evaluated for their in vitro antiplasmodial, antileishmanial, antifungal and antibacterial activities. Compounds 3 and 7 exhibited potent antifungal activity (IC50/MIC 0.58/1.25 and 0.96/2.5 µg/mL, respectively) against C. neoformans, whereas 3, 6 and 7 showed strong antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus with IC50/MIC values between 1.33–1.75/2.5–5 and 0.96–1.56/2.5 µg/mL, respectively. In addition, compounds 3 and 9 exhibited potent antileishmanial activity (IC50 0.08 and 0.20 µg/mL, respectively) against L. donovani, while 3 and 7 displayed weak antimalarial activity against Plasmodium falciparum, but 9 was inactive. PMID:20614808

  1. New C20-diterpenoid alkaloids from Aconitum vilmorrianum and structural revision of 2-O-acetylorochrine and orochrine.

    PubMed

    Tang, Tian-Xing; Chen, Qi-Feng; Liu, Xiao-Yu; Jian, Xi-Xian; Wang, Feng-Peng

    2016-04-01

    Three new C20-diterpenoid alkaloids vilmorrianines E (1), F (2), and G (3) were isolated from the whole plants of Aconitum vilmorrianum, along with one artifact N-chloromethyl vilmorrianine E hydrochloride (4), as well as two known alkaloids hemsleyaconitines F (5) and G (6). The structures of 1-4 were established by HR-ESI-MS, 1D-, 2D-NMR (HMQC, HMBC, and NOESY), and single-crystal X-ray diffraction analysis. In addition, the structures of naturally occurring 2-O-acetylorochrine (7) and orochrine (8) were revised to be the known alkaloids heterophylloidine (9) and deacetyl heterophylloidine (10), respectively, on the basis of consideration of transannular effect and chemical correlations. PMID:26479584

  2. Structure-analgesic activity relationship studies on the C(18)- and C(19)-diterpenoid alkaloids.

    PubMed

    Wang, Jian-Li; Shen, Xiang-Li; Chen, Qiao-Hong; Qi, Gong; Wang, Wei; Wang, Feng-Peng

    2009-08-01

    For evaluation of C(18)- and C(19)-diterpenoid alkaloids as analgesics, three C(19)-diterpenoid alkaloids were isolated from the roots of Aconitum hemsleyanum var. circinatum and A. transsecutum; and twenty-five semisynthetic C(18)- or C(19)-diterpenoid alkaloids were prepared from lappaconitine, crassicauline A or yunaconitine. In a mice acetic acid-induced abdominal constriction assay, four crassicauline A analogs and three yunaconitine analogs exhibited good analgesic activities with 77.8-94.1% inhibition range in 0.1-10 mg/kg subcutaneous (s.c.) dose range at the point of 20 min after drug administration. Among them, 8-O-deacetyl-8-O-ethylcrassicauline A (ED(50)=0.0972 mg/kg) and 8-O-ethylyunaconitine (ED(50)=0.0591 mg/kg) were the most potent analgesics relative to the reference drugs lappaconitine (ED(50)=3.50 mg/kg) and crassicauline A (ED(50)=0.0480 mg/kg). Analgesic activity data of these C(18)- and C(19)-diterpenoid alkaloids indicate that a tertiary amine in ring A, an acetoxyl or an ethoxyl group at C-8, an aromatic ester at C-14, and the saturation state of the ring D are important structural features necessary to the analgesic activity of the C(19)-diterpenoid alkaloids. PMID:19652403

  3. Cytotoxic Clerodane Diterpenoids from the Leaves of Casearia grewiifolia.

    PubMed

    Nguyen, Ha T T; Truong, Ngan B; Doan, Huong T M; Litaudon, Marc; Retailleau, Pascal; Do, Thao T; Nguyen, Hung V; Chau, Minh V; Pham, Cuong V

    2015-11-25

    Two new clerodane diterpenoids (1 and 2) and the known compound caseanigrescen D (3) were isolated from the leaves of Casearia grewiifolia by bioassay-guided fractionation. Their structures were determined by analyses of MS and 2D NMR data. The absolute configurations of 1 and 3 were established by analysis of X-ray diffraction data. Compounds 1-3 were evaluated for their cytotoxicity against four cancer cell lines, KB (mouth epidermal carcinoma cells), HepG-2 (human liver hepatocellular carcinoma cells), LU-1 (human lung adenocarcinoma cells), and MCF-7 (human breast cancer cells). Caseagrewifolin B (2) had inhibitory activity against KB and HepG-2 cell lines with IC50 values of 6.2 to 7.0 μM, respectively. When tested against the normal cells (NIH/3T3), caseagrewifolin B (2) exhibited a significant selective inhibition against cancer cells in comparison with the normal cells. Caseanigrescen D (3) was cytotoxic against four cancer cell lines; however it had no selective inhibition compared with normal cells. PMID:26516994

  4. Bioactive ent-kaurane diterpenoids from Isodon serra.

    PubMed

    Wan, Jun; Liu, Miao; Jiang, Hua-Yi; Yang, Jin; Du, Xue; Li, Xiao-Nian; Wang, Wei-Guang; Li, Yan; Pu, Jian-Xin; Sun, Han-Dong

    2016-10-01

    Nine 7,20-epoxy-ent-kaurane diterpenoids (15-acetylmegathyrin B, serrin E, 14β-hydroxyrabdocoestin A, serrin F, serrin G, 11-epi-rabdocoestin A, serrin H, serrin I, and 15-acetylenanderianin N), along with seven known ones, were isolated from the aerial parts of Isodon serra. Their structures were elucidated by extensive spectroscopic analysis, and the absolute configuration of 15-acetylmegathyrin B was determined by signal-crystal X-ray diffraction. All of these compounds were evaluated for their cytotoxic activities against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480). Serrin F, rabdocoestin B and 1α,11β-dihydroxy-1α,11β-acetonide-7α,20-epoxy-ent-kaur-16-en-15-one showed cytotoxic activities against all cell lines, with IC50 values ranging from 0.7 to 4.6 μM; serrin F also strongly inhibited NO production in LPS-stimulated RAW264.7 cells. Otherwise, 14β-hydroxyrabdocoestin A, serrins H and I, as well as enanderianin N and megathyrin B, also exhibited inhibitory effects towards NO production, while no cytotoxicity against five cell lines was detected. PMID:27298277

  5. Clerodane-type diterpenoids from tuberous roots of Tinospora sagittata (Oliv.) Gagnep.

    PubMed

    Zhang, Geng; Ma, Haoran; Hu, Song; Xu, Hongfeng; Yang, Bo; Yang, Quanwei; Xue, Yongbo; Cheng, Lu; Jiang, Jie; Zhang, Jinwen; Wang, Fuqian; Zhang, Yonghui

    2016-04-01

    Three new clerodane type diterpenoids (2-4), together with one known analogues (1), were isolated from the tuberous roots of Tinospora sagittata (Oliv.) Gagnep. Compound 3 is an unusual clerodane diterpenoid with the carbonyl functionality at C-3, which represents the first example from this diterpenoid compounds class. The structures were established on the basis of spectroscopic data interpretation. The absolute configuration of 1 was determined for the first time by single-crystal X-ray diffraction analysis with CuKα irradiation. These isolates were evaluated for their cytotoxic activities against five human cancer cell lines and inhibitory activities on LPS-induced NO production in RAW264.7 cells. PMID:26924160

  6. Cytotoxic C20 Diterpenoid Alkaloids from the Australian Endemic Rainforest Plant Anopterus macleayanus.

    PubMed

    Levrier, Claire; Sadowski, Martin C; Nelson, Colleen C; Davis, Rohan A

    2015-12-24

    In order to identify new anticancer compounds from nature, a prefractionated library derived from Australian endemic plants was generated and screened against the prostate cancer cell line LNCaP using a metabolic assay. Fractions from the seeds, leaves, and wood of Anopterus macleayanus showed cytotoxic activity and were subsequently investigated using a combination of bioassay-guided fractionation and mass-directed isolation. This led to the identification of four new diterpenoid alkaloids, 6α-acetoxyanopterine (1), 4'-hydroxy-6α-acetoxyanopterine (2), 4'-hydroxyanopterine (3), and 11α-benzoylanopterine (4), along with four known compounds, anopterine (5), 7β-hydroxyanopterine (6), 7β,4'-dihydroxyanopterine (7), and 7β-hydroxy-11α-benzoylanopterine (8); all compounds were purified as their trifluoroacetate salt. The chemical structures of 1-8 were elucidated after analysis of 1D/2D NMR and MS data. Compounds 1-8 were evaluated for cytotoxic activity against a panel of human prostate cancer cells (LNCaP, C4-2B, and DuCaP) and nonmalignant cell lines (BPH-1 and WPMY-1), using a live-cell imaging system and a metabolic assay. All compounds showed potent cytotoxicity with IC50 values of <400 nM; compound 1 was the most active natural product from this series, with an IC50 value of 3.1 nM toward the LNCaP cell line. The live-cell imaging assay on 1-8 showed a concentration- and time-dependent effect on the cell morphology and proliferation of LNCaP cells. PMID:26600001

  7. Bioactive diterpenoids from Trigonostemon chinensis: Structures, NO inhibitory activities, and interactions with iNOS.

    PubMed

    Xu, Jing; Peng, Maoqin; Sun, Xiaocong; Liu, Xingyu; Tong, Ling; Su, Guochen; Ohizumi, Yasushi; Lee, Dongho; Guo, Yuanqiang

    2016-10-01

    A phytochemical investigation to obtain new NO inhibitors led to the isolation of two new (1 and 2) and four known (3-6) diterpenoids from Trigonostemon chinensis. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analyses, and the absolute configurations of new compounds were established by experimental and calculated ECD spectra. The inhibitory activities on lipopolysaccharide-induced NO production in murine microglial BV-2 cells of these diterpenoids were evaluated, and all of the compounds showed inhibitory effects. The interactions of bioactive compounds with iNOS protein were also studied by molecular docking. PMID:27570243

  8. Characterization of diterpenoids from Caesalpinia decapetala and their anti-TMV activities.

    PubMed

    Xu, Jing; Cao, Xiangrong; Liu, Feng; Ma, Jun; Liu, Xingyu; Tong, Ling; Su, Guochen; Ohizumi, Yasushi; Lee, Dongho; Wang, Lizhong; Guo, Yuanqiang

    2016-09-01

    Caesalpinia decapetala is a versatile medicinal plant belonging to the Fabaceae plant family. In our survey on plant secondary metabolites to obtain bioactive substances for the development of new agricultural anti-TMV agents, the chemical constituents of C. decapetala were investigated. This investigation led to the isolation of three new and ten known diterpenoids. Their structures including absolute configurations were elucidated based on the extensive NMR spectroscopic data analyses and the time-dependent density functional theory calculations. The following biological screenings revealed that most of these diterpenoids possessed anti-TMV activities. PMID:27491755

  9. LC-MS guided isolation of ent-kaurane diterpenoids from Nouelia insignis.

    PubMed

    Sun, Chang-Li; Geng, Chang-An; Chen, Xing-Long; Yang, Tong-Hua; Yin, Xiu-Juan; Huang, Xiao-Yan; Peng, Hua; Chen, Ji-Jun

    2016-06-01

    The preliminary LC-MS investigation on the stems of Nouelia insignis manifested the existence of diterpenoids. As a result, 15 ent-kaurane diterpenoids, including 7 new glycosides (nouelosides A-G, 1-7), were isolated under the direction of LC-MS analysis. The new compounds were determined by extensive spectroscopic analysis including HRESIMS, 1D and 2D NMR data and chemical methods. Compounds 6 and 15 with the exo-methylene cyclopentanone functional group exhibited obvious nitric oxide production inhibitory activity with IC50 values of 3.84±0.20 and 3.19±0.25μM. PMID:27094114

  10. New clerodane diterpenoids from the twigs and leaves of Croton euryphyllus.

    PubMed

    Pan, Zhenghong; Ning, Desheng; Wu, Xingde; Huang, Sisi; Li, Dianpeng; Lv, Shihong

    2015-03-15

    Three new nor-clerodane diterpenoids, crotoeurins A-C (1-3), together with four known ones were isolated from the twigs and leaves of Croton euryphyllus. Among them, crotoeurin A (1) is a new nor-clerodane diterpenoid dimer with a unique cyclobutane ring via a [2+2] cycloaddition. Their structures were elucidated by spectroscopic analyses and the stereochemistry of 1 was confirmed by single-crystal X-ray diffraction analysis. Compounds 1-3 exhibited neurite outgrowth-promoting activity on NGF-mediated PC12 cells at concentration of 10μM. PMID:25690785

  11. Diterpenoids from the Roots of Euphorbia fischeriana with Inhibitory Effects on Nitric Oxide Production.

    PubMed

    Lee, Jin Woo; Lee, Chul; Jin, Qinghao; Jang, Hari; Lee, Dongho; Lee, Ha-Jin; Shin, Jong Won; Han, Sang Bae; Hong, Jin Tae; Kim, Youngsoo; Lee, Mi Kyeong; Hwang, Bang Yeon

    2016-01-22

    Bioactivity-guided isolation of a methanolic extract of Euphorbia fischeriana led to the isolation of four new abietane-type diterpenoids, fischeriolides A-D (1-4), together with 11 known diterpenoids. Their structures were elucidated based on the interpretation of 1D and 2D NMR spectroscopic and HRESIMS data. The absolute configuration of compound 3 was determined by single-crystal X-ray diffraction analysis and electronic circular dichroism methods. Compounds 5-9 exhibited inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages with IC50 values in the range 4.9-12.6 μM. PMID:26702644

  12. Phytotoxic cis-clerodane diterpenoids from the Chinese liverwort Scapania stephanii.

    PubMed

    Li, Rui-Juan; Sun, Yi; Sun, Bin; Wang, Xiao-Ning; Liu, Shan-Shan; Zhou, Jin-Chuan; Ye, Jian-Ping; Zhao, Yu; Liu, Lei; Lee, Kuo-Hsiung; Lou, Hong-Xiang

    2014-09-01

    Five cis-clerodane diterpenoids, stephanialides A-E, along with seven known cis-clerodanes, scaparvins A-C, parvitexins B and C, 3-chloro-4-hydroxy-parvitexin A, and scapanialide B, were isolated from the Chinese liverwort Scapania stephanii. Their structures were established unequivocally on the basis of spectroscopic data. The absolute configuration of stephanialide A was determined by analysis of CD data using the octant rule. Phytotoxic activity evaluation showed that this type of diterpenoids can significantly inhibit root elongation of the seeds of Arabidopsis thaliana, Lepidium sativum and Brassica pekinensis. PMID:24947338

  13. Eutypenoids A–C: Novel Pimarane Diterpenoids from the Arctic Fungus Eutypella sp. D-1

    PubMed Central

    Zhang, Liu-Qiang; Chen, Xiao-Chong; Chen, Zhao-Qiang; Wang, Gui-Min; Zhu, Shi-Guo; Yang, Yi-Fu; Chen, Kai-Xian; Liu, Xiao-Yu; Li, Yi-Ming

    2016-01-01

    Eutypenoids A–C (1–3), pimarane diterpenoid alkaloid and two ring A rearranged pimarane diterpenoids, were isolated from the culture of Eutypella sp. D-1 obtained from high-latitude soil of the Arctic. Their structures, including absolute configurations, were authenticated on the basis of the mass spectroscopy (MS), nuclear magnetic resonance (NMR), X-ray crystallography, and electronic circular dichroism (ECD) analysis. The immunosuppressive effects of eutypenoids A–C (1–3) were studied using a ConA-induced splenocyte proliferation model, which suggested that 2 exhibited potent immunosuppressive activities. PMID:26959036

  14. (+)-Podocarpic Acid as Chiral Template in the Synthesis of Aphidicolane, Stemodane and Stemarane Diterpenoids †.

    PubMed

    La Bella, Angela; Leonelli, Francesca; Migneco, Luisa Maria; Marini Bettolo, Rinaldo

    2016-01-01

    In this review the synthetic work in the field of aphidicolane, stemodane and stemarane diterpenoids, in which readily available (+)-podocarpic acid (4) was used as chiral template for the construction of their polycyclic structures, is described as it developed along the years. In the frame of this work (+)-podocarpic acid (4) was a very useful tool in a model study leading to the syntheses of tetracyclic ketones 7 and 8, models of key intermediates 5a and 6 in the syntheses of (+)-aphidicolin (1) and (+)-stemodin (2a), respectively. (+)-Podocarpic acid (4) was also converted into (+)-2-deoxystemodinone (2d), allowing confirmation of the stemodane diterpenoids absolute configuration, into (+)-aphidicol-15-ene (36) and into Stemodia chilensis tetracyclic diterpenoid (+)-19-acetoxystemodan-12-ol (2f), allowing confirmation of its structure. (+)-Podocarpic acid (4) was then extensively used in the work which led to the synthesis of (+)-stemar-13-ene (57) and (+)-18-deoxystemarin (3b). Finally, (+)-4 was converted into (+)-2-deoxyoryzalexin S (66), which made it possible to demonstrate that the structure of (+)-66 could not be attributed to a Chilean Calceolaria isolated diterpenoid to which this structure had been assigned. PMID:27617995

  15. Diterpenoids from aerial parts of Flickingeria fimbriata and their nuclear factor-kappaB inhibitory activities.

    PubMed

    Li, Hang; Zhao, Jing-jun; Chen, Jin-long; Zhu, Long-ping; Wang, Dong-mei; Jiang, Lin; Yang, De-po; Zhao, Zhi-min

    2015-09-01

    Chemical investigation of the aerial parts of Flickingeria fimbriata (Bl.) Hawkes resulted in isolation of sixteen ent-pimarane diterpenoids, including five rare 16-nor-ent-pimarane diterpenoids, two 15,16-dinor-ent-pimarane diterpenoids and one ent-pimarane diterpenoid. Structures were mainly elucidated by extensive spectroscopic analysis, and their absolute configurations were unequivocally determined by the exciton chirality method, the modified Mosher's method, the CD experiments (including Snatzke's method) and chemical transformations, respectively. All the isolated compounds were screened for inhibitory effects on the nuclear factor-kappaB (NF-κB) in lipopolysaccharide (LPS) induced murine macrophage RAW264.7 cells, using a NF-κB-dependent luciferase reporter gene assay. Several of these compounds displayed comparable or even better activities than the positive control pyrrolidinedithiocarbamate (PDTC) (IC50=26.3 μM) with IC50 values in the range of 14.7-29.2 μM and structure-activity relationships are briefly proposed. PMID:26186245

  16. Characterization of CYP76AH4 clarifies phenolic diterpenoid biosynthesis in the Lamiaceae

    PubMed Central

    Zi, Jiachen; Peters, Reuben J.

    2013-01-01

    Miltiradiene (1), is the precursor of phenolic diterpenoids such as ferruginol (2), requiring aromatization and hydroxylation. While this has been attributed to a single cytochrome P450 (CYP76AH1), characterization of the rosemary ortholog CYP76AH4 led to the discovery that these CYPs simply hydroxylate the facilely oxidized aromatic intermediate abietatriene (3). PMID:24108414

  17. Polyacetylated labdane-type diterpenoids, ptychantins P-R from Chinese liverwort Ptychanthus striatus.

    PubMed

    Wu, Jing-Yi; Zhang, Jiao-Zhen; Kang, Ya-Qi; Wang, Xiao; Fan, Pei-Hong; Zhou, Jin-Chuan; Lou, Hong-Xiang

    2015-05-01

    Three new polyacetylated labdane diterpenoids ptychantins P-R (1-3) and four known compounds (4-7) were isolated from an EtOH extract of the Chinese liverwort Ptychanthus striatus (Lehm. & Lindenb.) Nees. Their structures were established by extensive analysis of spectroscopic data (IR, UV, HRESIMS, 1D NMR, and 2D NMR). PMID:25677361

  18. Comparative Transcriptomics Unravel Biochemical Specialization of Leaf Tissues of Stevia for Diterpenoid Production.

    PubMed

    Kim, Mi Jung; Jin, Jingjing; Zheng, Junshi; Wong, Limsoon; Chua, Nam-Hai; Jang, In-Cheol

    2015-12-01

    Stevia (Stevia rebaudiana) produces not only a group of diterpenoid glycosides known as steviol glycosides (SGs), but also other labdane-type diterpenoids that may be spatially separated from SGs. However, their biosynthetic routes and spatial distribution in leaf tissues have not yet been elucidated. Here, we integrate metabolome and transcriptome analyses of Stevia to explore the biosynthetic capacity of leaf tissues for diterpenoid metabolism. Tissue-specific chemical analyses confirmed that SGs were accumulated in leaf cells but not in trichomes. On the other hand, Stevia leaf trichomes stored other labdane-type diterpenoids such as oxomanoyl oxide and agatholic acid. RNA sequencing analyses from two different tissues of Stevia provided a comprehensive overview of dynamic metabolic activities in trichomes and leaf without trichomes. These metabolite-guided transcriptomics and phylogenetic and gene expression analyses clearly identified specific gene members encoding enzymes involved in the 2-C-methyl-d-erythritol 4-phosphate pathway and the biosynthesis of steviol or other labdane-type diterpenoids. Additionally, our RNA sequencing analysis uncovered copalyl diphosphate synthase (SrCPS) and kaurene synthase1 (SrKS1) homologs, SrCPS2 and KS-like (SrKSL), which were specifically expressed in trichomes. In vitro and in planta assays showed that unlike SrCPS and SrKS1, SrCPS2 synthesized labda-13-en-8-ol diphosphate and successively catalyzed the formation of manoyl oxide and epi-manoyl oxide in combination with SrKSL. Our findings suggest that Stevia may have evolved to use distinct metabolic pathways to avoid metabolic interferences in leaf tissues for efficient production of diverse secondary metabolites. PMID:26438788

  19. A new mulinane diterpenoid from the cushion shrub Azorella compacta growing in Perú

    PubMed Central

    Salgado, Francisco; Areche, Carlos; Sepúlveda, Beatriz; Simirgiotis, Mario J.; Cáceres, Fátima; Quispe, Cristina; Quispe, Lina; Cano, Teresa

    2014-01-01

    Background: Azorella compacta is a rare yellow-green compact resinous cushion shrub growing from the high Andes of southern Perú to northwestern Argentina, and which is a producer of biologically active and unique diterpenoids. Objective: This study investigated the secondary metabolites present in a Peruvian sample of Azorella compacta and the evaluation of gastroprotective activity of the isolated compounds in a gastric- induced ulcer model in mice. Material and Methods: Six secondary metabolites (diterpenoids 1-6) present in the dichloromethane (DCM) extract of A. compacta growing in Perú were isolated by a combination of Sephadex LH-20 permeation and silica gel chromatography and their chemical structures were elucidated by spectroscopic methods (NMR) and molecular modeling. The gastroprotective activity of the new compound 1 was evaluated on the HCl/EtOH-induced gastric lesion model in mice and compared to the activity showed by the known compounds. Results: A new mulinane diterpene along with five known diterpenoids have been isolated from a Peruvian sample of A. compacta and the gastroprotective results show that compound 1 is less active than the other known mulinane diterpenoids isolated. Conclusions: A. compacta growing in Perú showed the presence of the new mulinane 1, which was poorly active in the HCl/EtOH-induced gastric lesion model in mice. Indeed, the activity was lower than other diterpenoids (2-6) showing an oxygenated function at C-16 or/and C-20, which confirm the role of an oxygenated group (OH or carboxylic acid) for the gastroprotective activity of mulinane compounds. PMID:25298672

  20. Jaridonin, a novel ent-kaurene diterpenoid from Isodon rubescens, inducing apoptosis via production of reactive oxygen species in esophageal cancer cells.

    PubMed

    Ma, Yong-Cheng; Ke, Yu; Zi, Xiaolin; Zhao, Wen; Shi, Xiao-Jing; Liu, Hong-Min

    2013-07-01

    Isodon rubescens, a Chinese herb, has been used as a folk, botanical medicine in China for inflammatory diseases and cancer treatment for many years. Recently, we isolated a new ent-kaurene diterpenoid, named Jaridonin, from Isodon rubescens. The chemical structure of Jaridonin was verified by infrared (IR), nuclear magnetic resonance (NMR), and mass spectrum (MS) data as well as X-ray spectra. Jaridonin potently reduced viabilities of several esophageal cancer cell lines, including EC109, EC9706 and EC1. Jaridonin treatment resulted in typical apoptotic morphological characteristics, increased the number of annexin V-positive staining cells, as well as caused a G2/M arrest in cell cycle progression. Furthermore, Jaridonin resulted in a significant loss of mitochondrial membrane potential, release of cytochrome c into the cytosol, and then activation of Caspase-9 and -3, leading to activation of the mitochondria mediated apoptosis. Furthermore, these effects of Jaridonin were accompanied by marked reactive oxygen species (ROS) production and increased expression of p53, p21(waf1/Cip1) and Bax, whereas two ROS scavengers, N-acetyl-L-cysteine (LNAC) and Vitamin C, significantly attenuated the effects of Jaridonin on the mitochondrial membrane potential, DNA damage, expression of p53 and p21(waf1/Cip1) and reduction of cell viabilities. Taken together, our results suggest that a natural ent-kaurenoid diterpenoid, Jaridonin, is a novel apoptosis inducer and deserves further investigation as a new chemotherapeutic strategy for patients with esophageal cancer. PMID:23597192

  1. Atropurpuran – Missing Biosynthetic Link Leading to the Hetidine and Arcutine C20-Diterpenoid Alkaloids or an Oxidative Degradation Product?

    PubMed Central

    Weber, Manuel; Owens, Kyle; Sarpong, Richmond

    2015-01-01

    A possible biosynthetic link between atropurpuran, the hetidine diterpenoid alkaloids and the alkaloid arcutine and congeners is proposed. The feasibility of aspects of this biosynthesis, especially key 1,2-rearrangements, have been examined computationally. PMID:26028789

  2. Production of Bioactive Diterpenoids in the Euphorbiaceae Depends on Evolutionarily Conserved Gene Clusters[C][W][OPEN

    PubMed Central

    King, Andrew J.; Brown, Geoffrey D.; Gilday, Alison D.; Larson, Tony R.; Graham, Ian A.

    2014-01-01

    The Euphorbiaceae produce a diverse range of diterpenoids, many of which have pharmacological activities. These diterpenoids include ingenol mebutate, which is licensed for the treatment of a precancerous skin condition (actinic keratosis), and phorbol derivatives such as resiniferatoxin and prostratin, which are undergoing investigation for the treatment of severe pain and HIV, respectively. Despite the interest in these diterpenoids, their biosynthesis is poorly understood at present, with the only characterized step being the conversion of geranylgeranyl pyrophosphate into casbene. Here, we report a physical cluster of diterpenoid biosynthetic genes from castor (Ricinus communis), including casbene synthases and cytochrome P450s from the CYP726A subfamily. CYP726A14, CYP726A17, and CYP726A18 were able to catalyze 5-oxidation of casbene, a conserved oxidation step in the biosynthesis of this family of medicinally important diterpenoids. CYP726A16 catalyzed 7,8-epoxidation of 5-keto-casbene and CYP726A15 catalyzed 5-oxidation of neocembrene. Evidence of similar gene clustering was also found in two other Euphorbiaceae, including Euphorbia peplus, the source organism of ingenol mebutate. These results demonstrate conservation of gene clusters at the higher taxonomic level of the plant family and that this phenomenon could prove useful in further elucidating diterpenoid biosynthetic pathways. PMID:25172144

  3. Diterpenoids from the Chinese liverwort Heteroscyphus tener and their antiproliferative effects.

    PubMed

    Lin, Zhao-Min; Guo, Yan-Xia; Wang, Shu-Qi; Wang, Xiao-Ning; Chang, Wen-Qiang; Zhou, Jin-Chuan; Yuan, Huiqing; Lou, Hongxiang

    2014-06-27

    Four new ent-labdane diterpenoids, heteroscyphins A-D (1-4), and four known diterpenoids (5-8) were isolated from the Chinese liverwort Heteroscyphus tener (Steph.) Schiffn. The absolute configuration of compound 1 was defined by single-crystal X-ray diffraction using Cu Kα radiation. Cytotoxicity tests revealed that compounds 3 and 5 exhibited modest activity against seven cancer cell lines. Compound 5 showed inhibitory effects on prostate cancer (PCa) cell proliferation but with less inhibition on non-neoplastic prostate epithelial cells. Compound 5 markedly caused cell growth arrest at the G0/G1 phase and induced cellular apoptosis through ROS-mediated DNA damage in PCa cells. PMID:24940845

  4. Diterpenoids from the roots of Croton crassifolius and their anti-angiogenic activity.

    PubMed

    Wang, Jia-Jian; Chung, Hau Yin; Zhang, Yu-Bo; Li, Guo-Qiang; Li, Yao-Lan; Huang, Wei-Huan; Wang, Guo-Cai

    2016-02-01

    Six diterpenoids [crassifolin J, K, L, M, N and O] along with eleven known ones were isolated from the supercritical fluid extract (SFE) of the roots of Croton crassifolius (Euphorbiaceae). Their structures were elucidated using spectroscopic methods (IR, UV, HRESIMS, 1D and 2D NMR). The structure and stereochemistry of crassifolin J was confirmed by single-crystal X-ray diffraction analysis, and the absolute configurations of crassifolin K-M were determined by CD spectra. Twenty-three diterpenoids from this plant were screened for their anti-angiogenic activity using a wild-type zebrafish in vivo model. Four of the known compounds were active, of which penduliflaworosin possessed the best activity relative to the positive control (SU5416). Further study demonstrated that penduliflaworosin could inhibit vessel formation on Tg(fli1a:EGFP)y1-type zebrafish embryos. PMID:26725185

  5. Chemical and biological evaluation on scopadulane-type diterpenoids from Scoparia dulcis of Vietnamese origin.

    PubMed

    Phan, Minh Giang; Phan, Tong Son; Matsunami, Katsuyoshi; Otsuka, Hideaki

    2006-04-01

    From the aerial parts of Scoparia dulcis L. (Scrophulariaceae) grown in Vietnam, four scopadulane-type diterpenoids (4-7), of which 7 is new and was given the trivial name scopadulcic acid C, together with nine known compounds were isolated. Their structures were elucidated by spectroscopic analyses. The absolute configurations of 4-7 were ascertained by applying the modified Mosher's method to iso-dulcinol (6). The isolation of the lignans nirtetralin and niranthin for the first time from S. dulcis is also of chemotaxonomic interest. The cytotoxic activity in KB cells, inhibitory effect on LPS/IFNgamma-induced NO production, inhibition of multidrug resistance (MDR), and antibacterial and antifungal activities of the scopadulane-type diterpenoids 4-7 were examined in this study. PMID:16595962

  6. Cholinesterase-inhibitory diterpenoids and chemical constituents from aerial parts of Caryopteris mongolica.

    PubMed

    Murata, Toshihiro; Selenge, Erdenechimeg; Oikawa, Saki; Ageishi, Keita; Batkhuu, Javzan; Sasaki, Kenroh; Yoshizaki, Fumihiko

    2015-10-01

    A diterpenoid diglucoside (12,19-di-O-β-D-glucopyranosyl-11-hydroxyabieta-8,11,13-triene-19-one), isoscutellarein 7-O-[β-D-xylopyranosyl-(1→2)]-β-D-glucopyranoside, isoscutellarein 7-O-[α-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranoside, hypolaetin 7-O-[6″-O-(p-E-coumaroyl)]-β-D-glucopyranoside, hypolaetin 7-O-[6″-O-(E-caffeoyl)]-β-D-glucopyranoside, and 15 known compounds were isolated from aerial parts of the Mongolian medicinal plant Caryopteris mongolica. The cholinesterase-inhibitory activities of the constituents were estimated. The abietane diterpenoids (12-O-demethylcryptojaponol and 6α-hydroxydemethylcryptojaponol) showed potent inhibitory activity against acetylcholinesterase from human erythrocytes and electric eel, and against butyrylcholinesterase from horse serum. PMID:25900047

  7. Briarenolides K and L, new anti-inflammatory briarane diterpenoids from an octocoral Briareum sp. (Briareidae).

    PubMed

    Su, Yin-Di; Su, Tzu-Rong; Wen, Zhi-Hong; Hwang, Tsong-Long; Fang, Lee-Shing; Chen, Jih-Jung; Wu, Yang-Chang; Sheu, Jyh-Horng; Sung, Ping-Jyun

    2015-02-01

    Two new briarane-type diterpenoids, briarenolides K (1) and L (2), were isolated from an octocoral identified as Briareum sp. The structures of new briaranes 1 and 2 were elucidated by spectroscopic methods. In the in vitro anti-inflammatory effects test, briaranes 1 and 2 were found to significantly inhibit the accumulation of the pro-inflammatory iNOS protein of the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. PMID:25689566

  8. Structure elucidation and complete NMR spectral assignments of four new diterpenoids from Smallantus sonchifolius.

    PubMed

    Dou, De-Qiang; Tian, Fang; Qiu, Ying-Kun; Kang, Ting-Guo; Dong, Feng

    2008-08-01

    Four new diterpenoids, named smaditerpenic acid A-D, together with five known compounds, were isolated from the H(2)O extract of the leaves of Smallantus sonchifolius (yacon) cultivated in Liaoning, China and their structures were elucidated on the basis of one- and two-dimensional NMR (including (1)H, (13)C-NMR, (1)H-(1)H COSY, HSQC, TOCSY, HMBC, and ROESY), electrospray ionization mass spectrometry (ESI-MS), and chemical methods. PMID:18470882

  9. Two new eunicellin diterpenoids from the East China Sea gorgonian Muricella sp.

    PubMed

    Zhao, Chuan; Wang, Jia; Jin, De-Jun; Duan, Hong-Quan; Xing, Guo-Sheng; Tang, Sheng-An

    2016-09-01

    A phytochemical investigation on gorgonian Muricella sp. from East China Sea resulted in the isolation of eight eunicellin diterpenoids including two new ones, muricellins A-B (1, 2). Chemical structures of these compounds were elucidated by spectroscopic techniques (1D and 2D NMR and MS) and by comparison with data reported in the literature. Anti-rheumatoid arthritis activities of 1, 3, 4, and 6 have been evaluated. PMID:27004724

  10. ent-Atisane and ent-kaurane diterpenoids from Isodon rosthornii.

    PubMed

    Zhan, Rui; Li, Xiao-Nian; Du, Xue; Wang, Wei-Guang; Dong, Ke; Su, Jia; Li, Yan; Pu, Jian-Xin; Sun, Han-Dong

    2013-07-01

    A new ent-atisanoid (1) and three new ent-kauranoids (2-4) belonging to different types, along with four known compounds were isolated from Isodon rosthornii. Their structures were established by means of extensive spectroscopic analysis. The absolute configuration of 1 was further determined by X-ray diffraction. Compounds 1 and 5 are the first example of atisane-type diterpenoid from this plant. PMID:23660245

  11. A New Spatane Diterpenoid from the Cultured Soft Coral Sinularia leptoclados

    PubMed Central

    Tsai, Tsung-Chang; Wu, Yu-Jen; Su, Jui-Hsin; Lin, Wei-Tung; Lin, Yun-Sheng

    2013-01-01

    A new spatane diterpenoid, leptoclalin A (1), along with two previously reported known norcembranoid diterpenes (2 and 3), were isolated from a cultured soft coral Sinularia leptoclados. The structures were determined by extensive spectroscopic analyses and by comparison with the spectral data of related known compounds. Metabolite 1 is rarely found in spatane skeletons reported from soft corals. In addition, compound 1 exhibited weak cytotoxicity towards human tumor cell lines T-47 D and K-562. PMID:23306171

  12. Flexibilins A–C, New Cembrane-Type Diterpenoids from the Formosan Soft Coral, Sinularia flexibilis

    PubMed Central

    Hu, Li-Chung; Su, Jui-Hsin; Chiang, Michael Yen-Nan; Lu, Mei-Chin; Hwang, Tsong-Long; Chen, Yung-Husan; Hu, Wan-Ping; Lin, Nai-Cheng; Wang, Wei-Hsien; Fang, Lee-Shing; Kuo, Yueh-Hsiung; Sung, Ping-Jyun

    2013-01-01

    Three new cembrane-type diterpenoids, flexibilins A–C (1–3), along with a known cembrane, (−)-sandensolide (4), were isolated from the soft coral, Sinularia flexibilis. The structures of cembranes 1–4 were elucidated by spectroscopic methods. The structure of 4, including its absolute stereochemistry, was further confirmed by single-crystal X-ray diffraction analysis. Cembrane 2 displayed a moderate inhibitory effect on the release of elastase by human neutrophils. PMID:23752355

  13. Flexibilins A-C, new cembrane-type diterpenoids from the Formosan soft coral, Sinularia flexibilis.

    PubMed

    Hu, Li-Chung; Su, Jui-Hsin; Chiang, Michael Yen-Nan; Lu, Mei-Chin; Hwang, Tsong-Long; Chen, Yung-Husan; Hu, Wan-Ping; Lin, Nai-Cheng; Wang, Wei-Hsien; Fang, Lee-Shing; Kuo, Yueh-Hsiung; Sung, Ping-Jyun

    2013-06-01

    Three new cembrane-type diterpenoids, flexibilins A-C (1-3), along with a known cembrane, (-)-sandensolide (4), were isolated from the soft coral, Sinularia flexibilis. The structures of cembranes 1-4 were elucidated by spectroscopic methods. The structure of 4, including its absolute stereochemistry, was further confirmed by single-crystal X-ray diffraction analysis. Cembrane 2 displayed a moderate inhibitory effect on the release of elastase by human neutrophils. PMID:23752355

  14. Briarenolides U–Y, New Anti-Inflammatory Briarane Diterpenoids from an Octocoral Briareum sp. (Briareidae)

    PubMed Central

    Su, Yin-Di; Wu, Tung-Ying; Wen, Zhi-Hong; Su, Ching-Chyuan; Chen, Yu-Hsin; Chang, Yu-Chia; Wu, Yang-Chang; Sheu, Jyh-Horng; Sung, Ping-Jyun

    2015-01-01

    Five new 13,14-epoxybriarane diterpenoids, briarenolides U–Y (1–5), were isolated from the octocoral Briareum sp. The structures of briaranes 1–5 were elucidated by spectroscopic methods. Briarenolides U–Y (1–5) were found to significantly inhibit the expression of the pro-inflammatory inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein of the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. PMID:26633428

  15. New 9-Hydroxybriarane Diterpenoids from a Gorgonian Coral Briareum sp. (Briareidae)

    PubMed Central

    Su, Yin-Di; Sung, Chun-Sung; Wen, Zhi-Hong; Chen, Yu-Hsin; Chang, Yu-Chia; Chen, Jih-Jung; Fang, Lee-Shing; Wu, Yang-Chang; Sheu, Jyh-Horng; Sung, Ping-Jyun

    2016-01-01

    Six new 9-hydroxybriarane diterpenoids, briarenolides ZI–ZVI (1–6), were isolated from a gorgonian coral Briareum sp. The structures of briaranes 1–6 were elucidated by spectroscopic methods and by comparison of their spectroscopic data with those of related analogues. Briarenolides ZII (2) and ZVI (6) were found to significantly inhibit the expression of the pro-inflammatory inducible nitric oxide synthase (iNOS) protein of lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. PMID:26761004

  16. Enzymes for synthetic biology of ambroxide-related diterpenoid fragrance compounds.

    PubMed

    Zerbe, Philipp; Bohlmann, Jörg

    2015-01-01

    Ambrox and related ambroxides are highly priced in the fragrance industry, and valued for their delicate odor and fixative properties. Historically, ambrox was obtained from ambergris, a waxy excretion produced by sperm whales, now an endangered species. Synthetic ambroxides have replaced ambergris in perfume manufacture. Plant labdane diterpenoids can serve as starting material for ambroxide synthesis. Among these, the diterpene alcohol sclareol is the major industrial precursor obtained from cultivated clary sage (Salvia sclarea). In plants, a large family of diterpene synthase (diTPS) enzymes controls key reactions in diterpenoid biosynthesis. Advanced metabolite profiling and high-throughput sequencing of fragrant and medicinal plants have accelerated discovery of novel diTPS functions, providing a resource for combinatorial synthetic biology and metabolic engineering approaches. This chapter highlights recent progress on the discovery, characterization, and engineering of plant diTPSs with potential uses in ambroxide production. It features biosynthesis of sclareol, cis-abienol, and diterpene resin acids, as sources of genes and enzymes for diterpenoid bioproducts. PMID:25846965

  17. Molecular structure and vibrational bands and 13C chemical shift assignments of both enmein-type diterpenoids by DFT study

    NASA Astrophysics Data System (ADS)

    Wang, Tao; Wu, Yi fang; Wang, Xue liang

    2014-01-01

    We report here theoretical and experimental studies on the molecular structure and vibrational and NMR spectra of both natural enmein type diterpenoids molecule (6, 7-seco-ent-kaurenes enmein type), isolated from the leaves of Isodon japonica (Burm.f.) Hara var. galaucocalyx (maxin) Hara. The optimized geometry, total energy, NMR chemical shifts and vibrational wavenumbers of epinodosinol and epinodosin have been determined using B3LYP method with 6-311G (d,p) basis set. A complete vibrational assignment is provided for the observed IR spectra of studied compounds. The calculated wavenumbers and 13C c.s. are in an excellent agreement with the experimental values. Quantum chemical calculations at the B3LYP/6-311G (d,p) level of theory have been carried out on studied compounds to obtain a set of molecular electronic properties (MEP,HOMO, LUMO and gap energies ΔEg). Electrostatic potential surfaces have been mapped over the electron density isosurfaces to obtain information about the size, shape, charge density distribution and chemical reactivity of the molecules.

  18. Molecular structure and vibrational bands and 13C chemical shift assignments of both enmein-type diterpenoids by DFT study.

    PubMed

    Wang, Tao; Wu, Yi fang; Wang, Xue liang

    2014-01-01

    We report here theoretical and experimental studies on the molecular structure and vibrational and NMR spectra of both natural enmein type diterpenoids molecule (6, 7-seco-ent-kaurenes enmein type), isolated from the leaves of Isodon japonica (Burm.f.) Hara var. galaucocalyx (maxin) Hara. The optimized geometry, total energy, NMR chemical shifts and vibrational wavenumbers of epinodosinol and epinodosin have been determined using B3LYP method with 6-311G (d,p) basis set. A complete vibrational assignment is provided for the observed IR spectra of studied compounds. The calculated wavenumbers and 13C c.s. are in an excellent agreement with the experimental values. Quantum chemical calculations at the B3LYP/6-311G (d,p) level of theory have been carried out on studied compounds to obtain a set of molecular electronic properties (MEP,HOMO, LUMO and gap energies ΔEg). Electrostatic potential surfaces have been mapped over the electron density isosurfaces to obtain information about the size, shape, charge density distribution and chemical reactivity of the molecules. PMID:24013676

  19. Large-scale profiling of diterpenoid glycosides from Stevia rebaudiana using ultrahigh performance liquid chromatography/tandem mass spectrometry.

    PubMed

    Shafii, Behnaz; Vismeh, Ramin; Beaudry, Randy; Warner, Ryan; Jones, A Daniel

    2012-07-01

    The plant Stevia rebaudiana accumulates a suite of diterpenoid metabolites that are natural sweeteners finding increased use as sugar substitutes. To guide breeding of stevia plants that accumulate substances with desirable flavor in high yield, rapid and accurate methods are needed to profile these substances in plant populations. This report describes an 8-min ultrahigh performance liquid chromatography-tandem mass spectrometry method for separation and quantification of seven stevia glycosides including steviolbioside; stevioside; rebaudiosides A, B, and C; rubusoside; and dulcoside as well as aglycones steviol and isosteviol. This negative mode electrospray ionization/multiple reaction monitoring method yielded low limits of detection <1 ng/mL for steviol, 6 ng/mL for isosteviol, and <15 ng/mL for all stevia glycosides. Stevioside and Reb A, B, and C were quantified in more than 1,100 extracts from stevia leaves as part of a large-scale profiling exercise. Leaf tissue levels in this population spanned about two orders of magnitude for stevioside (2-125 mg/g dry weight), Reb A (2.5-164 mg/g), Reb B (0.5-50 mg/g), and Reb C (1.5-125 mg/g), but levels of individual metabolites exhibited independent variation. The wide spread of metabolite levels highlights the utility and importance of performing targeted metabolic profiling for large plant populations. PMID:22580424

  20. Studies on C20-Diterpenoid Alkaloids: Synthesis of the Hetidine Framework and Its Application to the Synthesis of Dihydronavirine and the Atisine Skeleton

    PubMed Central

    2015-01-01

    The full details of a synthesis of the hetidine framework of the C20-diterpenoid alkaloids and its conversion to the atisine core structure are reported. The application of the hetidine framework to the synthesis of dihydronavirine, which is the formal reduction product of the natural product navirine, is also described. Key to the success of these studies is the use of a Ga(III)-catalyzed cycloisomerization reaction of alkynylindenes to prepare a [6–7–6] framework that was advanced to the hetidine skeleton. Furthermore, a Michael/aldol sequence was developed for the construction of the bicyclo[2.2.2] framework that is characteristic of the hetidines and atisines. PMID:25004408

  1. neo-Clerodane diterpenoids from Scutellaria barbata mediated inhibition of P-glycoprotein in MCF-7/ADR cells.

    PubMed

    Xue, Gui-Min; Xia, Yuan-Zheng; Wang, Zhi-Min; Li, Ling-Nan; Luo, Jian-Guang; Kong, Ling-Yi

    2016-10-01

    Ten new (1-10) and seventeen known (11-27) neo-clerodane diterpenoids substituted with nicotinoyloxyl were isolated from the plant Scutellaria barbata and their structures were established by extensive spectroscopic analysis. Chemoreversal effects of these neo-clerodane diterpenoids on multidrug resistance were evaluated in breast cancer multidrug-resistant MCF-7/ADR cells that overexpress P-glycoprotein. Four compounds (11, 14, 16, and 18) exhibited better chemoreversal abilities than the classical P-gp inhibitor verapamil and the most potent compound 11 reduced IC50 value of adriamycin in MCF-7/ADR cells from 58.8 μM to 1.3 μM. Mechanistic investigations showed that compound 11 reversed multidrug resistance through suppressing the activity of P-gp and restraining the expression of P-glycoprotein. In the present study, the structure-activity relationships of neo-clerodane diterpenoids were also discussed. PMID:27240278

  2. New ent-Clerodane and Abietane Diterpenoids from the Roots of Kenyan Croton megalocarpoides Friis & M. G. Gilbert.

    PubMed

    Ndunda, Beth; Langat, Moses K; Mulholland, Dulcie A; Eastman, Harry; Jacob, Melissa R; Khan, Shabana I; Walker, Larry A; Muhammad, Ilias; Kerubo, Leonidah O; Midiwo, Jacob O

    2016-07-01

    The roots of the endangered medicinal plant Croton megalocarpoides collected in Kenya were investigated and twenty-two compounds isolated. Among them were twelve new ent-clerodane (1-12) and a new abietane (13) diterpenoids, alongside the known crotocorylifuran (4 a), two known abietane and four known ent-trachylobane diterpenoids, and the triterpenoids, lupeol and acetyl aleurotolic acid. The structures of the compounds were determined using NMR, HRMS and ECD. The isolated compounds were evaluated against a series of microorganisms (fungal and bacteria) and also against Plasmodium falciparum, however no activity was observed. PMID:27286332

  3. Engineering a Platform for Photosynthetic Pigment, Hormone and Cembrane-Related Diterpenoid Production in Nicotiana tabacum.

    PubMed

    Zhang, Hongying; Niu, Dexin; Wang, Jing; Zhang, Songtao; Yang, Yongxia; Jia, Hongfang; Cui, Hong

    2015-11-01

    Plants synthesize a large number of isoprenoids that are of nutritional, medicinal and industrial importance. 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) catalyzes the first committed step for plastidial isoprenoid biosynthesis. Here, we identified two DXR isogenes, designated NtDXR1 and NtDXR2, from tetraploid common tobacco (Nicotiana tabacum L.). Southern blotting and genotyping analysis revealed that two NtDXR genes existed in the tetraploid tobacco genome; NtDXR1 and NtDXR2 were separately derived from N. tomentosiformis and N. sylvestris. Both NtDXRs were localized in chloroplasts. Expression patterns indicated that NtDXR1 and NtDXR2 had similar expression profiles. NtDXR genes were highly expressed in leaves with or without trichomes; expression was relatively reduced in flowers and stems, weak in leaf trichomes and marginal in roots and seeds. Overexpressing NtDXR1 under control of the 35S promoter resulted in longer primary roots and enhancement of various photosynthetic pigments and hormones in leaves. In contrast, there were no significant changes in cembrane-related diterpenoids synthesized in glandular trichomes. To elucidate further the function of DXR in the biosynthesis of diterpenoids, overexpression vectors for NtDXR1 under the control of a trichome-specific CYP promoter were transferred to tobacco plants. CYP:NtDXR1 tobacco exhibited larger glandular cells and increased cembrane-related diterpenoids in leaf glandular trichomes. Moreover, transcripts of eight MEP (2-C-methyl-d-erythritol 4-phosphate) pathway genes were significantly up-regulated in NtDXR1-overexpressing tobacco plants, indicating that overexpression of NtDXR could boost the expression of downstream genes in the MEP pathway. Our results suggested that overexpression of NtDXR1 could increase the levels of photosynthetic pigments, leaf surface exudates and hormones though the MEP pathway. PMID:26363359

  4. Diterpene synthases of the biosynthetic system of medicinally active diterpenoids in Marrubium vulgare.

    PubMed

    Zerbe, Philipp; Chiang, Angela; Dullat, Harpreet; O'Neil-Johnson, Mark; Starks, Courtney; Hamberger, Björn; Bohlmann, Jörg

    2014-09-01

    Marrubium vulgare (Lamiaceae) is a medicinal plant whose major bioactive compounds, marrubiin and other labdane-related furanoid diterpenoids, have potential applications as anti-diabetics, analgesics or vasorelaxants. Metabolite and transcriptome profiling of M. vulgare leaves identified five different candidate diterpene synthases (diTPSs) of the TPS-c and TPS-e/f clades. We describe the in vitro and in vivo functional characterization of the M. vulgare diTPS family. In addition to MvEKS ent-kaurene synthase of general metabolism, we identified three diTPSs of specialized metabolism: MvCPS3 (+)-copalyl diphosphate synthase, and the functional diTPS pair MvCPS1 and MvELS. In a sequential reaction, MvCPS1 and MvELS produce a unique oxygenated diterpene scaffold 9,13-epoxy-labd-14-ene en route to marrubiin and an array of related compounds. In contrast with previously known diTPSs that introduce a hydroxyl group at carbon C-8 of the labdane backbone, the MvCPS1-catalyzed reaction proceeds via oxygenation of an intermediate carbocation at C-9, yielding the bicyclic peregrinol diphosphate. MvELS belongs to a subgroup of the diTPS TPS-e/f clade with unusual βα-domain architecture. MvELS is active in vitro and in vivo with three different prenyl diphosphate substrates forming the marrubiin precursor 9,13-epoxy-labd-14-ene, as identified by nuclear magnetic resonance (NMR) analysis, manoyl oxide and miltiradiene. MvELS fills a central position in the biosynthetic system that forms the foundation for the diverse repertoire of Marrubium diterpenoids. Co-expression of MvCPS1 and MvELS in engineered E. coli and Nicotiana benthamiana offers opportunities for producing precursors for an array of biologically active diterpenoids. PMID:24990389

  5. New labdane diterpenoids from Croton laui and their anti-inflammatory activities.

    PubMed

    Yang, Li; Zhang, Yu-Bo; Chen, Li-Feng; Chen, Neng-Hua; Wu, Zhong-Nan; Jiang, Si-Qi; Jiang, Lin; Li, Guo-Qiang; Li, Yao-Lan; Wang, Guo-Cai

    2016-10-01

    Nine new labdane diterpenoids (1-9) were isolated from the aerial parts of Croton laui, along with eight known analogues (10-17). Their structures were identified on the basis of the spectral data (IR, UV, HRESIMS, 1D and 2D NMR), and the structure of 8 was confirmed by single crystal X-ray diffraction analyses. In addition, compounds 1, 4, 7, 8, and 14 showed weak anti-inflammatory activities in LPS-stimulated RAW 264.7 cells. PMID:27575472

  6. A new ent-kaurane diterpenoid glycoside from Isodon japonica var. glaucocalyx.

    PubMed

    Xiang, Zhao-Bao; Wang, Guang-Li; Huang, Lan-Zhi; Heng, Lin-Sen; Li, Xiao-Hui

    2013-01-01

    A new ent-kaurane diterpenoid glycoside (1), named glaucocalyxin G, has been isolated from the n-butanol-soluble fraction of the dried whole plants of Isodon japonica var. glaucocalyx along with two known compounds, namely arjunglucoside (2) and kaempferol-3-O-rutinoside (3). The structures of the isolated compounds were assigned on the basis of their (1)H and (13)C NMR spectra including two-dimensional NMR techniques such as HMQC, HMBC, and NOESY experiments and comparison with the literature data. PMID:23614395

  7. Cytotoxic and anti-inflammatory ent-kaurane diterpenoids from Isodon wikstroemioides.

    PubMed

    Wu, Hai-Yan; Wang, Wei-Guang; Jiang, Hua-Yi; Du, Xue; Li, Xiao-Nian; Pu, Jian-Xin; Sun, Han-Dong

    2014-10-01

    Seven new ent-kaurane diterpenoids, isowikstroemins A-G (1-7), were isolated from EtOAc extracts of the aerial parts of Isodon wikstroemioides. Their structures were elucidated by extensive spectroscopic analysis. The isolates were evaluated for their cytotoxicity against five human tumor cell lines, and compounds 1-4 exhibited significant activity with IC50 values ranging from 0.9 to 7.0 μM. In addition, compounds 1, 2, 3, 4, and 7 exhibited inhibitory activity against nitric oxide (NO) production in LPS-activated RAW264.7 macrophages. PMID:25128423

  8. Hispidanins A-D: four new asymmetric dimeric diterpenoids from the rhizomes of Isodon hispida.

    PubMed

    Huang, Bo; Xiao, Chao-Jiang; Huang, Zhen-Yuan; Tian, Xin-Yan; Cheng, Xia; Dong, Xiang; Jiang, Bei

    2014-07-01

    Hispidanins A-D (1-4), four unprecedented asymmetric dimeric diterpenoids, were obtained from the rhizomes of Isodon hispida. Their structures were elucidated by extensive spectroscopic analysis (1D and 2D NMR, MS, UV, IR), as well as single-crystal X-ray diffraction analysis. Hispidanin B showed significant cytotoxicities against tumor cell lines SGC7901, SMMC7721, and K562, with IC50 values of 10.7, 9.8, and 13.7 μM, respectively. PMID:24956015

  9. Highly Rigid Labdane-Type Diterpenoids from a Chinese Liverwort and Light-Driven Structure Diversification.

    PubMed

    Zhou, Jinchuan; Zhang, Jiaozhen; Cheng, Aixia; Xiong, Yuanxin; Liu, Lei; Lou, Hongxiang

    2015-07-17

    Two unprecedented labdane-type diterpenoids haplomintrins A (1) and B (2) with six rings system were isolated from a Chinese liverwort Haplomitrium mnioides. Light-driven reaction of homologous haplomitrenonolides C (6), A (4), and D (3) afforded haplomintrins A-C (1, 2, and 7), respectively, while 4 was converted to more complex congeners haplomintrins D-G (8-11) through intramolecular cyclization. Formation of 1 and 2 from compounds 6 and 4, respectively, helps us to postulate that a photochemical reaction is involved in the biosynthetic pathway. These structure features can be used as molecular markers of H. mnioides, and their allelopathic effects are also preliminarily tested. PMID:26111119

  10. Acylated neo-clerodane type diterpenoids from the aerial parts of Scutellaria coleifolia Levl. (Lamiaceae).

    PubMed

    Kurimoto, Shin-Ichiro; Pu, Jian-Xin; Sun, Han-Dong; Shibata, Hirofumi; Takaishi, Yoshihisa; Kashiwada, Yoshiki

    2016-04-01

    Twenty new neo-clerodane type diterpenoids, scutefolides G1-S (1-20), were isolated from the 70 % aqueous acetone extract of the aerial parts of Scutellaria coleifolia. Their structures were elucidated by extensive spectroscopic analyses. The absolute configurations of 1, 2, 7, 8, 14 and 15 were determined by means of the CD exciton chirality method. Compounds 1, 2, 5, 7, 8, 12, 14, 15, 18 and 19 were evaluated for their cytotoxic activities against four human cancer cell lines, and anti-bacterial activities against methicillin-resistant Staphylococcus aureus. PMID:26825781

  11. Guanacastane-type diterpenoids from the insect-associated fungus Verticillium dahliae.

    PubMed

    Wu, Fa-Biao; Li, Tian-Xiao; Yang, Ming-Hua; Kong, Ling-Yi

    2016-01-01

    Four new guanacastane-type diterpenoids, namely dahlianes A (1), B (2), C (3), and D (4), were isolated from cultures of Verticillium dahliae. Their structures were elucidated on the basis of extensive spectroscopic data analysis. Their absolute configurations were determined by a combination of Mo2(OAc)4-induced electronic circular dichroism experiment and Mosher ester method. In cytotoxicity evaluation against human tumor cell lines, compounds 2 and 3 exhibited significant cytotoxicities against MCF-7 cell lines with IC50 values of 3.35 and 4.72 μM, respectively. PMID:26221875

  12. Two pimarane diterpenoids from Ephemerantha lonchophylla and their evaluation as modulators of the multidrug resistance phenotype.

    PubMed

    Na, G X; Wang, T S; Yin, L; Pan, Y; Guo, Y L; LeBlanc, G A; Reinecke, M G; Watson, W H; Krawiec, M

    1998-01-01

    Two new pimarane diterpenoids, lonchophylloids A (1) and B (2), were isolated from the stems of Ephemerantha lonchophylla. The structures of 1 and 2 were established predominantly through the application of extensive 1H-and 13C-NMR, 1D- and 2D-homonuclear and heteronuclear correlation NMR experiments, and X-ray diffraction methods. Consistent with structure--activity predictions, both compounds were capable of sensitizing cells that expressed the multidrug resistance phenotype to the toxicity of the anticancer drug doxorubicin. PMID:9461658

  13. New flavonol and diterpenoids from the endophytic fungus Aspergillus sp. YXf3.

    PubMed

    Yan, Tong; Guo, Zhi Kai; Jiang, Rong; Wei, Wei; Wang, Ting; Guo, Ye; Song, Yong Chun; Jiao, Rui Hua; Tan, Ren Xiang; Ge, Hui Ming

    2013-03-01

    One new flavonol, chlorflavonin A (1), four new diterpenoids, aspergiloids E-H (3, 5-7), together with eight known compounds (2, 4, 8-13) were isolated from solid fermentation of Aspergillus sp. (strain no. YXf3), an endophytic fungus from Ginkgo biloba. Their structures were determined through detailed spectroscopic analysis combined with comparison of NMR spectra data with reported ones. All of them were screened on cytotoxicity against KB, SGC-7901, SW1116, and A549 cell lines; compounds 4, 9-11 exhibited moderate activities with IC50 values ranging from 6.74 to 46.64 µM. PMID:23457022

  14. Antiviral chlorinated daphnane diterpenoid orthoesters from the bark and wood of Trigonostemon cherrieri.

    PubMed

    Allard, Pierre-Marie; Leyssen, Pieter; Martin, Marie-Thérèse; Bourjot, Mélanie; Dumontet, Vincent; Eydoux, Cécilia; Guillemot, Jean-Claude; Canard, Bruno; Poullain, Cyril; Guéritte, Françoise; Litaudon, Marc

    2012-12-01

    The chemical study of the bark and the wood of Trigonostemon cherrieri, a rare endemic plant of New Caledonia, led to the isolation of a series of highly oxygenated daphnane diterpenoid orthoesters (DDO) bearing an uncommon chlorinated moiety: trigocherrins A-F and trigocherriolides A-D. Herein, we describe the isolation and structure elucidation of the DDO (trigocherrins B-F and trigocherriolides A-D). We also report the antiviral activity of trigocherrins A, B and F (1, 2 and 6) and trigocherriolides A, B and C (7-9) against various emerging pathogens: chikungunya virus (CHIKV), Sindbis virus (SINV), Semliki forest virus (SFV) and dengue virus (DENV). PMID:22938995

  15. ent-Labdane Diterpenoids from the Aerial Parts of Eupatorium obtusissmum.

    PubMed

    Castillo, Quírico A; Triana, Jorge; Eiroa, José L; Calcul, Laurent; Rivera, Edwin; Wojtas, Lukasz; Padrón, José M; Boberieth, Lise; Keramane, Mehdi; Abel-Santos, Ernesto; Báez, Luis A; Germosén, Evelyn A

    2016-04-22

    Six new ent-labdane diterpenoids, uasdlabdanes A-F (1-6), were isolated from the aerial parts of Eupatorium obtusissmum. The new structures were elucidated through spectroscopic and spectrometric data analyses. The absolute configurations of compounds 1 and 2 were established by X-ray crystallography, and those of 3-6, by comparison of experimental and calculated electronic circular dichroism spectra. The antiproliferative activity of the compounds was studied in a panel of six representative human solid tumor cell lines and showed GI50 values ranging from 19 to >100 μM. PMID:27023255

  16. New biological potential of abietane diterpenoids isolated from Salvia austriaca against microbial virulence factors.

    PubMed

    Sadowska, Beata; Kuźma, Łukasz; Micota, Bartłomiej; Budzyńska, Aleksandra; Wysokińska, Halina; Kłys, Arkadiusz; Więckowska-Szakiel, Marzena; Różalska, Barbara

    2016-09-01

    The increasing importance of multi-resistant strains and microbial biofilms in the development of chronic infections has driven the search for more effective alternative therapy including plant-origin preparations. The present study evaluates the broadly-defined antimicrobial activity of two abietane diterpenoids isolated from Salvia austriaca transformed roots: taxodone and 15-deoxy-fuerstione. The direct biostatic/biocidal effect of these phytocompounds and their influence on Staphylococcus aureus and Candida albicans virulence factors/mechanisms (adhesion, biofilm formation, agglutination in human plasma, survival in the blood, germ tube and mycelium formation) were tested using in vitro assays. Both phytocompounds significantly inhibited microbial adhesion and biofilm formation when used at ½ and ¼ MIC. Additionally, taxodone was able to limit staphylococcal survival in human blood, as well as C. albicans germ tube formation and hyphal growth. The tested diterpenoids express significant anti-biofilm activity against both staphylococci and yeast, and adversely affect their virulence factors/mechanisms, which are relevant in the course of the infection in vivo. Therefore, they demonstrate considerable biomedical potential as complements for classic therapy with antibiotics. PMID:27417191

  17. Diterpenoids from Copaifera reticulata Ducke with larvicidal activity against Aedes aegypti (L.) (Diptera, Culicidae).

    PubMed

    Geris, Regina; Silva, Ionizete Garcia da; Silva, Heloísa Helena Garcia da; Barison, Andersson; Rodrigues-Filho, Edson; Ferreira, Antônio Gilberto

    2008-01-01

    The objective of this study was to evaluate the larvicidal activity of diterpenoids obtained from the oil-resin of Copaifera reticulata against Aedes aegypti larvae, the principal vector of dengue and urban yellow fever. Four diterpenes were obtained from oil-resin extraction with organic solvents and subsequent chromatographic and spectroscopic procedures allowed to isolation and identification of these compounds as 3-beta-acetoxylabdan-8(17)-13-dien-15-oic acid (1), alepterolic acid (2), 3-beta-hidroxylabdan-8(17)-en-15-oic acid (3), and ent-agatic acid (4). Each compound was previously dissolved in dimethylsulphoxide, and distilled water was added to obtain the desired concentrations. Twenty larvae of third instars were placed into plastic beckers, containing the solution test (25 mL), in a five repetitions scheme, and their mortality, indicated by torpor and darkening of the cephalic capsule, was recorded after 48 h. Probit analyses were used to determine lethal concentrations (LC50 and LC90) and their respective 95% confidence intervals. This study showed that only diterpenoids 1 and 2 exhibited larvicidal properties with LC50 of 0.8 ppm and 87.3 ppm, respectively, revealing the former as the most toxic compound against third instars of Ae. aegypti. Therefore, this compound seems to be an interesting source for new metabolite to be exploited. PMID:18383630

  18. Oscyp71Z2 involves diterpenoid phytoalexin biosynthesis that contributes to bacterial blight resistance in rice.

    PubMed

    Li, Wenqi; Shao, Min; Yang, Jie; Zhong, Weigong; Okada, Kazunori; Yamane, Hisakazu; Qian, Guoliang; Liu, Fengquan

    2013-06-01

    Bacterial blight is one of the most destructive rice diseases, which caused by Xoo, and results in yield losses, endangering worldwide food security. Diterpenoid phytoalexins, a type of antimicrobials produced in rice, are critical for resistance to fungal and bacterial pathogens. This article reports the characterization of the cytochrome P450 gene Oscyp71Z2, which belongs to the CYP71Z subfamily. Overexpression of Oscyp71Z2 in rice enhanced resistance to Xoo at the booting stage. The accumulation of phytoalexins was rapidly and strongly induced in Oscyp71Z2-overexpressing plants, and the transcript levels of genes related to the phytoalexin biosynthesis pathway were elevated. The H₂O₂ concentration in Oscyp71Z2-overexpressing plants was reduced in accordance with the increase in ROS-scavenging ability due to the induction of SOD as well as POD and CAT activation. We also showed that suppression of Oscyp71Z2 had no significantly effect on disease resistance to Xoo in rice. These results demonstrated that Oscyp71Z2 plays an important role in bacterial blight resistance by regulating the diterpenoid phytoalexin biosynthesis and H₂O₂ generation. PMID:23602104

  19. Bioactive diterpenoids and flavonoids from the aerial parts of Scoparia dulcis.

    PubMed

    Liu, Qing; Yang, Qi-Ming; Hu, Hai-Jun; Yang, Li; Yang, Ying-Bo; Chou, Gui-Xin; Wang, Zheng-Tao

    2014-07-25

    Six new diterpenoids, 4-epi-7α-O-acetylscoparic acid A (1), 7α-hydroxyscopadiol (2), 7α-O-acetyl-8,17β-epoxyscoparic acid A (3), neo-dulcinol (4), dulcinodal-13-one (5), and 4-epi-7α-hydroxydulcinodal-13-one (6), and a new flavonoid, dillenetin 3-O-(6″-O-p-coumaroyl)-β-D-glucopyranoside (10), along with 12 known compounds, were isolated from the aerial parts of Scoparia dulcis. The 7S absolute configuration of the new diterpenoids 1-4 and 6 was deduced by comparing their NOESY spectra with that of a known compound, (7S)-4-epi-7-hydroxyscoparic acid A (7), which was determined by the modified Mosher's method. The flavonoids scutellarein (11), hispidulin (12), apigenin (15), and luteolin (16) and the terpenoids 4-epi-scopadulcic acid B (9) and betulinic acid (19) showed more potent α-glucosidase inhibitory effects (with IC50 values in the range 13.7-132.5 μM) than the positive control, acarbose. In addition, compounds 1, 11, 12, 15, 16, and acerosin (17) exhibited peroxisome proliferator-activated receptor gamma (PPAR-γ) agonistic activity, with EC50 values ranging from 0.9 to 24.9 μM. PMID:24955889

  20. Diterpenoids and aromatic compounds from the three New Zealand liverworts Jamesoniella kirkii, Balantiopsis rosea, and Radula species.

    PubMed

    Nagashima, Fumihiro; Kuba, Yoshiyuki; Asakawa, Yoshinori

    2006-06-01

    Three new aromatics were isolated from the New Zealand liverwort Balantiopsis rosea. A new bibenzyl was isolated from an unidentified Radula species, together with known bibenzyls. Jamesoniella kirkii yielded three known ent-isopimarane and two ent-kaurane diterpenoids. Their structures were confirmed by NMR techniques, chemical reaction, and X-ray crystallographic analysis. PMID:16755068

  1. Sesqui- and diterpenoids from three New Zealand liverworts: Bazzania novae-zelandiae, Gackstroemia sp. and Dendromastigophora sp.

    PubMed

    Nagashima, Fumihiro; Kuba, Yoshiaki; Ogata, Atsushi; Asakawa, Yoshinori

    2010-01-01

    Two new sesquiterpenoids, 1 and 2, were isolated from the unidentified liverwort Gackstroemia species, and three known sesquiterpenoids, 3-5, and a known sesqui- (6) and diterpenoid (7) were isolated from Bazzania novae-zelandiae and the unidentified Dendromastigophora species, respectively. Their structures were determined by spectroscopic analysis. PMID:20013475

  2. A new diterpenoid and a new triterpenoid glucosyl ester from the leaves of Callicarpa japonica Thunb. var. luxurians Rehd.

    PubMed

    Ono, Masateru; Chikuba, Tomoyo; Mishima, Kenji; Yamasaki, Toru; Ikeda, Tsuyoshi; Yoshimitsu, Hitoshi; Nohara, Toshihiro

    2009-07-01

    A new abietane-type diterpenoid and a new oleanane-type triterpenoid glucosyl ester were isolated from the leaves of Callicarpa japonica Thunb. var. luxurians Rehd. (Verbenaceae) along with 11 known compounds, comprising seven triterpenoids, two sterols, a flavonoid, and an aliphatic glycoside. Their chemical structures were determined on the basis of spectroscopic data. PMID:19184273

  3. Natural and semisynthetic diterpenoids with antiviral and immunomodulatory activities block the ERK signaling pathway.

    PubMed

    Bueno, Carlos Alberto; Michelini, Flavia Mariana; Pertino, Mariano Walter; Gómez, Catalina Arredondo; Schmeda-Hirschmann, Guillermo; Alché, Laura Edith

    2015-10-01

    The pathogenesis of many viral infections lies on the damage caused by the immune response against the virus. Current antiviral drugs do not act on the inflammatory component of the disease. Thus, new compounds that inhibit both viral multiplication and the immunopathology elicited by the virus are an approach that should be considered. In the present study, we identified two jatropholones (2A and 5B) and one carnosic acid derivative (9C) that significantly inhibited multiplication of TK+ and TK- strains of HSV-1 in Vero cells. Compounds 2A, 5B and 9C also prevented HSV-1- and TLRs-induced inflammatory response in cultivated murine macrophages. In macrophages infected with HSV-1, the inhibitory effect of compounds 2A, 5B and 9C on TNF-α and IL-6 production could be associated with the block of ERK pathway, whereas NF-κB pathway was not hampered by any of the compounds. Besides, 2A, 5B and 9C also inhibited ERK pathway and reduced TNF-α production in macrophages stimulated with TLR2, TLR4 or TLR9 agonists and were able to hinder IL-6 secretion after activation with TLR2 or TLR4, but not with TLR9. The immunomodulatory effect of 2A, 5B and 9C in macrophages infected with HSV-1 may be a consequence of the inhibition of ERK pathway activated by TLRs. The availability of compounds with both antiviral and immunomodulatory properties which affect TLR signaling pathways might be a useful strategy to control the progress of virus-induced disease. PMID:25528328

  4. Jasmonoyl-l-isoleucine is required for the production of a flavonoid phytoalexin but not diterpenoid phytoalexins in ultraviolet-irradiated rice leaves.

    PubMed

    Miyamoto, Koji; Enda, Isami; Okada, Toshiki; Sato, Yumiko; Watanabe, Kohei; Sakazawa, Tomoko; Yumoto, Emi; Shibata, Kyomi; Asahina, Masashi; Iino, Moritoshi; Yokota, Takao; Okada, Kazunori; Yamane, Hisakazu

    2016-10-01

    Rice produces low-molecular-weight antimicrobial compounds known as phytoalexins, in response to not only pathogen attack but also abiotic stresses including ultraviolet (UV) irradiation. Rice phytoalexins are composed of diterpenoids and a flavonoid. Recent studies have indicated that endogenous jasmonyl-l-isoleucine (JA-Ile) is not necessarily required for the production of diterpenoid phytoalexins in blast-infected or CuCl2-treated rice leaves. However, JA-Ile is required for the accumulation of the flavonoid phytoalexin, sakuranetin. Here, we investigated the roles of JA-Ile in UV-induced phytoalexin production. We showed that UV-irradiation induces the biosynthesis of JA-Ile and its precursor jasmonic acid. We also showed that rice jasmonate biosynthesis mutants produced diterpenoid phytoalexins but not sakuranetin in response to UV, indicating that JA-Ile is required for the production of sakuranetin but not diterpenoid phytoalexins in UV-irradiated rice leaves. PMID:27240428

  5. ent-Kaurane Diterpenoids from Chinese Liverworts and Their Antitumor Activities through Michael Addition As Detected in Situ by a Fluorescence Probe.

    PubMed

    Lin, Zhaomin; Guo, Yanxia; Gao, Yanhui; Wang, Shuqi; Wang, Xiaoning; Xie, Zhiyu; Niu, Huanmin; Chang, Wenqiang; Liu, Lei; Yuan, Huiqing; Lou, Hongxiang

    2015-05-14

    It is generally accepted that the origin of the cytotoxicity of ent-kaurane diterpenoids is due to the formation of reactive oxygen species (ROS) and that the α,β-unsaturated carbonyl is a pivotal moiety. Herein we demonstrate the isolation of 32 new and 12 known ent-kaurane diterpenoids from two Chinese liverworts. These compounds and three semisynthesized derivatives were screened against human cancer cell lines. The results revealed that their anticancer activities are caused by ROS formation through Michael modification of the protein thiols and depletion of glutathione unselectively. We also found that N-acetylcysteine reverses the cytotoxicity of these diterpenoids by forming Michael adducts, not through a well-recognized ROS scavenging pathway as previously reported. In situ intracellular thiol detection helped us visualize the intracellular distribution of the diterpenoids and determine the potency of their cytotoxicity. An alkaline analogue was found to be more selective because of the altered subcellular distribution. PMID:25856683

  6. Simultaneous identification and analysis of cassane diterpenoids in Caesalpinia minax Hance by high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

    PubMed

    Wu, Shilong; Wu, Zhaohua; Fu, Chaofan; Wu, Caiyue; Yuan, Jiuzhi; Xian, Xiaoyan; Gao, Huiyuan

    2015-12-01

    Cassane diterpenoids were successfully and simultaneously identified in Caesalpinia minax Hance by high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. A total of 59 peaks were detected, and among them 51 compounds, including 41 furanocassane diterpenoids, 10 furanolactone cassane diterpenoids were simultaneously identified and characterized on the basis of the protonated molecule, retention behavior, and fragments in MS(2) . Ten compounds, including seven novel compounds, were identified or tentatively identified for the first time in C. minax. In a positive ion mode, the fragmentation pathways of cassane diterpenoids were also analyzed for the first time. The relative amounts of the five main diterpenoids (caesalpinin L, caesalpinin F2 , bondcellpin C, caesalpinin E, and ξ-caesalmin) were simultaneously quantified by high-performance liquid chromatography. Results showed that the newly discovered and known components of C. minax can be used to determine the material basis of bioactivity; this method can also be applied to analyze cassane diterpenoids in herbal medicines from the genus Caesalpinia belonging to the family Fabaceae. PMID:26394613

  7. Rapid Bioassay-Guided Isolation of Antibacterial Clerodane Type Diterpenoid from Dodonaea viscosa (L.) Jaeq.

    PubMed Central

    Khurram, Muhammad; Lawton, Linda A.; Edwards, Christine; Iriti, Marcello; Hameed, Abdul; Khan, Murad A.; Khan, Farman A.; ur Rahman, Shafiq

    2015-01-01

    Plant extracts are complex matrices and, although crude extracts are widely in use, purified compounds are pivotal in drug discovery. This study describes the application of automated preparative-HPLC combined with a rapid off-line bacterial bioassay, using reduction of a tetrazolium salt as an indicator of bacterial metabolism. This approach enabled the identification of fractions from Dodonaea viscosa that were active against Staphylococcus aureus and Escherichia coli, which, ultimately, resulted in the identification of a clerodane type diterpenoid, 6β-hydroxy-15,16-epoxy-5β, 8β, 9β, 10α-cleroda-3, 13(16), 14-trien-18-oic acid, showing bacteriostatic activity (minimum inhibitory concentration (MIC) = 64–128 µg/mL) against test bacteria. To the best of our knowledge, this is the first report on antibacterial activity of this metabolite from D. viscosa. PMID:26343638

  8. Notolutesins A-J, dolabrane-type diterpenoids from the Chinese liverwort Notoscyphus lutescens.

    PubMed

    Wang, Song; Li, Rui-Juan; Zhu, Rong-Xiu; Hu, Xiao-Yan; Guo, Yan-Xia; Zhou, Jin-Chuan; Lin, Zhao-Min; Zhang, Jiao-Zhen; Wu, Jing-Yi; Kang, Ya-Qi; Morris-Natschke, Susan L; Lee, Kuo-Hsiung; Yuan, Hui-Qing; Lou, Hong-Xiang

    2014-09-26

    Ten new dolabrane-type diterpenoids, notolutesins A-J (1-10), were isolated from the Chinese liverwort Notoscyphus lutescens, along with four known compounds. The structures of the new compounds were established on the basis of extensive spectroscopic data, and that of 1 was confirmed by single-crystal X-ray crystallography. The absolute configuration of 1 was determined by comparing its experimental and calculated electronic circular dichroism spectra. All of the isolates were evaluated for their cytotoxicity against a small panel of human cancer cell lines, and compound 1 exhibited an IC50 value of 6.2 μM against the PC3 human prostate cancer cell line. PMID:25226363

  9. ent-Atisane diterpenoids from Euphorbia fischeriana inhibit mammosphere formation in MCF-7 cells.

    PubMed

    Kuang, Xinzhu; Li, Wei; Kanno, Yuichiro; Yamashita, Naoya; Nemoto, Kiyomitsu; Asada, Yoshihisa; Koike, Kazuo

    2016-01-01

    The discovery of new drugs that target cancer stem cells (CSCs) is a critical approach to overcome the major difficulties of the metastasis, chemotherapeutic resistance and recurrence for successful cancer therapy. Chemical investigation of the roots of Euphorbia fischeriana resulted in the isolation of eight ent-atisane diterpenoids (1-8), including two new compounds: 19-O-β-D-glucopyranosyl-ent-atis-16-ene-3,14-dione (7) and 19-O-(6-galloyl)-β-D-glucopyranosyl-ent-atis-16-ene-3,14-dione (8). The structures were elucidated on extensive spectroscopic analyses, as well as chemical transformations. ent-3β-Hydroxyatis-16-ene-2,14-dione (5), 7 and its aglycon, ent-19-hydroxy-atis-16-ene-3,14-dione (7a), showed significant inhibitory activity on mammosphere formation in human breast cancer MCF-7 cells at a final concentration of 10 μM. PMID:26411465

  10. Abietane-type diterpenoids from the roots of Caryopteris mongolica and their cholinesterase inhibitory activities.

    PubMed

    Murata, Toshihiro; Ishikawa, Yoshinobu; Saruul, Erdenebileg; Selenge, Erdenechimeg; Sasaki, Kenroh; Umehara, Kaoru; Yoshizaki, Fumihiko; Batkhuu, Javzan

    2016-10-01

    Eleven abietane-type diterpenoids and two known abietanes were isolated from the roots of Caryopteris mongolica, and their structures were characterized. The absolute configurations at C-5 and C-10 were determined from the NMR data, including from the nuclear Overhauser effect and CD spectra, and the absolute configuration of C-16 in the hydroxypropyl group was determined via a modified Mosher's method. Furthermore, the previously unknown absolute configuration of the C-15 of cyrtophyllone B was determined to be in an R-configuration using X-ray crystallography. To estimate the preventive effects of the isolates for neurodegenerative disease development, their inhibitory activities against acetylcholinesterase (AChE) from human erythrocytes and butyrylcholinesterase (BChE) from horse serum were evaluated. PMID:27298275

  11. Jatrophane diterpenoid esters from Euphorbia sororia serving as multidrug resistance reversal agents.

    PubMed

    Lu, Dongli; Liu, Yongqiang; Aisa, Haji Akber

    2014-01-01

    Six (1-6) new jatrophane diterpenoid esters together with four known compounds (7-10) were isolated from the acetone extract of fructus Euphorbia sororia. Their structures were elucidated by the spectral technology, including the 2D NMR experiments (HMQC, HMBC and NOESY). The absolute configuration of compound 1 and compound 7 were first confirmed by X-ray crystallographic analysis. Compounds 1-7 were assayed for their antiproliferative activity in human cancer cell lines: human mammary adenocarcinoma (MCF-7) and human lung adenocarcinoma (A549). All the compounds were inactive for the cell lines. The multidrug-resistance reversal activity was also tested on KBv200 cells and compound 2 displayed strong multidrug resistance reversal activity, outperforming verapamil at 10 μM. PMID:24291755

  12. Diterpenoids from the Endophytic Fungus Botryosphaeria sp. P483 of the Chinese Herbal Medicine Huperzia serrata.

    PubMed

    Chen, Yan-Mei; Yang, Yin-He; Li, Xiao-Nian; Zou, Cheng; Zhao, Pei-Ji

    2015-01-01

    Two new tetranorlabdane diterpenoids, named botryosphaerins G (1) and H (2), were isolated from the solid fermentation products of Botryosphaeria sp. P483 along with seven known tetranorlabdane diterpenes (3-9). Their structures were elucidated by extensive analysis, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). Their absolute configuration was confirmed by single-crystal X-ray diffraction analyses using the anomalous scattering of Cu Kα radiation. All of the isolated compounds were tested for activity against phytopathogenic fungi and nematodes. Compounds 2 and 3 showed antifungal activity and compound 2 showed weak nematicidal activity. PMID:26393542

  13. Inhibition of Helicobacter pylori and Its Associate Urease by Labdane Diterpenoids Isolated from Andrographis paniculata.

    PubMed

    Shaikh, Rafik U; Dawane, Ashwini A; Pawar, Rajendra P; Gond, Dhananjay S; Meshram, Rohan J; Gacche, Rajesh N

    2016-03-01

    The present study was carried out to evaluate anti-Helicobacter pylori and its associated urease activity of labdane diterpenoids isolated from Andrographis paniculata. A molecular docking analysis was performed by using ArgusLab 4.0.1 software. The results obtained indicate that compound A possesses strong inhibition to H. pylori, 28 ± 2.98 (minimum inhibitory concentration, 9 µg/mL), and its urease, 85.54 ± 2.62% (IC50 , 20.2 µg/mL). Compounds B, C, and D also showed moderate inhibition to H. pylori and its urease. The obtained results were in agreement with the molecular docking analysis of compounds. The phytochemicals under investigation were found to be promising antibacterial agents. Moreover, the isolated compounds can be considered as a resource for searching novel anti-H. pylori agents possessing urease inhibition. PMID:26648323

  14. Cespitulones A and B, Cytotoxic Diterpenoids of a New Structure Class from the Soft Coral Cespitularia taeniata

    PubMed Central

    Lin, Yu-Chi; Wang, Shih-Sheng; Chen, Chung-Hsiung; Kuo, Yao-Haur; Shen, Ya-Ching

    2014-01-01

    Two novel diterpenoids, cespitulones A (1) and B (2), were isolated from extracts of the soft coral Cespitularia taeniata. Both compounds possess an unprecedented bicyclo [10.3.1] ring system with C-C bond connections between C-10 and C-20, and between C-20 and C-11. Their structures were elucidated on the basis of extensive spectroscopic analyses. Compound 1 exhibited significant cytotoxicity against human medulloblastoma and colon adenocarcinoma cancer cells. PMID:24905485

  15. Euphorikanin A, a Diterpenoid Lactone with a Fused 5/6/7/3 Ring System from Euphorbia kansui.

    PubMed

    Fei, Dong-Qing; Dong, Le-Le; Qi, Feng-Ming; Fan, Gai-Xia; Li, Hui-Hong; Li, Zheng-Yu; Zhang, Zhan-Xin

    2016-06-17

    Euphorikanin A (1), an unprecedented diterpenoid lactone which possesses a novel 5/6/7/3-fused tetracyclic ring skeleton, was isolated from the roots of Euphorbia kansui. The chemical structure and absolute stereochemistry were elucidated on the basis of extensive spectroscopic methods and single-crystal X-ray diffraction analysis. Compound 1 exhibited moderate cytotoxicity against two human tumor cell lines HeLa and NCI-446. A proposed biosynthetic pathway of compound 1 is also described. PMID:27230557

  16. Structure of a novel diterpenoid ester, fritillahupehin from bulbs of Fritillaria hupehensis Hsiao and K.C. Hsia.

    PubMed

    Ruan, Hanli; Zhang, Yonghui; Wu, Jizhou; Deng, Shukai; Sun, Handong; Fujita, Tetsuro

    2002-07-01

    A new diterpenoid ester, fritillahupehin (1) together with three known fatty acids: palmitic acid (2), lignoceric acid (3) and azelaic acid (4) were isolated from the bulbs of Fritillaria hupehensis Hsiao and K.C. Hsia. The structure of fritillahupehin has been established to be ent-kauran-16beta-yl lignocerate by means of spectroscopic and chemical evidence. Compounds 2-4 were isolated from Fritillaria sp. for the first time. PMID:12234570

  17. A Novel Aromatic-Ring-Hydroxylating Dioxygenase from the Diterpenoid-Degrading Bacterium Pseudomonas abietaniphila BKME-9

    PubMed Central

    Martin, Vincent J. J.; Mohn, William W.

    1999-01-01

    Pseudomonas abietaniphila BKME-9 is able to degrade dehydroabietic acid (DhA) via ring hydroxylation by a novel dioxygenase. The ditA1, ditA2, and ditA3 genes, which encode the α and β subunits of the oxygenase and the ferredoxin of the diterpenoid dioxygenase, respectively, were isolated and sequenced. The ferredoxin gene is 9.2 kb upstream of the oxygenase genes and 872 bp upstream of a putative meta ring cleavage dioxygenase gene, ditC. A Tn5 insertion in the α subunit gene, ditA1, resulted in the accumulation by the mutant strain BKME-941 of the pathway intermediate, 7-oxoDhA. Disruption of the ferredoxin gene, ditA3, in wild-type BKME-9 by mutant-allele exchange resulted in a strain (BKME-91) with a phenotype identical to that of the mutant strain BKME-941. Sequence analysis of the putative ferredoxin indicated that it is likely to be a [4Fe-4S]- or [3Fe-4S]-type ferredoxin and not a [2Fe-2S]-type ferredoxin, as found in all previously described ring-hydroxylating dioxygenases. Expression in Escherichia coli of ditA1A2A3, encoding the diterpenoid dioxygenase without its putative reductase component, resulted in a functional enzyme. The diterpenoid dioxygenase attacks 7-oxoDhA, and not DhA, at C-11 and C-12, producing 7-oxo-11,12-dihydroxy-8,13-abietadien acid, which was identified by 1H nuclear magnetic resonance, UV-visible light, and high-resolution mass spectrometry. The organization of the genes encoding the various components of the diterpenoid dioxygenase, the phylogenetic distinctiveness of both the α subunit and the ferredoxin component, and the unusual Fe-S cluster of the ferredoxin all suggest that this enzyme belongs to a new class of aromatic ring-hydroxylating dioxygenases. PMID:10217753

  18. The Diterpenoid 7-Keto-Sempervirol, Derived from Lycium chinense, Displays Anthelmintic Activity against both Schistosoma mansoni and Fasciola hepatica

    PubMed Central

    Edwards, Jennifer; Brown, Martha; Peak, Emily; Bartholomew, Barbara; Nash, Robert J.; Hoffmann, Karl F.

    2015-01-01

    Background Two platyhelminths of biomedical and commercial significance are Schistosoma mansoni (blood fluke) and Fasciola hepatica (liver fluke). These related trematodes are responsible for the chronic neglected tropical diseases schistosomiasis and fascioliasis, respectively. As no vaccine is currently available for anti-flukicidal immunoprophylaxis, current treatment is mediated by mono-chemical chemotherapy in the form of mass drug administration (MDA) (praziquantel for schistosomiasis) or drenching (triclabendazole for fascioliasis) programmes. This overreliance on single chemotherapeutic classes has dramatically limited the number of novel chemical entities entering anthelmintic drug discovery pipelines, raising significant concerns for the future of sustainable blood and liver fluke control. Methodology/ Principle Findings Here we demonstrate that 7-keto-sempervirol, a diterpenoid isolated from Lycium chinense, has dual anthelmintic activity against related S. mansoni and F. hepatica trematodes. Using a microtiter plate-based helminth fluorescent bioassay (HFB), this activity is specific (Therapeutic index = 4.2, when compared to HepG2 cell lines) and moderately potent (LD50 = 19.1 μM) against S. mansoni schistosomula cultured in vitro. This anti-schistosomula effect translates into activity against both adult male and female schistosomes cultured in vitro where 7-keto-sempervirol negatively affects motility/behaviour, surface architecture (inducing tegumental holes, tubercle swelling and spine loss/shortening), oviposition rates and egg morphology. As assessed by the HFB and microscopic phenotypic scoring matrices, 7-keto-sempervirol also effectively kills in vitro cultured F. hepatica newly excysted juveniles (NEJs, LD50 = 17.7 μM). Scanning electron microscopy (SEM) evaluation of adult F. hepatica liver flukes co-cultured in vitro with 7-keto-sempervirol additionally demonstrates phenotypic abnormalities including breaches in tegumental integrity and

  19. Noncariogenic intense natural sweeteners.

    PubMed

    Kinghorn, A D; Kaneda, N; Baek, N I; Kennelly, E J; Soejarto, D D

    1998-09-01

    There is a definite relationship between the dietary consumption of sucrose and the incidence of dental caries. Noncaloric sucrose substitutes for use in the sweetening of foods, beverages, and medicines may be either synthetic compounds or natural products. In the United States, four potently sweet artificial sweeteners are approved, namely, saccharin, aspartame, acesulfame potassium, and sucralose. Highly sweet plant constituents are used in Japan and some other countries, including the diterpene glycoside stevioside and the protein thaumatin. Recent progress in a research project oriented towards the discovery and evaluation of novel potentially noncariogenic sweeteners from plants has focused on substances in the sesquiterpenoid, diterpenoid, triterpenoid, steroidal saponin, and proanthocyanidin structural classes. The feasibility of using Mongolian gerbil electrophysiological and behavioral assays to monitor the sweetness of plant extracts, chromatographic fractions, and pure isolates has been investigated. An in vivo cariogenicity study on the commercially available natural sweeteners stevioside and rebaudioside A has been carried out. PMID:9735874

  20. Triphenylphosphonium Cations of the Diterpenoid Isosteviol: Synthesis and Antimitotic Activity in a Sea Urchin Embryo Model.

    PubMed

    Strobykina, Irina Yu; Belenok, Mayya G; Semenova, Marina N; Semenov, Victor V; Babaev, Vasiliy M; Rizvanov, Ildar Kh; Mironov, Vladimir F; Kataev, Vladimir E

    2015-06-26

    A series of novel triphenylphosphonium (TPP) cations of the diterpenoid isosteviol (1, 16-oxo-ent-beyeran-19-oic acid) have been synthesized and evaluated in an in vivo phenotypic sea urchin embryo assay for antimitotic activity. The TPP moiety was applied as a carrier to provide selective accumulation of a connected compound into mitochondria. When applied to fertilized eggs, the targeted isosteviol TPP conjugates induced mitotic arrest with the formation of aberrant multipolar mitotic spindles, whereas both isosteviol and the methyltriphenylphosphonium cation were inactive. The structure-activity relationship study revealed the essential role of the TPP group for the realization of the isosteviol effect, while the chemical structure and the length of the linker only slightly influenced the antimitotic potency. The results obtained using the sea urchin embryo model suggested that TPP conjugates of isosteviol induced mitotic spindle defects and mitotic arrest presumably by affecting mitochondrial DNA. Since targeting mitochondria is considered as an encouraging strategy for cancer therapy, TPP-isosteviol conjugates may represent promising candidates for further design as anticancer agents. PMID:26042548

  1. Isopimarane diterpenoids from Kaempferia pulchra rhizomes collected in Myanmar and their Vpr inhibitory activity.

    PubMed

    Win, Nwet Nwet; Ito, Takuya; Matsui, Takashi; Aimaiti, Simayijiang; Kodama, Takeshi; Ngwe, Hla; Okamoto, Yasuko; Tanaka, Masami; Asakawa, Yoshinori; Abe, Ikuro; Morita, Hiroyuki

    2016-04-01

    Viral protein R (Vpr), an accessory gene of HIV-1, plays important roles in viral pathogenesis. Screening of Myanmar medicinal plants that are popular as primary treatments for HIV/AIDS and for HIV-related problems revealed the potent anti-Vpr activity of the CHCl3-soluble extract of Kaempferia pulchra rhizomes, in comparison with that of the positive control, damnacanthal. Fractionation of the active CHCl3-soluble extract led to the identification of 30 isopimarane diterpenoids, including kaempulchraols A-W (1-23). All isolates were assayed for anti-Vpr activity against TREx-HeLa-Vpr cells, in which Vpr expression is tightly regulated by tetracycline. Kaempulchraols B (2), D (4), G (7), Q (17), T (20), U (21), and W (23) exhibited potent anti-Vpr activity, at concentrations ranging from 1.56 to 6.25μM. The structure-activity relationships of the active kaempulchraols suggested that the presence of a hydroxy group at C-14 in an isopimara-8(9),15-diene skeleton and the presence of an acetoxy group at C-1 or C-7 in an isopimara-8(14),15-diene skeleton are the critical factors for the inhibitory effects against TREx-HeLa-Vpr cells. PMID:26916438

  2. Bioactive Enmein-Type ent-Kaurane Diterpenoids from Isodon phyllostachys.

    PubMed

    Yang, Jin; Wang, Wei-Guang; Wu, Hai-Yan; Du, Xue; Li, Xiao-Nian; Li, Yan; Pu, Jian-Xin; Sun, Han-Dong

    2016-01-22

    Thirty-two enmein-type ent-kaurane diterpenoids, including 13 new compounds, were isolated from the aerial parts of Isodon phyllostachys. Compounds 1 and 2 are the first examples of 3,20:6,20-diepoxyenmein-type ent-kauranoids, and the structures of these new compounds were established mainly by analyzing NMR and HREIMS data. The absolute configurations of 1 and 8 and the relative configuration of 9 were determined using single-crystal X-ray diffraction. Compounds 11, 15, 20, and 21 were active against five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480), with IC50 values ranging from 1.2 to 5.0 μM. Compounds 3, 11, 15, 17, 20, 21, 25, and 29 strongly inhibited NO production in LPS-stimulated RAW264.7 cells, with IC50 values ranging from 0.74 to 4.93 μM. PMID:26757019

  3. In vivo activity of benzoyl ester clerodane diterpenoid derivatives from Dodonaea polyandra.

    PubMed

    Simpson, Bradley S; Claudie, David J; Gerber, Jacobus P; Pyke, Simon M; Wang, Jiping; McKinnon, Ross A; Semple, Susan J

    2011-04-25

    Four new benzoyl ester clerodane diterpenoids, 15,16-epoxy-8α-(benzoyloxy)methylcleroda-3,13(16),14-trien-18-oic acid (1), 15,16-epoxy-8α-(benzoyloxy)methyl-2α-hydroxycleroda-3,13(16),14-trien-18-oic acid (2), 15,16-epoxy-8α-(benzoyloxy)methyl-2-oxocleroda-3,13(16),14-trien-18-oic acid (3), and 15,16-epoxy-2α-benzoyloxycleroda-3,13(16),14-trien-18-oic acid (4), have been isolated from the leaves and stems of Dodonaea polyandra. The anti-inflammatory activities of compounds 1, 2, and 4 were evaluated by means of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema. Compounds 2 and 4 exhibited maximum inhibition of inflammation (70-76%) at doses of 0.22 and 0.9 μmol/ear, respectively. Modest activity (~45% inhibition) was maintained at nanomole/ear doses. PMID:21381684

  4. Peltate glandular trichomes of Colquhounia seguinii harbor new defensive clerodane diterpenoids.

    PubMed

    Li, Chun-Huan; Liu, Yan; Hua, Juan; Luo, Shi-Hong; Li, Sheng-Hong

    2014-09-01

    Glandular trichomes produce a wide variety of secondary metabolites that are considered as major defensive chemicals against herbivore attack. The morphology and secondary metabolites of the peltate glandular trichomes of a lianoid Labiatae, Colquhounia seguinii Vaniot, were investigated. Three new clerodane diterpenoids, seguiniilactones A-C (1-3), were identified through precise trichome collection with laser microdissection, metabolic analysis with ultra performance liquid chromatography-tandem mass spectrometer, target compound isolation with classical phytochemical techniques, structure elucidation with spectroscopic methods. All compounds showed significant antifeedant activity against a generalist plant-feeding insect Spodoptera exigua. Seguiniilactone A (1) was approximately 17-fold more potent than the commercial neem oil. α-Substituted α,β-unsaturated γ-lactone functionality was found to be crucial for strong antifeedant activity of this class of compounds. Quantitative results indicated that the levels of these compounds in the peltate glandular trichomes and leaves were sufficiently high to deter the feeding by generalist insects. Moderate antifungal activity was observed for seguiniilactone C (3) against six predominant fungal species isolated from the diseased leaves of C. seguinii, while seguiniilactones A and B were generally inactive. These findings suggested that seguiniilactones A-C might be specialized secondary metabolites in peltate glandular trichomes for the plant defense against insect herbivores and pathogens. PMID:25048077

  5. Scapaundulin C, a novel labdane diterpenoid isolated from Chinese liverwort Scapania undulate, inhibits acetylcholinesterase activity.

    PubMed

    Kang, Ya-Qi; Zhou, Jin-Chuan; Fan, Pei-Hong; Wang, Shu-Qi; Lou, Hong-Xiang

    2015-12-01

    In the present study, scapaundulin C (1), a new labdane diterpenoid, and four related known compounds scapaundulin A (2), 5α, 8α, 9α-trihydroxy-13E-labden-12-one (3), 5α, 8α-dihydroxy-13E-labden-12-one (4), and (13S)-15-hydroxylabd-8 (17)-en-19-oic acid (5), were isolated from the Chinese liverwort Scapania undulate (L.) Dum., using column chromatography. The structures of these compounds were determined on the basis of 1D- and 2D-NMR analyses. The acetylcholinesterase (AchE) inhibitory activity was evaluated using a bioautographic TLC assay and the cytotoxic activity was evaluated by the MTT method. All the compounds were reported for the first time to exhibit moderate AchE inhibitory activity with minimal inhibitory quantities ranging from 250 to 500 ng. All the compounds were tested for their cytotoxicity against five human tumor cell lines, A549, K562, A2780, Hela, and HT29, and compounds 3 and 4 exhibited moderate inhibitory effects on the growth of A2780 cells. PMID:26721712

  6. Jatrophane and ingenane-type diterpenoids from Euphorbia kansui inhibit the LPS-induced NO production in RAW 264.7 cells.

    PubMed

    Lee, Jin Woo; Jin, Qinghao; Jang, Hari; Lee, Dongho; Han, Sang Bae; Kim, Youngsoo; Hong, Jin Tae; Lee, Mi Kyeong; Hwang, Bang Yeon

    2016-07-15

    Bioactivity-guided fractionation of the MeOH extract from the roots of Euphorbia kansui resulted in the isolation of two new jatrophane-type diterpenoids, kanesulones A (1) and B (2), together with six known jatrophane-type diterpenoids (3-8) and ten known ingenane-type diterpenoids (9-18). Their chemical structures were elucidated on the basis of spectroscopic data interpretation, especially 1D and 2D NMR such as HMQC, HMBC, COSY and NOESY, and HRESIMS data as well as CD analysis. Compounds 1-8 and 11-18 exhibited the inhibitory effects on LPS-induced nitric oxide production with IC50 values ranging from 0.7 to 46.5μM in RAW 264.7 macrophages. PMID:27246615

  7. Characterization of isoquinoline alkaloids, diterpenoids and steroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittata and Tinospora capillipes) by high-performance liquid chromatography/electrospray ionization with multistage mass spectrometry.

    PubMed

    Zhang, Yufeng; Shi, Qirong; Shi, Peiying; Zhang, Weidong; Cheng, Yiyu

    2006-01-01

    This study sought to determine the primary components (isoquinoline alkaloids, diterpenoids and steroids) in crude extracts of the Chinese herb Jin-Guo-Lan, prepared from the roots of Tinospora sagittata and T. capillipes, by liquid chromatography/electrospray ionization multistage mass spectrometry coupled with diode-array detection (LC-DAD/ESI-MS(n)). After separation on a reversed-phase C(18) column using gradient elution, positive and negative ESI-MS experiments were performed. In positive ion mode, the three types of compounds showed very different characteristic ions: strong [M](+) or [M+H](+) ions were observed for isoquinoline alkaloids; [M+NH(4)](+) and/or [M+H-CO(2)](+) for diterpenoids; [M+H-nH(2)O](+) (n=1-3) for steroids. These adduct ions and/or fragments were used to deduce the mass and categories of known and unknown components in crude extracts, and their structures were further confirmed by ESI-MS(n) in positive ion mode. Moreover, UV absorption peaks obtained from DAD provided useful functional group information to aid the MS(n)-based identification. As a result, 11 compounds were unambiguously identified by comparing with standard compounds and 13 compounds were tentatively identified or deduced according to their MS(n) data. Two of these compounds (13-hydroxycolumbamine and 13-hydroxyjatrorrhizine) were found to be new compounds and another one (13-hydroxypalmatine) was detected for the first time as a natural product. In addition, a [M-*CH(3)-H(2)O](*+) ion in MS(2) of [M](+) after in-source collision-induced dissociation was used to differentiate positional isomers of protoberberine alkaloids, columbamine and jatrorrhizine. Although the roots of T. sagittata and T. capillipes contain almost identical compounds, the content of the compounds in them is dramatically different, suggesting the necessity for further comparison of the bioactivities of the two species. PMID:16817243

  8. CYP701A8: a rice ent-kaurene oxidase paralog diverted to more specialized diterpenoid metabolism.

    PubMed

    Wang, Qiang; Hillwig, Matthew L; Wu, Yisheng; Peters, Reuben J

    2012-03-01

    All higher plants contain an ent-kaurene oxidase (KO), as such a cytochrome P450 (CYP) 701 family member is required for gibberellin (GA) phytohormone biosynthesis. While gene expansion and functional diversification of GA-biosynthesis-derived diterpene synthases into more specialized metabolism has been demonstrated, no functionally divergent KO/CYP701 homologs have been previously identified. Rice (Oryza sativa) contains five CYP701A subfamily members in its genome, despite the fact that only one (OsKO2/CYP701A6) is required for GA biosynthesis. Here we demonstrate that one of the other rice CYP701A subfamily members, OsKOL4/CYP701A8, does not catalyze the prototypical conversion of the ent-kaurene C4α-methyl to a carboxylic acid, but instead carries out hydroxylation at the nearby C3α position in a number of related diterpenes. In particular, under conditions where OsKO2 catalyzes the expected conversion of ent-kaurene to ent-kaurenoic acid required for GA biosynthesis, OsKOL4 instead efficiently reacts with ent-sandaracopimaradiene and ent-cassadiene to produce the corresponding C3α-hydroxylated diterpenoids. These compounds are expected intermediates in biosynthesis of the oryzalexin and phytocassane families of rice antifungal phytoalexins, respectively, and can be detected in rice plants under the appropriate conditions. Thus, it appears that OsKOL4 plays a role in the more specialized diterpenoid metabolism of rice, and our results provide evidence for divergence of a KO/CYP701 family member from GA biosynthesis. This further expands the range of enzymes recruited from the ancestral GA primary pathway to the more complex and specialized labdane-related diterpenoid metabolic network found in rice. PMID:22247270

  9. Scapairrins A-Q, Labdane-Type Diterpenoids from the Chinese Liverwort Scapania irrigua and Their Cytotoxic Activity.

    PubMed

    Zhang, Jiaozhen; Li, Yi; Zhu, Rongxiu; Li, Lin; Wang, Yongjie; Zhou, Jinchuan; Qiao, Yanan; Zhang, Zhenwei; Lou, Hongxiang

    2015-08-28

    Seventeen new labdane-type diterpenoids, scapairrins A-Q (1-17), including six pairs of diastereoisomers, and three known analogues (18-20) were isolated from the Chinese liverwort Scapania irrigua. The structures of 1-17 were determined based on a combination of the analysis of their MS and NMR spectroscopic data, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Cytotoxicity testing showed that compounds 7-10 exhibited inhibitory activities against a small panel of human cancer cell lines. PMID:26252628

  10. A novel isopimarane diterpenoid with acetylcholinesterase inhibitory activity from Nepeta sorgerae, an endemic species to the Nemrut Mountain.

    PubMed

    Yilmaz, Anil; Cağlar, Pinar; Dirmenci, Tuncay; Gören, Nezhun; Topçu, Gülaçti

    2012-06-01

    From the dichloromethane extract of Nepeta sorgerae, the isolation and structure elucidation are now reported of a new isopimarane diterpenoid, named sorgerolone, and two known triterpenoids, oleanolic acid and ursolic acid. Antioxidant activity of the extracts and the isolated terpenoids was determined by the DPPH free radical scavenging and lipid peroxidation inhibition (beta-carotene bleaching) methods. Anticholinesterase activity of the extracts and isolates was investigated by Ellman's method against AChE and BChE enzymes. Although the antioxidant activity results were low, the AChE enzyme inhibition of the extracts and terpenoids was very promising. PMID:22816286

  11. Inhibitory effect of Andrographis paniculata extract and its active diterpenoids on platelet aggregation.

    PubMed

    Thisoda, Piengpen; Rangkadilok, Nuchanart; Pholphana, Nanthanit; Worasuttayangkurn, Luksamee; Ruchirawat, Somsak; Satayavivad, Jutamaad

    2006-12-28

    Andrographis paniculata has been widely used for the prevention and treatment of common cold especially in Asia and Scandinavia. The three active diterpenoids from this plant, including aqueous plant extracts, were investigated for the inhibitory effect on platelet aggregation in vitro. The results indicated that andrographolide (AP(1)) and 14-deoxy-11,12-didehydroandrographolide (AP(3)) significantly inhibited thrombin-induced platelet aggregation in a concentration-(1-100 microM) and time-dependent manner while neoandrographolide (AP(4)) had little or no activity. AP(3) exhibited higher antiplatelet activity than AP(1) with IC(50) values ranging from 10 to 50 microM. The inhibitory mechanism of AP(1) and AP(3) on platelet aggregation was also evaluated and the results indicated that the inhibition of extracellular signal-regulated kinase1/2 (ERK1/2) pathway may contribute to antiplatelet activity of these two compounds. In addition, standardized aqueous extracts of A. paniculata containing different amounts of AP(3) inhibited thrombin-induced aggregation to different degrees. The extracts significantly decreased platelet aggregation in a concentration-(10-100 microg/ml) and time-dependent manner. However, the extract with high level of AP(3) (Extract B) (IC(50) values=50-75 microg/ml) showed less inhibitory activity against thrombin than the extract with lower level of AP(3) (Extract A) (IC(50) values=25-50 microg/ml). These results indicate that the standardized A. paniculata extract may contain other antiplatelet compounds rather than AP(1) and AP(3), which contribute to high antiplatelet activity. Therefore, the consumption of A. paniculata products may help to prevent or treat some cardiovascular disorders i.e. thrombosis; however, it should be used with caution by patients with bleeding disorders. PMID:17081514

  12. Immunomodulatory Effect of Marine Cembrane-Type Diterpenoids on Dendritic Cells

    PubMed Central

    Lin, Ching-Yen; Lu, Mei-Chin; Su, Jui-Hsin; Chu, Ching-Liang; Shiuan, David; Weng, Ching-Feng; Sung, Ping-Jyun; Huang, Kao-Jean

    2013-01-01

    Dendritic cells (DCs) are antigen presenting cells, which can present antigens to T-cells and play an important role in linking innate and adaptive immunity. DC maturation can be induced by many stimuli, including pro-inflammatory cytokines and bacterial products, such as lipopolysaccharides (LPS). Here, we examined the immunomodulatory effects of marine cembrane compounds, (9E,13E)-5-acetoxy-6-hydroxy-9,13-dimethyl-3-methylene-3,3a,4,5,6,7,8,11,12,14a-decahydro-2H-cyclotrideca[b]furan-2-one (1), (9E,13E)-5-acetoxy-6-acetyl-9,13-dimethyl-3-methylene-3,3a,4,5,6,7,8,11,12,14a-decahydro-2H-cyclotrideca[b]furan-2-one (2), lobocrassin B (3), (−)14-deoxycrassin (4), cembranolide B (5) and 13-acetoxysarcocrassolide (6) isolated from a soft coral, Lobophytum crassum, on mouse bone marrow-derived dendritic cells (BMDCs). The results revealed that cembrane-type diterpenoids, especially lobocrassin B, effectively inhibited LPS-induced BMDC activation by inhibiting the production of TNF-α. Pre-treatment of BMDCs with Lobocrassin B for 1 h is essential to prohibit the following activation induced by various toll-like receptor (TLR) agonists, such as LPS, zymosan, lipoteichoic acid (LTA) and Pam2CSK4. Inhibition of NF-κB nuclear translocation by lobocrassin B, which is a key transcription factor for cytokine production in TLR signaling, was evident as assayed by high-content image analysis. Lobocrassin B attenuated DC maturation and endocytosis as the expression levels of MHC class II and the co-stimulatory molecules were downregulated, which may affect the function of DCs to initiate the T-cell responses. Thus, lobocrassin B may have the potential in treatment of immune dysregulated diseases in the future. PMID:23609581

  13. Cytotoxic and Pro-Apoptotic Effects of Cassane Diterpenoids from the Seeds of Caesalpinia sappan in Cancer Cells.

    PubMed

    Bao, Han; Zhang, Le-Le; Liu, Qian-Yu; Feng, Lu; Ye, Yang; Lu, Jin-Jian; Lin, Li-Gen

    2016-01-01

    The chemical study on the seeds of Caesalpinia sappan led to the isolation of five new cassane diterpenoids, phanginins R‒T (1-3) and caesalsappanins M and N (4 and 5), together with seven known compounds 6-12. Their structures were elucidated on the basis of NMR and HRESIMS analyses. The absolute configurations of compounds 1 and 4 were determined by the corresponding CD spectra. All the isolated compounds were tested for their cytotoxicity against ovarian cancer A2780 and HEY, gastric cancer AGS, and non-small cell lung cancer A549 cells. Compound 1 displayed significant toxicity against the four cell lines with the IC50 values of 9.9 ± 1.6 µM, 12.2 ± 6.5 µM, 5.3 ± 1.9 µM, and 12.3 ± 3.1 µM, respectively. Compound 1 induced G1 phase cell cycle arrest in A2780 cells. Furthermore, compound 1 dose-dependently induced A2780 cells apoptosis as evidenced by Hoechst 33342 staining, Annexin V positive cells, the up-regulated cleaved-PARP and the enhanced Bax/Bcl-2 ratio. What's more, compound 1 also promoted the expression of the tumor suppressor p53 protein. These findings indicate that cassane diterpenoids might have potential as anti-cancer agents, and further in vivo animal studies and structural modification investigation are needed. PMID:27322234

  14. Distribution and carbon isotope patterns of diterpenoids and triterpenoids in modern temperate C3 trees and their geochemical significance

    NASA Astrophysics Data System (ADS)

    Diefendorf, Aaron F.; Freeman, Katherine H.; Wing, Scott L.

    2012-05-01

    Tricyclic diterpenoids and pentacyclic triterpenoids are nearly exclusively produced by gymnosperms and angiosperms, respectively. Even though both classes of terpenoids have long been recognized as plant biomarkers, their potential use as phylogenetically specific δ13C proxies remains largely unexplored. Little is known of how terpenoid abundance and carbon isotope composition vary either with plant phylogenetic position, functional group, or during synthesis. Here, we report terpenoid abundances and isotopic data for 44 tree species in 21 families, representing both angiosperms and gymnosperms, and both deciduous and evergreen leaf habits. Di- and triterpenoid abundances are significantly higher in evergreens compared to deciduous species, reflecting differences in growth strategies and increased chemical investment in longer-lived leaves. Carbon isotope abundances of terpenoid lipids are similar to leaf tissues, indicating biosynthetic isotope effects are small for both the MVA (-0.4‰) and MEP (-0.6‰) pathways. Leaf and molecular isotopic patterns for modern plants are consistent with observations of amber, resins and plant biomarkers in ancient sediments. The δ13C values of ancient diterpenoids are higher than triterpenoids by 2-5‰, consistent with observed isotopic differences between gymnosperms and angiosperms leaves, and support the relatively small lipid biosynthetic effects reported here. All other factors being equal, evergreen plants will dominate the abundance of terpenoids contributed to soils, sediments and ancient archives, with similar inputs estimated for angiosperm and gymnosperm trees when scaled by litter flux.

  15. Serrulatane Diterpenoid from Eremophila neglecta Exhibits Bacterial Biofilm Dispersion and Inhibits Release of Pro-inflammatory Cytokines from Activated Macrophages.

    PubMed

    Mon, Htwe H; Christo, Susan N; Ndi, Chi P; Jasieniak, Marek; Rickard, Heather; Hayball, John D; Griesser, Hans J; Semple, Susan J

    2015-12-24

    The purpose of this study was to assess the biofilm-removing efficacy and inflammatory activity of a serrulatane diterpenoid, 8-hydroxyserrulat-14-en-19-oic acid (1), isolated from the Australian medicinal plant Eremophila neglecta. Biofilm breakup activity of compound 1 on established Staphylococcus epidermidis and Staphylococcus aureus biofilms was compared to the antiseptic chlorhexidine and antibiotic levofloxacin. In a time-course study, 1 was deposited onto polypropylene mesh to mimic a wound dressing and tested for biofilm removal. The ex-vivo cytotoxicity and effect on lipopolysaccharide-induced pro-inflammatory cytokine release were studied in mouse primary bone-marrow-derived macrophage (BMDM) cells. Compound 1 was effective in dispersing 12 h pre-established biofilms with a 7 log10 reduction of viable bacterial cell counts, but was less active against 24 h biofilms (approximately 2 log10 reduction). Compound-loaded mesh showed dosage-dependent biofilm-removing capability. In addition, compound 1 displayed a significant inhibitory effect on tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) secretion from BMDM cells, but interleukin-1 beta (IL-1β) secretion was not significant. The compound was not cytotoxic to BMDM cells at concentrations effective in removing biofilm and lowering cytokine release. These findings highlight the potential of this serrulatane diterpenoid to be further developed for applications in wound management. PMID:26636180

  16. The diterpenoid ent-16-kauren-19-oic acid acts as an uncoupler of the bacterial respiratory chain.

    PubMed

    Torres-Bustos, Janet; Farías, Leonardo; Urzúa, Alejandro; Mendoza, Leonora; Wilkens, Marcela

    2009-06-01

    ent-16-Kauren-19-oic acid is a bacteriolytic diterpenoid present in the resin of the medicinal plant Pseudognaphalium vira vira. The compound and its methyl ester showed strong activity against gram-positive bacteria, whereas the derivative 3beta-hydroxy-ent-kauren-19-oic acid was inactive against all assayed bacteria at the maximal concentration used (250 microg/mL). The bacteriolytic effect of ent-16-kauren-19-oic acid (5 microg/mL) was confirmed with cultures of Bacillus cereus and Staphylococcus aureus, whereas the methyl derivative (12 microg/mL) showed only a bacteriostatic effect. Both compounds stimulated oxygen consumption and proton conduction of whole cells, as reflected by an abrupt increase in the extracellular pH. These results indicate that ent-16-kauren-19-oic acid acts as a respiratory chain uncoupler, and that this function is strongly affected by minor structural substitutions, suggesting a tight activity-structure relationship. The ultimate effect of the uncoupling mechanism demonstrated by ent-16-kauren-19-oic acid is bacterial lysis. The disruption of the bacterial membrane integrity caused by the diterpenoid compound was determined using SYTOX Green stain and visualized by fluorescence microscopy. PMID:19296427

  17. Novel nitric oxide-releasing spirolactone-type diterpenoid derivatives with in vitro synergistic anticancer activity as apoptosis inducer.

    PubMed

    Li, Dahong; Han, Tong; Tian, Kangtao; Tang, Shuang; Xu, Shengtao; Hu, Xu; Wang, Lei; Li, Zhanlin; Hua, Huiming; Xu, Jinyi

    2016-09-01

    Herein, we reported the cytotoxicity, NO-releasing property, and apoptosis induced ability of two series of novel nitric oxide-releasing spirolactone-type diterpenoid derivatives (10a-f and 15a-f). All the title compounds were more potent than oridonin (7) and parent compound (9 or 14) against human tumor Bel-7402, K562, MGC-803 and CaEs-17 cells. SARs were concluded based on above data. Compound 15d exhibited the strongest antiproliferative activity with the IC50 of 0.86, 1.74, 1.16 and 3.75μM, respectively, and could produce high level (above 25μM) of NO at the time point of 60min. Further mechanism evaluation showed that 15d could induce S phase cell cycle arrest and apoptosis at low micromolar concentrations in Bel-7402 cells via mitochondria-related pathways. It was expected that the remarkable biological profile of the synthetic NO-releasing spirolactone-type diterpenoid analogs make them possible as promising candidates for the development of anticancer agents. PMID:27491707

  18. Different AhR binding sites of diterpenoid ligands from Andrographis paniculata caused differential CYP1A1 induction in primary culture in mouse hepatocytes.

    PubMed

    Chatuphonprasert, Waranya; Remsungnen, Tawun; Nemoto, Nobuo; Jarukamjorn, Kanokwan

    2011-12-01

    Andrographis paniculata has been employed as a folklore remedy. Andrographolide (Andro), 14-deoxy-11,12-didehydroandrographolide (DHA), andrographiside (AS), and neoandrographolide (Neo), are major diterpenoids isolated from this plant. In the present study, influence of the four diterpenoids on CYP1A1 mRNA expression was investigated in primary cultured mouse hepatocytes. Additionally, binding of these compounds to aryl hydrocarbon receptor (AhR) was examined using molecular docking analysis to clarify mechanism of CYP1A1 induction. Andro and DHA induced CYP1A1 expression by itself, and co-treatment with a CYP1A1 inducer (BNF, beta-naphthoflavone) showed a synergistic increase of CYP1A1 expression. Andro demonstrated higher enhancing activity than DHA at every similar concentration. On the other hand, Neo suppressed BNF-induced CYP1A1 expression, but AS did not modify the induction. Results from molecular docking analysis of BNF and four diterpenoids on ligand binding domain of AhR were consistent with levels of CYP1A1 mRNA expressions. Furthermore, difference of binding sites of BNF in the presence of diterpenoids might affect the synergism or inhibition of CYP1A1 expression. These results suggest that use of A. paniculata as a health supplement should be concerned in term of herb-drugs interactions or risk of carcinogenesis, according to its ability to influence CYP1A1 expression. PMID:21963808

  19. Anticancer Activity of Novel Daphnane Diterpenoids from Daphne genkwa through Cell-Cycle Arrest and Suppression of Akt/STAT/Src Signalings in Human Lung Cancer Cells.

    PubMed

    Jo, Si-Kyoung; Hong, Ji-Young; Park, Hyen Joo; Lee, Sang Kook

    2012-11-01

    Although the immense efforts have been made for cancer prevention, early diagnosis, and treatment, cancer morbidity and mortality has not been decreased during last forty years. Especially, lung cancer is top-ranked in cancer-associated human death. Therefore, effective strategy is strongly required for the management of lung cancer. In the present study, we found that novel daphnane diterpenoids, yuanhualine (YL), yuanhuahine (YH) and yuanhuagine (YG) isolated from the flower of Daphne genkwa (Thymelaeaceae), exhibited potent anti-proliferative activities against human lung A549 cells with the IC50 values of 7.0, 15.2 and 24.7 nM, respectively. Flow cytometric analysis revealed that the daphnane diterpenoids induced cell-cycle arrest in the G0/G1 as well as G2/M phase in A549 cells. The cell-cycle arrests were well correlated with the expression of checkpoint proteins including the up-regulation of cyclin-dependent kinase inhibitor p21 and p53 and down-regulation of cyclin A, cyclin B1, cyclin E, cyclin dependent kinase 4, cdc2, phosphorylation of Rb and cMyc expression. In the analysis of signal transduction molecules, the daphnane diterpenoids suppressed the activation of Akt, STAT3 and Src in human lung cancer cells. The daphnane diterpenoids also exerted the potent anti-proliferative activity against anticancer-drug resistant cancer cells including gemcitabine-resistant A549, gefitinib-, erlotinib-resistant H292 cells. Synergistic effects in the growth inhibition were also observed when yuanhualine was combined with gemcitabine, gefitinib or erlotinib in A549 cells. Taken together, these findings suggest that the novel daphnane diterpenoids might provide lead candidates for the development of therapeutic agents for human lung cancers. PMID:24009843

  20. Biosynthesis of the Diterpenoid Lycosantalonol via Nerylneryl Diphosphate in Solanum lycopersicum

    PubMed Central

    Matsuba, Yuki; Zi, Jiachen; Jones, A. Daniel; Peters, Reuben J.; Pichersky, Eran

    2015-01-01

    We recently reported that three genes involved in the biosynthesis of monoterpenes in trichomes, a cis-prenyltransferase named neryl diphosphate synthase 1 (NDPS1) and two terpene synthases (TPS19 and TPS20), are present in close proximity to each other at the tip of chromosome 8 in the genome of the cultivated tomato (Solanum lycopersicum). This terpene gene “cluster” also contains a second cis-prenyltransferase gene (CPT2), three other TPS genes, including TPS21, and the cytochrome P450-oxidoreductase gene CYP71BN1. CPT2 encodes a neryneryl diphosphate synthase. Co-expression in E. coli of CPT2 and TPS21 led to the formation of the diterpene lycosantalene, and co-expression in E. coli of CPT2, TPS21 and CYP71BN1 led to the formation of lycosantalonol, an oxidation product of lycosantalene. Here we show that maximal expression of all three genes occurs in the petiolule part of the leaf, but little expression of these genes occurs in the trichomes present on the petiolules. While lycosantalene or lycosantalonol cannot be detected in the petiolules of wild-type plants (or anywhere else in the plant), lycosantalene and lycosantalonol are detected in petiolules of transgenic tomato plants expressing CPT2 under the control of the 35S CaMV promoter. These results suggest that lycosantalene and lycosantalonol are produced in the petiolules and perhaps in other tissues of wild-type plants, but that low rate of synthesis, controlled by the rate-limiting enzyme CPT2, results in product levels that are too low for detection under our current methodology. It is also possible that these compounds are further modified in the plant. The involvement of CPT2, TPS21 and CYP71BN1 in a diterpenoid biosynthetic pathway outside the trichomes, together with the involvement of other genes in the cluster in the synthesis of monoterpenes in trichomes, indicates that this cluster is further evolving into “sub-clusters” with unique biochemical, and likely physiological, roles. PMID

  1. Cassane-type diterpenoids from Caesalpinia echinata (Leguminosae) and their NF-κB signaling inhibition activities.

    PubMed

    Mitsui, Taichi; Ishihara, Risa; Hayashi, Ken-ichiro; Matsuura, Nobuyasu; Akashi, Haruo; Nozaki, Hiroshi

    2015-08-01

    Fourteen cassane-type diterpenoids, echinalides H-U, were isolated from the stem of Caesalpinia echinata Lam. (Leguminosae). The structures of the echinalides were elucidated by spectroscopic investigation, including 2D NMR spectroscopic analysis. The structures of echinalide H and echinalide T were further confirmed by single-crystal X-ray diffraction. The absolute configurations of echinalides H, I, J and K were determined by CD spectroscopy. Additionally, the absolute configurations of echinalide L and M were determined by chemical conversion from echinalide H. These compounds were evaluated for inhibitory activity against nuclear factor κB (NF-κB). Echinalide M showed the most potent inhibitory activity (47±11% at 5μM) toward NF-κB-responsive gene expression. PMID:25886884

  2. Antimicrobial Activity of neo-Clerodane Diterpenoids isolated from Lamiaceae Species against Pathogenic and Food Spoilage Microorganisms.

    PubMed

    Bozov, Petko; Girova, Tania; Prisadova, Natalia; Hristova, Yana; Gochev, Velizar

    2015-11-01

    Antimicrobial activity of nineteen neo-clerodane diterpenoids, isolated from the acetone extracts of the aerial parts of Scutellaria and Salvia species (Lamiaceae) were tested against thirteen strains belonging to nine different species of pathogenic and food spoilage bacteria Aeromonas hydrophila, Bacillus cereus, Escherichia coli, Listeria monocytogenes, Proteus vulgaris, Pseudomonas aeruginosa, Pseudomonas fluorescens, Salmonella abony and Staphylococcus aureus as well as against two yeast strains belonging to species Candida albicans. Seven of the evaluated compounds scutalpin A, scutalpin E, scutalpin F, salviarin, splenolide A, splenolide B and splendidin demonstrated antimicrobial activity against used test microbial strains, the rest of the compounds were inactive within the studied concentration range. Among all of the tested compounds the highest antimicrobial activity was detected for scutalpin A against Staphylococcus aureus (MIC 25 µg/mL). PMID:26749799

  3. Kujigamberol, a new dinorlabdane diterpenoid isolated from 85million years old Kuji amber using a biotechnological assay.

    PubMed

    Kimura, Ken-ichi; Minamikawa, Yuki; Ogasawara, Yukiko; Yoshida, Jun; Saitoh, Kei-ichi; Shinden, Hisao; Ye, Yue Qi; Takahashi, Shunya; Miyakawa, Tokichi; Koshino, Hiroyuki

    2012-07-01

    A new compound, 15,20-dinor-5,7,9-labdatriene-18-ol (1), named kujigamberol, was isolated from amber, fossilized tree resin from the Kuji area in Japan, has been dated as being 85 million years old (late Cretaceous). Kujigamberol was identified using the hypersensitive mutant yeast (zds1∆ erg3∆ pdr1∆ pdr3∆) with respect to Ca(2+)-signal transduction. The structure was elucidated on the basis of spectroscopic analysis including 1D NMR, 2D NMR and HR-EI-MS. It was different from known diterpenoids with a similar activity isolated from Baltic amber (agathic acid 15-monomethyl ester (2), dehydroabietic acid (3) and pimaric acid (4)). Kujigamberol showed glycogen synthase kinase-3β (GSK-3β) inhibition activity involving the growth restored activity against the mutant yeast and was cytotoxic to HL60 cells (IC(50)=19.6 μM). PMID:22507387

  4. Recombination of diterpenoid structure units: synthesis of antitumor amides bearing functionalized bicyclo[3.2.1]octane ring.

    PubMed

    Mao, Zewei; Li, Yan; Chen, Jingbo; Wang, Yuanyuan; Zhang, Hongbin

    2010-07-15

    In this work, 23 new amides (14-36) bearing a representative diterpenoid structure unit, the functionalized bicyclo[3.2.1]octane ring, have been synthesized and its antitumor potential is studied. In vitro studies demonstrate that a number of amides with the bicyclo[3.2.1]oct-3-en-2-one subunit are active against HL-60, SMMC-7721, A-549, SK-BR-3, and PANC-1 tumor cell lines. The hybrid derivative, compound 20, was found to be the most potent compound (IC(50)=1.05 microM against HL-60) and more active than cisplatin (DDP), the positive control. Additionally, compound 20 exhibited broad spectrum in vitro anticancer activity with IC(50) values of 1.1-4.3 microM against the five tested cancer cell lines. PMID:20621726

  5. Higginsianins A and B, Two Diterpenoid α-Pyrones Produced by Colletotrichum higginsianum, with in Vitro Cytostatic Activity.

    PubMed

    Cimmino, Alessio; Mathieu, Veronique; Masi, Marco; Baroncelli, Riccardo; Boari, Angela; Pescitelli, Gennaro; Ferderin, Marlène; Lisy, Romana; Evidente, Marco; Tuzi, Angela; Zonno, Maria Chiara; Kornienko, Alexander; Kiss, Robert; Evidente, Antonio

    2016-01-22

    Two new diterpenoid α-pyrones, named higginsianins A (1) and B (2), were isolated from the mycelium of the fungus Colletotrichum higginsianum grown in liquid culture. They were characterized as 3-[5a,9b-dimethyl-7-methylene-2-(2-methylpropenyl)dodecahydronaphtho[2,1-b]furan-6-ylmethyl]-4-hydroxy-5,6-dimethylpyran-2-one and 4-hydroxy-3-[6-hydroxy-5,8a-dimethyl-2-methylene-5-(4-methylpent-3-enyl)decahydronaphthalen-1-ylmethyl]-5,6-dimethylpyran-2-one, respectively, by using NMR, HRESIMS, and chemical methods. The structure and relative configuration of higginsianin A (1) were confirmed by X-ray diffractometric analysis, while its absolute configuration was assigned by electronic circular dichroism (ECD) experiments and calculations using a solid-state ECD/TDDFT method. The relative and absolute configuration of higginsianin B (2), which did not afford crystals suitable for X-ray analysis, were determined by NMR analysis and by ECD in comparison with higginsianin A. 1 and 2 were the C-8 epimers of subglutinol A and diterpenoid BR-050, respectively. The evaluation of 1 and 2 for antiproliferative activity against a panel of six cancer cell lines revealed that the IC50 values, obtained with cells reported to be sensitive to pro-apoptotic stimuli, are by more than 1 order of magnitude lower than their apoptosis-resistant counterparts (1 vs >80 μM). Finally, three hemisynthetic derivatives of 1 were prepared and evaluated for antiproliferative activity. Two of these possessed IC50 values and differential sensitivity profiles similar to those of 1. PMID:26697898

  6. Exploring the ester-exchange reactions of diester-diterpenoid alkaloids in the aconite decoction process by electrospray ionization tandem mass spectrometry.

    PubMed

    Wang, Yong; Shi, Lei; Song, Fengrui; Liu, Zhiqiang; Liu, Shuying

    2003-01-01

    The chemical components in the decoctions of Chinese herbal medicines are not always the same as those in the crude herbs because of the insolubility or instability of some compounds. In this work electrospray ionization tandem mass spectrometry was used to explore the ester-exchange reactions for aconitine-type diester-diterpenoid alkaloids occurring during the process of decocting aconite root. The aconitines were screened in a diverse range of samples, including crude aconite, decoction of crude aconite, residues from decoction of crude aconite, prepared aconite, decoction of prepared aconite, decoction of prepared aconite with added palmitic acid, and decoction of a mixture of mesaconitine and hypaconitine standards with liquorice root. It was found that diester-diterpenoid aconitines were converted into lipo-alkaloids as well as monoester alkaloids by the decoction of aconite. PMID:12569436

  7. A Cytochrome P450-Mediated Intramolecular Carbon-Carbon Ring Closure in the Biosynthesis of Multidrug-Resistance-Reversing Lathyrane Diterpenoids.

    PubMed

    King, Andrew J; Brown, Geoffrey D; Gilday, Alison D; Forestier, Edith; Larson, Tony R; Graham, Ian A

    2016-09-01

    The Euphorbiaceae produce a wide variety of bioactive diterpenoids. These include the lathyranes, which have received much interest due to their ability to inhibit the ABC transporters responsible for the loss of efficacy of many chemotherapy drugs. The lathyranes are also intermediates in the biosynthesis of range of other bioactive diterpenoids with potential applications in the treatment of pain, HIV and cancer. We report here a gene cluster from Jatropha curcas that contains the genes required to convert geranylgeranyl pyrophosphate into a number of diterpenoids, including the lathyranes jolkinol C and epi-jolkinol C. The conversion of casbene to the lathyranes involves an intramolecular carbon-carbon ring closure. This requires the activity of two cytochrome P450s that we propose form a 6-hydroxy-5,9-diketocasbene intermediate, which then undergoes an aldol reaction. The discovery of the P450 genes required to convert casbene to lathyranes will allow the scalable heterologous production of these potential anticancer drugs, which can often only be sourced in limited quantities from their native plant. PMID:27272333

  8. HPLC-UV and HPLC-positive-ESI-MS analysis of the diterpenoid fraction from caper spurge (Euphorbia lathyris) seed oil.

    PubMed

    Bicchi, C; Appendino, G; Cordero, C; Rubiolo, P; Ortelli, D; Veuthey, J L

    2001-01-01

    Caper spurge (Euphorbia lathyris L.) seed oil contains a series of diterpenoids known as Euphorbia factors, or L-factors, L1-L9. They are esters of several polyols (lathyrol, epoxylathyrol, hydroxylathyrol and ingenol) and account for about 3-5% of the oil. The percentage of ingenol-based L-factors is very low, less than 5% of the diterpenoid fraction, but some of them (factors L5 and L6) are responsible for the irritant and co-carcinogenic activities of the oil. This paper reports an HPLC-UV and HPLC-positive-ESI-MS analysis of the diterpenoid fraction of caper spurge seed oil before and after selective hydrolysis of ingenol-based L-factors. Separation of lathyrane polyols and esters, and ingenol and its esters was achieved using a chromatographic system consisting of a C18 stationary phase and acetonitrile: water as mobile phase. A new macrocyclic constituent, the deoxy Euphorbia factor L1, was identified in the oil. PMID:11705332

  9. Structure elucidation of organic compounds from natural sources using 1D and 2D NMR techniques

    NASA Astrophysics Data System (ADS)

    Topcu, Gulacti; Ulubelen, Ayhan

    2007-05-01

    In our continuing studies on Lamiaceae family plants including Salvia, Teucrium, Ajuga, Sideritis, Nepeta and Lavandula growing in Anatolia, many terpenoids, consisting of over 50 distinct triterpenoids and steroids, and over 200 diterpenoids, several sesterterpenoids and sesquiterpenoids along with many flavonoids and other phenolic compounds have been isolated. For Salvia species abietanes, for Teucrium and Ajuga species neo-clerodanes for Sideritis species ent-kaurane diterpenes are characteristic while nepetalactones are specific for Nepeta species. In this review article, only some interesting and different type of skeleton having constituents, namely rearranged, nor- or rare diterpenes, isolated from these species will be presented. For structure elucidation of these natural diterpenoids intensive one- and two-dimensional NMR techniques ( 1H, 13C, APT, DEPT, NOE/NOESY, 1H- 1H COSY, HETCOR, COLOC, HMQC/HSQC, HMBC, SINEPT) were used besides mass and some other spectroscopic methods.

  10. ent-kaurane diterpenoids from Croton tonkinensis induce apoptosis in colorectal cancer cells through the phosphorylation of JNK mediated by reactive oxygen species and dual-specificity JNK kinase MKK4.

    PubMed

    Thuong, Phuong Thien; Khoi, Nguyen Minh; Ohta, Saho; Shiota, Shinichiro; Kanta, Hironori; Takeuchi, Kenji; Ito, Fumiaki

    2014-01-01

    To search for new chemotherapeutic agents to treat colorectal cancer, we isolated a number of natural ent-kaurane diterpenoids from the plant Croton tonkinensis. Among them, only CeKDs with the 15-oxo-16-ene moiety induced the apoptosis of colorectal cancer cell lines Caco-2 and LS180. The active CeKD induced the activation of ERK and JNK, but the inactive ones induced that of ERK, but not that of JNK. It thus appears that JNK seemed to play an important role in the apoptotic activity of the active compounds. The dualspecificity JNK kinase MKK4 was activated in both colorectal cancer cells treated with the active CeKD, but MKK7 was not activated. Further, the active CeKD, but not the inactive one, enhanced the generation of intracellular reactive oxygen species (ROS) in both cells. CeKD-induced cell apoptosis and ROS generation, as well as JNK activation, were inhibited by the antioxidant N-acetyl-L-cysteine. These findings suggest that ROS stimulated the phosphorylation of JNK mediated by MKK4 and played a critical role in CeKD-induced apoptosis in colorectal cancer cells. PMID:24476312

  11. Natural compounds in the synthesis of chiral organophosphorous ligands

    NASA Astrophysics Data System (ADS)

    Tolstikov, Alexander G.; Khlebnikova, Tatiana B.; Tolstikova, Olga V.; Tolstikov, Genrikh A.

    2003-09-01

    Methods for the synthesis of chiral organophosphorus compounds based on natural optically active compounds (hydroxy acids, amino acids and their derivatives, mono- and disaccharides, mono- and diterpenoids, steroids) are discussed. Particular attention is given to the synthesis of bisphosphines and bisphosphinites. These compounds serve as ligands for transition metal complexes, which catalyse asymmetric hydrogenation. Data on the enantioselectivity of hydrogenation of unsaturated precursors of amino acids and unsaturated prochiral acids as well as on information on the enantioselectivity of hydrosilylation of ketones are surveyed.

  12. NO-Releasing Enmein-Type Diterpenoid Derivatives with Selective Antiproliferative Activity and Effects on Apoptosis-Related Proteins.

    PubMed

    Li, Dahong; Hu, Xu; Han, Tong; Liao, Jie; Xiao, Wei; Xu, Shengtao; Li, Zhanlin; Wang, Zhenzhong; Hua, Huiming; Xu, Jinyi

    2016-01-01

    A series of nine enmein-type ent-kaurane diterpenoid and furoxan-based nitric oxide (NO) donor hybrids (10a-i) were designed and synthesized from commercially available oridonin (1). These hybrids were evaluated for their antiproliferative activity against Bel-7402, K562, MGC-803, and CaEs-17 human cancer cell lines and L-02 normal liver cells. The antiproliferative activity against tumor cells was stronger than the lead compound 1 and parent molecule 9 in most cases. Especially, compound 10f showed the strongest activity against human hepatocarcinoma Bel-7402 cell line with an IC50 of 0.81 μM and could also release 33.7 μmol/L NO at the time point of 60 min. Compounds 10a-i also showed cytotoxic selectivity between tumor and normal liver cells with IC50 ranging from 22.1 to 33.9 μM. Furthermore, the apoptotic properties on Bel-7402 cells revealed that 10f could induce S phase cell cycle arrest and apoptosis at low micromolar concentrations. The effects of 10f on apoptosis-related proteins were also investigated. The potent antiproliferative activities and mechanistic studies warrant further preclinical investigations. PMID:27617998

  13. hERG Channel Inhibitory Daphnane Diterpenoid Orthoesters and Polycephalones A and B with Unprecedented Skeletons from Gnidia polycephala.

    PubMed

    De Mieri, Maria; Du, Kun; Neuburger, Markus; Saxena, Priyanka; Zietsman, Pieter C; Hering, Steffen; van der Westhuizen, Jan H; Hamburger, Matthias

    2015-07-24

    The hERG channel is an important antitarget in safety pharmacology. Several drugs have been withdrawn from the market or received severe usage restrictions because of hERG-related cardiotoxicity. In a screening of medicinal plants for hERG channel inhibition using a two-microelectrode voltage clamp assay with Xenopus laevis oocytes, a dichloromethane extract of the roots of Gnidia polycephala reduced the peak tail hERG current by 58.8 ± 13.4% (n = 3) at a concentration of 100 μg/mL. By means of HPLC-based activity profiling daphnane-type diterpenoid orthoesters (DDOs) 1, 4, and 5 were identified as the active compounds [55.4 ± 7.0% (n = 4), 42.5 ± 16.0% (n = 3), and 51.3 ± 9.4% (n = 4), respectively, at 100 μM]. In a detailed phytochemical profiling of the active extract, 16 compounds were isolated and characterized, including two 2-phenylpyranones (15 and 16) with an unprecedented tetrahydro-4H-5,8-epoxypyrano[2,3-d]oxepin-4-one skeleton, two new DDOs (3 and 4), two new guaiane sesquiterpenoids (11 and 12), and 10 known compounds (1, 2, 5-10, 13, and 14). Structure elucidation was achieved by extensive spectroscopic analysis (1D and 2D NMR, HRMS, and electronic circular dichroism), computational methods, and X-ray crystallography. PMID:26091146

  14. Inhibition of caspase-9 by oridonin, a diterpenoid isolated from Rabdosia rubescens, augments apoptosis in human laryngeal cancer cells

    PubMed Central

    KANG, NING; CAO, SHI-JIE; ZHOU, YAN; HE, HAO; TASHIRO, SHIN-ICHI; ONODERA, SATOSHI; QIU, FENG; IKEJIMA, TAKASHI

    2015-01-01

    Rabdosia rubescens, a commonly used traditional Chinese medicine, has increasingly gained attention for its use as an antitumor herb. Oridonin, a bioactive diterpenoid isolated from Rabdosia rubescens, has been reported to induce apoptosis in human laryngeal cancer HEp-2 cells by our group. Here, we made unexpected observations that the caspase-9 inhibitor (C9i) enhanced apoptosis in response to selected stimuli, and HEp-2 cells which were made deficient in caspase-9 using siRNA exhibited no resistance to apoptotic signals and actually demonstrated increased apoptotic sensitivity to oridonin. The results were reversed by the transfection of an exogenous caspase-9 expression vector. Caspase-9 reduced sensitivity to apoptotic stimuli through reactive oxygen species (ROS)-suppressing and autophagy-promoting methods. ROS triggered the progression of apoptosis through activation of both the caspase-9-independent mitochondrial pathway and death receptor pathways, and the autophagy had an anti-apoptotic function in oridonin-treated HEp-2 cells. These collective results suggest that oridonin targets caspase-9 to alter ROS production and autophagy situation to promote HEp-2 cell apoptosis. Therefore, oridonin has the potential to be developed as an anticancer agent, and the combination of oridonin with those agents leading to reduction of caspase-9 expression in tumor cells could represent a novel approach to human laryngeal cancer treatment. PMID:26648189

  15. Six new cytotoxic and anti-inflammatory 11, 20-epoxy-ent-kaurane diterpenoids from Isodon wikstroemioides.

    PubMed

    Wu, Hai-Yan; Wang, Wei-Guang; Du, Xue; Yang, Jin; Pu, Jian-Xin; Sun, Han-Dong

    2015-05-01

    The present study was designed to determine the chemical constituents of EtOAc extracts of the aerial parts of Isodon wikstroemioides. Compounds 1-8 were isolated and purified by normal-phase silica gel and reversed-phase C18silica gel column chromatography and HPLC. Their structures were elucidated by extensive spectroscopic methods. Most of them were evaluated for their in vitro cytotoxicity against human cancer HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cells and their inhibitory activity against nitric oxide (NO) production in LPS-activated RAW264.7 macrophages. Among the eight 11, 20-epoxy-ent-kauranoids isolated, compounds 1-6 (isowikstroemins H-M) were new diterpenoids. Compounds 1, 3, and 7 exhibited significant cytotoxicity with IC50 values ranging from (0.84 ± 0.02) to (4.09 ± 0.34) μmol · L(-1), while compounds 4 and 5 showed selective cytotoxicity. In addition, compounds 1, 3, 4, and 7 exhibited inhibitory activity against nitric oxide (NO) production in LPS-activated RAW264.7 macrophages. These results provide a basis for future development of these compounds as anti-cancer and anti-inflammatory agents. PMID:25986288

  16. Overexpression of the bZIP transcription factor OsbZIP79 suppresses the production of diterpenoid phytoalexin in rice cells.

    PubMed

    Miyamoto, Koji; Nishizawa, Yoko; Minami, Eiichi; Nojiri, Hideaki; Yamane, Hisakazu; Okada, Kazunori

    2015-01-15

    Phytoalexins are antimicrobial specialised metabolites that are produced by plants in response to pathogen attack. Momilactones and phytocassanes are major diterpenoid phytoalexins in rice that are synthesised from geranylgeranyl diphosphate that is derived from the methylerythritol phosphate (MEP) pathway. We have previously reported that rice cells overexpressing the basic leucine zipper (bZIP) transcription factor OsTGAP1 exhibit a hyperaccumulation of momilactones and phytocassanes, with hyperinductive expression of momilactone and phytocassane biosynthetic genes and MEP pathway genes, upon response to a chitin oligosaccharide elicitor. For a better understanding of OsTGAP1-mediated regulation of diterpenoid phytoalexin production, we identified OsTGAP1-interacting proteins using yeast two-hybrid screening. Among the OsTGAP1-interacting protein candidates, a TGA factor OsbZIP79 was investigated to verify its physical interaction with OsTGAP1 and involvement in the regulation of phytoalexin production. An in vitro pull-down assay demonstrated that OsTGAP1 and OsbZIP79 exhibited a heterodimeric as well as a homodimeric interaction. A bimolecular fluorescence complementation analysis also showed the interaction between OsTGAP1 and OsbZIP79 in vivo. Intriguingly, whereas OsbZIP79 transactivation activity was observed in a transient reporter assay, the overexpression of OsbZIP79 resulted in suppression of the elicitor-inducible expression of diterpenoid phytoalexin biosynthetic genes, and thus caused a decrease in the accumulation of phytoalexin in rice cells. These results suggest that OsbZIP79 functions as a negative regulator of phytoalexin production triggered by a chitin oligosaccharide elicitor in rice cells, although it remains open under which conditions OsbZIP79 can work with OsTGAP1. PMID:25462074

  17. Simultaneous determination of seven major diterpenoids in Siegesbeckia pubescens Makino by high-performance liquid chromatography coupled with evaporative light scattering detection.

    PubMed

    Huo, Linan; Jiang, Zhen; Li, Huining; Wang, Mingsheng; Ye, Xiaoxia; Ji, Bin; Guo, Xingjie

    2012-10-01

    A novel HPLC method with evaporative light scattering detection was developed for the simultaneous quantification of seven major diterpenoids of two types, including ent-pimarane type: Kirenol, Hythiemoside B, Darutigenol, and ent-kaurane type: ent-16β,17,18-trihydroxy-kauran-19-oic acid, ent-17,18-dihydroxy-kauran-19-oic acid, ent-16β,17-dihydroxy-kauran-19-oic acid, 16α-hydro-ent-kauran-17,19-dioic acid in the aerial parts of Siegesbeckia pubescens Makino, an important traditional Chinese medicinal herb. Chromatographic separation was achieved on a Waters Symmetry Shield(TM) RP18 column (250 mm× 4.6 mm id, 5 μm) with a gradient mobile phase (A: 0.3% v/v aqueous formic acid and B: acetonitrile) at a flow rate of 1.0 mL/min. The drift tube temperature of evaporative light scattering detection was set at 103°C, and nitrogen flow rate was 3.0 L/min. The method was validated for accuracy, precision, LOD, and LOQ. All calibration curves showed a good linear relationship (r > 0.999) in test range. Precision was evaluated by intra- and interday tests that showed RSDs were less than 3.5%. Accuracy validation showed that the recovery was between 96.5 and 102.0% with RSDs below 2.8%. The validated method was successfully applied to determine the contents of seven diterpenoids in the different parts of Siegesbeckia pubescens Makino from two sources and to determine the contents of ent-pimarane, ent-kaurane, and total diterpenoids. PMID:22887919

  18. CYP701A8: A Rice ent-Kaurene Oxidase Paralog Diverted to More Specialized Diterpenoid Metabolism1[W][OA

    PubMed Central

    Wang, Qiang; Hillwig, Matthew L.; Wu, Yisheng; Peters, Reuben J.

    2012-01-01

    All higher plants contain an ent-kaurene oxidase (KO), as such a cytochrome P450 (CYP) 701 family member is required for gibberellin (GA) phytohormone biosynthesis. While gene expansion and functional diversification of GA-biosynthesis-derived diterpene synthases into more specialized metabolism has been demonstrated, no functionally divergent KO/CYP701 homologs have been previously identified. Rice (Oryza sativa) contains five CYP701A subfamily members in its genome, despite the fact that only one (OsKO2/CYP701A6) is required for GA biosynthesis. Here we demonstrate that one of the other rice CYP701A subfamily members, OsKOL4/CYP701A8, does not catalyze the prototypical conversion of the ent-kaurene C4α-methyl to a carboxylic acid, but instead carries out hydroxylation at the nearby C3α position in a number of related diterpenes. In particular, under conditions where OsKO2 catalyzes the expected conversion of ent-kaurene to ent-kaurenoic acid required for GA biosynthesis, OsKOL4 instead efficiently reacts with ent-sandaracopimaradiene and ent-cassadiene to produce the corresponding C3α-hydroxylated diterpenoids. These compounds are expected intermediates in biosynthesis of the oryzalexin and phytocassane families of rice antifungal phytoalexins, respectively, and can be detected in rice plants under the appropriate conditions. Thus, it appears that OsKOL4 plays a role in the more specialized diterpenoid metabolism of rice, and our results provide evidence for divergence of a KO/CYP701 family member from GA biosynthesis. This further expands the range of enzymes recruited from the ancestral GA primary pathway to the more complex and specialized labdane-related diterpenoid metabolic network found in rice. PMID:22247270

  19. New semisynthetic antimicrobial labdane-type diterpenoids derived from the resin "ladano" of Cistus creticus.

    PubMed

    Kalpoutzakis, E; Aligiannis, N; Mitaku, S; Chinou, I; Harvala, C; Skaltsounis, A L

    2001-01-01

    The antimicrobial activity of fifteen semisynthetic labdane-type diterpenes derived from the two major natural compounds 3 and 4 of the resin "ladano" of Cistus creticus is reported. The chloroethyl carbamidic esters 15 and 20 showed the strongest antimicrobial activity against Gram(+), Gram(-) bacteria and pathogenic fungi. PMID:11302213

  20. Kaurane-type diterpenoids from Chromoleana odorata, their X-ray diffraction studies and potent α-glucosidase inhibition of 16-kauren-19-oic acid.

    PubMed

    Wafo, Pascal; Kamdem, Ramsay S T; Ali, Zulfiqar; Anjum, Shazia; Begum, Afshan; Oluyemisi, Ogbole O; Khan, Shamsun N; Ngadjui, Bonaventure T; Etoa, Xavier F; Choudhary, Muhammed Iqbal

    2011-06-01

    A new diterpenoid, 15-angeloyloxy-16,17-epoxy-19-kauronic acid (1), along with five known metabolites, 16-kauren-19-oic acid (2), 6'-hydroxy-2',3',4,4'-tetramethoxychalcone (3), isosakuranetin (4), acacetin (5), and kaempferide (6) was isolated from the organic extracts of the roots of Chromoleana odorata. Their structures were determined by spectroscopic evidences. The structures of 1 and 2 were further confirmed by single-crystal X-ray diffraction studies. Compound 2 exhibited significant α-glucosidase inhibitory and antibacterial activities against Escherichia coli and Bacillus subtilis. PMID:21316426

  1. ent-Abietane-type diterpenoids from the roots of Euphorbia ebracteolata with their inhibitory activities on LPS-induced NO production in RAW 264.7 macrophages.

    PubMed

    Liu, Zhi-guo; Li, Zhan-lin; Li, Da-Hong; Li, Ning; Bai, Jiao; Zhao, Feng; Meng, Da-li; Hua, Hui-ming

    2016-01-01

    Ten ent-abietane diterpenoids (1-10), including four new (1-4) and six known ones (5-10) were isolated from the roots of Euphorbia ebracteolata. Their structures were determined by 1D, 2D NMR, and HRESIMS. Compounds 2, 4, and 7 exhibited significant inhibitory activities on lipopolysaccharide (LPS)-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 0.69, 1.97, and 0.88μM, respectively. A primary structure-activity relationship was also discussed. PMID:26615888

  2. Inhibition of the gastric H+,K+ -ATPase by plectrinone A, a diterpenoid isolated from Plectranthus barbatus Andrews.

    PubMed

    Schultz, Carla; Bossolani, Myllene P; Torres, Luce M B; Lima-Landman, Maria Teresa R; Lapa, Antonio J; Souccar, Caden

    2007-04-20

    This work assessed the mechanism underlying the antisecretory gastric acid effect of Plectranthus barbatus Andrews (Lamiaceae) and active constituents. Popularly known as "false-boldo", this plant is used in Brazilian folk medicine to treat gastrointestinal and hepatic ailments. The plant aqueous extract (AE) and isolated compounds were assayed in vivo in pylorus-ligated mice, and in vitro on acid secretion measured as [(14)C]-aminopyrine ([(14)C]-AP) accumulation in rabbit gastric glands and gastric H(+),K(+)-ATPase preparations. Injected into the duodenal lumen, the AE of the plant leaves (0.5 and 1.0 g/kg) decreased the volume (62 and 76%) and total acidity (23 and 50%) of gastric acid secretion in pylorus-ligated mice. Bioguided purification of the AE yielded an active fraction (IC(50)=24 microg/ml) that inhibited acid secretion in rabbit gastric glands with a potency 10 to 18 times greater than that of the originating extract, on both the basal and stimulated acid secretion by histamine (His) (1 microM) or bethanechol (100 microM). At the same concentrations the gastric H(+),K(+)-ATPase activity was also inhibited. The active constituent was chemically identified as the abietanoid dienedione plectrinone A which reduced the H(+),K(+)-ATPase activity with IC(50)=171 microM. The results indicate that inhibition of the gastric proton pump by this diterpenoid may account for the antisecretory acid effect and reputed anti ulcer activity of Plectranthus barbatus. PMID:17166678

  3. Bioassay-guided isolation of an anti-ulcer diterpenoid from Croton reflexifolius: role of nitric oxide, prostaglandins and sulfhydryls.

    PubMed

    Reyes-Trejo, Benito; Sánchez-Mendoza, María Elena; Becerra-García, Anabel Ariana; Cedillo-Portugal, Ernestina; Castillo-Henkel, Carlos; Arrieta, Jesús

    2008-07-01

    Croton reflexifolius H. B. K (Euphorbiaceae) is a very common medicinal plant in the Huastecan region of Mexico that, according to local folk medicine, is considered useful in the treatment of gastritis and gastric ulcer. We have aimed to test the validity of this practice by using the experimental model of an ethanol-induced gastric ulcer in male Wistar rats. The results showed that C. reflexifolius had gastroprotector activity, that the hexane extract had the highest protective activity (64.38+/-7.72%), and that polyalthic acid isolated from this extract was the main active gastroprotector agent. Rats treated orally with polyalthic acid showed a gastroprotective effect similar to that elicited by carbenoxolone. As with carbenoxolone, the effect elicited by polyalthic acid was attenuated by pretreatment with either N(G)-nitro-L-arginine methyl ester (70 mgkg(-1), i.p.), a nitric oxide (NO) synthase inhibitor, or N-ethylmaleimide (10 mgkg(-1), s.c.), a blocker of sulfhydryl groups. This suggested that the gastroprotective mechanism of this diterpenoid involved the participation of both NO and endogenous sulfhydryl groups. Contrary to carbenoxolone, the gastroprotective effect of polyalthic acid was not affected by the inhibition of prostaglandin synthesis with indometacin (10 mgkg(-1), s. c.). In conclusion, Croton reflexifolius contains compounds with gastroprotector activity. Polyalthic acid, which was isolated from this plant, was the main compound with gastroprotector activity, having effectiveness similar to that found with the use of carbenoxolone. Whereas NO and sulfhydryl groups were involved in the mechanisms of gastroprotective action of polyalthic acid, prostaglandins were not. PMID:18549681

  4. Enantioselective Total Syntheses of Various Amphilectane and Serrulatane Diterpenoids via Cope Rearrangements.

    PubMed

    Yu, Xuerong; Su, Fan; Liu, Chang; Yuan, Haosen; Zhao, Shan; Zhou, Zhiyao; Quan, Tianfei; Luo, Tuoping

    2016-05-18

    Ampilectane and serrulatane natural products are structurally and stereochemically complex compounds that display various potent pharmacological activities ranging from anti-inflammatory to antituberculosis. A general synthetic route toward this family of natural products has been developed, which accomplished a number of amphilectane and serrulatane natural products. The key step employed a stereoselective Cope rearrangement either promoted by gold catalysis or thermal conditions, while a regioselective gold-catalyzed 6-endo-dig cyclization was optimized to afford a precursor. The preparation of the chiral β-ketoester as a starting material was established via an optimized asymmetric 1,4-addition followed by trapping with Mander's reagent, and this initially installed stereogenic center provided good control in the subsequent introduction of all the other stereocenters. A rarely investigated one-pot conversion of α-pyrone into phenol was also examined to enable the syntheses. DFT calculations explain the high stereoselectivity of the Cope rearrangement of the intermediate that eventually led to amphilectolide and caribenol A. PMID:27115064

  5. Qualitative and quantitative characterization of phenolic and diterpenoid constituents in Danshen (Salvia miltiorrhiza) by comprehensive two-dimensional liquid chromatography coupled with hybrid linear ion trap Orbitrap mass.

    PubMed

    Cao, Ji-Liang; Wei, Jin-Chao; Hu, Yuan-Jia; He, Cheng-Wei; Chen, Mei-Wan; Wan, Jian-Bo; Li, Peng

    2016-01-01

    Danshen is one of the most frequently used traditional Chinese herbs owing to its remarkable and reliable therapeutic effects. Phenolic acids and diterpenoids have proved to be the bioactive substance groups. In order to fully profile its chemical compositions and explore new potential bioactive compounds, a comprehensive two-dimensional liquid chromatography system coupled to DAD detector and hybrid linear ion trap (LTQ) Orbitrap mass spectrometry (LC × LC-DAD-ESI/HRMS/MS(n)) was set up in this study based on the column combination of Hypersil gold CN (150 mm × 1 mm, 3 μm) and Accucore C18 (50 mm × 4.6 mm, 2.6 μm). Using the optimal segment gradient program, phenolic acids and diterpenoids were separated into two independent groups and a total of 328 peaks were successfully detected on the contour plot of Danshen. By means of the accurate mass and reliable MS(n) data, 102 compounds were identified or tentatively identified and 7 of them were discovered from Danshen for the first time. Moreover, the LC × LC-DAD system was validated for the quantitative analysis of 14 bioactive analytes using the contour plot, exhibiting satisfactory linearity (r ≥ 0.9976) and high precision for both peak locating (≤ 1.07%) and peak volume calculating (0.34%-4.11%). The established method could afford powerful separation capability, reliable identification data and accurate quantitative results, which is very suitable for analysis of complex herbal samples. PMID:26687169

  6. Henryin, an ent-kaurane Diterpenoid, Inhibits Wnt Signaling through Interference with β-Catenin/TCF4 Interaction in Colorectal Cancer Cells

    PubMed Central

    Li, Xingyao; Pu, Jianxin; Jiang, Shiyou; Su, Jia; Kong, Lingmei; Mao, Bingyu; Sun, Handong; Li, Yan

    2013-01-01

    Aberrant Wnt/β-catenin signaling has been strongly associated with the tumorigenesis of human colorectal cancer. Inhibitors of this pathway may then offer therapeutic strategies as well as chemoprevention for this malignant disease. Henryin is an ent-kaurane diterpenoid isolated from Isodonrubescens var. lushanensis, a plant long been used in folk medicine to prevent inflammation and gastrointestinal disease. In the present study, we report that henryin selectively inhibits the proliferation of human colorectal cancer cells with a GI50 value in the nano-molar range. Microarray analysis and reporter assays showed that henryin worked as a novel antagonist of Wnt signaling pathway. Henryin reduced the expression of Cyclin D1 and C-myc, and induced G1/S phase arrest in HCT116 cells. Concurrently, henryin did not affect the cytosol-nuclear distribution of soluble β-catenin, but impaired the association of β-catenin/TCF4 transcriptional complex likely through directly blocking the binding of β-catenin to TCF4. We also then analyzed the structure-activity relationship among the ent-kaurane type diterpenoids. Our data suggests that henryin, as a novel inhibitor of Wnt signaling, could be a potential candidate for further preclinical evaluation for colon cancer treatment, and as such warrants further exploration. PMID:23844215

  7. Toxicity of Porella chilensis sesqui- and diterpenoids against larvae of the corn pest Spodoptera frugiperda (J.E. Smith) (Lepidotera: Noctuidae).

    PubMed

    Corzo, F L; Gilabert, M; Alcaide, M F; Bardón, A

    2012-10-01

    Porella, the largest genus of the family Porellaceae (Hepaticae) is widespread in the tropical and subtropical regions of South America. Most Porella species are rich sources of sesqui- and diterpenoids, many of which show interesting biological activities. Secondary metabolites produced by plants can interact with insects and act as antifeedants and growth regulators affecting hormone and nervous systems as well as stomach and muscle tissues. A previous chemical investigation of a Patagonian collection of Porella chilensis yielded sesqui- and diterpenoids that were now evaluated for their effects against Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), a serious pest affecting corn crops mainly in the Americas. Four pinguisanes (1-4), three fusicoccanes (5-7), and one aromadendrane (8) from P. chilensis displayed larvicidal activity against S. frugiperda when incorporated to the larval diet at 100 and 200 μg/g of diet with a significant decrease in the larval growing rate. The observed effects were in part produced by severe alterations of the epithelial cells of the midgut as indicated by our histological studies. PMID:23950093

  8. In vivo and in vitro metabolites from the main diester and monoester diterpenoid alkaloids in a traditional chinese herb, the aconitum species.

    PubMed

    Zhang, Min; Peng, Chong-Sheng; Li, Xiao-Bo

    2015-01-01

    Diester diterpenoid alkaloids (DDAs), such as aconitine (AC), mesaconitine (MA), and hypaconitine (HA), are both pharmacologically active compounds and toxic ingredients in a traditional Chinese herb, the Aconitum species. Many DDA metabolism studies have been performed to explore mechanisms for reducing toxicity in these compounds and in Aconitum species extracts for safe clinical administration. In this review, we summarize recent progress on the metabolism of toxic AC, MA, and HA and corresponding monoester diterpenoid alkaloids (MDAs) in the gastrointestinal tract and liver in different animal species and humans in vivo and/or in vitro, where these alkaloids are primarily metabolized by cytochrome P450 enzymes, carboxylesterases, and intestinal bacteria, which produces phase I metabolites, ester hydrolysed products, and lipoalkaloids. Furthermore, we classify metabolites detected in the blood and urine, where the aforementioned metabolites are absorbed and excreted. Less toxic MDAs and nontoxic alcohol amines are the primary DDA metabolites detected in the blood. Most other DDAs metabolites produced in the intestine and liver detected in the urine have not been reported in the blood. We propose an explanation for this nonconformity. Finally, taking AC, for instance, we generalize a process of toxicity reduction in the body after oral AC administration for the first time. PMID:25705235

  9. Extraction of three bioactive diterpenoids from Andrographis paniculata: effect of the extraction techniques on extract composition and quantification of three andrographolides using high-performance liquid chromatography.

    PubMed

    Kumar, Satyanshu; Dhanani, Tushar; Shah, Sonal

    2014-10-01

    Andrographis paniculata (Burm.f.) wall.ex Nees (Acanthaceae) or Kalmegh is an important medicinal plant finding uses in many Ayurvedic formulations. Diterpenoid compounds andrographolides (APs) are the main bioactive phytochemicals present in leaves and herbage of A. paniculata. The efficiency of supercritical fluid extraction (SFE) using carbon dioxide was compared with the solid-liquid extraction techniques such as solvent extraction, ultrasound-assisted solvent extraction and microwave-assisted solvent extraction with methanol, water and methanol-water as solvents. Also a rapid and validated reverse-phase high-performance liquid chromatography-diode array detection method was developed for the simultaneous determination of the three biologically active compounds, AP, neoandrographolide and andrograpanin, in the extracts of A. paniculata. Under the best SFE conditions tested for diterpenoids, which involved extraction at 60°C and 100 bar, the extractive efficiencies were 132 and 22 µg/g for AP and neoandrographolide, respectively. The modifier percentage significantly affected the extraction efficiency. PMID:24170124

  10. A Simple and Sensitive LC-MS/MS Method for Determination of Four Major Active Diterpenoids from Andrographis paniculata in Human Plasma and Its Application to a Pilot Study.

    PubMed

    Pholphana, Nanthanit; Panomvana, Duangchit; Rangkadilok, Nuchanart; Suriyo, Tawit; Ungtrakul, Teerapat; Pongpun, Wanwisa; Thaeopattha, Saichit; Satayavivad, Jutamaad

    2016-01-01

    Andrographis paniculata contains four major active diterpenoids, including andrographolide (1), 14-deoxy-11, 12-didehydroandrographolide (2), neoandrographolide (3), and 14-deoxyandrographolide (4), which exhibit differences in types and/or degrees of their pharmacological activity. Previous pharmacokinetic studies in humans reported only the parameters of compound 1 and its analytical method in human plasma. The purpose of this study was to develop a simple, sensitive, and selective liquid chromatography tandem-mass spectrometry technique for the simultaneous determination of all four major active diterpenoids in the A. paniculata product in human plasma. These four diterpenoids in plasma samples were extracted by a simple protein precipitation method with methanol and separated on a Kinetex C18 column using a gradient system with a mobile phase of acetonitrile and water. The liquid chromatography tandem-mass spectrometry was performed in the negative mode, and the multiple reaction monitoring mode was used for the quantitation. The method showed a good linearity over a wide concentration range of 2.50-500 ng/mL for 1 and over the range of 1.00-500 ng/mL for the other diterpenoids with a correlation coefficient R(2) > 0.995. The lower limit of quantification of 1 was found to be 2.50 ng/mL, while those of the other diterpenoids were 1.00 ng/mL. The intraday and interday accuracy (relative error) ranged from 0.03 % to 10.03 %, and the intraday and interday precisions (relative standard deviation) were in the range of 2.05-9.67 %. The extraction recovery (86.54-111.56 %) with a relative standard deviation of 2.78-8.61 % and the matrix effect (85.15-112.36 %) were within the acceptance criteria. Moreover, these four major active diterpenoids were stable in plasma samples at the studied storage conditions with a relative error ≤-9.79 % and a relative standard deviation ≤ 9.26 %. Hence, this present method was successfully validated

  11. Synthesis of novel diterpenoid analogs with in-vivo antitumor activity.

    PubMed

    Wang, Ying-Ying; He, Yuan; Yang, Lian-Fang; Peng, Shi-Hong; He, Xiao-Long; Wang, Jin-Hua; Lv, Fang; Hao, Yun; Liu, Ming-Yao; Yi, Zhengfang; Qiu, Wen-Wei

    2016-09-14

    A lead compound 7 has antitumor effect, which was discovered by screening our small synthetic natural product-like compound (NPL) library. Based on the lead compound, a series of novel tricyclic diterpene analogs were synthesized and investigated for their activity against the growth of various tumor cell lines using the sulforhodamine B (SRB) assay. To our delight, most aromatic amide compounds exhibited more potent antitumor activity than the lead compound. The most active compound 19 (QW30) showed an average IC50 0.33 μM, which was 15-fold more potent than the lead compound. Most of the compounds with potent antitumor activity displayed less toxic on normal human fibroblasts (HAF) in comparison with the tumor cell lines. Especially 19, its selectivity indexes (SI) between HAF and cancer cell lines was 17.3 times better than the positive control compound podophyllotoxin. The apoptosis, colony formation and transwell migration assays of 7 and 19 were performed on T47D cell line. The in-vivo antitumor effect of 19 was also observed in T47D tumor-bearing mice without obvious toxicity. PMID:27187855

  12. Anti-Candida Cassane-Type Diterpenoids from the Root Bark of Swartzia simplex.

    PubMed

    Favre-Godal, Quentin; Dorsaz, Stephane; Queiroz, Emerson F; Marcourt, Laurence; Ebrahimi, Samad N; Allard, Pierre-Marie; Voinesco, Francine; Hamburger, Matthias; Gupta, Mahabir P; Gindro, Katia; Sanglard, Dominique; Wolfender, Jean-Luc

    2015-12-24

    A dichloromethane extract of the roots from the Panamanian plant Swartzia simplex exhibited a strong antifungal activity in a bioautography assay against a genetically modified hypersusceptible strain of Candida albicans. At-line HPLC activity based profiling of the crude extract enabled a precise localization of the antifungal compounds, and dereplication by UHPLC-HRESIMS indicated the presence of potentially new metabolites. Transposition of the HPLC reversed-phase analytical conditions to medium-pressure liquid chromatography (MPLC) allowed an efficient isolation of the major constituents. Minor compounds of interest were isolated from the MPLC fractions using semipreparative HPLC. Using this strategy, 14 diterpenes (1-14) were isolated, with seven (5-10, 14) being new antifungal natural products. The new structures were elucidated using NMR spectroscopy and HRESIMS analysis. The absolute configurations of some of the compounds were elucidated by electronic circular dichroism spectroscopy. The antifungal properties of these compounds were evaluated as their minimum inhibitory concentrations in a dilution assay against both hypersusceptible and wild-type strains of C. albicans and by assessment of their antibiofilm activities. The potential cytological effects on the ultrastructure of C. albicans of the antifungal compounds isolated were evaluated on thin sections by transmission electron microscopy. PMID:26654828

  13. Differentiation of Isodon japonica and Adulterants Based on Identification and Quantitation 14 Diterpenoids Using LC-MS-MS Library Search Approach and Hierarchical Cluster Analysis.

    PubMed

    Jin, Yiran; Tian, Tingting; Ma, Yinghua; Liu, Minyan; Xie, Weiwei; Wang, Xin; Xu, Huijun; Du, Yingfeng

    2016-03-01

    The aim of this study was to investigate the chemical differences between genunine Isodon japonica and its adulterants. A linear ion trap liquid chromatography with tandem mass spectrometry analytical method has been developed for the identification and quantification of 14 major diterpenoids in I. japonica. Data acquisition was multiple reaction monitoring transitions mode followed by an information-dependent acquisition using the enhanced product ion (EPI) scan in a single run. The target compounds were further identified and confirmed using an EPI spectral library. Overall validation of the assay was carried out including linearity, accuracy, precision, limits of detection and quantification. The results demonstrated that the method was selective, sensitive and reliable. The determination results of 21 batches of I. japonica and adulterants were then analyzed and differentiated by hierarchical clustering analysis. PMID:26489434

  14. [Our investigation on the chemistry of biologically active natural products. With the object of exploitation for structure determination methods, and elucidation of vital function].

    PubMed

    Komori, T

    1993-03-01

    Our investigation on the chemistry of biologically active natural products during the last 40 years since 1953 are reviewed in this paper. The following subjects are discussed: I. photochemical relationship between rhodopsin and compounds related to areca alkaloid, II. furanoid diterpenoid constituents from dioscoreaceae plants and colombo root, III. field desorption and fast atom bombardment mass spectrometry of biologically active natural glycosides and glycosphingolipids, IV. investigation of biologically active marine natural products, 1) constituents of steroid glycoside sulfates from Asteroidea, 2) spine toxins from Acanthaster planci, 3) constituents of triterpenoid glycoside sulfates from Holothuroidea, 4) constituents of isoprenoids from Opisthobranchia and Octocorallia, 5) constituents of glycosphingolipids from Asteroidea. PMID:8509990

  15. Seed dormancy breaking diterpenoids from the liverwort Plagiochila sciophila and their differentiation inducing activity in human promyelocytic leukemia HL-60 cells.

    PubMed

    Kenmoku, Hiromichi; Tada, Hiroyuki; Oogushi, Megumi; Esumi, Tomoyuki; Takahashi, Hironobu; Noji, Masaaki; Sassa, Takeshi; Toyota, Masao; Asakawa, Yoshinori

    2014-07-01

    To obtain the structural diversity of bioactive compounds similar to cotylenins and fusicoccins that modulate 14-3-3 protein-protein interactions in eukaryotes, screening tests were carried out using the lettuce seed dormancy breaking-assay. An acetone extract of the liverwort Plagiochila sciophila exhibited significant activity against the seeds in the presence of the plant hormone abscisic acid. Activity-guided fractionation of the extract afforded the isolation of seven novel fusicoccane-type diterpenoids, named fusicosciophins A-E (1-5), 8-deacetyl (6) and 9-deacetyl fusicosciophin E (7). Their structures were determined by spectroscopic methods and X-ray crystallographic analyses. All the pure isolated compounds (1-7) exhibited moderate lettuce seed dormancy breaking activity. In addition, the differentiation-inducing activity and cytotoxicity of these isolates, together with fusicoccin A (FC-A) and all-trans retinoic acid (ATRA), were evaluated in human promyelocytic leukemia HL-60 cells and human mouth epidermal carcinoma KB cells, respectively. Fusicosciophins (2 and 4) and FC-A exhibited moderate differentiation-inducing activity (EC50 31.2-59.1 microM) compared with ATRA (EC50 0.3 microM), while 2, 4 and ATRA exhibited higher selectivity indices (IC50/EC50 >3.38-667) than FC-A (IC50/EC50 1.05). This is the first report on the isolation of fusicoccane-type diterpenoids from liverworts having seed dormancy breaking activity and differentiation-inducing activity in mammal cells. PMID:25230492

  16. Total syntheses of cyanthiwigins B, F, and G.

    PubMed

    Enquist, John A; Virgil, Scott C; Stoltz, Brian M

    2011-08-29

    A concise and versatile approach toward the preparation of the cyanthiwigin family of cyathane natural products is described. By leveraging a unique double asymmetric catalytic alkylation procedure it is possible to quickly establish two of the most critical stereocenters of the cyanthiwigin framework with high levels of selectivity and expediency. The synthetic route additionally employs both a tandem ring-closing cross-metathesis reaction, and an aldehyde-olefin radical cyclization process, in order to rapidly arrive at the tricyclic cyathane core of the cyanthiwigin molecules. From this unifying intermediate, the preparations of cyanthiwigins B, F, and G are attained swiftly and without the need for protecting groups. PMID:21769952

  17. Diterpenoids from Casearia sylvestris

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two highly oxygenated clerodane diterpenes casearins U (1) and V (2) and two ent-kaurane diterpene glucosides sylvestrisides A (3) and B (4) were isolated from the leaves of Casearia sylvestris, together with 13 known compounds. Their structures were established on the basis of 1D and 2D NMR spectro...

  18. Neutral fragment filtering for rapid identification of new diester-diterpenoid alkaloids in roots of Aconitum carmichaeli by ultra-high-pressure liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry.

    PubMed

    Zhang, Jing; Huang, Zhi Hai; Qiu, Xiao Hui; Yang, Yi Ming; Zhu, Da Yuan; Xu, Wen

    2012-01-01

    A rapid and effective method was developed for separation and identification of diester-diterpenoid alkaloids (DDA) in the roots of Aconitum carmichaeli by ultra-high-pressure liquid chromatography coupled with high resolution LTQ-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap-MS(n)). According to accurate mass measurement and the characteristic neutral loss filtering strategy, a total of 42 diester-diterpenoid alkaloids (DDA) were rapidly detected and characterized or tentatively identified. Meanwhile, the proposed fragmentation pathways and the major diagnostic fragment ions of aconitine, mesaconitine and hypaconitine were investigated to trace DDA derivatives in crude plant extracts. 23 potential new compounds were successfully screened and characterized in Aconitum carmichaeli, including 16 short chain fatty acyls DDA, 4 N-dealkyl DDA and several isomers of aconitine, mesaconitine and hypaconitine. PMID:23285005

  19. Cytotoxic and natural killer cell stimulatory constituents of Phyllanthus songboiensis

    PubMed Central

    Ren, Yulin; Yuan, Chunhua; Deng, Youcai; Kanagasabai, Ragu; Ninh, Tran Ngoc; Tu, Vuong Tan; Chai, Hee-Byung; Soejarto, Djaja D.; Fuchs, James R.; Yalowich, Jack C.; Yu, Jianhua; Kinghorn, A. Douglas

    2014-01-01

    A dichapetalin-type triterpenoid and a dibenzylbutyrolactone-type lignan, together with five known lignans, a known aromatic diterpenoid, and a known acylated phytosterol, were isolated from the aerial parts of Phyllanthus songboiensis, collected in Vietnam. Their structures were determined by interpretation of the spectroscopic data, and the inhibitory activity toward the HT-29 human colon cancer cells of all isolates was evaluated by a cytotoxicity assay. The known arylnaphthalene lignan, (+)-acutissimalignan A, was highly cytotoxic toward HT-29 cells, with an IC50 value of 19 nM, but this compound was inactive as a DNA topoisomerase IIα (topo IIα) poison. The known phytosterol, (−)-β-sitosterol-3-O-β-D-(6-O-palmitoyl)glucopyranoside, was found to stimulate natural killer (NK) cells at a concentration of 10 μM in the presence of interleukin 12 (IL-12). PMID:25596805

  20. Jatrophane Diterpenoids as Modulators of P-Glycoprotein-Dependent Multidrug Resistance (MDR): Advances of Structure-Activity Relationships and Discovery of Promising MDR Reversal Agents.

    PubMed

    Zhu, Jianyong; Wang, Ruimin; Lou, Lanlan; Li, Wei; Tang, Guihua; Bu, Xianzhang; Yin, Sheng

    2016-07-14

    The phytochemical study of Pedilanthus tithymaloides led to the isolation of 13 jatrophane diterpenoids (1-13), of which eight (1-8) are new. Subsequent structural modification of the major components by esterification, hydrolysis, hydrogenation, or epoxidation yielded 22 new derivatives (14-35). Thus, a jatrophane library containing two series of compounds was established to screen for P-glycoprotein (Pgp)-dependent MDR modulators. The activity was evaluated through a combination of Rho123 efflux and chemoreversal assays on adriamycin resistant human hepatocellular carcinoma cell line HepG2 (HepG2/ADR) and adriamycin resistant human breast adenocarcinoma cell line MCF-7 (MCF-7/ADR). Compounds 19, 25, and 26 were identified as potent MDR modulators with greater chemoreversal ability and less cytotoxicity than the third-generation drug tariquidar. The structure-activity relationship (SAR) was discussed, which showed that modifications beyond just increasing the lipophilicity of this class of Pgp inhibitors are beneficial to the activity. Compound 26, which exhibited a remarkable metabolic stability in vitro and a favorable antitumor effect in vivo, would serve as a promising lead for the development of new MDR reversal agents. PMID:27328029

  1. Gastroprotective effects of new diterpenoid derivatives from Azorella cuatrecasasii Mathias & Constance obtained using a β-cyclodextrin complex with microbial and chemical transformations.

    PubMed

    Sepúlveda, Beatriz; Quispe, Cristina; Simirgiotis, Mario; García-Beltrán, Olimpo; Areche, Carlos

    2016-07-15

    Mulinane diterpenoids isolated from Azorella species have displayed gastroprotective effects in animal models. In this study we have transformed the main constituent, mulin-11,13-dien-20 oic acid from this plant using the filamentous fungus Mucor plumbeus and a β-cyclodextrin inclusion complex and we have obtained two main products with good yields (33% and 15% for compound 4 and 5, respectively) for further preparation of semisynthetic derivatives to evaluate their gastroprotective effects. In addition, one of the compounds isolated from Azorella cuatrecasasii was new (9-epi-13α-hydroxymulinene 1). Six new derivatives 4a-4c and 5a-5c were then prepared by simple chemical transformations. The structures of all compounds were elucidated by spectroscopic means based on 1D and 2D-NMR techniques. Some 8 diterpenes were evaluated for their gastroprotective effects in the ethanol/HCl-induced ulcer model in mice at 20mg/kg. The highest gastroprotective activity was shown by 7α,16-dihydroxymulin-11,13-dien-20-oic acid 5, which was higher than the reference drug lansoprazole, while 16-hydroxymulin-11,13-dien-20-oic acid 4 was as active as lansoprazole. PMID:27262597

  2. [Synthesis and antituberculosis activity of the derivatives of glycoside steviolbioside from the plant Stevia rebaudiana and diterpenoid isosteviol containing hydrazone, hydrazide and pyridinoyl moieties].

    PubMed

    Kataev, V E; Strobykina, I Iu; Andreeva, O V; Garifullin, B F; Sharipova, R R; Mironov, V F; Chestnova, R V

    2011-01-01

    Conjugates of antitubercular drug Isoniazid (hydrazide of isonicotinic acid), nicotinic and alpha-picolinic acid hydrazides and glycoside steviolbioside from the plant Stevia rebaudiana as well as the product of its acid hydrolysis, diterpenoid isosteviol, were synthesized. Besides, isosteviol hydrazide and hydrazone derivatives as well as conjugates containing two isosteviol moieties connected by dihydrazide linker were also obtained. Both initial compounds and their synthetic derivatives inhibit the growth of Mycobacterium tuberculosis (H37Rv in vitro). The minimum concentration at which the growth of M. tuberculosis was inhibited by 100% (MIC) for stevioside and steviolbioside equals 7.5 and 3.8 microg/mL, respectively. MIC values for conjugates of the hydrazides of pyridine carbonic acids and steviolbioside as well as isosteviol are in the ranges 5-10 and 10-20 microg/mL, respectively. Maximum inhibitory effect against M. tuberculosis showed the conjugates of isosteviol and adipic acid dihydrazide (MIC values ranged from 1.7 to 3.1 microg/mL). Antitubercular activity of the compounds studied is higher than the activity of antitubercular drug Pyrizanamide (MIC = 12.5-20 microg/mL) but lower than the activity of antitubercular drug Isoniazid (MIC = 0.02-0.04 microg/mL). PMID:22096997

  3. Polyandric acid A, a clerodane diterpenoid from the Australian medicinal plant Dodonaea polyandra, attenuates pro-inflammatory cytokine secretion in vitro and in vivo.

    PubMed

    Simpson, Bradley S; Luo, Xianling; Costabile, Maurizio; Caughey, Gillian E; Wang, Jiping; Claudie, David J; McKinnon, Ross A; Semple, Susan J

    2014-01-24

    Dodonaea polyandra is a medicinal plant used traditionally by the Kuuku I'yu (Northern Kaanju) indigenous people of Cape York Peninsula, Australia. The most potent of the diterpenoids previously identified from this plant, polyandric acid A (1), has been examined for inhibition of pro-inflammatory cytokine production and other inflammatory mediators using well-established acute and chronic mouse ear edema models and in vitro cellular models. Topical application of 1 significantly inhibited interleukin-1β production in mouse ear tissue in an acute model. In a chronic skin inflammation model, a marked reduction in ear thickness, associated with significant reduction in myeloperoxidase accumulation, was observed. Treatment of primary neonatal human keratinocytes with 1 followed by activation with phorbol ester/ionomycin showed a significant reduction in IL-6 secretion. The present study provides evidence that the anti-inflammatory properties of 1 are due to inhibition of pro-inflammatory cytokines associated with skin inflammation and may be useful in applications for skin inflammatory conditions including psoriasis and dermatitis. PMID:24400858

  4. Toxicity assessment of nine types of decoction pieces from the daughter root of Aconitum carmichaeli (Fuzi) based on the chemical analysis of their diester diterpenoid alkaloids.

    PubMed

    Lu, Guanghua; Dong, Zhengqi; Wang, Qing; Qian, Guangsheng; Huang, Wenhua; Jiang, Zhihong; Leung, Kelvin Sze-Yin; Zhao, Zhongzhen

    2010-05-01

    Various processed types of FUZI (the daughter roots of the highly toxic plant Aconitum carmichaeli Debx, FZ) decoction pieces (the herbal materials processed according to the specifications of Chinese medicine manuals; " YINPIAN" in Chinese transliteration) are widely used in traditional medicine to treat various diseases, but their toxicities are not known. Nine types of FZ decoction pieces, including one raw slice and eight processed forms, were therefore prepared, each in 7 to 10 batches, to assess for their toxicity. Altogether 84 FZ samples were quantified on the amount of highly toxic diester diterpenoid alkaloids, i.e., aconitine, mesaconitine and hypaconitine by a newly developed HPLC method with HPLC-DAD and LC-MS techniques. The comparison of the processed FZ to raw slices of the root showed that the amount of each analyte in the processed FZ was drastically decreased. The sum of the three toxic compounds in the 8 types of processed FZ was only 3.91-34.80 % of this value in the FZ raw slice. This implies that the toxicity of processed FZ was decreased significantly. The amounts of toxic components in the 8 types of processed FZ varied significantly, often by a power of ten, indicating that the dosage of these herbs, when prescribed for clinical uses, should be cautiously set in order to avoid poisoning incidents. PMID:20013637

  5. Characterization and evaluation of an oral microemulsion containing the antitumor diterpenoid compound ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid

    PubMed Central

    Lu, Yingnian; Wu, Kefeng; Li, Li; He, Yuhui; Cui, Liao; Liang, Nianci; Mu, Bozhong

    2013-01-01

    The objective of this study was to develop an oral microemulsion formulation of the antitumor diterpenoid agent, ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (henceforth referred to as 5F), to enhance its bioavailability and evaluate its hepatotoxicity. Pseudoternary phase diagrams showed that the optimal microemulsion formulation contained 45% water, 10% castor oil as the oil phase, 15% Cremophor EL as the surfactant, and 30% as a cosurfactant mixture of 1,2-propanediol and polyethylene glycol (PEG)-400 (2:1, w/w). The microemulsion preparation was characterized and its droplet diameter was within 50 nm. Release of 5F in vitro from the microemulsion was slightly increased compared with a suspension containing the same amount of active drug. Pharmacokinetic parameters in vivo indicated that bioavailability was markedly improved, with the relative bioavailability being 616.15% higher for the microemulsion than for the suspension. Toxicity tests showed that the microemulsion had no hepatotoxicity in mice. These results suggest the potential for 5F microemulsion to be administered by the oral route. PMID:23690685

  6. Differential control of growth, cell cycle progression, and expression of NF-{kappa}B in human breast cancer cells MCF-7, MCF-10A, and MDA-MB-231 by ponicidin and oridonin, diterpenoids from the chinese herb Rabdosia rubescens

    SciTech Connect

    Hsieh Tzechen; Wijeratne, E. Kithsiri; Liang Jingyu; Gunatilaka, A. Leslie; Wu, Joseph M. . E-mail: Joseph_Wu@nymc.edu

    2005-11-11

    Ponicidin and oridonin are novel diterpenoids isolated from Rabdosia rubescens. We tested their effects in MCF-7 and MDA-MB-231 cells, as representing low and high invasive breast carcinoma, with normal MCF-10A cells. Clonogenicity and proliferation in MCF-7 cells were inhibited more significantly by ponicidin than oridonin, while the reverse was observed in MCF-10A cells. Ponicidin and oridonin induced S/G{sub 2}M arrest and G{sub 1}/S block in MCF-7 cells. In MCF-10A cells treated with either diterpenoid, induction of apoptosis was observed. Moreover, oridonin almost completely blocked MCF-10A progression from S to G{sub 2}/M phase; in contrast, ponicidin-treated MCF-10A cells showed no discernable changes in cell cycle phase distribution. Neither diterpenoid affected growth of MDA-MB-231 cells, at the dose range effective for MCF-7 or MCF-10A cells. Ponicidin-treated MCF-7 cells expressed reduced levels of cyclin B1, cdc2, transcription factor E2F, and Rb including phosphorylation at S780. Less pronounced effects were found in cells treated with oridonin. Neither compound altered cyclin D1 and cdk4 in MCF-7 cells. In MCF-10A cells, oridonin was more active than ponicidin in inhibiting the expression of cyclin B1, cdc2, S780-phosphorylated Rb, and E2F. To further investigate induction of apoptosis in MCF-10A cells, we measured changes in NF-{kappa}B. Decreases in p65 or p50 forms of NF-{kappa}B and its upstream regulator I-{kappa}B were found in oridonin-treated MCF-10A and not MCF-7 cells. Taken together, these results provide a mechanistic framework for the cellular effects of ponicidin and oridonin in different stage breast cancer cells.

  7. LC-MS and 1H NMR as an improved dereplication tool to identify antifungal diterpenoids from Sagittaria latifolia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A dereplication strategy using a combination of liquid chromatography-mass spectrometry (LC-MS) and proton nuclear magnetic resonance spectroscopy (1H NMR) to facilitate compound identification towards antifungal natural product discovery is presented. This analytical approach takes advantage of th...

  8. Diterpenoid (poly)esters and a ring A-seco-phorboid from the aerial parts of Euphorbia macroclada Boiss.

    PubMed

    Shokoohinia, Yalda; Sajjadi, Seyed-Ebrahim; Zolfaghari, Behzad; Chianese, Giuseppina; Appendino, Giovanni; Taglialatela-Scafati, Orazio

    2010-10-01

    Euphorbia macroclada Boiss., a spurge endemic to the Iranian plateau, afforded four pre-myrsinane polyesters, three α-phorboids and one A-seco-phorboid, a type of compound so far unreported within natural products. All new compounds were structurally elucidated by spectroscopic methods, and especially 2D NMR measurements. PMID:20566387

  9. An ent-kaurane diterpenoid from Croton tonkinensis induces apoptosis by regulating AMP-activated protein kinase in SK-HEP1 human hepatocellular carcinoma cells.

    PubMed

    Sul, Young Hoon; Lee, Myung Sun; Cha, Eun Young; Thuong, Phuong Thien; Khoi, Nguyen Minh; Song, In Sang

    2013-01-01

    Hepatocellular carcinoma (HCC) is the most common type of liver cancer with high mortality worldwide. Traditional chemotherapy for HCC is not widely accepted by clinical practitioners because of its toxic side effects. Thus, there is a need to identify chemotherapeutic drugs against HCC. AMP-activated protein kinase (AMPK) is a biologic sensor for cellular energy status that acts a tumor suppressor and a potential cancer therapeutic target. The traditional Vietnamese medicinal plant Croton tonkinensis shows cytotoxicity in various cancer cells; however, its anticancer mechanism remains unclear. In this study, we determined whether the ent-kaurane diterpenoid ent-18-acetoxy-7β-hydroxy kaur-15-oxo-16-ene (CrT1) isolated from this plant plays a role as a chemotherapeutic drug targeting AMPK. CrT1 blocked proliferation in dose- and time-dependent manners in human hepatocellular carcinoma SK-HEP1 cells. CrT1 induced sub-G(1) arrest and caspase-dependent apoptosis. CrT1 activated caspase-3, -7, -8, -9, and poly(ADP-ribose) polymerase, and its effect was inhibited by z-VAD-fmk suppressing caspase-3 cleavage. CrT1 induced increases in p53 and Bax levels but decreased Bcl(2) levels. In addition, CrT1 resulted in increased translocation of cytochrome c into the cytoplasm. We showed that CrT1-activated AMPK activation was followed by modulating the mammalian target of rapamycin/p70S6K pathway and was inactivated by treating cells with compound C. Treatment with CrT1 and aminoimidazole carboxamide ribonucleotide (AICAR) synergistically activated AMPK. CrT1-induced AMPK activation regulated cell viability and apoptosis. These results suggest that CrT1 is a novel AMPK activator and that AMPK activation in SK-HEP1 cells is responsible for CrT1-induced anticancer activity including apoptosis. PMID:23302650

  10. A semisynthetic diterpenoid lactone inhibits NF-κB signalling to ameliorate inflammation and airway hyperresponsiveness in a mouse asthma model.

    PubMed

    Lim, J C-W; Goh, F-Y; Sagineedu, S-R; Yong, A C-H; Sidik, S M; Lajis, N H; Wong, W S F; Stanslas, J

    2016-07-01

    Andrographolide (AGP) and 14-deoxy-11,12-didehydroandrographolide (DDAG), two main diterpenoid constituents of Andrographis paniculata were previously shown to ameliorate asthmatic symptoms in a mouse model. However, due to inadequacies of both compounds in terms of drug-likeness, DDAG analogues were semisynthesised for assessment of their anti-asthma activity. A selected analogue, 3,19-diacetyl-14-deoxy-11,12-didehydroandrographolide (SRS27), was tested for inhibitory activity of NF-κB activation in TNF-α-induced A549 cells and was subsequently evaluated in a mouse model of ovalbumin (OVA)-induced asthma. Female BALB/c mice, 6-8weeks old were sensitized on days 0 and 14, and challenged on days 22, 23 and 24 with OVA. Compound or vehicle (3% dimethyl sulfoxide) was administered intraperitoneally 1h before and 11h after each OVA aerosol challenge. On day 25, pulmonary eosinophilia, airway hyperresponsiveness, mucus hypersecretion, inflammatory cytokines such as IL-4, -5 and -13 in BAL fluid, gene expression of inflammatory mediators such as 5-LOX, E-selectin, VCAM-1, CCL5, TNF-α, AMCase, Ym2, YKL-40, Muc5ac, CCL2 and iNOS in animal lung tissues, and serum IgE were determined. SRS27 at 30μM was found to suppress NF-κB nuclear translocation in A549 cells. In the ovalbumin-induced mouse asthma model, SRS27 at 3mg/kg displayed a substantial decrease in pulmonary eosinophilia, BAL fluid inflammatory cytokines level, serum IgE production, mucus hypersecretion and gene expression of inflammatory mediators in lung tissues. SRS27 is the first known DDAG analogue effective in ameliorating inflammation and airway hyperresponsiveness in the ovalbumin-induced mouse asthma model. PMID:27089844

  11. Diterpanes, triterpanes, steranes, and aromatic hydrocarbons in natural bitumens and pyrolysates from different humic coals

    NASA Astrophysics Data System (ADS)

    Lu, Shan-Tan; Kaplan, Isaac R.

    1992-07-01

    Data are presented on the distribution of diterpanes, triterpanes, steranes, and aromatic hydrocarbons in the natural bitumens extracted from unheated coals identified as Rocky Mountain coal (RMC), Australian Gippsland Latrobe Eocene coal (GEC), Australian Gippsland Latrobe Cretaceous coal (GCC), and Texas Wilcox lignite (WL), as well as from pyrolysates obtained from heating of these coals. It was found that pentacyclic triterpanes are dominant in GEC, GCC, and WL, whereas diterpanes strongly predominate in the bitumen of RMC, indicating that resin is a more important constituent of RMC than of the other coals and that it releases the diterpenoids at an early stage of diagenesis. It was also found that the composition of diterpanes is different among these coals and that the distributions of sterane and triterpane in the natural bitumen of coals are very different from those of pyrolysates.

  12. Diterpanes, triterpanes, steranes, and aromatic hydrocarbons in natural bitumens and pyrolysates from different humic coals

    NASA Technical Reports Server (NTRS)

    Lu, Shan-Tan; Kaplan, Isaac R.

    1992-01-01

    Data are presented on the distribution of diterpanes, triterpanes, steranes, and aromatic hydrocarbons in the natural bitumens extracted from unheated coals identified as Rocky Mountain coal (RMC), Australian Gippsland Latrobe Eocene coal (GEC), Australian Gippsland Latrobe Cretaceous coal (GCC), and Texas Wilcox lignite (WL), as well as from pyrolysates obtained from heating of these coals. It was found that pentacyclic triterpanes are dominant in GEC, GCC, and WL, whereas diterpanes strongly predominate in the bitumen of RMC, indicating that resin is a more important constituent of RMC than of the other coals and that it releases the diterpenoids at an early stage of diagenesis. It was also found that the composition of diterpanes is different among these coals and that the distributions of sterane and triterpane in the natural bitumen of coals are very different from those of pyrolysates.

  13. Discovery and development of natural product oridonin-inspired anticancer agents.

    PubMed

    Ding, Ye; Ding, Chunyong; Ye, Na; Liu, Zhiqing; Wold, Eric A; Chen, Haiying; Wild, Christopher; Shen, Qiang; Zhou, Jia

    2016-10-21

    Natural products have historically been, and continue to be, an invaluable source for the discovery of various therapeutic agents. Oridonin, a natural diterpenoid widely applied in traditional Chinese medicines, exhibits a broad range of biological effects including anticancer and anti-inflammatory activities. To further improve its potency, aqueous solubility and bioavailability, the oridonin template serves as an exciting platform for drug discovery to yield better candidates with unique targets and enhanced drug properties. A number of oridonin derivatives (e.g. HAO472) have been designed and synthesized, and have contributed to substantial progress in the identification of new agents and relevant molecular mechanistic studies toward the treatment of human cancers and other diseases. This review summarizes the recent advances in medicinal chemistry on the explorations of novel oridonin analogues as potential anticancer therapeutics, and provides a detailed discussion of future directions for the development and progression of this class of molecules into the clinic. PMID:27344488

  14. A strategy for the separation of diterpenoid isomers from the root of Aralia continentalis by countercurrent chromatography: The distribution ratio as a substitute for the partition coefficient and a three-phase solvent system.

    PubMed

    Lee, Kyoung Jin; Song, Kwang Ho; Choi, Wonmin; Kim, Yeong Shik

    2015-08-01

    Aralia continentalis (Araliaceae) is widely used as a medicinal plant in East Asia. Previous studies have indicated that diterpenoid isomers (kaurenoic acid, continentalic acid, and ent-continentalic acid) are the major bioactive compounds of this plant. A new strategy was developed to alleviate difficulties in the separation of these isomers from this plant. A three-phase solvent system was applied to separate the isomers, and furthermore, the distribution ratio (Kc) was introduced as a substitute for the partition coefficient (KD). For compounds exhibiting a single equilibrium, their distributions in two immiscible phases were only affected by the partition coefficient of each solute. However, compounds that have a dissociating functional group (e.g., -COOH) are involved in two types of equilibrium in the two-phase system. In this case, the partitioning behaviors of the solutes are greatly affected by the pH of the solution. A mathematical prediction was applied for adjusting the solutions to the proper pH values. To prevent non-used phase (medium phase) waste, both the stationary phase (upper phase) and mobile phase (lower phase) were prepared on-demand without pre-saturation with the application of (1)H NMR. Each fraction obtained was collected and dried, yielding the following diterpenoid isomers from the 50mg injected sample: kaurenoic acid (19.7mg, yield: 39%) and ent-continentalic acid (21.3mg, yield: 42%). PMID:26138601

  15. Epigenetic Genome Mining of an Endophytic Fungus Leads to Pleiotropic Biosynthesis of Natural Products

    PubMed Central

    Mao, Xu-Ming; Xu, Wei; Li, Dehai; Yin, Wen-Bing; Chooi, Yit-Heng; Li, Yong-Quan

    2015-01-01

    The small molecule biosynthetic potential of most filamentous fungi remains largely unexplored and represents an attractive source for new compound discovery. Genome sequencing of Calcarisporium arbuscula, a mushroom endophytic fungus, revealed 68 core genes that are involved in natural products biosynthesis. This is in sharp contrast to predominant production of the ATPase inhibitors aurovertin B (1) and D (2). Inactivation of a histone H3 deacetylase HdaA led to pleiotropic activation and overexpression of more than 75% of the biosynthetic genes. Sampling of the overproduced compounds led to isolation of ten compounds of which four contain new structures, including the cyclic peptides arbumycin (3) and arbumelin (4); the diterpenoid arbuscullic acid A (11); and a meroterpenoid arbuscullic acid B (12). Such epigenetic modification therefore provides a rapid and global approach to mine the chemical diversity of endophytic fungi. PMID:26013262

  16. Discovery of Highly Sweet Compounds from Natural Sources

    NASA Astrophysics Data System (ADS)

    Kinghorn, A. Douglas; Kennelly, Edward J.

    1995-08-01

    Sucrose, the most widely used sweetener globally, is of plant origin. In addition, a number of other plant constituents are employed as dietary sucrose substitutes in one or more countries, including the diterpenoid, stevioside, the triterpenoid, glycyrrhizin, and the protein, thaumatin. Accordingly, there has been much interest in discovering further examples of potently sweet compounds of natural origin, for potential use in foods, beverages, and medicines. Approximately 75 plant-derived compounds are presently known, mainly representative of the flavonoid, proanthocyandin, protein, steroidal saponin, and terpenoid chemotypes. In our program directed towards the elucidation of further highly sweet molecules from plants, candidate sweet-tasting plants for laboratory investigation are obtained from ethnobotanical observations in the field or in the existing literature. Examples of novel sweet-tasting compounds obtained so far are the sesquiterpenoids, hernandulcin and 4beta-hydroxyhemandulcin; the triterpenoids, abrusosides A-D; a semi-synthetic dihydroflavonol based on the naturally occurring substance, dihydroquercetin 3-acetate; and the proanthocyanidin, selligueain A. Natural product sweeteners may be of potential commercial use per se, and can be used for synthetic modification to produce improved sweeteners, and can also be of value scientifically to aid in the better understanding of structure-sweetness relationships.

  17. Natural organic compounds as tracers for biomass combustion in aerosols

    SciTech Connect

    Simoneit, B.R.T. |; Abas, M.R. bin |; Cass, G.R. |; Rogge, W.F. |; Mazurek, M.A.; Standley, L.J.; Hildemann, L.M.

    1995-08-01

    Biomass combustion is an important primary source of carbonaceous particles in the global atmosphere. Although various molecular markers have already been proposed for this process, additional specific organic tracers need to be characterized. The injection of natural product organic tracers to smoke occurs primarily by direct volatilization/steam stripping and by thermal alteration based on combustion temperature. The degree of alteration increases as the burn temperature rises and the moisture content of the fuel decreases. Although the molecular composition of organic matter in smoke particles is highly variable, the molecular structures of the tracers are generally source specific. The homologous compound series and biomarkers present in smoke particles are derived directly from plant wax, gum and resin by volatilization and secondarily from pyrolysis of biopolymers, wax, gum and resin. The complexity of the organic components of smoke aerosol is illustrated with examples from controlled burns of temperate and tropical biomass fuels. Burning of biomass from temperate regions (i.e., conifers) yields characteristic tracers from diterpenoids as well as phenolics and other oxygenated species, which are recognizable in urban airsheds. The major organic components of smoke particles from tropical biomass are straight-chain, aliphatic and oxygenated compounds and triterpenoids. The precursor-to-product approach of organic geochemistry can be applied successfully to provide tracers for studying smoke plume chemistry and dispersion.

  18. Temporal naturalism

    NASA Astrophysics Data System (ADS)

    Smolin, Lee

    2015-11-01

    Two people may claim both to be naturalists, but have divergent conceptions of basic elements of the natural world which lead them to mean different things when they talk about laws of nature, or states, or the role of mathematics in physics. These disagreements do not much affect the ordinary practice of science which is about small subsystems of the universe, described or explained against a background, idealized to be fixed. But these issues become crucial when we consider including the whole universe within our system, for then there is no fixed background to reference observables to. I argue here that the key issue responsible for divergent versions of naturalism and divergent approaches to cosmology is the conception of time. One version, which I call temporal naturalism, holds that time, in the sense of the succession of present moments, is real, and that laws of nature evolve in that time. This is contrasted with timeless naturalism, which holds that laws are immutable and the present moment and its passage are illusions. I argue that temporal naturalism is empirically more adequate than the alternatives, because it offers testable explanations for puzzles its rivals cannot address, and is likely a better basis for solving major puzzles that presently face cosmology and physics. This essay also addresses the problem of qualia and experience within naturalism and argues that only temporal naturalism can make a place for qualia as intrinsic qualities of matter.

  19. Natural Beauty

    ERIC Educational Resources Information Center

    Coy, Mary

    2006-01-01

    In this article, the author describes how her art class students were able to create, in just four class periods, clay relief plaques depicting nature. A lesson on texture speeds up the completion of such a project. Seeing that clay is a natural material with its own unique texture, it seemed fitting that the final product should depict a variety…

  20. Nature Detectives

    ERIC Educational Resources Information Center

    Harr, Natalie; Lee, Richard E.; Jr.

    2010-01-01

    Richard Louv's "Last Child in the Woods" (2008) added to a growing consensus to get children outside and experiencing nature. Using ideas from place-based education, the authors present a simple year-long project that brings science, nature, and other curriculum standards to life right in your school yard. With a focus on journaling, this project…

  1. Matematica Natural.

    ERIC Educational Resources Information Center

    Lozano, Patricia; Medearis, Linda

    Matematica Natural (Natural Mathematics) is a mathematics curriculum for young children based on the assumption that they learn mathematics through concrete, real life, relevant experiences and that educational differences rather than cultural differences influence math achievement. The curriculum uses hands-on materials and activities to teach…

  2. Natural Gas

    NASA Astrophysics Data System (ADS)

    Maddox, Robert N.; Moshfeghian, Mahmood; Ldol, James D.; Johannes, Arland H.

    Natural gas is a naturally occurring mixture of simple hydrocarbons and nonhydrocarbons that exists as a gas at ordinary pressures and temperatures. In the raw state, as produced from the earth, natural gas consists principally of methane (CH4) and ethane (C2H4), with fractional amounts of propane (C3H8), butane (C4H10), and other hydrocarbons, pentane (C5H12) and heavier. Occasionally, small traces of light aromatic hydrocarbons such as benzene and toluene may also be present.

  3. Inside Nature

    NASA Astrophysics Data System (ADS)

    Taroni, Andrea

    2015-03-01

    Since its launch in 1869, Nature has seen its mission as two-fold: facilitating the prompt communication of the most important scientific developments to the relevant research communities, while at the same time fostering a greater appreciation of these great works of science amongst the wider public. Although the publishing landscape for scientific research is currently undergoing a period of rapid change, these core principles remain largely unchanged. In this talk, I will endeavour to explain how Nature editors - in particular those based at Nature Physics- apply these principles in practice, and so determine which few of the many excellent research submissions that we receive make it through to publication.

  4. The Nature of Natural Languages.

    ERIC Educational Resources Information Center

    Pierce, Joe E.

    A variety of types of evidence are examined to help determine the true nature of "deep structure" and what, if any, implications this has for linguistic theory as well as culture theory generally. The evidence accumulated over the past century on the nature of phonetic and phonemic systems is briefly discussed, and the following areas of analysis…

  5. Triptolide, a diterpenoid triepoxide, induces antitumor proliferation via activation of c-Jun NH{sub 2}-terminal kinase 1 by decreasing phosphatidylinositol 3-kinase activity in human tumor cells

    SciTech Connect

    Miyata, Yoshiki; Sato, Takashi . E-mail: satotak@ps.toyaku.ac.jp; Ito, Akira

    2005-11-04

    Triptolide, a diterpenoid triepoxide extracted from the Chinese herb Tripterygium wilfordii Hook f., exerts antitumorigenic actions against several tumor cells, but the intracellular target signal molecule(s) for this antitumorigenesis activity of triptolide remains to be identified. In the present study, we demonstrated that triptolide, in a dose-dependent manner, inhibited the proliferation of human fibrosarcoma HT-1080, human squamous carcinoma SAS, and human uterine cervical carcinoma SKG-II cells. In addition, triptolide was found to decrease phosphatidylinositol 3-kinase (PI3K) activity. A PI3K inhibitor, LY-294002, mimicked the triptolide-induced antiproliferative activity in HT-1080, SAS, and SKG-II cells. There was no change in the activity of Akt or protein kinase C (PKC), both of which are downstream effectors in the PI3K pathway. Furthermore, the phosphorylation of Ras, Raf, and mitogen-activated protein/extracellular signal-regulated kinase 1/2 was not modified in HT-1080 cells treated with triptolide. However, the phosphorylation of c-Jun NH{sub 2}-terminal kinase 1 (JNK1) was found to increase in both triptolide- and LY-294002-treated cells. Furthermore, the triptolide-induced inhibition of HT-1080 cell proliferation was not observed by JNK1 siRNA-treatment. These results provide novel evidence that PI3K is a crucial target molecule in the antitumorigenic action of triptolide. They further suggest a possible triptolide-induced inhibitory signal for tumor cell proliferation that is initiated by the decrease in PI3K activity, which in turn leads to the augmentation of JNK1 phosphorylation via the Akt and/or PKC-independent pathway(s). Moreover, it is likely that the activation of JNK1 is required for the triptolide-induced inhibition of tumor proliferation.

  6. Cloning, molecular characterization and functional analysis of 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase (HDR) gene for diterpenoid tanshinone biosynthesis in Salvia miltiorrhiza Bge. f. alba.

    PubMed

    Hao, Gangping; Shi, Renjiu; Tao, Ru; Fang, Qian; Jiang, Xingyu; Ji, Haiwei; Feng, Lei; Huang, Luqi

    2013-09-01

    The enzyme 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase (HDR) is a terminal-acting enzyme in the plastid MEP pathway, which produce isoprenoid precursors. The full-length cDNA of HDR, designated SmHDR1 (Genbank Accession No. JX516088), was isolated for the first time from Salvia miltiorrhiza Bge. f. alba. SmHDR1 contains a 1389-bp open reading frame encoding 463 amino acids. The deduced SmHDR1 protein, which shows high identity to HDRs of other plant species, is predicted to possess a chloroplast transit peptide at the N-terminus and four conserved cysteine residues. Transcription pattern analysis revealed that SmHDR1 has high levels of transcription in leaves and low levels of transcription in roots and stems. The expression of SmHDR1 was induced by 0.1 mM methyl-jasmonate (MeJA) and salicylic acid (SA), but not by 0.1 mM abscisic acid (ABA), in the hairy roots of S. miltiorrhiza Bge. f. alba. Complementation of SmHDR1 in the Escherichia coli HDR mutant MG1655 ara < > ispH demonstrated the function of this enzyme. A functional color assay in E. coli showed that SmHDR1 accelerates the biosynthesis of β-carotene, indicating that SmHDR1 encodes a functional protein. Overexpression of SmHDR1 enhanced the production of tanshinones in cultured hairy roots of S. miltiorrhiza Bge. f. alba. These results indicate that SmHDR1 is a novel and important enzyme involved in the biosynthesis of diterpenoid tanshinones in S. miltiorrhiza Bge. f. alba. PMID:23770591

  7. Evident and latent plasticity across the rice diterpene synthase family with potential implications for the evolution of diterpenoid metabolism in the cereals

    PubMed Central

    Morrone, Dana; Hillwig, Matthew L.; Mead, Matthew E.; Lowry, Luke; Fulton, D. Bruce; Peters, Reuben J.

    2013-01-01

    SYNOPSIS The evolution of natural products biosynthetic pathways can be envisioned to occur via a number of mechanisms. Here we provide evidence that latent plasticity plays a role in such metabolic evolution. In particular, rice (Oryza sativa) produces both ent- and syn-copalyl diphosphate (CPP), which are substrates for downstream diterpene synthases. Here we report that several members of this enzymatic family exhibit dual reactivity with some pairing of ent-, syn-, or normal CPP stereochemistry. Evident plasticity was observed, as a previously reported ent-sandaracopimaradiene synthase also converts syn-CPP to syn-labda-8(17),12E,14-triene, which can be found in planta. Notably, normal CPP is not naturally found in rice. Thus, the presence of diterpene synthases that react with this non-native metabolite reveals latent enzymatic/metabolic plasticity, providing biochemical capacity for utilization of such a novel substrate (i.e., normal CPP) that may arise during evolution, the implications of which are discussed. PMID:21323642

  8. Evident and latent plasticity across the rice diterpene synthase family with potential implications for the evolution of diterpenoid metabolism in the cereals.

    PubMed

    Morrone, Dana; Hillwig, Matthew L; Mead, Matthew E; Lowry, Luke; Fulton, D Bruce; Peters, Reuben J

    2011-05-01

    The evolution of natural product biosynthetic pathways can be envisioned to occur via a number of mechanisms. In the present study we provide evidence that latent plasticity plays a role in such metabolic evolution. In particular, rice (Oryza sativa) produces both ent- and syn-CPP (copalyl diphosphate), which are substrates for downstream diterpene synthases. In the present paper we report that several members of this enzymatic family exhibit dual reactivity with some pairing of ent-, syn- or normal CPP stereochemistry. Evident plasticity was observed, as a previously reported ent-sandaracopimaradiene synthase also converts syn-CPP into syn-labda-8(17),12E,14-triene, which can be found in planta. Notably, normal CPP is not naturally found in rice. Thus the presence of diterpene synthases that react with this non-native metabolite reveals latent enzymatic/metabolic plasticity, providing biochemical capacity for utilization of such a novel substrate (i.e. normal CPP) which may arise during evolution, the implications of which are discussed. PMID:21323642

  9. Natural restoration

    SciTech Connect

    Kamlet, K.S.

    1993-02-01

    After a company pays millions of dollars to clean up contaminated site, its liability may not be over. It may have to spend tens of millions more to restore damaged natural resources under an oft-overlooked Superfund program. Examples of liability are cited in this report from the Exxon Valdez oil spill and a pcb leak which contaminated a harbor.

  10. Natural disasters.

    PubMed

    Cullen, J M

    1980-09-01

    This presentation covers the various types of natural disasters which are faced by investigators throughout the world. Each geophysical substance is discussed, including earth, air and water, and secondary effects including fire. Additionally, four myths associated with disasters are reviewed. PMID:7234811

  11. Nature Watch

    ERIC Educational Resources Information Center

    Sterling, Donna R.

    2010-01-01

    Children are naturally curious about the world in which they live. To focus this sense of wonder, have your students investigate their local habitat as it changes over the year. This multiseason study will build connections and add relevance to the habitats that children learn about. This series of activities for grades 4-6 explores the changing…

  12. Uranium, natural

    Integrated Risk Information System (IRIS)

    Uranium , natural ; CASRN 7440 - 61 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogeni

  13. Nature's Palette

    ERIC Educational Resources Information Center

    McBride, Brooke B.; Brewer, Carol A.

    2010-01-01

    Flower petals, acorn hats, exoskeletons of beetles, and lichens are just a few of the objects students may find in a surprising array of vivid colors. These tiny examples from nature's palette can be discovered in a school yard, a park, or even along the edges of a paved sidewalk...it simply takes careful observation! This article describes a…

  14. Natural thermodynamics

    NASA Astrophysics Data System (ADS)

    Annila, Arto

    2016-02-01

    The principle of increasing entropy is derived from statistical physics of open systems assuming that quanta of actions, as undividable basic build blocks, embody everything. According to this tenet, all systems evolve from one state to another either by acquiring quanta from their surroundings or by discarding quanta to the surroundings in order to attain energetic balance in least time. These natural processes result in ubiquitous scale-free patterns: skewed distributions that accumulate in a sigmoid manner and hence span log-log scales mostly as straight lines. Moreover, the equation for least-time motions reveals that evolution is by nature a non-deterministic process. Although the obtained insight in thermodynamics from the notion of quanta in motion yields nothing new, it accentuates that contemporary comprehension is impaired when modeling evolution as a computable process by imposing conservation of energy and thereby ignoring that quantum of actions are the carriers of energy from the system to its surroundings.

  15. Natural antioxidants.

    PubMed

    Berson, Diane S

    2008-07-01

    The constant exposure of the skin to oxidative stress results in damage to cellular DNA and cell membrane lipids and proteins. To combat this problem, the skin contains a number of antioxidants that protect against oxidative injury. However, these cutaneous antioxidants can be depleted by sun exposure and environmental insults, resulting in an overload of oxidation products. Thus, topical antioxidants that replenish the antioxidant capacity of the skin have the potential to prevent oxidative damage. A number of natural antioxidant ingredients also have anti-inflammatory properties, and can be used in the treatment of oxidative damage such as photoaging and perhaps even skin cancer. This article summarizes the active components, pharmacologic properties, and clinical effectiveness of a number of natural antioxidant ingredients including soy, feverfew, mushroom extracts, teas, Coffea arabica (CoffeeBerry), Pinus pinaster (Pycnogenol), and Polypodium leucotomos. Recent clinical trials suggest that these compounds have promising efficacy in the topical treatment of oxidative stress-induced dermatoses. PMID:18681153

  16. Natural Hazards

    NASA Astrophysics Data System (ADS)

    Bryant, Edward

    2005-02-01

    This updated new edition presents a comprehensive, inter-disciplinary analysis of the complete range of natural hazards. Edward Bryant describes and explains how hazards occur, examines prediction methods, considers recent and historical hazard events and explores the social impact of such disasters. Supported by over 180 maps, diagrams and photographs, this standard text is an invaluable guide for students and professionals in the field. First Edition Hb (1991): 0-521-37295-X First Edition Pb (1991): 0-521-37889-3

  17. Natural Strain

    NASA Technical Reports Server (NTRS)

    Freed, Alan D.

    1997-01-01

    Logarithmic strain is the preferred measure of strain used by materials scientists, who typically refer to it as the "true strain." It was Nadai who gave it the name "natural strain," which seems more appropriate. This strain measure was proposed by Ludwik for the one-dimensional extension of a rod with length l. It was defined via the integral of dl/l to which Ludwik gave the name "effective specific strain." Today, it is after Hencky, who extended Ludwik's measure to three-dimensional analysis by defining logarithmic strains for the three principal directions.

  18. Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation.

    PubMed

    Yu, Zu-Yin; Xiao, He; Wang, Li-Mei; Shen, Xing; Jing, Yu; Wang, Lin; Sun, Wen-Feng; Zhang, Yan-Feng; Cui, Yu; Shan, Ya-Jun; Zhou, Wen-Bing; Xing, Shuang; Xiong, Guo-Lin; Liu, Xiao-Lan; Dong, Bo; Feng, Jian-Nan; Wang, Li-Sheng; Luo, Qing-Liang; Zhao, Qin-Shi; Cong, Yu-Wen

    2016-05-01

    All-trans retinoic acid (ATRA)-based cell differentiation therapy has been successful in treating acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia (AML). However, other subtypes of AML display resistance to ATRA-based treatment. In this study, we screened natural, plant-derived vibsane-type diterpenoids for their ability to induce differentiation of myeloid leukemia cells, discovering that vibsanin A potently induced differentiation of AML cell lines and primary blasts. The differentiation-inducing activity of vibsanin A was mediated through direct interaction with and activation of protein kinase C (PKC). Consistent with these findings, pharmacological blockade of PKC activity suppressed vibsanin A-induced differentiation. Mechanistically, vibsanin A-mediated activation of PKC led to induction of the ERK pathway and decreased c-Myc expression. In mouse xenograft models of AML, vibsanin A administration prolonged host survival and inhibited PKC-mediated inflammatory responses correlated with promotion of skin tumors in mice. Collectively, our results offer a preclinical proof of concept for vibsanin A as a myeloid differentiation-inducing compound, with potential application as an antileukemic agent. Cancer Res; 76(9); 2698-709. ©2016 AACR. PMID:26984756

  19. Theoretical and experimental study of aparisthman: A natural product with anti-ulcer activity

    NASA Astrophysics Data System (ADS)

    Brasil, D. S. B.; Moreira, R. Y. O.; Müller, A. H.; Alves, C. N.

    Aparisthman is a furan diterpenoid with a clerodane skeleton isolated from Aparisthmium cordatum (Juss.) Bail. (Euphorbiaceae). This natural product presents significant anti-ulcer activity to the level of cimetidine (Tagamet®), a compound used for the treatment of ulcers provoked by stress. The structure of X-ray diffraction of the aparisthman was compared with theoretical calculations and the results showed that the theory is in accordance with the experimental data. The infrared (IR) and nuclear magnetic resonance (NMR) spectra also were obtained and compared with theoretical calculations. The B3LYP theory level, with the 6-31G(d,p) basis set, leads the value to the IR absorption close to the value experimentally observed. NMR theoretical obtained with HF/6-311+G(2d,p) shows little deviation of experimental results. Calculations of molecular electrostatic potential and stabilization energies suggest that the protonation of aparisthman will be able to occur on carbonyl oxygen atom (O4).

  20. Natural products and altered derivatives as tracers for biomass combustion in aerosols

    SciTech Connect

    Simoneit, B.R.T.; Radzi bin Abas, M.; Cass, G.R.

    1995-12-01

    Biomass combustion is an important primary source of carbonaceous particles in the global atmosphere. Various molecular markers have been proposed for this process but additional specific tracers are needed. The injection of natural product organic compounds into smoke occurs primarily by direct volatilization/steam stripping and by pyrolysis. Although the composition of organic matter in smoke particles is highly variable, the molecular structures of the tracers are generally source specific. Homologous compounds and biomarkers present in smoke are derived directly from plant wax, gum and resin by volatilization and secondarily from pyrolysis of biopolymers (e.g., lignin, cutin, suberin), wax, gum and resin. The component complexity is illustrated with examples from controlled bums of temperate and tropical biomass fuels. Conifer smoke contains characteristic tracers from diterpenoids as well as phenolics and other oxygenated species. These are recognizable in urban airsheds. The major organic components of smoke from tropical biomass are straight-chain, aliphatic and oxygenated compounds and triterpenoids. Several compounds are potential key indicators for combustion of such biomass. The precursor to product approach of organic geochemistry can be applied successfully to provide molecular tracers for studying smoke plume chemistry and dispersion.

  1. Natural Strain

    NASA Technical Reports Server (NTRS)

    Freed, Alan D.

    1995-01-01

    The purpose of this paper is to present a consistent and thorough development of the strain and strain-rate measures affiliated with Hencky. Natural measures for strain and strain-rate, as I refer to them, are first expressed in terms of of the fundamental body-metric tensors of Lodge. These strain and strain-rate measures are mixed tensor fields. They are mapped from the body to space in both the Eulerian and Lagrangian configurations, and then transformed from general to Cartesian fields. There they are compared with the various strain and strain-rate measures found in the literature. A simple Cartesian description for Hencky strain-rate in the Lagrangian state is obtained.

  2. Abietane diterpenoids from Caryopteris incana (Thunb.) Miq.

    PubMed

    Zhao, Sen-Miao; Chou, Gui-Xin; Yang, Qing-Shan; Wang, Wei; Zhou, Jian-Li

    2016-04-14

    Twelve new diterpenes, caryopincaolide A-L (1-4, 11-12, 16-19, 27-28), together with twenty-eight known diterpenes, have been isolated from the whole plant of Caryopteris incana (Thunb.) Miq. Their structures were elucidated on the basis of 1D and 2D NMR, IR, X-ray crystal diffraction and mass spectroscopic data, as well as ECD calculations. All compounds were tested for in vitro dipeptidyl peptidase IV (DPP-IV) inhibitory activity, with compounds 3, 4, 28, 29, and 40 exhibiting DPP-IV inhibitory effects with IC50 values ranging from 54.2 to 228.9 μM. Compounds 1, 3 and 4 also showed potent activity toward the inhibition of the growth of human cancer cells and 1 can induce apoptosis in Hey and A-549 cells. PMID:26952788

  3. Cytotoxic macrocyclic diterpenoid esters from Euphorbia cornigera.

    PubMed

    Baloch, Imam Bakhsh; Baloch, Musa Kaleem; Saqib, Qazi Najam

    2006-07-01

    Root extract of Euphorbia cornigera Boiss. (Euphorbiaceae) was separated into seven (compound 1-7) isolates through multiple Craig's distributions and preparative HPLC. The structures and relative configuration of theses compounds were established via spectral analyses as 7,8,12- O-triacetyl-3- O-(2-methylbutanoyl)-ingol (1), 3,8,12- O-triacetyl-7- O-(2-methylbutanoyl = -ingol (2), 3,7,12- O-triacetyl-8- O-(2-methylbutanoyl)-ingol (3), 3,7,8- O-triacetyl-12- O-(2-methylbutanoyl)-ingol (4), 7,12- O-diacetyl-3- O-(2-methylbutanoyl)-8- O-methylingol (5), 3,12- O-diacetyl-7- O-(2-methylbutanoyl)-8- O-methylingol (6) and 3,7- O-diacetyl-12- O-(2-methylbutanoyl)-8- O-methylingol (7). All these compounds, except for 2, are novel metabolites and have not been reported earlier. It has further been demonstrated that all the compounds (1 - 7) are cytotoxic. PMID:16881017

  4. Supramolecular design of biocompatible nanocontainers based on amphiphilic derivatives of a natural compound isosteviol.

    PubMed

    Gabdrakhmanov, Dinar R; Voronin, Mikhail A; Zakharova, Lucia Ya; Konovalov, Alexander I; Khaybullin, Ravil N; Strobykina, Irina Yu; Kataev, Vladimir E; Faizullin, Dzhigangir A; Gogoleva, Natalia E; Konnova, Tatiana A; Salnikov, Vadim V; Zuev, Yuriy F

    2013-10-21

    Two diterpenoid surfactants with ammonium head groups and bromide (S1) or tosylate (S2) counterions have been synthesized. Exploration of these biomimetic species made it possible to demonstrate that even minor structural changes beyond their chemical nature may dramatically affect their solution behavior. While their aggregation thresholds differ inconsiderably, morphological behavior and affinity to lipid bilayer are strongly dependent on the counterion nature. Compound S2 demonstrates properties of typical surfactants and forms small micelle-like aggregates above critical micelle concentration. For surfactant S1, two critical concentrations and two types of aggregates occur. Structural transitions have been observed between small micelles and aggregates with higher aggregation numbers and hydrodynamic diameter of ca. 150 nm. Unlike S2, surfactant S1 is shown to integrate with liposomes based on dipalmitoylphosphatidylcholine, resulting in a decrease of the temperature of the main phase transition. Both surfactants demonstrate an effective complexation capacity toward oligonucleotide (ONu), which is supported by recharging the surfactant-ONu complexes and the ethidium bromide exclusion at a low N/P ratio. Meanwhile, a very weak complexation of plasmid DNA with the surfactants has been revealed in the gel electrophoresis experiment. The DNA transfer to bacterial cells mediated by the surfactant S1 is shown to depend on the protocol used. In the case of the electroporation, the inhibition of the cell transformation occurs in the presence of the surfactant, while upon the chemical treatment no surfactant effect has been observed. The variability in the morphology, the biocompatibility, the nanoscale dimension and the high binding capacity toward the DNA decamer make it possible to nominate the designed surfactants as promising carriers for biosubstrates or as a helper surfactant for the mixed liposome-surfactant nanocontainers. PMID:23985972

  5. Natural products for treatment of bone erosive diseases: The effects and mechanisms on inhibiting osteoclastogenesis and bone resorption.

    PubMed

    An, Jing; Hao, Dingjun; Zhang, Qian; Chen, Bo; Zhang, Rui; Wang, Yi; Yang, Hao

    2016-07-01

    Excessive bone resorption plays a central role on the development of bone erosive diseases, including osteoporosis, rheumatoid arthritis, and periodontitis. Osteoclasts, bone-resorbing multinucleated cells, are differentiated from hemopoietic progenitors of the monocyte/macrophage lineage. Regulation of osteoclast differentiation is considered an effective therapeutic target to the treatment of pathological bone loss. Natural plant-derived products, with potential therapeutic and preventive activities against bone-lytic diseases, have received increasing attention in recent years because of their whole regulative effects and specific pharmacological activities, which are more suitable for long-term use than chemically synthesized medicines. In this review, we summarized the detailed research progress on the active compounds derived from medical plants with potential anti-resorptive effects and their molecular mechanisms on inhibiting osteoclast formation and function. The active ingredients derived from natural plants that are efficacious in suppressing osteoclastogenesis and bone resorption include flavonoids, terpenoids (sesquiterpenoids, diterpenoids, triterpenoids), glycosides, lignans, coumarins, alkaloids, polyphenols, limonoids, quinones and others (steroid, oxoxishhone, fatty acid). Studies have shown that above natural products exert the inhibitory effects via regulating many factors involved in the process of osteoclast differentiation and bone resorption, including the essential cytokines (RANKL, M-CSF), transcription factors (NFATc1, c-Fos), signaling pathways (NF-κB, MAPKs, Src/PI3K/Akt, the calcium ion signaling), osteoclast-specific genes (TRAP, CTSK, MMP-9, integrin β3, OSCAR, DC-STAMP, Atp6v0d2) and local factors (ROS, LPS, NO). The development of osteoclast-targeting natural products is of great value for the prevention or treatment of bone diseases and for bone regenerative medicine. PMID:27131574

  6. Two new natural products from Croton kongensis Gagnep.

    PubMed

    Sun, Lin; Meng, Zhaoqing; Li, Zhaoliang; Yang, Biao; Wang, Zhenzhong; Ding, Gang; Xiao, Wei

    2014-01-01

    A new diterpenoid, 14β-hydroxy-3-oxo-ent-kaur-16-ene (1), and a new nor-lignan, 8S-( - )-8-(4-hydroxy-3-methoxybenzoyl)-dihydrofuran-8(8'H)-one (4), along with five known compounds were isolated from the twigs and leaves of Croton kongensis Gagnep. Their isolations were clarified and structures were elucidated by the extensive spectroscopic analyses, especially 2D NMR experiments. PMID:24684202

  7. Natural gas as a natural' solution

    SciTech Connect

    McCormick, W.T. Jr.

    1991-05-15

    This article promotes natural gas use as a means to cut US dependence on imported oil by some 28 percent over the next ten years, while improving energy efficiency and solving a portion of the global warming and acid rain problems. Topics of discussion include fuel substitution, the Clean Air Act, natural gas capacity and distribution, and natural gas exploration.

  8. Natural Language Processing.

    ERIC Educational Resources Information Center

    Chowdhury, Gobinda G.

    2003-01-01

    Discusses issues related to natural language processing, including theoretical developments; natural language understanding; tools and techniques; natural language text processing systems; abstracting; information extraction; information retrieval; interfaces; software; Internet, Web, and digital library applications; machine translation for…

  9. The nature and ethics of natural experiments.

    PubMed

    Dawson, Angus; Sim, Julius

    2015-10-01

    Natural experiments are an important methodology often used to answer research questions that would, otherwise, be impossible to address, or employed because of ethical concerns about the use of randomisation to interventions that carry known risks. The UK Medical Research Council (MRC) recently produced an extremely useful document discussing the nature and significance of natural experiments within medical and public health research. In this paper, however, we suggest that the MRC document's definition of the term 'natural experiment' is insufficiently precise. In response, we offer a taxonomy of different types of natural experiments and related methods, and explore the ethical implications of these different types. We argue that while the ethical issues that may arise within natural experiments in relation to risks of harm or informed consent may differ from those within the randomised controlled trial, they are not thereby less pressing. The implications of the argument are explored and recommendations made for those involved in research governance. PMID:26187285

  10. Immune up regulatory response of a non-caloric natural sweetener, stevioside.

    PubMed

    Sehar, Irum; Kaul, Anpurna; Bani, Sarang; Pal, Harish Chandra; Saxena, Ajit Kumar

    2008-05-28

    Immunomodulation is a process, which alters the immune system of an organism by interfering with its functions. This interference results in either immunostimulation or immunosuppression. An immunomodulator is any substance that helps to regulate the immune system. This "regulation" is a normalization process, so that an immunomodulator helps to optimise immune response. Immunomodulators are becoming very popular in the worldwide natural health industry as these do not tend to boost immunity, but to normalize it. Keeping this in view, major efforts have to be directed to modulate the immune responses, to permit effective treatment of various ailments associated with immune system and thus the development of a safe and effective immunomodulator for clinical us. Leaves of Stevia rebaudiana are a source of several sweet glycosides of steviol. The major glycoside, stevioside, diterpenoid glycoside--is used in oriental countries as a food sweetener. Its medical use is also reported as a heart tonic. Besides, it is used against obesity, hypertension, and stomach burn and to lower uric acid levels. Here in this study, stevioside was tested for its immunomodulatory activity on different parameters of the immune system at three different doses (6.25, 12.5 and 25 mg/kg p.o.) on normal as well as cyclophosphamide treated mice. Stevioside was found effective in increasing phagocytic activity, haemagglutination antibody titre and delayed type hypersensitivity. In parallel, stevioside substantially increase proliferation in the LPS and Con A stimulated B and T cells, respectively. Present study, therefore, reveals that the drug holds promise as immunomodulating agent, which acts by stimulating both humoral as well as cellular immunity and phagocytic function. PMID:18405890

  11. Naturally occurring chemical carcinogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Natural products are chemicals found in nature which have unique pharmacological effects. Humans are exposed to many of these bioactive naturally occurring chemicals via the air breathed, the water drunk and the food eaten. Exposure also occurs in clinical settings. Naturally occurring chemicals ...

  12. The Nature of Natural Hazards Communication (Invited)

    NASA Astrophysics Data System (ADS)

    Kontar, Y. Y.

    2013-12-01

    Some of the many issues of interest to natural hazards professionals include the analysis of proactive approaches to the governance of risk from natural hazards and approaches to broaden the scope of public policies related to the management of risks from natural hazards, as well as including emergency and environmental management, community development and spatial planning related to natural hazards. During the talk we will present results of scientific review, analysis and synthesis, which emphasize same new trends in communication of the natural hazards theories and practices within an up-to-the-minute context of new environmental and climate change issues, new technologies, and a new focus on resiliency. The presentation is divided into five sections that focus on natural hazards communication in terms of education, risk management, public discourse, engaging the public, theoretical perspectives, and new media. It includes results of case studies and best practices. It delves into natural hazards communication theories, including diffusion, argumentation, and constructivism, to name a few. The presentation will provide information about: (1) A manual of natural hazards communication for scientists, policymakers, and media; (2) An up-to-the-minute context of environmental hazards, new technologies & political landscape; (3) A work by natural hazards scientists for geoscientists working with social scientists and communication principles; (4) A work underpinned by key natural hazards communication theories and interspersed with pragmatic solutions; (5) A work that crosses traditional natural hazards boundaries: international, interdisciplinary, theoretical/applied. We will further explore how spatial planning can contribute to risk governance by influencing the occupation of natural hazard-prone areas, and review the central role of emergency management in risk policy. The goal of this presentation is to contribute to the augmentation of the conceptual framework

  13. Crystal structure and theoretical study of IR and 1H and 13C NMR spectra of cordatin, a natural product with antiulcerogenic activity

    NASA Astrophysics Data System (ADS)

    Brasil, Davi S. B.; Alves, Cláudio N.; Guilhon, Giselle M. S. P.; Muller, Adolfo H.; Secco, Ricardo De S.; Peris, Gabriel; Llusar, Rosa

    Cordatin is a furan diterpenoid with a clerodane skeleton isolated from Croton palanostigma Klotzsch (Euphorbiaceae). This natural product shows significant antiulcerogenic activity, similar to cimetidine (Tagamet®), a compound used for the treatment of peptic ulcers. The crystal structure of cordatin was obtained by X-ray diffraction and its geometrical parameters were compared with theoretical calculations at the B3LYP theory level. The IR and NMR (1H and 13C chemical shifts and coupling constants) spectra were obtained and compared with the theoretical calculations. The B3LYP theory level, with the 6-31G(d,p) and 6-311G(d,p) basis set, provided IR absorption values close to the experimental data. Moreover, theoretical NMR parameters obtained in both gas phase and chloroform solvent at the B3PW91/DGDZVP, B3LYP/6-311+G(2d,p), and B3PW91/6-311+G(2d,p) levels showed good correlations with the experimental results.

  14. Demonstrating Natural Selection

    ERIC Educational Resources Information Center

    Hinds, David S.; Amundson, John C.

    1975-01-01

    Describes laboratory exercises with chickens selecting their food from dyed and natural corn kernels as a method of demonstrating natural selection. The procedure is based on the fact that organisms that blend into their surroundings escape predation. (BR)

  15. Natural Gas Monthly

    EIA Publications

    2016-01-01

    Highlights activities, events, and analyses associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer related activities and underground storage data are also reported.

  16. Colours From Nature

    ERIC Educational Resources Information Center

    Simon, Wilma

    1974-01-01

    In reference to American Indian ceremonial art, the importance of using natural pigments is emphasized, since the superior color values of natural dyes better reflect religious and philosophical depth and meaning. (JC)

  17. Nature's Nature: Ideas of Nature in Curricula for Environmental Education

    ERIC Educational Resources Information Center

    St Maurice, Henry

    2006-01-01

    Two contrasting sets of ideas about nature in environmental education are described. An analytical framework is developed from inter-disciplinary histories of ideas and used in evaluating a specific curriculum. In conclusion, some general implications are suggested for curricula in environmental education. [This article was reprinted from…

  18. Natural gas annual 1994

    SciTech Connect

    1995-11-17

    The Natural Gas Annual provides information on the supply and disposition of natural gas to a wide audience including industry, consumers, Federal and State agencies, and educational institutions. The 1994 data are presented in a sequence that follows natural gas (including supplemental supplies) from its production to its end use. This is followed by tables summarizing natural gas supply and disposition from 1990 to 1994 for each Census Division and each State. Annual historical data are shown at the national level.

  19. Natural gas annual 1995

    SciTech Connect

    1996-11-01

    The Natural Gas Annual provides information on the supply and disposition of natural gas to a wide audience including industry, consumers, Federal and State agencies, and educational institutions. The 1995 data are presented in a sequence that follows natural gas (including supplemental supplies) from its production to its end use. This is followed by tables summarizing natural gas supply and disposition from 1991 to 1995 for each Census Division and each State. Annual historical data are shown at the national level.

  20. Learning in Nature

    ERIC Educational Resources Information Center

    Brody, Michael

    2005-01-01

    This paper traces the evolution of a theory of learning in nature in order to explain how people learn in natural settings. The intellectual roots of the theory in informal learning, cognition, affective development, experiential and meaningful learning are described and the synthesis into a comprehensive theory of learning in nature are…

  1. Nature in the City.

    ERIC Educational Resources Information Center

    Ferbert, Mary Lou

    1981-01-01

    Describes a science program developed by the Cleveland Museum of Natural History, "Nature in the City," in which students and teachers learn together about the natural community surrounding their school. Includes program's rationale, list of "adventures," and methods. Discusses strategies of Sherlock Holmes'"adventure" focusing on animal tracks…

  2. Capturing nature's diversity.

    PubMed

    Pascolutti, Mauro; Campitelli, Marc; Nguyen, Bao; Pham, Ngoc; Gorse, Alain-Dominique; Quinn, Ronald J

    2015-01-01

    Natural products are universally recognized to contribute valuable chemical diversity to the design of molecular screening libraries. The analysis undertaken in this work, provides a foundation for the generation of fragment screening libraries that capture the diverse range of molecular recognition building blocks embedded within natural products. Physicochemical properties were used to select fragment-sized natural products from a database of known natural products (Dictionary of Natural Products). PCA analysis was used to illustrate the positioning of the fragment subset within the property space of the non-fragment sized natural products in the dataset. Structural diversity was analysed by three distinct methods: atom function analysis, using pharmacophore fingerprints, atom type analysis, using radial fingerprints, and scaffold analysis. Small pharmacophore triplets, representing the range of chemical features present in natural products that are capable of engaging in molecular interactions with small, contiguous areas of protein binding surfaces, were analysed. We demonstrate that fragment-sized natural products capture more than half of the small pharmacophore triplet diversity observed in non fragment-sized natural product datasets. Atom type analysis using radial fingerprints was represented by a self-organizing map. We examined the structural diversity of non-flat fragment-sized natural product scaffolds, rich in sp3 configured centres. From these results we demonstrate that 2-ring fragment-sized natural products effectively balance the opposing characteristics of minimal complexity and broad structural diversity when compared to the larger, more complex fragment-like natural products. These naturally-derived fragments could be used as the starting point for the generation of a highly diverse library with the scope for further medicinal chemistry elaboration due to their minimal structural complexity. This study highlights the possibility to capture a

  3. Capturing Nature's Diversity

    PubMed Central

    Pascolutti, Mauro; Campitelli, Marc; Nguyen, Bao; Pham, Ngoc; Gorse, Alain-Dominique; Quinn, Ronald J.

    2015-01-01

    Natural products are universally recognized to contribute valuable chemical diversity to the design of molecular screening libraries. The analysis undertaken in this work, provides a foundation for the generation of fragment screening libraries that capture the diverse range of molecular recognition building blocks embedded within natural products. Physicochemical properties were used to select fragment-sized natural products from a database of known natural products (Dictionary of Natural Products). PCA analysis was used to illustrate the positioning of the fragment subset within the property space of the non-fragment sized natural products in the dataset. Structural diversity was analysed by three distinct methods: atom function analysis, using pharmacophore fingerprints, atom type analysis, using radial fingerprints, and scaffold analysis. Small pharmacophore triplets, representing the range of chemical features present in natural products that are capable of engaging in molecular interactions with small, contiguous areas of protein binding surfaces, were analysed. We demonstrate that fragment-sized natural products capture more than half of the small pharmacophore triplet diversity observed in non fragment-sized natural product datasets. Atom type analysis using radial fingerprints was represented by a self-organizing map. We examined the structural diversity of non-flat fragment-sized natural product scaffolds, rich in sp3 configured centres. From these results we demonstrate that 2-ring fragment-sized natural products effectively balance the opposing characteristics of minimal complexity and broad structural diversity when compared to the larger, more complex fragment-like natural products. These naturally-derived fragments could be used as the starting point for the generation of a highly diverse library with the scope for further medicinal chemistry elaboration due to their minimal structural complexity. This study highlights the possibility to capture a

  4. Natural gas marketing II

    SciTech Connect

    Not Available

    1988-01-01

    This book covers all aspects of gas marketing, from the basic regulatory structure to the latest developments in negotiating agreements and locating markets. Topics include: Federal regulation of the gas industry; Fundamentals of gas marketing contracts; FERC actions encouraging competitive markets; Marketing conditions from the pipelines' perspective; State non-utility regulation of natural gas production, transportation, and marketing; Natural gas wellhead agreements and tariffs; Natural gas processing agreements; Effective management of producer's natural gas contracts; Producer-pipeline litigation; Natural gas purchasing from the perspective of industrial gas users; Gas marketing by co-owners: problems of disproportionate sales, gas balancing, and accounting to royalty owners; Alternatives and new directions in marketing.

  5. On nature and bioethics.

    PubMed

    Peterson, Paul Silas

    2010-01-01

    The account of nature and humanity's relationship to nature are of central importance for bioethics. The Scientific Revolution was a critical development in the history of this question and many contemporary accounts of nature find their beginnings here. While the innovative approach to nature going out of the seventeenth century was reliant upon accounts of nature from the early modern period, the Middle Ages, late-antiquity and antiquity, it also parted ways with some of the understandings of nature from these epochs. Here I analyze this development and suggests that some of the insights from older understandings of nature may be helpful for bioethics today, even if there can be no simple return to them. PMID:21644431

  6. Nature, Education, and the Natural Woman

    ERIC Educational Resources Information Center

    Miller, Peter J.

    1974-01-01

    An examination of 18th and 19th century naturalistic educational theory reveals that appeals to nature confirmed and strengthened contemporary attitudes and practices restricting woman's access to knowledge and her freedom to make decisions and to act. (Author/DW)

  7. Nature and health.

    PubMed

    Hartig, Terry; Mitchell, Richard; de Vries, Sjerp; Frumkin, Howard

    2014-01-01

    Urbanization, resource exploitation, and lifestyle changes have diminished possibilities for human contact with nature in urbanized societies. Concern about the loss has helped motivate research on the health benefits of contact with nature. Reviewing that research here, we focus on nature as represented by aspects of the physical environment relevant to planning, design, and policy measures that serve broad segments of urbanized societies. We discuss difficulties in defining "nature" and reasons for the current expansion of the research field, and we assess available reviews. We then consider research on pathways between nature and health involving air quality, physical activity, social cohesion, and stress reduction. Finally, we discuss methodological issues and priorities for future research. The extant research does describe an array of benefits of contact with nature, and evidence regarding some benefits is strong; however, some findings indicate caution is needed in applying beliefs about those benefits, and substantial gaps in knowledge remain. PMID:24387090

  8. Natural vacuum electronics

    NASA Technical Reports Server (NTRS)

    Leggett, Nickolaus

    1990-01-01

    The ambient natural vacuum of space is proposed as a basis for electron valves. Each valve is an electron controlling structure similiar to a vacuum tube that is operated without a vacuum sustaining envelope. The natural vacuum electron valves discussed offer a viable substitute for solid state devices. The natural vacuum valve is highly resistant to ionizing radiation, system generated electromagnetic pulse, current transients, and direct exposure to space conditions.

  9. Natural language watermarking

    NASA Astrophysics Data System (ADS)

    Topkara, Mercan; Taskiran, Cuneyt M.; Delp, Edward J., III

    2005-03-01

    In this paper we discuss natural language watermarking, which uses the structure of the sentence constituents in natural language text in order to insert a watermark. This approach is different from techniques, collectively referred to as "text watermarking," which embed information by modifying the appearance of text elements, such as lines, words, or characters. We provide a survey of the current state of the art in natural language watermarking and introduce terminology, techniques, and tools for text processing. We also examine the parallels and differences of the two watermarking domains and outline how techniques from the image watermarking domain may be applicable to the natural language watermarking domain.

  10. Natural products for treatment of osteoporosis: The effects and mechanisms on promoting osteoblast-mediated bone formation.

    PubMed

    An, Jing; Yang, Hao; Zhang, Qian; Liu, Cuicui; Zhao, Jingjing; Zhang, Lingling; Chen, Bo

    2016-02-15

    Osteoporosis is a systemic metabolic bone disease characterized by a reduction in bone mass, bone quality, and microarchitectural deterioration. An imbalance in bone remodeling that is caused by more osteoclast-mediated bone resorption than osteoblast-mediated bone formation results in such pathologic bone disorder. Traditional Chinese medicines (TCM) have long been used to prevent and treat osteoporosis and have received extensive attentions and researches at home and abroad, because they have fewer adverse reactions and are more suitable for long-term use compared with chemically synthesized medicines. Here, we put the emphasis on osteoblasts, summarized the detailed research progress on the active compounds derived from TCM with potential anti-osteoporosis effects and their molecular mechanisms on promoting osteoblast-mediated bone formation. It could be concluded that TCM with kidney-tonifying, spleen-tonifying, and stasis-removing effects all have the potential effects on treating osteoporosis. The active ingredients derived from TCM that possess effects on promoting osteoblasts proliferation and differentiation include flavonoids, glycosides, coumarins, terpenoids (sesquiterpenoids, monoterpenoids, diterpenoids), phenolic acids, phenols and others (tetrameric stilbene, anthraquinones, diarylheptanoids). And it was confirmed that the bone formation effect induced by the above natural products was regulated by the expressions of bone specific matrix proteins (ALP, BSP, OCN, OPN, COL I), transcription factor (Runx2, Cbfa1, Osx), signal pathways (MAPK, BMP), local factors (ROS, NO), OPG/RANKL system of osteoblasts and estrogen-like biological activities. All the studies provided theoretical basis for clinical application, as well as new drug research and development on treating osteoporosis. PMID:26796578

  11. Nature of Science Is...

    ERIC Educational Resources Information Center

    Lederman, Judith Sweeney; Lederman, Norman G.

    2005-01-01

    The phrase "nature of science" refers to the characteristics of scientific knowledge that necessarily result from the scientific investigations that scientists conduct to develop knowledge. Yet, these characteristics are assumed by many to be "difficult" to teach. Not so. Many important aspects of nature of science can be directly linked to…

  12. Natural Resources Bibliography.

    ERIC Educational Resources Information Center

    Hoadley, Irene Braden

    This bibliography presents a modern definition of the conceptual framework from which to view natural resources, and affords access to information which examines resources from the social scientists point of view. It presents five broad divisions of activity or variables which include (1) Natural and Human Resources, (2) Epistomological and…

  13. Nature's Advice Book

    ERIC Educational Resources Information Center

    Mahlin, Kathryn; Robertson, Amy

    2005-01-01

    What do can people learn from the world around them? Can a tree really teach something about life? Many times teachers provide students with facts about nature but fail to consider what one can learn from the natural world around them. After many months of exploring various ecosystems such as the prairie, rain forest, and desert, one of the…

  14. Natural Concepts in Pigeons

    ERIC Educational Resources Information Center

    Herrnstein, R. J.; And Others

    1976-01-01

    Pigeons learned discrimination rapidly and responded differentially to pictures seen for the first time. The essential feature of a natural discrimination--which is the ability to cope with natural ranges of variation--was approached and earlier experimental results were extended using other classes of stimuli. (Author/RK)

  15. Modeling Natural Selection

    ERIC Educational Resources Information Center

    Bogiages, Christopher A.; Lotter, Christine

    2011-01-01

    In their research, scientists generate, test, and modify scientific models. These models can be shared with others and demonstrate a scientist's understanding of how the natural world works. Similarly, students can generate and modify models to gain a better understanding of the content, process, and nature of science (Kenyon, Schwarz, and Hug…

  16. Natural short sleeper

    MedlinePlus

    ... Sleep - natural short sleeper Images Natural short sleeper Sleep patterns in the young and aged References Knutson KL, Van Cauter E, Rathouz PJ, et al. Trends in the prevalence of short sleepers in the USA: 1975-2006. Sleep. Update Date 12/2/2014 Updated by: Andrew ...

  17. Geopolitics of natural gas

    SciTech Connect

    Russell, J.

    1983-01-01

    This examines the role of gas in the world energy supply/demand. Special attention is paid to Western Europe, the Soviet Union, and the natural gas exporting countries. Forecasts of global energy demand until 2000 and data on Western Europe's proven natural gas reserves as per January 1982 are provided.

  18. Sketching in Nature

    ERIC Educational Resources Information Center

    Hobart, April

    2005-01-01

    Nature journaling is a useful skill for science students, independent of whether they also consider themselves artists. A pencil and sketchbook can be carried anywhere to record ecological information in many ways. A traditional page in a nature journal may consist of quick studies of plant and animal life sketched out as rudimentary line drawings…

  19. CONNECTICUT NATURAL DIVERSITY DATABASE

    EPA Science Inventory

    This is a statewide datalayer at 1:24,000 scale of general areas of concern with regards to state and federally listed Endangered, Threatened, and Special Concern species and significant natural communities. Locations of species and natural communities are based on data collecte...

  20. Nature Experience and Education

    ERIC Educational Resources Information Center

    Rathunde, Kevin

    2013-01-01

    Kevin Rathunde turns his research lens to the task of finding out the relevance of the natural world, its impact on adolescent motivation, and its positive sustaining of concentration and focus. He cites "disembodiment and denaturing" as needing to be countered by contact with nature, leading to higher creativity, less drudgery, and more…

  1. Birds. Nature Discovery I.

    ERIC Educational Resources Information Center

    Stone, Sally F.

    The birds of New England and their particular habitats are explored in this guide which is part of a series of Nature Discovery publications. The materials are designed to directly supplement the natural science curricula and to complement other subject areas including social studies, language arts, music, and art. The program is designed for…

  2. Natural Science Centers: Directory.

    ERIC Educational Resources Information Center

    Natural Science for Youth Foundation, Roswell, GA.

    A nature center is defined as an organized and permanent nonprofit institution which is essentially educational, scientific, and cultural in purpose with professional staff, and open to the public on some regular schedule. A nature center manages and interprets its lands, native plants and animals and facilities to promote an understanding of…

  3. Island Natural Science School.

    ERIC Educational Resources Information Center

    Toronto Board of Education (Ontario).

    Prepared for students in grade six attending the Island Natural Science School, Toronto, Ontario, Canada, this booklet offers information and suggests activities in the areas of ecology, conservation, natural resources, and outdoor recreation. Introductory material describes island lore, its formation and significant features, followed by units of…

  4. Nature Foil Reliefs

    ERIC Educational Resources Information Center

    Lane, Shaw J.

    2012-01-01

    Nature has always been a source of inspiration for artists across the centuries. Artists such as Leonardo da Vinci, Georgia O'Keeffe, Ansel Adams, and Andy Goldsworthy all drew inspiration for their work from nature. Seeds come from the dried pods, which when planted and cared for, bear fruit. In this article, the author describes how her…

  5. Introduction to Exploring Nature

    ERIC Educational Resources Information Center

    Early Childhood Today, 2006

    2006-01-01

    Children are fascinated with the world of nature. From the tiniest of seeds to the highest of birds, they wonder "Why?" "How?" and "What can I do with it?" This paper provides intriguing nature activities that provide a solid starting point for expanding children's thinking and learning. Through these activities, children will be building skills…

  6. Thermoacoustic natural gas liquefier

    SciTech Connect

    Swift, G.; Gardner, D.; Hayden, M.; Radebaugh, R.; Wollan, J.

    1996-07-01

    This is the final report of a two-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). This project sought to develop a natural-gas-powered natural-gas liquefier that has absolutely no moving parts and requires no electrical power. It should have high efficiency, remarkable reliability, and low cost. The thermoacoustic natural-gas liquefier (TANGL) is based on our recent invention of the first no-moving-parts cryogenic refrigerator. In short, our invention uses acoustic phenomena to produce refrigeration from heat, with no moving parts. The required apparatus comprises nothing more than heat exchangers and pipes, made of common materials, without exacting tolerances. Its initial experimental success in a small size lead us to propose a more ambitious application: large-energy liquefaction of natural gas, using combustion of natural gas as the energy source. TANGL was designed to be maintenance-free, inexpensive, portable, and environmentally benign.

  7. Living in cities, naturally.

    PubMed

    Hartig, Terry; Kahn, Peter H

    2016-05-20

    Natural features, settings, and processes in urban areas can help to reduce stress associated with urban life. In this and other ways, public health benefits from, street trees, green roofs, community gardens, parks and open spaces, and extensive connective pathways for walking and biking. Such urban design provisions can also yield ecological benefits, not only directly but also through the role they play in shaping attitudes toward the environment and environmental protection. Knowledge of the psychological benefits of nature experience supports efforts to better integrate nature into the architecture, infrastructure, and public spaces of urban areas. PMID:27199417

  8. Nature limits filarial transmission

    PubMed Central

    Chandra, Goutam

    2008-01-01

    Lymphatic filariasis, caused by Wuchereria bancrofti, Brugia malayi and B. timori is a public health problem of considerable magnitude of the tropics and subtropics. Presently 1.3 billion people are at risk of lymphatic filariasis (LF) infection and about 120 million people are affected in 83 countries. In this context it is worth mentioning that 'nature' itself limits filarial transmission to a great extent in a number of ways such as by reducing vector populations, parasitic load and many other bearings. Possibilities to utilize these bearings of natural control of filariasis should be searched and if manipulations on nature, like indiscriminate urbanization and deforestation, creating sites favourable for the breeding of filarial vectors and unsanitary conditions, water pollution with organic matters etc., are reduced below the threshold level, we will be highly benefited. Understandings of the factors related to natural phenomena of control of filariasis narrated in this article may help to adopt effective control strategies. PMID:18500974

  9. Optimizing Natural Fertility

    MedlinePlus

    ... can I do to improve my chances of conceiving naturally? Before attempting pregnancy, a woman should make ... should seek advice from a medical professional before conceiving (becoming pregnant). What are my chances of conceiving? ...

  10. Make a Nature Trail

    ERIC Educational Resources Information Center

    Johnson, Janice K.

    1973-01-01

    Discusses the planning, construction, use, and maintenance of a nature trail. Ideal for demonstrating interrelationships between plants and animals, conservation practices, wildlife management, plant succession, forestry, geologic features and other scientific phenomena. (JR)

  11. Modified natural neighbor interpolant

    NASA Astrophysics Data System (ADS)

    Traversoni, Leonardo

    1992-11-01

    Based on the idea of Natural Neighbor Interpolant presented by Sibson in 1980, this paper shows how combining it with the concept of Covering Spheres, new and more practical algorithms can be made as well as a more complete theory.

  12. Is image steganography natural?

    PubMed

    Martín, Alvaro; Sapiro, Guillermo; Seroussi, Gadiel

    2005-12-01

    Steganography is the art of secret communication. Its purpose is to hide the presence of information, using, for example, images as covers. We experimentally investigate if stego-images, bearing a secret message, are statistically "natural." For this purpose, we use recent results on the statistics of natural images and investigate the effect of some popular steganography techniques. We found that these fundamental statistics of natural images are, in fact, generally altered by the hidden "nonnatural" information. Frequently, the change is consistently biased in a given direction. However, for the class of natural images considered, the change generally falls within the intrinsic variability of the statistics, and, thus, does not allow for reliable detection, unless knowledge of the data hiding process is taken into account. In the latter case, significant levels of detection are demonstrated. PMID:16370457

  13. Web life: Ask Nature

    NASA Astrophysics Data System (ADS)

    2012-11-01

    Ask Nature is a site devoted to biomimicry, an interdisciplinary field in which practitioners study how animals and plants solve problems, and then use those solutions to develop better human technologies.

  14. Parallels with nature

    NASA Astrophysics Data System (ADS)

    2014-10-01

    Adam Nelson and Stuart Warriner, from the University of Leeds, talk with Nature Chemistry about their work to develop viable synthetic strategies for preparing new chemical structures in parallel with the identification of desirable biological activity.

  15. Tifft Farm Nature Preserve.

    ERIC Educational Resources Information Center

    Benjamin, Thomas B.; Gannon, David J.

    1980-01-01

    Described are the creation, development, activities, and programs of Tifft Farm, a 264-acre nature preserve and environmental education center in Buffalo, New York, constructed on a sanitary landfill. (BT)

  16. Natural gas monthly

    SciTech Connect

    1996-05-01

    This document highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Data presented include volume and price, production, consumption, underground storage, and interstate pipeline activities.

  17. Natural Gas Emergencies

    MedlinePlus

    ... by the Cass (ND) and Clay (MN) Emergency Planning Partnerships. Adapted with funding provided by Fargo Cass Public Health through the Cities Readiness Initiative (CRI) English – Natural Gas Emergencies - Last ...

  18. Nature's ups and downs

    NASA Astrophysics Data System (ADS)

    Rodgers, Peter

    2015-12-01

    When Norman Lockyer, an astronomer and science writer with a day job as a clerk at the War Office in London, approached the publishing house Macmillan and Company in 1869 with a proposal for a new weekly journal about science, few could have predicted the outcome. The journal in question was Nature, and given its influence over the past 146 years, it is hard to believe that Melinda Baldwin's Making Nature is the first full-length book to be written about it.

  19. Lesson "Balance in Nature

    NASA Astrophysics Data System (ADS)

    Chapanova, V.

    2012-04-01

    Lesson "Balance in Nature" This simulation game-lesson (Balance in Nature) gives an opportunity for the students to show creativity, work independently, and to create models and ideas. It creates future-oriented thought connected to their experience, allowing them to propose solutions for global problems and personal responsibility for their activities. The class is divided in two teams. Each team chooses questions. 1. Question: Pollution in the environment. 2. Question: Care for nature and climate. The teams work on the chosen tasks. They make drafts, notes and formulate their solutions on small pieces of paper, explaining the impact on nature and society. They express their points of view using many different opinions. This generates alternative thoughts and results in creative solutions. With the new knowledge and positive behaviour defined, everybody realizes that they can do something positive towards nature and climate problems and the importance of individuals for solving global problems is evident. Our main goal is to recover the ecological balance, and everybody explains his or her own well-grounded opinions. In this work process the students obtain knowledge, skills and more responsible behaviour. This process, based on his or her own experience, dialogue and teamwork, helps the participant's self-development. Making the model "human↔ nature" expresses how human activities impact the natural Earth and how these impacts in turn affect society. Taking personal responsibility, we can reduce global warming and help the Earth. By helping nature we help ourselves. Teacher: Veselina Boycheva-Chapanova " Saint Patriarch Evtimii" Scholl Str. "Ivan Vazov"-19 Plovdiv Bulgaria

  20. Natural Hazards, Second Edition

    NASA Astrophysics Data System (ADS)

    Rouhban, Badaoui

    Natural disaster loss is on the rise, and the vulnerability of the human and physical environment to the violent forces of nature is increasing. In many parts of the world, disasters caused by natural hazards such as earthquakes, floods, landslides, drought, wildfires, intense windstorms, tsunami, and volcanic eruptions have caused the loss of human lives, injury, homelessness, and the destruction of economic and social infrastructure. Over the last few years, there has been an increase in the occurrence, severity, and intensity of disasters, culminating with the devastating tsunami of 26 December 2004 in South East Asia.Natural hazards are often unexpected or uncontrollable natural events of varying magnitude. Understanding their mechanisms and assessing their distribution in time and space are necessary for refining risk mitigation measures. This second edition of Natural Hazards, (following a first edition published in 1991 by Cambridge University Press), written by Edward Bryant, associate dean of science at Wollongong University, Australia, grapples with this crucial issue, aspects of hazard prediction, and other issues. The book presents a comprehensive analysis of different categories of hazards of climatic and geological origin.

  1. Blackouts and natural risks

    NASA Astrophysics Data System (ADS)

    Danihelka, P.; Paldusová, E.; Dobeš, P.

    2009-04-01

    "Blackout" has become the common definition for the situation when electricity supply and demand are not balanced and security of supply fails. These failures have many impacts besides the lights going out, but this term is used commonly. Blackouts have drastic impacts for the society on whole and its citizens and some of them can influence big areas and last for long period, so the consequences are catastrophic. Even if at the European scale, the large extend blackouts are supposed to be exceptional, real frequency is relatively high, approximately once per two years. According to statistics, blackouts are often caused by natural causes, especially lightning. An example of lightning caused blackout is New York blackout 1977, leading to the stand-by of nuclear power plant Indian Point and with overall cost more than 300 mil. USD. There is a clear a distinction between those blackouts caused by nature and those that were caused by other faults. Usually, the nature-caused disturbances as Canada 1988, Sweden 2005 and France 1999, stay inside one country. However, their duration can extend to several weeks, and thus the costs of the interruptions and social impacts are high. Blackouts of only technologic and/or anthropogenic origin are frequently shorter, but may concern more end-users, when cascading from one country to another. Lightning is not the only natural event causing blackouts. Eighteen various case studies of blackout caused by natural events different then lightning were studied and following natural phenomenon found as a root causes: 1x forest fire, 1x snow calamity, 1x ice storm, 1x landslide, 1x high temperature, 1x geomagnetic storm, 2x earthquake, 2x inundation, 2x contact of line with trees, 6x storm (wind, hurricane…). We can conclude, that natural event are frequent cause of blackout of medium or large extend and this phenomena should be studied more in details. This contribution was supported by Ministry of Environment of the Czech Republic.

  2. Neuroimmunoregulation and natural immunity.

    PubMed

    Berczi, I; Chow, D A; Sabbadini, E R

    1998-09-01

    The development and function of the immune system is regulated by neuroendocrine factors. Immune function may be divided into adaptive and natural immunity. Adaptive immune responses are driven by specific determinants of the antigen (epitopes), require 5-10 d to fully develop, and show an accelerated or memory response after repeated exposure to the same antigen. Natural immunity may be divided into host defense mediated by non-immune factors (e.g., antimicrobial proteins, enzymes, mucus etc.) and polyspecific responses of the immune system. This polyspecific response relies on natural antibodies and on some other serum proteins (e.g., lipopolysaccharide-binding protein-LBP, C-reactive protein-CRP), and on surface receptors of macrophages, natural killer cells and B and T lymphocytes for activation. Highly conserved homologous (crossreactive) epitopes, or homotopes for short, are recognized by the natural immune system. Natural antibodies, LBP, and CRP are capable of activating the entire immune system after combination with the appropriate homotope. During febrile illness natural immune host defense is promptly elevated because of the rapid rise of natural antibodies, LBP, and CRP in the serum. This is known as the acute phase response (APR), which is initiated by a sudden rise of cytokines in the circulation, such as IL-1, IL-6, and TNF-alpha. The cytokines act on the brain, the neuroendocrine system, and on other tissues and organs, which leads to fever and profound hormonal and metabolic changes. The hypothalamus-pituitary adrenal axis is activated and serves as the primary regulator of immune and inflammatory reactions. Insulin, glucagon, and catecholeamine levels are also raised. Bone marrow activity and leukocyte function are high and the liver is converted to the rapid production of acute-phase proteins (APP). APP include LBP, CRP, fibrinogen, some complement components, enzyme inhibitors, and anti-inflammatory proteins, which may rise in the serum from

  3. Enhance Nature Exploration with Technology

    ERIC Educational Resources Information Center

    Holloway, Patricia; Mahan, Carol

    2012-01-01

    Kids and nature seem like a natural combination, but what was natural a generation ago is different today. Children are spending less time outdoors but continue to need nature for their physical, emotional, and mental development. This fact has led author Richard Louv to suggest that today's children are suffering from "nature-deficit disorder"…

  4. Nature/culture/seawater.

    PubMed

    Helmreich, Stefan

    2011-01-01

    Seawater has occupied an ambiguous place in anthropological categories of "nature" and "culture." Seawater as nature appears as potentiality of form and uncontainable flux; it moves faster than culture - with culture frequently figured through land-based metaphors - even as culture seeks to channel water's (nature's) flow. Seawater as culture manifests as a medium of pleasure, sustenance, travel, disaster. I argue that, although seawater's qualities in early anthropology were portrayed impressionistically, today technical, scientific descriptions of water's form prevail. For example, processes of globalization - which may also be called "oceanization" - are often described as "currents," "flows," and "circulations." Examining sea-set ethnography, maritime anthropologies, and contemporary social theory, I propose that seawater has operated as a “theory machine” for generating insights about human cultural organization. I develop this argument with ethnography from the Sargasso Sea and in the Sea Islands. I conclude with a critique of appeals to water's form in social theory. PMID:21560270

  5. Natural photonic crystals

    NASA Astrophysics Data System (ADS)

    Vigneron, Jean Pol; Simonis, Priscilla

    2012-10-01

    Photonic structures appeared in nature several hundred millions years ago. In the living world, color is used for communication and this important function strongly impacts the individual chances of survival as well as the chances to reproduce. This has a statistical influence on species populations. Therefore, because they are involved in evolution, natural color-generating structures are - from some point of view - highly optimized. In this short review, a survey is presented of the development of natural photonic crystal-type structures occurring in insects, spiders, birds, fishes and other marine animals, in plants and more, from the standpoint of light-waves propagation. One-, two-, and three-dimensional structures will be reviewed with selected examples.

  6. On natural inflation

    SciTech Connect

    Freese, Katherine; Kinney, William H.

    2004-10-15

    We reexamine the model of natural inflation, in which the inflaton potential is flat due to shift symmetries. The original version of the model, where the inflaton is a pseudo-Nambu-Goldstone boson with potential of the form V({phi})={lambda}{sup 4}[1{+-}cos({phi}/f)], is studied in light of recent data. We find that the model is alive and well. Successful inflation as well as data from the Wilkinson Microwave Anisotropy Probe require f>0.6m{sub Pl} (where m{sub Pl}=1.22x10{sup 19} GeV) and {lambda}{approx}m{sub GUT} (where m{sub GUT}{approx}10{sup 16} GeV), scales which can be accommodated in particle physics models. The detectability of tensor modes from natural inflation in upcoming microwave background experiments is discussed. We find that natural inflation predicts a tensor/scalar ratio within reach of future observations.

  7. Natural gas monthly

    SciTech Connect

    Not Available

    1982-11-01

    This report presents data on the supply and disposition of natural gas in the USA during July 1982, as well as data on production, storage, imports, exports, and consumption. Selected data are also presented on the activities of the major interstate pipeline companies. Volumes of natural gas in storage continue to run slightly ahead of year-ago levels, especially for interstate operators. Weighted average prices received for gas sold by major interstate pipeline companies during July of 19982 ranged from a low of $2.61 per thousand cubic feet (Mcf) for Kansas-Nebraska to a high of $7.09 per Mcf for Pacific Gas. These variations are attributable to the sources of supply available to the various pipeline companies and the market structures of each. September 1982 applications for determination of a maximum lawful price under the Natural Gas Policy Act (NGPA) increased slightly for new gas (Section 102) and decreased significantly for high-cost gas (Section 107) when compared to August. Natural gas ceiling prices prescribed by the NGPA continued to move upward through the application of prescribed monthly inflation adjustments. In the 3-year period from November 1979 through November 1982, the price ceiling for new gas, for example, increased from $2.314 to $3.249 per million (MM) Btu's. The highest ceiling price permitted under the NGPA is natural gas produced from tight formations set for November 1982 at $5.396 per MMBtu. Market natural gas production during September of 1982 was 1444 billion cubic feet (Bcf) compared to the September 1981 level of 1578 Bcf. Consumption during the same period also declined from 1266 Bcf to 1176 Bcf.

  8. Brontides: natural explosive noises.

    PubMed

    Gold, T; Soter, S

    1979-04-27

    Episodes of explosive noises of natural origin, or brontides, have been well documented, often in association with seismic activity and in a few cases as precursors to major earthquakes. Ground-to-air acoustic transmission from shallow earthquakes can account for many of these episodes, but not for all, and other causes, such as the sudden eruption of gas from high-pressure sources in the ground may at times have been responsible. Confusion with distant thunder or artillery at times of anomalous sound propagation complicates the analysis, and more recently the greatly increased frequency of artificial explosive noises and sonic booms has tended to mask the recognition of natural brontides. PMID:17757998

  9. Natural Cycles, Gases

    NASA Technical Reports Server (NTRS)

    Douglass, Anne R.; Jackman, Charles H.; Rood, R. B.; Aikin, A. C.; Stolarski, R. S.; Mccormick, M. P.; Fahey, David W.

    1992-01-01

    The major gaseous components of the exhaust of stratospheric aircraft are expected to be the products of combustion (CO2 and H2O), odd nitrogen (NO, NO2 HNO3), and products indicating combustion inefficiencies (CO and total unburned hydrocarbons). The species distributions are produced by a balance of photochemical and transport processes. A necessary element in evaluating the impact of aircraft exhaust on the lower stratospheric composition is to place the aircraft emissions in perspective within the natural cycles of stratospheric species. Following are a description of mass transport in the lower stratosphere and a discussion of the natural behavior of the major gaseous components of the stratospheric aircraft exhaust.

  10. Natural language modeling

    SciTech Connect

    Sharp, J.K.

    1997-11-01

    This seminar describes a process and methodology that uses structured natural language to enable the construction of precise information requirements directly from users, experts, and managers. The main focus of this natural language approach is to create the precise information requirements and to do it in such a way that the business and technical experts are fully accountable for the results. These requirements can then be implemented using appropriate tools and technology. This requirement set is also a universal learning tool because it has all of the knowledge that is needed to understand a particular process (e.g., expense vouchers, project management, budget reviews, tax, laws, machine function).

  11. Measuring natural resource scarcity

    SciTech Connect

    Halvorsen, R.; Smith, T.R.

    1984-10-01

    Conclusions concerning trends in natural resource scarcity may depend critically on the choice of scarcity index. Unfortunately, the prevalence of vertical integration in natural resource industries has hindered the use of some otherwise desirable scarcity measures. In this paper duality theory is used to derive an econometric procedure for estimating one such measure, the shadow price of the resource in situ. Empirical results for the Canadian metal mining industry indicate that resource scarcity as measured by this shadow price has decreased substantially over time. 23 refernces, 1 table.

  12. Natural environment analysis

    NASA Technical Reports Server (NTRS)

    Frost, W.

    1985-01-01

    The influence of terrain features on wind loading of the space shuttle while on the launch pad, or during early liftoff, was investigated both qualitatively and quantitatively. The climatology and meteorology producing macroscale wind patterns and characteristics for the Vandenburg Air Force Base launch site are described. Field test data are analyzed, and the nature and characteristic of flow disturbances due to the various terrain features, both natural and man-made, are reviewed. The magnitude of these wind loads are estimated. Finally, effects of turbulence are discussed. It is concluded that the influence of complex terrain can create significant wind loading on the vehicle.

  13. SIGNIFICANT NATURAL HERITAGE AREAS (NC)

    EPA Science Inventory

    The North Carolina Department of Environment and Natural Resources, Division of Parks and Recreation, Natural Heritage Program in cooperation with the NC Center for Geographic Information & Analysis, developed the Significant Natural Heritage Areas digital data to determine the a...

  14. Natural Resources Education Notebook.

    ERIC Educational Resources Information Center

    Weber, Eldon C.

    This notebook was developed cooperatively by the United States Soil Conservation Service and Iowa State University to be used by teachers in providing instruction regarding certain aspects of natural resources. It includes four sections which provide: (1) an instructional plan about the conservation provisions of the 1985 Food Security Act; (2) an…

  15. Natural Gas Annual

    EIA Publications

    2015-01-01

    Provides information on the supply and disposition of natural gas in the United States. Production, transmission, storage, deliveries, and price data are published by state for the current year. Summary data are presented for each state for the previous 5 years.

  16. Drawing Closer to Nature

    ERIC Educational Resources Information Center

    London, Peter

    2004-01-01

    This article discusses how drawing closer to nature, two profoundly important and powerful qualities are experienced. First, the entire world takes on a new degree of poignancy, luminosity, preciousness, subtlety, mystery, and intimacy. Second, the author points out how we increasingly experience ourselves in just the same way: poignant, luminous,…

  17. Radioactivity: A Natural Phenomenon.

    ERIC Educational Resources Information Center

    Ronneau, C.

    1990-01-01

    Discussed is misinformation people have on the subject of radiation. The importance of comparing artificial source levels of radiation to natural levels is emphasized. Measurements of radioactivity, its consequences, and comparisons between the risks induced by radiation in the environment and from artificial sources are included. (KR)

  18. A Natural Hazards Workbook.

    ERIC Educational Resources Information Center

    Kohler, Fred

    This paper discusses the development of and provides examples of exercises from a student workbook for a college-level course about natural hazards. The course is offered once a year to undergraduates at Western Illinois University. Students are introduced to 10 hazards (eight meteorological plus earthquakes and volcanoes) through slides, movies,…

  19. Natural vegetation inventory

    NASA Technical Reports Server (NTRS)

    Schrumpf, B. J.

    1973-01-01

    Unique characteristics of ERTS imagery can be used to inventory natural vegetation. While satellite images can seldom be interpreted and identified directly in terms of vegetation types, such types can be inferred by interpretation of physical terrain features and through an understanding of the ecology of the vegetation.

  20. Geopolitics of natural gas

    SciTech Connect

    Not Available

    1983-11-09

    With almost as many vital economic interests as there were attendees, two natural gas international conferences were held in North America during September and October, to share experience and forecasts. On September 26, the Canadian Energy Research Institute (CERI) and the Calgary Chamber of Commerce sponsored the International Gas Markets Conference and drew 400 persons. And on October 5-6, at the University of Colorado at Boulder, USA, the International Research Center for Energy and Economic Development (ICEED) held its Tenth International Energy Conference on Economic and Political Issues of Natural Gas in International Trade, drawing some 200 experts. The latter seminar was preceded by a two-day seminar on Asian Energy Supplies and Requirements, which also featured natural gas in many of its presentations. To provide an overview of some of these pressing questions, Energy Detente reports on these two comprehensive seminars on natural gas. This issue also presents the fuel price/tax series and the principal industrial fuel prices for the Eastern Hemisphere for November 1983.

  1. A Biospheric Natural History.

    ERIC Educational Resources Information Center

    Thomashow, Mitchell

    2001-01-01

    A group of Maine birdwatchers recognizes that the presence or absence of migrating songbirds is related to complex biospheric patterns. For schoolchildren, community groups, and environmental scientists, such local natural history observations can be a pathway to perceiving and understanding global ecological change and then to developing…

  2. Picturing the Natural World

    ERIC Educational Resources Information Center

    Salia, Hannah

    2011-01-01

    How is the natural environment in the neighborhood representative of the larger biosphere in which people live? Studying the local birds and flora of the Pacific Northwest in the context of the local parks and ponds provided a rich opportunity for third-grade students at St. Thomas School in Medina, Washington, to explore and learn about…

  3. Picturing the Natural Environment

    ERIC Educational Resources Information Center

    Johnson, Phyllis Scott

    2011-01-01

    Around Scout Island Education Center, a site used by schools in Fresno County to explore the area's natural environment, a total of 200 cylinder-shaped concrete stools display tiles representing small mammals, flying insects, birds, wildflowers, and more. Twenty sets have been created by elementary, middle, and high-school art students as part of…

  4. Nature, Education and Things

    ERIC Educational Resources Information Center

    Rømer, Thomas Aastrup

    2013-01-01

    In this essay it is argued that the educational philosophy of John Dewey gains in depth and importance by being related to his philosophy of nature, his metaphysics. The result is that any experiental process is situated inside an event, an existence, a thing, and I try to interpret this "thing" as schools or major cultural events such…

  5. Demystifying Nature of Science

    ERIC Educational Resources Information Center

    Lederman, Judith; Bartels, Selina; Lederman, Norman; Gnanakkan, Dionysius

    2014-01-01

    With the emergence of the "Next Generation Science Standards" ("NGSS"; NGSS Lead States 2013), it is apparent that teaching and learning about nature of science (NOS) continues to be an important goal of science education for all K-12 students. With this emphasis on NOS, early childhood teachers are asking how to design…

  6. Nature in the City.

    ERIC Educational Resources Information Center

    Melber, Leah W.

    2000-01-01

    Presents three science activities targeted to help urban students learn about nature: (1) observing coloration patterns of pigeons; (2) measuring local rainfall and comparing it to other areas; and (3) conducting a biodiversity study by observing a patch of lawn. (YDS)

  7. The Nature of Atoms.

    ERIC Educational Resources Information Center

    Holden, Alan

    This monograph was written for the purpose of presenting physics to college students who are not preparing for careers in physics. It deals with the nature of atoms, and treats the following topics: (1) the atomic hypothesis, (2) the chemical elements, (3) models of an atom, (4) a particle in a one-dimensional well, (5) a particle in a central…

  8. Designing Nature's Way

    ERIC Educational Resources Information Center

    Fisher, Diane

    2005-01-01

    In the case of cars and other engineered objects, humans go about the design process in a very intentional way. They pretty much know what they are aiming for. The activity described in this article demonstrates how a computer can simulate biological evolution and the laws of natural selection. The article is divided into the following sections:…

  9. Saving Natural Areas.

    ERIC Educational Resources Information Center

    Buchinger, Maria

    This manual serves as a handbook for those involved in the art of land saving. The various topics in the booklet are dealt with in great detail since little has been published on the preservation of natural areas in international publications. Most of the document is derived from articles, books, and publications published by, or describing the…

  10. A Natural Integration

    ERIC Educational Resources Information Center

    Coskie, Tracy; Hornof, Michelle; Trudel, Heidi

    2007-01-01

    A five-week study taught students how to write a field guide that identified the plants in a small wooded area they passed through on their way to their school playground. By creating this authentic genre of science writing, students came to understand and care for the natural world in their immediate environment. They also developed important…

  11. The Natural Learning Process

    ERIC Educational Resources Information Center

    Criss, Ellen

    2008-01-01

    Teacher-educator and researcher Daniel L. Kohut suggests in "Musical Performance: Learning Theory and Pedagogy" that there are many problems that result from the way music teachers often teach. Most teachers focus on the process, not the goal. The Natural Learning Process that Kohut advocates is the same process that young children use when they…

  12. Reinventing Natural Selection

    ERIC Educational Resources Information Center

    Geraedts, Caspar L.; Boersma, Kerst Th.

    2006-01-01

    Although many research studies report students' Lamarckian misconceptions, only a few studies present learning and teaching strategies that focus on the successful development of the concept of natural selection. The learning and teaching strategy for upper secondary students (aged 15-16) presented in this study conducted in The Netherlands is…

  13. POTENTIAL NATURAL VEGETATION COVERAGE

    EPA Science Inventory

    "Potential natural vegetation is defined as the vegetation that would exist today if humans were removed from the scene and if the plant succession after their removal were telescoped into a single moment. The time compression eliminates the effects of future climatic fluc...

  14. Saving Natural Inflation

    NASA Astrophysics Data System (ADS)

    Croon, Djuna; Sanz, Verónica

    2015-02-01

    Slow-roll inflation requires the inflaton field to have an exceptionally flat potential, which combined with measurements of the scale of inflation demands some degree of fine-tuning. Alternatively, the flatness of the potential could be due to the inflaton's origin as a pseudo-Goldstone boson, as in Natural Inflation. Alas, consistency with Planck data places the original proposal of Natural Inflation in a tight spot, as it requires a trans-Planckian excursion of the inflaton. Although one can still tune the renormalizable potential to sub-Planckian values, higher order corrections from quantum gravity or sources of breaking of the Goldstone symmetry would ruin the predictivity of the model. In this paper we show how in more realistic models of Natural Inflation one could achieve inflation without a trans-Planckian excursion of the field. We show how a variant of Extra-natural inflation with bulk fermions can achieve the desired goal and discuss its four-dimensional duals. We also present a new type of four dimensional models inspired in Little Higgs and Composite Higgs models which can lead to sub-Planckian values of the inflaton field.

  15. Natural hazards science strategy

    USGS Publications Warehouse

    Holmes, Jr., Robert R.; Jones, Lucile M.; Eidenshink, Jeffery C.; Godt, Jonathan W.; Kirby, Stephen H.; Love, Jeffrey J.; Neal, Christina A.; Plant, Nathaniel G.; Plunkett, Michael L.; Weaver, Craig S.; Wein, Anne; Perry, Suzanne C.

    2012-01-01

    The mission of the U.S. Geological Survey (USGS) in natural hazards is to develop and apply hazard science to help protect the safety, security, and economic well-being of the Nation. The costs and consequences of natural hazards can be enormous, and each year more people and infrastructure are at risk. USGS scientific research - founded on detailed observations and improved understanding of the responsible physical processes - can help to understand and reduce natural hazard risks and to make and effectively communicate reliable statements about hazard characteristics, such as frequency, magnitude, extent, onset, consequences, and where possible, the time of future events. To accomplish its broad hazard mission, the USGS maintains an expert workforce of scientists and technicians in the earth sciences, hydrology, biology, geography, social and behavioral sciences, and other fields, and engages cooperatively with numerous agencies, research institutions, and organizations in the public and private sectors, across the Nation and around the world. The scientific expertise required to accomplish the USGS mission in natural hazards includes a wide range of disciplines that this report refers to, in aggregate, as hazard science. In October 2010, the Natural Hazards Science Strategy Planning Team (H-SSPT) was charged with developing a long-term (10-year) Science Strategy for the USGS mission in natural hazards. This report fulfills that charge, with a document hereinafter referred to as the Strategy, to provide scientific observations, analyses, and research that are critical for the Nation to become more resilient to natural hazards. Science provides the information that decisionmakers need to determine whether risk management activities are worthwhile. Moreover, as the agency with the perspective of geologic time, the USGS is uniquely positioned to extend the collective experience of society to prepare for events outside current memory. The USGS has critical statutory

  16. Natural products as photoprotection.

    PubMed

    Saewan, Nisakorn; Jimtaisong, Ampa

    2015-03-01

    The rise in solar ultraviolet radiation on the earth's surface has led to a depletion of stratospheric ozone over recent decades, thus accelerating the need to protect human skin against the harmful effects of UV radiation such as erythema, edema, hyperpigmentation, photoaging, and skin cancer. There are many different ways to protect skin against UV radiation's harmful effects. The most popular way to reduce the amount of UV radiation penetrating the skin is topical application of sunscreen products that contain UV absorbing or reflecting active molecules. Based on their protection mechanism, the active molecules in sunscreens are broadly divided into inorganic and organic agents. Inorganic sunscreens reflect and scatter UV and visible radiation, while organic sunscreens absorb UV radiation and then re-emit energy as heat or light. These synthetic molecules have limited concentration according to regulation concern. Several natural compounds with UV absorption property have been used to substitute for or to reduce the quantity of synthetic sunscreen agents. In addition to UV absorption property, most natural compounds were found to act as antioxidants, anti-inflammatory, and immunomodulatory agents, which provide further protection against the damaging effects of UV radiation exposure. Compounds derived from natural sources have gained considerable attention for use in sunscreen products and have bolstered the market trend toward natural cosmetics. This adds to the importance of there being a wide selection of active molecules in sunscreen formulations. This paper summarizes a number of natural products derived from propolis, plants, algae, and lichens that have shown potential photoprotection properties against UV radiation exposure-induced skin damage. PMID:25582033

  17. Why Is Nature Beneficial?: The Role of Connectedness to Nature

    ERIC Educational Resources Information Center

    Mayer, F. Stephan; Frants, Cynthia McPherson; Bruehlman-Senecal, Emma; Dolliver, Kyffin

    2009-01-01

    Three studies examine the effects of exposure to nature on positive affect and ability to reflect on a life problem. Participants spent 15 min walking in a natural setting (Studies 1, 2, & 3), an urban setting (Study 1), or watching videos of natural and urban settings (Studies 2 & 3). In all three studies, exposure to nature increased…

  18. Design, science and naturalism

    NASA Astrophysics Data System (ADS)

    Deming, David

    2008-09-01

    The Design Argument is the proposition that the presence of order in the universe is evidence for the existence of God. The Argument dates at least to the presocratic Greek philosophers, and is largely based on analogical reasoning. Following the appearance of Aquinas' Summa Theologica in the 13th century, the Christian Church in Europe embraced a Natural Theology based on observation and reason that allowed it to dominate the entire world of knowledge. Science in turn advanced itself by demonstrating that it could be of service to theology, the recognized queen of the sciences. During the heyday of British Natural Theology in the 17th and 18th centuries, the watchmaker, shipbuilder, and architect analogies were invoked reflexively by philosophers, theologians, and scientists. The Design Argument was not systematically and analytically criticized until David Hume wrote Dialogues on Natural Religion in the 1750s. After Darwin published Origin of Species in 1859, Design withered on the vine. But in recent years, the Argument has been resurrected under the appellation "intelligent design," and been the subject of political and legal controversy in the United States. Design advocates have argued that intelligent design can be formulated as a scientific hypothesis, that new scientific discoveries validate a design inference, and that naturalism must be removed as a methodological requirement in science. If science is defined by a model of concentric epistemological zonation, design cannot be construed as a scientific hypothesis because it is inconsistent with the core aspects of scientific methodology: naturalism, uniformity, induction, and efficient causation. An analytical examination of claims by design advocates finds no evidence of any type to support either scientific or philosophical claims that design can be unambiguously inferred from nature. The apparent irreducible complexity of biological mechanisms may be explained by exaptation or scaffolding. The argument

  19. Epidemics after Natural Disasters

    PubMed Central

    Gayer, Michelle; Connolly, Maire A.

    2007-01-01

    The relationship between natural disasters and communicable diseases is frequently misconstrued. The risk for outbreaks is often presumed to be very high in the chaos that follows natural disasters, a fear likely derived from a perceived association between dead bodies and epidemics. However, the risk factors for outbreaks after disasters are associated primarily with population displacement. The availability of safe water and sanitation facilities, the degree of crowding, the underlying health status of the population, and the availability of healthcare services all interact within the context of the local disease ecology to influence the risk for communicable diseases and death in the affected population. We outline the risk factors for outbreaks after a disaster, review the communicable diseases likely to be important, and establish priorities to address communicable diseases in disaster settings. PMID:17370508

  20. Responses to natural disasters

    NASA Astrophysics Data System (ADS)

    Maggs, William Ward

    Since 1964, natural disasters caused by earthquakes, volcanic eruptions, or extreme weather in the form of floods, droughts, or hurricanes, have been responsible for more than 2,756,000 deaths worldwide in nations other than the United States, the Soviet Union, and the Eastern European Bloc, according to figures tabulated by the Office of Foreign Disaster Assistance (OFDA) of the Agency for International Development (AID). Over 95% of these fatalities occurred in developing or third world countries. Damage resulting from these calamities has been severe but extremely difficult to estimate in monetary terms. In 1986, U.S. government and voluntary agencies spent $303 million on natural disaster assistance around the world, 79% of total world assistance. In 1985 the U.S. total was nearly $900 million, 48% of the $1.84 billion world total.

  1. Principles of Natural Photosynthesis.

    PubMed

    Krewald, Vera; Retegan, Marius; Pantazis, Dimitrios A

    2016-01-01

    Nature relies on a unique and intricate biochemical setup to achieve sunlight-driven water splitting. Combined experimental and computational efforts have produced significant insights into the structural and functional principles governing the operation of the water-oxidizing enzyme Photosystem II in general, and of the oxygen-evolving manganese-calcium cluster at its active site in particular. Here we review the most important aspects of biological water oxidation, emphasizing current knowledge on the organization of the enzyme, the geometric and electronic structure of the catalyst, and the role of calcium and chloride cofactors. The combination of recent experimental work on the identification of possible substrate sites with computational modeling have considerably limited the possible mechanistic pathways for the critical O-O bond formation step. Taken together, the key features and principles of natural photosynthesis may serve as inspiration for the design, development, and implementation of artificial systems. PMID:26099285

  2. Notes on natural inflation

    SciTech Connect

    Yonekura, Kazuya

    2014-10-01

    In the so-called natural inflation, an axion-like inflaton is assumed to have a cosine-type periodic potential. This is not the case in a very simple model in which the axion-like inflaton is coupled to an SU(N) (or other) pure Yang–Mills, at least in the large N limit as pointed out by Witten. It has a multi-valued potential, which is effectively quadratic, i.e., there is only a mass term in the large N limit. Thanks to this property, chaotic inflation can be realized more naturally with the decay constant of the axion-like inflaton less than the Planck scale. We demonstrate these points explicitly by using softly broken N=1 Super-Yang-Mills which allows us to treat finite N. This analysis also suggests that moderately large gauge groups such as E{sub 8} are good enough with a Planck scale decay constant.

  3. Reasons to Conserve Nature.

    PubMed

    Pearson, Richard G

    2016-05-01

    Is it sufficient to base arguments for conservation on the intrinsic value of nature, regardless of the services and economic benefits that biodiversity provides for humans? This question underlies much recent debate that has been at times acrimonious and has led to calls for a more inclusive approach to conservation. Yet melding different ideologies within a unified conceptual framework has proven difficult. Here I describe an approach that recognizes the importance of the level of biological organization and spatial extent in determining the strength of alternative arguments for why we should conserve nature. I argue that the framework helps reconcile contrasting viewpoints and brings clarity to when different conservation management approaches (for instance, regulation versus monetary valuation) are most appropriate. PMID:26936225

  4. Safer Liquid Natural Gas

    NASA Technical Reports Server (NTRS)

    1976-01-01

    After the disaster of Staten Island in 1973 where 40 people were killed repairing a liquid natural gas storage tank, the New York Fire Commissioner requested NASA's help in drawing up a comprehensive plan to cover the design, construction, and operation of liquid natural gas facilities. Two programs are underway. The first transfers comprehensive risk management techniques and procedures which take the form of an instruction document that includes determining liquid-gas risks through engineering analysis and tests, controlling these risks by setting up redundant fail safe techniques, and establishing criteria calling for decisions that eliminate or accept certain risks. The second program prepares a liquid gas safety manual (the first of its kind).

  5. Hybrid Natural Inflation

    NASA Astrophysics Data System (ADS)

    Ross, Graham G.; Germán, Gabriel; Vázquez, J. Alberto

    2016-05-01

    We construct two simple effective field theory versions of Hybrid Natural Inflation (HNI) that illustrate the range of its phenomenological implications. The resulting inflationary sector potential, V = Δ4(1 + acos( ϕ/f)), arises naturally, with the inflaton field a pseudo-Nambu-Goldstone boson. The end of inflation is triggered by a waterfall field and the conditions for this to happen are determined. Also of interest is the fact that the slow-roll parameter ɛ (and hence the tensor r) is a non-monotonic function of the field with a maximum where observables take universal values that determines the maximum possible tensor to scalar ratio r. In one of the models the inflationary scale can be as low as the electroweak scale. We explore in detail the associated HNI phenomenology, taking account of the constraints from Black Hole production, and perform a detailed fit to the Planck 2015 temperature and polarisation data.

  6. Naturally selecting solutions

    PubMed Central

    Manning, Timmy; Sleator, Roy D; Walsh, Paul

    2013-01-01

    For decades, computer scientists have looked to nature for biologically inspired solutions to computational problems; ranging from robotic control to scheduling optimization. Paradoxically, as we move deeper into the post-genomics era, the reverse is occurring, as biologists and bioinformaticians look to computational techniques, to solve a variety of biological problems. One of the most common biologically inspired techniques are genetic algorithms (GAs), which take the Darwinian concept of natural selection as the driving force behind systems for solving real world problems, including those in the bioinformatics domain. Herein, we provide an overview of genetic algorithms and survey some of the most recent applications of this approach to bioinformatics based problems. PMID:23222169

  7. Natural environment analysis

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Qualitative analyses (and quantitatively to the extend possible) of the influence of terrain features on wind loading of the space shuttle while on the launch pad, or during early liftoff, are presented. Initially, the climatology and meteorology producing macroscale wind patterns and characteristics fot he Vandenburg Air Force Base (VAFB) launch site are described. Also, limited field test data are analyzed, and then the nature and characteristic of flow disturbances due to the various terrain features, both natural and man-made, are then reviewed. Following this, the magnitude of these wind loads are estimated. Finally, effects of turbulence are discussed. The study concludes that the influence of complex terrain can create significant wind loading on the vehicle. Because of the limited information, it is not possible to quantify the magnitude of these loads.

  8. Notes on natural inflation

    NASA Astrophysics Data System (ADS)

    Yonekura, Kazuya

    2014-10-01

    In the so-called natural inflation, an axion-like inflaton is assumed to have a cosine-type periodic potential. This is not the case in a very simple model in which the axion-like inflaton is coupled to an SU(N) (or other) pure Yang-Mills, at least in the large N limit as pointed out by Witten. It has a multi-valued potential, which is effectively quadratic, i.e., there is only a mass term in the large N limit. Thanks to this property, chaotic inflation can be realized more naturally with the decay constant of the axion-like inflaton less than the Planck scale. We demonstrate these points explicitly by using softly broken Script N=1 Super-Yang-Mills which allows us to treat finite N. This analysis also suggests that moderately large gauge groups such as E8 are good enough with a Planck scale decay constant.

  9. Natural Products for Antithrombosis

    PubMed Central

    Chen, Cen; Zhang, Qian; Wang, Feng-Qin; Hu, Yuan-Jia; Xia, Zhi-Ning

    2015-01-01

    Thrombosis is considered to be closely related to several diseases such as atherosclerosis, ischemic heart disease and stroke, as well as rheumatoid arthritis, hyperuricemia, and various inflammatory conditions. More and more studies have been focused on understanding the mechanism of molecular and cellular basis of thrombus formation as well as preventing thrombosis for the treatment of thrombotic diseases. In reality, there is considerable interest in the role of natural products and their bioactive components in the prevention and treatment of thrombosis related disorders. This paper briefly describes the mechanisms of thrombus formation on three aspects, including coagulation system, platelet activation, and aggregation, and change of blood flow conditions. Furthermore, the natural products for antithrombosis by anticoagulation, antiplatelet aggregation, and fibrinolysis were summarized, respectively. PMID:26075003

  10. Natural Underwater Adhesives

    PubMed Central

    Stewart, Russell J.; Ransom, Todd C.; Hlady, Vladimir

    2011-01-01

    The general topic of this review is protein-based underwater adhesives produced by aquatic organisms. The focus is on mechanisms of interfacial adhesion to native surfaces and controlled underwater solidification of natural water-borne adhesives. Four genera that exemplify the broad range of function, general mechanistic features, and unique adaptations are discussed in detail: blue mussels, acorn barnacles, sandcastle worms, and freshwater caddisfly larva. Aquatic surfaces in nature are charged and in equilibrium with their environment, populated by an electrical double layer of ions as well as adsorbed natural polyelectrolytes and microbial biofilms. Surface adsorption of underwater bioadhesives likely occurs by exchange of surface bound ligands by amino acid sidechains, driven primarily by relative affinities and effective concentrations of polymeric functional groups. Most aquatic organisms exploit modified amino acid sidechains, in particular phosphorylated serines and hydroxylated tyrosines (dopa), with high-surface affinity that form coordinative surface complexes. After delivery to the surfaces as a fluid, permanent natural adhesives solidify to bear sustained loads. Mussel plaques are assembled in a manner superficially reminiscent of in vitro layer-by-layer strategies, with sequentially delivered layers associated through Fe(dopa)3 coordination bonds. The adhesives of sandcastle worms, caddisfly larva, and barnacles may be delivered in a form somewhat similar to in vitro complex coacervation. Marine adhesives are secreted, or excreted, into seawater that has a significantly higher pH and ionic strength than the internal environment. Empirical evidence suggests these environment triggers could provide minimalistic, fail-safe timing mechanisms to prevent premature solidification (insolubilization) of the glue within the secretory system, yet allow rapid solidification after secretion. Underwater bioadhesives are further strengthened by secondary covalent

  11. Nature's Greatest Puzzles

    SciTech Connect

    Quigg, Chris; /Fermilab

    2005-02-01

    It is a pleasure to be part of the SLAC Summer Institute again, not simply because it is one of the great traditions in our field, but because this is a moment of great promise for particle physics. I look forward to exploring many opportunities with you over the course of our two weeks together. My first task in talking about Nature's Greatest Puzzles, the title of this year's Summer Institute, is to deconstruct the premise a little bit.

  12. Geomorphology and natural hazards

    NASA Astrophysics Data System (ADS)

    Gares, Paul A.; Sherman, Douglas J.; Nordstrom, Karl F.

    1994-08-01

    Natural hazards research was initiated in the 1960's by Gilbert White and his students who promulgated a research paradigm that involved assessing risk from a natural event, identifying adjustments to cope with the hazard, determining people's perception of the event, defining the process by which people choose adjustments, and estimating the effects of public policy on the choice process. Studies of the physical system played an important role in early research, but criticismsof the paradigm resulted in a shift to a prominence of social science. Geomorphologists are working to fill gaps in knowledge of the physical aspects of individual hazards, but use of the information by social scientists will only occur if information is presented in a format that is useful to them. One format involves identifying the hazard according to seven physical parameters established by White and his colleagues: magnitude, frequency, duration, areal extent, speed of onset, spatial dispersion, and temporal spacing. Geomorphic hazards are regarded as related to landscape changes that affect human systems. The processes that produce the changes are rarely geomorphic in nature, but are better regarded as atmospheric or hydrologic. An examination of geomorphic hazards in four fields — soil erosion, mass movement, coastal erosion and fluvial erosion — demonstrates that advances in those fields may be evaluated in terms of the seven parameters. Geomorphologists have contributed to hazard research by focusing on the dynamics of the landforms. The prediction of occurence, the determination of spatial and temporal characteristics, the impact of physical characteristics on people's perception, and the impact of physical characteristics on adjustment formulation. Opportunities for geomorphologists to improve our understanding of geomorphic hazards include research into the characteristics of the events particularly with respect to predicting the occurence, and increased evaluation of the

  13. Natural family planning revisited.

    PubMed

    Al-Ateeg, Fahad A

    2004-03-01

    The article focuses on the role of natural family planning NFP as a component of reproductive health. It distinguishes NFP from the concept of fertility awareness method. Furthermore, the effectiveness of NFP as determined by previous studies is presented and the advantages and disadvantages of NFP are highlighted. Additionally, factors that influence the use of NFP methods are examined. Finally, delivery strategies and options for mainstreaming NFP into reproductive health services are identified and discussed. PMID:15048163

  14. Religion is natural.

    PubMed

    Bloom, Paul

    2007-01-01

    Despite its considerable intellectual interest and great social relevance, religion has been neglected by contemporary developmental psychologists. But in the last few years, there has been an emerging body of research exploring children's grasp of certain universal religious ideas. Some recent findings suggest that two foundational aspects of religious belief - belief in mind-body dualism, and belief in divine agents -- come naturally to young children. This research is briefly reviewed, and some future directions are discussed. PMID:17181713

  15. Harnessing natural ventilation benefits.

    PubMed

    O'Leary, John

    2013-04-01

    Making sure that a healthcare establishment has a good supply of clean fresh air is an important factor in keeping patients, staff, and visitors, free from the negative effects of CO2 and other contaminants. John O'Leary of Trend Controls, a major international supplier of building energy management solutions (BEMS), examines the growing use of natural ventilation, and the health, energy-saving, and financial benefits, that it offers. PMID:23678661

  16. Thermoacoustic natural gas liquefier

    SciTech Connect

    Swift, G.W.

    1997-05-01

    Cryenco and Los Alamos are collaborating to develop a natural-gas-powered natural-gas liquefier that will have no moving parts and require no electrical power. It will have useful efficiency, remarkable reliability, and low cost. The liquefaction of natural gas, which occurs at only 115 Kelvin at atmospheric pressure, has previously required rather sophisticated refrigeration machinery. The 1990 invention of the thermoacoustically driven orifice pulse-tube refrigerator (TA-DOPTR) provides cryogenic refrigeration with no moving parts for the first time. In short, this invention uses acoustic phenomena to produce refrigeration from heat. The required apparatus consists of nothing more than helium-filled heat exchangers and pipes, made of common materials, without exacting tolerances. In the Cryenco-Los Alamos collaboration, the authors are developing a version of this invention suitable for use in the natural-gas industry. The project is known as acoustic liquefier for short. The present program plans call for a two-phase development. Phase 1, with capacity of 500 gallon per day (i.e., approximately 40,000 scfd, requiring a refrigeration power of about 7 kW), is large enough to illuminate all the issues of large-scale acoustic liquefaction without undue cost, and to demonstrate the liquefaction of 60--70% of input gas, while burning 30--40%. Phase 2 will target versions of approximately 10{sup 6} scfd = 10,000 gallon per day capacity. In parallel with both, they continue fundamental research on the technology, directed toward increased efficiency, to build scientific foundations and a patent portfolio for future acoustic liquefiers.

  17. Microflyers: inspiration from nature

    NASA Astrophysics Data System (ADS)

    Sirohi, Jayant

    2013-04-01

    Over the past decade, there has been considerable interest in miniaturizing aircraft to create a class of extremely small, robotic vehicles with a gross mass on the order of tens of grams and a dimension on the order of tens of centimeters. These are collectively refered to as micro aerial vehicles (MAVs) or microflyers. Because the size of microflyers is on the same order as that of small birds and large insects, engineers are turning to nature for inspiration. Bioinspired concepts make use of structural or aerodynamic mechanisms that are observed in insects and birds, such as elastic energy storage and unsteady aerodynamics. Biomimetic concepts attempt to replicate the form and function of natural flyers, such as flapping-wing propulsion and external appearance. This paper reviews recent developments in the area of man-made microflyers. The design space for microflyers will be described, along with fundamental physical limits to miniaturization. Key aerodynamic phenomena at the scale of microflyers will be highlighted. Because the focus is on bioinspiration and biomimetics, scaled-down versions of conventional aircraft, such as fixed wing micro air vehicles and microhelicopters will not be addressed. A few representative bioinspired and biomimetic microflyer concepts developed by researchers will be described in detail. Finally, some of the sensing mechanisms used by natural flyers that are being implemented in man-made microflyers will be discussed.

  18. Future natural gas supplies

    NASA Astrophysics Data System (ADS)

    Despite recent optimism about the outlook for the future supply of domestic conventional natural gas, the Congressional Office of Technology Assessment (OTA) finds insufficient evidence to clearly justify either an optimistic or a pessimistic view. In a technical memorandum entitled “U.S. Natural Gas Availability: Conventional Gas Supply Through the Year 2000,” released recently by Rep. Philip R. Sharp (D-Ind,), chairman of the Subcommittee on Fossil and Synthetic Fuels of the Committee on Energy and Commerce, OTA concluded that substantial technical uncertainties prevented a reliable estimation of the likely natural gas production rates for later in this century. Even ignoring the potential for significant changes in gas prices and technology, OTA estimated that conventional gas production by the lower 48 states in the year 2000 could range from 9 to 19 trillion cubic feet (TCF) (0.25 to 0.53 trillion cubic meters), compared to 1982 production of 17.5 TCF. Similarly, production in the year 1990 could range from 13 to 20 TCF.

  19. Natural language generation

    NASA Astrophysics Data System (ADS)

    Maybury, Mark T.

    The goal of natural language generation is to replicate human writers or speakers: to generate fluent, grammatical, and coherent text or speech. Produced language, using both explicit and implicit means, must clearly and effectively express some intended message. This demands the use of a lexicon and a grammar together with mechanisms which exploit semantic, discourse and pragmatic knowledge to constrain production. Furthermore, special processors may be required to guide focus, extract presuppositions, and maintain coherency. As with interpretation, generation may require knowledge of the world, including information about the discourse participants as well as knowledge of the specific domain of discourse. All of these processes and knowledge sources must cooperate to produce well-written, unambiguous language. Natural language generation has received less attention than language interpretation due to the nature of language: it is important to interpret all the ways of expressing a message but we need to generate only one. Furthermore, the generative task can often be accomplished by canned text (e.g., error messages or user instructions). The advent of more sophisticated computer systems, however, has intensified the need to express multisentential English.

  20. NATURAL PRODUCTS FOR PEST MANAGEMENT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The topic of natural products as pesticides is reviewed, with a discussion of the advantages and disadvantages of adopting a natural product-based strategy for pesticide discovery. Current and past natural product and natural product-based herbicides, insecticides, fungicides, molluscicides, rodent...

  1. NATURAL RESOURCES ASSESSMENT

    SciTech Connect

    D.F. Fenster

    2000-12-11

    The purpose of this report is to summarize the scientific work that was performed to evaluate and assess the occurrence and economic potential of natural resources within the geologic setting of the Yucca Mountain area. The extent of the regional areas of investigation for each commodity differs and those areas are described in more detail in the major subsections of this report. Natural resource assessments have focused on an area defined as the ''conceptual controlled area'' because of the requirements contained in the U.S. Nuclear Regulatory Commission Regulation, 10 CFR Part 60, to define long-term boundaries for potential radionuclide releases. New requirements (proposed 10 CFR Part 63 [Dyer 1999]) have obviated the need for defining such an area. However, for the purposes of this report, the area being discussed, in most cases, is the previously defined ''conceptual controlled area'', now renamed the ''natural resources site study area'' for this report (shown on Figure 1). Resource potential can be difficult to assess because it is dependent upon many factors, including economics (demand, supply, cost), the potential discovery of new uses for resources, or the potential discovery of synthetics to replace natural resource use. The evaluations summarized are based on present-day use and economic potential of the resources. The objective of this report is to summarize the existing reports and information for the Yucca Mountain area on: (1) Metallic mineral and mined energy resources (such as gold, silver, etc., including uranium); (2) Industrial rocks and minerals (such as sand, gravel, building stone, etc.); (3) Hydrocarbons (including oil, natural gas, tar sands, oil shales, and coal); and (4) Geothermal resources. Groundwater is present at the Yucca Mountain site at depths ranging from 500 to 750 m (about 1,600 to 2,500 ft) below the ground surface. Groundwater resources are not discussed in this report, but are planned to be included in the hydrology

  2. Why Nature Chose Selenium.

    PubMed

    Reich, Hans J; Hondal, Robert J

    2016-04-15

    The authors were asked by the Editors of ACS Chemical Biology to write an article titled "Why Nature Chose Selenium" for the occasion of the upcoming bicentennial of the discovery of selenium by the Swedish chemist Jöns Jacob Berzelius in 1817 and styled after the famous work of Frank Westheimer on the biological chemistry of phosphate [Westheimer, F. H. (1987) Why Nature Chose Phosphates, Science 235, 1173-1178]. This work gives a history of the important discoveries of the biological processes that selenium participates in, and a point-by-point comparison of the chemistry of selenium with the atom it replaces in biology, sulfur. This analysis shows that redox chemistry is the largest chemical difference between the two chalcogens. This difference is very large for both one-electron and two-electron redox reactions. Much of this difference is due to the inability of selenium to form π bonds of all types. The outer valence electrons of selenium are also more loosely held than those of sulfur. As a result, selenium is a better nucleophile and will react with reactive oxygen species faster than sulfur, but the resulting lack of π-bond character in the Se-O bond means that the Se-oxide can be much more readily reduced in comparison to S-oxides. The combination of these properties means that replacement of sulfur with selenium in nature results in a selenium-containing biomolecule that resists permanent oxidation. Multiple examples of this gain of function behavior from the literature are discussed. PMID:26949981

  3. Nature, nurture and epigenetics.

    PubMed

    Crews, David; Gillette, Ross; Miller-Crews, Isaac; Gore, Andrea C; Skinner, Michael K

    2014-12-01

    Real life by definition combines heritability (e.g., the legacy of exposures) and experience (e.g. stress during sensitive or 'critical' periods), but how to study or even model this interaction has proven difficult. The hoary concept of evaluating traits according to nature versus nurture continues to persist despite repeated demonstrations that it retards, rather than advances, our understanding of biological processes. Behavioral genetics has proven the obvious, that genes influence behavior and, vice versa, that behavior influences genes. The concept of Genes X Environment (G X E) and its modern variants was viewed as an improvement on nature-nurture but has proven that, except in rare instances, it is not possible to fractionate phenotypes into these constituent elements. The entanglement inherent in terms such as nature-nurture or G X E is a Gordian knot that cannot be dissected or even split. Given that the world today is not what it was less than a century ago, yet the arbitrator (differential survival and reproduction) has stayed constant, de novo principles and practices are needed to better predict what the future holds. Put simply, the transformation that is now occurring within and between individuals as a product of global endocrine disruption is quite independent of what has been regarded as evolution by selection. This new perspective should focus on how epigenetic modifications might revise approaches to understand how the phenotype and, in particular its components, is shaped. In this review we summarize the literature in this developing area, focusing on our research on the fungicide vinclozolin. PMID:25102229

  4. Nature Inspired Surface Coatings

    NASA Astrophysics Data System (ADS)

    Rubner, Michael

    2011-04-01

    Materials Scientists more and more are looking to nature for clues on how to create highly functional surface coatings with exceptional properties. The fog harvesting capabilities of the Namib Desert beetle, the beautiful iridescent colors of the hummingbird, and the super water repellant abilities of the Lotus leaf are but a few examples of the amazing properties developed over many years in the natural world. Nature also makes extensive use of the pH-dependent behavior of weak functional groups such as carboxylic acid and amine functional groups. This presentation will explore synthetic mimics to the nano- and microstructures responsible for these fascinating properties. For example, we have demonstrated a pH-induced porosity transition that can be used to create porous films with pore sizes that are tunable from the nanometer scale to the multiple micron scale. The pores of these films, either nano- or micropores, can be reversibly opened and closed by changes in solution pH. The ability to engineer pH-gated porosity transitions in heterostructured thin films has led to the demonstration of broadband anti-reflection coatings that mimic the anti-reflection properties of the moth eye and pH-tunable Bragg reflectors with a structure and function similar to that found in hummingbird wings and the Longhorn beetle. In addition, the highly textured honeycomb-like surfaces created by the formation of micron-scale pores are ideally suited for the creation of superhydrophobic surfaces that mimic the behavior of the self-cleaning lotus leaf. The development of synthetic "backbacks" on immune system cells that may one day ferry drugs to disease sites will also be discussed.

  5. World Natural Gas Model

    Energy Science and Technology Software Center (ESTSC)

    1994-12-01

    RAMSGAS, the Research and Development Analysis Modeling System World Natural Gas Model, was developed to support planning of unconventional gaseoues fuels research and development. The model is a scenario analysis tool that can simulate the penetration of unconventional gas into world markets for oil and gas. Given a set of parameter values, the model estimates the natural gas supply and demand for the world for the period from 1980 to 2030. RAMSGAS is based onmore » a supply/demand framwork and also accounts for the non-renewable nature of gas resources. The model has three fundamental components: a demand module, a wellhead production cost module, and a supply/demand interface module. The demand for gas is a product of total demand for oil and gas in each of 9 demand regions and the gas share. Demand for oil and gas is forecast from the base year of 1980 through 2030 for each demand region, based on energy growth rates and price-induced conservation. For each of 11 conventional and 19 unconventional gas supply regions, wellhead production costs are calculated. To these are added transportation and distribution costs estimates associated with moving gas from the supply region to each of the demand regions and any economic rents. Based on a weighted average of these costs and the world price of oil, fuel shares for gas and oil are computed for each demand region. The gas demand is the gas fuel share multiplied by the total demand for oil plus gas. This demand is then met from the available supply regions in inverse proportion to the cost of gas from each region. The user has almost complete control over the cost estimates for each unconventional gas source in each year and thus can compare contributions from unconventional resources under different cost/price/demand scenarios.« less

  6. Marine natural products.

    PubMed

    Blunt, John W; Copp, Brent R; Keyzers, Robert A; Munro, Murray H G; Prinsep, Michèle R

    2016-03-01

    This review covers the literature published in 2014 for marine natural products (MNPs), with 1116 citations (753 for the period January to December 2014) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1378 in 456 papers for 2014), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included. PMID:26837534

  7. Marine natural products.

    PubMed

    Blunt, John W; Copp, Brent R; Keyzers, Robert A; Munro, Murray H G; Prinsep, Michèle R

    2014-01-17

    This review covers the literature published in 2012 for marine natural products, with 1035 citations (673 for the period January to December 2012) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1241 for 2012), together with the relevant biological activities, source organisms and country of origin. Biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included. PMID:24389707

  8. Marine natural products.

    PubMed

    Blunt, John W; Copp, Brent R; Keyzers, Robert A; Munro, Murray H G; Prinsep, Michèle R

    2015-02-01

    This review covers the literature published in 2013 for marine natural products (MNPs), with 982 citations (644 for the period January to December 2013) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1163 for 2013), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included. PMID:25620233

  9. Marine natural products.

    PubMed

    Blunt, John W; Copp, Brent R; Keyzers, Robert A; Munro, Murray H G; Prinsep, Michèle R

    2013-02-01

    This review covers the literature published in 2011 for marine natural products, with 870 citations (558 for the period January to December 2011) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1152 for 2011), together with the relevant biological activities, source organisms and country of origin. Biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included. PMID:23263727

  10. "Naturally occurring asbestos

    NASA Astrophysics Data System (ADS)

    Cagnard, F.; Lahondère, D.; Blein, O.; Lahfid, A.; Wille, G.

    2012-04-01

    The term asbestos refers to six silicate minerals from amphibole and serpentine groups. By definition, it consists in bundles of thin and flexible long fibers, with high-tensile strength, and chemical and heat resistance. In contrast to asbestos found within commercial products and mining, the specific term ''naturally occurring asbestos'' (NOA) refers to asbestiform minerals occurring within rocks or soils that can be released by human activities or weathering processes. The fact that the exposure to asbestos is related to lung pathologies is now widely demonstrated (e.g. asbestosis, mesothelioma and lung cancer). However, if health risks associated with exposure to NOA exist, they are not yet well documented. The crystallization of natural asbestos occurs in specific Mg-rich lithologies associated with peculiar structural and metamorphic conditions. By recognizing and combining such specific geologic criteria, the presence or the absence of asbestos in bedrock terrains can be reasonably predicted and maps of NOA hazard can be drawn. We present here new results of geological mapping and petrological study concerning the evaluation of the NOA hazard in the Alps and Corsica, in France. The three folds approach consists in (1) a determination of lithologies with potential NOA from a bibliographic compilation and extraction of target zones from a geological geodatabase (2) a geological mapping of the target zones followed by a petrological characterization of sampled asbestiform minerals in the laboratory (optical microscopy, TEM, SEM, and Raman spectroscopy technics), and (3) the drawing of the final map of NOA hazard, at regional-scale. Occurrence criteria can be retained as follows: 1. NOA are abundant in the internal zones of the Alps and Corsica, especially within ophiolitic complexes. Natural asbestos are mostly concentrated within ultramafic rocks but can also occur within basic lithologies such as Mg-metagabbros, metabasalts and meta-pillow-lavas, 2. Asbestos

  11. Natural remedies for scleroderma.

    PubMed

    Gaby, Alan R

    2006-09-01

    Scleroderma is an autoimmune disease of the connective tissue characterized by fibrosis and thickening of various tissues. It can be limited to the skin or affect multiple organs, and its course ranges from slowly to rapidly progressive. Penicillamine, glucocorticoids, and other drugs are used to treat scleroderma, but none of these treatments has a high degree of efficacy. This article reviews several promising natural treatments for scleroderma, including para-aminobenzoic acid, vitamin E, vitamin D, evening primrose oil, estriol, N-acetylcysteine, bromelain, and an avocado/soybean extract. PMID:17217320

  12. Modulated natural inflation

    NASA Astrophysics Data System (ADS)

    Kappl, Rolf; Nilles, Hans Peter; Winkler, Martin Wolfgang

    2016-02-01

    We discuss some model-independent implications of embedding (aligned) axionic inflation in string theory. As a consequence of string theoretic duality symmetries the pure cosine potentials of natural inflation are replaced by modular functions. This leads to "wiggles" in the inflationary potential that modify the predictions with respect to CMB-observations. In particular, the scalar power spectrum deviates from the standard power law form. As a by-product one can show that trans-Planckian excursions of the aligned effective axion are compatible with the weak gravity conjecture.

  13. Turbulent Plumes in Nature

    NASA Astrophysics Data System (ADS)

    Woods, Andrew W.

    2010-01-01

    This review describes a range of natural processes leading to the formation of turbulent buoyant plumes, largely relating to volcanic processes, in which there are localized, intense releases of energy. Phenomena include volcanic eruption columns, bubble plumes in lakes, hydrothermal plumes, and plumes beneath the ice in polar oceans. We assess how the dynamics is affected by heat transfer, particle fallout and recycling, and Earth's rotation, as well as explore some of the mixing of the ambient fluid produced by plumes in a confined geometry.

  14. Gluino meets flavored naturalness

    NASA Astrophysics Data System (ADS)

    Blanke, Monika; Fuks, Benjamin; Galon, Iftah; Perez, Gilad

    2016-04-01

    We study constraints from LHC run I on squark and gluino masses in the presence of squark flavor violation. Inspired by the concept of `flavored naturalness', we focus on the impact of a non-zero stop-scharm mixing and mass splitting in the right-handed sector. To this end, we recast four searches of the ATLAS and CMS collaborations, dedicated either to third generation squarks, to gluino and squarks of the first two generations, or to charm-squarks. In the absence of extra structure, the mass of the gluino provides an additional source of fine tuning and is therefore important to consider within models of flavored naturalness that allow for relatively light squark states. When combining the searches, the resulting constraints in the plane of the lightest squark and gluino masses are rather stable with respect to the presence of flavor-violation, and do not allow for gluino masses of less than 1.2 TeV and squarks lighter than about 550 GeV. While these constraints are stringent, interesting models with sizable stop-scharm mixing and a relatively light squark state are still viable and could be observed in the near future.

  15. Nature against depression.

    PubMed

    El-Alfy, A T; Abourashed, E A; Matsumoto, R R

    2012-01-01

    Depression is a major health problem currently recognized as a leading cause of morbidity worldwide. In the United States alone, depression affects approximately 20% of the population. With current medications suffering from major shortcomings that include slow onset of action, poor efficacy, and unwanted side effects, the search for new and improved antidepressants is ever increasing. In an effort to evade side effects, people have been resorting to popular traditional herbal medicines to relieve the symptoms of depression, and there is a need for more empirical knowledge about their use and effectiveness. This review provides an overview of the current knowledge state regarding a variety of natural plant products commonly used in depression. Herbal medicines discussed that have been used in clinical trials for the treatment of mild to moderate depression states include the popular St. John's wort, saffron, Rhodiola, lavender, Echium, and the Chinese formula banxia houpu. In addition, new emerging herbal products that have been studied in different animal models are discussed including Polygala tenuifolia, the traditional Chinese herbal SYJN formula, gan mai da zao, and Cannabis sativa constituents. A comprehensive review of the chemical, pharmacological, and clinical aspects of each of the reviewed products is provided. Finally, recent preclinical studies reporting the antidepressant action of marine-derived natural products are discussed at the end of the review. PMID:22414105

  16. Extensions of Natural Hamiltonians

    NASA Astrophysics Data System (ADS)

    Rastelli, G.

    2014-03-01

    Given an n-dimensional natural Hamiltonian L on a Riemannian or pseudo-Riemannian manifold, we call "extension" of L the n+1 dimensional Hamiltonian H = ½p2u + α(u)L + β(u) with new canonically conjugated coordinates (u,pu). For suitable L, the functions α and β can be chosen depending on any natural number m such that H admits an extra polynomial first integral in the momenta of degree m, explicitly determined in the form of the m-th power of a differential operator applied to a certain function of coordinates and momenta. In particular, if L is maximally superintegrable (MS) then H is MS also. Therefore, the extension procedure allows the creation of new superintegrable systems from old ones. For m=2, the extra first integral generated by the extension procedure determines a second-order symmetry operator of a Laplace-Beltrami quantization of H, modified by taking in account the curvature of the configuration manifold. The extension procedure can be applied to several Hamiltonian systems, including the three-body Calogero and Wolfes systems (without harmonic term), the Tremblay-Turbiner-Winternitz system and n-dimensional anisotropic harmonic oscillators. We propose here a short review of the known results of the theory and some previews of new ones.

  17. Natural medicaments in dentistry

    PubMed Central

    Sinha, Dakshita J.; Sinha, Ashish A.

    2014-01-01

    The major objective in root canal treatment is to disinfect the entire root canal system. Cleaning, shaping, and use of antimicrobial medicaments are effective in reducing the bacterial load to some extent, but some bacteria do remain behind and multiply, causing reinfection. Taking into consideration the ineffectiveness, potential side-effects and safety concerns of synthetic drugs, the herbal alternatives for endodontic usage might prove to be advantageous. Over the past decade, interest in drugs derived from medicinal plants has markedly increased. Phytomedicine has been used in dentistry as anti-inflammatory, antibiotic, analgesic, sedative and also as endodontic irrigant. Herbal preparations can be derived from the root, leaves, seeds, stem, and flowers. The PubMed database search revealed that the reference list for natural medicaments featured 1480 articles and in dentistry 173 articles. A forward search was undertaken on the selected articles and author names. This review focuses on various natural drugs and products as well as their therapeutic applications when used as phytomedicine in dentistry. PMID:25558153

  18. Naturally Occurring Food Toxins

    PubMed Central

    Dolan, Laurie C.; Matulka, Ray A.; Burdock, George A.

    2010-01-01

    Although many foods contain toxins as a naturally-occurring constituent or, are formed as the result of handling or processing, the incidence of adverse reactions to food is relatively low. The low incidence of adverse effects is the result of some pragmatic solutions by the US Food and Drug Administration (FDA) and other regulatory agencies through the creative use of specifications, action levels, tolerances, warning labels and prohibitions. Manufacturers have also played a role by setting limits on certain substances and developing mitigation procedures for process-induced toxins. Regardless of measures taken by regulators and food producers to protect consumers from natural food toxins, consumption of small levels of these materials is unavoidable. Although the risk for toxicity due to consumption of food toxins is fairly low, there is always the possibility of toxicity due to contamination, overconsumption, allergy or an unpredictable idiosyncratic response. The purpose of this review is to provide a toxicological and regulatory overview of some of the toxins present in some commonly consumed foods, and where possible, discuss the steps that have been taken to reduce consumer exposure, many of which are possible because of the unique process of food regulation in the United States. PMID:22069686

  19. Thermoacoustic natural gas liquefier

    SciTech Connect

    Swift, G.W.

    1995-06-01

    In collaboration with Cryenco Inc. and NIST-Boulder, we intend to develop a natural gas-powered natural-gas liquefier which has absolutely no moving parts and requires no electrical power. It will have high efficiency, remarkable reliability, and low cost. Progress on the liquefier to be constructed at Cryenco continues satisfactorily. The thermoacoustic driver is still ahead of the pulse tube refrigerator, because of NIST`s schedule. We completed the thermoacoustics design in the fall of 1994, with Los Alamos providing physics input and checks of all aspects, and Cryenco providing engineering to ASME code, drafting, etc. Completion of this design represents a significant amount of work, especially in view of the many unexpected problems encountered. Meanwhile, Cryenco and NIST have almost completed the design of the pulse tube refrigerator. At Los Alamos, we have assembled a half-size scale model of the thermoacoustic portion of the 500 gal/day TANGL. This scale model will enable easy experimentation in harmonic suppression techniques, new stack geometries, new heat-exchanger geometries, resonator coiling, and other areas. As of March 1995, the scale model is complete and we are performing routine debugging tests and modifications.

  20. [Natural philosophy in medieval medicine].

    PubMed

    Riha, Ortrun

    2007-01-01

    Medieval medicine is not much interested in natural philosophy. Nevertheless, it is based upon clear methodological and epistemological principles, where the word 'nature' is used in several ways. The natural 'virtues' of things--including magical ones--are most important for therapy. Human health is influenced by stars (planets, zodiac) and seasons, and the physician has to take into account such cosmic effects. The chances of healing depend on the patients' 'nature' in relation to the power of illness. A strong nature makes medicine superfluous, an overwhelming disease cannot be beaten. Thus, medicine is limited to 'neutral' situations when supporting the patient makes his 'nature' win. PMID:18447188

  1. Natural gas monthly, April 1999

    SciTech Connect

    1999-05-06

    The Natural Gas Monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information. There are two feature articles in this issue: Natural gas 1998: Issues and trends, Executive summary; and Special report: Natural gas 1998: A preliminary summary. 6 figs., 28 tabs.

  2. Nature's loss, Immunologists gain?

    PubMed

    Aluvihare

    2000-01-01

    Nature Reviews Molecular Cell Biology Nature Publishing Group (2000). ISSN 1471-0072. Monthly First there was Annual Reviews, then came the monthly Elsevier Trends Journals, both of which try to identify hot topics in their chosen fields. The Current Opinion journals followed several years later, and Current Opinion in Cell Biology is presently one of the highest 'impact factor' review journals, with a distinguished board of editors and advisors and a systematic approach to regular coverage of the major fields of cell biology. Important topics are visited once a year, whether or not something specially exciting happened in the last 12 months. Add to this list Seminars in Cell and Developmental Biology, the FASEB journal and the countless minireviews in 'real' journals, and you begin to wonder how anyone finds any time for doing experiments, or indeed reading the primary literature. So, into this already crowded field arrive three important newcomers: Nature Reviews in Molecular Cell Biology, Genetics, and Neurosciences, of which the first two will probably interest readers of Journal of Cell Science the most. Backed by the name and money of Nature and edited by experienced Nature staff, it is hard to see how these publications can possibly do other than succeed with writers and readers alike. What's inside the first issue? The cover of Nature Reviews in Molecular Cell Biology presents a 3-colour montage of a blue cell nucleus surrounded by splotches of green GPI-anchored GFP overlaid by orange actin stress fibres that seem to come from somewhere else. This image trails a comprehensive review from Kai Simons and Derek Toomre about Lipid Rafts. There are another five major review articles: calcium puffs and sparks, rings around DNA, HIV inhibitors, kinesin and the circadian clock provide a rich and varied mix of topics from authors who know what they're talking about. Surrounding this core is an entertaining mixture of 'highlights' at the front: news and views about

  3. Antimicrobial and antiparastic abietane diterpenoids from Cupressus sempervirens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cupressus sempervirens L. (Cupressaceae) is a species of cypress native to the eastern Mediterranean region. The ethanol extract of the powdered cone (fruits) of this plant, collected from Oxford, Mississippi, USA during the fall of 2010, exhibited potent antimicrobial and antiparastic a...

  4. Identity, regulation, and activity of inducible diterpenoid phytoalexins in maize

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phytoalexins constitute a broad category of pathogen and insect-inducible biochemicals that locally protect plant tissues. Due to their agronomic significance, maize and rice have been extensively investigated for their terpenoid-based defenses which include insect-inducible monoterpene and sesquite...

  5. Discrimination between several diterpenoid compounds in feeding by Gambusia affinis.

    PubMed

    Aceret, T L; Sammarco, P W; Coll, J C; Uchio, Y

    2001-01-01

    The alcyonacean soft coral Sinularia flexibilis Quoy and Gaimard produces a number of bioactive complementary (secondary) metabolites. The ability of three of these diterpenes - flexibilide, sinulariolide and dihydroflexibilide - to elicit differential discriminatory feeding behavior in Gambusia affinis was assessed in a feeding deterrence study. Terpene-impregnated fish flakes were offered to fish trained to feed on such food, and their responses (acceptance, rejection, avoidance, or no response) were assessed as indicative of feeding deterrence. Food treated with sinulariolide (a compound previously determined to be non-bioactive) was generally accepted at a 1% concentration. It was avoided and rejected, however, at a concentration of 10%, a concentration level generally restricted to polyp-rich branchlets. This indicated negative olfactory and palatability cues, respectively. Flexibilide-treated flakes were accepted to some extent by the fish at the 1% concentration, but strongly avoided at the 10% concentration, indicating effective feeding deterrence via olfaction. Dihydroflexibilide-impregnated flakes were strongly rejected even at low concentrations (1%) after tasting, indicating a negative palatibility cue. They were strongly avoided or rejected at higher concentrations (10%), indicating a negative olfactory cue as well. This response at higher concentrations indicates that sinulariolide and flexibilide become effective at concentrations between 1% and 10%. Such concentrations may be found in the polypary (polyp-bearing portion) of the soft coral colonies. Dihydroflexibilide elicited the strongest negative palatability response from these test fish. The feeding deterrence characteristics of the compounds determined here represent the potentials of individual compounds to elicit differential feeding responses in organisms like Gambusia which are capable of discriminating between different but closely related complementary (secondary) metabolites. PMID:11166674

  6. 8,15-epoxylabdane and norlabdane diterpenoids from Eragrostis viscosa.

    PubMed

    Sebastião, N'Soki N; Cordeiro, Inês J S; dos Santos, Aldenir F; Gaspar, Jorge F; Martins, Célia; Rueff, José; Diakanamwa, Carlos; Sant'Ana, Antônio E G; de Mendonça, Dina I M D

    2010-05-01

    Four labdanes with a 8alpha,15-epoxy ring (8alpha,15-epoxylabdan-16beta-oic acid; 8alpha,15-epoxy-16-norlabdan-13-one; 8alpha,15-epoxy-16-norlabdane; and 16-acetoxy-8alpha,15-epoxylabdane) and the known compound ambreinolide were isolated from the hexane extract of the aerial parts of the grass Eragrostis viscosa. The structures of all compounds were established based on spectroscopic data and the X-ray analysis of 8alpha,15-epoxy-16-norlabdan-13-one. The hexane extract presented moderate activity against the snail Biomphalaria glabrata. 8alpha,15-Epoxylabdan-16beta-oic acid showed no mutagenic activity for doses up to 1000 microg/plate and no significant clastogenic activity for doses up to 100 microg/ml. PMID:20189613

  7. New Xenia diterpenoids from the Indonesian soft coral Xenia sp.

    PubMed

    Anta, Cristina; González, Noemí; Santafé, Gilmar; Rodríguez, Jaime; Jiménez, Carlos

    2002-05-01

    Two new xeniolides, xeniolide-F (1) and 9-hydroxyxeniolide-F (2), along with isoxeniolide-A (3) and 7,8-oxido-isoxeniolide-A (4), have been isolated from Xenia sp. and their structures established on the basis of extensive NMR and MS studies. PMID:12027764

  8. Liquefied Natural Gas Transfer

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Chicago Bridge & Iron Company's tanks and associated piping are parts of system for transferring liquefied natural gas from ship to shore and storing it. LNG is a "cryogenic" fluid meaning that it must be contained and transferred at very low temperatures, about 260 degrees below Fahrenheit. Before the LNG can be pumped from the ship to the storage tanks, the two foot diameter transfer pipes must be cooled in order to avoid difficulties associated with sharp differences of temperature between the supercold fluid and relatively warm pipes. Cooldown is accomplished by sending small steady flow of the cryogenic substance through the pipeline; the rate of flow must be precisely controlled or the transfer line will be subjected to undesirable thermal stress.

  9. Natural flexible dermal armor.

    PubMed

    Yang, Wen; Chen, Irene H; Gludovatz, Bernd; Zimmermann, Elizabeth A; Ritchie, Robert O; Meyers, Marc A

    2013-01-01

    Fish, reptiles, and mammals can possess flexible dermal armor for protection. Here we seek to find the means by which Nature derives its protection by examining the scales from several fish (Atractosteus spatula, Arapaima gigas, Polypterus senegalus, Morone saxatilis, Cyprinius carpio), and osteoderms from armadillos, alligators, and leatherback turtles. Dermal armor has clearly been developed by convergent evolution in these different species. In general, it has a hierarchical structure with collagen fibers joining more rigid units (scales or osteoderms), thereby increasing flexibility without significantly sacrificing strength, in contrast to rigid monolithic mineral composites. These dermal structures are also multifunctional, with hydrodynamic drag (in fish), coloration for camouflage or intraspecies recognition, temperature and fluid regulation being other important functions. The understanding of such flexible dermal armor is important as it may provide a basis for new synthetic, yet bioinspired, armor materials. PMID:23161399

  10. Natural dispersion revisited.

    PubMed

    Johansen, Øistein; Reed, Mark; Bodsberg, Nils Rune

    2015-04-15

    This paper presents a new semi-empirical model for oil droplet size distributions generated by single breaking wave events. Empirical data was obtained from laboratory experiments with different crude oils at different stages of weathering. The paper starts with a review of the most commonly used model for natural dispersion, which is followed by a presentation of the laboratory study on oil droplet size distributions formed by breaking waves conducted by SINTEF on behalf of the NOAA/UNH Coastal Response Research Center. The next section presents the theoretical and empirical foundation for the new model. The model is based on dimensional analysis and contains two non-dimensional groups; the Weber and Reynolds number. The model was validated with data from a full scale experimental oil spill conducted in the Haltenbanken area offshore Norway in July 1982, as described in the last section of the paper. PMID:25752537

  11. Dengue fever: natural management.

    PubMed

    Qadir, Muhammad Imran; Abbas, Khizar; Tahir, Madeha; Irfan, Muhammad; Raza Bukhari, Syeda Fiza; Ahmed, Bilal; Hanif, Muhammad; Rasul, Akhtar; Ali, Muhammad

    2015-03-01

    Dengue fever is caused by the mosquito-borne dengue virus (DENV) serotypes 1-4, and is the most common arboviral infection of humans in subtropical and tropical regions of the world. Dengue virus infections can present with a spacious range of clinical signs, from a mild feverish illness to a life-threatening shock syndrome. Till now, there is no approved vaccine or drug against this virus. Therefore, there is an urgent need of development of alternative solutions for dengue. Several plant species have been reported with anti-dengue activity. Many herbal/natural drugs, most of which are commonly used as nutritional components, have been used as antiviral, larvicidal, mosquitocidal and mosquito repellents that may be used against dengue. The objective of this review article was to provide current approaches for the treatment and management/prevention of dengue fever by targeting viral proteins involved in replication cycle of the virus and different developmental stages of mosquito. PMID:25730815

  12. Natural Radioactivity in Bananas

    SciTech Connect

    Zagatto, V. A. B.; Medina, N. H.; Okuno, E.; Umisedo, N. K.

    2008-08-07

    The content of {sup 40}K natural radionuclide in bananas (Musa sapientum) from the Vale do Ribeira region, Sao Paulo, Brazil, has been measured. We have collected several samples of bananas prata and nanica, its peels, leaves, and also different soils where the banana tree was planted, such as soil with a standard amount of fertilizer, the fertilizer itself and also soil without fertilizer for comparison. We have used the gamma-ray spectroscopy technique with a NaI(T1) crystal inside a 12 cm thick lead shield to detect the gamma-radiation. The results indicate that only part of the available potassium is absorbed by the plant, which is mainly concentrated in the banana peel.

  13. New probe of naturalness.

    PubMed

    Craig, Nathaniel; Englert, Christoph; McCullough, Matthew

    2013-09-20

    Any new scalar fields that perturbatively solve the hierarchy problem by stabilizing the Higgs boson mass also generate new contributions to the Higgs boson field-strength renormalization, irrespective of their gauge representation. These new contributions are physical, and in explicit models their magnitude can be inferred from the requirement of quadratic divergence cancellation; hence, they are directly related to the resolution of the hierarchy problem. Upon canonically normalizing the Higgs field, these new contributions lead to modifications of Higgs couplings that are typically great enough that the hierarchy problem and the concept of electroweak naturalness can be probed thoroughly within a precision Higgs boson program. Specifically, at a lepton collider this can be achieved through precision measurements of the Higgs boson associated production cross section. This would lead to indirect constraints on perturbative solutions to the hierarchy problem in the broadest sense, even if the relevant new fields are gauge singlets. PMID:24093250

  14. The nature of confidentiality.

    PubMed Central

    Thompson, I E

    1979-01-01

    This paper examines confidentiality and its nature and analyses the guidelines laid down by the Hippocratic Oath as well as the British and World Medical Associations for maintaining such confidentiality between doctor and patient. There are exceptions to practically any code of rules and this is true also for confidentiality. Some of these exceptions make it appear that very little is confidential. The three values implicit in confidentiality would seem to be privacy, confidence and secrecy. Each of these values is discussed and developed in this paper. In conclusion, the question is suggested that maybe in the face of death, doctor and patient need to re-examine the pre-suppositions of privacy, confidence and secrecy on which the confidential relationship is based. PMID:469872

  15. Natural Radioactivity in Bananas

    NASA Astrophysics Data System (ADS)

    Zagatto, V. A. B.; Medina, N. H.; Okuno, E.; Umisedo, N. K.

    2008-08-01

    The content of 40K natural radionuclide in bananas (Musa sapientum) from the Vale do Ribeira region, São Paulo, Brazil, has been measured. We have collected several samples of bananas prata and nanica, its peels, leaves, and also different soils where the banana tree was planted, such as soil with a standard amount of fertilizer, the fertilizer itself and also soil without fertilizer for comparison. We have used the gamma-ray spectroscopy technique with a NaI(T1) crystal inside a 12 cm thick lead shield to detect the gamma-radiation. The results indicate that only part of the available potassium is absorbed by the plant, which is mainly concentrated in the banana peel.

  16. Carotenoid Distribution in Nature.

    PubMed

    Alcaíno, Jennifer; Baeza, Marcelo; Cifuentes, Víctor

    2016-01-01

    Carotenoids are naturally occurring red, orange and yellow pigments that are synthesized by plants and some microorganisms and fulfill many important physiological functions. This chapter describes the distribution of carotenoid in microorganisms, including bacteria, archaea, microalgae, filamentous fungi and yeasts. We will also focus on their functional aspects and applications, such as their nutritional value, their benefits for human and animal health and their potential protection against free radicals. The central metabolic pathway leading to the synthesis of carotenoids is described as the three following principal steps: (i) the synthesis of isopentenyl pyrophosphate and the formation of dimethylallyl pyrophosphate, (ii) the synthesis of geranylgeranyl pyrophosphate and (iii) the synthesis of carotenoids per se, highlighting the differences that have been found in several carotenogenic organisms and providing an evolutionary perspective. Finally, as an example, the synthesis of the xanthophyll astaxanthin is discussed. PMID:27485217

  17. Nature Neuroscience Review

    PubMed Central

    Maze, Ian; Shen, Li; Zhang, Bin; Garcia, Benjamin A.; Shao, Ningyi; Mitchell, Amanda; Sun, HaoSheng; Akbarian, Schahram; Allis, C. David; Nestler, Eric J.

    2014-01-01

    Over the past decade, rapid advances in epigenomics research have extensively characterized critical roles for chromatin regulatory events during normal periods of eukaryotic cell development and plasticity, as well as part of aberrant processes implicated in human disease. Application of such approaches to studies of the central nervous system (CNS), however, is more recent. Here, we provide a comprehensive overview of currently available tools to analyze neuroepigenomics data, as well as a discussion of pending challenges specific to the field of neuroscience. Integration of numerous unbiased genome-wide and proteomic approaches will be necessary to fully understand the neuroepigenome and the extraordinarily complex nature of the human brain. This will be critical to the development of future diagnostic and therapeutic strategies aimed at alleviating the vast array of heterogeneous and genetically distinct disorders of the CNS. PMID:25349914

  18. Natural Air Purifier

    NASA Technical Reports Server (NTRS)

    1993-01-01

    NASA environmental research has led to a plant-based air filtering system. Dr. B.C. Wolverton, a former NASA engineer who developed a biological filtering system for space life support, served as a consultant to Terra Firma Environmental. The company is marketing the BioFilter, a natural air purifier that combines activated carbon and other filter media with living plants and microorganisms. The filter material traps and holds indoor pollutants; plant roots and microorganisms then convert the pollutants into food for the plant. Most non-flowering house plants will work. After pollutants have been removed, the cleansed air is returned to the room through slits in the planter. Terra Firma is currently developing a filter that will also disinfect the air.

  19. Natural killer cell deficiency

    PubMed Central

    Orange, Jordan S.

    2013-01-01

    Natural killer (NK) cells are part of the innate immune defense against infection and cancer, and are especially useful in combating certain viral pathogens. The utility of NK cells in human health has been underscored by a growing number of individuals who are deficient in NK cells and/or their functions. This can be in the context of a broader genetically-defined congenital immunodeficiency of which there are over forty presently known to impair NK cells. The abnormality of NK cells, however, in certain cases represents the majority immunological defect. In aggregate, these conditions are termed NK cell deficiency. Recent advances have added clarity to this diagnosis and identified defects in three different genes that can cause NK cell deficiency as well as some of the underlying biology. Appropriate consideration of these diagnoses and patients raises the potential for rational therapeutic options and further innovation. PMID:23993353

  20. Pest management with natural products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The 2012 Philadelphia ACS Symposium on Natural Products for Pest Management introduced recent discoveries and applications of natural products from insect, terrestrial plant, microbial, and synthetic sources for the management of insects, weeds, plant pathogenic microbes, and nematodes. The symposiu...

  1. Natural products: Emulation illuminates biosynthesis

    NASA Astrophysics Data System (ADS)

    Mercer, Jaron A. M.; Burns, Noah Z.

    2015-11-01

    A concise synthesis of the fungal natural product epicolactone suggests that this highly stereochemically complex yet racemic natural product may come from a cascade reaction between two polyhydroxylated arenes.

  2. Natural Gas Exports from Iran

    EIA Publications

    2012-01-01

    This assessment of the natural gas sector in Iran, with a focus on Iran’s natural gas exports, was prepared pursuant to section 505 (a) of the Iran Threat Reduction and Syria Human Rights Act of 2012 (Public Law No: 112-158). As requested, it includes: (1) an assessment of exports of natural gas from Iran; (2) an identification of the countries that purchase the most natural gas from Iran; (3) an assessment of alternative supplies of natural gas available to those countries; (4) an assessment of the impact a reduction in exports of natural gas from Iran would have on global natural gas supplies and the price of natural gas, especially in countries identified under number (2); and (5) such other information as the Administrator considers appropriate.

  3. Natural gas monthly, April 1995

    SciTech Connect

    1995-04-27

    The Natural Gas Monthly highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information. 6 figs., 31 tabs.

  4. Natural Gas Monthly, March 1996

    SciTech Connect

    1996-03-25

    The Natural Gas Monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information.

  5. Natural gas monthly: December 1993

    SciTech Connect

    Not Available

    1993-12-01

    The Natural Gas Monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. Articles are included which are designed to assist readers in using and interpreting natural gas information.

  6. Natural gas monthly, June 1993

    SciTech Connect

    Not Available

    1993-06-22

    The Natural Gas Monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information.

  7. Natural gas monthly, November 1993

    SciTech Connect

    Not Available

    1993-11-29

    The Natural Gas Monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground state data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information.

  8. Natural gas monthly, August 1994

    SciTech Connect

    Not Available

    1994-08-24

    The Natural Gas Monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information.

  9. Natural gas monthly, June 1997

    SciTech Connect

    1997-06-01

    The Natural Gas Monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information. 6 figs., 24 tabs.

  10. Natural gas monthly, July 1998

    SciTech Connect

    1998-07-01

    The Natural Gas Monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information. 6 figs., 25 tabs.

  11. Supramolecular complexations of natural products.

    PubMed

    Schneider, Hans-Jörg; Agrawal, Pawan; Yatsimirsky, Anatoly K

    2013-08-21

    Complexations of natural products with synthetic receptors as well as the use of natural products as host compounds are reviewed, with an emphasis on possible practical uses or on biomedical significance. Applications such as separation, sensing, enzyme monitoring, and protection of natural drugs are first outlined. We then discuss examples of complexes with all important classes of natural compounds, such as amino acids, peptides, nucleosides/nucleotides, carbohydrates, catecholamines, flavonoids, terpenoids/steroids, alkaloids, antibiotics and toxins. PMID:23703643

  12. Natural gas monthly, July 1993

    SciTech Connect

    Not Available

    1993-07-27

    The Natural Gas Monthly NGM highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information.

  13. Natural gas monthly, June 1999

    SciTech Connect

    1999-06-01

    The Natural Gas Monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information. 6 figs., 25 tabs.

  14. Natural gas monthly, May 1999

    SciTech Connect

    1999-05-01

    The Natural Gas Monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time the NGM features articles designed to assist readers in using and interpreting natural gas information. 6 figs., 27 tabs.

  15. US crude oil, natural gas, and natural gas liquids reserves

    SciTech Connect

    Not Available

    1990-10-05

    This report presents estimates of proved reserves of crude oil, natural gas, and natural gas liquids as of December 31, 1989, and production volumes for the year 1989 for the total United States and for selected states and state sub-divisions. Estimates are presented for the following four categories of natural gas: total gas (wet after lease separation), its two major components (nonassociated and associated-dissolved gas), and total dry gas (wet gas adjusted for the removal of liquids at natural gas processing plants). In addition, two components of natural gas liquids, lease condensate and natural gas plant liquids, have their reserves and production reported separately. Also included is information on indicated additional crude oil reserves and crude oil, natural gas, and lease condensate reserves in nonproducing reservoirs. 28 refs., 9 figs., 15 tabs.

  16. Natural gas monthly, December 1998

    SciTech Connect

    1998-12-01

    The Natural Gas Monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. 6 figs., 28 tabs.

  17. Advances in the Natural transform

    NASA Astrophysics Data System (ADS)

    Belgacem, F. B. M.; Silambarasan, R.

    2012-11-01

    The literature review of the Natural transform and the existing definitions and connections to the Laplace and Sumudu transforms are discussed in this communication. Along with the complex inverse Natural transform and Heaviside's expansion formula, the relation of Bessel's function to Natural transform (and hence Laplace and Sumudu transforms) are defined.

  18. Percents Are Not Natural Numbers

    ERIC Educational Resources Information Center

    Jacobs, Jennifer A.

    2013-01-01

    Adults are prone to treating percents, one representational format of rational numbers, as novel cases of natural number. This suggests that percent values are not differentiated from natural numbers; a conceptual shift from the natural numbers to the rational numbers has not yet occurred. This is most surprising, considering people are inundated…

  19. Nature and Nationhood: Danish Perspectives

    ERIC Educational Resources Information Center

    Schnack, Karsten

    2009-01-01

    In this paper, I shall discuss Danish perspectives on nature, showing the interdependence of conceptions of "nature" and "nationhood" in the formations of a particular cultural community. Nature, thus construed, is never innocent of culture and cannot therefore simply be "restored" to some pristine, pre-lapsarian state. On the other hand,…

  20. Children's Moral Relationships with Nature.

    ERIC Educational Resources Information Center

    Kahn, Peter H., Jr.; McCoy, Ann

    Two studies of the development of children's moral relationships with nature addressed such questions as: (1) What does it mean to say that we have an obligation not to harm the natural environment? (2) Does the natural environment feel pain? (3) Does it have rights? or (4) Is moral obligation an inappropriate construct by which to understand the…

  1. Natural gas monthly, February 1999

    SciTech Connect

    1999-02-01

    The Natural Gas Monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. 6 figs., 28 tabs.

  2. Natural gas monthly, January 1999

    SciTech Connect

    1999-02-01

    The Natural Gas Monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. 6 figs., 28 tabs.

  3. Natural gas monthly, November 1998

    SciTech Connect

    1998-11-01

    The Natural Gas Monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. 6 figs., 27 tabs.

  4. Naturalness and supersymmetry

    NASA Astrophysics Data System (ADS)

    Agashe, Kaustubh Sadanand

    In the Standard Model of elementary particle physics, electroweak symmetry breaking is achieved by a Higgs scalar doublet with a negative (mass)2. The Standard Model has the well known gauge hierarchy problem: quadratically divergent quantum corrections drive the Higgs mass and thus the weak scale to the scale of new physics. Thus, if the scale of new physics is say the Planck scale, then correct electroweak symmetry breaking requires a fine tuning between the bare Higgs mass and the quantum corrections. Supersymmetry, a symmetry between fermions and bosons, solves the gauge hierarchy problem of the Standard Model: the quadratically divergent corrections to the Higgs mass cancel between fermions and bosons. The remaining corrections to the Higgs mass are proportional to the supersymmetry breaking masses for the supersymmetric partners (the sparticles) of the Standard Model particles. The large top quark Yukawa coupling results in a negative Higgs (mass)2. Thus, electroweak symmetry breaking occurs naturally at the correct scale if the masses of the sparticles are close to the weak scale. In this thesis, we argue that the supersymmetric Standard Model, while avoiding the fine tuning in electroweak symmetry breaking, requires unnaturalness/fine tuning in some (other) sector of the theory. For example, Baryon and Lepton number violating operators are allowed which lead to proton decay and flavor changing neutral currents. We study some of the constraints from the latter in this thesis. We have to impose an R-parity for the theory to be both natural and viable. In the absence of flavor symmetries, the supersymmetry breaking masses for the squarks and sleptons lead to too large flavor changing neutral currents. We show that two of the solutions to this problem, gauge mediation of supersymmetry breaking and making the scalars of the first two generations heavier than a few TeV, reintroduce fine tuning in electroweak symmetry breaking. We also construct a model of low

  5. Natural resolution of inflammation.

    PubMed

    Freire, Marcelo O; Van Dyke, Thomas E

    2013-10-01

    Inflammation is a protective response essential for maintaining human health and for fighting disease. As an active innate immune reaction to challenge, inflammation gives rise to clinical cardinal signs: rubor, calor, dolor, tumor and functio laesa. Termination of acute inflammation was previously recognized as a passive process; a natural decay of pro-inflammatory signals. We now understand that the natural resolution of inflammation involves well-integrated, active, biochemical programs that return tissues to homeostasis. This review focuses on recent advances in the understanding of the role of endogenous lipid mediators that modulate cellular fate and inflammation. Biosynthesis of eicosanoids and other lipids in exudates coincides with changes in the types of inflammatory cells. Resolution of inflammation is initiated by an active class switch in lipid mediators, such as classic prostaglandins and leukotrienes, to the production of proresolution mediators. Endogenous pro-resolving lipid mediators, including arachidonic acid-derived lipoxins, aspirin-triggered lipoxins, ω3-eicosapentaenoic acid-derived resolvins of the E-series, docosahexaenoic acid-derived resolvins of the D-series, protectins and maresins, are biosynthesized during the resolution phase of acute inflammation. Depending on the type of injury and the type of tissue, the initial cells that respond are polymorphonuclear leukocytes, monocytes/macrophages, epithelial cells or endothelial cells. The selective interaction of specific lipid mediators with G protein-coupled receptors expressed on innate immune cells (e.g. G protein-coupled receptor 32, lipoxin A4 receptor/formyl peptide receptor2, chemokine-like receptor 1, leukotriene B4 receptor type 1 and cabannoid receptor 2) induces cessation of leukocyte infiltration; vascular permeability/edema returns to normal with polymorphonuclear neutrophil death (mostly via apoptosis), the nonphlogistic infiltration of monocyte/macrophages and the removal

  6. Natural gas conversion process

    SciTech Connect

    Gondouin, O.M.

    1987-11-10

    An improved process for converting all natural gas hydrocarbon components with carbon numbers of 1 to 4 into liquid hydrocarbons with carbon numbers equal to or greater than 5, and into a hydrogen-rich gaseous by-product which is described comprising the following steps: A. Splitting the natural gas feed into a rich gas stream comprising C/sub 2/, C/sub 3/ and C/sub 4/ hydrocarbons and a lean gas stream comprising C/sub 1/ and C/sub 2/ hydrocarbons; B. Catalytically converting the rich gas stream in a catalytic bed reactor in which the gas-suspended solid phase is a catalyst maintained at a temperature not exceeding 600/sup 0/C.; Separating the gaseous effluent from the catalytic bed reactor into (1) a hydrogen-rich stream; (2) a lean gas stream comprising hydrogen, C/sub 1/ and C/sub 2/ hydrocarbons, (3) a rich gas stream comprising C/sub 2/ and C/sub 3/ and C/sub 4/ hydrocarbons and (4) a liquid product stream comprising C/sub 5/ + hydrocarbons; D. Pre-heating all lean gas streams, including recycle, in a furnace; E. Transferring the catalyst into a short residence time reactor; F. Reacting an ionized plasma derived from the hydrogen stream with the pre-heated lean gas stream; G. Separating the gas-solid stream resulting from the reaction into a spent catalyst phase stream and a gaseous effluent stream; H. Separating the gaseous effluent stream from the disengagement means into four streams; I. Regenerating the spent catalyst stream in a regenerator by combustion of the carbon build-up on the spent catalyst in an oxidizing gas stream; J. Transferring the regenerated catalyst back into the catalytic bed reactor and into the short residence time reactor; K. Recycling all rich gas streams obtained in steps C and H back to the catalytic bed reactor; L. Recycling the lean gas stream obtained in step H back to the pre-heating furnace of step D.

  7. Natural Products for Cancer Prevention

    PubMed Central

    Greenlee, Heather

    2013-01-01

    OBJECTIVES To review the clinical trial literature on the use and effects of natural products for cancer prevention. DATA SOURCES Clinical trials published in PubMed. CONCLUSION There is a growing body of literature on the use of natural products for cancer prevention. To date, few trials have demonstrated conclusive benefit. Current guidelines recommend against the use of natural products for cancer prevention. IMPLICATIONS FOR NURSING PRACTICE Clinicians should ask patients about their use of natural products and motivations for use. If patients are using natural products specifically for cancer prevention, they should be counseled on the current guidelines, as well as their options for other cancer prevention strategies. PMID:22281308

  8. Natural gas monthly, June 1996

    SciTech Connect

    1996-06-24

    The natural gas monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information. The feature article for this month is Natural Gas Industry Restructuring and EIA Data Collection.

  9. Natural gas monthly, August 1993

    SciTech Connect

    Not Available

    1993-08-25

    The Natural Gas Monthly (NGM) is prepared in the Data Operations Branch of the Reserves and Natural Gas Division, Office of Oil and Gas, Energy Information Administration (EIA), US Department of Energy (DOE). The NGM highhghts activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information.

  10. Natural gas monthly, November 1996

    SciTech Connect

    1996-11-01

    The report highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the Natural Gas Monthly features articles designed to assist readers in using and interpreting natural gas information. The feature article this month is ``US natural gas imports and exports-1995``. 6 figs., 24 tabs.

  11. Natural gas monthly, August 1995

    SciTech Connect

    1995-08-24

    The Natural Gas Monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information. This month`s feature article is on US Natural Gas Imports and Exports 1994.

  12. Natural gas monthly, July 1997

    SciTech Connect

    1997-07-01

    The Natural Gas Monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information. The feature article this month is entitled ``Intricate puzzle of oil and gas reserves growth.`` A special report is included on revisions to monthly natural gas data. 6 figs., 24 tabs.

  13. Natural gas monthly: April 1996

    SciTech Connect

    1996-04-01

    The Natural Gas Monthly highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information. This month`s feature article focuses on preliminary highlights from the 1995 natural gas industry. 7 figs., 25 tabs.

  14. Natural gas monthly, October 1996

    SciTech Connect

    1996-10-01

    The Natural Gas Monthly (NGM) is prepared in the Data Operations Branch of the Reserves and Natural Gas Division, Office of Oil and Gas, Energy Information Administration (EIA), U.S. Department of Energy (DOE). The NGM highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information.

  15. Natural Gas Monthly, October 1993

    SciTech Connect

    Not Available

    1993-11-10

    The (NGM) Natural Gas Monthly highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information. This month`s feature articles are: US Production of Natural Gas from Tight Reservoirs: and Expanding Rule of Underground Storage.

  16. Natural gas monthly, April 1997

    SciTech Connect

    1997-04-01

    The Natural Gas Monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are present3ed each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information. The feature article is entitled ``Natural gas pipeline and system expansions.`` 6 figs., 27 tabs.

  17. Natural gas monthly, October 1997

    SciTech Connect

    1997-10-01

    The Natural Gas Monthly highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information. The feature article in this issue is a special report, ``Comparison of Natural Gas Storage Estimates from the EIA and AGA.`` 6 figs., 26 tabs.

  18. Natural gas monthly, June 1994

    SciTech Connect

    Not Available

    1994-06-01

    The Natural Gas Monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information. The feature article this month is the executive summary from Natural Gas 1994: Issues and Trends. 6 figs., 31 tabs.

  19. Natural gas monthly, May 1997

    SciTech Connect

    1997-05-01

    The Natural Gas Monthly highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information. The feature article this month is ``Restructuring energy industries: Lessons from natural gas.`` 6 figs., 26 tabs.

  20. Natural gas marketing and transportation

    SciTech Connect

    Not Available

    1991-01-01

    This book covers: Overview of the natural gas industry; Federal regulation of marketing and transportation; State regulation of transportation; Fundamentals of gas marketing contracts; Gas marketing options and strategies; End user agreements; Transportation on interstate pipelines; Administration of natural gas contracts; Structuring transactions with the nonconventional source fuels credit; Take-or-pay wars- a cautionary analysis for the future; Antitrust pitfalls in the natural gas industry; Producer imbalances; Natural gas futures for the complete novice; State non-utility regulation of production, transportation and marketing; Natural gas processing agreements and Disproportionate sales, gas balancing, and accounting to royalty owners.