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Sample records for hypericum natural products

  1. New Synthetic Methods for Hypericum Natural Products

    SciTech Connect

    Jeon, Insik

    2006-01-01

    Organic chemistry has served as a solid foundation for interdisciplinary research areas, such as molecular biology and medicinal chemistry. An understanding of the biological activities and structural elucidations of natural products can lead to the development of clinically valuable therapeutic options. The advancements of modern synthetic methodologies allow for more elaborate and concise natural product syntheses. The theme of this study centers on the synthesis of natural products with particularly challenging structures and interesting biological activities. The synthetic expertise developed here will be applicable to analog syntheses and to other research problems.

  2. Hypercohones D-G, New Polycyclic Polyprenylated Acylphloroglucinol Type Natural Products from Hypericum cohaerens.

    PubMed

    Zhang, Jing-Jing; Yang, Xing-Wei; Ma, Jun-Zeng; Liu, Xia; Yang, Li-Xin; Yang, Sheng-Chao; Xu, Gang

    2014-04-01

    Four new polycyclic polyprenylated acylphloroglucinol type metabolites, hypercohones D-G (1-4), along with four known analogues (5-8), were isolated from the aerial parts of Hypericum cohaerens. The structures of these isolates were elucidated by extensive spectroscopic methods. The inhibitory activities of these isolates against five human cancer cell lines in vitro were also tested.

  3. Hyperforin production in Hypericum perforatum root cultures.

    PubMed

    Gaid, Mariam; Haas, Paul; Beuerle, Till; Scholl, Stephan; Beerhues, Ludger

    2016-03-20

    Extracts of the medicinal plant Hypericum perforatum are used to treat depression and skin irritation. A major API is hyperforin, characterized by sensitivity to light, oxygen and temperature. Total synthesis of hyperforin is challenging and its content in field-grown plants is variable. We have established in vitro cultures of auxin-induced roots, which are capable of producing hyperforin, as indicated by HPLC-DAD and ESI-MS analyses. The extraction yield and the productivity upon use of petroleum ether after solvent screening were ∼5 mg/g DW and ∼50 mg/L culture after six weeks of cultivation. The root cultures also contained secohyperforin and lupulones, which were not yet detected in intact plants. In contrast, they lacked another class of typical H. perforatum constituents, hypericins, as indicated by the analysis of methanolic extracts. Hyperforins and lupulones were stabilized and enriched as dicyclohexylammonium salts. Upon up-scaling of biomass production and downstream processing, H. perforatum root cultures may provide an alternative platform for the preparation of medicinal extracts and the isolation of APIs.

  4. Inhibition of bacterial growth and biofilm production by constituents from Hypericum spp.

    PubMed

    Sarkisian, S A; Janssen, M J; Matta, H; Henry, G E; Laplante, K L; Rowley, D C

    2012-07-01

    Biofilm embedded bacterial pathogens such as Staphylococcus spp., Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii are difficult to eradicate and are major sources of bacterial infections. New drugs are needed to combat these pathogens. Hypericum is a plant genus that contains species known to have antimicrobial properties. However, the specific constituents responsible for the antimicrobial properties are not entirely known, nor have most compounds been tested as inhibitors of biofilm development. The investigation presented here tested seven secondary metabolites isolated from the species Hypericum densiflorum, Hypericum ellipticum, Hypericum prolificum, and Hypericum punctatum as inhibitors of bacterial growth and biofilm production. Assays were conducted against Staphylococcus epidermidis, Staphylococcus aureus, clinical methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii. Five of the seven compounds demonstrated growth inhibition against the Gram-positive bacteria with minimum inhibitory concentrations (MIC) ranging from 1.95 µg/mL to 7.81 µg/mL. Four of the secondary metabolites inhibited biofilm production by certain Gram-positive strains at sub-MIC concentrations.

  5. Nature cures nature: Hypericum perforatum attenuates physical withdrawal signs in opium dependent rats.

    PubMed

    Khan, Munasib; Subhan, Fazal; Khan, Arif-Ullah; Abbas, Muzaffar; Ali, Gowhar; Rauf, Khalid; Gilani, Anwarul Hassan

    2014-05-01

    Hypericum perforatum Linn. (Hypericaceae) (St. John's wort) attenuates opium withdrawal signs. To explore the therapeutic potential of Hypericum perforatum in the management of opium-induced withdrawal syndrome. The effect of the Hypericum perforatum hydro-ethanol extract was investigated for potential to reverse naloxone (0.25 mg/kg)-induced opium withdrawal physical signs. Rats received opium extract (80-650 mg/kg) twice daily for 8 days along with Hypericum perforatum (20 mg/kg, orally) twice daily in chronic treatment and the same single dose 1 h before induction of withdrawal syndrome in the acute treated group. Hypericum perforatum reduced stereotype jumps and wet dog shake number in the chronic treatment compared to the saline control group (F(2, 24) = 3.968, p < 0. 05) and (F(2, 24) = 3.689, p < 0.05), respectively. The plant extract in the acutely treated group reduced diarrhea (F(2, 24) = 4.850, p < 0. 05 vs. saline). It decreased rectal temperature by chronic treatment at 30 min (F(2, 24) = 4.88, p < 0.05), 60 min (F(2, 240 = 5.364, p < 0.01) and 120 min (F(2, 24) = 4.907, p < 0.05). This study reveals that the extract of Hypericum perforatum attenuates some physical signs of opium withdrawal syndrome possibly through direct or indirect interaction with opioid receptors. Further study is needed to clarify its mechanism.

  6. Comparative authentication of Hypericum perforatum herbal products using DNA metabarcoding, TLC and HPLC-MS.

    PubMed

    Raclariu, Ancuta Cristina; Paltinean, Ramona; Vlase, Laurian; Labarre, Aurélie; Manzanilla, Vincent; Ichim, Mihael Cristin; Crisan, Gianina; Brysting, Anne Krag; de Boer, Hugo

    2017-05-02

    Many herbal products have a long history of use, but there are increasing concerns over product efficacy, safety and quality in the wake of recent cases exposing discrepancies between labeling and constituents. When it comes to St. John's wort (Hypericum perforatum L.) herbal products, there is limited oversight, frequent off-label use and insufficient monitoring of adverse drug reactions. In this study, we use amplicon metabarcoding (AMB) to authenticate 78 H. perforatum herbal products and evaluate its ability to detect substitution compared to standard methods using thin-layer chromatography (TLC) and high performance liquid chromatography coupled with mass spectrometry (HPLC-MS). Hypericum perforatum was detected in 68% of the products using AMB. Furthermore, AMB detected incongruence between constituent species and those listed on the label in all products. Neither TLC nor HPLC-MS could be used to unambiguously identify H. perforatum. They are accurate methods for authenticating presence of the target compounds, but have limited efficiency in detecting infrageneric substitution and do not yield any information on other plant ingredients in the products. Random post-marketing AMB of herbal products by regulatory agencies could raise awareness among consumers of substitution and would provide an incentive to manufacturers to increase quality control from raw ingredients to commercialized products.

  7. Essential Oil and Volatile Components of the Genus Hypericum (Hypericaceae)

    PubMed Central

    Crockett, Sara L.

    2010-01-01

    The flowering plant genus Hypericum (Hypericaceae) contains the well-known medicinally valuable species Hypericum perforatum (common St. John’s wort). Species of Hypericum contain many bioactive constituents, including proanthocyanins, flavonoids, biflavonoids, xanthones, phenylpropanes and naphthodianthrones that are characterized by their relative hydrophilicity, as well as acylphloroglucinols and essential oil components that are more hydrophobic in nature. A concise review of the scientific literature pertaining to constituents of Hypericum essential oils and volatile fractions is presented. PMID:20923012

  8. Prenylated phenyl polyketides and acylphloroglucinols from Hypericum peplidifolium.

    PubMed

    Fobofou, Serge Alain Tanemossu; Harmon, Chelsea Rebecca; Lonfouo, Antoine Honoré Nkuete; Franke, Katrin; Wright, Stephen M; Wessjohann, Ludger A

    2016-04-01

    In search for new or chemo-taxonomically relevant bioactive compounds from chemically unexplored Hypericum species, four previously undescribed natural products, named peplidiforones A-D were isolated and characterized from Hypericum peplidifolium A. Rich., together with six known compounds. The structures of all compounds were elucidated by extensive 1D- and 2D-NMR experiments, high resolution mass spectrometric analyses (HR-MS), and by comparison with data reported in the literature. Seven of these compounds are phenyl polyketides while three are acylphloroglucinol type compounds. Peplidiforone C, which possesses an unusual carbon skeleton consisting of a furan ring substituted by a 2,2-dimethylbut-3-enoyl moiety, is the first example of a prenylated furan derivative isolated from the genus Hypericum. The cytotoxicity, antifungal, and anti-herpes simplex virus type 1 (HSV-1) activities of extracts and compounds are described.

  9. The essential oils of the aerial parts of two Hypericum taxa (Hypericum triquetrifolium and Hypericum aviculariifolium subsp. depilatum var. depilatum (Clusiaceae)) from Turkey.

    PubMed

    Yuce, Ebru; Bagci, Eyup

    2012-11-01

    In this study, essential oil compositions of two Hypericum L. taxa (Hypericum triquetrifolium Turra. and Hypericum aviculariifolium Jaub. et Spach subsp. depilatum var. depilatum (Freyn et Bornm.) Robson) naturally grown in Turkey were determined using gas chromatography and gas chromatography-mass spectrometry systems. The essential oils were obtained by hydrodistillation from the aerial parts of plants. A total of 45 compounds were identified in the essential oils of H. triquetrifolium; 1-hexanal (18.8%), 3-methylnonane (12.5%) and α-pinene (12.3%). In this study, 41 components were identified in H. aviculariifolium subsp. depilatum var. depilatum oil; α-pinene (52.1%), germacrene D (8.5%) and β-pinene (3.6%) were the predominant constituents. The essential oil analysis showed that monoterpene concentrations were higher than that of the sesquiterpenes in both oils. The results were discussed in the meaning of the usefulness of these plants and their chemicals as natural products and potential usage in chemotaxonomy.

  10. Effects of Polysaccharide Elicitors on Secondary Metabolite Production and Antioxidant Response in Hypericum perforatum L. Shoot Cultures

    PubMed Central

    Gadzovska Simic, Sonja; Maury, Stéphane; Delaunay, Alain; Joseph, Claude; Hagège, Daniel

    2014-01-01

    The effects of polysaccharide elicitors such as chitin, pectin, and dextran on the production of phenylpropanoids (phenolics and flavonoids) and naphtodianthrones (hypericin and pseudohypericin) in Hypericum perforatum shoot cultures were studied. Nonenzymatic antioxidant properties (NEAOP) and peroxidase (POD) activity were also observed in shoot extracts. The activities of phenylalanine ammonia lyase (PAL) and chalcone-flavanone isomerase (CHFI) were monitored to estimate channeling in phenylpropanoid/flavonoid pathways of elicited shoot cultures. A significant suppression of the production of total phenolics and flavonoids was observed in elicited shoots from day 14 to day 21 of postelicitation. This inhibition of phenylpropanoid production was probably due to the decrease in CHFI activity in elicited shoots. Pectin and dextran promoted accumulation of naphtodianthrones, particularly pseudohypericin, within 21 days of postelicitation. The enhanced accumulation of naphtodianthrones was positively correlated with an increase of PAL activity in elicited shoots. All tested elicitors induced NEAOP at day 7, while chitin and pectin showed increase in POD activity within the entire period of postelicitation. The POD activity was in significantly positive correlation with flavonoid and hypericin contents, suggesting a strong perturbation of the cell redox system and activation of defense responses in polysaccharide-elicited H. perforatum shoot cultures. PMID:25574489

  11. Effects of polysaccharide elicitors on secondary metabolite production and antioxidant response in Hypericum perforatum L. shoot cultures.

    PubMed

    Gadzovska Simic, Sonja; Tusevski, Oliver; Maury, Stéphane; Delaunay, Alain; Joseph, Claude; Hagège, Daniel

    2014-01-01

    The effects of polysaccharide elicitors such as chitin, pectin, and dextran on the production of phenylpropanoids (phenolics and flavonoids) and naphtodianthrones (hypericin and pseudohypericin) in Hypericum perforatum shoot cultures were studied. Nonenzymatic antioxidant properties (NEAOP) and peroxidase (POD) activity were also observed in shoot extracts. The activities of phenylalanine ammonia lyase (PAL) and chalcone-flavanone isomerase (CHFI) were monitored to estimate channeling in phenylpropanoid/flavonoid pathways of elicited shoot cultures. A significant suppression of the production of total phenolics and flavonoids was observed in elicited shoots from day 14 to day 21 of postelicitation. This inhibition of phenylpropanoid production was probably due to the decrease in CHFI activity in elicited shoots. Pectin and dextran promoted accumulation of naphtodianthrones, particularly pseudohypericin, within 21 days of postelicitation. The enhanced accumulation of naphtodianthrones was positively correlated with an increase of PAL activity in elicited shoots. All tested elicitors induced NEAOP at day 7, while chitin and pectin showed increase in POD activity within the entire period of postelicitation. The POD activity was in significantly positive correlation with flavonoid and hypericin contents, suggesting a strong perturbation of the cell redox system and activation of defense responses in polysaccharide-elicited H. perforatum shoot cultures.

  12. Pilot-scale culture of Hypericum perforatum L. adventitious roots in airlift bioreactors for the production of bioactive compounds.

    PubMed

    Cui, Xi-Hua; Murthy, Hosakatte Niranjana; Paek, Kee-Yoeup

    2014-09-01

    Hypericum perforatum L. (St. John's Wort) is an important medicinal plant which is widely used in the treatment for depression and irritable bowel syndrome. It is also used as a dietary supplement. Major bioactive phytochemicals of H. perforatum are phenolics and flavonoids. Quality of these phytochemicals is dramatically influenced by environmental and biological factors in the field grown plants. As an alternative, we have developed adventitious root cultures in large-scale bioreactors for the production of useful phytochemicals. Adventitious roots of H. perforatum were cultured in 500 l pilot-scale airlift bioreactors using half-strength Murashige and Skoog medium with an ammonium and nitrate ratio of 5:25 mM and supplemented with 1.0 mg l(-1) indole butyric acid, 0.1 mg l(-1) kinetin, and 3 % sucrose for the production of bioactive phenolics and flavonoids. Then 4.6 and 6.3 kg dry biomass were realized in the 500 l each of drum-type and balloon-type bioreactors, respectively. Accumulation of 66.9 mg g(-1) DW of total phenolics, 48.6 mg g(-1) DW of total flavonoids, 1.3 mg g(-1) DW of chlorogenic acid, 0.01 mg g(-1) DW of hyperin, 0.04 mg g(-1) DW of hypericin, and 0.01 mg g(-1) DW of quercetin could be achieved with adventitious roots cultured in 500 l balloon-type airlift bioreactors. Our findings demonstrate the possibilities of using H. perforatum adventitious root cultures for the production of useful phytochemicals to meet the demand of pharmaceutical and food industry.

  13. Phytochemical analysis and in vitro biological activity of three Hypericum species from the Canary Islands (Hypericum reflexum, Hypericum canariense and Hypericum grandifolium).

    PubMed

    Zorzetto, Christian; Sánchez-Mateo, Candelaria C; Rabanal, Rosa M; Lupidi, Giulio; Petrelli, Dezemona; Vitali, Luca A; Bramucci, Massimo; Quassinti, Luana; Caprioli, Giovanni; Papa, Fabrizio; Ricciutelli, Massimo; Sagratini, Gianni; Vittori, Sauro; Maggi, Filippo

    2015-01-01

    In the present work we carried out a phytochemical and biological investigation on three Hypericum species, i.e. Hypericum reflexum, Hypericum canariense and Hypericum grandifolium, from the Canary Islands where they are traditionally used as diuretic, wound healing, vermifuge, sedative and antidepressive agents. The polar extracts of the top flowering aerial parts, prepared by Soxhlet apparatus using a methanol-acetone (1:1) extracting mixture, were analyzed by HPLC-DAD and HPLC-MS for the content of eight biomarkers such as hypericin, hyperforin, chlorogenic acid, rutin, hyperoside, isoquercitrin, quercitrin and quercetin, whereas the hydrodistilled essential oils were analyzed by GC-FID and GC-MS. The three Hypericum species had different results in both polar and volatile constituents, H. reflexum being the only one endowed with a small amount of naphtodianthrones (hypericin and pseudohypericin), and containing high levels of chlorogenic acid, rutin and volatile mono- and sesquiterpenes. After chemical characterization, all products were in vitro biologically assayed for antiproliferative activity on human tumor cell lines by MTT assay, for antioxidant potential by DPPH, ABTS and FRAP assays, and for antimicrobial activity by the agar disc diffusion and microdilution methods. Results revealed interesting bioactivities and differences between polar extracts and essential oils, with the former being endowed with significant antioxidant activity and the latter with comparable inhibition effects on the tumor cells (A375, MDA-MB 231 and HCT 116) to that of cisplatin.

  14. An overview of anticancer activity of Garcinia and Hypericum.

    PubMed

    Brito, Lavínia de C; Rangel Berenger, Ana Luiza; Figueiredo, Maria Raquel

    2017-03-28

    Cancer is one of the leading causes of death worldwide (approximately 8.2 million cases/year) and, over the next two decades, a 70% increase in new cancer cases is expected. Through analysis of the available drugs between the years of 1930 and 2014, it was found that 48% were either natural products or their derivatives. This proportion increased to 66% when semi-synthetic products were included. The family Clusiaceae Juss. (Malpighiales) includes approximately 1000 species distributed throughout all tropical and temperate regions. The phytochemical profile of this family includes many chemicals with interesting pharmacological activities, including anticancer activities. This study includes an overview of the in vitro and in vivo anticancer activity of secondary metabolites from Garcinia and Hypericum and the mechanisms involved in this activity. Hypericum no longer belong to Clusiaceae family, but was considered in the past by taxonomists, due to similarities with this family. Research in the area has shown that several compounds belonging to different chemical classes exhibit activity in several tumor cell lines in different experimental models. This review shows the significant antineoplasic activity of these compounds, in particular of these two genera and validates the importance of natural products in the search for anticancer drugs.

  15. Do other Hypericum species have medical potential as St. John's wort (Hypericum perforatum)?

    PubMed

    Stojanović, G; Ðorđević, A; Šmelcerović, A

    2013-01-01

    species are: H. sampsonii, H. ascyron, H. foliosum, H. geminiflorum and H. scabrum. However, only a few studies concerning the activity of extracts and isolated compounds were done in vivo. Also, data on the safe usage of Hypericum constituents as phytotherapeutics are scarce. Since some of Hypericum species are scarcely distributed or endemic as well as some of the secondary metabolites are presented in very small amounts, bio-production, especially endophytes, could represent an abundant and reliable source of pharmacologically active metabolites of Hypericum species for exploitation in pharmaceutical industry.

  16. Inhibition of Prostaglandin E2 Production by Anti-inflammatory Hypericum perforatum Extracts and Constituents in RAW264.7 Mouse Macrophage Cells

    PubMed Central

    Hammer, Kimberly D. P.; Hillwig, Matthew L.; Solco, Avery K. S.; Dixon, Philip M.; Delate, Kathleen; Murphy, Patricia A.; Wurtele, Eve S.; Birt, Diane F.

    2008-01-01

    Hypericum perforatum (Hp) is commonly known for its antiviral, antidepressant, and cytotoxic properties, but traditionally Hp was also used to treat inflammation. In this study, the anti-inflammatory activity and cytotoxicity of different Hp extractions and accessions and constituents present within Hp extracts were characterized. In contrast to the antiviral activity of Hp, the anti-inflammatory activity observed with all Hp extracts was light-independent. When pure constituents were tested, the flavonoids, amentoflavone, hyperforin, and light-activated pseudohypericin, displayed anti-inflammatory activity, albeit at concentrations generally higher than the amount present in the Hp extracts. Constituents that were present in the Hp extracts at concentrations that inhibited the production of prostaglandin E2 (PGE2) were pseudohypericin and hyperforin, suggesting that they are the primary anti-inflammatory constituents along with the flavonoids, and perhaps the interactions of these constituents and other unidentified compounds are important for the anti-inflammatory activity of the Hp extracts. PMID:17696442

  17. Taxonomy and Chemotaxonomy of the Genus Hypericum

    PubMed Central

    Crockett, Sara L.; Robson, Norman K. B.

    2012-01-01

    The genus Hypericum L. (St. John’s Wort, Hypericaceae) includes, at the most recent count, 469 species that are either naturally occurring on, or which have been introduced to, every continent in the world, except Antarctica. These species occur as herbs, shrubs, and infrequently trees, and are found in a variety of habitats in temperate regions and in high mountains in the tropics, avoiding only zones of extreme aridity, temperature and/or salinity. Monographic work on the genus has resulted in the recognition and description of 36 taxonomic sections, delineated by specific combinations of morphological characteristics and biogeographic distribution ranges. Hypericum perforatum L. (Common St. John’s wort, section Hypericum), one of the best-known members of the genus, is an important medicinal herb of which extracts are taken for their reported activity against mild to moderate depression. Many other species have been incorporated in traditional medicine systems in countries around the world, or are sold as ornamentals. Several classes of interesting bioactive secondary metabolites, including naphthodianthrones (e.g. hypericin and pseudohypericin), flavonol glycosides (e.g. isoquercitrin and hyperoside), biflavonoids (e.g. amentoflavone), phloroglucinol derivatives (e.g. hyperforin and adhyperforin) and xanthones have been identified from members of the genus. A general overview of the taxonomy of the genus and the distribution of relevant secondary metabolites is presented. PMID:22662019

  18. Production and laser-induced fluorescence spectroscopy (L.I.F.S.) of different Hypericum perforatum L. extracts

    NASA Astrophysics Data System (ADS)

    Skalkos, Dimitris; Filippidis, George; Kapsokalyvas, Dimitris; Meyer, Heiko; Papazoglou, Theodore; Karentzou, Eleni; Dimitriou, Heleni; Kalmanti, M.

    2005-04-01

    We are reporting elsewhere, the promising photodynamic effect of Hypericum perforatum L. extract (PMF) against T24, NBT-II tumor bladder cells, and HL-60 leukemic cells (using 630nm, and 530nm laser light respectively). The main advantages of the extract as a photosensitizer are its low cost, extensive availability, adequate solubility, minimal toxicity, and use with a range of wavelengths. Extraction of dry herb with methanol yields the methanolic extract (ME) in 11%, which is then fractionated using liquid / liquid extraction, yielding the polar methanolic fraction (PMF) in 9,9% overall yield. Hypericin, a photosensitizing ingredient of the herb, was found in these extracts in concentrations as low as 0,51%, and 0,57% respectively. Laser induced fluorescence spectra from the ME and PMF were recorded in order to evaluate their photodiagnostic capacity. An Argon-ion laser was employed for the excitation of the samples. It was shown that the extracts resulted in different fluorescence spectra related both to their intensity, and shape. The intensities of these spectra were only 8 times less compared to the fluorescence of pure hypericin. The dependence of the signal on the pH of the medium of pure hypericin and of PMF was also investigated in order to determine specific spectra variations. According to the results hypericin fluorescence signal fades smoothly in highly acidic medium, while it decreases sharply in highly basic environment. On the contrary PMF gives a slow decrease of fluorescence in both acidic and basic medium. These data suggest that PMF-induced fluorescence is highly sensitive in basic and acidic environment.

  19. Effects of Hypericum Perforatum, in a rodent model of periodontitis

    PubMed Central

    2010-01-01

    Background Hypericum perforatum is a medicinal plant species containing many polyphenolic compounds, namely flavonoids and phenolic acids. In this study we evaluate the effect of Hypericum perforatum in animal model of periodontitis. Methods Periodontitis was induced in adult male Sprague-Dawley rats by placing a nylon thread ligature around the lower 1st molars. Hypericum perforatum was administered at the dose of 2 mg/kg os, daily for eight days. At day 8, the gingivomucosal tissue encircling the mandibular first molar was removed. Results Periodontitis in rats resulted in an inflammatory process characterized by edema, neutrophil infiltration and cytokine production that was followed by the recruitment of other inflammatory cells, production of a range of inflammatory mediators such as NF-κB and iNOS expression, the nitration of tyrosine residues and activation of the nuclear enzyme poly (ADP-ribose) polymerase; apoptosis and the degree of gingivomucosal tissues injury. We report here that Hypericum perforatum exerts potent anti-inflammatory effects significantly reducing all of the parameters of inflammation as described above. Conclusions Taken together, our results clearly demonstrate that treatment with Hypericum reduces the development of inflammation and tissue injury, events associated with periodontitis. PMID:21092263

  20. Pistil Transcriptome Analysis to Disclose Genes and Gene Products Related to Aposporous Apomixis in Hypericum perforatum L.

    PubMed Central

    Galla, Giulio; Zenoni, Sara; Avesani, Linda; Altschmied, Lothar; Rizzo, Paride; Sharbel, Timothy F.; Barcaccia, Gianni

    2017-01-01

    Unlike sexual reproduction, apomixis encompasses a number of reproductive strategies, which permit maternal genome inheritance without genetic recombination and syngamy. The key biological features of apomixis are the circumvention of meiosis (i.e., apomeiosis), the differentiation of unreduced embryo sacs and egg cells, and their autonomous development in functional embryos through parthenogenesis, and the formation of viable endosperm either via fertilization-independent means or following fertilization with a sperm cell. Despite the importance of apomixis for breeding of crop plants and although much research has been conducted to study this process, the genetic control of apomixis is still not well understood. Hypericum perforatum is becoming an attractive model system for the study of aposporous apomixis. Here we report results from a global gene expression analysis of H. perforatum pistils collected from sexual and aposporous plant accessions for the purpose of identifying genes, biological processes and molecular functions associated with the aposporous apomixis pathway. Across two developmental stages corresponding to the expression of aposporous apomeiosis and parthenogenesis in ovules, a total of 224 and 973 unigenes were found to be significantly up- and down-regulated with a fold change ≥ 2 in at least one comparison, respectively. Differentially expressed genes were enriched for multiple gene ontology (GO) terms, including cell cycle, DNA metabolic process, and single-organism cellular process. For molecular functions, the highest scores were recorded for GO terms associated with DNA binding, DNA (cytosine-5-)-methyltransferase activity and heterocyclic compound binding. As deregulation of single components of the sexual developmental pathway is believed to be a trigger of the apomictic reproductive program, all genes involved in sporogenesis, gametogenesis and response to hormonal stimuli were analyzed in great detail. Overall, our data suggest that

  1. Pistil Transcriptome Analysis to Disclose Genes and Gene Products Related to Aposporous Apomixis in Hypericum perforatum L.

    PubMed

    Galla, Giulio; Zenoni, Sara; Avesani, Linda; Altschmied, Lothar; Rizzo, Paride; Sharbel, Timothy F; Barcaccia, Gianni

    2017-01-01

    Unlike sexual reproduction, apomixis encompasses a number of reproductive strategies, which permit maternal genome inheritance without genetic recombination and syngamy. The key biological features of apomixis are the circumvention of meiosis (i.e., apomeiosis), the differentiation of unreduced embryo sacs and egg cells, and their autonomous development in functional embryos through parthenogenesis, and the formation of viable endosperm either via fertilization-independent means or following fertilization with a sperm cell. Despite the importance of apomixis for breeding of crop plants and although much research has been conducted to study this process, the genetic control of apomixis is still not well understood. Hypericum perforatum is becoming an attractive model system for the study of aposporous apomixis. Here we report results from a global gene expression analysis of H. perforatum pistils collected from sexual and aposporous plant accessions for the purpose of identifying genes, biological processes and molecular functions associated with the aposporous apomixis pathway. Across two developmental stages corresponding to the expression of aposporous apomeiosis and parthenogenesis in ovules, a total of 224 and 973 unigenes were found to be significantly up- and down-regulated with a fold change ≥ 2 in at least one comparison, respectively. Differentially expressed genes were enriched for multiple gene ontology (GO) terms, including cell cycle, DNA metabolic process, and single-organism cellular process. For molecular functions, the highest scores were recorded for GO terms associated with DNA binding, DNA (cytosine-5-)-methyltransferase activity and heterocyclic compound binding. As deregulation of single components of the sexual developmental pathway is believed to be a trigger of the apomictic reproductive program, all genes involved in sporogenesis, gametogenesis and response to hormonal stimuli were analyzed in great detail. Overall, our data suggest that

  2. Hypericum caprifoliatum and Hypericum connatum affect human trophoblast-like cells differentiation and Ca2+ influx

    PubMed Central

    da Conceição, Aline O.; von Poser, Gilsane Lino; Barbeau, Benoit; Lafond, Julie

    2014-01-01

    Objective To study the effect of crude methanol and n-hexane extracts of Hypericum connatum (H. connatum) and Hypericum caprifoliatum on trophoblast-like cells. Methods BeWo and JEG-3 trophoblast-like cells were submitted to different extract concentrations (1, 5, 10 and 15 µg/mL) and evaluated in relation to cell viability and in vitro trophoblast differentiation and function. Cell viability was evaluated using WST-1 reagent. Differentiation was measured by luciferase production, hCG production/release, and mitogen-activated protein kinase signaling pathway activation. The function of the trophoblast-like cells was measured by 45Ca2+ influx evaluation. Results The results showed a decrease in cell viability/proliferation. Both plants and different extracts induced a significant decrease in hCG production/release and luciferase production. H. connatum did not cause mitogen-activated protein kinase signaling pathway disturbance; however, Hypericum caprifoliatum n-hexane extract at 15 µg/mL inhibited extracellular signal-regulated kinase 1/2 activation. The significant increase in Ca2+ influx by JEG-3 cells was seen after short and long incubation times with H. connatum methanolic extract at 15 µg/mL. Conclusions The results indicated that these two Hypericum species extracts can interfere on trophoblast differentiation and Ca2+ influx, according to their molecular diversity. Although in vivo experiments are necessary to establish their action on placental formation and function, this study suggests that attention must be paid to the potential toxic effect of these plants. PMID:25182721

  3. 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

  4. 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. © 2015 Wiley Periodicals, Inc.

  5. Chemical composition and bioactivity of essential oils of Hypericum helianthemoides, Hypericum perforatum and Hypericum scabrum.

    PubMed

    Ghasemi Pirbalouti, Abdollah; Fatahi-Vanani, Maryam; Craker, Lyle; Shirmardi, Hamzeali

    2014-02-01

    A number Hypericum species are well known for their therapeutic efficacy and use in traditional medicine. The various species of Hypericum have been traditionally used for the treatment of wounds, eczema, burns, trauma, rheumatism, neuralgia, gastroenteritis, ulcers, hysteria, bedwetting and depression. This study evaluated the in vitro antioxidant, antibacterial and phytochemical properties of essential oils of Hypericum helianthemoides (Spach) Boiss., Hypericum perforatum L. and Hypericum scabrum L. (Hypericaceae) collected from alpine region of Southwest Iran. The essential oils obtained from dried flowering aerial parts of three Hypericum species were analyzed by gas chromatography and gas chromatography/mass spectrometry to determine chemical compositions. The antibacterial activity of essential oils within concentration ranges from 16 to 500 µg/mL was individually evaluated against Bacillus cereus, Listeria monocytogenes. Proteus vulgaris and Salmonella typhimurium. The 1,1-diphenyl-2-picrilhydrazyl (DPPH) radical scavenging activity of essential oils was determined using DPPH assay. Essential oil yield of H. helianthemoides. H. scabrum and H. perforatum were 0.12, 0.20 and 0.21 mL/100 g dried material, respectively. The major constituents of the essential oils were α-pinene (12.52-49.96%), β-pinene (6.34-9.70%), (E)-β-ocimene (4.44-12.54%), β-caryophyllene (1.19-5.67%), and germacrene-D (2.34-6.92%). The essential oils of three Hypericum species indicated moderate-to-good inhibitory activities against four bacteria, especially against L. monocytogenes. The essential oils of the three studied Hypericum species sourced in alpine region of West Iran were rich in monoterpene and sesquiterpenes hydrocarbons. Among the three tested species, the essential oil of H. scabrum showed the highest antibacterial and antioxidant activities.

  6. Bioactive compounds from Hypericum humifusum and Hypericum perfoliatum: inhibition potential of polyphenols with acetylcholinesterase and key enzymes linked to type-2 diabetes.

    PubMed

    Béjaoui, Afef; Ben Salem, Issam; Rokbeni, Nesrine; M'rabet, Yassine; Boussaid, Mohamed; Boulila, Abdennacer

    2017-12-01

    Natural products are reported to have a wide spectrum of pharmacological properties such as antimicrobial, anti-inflammatory and anti-cholinesterase. The genus Hypericum (Hypericaceae) is a source of a variety of molecules with different biological activities, notably hypericin and various phenolics. The goals of the present work were the determination of total phenolic and flavonoid content, hypericin and hyperforin concentration as well as the evaluation of biological of Hypericum humifusum L. (Hhu) and Hypericum perfoliatum L. (Hper). The various extracts of aerial parts were powdered, and then extracted with methanol. Antibacterial activity was performed according to minimum inhibitory concentration (MIC) and minimum bactericidal (MBC) methods against four Gram-positive bacteria, four Gram-negative bacteria and yeast. The results revealed that H. humifusum, bear the highest total phenolic and flavonoid content (48-113 mg GAE/g and 8-41 mg RE/g, respectively) as well as hypericin (60-90 mg/g) and hyperforin (8-30 mg/g) concentration. Both species showed significant antioxidant activity as revealed by DPPH, FRAP, ABTS, and metal chelating assays. H. humifusum exhibited a strong acetylcholinesterase (3.86-4.57 mg GALAEs/g), α-glucosidase (0.73-2.55 mmol ACEs/g) and α-amylase (3-8 mmol ACEs/g) inhibitory activity. The extract of H. humifusum exhibited strong antibacterial activity mainly against Staphylococcus epidermidis, Staphylococus aureus, and Enterococcus faecium (MIC values ranging from 200 to 250 μg/mL). The highest antifungal activity was showed for H. perfoliatum extract (MIC value = 250 μg/mL). The data suggest that H. humifusum could be used as valuable new natural agents with functional properties for pharmacology industries.

  7. 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.

  8. 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.

  9. Interaction between different extracts of Hypericum perforatum L. from Serbia and pentobarbital, diazepam and paracetamol.

    PubMed

    Rašković, Aleksandar; Cvejić, Jelena; Stilinović, Nebojša; Goločorbin-Kon, Svetlana; Vukmirović, Saša; Mimica-Dukić, Neda; Mikov, Momir

    2014-03-28

    Herb-drug interactions are an important safety concern and this study was conducted regarding the interaction between the natural top-selling antidepressant remedy Hypericum perforatum (Hypericaceae) and conventional drugs. This study examined the influence of acute pretreatment with different extracts of Hypericum perforatum from Serbia on pentobarbital-induced sleeping time, impairment of motor coordination caused by diazepam and paracetamol pharmacokinetics in mice. Ethanolic extract, aqueous extract, infusion, tablet and capsule of Hypericum perforatum were used in this experiment. The profile of Hypericum perforatum extracts as well as paracetamol plasma concentration was determined using RP-HPLC analysis. By quantitative HPLC analysis of active principles, it has been proven that Hypericum perforatum ethanolic extract has the largest content of naphtodianthrones: hypericin (57.77 µg/mL) and pseudohypericin (155.38 µg/mL). Pretreatment with ethanolic extract of Hypericum perforatum potentiated the hypnotic effect of pentobarbital and impairment of motor coordination caused by diazepam to the greatest extent and also increased paracetamol plasma concentration in comparison to the control group. These results were in correlation with naphtodianthrone concentrations. The obtained results have shown a considerable influence of Hypericum perforatum on pentobarbital and diazepam pharmacodynamics and paracetamol pharmacokinetics.

  10. Rare biscoumarin derivatives and flavonoids from Hypericum riparium.

    PubMed

    Tanemossu, Serge Alain Fobofou; Franke, Katrin; Arnold, Norbert; Schmidt, Jürgen; Wabo, Hippolyte Kamdem; Tane, Pierre; Wessjohann, Ludger A

    2014-09-01

    Hypericum riparium A. Chev. is a Cameroonian medicinal plant belonging to the family Guttiferae. Chemical investigation of the methanol extract of the stem bark of H. riparium led to the isolation of four natural products, 7,7'-dihydroxy-6,6'-biscoumarin (1), 7,7'-dihydroxy-8,8'-biscoumarin (2), 7-methoxy-6,7'-dicoumarinyl ether (3), 2'-hydroxy-5'-(7″-methoxycoumarin-6″-yl)-4'-methoxyphenylpropanoic acid (4), together with one known 7,7'-dimethoxy-6,6'-biscoumarin (5), two flavones, 2'-methoxyflavone (6) and 3'-methoxy flavone (7), and two steroids, stigmast-4-en-3-one (8) and ergosta-4,6,8,22-tetraen-3-one (9). In addition, tetradecanoic acid (10), n-pentadecanoic acid (11), hexadecanoic acid (12), cis-10-heptadecenoic acid (13), octadecanoic acid (14) campesterol (15), stigmasterol (16), β-sitosterol (17), stigmastanol (18), β-eudesmol (19), 1-hexadecanol (20), and 1-octadecanol (21) were identified by GC-MS analysis. Compound 4 consists of a phenylpropanoic acid derivative fused with a coumarin unit, while compounds 2 and 3 are rare members of C8-C8' and C7-O-C6 linked biscoumarins. Their structures were elucidated by UV, IR, extensive 1D- and 2D-NMR experiments and electrospray (ESI) high resolution mass spectrometry (MS) including detailed MS/MS studies. This is the first report on the isolation of biscoumarins from the genus Hypericum, although simple coumarin derivatives have been reported from this genus in the literature. The cytotoxic activities of compounds 2-5 were evaluated against the human prostate cancer cell line PC-3 and the colon cancer cell line HT-29. They do not exhibit any significant cytotoxic activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Natural Product Molecular Fossils.

    PubMed

    Falk, Heinz; Wolkenstein, Klaus

    2017-01-01

    The natural products synthesized by organisms that were living a long time ago gave rise to their molecular fossils. These can consist of either the original unchanged compounds or they may undergo peripheral transformations in which their skeletons remain intact. In cases when molecular fossils can be traced to their organismic source, they are termed "geological biomarkers".This contribution describes apolar and polar molecular fossils and, in particular biomarkers, along the lines usually followed in organic chemistry textbooks, and points to their bioprecursors when available. Thus, the apolar compounds are divided in linear and branched alkanes followed by alicyclic compounds and aromatic and heterocyclic molecules, and, in particular, the geoporphyrins. The polar molecular fossils contain as functional groups or constituent units ethers, alcohols, phenols, carbonyl groups, flavonoids, quinones, and acids, or are polymers like kerogen, amber, melanin, proteins, or nucleic acids. The final sections discuss the methodology used and the fundamental processes encountered by the biomolecules described, including diagenesis, catagenesis, and metagenesis.

  12. Marine natural products.

    PubMed

    Blunt, John W; Copp, Brent R; Hu, Wan-Ping; Munro, Murray H G; Northcote, Peter T; Prinsep, Michèle R

    2009-02-01

    This review covers the literature published in 2007 for marine natural products, with 948 citations(627 for the period January to December 2007) referring to compounds isolated from marine microorganisms and phytoplankton, green algae, brown algae, red algae, sponges, cnidarians,bryozoans, molluscs, tunicates, echinoderms and true mangrove plants. The emphasis is on new compounds (961 for 2007), 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.1 Introduction, 2 Reviews, 3 Marine microorganisms and phytoplankton, 4 Green algae, 5 Brown algae, 6 Red algae, 7 Sponges, 8 Cnidarians, 9 Bryozoans, 10 Molluscs, 11 Tunicates (ascidians),12 Echinoderms, 13 Miscellaneous, 14 Conclusion, 15 References.

  13. Pest management with natural products

    USDA-ARS?s Scientific Manuscript database

    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...

  14. A Natural Love of Natural Products

    PubMed Central

    2008-01-01

    Recent research on the chemistry of natural products from the author’s group that led to the receipt of the ACS Ernest Guenther Award in the Chemistry of Natural Products is reviewed. REDOR NMR and synthetic studies established the T-taxol conformation as the bioactive tubulin-binding conformation, and these results were confirmed by the synthesis of compounds which clearly owed their activity or lack of activity to whether or not they could adopt the T-taxol conformation. Similar studies with the epothilones suggest that the current tubulin-binding model needs to be modified. Examples of natural products discovery and biodiversity conservation in Suriname and Madagascar are also presented, and it is concluded that natural products chemistry will continue to make significant contributions to drug discovery. PMID:18459734

  15. 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

  16. Conservation Strategies in the Genus Hypericum via Cryogenic Treatment

    PubMed Central

    Bruňáková, Katarína; Čellárová, Eva

    2016-01-01

    In the genus Hypericum, cryoconservation offers a strategy for maintenance of remarkable biodiversity, emerging from large inter- and intra-specific variability in morphological and phytochemical characteristics. Long-term cryostorage thus represents a proper tool for preservation of genetic resources of endangered and threatened Hypericum species or new somaclonal variants with unique properties. Many representatives of the genus are known as producers of pharmacologically important polyketides, namely naphthodianthrones and phloroglucinols. As a part of numerous in vitro collections, the nearly cosmopolitan Hypericum perforatum – Saint John’s wort – has become a suitable model system for application of biotechnological approaches providing an attractive alternative to the traditional methods for secondary metabolite production. The necessary requirements for efficient cryopreservation include a high survival rate along with an unchanged biochemical profile of plants regenerated from cryopreserved cells. Understanding of the processes which are critical for recovery of H. perforatum cells after the cryogenic treatment enables establishment of cryopreservation protocols applicable to a broad number of Hypericum species. Among them, several endemic taxa attract a particular attention due to their unique characteristics or yet unrevealed spectrum of bioactive compounds. In this review, recent advances in the conventional two-step and vitrification-based cryopreservation techniques are presented in relation to the recovery rate and biosynthetic capacity of Hypericum spp. The pre-cryogenic treatments which were identified to be crucial for successful post-cryogenic recovery are discussed. Being a part of genetic predisposition, the freezing tolerance as a necessary precondition for successful post-cryogenic recovery is pointed out. Additionally, a beneficial influence of cold stress on modulating naphthodianthrone biosynthesis is outlined. PMID:27200032

  17. Conservation Strategies in the Genus Hypericum via Cryogenic Treatment.

    PubMed

    Bruňáková, Katarína; Čellárová, Eva

    2016-01-01

    In the genus Hypericum, cryoconservation offers a strategy for maintenance of remarkable biodiversity, emerging from large inter- and intra-specific variability in morphological and phytochemical characteristics. Long-term cryostorage thus represents a proper tool for preservation of genetic resources of endangered and threatened Hypericum species or new somaclonal variants with unique properties. Many representatives of the genus are known as producers of pharmacologically important polyketides, namely naphthodianthrones and phloroglucinols. As a part of numerous in vitro collections, the nearly cosmopolitan Hypericum perforatum - Saint John's wort - has become a suitable model system for application of biotechnological approaches providing an attractive alternative to the traditional methods for secondary metabolite production. The necessary requirements for efficient cryopreservation include a high survival rate along with an unchanged biochemical profile of plants regenerated from cryopreserved cells. Understanding of the processes which are critical for recovery of H. perforatum cells after the cryogenic treatment enables establishment of cryopreservation protocols applicable to a broad number of Hypericum species. Among them, several endemic taxa attract a particular attention due to their unique characteristics or yet unrevealed spectrum of bioactive compounds. In this review, recent advances in the conventional two-step and vitrification-based cryopreservation techniques are presented in relation to the recovery rate and biosynthetic capacity of Hypericum spp. The pre-cryogenic treatments which were identified to be crucial for successful post-cryogenic recovery are discussed. Being a part of genetic predisposition, the freezing tolerance as a necessary precondition for successful post-cryogenic recovery is pointed out. Additionally, a beneficial influence of cold stress on modulating naphthodianthrone biosynthesis is outlined.

  18. Evaluation of the cytotoxicity, mutagenicity and antimutagenicity of a natural antidepressant, Hypericum perforatum L. (St. John’s wort), on vegetal and animal test systems

    PubMed Central

    2013-01-01

    Background St. John’s wort (Hypericum perforatum L.) is an herbaceous plant that is native to Europe, West Asia and North Africa and that is recognized and used worldwide for the treatment of mild and moderate depression. It also has been shown to be therapeutic for the treatment of burns, bruises and swelling and can be used for its wound healing, antiviral, antimicrobial, antioxidant, analgesic, hepato-protective and anxiolytic properties. The aim of this study was to evaluate the potential cytotoxic, mutagenic and antimutagenic action of H. Perforatum. Methods Meristematic cells were used as the test system for Allium cepa L., and bone marrow cells from Rattus norvegicus, ex vivo, were used to calculate the mitotic index and the percentage of chromosomal aberration. Statistical analysis was performed using the chi-square test. Results This medicinal plant had no cytotoxic potential in the vegetal test system evaluated. In the animal test system, none of the acute treatments, including intraperitoneal gavage and subchronic gavage, were cytotoxic or mutagenic. Moreover, this plant presented antimutagenic activity against the clastogenic action of cyclophosphamide, as confirmed in pre-treatment (76% reduction in damage), simultaneous treatment (95%) and post-treatment (97%). Conclusions Thus, the results of this study suggest that the administration of H. perforatum, especially by gavage similar to oral consumption used by humans, is safe and with beneficial antimutagenic potential. PMID:23647762

  19. Natural products as aromatase inhibitors.

    PubMed

    Balunas, Marcy J; Su, Bin; Brueggemeier, Robert W; Kinghorn, A Douglas

    2008-08-01

    With the clinical success of several synthetic aromatase inhibitors (AIs) in the treatment of postmenopausal estrogen receptor-positive breast cancer, researchers have also been investigating the potential of natural products as AIs. Natural products from terrestrial and marine organisms provide a chemically diverse array of compounds not always available through current synthetic chemistry techniques. Natural products that have been used traditionally for nutritional or medicinal purposes (e.g., botanical dietary supplements) may also afford AIs with reduced side effects. A thorough review of the literature regarding natural product extracts and secondary metabolites of plant, microbial, and marine origin that have been shown to exhibit aromatase inhibitory activity is presented herein.

  20. Natural disturbance production functions

    Treesearch

    Jeffrey P. Prestemon; D. Evan Mercer; John M. Pye

    2008-01-01

    Natural disturbances in forests are driven by physical and biological processes. Large, landscape scale disturbances derive primarily from weather (droughts, winds, ice storms, and floods), geophysical activities (earthquakes, volcanic eruptions), fires, insects, and diseases. Humans have invented ways to minimize their negative impacts and reduce their rates of...

  1. Hypericum triquetrifolium—Derived Factors Downregulate the Production Levels of LPS-Induced Nitric Oxide and Tumor Necrosis Factor-α in THP-1 Cells

    PubMed Central

    Saad, Bashar; AbouAtta, Bernadette Soudah; Basha, Walid; Hmade, Alaa; Kmail, Abdalsalam; Khasib, Said; Said, Omar

    2011-01-01

    Based on knowledge from traditional Arab herbal medicine, this in vitro study aims to examine the anti-inflammatory mechanism of Hypericum triquetrifolium by measuring the expression and release of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukine-6 (IL-6), and inducible nitric oxide synthase (iNOS) in human monocytic cells, THP-1. The effects were assessed by measuring the levels of secretory proteins and mRNA of TNF-α and IL-6, the levels of nitric oxide (NO) secretion and the expression of iNOS in THP-1 cells. Cells were treated with 5 μg lipopolysaccharide/ml (LPS) in the presence and absence of increasing concentrations of extracts from the aerial parts of H. triquetrifolium. During the entire experimental period, we used extract concentrations (up to 250 μg mL−1) that had no cytotoxic effects, as measured with MTT and LDH assays. Hypericum triquetrifolium extracts remarkably suppressed the LPS-induced NO release, significantly attenuated the LPS-induced transcription of iNOS and inhibited in a dose-dependent manner the expression and release of TNF-α. No significant effects were observed on the release of IL-6. Taken together, these results suggest that H. triquetrifolium probably exerts anti-inflammatory effects through the suppression of TNF-α and iNOS expressions. PMID:18955363

  2. Hypericum triquetrifolium-Derived Factors Downregulate the Production Levels of LPS-Induced Nitric Oxide and Tumor Necrosis Factor-α in THP-1 Cells.

    PubMed

    Saad, Bashar; Abouatta, Bernadette Soudah; Basha, Walid; Hmade, Alaa; Kmail, Abdalsalam; Khasib, Said; Said, Omar

    2011-01-01

    Based on knowledge from traditional Arab herbal medicine, this in vitro study aims to examine the anti-inflammatory mechanism of Hypericum triquetrifolium by measuring the expression and release of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukine-6 (IL-6), and inducible nitric oxide synthase (iNOS) in human monocytic cells, THP-1. The effects were assessed by measuring the levels of secretory proteins and mRNA of TNF-α and IL-6, the levels of nitric oxide (NO) secretion and the expression of iNOS in THP-1 cells. Cells were treated with 5 μg lipopolysaccharide/ml (LPS) in the presence and absence of increasing concentrations of extracts from the aerial parts of H. triquetrifolium. During the entire experimental period, we used extract concentrations (up to 250 μg mL(-1)) that had no cytotoxic effects, as measured with MTT and LDH assays. Hypericum triquetrifolium extracts remarkably suppressed the LPS-induced NO release, significantly attenuated the LPS-induced transcription of iNOS and inhibited in a dose-dependent manner the expression and release of TNF-α. No significant effects were observed on the release of IL-6. Taken together, these results suggest that H. triquetrifolium probably exerts anti-inflammatory effects through the suppression of TNF-α and iNOS expressions.

  3. Natural products: Taming reactive benzynes

    NASA Astrophysics Data System (ADS)

    Tasker, Sarah Z.; Hergenrother, Paul J.

    2017-06-01

    Natural products often serve as sources of new drugs, either directly or after synthetic modification, but site-selective functionalization of complex small molecules is challenging. Now, a method has been developed that enables selective modification of a wide range of natural products by engaging a benzyne intermediate in a variety of reaction modes.

  4. Benzoylphloroglucinol derivatives from Hypericum scabrum.

    PubMed

    Matsuhisa, Michiko; Shikishima, Yasuhiro; Takaishi, Yoshihisa; Honda, Gisho; Ito, Michiho; Takeda, Yoshio; Shibata, Hirohumi; Higuti, Tomihiko; Kodzhimatov, Olimjon K; Ashurmetov, Ozodbek

    2002-03-01

    Nine new polyprenylated benzoylphloroglucinol derivatives, hyperibones A-I (1-9), were isolated from the aerial parts of the Uzbekistan medicinal plant Hypericum scabrum. Their structures were determined mainly on the basis of spectroscopic evidence (2D NMR and HRMS). Compounds 1, 2, and 4 showed mild in vitro antibacterial activity against methicillin-resistance Staphylococus aureus (MRSA) and methicillin-sensitive Staphylococus aureus (MSSA).

  5. Natural products and diabetes treatment.

    PubMed

    Gori, M; Campbell, R K

    1998-01-01

    Many natural products are promoted to improve the health status of patients with diabetes by people making a profit on these products. Few of these claims have any scientific basis. Certain natural products are potentially damaging to patients with chronic diseases, especially if the products are used instead of proven scientific treatment regimens. Many individuals believe that if a product is natural it must be effective and safe. What is ironic is that if the products were safe and effective, and if studies would have been done on humans to prove safety and effectiveness, the sales of the products would greatly increase (as opposed to present limited sales as herbs from health food stores). Some of the products do have a beneficial effect, especially as a placebo if the patient believes that the product is going to work. As can be seen from the summary of products that are listed here that claim to improve the treatment of patients with diabetes, very few are available in a standard form that would produce a known positive effect. The few products that do have a mild impact on lowering blood glucose levels are much less effective than standard treatments. In a recent review of the role of plant-derived drugs and herbal medicines in healthcare, no natural products were listed as having a beneficial effect on diabetes. Diabetes care providers need to confront the issue of the use of natural products with their patients. Patients should be taught the importance of using proven, effective treatment regimens. Any patient who decides to use a natural product should be followed closely to make sure that no toxic effects occur and that treatment objectives are achieved.

  6. Hypericum sampsonii induces apoptosis and nuclear export of retinoid X receptor-alpha.

    PubMed

    Zeng, Jin-Zhang; Sun, De-Fu; Wang, Li; Cao, Xihua; Qi, Jian-Bin; Yang, Ting; Hu, Chang-Qi; Liu, Wen; Zhang, Xiao-Kun

    2006-10-01

    Natural products derived from plants provide a rich source for development of new anticancer drugs. Recent studies suggest that modulation of subcellular localization of retinoid X receptor-alpha (RXRalpha) represents a potential approach for inducing cancer cell apoptosis. In this study, we screened a herbal library for inducing translocation of RXRalpha from the nucleus to the cytoplasm. Our results revealed that the extract of Hypericum sampsonii, a member of the genus Hypericum, had remarkable effect on RXRalpha subcellular localization in various cancer cells. Treatment of NIH-H460 human lung cancer cells with H. sampsonii extract resulted in relocalization of RXRalpha from the nucleus to the cytoplasm. Cytoplasmic RXRalpha induced by H. sampsonii was associated with mitochondria, accompanied with cytochrome c release and apoptosis. H. sampsonii extract effectively inhibited the growth of various cancer cell lines, including NIH-H460 lung cancer, MGC-803 stomach cancer and SMMC7721 liver cancer cells. The growth inhibitory effect of H. sampsonii extract depended on levels of RXRalpha, as it failed to inhibit the growth of CV-1 cells lacking detectable RXRalpha, whereas transfection of RXRalpha into CV-1 cells restored its apoptotic response to H. sampsonii. Furthermore, the apoptotic effect of H. sampsonii was significantly enhanced when RXRalpha was overexpressed in NIH-H460 cells. Together, our results demonstrate that H. sampsonii contains ingredient(s) that induce apoptosis of cancer cells by modulating subcellular localization of RXRalpha.

  7. Tricyclic Acylphloroglucinols from Hypericum lanceolatum and Regioselective Synthesis of Selancins A and B.

    PubMed

    Fobofou, Serge A T; Franke, Katrin; Porzel, Andrea; Brandt, Wolfgang; Wessjohann, Ludger A

    2016-04-22

    The chemical investigation of the chloroform extract of Hypericum lanceolatum guided by (1)H NMR, ESIMS, and TLC profiles led to the isolation of 11 new tricyclic acylphloroglucinol derivatives, named selancins A-I (1-9) and hyperselancins A and B (10 and 11), along with the known compound 3-O-geranylemodin (12), which is described for a Hypericum species for the first time. Compounds 8 and 9 are the first examples of natural products with a 6-acyl-2,2-dimethylchroman-4-one core fused with a dimethylpyran unit. The new compounds 1-9 are rare acylphloroglucinol derivatives with two fused dimethylpyran units. Compounds 10 and 11 are derivatives of polycyclic polyprenylated acylphloroglucinols related to hyperforin, the active component of St. John's wort. Their structures were elucidated by UV, IR, extensive 1D and 2D NMR experiments, HRESIMS, and comparison with the literature data. The absolute configurations of 5, 8, 10, and 11 were determined by comparing experimental and calculated electronic circular dichroism spectra. Compounds 1 and 2 were synthesized regioselectively in two steps. The cytotoxicity of the crude extract (88% growth inhibition at 50 μg/mL) and of compounds 1-6, 8, 9, and 12 (no significant growth inhibition up to a concentration of 10 mM) against colon (HT-29) and prostate (PC-3) cancer cell lines was determined. No anthelmintic activity was observed for the crude extract.

  8. In vitro cytotoxicity and antitumour properties of Hypericum mysorense and Hypericum patulum.

    PubMed

    Vijayan, P; Vinod Kumar, S; Dhanaraj, S A; Mukherjee, P K; Suresh, B

    2003-09-01

    The methanol extracts of the aerial parts of Hypericum mysorense and Hypericum patulum were tested for in vitro cytotoxicity on HEp-2, RD and Vero cell lines and antitumour activity using DLA and HEp-2 cell lines. The cell viability and morphological changes were assessed. Of these extracts, Hypericum patulum (stem) extract showed strong cytotoxicity against all the cell lines used. The CTC50 of the Hypericum patulum (stem) extract was 1.71 microg/mL for HEp-2, 1.53 microg/mL for RD and 2.23 microg/mL for Vero cell lines. The Hypericum patulum (leaves) and Hypericum mysorense (aerial parts) extracts showed moderate cytotoxicity and Hypericum patulum (aerial parts) extract did not show any cytotoxicity up to 1,000 microg/mL concentration. In the clonogenic assay, no colony formation was observed at a concentration of 300 micro g/mL and above for Hypericum mysorense (aerial parts), 400 microg/mL and above for Hypericum patulum (leaves) and 500 microg/mL and above for Hypericum patulum (stem) extracts. In the short term antitumour studies using DLA cells, 50% viability was observed in the concentration range 100-200 microg/mL for Hypericum patulum (leaves and stem) and 200-400 microg/mL for Hypericum mysorense (aerial) extract. In the long term antitumour activity using the HEp-2 cell line, no colony formation was observed over a concentration of 1.6 microg/mL for the Hypericum patulum (stem) extract. Copyright 2003 John Wiley & Sons, Ltd.

  9. Attitudes and knowledge toward natural products safety in the pharmacy setting: an Italian study.

    PubMed

    Cuzzolin, Laura; Benoni, Giuseppina

    2009-07-01

    The lack of a professional supervision may expose consumers of natural products to risks; pharmacists play an important role in giving information about these substances. A survey was designed to investigate the attitudes and knowledge of consumers and pharmacists toward the safety of natural products. Twenty-three pharmacies participated in the project. On the basis of a pre-structured 17-item questionnaire, face-to-face interviews were conducted with consumers buying a natural product over a 6-month period. A further 8 items had to be compiled by pharmacists about the purchased product. During the study period, 1420 interviews were carried out. The most frequently purchased products were echinacea, propolis, garlic, guggul, ginkgo, liquorice, ginseng, glucomannan, guarana, valerian, and passionflower; 71.8% of consumers reported to have been taking conventional medicines along with natural products. Some (3.9%) referred to adverse effects in the last year: allergic reactions after cartilage of shark, propolis and thyme; anxiety after hypericum; hypotension and tachycardia after a mix containing chamomile, valerian and melissa; pyrosis and stomach-ache after laxative-depurative herbs. Pharmacists referred to some adverse effects observed in the past in relation to the products bought by consumers involved in this study. Findings from this study demonstrate that in general consumers need information on herbal safety and pharmacists are more likely to answer correctly about the use of herbs rather than about cautions, adverse effects and interactions.

  10. Bioactive natural products from Lysobacter

    PubMed Central

    Xie, Yunxuan; Wright, Stephen; Shen, Yuemao

    2012-01-01

    The gliding Gram-negative Lysobacter bacteria are emerging as a promising source of new bioactive natural products. These ubiquitous freshwater and soil microorganisms are fast growing, simple to use and maintain, and genetically amenable for biosynthetic engineering. This Highlight reviews a group of biologically active and structurally distinct natural products from the genus Lysobacter, with a focus on their biosyntheses. Although Lysobacter sp. are known as prolific producers of bioactive natural products, detailed molecular mechanistic studies of their enzymatic assembly have been surprisingly scarce. We hope to provide a snapshot of the important work done on the lysobacterial natural products and to provide useful information for future biosynthetic engineering of novel antibiotics in Lysobacter. PMID:22898908

  11. Natural Products as Aromatase Inhibitors

    PubMed Central

    Balunas, Marcy J.; Su, Bin; Brueggemeier, Robert W.; Kinghorn, A. Douglas

    2010-01-01

    With the clinical success of several synthetic aromatase inhibitors (AIs) in the treatment of postmenopausal estrogen receptor-positive breast cancer, researchers have also been investigating also the potential of natural products as AIs. Natural products from terrestrial and marine organisms provide a chemically diverse array of compounds not always available through current synthetic chemistry techniques. Natural products that have been used traditionally for nutritional or medicinal purposes (e.g., botanical dietary supplements) may also afford AIs with reduced side effects. A thorough review of the literature regarding natural product extracts and secondary metabolites of plant, microbial, and marine origin that have been shown to exhibit aromatase inhibitory activity is presented herein. PMID:18690828

  12. Forest Products Laboratory natural finish

    Treesearch

    J. M. Black; D. F. Laughnan; E. A. Mraz

    1979-01-01

    A simple and durable exterior natural finish developed at the Forest Products Laboratory is described. The finish is classified as a semi-transparent oil-base penetrating stain that effectively retains much of the natural grain and texture of wood when exposed to the weather. The directions for preparation are included as are the recommendations for application to both...

  13. Effect on prolactin secretion of Echinacea purpurea, hypericum perforatum and Eleutherococcus senticosus.

    PubMed

    Di Carlo, G; Pacilio, M; Capasso, R; Di Carlo, R

    2005-09-01

    It has been recently reported that prolactin (PRL) plays an important role in immune system regulation. In this study we investigated the activity of three natural drugs with immunomodulatory activity: Echinacea purpurea (EP), Hypericum perforatum (HP) and Eleutherococcus senticosus (ES) on PRL production. Male rats were orally treated with two different doses (30 and 100 mg/kg) of extract of these drugs for 3 or 15 days. A 3-day treatment was not able to modify PRL serum levels, whereas a 15-day treatment with EP and HP at the higher dose significantly inhibits PRL production. A treatment with ES was always ineffective. A possible mechanism for this effect could be that both HP and EP extracts display a direct dopaminergic activity, although an involvement of the GABA-ergic system cannot be excluded.

  14. Natural products used for diabetes.

    PubMed

    Shapiro, Karen; Gong, William C

    2002-01-01

    To review the efficacy and safety of natural products commonly used for diabetes. English and Spanish-language journals retrieved through a MEDLINE search of articles published between 1960 and December 2001 using these index terms: Opuntia, karela, gymnema, tecoma, alpha lipoic acid, thioctic acid, ginseng, panaxans, and diabetes. Natural products have long been used in traditional systems of medicine for diabetes. Products in common use include nopal (prickly pear cactus), fenu-greek, karela (bitter melon), gymnema, ginseng, tronadora, chromium, and alpha-lipoic acid. The popularity of these products varies among people of different ethnicities. Nopal is the most commonly used herbal hypoglycemic among persons of Mexican descent. Karela is more commonly used by persons from Asian countries. Some of these agents have gained universal appeal. For a select number of products, studies have revealed single or multiple mechanisms of action. For several of these, high soluble fiber content is a contributing factor. Based on the available evidence, several natural products in common use can lower blood glucose in patients with diabetes. Commonly used natural products often have a long history of traditional use, and pharmacists who have a stronger understanding of these products are better positioned to counsel patients on their appropriate use.

  15. Natural Products as Chemical Probes

    PubMed Central

    Carlson, Erin E.

    2010-01-01

    Natural products have evolved to encompass a broad spectrum of chemical and functional diversity. It is this diversity, along with their structural complexity, that enables nature’s small molecules to target a nearly limitless number of biological macromolecules and to often do so in a highly selective fashion. Because of these characteristics, natural products have seen great success as therapeutic agents. However, this vast pool of compounds holds much promise beyond the development of future drugs. These features also make them ideal tools for the study of biological systems. Recent examples of the use of natural products and their derivatives as chemical probes to explore biological phenomena and assemble biochemical pathways are presented here. PMID:20509672

  16. Synthesis of Polycyclic Natural Products

    SciTech Connect

    Nguyen, Tuan Hoang

    2003-01-01

    With the continuous advancements in molecular biology and modern medicine, organic synthesis has become vital to the support and extension of those discoveries. The isolations of new natural products allow for the understanding of their biological activities and therapeutic value. Organic synthesis is employed to aid in the determination of the relationship between structure and function of these natural products. The development of synthetic methodologies in the course of total syntheses is imperative for the expansion of this highly interdisciplinary field of science. In addition to the practical applications of total syntheses, the structural complexity of natural products represents a worthwhile challenge in itself. The pursuit of concise and efficient syntheses of complex molecules is both gratifying and enjoyable.

  17. A melatonin-rich germplasm line of St John's wort (Hypericum perforatum L.).

    PubMed

    Murch, Susan J; Saxena, Praveen K

    2006-10-01

    The objective of this study was to evaluate the possibility of selecting genetic variants of plants with enhanced concentrations of the indoleamine melatonin. A germplasm line of the medicinal plant species, St John's wort (Hypericum perforatum L.), with high levels of melatonin was selected in vitro using mutagenized tissues. The germplasm line has remained stable over a 5-yr period and contained >12-fold (1200%) melatonin content compared with the wild-type plant. Melatonin is a ubiquitous, highly conserved molecule with known therapeutic roles in the treatment of sleep disorders, depression, aging, inhibition of cancer cell growth and as a free radical scavenger and antioxidant. The selected melatonin-rich germplasm line of St John's wort may facilitate fundamental studies on melatonin biosynthesis, metabolism and new developments in natural products for treatment of human diseases.

  18. Natural products: DNA double whammy

    NASA Astrophysics Data System (ADS)

    Gates, Kent S.

    2014-06-01

    The lomaiviticins are exceedingly potent antibiotic agents, but the mechanism responsible for this activity has so far been unclear. Now, efficient generation of double-strand breaks in DNA by lomaiviticin A has been linked to the remarkable cytotoxicity of these diazobenzofluorene-containg natural products.

  19. EIA's Natural Gas Production Data

    EIA Publications

    2009-01-01

    This special report examines the stages of natural gas processing from the wellhead to the pipeline network through which the raw product becomes ready for transportation and eventual consumption, and how this sequence is reflected in the data published by the Energy Information Administration (EIA).

  20. Marine natural products: synthetic aspects.

    PubMed

    Morris, Jonathan C; Phillips, Andrew J

    2008-02-01

    An overview of marine natural products synthesis during 2006 is provided. As with earlier installments in this series, the emphasis is on total syntheses of molecules of contemporary interest, new total syntheses, and syntheses that have resulted in structure confirmation or stereochemical assignments.

  1. Marine natural products: synthetic aspects.

    PubMed

    Morris, Jonathan C; Nicholas, Gillian M; Phillips, Andrew J

    2007-02-01

    An overview of marine natural products synthesis during 2005 is provided. In a similar vein to earlier installments in this series, the emphasis is on total syntheses of molecules of contemporary interest, new total syntheses, and syntheses that have resulted in structure confirmation or stereochemical assignments.

  2. White Paper on Natural Products.

    PubMed

    Gabay, Michael; Smith, Judith A; Chavez, Mary L; Goldwire, Micheline; Walker, Scot; Coon, Scott A; Gosser, Rena; Hume, Anne L; Musselman, Megan; Phillips, Jennifer; Abe, Andrew M

    2017-01-01

    The American College of Clinical Pharmacy (ACCP) published an initial white paper on herbal products in 2000. Since then, the global market for natural products has continued to expand, with tens of millions of consumers using such products on an annual basis in the United States alone. However, despite this expansion, natural products remain largely unregulated compared with prescription medications, have moderate- to low-level clinical evidence for efficacy, and continue to have safety concerns, including adulteration and misbranding. As comprehensive medication management experts, clinical pharmacists are uniquely qualified to navigate these concerns and advise patients appropriately. To develop and recommend a suitable care plan involving natural products, clinical pharmacists must establish a strong pharmacist-patient relationship, assess the appropriateness of therapy, educate the patient regarding key issues, and continuously monitor and follow up on the effectiveness of the care plan. This process should not only occur in an individual community or hospital setting, but also whenever a patient transitions from one care setting to another in cooperation with other clinicians.

  3. Natural Products from Mangrove Actinomycetes

    PubMed Central

    Xu, Dong-Bo; Ye, Wan-Wan; Han, Ying; Deng, Zi-Xin; Hong, Kui

    2014-01-01

    Mangroves are woody plants located in tropical and subtropical intertidal coastal regions. The mangrove ecosystem is becoming a hot spot for natural product discovery and bioactivity survey. Diverse mangrove actinomycetes as promising and productive sources are worth being explored and uncovered. At the time of writing, we report 73 novel compounds and 49 known compounds isolated from mangrove actinomycetes including alkaloids, benzene derivatives, cyclopentenone derivatives, dilactones, macrolides, 2-pyranones and sesquiterpenes. Attractive structures such as salinosporamides, xiamycins and novel indolocarbazoles are highlighted. Many exciting compounds have been proven as potential new antibiotics, antitumor and antiviral agents, anti-fibrotic agents and antioxidants. Furthermore, some of their biosynthetic pathways have also been revealed. This review is an attempt to consolidate and summarize the past and the latest studies on mangrove actinomycetes natural product discovery and to draw attention to their immense potential as novel and bioactive compounds for marine drugs discovery. PMID:24798926

  4. Glycosylation and Activities of Natural Products.

    PubMed

    Huang, Gangliang; Lv, Meijiao; Hu, Jinchuan; Huang, Kunlin; Xu, Hong

    2016-01-01

    Natural products are widely found in nature, their number and variety are numerous, the structures are complex and diverse. These natural products have many physiological and pharmacological activities. Glycosylation can increase the diversity of structure and function of natural product, it has become the focus of drug research and development. The impacts of glycosylation of natural products to water solubility, pharmacological activities, bioavailability, or others were described in this review, which provides a reference for the development and application of glycosylated natural products.

  5. [Discussion on clinical efficacy of Hypericum perforatum for depression abroad].

    PubMed

    Yang, De-Po; Gan, Liang-Chun; Hu, Hai-Yan

    2004-05-01

    The development of molecular pharmacology and neuropharmacology accelerated the studies on molecular mechanism of Hypericum perforatum for depression. The clinical trials indicated that this galenical was superior to the traditional synthetic drugs for antidepression. This preparation had good tolerability and safety. Clinical pharmacokinetics and pharmacodynamics provided further evidence for clinical application of Hypericum. The clinical efficacy of Hypericum for depression was notable and credible.

  6. Genetic Diversity in Hypericum and AFLP Markers for Species-specific Identification of H. perforatum L.

    USDA-ARS?s Scientific Manuscript database

    Naturally occurring bioactive compounds originating from plant material are being used worldwide as medicinal treatments for maladies ranging from depression to the common cold. One of the more widely used of these herbal remedies is Hypericum perforatum, commonly known as St. John's Wort. However...

  7. Marine natural products: synthetic aspects.

    PubMed

    Morris, Jonathan C; Phillips, Andrew J

    2009-02-01

    An overview of marine natural products synthesis during 2007 is provided. As with earlier installments in this series, the emphasis is on total syntheses of molecules of contemporary interest, new total syntheses, and syntheses that have resulted in structure confirmation or stereochemical assignments.1 Introduction, 2 Review articles, 3 Azaspiracid, 4 Polyethers, 5 Guanidinium alkaloids, 6 Amphidinolides, 7 Total syntheses of other compounds, 8 Acknowledgements, 9 References.

  8. Hypericum in infection: Identification of anti-viral and anti-inflammatory constituents

    PubMed Central

    Birt, Diane F; Widrlechner, Mark P; Hammer, Kimberly DP; Hillwig, Matthew L; Wei, Jingqiang; Kraus, George A; Murphy, Patricia A; McCoy, JoeAnn; Wurtele, Eve S; Neighbors, Jeffrey D; Wiemer, David F; Maury, Wendy J; Price, Jason P

    2009-01-01

    The Iowa Center for Research on Botanical Dietary Supplements seeks to optimize Echinacea, Hypericum, and Prunella botanical supplements for human-health benefit, emphasizing antiviral, anti-inflammatory and anti-pain activities. This mini-review reports on ongoing studies on Hypericum. The Center uses the genetically diverse, well-documented Hypericum populations collected and maintained at the USDA-ARS North Central Regional Plant Introduction Station (NCRPIS), and the strength of research in synthetic chemistry at Iowa State University to tap natural diversity, to help discover key constituents and interactions among constituents that impact bioactivity and toxicity. The NCRPIS has acquired more than 180 distinct populations of Hypericum, with a focus on Hypericum perforatum L. (Hypericaceae), representing about 13% of currently recognized taxa. Center chemists have developed novel synthetic pathways for key flavones, acyl phloroglucinols, hyperolactones and a tetralin that have been found in Hypericum, and these compounds are used as standards and for bioactivity studies. Both light-dependent and light-independent anti-viral activities have been identified by using bioactivity-guided fractionation of H. perforatum and a HIV-1 infection test system. Our Center has focused on light-independent activity, potentially due to novel chemicals, and polar fractions are undergoing further fractionation. Anti-inflammatory activity has been found to be light-independent, and fractionation of a flavonoid-rich extract revealed four compounds (amentoflavone, chlorogenic acid, pseudohypericin and quercetin) that interacted in the light to inhibit lipopolysaccharide-induced prostaglandin E2 activity. The Center continues to explore novel populations of H. perforatum and related species to identify constituents and interactions of constituents that contribute to potential health benefits related to infection. PMID:19907671

  9. Molluscicidal activity of crude water and hexane extracts of Hypericum species to snails (Radix peregra).

    PubMed

    Teixeira, Tânia; Rainha, Nuno; Rosa, José Silvino; Lima, Elisabete; Baptista, José

    2012-04-01

    In spite of intense research on both chemical constituency and biological activity of Hypericum species, potential applications of their active components for pest control have been less well investigated. In the present study, Hypericum androsaemum (tutsan), Hypericum foliosum (malfurada), and Hypericum undulatum (wavy St. John's wort) aqueous and hexane extracts were studied for their molluscicidal and ovicidal activities against Radix peregra. The molluscicidal activity of the aqueous extracts was low, except for H. androsaemum infusion (median lethal concentration [LC50](adults)  = 317.1 ppm; LC50(juveniles)  = 415 ppm), and less important compared with the toxicity of all three hexane extracts tested: H. androsaemum (LC50(adults)  = 30.47 ppm; LC50(juveniles)  = 73.25 ppm), H. undulatum (LC50(adults)  = 30.55 ppm; LC50(juveniles)  = 60.54 ppm), and H. foliosum (LC50(adults)  = 48.61 ppm; LC50(juveniles)  = 38.81 ppm). An ovicidal effect was observed only with H. androsaemum infusion (1.85% of hatching at 500 ppm) and H. foliosum hexane extract (0.0% of hatching at 100 ppm). A preliminary phytochemical investigation of the lipophylic extracts from these Hypericum sp. revealed a different chemical profile and confirmed the presence of ursolic acid only in H. undulatum as the main compound. The present study indicates that products from hexane extracts of the Hypericum sp. analyzed may be used as potential molluscicides to control snails responsible for transmitting fasciolosis.

  10. Natural products for cancer chemotherapy

    PubMed Central

    Demain, Arnold L.; Vaishnav, Preeti

    2011-01-01

    Summary For over 40 years, natural products have served us well in combating cancer. The main sources of these successful compounds are microbes and plants from the terrestrial and marine environments. The microbes serve as a major source of natural products with anti‐tumour activity. A number of these products were first discovered as antibiotics. Another major contribution comes from plant alkaloids, taxoids and podophyllotoxins. A vast array of biological metabolites can be obtained from the marine world, which can be used for effective cancer treatment. The search for novel drugs is still a priority goal for cancer therapy, due to the rapid development of resistance to chemotherapeutic drugs. In addition, the high toxicity usually associated with some cancer chemotherapy drugs and their undesirable side‐effects increase the demand for novel anti‐tumour drugs active against untreatable tumours, with fewer side‐effects and/or with greater therapeutic efficiency. This review points out those technologies needed to produce the anti‐tumour compounds of the future. PMID:21375717

  11. A Perspective on Hypericum perforatum Genetic Transformation.

    PubMed

    Hou, Weina; Shakya, Preeti; Franklin, Gregory

    2016-01-01

    Hypericum perforatum (St John's wort) is a reservoir of diverse classes of biologically active and high value secondary metabolites, which captured the interest of both researchers and the pharmaceutical industry alike. Several studies and clinical trials have shown that H. perforatum extracts possess an astounding array of pharmacological properties. These properties include antidepressant, anti-inflammatory, antiviral, anti-cancer, and antibacterial activities; and are largely attributed to the naphtodianthrones and xanthones found in the genus. Hence, improving their production via genetic manipulation is an important strategy. In spite of the presence of contemporary genome editing tools, genetic improvement of this genus remains challenging without robust transformation methods in place. In the recent past, we found that H. perforatum remains recalcitrant to Agrobacterium tumefaciens mediated transformation partly due to the induction of plant defense responses coming into play. However, H. perforatum transformation is possible via a non-biological method, biolistic bombardment. Some research groups have observed the induction of hairy roots in H. perforatum after Agrobacterium rhizogenes co-cultivation. In this review, we aim at updating the available methods for regeneration and transformation of H. perforatum. In addition, we also propose a brief perspective on certain novel strategies to improve transformation efficiency in order to meet the demands of the pharmaceutical industry via metabolic engineering.

  12. A Perspective on Hypericum perforatum Genetic Transformation

    PubMed Central

    Hou, Weina; Shakya, Preeti; Franklin, Gregory

    2016-01-01

    Hypericum perforatum (St John's wort) is a reservoir of diverse classes of biologically active and high value secondary metabolites, which captured the interest of both researchers and the pharmaceutical industry alike. Several studies and clinical trials have shown that H. perforatum extracts possess an astounding array of pharmacological properties. These properties include antidepressant, anti-inflammatory, antiviral, anti-cancer, and antibacterial activities; and are largely attributed to the naphtodianthrones and xanthones found in the genus. Hence, improving their production via genetic manipulation is an important strategy. In spite of the presence of contemporary genome editing tools, genetic improvement of this genus remains challenging without robust transformation methods in place. In the recent past, we found that H. perforatum remains recalcitrant to Agrobacterium tumefaciens mediated transformation partly due to the induction of plant defense responses coming into play. However, H. perforatum transformation is possible via a non-biological method, biolistic bombardment. Some research groups have observed the induction of hairy roots in H. perforatum after Agrobacterium rhizogenes co-cultivation. In this review, we aim at updating the available methods for regeneration and transformation of H. perforatum. In addition, we also propose a brief perspective on certain novel strategies to improve transformation efficiency in order to meet the demands of the pharmaceutical industry via metabolic engineering. PMID:27446112

  13. Molecularly imprinted polymer for specific extraction of hypericin from Hypericum perforatum L. herbal extract.

    PubMed

    Li, Zhaozhou; Qin, Cuili; Li, Daomin; Hou, Yuze; Li, Songbiao; Sun, Junjie

    2014-09-01

    The molecularly imprinted polymers (MIPs) were prepared by an oxidation-reduction polymerization system using a non-covalent molecularly imprinting strategy with hypericin as the template, acrylamide as the functional monomer and pentaerythritol triacrylate as the cross-linker in the porogen of acetone. The UV spectrum revealed that a cooperative hydrogen-bonding complex between hypericin and acrylamide might be formed at the ratio of 1:6 in the prepolymerized system. Two classes of the binding sites were produced in the resulting hypericin-imprinted polymer with the dissociation constants of 16.61μgL(-1) and 69.35μgL(-1), and the affinity binding sites of 456.53μgg(-1) and 603.06μgg(-1), respectively. The synthesized MIPs were characterized by scanning electron microscope, thermogravimetric and differential thermal analysis. High-performance liquid chromatography was used to investigate the adsorption and recognition properties of the MIPs. Selective binding of the template molecule was demonstrated in comparison to the analog pseudohypericin. After the Hypericum perforatum L. plant being air dried and finely ground, an extract was prepared by shaking the powder in a methanol-water solution (80:20, v/v), vacuum filtration though a Büchner funnel, liquid-liquid extraction with ethyl ether and ethyl acetate, and evaporating on a rotary evaporator until dry. With the sorbents of the optimized MIPs, a molecularly imprinted solid-phase extraction (MISPE) procedure was developed for enrichment and separation of hypericin from the Hypericum extract in the presence of interfering substances. The selective extraction of hypericin from herbal medicine was achieved with the recovery of 82.30%. The results showed that MISPE can be a useful tool for specific isolation and effective clean-up of target compounds from natural products. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Hypericum pollen determines the presence of burglars at the scene of a crime: an example of forensic palynology.

    PubMed

    Mildenhall, D C

    2006-11-22

    Two male intruders entered a house in which the sole female occupant slept having left the back door unlocked for the return of her live-in boyfriend. She awoke and saw strangers in her bedroom. The intruders ran off, one leaving a jacket behind on the kitchen floor. One of the intruders subsequently returned to recover his jacket, but in his rush to leave the house he brushed against a flowering Hypericum bush growing just outside the back door. A suspect was arrested later that day and charged with indecent assault on a female and burglary, but denied any involvement and refused to name any associate. A day following the offence the suspect's clothes were taken for forensic examination. Pollen analysis of selected parts of his clothing showed that his track pants contained 14% Hypericum pollen, denim jacket 24%, and polo shirt 27.5%. Traces of Hypericum pollen occurred on other items. Most of these pollen grains still had their cell contents preserved and were on the clothing in clumps consistent with having recently been collected by the clothing and not having been aerially dispersed. The pollen from the Hypericum bush was identical in colour, shape, development, and size range to the pollen from the clothing. The clothes had so much Hypericum pollen on them that they had to have been in direct and intimate contact with a flowering bush. Pollen evidence is by its nature circumstantial and often cannot be used on its own to convict, or more strictly to determine the truth. The suspect may have been in contact with Hypericum elsewhere, but detailed investigations indicated that this was unlikely. In 30 years of New Zealand forensic work Hypericum had only ever been found on clothing in trace amounts. This is but one way in which forensic palynology can assist law enforcement agencies to determine the history behind a criminal action, and demonstrates that forensic palynology should be considered as an integral part of any criminal investigation.

  15. Natural and engineered biosynthesis of fluorinated natural products.

    PubMed

    Walker, Mark C; Chang, Michelle C Y

    2014-09-21

    Both natural products and synthetic organofluorines play important roles in the discovery and design of pharmaceuticals. The combination of these two classes of molecules has the potential to be useful in the ongoing search for new bioactive compounds but our ability to produce site-selectively fluorinated natural products remains limited by challenges in compatibility between their high structural complexity and current methods for fluorination. Living systems provide an alternative route to chemical fluorination and could enable the production of organofluorine natural products through synthetic biology approaches. While the identification of biogenic organofluorines has been limited, the study of the native organisms and enzymes that utilize these compounds can help to guide efforts to engineer the incorporation of this unusual element into complex pharmacologically active natural products. This review covers recent advances in understanding both natural and engineered production of organofluorine natural products.

  16. Hot springs and cool natural products.

    PubMed

    Kwon, Ho Jeong; Lee, Choong Hwan; Osada, Hiroyuki; Yoshida, Minoru; Imoto, Masaya

    2008-08-01

    Natural products have played a unique role in providing new tools and insights in chemical biology. The tremendous value of natural products was highlighted by scientists from Korea and Japan at the 4(th) Korea-Japan Chemical Biology symposium.

  17. Identification of anti-inflammatory constituents in Hypericum perforatum and Hypericum gentianoides extracts using RAW 264.7 mouse macrophages

    PubMed Central

    Huang, Nan; Rizshsky, Ludmila; Hauck, Cathy; Nikolau, Basil J.; Murphy, Patricia A.; Birt, Diane F.

    2011-01-01

    Hypericum perforatum (St. John’s wort) is an herb widely used as supplement for mild to moderate depression. Our prior studies revealed synergistic anti-inflammatory activity associated with 4 bioactive compounds in a fraction of H. perforatum ethanol extract. Whether these 4 compounds also contributed to the ethanol extract activity was addressed in the research reported here. Despite the popularity of H. perforatum, other Hypericum species with different phytochemical profiles could have their anti-inflammatory potentials attributed to these or other compounds. In the current study, ethanol extracts of different Hypericum species were compared for their inhibitory effect on LPS-induced prostaglandin E2 (PGE2) and nitric oxide (NO) production in RAW 264.7 mouse macrophages. Among these extracts, those made from H. perforatum and H. gentianoides demonstrated stronger overall efficacy. LC-MS analysis indicated the 4 compounds in H. perforatum extract and pseudohypericin in all active fractions. The 4 compounds accounted for a significant part of the extract’s inhibitory activity on PGE2, NO, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in RAW 264.7 as well as peritoneal macrophages. Pseudohypericin was the most important contributor of the anti-inflammatory potential among the 4 compounds. The lipophilic fractions of H. gentianoides extract, which did not contain the previously identified active constituents, decreased PGE2 and NO potently. These fractions were rich in acylphloroglucinols, including uliginosin A that accounted for a proportion of the anti-inflammatory activity observed with the active fractions. Overall, the current study revealed a different group of major anti-inflammatory constituents in H. gentianoides, while showing that a previously identified 4 compounds combination was important for H. perforatum’s anti-inflammatory potential. PMID:21855951

  18. Enantiomeric Natural Products: Occurrence and Biogenesis**

    PubMed Central

    Finefield, Jennifer M.; Sherman, David H.; Kreitman, Martin; Williams, Robert M.

    2012-01-01

    In Nature, chiral natural products are usually produced in optically pure form; however, on occasion Nature is known to produce enantiomerically opposite metabolites. These enantiomeric natural products can arise in Nature from a single species, or from different genera and/or species. Extensive research has been carried out over the years in an attempt to understand the biogenesis of naturally occurring enantiomers, however, many fascinating puzzles and stereochemical anomalies still remain. PMID:22555867

  19. New Potential Pharmaceutical Applications of Hypericum Species.

    PubMed

    Marrelli, Mariangela; Statti, Giancarlo; Conforti, Filomena; Menichini, Francesco

    2016-01-01

    The genus Hypericum includes more than 450 species distributed in Europe, North America, North Africa and West Asia. These plants are widely used in folk medicine for the treatment of inflammation, bacterial and viral infections, burns and gastric disorders. The use for alleviating inflammation and promoting wound healing is well known for H. Perforatum L. (St. John's wort) and other species. Because of its pharmacological activity, H. perforatum L. is one of the most important species of this genus. This plant has been largely utilized for its efficacy in the treatment of mild to moderate depression. However, some other species have been utilized in traditional medicine and have been studied for their phytochemical composition and for their biological activities to date. Hypericum species contain biologically active secondary metabolites belonging to at least ten different classes, with prevalence of naphthodianthrones (hypericin and pseudohypericin), phloroglucinols (hyperforin), flavonoids (rutin, hyperoside, isoquercitrin, quercitrin, quercetin, amentoflavone) and phenylpropanoids (chlorogenic acid). However, great variations in contents have been reported for wild populations worldwide. The purpose of this review is to provide an overview of most recent studies about potential pharmaceutical applications of plants belonging to Hypericum genus. The most interesting isolated active principles and both in vitro and in vivo effects of Hypericum extracts are presented and discussed.

  20. Misassigned natural products and their revised structures.

    PubMed

    Yoo, Hye-Dong; Nam, Sang-Jip; Chin, Young-Won; Kim, Min-Sun

    2016-02-01

    Natural products are a major pipeline for drug development and are responsible for more than 50 % of drugs on the market. NMR is a fundamental and powerful tool for the structure determination of natural products. It is essential to provide unambiguous chemical structure information on natural products in drug development research, including the structure-activity relationship, derivatization and pharmacokinetic/pharmacodynamic studies. Advancement of NMR instruments has made it possible to deal with nanomole-scale natural products for structure elucidation, but misinterpretation of NMR spectra still occurs. We review 21 natural products with revised chemical structures and the methods used for those revisions.

  1. Hypericum perforatum methanolic extract inhibits growth of human prostatic carcinoma cell line orthotopically implanted in nude mice.

    PubMed

    Martarelli, D; Martarelli, B; Pediconi, D; Nabissi, M I; Perfumi, M; Pompei, P

    2004-07-08

    The antiproliferative effect of serotonin-reuptake inhibitors (SSRI) and serotonin antagonists has been demonstrated in prostate tumors. Since Hypericum perforatum components act as serotonin-reuptake inhibitors and exert cytotoxic effects on several human cancer cell lines, in this work we analyzed the effect of a treatment with Hypericum perforatum extract (HPE) on the growth of human prostate cancer cells in vitro and in vivo. This study highlighted a significant reduction of tumor growth and number of metastasis suggesting that this natural compound may be useful in the treatment of prostate cancer. Copyright 2004 Elsevier Ireland Ltd.

  2. Super Natural II--a database of natural products.

    PubMed

    Banerjee, Priyanka; Erehman, Jevgeni; Gohlke, Björn-Oliver; Wilhelm, Thomas; Preissner, Robert; Dunkel, Mathias

    2015-01-01

    Natural products play a significant role in drug discovery and development. Many topological pharmacophore patterns are common between natural products and commercial drugs. A better understanding of the specific physicochemical and structural features of natural products is important for corresponding drug development. Several encyclopedias of natural compounds have been composed, but the information remains scattered or not freely available. The first version of the Supernatural database containing ∼ 50,000 compounds was published in 2006 to face these challenges. Here we present a new, updated and expanded version of natural product database, Super Natural II (http://bioinformatics.charite.de/supernatural), comprising ∼ 326,000 molecules. It provides all corresponding 2D structures, the most important structural and physicochemical properties, the predicted toxicity class for ∼ 170,000 compounds and the vendor information for the vast majority of compounds. The new version allows a template-based search for similar compounds as well as a search for compound names, vendors, specific physical properties or any substructures. Super Natural II also provides information about the pathways associated with synthesis and degradation of the natural products, as well as their mechanism of action with respect to structurally similar drugs and their target proteins. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Counting on natural products for drug design

    NASA Astrophysics Data System (ADS)

    Rodrigues, Tiago; Reker, Daniel; Schneider, Petra; Schneider, Gisbert

    2016-06-01

    Natural products and their molecular frameworks have a long tradition as valuable starting points for medicinal chemistry and drug discovery. Recently, there has been a revitalization of interest in the inclusion of these chemotypes in compound collections for screening and achieving selective target modulation. Here we discuss natural-product-inspired drug discovery with a focus on recent advances in the design of synthetically tractable small molecules that mimic nature's chemistry. We highlight the potential of innovative computational tools in processing structurally complex natural products to predict their macromolecular targets and attempt to forecast the role that natural-product-derived fragments and fragment-like natural products will play in next-generation drug discovery.

  4. Antioxidant activity of Hypericum hookerianum Wight and Arn.

    PubMed

    Raghu Chandrashekhar, H; Venkatesh, P; Ponnusankar, S; Vijayan, P

    2009-01-01

    Methanolic extracts of leaf, root, flower and aerial parts of Hypericum hookerianum were assessed for in vitro antioxidant activity using eight different models. Total antioxidant capacity, phenol and flavanol content of the extracts were determined to correlate between their antioxidant activity and constituents present therein. Results of in vitro antioxidant study suggest that extracts from leaf and flower have strong antioxidant potential. Leaf extract (100 & 200 mg kg(-1) b.w. p.o.) that showed maximum activity was selected for in vivo antioxidant studies using a CCl(4)-intoxicated rat model. The effects of extracts on lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) in serum and liver homogenate were analysed. CCl(4) treatment caused a significant increase in the level of CAT and SOD and a significant decrease in the level of LPO in a dose-dependent manner when compared to CCl(4) treated control. The results indicate the strong antioxidant nature of H. hookerianum leaf extract.

  5. Macrolactam analogues of macrolide natural products.

    PubMed

    Hügel, Helmut M; Smith, Andrew T; Rizzacasa, Mark A

    2016-12-07

    The chemical modification of macrolide natural products into aza- or lactam analogues is a strategy employed to improve their metabolic stability and biological activity. The methods for the synthesis of several lactam analogues of macrolide natural products are highlighted and aspects of their biological properties presented.

  6. Functional chromatographic technique for natural product isolation†

    PubMed Central

    Lau, Eric C.; Mason, Damian J.; Eichhorst, Nicole; Engelder, Pearce; Mesa, Celestina; Kithsiri Wijeratne, E. M.; Gunaherath, G. M. Kamal B.; Leslie Gunatilaka, A. A.

    2015-01-01

    Natural product discovery arises through a unique interplay between chromatographic purification and biological assays. Currently, most techniques used for natural product purification deliver leads without a defined biological action. We now describe a technique, referred to herein as functional chromatography, that deploys biological affinity as the matrix for compound isolation. PMID:25588099

  7. Natural products against cancer angiogenesis.

    PubMed

    Khalid, El Bairi; Ayman, El-Meghawry El-Kenawy; Rahman, Heshu; Abdelkarim, Guaadaoui; Najda, Agnieszka

    2016-11-01

    The process of angiogenesis is quite well-known nowadays. Some medicines and extracts affecting this process are already used routinely in supporting the conventional treatment of many diseases that are considered angiogenic such as cancer. However, we must be aware that the area of currently used drugs of this type is much narrower than the theoretical possibilities existing in therapeutic angiogenesis. Plant substances are a large and diverse group of compounds that are found naturally in fruits, vegetables, spices, and medicinal plants. They also have different anticancer properties. The aim of this literature review article is to present the current state of knowledge concerning the molecular targets of tumor angiogenesis and the active substances (polyphenols, alkaloids, phytohormones, carbohydrates, and terpenes) derived from natural sources, whose activity against cancer angiogenesis has been confirmed.

  8. Stereoselective Halogenation in Natural Product Synthesis.

    PubMed

    Chung, Won-jin; Vanderwal, Christopher D

    2016-03-24

    At last count, nearly 5000 halogenated natural products have been discovered. In approximately half of these compounds, the carbon atom to which the halogen is bound is sp(3) -hybridized; therefore, there are an enormous number of natural products for which stereocontrolled halogenation must be a critical component of any synthesis strategy. In this Review, we critically discuss the methods and strategies used for stereoselective introduction of halogen atoms in the context of natural product synthesis. Using the successes of the past, we also attempt to identify gaps in our synthesis technology that would aid the synthesis of halogenated natural products, as well as existing methods that have not yet seen application in complex molecule synthesis. The chemistry described herein demonstrates yet again how natural products continue to provide the inspiration for critical advances in chemical synthesis.

  9. Synthesis of natural product inspired compound collections.

    PubMed

    Kumar, Kamal; Waldmann, Herbert

    2009-01-01

    Natural products, their derivatives, and their analogues are among the most important sources for new drug candidates and tools for chemical biology and medicinal chemistry research. Therefore, there is a need for the development of efficient synthesis methods which give access to natural product derived and inspired compound collections. To meet this challenge, the requirements of multistep stereoselective syntheses, and the logic and methodology of natural product total synthesis need to be translated and adapted to the methods and formats for the synthesis of compound collections. Recent developments in the synthesis of natural product inspired compound collections having carbocyclic and heterocyclic scaffolds highlight the fact that this goal can be successfully attained. The progress made has paved the way for the integration of natural product inspired compound collections into medicinal chemistry and chemical biology research.

  10. Bioactive natural products from novel microbial sources.

    PubMed

    Challinor, Victoria L; Bode, Helge B

    2015-09-01

    Despite the importance of microbial natural products for human health, only a few bacterial genera have been mined for the new natural products needed to overcome the urgent threat of antibiotic resistance. This is surprising, given that genome sequencing projects have revealed that the capability to produce natural products is not a rare feature among bacteria. Even the bacteria occurring in the human microbiome produce potent antibiotics, and thus potentially are an untapped resource for novel compounds, potentially with new activities. This review highlights examples of bacteria that should be considered new sources of natural products, including anaerobes, pathogens, and symbionts of humans, insects, and nematodes. Exploitation of these producer strains, combined with advances in modern natural product research methodology, has the potential to open the way for a new golden age of microbial therapeutics.

  11. Inhibition of MAO and COMT by hypericum extracts and hypericin.

    PubMed

    Thiede, H M; Walper, A

    1994-10-01

    The influence of hypericin, hypericum total extract, and hypericum fractions on the activity of MAO and COMT, prepared in vitro from pork liver, were investigated in several concentration steps. An inhibition of MAO could be shown in the following concentrations (extract correlated to a mean molecular value of 500): hypericin to 10(-3) mol/L, hypericum total extract to 10(-4) mol/L, one extract fraction up to 10(-5). A COMT inhibition could not be shown for hypericin, with hypericum extract to 10(-4) mol/L and with two extract fractions also up to 10(-4) mol/L. The MAO inhibiting fraction contained hypericins as well as flavonols, the COMT-inhibition fraction being mainly flavonols and xanthones. The concentrations of inhibition shown might not be sufficient to explain the clinically proven antidepressive effect of hypericum particularly with regard to the inhibition of MAO activity.

  12. Natural products: Hunting microbial metabolites

    NASA Astrophysics Data System (ADS)

    Schmidt, Eric W.

    2015-05-01

    Symbiotic bacteria synthesize many specialized small molecules; however, establishing the role these chemicals play in human health and disease has been difficult. Now, the chemical structure and mechanism of the Escherichia coli product colibactin provides insight into the link between this secondary metabolite and colorectal cancer.

  13. Phenolic profile of dark-grown and photoperiod-exposed Hypericum perforatum L. Hairy root cultures.

    PubMed

    Tusevski, Oliver; Petreska Stanoeva, Jasmina; Stefova, Marina; Simic, Sonja Gadzovska

    2013-01-01

    Hypericum perforatum L. is a medicinal plant considered as an important natural source of secondary metabolites with a wide range of pharmacological attributes. Hairy roots (HR) were induced from root segments of in vitro grown seedlings from H. perforatum after cocultivation with Agrobacterium rhizogenes A4. Investigations have been made to study the production of phenolic compounds in dark-grown (HR1) and photoperiod-exposed (HR2) cultures. The chromatographic analysis of phenolic acids, flavonols, flavan-3-ols, and xanthones revealed marked differences between HR1 and HR2 cultures. The production of quinic acid, kaempferol, and seven identified xanthones was increased in HR2. Moreover, HR2 showed a capability for de novo biosynthesis of two phenolic acids (3-p-coumaroylquinic acid and 3-feruloylquinic acid), three flavonol glycosides (kaempferol hexoside, hyperoside, and quercetin acetylglycoside), and five xanthones (tetrahydroxy-one-methoxyxanthone, 1,3,5-trihydroxy-6-methoxyxanthone, 1,3,5,6-tetrahydroxy-2-prenylxanthone, paxanthone, and banaxanthone E). On the other side, HR1 cultures were better producers of flavan-3-ols (catechin, epicatechin, and proanthocyanidin dimers) than HR2. This is the first comparative study on phenolic profile of H. perforatum HR cultures grown under dark and photoperiod conditions.

  14. Phenolic Profile of Dark-Grown and Photoperiod-Exposed Hypericum perforatum L. Hairy Root Cultures

    PubMed Central

    Petreska Stanoeva, Jasmina; Stefova, Marina; Simic, Sonja Gadzovska

    2013-01-01

    Hypericum perforatum L. is a medicinal plant considered as an important natural source of secondary metabolites with a wide range of pharmacological attributes. Hairy roots (HR) were induced from root segments of in vitro grown seedlings from H. perforatum after cocultivation with Agrobacterium rhizogenes A4. Investigations have been made to study the production of phenolic compounds in dark-grown (HR1) and photoperiod-exposed (HR2) cultures. The chromatographic analysis of phenolic acids, flavonols, flavan-3-ols, and xanthones revealed marked differences between HR1 and HR2 cultures. The production of quinic acid, kaempferol, and seven identified xanthones was increased in HR2. Moreover, HR2 showed a capability for de novo biosynthesis of two phenolic acids (3-p-coumaroylquinic acid and 3-feruloylquinic acid), three flavonol glycosides (kaempferol hexoside, hyperoside, and quercetin acetylglycoside), and five xanthones (tetrahydroxy-one-methoxyxanthone, 1,3,5-trihydroxy-6-methoxyxanthone, 1,3,5,6-tetrahydroxy-2-prenylxanthone, paxanthone, and banaxanthone E). On the other side, HR1 cultures were better producers of flavan-3-ols (catechin, epicatechin, and proanthocyanidin dimers) than HR2. This is the first comparative study on phenolic profile of H. perforatum HR cultures grown under dark and photoperiod conditions. PMID:24453880

  15. Quality and antitumour activity evaluation of extract of Hypericum ascyron.

    PubMed

    Li, Xiu-Mei; Luo, Xue-Gang; Ma, Ning; Li, Kun; Li, Wen; Ma, De-Yun; Zhang, Tong-Cun

    2015-01-01

    Similarity assessment of complex chromatographic profiles is a potential tool for the identification and quality control of herbal medicinal products to guarantee the expected biological activity. In this paper, a high-performance liquid chromatography method was established for controlling the quality of extract of Hypericum ascyron for the first time. With this method, the correlation coefficients of similarity of 10 batches extract of H. ascyron were >0.97. The extract of H. ascyron displayed steadily inhibitorty activities on the growth of human cervical cancer Hela cell lines. Therefore, the present study successfully set up a sensitive efficient method which might confirm stable biological activity of the extract of H. ascyron. Copyright © 2014 John Wiley & Sons, Ltd.

  16. An in vitro and hydroponic growing system for hypericin, pseudohypericin, and hyperforin production of St. John's wort (Hypericum perforatum CV new stem).

    PubMed

    Murch, Susan J; Rupasinghe, H P Vasantha; Saxena, Praveen K

    2002-12-01

    While the interest in medicinal plants continues to grow, there is a lack of basic information with respect to efficient protocols for plant production. Recently, in vitro regeneration protocols have been developed to provide masses of sterile, consistent St. John's wort. The current study assessed the potential for acclimatization of in vitro grown St. John's wort plantlets to a nutrient film technique (NFT) hydroponic system in a controlled environment greenhouse. Quantitative analyses of hypericin, hyperforin and pseudohypericin in flower tissues were used as the parameters to assess the quality of the greenhouse-grown plants. The three bioactive compounds were found to be present in similar or higher amounts than previously reported values for field-grown plants. These data provide evidence that greenhouse hydroponic systems can be effectively used for the efficient production of St. John's wort and other medicinal plants.

  17. Targeting nuclear receptors with marine natural products.

    PubMed

    Yang, Chunyan; Li, Qianrong; Li, Yong

    2014-01-27

    Nuclear receptors (NRs) are important pharmaceutical targets because they are key regulators of many metabolic and inflammatory diseases, including diabetes, dyslipidemia, cirrhosis, and fibrosis. As ligands play a pivotal role in modulating nuclear receptor activity, the discovery of novel ligands for nuclear receptors represents an interesting and promising therapeutic approach. The search for novel NR agonists and antagonists with enhanced selectivities prompted the exploration of the extraordinary chemical diversity associated with natural products. Recent studies involving nuclear receptors have disclosed a number of natural products as nuclear receptor ligands, serving to re-emphasize the translational possibilities of natural products in drug discovery. In this review, the natural ligands of nuclear receptors will be described with an emphasis on their mechanisms of action and their therapeutic potentials, as well as on strategies to determine potential marine natural products as nuclear receptor modulators.

  18. Targeting Nuclear Receptors with Marine Natural Products

    PubMed Central

    Yang, Chunyan; Li, Qianrong; Li, Yong

    2014-01-01

    Nuclear receptors (NRs) are important pharmaceutical targets because they are key regulators of many metabolic and inflammatory diseases, including diabetes, dyslipidemia, cirrhosis, and fibrosis. As ligands play a pivotal role in modulating nuclear receptor activity, the discovery of novel ligands for nuclear receptors represents an interesting and promising therapeutic approach. The search for novel NR agonists and antagonists with enhanced selectivities prompted the exploration of the extraordinary chemical diversity associated with natural products. Recent studies involving nuclear receptors have disclosed a number of natural products as nuclear receptor ligands, serving to re-emphasize the translational possibilities of natural products in drug discovery. In this review, the natural ligands of nuclear receptors will be described with an emphasis on their mechanisms of action and their therapeutic potentials, as well as on strategies to determine potential marine natural products as nuclear receptor modulators. PMID:24473166

  19. Electrophilic natural products and their biological targets.

    PubMed

    Gersch, Malte; Kreuzer, Johannes; Sieber, Stephan A

    2012-06-01

    The study of biologically active natural products has resulted in seminal contributions to our understanding of living systems. In the case of electrophilic natural products, the covalent nature of their interaction has largely facilitated the identification of their biological binding partners. In this review, we provide a comprehensive compilation of electrophilic natural products from all major chemical classes together with their biological targets. Covering Michael acceptor systems, ring-strained compounds and other electrophiles, such as esters or carbamates, we highlight representative and instructive examples for over 20 electrophilic moieties. The fruitful cooperation of natural product chemistry, medicinal chemistry and chemical biology has produced a collection of well-studied examples for how electrophilic natural products exert their biological functions that range from antibiotic to antitumor effects. Special emphasis is put on the elucidation of their respective biological targets via activity-based protein profiling, which together with the recent advancements in mass spectrometry has been crucial to the success of the field. The wealth of naturally occurring electrophilic moieties and their chemical complexity enables binding of a large variety of biological targets, such as enzymes of all classes, nonenzymatic proteins, DNA and other cellular compounds. With approximately 30,000 genes in the human genome but only 266 confirmed protein drug targets, the study of biologically active, electrophilic natural products has the potential to provide insights into fundamental biological processes and to greatly aid the discovery of new drug targets.

  20. Natural gas production verification tests

    SciTech Connect

    Not Available

    1992-02-01

    This Environmental Assessment (EA) has been prepared by the Department of Energy (DOE) in compliance with the requirements of the National Environmental Policy Act of 1969. The Department of Energy (DOE) proposes to fund, through a contract with Petroleum Consulting Services, Inc. of Canton, Ohio, the testing of the effectiveness of a non-water based hydraulic fracturing treatment to increase gas recovery from low-pressure, tight, fractured Devonian Shale formations. Although Devonian Shales are found in the Appalachian, Michigan, and Illinois Basins, testing will be done only in the dominant, historical five state area of established production. The objective of this proposed project is to assess the benefits of liquid carbon dioxide (CO{sub 2})/sand stimulations in the Devonian Shale. In addition, this project would evaluate the potential nondamaging (to the formation) properties of this unique fracturing treatment relative to the clogging or chocking of pores and fractures that act as gas flow paths to the wellbore in the target gas-producing zones of the formation. This liquid CO{sub 2}/sand fracturing process is water-free and is expected to facilitate gas well cleanup, reduce the time required for post-stimulation cleanup, and result in improved production levels in a much shorter time than is currently experienced.

  1. Biodegradation potential of a modified natural product

    SciTech Connect

    Sajjad, W.

    1996-12-31

    Biodegradation potential of a modified natural product for treating petroleum contaminated soils was investigated along with some commercially available microbial cultures in three different scales from a laboratory to pilot to case studies. The modified natural product is lignocellulosic in nature and proprietary product of a company in Iowa. The production process of this product involves mechanical size reduction, blending/coating, and aerobic digestion of hay, corn cob residue, straw or crop residue in presence of poultry manure. The degradation kinetics of the petroleum products in the contaminated soils were measured both directly and indirectly. Residual petroleum products in different soils (treated and untreated) at various time periods were quantified by gas chromatographic (GC) analysis on extracted samples. The indirect assessment of the kinetics of biological activity involved the measurement of CO{sub 2} evolved from flasks (250 ml capacity) containing contaminated soil (about 50 ml) with various treatments. The results indicated that the biodegradation kinetics of petroleum products in the contaminated soils were significantly improved by treatment with this modified natural product. In most cases tested, this product performed significantly better than the available commercial bacterial cultures for biological removal of petroleum products from contaminated soils. This study also demonstrated the significance of temperature and moisture content in biodegradation kinetics.

  2. Hypericum perforatum-induced hepatotoxicity with possible association with copaiba (Copaifera langsdorffii Desf):case report

    PubMed Central

    Agollo, Marjorie Costa; Miszputen, Sender Jankiel; Diament, Jayme

    2014-01-01

    We report a case of liver damage in an elderly patient after the use of herbal products of Hypericum perforatum and copaiba (Copaifera langsdorffii Desf). Hepatotoxicity related to Hypericum perforatum is anecdotally known, but for copaiba, widely used as anti-inflammatory, there is just experimental data in the national literature. This report aimed to draw attention to the possible toxic effects of this association as well as to the clinical recovery of the patient after discontinuing their use. There is a tendency to suspect of the action of drugs to justify a non-viral acute liver injury, because of the large number of drugs responsible for hepatotoxicity. There are experiments and clinical reports in the literature describing some herbal products, including Hypericum perforatum, as the causative agents of this aggression, and are considered innocuous and used with no restrictions. We must remember that adverse reactions also occur with these substances; hence, they should be investigated when collecting the patient´s history, for leading to severe liver failure. PMID:25167337

  3. Hypericum perforatum-induced hepatotoxicity with possible association with copaiba (Copaifera langsdorffii Desf):case report.

    PubMed

    Agollo, Marjorie Costa; Miszputen, Sender Jankiel; Diament, Jayme

    2014-09-01

    We report a case of liver damage in an elderly patient after the use of herbal products of Hypericum perforatum and copaiba (Copaifera langsdorffii Desf). Hepatotoxicity related to Hypericum perforatum is anecdotally known, but for copaiba, widely used as anti-inflammatory, there is just experimental data in the national literature. This report aimed to draw attention to the possible toxic effects of this association as well as to the clinical recovery of the patient after discontinuing their use. There is a tendency to suspect of the action of drugs to justify a non-viral acute liver injury, because of the large number of drugs responsible for hepatotoxicity. There are experiments and clinical reports in the literature describing some herbal products, including Hypericum perforatum, as the causative agents of this aggression, and are considered innocuous and used with no restrictions. We must remember that adverse reactions also occur with these substances; hence, they should be investigated when collecting the patient´s history, for leading to severe liver failure.

  4. Marine actinomycete diversity and natural product discovery.

    PubMed

    Jensen, Paul R; Mincer, Tracy J; Williams, Philip G; Fenical, William

    2005-01-01

    Microbial natural products remain an important resource for drug discovery yet the microorganisms inhabiting the world's oceans have largely been overlooked in this regard. The recent discovery of novel secondary metabolites from taxonomically unique populations of marine actinomycetes suggests that these bacteria add an important new dimension to microbial natural product research. Continued efforts to characterize marine actinomycete diversity and how adaptations to the marine environment affect secondary metabolite production will create a better understanding of the potential utility of these bacteria as a source of useful products for biotechnology.

  5. Cancer wars: natural products strike back

    PubMed Central

    Basmadjian, Christine; Zhao, Qian; Bentouhami, Embarek; Djehal, Amel; Nebigil, Canan G.; Johnson, Roger A.; Serova, Maria; de Gramont, Armand; Faivre, Sandrine; Raymond, Eric; Désaubry, Laurent G.

    2014-01-01

    Natural products have historically been a mainstay source of anticancer drugs, but in the 90's they fell out of favor in pharmaceutical companies with the emergence of targeted therapies, which rely on antibodies or small synthetic molecules identified by high throughput screening. Although targeted therapies greatly improved the treatment of a few cancers, the benefit has remained disappointing for many solid tumors, which revitalized the interest in natural products. With the approval of rapamycin in 2007, 12 novel natural product derivatives have been brought to market. The present review describes the discovery and development of these new anticancer drugs and highlights the peculiarities of natural product and new trends in this exciting field of drug discovery. PMID:24822174

  6. Cancer wars: Natural products strike back

    NASA Astrophysics Data System (ADS)

    Basmadjian, Christine; Zhao, Qian; Djehal, Amel; Bentouhami, Embarek; Nebigil, Canan; Johnson, Roger; Serova, Maria; De Gramont, Armand; Faivre, Sandrine; Raymond, Eric; Désaubry, Laurent

    2014-05-01

    Natural products have historically been a mainstay source of anticancer drugs, but in the 90’s they fell out of favor in pharmaceutical companies with the emergence of targeted therapies, which rely on antibodies or small synthetic molecules identified by high throughput screening. Although targeted therapies greatly improved the treatment of a few cancers, the benefit has remained disappointing for many sol¬¬id tumors, which revitalized the interest in natural products. With the approval of rapamycin in 2007, twelve novel natural product derivatives have been brought to market. The present review describes the discovery and development of these new anticancer drugs and highlights the peculiarities of natural product and new trends in this exciting field of drug discovery.

  7. Biosynthesis of terpenoid natural products in fungi.

    PubMed

    Schmidt-Dannert, Claudia

    2015-01-01

    Tens of thousands of terpenoid natural products have been isolated from plants and microbial sources. Higher fungi (Ascomycota and Basidiomycota) are known to produce an array of well-known terpenoid natural products, including mycotoxins, antibiotics, antitumor compounds, and phytohormones. Except for a few well-studied fungal biosynthetic pathways, the majority of genes and biosynthetic pathways responsible for the biosynthesis of a small number of these secondary metabolites have only been discovered and characterized in the past 5-10 years. This chapter provides a comprehensive overview of the current knowledge on fungal terpenoid biosynthesis from biochemical, genetic, and genomic viewpoints. Enzymes involved in synthesizing, transferring, and cyclizing the prenyl chains that form the hydrocarbon scaffolds of fungal terpenoid natural products are systematically discussed. Genomic information and functional evidence suggest differences between the terpenome of the two major fungal phyla--the Ascomycota and Basidiomycota--which will be illustrated for each group of terpenoid natural products.

  8. Sources for Leads: Natural Products and Libraries.

    PubMed

    van Herwerden, Eric F; Süssmuth, Roderich D

    2016-01-01

    Natural products have traditionally been a major source of leads in the drug discovery process. However, the development of high-throughput screening led to an increased interest in synthetic methods that enabled the rapid construction of large libraries of molecules. This resulted in the termination or downscaling of many natural product research programs, but the chemical libraries did not necessarily produce a larger amount of drug leads. On one hand, this chapter explores the current state of natural product research within the drug discovery process. On the other hand it evaluates the efforts made to increase the amount of leads generated from chemical libraries and considers what role natural products could play here.

  9. Total synthesis of alkyl citrate natural products.

    PubMed

    Rizzacasa, Mark A; Sturgess, Dayna

    2014-03-07

    This review highlights the synthesis of members of the alkyl citrate family of natural products. The focus is on the stereoselective construction of the alkyl citrate moiety common to these compounds.

  10. Cancer wars: natural products strike back.

    PubMed

    Basmadjian, Christine; Zhao, Qian; Bentouhami, Embarek; Djehal, Amel; Nebigil, Canan G; Johnson, Roger A; Serova, Maria; de Gramont, Armand; Faivre, Sandrine; Raymond, Eric; Désaubry, Laurent G

    2014-01-01

    Natural products have historically been a mainstay source of anticancer drugs, but in the 90's they fell out of favor in pharmaceutical companies with the emergence of targeted therapies, which rely on antibodies or small synthetic molecules identified by high throughput screening. Although targeted therapies greatly improved the treatment of a few cancers, the benefit has remained disappointing for many solid tumors, which revitalized the interest in natural products. With the approval of rapamycin in 2007, 12 novel natural product derivatives have been brought to market. The present review describes the discovery and development of these new anticancer drugs and highlights the peculiarities of natural product and new trends in this exciting field of drug discovery.

  11. High impact technologies for natural products screening.

    PubMed

    Koehn, Frank E

    2008-01-01

    Natural products have historically been a rich source of lead molecules in drug discovery. However, natural products have been de-emphasized as high throughput screening resources in the recent past, in part because of difficulties in obtaining high quality natural products screening libraries, or in applying modern screening assays to these libraries. In addition, natural products programs based on screening of extract libraries, bioassay-guided isolation, structure elucidation and subsequent production scale-up are challenged to meet the rapid cycle times that are characteristic of the modern HTS approach. Fortunately, new technologies in mass spectrometry, NMR and other spectroscopic techniques can greatly facilitate the first components of the process - namely the efficient creation of high-quality natural products libraries, bimolecular target or cell-based screening, and early hit characterization. The success of any high throughput screening campaign is dependent on the quality of the chemical library. The construction and maintenance of a high quality natural products library, whether based on microbial, plant, marine or other sources is a costly endeavor. The library itself may be composed of samples that are themselves mixtures - such as crude extracts, semi-pure mixtures or single purified natural products. Each of these library designs carries with it distinctive advantages and disadvantages. Crude extract libraries have lower resource requirements for sample preparation, but high requirements for identification of the bioactive constituents. Pre-fractionated libraries can be an effective strategy to alleviate interferences encountered with crude libraries, and may shorten the time needed to identify the active principle. Purified natural product libraries require substantial resources for preparation, but offer the advantage that the hit detection process is reduced to that of synthetic single component libraries. Whether the natural products library

  12. Natural products from the genus tephrosia.

    PubMed

    Chen, Yinning; Yan, Tao; Gao, Chenghai; Cao, Wenhao; Huang, Riming

    2014-01-27

    The genus Tephrosia, belonging to the Leguminosae family, is a large pantropical genus of more than 350 species, many of which have important traditional uses in agriculture. This review not only outlines the source, chemistry and biological evaluations of natural products from the genus Tephrosia worldwide that have appeared in literature from 1910 to December 2013, but also covers work related to proposed biosynthetic pathways and synthesis of some natural products from the genus Tephrosia, with 105 citations and 168 new compounds.

  13. Hypolipidemic and Antiobesity-Like Activity of Standardised Extract of Hypericum perforatum L. in Rats.

    PubMed

    Husain, Gulam Mohammed; Chatterjee, Shyam Sunder; Singh, Paras Nath; Kumar, Vikas

    2011-01-01

    Hypericum perforatum is known to have diverse medicinal uses for centuries. The antidepressant activity of Hypericum perforatum is widely accepted and proved in both animal and clinical studies. Present study was undertaken to investigate the effect of Hypericum perforatum in a battery of animal models for metabolic disorder. Hypericum is tested for hypolipidemic activity in normal rats, antiobesity activity in high-fat-diet induced obese rats, and fructose-fed rats. Hypericum was orally administered as suspension in 0.3% carboxymethyl cellulose at the doses of 100 and 200 mg/kg body weight for 15 consecutive days. Hypericum significantly lowered total cholesterol and low-density cholesterol in normal rats. Hypericum significantly inhibited weight gain in high-fat-fed rats. In fructose-fed rats, Hypericum normalised the dyslipidemia induced by fructose feeding and improved the insulin sensitivity. Taken together, Hypericum could be the antidepressant therapy of choice for patients suffering from comorbid diabetes and obesity.

  14. Radical scavenging and antioxidant activities of methanolic extracts from Hypericum species growing in Bulgaria

    PubMed Central

    Zheleva-Dimitrova, Dimitrina; Nedialkov, Paraskev; Kitanov, Gerassim

    2010-01-01

    Thirteen Hypericum species growing in Bulgaria were investigated for free radical-scavenging activity, antioxidant activity, total tannins and total flavonoids contents. Methanolic extracts from the Hypericum species were analyzed for radical scavenging and antioxidant activities using DPPH-, ABTS- free radicals, total antioxidant activity and inhibition of lipid peroxidation by ferric thiocyanate (FTC) method. Butylated hydroxytoluene and ascorbic acid were used as positive controls. Methanolic extracts from H. cerastoides, H. perforatum and H. maculatum demonstrate the highest antioxidant activities and are potential sources of natural antioxidant compounds. The quantification of tannins and flavanoids were determined in Hypericum species using Folin-Chiocalteu reagent and AlCl3, respectively. The amounts of the tannins ranged from 1.30 ± 0.01 mg/100 g dw in H. elegans to 8.67 ± 0.02 g/100 g dw in H. perforatum. The highest concentration of flavonoids was found in H. cerastoides (1.22 ± 0.02 g/100g dw), and the lowest amount was established in H. olympicum (0.20 ± 0.03 g/100g dw). PMID:20668569

  15. How EIA Estimates Natural Gas Production

    EIA Publications

    2004-01-01

    The Energy Information Administration (EIA) publishes estimates monthly and annually of the production of natural gas in the United States. The estimates are based on data EIA collects from gas producing states and data collected by the U. S. Minerals Management Service (MMS) in the Department of Interior. The states and MMS collect this information from producers of natural gas for various reasons, most often for revenue purposes. Because the information is not sufficiently complete or timely for inclusion in EIA's Natural Gas Monthly (NGM), EIA has developed estimation methodologies to generate monthly production estimates that are described in this document.

  16. Polyisoprenylated benzoylphloroglucinol derivatives from Hypericum scabrum.

    PubMed

    Gao, Wan; Hu, Jia-Wen; Xu, Fang; Wei, Can-Jing; Shi, Meng-Jiao; Zhao, Jun; Wang, Jia-Jia; Zhen, Bo; Ji, Teng-Fei; Xing, Jian-Guo; Gu, Zheng-Yi; Xu, Fang

    2016-12-01

    Four new polyisoprenylated benzoylphloroglucinol derivatives, hyperscabrones J-M (1-4), were isolated from the air-dried aerial parts of Hypericum scabrum. Their structures were elucidated by spectroscopic methods and were subsequently confirmed by comparing with data of known compounds. The absolute configuration of the bicyclo[3.3.1]nonane-2,4,9-trione core was defined by the experimental and calculated electronic circular dichroism (ECD) spectra. The evaluation of their hepatoprotective activities against paracetamol-induced HepG2 cell damage showed that compounds 2 and 4 exhibited significant hepatoprotection at 10μM.

  17. Polyprenylated Tetraoxygenated Xanthones from the Roots of Hypericum monogynum and Their Neuroprotective Activities.

    PubMed

    Xu, Wen-Jun; Li, Rui-Jun; Quasie, Olga; Yang, Ming-Hua; Kong, Ling-Yi; Luo, Jun

    2016-08-26

    Ten new polyprenylated tetraoxygenated xanthones, monogxanthones A-J (1-10), together with eight known analogues (4b, 11-17) were identified from the roots of Hypericum monogynum. The structures of these new polyprenylated xanthones (1-10), a class of compounds rarely found in plants of the genus Hypericum, were elucidated by the interpretation of their HRESIMS, 1D and 2D NMR, and electronic circular dichroism data. Compounds 1 and 2 exhibited neuroprotective effects against corticosterone (Cort)-induced lesions of PC12 cells at concentrations of 6.25, 12.50, and 25.00 μM, with cell viability greater than 75%, as well as inhibitory effects on nitric oxide production in lipopolysaccharide-induced BV2 microglia cells, with IC50 values of 7.47 ± 0.65 and 9.60 ± 0.12 μM, respectively. Collectively, these results shed new light on the potential of polyprenylated xanthones from the genus Hypericum in the development of antidepression therapies.

  18. Naturally occurring products in cancer therapy

    PubMed Central

    Rajesh, E.; Sankari, Leena S.; Malathi, L.; Krupaa, Jayasri R.

    2015-01-01

    Natural products have been used for the treatment of various diseases and are becoming an important research area for drug discovery. These products, especially phytochemicals have been extensively studies and have exhibited anti-carcinogenic activities by interfering with the initiation, development and progression of cancer through the modulation of various mechanisms including cellular proliferation, differentiation, apoptosis, angiogenesis, and metastasis. This concept is gaining attention because it is a cost-effective alternative to cancer treatment. In this article, we have discussed some of the naturally occurring products used in cancer treatment. PMID:26015704

  19. Natural product discovery: past, present, and future.

    PubMed

    Katz, Leonard; Baltz, Richard H

    2016-03-01

    Microorganisms have provided abundant sources of natural products which have been developed as commercial products for human medicine, animal health, and plant crop protection. In the early years of natural product discovery from microorganisms (The Golden Age), new antibiotics were found with relative ease from low-throughput fermentation and whole cell screening methods. Later, molecular genetic and medicinal chemistry approaches were applied to modify and improve the activities of important chemical scaffolds, and more sophisticated screening methods were directed at target disease states. In the 1990s, the pharmaceutical industry moved to high-throughput screening of synthetic chemical libraries against many potential therapeutic targets, including new targets identified from the human genome sequencing project, largely to the exclusion of natural products, and discovery rates dropped dramatically. Nonetheless, natural products continued to provide key scaffolds for drug development. In the current millennium, it was discovered from genome sequencing that microbes with large genomes have the capacity to produce about ten times as many secondary metabolites as was previously recognized. Indeed, the most gifted actinomycetes have the capacity to produce around 30-50 secondary metabolites. With the precipitous drop in cost for genome sequencing, it is now feasible to sequence thousands of actinomycete genomes to identify the "biosynthetic dark matter" as sources for the discovery of new and novel secondary metabolites. Advances in bioinformatics, mass spectrometry, proteomics, transcriptomics, metabolomics and gene expression are driving the new field of microbial genome mining for applications in natural product discovery and development.

  20. Antitumor activity of Hypericum hookerianum against DLA induced tumor in mice and its possible mechanism of action.

    PubMed

    Dongre, Santoshkumar H; Badami, Shrishailappa; Godavarthi, Ashok

    2008-01-01

    A large number of plants belonging to the genus Hypericum and their phytoconstituents are known to possess potent anticancer nature. Earlier studies from our laboratories indicated a strong cytotoxic nature of the methanol extract of Hypericum hookerianum stem (MEHH). In the present study, the in vivo antitumor activity of MEHH against the Dalton's lymphoma ascitic (DLA) model was determined at 100 and 200 mg/kg body weight given orally for 10 days. The results indicate that administration of the extract not only increased the survival of animals with ascites tumor, decreased the body weight induced by the tumor burden and reduced the packed cell volume and viable tissue cell count, but also altered many hematological parameters changed during tumor progression indicating the potent antitumor nature of the extract. Hematological and biochemical analysis were carried out to prove the anticancer and antioxidant nature of the extract. Copyright (c) 2007 John Wiley & Sons, Ltd.

  1. Using Genomics for Natural Product Structure Elucidation.

    PubMed

    Tietz, Jonathan I; Mitchell, Douglas A

    2016-01-01

    Natural products (NPs) are the most historically bountiful source of chemical matter for drug development-especially for anti-infectives. With insights gleaned from genome mining, interest in natural product discovery has been reinvigorated. An essential stage in NP discovery is structural elucidation, which sheds light not only on the chemical composition of a molecule but also its novelty, properties, and derivatization potential. The history of structure elucidation is replete with techniquebased revolutions: combustion analysis, crystallography, UV, IR, MS, and NMR have each provided game-changing advances; the latest such advance is genomics. All natural products have a genetic basis, and the ability to obtain and interpret genomic information for structure elucidation is increasingly available at low cost to non-specialists. In this review, we describe the value of genomics as a structural elucidation technique, especially from the perspective of the natural product chemist approaching an unknown metabolite. Herein we first introduce the databases and programs of interest to the natural products chemist, with an emphasis on those currently most suited for general usability. We describe strategies for linking observed natural product-linked phenotypes to their corresponding gene clusters. We then discuss techniques for extracting structural information from genes, illustrated with numerous case examples. We also provide an analysis of the biases and limitations of the field with recommendations for future development. Our overview is not only aimed at biologically-oriented researchers already at ease with bioinformatic techniques, but also, in particular, at natural product, organic, and/or medicinal chemists not previously familiar with genomic techniques.

  2. Computational approaches to natural product discovery

    PubMed Central

    Medema, Marnix H.; Fischbach, Michael A.

    2016-01-01

    From the earliest Streptomyces genome sequences, the promise of natural product genome mining has been captivating: genomics and bioinformatics would transform compound discovery from an ad hoc pursuit to a high-throughput endeavor. Until recently, however, genome mining has advanced natural product discovery only modestly. Here, we argue that the development of algorithms to mine the continuously increasing amounts of (meta)genomic data will enable the promise of genome mining to be realized. We review computational strategies that have been developed to identify biosynthetic gene clusters in genome sequences and predict the chemical structures of their products. We then discuss networking strategies that can systematize large volumes of genetic and chemical data, and connect genomic information to metabolomic and phenotypic data. Finally, we provide a vision of what natural product discovery might look like in the future, specifically considering long-standing questions in microbial ecology regarding the roles of metabolites in interspecies interactions. PMID:26284671

  3. Computational approaches to natural product discovery.

    PubMed

    Medema, Marnix H; Fischbach, Michael A

    2015-09-01

    Starting with the earliest Streptomyces genome sequences, the promise of natural product genome mining has been captivating: genomics and bioinformatics would transform compound discovery from an ad hoc pursuit to a high-throughput endeavor. Until recently, however, genome mining has advanced natural product discovery only modestly. Here, we argue that the development of algorithms to mine the continuously increasing amounts of (meta)genomic data will enable the promise of genome mining to be realized. We review computational strategies that have been developed to identify biosynthetic gene clusters in genome sequences and predict the chemical structures of their products. We then discuss networking strategies that can systematize large volumes of genetic and chemical data and connect genomic information to metabolomic and phenotypic data. Finally, we provide a vision of what natural product discovery might look like in the future, specifically considering longstanding questions in microbial ecology regarding the roles of metabolites in interspecies interactions.

  4. Natural products as sources for new pesticides.

    PubMed

    Cantrell, Charles L; Dayan, Franck E; Duke, Stephen O

    2012-06-22

    Natural products as pesticides have been reviewed from several perspectives in the past, but no prior treatment has examined the impact of natural product and natural product-based pesticides on the U.S. market, as a function of new active ingredient registrations with the Environmental Protection Agency (EPA). Thus, EPA registration details of new active ingredients for all conventional pesticide registrations and biopesticide registrations were compiled from the years 1997-2010. Conventional pesticide registrations and biopesticide registrations were examined both collectively and independently for all 277 new active ingredients (NAI) and subsequently categorized and sorted into four types: biological (B), natural product (NP), synthetic (S), and synthetic natural derived (SND). When examining conventional pesticides alone, the S category accounted for the majority of NAI registrations, with 78.0%, followed by SND with 14.7%, NP with 6.4%, and B with 0.9%. Biopesticides alone were dominated by NPs with 54.8%, followed by B with 44.6%, SND with 0.6%, and 0% for S. When examining conventional pesticides and biopesticides combined, NPs accounted for the majority of NAI registrations, with 35.7%, followed by S with 30.7%, B with 27.4%, and SND with 6.1%. Despite the common perception that natural products may not be the best sources for NAI as pesticides, when both conventional and biopesticides are examined collectively, and considering that NP, SND, and B all have origins from natural product research, it can be argued that their combined impact with the EPA from 1997 to 2010 accounted for 69.3% of all NAI registrations.

  5. Synthetic Biological Approaches to Natural Product Biosynthesis

    PubMed Central

    Winter, Jaclyn M; Tang, Yi

    2012-01-01

    Small molecules produced in Nature continue to be an inspiration for the development of new therapeutic agents. These natural products possess exquisite chemical diversity, which gives rise to their wide range of biological activities. In their host organism, natural products are assembled and modified by dedicated biosynthetic pathways that Nature has meticulously developed. Often times, the complex structures or chemical modifications instated by these pathways are difficult to replicate using traditional synthetic methods. An alternative approach for creating or enhancing the structural variation of natural products is through combinatorial biosynthesis. By rationally reprogramming and manipulating the biosynthetic machinery responsible for their production, unnatural metabolites that were otherwise inaccessible can be obtained. Additionally, new chemical structures can be synthesized or derivatized by developing the enzymes that carry out these complicated chemical reactions into biocatalysts. In this review, we will discuss a variety of combinatorial biosynthetic strategies, their technical challenges, and highlight some recent (since 2007) examples of rationally designed unnatural metabolites, as well as platforms that have been established for the production and modification of clinically important pharmaceutical compounds. PMID:22221832

  6. THE BIOLOGICAL ACTIVITIES OF HYPERICUM PERFORATUM L.

    PubMed Central

    Okmen, Gulten; Balpınar, Neslihan

    2017-01-01

    Background: Mastitis reduces milk yield and alters milk composition. Antibiotics are widely used in the treatment of the disease. However, this widespread use of antibiotics causes both antibiotic residues in milks and antibiotic resistance developed in bacteria. Today’s researches are focused on discovering and using new antibiotics against bacteria. Objective: The aim of this work was to discover the antibacterial effects of Hypericum perforatum L. extracts against mastitis pathogens, and its other biological activities. Material and Methods: Kirby-Bauer assay was applied to the extracts. The other antibacterial activity was MIC for plant extracts. The non-enzymatic antioxidant activity was found using 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH). Results: The extract was showed maximum inhibition zone against two bacteria (Coagulase-negative Staphylococci-33 and 37; CNS 33 and 37), and the zone was 17 mm. A bacterium (CNS - 22) showed the lowest sensitivity to 812.5 μg/mL concentration. In addition, the extract was tried against the stable DPPH for antioxidant activity. As a result, the extract showed a strength antioxidant activity. Trolox equivalent is 0.83 mM. Conclusion: The extract of Hypericum perforatum have antibacterial, antioxidant and antimutagenic potentials. PMID:28480399

  7. Naturally Efficient Emitters: Luminescent Organometallic Complexes Derived from Natural Products

    NASA Astrophysics Data System (ADS)

    Zhang, Wen-Hua; Young, David J.

    2013-08-01

    Naturally occurring molecules offer intricate structures and functionality that are the basis of modern medicinal chemistry, but are under-represented in materials science. Herein, we review recent literature describing the use of abundant and relatively inexpensive, natural products for the synthesis of ligands for luminescent organometallic complexes used for organic light emitting diodes (OLEDs) and related technologies. These ligands are prepared from the renewable starting materials caffeine, camphor, pinene and cinchonine and, with the exception of caffeine, impart performance improvements to the emissive metal complexes and resulting OLED devices, with emission wavelengths that span the visible spectrum from blue to red. The advantages of these biologically-derived molecules include improved solution processibility and phase homogeneity, brighter luminescence, higher quantum efficiencies and lower turn-on voltages. While nature has evolved these carbon-skeletons for specific purposes, they also offer some intriguing benefits in materials science and technology.

  8. A new polyisoprenylated phloroglucinol derivative from Hypericum perfoliatum (Clusiaceae).

    PubMed

    Benkiki, Naòma; Kabouche, Zahia; Tillequin, François; Vérité, Philippe; Chosson, Elizabeth; Seguin, Elisabeth

    2003-01-01

    Hyperfoliatin, a new polyisoprenylated phloroglucinol derivative was isolated from the aerial parts of Hypericum perfoliatum (Clusiaceae) collected in Algeria. The structure of hyperfoliatin was elucidated on the basis of its spectral data, mainly MS and multiple-pulse NMR.

  9. Two new prenylated phloroglucinol derivatives from Hypericum scabrum.

    PubMed

    Yang, Jian-Bo; Liu, Rang-Dong; Ren, Jin; Wei, Qian; Wang, Ai-Guo; Su, Ya-Lun

    2016-05-01

    Two new prenylated phloroglucinol derivatives (1-2), and a known compound furohyperforim isomer 2 (3), were isolated from the aerial parts of Hypericum scabrum. Their structures were elucidated by various spectroscopic methods, including MS, IR, UV, and NMR.

  10. Countercurrent Separation of Natural Products: An Update.

    PubMed

    Friesen, J Brent; McAlpine, James B; Chen, Shao-Nong; Pauli, Guido F

    2015-07-24

    This work assesses the current instrumentation, method development, and applications in countercurrent chromatography (CCC) and centrifugal partition chromatography (CPC), collectively referred to as countercurrent separation (CCS). The article provides a critical review of the CCS literature from 2007 since our last review (J. Nat. Prod. 2008, 71, 1489-1508), with a special emphasis on the applications of CCS in natural products research. The current state of CCS is reviewed in regard to three continuing topics (instrumentation, solvent system development, theory) and three new topics (optimization of parameters, workflow, bioactivity applications). The goals of this review are to deliver the necessary background with references for an up-to-date perspective of CCS, to point out its potential for the natural product scientist, and thereby to induce new applications in natural product chemistry, metabolome, and drug discovery research involving organisms from terrestrial and marine sources.

  11. Countercurrent Separation of Natural Products: An Update

    PubMed Central

    2015-01-01

    This work assesses the current instrumentation, method development, and applications in countercurrent chromatography (CCC) and centrifugal partition chromatography (CPC), collectively referred to as countercurrent separation (CCS). The article provides a critical review of the CCS literature from 2007 since our last review (J. Nat. Prod.2008, 71, 1489–1508), with a special emphasis on the applications of CCS in natural products research. The current state of CCS is reviewed in regard to three continuing topics (instrumentation, solvent system development, theory) and three new topics (optimization of parameters, workflow, bioactivity applications). The goals of this review are to deliver the necessary background with references for an up-to-date perspective of CCS, to point out its potential for the natural product scientist, and thereby to induce new applications in natural product chemistry, metabolome, and drug discovery research involving organisms from terrestrial and marine sources. PMID:26177360

  12. Early state research on antifungal natural products.

    PubMed

    Negri, Melyssa; Salci, Tânia P; Shinobu-Mesquita, Cristiane S; Capoci, Isis R G; Svidzinski, Terezinha I E; Kioshima, Erika Seki

    2014-03-07

    Nosocomial infections caused by fungi have increased greatly in recent years, mainly due to the rising number of immunocompromised patients. However, the available antifungal therapeutic arsenal is limited, and the development of new drugs has been slow. Therefore, the search for alternative drugs with low resistance rates and fewer side effects remains a major challenge. Plants produce a variety of medicinal components that can inhibit pathogen growth. Studies of plant species have been conducted to evaluate the characteristics of natural drug products, including their sustainability, affordability, and antimicrobial activity. A considerable number of studies of medicinal plants and alternative compounds, such as secondary metabolites, phenolic compounds, essential oils and extracts, have been performed. Thus, this review discusses the history of the antifungal arsenal, surveys natural products with potential antifungal activity, discusses strategies to develop derivatives of natural products, and presents perspectives on the development of novel antifungal drug candidates.

  13. Natural Products and Ion Channel Pharmacology

    PubMed Central

    Teichert, Russell W.; Olivera, Baldomero M.

    2014-01-01

    An accelerated rate of natural-product discovery is critical for the future of ion channel pharmacology. For the full potential of natural products to be realized, an interdisciplinary initiative is required that combines chemical ecology and ion channel physiology. A prime source of future drug leads targeted to ion channels is the vast assortment of compounds that mediate biotic interactions in the marine environment. Many animals have evolved a chemical strategy to change the behavior of their prey, predators or competitors, which appears to require a large set of ion-channel targeted compounds acting in concert. Some of these compounds (e.g. Ziconotide (Prialt)) have already found important biomedical applications. The elucidation of molecular mechanisms mediating biotic interactions should yield a rich stream of potent and selective natural products for the drug pipeline. PMID:21426200

  14. Natural Product Sugar Biosynthesis and Enzymatic Glycodiversification**

    PubMed Central

    Thibodeaux, Christopher J.; Melançon, Charles E.; Liu, Hung-wen

    2009-01-01

    Many biologically active small molecule natural products produced by microorganisms derive their activities from sugar substituents. Changing the structures of these sugars can have a profound impact on the biological properties of the parent compounds. This realization has inspired attempts to derivatize the sugar moieties of these natural products through exploitation of the sugar biosynthetic machinery. This approach requires an understanding of the biosynthetic pathway of each target sugar and detailed mechanistic knowledge of the key enzymes. Scientists have begun to unravel the biosynthetic logic behind the assembly of many glycosylated natural products, and have found that a core set of enzyme activities is mixed and matched to synthesize the diverse sugar structures observed in nature. Remarkably, many of these sugar biosynthetic enzymes and glycosyltransferases also exhibit relaxed substrate specificity. The promiscuity of these enzymes has prompted efforts to modify the sugar structures and/or alter the glycosylation patterns of natural products via metabolic pathway engineering and/or enzymatic glycodiversification. In applied biomedical research, these studies will enable the development of new glycosylation tools and generate novel glycoforms of secondary metabolites with useful biological activity. PMID:19058170

  15. Natural products as probes in pharmaceutical research.

    PubMed

    Schmitt, Esther K; Hoepfner, D; Krastel, P

    2016-03-01

    From the start of the pharmaceutical research natural products played a key role in drug discovery and development. Over time many discoveries of fundamental new biology were triggered by the unique biological activity of natural products. Unprecedented chemical structures, novel chemotypes, often pave the way to investigate new biology and to explore new pathways and targets. This review summarizes the recent results in the area with a focus on research done in the laboratories of Novartis Institutes for BioMedical Research. We aim to put the technological advances in target identification techniques in the context to the current revival of phenotypic screening and the increasingly complex biological questions related to drug discovery.

  16. Anti-Inflammatory Activity of Natural Products.

    PubMed

    Azab, Abdullatif; Nassar, Ahmad; Azab, Abed N

    2016-10-01

    This article presents highlights of the published literature regarding the anti-inflammatory activities of natural products. Many review articles were published in this regard, however, most of them have presented this important issue from a regional, limited perspective. This paper summarizes the vast range of review and research articles that have reported on the anti-inflammatory effects of extracts and/or pure compounds derived from natural products. Moreover, this review pinpoints some interesting traditionally used medicinal plants that were not investigated yet.

  17. Antiviral Natural Products and Herbal Medicines

    PubMed Central

    Lin, Liang-Tzung; Hsu, Wen-Chan; Lin, Chun-Ching

    2014-01-01

    Viral infections play an important role in human diseases, and recent outbreaks in the advent of globalization and ease of travel have underscored their prevention as a critical issue in safeguarding public health. Despite the progress made in immunization and drug development, many viruses lack preventive vaccines and efficient antiviral therapies, which are often beset by the generation of viral escape mutants. Thus, identifying novel antiviral drugs is of critical importance and natural products are an excellent source for such discoveries. In this mini-review, we summarize the antiviral effects reported for several natural products and herbal medicines. PMID:24872930

  18. Natural gas product and strategic analysis

    SciTech Connect

    Layne, A.W.; Duda, J.R.; Zammerilli, A.M.

    1993-12-31

    Product and strategic analysis at the Department of Energy (DOE)/Morgantown Energy Technology Center (METC) crosscuts all sectors of the natural gas industry. This includes the supply, transportation, and end-use sectors of the natural-gas market. Projects in the Natural Gas Resource and Extraction supply program have been integrated into a new product focus. Product development facilitates commercialization and technology transfer through DOE/industry cost-shared research, development, and demonstration (RD&D). Four products under the Resource and Extraction program include Resource and Reserves; Low Permeability Formations; Drilling, Completion, and Stimulation: and Natural Gas Upgrading. Engineering process analyses have been performed for the Slant Hole Completion Test project. These analyses focused on evaluation of horizontal-well recovery potential and applications of slant-hole technology. Figures 2 and 3 depict slant-well in situ stress conditions and hydraulic fracture configurations. Figure 4 presents Paludal Formation coal-gas production curves used to optimize the hydraulic fracture design for the slant well. Economic analyses have utilized data generated from vertical test wells to evaluate the profitability of horizontal technology for low-permeability formations in Yuma County, Colorado, and Maverick County, Texas.

  19. Natural antioxidants in meat and poultry products.

    PubMed

    Karre, Liz; Lopez, Keyla; Getty, Kelly J K

    2013-06-01

    In response to recent claims that synthetic antioxidants have the potential to cause toxicological effects and consumers' increased interest in purchasing natural products, the meat and poultry industry has been seeking sources of natural antioxidants. Due to their high phenolic compound content, fruits and other plant materials provide a good alternative to conventional antioxidants. Plum, grape seed extract, cranberry, pomegranate, bearberry, pine bark extract, rosemary, oregano, and other spices functions as antioxidants in meat and poultry products. Pomegranate, pine bark extract, cinnamon, and cloves have exhibited stronger antioxidant properties than some synthetic options. Plum products, grape seed extract, pine bark extract, rosemary, and some spices all have been shown to affect the color of finished meat or poultry products; however, in some products such as pork sausage or uncured meats, an increase in red color may be desired. When selecting a natural antioxidant, sensory and quality impact on the product should be considered to achieve desired traits. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Metabolic Engineering for the Production of Natural Products

    PubMed Central

    Pickens, Lauren B.; Tang, Yi; Chooi, Yit-Heng

    2014-01-01

    Natural products and natural product derived compounds play an important role in modern healthcare as frontline treatments for many diseases and as inspiration for chemically synthesized therapeutics. With advances in sequencing and recombinant DNA technology, many of the biosynthetic pathways responsible for the production of these chemically complex and pharmaceutically valuable compounds have been elucidated. With an ever expanding toolkit of biosynthetic components, metabolic engineering is an increasingly powerful method to improve natural product titers and generate novel compounds. Heterologous production platforms have enabled access to pathways from difficult to culture strains; systems biology and metabolic modeling tools have resulted in increasing predictive and analytic capabilities; advances in expression systems and regulation have enabled the fine-tuning of pathways for increased efficiency, and characterization of individual pathway components has facilitated the construction of hybrid pathways for the production of new compounds. These advances in the many aspects of metabolic engineering have not only yielded fascinating scientific discoveries but also make it an increasingly viable approach for the optimization of natural product biosynthesis. PMID:22432617

  1. An automated Genomes-to-Natural Products platform (GNP) for the discovery of modular natural products.

    PubMed

    Johnston, Chad W; Skinnider, Michael A; Wyatt, Morgan A; Li, Xiang; Ranieri, Michael R M; Yang, Lian; Zechel, David L; Ma, Bin; Magarvey, Nathan A

    2015-09-28

    Bacterial natural products are a diverse and valuable group of small molecules, and genome sequencing indicates that the vast majority remain undiscovered. The prediction of natural product structures from biosynthetic assembly lines can facilitate their discovery, but highly automated, accurate, and integrated systems are required to mine the broad spectrum of sequenced bacterial genomes. Here we present a genome-guided natural products discovery tool to automatically predict, combinatorialize and identify polyketides and nonribosomal peptides from biosynthetic assembly lines using LC-MS/MS data of crude extracts in a high-throughput manner. We detail the directed identification and isolation of six genetically predicted polyketides and nonribosomal peptides using our Genome-to-Natural Products platform. This highly automated, user-friendly programme provides a means of realizing the potential of genetically encoded natural products.

  2. An automated Genomes-to-Natural Products platform (GNP) for the discovery of modular natural products

    PubMed Central

    Johnston, Chad W.; Skinnider, Michael A.; Wyatt, Morgan A.; Li, Xiang; Ranieri, Michael R. M.; Yang, Lian; Zechel, David L.; Ma, Bin; Magarvey, Nathan A.

    2015-01-01

    Bacterial natural products are a diverse and valuable group of small molecules, and genome sequencing indicates that the vast majority remain undiscovered. The prediction of natural product structures from biosynthetic assembly lines can facilitate their discovery, but highly automated, accurate, and integrated systems are required to mine the broad spectrum of sequenced bacterial genomes. Here we present a genome-guided natural products discovery tool to automatically predict, combinatorialize and identify polyketides and nonribosomal peptides from biosynthetic assembly lines using LC–MS/MS data of crude extracts in a high-throughput manner. We detail the directed identification and isolation of six genetically predicted polyketides and nonribosomal peptides using our Genome-to-Natural Products platform. This highly automated, user-friendly programme provides a means of realizing the potential of genetically encoded natural products. PMID:26412281

  3. Chocolate: A Marvelous Natural Product of Chemistry

    ERIC Educational Resources Information Center

    Tannenbaum, Ginger

    2004-01-01

    The study of chocolate, a natural product, can be beneficial for the chemistry students as they ask frequently about the relevancy of their chemistry classes. The history of chocolate, its chemical and physical changes during processing, its composition, different crystalline forms, tempering and its viscosity are discussed.

  4. Flow chemistry syntheses of natural products.

    PubMed

    Pastre, Julio C; Browne, Duncan L; Ley, Steven V

    2013-12-07

    The development and application of continuous flow chemistry methods for synthesis is a rapidly growing area of research. In particular, natural products provide demanding challenges to this developing technology. This review highlights successes in the area with an emphasis on new opportunities and technological advances.

  5. Marine Natural Products as Prototype Agrochemical Agents

    PubMed Central

    Peng, Jiangnan; Shen, Xiaoyu; El Sayed, Khalid A.; Dunbar, D. C Harles; Perry, Tony L.; Wilkins, Scott P.; Hamann, Mark T.; Bobzin, Steve; Huesing, Joseph; Camp, Robin; Prinsen, Mike; Krupa, Dan; Wideman, Margaret A.

    2016-01-01

    In the interest of identifying new leads that could serve as prototype agrochemical agents, 18 structurally diverse marine-derived compounds were examined for insecticidal, herbicidal, and fungicidal activities. Several new classes of compounds have been shown to be insecticidal, herbicidal, and fungicidal, which suggests that marine natural products represent an intriguing source for the discovery of new agrochemical agents. PMID:12670165

  6. Plants as natural antioxidants for meat products

    NASA Astrophysics Data System (ADS)

    Tomović, V.; Jokanović, M.; Šojić, B.; Škaljac, S.; Ivić, M.

    2017-09-01

    The meat industry is demanding antioxidants from natural sources to replace synthetic antioxidants because of the negative health consequences or beliefs regarding some synthetic ones. Plants materials provide good alternatives. Spices and herbs, generally used for their flavouring characteristics, can be added to meat products in various forms: whole, ground, or as isolates from their extracts. These natural antioxidants contain some active compounds, which exert antioxidative potential in meat products. This antioxidant activity is most often due to phenolic acids, phenolic diterpenes, flavonoids and volatile oils. Each of these compounds often has strong H-donating activity, thus making them extremely effective antioxidants; some compounds can chelate metals and donate H to oxygen radicals, thus slowing oxidation via two mechanisms. Numerous studies have demonstrated the efficacy of natural antioxidants when used in meat products. Based on this literature review, it can be concluded that natural antioxidants are added to fresh and processed meat and meat products to delay, retard, or prevent lipid oxidation, retard development of off-flavours (rancidity), improve colour stability, improve microbiological quality and extend shelf-life, without any damage to the sensory or nutritional properties.

  7. New Methodology for Natural Gas Production Estimates

    EIA Publications

    2010-01-01

    A new methodology is implemented with the monthly natural gas production estimates from the EIA-914 survey this month. The estimates, to be released April 29, 2010, include revisions for all of 2009. The fundamental changes in the new process include the timeliness of the historical data used for estimation and the frequency of sample updates, both of which are improved.

  8. Chocolate: A Marvelous Natural Product of Chemistry

    ERIC Educational Resources Information Center

    Tannenbaum, Ginger

    2004-01-01

    The study of chocolate, a natural product, can be beneficial for the chemistry students as they ask frequently about the relevancy of their chemistry classes. The history of chocolate, its chemical and physical changes during processing, its composition, different crystalline forms, tempering and its viscosity are discussed.

  9. Natural Products for Chemoprevention of Breast Cancer

    PubMed Central

    Ko, Eun-Yi; Moon, Aree

    2015-01-01

    Breast cancer is the primary cause of cancer death in women. Although current therapies have shown some promise against breast cancer, there is still no effective cure for the majority of patients in the advanced stages of breast cancer. Development of effective agents to slow, reduce, or reverse the incidence of breast cancer in high-risk women is necessary. Chemoprevention of breast cancer by natural products is advantageous, as these compounds have few side effects and low toxicity compared to synthetic compounds. In the present review, we summarize natural products which exert chemopreventive activities against breast cancer, such as curcumin, sauchinone, lycopene, denbinobin, genipin, capsaicin, and ursolic acid. This review examines the current knowledge about natural compounds and their mechanisms that underlie breast cancer chemopreventive activity both in vitro and in vivo. The present review may provide information on the use of these compounds for the prevention of breast cancer. PMID:26734584

  10. Natural products in modern life science

    PubMed Central

    Göransson, Ulf; Alsmark, Cecilia; Wedén, Christina; Backlund, Anders

    2010-01-01

    With a realistic threat against biodiversity in rain forests and in the sea, a sustainable use of natural products is becoming more and more important. Basic research directed against different organisms in Nature could reveal unexpected insights into fundamental biological mechanisms but also new pharmaceutical or biotechnological possibilities of more immediate use. Many different strategies have been used prospecting the biodiversity of Earth in the search for novel structure–activity relationships, which has resulted in important discoveries in drug development. However, we believe that the development of multidisciplinary incentives will be necessary for a future successful exploration of Nature. With this aim, one way would be a modernization and renewal of a venerable proven interdisciplinary science, Pharmacognosy, which represents an integrated way of studying biological systems. This has been demonstrated based on an explanatory model where the different parts of the model are explained by our ongoing research. Anti-inflammatory natural products have been discovered based on ethnopharmacological observations, marine sponges in cold water have resulted in substances with ecological impact, combinatory strategy of ecology and chemistry has revealed new insights into the biodiversity of fungi, in depth studies of cyclic peptides (cyclotides) has created new possibilities for engineering of bioactive peptides, development of new strategies using phylogeny and chemography has resulted in new possibilities for navigating chemical and biological space, and using bioinformatic tools for understanding of lateral gene transfer could provide potential drug targets. A multidisciplinary subject like Pharmacognosy, one of several scientific disciplines bridging biology and chemistry with medicine, has a strategic position for studies of complex scientific questions based on observations in Nature. Furthermore, natural product research based on intriguing scientific

  11. Natural products in modern life science.

    PubMed

    Bohlin, Lars; Göransson, Ulf; Alsmark, Cecilia; Wedén, Christina; Backlund, Anders

    2010-06-01

    With a realistic threat against biodiversity in rain forests and in the sea, a sustainable use of natural products is becoming more and more important. Basic research directed against different organisms in Nature could reveal unexpected insights into fundamental biological mechanisms but also new pharmaceutical or biotechnological possibilities of more immediate use. Many different strategies have been used prospecting the biodiversity of Earth in the search for novel structure-activity relationships, which has resulted in important discoveries in drug development. However, we believe that the development of multidisciplinary incentives will be necessary for a future successful exploration of Nature. With this aim, one way would be a modernization and renewal of a venerable proven interdisciplinary science, Pharmacognosy, which represents an integrated way of studying biological systems. This has been demonstrated based on an explanatory model where the different parts of the model are explained by our ongoing research. Anti-inflammatory natural products have been discovered based on ethnopharmacological observations, marine sponges in cold water have resulted in substances with ecological impact, combinatory strategy of ecology and chemistry has revealed new insights into the biodiversity of fungi, in depth studies of cyclic peptides (cyclotides) has created new possibilities for engineering of bioactive peptides, development of new strategies using phylogeny and chemography has resulted in new possibilities for navigating chemical and biological space, and using bioinformatic tools for understanding of lateral gene transfer could provide potential drug targets. A multidisciplinary subject like Pharmacognosy, one of several scientific disciplines bridging biology and chemistry with medicine, has a strategic position for studies of complex scientific questions based on observations in Nature. Furthermore, natural product research based on intriguing scientific

  12. Natural production of biological optical systems

    NASA Astrophysics Data System (ADS)

    Choi, Seung Ho; Kim, Young L.

    2015-03-01

    Synthesis and production in nature often provide ideas to design and fabricate advanced biomimetic photonic materials and structures, leading to excellent physical properties and enhanced performance. In addition, the recognition and utilization of natural or biological substances have been typical routes to develop biocompatible and biodegradable materials for medical applications. In this respect, biological lasers utilizing such biomaterials and biostructures have been received considerable attention, given a variety of implications and potentials for bioimaging, biosensing, implantation, and therapy. However, without relying on industrial facilities, eco-friendly massive production of such optical components or systems has not yet been investigated. We show examples of bioproduction of biological lasers using agriculture and fisheries. We anticipate that such approaches will open new possibilities for scalable eco-friendly `green' production of biological photonics components and systems.

  13. [Status of libraries and databases for natural products at abroad].

    PubMed

    Zhao, Li-Mei; Tan, Ning-Hua

    2015-01-01

    For natural products are one of the important sources for drug discovery, libraries and databases of natural products are significant for the development and research of natural products. At present, most of compound libraries at abroad are synthetic or combinatorial synthetic molecules, resulting to access natural products difficult; for information of natural products are scattered with different standards, it is difficult to construct convenient, comprehensive and large-scale databases for natural products. This paper reviewed the status of current accessing libraries and databases for natural products at abroad and provided some important information for the development of libraries and database for natural products.

  14. Regulation of natural health products in Canada.

    PubMed

    Smith, Alysyn; Jogalekar, Sumedha; Gibson, Adam

    2014-12-02

    In Canada, all natural health products (NHPs) are regulated by Health Canada (HC) under the Food and Drugs Act and the Natural Health Product Regulations. All authorized products undergo pre-market assessment for safety, efficacy and quality and the degree of pre-market oversight varies depending on the risk of the product. In Canada, over 70,000 products have been authorized for sale and over 2000 sites have been licensed to produce NHPs. In the management of NHPs on the Canadian market, HC employs a number of active and collaborative methods to address the most common issues such as contamination, adulteration and deceptive or misleading advertising practices. HC is currently evolving its approaches to NHPs to recognize them as part of the larger group of health products available without a prescription. As such, the regulatory responsibility for all over-the-counter (OTC) drugs, including non-prescription drugs and NHPs, has been transferred to a single federal division. As a result of this transition a number of benefits are being realized with respect to government efficiency, clarity for industry, support for new innovations and consolidated government interactions with the Canadian market. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Acylphloroglucinol and xanthones from Hypericum ellipticum.

    PubMed

    Manning, Kylie; Petrunak, Elyse; Lebo, Michelle; González-Sarrías, Antonio; Seeram, Navindra P; Henry, Geneive E

    2011-05-01

    An acylphloroglucinol, elliptophenone A, and two xanthones, elliptoxanthone A and elliptoxanthone B, were isolated from the aerial portions of Hypericum ellipticum together with three known xanthones, 1,3,7-trihydroxy-8-(3-methyl-2-butenyl)-9H-xanthen-9-one, 1,6-dihydroxy-4-methoxy-9H-xanthen-9-one, and 1,4,5-trihydroxy-9H-xanthen-9-one. Their structures were determined by spectroscopic analyses. The acylphloroglucinol and xanthones were evaluated for cytotoxicity using three human colon cancer cell lines cell lines (HT-29, HCT-116 and Caco-2) and a normal human colon cell line (CCD-18Co). Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Cytotoxic polycyclic polyprenylated acylphloroglucinols from Hypericum attenuatum.

    PubMed

    Zhou, Zhong-bo; Zhang, Yang-mei; Pan, Ke; Luo, Jian-guang; Kong, Ling-yi

    2014-06-01

    Six new polycyclic polyprenylated acylphloroglucinols, attenuatumiones A-F (1-6), together with twelve known analogs (7-18) were isolated from the whole plant of Hypericum attenuatum. Their structures were elucidated by spectroscopic methods, and the absolute configuration of C-13 in attenuatumione C (3) was deduced via the circular dichroism datum of the in situ formed [Rh2(OCOCF3)4] complexes. All isolates were evaluated for the cytotoxic activities on three human cancer cell lines. Compound 3 showed moderate cytotoxic activities with IC50 values of 10.12 and 10.56 μM against SMMC7721 and U2OS, respectively. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Spirocyclic acylphloroglucinol derivatives from Hypericum beanii.

    PubMed

    Chen, Xuan-Qin; Li, Yan; Li, Kun-Zhi; Peng, Li-Yan; He, Juan; Wang, Kou; Pan, Zheng-Hong; Cheng, Xiao; Li, Ming-Ming; Zhao, Qin-Shi; Xu, Gang

    2011-01-01

    Four new acylphloroglucinols with an unusual 6/6/5 spirocyclic skeleton, hyperbeanols A-D (1-4), were isolated from the methanol extract of Hypericum beanii along with 16 known compounds. Their structures were established on the basis of spectroscopic and X-ray diffraction analysis. Hyperbeanols A-C were three stereoisomers different only at the relative configuration of C-4 and C-13, which were distinguished by the nuclear Overhauser effect spectroscopy (NOESY) spectroscopic data in combination with the single X-ray analysis of hyperbeanol A (1). The cytotoxic activity of hyperbeanols A-D against the cancer cell lines SK-BR-3, HL-60, SMMC-7721, PANC-1, MCF-7, and K562 was also evaluated.

  18. Natural gas production and consumption 1979

    SciTech Connect

    Not Available

    1981-01-01

    Total marketed production of natural gas in the United States during 1979 was 20,471 billion cubic feet, an increase of approximately 497 billion cubic feet, or 2.5 percent over 1978. Texas and Louisiana, the two leading producing states, accounted for 70.5 percent of total 1979 marketed production. In 1979, deliveries of natural gas to residential, commercial, industrial, electric utilities, and other consumers totaled 18,141 billion cubic feet. Total consumption, which includes lease, plant, and pipeline fuel in addition to deliveries to consumers, was 20,241 billion cubic feet in 1979 compared to 19,627 billion cubic feet in 1978, an increase of 3.1 percent. Movements of natural gas into and out of each state are presented. Louisiana accounted for the largest quantity of net deliveries, 5,107 billion cubic feet, followed by Texas and Oklahoma with net deliveries of 2,772 billion cubic feet and 914 billion cubic feet, respectively. Imports of natural gas by pipeline from Canada and as liquefied natural gas (LNG) from Algeria totaled 1,253 billion cubic feet in 1979. Total imports increased 288 billion cubic feet, or 29.8 percent, from 1978 levels. Exports of LNG to Japan and pipeline shipments to Canada and Mexico increased 6.0 percent from 52.5 billion cubic feet in 1978 to 55.7 billion cubic feet in 1979. LNG shipments to Japan accounted for 92.1 percent of total exports in 1979.

  19. Biologically active proteins from natural product extracts.

    PubMed

    O'Keefe, B R

    2001-10-01

    The term "biologically active proteins" is almost redundant. All proteins produced by living creatures are, by their very nature, biologically active to some extent in their homologous species. In this review, a subset of these proteins will be discussed that are biologically active in heterologous systems. The isolation and characterization of novel proteins from natural product extracts including those derived from microorganisms, plants, insects, terrestrial vertebrates, and marine organisms will be reviewed and grouped into several distinct classes based on their biological activity and their structure.

  20. Natural product inhibitors of ocular angiogenesis

    PubMed Central

    Sulaiman, Rania S.; Basavarajappa, Halesha D.; Corson, Timothy W.

    2014-01-01

    Natural products are characterized by high chemical diversity and biochemical specificity; therefore, they are appealing as lead compounds for drug discovery. Given the importance of angiogenesis to many pathologies, numerous natural products have been explored as potential anti-angiogenic drugs. Ocular angiogenesis underlies blinding eye diseases such as retinopathy of prematurity (ROP) in children, proliferative diabetic retinopathy (DR) in adults of working age, and age-related macular degeneration (AMD) in the elderly. Despite the presence of effective therapy in many cases, these diseases are still a significant health burden. Anti-VEGF biologics are the standard of care, but may cause ocular or systemic side effects after intraocular administration and patients may be refractory. Many anti-angiogenic compounds inhibit tumor growth and metastasis alone or in combination therapy, but a more select subset of them has been tested in the context of ocular neovascular diseases. Here, we review the promise of natural products as anti-angiogenic agents, with a specific focus on retinal and choroidal neovascularization. The multifunctional curcumin and the chalcone isoliquiritigenin have demonstrated promising anti-angiogenic effects in mouse models of DR and choroidal neovascularization (CNV) respectively. The homoisoflavanone cremastranone and the flavonoid deguelin have been shown to inhibit ocular neovascularization in more than one disease model. The isoflavone genistein and the flavone apigenin on the other hand are showing potential in the prevention of retinal and choroidal angiogenesis with long-term administration. Many other products with antiangiogenic potential in vitro such as the lactone withaferin A, the flavonol quercetin, and the stilbenoid combretastatin A4 are awaiting investigation in different ocular disease relevant animal models. These natural products may serve as lead compounds for the design of more specific, efficacious, and affordable

  1. [The HMPC monograph on Hypericum: Background, development, contents].

    PubMed

    Länger, Reinhard

    2010-12-01

    The adoption of the EU community monograph on Hypericum constitutes a milestone in the process of harmonisation of herbal medicinal products within the European Community. The assessment of the published clinical data revealed that for two types of extracts the evidence of the efficacy in mild to moderate depressive episodes compared to placebo or standard medication was found to be acceptable. Additionally, a sufficient efficacy in relapse prophylaxis could be demonstrated for these two herbal preparations. For some other dry extracts, the efficacy in the short-term treatment of symptoms in mild depressive disorders was found to be substantiated. Short-term treatment with preparations containing low amounts of hyperforin did not increase cytochrome P450 enzyme activity. Therefore the oral administration of traditional herbal preparations is restricted to two weeks. In the case that an applicant demonstrates that the daily intake of hyperforin is below 1 mg the warnings on interactions may be omitted in traditional herbal medicinal products. Additionally the cutaneous administration of traditional liquid herbal preparations for the traditional use in symptomatic treatment of minor inflammations of the skin and as an aid in healing minor wounds was included in the monograph.

  2. New chemistry from natural product biosynthesis.

    PubMed

    Hubert, Catherine B; Barry, Sarah M

    2016-06-15

    Catalysts are a vital part of synthetic chemistry. However, there are still many important reactions for which catalysts have not been developed. The use of enzymes as biocatalysts for synthetic chemistry is growing in importance due to the drive towards sustainable methods for producing both bulk chemicals and high value compounds such as pharmaceuticals, and due to the ability of enzymes to catalyse chemical reactions with excellent stereoselectivity and regioselectivity. Such challenging transformations are a common feature of natural product biosynthetic pathways. In this mini-review, we discuss the potential to use biosynthetic pathways as a starting point for biocatalyst discovery. We introduce the reader to natural product assembly and tailoring, then focus on four classes of enzyme that catalyse C─H bond activation reactions to functionalize biosynthetic precursors. Finally, we briefly discuss the challenges involved in novel enzyme discovery.

  3. Trypanocidal Activity of Marine Natural Products

    PubMed Central

    Jones, Amy J.; Grkovic, Tanja; Sykes, Melissa L.; Avery, Vicky M.

    2013-01-01

    Marine natural products are a diverse, unique collection of compounds with immense therapeutic potential. This has resulted in these molecules being evaluated for a number of different disease indications including the neglected protozoan diseases, human African trypanosomiasis and Chagas disease, for which very few drugs are currently available. This article will review the marine natural products for which activity against the kinetoplastid parasites; Trypanosoma brucei brucei, T.b. rhodesiense and T. cruzi has been reported. As it is important to know the selectivity of a compound when evaluating its trypanocidal activity, this article will only cover molecules which have simultaneously been tested for cytotoxicity against a mammalian cell line. Compounds have been grouped according to their chemical structure and representative examples from each class were selected for detailed discussion. PMID:24152565

  4. Genome Mining for Ribosomally Synthesized Natural Products

    PubMed Central

    Velásquez, Juan E.; van der Donk, Wilfred

    2011-01-01

    In recent years, the number of known peptide natural products that are synthesized via the ribosomal pathway has rapidly grown. Taking advantage of sequence homology among genes encoding precursor peptides or biosynthetic proteins, in silico mining of genomes combined with molecular biology approaches has guided the discovery of a large number of new ribosomal natural products, including lantipeptides, cyanobactins, linear thiazole/oxazole-containing peptides, microviridins, lasso peptides, amatoxins, cyclotides, and conopeptides. In this review, we describe the strategies used for the identification of these ribosomally-synthesized and posttranslationally modified peptides (RiPPs) and the structures of newly identified compounds. The increasing number of chemical entities and their remarkable structural and functional diversity may lead to novel pharmaceutical applications. PMID:21095156

  5. Natural products from filamentous fungi and production by heterologous expression.

    PubMed

    Alberti, Fabrizio; Foster, Gary D; Bailey, Andy M

    2017-01-01

    Filamentous fungi represent an incredibly rich and rather overlooked reservoir of natural products, which often show potent bioactivity and find applications in different fields. Increasing the naturally low yields of bioactive metabolites within their host producers can be problematic, and yield improvement is further hampered by such fungi often being genetic intractable or having demanding culturing conditions. Additionally, total synthesis does not always represent a cost-effective approach for producing bioactive fungal-inspired metabolites, especially when pursuing assembly of compounds with complex chemistry. This review aims at providing insights into heterologous production of secondary metabolites from filamentous fungi, which has been established as a potent system for the biosynthesis of bioactive compounds. Numerous advantages are associated with this technique, such as the availability of tools that allow enhanced production yields and directing biosynthesis towards analogues of the naturally occurring metabolite. Furthermore, a choice of hosts is available for heterologous expression, going from model unicellular organisms to well-characterised filamentous fungi, which has also been shown to allow the study of biosynthesis of complex secondary metabolites. Looking to the future, fungi are likely to continue to play a substantial role as sources of new pharmaceuticals and agrochemicals-either as producers of novel natural products or indeed as platforms to generate new compounds through synthetic biology.

  6. Isolation of bioactive natural products from myxomycetes.

    PubMed

    Ishibashi, Masami

    2005-11-01

    The Myxomycetes (true slime molds) are an unusual group of primitive organisms that may be assigned to one of the lowest classes of eukaryotes. As their fruit bodies are very small and it is very difficult to collect much quantity of slime molds, few studies have been made on the chemistry of myxomycetes. Cultivation of the plasmodium of myxomycetes in a practical scale for natural products chemistry studies is known only for very limited species. Here is described a review on the recent results on isolation of bioactive natural products from myxomycetes obtained in these two years in the laboratories. Spore germination experiments were studied of hundreds of field-collected myxomycetes collected in Japan and succeeded in laboratory culture of plasmodia of several myxomycetes in a practical scale for natural products chemistry studies. As a result, pyrroloiminoquinones, polyene yellow pigments, and a peptide lactone from cultured plasmodia of Didymium iridis, Physarum rigidum and P. melleum, respectively were isolated. New naphthoquinone pigments, cycloanthranilylprolines, tyrosine-kinase inhibitory bisindoles, and a cytotoxic triterpenoid aldehyde lactone were also isolated from field-collected fruit bodies of Cribraria purpurea, Fuligo candida, Tubifera casparyi, and Tubifera dimorphotheca, respectively.

  7. Natural and Heterologous Production of Bacteriocins

    NASA Astrophysics Data System (ADS)

    Cintas, Luis M.; Herranz, Carmen; Hernández, Pablo E.

    Bacteriocins are ribosomally synthesized antimicrobial peptides produced by bacteria, and their use as natural and nontoxic food preservatives has been the source of considerable interest for the research community. In addition, bacteriocins have been investigated for their potential use in human and veterinary applications and in the animal production field. In the native bacterial strain, most bacteriocins are synthesized as biologically inactive precursors, with N-terminal extensions, that are cleaved concomitantly during export of the bacteriocin by dedicated ABC transporters, or the general secretory pathway (GSP) or Sec-dependent pathway. However, a few bacteriocins are synthesized without an N-terminal extension, and others are circularized through a head-to-tail peptide bond, complicating the elucidation of their processing and transport across the cytoplasmic membrane. The high cost of synthetic bacteriocin synthesis and their low yields from many natural producers recommends the exploration of recombinant microbial systems for the heterologous production of bacteriocins. Other advantages of such systems include production of bacteriocins in safer hosts, increased bacteriocin production, control of bacteriocin gene expression, production of food ingredients with antimicrobial activity, construction of multibacteriocinogenic strains with a wider antagonistic spectrum, a better adaptation of the selected hosts to food environments, and providing antagonistic properties to lactic acid bacteria (LAB) used as starter, protective, or probiotic cultures. The recombinant production of bacteriocins mostly relies on the use of expression vectors that replicate in Gram-negative bacteria, Gram-positive bacteria, and yeasts, whereas the production of bacteriocins in heterologous LAB hosts may be essentially based on the expression of native biosynthetic genes, by exchanging or replacing leader peptides and/or dedicated processing and secretion systems (ABC transporters

  8. Air/light-free hyphenated extraction/analysis system: supercritical fluid extraction on-line coupled with liquid chromatography-UV absorbance/electrospray mass spectrometry for the determination of hyperforin and its degradation products in Hypericum pertoratum.

    PubMed

    Wang, Zhenyu; Ashraf-Khorassani, Mehdi; Taylor, Larry T

    2004-11-15

    Hyperforin, which is a major active constituent of the antidepression herbal medicine-Hypericum pertoratum (St. John's wort), is very sensitive to oxygen and light. Our paper reports for the first time an air/light-free extraction-separation-detection hyphenated system and its application to St. John's wort. It involves on-line coupling of supercritical fluid extraction with liquid chromatography-UV absorbance/electrospray ionization mass spectrometry (SFE-LC-UV/ESI-MS). Mass spectral data on the extract that was produced on-line suggested the presence of the major degradation compound of hyperforin-furohyperforin and two of its analogues. Thus, some degradation process must have already occurred in our sample during plant drying or storage. The feasibility of quantitative extraction and analysis of hyperforin by on-line SFE-LC was made possible by optimizing the extraction pressure, temperature, and CO(2) modifier content. High recovery ( approximately 90%) relative to liquid-solid extraction was achieved under optimized conditions.

  9. Topical application of St. John's wort (Hypericum perforatum).

    PubMed

    Wölfle, Ute; Seelinger, Günter; Schempp, Christoph M

    2014-02-01

    St. John's wort (Hypericum perforatum) has been intensively investigated for its antidepressive activity, but dermatological applications also have a long tradition. Topical St. John's wort preparations such as oils or tinctures are used for the treatment of minor wounds and burns, sunburns, abrasions, bruises, contusions, ulcers, myalgia, and many others. Pharmacological research supports the use in these fields. Of the constituents, naphthodianthrones (e.g., hypericin) and phloroglucinols (e.g., hyperforin) have interesting pharmacological profiles, including antioxidant, anti-inflammatory, anticancer, and antimicrobial activities. In addition, hyperforin stimulates growth and differentiation of keratinocytes, and hypericin is a photosensitizer which can be used for selective treatment of nonmelanoma skin cancer. However, clinical research in this field is still scarce. Recently, sporadic trials have been conducted in wound healing, atopic dermatitis, psoriasis, and herpes simplex infections, partly with purified single constituents and modern dermatological formulations. St. John's wort also has a potential for use in medical skin care. Composition and stability of pharmaceutical formulations vary greatly depending on origin of the plant material, production method, lipophilicity of solvents, and storage conditions, and this must be regarded with respect to practical as well as scientific purposes. Georg Thieme Verlag KG Stuttgart · New York.

  10. Neurotrophic Natural Products: Chemistry and Biology

    PubMed Central

    Xu, Jing; Lacoske, Michelle H.

    2014-01-01

    Neurodegenerative diseases and spinal cord injury affect approximately 50 million people worldwide, bringing the total healthcare cost to over 600 billion dollars per year. Nervous system growth factors, that is, neurotrophins, are a potential solution to these disorders, since they could promote nerve regeneration. An average of 500 publications per year attests to the significance of neurotrophins in biomedical sciences and underlines their potential for therapeutic applications. Nonetheless, the poor pharmacokinetic profile of neurotrophins severely restricts their clinical use. On the other hand, small molecules that modulate neurotrophic activity offer a promising therapeutic approach against neurological disorders. Nature has provided an impressive array of natural products that have potent neurotrophic activities. This Review highlights the current synthetic strategies toward these compounds and summarizes their ability to induce neuronal growth and rehabilitation. It is anticipated that neurotrophic natural products could be used not only as starting points in drug design but also as tools to study the next frontier in biomedical sciences: the brain activity map project. PMID:24353244

  11. Natural antimicrobial production by the amnion.

    PubMed

    Stock, Sarah J; Kelly, Rodney W; Riley, Simon C; Calder, Andrew A

    2007-03-01

    The purpose of this study was to determine the expression of natural antimicrobials in primary cultured amnion epithelial cells and to examine their regulation by interleukin-1 beta (IL-1beta). Primary amnion epithelial cells were cultured from samples that were obtained at prelabor cesarean section (n = 12) and stimulated with IL-1beta. Natural antimicrobial messenger RNA expression was determined by real-time quantitative polymerase chain reaction, and protein was measured by enzyme-linked immunosorbent assay. Data was analyzed by analysis of variance. Primary amnion epithelial cells express messenger RNA for human beta defensin (HBD) 1 to 3, secretory leukocyte protease inhibitor and elafin, but not HBD4. IL-1beta 10 ng/mL stimulates HBD2 messenger RNA in a biphasic pattern, with a 51-fold increase at 6 hours and a 67-fold at 12 hours (P < .001). HBD2 protein production is significantly increased by 24 hours (P < .05). The amnion produces potent natural antimicrobials that may help protect the pregnancy from infection. HBD2 production is dramatically upregulated by the labor-associated inflammatory cytokine IL-1beta.

  12. Natural products as potential anticonvulsants: caffeoylquinic acids.

    PubMed

    Kim, Hyo Geun; Oh, Myung Sook

    2012-03-01

    Current anticonvulsant therapies are generally directed at symptomatic treatment by suppressing excitability within the brain. Consequently, they have adverse effects such as cognitive impairment, dependence, and abuse. The need for more effective and less toxic anticonvulsants has generated renewed interest in natural products for the treatment of convulsions. Caffeoylquinic acids (CQs) are naturally occurring phenolic acids that are distributed widely in plants. There has been increasing interest in the biological activities of CQs in diseases of the central nervous system. In this issue, Nugroho et al. give evidence for the anticonvulsive effect of a CQ-rich extract from Aster glehni Franchet et Sckmidt. They optimized the extract solvent conditions, resulting in high levels of CQs and peroxynitrite-scavenging activity. Then, they investigated the sedative and anticonvulsive effects in pentobarbital- and pentylenetetrazole-induced models in mice. The CQ-rich extract significantly inhibited tonic convulsions as assessed by onset time, tonic extent, and mortality. They suggested that the CQ-rich extract from A. glehni has potential for treating convulsions. This report provides preclinical data which may be used for the development of anticonvulsants from natural products.

  13. Microbial production of natural raspberry ketone.

    PubMed

    Beekwilder, Jules; van der Meer, Ingrid M; Sibbesen, Ole; Broekgaarden, Mans; Qvist, Ingmar; Mikkelsen, Joern D; Hall, Robert D

    2007-10-01

    Raspberry ketone is an important compound for the flavour industry. It is frequently used in products such as soft drinks, sweets, puddings and ice creams. The compound can be produced by organic synthesis. Demand for "natural" raspberry ketone is growing considerably. However, this product is extremely expensive. Consequently, there is a remaining desire to better understand how raspberry ketone is synthesized in vivo, and which genes and enzymes are involved. With this information we will then be in a better position to design alternative production strategies such as microbial fermentation. This article focuses on the identification and application of genes potentially linked to raspberry ketone synthesis. We have isolated candidate genes from both raspberry and other plants, and these have been introduced into bacterial and yeast expression systems. Conditions have been determined that result in significant levels of raspberry ketone, up to 5 mg/L. These results therefore lay a strong foundation for a potentially renewable source of "natural" flavour compounds making use of plant genes.

  14. Phylogenetic approaches to natural product structure prediction.

    PubMed

    Ziemert, Nadine; Jensen, Paul R

    2012-01-01

    Phylogenetics is the study of the evolutionary relatedness among groups of organisms. Molecular phylogenetics uses sequence data to infer these relationships for both organisms and the genes they maintain. With the large amount of publicly available sequence data, phylogenetic inference has become increasingly important in all fields of biology. In the case of natural product research, phylogenetic relationships are proving to be highly informative in terms of delineating the architecture and function of the genes involved in secondary metabolite biosynthesis. Polyketide synthases and nonribosomal peptide synthetases provide model examples in which individual domain phylogenies display different predictive capacities, resolving features ranging from substrate specificity to structural motifs associated with the final metabolic product. This chapter provides examples in which phylogeny has proven effective in terms of predicting functional or structural aspects of secondary metabolism. The basics of how to build a reliable phylogenetic tree are explained along with information about programs and tools that can be used for this purpose. Furthermore, it introduces the Natural Product Domain Seeker, a recently developed Web tool that employs phylogenetic logic to classify ketosynthase and condensation domains based on established enzyme architecture and biochemical function. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Production of natural products through metabolic engineering of Saccharomyces cerevisiae.

    PubMed

    Krivoruchko, Anastasia; Nielsen, Jens

    2015-12-01

    Many high-value metabolites are produced in nature by organisms that are not ideal for large-scale production. Therefore, interest exists in expressing the biosynthetic pathways of these compounds in organisms that are more suitable for industrial production. Recent years have seen developments in both the discovery of various biosynthetic pathways, as well as development of metabolic engineering tools that allow reconstruction of complex pathways in microorganisms. In the present review we discuss recent advances in reconstruction of the biosynthetic pathways of various high-value products in the yeast Saccharomyces cerevisiae, a commonly used industrial microorganism. Key achievements in the production of different isoprenoids, aromatics and polyketides are presented and the metabolic engineering strategies underlying these accomplishments are discussed.

  16. Crystal Structure of Hyp-1, a Hypericum perforatum PR-10 Protein, in Complex with Melatonin.

    PubMed

    Sliwiak, Joanna; Dauter, Zbigniew; Jaskolski, Mariusz

    2016-01-01

    Hyp-1, a PR-10-fold protein from Hypericum perforatum, was crystallized in complex with melatonin (MEL). The structure confirms the conserved protein fold and the presence of three unusual ligand binding sites, two of which are internal chambers (1,2), while the third one (3) is formed as an invagination of the protein surface. The MEL ligand in site 1 is well defined while that in site 3 seems to be rotating between the side chains of Lys33 and Tyr150 that act as a molecular vise. The patch of electron density in site 2 does not allow unambiguous modeling of a melatonin molecule but suggests a possible presence of its degradation product. This pattern of ligand occupation is reproducible in repeated crystallization/structure determination experiments. Although the binding of melatonin by Hyp-1 does not appear to be very strong (for example, MEL cannot displace the artificial fluorescence probe ANS), it is strong enough to suggest a physiological role of this interaction. For example, trans-zeatin, which is a common ligand of PR-10 proteins, does not overcompete melatonin for binding to Hyp-1 as it does not affect the crystallization process of the Hyp-1/MEL complex, and among a number of potential natural mediators tested, melatonin was the only one to form a crystalline complex with Hyp-1 with the use of standard crystallization screens. Hyp-1 is the second protein in the Protein Data Bank for which melatonin binding has been demonstrated crystallographically, the first one being human quinone reductase.

  17. Crystal Structure of Hyp-1, a Hypericum perforatum PR-10 Protein, in Complex with Melatonin

    PubMed Central

    Sliwiak, Joanna; Dauter, Zbigniew; Jaskolski, Mariusz

    2016-01-01

    Hyp-1, a PR-10-fold protein from Hypericum perforatum, was crystallized in complex with melatonin (MEL). The structure confirms the conserved protein fold and the presence of three unusual ligand binding sites, two of which are internal chambers (1,2), while the third one (3) is formed as an invagination of the protein surface. The MEL ligand in site 1 is well defined while that in site 3 seems to be rotating between the side chains of Lys33 and Tyr150 that act as a molecular vise. The patch of electron density in site 2 does not allow unambiguous modeling of a melatonin molecule but suggests a possible presence of its degradation product. This pattern of ligand occupation is reproducible in repeated crystallization/structure determination experiments. Although the binding of melatonin by Hyp-1 does not appear to be very strong (for example, MEL cannot displace the artificial fluorescence probe ANS), it is strong enough to suggest a physiological role of this interaction. For example, trans-zeatin, which is a common ligand of PR-10 proteins, does not overcompete melatonin for binding to Hyp-1 as it does not affect the crystallization process of the Hyp-1/MEL complex, and among a number of potential natural mediators tested, melatonin was the only one to form a crystalline complex with Hyp-1 with the use of standard crystallization screens. Hyp-1 is the second protein in the Protein Data Bank for which melatonin binding has been demonstrated crystallographically, the first one being human quinone reductase. PMID:27242869

  18. Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extract.

    PubMed

    Müller, W E; Singer, A; Wonnemann, M; Hafner, U; Rolli, M; Schäfer, C

    1998-06-01

    Hydroalcoholic hypericum extract inhibits the synaptosomal uptake of serotonin, norepinephrine, and dopamine with about similar affinities and leads to a significant down-regulation of cortical beta-adrenoceptors and 5-HT2-receptors after subchronic treatment of rats. While neither hypericine nor kaempferol did show any reuptake inhibiting properties, hyperforin was identified as the unspecific reuptake inhibitor of hypericum extracts with half-maximal inhibitory concentrations for the three synaptosomal uptake systems mentioned above between 80 and 200 nmol/l. Moreover, a hyperforin-enriched (38%) CO2 extract also leads to a significant beta-receptor down-regulation after subchronic treatment. The data suggest hyperforin as the active principle of hypericum extracts in biochemical models of antidepressant activity.

  19. Natural products from microbes associated with insects

    PubMed Central

    Guo, Huijuan; Rischer, Maja; Poulsen, Michael

    2016-01-01

    Summary Here we review discoveries of secondary metabolites from microbes associated with insects. We mainly focus on natural products, where the ecological role has been at least partially elucidated, and/or the pharmaceutical properties evaluated, and on compounds with unique structural features. We demonstrate that the exploration of specific microbial–host interactions, in combination with multidisciplinary dereplication processes, has emerged as a successful strategy to identify novel chemical entities and to shed light on the ecology and evolution of defensive associations. PMID:26977191

  20. Metabolomics and dereplication strategies in natural products.

    PubMed

    Tawfike, Ahmed Fares; Viegelmann, Christina; Edrada-Ebel, Ruangelie

    2013-01-01

    Metabolomic methods can be utilized to screen diverse biological sources of potentially novel and sustainable sources of antibiotics and pharmacologically-active drugs. Dereplication studies by high resolution Fourier transform mass spectrometry coupled to liquid chromatography (LC-HRFTMS) and nuclear magnetic resonance (NMR) spectroscopy can establish the chemical profile of endophytic and/or endozoic microbial extracts and their plant or animal sources. Identifying the compounds of interest at an early stage will aid in the isolation of the bioactive components. Therefore metabolite profiling is important for functional genomics and in the search for new pharmacologically active compounds. Using the tools of metabolomics through the employment of LC-HRFTMS as well as high resolution NMR will be a very efficient approach. Metabolomic profiling has found its application in screening extracts of macroorganisms as well as in the isolation and cultivation of suspected microbial producers of bioactive natural products.Metabolomics is being applied to identify and biotechnologically optimize the production of pharmacologically active secondary metabolites. The links between metabolome evolution during optimization and processing factors can be identified through metabolomics. Information obtained from a metabolomics dataset can efficiently establish cultivation and production processes at a small scale which will be finally scaled up to a fermenter system, while maintaining or enhancing synthesis of the desired compounds. MZmine (BMC Bioinformatics 11:395-399, 2010; http://mzmine.sourceforge.net/download.shtml ) and SIEVE ( http://www.vastscientific.com/resources/index.html ; Rapid Commun Mass Spectrom 22:1912-1918, 2008) softwares are utilized to perform differential analysis of sample populations to find significant expressed features of complex biomarkers between parameter variables. Metabolomes are identified with the aid of existing high resolution MS and NMR

  1. Gas extrusion in natural products total synthesis.

    PubMed

    Jiang, Xuefeng; Shi, Lei; Liu, Hui; Khan, Akbar H; Chen, Jason S

    2012-11-14

    The thermodynamic driving force from the release of a gaseous molecule drives a broad range of synthetic transformations. This review focuses on gas expulsion in key reactions within natural products total syntheses, selected from the past two decades. The highlighted examples survey transformations that generate sulfur dioxide, carbon dioxide, carbonyl sulfide, or nitrogen through polar, radical, pericyclic, photochemical, or organometallic mechanisms. Of particular interest are applications wherein the gas extrusion enables formation of a synthetically challenging motif, such as an unusually hindered or strained bond.

  2. The chemistry of isoindole natural products

    PubMed Central

    Speck, Klaus

    2013-01-01

    Summary This review highlights the chemical and biological aspects of natural products containing an oxidized or reduced isoindole skeleton. This motif is found in its intact or modified form in indolocarbazoles, macrocyclic polyketides (cytochalasan alkaloids), the aporhoeadane alkaloids, meroterpenoids from Stachybotrys species and anthraquinone-type alkaloids. Concerning their biological activity, molecular structure and synthesis, we have limited this review to the most inspiring examples. Within different congeners, we have selected a few members and discussed the synthetic routes in more detail. The putative biosynthetic pathways of the presented isoindole alkaloids are described as well. PMID:24204418

  3. Fungal natural products in research and development.

    PubMed

    Schueffler, Anja; Anke, Timm

    2014-10-01

    To date approximately 100 000 fungal species are known although far more than one million are expected. The variety of species and the diversity of their habitats, some of them less exploited, allow the conclusion that fungi continue to be a rich source of new metabolites. Besides the conventional fungal isolates, an increasing interest in endophytic and in marine-derived fungi has been noticed. In addition new screening strategies based on innovative chemical, biological, and genetic approaches have led to novel fungal metabolites in recent years. The present review focuses on new fungal natural products published from 2009 to 2013 highlighting the originality of the structures and their biological potential. Furthermore synthetic products based on fungal metabolites as well as new developments in the uses or the biological activity of known compounds or new derivatives are discussed.

  4. Multimodular biocatalysts for natural product assembly

    NASA Astrophysics Data System (ADS)

    Schwarzer, Dirk; Marahiel, Mohamed A.

    2001-03-01

    Nonribosomal peptides and polyketides represent a large class of natural products that show an extreme structural diversity and broad pharmacological relevance. They are synthesized from simple building blocks such as amino or carboxy acids and malonate derivatives on multimodular enzymes called nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs), respectively. Although utilizing different substrates, NRPSs and PKSs show striking similarities in the modular architecture of their catalytic domains and product assembly-line mechanism. Among these compounds are well known antibiotics (penicillin, vancomycin and erythromycin) as well as potent immunosuppressive agents (cyclosporin, rapamycin and FK 506). This review focuses on the modular organization of NRPSs, PKSs and mixed NRPS/PKS systems and how modules and domains that build up the biosynthetic templates can be exploited for the rational design of recombinant enzymes capable of synthesizing novel compounds.

  5. In vitro pollen germination in Hypericum perforatum L. and Hypericum rumeliacum Boiss.

    PubMed

    Arda, Hayati; Meric, Ciler; Unal, Sabriye

    2006-03-01

    In vitro pollen germination and pollen tube growth investigations are valuable tools used in identification of the effects of environmental factors and genotypic differences on pollen viability, pollen germination and tube elongation. In this study pollen viability, in vitro pollen germination capacity, abnormality ratios and tube length in germinated pollens of Hypericum perforatum L. and H. rumeliacum Boiss. were investigated. Both of these species has spheroid-shaped and tricolporate pollen grains. The diameters of Hypericum perforatum and H. rumeliacum pollens were found as 24 +/- 3 microm and 19 +/- 2 microm, respectively. Pollen viability of H. perforatum and H. rumeliacum was found as 83% and 72%, respectively. The germination percentages were found as 12.85% for H. perforatum and 64.42% for H. rumeliacurm. Tube lengths in germinated pollens of both taxa were measured approximately as 95.25 +/- 38 microm in H. perforatum and 165.92 +/- 53 microm in H. rumeliacium 4 h after inoculation. In germinated pollen grains of H. perlbratum and H. rumeliacumn abnormality percentages were determined as 13.23% and 43.97%, respectively. In germinated pollens of these two species, highly significant (P < 0.00001) differences in in vitro germination percents and abnormality percents were observed. Abnormalities such as swollen tube tip, branched tube, spiralled tube and excessive tube formation were observed in pollen tubes. The results of this study showed that there were obvious differences in pollen germinability between these two species growing under the same environmental conditions.

  6. Amorfrutins are potent antidiabetic dietary natural products.

    PubMed

    Weidner, Christopher; de Groot, Jens C; Prasad, Aman; Freiwald, Anja; Quedenau, Claudia; Kliem, Magdalena; Witzke, Annabell; Kodelja, Vitam; Han, Chung-Ting; Giegold, Sascha; Baumann, Matthias; Klebl, Bert; Siems, Karsten; Müller-Kuhrt, Lutz; Schürmann, Annette; Schüler, Rita; Pfeiffer, Andreas F H; Schroeder, Frank C; Büssow, Konrad; Sauer, Sascha

    2012-05-08

    Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARγ-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes, Glycyrrhiza foetida and Amorpha fruticosa, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARγ, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARγ drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARγ-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease.

  7. Amorfrutins are potent antidiabetic dietary natural products

    PubMed Central

    Weidner, Christopher; de Groot, Jens C.; Prasad, Aman; Freiwald, Anja; Quedenau, Claudia; Kliem, Magdalena; Witzke, Annabell; Kodelja, Vitam; Han, Chung-Ting; Giegold, Sascha; Baumann, Matthias; Klebl, Bert; Siems, Karsten; Müller-Kuhrt, Lutz; Schürmann, Annette; Schüler, Rita; Pfeiffer, Andreas F. H.; Schroeder, Frank C.; Büssow, Konrad; Sauer, Sascha

    2012-01-01

    Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARγ-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes, Glycyrrhiza foetida and Amorpha fruticosa, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARγ, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARγ drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARγ-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease. PMID:22509006

  8. Natural Products: Insights into Leishmaniasis Inflammatory Response

    PubMed Central

    Rodrigues, Igor A.; Mazotto, Ana Maria; Cardoso, Verônica; Alves, Renan L.; Amaral, Ana Claudia F.; Silva, Jefferson Rocha de Andrade; Pinheiro, Anderson S.; Vermelho, Alane B.

    2015-01-01

    Leishmaniasis is a vector-borne disease that affects several populations worldwide, against which there are no vaccines available and the chemotherapy is highly toxic. Depending on the species causing the infection, the disease is characterized by commitment of tissues, including the skin, mucous membranes, and internal organs. Despite the relevance of host inflammatory mediators on parasite burden control, Leishmania and host immune cells interaction may generate an exacerbated proinflammatory response that plays an important role in the development of leishmaniasis clinical manifestations. Plant-derived natural products have been recognized as bioactive agents with several properties, including anti-protozoal and anti-inflammatory activities. The present review focuses on the antileishmanial activity of plant-derived natural products that are able to modulate the inflammatory response in vitro and in vivo. The capability of crude extracts and some isolated substances in promoting an anti-inflammatory response during Leishmania infection may be used as part of an effective strategy to fight the disease. PMID:26538837

  9. Dimeric acylphloroglucinols from Hypericum austrobrasiliense exhibiting antinociceptive activity in mice.

    PubMed

    Bridi, Henrique; Ccana-Ccapatinta, Gari V; Stolz, Eveline D; Meirelles, Gabriela C; Bordignon, Sérgio A L; Rates, Stela M K; von Poser, Gilsane L

    2016-02-01

    Three dimeric acylphloroglucinols, austrobrasilol A, austrobrasilol B and isoaustrobrasilol B were isolated from the flowers of Hypericum austrobrasiliense (Hypericaceae, section Trigynobrathys). Their structures were elucidated using mass spectrometry and NMR experiments (1D and 2D), and by comparison with previously reported data for other dimeric acylphloroglucinols isolated from Hypericum and Elaphoglossum genera. The three compounds were orally administered in mice at equimolar doses to uliginosin B (15mg/kg, p.o.) displaying antinociceptive activity in the hot-plate test. The compounds did not induce motor impairment in the rotarod apparatus.

  10. Plant cell culture strategies for the production of natural products.

    PubMed

    Ochoa-Villarreal, Marisol; Howat, Susan; Hong, SunMi; Jang, Mi Ok; Jin, Young-Woo; Lee, Eun-Kyong; Loake, Gary J

    2016-03-01

    Plants have evolved a vast chemical cornucopia to support their sessile lifestyles. Man has exploited this natural resource since Neolithic times and currently plant-derived chemicals are exploited for a myriad of applications. However, plant sources of most high-value natural products (NPs) are not domesticated and therefore their production cannot be undertaken on an agricultural scale. Further, these plant species are often slow growing, their populations limiting, the concentration of the target molecule highly variable and routinely present at extremely low concentrations. Plant cell and organ culture constitutes a sustainable, controllable and environmentally friendly tool for the industrial production of plant NPs. Further, advances in cell line selection, biotransformation, product secretion, cell permeabilisation, extraction and scale-up, among others, are driving increases in plant NP yields. However, there remain significant obstacles to the commercial synthesis of high-value chemicals from these sources. The relatively recent isolation, culturing and characterisation of cambial meristematic cells (CMCs), provides an emerging platform to circumvent many of these potential difficulties. [BMB Reports 2016; 49(3): 149-158].

  11. Plant cell culture strategies for the production of natural products

    PubMed Central

    Ochoa-Villarreal, Marisol; Howat, Susan; Hong, SunMi; Jang, Mi Ok; Jin, Young-Woo; Lee, Eun-Kyong; Loake, Gary J.

    2016-01-01

    Plants have evolved a vast chemical cornucopia to support their sessile lifestyles. Man has exploited this natural resource since Neolithic times and currently plant-derived chemicals are exploited for a myriad of applications. However, plant sources of most high-value natural products (NPs) are not domesticated and therefore their production cannot be undertaken on an agricultural scale. Further, these plant species are often slow growing, their populations limiting, the concentration of the target molecule highly variable and routinely present at extremely low concentrations. Plant cell and organ culture constitutes a sustainable, controllable and environmentally friendly tool for the industrial production of plant NPs. Further, advances in cell line selection, biotransformation, product secretion, cell permeabilisation, extraction and scale-up, among others, are driving increases in plant NP yields. However, there remain significant obstacles to the commercial synthesis of high-value chemicals from these sources. The relatively recent isolation, culturing and characterisation of cambial meristematic cells (CMCs), provides an emerging platform to circumvent many of these potential difficulties. [BMB Reports 2016; 49(3): 149-158] PMID:26698871

  12. Antibacterial natural products in medicinal chemistry--exodus or revival?

    PubMed

    von Nussbaum, Franz; Brands, Michael; Hinzen, Berthold; Weigand, Stefan; Häbich, Dieter

    2006-08-04

    To create a drug, nature's blueprints often have to be improved through semisynthesis or total synthesis (chemical postevolution). Selected contributions from industrial and academic groups highlight the arduous but rewarding path from natural products to drugs. Principle modification types for natural products are discussed herein, such as decoration, substitution, and degradation. The biological, chemical, and socioeconomic environments of antibacterial research are dealt with in context. Natural products, many from soil organisms, have provided the majority of lead structures for marketed anti-infectives. Surprisingly, numerous "old" classes of antibacterial natural products have never been intensively explored by medicinal chemists. Nevertheless, research on antibacterial natural products is flagging. Apparently, the "old fashioned" natural products no longer fit into modern drug discovery. The handling of natural products is cumbersome, requiring nonstandardized workflows and extended timelines. Revisiting natural products with modern chemistry and target-finding tools from biology (reversed genomics) is one option for their revival.

  13. Natural product synthesis at the interface of chemistry and biology

    PubMed Central

    2014-01-01

    Nature has evolved to produce unique and diverse natural products that possess high target affinity and specificity. Natural products have been the richest sources for novel modulators of biomolecular function. Since the chemical synthesis of urea by Wöhler, organic chemists have been intrigued by natural products, leading to the evolution of the field of natural product synthesis over the past two centuries. Natural product synthesis has enabled natural products to play an essential role in drug discovery and chemical biology. With the introduction of novel, innovative concepts and strategies for synthetic efficiency, natural product synthesis in the 21st century is well poised to address the challenges and complexities faced by natural product chemistry and will remain essential to progress in biomedical sciences. PMID:25043880

  14. Natural product synthesis at the interface of chemistry and biology.

    PubMed

    Hong, Jiyong

    2014-08-11

    Nature has evolved to produce unique and diverse natural products that possess high target affinity and specificity. Natural products have been the richest sources for novel modulators of biomolecular function. Since the chemical synthesis of urea by Wöhler, organic chemists have been intrigued by natural products, leading to the evolution of the field of natural product synthesis over the past two centuries. Natural product synthesis has enabled natural products to play an essential role in drug discovery and chemical biology. With the introduction of novel, innovative concepts and strategies for synthetic efficiency, natural product synthesis in the 21st century is well poised to address the challenges and complexities faced by natural product chemistry and will remain essential to progress in biomedical sciences. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Natural products - modifying metabolite pathways in plants.

    PubMed

    Staniek, Agata; Bouwmeester, Harro; Fraser, Paul D; Kayser, Oliver; Martens, Stefan; Tissier, Alain; van der Krol, Sander; Wessjohann, Ludger; Warzecha, Heribert

    2013-10-01

    The diversity of plant natural product (PNP) molecular structures is reflected in the variety of biochemical and genetic pathways that lead to their formation and accumulation. Plant secondary metabolites are important commodities, and include fragrances, colorants, and medicines. Increasing the extractable amount of PNP through plant breeding, or more recently by means of metabolic engineering, is a priority. The prerequisite for any attempt at metabolic engineering is a detailed knowledge of the underlying biosynthetic and regulatory pathways in plants. Over the past few decades, an enormous body of information about the biochemistry and genetics of biosynthetic pathways involved in PNPs production has been generated. In this review, we focus on the three large classes of plant secondary metabolites: terpenoids (or isoprenoids), phenylpropanoids, and alkaloids. All three provide excellent examples of the tremendous efforts undertaken to boost our understanding of biosynthetic pathways, resulting in the first successes in plant metabolic engineering. We further consider what essential information is still missing, and how future research directions could help achieve the rational design of plants as chemical factories for high-value products. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Pharmacological studies in an herbal drug combination of St. John's Wort (Hypericum perforatum) and passion flower (Passiflora incarnata): in vitro and in vivo evidence of synergy between Hypericum and Passiflora in antidepressant pharmacological models.

    PubMed

    Fiebich, Bernd L; Knörle, Rainer; Appel, Kurt; Kammler, Thomas; Weiss, Gabriele

    2011-04-01

    Extracts of Hypericum, Passiflora and Valeriana are used for the treatment of mild depression and anxiety. We were interested whether a combination of Hypericum and Passiflora exerts comparable effects to Hypericum alone. We used two well-established models for investigating extracts for their anti-depressant activity, namely the effects on synaptic uptake of serotonin and the forced-swimming-test. We show here for the first time, that Passiflora significantly enhances the pharmacological potency of Hypericum in both models. Our data suggest that anti-depressive therapeutic effects of Hypericum are possible with lower doses, when it is combined with Passiflora, than with mono-preparations of Hypericum.

  17. Spectroscopic Characterization of a Natural Product: Anethole

    NASA Astrophysics Data System (ADS)

    Barber, Victoria P.; Newby, Josh J.

    2013-06-01

    Anethole [(E)-1-methoxy-4-(1-propenyl)benzene] is a natural product molecule that is commonly recognized as the flavor component of anise, fennel, and licorice. Early jet-cooled spectroscopy of anethole showed the existence of two possible conformations, but did not address details of the vibronic structure. Here, we report the jet-cooled, laser-induced fluorescence and single vibronic level fluorescence spectra of anethole. Analysis of the spectra confirms the existence of two rotamers in the expansion that differ by the relative orientation of the methoxy and propenyl groups. The observed vibronic activity is similar to that of styrene and indicates planar symmetry of both rotamers. Vibrational assignments of anethole are assisted by density functional theory calculations and the results are compared with the analogous motions in styrene. V. H. Grassian, E. R. Bernstein, H. V. Secor and J. I. Seeman J. Phys. Chem. {93, 3470 (1989).

  18. Natural products: a safest approach for obesity.

    PubMed

    Vasudeva, Neeru; Yadav, Neerja; Sharma, Surendra Kumar

    2012-06-01

    Obesity is recognized as a social problem, associated with serious health risks and increased mortality. Numerous trials have been conducted to find and develop new anti-obesity drugs through herbal sources to minimize adverse reactions associated with the present anti-obesity drugs. The use of natural products as medicine has been documented for hundreds of years in various traditional systems of medicines throughout the world. This review focuses on the medicinal plants such as Achyranthus aspera, Camellia sinensis, Emblica officinalis, Garcinia cambogia, Terminalia arjuna, etc., being used traditionally in Ayurvedic, Unani, Siddha and Chinese, etc., systems of medicine. The review also highlights recent reported phytochemicals such as escins, perennisosides, dioscin, gracillin, etc., and the various extracts of the plants like Nelumbo nucifera, Panax japonicas, Cichorium intybus, Cyperus rotundus, Paeonia suffruticosa, etc., which have been successfully identified for the treatment of obesity.

  19. Didemnins, tamandarins and related natural products.

    PubMed

    Lee, Jisun; Currano, Judith N; Carroll, Patrick J; Joullié, Madeleine M

    2012-03-01

    Since the discovery and isolation of the didemnin family of marine depsipeptides in 1981, the synthesis and biological activity of its congeners have been of great interest to the scientific community. The didemnins have demonstrated antitumor, antiviral, and immunosuppressive activity at low nano- and femtomolar levels. Of the congeners, didemnin B was the first marine natural product to reach phase II clinical trials in the United States, stimulating many analogue syntheses to date. About two decades later, tamandarins A and B were isolated, and were found to possess very similar structure and biological activity to that of the didemnin B. These compounds have shown impressive biological activity and some progress has been made in establishing structure-activity relationships. However, their molecular mechanism of action still remains unclear. This review highlights the long-standing study of didemnins and its critical application towards the understanding of the molecular mechanism of action of tamandarins and their potential use as therapeutic agents.

  20. Novel Chemical Space Exploration via Natural Products

    PubMed Central

    Rosén, Josefin; Gottfries, Johan; Muresan, Sorel; Backlund, Anders; Oprea, Tudor I.

    2009-01-01

    Natural products (NPs) are a rich source of novel compound classes and new drugs. In the present study we have used the chemical space navigation tool ChemGPS-NP to evaluate the chemical space occupancy by NPs and bioactive medicinal chemistry compounds from the database WOMBAT. The two sets differ notable in coverage of chemical space, and tangible lead-like NPs were found to cover regions of chemical space that lack representation in WOMBAT. Property based similarity calculations were performed to identify NP neighbours of approved drugs. Several of the NPs revealed by this method, were confirmed to exhibit the same activity as their drug neighbours. The identification of leads from a NP starting point may prove a useful strategy for drug discovery, in the search for novel leads with unique properties. PMID:19265440

  1. Mixed fermentation for natural product drug discovery.

    PubMed

    Pettit, Robin K

    2009-05-01

    Natural products continue to play a major role in drug discovery and development. However, chemical redundancy is an ongoing problem. Genomic studies indicate that certain groups of bacteria and fungi have dozens of secondary metabolite pathways that are not expressed under standard laboratory growth conditions. One approach to more fully access the metabolic potential of cultivatable microbes is mixed fermentation, where the presence of neighboring microbes may induce secondary metabolite synthesis. Research to date indicates that mixed fermentation can result in increased antibiotic activity in crude extracts, increased yields of previously described metabolites, increased yields of previously undetected metabolites, analogues of known metabolites resulting from combined pathways and, importantly, induction of previously unexpressed pathways for bioactive constituents.

  2. Novel chemical space exploration via natural products.

    PubMed

    Rosén, Josefin; Gottfries, Johan; Muresan, Sorel; Backlund, Anders; Oprea, Tudor I

    2009-04-09

    Natural products (NPs) are a rich source of novel compound classes and new drugs. In the present study we have used the chemical space navigation tool ChemGPS-NP to evaluate the chemical space occupancy by NPs and bioactive medicinal chemistry compounds from the database WOMBAT. The two sets differ notably in coverage of chemical space, and tangible leadlike NPs were found to cover regions of chemical space that lack representation in WOMBAT. Property based similarity calculations were performed to identify NP neighbors of approved drugs. Several of the NPs revealed by this method were confirmed to exhibit the same activity as their drug neighbors. The identification of leads from a NP starting point may prove a useful strategy for drug discovery in the search for novel leads with unique properties.

  3. Use of natural health products in children

    PubMed Central

    Pike, Andrea; Etchegary, Holly; Godwin, Marshall; McCrate, Farah; Crellin, John; Mathews, Maria; Law, Rebecca; Newhook, Leigh Anne; Kinden, Jody

    2013-01-01

    Abstract Objective To gain a more thorough understanding of why parents choose to give their children natural health products (NHPs), parents’ sources of information about NHPs, and the extent of disclosure and conversation with family doctors about the use of NHPs. Design Qualitative study. Setting Newfoundland and Labrador. Participants Parents of children who were using NHPs (N = 20). Methods Individual, semistructured interviews were carried out with parents to obtain a better understanding of the reasoning behind the use of NHPs. Key themes emerging from the qualitative data were identified according to a number of criteria, including relevance to the research objectives, frequency with which a theme was mentioned, relative importance of the themes based on the amount of text taken up to address an issue, and emphasis (eg, emphatic or emotional speech). Main findings The types of NHPs used by parents participating in this study varied, except for the use of multivitamins. In addition, use of the products themselves was variable and inconsistent. Parents reported few concerns about the use of NHPs. The most commonly reported source of information about NHPs was family and friends. Most participants had not spoken to their family doctors about the use of NHPs. Conclusion Participants considered NHPs to be “natural” and seemed to equate this assessment with safety. This might explain why these parents sought advice and information from family and friends rather than from their family doctors and often failed to disclose the use of NHPs to their children’s family doctors. PMID:23946044

  4. Chocolate: A Marvelous Natural Product of Chemistry

    NASA Astrophysics Data System (ADS)

    Tannenbaum, Ginger

    2004-08-01

    Chocolate is a natural product as ubiquitous as television. Of course, it is eaten, but it is also found in air fresheners, marking pens, flavoring in a multitude of products including soda pop, and as an aroma in "chocolate-dyed" T-shirts. However, most of us are completely unaware of the complex chemical reactions that take place to produce chocolate and the necessary technology that has evolved to produce chocolate and all its byproducts. Processing results in a mixture of many components, an interesting contrast to most of the simple, one-step reactions introduced at the high school level. This article is a survey of chocolate from tree to table. After a brief introduction to the history of chocolate and how and where it is grown, the manufacturing process is examined, and the chemistry is explored. A bit of the jargon used in the industry is mentioned. Cocoa butter is a significant ingredient in chocolate, and an investigation of it introduces triglycerides, fatty acids, polymorphic behavior, and molecular packing of the fats in chocolate and how they affect the tempering process. There is a brief discussion of chocolate's non-Newtonian behavior and the resulting challenges presented in the manufacturing process. See Featured Molecules Featured on the Cover

  5. Natural Products as a Foundation for Drug Discovery

    PubMed Central

    Beutler, John A.

    2009-01-01

    Natural products have contributed to the development of many drugs for diverse indications. While most U.S. pharmaceutical companies have reduced or eliminated their in-house natural product groups, new paradigms and new enterprises have evolved to carry on a role for natural products in the pharmaceutical industry. Many of the reasons for the decline in popularity of natural products are being addressed by the development of new techniques for screening and production. This overview aims to inform pharmacologists of current strategies and techniques that make natural products a viable strategic choice for inclusion in drug discovery programs. PMID:20161632

  6. Cordyceps fungi: natural products, pharmacological functions and developmental products.

    PubMed

    Zhou, Xuanwei; Gong, Zhenghua; Su, Ying; Lin, Juan; Tang, Kexuan

    2009-03-01

    Parasitic Cordyceps fungi, such as Cordyceps sinensis, is a parasitic complex of fungus and caterpillar, which has been used for medicinal purposes for centuries particularly in China, Japan and other Asian countries. This article gives a general idea of the latest developments in C. sinensis research, with regard to the active chemical components, the pharmacological effects and the research and development of products in recent years. The common names for preparations include DongChongXiaCao in Chinese, winter worm summer grass in English. It has many bioactive components, such as 3'-deoxyadenosine, cordycepic acid and Cordyceps polysaccharides. It is commonly used to replenish the kidney and soothe the lung, and for the treatment of fatigue. It also can be used to treat conditions such as night sweating, hyposexuality, hyperglycaemia, hyperlipidaemia, asthenia after severe illness, respiratory disease, renal dysfunction, renal failure, arrhythmias and other heart disease and liver disease. Because of its rarity and outstanding curative effects, several mycelia strains have been isolated from natural Cordyceps and manufactured by fermentation technology, and are commonly sold as health food products. In addition, some substitutes such as C. militaris and adulterants also have been used; therefore, quality control of C. sinensis and its products is very important to ensure their safety and efficacy. Recent research advances in the study of Cordyceps, including Cordyceps mushrooms, chemical components, pharmacological functions and developmental products, has been reviewed and discussed. Developing trends in the field have also been appraised.

  7. [Content of rare earth elements in wild Hypericum japonicum Thunb].

    PubMed

    Wei, Zhen-Lin; Rui, Yu-Kui; Tian, Zhi-Huan

    2009-06-01

    Rare earth elements are important nutritional elements for human health, and today more and more attention has been paid to the effective components in Chinese traditional medicine, especially to rare earth elements. Fifteen rare earth elements in wild hypericum japonicum Thunb were analyzed by the methods of ICP-MS. The results showed that the concentrations of La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Yb, Tm, Lu and Y ranged from 6 ng x g(-1) x DW to 14 522 ng x g(-1) x DW, and among them the concentrations of La, Ce and Nd were higher than 2 000 ng x g(-1) x DW. Compared with the concentration of rare earth elements in rice, corn, wheat and barley, the total concentration of rare earth elements in hypericum japonicum Thunb was much higher, which could be the mechanism of curative effect of hypericum japonicum Thunb on liverish diseases. The character of elements and the content of rare earth elements in soil should be responsible for the difference, but the distributive mechanism of rare earth elements in hypericum japonicum Thunb should be further studied.

  8. Secondary metabolites of seven Hypericum species growing in Turkey.

    PubMed

    Cirak, Cuneyt; Radusiene, Jolita; Jakstas, Valdas; Ivanauskas, Liudas; Seyis, Fatih; Yayla, Fatih

    2016-10-01

    Context The genus Hypericum (Hypericaceae) has attracted remarkable scientific interest as its members have yielded many bioactive compounds. Objective The current study presents investigations on the accumulation of hypericin, pseudohypericin, hyperforin, adhyperforin, chlorogenic acid, neochlorogenic acid, caffeic acid, 2,4-dihydroxybenzoic acid, 13,118-biapigenin, hyperoside, isoquercitrin, quercitrin, quercetin, avicularin, rutin, (+)-catechin and (-)-epicatechin in seven Hypericum (Hypericaceae) species growing wild in Turkey, namely, H. aviculariifolium Jaup. and Spach subsp. aviculariifolium (Freyn and Bornm.) Robson var. albiflorum (endemic), H. bithynicum Boiss., H. calycinum L., H. cardiophyllum Boiss., H. elongatum L. subsp. microcalycinum (Boiss. and Heldr.) Robson, H. hirsutum L. and H. xylosteifolium (Spach) N. Robson. Materials and methods The plant materials were collected at flowering period and dissected in different tissues. Air-dried plant material including stems, leaves and flowers was mechanically powdered with a laboratory mill and samples (0.1 g) were extracted in 10 mL of 100% methanol by ultrasonication at 40 °C for 30 min for HPLC-PDA analyses. Results Accumulation levels of the investigated compounds varied greatly depending on species and plant part. Discussion For the first time, the detailed chemical profiles of corresponding Turkish Hypericum species were reported and the results were discussed from a phytochemical point of view. Conclusions The present data have importance in evaluation of plant resources of Hypericum genus in selecting the new potential sources of bioactive compounds.

  9. Variation in Breeding Systems in Hypericum Perforatum and Prunella Vulgaris

    USDA-ARS?s Scientific Manuscript database

    The effective conservation of new crop germplasm and its efficient use in new-crop development both rely on a clear understanding of the crop's reproductive biology. Hypericum perforatum (St. John's wort) and Prunella vulgaris (Common selfheal) are two medicinal plant species with potential for crop...

  10. Cytotoxic Activity and Apoptosis Induction of Hypericum scabrum L.

    PubMed

    Hamzeloo-Moghadam, Maryam; Khalaj, Amir; Malekmohammadi, Maryam

    2015-10-01

    One of the acquired biological hallmarks of tumor multistep development is the resistance of cancer cells to apoptosis; therefore, induction of apoptosis is an important therapeutic approach. Hypericum species are spread throughout the world and have been investigated for their biological properties. Our previous studies had demonstrated cytotoxicity of Hypericum scabrum L. methanol extract against some tumor cell lines, suggesting the species for further studies. The objectives of the present study were to determine the most cytotoxic fraction of Hypericum scabrum L. and to assess the apoptosis induction ability of the most effective fraction as well as its methanol extract. The laboratory evidence has been presented to support the potency of Iranian Traditional Medicine (ITM) medicinal plants as a source of different biological activity surveys and drug discoveries. The present research is a descriptive study. The sampling strategy was based on ITM data of cancer phytotherapy. Hypericum scabrum was collected from Alborz province, Iran (2012) and the herbarium specimen was taxonomically identified. The petroleum ether, dichloromethane, and methanol fractions have been evaluated for cytotoxicity against M-CF7, A-549, HT-29, and HepG-2 cell lines through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT assay. The apoptosis induction ability has been assessed by activated caspase-3 inspection and Annexin V FITC/PI (propidium iodide) assays. Di-chloromethane fraction demonstrated IC50 values of 25.72 μg/mL and 24.73 μg/mL against HT-29 and HepG-2 cell lines, respectively and IC50 values of petroleum ether fraction were 22.6 μg/mL and 18.31 μg/mL against HT-29 and HepG-2, respectively. The methanol fraction did not show cytotoxic activity. Both the methanol extract and the petroleum ether fraction of Hypericum scabrum L. revealed apoptosis induction ability. Considering the strong historical background about the therapeutic potential of the genus

  11. Cytotoxic Activity and Apoptosis Induction of Hypericum scabrum L.

    PubMed Central

    Hamzeloo-Moghadam, Maryam; Khalaj, Amir; Malekmohammadi, Maryam

    2015-01-01

    Background: One of the acquired biological hallmarks of tumor multistep development is the resistance of cancer cells to apoptosis; therefore, induction of apoptosis is an important therapeutic approach. Hypericum species are spread throughout the world and have been investigated for their biological properties. Objectives: Our previous studies had demonstrated cytotoxicity of Hypericum scabrum L. methanol extract against some tumor cell lines, suggesting the species for further studies. The objectives of the present study were to determine the most cytotoxic fraction of Hypericum scabrum L. and to assess the apoptosis induction ability of the most effective fraction as well as its methanol extract. The laboratory evidence has been presented to support the potency of Iranian Traditional Medicine (ITM) medicinal plants as a source of different biological activity surveys and drug discoveries. Materials and Methods: The present research is a descriptive study. The sampling strategy was based on ITM data of cancer phytotherapy. Hypericum scabrum was collected from Alborz province, Iran (2012) and the herbarium specimen was taxonomically identified. The petroleum ether, dichloromethane, and methanol fractions have been evaluated for cytotoxicity against M-CF7, A-549, HT-29, and HepG-2 cell lines through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT assay. The apoptosis induction ability has been assessed by activated caspase-3 inspection and Annexin V FITC/PI (propidium iodide) assays. Results: Di-chloromethane fraction demonstrated IC50 values of 25.72 μg/mL and 24.73 μg/mL against HT-29 and HepG-2 cell lines, respectively and IC50 values of petroleum ether fraction were 22.6 μg/mL and 18.31 μg/mL against HT-29 and HepG-2, respectively. The methanol fraction did not show cytotoxic activity. Both the methanol extract and the petroleum ether fraction of Hypericum scabrum L. revealed apoptosis induction ability. Conclusions: Considering the

  12. Efficacy and tolerability of Hypericum extract for the treatment of mild to moderate depression.

    PubMed

    Kasper, Siegfried; Caraci, Filippo; Forti, Bruno; Drago, Filippo; Aguglia, Eugenio

    2010-11-01

    Depression is a common condition in the community with a significant impact on affected individuals, their relatives and society. Many patients with depression do not seek treatment and are often concerned about the possible adverse effects of antidepressant drugs. Extract of Hypericum perforatum (St. John's wort) has long been recognized as a treatment for depression. Several published trials and meta-analyses have demonstrated the efficacy and tolerability of Hypericum extract for mild to moderate depression. Recent comparative trials of Hypericum extract and other antidepressants, including selective serotonin reuptake inhibitors (SSRIs), provide support for Hypericum extract efficacy. However, since the constituents of Hypericum extract differ between the individual manufacturers, the efficacy cannot be extrapolated from one extract to another. In this review, WS 5572, LI 160, WS 5570 and ZE 117 Hypericum extracts have been shown to be significantly more effective than placebo with at least similar efficacy and better tolerability compared to standard antidepressant drugs.

  13. Use of natural health products in children

    PubMed Central

    Godwin, Marshall; Crellin, John; Mathews, Maria; Chowdhury, Nurun L.; Newhook, Leigh Anne; Pike, Andrea; McCrate, Farah; Law, Rebecca

    2013-01-01

    Abstract Objective To determine how common it is for parents to give natural health products (NHPs) to their children, which NHPs are being used, why they are being used, and parents’ assessments of the benefits and side effects of NHPs. Design Survey. Setting Newfoundland and Labrador. Participants Parents waiting in their family doctors’ offices. Main outcome measures Parent and child demographic characteristics; pediatric chronic medical conditions affecting the children; prescribed medications, over-the-counter medications, and NHPs used by the children; why the medications and NHPs were being used, the dose, and parents’ assessments of the effectiveness and side effects; and where parents had heard about the NHPs, whether they had told their physicians that the children were taking the products, and where they had obtained the products. Results A total of 202 (53.4%) of the 378 eligible adults who were approached completed the survey. This represented 333 children. Mean (SD) age of the children was 5.1 (3.3) years. Overall, 28.7% of parents reported using nonvitamin NHPs for their children. A total of 137 children (41.1%) had taken NHPs (including vitamins); 61.1% of the NHPs being used were vitamins. The remainder fell under teas (primarily chamomile and green teas), echinacea, fish or omega-3 oils, and a large category of “other” products. These NHPs were most commonly used to improve general health, improve immunity, and prevent colds and infections. Approximately half of the parents (51.7%) believed their children had benefited from taking NHPs, and 4.4% believed their children had experienced adverse side effects. Slightly less than half of the parents (45.0%) had informed their physicians that their children were taking NHPs. Conclusion Overall, 45.5% of parents attending physicians’ offices reported using NHPs in their children. If vitamins are not included in the definition of NHPs, this rate drops to 28.7%. Parents most commonly use NHPs

  14. [The recent research progress of chemistry of marine natural products].

    PubMed

    Shi, Qing-wen; Li, Li-geng; Wang, Yu-fang; Huo, Chang-hong; Zhang, Man-li

    2010-10-01

    Ocean is a unique and excellent resource that provides a diverse array of intriguing natural products. Marine natural products have demonstrated significant and extremely potent biological activities and have captured the attention of natural products chemists in the past few decades. It is increasingly recognized that a wealth of fascinating natural products and novel chemical entities will play a dominant role in the discovery of useful leads for the development of pharmaceutical agents and provide useful probes to lead to breakthroughs in a variety of life-science fields. This article focused on the research progress of chemistry of marine natural products in recent five years.

  15. Oxygen-containing fragments in natural products.

    PubMed

    Titarenko, Zoya; Vasilevich, Natalya; Zernov, Vladimir; Kirpichenok, Michael; Genis, Dmitry

    2013-02-01

    An analysis of the chemical environment of the oxygen atoms in the DNP database compared to the CMC and SCD databases was performed. Some structural clusters were identified which are predominant among the natural products and can be considered as distinctive features of NPs. Fifty-three oxygen-containing structural fragments that are distinctive for the DNP (distinctive set of fragments DSF) in comparison with the SCD have been identified. A new descriptor Mc was introduced for describing the ratio of atoms involved in the DSF to the total number of heavy atoms. A significant difference in the Mc values among the reference databases allowed the use of a specific cluster of the DSF as a tool for performing similarity searches for oxygen-containing NP molecules, or for evaluation or comparison of databases according to their NP-likeness. An example illustrating that the suggested approach could allow not only estimating the NP-likeness, but also serve as a tool for designing new NP-like compounds is provided. The suggested approach for NP-likeness evaluation moves away from the traditional ideas of scaffolds, cycles, linkers and substituents.

  16. Oxygen-containing fragments in natural products

    NASA Astrophysics Data System (ADS)

    Titarenko, Zoya; Vasilevich, Natalya; Zernov, Vladimir; Kirpichenok, Michael; Genis, Dmitry

    2013-02-01

    An analysis of the chemical environment of the oxygen atoms in the DNP database compared to the CMC and SCD databases was performed. Some structural clusters were identified which are predominant among the natural products and can be considered as distinctive features of NPs. Fifty-three oxygen-containing structural fragments that are distinctive for the DNP (distinctive set of fragments DSF) in comparison with the SCD have been identified. A new descriptor Mc was introduced for describing the ratio of atoms involved in the DSF to the total number of heavy atoms. A significant difference in the Mc values among the reference databases allowed the use of a specific cluster of the DSF as a tool for performing similarity searches for oxygen-containing NP molecules, or for evaluation or comparison of databases according to their NP-likeness. An example illustrating that the suggested approach could allow not only estimating the NP-likeness, but also serve as a tool for designing new NP-like compounds is provided. The suggested approach for NP-likeness evaluation moves away from the traditional ideas of scaffolds, cycles, linkers and substituents.

  17. Natural products and combinatorial chemistry: back to the future.

    PubMed

    Ortholand, Jean-Yves; Ganesan, A

    2004-06-01

    The introduction of high-throughput synthesis and combinatorial chemistry has precipitated a global decline in the screening of natural products by the pharmaceutical industry. Some companies terminated their natural products program, despite the unproven success of the new technologies. This was a premature decision, as natural products have a long history of providing important medicinal agents. Furthermore, they occupy a complementary region of chemical space compared with the typical synthetic compound library. For these reasons, the interest in natural products has been rekindled. Various approaches have evolved that combine the power of natural products and organic chemistry, ranging from the combinatorial total synthesis of analogues to the exploration of natural product scaffolds and the design of completely unnatural molecules that resemble natural products in their molecular characteristics.

  18. A Historical Overview of Natural Products in Drug Discovery

    PubMed Central

    Dias, Daniel A.; Urban, Sylvia; Roessner, Ute

    2012-01-01

    Historically, natural products have been used since ancient times and in folklore for the treatment of many diseases and illnesses. Classical natural product chemistry methodologies enabled a vast array of bioactive secondary metabolites from terrestrial and marine sources to be discovered. Many of these natural products have gone on to become current drug candidates. This brief review aims to highlight historically significant bioactive marine and terrestrial natural products, their use in folklore and dereplication techniques to rapidly facilitate their discovery. Furthermore a discussion of how natural product chemistry has resulted in the identification of many drug candidates; the application of advanced hyphenated spectroscopic techniques to aid in their discovery, the future of natural product chemistry and finally adopting metabolomic profiling and dereplication approaches for the comprehensive study of natural product extracts will be discussed. PMID:24957513

  19. Construction of a 3D-shaped, natural product like fragment library by fragmentation and diversification of natural products.

    PubMed

    Prescher, Horst; Koch, Guido; Schuhmann, Tim; Ertl, Peter; Bussenault, Alex; Glick, Meir; Dix, Ina; Petersen, Frank; Lizos, Dimitrios E

    2017-02-01

    A fragment library consisting of 3D-shaped, natural product-like fragments was assembled. Library construction was mainly performed by natural product degradation and natural product diversification reactions and was complemented by the identification of 3D-shaped, natural product like fragments available from commercial sources. In addition, during the course of these studies, novel rearrangements were discovered for Massarigenin C and Cytochalasin E. The obtained fragment library has an excellent 3D-shape and natural product likeness, covering a novel, unexplored and underrepresented chemical space in fragment based drug discovery (FBDD). Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Hit identification of IKKβ natural product inhibitor

    PubMed Central

    2013-01-01

    Background The nuclear factor-κB (NF-κB) proteins are a small group of heterodimeric transcription factors that play an important role in regulating the inflammatory, immune, and apoptotic responses. NF-κB activity is suppressed by association with the inhibitor IκB. Aberrant NF-κB signaling activity has been associated with the development of cancer, chronic inflammatory diseases and auto-immune diseases. The IKK protein complex is comprised of IKKα, IKKβ and NEMO subunits, with IKKβ thought to play the dominant role in modulating NF-κB activity. Therefore, the discovery of new IKKβ inhibitors may offer new therapeutic options for the treatment of cancer and inflammatory diseases. Results A structure-based molecular docking approach has been employed to discover novel IKKβ inhibitors from a natural product library of over 90,000 compounds. Preliminary screening of the 12 highest-scoring compounds using a luciferase reporter assay identified 4 promising candidates for further biological study. Among these, the benzoic acid derivative (1) showed the most promising activity at inhibiting IKKβ phosphorylation and TNF-α-induced NF-κB signaling in vitro. Conclusions In this study, we have successfully identified a benzoic acid derivative (1) as a novel IKKβ inhibitor via high-throughput molecular docking. Compound 1 was able to inhibit IKKβ phosphorylation activity in vitro, and block IκBα protein degradation and subsequent NF-κB activation in human cells. Further in silico optimization of the compound is currently being conducted in order to generate more potent analogues for biological tests. PMID:23294515

  1. Role of natural product diversity in chemical biology.

    PubMed

    Hong, Jiyong

    2011-06-01

    Through the natural selection process, natural products possess a unique and vast chemical diversity and have been evolved for optimal interactions with biological macromolecules. Owing to their diversity, target affinity, and specificity, natural products have demonstrated enormous potential as modulators of biomolecular function, been an essential source for drug discovery, and provided design principles for combinatorial library development.

  2. Natural Product Biosynthetic Diversity and Comparative Genomics of the Cyanobacteria.

    PubMed

    Dittmann, Elke; Gugger, Muriel; Sivonen, Kaarina; Fewer, David P

    2015-10-01

    Cyanobacteria are an ancient lineage of slow-growing photosynthetic bacteria and a prolific source of natural products with intricate chemical structures and potent biological activities. The bulk of these natural products are known from just a handful of genera. Recent efforts have elucidated the mechanisms underpinning the biosynthesis of a diverse array of natural products from cyanobacteria. Many of the biosynthetic mechanisms are unique to cyanobacteria or rarely described from other organisms. Advances in genome sequence technology have precipitated a deluge of genome sequences for cyanobacteria. This makes it possible to link known natural products to biosynthetic gene clusters but also accelerates the discovery of new natural products through genome mining. These studies demonstrate that cyanobacteria encode a huge variety of cryptic gene clusters for the production of natural products, and the known chemical diversity is likely to be just a fraction of the true biosynthetic capabilities of this fascinating and ancient group of organisms. Copyright © 2015. Published by Elsevier Ltd.

  3. Natural products as a foundation for drug discovery.

    PubMed

    Beutler, John A

    2009-09-01

    Natural products have provided chemical leads for the development of many drugs for diverse indications. While most U.S. pharmaceutical firms have reduced or eliminated their in-house natural product groups, there is a renewed interest in this source of new chemical entities. Many of the reasons for the past decline in popularity of natural products are being addressed by the development of new techniques for screening and production. The aim of this unit is to review current strategies and techniques that increase the value of natural products as a source for novel drug candidates.

  4. Industrial natural product chemistry for drug discovery and development.

    PubMed

    Bauer, Armin; Brönstrup, Mark

    2014-01-01

    Covering: up to March 2013. In addition to their prominent role in basic biological and chemical research, natural products are a rich source of commercial products for the pharmaceutical and other industries. Industrial natural product chemistry is of fundamental importance for successful product development, as the vast majority (ca. 80%) of commercial drugs derived from natural products require synthetic efforts, either to enable economical access to bulk material, and/or to optimize drug properties through structural modifications. This review aims to illustrate issues on the pathway from lead to product, and how they have been successfully addressed by modern natural product chemistry. It is focused on natural products of current relevance that are, or are intended to be, used as pharmaceuticals.

  5. Use of natural health products in children

    PubMed Central

    Godwin, Marshall; McCrate, Farah; Newhook, Leigh Anne; Pike, Andrea; Crellin, John; Law, Rebecca; Mathews, Maria; Chowdhury, Nurun L.

    2013-01-01

    Abstract Objective To determine the experiences of family physicians in Newfoundland and Labrador with parents’ use of natural health products (NHPs) for their children and to assess physicians’ attitudes toward use of NHPs in children. Design A survey using the Dillman approach. Setting Newfoundland and Labrador. Participants All family physicians in the province. Main outcome measures Physician demographic characteristics; whether physicians inquire about the use of NHPs in children; the degree to which they think patients disclose use of NHPs in children; whether they counsel parents about the potential benefits or harms of NHPs; their own opinions about the usefulness of NHPs; whether they recommend NHPs in children and for what reasons; and the particular NHPs they have seen used in children and for what reasons. Results A total of 159 (33.1%) family physicians responded; 65.4% were men, 71.7% were Canadian medical graduates, and 46.5% practised in rural areas. Overall, 18.8% of family physicians said they regularly or frequently asked about NHP use; 24.7% counseled patients about potential harms. Only 1.9% of physicians believed NHPs were usually beneficial, but a similarly small number (8.4%) thought they were usually harmful. Most respondents were somewhat neutral; 59.7% said they never recommend NHPs for children, and a further 37.0% said they would only “sometimes” recommend NHPs. Conclusion Most physicians believed that NHPs were probably of little benefit but not likely to be harmful. Most NHPs used were vitamins and minerals. Physicians recognized that NHPs were often used by parents for children, but in general they believed NHPs had little effect on their day-to-day medical practices. Thirty-eight (24.7%) of the 154 physicians had at least once recommended an NHP (including vitamins) for their pediatric patients. Physicians believed that parents did not often disclose use of NHPs for their children, but at the same time physicians generally

  6. Marine Natural Products: A Way to New Drugs

    PubMed Central

    2009-01-01

    The investigation of marine natural products (low molecular weight bioregulators) is a rapidly developing scientific field at the intersection of biology and chemistry. Investigations aimed at detecting, identifying, and understanding the structure of marine natural products have led to the discovery of 20,000 new substances, including those characterized by an extremely high physiological activity. Some results and prospects of works aimed at creating new drugs on the basis of marine natural products are discussed herein. PMID:22649599

  7. Dearomatization Strategies in the Synthesis of Complex Natural Products

    PubMed Central

    Roche, Stéphane P.; Porco, John A.

    2014-01-01

    Evolution in the field of the total synthesis of natural products has led to exciting developments over the last decade. Numerous chemo-selective and enantioselective methodologies have emerged from total syntheses, resulting in efficient access to many important natural product targets. This Review highlights recent developments concerning dearomatization, a powerful strategy for the total synthesis of architecturally complex natural products wherein planar, aromatic scaffolds are converted to three-dimensional molecular architectures. PMID:21506209

  8. Marine natural products: a way to new drugs.

    PubMed

    Stonik, V A

    2009-07-01

    The investigation of marine natural products (low molecular weight bioregulators) is a rapidly developing scientific field at the intersection of biology and chemistry. Investigations aimed at detecting, identifying, and understanding the structure of marine natural products have led to the discovery of 20,000 new substances, including those characterized by an extremely high physiological activity. Some results and prospects of works aimed at creating new drugs on the basis of marine natural products are discussed herein.

  9. Biosynthesis of therapeutic natural products using synthetic biology.

    PubMed

    Awan, Ali R; Shaw, William M; Ellis, Tom

    2016-10-01

    Natural products are a group of bioactive structurally diverse chemicals produced by microorganisms and plants. These molecules and their derivatives have contributed to over a third of the therapeutic drugs produced in the last century. However, over the last few decades traditional drug discovery pipelines from natural products have become far less productive and far more expensive. One recent development with promise to combat this trend is the application of synthetic biology to therapeutic natural product biosynthesis. Synthetic biology is a young discipline with roots in systems biology, genetic engineering, and metabolic engineering. In this review, we discuss the use of synthetic biology to engineer improved yields of existing therapeutic natural products. We further describe the use of synthetic biology to combine and express natural product biosynthetic genes in unprecedented ways, and how this holds promise for opening up completely new avenues for drug discovery and production.

  10. Two New Bioactive α-Pyrones from Hypericum japonicum.

    PubMed

    Hu, Linzhen; Wang, Zhenzhen; Zhang, Jinwen; Lu, Yuanyuan; Wang, Kaiping; Xue, Yongbo; Zhang, Yu; Zhang, Yonghui

    2016-04-19

    Hypericum japonicum (Guttiferae), a type of annual or perennial herb, has been historically applied to cure infectious hepatitis, acute and chronic hepatitis, gastrointestinal disorder, and internal hemorrhage. In our successive studies on the genus Hypericum, two new α-pyrones termed japopyrones A and B (1 and 2) were isolated from H. japonicum. Their structures and absolute configurations were established by the comprehensive analyses of spectroscopic data, the application of the Single-crystal X-ray diffraction structural analysis, and the experimental electronic circular dichroism (ECD) spectra. Bioactivity screenings suggested that compound 2 possessed the potential inhibition efficacy on lytic replication of Kaposi's sarcoma associated herpesvirus (KSHV) with an IC50 29.46 μM and a selective index of higher than 6.79, respectively.

  11. Inhibition of MAO by fractions and constituents of hypericum extract.

    PubMed

    Bladt, S; Wagner, H

    1994-10-01

    The inhibition of monoamine oxidase (MAO) by six fractions from hypericum extract and three characteristic constituents (as pure substances) were analyzed in vitro and ex vivo to study the antidepressive mechanism of action. Rat brain homogenates were used as the in vitro model, while the ex vivo analysis was performed after intraperitoneal application of the test substances to albino rats. Massive inhibition of MAO-A could be shown with the total extract and all fractions only at the concentration of 10(-3) mol/L. At 10(-4) mol/L, one fraction rich in flavonoides showed an inhibition of 39%, and all other fractions demonstrated less than 25% inhibition. Using pure hypericin as well as in all ex vivo experiments, no relevant inhibiting effects could be shown. From the results it can be concluded that the clinically proven antidepressive effect of hypericum extract cannot be explained in terms of MAO inhibition.

  12. Xanthones from Hypericum chinense and their cytotoxicity evaluation.

    PubMed

    Tanaka, Naonobu; Kashiwada, Yoshiki; Kim, Sang-Yong; Sekiya, Michiko; Ikeshiro, Yasumasa; Takaishi, Yoshihisa

    2009-01-01

    A xanthonolignoid, 2-O-demethylkielcorin, and a phenylxanthone, chinexanthone A, were isolated from stems of Hypericum chinense together with four known xanthonolignoids and seven known xanthones. Their structures were established by spectroscopic analysis, as their optical properties and absolute stereochemistry determined. The cytotoxicities of the isolated xanthone derivatives as well as additional 32 xanthones against a panel of human cancer cell lines were also evaluated.

  13. Polycyclic polyprenylated acylphloroglucinols and cytotoxic constituents of Hypericum androsaemum.

    PubMed

    Wang, Kou; Wang, Yuan-Yuan; Gao, Xiu; Chen, Xuan-Qin; Peng, Li-Yan; Li, Yan; Xu, Gang; Zhao, Qin-Shi

    2012-06-01

    Two new polycyclic polyprenylated acylphloroglucinols (PPAPs), androforin A and hyperandrone A, together with twelve known compounds, were isolated from the aerial parts of Hypericum androsaemum. Their structures were established by detailed spectral analysis. In the cytotoxic assay, 1,4-O-diferuloylsecoisolariciresinol showed activities comparable with those of cisplatin, and acetyloleanolic acid exhibited moderate inhibitory effects against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cancer cell lines. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

  14. Identification and biosynthesis of acylphloroglucinols in Hypericum gentianoides.

    PubMed

    Crispin, Matthew C; Hur, Manhoi; Park, Taeseong; Kim, Young Hwan; Wurtele, Eve Syrkin

    2013-07-01

    Species of the genus Hypericum contain a rich array of unusual polyketides, however, only a small proportion of the over 450 Hypericum species, other than the popular medicinal supplement St. John's Wort (Hypericum perforatum), have even been chemically characterized. Hypericum gentianoides, a small annual used medicinally by Cherokee Americans, contains bioactive acylphloroglucinols. Here, we identify acylphloroglucinol constituents of H. gentianoides and determine a potential pathway to their synthesis. Liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS) and HPLC-UV indicate that the level of accumulation and profile of acylphloroglucinols in H. gentianoides vary little seasonally when grown in a greenhouse, but do vary with development and are highly dependent on the accession, highlighting the importance of the selection of plant material for study. We identify the chemical structures of the nine prevalent polyketides, based on LC/ESI-MS and hybrid quadrupole orthogonal time-of-flight (Q-TOF) mass spectrometry; these metabolites include one monomeric phlorisobutyrophenone (PIB) derivative and eight dimeric acylphloroglucinols. Q-TOF spectrometry was used to identify eight additional PIB derivatives that were not detected by LC/ESI-MS. These data lead us to propose that diacylphloroglucinols are synthesized via modification of PIB to yield diverse phloroglucinol and filicinic acids moieties, followed by dimerization of a phloroglucinol and a filicinic acid monomer to yield the observed complement of diacylphloroglucinols. The metabolomics data from H. gentianoides are accessible in plant metabolomics resource (PMR) (http://www.metnetdb.org/pmr), a public metabolomics database with analysis software for plants and microbial organisms.

  15. Hyperforin as a possible antidepressant component of hypericum extracts.

    PubMed

    Chatterjee, S S; Bhattacharya, S K; Wonnemann, M; Singer, A; Müller, W E

    1998-01-01

    We demonstrate that the phloroglucinol derivative hyperforin is not only the major lipophilic chemical constituent of the medicinal plant Hypericum perforatum (St. John's wort) but also a potent uptake inhibitor of serotonin (5-HT), dopamine (DA), noradrenaline (NA), GABA and L-Glutamate with IC50 values of about 0.05-0.10 microg/ml (5-HT, NA, DA, GABA) and about 0.5 microg/ml (L-glutamate) in synaptosomal preparations. Furthermore, potencies of two different hypericum extracts in two conventional pharmacological paradigms useful for the detection of antidepressants (behavioral despair, learned helplessness), closely correlate with their hyperforin contents. In addition, most till now known neuropharmacological properties of the clinically used hypericum extracts can also be demonstrated with pure hyperforin. It appears, therefore, that this non-nitrogenous constituent is a possible major active principle responsible for the observed clinical efficacies of the extract as an antidepressant and that it could also be a starting point for drug discovery projects engaged in the search of psychoactive drugs with novel mode of action.

  16. Collective synthesis of natural products by means of organocascade catalysis

    PubMed Central

    Jones, Spencer B.; Simmons, Bryon; Mastracchio, Anthony; MacMillan, David W. C.

    2012-01-01

    Organic chemists are now able to synthesize small quantities of almost any known natural product, given sufficient time, resources and effort. However, translation of the academic successes in total synthesis to the large-scale construction of complex natural products and the development of large collections of biologically relevant molecules present significant challenges to synthetic chemists. Here we show that the application of two nature-inspired techniques, namely organocascade catalysis and collective natural product synthesis, can facilitate the preparation of useful quantities of a range of structurally diverse natural products from a common molecular scaffold. The power of this concept has been demonstrated through the expedient, asymmetric total syntheses of six well-known alkaloid natural products: strychnine, aspidospermidine, vincadifformine, akuammicine, kopsanone and kopsinine. PMID:21753848

  17. Collective synthesis of natural products by means of organocascade catalysis.

    PubMed

    Jones, Spencer B; Simmons, Bryon; Mastracchio, Anthony; MacMillan, David W C

    2011-07-13

    Organic chemists are now able to synthesize small quantities of almost any known natural product, given sufficient time, resources and effort. However, translation of the academic successes in total synthesis to the large-scale construction of complex natural products and the development of large collections of biologically relevant molecules present significant challenges to synthetic chemists. Here we show that the application of two nature-inspired techniques, namely organocascade catalysis and collective natural product synthesis, can facilitate the preparation of useful quantities of a range of structurally diverse natural products from a common molecular scaffold. The power of this concept has been demonstrated through the expedient, asymmetric total syntheses of six well-known alkaloid natural products: strychnine, aspidospermidine, vincadifformine, akuammicine, kopsanone and kopsinine. ©2011 Macmillan Publishers Limited. All rights reserved

  18. Engineered Biosynthesis of Natural Products in Heterologous Hosts

    PubMed Central

    Luo, Yunzi; Li, Bing-Zhi; Liu, Duo; Zhang, Lu; Chen, Yan; Jia, Bin; Zeng, Bo-Xuan; Zhao, Huimin; Yuan, Ying-Jin

    2015-01-01

    Natural products produced by microorganisms and plants are a major resource of antibacterial and anticancer drugs as well as industrially useful compounds. However, the native producers often suffer from low productivity and titers. Here we summarize the recent applications of heterologous biosynthesis for the production of several important classes of natural products such as terpenoids, flavonoids, alkaloids, and polyketides. In addition, we will discuss the new tools and strategies at multi-scale levels including gene, pathway, genome and community levels for highly efficient heterologous biosynthesis of natural products. PMID:25960127

  19. The natural production of organobromine compounds.

    PubMed

    Gribble, G W

    2000-03-01

    Organobromine chemicals are produced naturally by an array of biological and other chemical processes in our environment. Some of these compounds are identical to man-made organobromine compounds, such as methyl bromide, bromoform, and bromophenols, but many others are entirely new moleclar entities, often possessing extraordinary and important biological properties. Although only a few natural organobromine compounds had been discovered up to 1968, this number as of early 1999 is more than 1,600, and new examples are being discovered continually. Organobromine compounds are produced naturally by marine creatures (sponges, corals, sea slugs, tunicates, sea fans) and seaweed, plants, fungi, lichen, algae, bacteria, microbes, and some mammals. Many of these organobromine compounds are used in chemical defense, to facilitate food gathering, or as hormones.

  20. Chemical composition and larvicidal activity of several essential oils from Hypericum species from Tunisia.

    PubMed

    Rouis, Zyed; Laamari, Ali; Abid, Nabil; Elaissi, Ameur; Cioni, Pier Luigi; Flamini, Guido; Aouni, Mahjoub

    2013-02-01

    The chemical composition of the essential oils extracted from some Tunisian Hypericum species and their larvicidal activity against Culex pipiens larvae were evaluated. The chemical compositions of the essential oils from the aerial plant parts were analyzed using gas chromatography-mass spectrometry. One hundred and thirty-four compounds were identified, ranging between 85.1 and 95.4 % of the oil's composition. The components were monoterpene hydrocarbons, oxygenated monoterpenes, sesquiterpene hydrocarbons, oxygenated sesquiterpenes, non-terpenic hydrocarbons, and others. The larvicidal activity of the essential oils was evaluated using a method recommended by WHO. Larvicidal tests revealed that essential oils from the Hypericum species have a significant larvicidal activity against C. pipiens, with LC(50) ranging between 102.82 and 194.70 ppm. The most powerful essential oils against these larvae were Hypericum tomentosum and Hypericum humifusum samples, followed by the essential oil of Hypericum perforatum.

  1. Pharmacological profile of hypericum extract. Effect on serotonin uptake by postsynaptic receptors.

    PubMed

    Perovic, S; Müller, W E

    1995-11-01

    In the present study is is reported that the methanolic Hypericum extract LI 160 (Jarsin 300) exerts no protective effect against N-methyl-D-aspartate (NMDA-) or gp120- (from the HIV virus) induced cytotoxicity. Moreover, it is established that Hypericum extract causes no activation of arachidonic acid release from neurons activated by gp120; hence it displays no sensitization effect on the NMDA receptor channel. The main outcome of this study is the finding that Hypericum extract causes a 50% inhibition (IC50 value) of serotonin uptake by rat synaptosomes at a concentration of 6.2 microglml. Therefore it is concluded that the antidepressant activity of Hypericum extract is due to an inhibition of serotonin uptake by postsynaptic receptors. Future studies might focus on the effect of Hypericum extract on serotonin binding to neurons, serotonin storage in granules, the rate of synthesis of serotonin, and on the activity of monoamine oxidase.

  2. Structure Elucidation of a Natural Product.

    ERIC Educational Resources Information Center

    Letcher, Roy M.

    1983-01-01

    Describes an experiment simulating a real-life structure elucidation problem through isolation, characterization, and chemical transformation of an "unknown," naturally occurring monoterpene, with extensive use being made of spectroscopy and aided by biogenetic considerations. Information given to students, procedures, results, and discussion of…

  3. Structure Elucidation of a Natural Product.

    ERIC Educational Resources Information Center

    Letcher, Roy M.

    1983-01-01

    Describes an experiment simulating a real-life structure elucidation problem through isolation, characterization, and chemical transformation of an "unknown," naturally occurring monoterpene, with extensive use being made of spectroscopy and aided by biogenetic considerations. Information given to students, procedures, results, and discussion of…

  4. Metal content monitoring in Hypericum perforatum pharmaceutical derivatives by atomic absorption and emission spectrometry.

    PubMed

    Gomez, María R; Soledad, Cerutti; Olsina, Roberto A; Silva, María F; Martínez, Luis D

    2004-02-18

    Metals have been investigated in different plant materials in order to establish their normal concentration range and consider their role in plants as part of human medicinal treatment. Metal monitoring as a pattern recognition method is a promising tool in the characterization and/or standardization of phytomedicines. In the present work measurable amounts of Ca, Cu, K, Li, Mg, Mn, Na, Ni, and Zn were detected in phytopharmaceutical derivatives of Hypericum perforatum by atomic techniques. Atomic methodologies like flame atomic absorption spectrometry (FAAS) and electrothermal atomic absorption spectrometry (ETAAS) allow reliable determination of mineral content in pharmaceutical quality control of medicinal plants. Additionally, capillary electrophoresis (CE) patterns of characteristic components (fingerprints) have been performed for the search of adulterants in phytopharmaceutical products.

  5. Characterizing the Metabolic Fingerprint and Anti-inflammatory Activity of Hypericum gentianoides

    PubMed Central

    Hillwig, Matthew L.; Hammer, Kimberly D. P.; Birt, Diane F.; Wurtele, Eve Syrkin

    2009-01-01

    In this paper we characterize the metabolic fingerprint and first reported anti-inflammatory activity of Hypericum gentianoides. H. gentianoides has a history of medical use by Native Americans, but it has been studied very little for biological activity. High-performance liquid chromatography (HPLC) and liquid chromatography–electrospray ionization–mass spectrometry (LC-ESI-MS) analyses of a methanol extract show that H. gentianoides contains a family of over nine related compounds that have retention times, mass spectra, and a distinctive UV absorption spectra characteristic of certain acyl-phloroglucinols. These metabolites are abundant relative to other secondary products present in H. gentianoides, accounting for approximately 0.2 g per gram of dry plant tissue. H. gentianoides methanol extracts and a specific semipreparative HPLC fraction from these extracts containing the putative acyl-phloroglucinols reduce prostaglandin E2 synthesis in mammalian macrophages. PMID:18512936

  6. New natural products as new leads for antibacterial drug discovery.

    PubMed

    Brown, Dean G; Lister, Troy; May-Dracka, Tricia L

    2014-01-15

    Natural products have been a rich source of antibacterial drugs for many decades, but investments in this area have declined over the past two decades. The purpose of this review article is to provide a recent survey of new natural product classes and the mechanisms by which they work.

  7. Harnessing natural product assembly lines: structure, promiscuity, and engineering

    PubMed Central

    Ladner, Christopher C; Williams, Gavin J

    2015-01-01

    Many therapeutically relevant natural products are biosynthesized by the action of giant mega-enzyme assembly lines. By leveraging the specificity, promiscuity, and modularity of assembly lines, a variety of strategies have been developed that enable the biosynthesis of modified natural products. This review briefly summarizes recent structural advances related to natural product assembly lines, discusses chemical approaches to probing assembly line structures in the absence of traditional biophysical data, and surveys efforts that harness the inherent or engineered promiscuity of assembly lines for the synthesis of non-natural polyketides and nonribosomal peptide analogues. PMID:26527577

  8. High rate of methane leakage from natural gas production

    NASA Astrophysics Data System (ADS)

    Balcerak, Ernie

    2013-10-01

    Natural gas production is growing as the United States seeks domestic sources of relatively clean energy. Natural gas combustion produces less carbon dioxide emissions than coal or oil for the amount of energy produced. However, one source of concern is that some natural gas leaks to the atmosphere from the extraction point, releasing methane, a potent greenhouse gas.

  9. Marinopyrroles: Unique Drug Discoveries Based on Marine Natural Products.

    PubMed

    Li, Rongshi

    2016-01-01

    Natural products provide a successful supply of new chemical entities (NCEs) for drug discovery to treat human diseases. Approximately half of the NCEs are based on natural products and their derivatives. Notably, marine natural products, a largely untapped resource, have contributed to drug discovery and development with eight drugs or cosmeceuticals approved by the U.S. Food and Drug Administration and European Medicines Agency, and ten candidates undergoing clinical trials. Collaborative efforts from drug developers, biologists, organic, medicinal, and natural product chemists have elevated drug discoveries to new levels. These efforts are expected to continue to improve the efficiency of natural product-based drugs. Marinopyrroles are examined here as a case study for potential anticancer and antibiotic agents. © 2015 Wiley Periodicals, Inc.

  10. Natural Products Version 2.0: Connecting Genes to Molecules

    PubMed Central

    Walsh, Christopher T.; Fischbach, Michael A.

    2009-01-01

    Natural products have played a prominent role in the history of organic chemistry, and they continue to be important as drugs, biological probes, and targets of study for synthetic and analytical chemists. In this perspective, we explore how connecting Nature’s small molecules to the genes that encode them has sparked a renaissance in natural product research, focusing primarily on the biosynthesis of polyketides and nonribosomal peptides. We survey monomer biogenesis, coupling chemistries from templated and non-templated pathways, and the broad set of tailoring reactions and hybrid pathways that give rise to the diverse scaffolds and functionalization patterns of natural products. We conclude by considering two questions: What would it take to find all natural product scaffolds? What kind of scientists will be studying natural products in the future? PMID:20121095

  11. Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis

    PubMed Central

    Crane, Erika A.

    2016-01-01

    Abstract Natural products have had an immense influence on science and have directly led to the introduction of many drugs. Organic chemistry, and its unique ability to tailor natural products through synthesis, provides an extraordinary approach to unlock the full potential of natural products. In this Review, an approach based on natural product derived fragments is presented that can successfully address some of the current challenges in drug discovery. These fragments often display significantly reduced molecular weights, reduced structural complexity, a reduced number of synthetic steps, while retaining or even improving key biological parameters such as potency or selectivity. Examples from various stages of the drug development process up to the clinic are presented. In addition, this process can be leveraged by recent developments such as genome mining, antibody–drug conjugates, and computational approaches. All these concepts have the potential to identify the next generation of drug candidates inspired by natural products. PMID:26833854

  12. Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis.

    PubMed

    Crane, Erika A; Gademann, Karl

    2016-03-14

    Natural products have had an immense influence on science and have directly led to the introduction of many drugs. Organic chemistry, and its unique ability to tailor natural products through synthesis, provides an extraordinary approach to unlock the full potential of natural products. In this Review, an approach based on natural product derived fragments is presented that can successfully address some of the current challenges in drug discovery. These fragments often display significantly reduced molecular weights, reduced structural complexity, a reduced number of synthetic steps, while retaining or even improving key biological parameters such as potency or selectivity. Examples from various stages of the drug development process up to the clinic are presented. In addition, this process can be leveraged by recent developments such as genome mining, antibody-drug conjugates, and computational approaches. All these concepts have the potential to identify the next generation of drug candidates inspired by natural products.

  13. Antimycobacterial susceptibility testing methods for natural products research

    PubMed Central

    Sánchez, Juan Gabriel Bueno; Kouznetsov, Vladimir V.

    2010-01-01

    The emergence of multidrug-resistant strains of Mycobacterium tuberculosis underscores the need of continuous developments on new and efficient methods to determine the susceptibility of isolates of M. tuberculosis in the search for novel antimicrobial agents. Natural products constitute an important source of new drugs, but design and implementation of antimycobacterial susceptibility testing methods are necessary for evaluate the different extracts and compounds. A number of biological assay methodologies are in current use, ranging from the classical disk diffusion and broth dilution assay format, to radiorespirometric (BACTEC), dye-based, and fluorescent/luminescence reporter assays. This review presents an analysis on the in vitro susceptibility testing methods developed for determinate antitubercular activity in natural products and related compounds (semi-synthetic natural products and natural products-derived compounds) and the criteria to select the adequate method for determination of biological activity of new natural products. PMID:24031490

  14. Bioactive natural products from Papua New Guinea marine sponges.

    PubMed

    Noro, Jeffery C; Kalaitzis, John A; Neilan, Brett A

    2012-10-01

    The discovery of novel natural products for drug development relies heavily upon a rich biodiversity, of which the marine environment is an obvious example. Marine natural product research has spawned several drugs and many other candidates, some of which are the focus of current clinical trials. The sponge megadiversity of Papua New Guinea is a rich but underexplored source of bioactive natural products. Here, we review some of the many natural products derived from PNG sponges with an emphasis on those with interesting biological activity and, therefore, drug potential. Many bioactive natural products discussed here appear to be derived from non-ribosomal peptide and polyketide biosynthesis pathways, strongly suggesting a microbial origin of these compounds. With this in mind, we also explore the notion of sponge-symbiont biosynthesis of these bioactive compounds and present examples to support the working hypothesis.

  15. Novel Artificial Natural Products Against Breast Cancer Through Combinatorial Biosynthesis

    DTIC Science & Technology

    2002-07-01

    compounds normally produced by a certain strain. Our investigations on the discovery of novel natural metabolites using type II polyketide synthase ...limitations, shall be included on any reproduction hereof which includes any part of the portions subject to such limitations. THIS TECHNICAL REPORT HAS... polyketides remain the central group of natural products in this research area, since this class of natural products form one of the largest and most

  16. Marine actinobacteria: new opportunities for natural product search and discovery.

    PubMed

    Bull, Alan T; Stach, James E M

    2007-11-01

    It is widely accepted that new drugs, especially antibiotics, are urgently required, and that the most propitious source remains natural products. We argue that in exploring new sources of bioactive natural products the marine environment warrants particular attention, in view of the remarkable diversity of microorganisms and metabolic products. Recent reports of new chemical entities and first-in-class drug candidates, and confirmation of indigenous marine actinobacteria, make exciting discoveries even more likely given the unrivalled capacity of this class of bacteria to produce exploitable natural products.

  17. Challenges and Triumphs to Genomics-Based Natural Product Discovery

    PubMed Central

    Jensen, Paul R.; Chavarria, Krystle L.; Fenical, William; Moore, Bradley S.; Ziemert, Nadine

    2013-01-01

    Genome sequencing is rapidly changing the field of natural products research by providing opportunities to assess the biosynthetic potential of strains prior to chemical analysis or biological testing. Ready access to sequence data is driving the development of new bioinformatic tools and methods to identify the products of silent or cryptic pathways. While genome mining has fast become a useful approach to natural product discovery, it has also become clear that identifying pathways of interest is much easier than finding the associated products. This has led to bottlenecks in the discovery process that must be overcome for the potential of genomics-based natural product discovery to be fully realized. In this perspective, we address some of these challenges in the context of our work with the marine actinomycete genus Salinispora, which is proving to be a useful model with which to apply genome mining as an approach to natural product discovery. PMID:24104399

  18. Strategies for target identification of antimicrobial natural products.

    PubMed

    Farha, Maya A; Brown, Eric D

    2016-05-04

    Covering: 2000 to 2015Despite a pervasive decline in natural product research at many pharmaceutical companies over the last two decades, natural products have undeniably been a prolific and unsurpassed source for new lead antibacterial compounds. Due to their inherent complexity, natural extracts face several hurdles in high-throughout discovery programs, including target identification. Target identification and validation is a crucial process for advancing hits through the discovery pipeline, but has remained a major bottleneck. In the case of natural products, extremely low yields and limited compound supply further impede the process. Here, we review the wealth of target identification strategies that have been proposed and implemented for the characterization of novel antibacterials. Traditionally, these have included genomic and biochemical-based approaches, which, in recent years, have been improved with modern-day technology and better honed for natural product discovery. Further, we discuss the more recent innovative approaches for uncovering the target of new antibacterial natural products, which have resulted from modern advances in chemical biology tools. Finally, we present unique screening platforms implemented to streamline the process of target identification. The different innovative methods to respond to the challenge of characterizing the mode of action for antibacterial natural products have cumulatively built useful frameworks that may advocate a renovated interest in natural product drug discovery programs.

  19. Catalytic inhibition of human DNA topoisomerase IIalpha by hypericin, a naphthodianthrone from St. John's wort (Hypericum perforatum).

    PubMed

    Peebles, K A; Baker, R K; Kurz, E U; Schneider, B J; Kroll, D J

    2001-10-15

    St. John's wort (Hypericum perforatum) is the most widely used herbal medicine for the treatment of depression. However, concerns have arisen about the potential of its interaction with other drugs due to the induction of cytochrome P450 isozymes 1A2 and 3A4 by the components hypericin and hyperforin, respectively. Structurally similar natural products are often employed as antitumor agents due to their action as inhibitors of DNA topoisomerases, nuclear enzymes that modify DNA during cellular proliferation. Preliminary findings that hypericin inhibited the DNA relaxation activity of topoisomerase IIalpha (topo II; EC 5.99.1.3) led us to investigate the mechanism of enzyme inhibition. Rather than stabilizing the enzyme in covalent complexes with DNA (cleavage complexes), hypericin inhibited the enzyme prior to DNA cleavage. In vitro assays indicate that hypericin is a potent antagonist of cleavage complex stabilization by the chemotherapeutics etoposide and amsacrine. This antagonism appears to be due to the ability of hypericin to intercalate or distort DNA structure, thereby precluding topo II binding and/or DNA cleavage. Supporting its non-DNA damaging, catalytic inhibition of topo II, hypericin was shown to be equitoxic to both wild-type and amsacrine-resistant HL-60 leukemia cell lines. Moreover, hypericin was incapable of stimulating DNA damage-responsive gene promoters that are activated by etoposide. As with the in vitro topo II assay, antagonism of DNA damage stimulated by 30 microM etoposide was evident in leukemia cells pretreated with 5 microM hypericin. Since many cancer patients experience clinical depression and concomitantly self-medicate with herbal remedies, extracts of St. John's wort should be investigated further for their potential to antagonize topo II-directed chemotherapy regimens.

  20. Spatial and Temporal Control of Fungal Natural Product Synthesis

    PubMed Central

    Lim, Fang Yun; Keller, Nancy P.

    2014-01-01

    Despite their oftentimes-elusive ecological role, fungal natural products have, for better or worse, impacted our daily lives tremendously owing to their diverse and potent bioactive properties. This Janus-faced nature of fungal natural products inevitably ushered in a field of research dedicated towards understanding the ecology, organisms, genes, enzymes, and biosynthetic pathways that give rise to this arsenal of diverse and complex chemistry. Ongoing research in fungal secondary metabolism has not only increased our appreciation for fungal natural products as an asset but also sheds light on the pivotal role that these once-regarded “metabolic wastes” play in fungal biology, defense, and stress response in addition to their potential contributions towards human mycoses. Full orchestration of secondary metabolism requires not only the seamless coordination between temporal and spatial control of SM-associated machineries (e.g. enzymes, cofactors, intermediates, and end-products) but also integration of these machineries into primary metabolic processes and established cellular mechanisms. An intriguing, but little known aspect of microbial natural product synthesis lies in the spatial organization of both pathway intermediates and enzymes responsible for the production of these compounds. In this highlight, we summarize some major breakthroughs in understanding the genes and regulation of fungal natural product synthesis and introduce the current state of knowledge on the spatial and temporal control of fungal natural product synthesis. PMID:25142354

  1. Spatial and temporal control of fungal natural product synthesis.

    PubMed

    Lim, Fang Yun; Keller, Nancy P

    2014-10-01

    Despite their oftentimes-elusive ecological role, fungal natural products have, for better or worse, impacted our daily lives tremendously owing to their diverse and potent bioactive properties. This Janus-faced nature of fungal natural products inevitably ushered in a field of research dedicated towards understanding the ecology, organisms, genes, enzymes, and biosynthetic pathways that give rise to this arsenal of diverse and complex chemistry. Ongoing research in fungal secondary metabolism has not only increased our appreciation for fungal natural products as an asset but also sheds light on the pivotal role that these once-regarded "metabolic wastes" play in fungal biology, defense, and stress response in addition to their potential contributions towards human mycoses. Full orchestration of secondary metabolism requires not only the seamless coordination between temporal and spatial control of SM-associated machineries (e.g. enzymes, cofactors, intermediates, and end-products) but also integration of these machineries into primary metabolic processes and established cellular mechanisms. An intriguing, but little known aspect of microbial natural product synthesis lies in the spatial organization of both pathway intermediates and enzymes responsible for the production of these compounds. In this highlight, we summarize some major breakthroughs in understanding the genes and regulation of fungal natural product synthesis and introduce the current state of knowledge on the spatial and temporal control of fungal natural product synthesis.

  2. Antioxidant, antimicrobial activities and fatty acid components of flower, leaf, stem and seed of Hypericum scabrum.

    PubMed

    Shafaghat, Ali

    2011-11-01

    The hexane extracts of flower, leaf, stem, and seed of Hypericum scabrum, which were collected from northwestern Iran, were obtained by extraction in a Soxhlet apparatus. The fatty acids were converted to methyl esters and determined by gas chromatography/flame ionization detector (GC/FID) and gas chromatography/mass spectrometry (GC/MS) systems. The hexane extract from the flower, leaf, stem, and seed contained 39.1%, 43.2%, 29.0%, and 37.6% of omega-3 fatty acids, respectively. The other main components of the flower extract were tetracosane (12.2%) and palmitic acid (9.3%), and that of the leaf extract was palmitic acid (7.4%). The stem and seed extracts contained bis(2-ethylhexyl)phthalate (18.7% and 35.7%), nonacosane (11.7% and 3.9%) and linoleic acid (6.5% and 6.9%) as major components. The hexane extracts of different parts from H. scabrum represent an important source of omega-3 fatty acids in several Hypericum species. The antioxidant activity of all hexane extracts was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method. The results indicate that hexane extracts from different parts of H. scabrum possess considerable antioxidant activity. The highest radical scavenging activity was detected in seed, which had an IC50 = 165 microg/mL. The antimicrobial activity of the extracts of those samples were determined against seven Gram-positive and Gram-negative bacteria (Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, S. epidermidis, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae), as well as three fungi (Candida albicans, Saccharomyces cerevisiae, and Aspergillus niger). The bioassay showed that the oil exhibited moderate antimicrobial activity. This study reveals that the all parts of this plant are attractive sources of fatty acid components, especially the essential ones, as well as of effective natural antioxidants.

  3. From nature to market: examples of natural products that became drugs.

    PubMed

    de Fátima, Angelo; Terra, Bruna Silva; da Silva, Cleiton Moreira; da Silva, Daniel Leite; Araujo, Debora Pereira; da Silva Neto, Leonardo; Nascimento de Aquino, Roney Anderson

    2014-01-01

    Nature is an irrefutable source of inspiration for the modern man in many aspects. The observation and understanding of nature have allowed the development of new materials, new sources of energies, new drugs etc. Specifically, natural products provide a great contribution to the development of new agents for the treatment of infections and antitumor agents. However, obtaining natural products directly from animals, fungi, bacteria, plants etc has been considered not enough to attend the high demand by pharmaceutical industries. In this regard, various strategies based on biotechnological processes or synthetic approaches have been developed. In this scenario the total synthesis can be undoubtedly a useful and powerful tool for obtaining higher amounts of natural products and/or structural modifications thereof. Herein, we emphasize successful examples of total synthesis of galanthamine, morphine, paclitaxel and podophyllotoxin - natural products approved as pharmaceuticals.

  4. Fungi as a source of natural coumarins production.

    PubMed

    Costa, Tania Maria; Tavares, Lorena Benathar Ballod; de Oliveira, Débora

    2016-08-01

    Natural coumarins and derivatives are compounds that occur naturally in several organisms (plant, bacteria, and fungi) consisting of fused benzene and α-pyrone rings. These compounds show high technological potential applications in agrochemical, food, pharmaceuticals, and cosmetics industries. Therefore, the need for bulk production of coumarins and the advancement of the chemical and pharmaceutical industries led to the development of synthetic coumarin. However, biotransformation process, synthetic bioengineering, metabolic engineering, and bioinformatics have proven effective in the production of natural products. Today, these biological systems are recognized as green chemistry innovation and business strategy. This review article aims to report the potential of fungi for synthesis of coumarin. These microorganisms are described as a source of natural products capable of synthesizing many bioactive metabolites. The features, classification, properties, and industrial applications of natural coumarins as well as new molecules obtained by basidiomycetes and ascomycetes fungi are reported in order to explore a topic not yet discussed in the scientific literature.

  5. Natural gas production verification tests. Environmental assessment

    SciTech Connect

    Not Available

    1992-02-01

    This Environmental Assessment (EA) has been prepared by the Department of Energy (DOE) in compliance with the requirements of the National Environmental Policy Act of 1969. The Department of Energy (DOE) proposes to fund, through a contract with Petroleum Consulting Services, Inc. of Canton, Ohio, the testing of the effectiveness of a non-water based hydraulic fracturing treatment to increase gas recovery from low-pressure, tight, fractured Devonian Shale formations. Although Devonian Shales are found in the Appalachian, Michigan, and Illinois Basins, testing will be done only in the dominant, historical five state area of established production. The objective of this proposed project is to assess the benefits of liquid carbon dioxide (CO{sub 2})/sand stimulations in the Devonian Shale. In addition, this project would evaluate the potential nondamaging (to the formation) properties of this unique fracturing treatment relative to the clogging or chocking of pores and fractures that act as gas flow paths to the wellbore in the target gas-producing zones of the formation. This liquid CO{sub 2}/sand fracturing process is water-free and is expected to facilitate gas well cleanup, reduce the time required for post-stimulation cleanup, and result in improved production levels in a much shorter time than is currently experienced.

  6. Solid-phase enrichment and analysis of electrophilic natural products

    PubMed Central

    Wesche, Frank; He, Yue

    2017-01-01

    In search for new natural products, which may lead to the development of new drugs for all kind of applications, novel methods are needed. Here we describe the identification of electrophilic natural products in crude extracts via their reactivity against azide as a nucleophile followed by their subsequent enrichment using a cleavable azide-reactive resin (CARR). Using this approach, natural products carrying epoxides and α,β-unsaturated enones as well as several unknown compounds were identified in crude extracts from entomopathogenic Photorhabdus bacteria. PMID:28382178

  7. Genetic regulation and manipulation for natural product discovery.

    PubMed

    Chen, Jianwei; Wu, Qihao; Hawas, Usama W; Wang, Hong

    2016-04-01

    Natural products are an important source of modern medical development, e.g., antibiotics, anticancers, immune modulators, etc. and will continue to be a powerful driving force for the discovery of novel potential drugs. In the heterologous hosts, natural products are biosynthesized using dedicated metabolic networks. By gene engineering, pathway reconstructing, and enzyme engineering, metabolic networks can be modified to synthesize novel compounds containing enhanced structural feature or produce a large quantity of known valuable bioactive compounds. The review introduces some important technical platforms and relevant examples of genetic regulation and manipulation to improve natural product titers or drive novel secondary metabolite discoveries.

  8. Ribosomal Peptide Natural Products: Bridging the Ribosomal and Nonribosomal Worlds

    PubMed Central

    McIntosh, John A.; Donia, Mohamed S.; Schmidt, Eric W.

    2010-01-01

    Ribosomally synthesized bacterial natural products rival the nonribosomal peptides in their structural and functional diversity. The last decade has seen substantial progress in the identification and characterization of biosynthetic pathways leading to ribosomal peptide natural products with new and unusual structural motifs. In some of these cases, the motifs are similar to those found in nonribosomal peptides, and many are constructed by convergent or even paralogous enzymes. Here, we summarize the major structural and biosynthetic categories of ribosomally synthesized bacterial natural products and, where applicable, compare them to their homologs from nonribosomal biosynthesis. PMID:19642421

  9. Biosynthetic engineering of natural products for lead optimization and development.

    PubMed

    Wilkinson, Barrie; Moss, Steven J

    2005-11-01

    It is now possible to rapidly and rationally modify, at a genetic level, the machinery responsible for natural product biosynthesis. This provides the opportunity to design new structures and to optimize natural product lead compounds in a way that would be extremely difficult through synthetic chemistry means alone. The technology can also be used to overcome limitations of compound supply, which might otherwise preclude natural products from progressing into clinical trials. Described herein are some recent examples which highlight how biosynthetic engineering has been applied to drug discovery and development, and which attempt, in particular, to demonstrate how the technology functions most effectively when combined with synthetic organic and medicinal chemistry.

  10. Accessing the Hidden Majority of Marine Natural Products Through Metagenomics

    PubMed Central

    Donia, Mohamed S.; Ruffner, Duane E.; Cao, Sheng

    2012-01-01

    Tiny marine animals represent an untapped reservoir for undiscovered, bioactive natural products. However, their small size and extreme chemical variability preclude traditional chemical approaches to discovering new bioactive compounds. Here, we use a metagenomic method to directly discover and rapidly access cyanobactin class natural products from these variable samples, providing proof-of-concept for genome based discovery and supply of marine natural products. We also address practical optimization of complex, multistep ribosomal peptide pathways in heterologous hosts, which is still very challenging. The resulting methods and concepts will be applicable to ribosomal peptide and other biosynthetic pathways. PMID:21542088

  11. Manufacturing Natural Killer Cells as Medicinal Products.

    PubMed

    Chabannon, Christian; Mfarrej, Bechara; Guia, Sophie; Ugolini, Sophie; Devillier, Raynier; Blaise, Didier; Vivier, Eric; Calmels, Boris

    2016-01-01

    Natural Killer (NK) cells are innate lymphoid cells (ILC) with cytotoxic and regulatory properties. Their functions are tightly regulated by an array of inhibitory and activating receptors, and their mechanisms of activation strongly differ from antigen recognition in the context of human leukocyte antigen presentation as needed for T-cell activation. NK cells thus offer unique opportunities for new and improved therapeutic manipulation, either in vivo or in vitro, in a variety of human diseases, including cancers. NK cell activity can possibly be modulated in vivo through direct or indirect actions exerted by small molecules or monoclonal antibodies. NK cells can also be adoptively transferred following more or less substantial modifications through cell and gene manufacturing, in order to empower them with new or improved functions and ensure their controlled persistence and activity in the recipient. In the present review, we will focus on the technological and regulatory challenges of NK cell manufacturing and discuss conditions in which these innovative cellular therapies can be brought to the clinic.

  12. Manufacturing Natural Killer Cells as Medicinal Products

    PubMed Central

    Chabannon, Christian; Mfarrej, Bechara; Guia, Sophie; Ugolini, Sophie; Devillier, Raynier; Blaise, Didier; Vivier, Eric; Calmels, Boris

    2016-01-01

    Natural Killer (NK) cells are innate lymphoid cells (ILC) with cytotoxic and regulatory properties. Their functions are tightly regulated by an array of inhibitory and activating receptors, and their mechanisms of activation strongly differ from antigen recognition in the context of human leukocyte antigen presentation as needed for T-cell activation. NK cells thus offer unique opportunities for new and improved therapeutic manipulation, either in vivo or in vitro, in a variety of human diseases, including cancers. NK cell activity can possibly be modulated in vivo through direct or indirect actions exerted by small molecules or monoclonal antibodies. NK cells can also be adoptively transferred following more or less substantial modifications through cell and gene manufacturing, in order to empower them with new or improved functions and ensure their controlled persistence and activity in the recipient. In the present review, we will focus on the technological and regulatory challenges of NK cell manufacturing and discuss conditions in which these innovative cellular therapies can be brought to the clinic. PMID:27895646

  13. Taxonomy, Physiology, and Natural Products of Actinobacteria

    PubMed Central

    Vatsa, Parul; Sanchez, Lisa; Gaveau-Vaillant, Nathalie; Jacquard, Cedric; Klenk, Hans-Peter; Clément, Christophe; Ouhdouch, Yder

    2015-01-01

    SUMMARY Actinobacteria are Gram-positive bacteria with high G+C DNA content that constitute one of the largest bacterial phyla, and they are ubiquitously distributed in both aquatic and terrestrial ecosystems. Many Actinobacteria have a mycelial lifestyle and undergo complex morphological differentiation. They also have an extensive secondary metabolism and produce about two-thirds of all naturally derived antibiotics in current clinical use, as well as many anticancer, anthelmintic, and antifungal compounds. Consequently, these bacteria are of major importance for biotechnology, medicine, and agriculture. Actinobacteria play diverse roles in their associations with various higher organisms, since their members have adopted different lifestyles, and the phylum includes pathogens (notably, species of Corynebacterium, Mycobacterium, Nocardia, Propionibacterium, and Tropheryma), soil inhabitants (e.g., Micromonospora and Streptomyces species), plant commensals (e.g., Frankia spp.), and gastrointestinal commensals (Bifidobacterium spp.). Actinobacteria also play an important role as symbionts and as pathogens in plant-associated microbial communities. This review presents an update on the biology of this important bacterial phylum. PMID:26609051

  14. Production of Substitute Natural Gas from Coal

    SciTech Connect

    Andrew Lucero

    2009-01-31

    The goal of this research program was to develop and demonstrate a novel gasification technology to produce substitute natural gas (SNG) from coal. The technology relies on a continuous sequential processing method that differs substantially from the historic methanation or hydro-gasification processing technologies. The thermo-chemistry relies on all the same reactions, but the processing sequences are different. The proposed concept is appropriate for western sub-bituminous coals, which tend to be composed of about half fixed carbon and about half volatile matter (dry ash-free basis). In the most general terms the process requires four steps (1) separating the fixed carbon from the volatile matter (pyrolysis); (2) converting the volatile fraction into syngas (reforming); (3) reacting the syngas with heated carbon to make methane-rich fuel gas (methanation and hydro-gasification); and (4) generating process heat by combusting residual char (combustion). A key feature of this technology is that no oxygen plant is needed for char combustion.

  15. Taxonomy, Physiology, and Natural Products of Actinobacteria.

    PubMed

    Barka, Essaid Ait; Vatsa, Parul; Sanchez, Lisa; Gaveau-Vaillant, Nathalie; Jacquard, Cedric; Klenk, Hans-Peter; Clément, Christophe; Ouhdouch, Yder; van Wezel, Gilles P

    2016-03-01

    Actinobacteria are Gram-positive bacteria with high G+C DNA content that constitute one of the largest bacterial phyla, and they are ubiquitously distributed in both aquatic and terrestrial ecosystems. Many Actinobacteria have a mycelial lifestyle and undergo complex morphological differentiation. They also have an extensive secondary metabolism and produce about two-thirds of all naturally derived antibiotics in current clinical use, as well as many anticancer, anthelmintic, and antifungal compounds. Consequently, these bacteria are of major importance for biotechnology, medicine, and agriculture. Actinobacteria play diverse roles in their associations with various higher organisms, since their members have adopted different lifestyles, and the phylum includes pathogens (notably, species of Corynebacterium, Mycobacterium, Nocardia, Propionibacterium, and Tropheryma), soil inhabitants (e.g., Micromonospora and Streptomyces species), plant commensals (e.g., Frankia spp.), and gastrointestinal commensals (Bifidobacterium spp.). Actinobacteria also play an important role as symbionts and as pathogens in plant-associated microbial communities. This review presents an update on the biology of this important bacterial phylum. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  16. Effect of Hypericum perforatum L. Extract on Insulin Resistance and Lipid Metabolic Disorder in High-Fat-Diet Induced Obese Mice

    PubMed Central

    Tian, Jin-ying; Tao, Rong-ya; Zhang, Xiao-lin; Liu, Qian; He, Yi-bo; Su, Ya-lun; Ji, Teng-fei; Ye, Fei

    2015-01-01

    Natural product Hypericum perforatum L. has been used in folk medicine to improve mental performance. However, the effect of H. perforatum L. on metabolism is still unknown. In order to test whether H. perforatum L. extract (EHP) has an effect on metabolic syndrome, we treated diet induced obese (DIO) C57BL/6J mice with the extract. The chemical characters of EHP were investigated with thin-layer chromatography, ultraviolet, high-performance liquid chromatography (HPLC), and HPLC-mass spectrometry fingerprint analysis. Oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and the glucose infusion rate (GIR) in hyperinsulinemic–euglycemic clamp test were performed to evaluate the glucose metabolism and insulin sensitivity. Skeletal muscle was examined for lipid metabolism. The results suggest that EHP can significantly improve the glucose and lipid metabolism in DIO mice. In vitro, EHP inhibited the catalytic activity of recombinant human protein tyrosine phosphatase 1B (PTP1B) and reduced the protein and mRNA levels of PTP1B in the skeletal muscle. Moreover, expressions of genes related to fatty acid uptake and oxidation were changed by EHP in the skeletal muscle. These results suggest that EHP may improve insulin resistance and lipid metabolism in DIO mice. © 2014 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd. PMID:25266458

  17. Effect of Hypericum perforatum L. extract on insulin resistance and lipid metabolic disorder in high-fat-diet induced obese mice.

    PubMed

    Tian, Jin-ying; Tao, Rong-ya; Zhang, Xiao-lin; Liu, Qian; He, Yi-Bo; Su, Ya-lun; Ji, Teng-fei; Ye, Fei

    2015-01-01

    Natural product Hypericum perforatum L. has been used in folk medicine to improve mental performance. However, the effect of H. perforatum L. on metabolism is still unknown. In order to test whether H. perforatum L. extract (EHP) has an effect on metabolic syndrome, we treated diet induced obese (DIO) C57BL/6J mice with the extract. The chemical characters of EHP were investigated with thin-layer chromatography, ultraviolet, high-performance liquid chromatography (HPLC), and HPLC-mass spectrometry fingerprint analysis. Oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and the glucose infusion rate (GIR) in hyperinsulinemic-euglycemic clamp test were performed to evaluate the glucose metabolism and insulin sensitivity. Skeletal muscle was examined for lipid metabolism. The results suggest that EHP can significantly improve the glucose and lipid metabolism in DIO mice. In vitro, EHP inhibited the catalytic activity of recombinant human protein tyrosine phosphatase 1B (PTP1B) and reduced the protein and mRNA levels of PTP1B in the skeletal muscle. Moreover, expressions of genes related to fatty acid uptake and oxidation were changed by EHP in the skeletal muscle. These results suggest that EHP may improve insulin resistance and lipid metabolism in DIO mice.

  18. Effects of Hypericum perforatum extract on diabetes-induced learning and memory impairment in rats.

    PubMed

    Hasanein, Parisa; Shahidi, Siamak

    2011-04-01

    Cognitive impairment occurs in diabetes mellitus. Hypericum perforatum has been used in folk medicine to improve mental performance. Here it is hypothesized that chronic treatment with an extract of Hypericum perforatum (6, 12 and 25 mg/kg, p.o.) would have effects on passive avoidance learning (PAL) and memory in control and streptozotocin-induced diabetic rats. Treatments were begun at the onset of hyperglycaemia. PAL was assessed 30 days later. A retention test was done 24 h after training. At the end, the animals were weighed and blood samples were drawn for plasma glucose measurement. Diabetes caused impairment in acquisition and retrieval processes of PAL and memory. Hypericum treatment (12 and 25 mg/kg) improved learning and memory in control rats and reversed learning and memory deficits in diabetic rats. A dose of 6 mg/kg did not affect cognitive function. Hypericum administration did not alter the body weight and plasma glucose levels. Antioxidant properties and cholinergic facilitatory effects of Hypericum may be involved in its nootropic effects. These results show that Hypericum perforatum prevented the deleterious effects of diabetes on PAL and memory. As Hypericum would be free of major side effects compared with other nootropic medications, it may provide a new potential alternative for demented diabetic patients.

  19. Molecular phylogenetics and morphological evolution of St. John's wort (Hypericum; Hypericaceae).

    PubMed

    Nürk, Nicolai M; Madriñán, Santiago; Carine, Mark A; Chase, Mark W; Blattner, Frank R

    2013-01-01

    Phylogenetic hypotheses for the large cosmopolitan genus Hypericum (St. John's wort) have previously been based on morphology, and molecular studies have thus far included only a few species. In this study, we used 360 sequences of the internal transcribed spacer (ITS) region of nuclear ribosomal DNA (nrDNA) for 206 species representing Hypericum (incl. Triadenum and Thornea) and three other genera of Hypericaceae to generate an explicit phylogenetic hypothesis for the genus using parsimony and model-based methods. The results indicate that the small genus Triadenum is nested in a clade within Hypericum containing most of the New World species. Sister to Hypericum is Thornea from Central America. Within Hypericum, three large clades and two smaller grades were found; these are based on their general morphology, especially characters used previously in taxonomy of the genus. Relative to the most recent classification, around 60% of the sections of Hypericum were monophyletic. We used a Bayesian approach to reconstruct ancestral states of selected morphological characters, which resulted in recognition of characters that support major clades within the genus and a revised interpretation of morphological evolution in Hypericum. The shrubby habit represents the plesiomorphic state from which herbs evolved several times. Arborescent species have radiated convergently in high-elevation habitats in tropical Africa and South America.

  20. Technology development for natural product biosynthesis in Saccharomyces cerevisiae.

    PubMed

    Billingsley, John M; DeNicola, Anthony B; Tang, Yi

    2016-12-01

    The explosion of genomic sequence data and the significant advancements in synthetic biology have led to the development of new technologies for natural products discovery and production. Using powerful genetic tools, the yeast Saccharomyces cerevisiae has been engineered as a production host for natural product pathways from bacterial, fungal, and plant species. With an expanding library of characterized genetic parts, biosynthetic pathways can be refactored for optimized expression in yeast. New engineering strategies have enabled the increased production of valuable secondary metabolites by tuning metabolic pathways. Improvements in high-throughput screening methods have facilitated the rapid identification of variants with improved biosynthetic capabilities. In this review, we focus on the molecular tools and engineering strategies that have recently empowered heterologous natural product biosynthesis.

  1. Opportunities for natural products in 21(st) century antibiotic discovery.

    PubMed

    Wright, Gerard D

    2017-07-01

    Natural products and their derivatives are mainstays of our antibiotic drugs, but they are increasingly in peril. The combination of widespread multidrug resistance in once susceptible bacterial pathogens, disenchantment with natural products as sources of new drugs, lack of success using synthetic compounds and target-based discovery methods, along with shifting economic and regulatory issues, conspire to move investment in research and development away from the antibiotics arena. The result is a growing crisis in antibiotic drug discovery that threatens modern medicine. 21(st) century natural product research is perfectly positioned to fill the antibiotic discovery gap and bring new drug candidates to the clinic. Innovations in genomics and techniques to explore new sources of antimicrobial chemical matter are revealing new chemistry. Increasing appreciation of the value of narrow-spectrum drugs and re-examination of once discarded chemical scaffolds coupled with synthetic biology methods to generate new compounds and improve yields offer new strategies to revitalize once moribund natural product programs. The increasing awareness that the combination of antibiotics with adjuvants, non-antibiotic compounds that overcome resistance and enhance drug activity, can rescue older chemical scaffolds, and concepts such as blocking pathogen virulence present orthogonal strategies to traditional antibiotics. In all these areas, natural products offer chemical matter, shaped by natural selection, that is privileged in this therapeutic area. Natural product research is poised to regain prominence in delivering new drugs to solve the antibiotic crisis.

  2. Biosynthesis of natural products containing β-amino acids.

    PubMed

    Kudo, Fumitaka; Miyanaga, Akimasa; Eguchi, Tadashi

    2014-08-01

    Covering: up to January, 2014. We focus here on β-amino acids as components of complex natural products because the presence of β-amino acids produces structural diversity in natural products and provides characteristic architectures beyond those of ordinary α-L-amino acids, thus generating significant and unique biological functions in nature. In this review, we first survey the known bioactive β-amino acid-containing natural products including nonribosomal peptides, macrolactam polyketides, and nucleoside-β-amino acid hybrids. Next, the biosynthetic enzymes that form β-amino acids from α-amino acids and the de novo synthesis of β-amino acids are summarized. Then, the mechanisms of β-amino acid incorporation into natural products are reviewed. Because it is anticipated that the rational swapping of the β-amino acid moieties with various side chains and stereochemistries by biosynthetic engineering should lead to the creation of novel architectures and bioactive compounds, the accumulation of knowledge regarding β-amino acid-containing natural product biosynthetic machinery could have a significant impact in this field. In addition, genome mining of characteristic β-amino acid biosynthetic genes and unique β-amino acid incorporation machinery could lead to the discovery of new β-amino acid-containing natural products.

  3. Raman spectra of carotenoids in natural products

    NASA Astrophysics Data System (ADS)

    Withnall, Robert; Chowdhry, Babur Z.; Silver, Jack; Edwards, Howell G. M.; de Oliveira, Luiz F. C.

    2003-08-01

    Resonance Raman spectra of naturally occurring carotenoids have been obtained from nautilus, periwinkle ( Littorina littorea) and clam shells under 514.5 nm excitation and these spectra are compared with the resonance Raman spectra obtained in situ from tomatoes, carrots, red peppers and saffron. The tomatoes, carrots and red peppers gave rise to resonance Raman spectra exhibiting a ν1 band at ca. 1520 cm -1, in keeping with its assignment to carotenoids with ca. nine conjugated carboncarbon double bonds in their main chains, whereas the resonance Raman spectrum of saffron showed a ν1 band at 1537 cm -1 which can be assigned to crocetin, having seven conjugated carboncarbon double bonds. A correlation between ν1 wavenumber location and effective conjugated chain length has been used to interpret the data obtained from the shells, and the wavenumber position (1522 cm -1) of the ν1 band of the carotenoid in the orange clam shell suggests that it contains nine conjugated double bonds in the main chain. However, the black periwinkle and nautilus shells exhibit ν1 bands at 1504 and 1496 cm -1, respectively. On the basis of the correlation between ν1 wavenumber location and effective conjugated chain length, this indicates that they contain carotenoids with longer conjugated chains, the former having ca. 11 double bonds and the latter ca. 13 or even more. Raman spectra of the nautilus, periwinkle and clam shells also exhibited a strong band at 1085 cm -1 and a doublet with components at 701 and 705 cm -1, which can be assigned to biogenic calcium carbonate in the aragonite crystallographic form.

  4. Effects of Food Natural Products on the Biotransformation of PCBs

    PubMed Central

    James, Margaret O.; Sacco, James C.; Faux, Laura R

    2008-01-01

    Many food products, particularly fruits and vegetables, contain natural products that affect biotransformation enzymes. These may be expected to affect the rate of biotransformation of PCBs that are metabolized by the affected enzymes. The first step in PCB metabolism is cytochrome P450-dependent monooxygenation. Natural products present in cruciferous vegetables have been shown to selectively up-regulate CYP1A1 and CYP1A2 isozymes on chronic ingestion, and may lead to increased metabolism of those PCB congeners that are substrates for the induced P450s. On the other hand, several natural products selectively inhibit monooxygenation, especially in the intestine, and may lead to increased bioavailability and reduced metabolism of dietary PCBs. Food natural products are known to affect phase II pathways important in the detoxication of hydroxylated PCBs, namely UDP-glucuronosyltransferase and PAPS-sulfotransferase. Continual dietary exposure to chrysin and quercetin, found in fruits and vegetables, induces UGT1A1 and may reduce exposure to hydroxylated PCBs through increased glucuronidation. These and other natural products are also inhibitors of glucuronidation and sulfonation, potentially leading to transient decreases in the elimination of hydroxylated PCBs. In summary, the expected effects of food natural products on PCB biotransformation are complex and may be biphasic, with initial inhibition followed by enhanced biotransformation through monooxygenation and conjugation pathways. PMID:19255595

  5. Effects of Food Natural Products on the Biotransformation of PCBs.

    PubMed

    James, Margaret O; Sacco, James C; Faux, Laura R

    2008-03-01

    Many food products, particularly fruits and vegetables, contain natural products that affect biotransformation enzymes. These may be expected to affect the rate of biotransformation of PCBs that are metabolized by the affected enzymes. The first step in PCB metabolism is cytochrome P450-dependent monooxygenation. Natural products present in cruciferous vegetables have been shown to selectively up-regulate CYP1A1 and CYP1A2 isozymes on chronic ingestion, and may lead to increased metabolism of those PCB congeners that are substrates for the induced P450s. On the other hand, several natural products selectively inhibit monooxygenation, especially in the intestine, and may lead to increased bioavailability and reduced metabolism of dietary PCBs. Food natural products are known to affect phase II pathways important in the detoxication of hydroxylated PCBs, namely UDP-glucuronosyltransferase and PAPS-sulfotransferase. Continual dietary exposure to chrysin and quercetin, found in fruits and vegetables, induces UGT1A1 and may reduce exposure to hydroxylated PCBs through increased glucuronidation. These and other natural products are also inhibitors of glucuronidation and sulfonation, potentially leading to transient decreases in the elimination of hydroxylated PCBs. In summary, the expected effects of food natural products on PCB biotransformation are complex and may be biphasic, with initial inhibition followed by enhanced biotransformation through monooxygenation and conjugation pathways.

  6. Natural product proteomining, a quantitative proteomics platform, allows rapid discovery of biosynthetic gene clusters for different classes of natural products.

    PubMed

    Gubbens, Jacob; Zhu, Hua; Girard, Geneviève; Song, Lijiang; Florea, Bogdan I; Aston, Philip; Ichinose, Koji; Filippov, Dmitri V; Choi, Young H; Overkleeft, Herman S; Challis, Gregory L; van Wezel, Gilles P

    2014-06-19

    Information on gene clusters for natural product biosynthesis is accumulating rapidly because of the current boom of available genome sequencing data. However, linking a natural product to a specific gene cluster remains challenging. Here, we present a widely applicable strategy for the identification of gene clusters for specific natural products, which we name natural product proteomining. The method is based on using fluctuating growth conditions that ensure differential biosynthesis of the bioactivity of interest. Subsequent combination of metabolomics and quantitative proteomics establishes correlations between abundance of natural products and concomitant changes in the protein pool, which allows identification of the relevant biosynthetic gene cluster. We used this approach to elucidate gene clusters for different natural products in Bacillus and Streptomyces, including a novel juglomycin-type antibiotic. Natural product proteomining does not require prior knowledge of the gene cluster or secondary metabolite and therefore represents a general strategy for identification of all types of gene clusters. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Natural and within-farmland biodiversity enhances crop productivity.

    PubMed

    Carvalheiro, Luísa Gigante; Veldtman, Ruan; Shenkute, Awraris Getachew; Tesfay, Gebreamlak Bezabih; Pirk, Christian Walter Werner; Donaldson, John Sydney; Nicolson, Susan Wendy

    2011-03-01

    Ongoing expansion of large-scale agriculture critically threatens natural habitats and the pollination services they offer. Creating patches with high plant diversity within farmland is commonly suggested as a measure to benefit pollinators. However, farmers rarely adopt such practice, instead removing naturally occurring plants (weeds). By combining pollinator exclusion experiments with analysis of honeybee behaviour and flower-visitation webs, we found that the presence of weeds allowed pollinators to persist within sunflower fields, maximizing the benefits of the remaining patches of natural habitat to productivity of this large-scale crop. Weed diversity increased flower visitor diversity, hence ameliorating the measured negative effects of isolation from natural habitat. Although honeybees were the most abundant visitors, diversity of flower visitors enhanced honeybee movement, being the main factor influencing productivity. Conservation of natural patches combined with promoting flowering plants within crops can maximize productivity and, therefore, reduce the need for cropland expansion, contributing towards sustainable agriculture.

  8. Investigation of the Antioxidant and Hepatoprotective Potential of Hypericum mysorense

    PubMed Central

    Hariharapura, Raghu C.; Srinivasan, Ramamurthy; Ashok, Godavarthi; Dongre, Santoshkumar H.; Jagani, Hitesh V.; Vijayan, Pottekkad

    2014-01-01

    Background: Hypericum is a well-known plant genus in herbal medicine. Hypericum mysorense (Family: Hypericaceae), a plant belonging to the same genus, is well known in folklore medicine for its varied therapeutic potential. Objective: The aim of the present study was to investigate the different parts of the plant for antioxidant and hepatoprotective properties. Materials and Methods: The methanol extracts of Hypericum mysorense prepared from various parts of the plant were tested in vitro for their free radical scavenging activity against ABTS• (diammonium salt), DPPH• (1,1-diphenyl-2-picrylhydrazyl), NO•, O2•− and •OH radicals, using standard systems of assays. The total antioxidant capacity, total phenolic and total flavonoid content of the extracts were analyzed. Further, the leaf and flowering top extracts were tested for their in vivo antioxidant and hepatoprotective activities on Wistar rats using a carbon tetrachloride-induced hepatic injury model. Results: The leaf and flowering top extract showed potent antioxidant activity and also possessed highest total phenolic and flavonoid content. The antioxidant activity and the total phenolic and flavonoid content present in these extracts showed a good correlation. The leaf and flowering top extracts at 200 mg/kg restored aspartate amino transferase (ASAT), alanine amino transferase (ALAT), alkaline phosphatase (ALP), total bilirubin and protein levels significantly in CCl4-intoxicated rats. The tested extracts also showed a significant (p < 0.001) reduction in 2-thiobarbituric acid reactive substance (TBARS) levels with an increase in SOD and CAT levels. The histopathology of liver did not show any toxicity after the treatment with the extracts. The active extracts were standardized using two marker compounds, hyperoside and rutin, which were isolated from the plant by HPLC. HPLC studies revealed that the maximum concentration of hyperoside and rutin is present in the flowering top extract. PMID

  9. Investigation of the Antioxidant and Hepatoprotective Potential of Hypericum mysorense.

    PubMed

    Hariharapura, Raghu C; Srinivasan, Ramamurthy; Ashok, Godavarthi; Dongre, Santoshkumar H; Jagani, Hitesh V; Vijayan, Pottekkad

    2014-08-12

    Hypericum is a well-known plant genus in herbal medicine. Hypericum mysorense (Family: Hypericaceae), a plant belonging to the same genus, is well known in folklore medicine for its varied therapeutic potential. The aim of the present study was to investigate the different parts of the plant for antioxidant and hepatoprotective properties. The methanol extracts of Hypericum mysorense prepared from various parts of the plant were tested in vitro for their free radical scavenging activity against ABTS(•) (diammonium salt), DPPH(•) (1,1-diphenyl-2-picrylhydrazyl), NO(•), O₂(•-) and (•)OH radicals, using standard systems of assays. The total antioxidant capacity, total phenolic and total flavonoid content of the extracts were analyzed. Further, the leaf and flowering top extracts were tested for their in vivo antioxidant and hepatoprotective activities on Wistar rats using a carbon tetrachloride-induced hepatic injury model. The leaf and flowering top extract showed potent antioxidant activity and also possessed highest total phenolic and flavonoid content. The antioxidant activity and the total phenolic and flavonoid content present in these extracts showed a good correlation. The leaf and flowering top extracts at 200 mg/kg restored aspartate amino transferase (ASAT), alanine amino transferase (ALAT), alkaline phosphatase (ALP), total bilirubin and protein levels significantly in CCl₄-intoxicated rats. The tested extracts also showed a significant (p < 0.001) reduction in 2-thiobarbituric acid reactive substance (TBARS) levels with an increase in SOD and CAT levels. The histopathology of liver did not show any toxicity after the treatment with the extracts. The active extracts were standardized using two marker compounds, hyperoside and rutin, which were isolated from the plant by HPLC. HPLC studies revealed that the maximum concentration of hyperoside and rutin is present in the flowering top extract.

  10. Use of Brown Algae to Demonstrate Natural Products Techniques.

    ERIC Educational Resources Information Center

    Porter, Lee A.

    1985-01-01

    Background information is provided on the natural products found in marine organisms in general and the brown algae in particular. Also provided are the procedures needed to isolate D-mannitol (a primary metabolite) and cholesterol from brown algae. (JN)

  11. Revealing the macromolecular targets of complex natural products.

    PubMed

    Reker, Daniel; Perna, Anna M; Rodrigues, Tiago; Schneider, Petra; Reutlinger, Michael; Mönch, Bettina; Koeberle, Andreas; Lamers, Christina; Gabler, Matthias; Steinmetz, Heinrich; Müller, Rolf; Schubert-Zsilavecz, Manfred; Werz, Oliver; Schneider, Gisbert

    2014-12-01

    Natural products have long been a source of useful biological activity for the development of new drugs. Their macromolecular targets are, however, largely unknown, which hampers rational drug design and optimization. Here we present the development and experimental validation of a computational method for the discovery of such targets. The technique does not require three-dimensional target models and may be applied to structurally complex natural products. The algorithm dissects the natural products into fragments and infers potential pharmacological targets by comparing the fragments to synthetic reference drugs with known targets. We demonstrate that this approach results in confident predictions. In a prospective validation, we show that fragments of the potent antitumour agent archazolid A, a macrolide from the myxobacterium Archangium gephyra, contain relevant information regarding its polypharmacology. Biochemical and biophysical evaluation confirmed the predictions. The results obtained corroborate the practical applicability of the computational approach to natural product 'de-orphaning'.

  12. Public databases of plant natural products for computational drug discovery.

    PubMed

    Tung, Chun-Wei

    2014-01-01

    Plant natural products have been intensively investigated during the past decades with a considerable amount of generated data. Databases are subsequently developed to facilitate the management and analysis of accumulated information including plant species, chemical compounds, structures and bioactivities. With the support of databases, the screening of novel bioactivities for plant natural products can benefit from advanced computational methods to accelerate the progress of drug discovery. This overview describes the contents of publicly available databases useful for computational research of plant natural products. Based on the databases, quantitative structure-activity relationship models and protein-ligand docking methods can be developed and applied to analyze and screen bioactive compounds. More public and structured databases with unique contents, search functions and links to major databases are needed for efficiently exploring the chemical space of plant natural products.

  13. Use of Brown Algae to Demonstrate Natural Products Techniques.

    ERIC Educational Resources Information Center

    Porter, Lee A.

    1985-01-01

    Background information is provided on the natural products found in marine organisms in general and the brown algae in particular. Also provided are the procedures needed to isolate D-mannitol (a primary metabolite) and cholesterol from brown algae. (JN)

  14. Protein Engineering Towards Natural Product Synthesis and Diversification

    PubMed Central

    Zabala, Angelica O.; Cacho, Ralph A.; Tang, Yi

    2014-01-01

    A dazzling array of enzymes is used by nature in making structurally complex natural products. These enzymes constitute a molecular toolbox that may be used in the construction and fine-tuning of pharmaceutically active molecules. Aided by technological advancements in protein engineering, it is now possible to tailor the activities and specificities of these enzymes as biocatalysts in the production of both natural products and their unnatural derivatives. These efforts are crucial in drug discovery and development, where there is a continuous quest for more potent agents. Both rational and random evolution techniques have been utilized in engineering these enzymes. This review will highlight some examples from several large families of natural products. PMID:22006344

  15. Revealing the macromolecular targets of complex natural products

    NASA Astrophysics Data System (ADS)

    Reker, Daniel; Perna, Anna M.; Rodrigues, Tiago; Schneider, Petra; Reutlinger, Michael; Mönch, Bettina; Koeberle, Andreas; Lamers, Christina; Gabler, Matthias; Steinmetz, Heinrich; Müller, Rolf; Schubert-Zsilavecz, Manfred; Werz, Oliver; Schneider, Gisbert

    2014-12-01

    Natural products have long been a source of useful biological activity for the development of new drugs. Their macromolecular targets are, however, largely unknown, which hampers rational drug design and optimization. Here we present the development and experimental validation of a computational method for the discovery of such targets. The technique does not require three-dimensional target models and may be applied to structurally complex natural products. The algorithm dissects the natural products into fragments and infers potential pharmacological targets by comparing the fragments to synthetic reference drugs with known targets. We demonstrate that this approach results in confident predictions. In a prospective validation, we show that fragments of the potent antitumour agent archazolid A, a macrolide from the myxobacterium Archangium gephyra, contain relevant information regarding its polypharmacology. Biochemical and biophysical evaluation confirmed the predictions. The results obtained corroborate the practical applicability of the computational approach to natural product ‘de-orphaning’.

  16. Protein engineering towards natural product synthesis and diversification.

    PubMed

    Zabala, Angelica O; Cacho, Ralph A; Tang, Yi

    2012-02-01

    A dazzling array of enzymes is used by nature in making structurally complex natural products. These enzymes constitute a molecular toolbox that may be used in the construction and fine-tuning of pharmaceutically active molecules. Aided by technological advancements in protein engineering, it is now possible to tailor the activities and specificities of these enzymes as biocatalysts in the production of both natural products and their unnatural derivatives. These efforts are crucial in drug discovery and development, where there is a continuous quest for more potent agents. Both rational and random evolution techniques have been utilized in engineering these enzymes. This review will highlight some examples from several large families of natural products.

  17. Mining the Metabiome: Identifying Novel Natural Products from Microbial Communities

    PubMed Central

    Milshteyn, Aleksandr; Schneider, Jessica S.; Brady, Sean F.

    2014-01-01

    Summary Microbial-derived natural products provide the foundation for most of the chemotherapeutic arsenal available to contemporary medicine. In the face of a dwindling pipeline of new lead structures identified by traditional culturing techniques and an increasing need for new therapeutics, surveys of microbial biosynthetic diversity across environmental metabiomes have revealed enormous reservoirs of as yet untapped natural products chemistry. In this review we touch on the historical context of microbial natural product discovery and discuss innovations and technological advances that are facilitating culture-dependent and culture-independent access to new chemistry from environmental microbiomes with the goal of re-invigorating the small molecule therapeutics discovery pipeline. We highlight the successful strategies that have emerged and some of the challenges that must be overcome to enable the development of high-throughput methods for natural product discovery from complex microbial communities. PMID:25237864

  18. Cytotoxic activity of antioxidant constituents from Hypericum triquetrifolium Turra.

    PubMed

    Conforti, F; Loizzo, M R; Statti, A G; Menichini, F

    2007-01-01

    The Sulforodamine B (SRB) assay was used to test cytotoxicity against four human cancer cell lines and one normal cell line of antioxidant constituents isolated from Hypericum triquetrifolium Turra. Methanolic extract and pure compounds were tested against the large cell lung carcinoma cell line COR-L23, the hepatocellular carcinoma cell line HepG-2, renal cell adenocarcinoma ACHN, the amelanotic melanoma cell line C32 and normal human foetal lung MRC5. The results showed that I3-II8-biapigenin exhibited strong cytotoxic activity (IC50 = 5.73 micro g mL(-1)) showing a certain degree of selectivity against the different cell types.

  19. Bioactive acylphloroglucinols with adamantyl skeleton from Hypericum sampsonii.

    PubMed

    Zhu, Hucheng; Chen, Chunmei; Yang, Jing; Li, Xiao-Nian; Liu, Junjun; Sun, Bin; Huang, Sheng-Xiong; Li, Dongyan; Yao, Guangmin; Luo, Zengwei; Li, Yan; Zhang, Jinwen; Xue, Yongbo; Zhang, Yonghui

    2014-12-19

    Hyperisampsins A-D (1-4), with tetracyclo[6.3.1.1(3,10).0(3,7)]tridecane skeletons and seven biogenetically related congeners (5-11), were isolated from Hypericum sampsonii. Their structures were elucidated by comprehensive spectroscopic techniques. The absolute configuration of 1 was established by ECD calculations, and those of 5 and 9 were confirmed by single X-ray crystallographic analyses. Hyperisampsins A and D showed potent anti-HIV activities with EC50 of 2.97 and 0.97 μM and selectivity index of 4.80 and 7.70, respectively.

  20. Isocoumarins, miraculous natural products blessed with diverse pharmacological activities.

    PubMed

    Saeed, Aamer

    2016-06-30

    Isocoumarins are lactonic natural products abundant in microbes and higher plants. These are considered an amazing scaffold consecrated with more or less all types of pharmacological applications. This review is complementary to the earlier reviews and aims to focus the overlooked aspects of their fascinating chemistry with special emphasis on their classification and diverse biological activities with some SAR conclusions. The most recent available literature on the structural diversity and biological activity of these natural products has been reviewed.

  1. Marine natural products sourced from marine-derived Penicillium fungi.

    PubMed

    Ma, Hong-Guang; Liu, Qiang; Zhu, Guo-Liang; Liu, Hai-Shan; Zhu, Wei-Ming

    2016-01-01

    Marine micro-organisms have been proven to be a major source of marine natural products (MNPs) in recent years, in which filamentous fungi are a vital source of bioactive natural products for their large metagenomes and more complex genetic backgrounds. This review highlights the 390 new MNPs from marine-derived Penicillium fungi during 1991 to 2014. These new MNPs are categorized based on the environment sources of the fungal hosts and their bioactivities are summarized.

  2. Application of MALDI Mass Spectrometry in Natural Products Analysis.

    PubMed

    Silva, Ricardo; Lopes, Norberto Peporine; Silva, Denise Brentan

    2016-05-01

    This article presents the utility of mass spectrometry with a MALDI ionization source in natural products analysis. The advantages and drawbacks of this technique for natural products analyses will be presented and discussed. In addition, the structural determination of secondary metabolites using MALDI-MS/MS will be explored, which can guide MALDI experimental methods and stimulate new research in this area. Finally, several important approaches for MALDI data processing will be discussed.

  3. Syntheses of Cyclic Guanidine-Containing Natural Products.

    PubMed

    Ma, Yuyong; De, Saptarshi; Chen, Chuo

    2015-02-25

    Naturally occurring guanidine derivatives frequently display medicinally useful properties. Among them, the higher order pyrrole-imidazole alkaloids, the dragmacidins, the crambescidins/batzelladines, and the saxitoxins/tetradotoxins have stimulated the development of many new synthetic methods over the past decades. We provide here an overview of the syntheses of these cyclic guanidine-containing natural products.

  4. A comprehensive review of glycosylated bacterial natural products

    PubMed Central

    Elshahawi, Sherif I.; Shaaban, Khaled A.; Kharel, Madan K.

    2015-01-01

    A systematic analysis of all naturally-occurring glycosylated bacterial secondary metabolites reported in the scientific literature up through early 2013 is presented. This comprehensive analysis of 15 940 bacterial natural products revealed 3426 glycosides containing 344 distinct appended carbohydrates and highlights a range of unique opportunities for future biosynthetic study and glycodiversification efforts. PMID:25735878

  5. Syntheses of Cyclic Guanidine-Containing Natural Products

    PubMed Central

    Ma, Yuyong; De, Saptarshi; Chen, Chuo

    2014-01-01

    Naturally occurring guanidine derivatives frequently display medicinally useful properties. Among them, the higher order pyrrole-imidazole alkaloids, the dragmacidins, the crambescidins/batzelladines, and the saxitoxins/tetradotoxins have stimulated the development of many new synthetic methods over the past decades. We provide here an overview of the syntheses of these cyclic guanidine-containing natural products. PMID:25684829

  6. Biotechnological production of natural zero-calorie sweeteners.

    PubMed

    Philippe, Ryan N; De Mey, Marjan; Anderson, Jeff; Ajikumar, Parayil Kumaran

    2014-04-01

    The increasing public awareness of adverse health impacts from excessive sugar consumption has created increasing interest in plant-derived, natural low-calorie or zero-calorie sweeteners. Two plant species which contain natural sweeteners, Stevia rebaudiana and Siraitia grosvenorii, have been extensively profiled to identify molecules with high intensity sweetening properties. However, sweetening ability does not necessarily make a product viable for commercial applications. Some criteria for product success are proposed to identify which targets are likely to be accepted by consumers. Limitations of plant-based production are discussed, and a case is put forward for the necessity of biotechnological production methods such as plant cell culture or microbial fermentation to meet needs for commercial-scale production of natural sweeteners.

  7. Natural Product Biosynthesis in Escherichia coli: Mentha Monoterpenoids.

    PubMed

    Toogood, H S; Tait, S; Jervis, A; Ní Cheallaigh, A; Humphreys, L; Takano, E; Gardiner, J M; Scrutton, N S

    2016-01-01

    The era of synthetic biology heralds in a new, more "green" approach to fine chemical and pharmaceutical drug production. It takes the knowledge of natural metabolic pathways and builds new routes to chemicals, enables nonnatural chemical production, and/or allows the rapid production of chemicals in alternative, highly performing organisms. This route is particularly useful in the production of monoterpenoids in microorganisms, which are naturally sourced from plant essential oils. Successful pathways are constructed by taking into consideration factors such as gene selection, regulatory elements, host selection and optimization, and metabolic considerations of the host organism. Seamless pathway construction techniques enable a "plug-and-play" switching of genes and regulatory parts to optimize the metabolic functioning in vivo. Ultimately, synthetic biology approaches to microbial monoterpenoid production may revolutionize "natural" compound formation. © 2016 Elsevier Inc. All rights reserved.

  8. Selective molecular sequestration with concurrent natural product functionalization and derivatization: from crude natural product extracts to a single natural product derivative in one step.

    PubMed

    Krchňák, Viktor; Zajíček, Jaroslav; Miller, Patricia A; Miller, Marvin J

    2011-12-16

    A resin-bound nitroso compound sequestered a single unexpected component from crude plant seed extracts. Several plants, including Piper nigrum, Eugenia caryophyllata, and Pimenta dioica, were extracted with organic solvent in the presence of a nitroso-containing resin. The nitroso resin selectively sequestered a single compound, β-caryophyllene, via a chemo- and regioselective ene reaction. The ene product was released from the resin, and proper selection of the solid-phase linker and cleavage cocktail allowed concomitant further transformation of the primary ene product to a novel functionalized polycycle. Preliminary studies indicate that the new hydroxylamine-containing natural product derivatives have antibiotic activity.

  9. Natural fiber production, harvesting, and preliminary processing: options and opportunities

    USDA-ARS?s Scientific Manuscript database

    The utilization of natural fibers and plant oils in bio-products introduces numerous logistical challenges not typically encountered with non-agricultural resources. Once it has been determined that a plant material is suitable for commercial development, the production, harvesting, and processing s...

  10. Plant-Derived Natural Products for Parkinson's Disease Therapy.

    PubMed

    Sengupta, T; Vinayagam, J; Singh, R; Jaisankar, P; Mohanakumar, K P

    2016-01-01

    Plant-derived natural products have made their own niche in the treatment of neurological diseases since time immemorial. Parkinson's disease (PD), the second most prevalent neurodegenerative disorder, has no cure and the treatment available currently is symptomatic. This chapter thoughtfully and objectively assesses the scientific basis that supports the increasing use of these plant-derived natural products for the treatment of this chronic and progressive disorder. Proper considerations are made on the chemical nature, sources, preclinical tests and their validity, and mechanisms of behavioural or biochemical recovery observed following treatment with various plants derived natural products relevant to PD therapy. The scientific basis underlying the neuroprotective effect of 6 Ayurvedic herbs/formulations, 12 Chinese medicinal herbs/formulations, 33 other plants, and 5 plant-derived molecules have been judiciously examined emphasizing behavioral, cellular, or biochemical aspects of neuroprotection observed in the cellular or animal models of the disease. The molecular mechanisms triggered by these natural products to promote cell survivability and to reduce the risk of cellular degeneration have also been brought to light in this study. The study helped to reveal certain limitations in the scenario: lack of preclinical studies in all cases barring two; heavy dependence on in vitro test systems; singular animal or cellular model to establish any therapeutic potential of drugs. This strongly warrants further studies so as to reproduce and confirm these reported effects. However, the current literature offers scientific credence to traditionally used plant-derived natural products for the treatment of PD.

  11. Natural product-based nanomedicine: recent advances and issues.

    PubMed

    Watkins, Rebekah; Wu, Ling; Zhang, Chenming; Davis, Richey M; Xu, Bin

    2015-01-01

    Natural products have been used in medicine for many years. Many top-selling pharmaceuticals are natural compounds or their derivatives. These plant- or microorganism-derived compounds have shown potential as therapeutic agents against cancer, microbial infection, inflammation, and other disease conditions. However, their success in clinical trials has been less impressive, partly due to the compounds' low bioavailability. The incorporation of nanoparticles into a delivery system for natural products would be a major advance in the efforts to increase their therapeutic effects. Recently, advances have been made showing that nanoparticles can significantly increase the bioavailability of natural products both in vitro and in vivo. Nanotechnology has demonstrated its capability to manipulate particles in order to target specific areas of the body and control the release of drugs. Although there are many benefits to applying nanotechnology for better delivery of natural products, it is not without issues. Drug targeting remains a challenge and potential nanoparticle toxicity needs to be further investigated, especially if these systems are to be used to treat chronic human diseases. This review aims to summarize recent progress in several key areas relevant to natural products in nanoparticle delivery systems for biomedical applications.

  12. Natural product-based nanomedicine: recent advances and issues

    PubMed Central

    Watkins, Rebekah; Wu, Ling; Zhang, Chenming; Davis, Richey M; Xu, Bin

    2015-01-01

    Natural products have been used in medicine for many years. Many top-selling pharmaceuticals are natural compounds or their derivatives. These plant- or microorganism-derived compounds have shown potential as therapeutic agents against cancer, microbial infection, inflammation, and other disease conditions. However, their success in clinical trials has been less impressive, partly due to the compounds’ low bioavailability. The incorporation of nanoparticles into a delivery system for natural products would be a major advance in the efforts to increase their therapeutic effects. Recently, advances have been made showing that nanoparticles can significantly increase the bioavailability of natural products both in vitro and in vivo. Nanotechnology has demonstrated its capability to manipulate particles in order to target specific areas of the body and control the release of drugs. Although there are many benefits to applying nanotechnology for better delivery of natural products, it is not without issues. Drug targeting remains a challenge and potential nanoparticle toxicity needs to be further investigated, especially if these systems are to be used to treat chronic human diseases. This review aims to summarize recent progress in several key areas relevant to natural products in nanoparticle delivery systems for biomedical applications. PMID:26451111

  13. Screening strategies for discovery of antibacterial natural products.

    PubMed

    Singh, Sheo B; Young, Katherine; Miesel, Lynn

    2011-08-01

    Microbial-derived natural products have been a traditional source of antibiotics and antibiotic leads and continue to be effective sources of antibiotics today. The most important of these discoveries were made about 50 years ago. Chemical modifications of natural products discovered during those years continue to produce new clinical agents but their value is now, unfortunately, fading away owing to the exhaustion of opportunities of chemical modifications. The discovery of new natural antibiotics is directly linked to new screening technologies, particularly technologies that can help to eliminate the rediscovery of known antibiotics. In this article, we have reviewed the screening technologies from recent literature as well as originating from authors laboratories that were used for the screening of natural products. The article covers the entire spectrum of screening strategies, including classical empiric whole-cell assays to more sophisticated antisense based hypersensitive Staphylococcus aureus Fitness Test assays designed to screen all targets simultaneously. These technologies have led to the discovery of a series of natural product antibiotics, which have been summarized, including the discovery of platensimycin, platencin, nocathiacins, philipimycin, cyclothialidine and muryamycins. It is quite clear that natural products provide a tremendous opportunity to discover new antibiotics when combined with new hyper-sensitive whole-cell technologies.

  14. The chemical logic of plant natural product biosynthesis.

    PubMed

    Anarat-Cappillino, Gülbenk; Sattely, Elizabeth S

    2014-06-01

    Understanding the logic of plant natural product biosynthesis is important for three reasons: it guides the search for new natural products and pathways, illuminates the function of existing pathways in the context of host biology, and builds an enabling 'parts list' for plant and microbial metabolic engineering. In this review, we highlight the chemical themes that underlie a broad range of plant pathways, dividing pathways into two parts: scaffold-generating steps that draw on a limited set of chemistries, and tailoring reactions that produce a wide range of end products from a small number of common scaffolds.

  15. Metabolic engineering of natural product biosynthesis in actinobacteria.

    PubMed

    Bilyk, Oksana; Luzhetskyy, Andriy

    2016-12-01

    Actinomycetes are known to produce over two-thirds of all known secondary metabolites. We review here recent progress in the metabolic engineering of streptomycetes for natural product biosynthesis. Several examples of the yield improvement of polyketides (mithramycin and tylactone) and non-ribosomal peptides (balhimycin and daptomycin) demonstrate the power of precursor supply engineering. Another example is the manipulation of a regulatory network for increased production of nystatin and teicoplanin. The second part highlights new approaches in the derivatization of natural products via combination of mutasynthesis and genomic engineering.

  16. Natural Products Improving Hyperuricemia with Hepatorenal Dual Effects

    PubMed Central

    Hao, Shijun; Zhang, Chunlei

    2016-01-01

    This review aims to put forth an overview of natural products reducing uric acid level with hepatorenal dual effects. The prevalence of hyperuricemia increased rapidly in recent years and has closely interdependent relationship with other metabolic disorders. Current therapeutically used drugs including a few uricostatic and uricosuric chemical drugs are proved efficient to control serum uric acid level. However, their side effects as well as contraindication in some cases with liver, kidney injury, or other conditions frequently limit their clinic application. More attention thus has been paid to natural products as an alternative means in treating hyperuricemia. Many natural products have been proved efficient in downregulating uric acid level, among which some can improve hyperuricemia with hepatorenal dual effects. It means these natural products can regulate both the production and the excretion of uric acid by targeting the key metabolic enzymes mainly in liver or uric acid transporters in kidneys. Thus, these natural products could have stronger efficacy and broader application, which may be developed for the treatment of hyperuricemia in clinic. PMID:27847526

  17. Bioengineering natural product biosynthetic pathways for therapeutic applications.

    PubMed

    Wu, Ming-Cheng; Law, Brian; Wilkinson, Barrie; Micklefield, Jason

    2012-12-01

    With the advent of next-generation DNA sequencing technologies, the number of microbial genome sequences has increased dramatically, revealing a vast array of new biosynthetic gene clusters. Genomics data provide a tremendous opportunity to discover new natural products, and also to guide the bioengineering of new and existing natural product scaffolds for therapeutic applications. Notably, it is apparent that the vast majority of biosynthetic gene clusters are either silent or produce very low quantities of the corresponding natural products. It is imperative therefore to devise methods for activating unproductive biosynthetic pathways to provide the quantities of natural products needed for further development. Moreover, on the basis of our expanding mechanistic and structural knowledge of biosynthetic assembly-line enzymes, new strategies for re-programming biosynthetic pathways have emerged, resulting in focused libraries of modified products with potentially improved biological properties. In this review we will focus on the latest bioengineering approaches that have been utilised to optimise yields and increase the structural diversity of natural product scaffolds for future clinical applications.

  18. Effect of Hypericum perforatum on intraperitoneal adhesion formation in rats

    PubMed Central

    Hızlı, Fatih; Köşüş, Aydın; Yılmaz, Saynur; Köşüş, Nermin; Haltaş, Hacer; Dede, Hülya; Kafalı, Hasan

    2013-01-01

    Introduction The aim of this study was to evaluate the efficacy of Hypericum perforatum for prevention of adhesion formation in rats. Material and methods Twenty-four female wistar rats underwent left uterine horn adhesion model. Rats were randomised into 4 groups. Group 1 (Control): Closure of abdominal incision without any agent administration. Group 2: Closure of incision after administration of intraperitoneal (i.p.) Ringer's lactate solution. Group 3: Closure of incision after administration of i.p. olive oil (diluent of H. perforatum). Group 4: Hypericum perforatum extract (Ecodab®) was administered i.p. before the closure of incision. Fourteen days later, relaparatomy was performed and surgical adhesion scores, inflammation and fibrosis scores were noted. Groups were compared according to these scores. Results There was statistical significant difference between ringer's lactate group and olive oil group according to surgical adhesion score (p = 0.009). However, groups were not different according to inflammation and fibrosis scores (p > 0.05). Conclusions Despite antiinflammatory, antioxidants and antimicrobial properties of H. perforatum, our results revealed no positive effect of H. perforatum on the prevention of intraperitoneal adhesion formation. PMID:24904678

  19. PAL inhibitor evokes different responses in two Hypericum species.

    PubMed

    Klejdus, Bořivoj; Kováčik, Jozef; Babula, Petr

    2013-02-01

    Accumulation of secondary metabolites (general phenols, naphthodianthrones and phloroglucinol hyperforin) in Hypericum perforatum and Hypericum canariense after application of the inhibitor (2-aminoindane-2-phosphonic acid, AIP) of the pivotal enzyme of general phenylpropanoid pathway (phenylalanine ammonia-lyase, PAL) was studied. Shoots of H. perforatum revealed more expressive growth depression, concomitantly with the inhibition of PAL activity (-60%) and decrease in soluble phenols and individual phenolic acids in response to AIP. Hypericins (hypericin, pseudohypericin and protohypericin) decreased while hyperforin increased in AIP-cultured H. perforatum. On the contrary, growth changes, decreases in soluble phenols and individual phenolic acids were less-visible in H. canariense. This was also reflected in restoration of PAL activity (+330%) and selected flavonoids even increased. Hypericins and hyperforin were present in several orders of magnitude lower amounts in comparison with H. perforatum. Increase in proline indicates potential compensatory antioxidative mechanism if phenols are depleted. Microscopy revealed also differences in secondary xylem formation and lignification between species after exposure to AIP.

  20. Does species diversity limit productivity in natural grassland communities?

    USGS Publications Warehouse

    Grace, J.B.; Anderson, T.M.; Smith, M.D.; Seabloom, E.; Andelman, S.J.; Meche, G.; Weiher, E.; Allain, L.K.; Jutila, H.; Sankaran, M.; Knops, J.; Ritchie, M.; Willig, M.R.

    2007-01-01

    Theoretical analyses and experimental studies of synthesized assemblages indicate that under particular circumstances species diversity can enhance community productivity through niche complementarity. It remains unclear whether this process has important effects in mature natural ecosystems where competitive feedbacks and complex environmental influences affect diversity-productivity relationships. In this study, we evaluated diversity-productivity relationships while statistically controlling for environmental influences in 12 natural grassland ecosystems. Because diversity-productivity relationships are conspicuously nonlinear, we developed a nonlinear structural equation modeling (SEM) methodology to separate the effects of diversity on productivity from the effects of productivity on diversity. Meta-analysis was used to summarize the SEM findings across studies. While competitive effects were readily detected, enhancement of production by diversity was not. These results suggest that the influence of small-scale diversity on productivity in mature natural systems is a weak force, both in absolute terms and relative to the effects of other controls on productivity. ?? 2007 Blackwell Publishing Ltd/CNRS.

  1. Metabolome classification of commercial Hypericum perforatum (St. John's Wort) preparations via UPLC-qTOF-MS and chemometrics.

    PubMed

    Farag, Mohamed A; Wessjohann, Ludger A

    2012-03-01

    The growing interest in the efficacy of phytomedicines and herbal supplements but also the increase in legal requirements for safety and reliable contents of active principles drive the development of analytical methods for the quality control of complex, multicomponent mixtures as found in plant extracts of value for the pharmaceutical industry. Here, we describe an ultra-performance liquid chromatography method (UPLC) coupled with quadrupole time of flight mass spectrometry (qTOF-MS) measurements for the large scale analysis of H. perforatum plant material and its commercial preparations. Under optimized conditions, we were able to simultaneously quantify and identify 21 metabolites including 4 hyperforins, 3 catechins, 3 naphthodianthrones, 5 flavonoids, 3 fatty acids, and a phenolic acid. Principal component analysis (PCA) was used to ensure good analytical rigorousness and define both similarities and differences among Hypericum samples. A selection of batches from 9 commercially available H. perforatum products available on the German and Egyptian markets showed variable quality, particularly in hyperforins and fatty acid content. PCA analysis was able to discriminate between various preparations according to their global composition, including differentiation between various batches from the same supplier. To the best of our knowledge, this study provides the first approach utilizing UPLC-MS-based metabolic fingerprinting to reveal secondary metabolite compositional differences in Hypericum extract. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Effects of hypericum extract (LI 160) in biochemical models of antidepressant activity.

    PubMed

    Müller, W E; Rolli, M; Schäfer, C; Hafner, U

    1997-09-01

    Since the mechanism of the antidepressant activity of hypericum extract is not yet understood, we tested possible effects of standardized hypericum extract (LI 160) in several biochemical models relevant for the mechanism of action of other antidepressant drugs. While LI 160 was only a weak inhibitor of MAO-A and MAO-B activity, it inhibited the synaptosomal uptake of serotonin, dopamine and norepinephrine with about equal affinity-2 micrograms/ml). Moreover, subchronic treatment of rats with hypericum extract led to a significant down-regulation of beta-receptors and to a significant up-regulation of 5-HT2-receptors in the frontal cortex. The data might suggest that hypericum extract acts via similar biochemical mechanisms to other antidepressants (e.g. tricyclics).

  3. A Growing Disconnection From Nature Is Evident in Cultural Products.

    PubMed

    Kesebir, Selin; Kesebir, Pelin

    2017-03-01

    Human connection with nature is widely believed to be in decline even though empirical evidence is scarce on the magnitude and historical pattern of the change. Studying works of popular culture in English throughout the 20th century and later, we have documented a cultural shift away from nature that begins in the 1950s. Since then, references to nature have been decreasing steadily in fiction books, song lyrics, and film storylines, whereas references to the human-made environment have not. The observed temporal pattern is consistent with the explanatory role of increased virtual and indoors recreation options (e.g., television, video games) in the disconnect from nature, and it is inconsistent with a pure urbanization account. These findings are cause for concern, not only because they imply foregone physical and psychological benefits from engagement with nature, but also because cultural products are agents of socialization that can evoke curiosity, respect, and concern for the natural world.

  4. Computer-Aided Drug Design of Bioactive Natural Products.

    PubMed

    Prachayasittikul, Veda; Worachartcheewan, Apilak; Shoombuatong, Watshara; Songtawee, Napat; Simeon, Saw; Prachayasittikul, Virapong; Nantasenamat, Chanin

    2015-01-01

    Natural products have been an integral part of sustaining civilizations because of their medicinal properties. Past discoveries of bioactive natural products have relied on serendipity, and these compounds serve as inspiration for the generation of analogs with desired physicochemical properties. Bioactive natural products with therapeutic potential are abundantly available in nature and some of them are beyond exploration by conventional methods. The effectiveness of computational approaches as versatile tools for facilitating drug discovery and development has been recognized for decades, without exception, in the case of natural products. In the post-genomic era, scientists are bombarded with data produced by advanced technologies. Thus, rendering these data into knowledge that is interpretable and meaningful becomes an essential issue. In this regard, computational approaches utilize the existing data to generate knowledge that provides valuable understanding for addressing current problems and guiding the further research and development of new natural-derived drugs. Furthermore, several medicinal plants have been continuously used in many traditional medicine systems since antiquity throughout the world, and their mechanisms have not yet been elucidated. Therefore, the utilization of computational approaches and advanced synthetic techniques would yield great benefit to improving the world's health population and well-being.

  5. Culture-independent discovery of natural products from soil metagenomes.

    PubMed

    Katz, Micah; Hover, Bradley M; Brady, Sean F

    2016-03-01

    Bacterial natural products have proven to be invaluable starting points in the development of many currently used therapeutic agents. Unfortunately, traditional culture-based methods for natural product discovery have been deemphasized by pharmaceutical companies due in large part to high rediscovery rates. Culture-independent, or "metagenomic," methods, which rely on the heterologous expression of DNA extracted directly from environmental samples (eDNA), have the potential to provide access to metabolites encoded by a large fraction of the earth's microbial biosynthetic diversity. As soil is both ubiquitous and rich in bacterial diversity, it is an appealing starting point for culture-independent natural product discovery efforts. This review provides an overview of the history of soil metagenome-driven natural product discovery studies and elaborates on the recent development of new tools for sequence-based, high-throughput profiling of environmental samples used in discovering novel natural product biosynthetic gene clusters. We conclude with several examples of these new tools being employed to facilitate the recovery of novel secondary metabolite encoding gene clusters from soil metagenomes and the subsequent heterologous expression of these clusters to produce bioactive small molecules.

  6. Capillary electrophoresis of natural products: 2011-2012.

    PubMed

    Tubaon, Ria Marni S; Rabanes, Heide; Haddad, Paul R; Quirino, Joselito P

    2014-01-01

    Bioactive natural products are major sources of lead compounds for drug discovery and pharmaceutical development, therefore, innovative and current separation and characterization techniques are important for these compounds. Here, CE methods applied for the analysis of natural products published during 2011-2012 are reviewed. This is an updated version of an earlier review paper in this journal, which highlighted developments during 2006-2010. The major method developments over the review period centered on derivatization, chiral analysis, modes of detection, stacking or on-line sample concentration, and sample preparation (predominantly using extraction methods). The samples analyzed were herbal products, foods, soil, and biological samples. Developments also occurred in the areas of quality control, toxicology assessment, and enzyme-inhibitor screening. A table that summarizes the areas, source of natural product, nature of the bioactive analyte, CE conditions, LODs, and corresponding reference is provided. A short description on the theory of CE and insights on future activities of CE on natural products are also presented. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. The Traditional Medicine and Modern Medicine from Natural Products.

    PubMed

    Yuan, Haidan; Ma, Qianqian; Ye, Li; Piao, Guangchun

    2016-04-29

    Natural products and traditional medicines are of great importance. Such forms of medicine as traditional Chinese medicine, Ayurveda, Kampo, traditional Korean medicine, and Unani have been practiced in some areas of the world and have blossomed into orderly-regulated systems of medicine. This study aims to review the literature on the relationship among natural products, traditional medicines, and modern medicine, and to explore the possible concepts and methodologies from natural products and traditional medicines to further develop drug discovery. The unique characteristics of theory, application, current role or status, and modern research of eight kinds of traditional medicine systems are summarized in this study. Although only a tiny fraction of the existing plant species have been scientifically researched for bioactivities since 1805, when the first pharmacologically-active compound morphine was isolated from opium, natural products and traditional medicines have already made fruitful contributions for modern medicine. When used to develop new drugs, natural products and traditional medicines have their incomparable advantages, such as abundant clinical experiences, and their unique diversity of chemical structures and biological activities.

  8. Nepeta japonica Maximowicz extract from natural products inhibits lipid accumulation.

    PubMed

    Roh, Changhyun; Jung, Uhee

    2012-08-15

    To develop novel and crude anti-obesity drugs from natural products is a promising field to approach the solution to a global health problem such as obesity. The aim of this study was to screen crude anti-obesity drugs from 400 natural products on lipase inhibition activity in vitro. Among the natural products examined, 31 extracts showed significantly inhibition activity against porcine pancreatic lipase (triacylglycerol lipase, EC 3.1.1.3) by using spectrophotometry with 2,4-dinitrophenylbutyrate as a substrate. Furthermore, 31 natural products were investigated with regard to their lipid inhibition in 3T3-L1 cells. Among these, one of most promising was Nepeta japonica Maximowicz extract, which showed inhibition of triglyceride accumulation in 3T3-L1 adipocytes, suggesting anti-obesity activity. Also, the amount of glycerol released from cells into the medium was increased by treatment of Nepeta japonica Maximowicz extract at a concentration of 100 µg mL(-1) . The present study suggests that a promising crude anti-obesity drug screened from 400 natural products might be of therapeutic interest with respect to the treatment of obesity. Copyright © 2012 Society of Chemical Industry.

  9. Nucleophilic 1,4-additions for natural product discovery.

    PubMed

    Cox, Courtney L; Tietz, Jonathan I; Sokolowski, Karol; Melby, Joel O; Doroghazi, James R; Mitchell, Douglas A

    2014-09-19

    Natural products remain an important source of drug candidates, but the difficulties inherent to traditional isolation, coupled with unacceptably high rates of compound rediscovery, limit the pace of natural product detection. Here we describe a reactivity-based screening method to rapidly identify exported bacterial metabolites that contain dehydrated amino acids (i.e., carbonyl- or imine-activated alkenes), a common motif in several classes of natural products. Our strategy entails the use of a commercially available thiol, dithiothreitol, for the covalent labeling of activated alkenes by nucleophilic 1,4-addition. Modification is easily discerned by comparing mass spectra of reacted and unreacted cell surface extracts. When combined with bioinformatic analysis of putative natural product gene clusters, targeted screening and isolation can be performed on a prioritized list of strains. Moreover, known compounds are easily dereplicated, effectively eliminating superfluous isolation and characterization. As a proof of principle, this labeling method was used to identify known natural products belonging to the thiopeptide, lanthipeptide, and linaridin classes. Further, upon screening a panel of only 23 actinomycetes, we discovered and characterized a novel thiopeptide antibiotic, cyclothiazomycin C.

  10. Single crystal x-ray structural determination of natural products

    NASA Astrophysics Data System (ADS)

    Fun, Hoong-Kun; Boonnak, Nawong; Chantrapromma, Suchada

    2012-06-01

    Bioactive natural products have been extensively studied worldwide because natural products compounds with their great structural diversity have traditionally provided most of the drugs in use. Nevertheless the most important step in the drug discovery process is the structural characterization of isolated compounds with interesting biological activities. X-ray structure determination is a powerful technique for characterization because this technique is able to provide a lot of informations on stereochemistry and the detailed three-dimension structures made available can be corelated to activities of these structures. The advancement of X-ray crystallography makes the characterization procedure more precise, much easier and less time consumable. Moreover, this technique can directly and easily confirm whether these compounds are enantiomerically pure or racemate. In addition the absolute configuration of a natural products molecule can be easily determined by this technique. This work shall be based on the results from our natural products research. The absolute configuration of 6-Hydroxysalvinolone and Horminone, which were isolated from Premna obtusifolia will be presented. Three racemates, namely Panduratin A, Caged xanthone and Murrayazoline, which were isolated from the natural products sources will also be presented.

  11. Microbial genomics for the improvement of natural product discovery.

    PubMed

    Van Lanen, Steven G; Shen, Ben

    2006-06-01

    The quest for the discovery of novel natural products has entered a new chapter with the enormous wealth of genetic data that is now available. This information has been exploited by using whole-genome sequence mining to uncover cryptic pathways, or biosynthetic pathways for previously undetected metabolites. Alternatively, using known paradigms for secondary metabolite biosynthesis, genetic information has been 'fished out' of DNA libraries resulting in the discovery of new natural products and isolation of gene clusters for known metabolites. Novel natural products have been discovered by expressing genetic data from uncultured organisms or difficult-to-manipulate strains in heterologous hosts. Furthermore, improvements in heterologous expression have not only helped to identify gene clusters but have also made it easier to manipulate these genes in order to generate new compounds. Finally, and perhaps the most crucial aspect of the efficient and prosperous use of the abundance of genetic information, novel enzyme chemistry continues to be discovered, which has aided our understanding of how natural products are biosynthesized de novo, and enabled us to rework the current paradigms for natural product biosynthesis.

  12. Potential antimalarials from African natural products: A reviw

    PubMed Central

    Lawal, Bashir; Shittu, Oluwatosin Kudirat; Kabiru, Adamu Yusuf; Jigam, Ali Audu; Umar, Maimuna Bello; Berinyuy, Eustace Bonghan; Alozieuwa, Blessing Uchenna

    2015-01-01

    Malaria remains an overwhelming infectious disease with significant health challenges in African and other endemic countries globally. Resistance to antimalarial drugs has become one of the most momentous challenges to human health, and thus has necessitated the hunt for new and effective drugs. Consequently, few decades have witnessed a surfeit of research geared to validate the effectiveness of commonly used traditionally medicines against malaria fever. The present review work focuses on documenting natural products from African whose activity has been reported in vivo or in vitro against malaria parasite. Literature was collected using electronic search of published articles (Google Scholar, PubMed, Medline, Sciencedirect, and Science domain) that report on antiplasmodial activity of natural products from differernts Africa region. A total of 652 plant taxa from 146 families, 134 isolated antimalarial compounds from 39 plants species, 2 herbal formulations and 4 insect/products were found to be reported in literature from 1996 to 2015. Plants species from family Asteraceae (11.04%), Fababceae (8.128%), Euphorbiaceae (5.52%), Rubiaceas (5.52%), and Apocyanaceae (5.214%), have received more scientific validation than others. African natural products possess remarkable healing properties as revealed in the various citations as promising antimalarial agents. Some of these natural products from Africa demonstrate high, promising or low activities against Plasmodium parasite. This study also shows that natural products from Africa have a huge amount of novel antimalarial compounds that could serve as a leads for the development of new and effective antiplasmodial drugs. However, in a view of bridging the gap in knowledge, clinical validation of these natural products are of paramount importance. PMID:26649238

  13. Exploring cyanobacterial genomes for natural product biosynthesis pathways.

    PubMed

    Micallef, Melinda L; D'Agostino, Paul M; Al-Sinawi, Bakir; Neilan, Brett A; Moffitt, Michelle C

    2015-06-01

    Cyanobacteria produce a vast array of natural products, some of which are toxic to human health, while others possess potential pharmaceutical activities. Genome mining enables the identification and characterisation of natural product gene clusters; however, the current number of cyanobacterial genomes remains low compared to other phyla. There has been a recent effort to rectify this issue by increasing the number of sequenced cyanobacterial genomes. This has enabled the identification of biosynthetic gene clusters for structurally diverse metabolites, including non-ribosomal peptides, polyketides, ribosomal peptides, UV-absorbing compounds, alkaloids, terpenes and fatty acids. While some of the identified biosynthetic gene clusters correlate with known metabolites, genome mining also highlights the number and diversity of clusters for which the product is unknown (referred to as orphan gene clusters). A number of bioinformatic tools have recently been developed in order to predict the products of orphan gene clusters; however, in some cases the complexity of the cyanobacterial pathways makes the prediction problematic. This can be overcome by the use of mass spectrometry-guided natural product genome mining, or heterologous expression. Application of these techniques to cyanobacterial natural product gene clusters will be explored.

  14. JadX is a Disparate Natural Product Binding Protein.

    PubMed

    Robertson, Andrew W; Forget, Stephanie M; Martinez-Farina, Camilo F; McCormick, Nicole E; Syvitski, Raymond T; Jakeman, David L

    2016-02-24

    We report that JadX, a protein of previously undetermined function coded for in the jadomycin biosynthetic gene cluster of Streptomyces venezuelae ISP5230, affects both chloramphenicol and jadomycin production levels in blocked mutants. Characterization of recombinant JadX through protein-ligand interactions by chemical shift perturbation and WaterLOGSY NMR spectroscopy resulted in the observation of binding between JadX and a series of jadomycins and between JadX and chloramphenicol, another natural product produced by S. venezuelae ISP5230. These results suggest JadX to be an unusual class of natural product binding protein involved in binding structurally disparate natural products. The ability for JadX to bind two different natural products in vitro and the ability to affect production of these secondary metabolites in vivo suggest a potential role in regulation or signaling. This is the first example of functional characterization of these JadX-like proteins, and provides insight into a previously unobserved regulatory process.

  15. The case of Hypericum rochelii Griseb. & Schenk and Hypericum umbellatum A. Kern. essential oils: chemical composition and antimicrobial activity.

    PubMed

    Dorđević, Aleksandra; Lazarević, Jelena; Smelcerović, Andrija; Stojanović, Gordana

    2013-04-15

    The chemical composition and antimicrobial activity studies on the essential oils of Hypericum rochelii Griseb. & Schenk and Hypericum umbellatum A. Kern. have been carried out for the first time. Seventy-nine compounds were identified in the essential oil of H. rochelii with n-nonane (24.7%), β-pinene (22.4%), germacrene D (7.5%), n-undecane (6.8%) and α-pinene (5.8%) as main constituents. One hundred and twenty-six compounds were identified in H. umbellatum essential oil with germacrene D (6.1%), (E)-nerolidol (4.4%), n-nonane (4.0%), (E)-caryophyllene (3.0%) and caryophyllene oxide (3.0%) as the most abundant components. Both oils were characterized by the presence of many components which could have numerous applications in food, pharmaceutical and perfume industries. Taxa studied herein belong to the section Drosocarpium Spach, and their intrasectional placement based on the essential oil profiles was discussed. The oils were tested in a broth microdilution assay against five bacterial and two fungal strains and found to have mainly moderate antimicrobial effects.

  16. Inhibition of benzodiazepine binding in vitro by amentoflavone, a constituent of various species of Hypericum.

    PubMed

    Baureithel, K H; Büter, K B; Engesser, A; Burkard, W; Schaffner, W

    1997-06-01

    Flower extracts of Hypericum perforatum, Hypericum hirsutum, Hypericum patulum and Hypericum olympicum efficiently inhibited binding of [3H]flumazenil to rat brain benzodiazepine binding sites of the GABAA-receptor in vitro with IC50 values of 6.83, 6.97, 13.2 and 6.14 micrograms/ml, respectively. Single constituents of the extracts like hypericin, the flavones quercetin and luteolin, the glycosylated flavonoides rutin, hyperoside and quercitrin and the biflavone 13, II8-biapigenin did not inhibit binding up to concentrations of 1 microM. In contrast, amentoflavone revealed an IC50 = 14.9 +/- 1.9 nM on benzodiazepine binding in vitro. Comparative HPLC analyses of hypericin and amentoflavone in extracts of different Hypericum species revealed a possible correlation between the amentoflavone concentration and the inhibition of flumazenil binding. For hypericin no such correlation was observed. Our experimental data demonstrate that amentoflavone, in contrast to hypericin, presents a very active compound with regard to the inhibition of [3H]-flumazenil binding in vitro and thus might be involved in the antidepressant effects of Hypericum perforatum extracts.

  17. Preclinical data supporting/refuting the use of Hypericum perforatum in the treatment of depression.

    PubMed

    Crupi, Rosalia; Abusamra, Yousef Abdel Kareem; Spina, Edoardo; Calapai, Gioacchino

    2013-06-01

    Extracts of Hypericum perforatum (St. John's wort) have gained popularity as an alternative to synthetic antidepressants or behavioural therapy in the treatment of mild to moderate forms of depressive disorders. The present article reviews and discusses the available preclinical data that are in favour of or against the use of Hypericum perforatum as an antidepressant. Multiple chemical entities constitute extracts from Hypericum perforatum. The effects of Hypericum perforatum extracts have been compared with those of conventional antidepressants in different in vitro and in vivo biochemical studies of antidepressant-like activity and in behavioural pharmacology studies using animal models of depression. Recent investigations have indicated that Hypericum perforatum, like conventional antidepressants, is involved in the regulation of genes that control hypothalamic-pituitary-adrenal axis function and influence, at least in part, stress-induced effects on neuroplasticity and neurogenesis. From the available evidence it can be concluded that data supporting the use of Hypericum perforatum for the treatment of depression are present in literature. However, results from experiments carried out with extracts or pure compounds do not always resemble biochemical and pharmacological profile characteristic of synthetic antidepressants. In particular, the majority of findings in preclinical studies have been obtained with high doses of pure compounds and extracts that are not comparable to the concentrations of single active constituents after oral administration in humans.

  18. Establishment of new crops for the production of natural rubber.

    PubMed

    van Beilen, Jan B; Poirier, Yves

    2007-11-01

    Natural rubber is a unique biopolymer of strategic importance that, in many of its most significant applications, cannot be replaced by synthetic alternatives. The rubber tree Hevea brasiliensis is the almost exclusive commercial source of natural rubber currently and alternative crops should be developed for several reasons, including: a disease risk to the rubber tree that could potentially decimate current production, a predicted shortage of natural rubber supply, increasing allergic reactions to rubber obtained from the Brazilian rubber tree and a general shift towards renewables. This review summarizes our knowledge of plants that can serve as alternative sources of natural rubber, of rubber biosynthesis and the scientific gaps that must be filled to bring the alternative crops into production.

  19. Plant extracts as natural antioxidants in meat and meat products.

    PubMed

    Shah, Manzoor Ahmad; Bosco, Sowriappan John Don; Mir, Shabir Ahmad

    2014-09-01

    Antioxidants are used to minimize the oxidative changes in meat and meat products. Oxidative changes may have negative effects on the quality of meat and meat products, causing changes in their sensory and nutritional properties. Although synthetic antioxidants have already been used but in recent years, the demand for natural antioxidants has been increased mainly because of adverse effects of synthetic antioxidants. Thus most of the recent investigations have been directed towards the identification of natural antioxidants from various plant sources. Plant extracts have been prepared using different solvents and extraction methods. Grape seed, green tea, pine bark, rosemary, pomegranate, nettle and cinnamon have exhibited similar or better antioxidant properties compared to some synthetic ones. This review provides the recent information on plant extracts used as natural antioxidants in meat and meat products, specifically red meat.

  20. Natural product modulators to overcome multidrug resistance in cancer.

    PubMed

    Cort, Aysegul; Ozben, Tomris

    2015-01-01

    Multidrug resistance (MDR) is a condition that makes cells simultaneously unresponsive to different drugs, unrelated to their chemical structure and mechanism of action. MDR caused by the presence and overexpression of ABC transporters makes obstacles in cancer treatment and lower the effectiveness of chemotherapy. Natural products are investigated by many researchers as MDR modulators for their low toxicity and potent, selective behavior. When coadministered, MDR modulators compete with cytotoxic agents for binding to the active site of the membrane transporters and reduce drug efflux. Natural product-based drugs are important in struggling against drug resistance during cancer therapy. This review is focused on the potential mechanisms against drug resistance, the development of inhibitors for ABC drug transporters, natural product modulators, and nanoparticle drug delivery.

  1. Anti-cancer natural products isolated from chinese medicinal herbs

    PubMed Central

    2011-01-01

    In recent years, a number of natural products isolated from Chinese herbs have been found to inhibit proliferation, induce apoptosis, suppress angiogenesis, retard metastasis and enhance chemotherapy, exhibiting anti-cancer potential both in vitro and in vivo. This article summarizes recent advances in in vitro and in vivo research on the anti-cancer effects and related mechanisms of some promising natural products. These natural products are also reviewed for their therapeutic potentials, including flavonoids (gambogic acid, curcumin, wogonin and silibinin), alkaloids (berberine), terpenes (artemisinin, β-elemene, oridonin, triptolide, and ursolic acid), quinones (shikonin and emodin) and saponins (ginsenoside Rg3), which are isolated from Chinese medicinal herbs. In particular, the discovery of the new use of artemisinin derivatives as excellent anti-cancer drugs is also reviewed. PMID:21777476

  2. Bioactive natural products from Chinese marine flora and fauna.

    PubMed

    Zhou, Zhen-Fang; Guo, Yue-Wei

    2012-09-01

    In recent decades, the pharmaceutical application potential of marine natural products has attracted much interest from both natural product chemists and pharmacologists. Our group has long been engaged in the search for bioactive natural products from Chinese marine flora (such as mangroves and algae) and fauna (including sponges, soft corals, and mollusks), resulting in the isolation and characterization of numerous novel secondary metabolites spanning a wide range of structural classes and various biosynthetic origins. Of particular interest is the fact that many of these compounds show promising biological activities, including cytotoxic, antibacterial, and enzyme inhibitory effects. By describing representative studies, this review presents a comprehensive summary regarding the achievements and progress made by our group in the past decade. Several interesting examples are discussed in detail.

  3. Natural Products: An Alternative to Conventional Therapy for Dermatophytosis?

    PubMed

    Lopes, Graciliana; Pinto, Eugénia; Salgueiro, Lígia

    2017-02-01

    The increased incidence of fungal infections, associated with the widespread use of antifungal drugs, has resulted in the development of resistance, making it necessary to discover new therapeutic alternatives. Among fungal infections, dermatophytoses constitute a serious public health problem, affecting 20-25 % of the world population. Medicinal plants represent an endless source of bioactive molecules, and their volatile and non-volatile extracts are clearly recognized for being the historical basis of therapeutic health care. Because of this, the research on natural products with antifungal activity against dermatophytes has considerably increased in recent years. However, despite the recognized anti-dermatophytic potential of natural products, often advantageous face to commercial drugs, there is still a long way to go until their use in therapeutics. This review attempts to summarize the current status of anti-dermatophytic natural products, focusing on their mechanism of action, the developed pharmaceutical formulations and their effectiveness in human and animal models of infection.

  4. Dietary Natural Products for Prevention and Treatment of Liver Cancer

    PubMed Central

    Zhou, Yue; Li, Ya; Zhou, Tong; Zheng, Jie; Li, Sha; Li, Hua-Bin

    2016-01-01

    Liver cancer is the most common malignancy of the digestive system with high death rate. Accumulating evidences suggests that many dietary natural products are potential sources for prevention and treatment of liver cancer, such as grapes, black currant, plum, pomegranate, cruciferous vegetables, French beans, tomatoes, asparagus, garlic, turmeric, ginger, soy, rice bran, and some edible macro-fungi. These dietary natural products and their active components could affect the development and progression of liver cancer in various ways, such as inhibiting tumor cell growth and metastasis, protecting against liver carcinogens, immunomodulating and enhancing effects of chemotherapeutic drugs. This review summarizes the potential prevention and treatment activities of dietary natural products and their major bioactive constituents on liver cancer, and discusses possible mechanisms of action. PMID:26978396

  5. Microwave-assisted extraction in natural products isolation.

    PubMed

    Delazar, Abbas; Nahar, Lutfun; Hamedeyazdan, Sanaz; Sarker, Satyajit D

    2012-01-01

    Microwave-assisted extraction (MAE) or simply microwave extraction is a relatively new extraction technique that combines microwave and traditional solvent extraction. Application of microwaves for heating the solvents and plant tissues in extraction process, which increases the kinetic of extraction, is called microwave-assisted extraction. MAE has a number of advantages, e.g., shorter extraction time, less solvent, higher extraction rate and lower cost, over traditional method of extraction of compounds from various matrices, especially natural products. The use of MAE in natural products extraction started in the late 1980s, and through the technological developments, it has now become one of the popular and cost-effective extraction methods available today, and several advanced MAE instrumentations and methodologies have become available, e.g., pressurized microwave-assisted extraction (PMAE) and solvent-free microwave-assisted extraction (SFMAE). This chapter provides an overview of the MAE and presents a number of specific protocols for natural products extraction.

  6. Dietary Natural Products for Prevention and Treatment of Liver Cancer.

    PubMed

    Zhou, Yue; Li, Ya; Zhou, Tong; Zheng, Jie; Li, Sha; Li, Hua-Bin

    2016-03-10

    Liver cancer is the most common malignancy of the digestive system with high death rate. Accumulating evidences suggests that many dietary natural products are potential sources for prevention and treatment of liver cancer, such as grapes, black currant, plum, pomegranate, cruciferous vegetables, French beans, tomatoes, asparagus, garlic, turmeric, ginger, soy, rice bran, and some edible macro-fungi. These dietary natural products and their active components could affect the development and progression of liver cancer in various ways, such as inhibiting tumor cell growth and metastasis, protecting against liver carcinogens, immunomodulating and enhancing effects of chemotherapeutic drugs. This review summarizes the potential prevention and treatment activities of dietary natural products and their major bioactive constituents on liver cancer, and discusses possible mechanisms of action.

  7. Genomic basis for natural product biosynthetic diversity in the actinomycetes†

    PubMed Central

    Nett, Markus; Ikeda, Haruo; Moore, Bradley S.

    2010-01-01

    The phylum Actinobacteria hosts diverse high G + C, Gram-positive bacteria that have evolved a complex chemical language of natural product chemistry to help navigate their fascinatingly varied lifestyles. To date, 71 Actinobacteria genomes have been completed and annotated, with the vast majority representing the Actinomycetales, which are the source of numerous antibiotics and other drugs from genera such as Streptomyces, Saccharopolyspora and Salinispora. These genomic analyses have illuminated the secondary metabolic proficiency of these microbes – underappreciated for years based on conventional isolation programs – and have helped set the foundation for a new natural product discovery paradigm based on genome mining. Trends in the secondary metabolomes of natural product-rich actinomycetes are highlighted in this review article, which contains 199 references. PMID:19844637

  8. In situ natural product discovery via an artificial marine sponge.

    PubMed

    La Clair, James J; Loveridge, Steven T; Tenney, Karen; O'Neil-Johnson, Mark; Chapman, Eli; Crews, Phillip

    2014-01-01

    There is continuing international interest in exploring and developing the therapeutic potential of marine-derived small molecules. Balancing the strategies for ocean based sampling of source organisms versus the potential to endanger fragile ecosystems poses a substantial challenge. In order to mitigate such environmental impacts, we have developed a deployable artificial sponge. This report provides details on its design followed by evidence that it faithfully recapitulates traditional natural product collection protocols. Retrieving this artificial sponge from a tropical ecosystem after deployment for 320 hours afforded three actin-targeting jasplakinolide depsipeptides that had been discovered two decades earlier using traditional sponge specimen collection and isolation procedures. The successful outcome achieved here could reinvigorate marine natural products research, by producing new environmentally innocuous sources of natural products and providing a means to probe the true biosynthetic origins of complex marine-derived scaffolds.

  9. Marine Natural Products as Inhibitors of Hypoxic Signaling in Tumors

    PubMed Central

    Nagle, Dale G.; Zhou, Yu-Dong

    2010-01-01

    Marine natural products have become a major source of new chemical entities in the discovery of potential anticancer agents that potently suppress various antitumor molecular targets. As a consequence of insufficient vascularization, hypoxic regions form within rapidly growing solid tumor masses. Specific alterations of gene expression in these hypoxic tumor cells help facilitate the survival and metastatic spread of solid tumors. The transcriptional response to cellular hypoxia is primarily mediated by the transcription factor hypoxia-inducible factor-1 (HIF-1) that regulates the expression of more than 100 genes involved in cellular adaptation and survival under hypoxic stress. Clinical studies in cancer patients indicate that HIF-1 activation is directly correlated with advanced disease stages and treatment resistance. HIF-1 has emerged as an important tumor-selective molecular target for anticancer drug discovery. As a result, natural product-based inhibitors of HIF-1 activation have been identified from plants and microorganisms. Recently, structurally unique natural products from marine sponges, crinoids, and algae have been identified as HIF-1 activation inhibitors. The US National Cancer Institute’s Open Repository of marine invertebrate and algae extracts has proven to be a valuable source of natural product HIF-1 inhibitors. Among the active compounds identified, certain marine natural products have also been shown to suppress the hypoxic induction of HIF-1 target genes such as vascular endothelial growth factor (VEGF). Some of these marine HIF-1 inhibitors act by interfering with the generation of mitochondrial signaling molecules in hypoxic cells. However, the precise mechanisms of action for many newly identified marine natural product HIF-1 inhibitors remain unresolved. PMID:20622986

  10. Marine actinobacteria: an important source of bioactive natural products.

    PubMed

    Manivasagan, Panchanathan; Kang, Kyong-Hwa; Sivakumar, Kannan; Li-Chan, Eunice C Y; Oh, Hyun-Myung; Kim, Se-Kwon

    2014-07-01

    Marine environment is largely an untapped source for deriving actinobacteria, having potential to produce novel, bioactive natural products. Actinobacteria are the prolific producers of pharmaceutically active secondary metabolites, accounting for about 70% of the naturally derived compounds that are currently in clinical use. Among the various actinobacterial genera, Actinomadura, Actinoplanes, Amycolatopsis, Marinispora, Micromonospora, Nocardiopsis, Saccharopolyspora, Salinispora, Streptomyces and Verrucosispora are the major potential producers of commercially important bioactive natural products. In this respect, Streptomyces ranks first with a large number of bioactive natural products. Marine actinobacteria are unique enhancing quite different biological properties including antimicrobial, anticancer, antiviral, insecticidal and enzyme inhibitory activities. They have attracted global in the last ten years for their ability to produce pharmaceutically active compounds. In this review, we have focused attention on the bioactive natural products isolated from marine actinobacteria, possessing unique chemical structures that may form the basis for synthesis of novel drugs that could be used to combat resistant pathogenic microorganisms. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Marine Natural Products as Models to Circumvent Multidrug Resistance.

    PubMed

    Long, Solida; Sousa, Emília; Kijjoa, Anake; Pinto, Madalena M M

    2016-07-08

    Multidrug resistance (MDR) to anticancer drugs is a serious health problem that in many cases leads to cancer treatment failure. The ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which leads to premature efflux of drugs from cancer cells, is often responsible for MDR. On the other hand, a strategy to search for modulators from natural products to overcome MDR had been in place during the last decades. However, Nature limits the amount of some natural products, which has led to the development of synthetic strategies to increase their availability. This review summarizes the research findings on marine natural products and derivatives, mainly alkaloids, polyoxygenated sterols, polyketides, terpenoids, diketopiperazines, and peptides, with P-gp inhibitory activity highlighting the established structure-activity relationships. The synthetic pathways for the total synthesis of the most promising members and analogs are also presented. It is expected that the data gathered during the last decades concerning their synthesis and MDR-inhibiting activities will help medicinal chemists develop potential drug candidates using marine natural products as models which can deliver new ABC transporter inhibitor scaffolds.

  12. The impact of natural products upon modern drug discovery.

    PubMed

    Ganesan, A

    2008-06-01

    In the period 1970-2006, a total of 24 unique natural products were discovered that led to an approved drug. We analyze these successful leads in terms of drug-like properties, and show that they can be divided into two equal subsets. The first falls in the 'Lipinski universe' and complies with the Rule of Five. The second is a 'parallel universe' that violates the rules. Nevertheless, the latter compounds remain largely compliant in terms of logP and H-bond donors, highlighting the importance of these two metrics in predicting bioavailability. Natural products are often cited as an exception to Lipinski's rules. We believe this is because nature has learned to maintain low hydrophobicity and intermolecular H-bond donating potential when it needs to make biologically active compounds with high molecular weight and large numbers of rotatable bonds. In addition, natural products are more likely than purely synthetic compounds to resemble biosynthetic intermediates or endogenous metabolites, and hence take advantage of active transport mechanisms. Interestingly, the natural product leads in the Lipinski and parallel universe had an identical success rate (50%) in delivering an oral drug.

  13. NATURAL PRODUCTS: A CONTINUING SOURCE OF NOVEL DRUG LEADS

    PubMed Central

    Cragg, Gordon M.; Newman, David J.

    2013-01-01

    1. Background Nature has been a source of medicinal products for millennia, with many useful drugs developed from plant sources. Following discovery of the penicillins, drug discovery from microbial sources occurred and diving techniques in the 1970s opened the seas. Combinatorial chemistry (late 1980s), shifted the focus of drug discovery efforts from Nature to the laboratory bench. 2. Scope of Review This review traces natural products drug discovery, outlining important drugs from natural sources that revolutionized treatment of serious diseases. It is clear Nature will continue to be a major source of new structural leads, and effective drug development depends on multidisciplinary collaborations. 3. Major Conclusions The explosion of genetic information led not only to novel screens, but the genetic techniques permitted the implementation of combinatorial biosynthetic technology and genome mining. The knowledge gained has allowed unknown molecules to be identified. These novel bioactive structures can be optimized by using combinatorial chemistry generating new drug candidates for many diseases. 4 General Significance: The advent of genetic techniques that permitted the isolation / expression of biosynthetic cassettes from microbes may well be the new frontier for natural products lead discovery. It is now apparent that biodiversity may be much greater in those organisms. The numbers of potential species involved in the microbial world are many orders of magnitude greater than those of plants and multi-celled animals. Coupling these numbers to the number of currently unexpressed biosynthetic clusters now identified (>10 per species) the potential of microbial diversity remains essentially untapped. PMID:23428572

  14. Total synthesis and development of bioactive natural products

    PubMed Central

    TATSUTA, Kuniaki

    2008-01-01

    The first total synthesis and development of a variety of bioactive natural products have been accomplished by using carbohydrates as a chiral source. In addition, practically useful intermediates have been created, analogs of natural products have been prepared, their structure-activity relationships studied, and the large-scale preparations of medicinally useful compounds established. The key target molecules have been the “Big Four” antibiotics (macrolides, aminoglycosides, β-lactams and tetracyclines), pyranonaphthoquinone antibiotics, glycosidase inhibitors, and a side-chain of cephem antibiotics. PMID:18941289

  15. Myxobacterial natural product assembly lines: fascinating examples of curious biochemistry.

    PubMed

    Wenzel, Silke Christine; Müller, Rolf

    2007-12-01

    Over the last 20 years myxobacteria have made their way from highly exotic organisms to one of the major sources of microbial natural products with interesting biological activities. Recent progress towards achieving a better understanding of the genetics and the biochemistry of myxobacterial secondary metabolism, revealed the involvement of numerous exceptional combinations of polyketide synthases and nonribosomal peptide synthetases operating far from textbook biosynthetic logic. In this Highlight, selected examples of recently described systems are discussed in comparison to all myxobacterial natural product assembly lines known to date.

  16. Natural Product-Based Antibiotics: Synthesis and SAR-Studies.

    PubMed

    Prusov, Evgeny V

    2016-01-01

    Efficient control of the infectious diseases in the era of the emerging bacterial resistance demands consistent development of new antibiotic agents with novel modes of action. With some notable exceptions, the majority of the currently used antibiotics are natural product-derived compounds which were elaborated upon lead structures discovered by screening of various isolates. In this review, we summarized some selected examples of recent advances in the area of natural product based antibiotic development with particular emphasis on the synthetic and SAR-elucidation aspects.

  17. Diversifying Complexity by Domino Benzannulation of Polycyclic Natural Products.

    PubMed

    Tejedor, David; Delgado-Hernández, Samuel; Carballo, Rubén M; Dapueto, Rosina; Mena-Rejón, Gonzalo J; García-Tellado, Fernando

    2017-05-19

    Herein we describe a salicylaldehyde-annulation reaction as a plug and play toolkit to diversify the complexity of naturally occurring ketones. The protocol entails the transformation of the polycyclic natural ketone into its propargyl vinyl ether derivative (two synthetic steps) and its microwave-assisted imidazole-catalyzed domino rearrangement to generate the salicylaldehyde ring. This annexed unit allows further synthetic transformations: e.g., the installation of a pharmacophore module to generate natural product-pharmacophore hybrids endowed with unknown biological (pharmaceutical) annotations.

  18. Emerging Trends in the Discovery of Natural Product Antibacterials

    PubMed Central

    Bologa, Cristian G.; Ursu, Oleg; Oprea, Tudor; Melançon, Charles E.; Tegos, George P.

    2013-01-01

    This article highlights current trends and advances in exploiting natural sources for the deployment of novel and potent anti-infective countermeasures. The key challenge is to therapeutically target microbial pathogens exhibiting a variety of puzzling and evolutionary complex resistance mechanisms. Special emphasis is given to the strengths, weaknesses, and opportunities in the natural product antimicrobial drug discovery arena, and to emerging applications driven by advances in bioinformatics, chemical biology, and synthetic biology in concert with exploiting the microbial phenotype. These orchestrated efforts have identified a critical mass of lead natural antimicrobials chemical scaffolds and discovery technologies with high probability of successful implementation against emerging microbial pathogens. PMID:23890825

  19. An innovative model for regulating supplement products: natural health products in Canada.

    PubMed

    Nestmann, Earle R; Harwood, Melody; Martyres, Stephanie

    2006-04-03

    On 1 January 2004, Health Canada officially added a new term to the global list of synonyms for dietary supplements: natural health products (NHP). Developed with the intent of providing Canadian consumers with ready access to NHP that are safe, effective, and of high quality, the Natural Health Products Regulations (the NHP regulations) are applicable to the sale, manufacture, packaging, labelling, importation, distribution, and storage of NHP, and are administered by the recently formed Natural Health Products Directorate (NHPD) within Health Canada. This paper provides an overview of the process for regulating supplement products in Canada.

  20. Recent developments in automated structure elucidation of natural products.

    PubMed

    Steinbeck, Christoph

    2004-08-01

    Advancements in the field of Computer-Assisted Structure Elucidation (CASE) of Natural Products achieved in the past five years are discussed. This process starts with a dereplication procedure, supported by structure-spectrum databases. Both commercial and free products are available to support the procedure. A number of new programs,as well as advancements in existing ones, are presented. Finally, the option to validate the result by an independent procedure, a high quality ab initio quantum mechanical calculation, is discussed.

  1. Idaho Habitat and Natural Production Monitoring : Annual Report 1989.

    SciTech Connect

    Kiefer, Russell B.; Forster, Katharine A.

    1991-01-01

    Project 83-7 was established under the Northwest Power Planning Council's 1982 Fish and Wildlife Program to monitor natural production of anadromous fish, evaluate Bonneville Power Administration (BPA) habitat improvement projects, and develop a credit record for off-site mitigation projects in Idaho. Project 83-7 is divided into two subprojects: general and intensive monitoring. Primary objectives of the general monitoring subproject (Part 1) are to determine natural production increases due to habitat improvement projects in terms of parr production and to determine natural production status and trends in Idaho. The second objective is accomplished by combining parr density data from monitoring and evaluation of BPA habitat projects and from other Idaho Department of Fish and Game (IDFG) management and research activities. Primary objectives of the intensive monitoring subproject (Part 2) are to determine the number of returning chinook and steelhead adults necessary to achieve optimal smolt production and to develop mitigation accounting based on increases in smolt production. Two locations are being intensively studied to meet these objectives. Field work began in 1987 in the upper Salmon River and Crooked River (South Fork Clearwater River tributary). 22 refs., 10 figs., 17 tabs.

  2. Fishing for Nature's Hits: Establishment of the Zebrafish as a Model for Screening Antidiabetic Natural Products

    PubMed Central

    Tabassum, Nadia; Tai, Hongmei; Jung, Da-Woon; Williams, Darren R.

    2015-01-01

    Diabetes mellitus affects millions of people worldwide and significantly impacts their quality of life. Moreover, life threatening diseases, such as myocardial infarction, blindness, and renal disorders, increase the morbidity rate associated with diabetes. Various natural products from medicinal plants have shown potential as antidiabetes agents in cell-based screening systems. However, many of these potential “hits” fail in mammalian tests, due to issues such as poor pharmacokinetics and/or toxic side effects. To address this problem, the zebrafish (Danio rerio) model has been developed as a “bridge” to provide an experimentally convenient animal-based screening system to identify drug candidates that are active in vivo. In this review, we discuss the application of zebrafish to drug screening technologies for diabetes research. Specifically, the discovery of natural product-based antidiabetes compounds using zebrafish will be described. For example, it has recently been demonstrated that antidiabetic natural compounds can be identified in zebrafish using activity guided fractionation of crude plant extracts. Moreover, the development of fluorescent-tagged glucose bioprobes has allowed the screening of natural product-based modulators of glucose homeostasis in zebrafish. We hope that the discussion of these advances will illustrate the value and simplicity of establishing zebrafish-based assays for antidiabetic compounds in natural products-based laboratories. PMID:26681965

  3. Recent progress in natural products as DPP-4 inhibitors.

    PubMed

    Gao, Yuanyuan; Zhang, Yong; Zhu, Jianming; Li, Bo; Li, Zhao; Zhu, Weiliang; Shi, Jiye; Jia, Qi; Li, Yiming

    2015-01-01

    Diabetes mellitus is a chronic disease affecting patients' daily life and increasing patients' risk of other complication. Dipeptidyl peptidase-4 (DPP-4) is a serine aminopeptidase, which is one of the validated targets for Type 2 diabetes therapy due to its regulatory effect of incretin hormone. Seven DPP-4 inhibitors are commercially available nowadays on the market as Type 2 diabetes drugs. They are all chemically synthesized compounds with good therapeutic effects, but long-term safety remains unknown. On the other hand, nature provides a rich source for search of desired safe and effective medications; and actually more than half of the drugs on market are natural product related. Therefore, a systematic search for new DPP-4 inhibitors from nature sources seems to be of great utility for developing novel antidiabetic drugs. This review summarized recent progress of DPP-4 inhibitors from natural products, revealed that both pure natural products and the crude extracts of herbs or the hydrolyzates of proteins are active as DPP-4 inhibitors. Therefore, both could be served as useful clues for developing next generation of antidiabetes medicines via inhibiting DPP-4 activity.

  4. Production of hydrogen by thermocatalytic cracking of natural gas

    SciTech Connect

    Muradov, N.Z.

    1995-09-01

    It is universally accepted that in the next few decades hydrogen production will continue to rely on fossil fuels (primarily, natural gas). On the other hand, the conventional methods of hydrogen production from natural gas (for example, steam reforming) are complex multi-step processes. These processes also result in the emission of large quantities of CO{sub 2} into the atmosphere that produce adverse ecological effects. One alternative is the one-step thermocatalytic cracking (TCC) (or decomposition) of natural gas into hydrogen and carbon. Preliminary analysis indicates that the cost of hydrogen produced by thermal decomposition of natural gas is somewhat lower than the conventional processes after by-product carbon credit is taken. In the short term, this process can be used for on-site production of hydrogen-methane mixtures in gas-filling stations and for CO{sub x}-free production of hydrogen for fuel cell driven prime movers. The experimental data on the thermocatalytic cracking of methane over various catalysts and supports in a wide range of temperatures (500-900{degrees}C) are presented in this paper. Two types of reactors were designed and built at FSEC: continuous flow and pulse fix bed catalytic reactors. The temperature dependence of the hydrogen production yield using oxide type catalysts was studied. Alumina-supported Ni- and Fe-catalysts demonstrated relatively high efficiency in the methane cracking reaction at moderate temperatures (600-800{degrees}C). Kinetic curves of hydrogen production over metal and metal oxide catalysts at different temperatures are presented in the paper. Fe-catalyst demonstrated good stability (for several hours), whereas alumina-supported Pt-catalyst rapidly lost its catalytic activity.

  5. Mechanism Targeted Discovery of Antitumor Marine Natural Products

    PubMed Central

    Nagle, Dale G.; Zhou, Yu-Dong; Mora, Flor D.; Mohammed, Kaleem A.; Kim, Yong-Pil

    2010-01-01

    Antitumor drug discovery programs aim to identify chemical entities for use in the treatment of cancer. Many strategies have been used to achieve this objective. Natural products have always played a major role in anticancer medicine and the unique metabolites produced by marine organisms have increasingly become major players in antitumor drug discovery. Rapid advances have occurred in the understanding of tumor biology and molecular medicine. New insights into mechanisms responsible for neoplastic disease are significantly changing the general philosophical approach towards cancer treatment. Recently identified molecular targets have created exciting new means for disrupting tumor-specific cell signaling, cell division, energy metabolism, gene expression, drug resistance, and blood supply. Such tumor-specific treatments could someday decrease our reliance on traditional cytotoxicity-based chemotherapy and provide new less toxic treatment options with significantly fewer side effects. Novel molecular targets and state-of-the-art molecular mechanism-based screening methods have revitalized antitumor research and these changes are becoming an ever-increasing component of modern antitumor marine natural products research. This review describes marine natural products identified using tumor-specific mechanism-based assays for regulators of angiogenesis, apoptosis, cell cycle, macromolecule synthesis, mitochondrial respiration, mitosis, multidrug efflux, and signal transduction. Special emphasis is placed on natural products directly discovered using molecular mechanism-based screening. PMID:15279579

  6. Biological Activity of Recently Discovered Halogenated Marine Natural Products

    PubMed Central

    Gribble, Gordon W.

    2015-01-01

    This review presents the biological activity—antibacterial, antifungal, anti-parasitic, antiviral, antitumor, antiinflammatory, antioxidant, and enzymatic activity—of halogenated marine natural products discovered in the past five years. Newly discovered examples that do not report biological activity are not included. PMID:26133553

  7. The Utility of Metabolomics in Natural Product and Biomarker Characterization

    PubMed Central

    Cox, Daniel G.; Oh, Joonseok; Keasling, Adam; Colson, Kim

    2014-01-01

    Background Metabolomics is a well-established rapidly developing research field involving quantitative and qualitative metabolite assessment within biological systems. Recent improvements in metabolomics technologies reveal the unequivocal value of metabolomics tools in natural products discovery, gene-function analysis, systems biology and diagnostic platforms. Scope of review We review of some of the prominent metabolomics methodologies employed in data acquisition and analysis of natural products and disease-related biomarkers. Major conclusions This review demonstrates that metabolomics represents a highly adaptable technology with diverse applications ranging from environmental toxicology to disease diagnosis. Metabolomic analysis is shown to provide a unique snapshot of the functional genetic status of an organism by examining its biochemical profile, with relevance toward resolving phylogenetic associations involving horizontal gene transfer and distinguishing subgroups of genera possessing high genetic homology, as well as an increasing role in both elucidating biosynthetic transformations of natural products and detecting preclinical biomarkers of numerous disease states. General significance This review expands the interest in multiplatform combinatorial metabolomic analysis. The applications reviewed range from phylogenetic assignment, biosynthetic transformations of natural products, and the detection of preclinical biomarkers. PMID:25151044

  8. Low Carbon Technology Options for the Natural Gas Electricity Production

    EPA Science Inventory

    The ultimate goal of this task is to perform environmental and economic analysis of natural gas based power production technologies (different routes) to investigate and evaluate strategies for reducing emissions from the power sector. It is a broad research area. Initially, the...

  9. Use of space for development of commercial plant natural products

    NASA Astrophysics Data System (ADS)

    Draeger, Norman A.

    1997-01-01

    Plant experiments conducted in environments where conditions are carefully controlled reveal fundamental information about physiological processes. An important environmental parameter is gravity, the effects of which may be better understood in part through experiments conducted in space. New insights gained can be used to develop commercial plant natural products in industries such as pharmaceuticals and biocontrol.

  10. A New Golden Age of Natural Products Drug Discovery

    PubMed Central

    Shen, Ben

    2016-01-01

    The 2015 Nobel Prize in Physiology or Medicine has been awarded to William C. Campbell and Satoshi Omura, and Youyou Tu for the discovery of avermectins and artemisinin, respectively, therapies that revolutionized the treatment of devastating parasite diseases. With the recent technological advances, a New Golden Age of natural products drug discovery is dawning. PMID:26638061

  11. Natural products chemistry research 2010's progress in China.

    PubMed

    Ye, Yang; Li, Xi-Qiang; Tang, Chun-Ping; Yao, Sheng

    2012-01-01

    This article reviews the progresses made by Chinese scientists in the field of natural products chemistry in 2010. Selected compounds with unique structural features and/or promising bioactivities were described herein on the basis of structural types. Copyright © 2012 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  12. Natural products with health benefits from marine biological resources

    USDA-ARS?s Scientific Manuscript database

    The ocean is the cradle of lives, which provides a diverse array of intriguing natural products that has captured scientists’ attention in the past few decades due to their significant and extremely potent biological activities. In addition to being rich sources for pharmaceutical drugs, marine nat...

  13. A New Golden Age of Natural Products Drug Discovery.

    PubMed

    Shen, Ben

    2015-12-03

    The 2015 Nobel Prize in Physiology or Medicine has been awarded to William C. Campbell, Satoshi Omura, and Youyou Tu for the discovery of avermectins and artemisinin, respectively, therapies that revolutionized the treatment of devastating parasite diseases. With the recent technological advances, a New Golden Age of natural products drug discovery is dawning. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Low Carbon Technology Options for the Natural Gas Electricity Production

    EPA Science Inventory

    The ultimate goal of this task is to perform environmental and economic analysis of natural gas based power production technologies (different routes) to investigate and evaluate strategies for reducing emissions from the power sector. It is a broad research area. Initially, the...

  15. The Synthesis of Quinolone Natural Products from Pseudonocardia sp.

    PubMed Central

    Salvaggio, Flavia; Hodgkinson, James T.; Carro, Laura; Geddis, Stephen M.; Galloway, Warren R. J. D.; Welch, Martin

    2015-01-01

    Abstract The synthesis of four quinolone natural products from the actinomycete Pseudonocardia sp. is reported. The key step involved a sp2–sp3 Suzuki–Miyaura reaction between a common boronic ester lateral chain and various functionalised quinolone cores. The quinolones slowed growth of E. coli and S. aureus by inducing extended lag phases.

  16. Genomes to natural products PRediction Informatics for Secondary Metabolomes (PRISM).

    PubMed

    Skinnider, Michael A; Dejong, Chris A; Rees, Philip N; Johnston, Chad W; Li, Haoxin; Webster, Andrew L H; Wyatt, Morgan A; Magarvey, Nathan A

    2015-11-16

    Microbial natural products are an invaluable source of evolved bioactive small molecules and pharmaceutical agents. Next-generation and metagenomic sequencing indicates untapped genomic potential, yet high rediscovery rates of known metabolites increasingly frustrate conventional natural product screening programs. New methods to connect biosynthetic gene clusters to novel chemical scaffolds are therefore critical to enable the targeted discovery of genetically encoded natural products. Here, we present PRISM, a computational resource for the identification of biosynthetic gene clusters, prediction of genetically encoded nonribosomal peptides and type I and II polyketides, and bio- and cheminformatic dereplication of known natural products. PRISM implements novel algorithms which render it uniquely capable of predicting type II polyketides, deoxygenated sugars, and starter units, making it a comprehensive genome-guided chemical structure prediction engine. A library of 57 tailoring reactions is leveraged for combinatorial scaffold library generation when multiple potential substrates are consistent with biosynthetic logic. We compare the accuracy of PRISM to existing genomic analysis platforms. PRISM is an open-source, user-friendly web application available at http://magarveylab.ca/prism/.

  17. Use of space for development of commercial plant natural products

    SciTech Connect

    Draeger, N.A.

    1997-01-01

    Plant experiments conducted in environments where conditions are carefully controlled reveal fundamental information about physiological processes. An important environmental parameter is gravity, the effects of which may be better understood in part through experiments conducted in space. New insights gained can be used to develop commercial plant natural products in industries such as pharmaceuticals and biocontrol. {copyright} {ital 1997 American Institute of Physics.}

  18. [Key technologies in synthetic biology of natural products].

    PubMed

    Kuang, Xue-Jun; Zou, Li-Qiu; Li, Ying; Sun, Chao; Chen, Shi-Lin

    2016-11-01

    Natural products with complex and diverse structures are the major sources of new drugs. The biosynthesis of natural products is considered to be one of the best ways to solve the problems of complex and scarce natural products. DNA assembly technology and genome editing technology are two key technologies in the emerging interdisciplinary field of synthetic biology. A number of novel DNA assembly methods developed in the last few years have paved the way for the engineering of high molecular weight DNA molecules, including whole genomes, hence, it can realize the reconstruction of the metabolic pathways and speed up optimization process. A wide variety of new tools for microbial genome editing will be applied widely to modify the chassis genome to increase its adaptation with the exogenetic pathways. This article summarized the latest advance with respect to DNA assembly and genome editing, which aims to provide help for reconstruction and optimization of the synthetic biological systems of natural products. Copyright© by the Chinese Pharmaceutical Association.

  19. Natural Products for the Treatment of Type 2 Diabetes Mellitus.

    PubMed

    Ríos, José Luis; Francini, Flavio; Schinella, Guillermo R

    2015-08-01

    Type 2 diabetes mellitus is a metabolic disease characterized by persistent hyperglycemia. High blood sugar can produce long-term complications such as cardiovascular and renal disorders, retinopathy, and poor blood flow. Its development can be prevented or delayed in people with impaired glucose tolerance by implementing lifestyle changes or the use of therapeutic agents. Some of these drugs have been obtained from plants or have a microbial origin, such as galegine isolated from Galega officinalis, which has a great similarity to the antidiabetic drug metformin. Picnogenol, acarbose, miglitol, and voglibose are other antidiabetic products of natural origin. This review compiles the principal articles on medicinal plants used for treating diabetes and its comorbidities, as well as mechanisms of natural products as antidiabetic agents. Inhibition of α-glucosidase and α-amylase, effects on glucose uptake and glucose transporters, modification of mechanisms mediated by the peroxisome proliferator-activated receptor, inhibition of protein tyrosine phosphatase 1B activity, modification of gene expression, and activities of hormones involved in glucose homeostasis such as adiponectin, resistin, and incretin, and reduction of oxidative stress are some of the mechanisms in which natural products are involved. We also review the most relevant clinical trials performed with medicinal plants and natural products such as aloe, banaba, bitter melon, caper, cinnamon, cocoa, coffee, fenugreek, garlic, guava, gymnema, nettle, sage, soybean, green and black tea, turmeric, walnut, and yerba mate. Compounds of high interest as potential antidiabetics are: fukugetin, palmatine, berberine, honokiol, amorfrutins, trigonelline, gymnemic acids, gurmarin, and phlorizin.

  20. Natural Products as Source of Therapeutics against Parasitic Diseases.

    PubMed

    Hertweck, Christian

    2015-12-01

    An end to suffering: Parasitic infections with protozoa and worms cause unimaginable misery, in particular in the tropics. Fortunately, natural products, such as the antimalarial artemisinin (1) and the anthelmintic avermectin (2) were discovered and developed into therapeutics. These major achievements now culminated in the 2015 Nobel Prize for Medicine.

  1. Genomes to natural products PRediction Informatics for Secondary Metabolomes (PRISM)

    PubMed Central

    Skinnider, Michael A.; Dejong, Chris A.; Rees, Philip N.; Johnston, Chad W.; Li, Haoxin; Webster, Andrew L. H.; Wyatt, Morgan A.; Magarvey, Nathan A.

    2015-01-01

    Microbial natural products are an invaluable source of evolved bioactive small molecules and pharmaceutical agents. Next-generation and metagenomic sequencing indicates untapped genomic potential, yet high rediscovery rates of known metabolites increasingly frustrate conventional natural product screening programs. New methods to connect biosynthetic gene clusters to novel chemical scaffolds are therefore critical to enable the targeted discovery of genetically encoded natural products. Here, we present PRISM, a computational resource for the identification of biosynthetic gene clusters, prediction of genetically encoded nonribosomal peptides and type I and II polyketides, and bio- and cheminformatic dereplication of known natural products. PRISM implements novel algorithms which render it uniquely capable of predicting type II polyketides, deoxygenated sugars, and starter units, making it a comprehensive genome-guided chemical structure prediction engine. A library of 57 tailoring reactions is leveraged for combinatorial scaffold library generation when multiple potential substrates are consistent with biosynthetic logic. We compare the accuracy of PRISM to existing genomic analysis platforms. PRISM is an open-source, user-friendly web application available at http://magarveylab.ca/prism/. PMID:26442528

  2. Stereoselective Total Synthesis of Bioactive Marine Natural Product Biselyngbyolide B.

    PubMed

    Das, Sayantan; Paul, Debobrata; Goswami, Rajib Kumar

    2016-04-15

    A convergent strategy for the stereoselective total synthesis of biologically active marine natural product biselyngbyolide B has been developed. Key strategies of this synthesis include Jamison protocol of trans-hydroalumination/allylation for installation of C18-C23 olefin moiety and intramolecular Heck coupling for macrocyclization.

  3. Natural product derived insecticides: discovery and development of spinetoram.

    PubMed

    Galm, Ute; Sparks, Thomas C

    2016-03-01

    This review highlights the importance of natural product research and industrial microbiology for product development in the agricultural industry, based on examples from Dow AgroSciences. It provides an overview of the discovery and development of spinetoram, a semisynthetic insecticide derived by a combination of a genetic block in a specific O-methylation of the rhamnose moiety of spinosad coupled with neural network-based QSAR and synthetic chemistry. It also emphasizes the key role that new technologies and multidisciplinary approaches play in the development of current spinetoram production strains.

  4. Natural resins and bioactive natural products thereof as potential antimicrobial agents.

    PubMed

    Termentzi, Aikaterini; Fokialakis, Nikolas; Skaltsounis, Alexios Leandros

    2011-01-01

    Natural products and their derivatives have historically been invaluable as a source of therapeutic agents and have contributed to the discovery of antimicrobial agents. However, today with the development of drug-resistant strains, new scaffolds and new sources of bioactive compounds are needed. To this end, plant derived natural resins are reviewed for their potential application as antimicrobial agents. Natural gums, extracts of the whole resins, as well as specific extracts, fractions, essential oils and isolated compounds from the above resins are discussed in terms of their antifungal, antibacterial, and antiprotozoal activity.

  5. Synthetic Glycosides and Glycoconjugates of Low Molecular Weight Natural Products.

    PubMed

    Grynkiewicz, G; Szeja, W

    2016-01-01

    Enzymatically controlled transfer of saccharide moieties constitutes a fundamental biological process, essential for both primary and secondary metabolism. Natural products, including countless glycosides, with a rich tradition of use in ethnopharmacology, remain a prime source of inspiration for medicinal chemistry and molecular pharmacology, but their availability from biological sources is usually scarce, hampering attempts at application for new drug discovery and development. Chemical glycosylation on the other hand, although continuously undergoing sophisticated mechanistic studies, has nevertheless already matured as a set of methods which are able to provide substantial amounts of pure chemical entities: natural glycosides, as well as their congeners and mimics, necessary for the study of biological activity in quality assurance systems and required for drug development by pharmaceutical regulations. The paper presents a review of natural products and their analogues glycosylation, in a set of arbitrary selected examples, supplemented with comments on general advances in chemical glycosylation methodology and their applicability for particular categories of secondary metabolites.

  6. Natural Products as Platforms To Overcome Antibiotic Resistance.

    PubMed

    Rossiter, Sean E; Fletcher, Madison H; Wuest, William M

    2017-09-27

    Natural products have served as powerful therapeutics against pathogenic bacteria since the golden age of antibiotics of the mid-20th century. However, the increasing frequency of antibiotic-resistant infections clearly demonstrates that new antibiotics are critical for modern medicine. Because combinatorial approaches have not yielded effective drugs, we propose that the development of new antibiotics around proven natural scaffolds is the best short-term solution to the rising crisis of antibiotic resistance. We analyze herein synthetic approaches aiming to reengineer natural products into potent antibiotics. Furthermore, we discuss approaches in modulating quorum sensing and biofilm formation as a nonlethal method, as well as narrow-spectrum pathogen-specific antibiotics, which are of interest given new insights into the implications of disrupting the microbiome.

  7. Norlignans, acylphloroglucinols, and a dimeric xanthone from Hypericum chinense.

    PubMed

    Wang, Wei; Zeng, Yi Han; Osman, Khadijo; Shinde, Kamlesh; Rahman, Mukhlesur; Gibbons, Simon; Mu, Qing

    2010-11-29

    Two new norlignans, hyperiones A (1) and B (2), three new acylphloroglucinols, aspidinol C (3) and hyperaspidinols A (5) and B (6), the known compound aspidinol D (4), and the symmetrical dimeric xanthone hyperidixanthone (7) were isolated from Hypericum chinense. Their structures were established by spectroscopic analysis. In an antibacterial assay using a panel of multidrug-resistant (MDR) strains, compounds 3 and 4 exhibited promising activity against the NorA efflux protein overexpressing MDR Staphylococcus aureus strain SA-1199B with a minimum inhibitory concentration (MIC) of 2 μg/mL (8.4 μM) and 4 μg/mL (16.8 μM), respectively. The positive control antibiotic norfloxacin showed activity at MIC 32 μg/mL (100 μM).

  8. Secondary Metabolites of Hypericum leptophyllum Hochst., an Endemic Turkish Species

    PubMed Central

    Camas, Necdet; Radusiene, Jolita; Stanius, Zydrunas; Caliskan, Omer; Cirak, Cuneyt

    2012-01-01

    In the present study, the presence of the phloroglucinol derivative hyperforin, the naphthodianthrones hypericin and pseudohypericin, the phenylpropane chlorogenic acid and the flavonoids rutin, hyperoside, kaempferol, isoquercetine, quercitrine, and quercetine was investigated in Hypericum leptophyllum Hochst., an endemic Turkish species for the first time. The aerial parts representing a total of 30 individuals were collected at full flowering and dissected into floral, leaf, and stem tissues. After being dried at room temperature, the plant materials were assayed for secondary metabolite concentrations by HPLC. Aerial plant parts accumulated chlorogenic acid, hyperoside, isoquercetine, quercitrine, and quercetine, but they did not accumulate hyperforin, hypericin, pseudohypericin, rutin, and kaempferol. Accumulation levels of the detected compounds varied with plant tissues. Such kind of data could be useful for elucidation of the chemotaxonomical significance of the corresponding compounds and phytochemical evaluation of this endemic species. PMID:22649295

  9. Tomoeones A-H, cytotoxic phloroglucinol derivatives from Hypericum ascyron.

    PubMed

    Hashida, Waka; Tanaka, Naonobu; Kashiwada, Yoshiki; Sekiya, Michiko; Ikeshiro, Yasumasa; Takaishi, Yoshihisa

    2008-08-01

    Phloroglucinol derivatives tomoeones A-H (1-8) and three known compounds were isolated from leaves of Hypericum ascyron. Their structures were established based on spectroscopic analyses. They are all acylphloroglucinol derivatives possessing a spiro skeleton with geminal isoprenyl groups and a monoterpene moiety, and they are stereoisomers to each other at C-4 and C-13. They appear to be a class of phloroglucinol derivatives. Cytotoxicities of the isolated phloroglucinol derivatives against human tumor cell lines, including multidrug-resistant (MDR) cancer cell lines, were evaluated. Tomoeone F (6) demonstrated significant cytotoxicity against KB cells with an IC50 value of 6.2 microM. Compound 6 was also cytotoxic against MDR cancer cell lines (KB-C2 and K562/Adr), which was more potent than doxorubicin.

  10. Neuroprotective Activity of Hypericum perforatum and Its Major Components.

    PubMed

    Oliveira, Ana I; Pinho, Cláudia; Sarmento, Bruno; Dias, Alberto C P

    2016-01-01

    Hypericum perforatum is a perennial plant, with worldwide distribution, commonly known as St. John's wort. It has been used for centuries in traditional medicine for the treatment of several disorders, such as minor burns, anxiety, and mild to moderate depression. In the past years, its antidepressant properties have been extensively studied. Despite that, other H. perforatum biological activities, as its neuroprotective properties have also been evaluated. The present review aims to provide a comprehensive summary of the main biologically active compounds of H. perforatum, as for its chemistry, pharmacological activities, drug interactions and adverse reactions and gather scattered information about its neuroprotective abilities. As for this, it has been demonstrated that H. perforatum extracts and several of its major molecular components have the ability to protect against toxic insults, either directly, through neuroprotective mechanisms, or indirectly, through is antioxidant properties. H. perforatum has therefore the potential to become an effective neuroprotective therapeutic agent, despite further studies that need to be carried out.

  11. Hypericum perforatum use during pregnancy and pregnancy outcome.

    PubMed

    Kolding, Line; Pedersen, Lars Henning; Henriksen, Tine Brink; Olsen, Jørn; Grzeskowiak, Luke E

    2015-12-01

    Hypericum perforatum (HP; also known as St. John's Wort) is one of the most commonly used herbal therapies in the management of depressive illness. The aim of this study was to evaluate the potential side effects of HP during pregnancy on pregnancy outcome. Using data from the Danish National Birth Cohort (DNBC), we investigated outcomes among 38 HP exposed pregnancies compared to a group of 90,128 women. Associations between HP use and gestational age, preterm birth, birth weight, malformations and Apgar scores were investigated. Preterm birth did not differ across the groups. While the prevalence of malformations in the HP exposed group was slightly higher (8.1%) than observed in the control groups (3.3%; p=0.13), this was based on only three cases and was not of any specific pattern.

  12. Interaction of St John's wort (Hypericum perforatum) with clozapine.

    PubMed

    Van Strater, Annelies C P; Bogers, Jan P A M

    2012-03-01

    St John's wort (Hypericum perforatum) is notorious for its ability to induce the enzymes of the P450 system. Especially, it induces CYP1A2 and CYP3A4, enzymes that are closely involved in the metabolism of clozapine. We present a patient with schizophrenia, who was stable on a fixed dose with stable plasma level of clozapine, and who deteriorated after she started self-medicating with St John's wort. The reduced plasma clozapine level and the psychiatric condition normalized after the withdrawal of St John's wort. It is possible that, beside the induction of P450-enzymes, the induction of P-glycoprotein by St John's wort aggravated psychiatric deterioration of the patient. Physicians should be alert to patients self-medicating with over-the-counter medicines, especially when these medicines can lower clozapine concentrations below the therapeutic range.

  13. Identification and biosynthesis of acylphloroglucinols in Hypericum gentianoides

    PubMed Central

    Crispin, Matthew C.; Hur, Manhoi; Park, Taeseong; Kim, Young Hwan; Wurtele, Eve Syrkin

    2013-01-01

    Species of the genus Hypericum contain a rich array of unusual polyketides, however, only a small proportion of the over 450 Hypericum species, other than the popular medicinal supplement St. John’s Wort (H. perforatum), have even been chemically characterized. H. gentianoides, a small annual used medicinally by Cherokee Americans, contains bioactive acylphloroglucinols. Here, we identify acylphloroglucinol constituents of H. gentianoides and determine a potential pathway to their synthesis. Liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS) and HPLC-UV indicate that the level of accumulation and profile of acylphloroglucinols in H. gentianoides vary little seasonally when grown in a greenhouse, but do vary with development and are highly dependent on the accession, highlighting the importance of the selection of plant material for study. We identify the chemical structures of the nine prevalent polyketides, based on LC/ESI-MS and hybrid quadrupole orthogonal time-of-flight mass (Q-TOF) spectrometry; these metabolites include one monomeric phlorisobutyrophenone (PIB) derivative and eight dimeric acylphloroglucinols. Q-TOF spectrometry was used to identify eight additional PIB derivatives that were not detected by LC/ESI-MS. These data lead us to propose that diacylphloroglucinols are synthesized via modification of PIB to yield diverse phloroglucinol and filicinic acids moieties, followed by dimerization of a phloroglucinol and a filicinic acid monomer to yield the observed complement of diacylphloroglucinols. The metabolomics data from H. gentianoides are accessible in PMR (http://www.metnetdb.org/pmr), a public metabolomics database with analysis software for plants and microbial organisms. PMID:23600727

  14. The mutagenic, antimutagenic and antioxidant properties of Hypericum lydium.

    PubMed

    Boran, Rukiye; Ugur, Aysel

    2017-12-01

    There is a growing market demand for Hypericum sp., a pharmacologically active plant that has been traditionally used to treat various ailments. However, there have been limited studies on the extract or essential oil of Hypericum lydium Boiss (Hypericaceae). This study investigates for the first time the antioxidant, mutagenic and antimutagenic activity of an ethanol extract of H. lydium. Ethanol extract from aerial parts of H. lydium harvested from Turkey were tested for this mutagenic and antimutagenic activities (2.0-0.002 mg/plate) using Ames Salmonella/microsome test system. 4-Nitro-o-phenylenediamine (4-NPD) (3 μg/plate) for the Salmonella typhimurium TA98 and sodium azide (NaN3) (8 μg/plate) for the S. typhimurium TA100 were used as positive controls. The antioxidant activity, total antioxidant activity and phenolic constituent of the extract (2.0-0.002 mg/mL) was determined by the inhibition of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), β-carotene-linoleic acid model and by means of Folin-Ciocalteu reagent, respectively. The extract showed no sign of mutagenicity at the tested concentrations (0.002-2.0 mg/mL), and showed concentration-dependent antimutagenic activity against NaN3 and 4-NPD ranging from 26.8 to 81.5%. The extract was found to be an efficient scavenger of DPPH (IC50 0.165 ± 0.23 mg/mL) and to inhibit β-carotene-linoleic acid bleaching (IC50 0.39 ± 0.11 mg/mL). These findings indicate ethanol extract of H. lydium to be a safe and effective agent that may be incorporated into new strategies for the prevention of cancer and mutagenesis.

  15. Biosynthesis and Function of Polyacetylenes and Allied Natural Products

    PubMed Central

    Minto, Robert E.; Blacklock, Brenda J.

    2008-01-01

    Polyacetylenic natural products are a substantial class of often unstable compounds containing a unique carbon-carbon triple bond functionality, that are intriguing for their wide variety of biochemical and ecological functions, economic potential, and surprising mode of biosynthesis. Isotopic tracer experiments between 1960 and 1990 demonstrated that the majority of these compounds are derived from fatty acid and polyketide precursors. During the past decade, research into the metabolism of polyacetylenes has swiftly advanced, driven by the cloning of the first genes responsible for polyacetylene biosynthesis in plants, moss, fungi, and actinomycetes, and the initial characterization of the gene products. The current state of knowledge of the biochemistry and molecular genetics of polyacetylenic secondary metabolic pathways will be presented together with an up-to-date survey of new terrestrial and marine natural products, their known biological activities, and a discussion of their likely metabolic origins. PMID:18387369

  16. Manipulating Natural Product Biosynthetic Pathways via DNA Assembler

    PubMed Central

    Shao, Zengyi; Zhao, Huimin

    2014-01-01

    DNA assembler is an efficient synthetic biology method for constructing and manipulating biochemical pathways. The rapidly increasing number of sequenced genomes provides a rich source for discovery of gene clusters involved in synthesizing new natural products. However, both discovery and economical production are hampered by our limited knowledge in manipulating most organisms and the corresponding pathways. By taking advantage of yeast in vivo homologous recombination, DNA assembler synthesizes an entire expression vector containing the target biosynthetic pathway and the genetic elements needed for DNA maintenance and replication. Here we use the spectinabilin clusters originated from two hosts as examples to illustrate the guidelines of using DNA assembler for cluster characterization and silent cluster activation. Such strategies offer unprecedented versatility in cluster manipulation, bypass the traditional laborious strategies to elicit pathway expression, and provide a new platform for de novo cluster assembly and genome mining for discovering new natural products. PMID:24903884

  17. Synthetic biology tools for bioprospecting of natural products in eukaryotes.

    PubMed

    Unkles, Shiela E; Valiante, Vito; Mattern, Derek J; Brakhage, Axel A

    2014-04-24

    Filamentous fungi have the capacity to produce a battery of natural products of often unknown function, synthesized by complex metabolic pathways. Unfortunately, most of these pathways appear silent, many in intractable organisms, and their products consequently unidentified. One basic challenge is the difficulty of expressing a biosynthesis pathway for a complex natural product in a heterologous eukaryotic host. Here, we provide a proof-of concept solution to this challenge and describe how the entire penicillin biosynthesis pathway can be expressed in a heterologous host. The method takes advantage of a combination of improved yeast in vivo cloning technology, generation of polycistronic mRNA for the gene cluster under study, and an amenable and easily manipulated fungal host, i.e., Aspergillus nidulans. We achieve expression from a single promoter of the pathway genes to yield a large polycistronic mRNA by using viral 2A peptide sequences to direct successful cotranslational cleavage of pathway enzymes.

  18. Systematics-guided bioprospecting for bioactive microbial natural products.

    PubMed

    Liu, Xueting; Bolla, Krishna; Ashforth, Elizabeth Jane; Zhuo, Ying; Gao, Hong; Huang, Pei; Stanley, Sarah A; Hung, Deborah T; Zhang, Lixin

    2012-01-01

    Advances in the taxonomic characterization of microorganisms have accelerated the rate at which new producers of natural products can be understood in relation to known organisms. Yet for many reasons, chemical efforts to characterize new compounds from new microbes have not kept pace with taxonomic advances. That there exists an ever-widening gap between the biological versus chemical characterization of new microorganisms creates tremendous opportunity for the discovery of novel natural products through the calculated selection and study of organisms from unique, untapped, ecological niches. A systematics-guided bioprospecting, including the construction of high quality libraries of marine microbes and their crude extracts, investigation of bioactive compounds, and increasing the active compounds by precision engineering, has become an efficient approach to drive drug leads discovery. This review outlines the recent advances in these issues and shares our experiences on anti-infectious drug discovery and improvement of avermectins production as well.

  19. Manipulating natural product biosynthetic pathways via DNA assembler.

    PubMed

    Shao, Zengyi; Zhao, Huimin

    2014-06-03

    DNA assembler is an efficient synthetic biology method for constructing and manipulating biochemical pathways. The rapidly increasing number of sequenced genomes provides a rich source for discovery of gene clusters involved in synthesizing new natural products. However, both discovery and economical production are hampered by our limited knowledge in manipulating most organisms and the corresponding pathways. By taking advantage of yeast in vivo homologous recombination, DNA assembler synthesizes an entire expression vector containing the target biosynthetic pathway and the genetic elements needed for DNA maintenance and replication. Here we use the spectinabilin clusters originated from two hosts as examples to illustrate the guidelines of using DNA assembler for cluster characterization and silent cluster activation. Such strategies offer unprecedented versatility in cluster manipulation, bypass the traditional laborious strategies to elicit pathway expression, and provide a new platform for de novo cluster assembly and genome mining for discovering new natural products.

  20. Natural Products as a Source for Antileishmanial and Antitrypanosomal Agents.

    PubMed

    Scotti, Marcus Tullius; Scotti, Luciana; Ishiki, Hamilton; Ribeiro, Frederico Fávaro; Cruz, Rayssa Marques Duarte da; Oliveira, Michelle Pedrosa de; Mendonça, Francisco Jaime Bezerra

    2016-01-01

    Natural products are compounds extracted from plants, marine organisms, fungi or bacteria. Many researches for new drugs are based on these natural molecules, mainly by beneficial effects on health, health, efficacy, and therapeutic safety. Leishmaniosis, Chagas disease and African sleeping sickness are neglected diseases caused by the Leishmania and Trypanosoma ssp. parasites. These infections mainly affect population of developing countries; they have different symptoms, and may often lead to death. The therapeutic drugs available to treat these diseases are either obsolete, toxic, or have questionable efficacy, possibly through encountering resistance. Discovery of new, safe, effective, and affordable molecules is urgently needed. Natural organisms, as marine metabolites, alkaloids, flavonoids, steroids, terpene and coumarins provide innumerable molecules with the potential to treat these diseases. This study examines studies of natural bioactive compounds as antileishmanial and antitrypanosomal agents.

  1. Hypericum perforatum treatment: effect on behaviour and neurogenesis in a chronic stress model in mice

    PubMed Central

    2011-01-01

    Background Extracts of Hypericum perforatum (St. John's wort) have been traditionally recommended for a wide range of medical conditions, in particular mild-to-moderate depression. The present study was designed to investigate the effect of Hypericum perforatum treatment in a mouse model of anxiety/depressive-like behavior, induced by chronic corticosterone administration. Methods CD1 mice were submitted to 7 weeks corticosterone administration and then behavioral tests as Open Field (OF), Novelty-Suppressed Feeding (NSF), Forced Swim Test (FST) were performed. Cell proliferation in hippocampal dentate gyrus (DG) was investigated by both 5-bromo-2'-deoxyuridine (BrdU) and doublecortin (DCX) immunohistochemistry techniques and stereological procedure was used to quantify labeled cells. Golgi-impregnation method was used to evaluate changes in dendritic spines in DG. Hypericum perforatum (30 mg/Kg) has been administered for 3 weeks and then neural development in the adult hippocampus and behavioral changes have been examined. Results The anxiety/depressive-like state due to chronic corticosterone treatment was reversed by exogenous administration of Hypericum perforatum; the proliferation of progenitor cells in mice hippocampus was significantly reduced under chronic corticosterone treatment, whereas a long term treatment with Hypericum perforatum prevented the corticosterone-induced decrease in hippocampal cell proliferation. Corticosterone-treated mice exhibited a reduced spine density that was ameliorated by Hypericum perforatum administration. Conclusion These results provide evidence of morphological adaptations occurring in mature hippocampal neurons that might underlie resilient responses to chronic stress and contribute to the therapeutic effects of chronic Hypericum perforatum treatment. PMID:21272291

  2. Oxidative stress and antioxidant response in Hypericum perforatum L. plants subjected to low temperature treatment.

    PubMed

    Skyba, Matúš; Petijová, Linda; Košuth, Ján; Koleva, Dimitrina Petrova; Ganeva, Tsveta Gancheva; Kapchina-Toteva, Veneta Mihova; Cellárová, Eva

    2012-07-01

    Extreme low temperatures cause plants multiple stresses, among which oxidative stress is presumed to be the major component affecting the resultant recovery rate. Plants of Hypericum perforatum L., which are known especially for the photodynamic activities of hypericins capable of producing reactive oxygen species under exposure to visible light, were observed to display a substantial increase and persistence in active oxygen production at least two months after recovery from cryogenic treatment. In an effort to uncover the causative mechanism, the individual contributions of wounding during explant isolation, dehydration and cold were examined by means of antioxidant profiling. The investigation revealed activation of genes coding for enzymatic antioxidant catalase and superoxide dismutase at both the transcript and protein levels. Interestingly, plants responded more to wounding than to either low-temperature associated stressor, presumably due to tissue damage. Furthermore, superoxide dismutase zymograms showed the Cu/Zn isoforms as the most responsive, directing the ROS production particularly to chloroplasts. Transmission electron microscopy revealed chloroplasts as damaged structures with substantial thylakoid ruptures. Copyright © 2012 Elsevier GmbH. All rights reserved.

  3. Mitosis-targeting natural products for cancer prevention and therapy.

    PubMed

    Rao, Chinthalapally V; Kurkjian, Carla D; Yamada, Hiroshi Y

    2012-12-01

    Mitosis is a complex process resulting in division of a cell into two daughter cells, and its failure often results in the death of the daughter cells (via apoptotic, necrotic, or proliferative/senescent death). Many chemicals that inhibit the mitotic process (anti-mitotic drugs) have proven effective for killing cancer cells in vitro and in clinical settings. Among the most studied anti-mitotic drugs are plant-origin natural products including taxanes (e.g. paclitaxel, docetaxel) and vinca alkaloids (e.g. vincristine, vinblastine), whose validated target is the spindle microtubules. With the success of these agents, efforts have been made to develop other spindle poisons as well as to improve efficacy of existing spindle poisons with structural modifications. Novel drugs and natural products that inhibit other proteins involved in mitosis (nonmicrotubule targets) have been sought in hopes of expanding available cancer-directed therapies. Recently, significant advances have been made in the understanding of mitotic mechanisms in tumor cells as well as in normal epithelial cells. These advances help us to identify and develop potential natural agents for the prevention and treatment of cancer. This review will focus on natural products that target mitotic process and/or proteins involved in mitotic progression.

  4. Discovery of Novel Antiangiogenic Marine Natural Product Scaffolds

    PubMed Central

    Ebrahim, Hassan Y.; El Sayed, Khalid A.

    2016-01-01

    Marine natural products (MNPs) are recognized for their structural complexity, diversity, and novelty. The vast majority of MNPs are pharmacologically relevant through their ability to modulate macromolecular targets underlying human diseases. Angiogenesis is a fundamental process in cancer progression and metastasis. Targeting angiogenesis through selective modulation of linked protein kinases is a valid strategy to discover novel effective tumor growth and metastasis inhibitors. An in-house marine natural products mini-library, which comprises diverse MNP entities, was submitted to the Lilly’s Open Innovation Drug Discovery platform. Accepted structures were subjected to in vitro screening to discover mechanistically novel angiogenesis inhibitors. Active hits were subjected to additional angiogenesis-targeted kinase profiling. Some natural and semisynthetic MNPs, including multiple members of the macrolide latrunculins, the macrocyclic oxaquinolizidine alkaloid araguspongine C, and the sesquiterpene quinone puupehenone, showed promising results in primary and secondary angiogenesis screening modules. These hits inhibited vascular endothelial growth factor (VEGF)-mediated endothelial tube-like formation, with minimal cytotoxicity at relevant doses. Secondary kinase profiling identified six target protein kinases, all involved in angiogenesis signaling pathways. Molecular modeling and docking experiments aided the understanding of molecular binding interactions, identification of pharmacophoric epitopes, and deriving structure-activity relationships of active hits. Marine natural products are prolific resources for the discovery of chemically and mechanistically unique selective antiangiogenic scaffolds. PMID:26978377

  5. Discovery of Novel Antiangiogenic Marine Natural Product Scaffolds.

    PubMed

    Ebrahim, Hassan Y; El Sayed, Khalid A

    2016-03-11

    Marine natural products (MNPs) are recognized for their structural complexity, diversity, and novelty. The vast majority of MNPs are pharmacologically relevant through their ability to modulate macromolecular targets underlying human diseases. Angiogenesis is a fundamental process in cancer progression and metastasis. Targeting angiogenesis through selective modulation of linked protein kinases is a valid strategy to discover novel effective tumor growth and metastasis inhibitors. An in-house marine natural products mini-library, which comprises diverse MNP entities, was submitted to the Lilly's Open Innovation Drug Discovery platform. Accepted structures were subjected to in vitro screening to discover mechanistically novel angiogenesis inhibitors. Active hits were subjected to additional angiogenesis-targeted kinase profiling. Some natural and semisynthetic MNPs, including multiple members of the macrolide latrunculins, the macrocyclic oxaquinolizidine alkaloid araguspongine C, and the sesquiterpene quinone puupehenone, showed promising results in primary and secondary angiogenesis screening modules. These hits inhibited vascular endothelial growth factor (VEGF)-mediated endothelial tube-like formation, with minimal cytotoxicity at relevant doses. Secondary kinase profiling identified six target protein kinases, all involved in angiogenesis signaling pathways. Molecular modeling and docking experiments aided the understanding of molecular binding interactions, identification of pharmacophoric epitopes, and deriving structure-activity relationships of active hits. Marine natural products are prolific resources for the discovery of chemically and mechanistically unique selective antiangiogenic scaffolds.

  6. Antitumor Activity of the Methanol Extract of Hypericum hookerianum Stem Against Ehrlich Ascites Carcinoma in Swiss Albino Mice.

    PubMed

    Dongre, Santoshkumar H; Badami, Shrishailappa; Natesan, Senthilkumar; H, Raghu Chandrashekhar

    2007-04-01

    A large number of plants belonging to the Hypericum family are known to possess strong antitumor properties. The methanol extract of H. hookerianum Wight and Arnott stem (MEHH) exhibited potent in vitro cytotoxic activity against various cancerous cell lines. In the present study, the high performance liquid chromatography (HPLC) standardized MEHH was tested for in vivo antitumor properties against Ehrlich ascites carcinoma (EAC) tumor bearing mice at 100, 200, and 400 mg/kg body weight doses given orally once daily for 14 days. The results indicate that administration of the extract not only increased the survival of animals with ascites tumor, decreased the body weight induced by the tumor burden, and reduced packed cell volume and viable tissue cell count, but also altered many hematological parameters changed during tumor progression, indicating the potent antitumor nature of the extract. Among the three doses tested, the 200 mg/kg body weight dose was found to be the most potent.

  7. Redirecting photosynthetic reducing power toward bioactive natural product synthesis.

    PubMed

    Nielsen, Agnieszka Zygadlo; Ziersen, Bibi; Jensen, Kenneth; Lassen, Lærke Münter; Olsen, Carl Erik; Møller, Birger Lindberg; Jensen, Poul Erik

    2013-06-21

    In addition to the products of photosynthesis, the chloroplast provides the energy and carbon building blocks required for synthesis of a wealth of bioactive natural products of which many have potential uses as pharmaceuticals. In the course of plant evolution, energy generation and biosynthetic capacities have been compartmentalized. Chloroplast photosynthesis provides ATP and NADPH as well as carbon sources for primary metabolism. Cytochrome P450 monooxygenases (P450s) in the endoplasmic reticulum (ER) synthesize a wide spectrum of bioactive natural products, powered by single electron transfers from NADPH. P450s are present in low amounts, and the reactions proceed relatively slowly due to limiting concentrations of NADPH. Here we demonstrate that it is possible to break the evolutionary compartmentalization of energy generation and P450-catalyzed biosynthesis, by relocating an entire P450-dependent pathway to the chloroplast and driving the pathway by direct use of the reducing power generated by photosystem I in a light-dependent manner. The study demonstrates the potential of transferring pathways for structurally complex high-value natural products to the chloroplast and directly tapping into the reducing power generated by photosynthesis to drive the P450s using water as the primary electron donor.

  8. Effects of Hypericum perforatum extract on oxaliplatin-induced neurotoxicity: in vitro evaluations.

    PubMed

    Cinci, Lorenzo; Di Cesare Mannelli, Lorenzo; Maidecchi, Anna; Mattoli, Luisa; Ghelardini, Carla

    2017-05-01

    Hypericum perforatum L. has been used for centuries as a natural remedy for the treatment of many disorders. Neuropathic pain is a common side effect of oxaliplatin-based chemotherapy and often the cause of therapy discontinuation. Thanks to its anti-inflammatory and analgesic effects, the use of H. perforatum may be a novel therapeutic strategy for neuropathy. The aim of this paper was to evaluate the effect of H. perforatum hydrophilic extract on an in vitro model of oxaliplatin-induced neurotoxicity. The antioxidant potential of extract was first evaluated in cell-free models by the thiobarbituric acid-reactive substances assay and nitro blue tetrazolium oxidation test; the ability of H. perforatum extract to reduce oxaliplatin-induced caspase-3 activity in rat astrocytes and its potential interference with the cytotoxic effects of oxaliplatin in a colorectal cancer in vitro model (HT-29 cells) were also evaluated. The extract showed a significant antioxidant effect and was able to reduce caspase-3 activity in rat astrocytes. Of note, the extract alone exerted a cytotoxic effect in HT-29 cells and did not reduce the cytotoxicity of oxaliplatin in HT-29 cells. These data suggest that H. perforatum could be used as a novel therapeutic strategy for counteracting chemotherapy-induced neuropathy.

  9. Synthesis of a potent new antimalarial through natural products conjugation

    PubMed Central

    Bruno, Michela; Trucchi, Beatrice; Monti, Diego; Romeo, Sergio; Kaiser, Marcel; Verotta, Luisella

    2013-01-01

    Three natural products have been assembled to obtain a new antimalarial hit. (+)-Usnic acid was used as scaffold to design and synthesize new products, that were tested on asexual development for P. falciparum and P. berghei. Among them, the ester of (+)-usnic acid-4-aminobutyric acid 14 with dihydroartemisinin shows considerable in vivo antimalarial activity against P. berghei in mice, similar to the synthetic drug artesunate. Compound 14 behaves as a delivery system for dihydroartemisinin and combine the effects of the endoperoxide with the redox properties of the phenolic portions of (+)-usnic acid. PMID:23307699

  10. Strain Prioritization and Genome Mining for Enediyne Natural Products

    PubMed Central

    Yan, Xiaohui; Ge, Huiming; Huang, Tingting; Hindra; Yang, Dong; Teng, Qihui; Crnovčić, Ivana; Li, Xiuling; Rudolf, Jeffrey D.; Lohman, Jeremy R.; Gansemans, Yannick; Zhu, Xiangcheng; Huang, Yong; Zhao, Li-Xing; Jiang, Yi; Van Nieuwerburgh, Filip; Rader, Christoph

    2016-01-01

    ABSTRACT The enediyne family of natural products has had a profound impact on modern chemistry, biology, and medicine, and yet only 11 enediynes have been structurally characterized to date. Here we report a genome survey of 3,400 actinomycetes, identifying 81 strains that harbor genes encoding the enediyne polyketide synthase cassettes that could be grouped into 28 distinct clades based on phylogenetic analysis. Genome sequencing of 31 representative strains confirmed that each clade harbors a distinct enediyne biosynthetic gene cluster. A genome neighborhood network allows prediction of new structural features and biosynthetic insights that could be exploited for enediyne discovery. We confirmed one clade as new C-1027 producers, with a significantly higher C-1027 titer than the original producer, and discovered a new family of enediyne natural products, the tiancimycins (TNMs), that exhibit potent cytotoxicity against a broad spectrum of cancer cell lines. Our results demonstrate the feasibility of rapid discovery of new enediynes from a large strain collection. PMID:27999165

  11. Marine natural products: a new wave of drugs?

    PubMed Central

    Montaser, Rana; Luesch, Hendrik

    2011-01-01

    The largely unexplored marine world that presumably harbors the most biodiversity may be the vastest resource to discover novel ‘validated’ structures with novel modes of action that cover biologically relevant chemical space. Several challenges, including the supply problem and target identification, need to be met for successful drug development of these often complex molecules; however, approaches are available to overcome the hurdles. Advances in technologies such as sampling strategies, nanoscale NMR for structure determination, total chemical synthesis, fermentation and biotechnology are all crucial to the success of marine natural products as drug leads. We illustrate the high degree of innovation in the field of marine natural products, which in our view will lead to a new wave of drugs that flow into the market and pharmacies in the future. PMID:21882941

  12. Natural Product Compounds with Aromatase Inhibitory Activity: An Update

    PubMed Central

    Balunas, Marcy J.; Kinghorn, A. Douglas

    2010-01-01

    Several synthetic aromatase inhibitors are currently in clinical use for the treatment of postmenopausal women with hormone-receptor positive breast cancer. However, these treatments may lead to untoward side effects and so a search for new aromatase inhibitors continues, especially those for which the activity is promoter-specific, targeting the breast-specific promoters I.3 and II. Recently, numerous natural product compounds have been found to inhibit aromatase in non-cellular, cellular, and in vivo studies. These investigations, covering the last two years, as well as additional studies that have focused on the evaluation of natural product compounds as promoter-specific aromatase inhibitors or as aromatase inducers, are described in this review. PMID:20635310

  13. Dietary Natural Products for Prevention and Treatment of Breast Cancer

    PubMed Central

    Li, Ya; Li, Sha; Meng, Xiao; Zhang, Jiao-Jiao

    2017-01-01

    Breast cancer is the most common cancer among females worldwide. Several epidemiological studies suggested the inverse correlation between the intake of vegetables and fruits and the incidence of breast cancer. Substantial experimental studies indicated that many dietary natural products could affect the development and progression of breast cancer, such as soy, pomegranate, mangosteen, citrus fruits, apple, grape, mango, cruciferous vegetables, ginger, garlic, black cumin, edible macro-fungi, and cereals. Their anti-breast cancer effects involve various mechanisms of action, such as downregulating ER-α expression and activity, inhibiting proliferation, migration, metastasis and angiogenesis of breast tumor cells, inducing apoptosis and cell cycle arrest, and sensitizing breast tumor cells to radiotherapy and chemotherapy. This review summarizes the potential role of dietary natural products and their major bioactive components in prevention and treatment of breast cancer, and special attention was paid to the mechanisms of action. PMID:28698459

  14. Potential anti-inflammatory natural products from marine algae.

    PubMed

    Fernando, I P Shanura; Nah, Jae-Woon; Jeon, You-Jin

    2016-12-01

    Inflammatory diseases have become one of the leading causes of health issue throughout the world, having a considerable influence on healthcare costs. With the emerging developments in natural product, synthetic and combinatorial chemistry, a notable success has been achieved in discovering natural products and their synthetic structural analogs with anti-inflammatory activity. However, many of these therapeutics have indicated detrimental side effects upon prolonged usage. Marine algae have been identified as an underexplored reservoir of unique anti-inflammatory compounds. These include polyphenols, sulfated polysaccharides, terpenes, fatty acids, proteins and several other bioactives. Consumption of these marine algae could provide defense against the pathophysiology of many chronic inflammatory diseases. With further investigation, algal anti-inflammatory phytochemicals have the potential to be used as therapeutics or in the synthesis of structural analogs with profound anti-inflammatory activity with reduced side effects. The current review summarizes the latest knowledge about the potential anti-inflammatory compounds discovered from marine algae.

  15. Dietary Natural Products for Prevention and Treatment of Breast Cancer.

    PubMed

    Li, Ya; Li, Sha; Meng, Xiao; Gan, Ren-You; Zhang, Jiao-Jiao; Li, Hua-Bin

    2017-07-08

    Breast cancer is the most common cancer among females worldwide. Several epidemiological studies suggested the inverse correlation between the intake of vegetables and fruits and the incidence of breast cancer. Substantial experimental studies indicated that many dietary natural products could affect the development and progression of breast cancer, such as soy, pomegranate, mangosteen, citrus fruits, apple, grape, mango, cruciferous vegetables, ginger, garlic, black cumin, edible macro-fungi, and cereals. Their anti-breast cancer effects involve various mechanisms of action, such as downregulating ER-α expression and activity, inhibiting proliferation, migration, metastasis and angiogenesis of breast tumor cells, inducing apoptosis and cell cycle arrest, and sensitizing breast tumor cells to radiotherapy and chemotherapy. This review summarizes the potential role of dietary natural products and their major bioactive components in prevention and treatment of breast cancer, and special attention was paid to the mechanisms of action.

  16. Metal-Catalyzed Asymmetric Michael Addition in Natural Product Synthesis.

    PubMed

    Hui, Chunngai; Pu, Fan; Xu, Jing

    2016-12-19

    Asymmetric catalysis for chiral compound synthesis is a rapidly growing field in modern organic chemistry. Asymmetric catalytic processes have been indispensable for the synthesis of enantioselective materials to meet demands from various fields. Michael addition has been used extensively for the construction of C-C bonds under mild conditions. With the discovery and development of organo- and metal-catalyzed asymmetric Michael additions, the synthesis of enantioselective and/or diastereoselective Michael adducts has become possible and increasingly prevalent in the literature. In particular, metal-catalyzed asymmetric Michael addition has been employed as a key reaction in natural product synthesis for the construction of contiguous quaternary stereogenic center(s), which is still a difficult task in organic synthesis. Previously reported applications of metal-catalyzed asymmetric Michael additions in natural product synthesis are presented here and discussed in depth.

  17. Applications of natural zeolites on agriculture and food production.

    PubMed

    Eroglu, Nazife; Emekci, Mevlut; Athanassiou, Christos

    2017-03-14

    Zeolites are crystalline hydrated aluminosilicates with remarkable physical and chemical properties including losing and receiving water in a reverse way, adsorbing molecules that act as molecular sieves, and replacing their constituent cations without structural change. Commercial production of natural zeolites has accelerated during last fifty years. The Structure Commission of the International Zeolite Association recorded more than 200 zeolites which currently include more than 40 naturally occurring zeolites. Recent findings supported their role in stored-pest management as inert dust applications, pesticide and fertilizer carriers, soil amendments, animal feed additives, mycotoxin binders and food packaging materials. There are many advantages of inert dust application including low cost, non-neurotoxic action, low mammalian toxicity and safety for human consumption. Latest consumer trends and government protocols have shifted toward organic origin materials to replace synthetic chemical products. In the current review, we summarized most of the main uses of zeolites in food and agruculture, with specific paradigms that illustrate their important role.

  18. Systems Biology Approaches to Understand Natural Products Biosynthesis.

    PubMed

    Licona-Cassani, Cuauhtemoc; Cruz-Morales, Pablo; Manteca, Angel; Barona-Gomez, Francisco; Nielsen, Lars K; Marcellin, Esteban

    2015-01-01

    Actinomycetes populate soils and aquatic sediments that impose biotic and abiotic challenges for their survival. As a result, actinomycetes metabolism and genomes have evolved to produce an overwhelming diversity of specialized molecules. Polyketides, non-ribosomal peptides, post-translationally modified peptides, lactams, and terpenes are well-known bioactive natural products with enormous industrial potential. Accessing such biological diversity has proven difficult due to the complex regulation of cellular metabolism in actinomycetes and to the sparse knowledge of their physiology. The past decade, however, has seen the development of omics technologies that have significantly contributed to our better understanding of their biology. Key observations have contributed toward a shift in the exploitation of actinomycete's biology, such as using their full genomic potential, activating entire pathways through key metabolic elicitors and pathway engineering to improve biosynthesis. Here, we review recent efforts devoted to achieving enhanced discovery, activation, and manipulation of natural product biosynthetic pathways in model actinomycetes using genome-scale biological datasets.

  19. Synthesis of tetrodotoxin, a classic but still fascinating natural product.

    PubMed

    Nishikawa, Toshio; Isobe, Minoru

    2013-06-01

    Tetrodotoxin, a toxic principle of puffer fish intoxication, is one of the most famous marine natural products due to its densely functionalized structure and potent toxicity. Despite its small molecular size (MW 319 g mol⁻¹), tetrodotoxin has long been well known as a formidable molecule in natural product synthesis. We have devoted more than twenty years to developing synthetic strategies for this molecule, resulting in the preparation of a variety of analogues of tetrodotoxin for biological experiments. This account describes a brief history of tetrodotoxin research and an overview of our synthetic efforts toward tetrodotoxin with the underlying logic and strategy. Copyright © 2013 The Chemical Society of Japan and Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Optimizing patient care with "natural" products: treatment of hyperpigmentation.

    PubMed

    Woolery-Lloyd, Heather; Friedman, Adam

    2009-06-01

    Patients with skin of color suffer from different cutaneous issues when compared with skin of light complexion, and therefore management of the former must be representative of these variations. The most common pigmentary complaints in patients with skin of color are post-inflammatory hyperpigmentation, melasma and sun-induced hyperpigmentation. Often, patients with darker skin will turn to naturally occurring ingredients over synthetic analogues both to satisfy cultural preferences and to limit potential adverse effects that have been tied to synthetics. Science-based natural products can offer an attractive adjunct to conventional therapies that treat melasma, post-inflammatory hyperpigmentaion, and other dyschromias. Increasing data on the biological effects and the efficacy of natural therapies support the use of these complementary therapies in treating hyperpigmentation.

  1. Botulinum neurotoxin A protease: discovery of natural product exosite inhibitors.

    PubMed

    Silhár, Peter; Capková, Katerina; Salzameda, Nicholas T; Barbieri, Joseph T; Hixon, Mark S; Janda, Kim D

    2010-03-10

    A new mechanistic class of BoNT/A zinc metalloprotease inhibitors, from Echinacea, exemplified by the natural product d-chicoric acid (I1) is disclosed. A detailed evaluation of chicoric acid's mechanism of inhibition reveals that the inhibitor binds to an exosite, displays noncompetitive partial inhibition, and is synergistic with a competitive active site inhibitor when used in combination. Other components found in Echinacea, I3 and I4, were also inhibitors of the protease.

  2. Cytotoxic Natural Products from Marine Sponge-Derived Microorganisms

    PubMed Central

    Zhang, Huawei; Zhao, Ziping; Wang, Hong

    2017-01-01

    A growing body of evidence indicates that marine sponge-derived microbes possess the potential ability to make prolific natural products with therapeutic effects. This review for the first time provides a comprehensive overview of new cytotoxic agents from these marine microbes over the last 62 years from 1955 to 2016, which are assorted into seven types: terpenes, alkaloids, peptides, aromatics, lactones, steroids, and miscellaneous compounds. PMID:28287431

  3. Mass spectrometry of Natural Products: Current, Emerging and Future Technologies

    PubMed Central

    Bouslimani, Amina; Sanchez, Laura M; Garg, Neha; Dorrestein, Pieter C

    2014-01-01

    Although mass spectrometry is a century old technology, we are entering into an exciting time for the analysis of molecular information directly from complex biological systems. In this viewpoint article, we highlight emerging mass spectrometric methods and tools used by the natural product community and give a perspective of future directions where the mass spectrometry field is migrating towards over the next decade. PMID:24801551

  4. Effect of Hypericum perforatum Extract in an Experimental Model of Binge Eating in Female Rats.

    PubMed

    Micioni Di Bonaventura, Maria Vittoria; Vitale, Giovanni; Massi, Maurizio; Cifani, Carlo

    2012-01-01

    Purpose. The present study evaluated the effect of Hypericum perforatum dry extract in an experimental model of binge eating (BE). Methods. BE for highly palatable food (HPF) was evoked in female rats by three 8-day cycles of food restriction/re-feeding and acute stress on the test day (day 25). Stress was induced by preventing access to HPF for 15 min, while rats were able to see and smell it. Hypericum perforatum dry extract was given by gavage. Results. Only rats exposed to both food restrictions and stress exhibited BE. The doses of 250 and 500 mg/kg of Hypericum perforatum extract significantly reduced the BE episode, while 125 mg/kg was ineffective. The same doses did not affect HPF intake in the absence of BE. The dose of 250 mg/kg did not significantly modify stress-induced increase in serum corticosterone levels, suggesting that the effect on BE is not due to suppression of the stress response The combined administration of 125 mg/kg of Hypericum perforatum together with Salidroside, active principle of Rhodiola rosea, produced a synergic effect on BE. Conclusions. The present results indicate for the first time that Hypericum perforatum extracts may have therapeutic properties in bingeing-related eating disorders.

  5. Effect of Hypericum perforatum Extract in an Experimental Model of Binge Eating in Female Rats

    PubMed Central

    Micioni Di Bonaventura, Maria Vittoria; Vitale, Giovanni; Massi, Maurizio; Cifani, Carlo

    2012-01-01

    Purpose. The present study evaluated the effect of Hypericum perforatum dry extract in an experimental model of binge eating (BE). Methods. BE for highly palatable food (HPF) was evoked in female rats by three 8-day cycles of food restriction/re-feeding and acute stress on the test day (day 25). Stress was induced by preventing access to HPF for 15 min, while rats were able to see and smell it. Hypericum perforatum dry extract was given by gavage. Results. Only rats exposed to both food restrictions and stress exhibited BE. The doses of 250 and 500 mg/kg of Hypericum perforatum extract significantly reduced the BE episode, while 125 mg/kg was ineffective. The same doses did not affect HPF intake in the absence of BE. The dose of 250 mg/kg did not significantly modify stress-induced increase in serum corticosterone levels, suggesting that the effect on BE is not due to suppression of the stress response The combined administration of 125 mg/kg of Hypericum perforatum together with Salidroside, active principle of Rhodiola rosea, produced a synergic effect on BE. Conclusions. The present results indicate for the first time that Hypericum perforatum extracts may have therapeutic properties in bingeing-related eating disorders. PMID:22997570

  6. In vitro receptor binding and enzyme inhibition by Hypericum perforatum extract.

    PubMed

    Cott, J M

    1997-09-01

    Hypericum perforatum L. Hypericaceae (St. John's wort), has been used since the time of ancient Greece for its many medicinal properties. Modern usage is still quite diverse and includes wound healing, kidney and lung ailments, insomnia and depression. This plant has been known to contain a red pigment, hypericin, and similar compounds, which have been assumed to be the primary active constituent(s) in this plant genus. A crude Hypericum extract was tested in a battery of 39 in vitro receptor assays, and two enzyme assays. A sample of pure hypericin was also tested. Hypericin had affinity only for NMDA receptors while the crude extract had significant receptor affinity for adenosine (nonspecific), GABAA, GABAB, benzodiazepine, inositol triphosphate, and monoamine oxidase (MAO) A and B. With the exception of GABAA and GABAB, the concentrations of Hypericum exact required for these in vitro activities are unlikely to be attained after oral administration in whole animals or humans. These data are consistent with recent pharmacologic evidence suggesting that other constituents of this plant may be of greater importance for the reported psychotherapeutic activity. Alternative pharmacologic mechanisms for Hypericum's antidepressant activity are critically reviewed and the possible importance of GABA receptor binding in the pharmacology of Hypericum is highlighted. Some of these results have been previously reported.

  7. An Update on Natural Products with Carbonic Anhydrase Inhibitory Activity.

    PubMed

    Karioti, Anastasia; Carta, Fabrizio; Supuran, Claudiu T

    2016-01-01

    Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological processes. They represent a typical example of enzyme convergent evolution, as six genetically unrelated families of such enzymes were described so far. It is more than 70 years that synthetic compounds, mainly sulfonamides, have been used in clinical practice as diuretics and systemic acting antiglaucoma drugs. Recent studies using natural product libraries and isolated constituents from natural sources (such as fungi and plants) have disclosed novel chemotypes possessing carbonic anhydrase inhibition activities. These natural sources offer new opportunities in the search for new and more effective carbonic anhydrase inhibitors, and may serve as new leads for the design and development of future drugs. This review will discuss the most recent advances in the search of naturally occurring products and their synthetic derivatives that inhibit the CAs and their mechanisms of action at molecular level. Plant extracts are not considered in the present review.

  8. Rationale for a natural products approach to herbicide discovery.

    PubMed

    Dayan, Franck E; Owens, Daniel K; Duke, Stephen O

    2012-04-01

    Weeds continue to evolve resistance to all the known modes of herbicidal action, but no herbicide with a new target site has been commercialized in nearly 20 years. The so-called 'new chemistries' are simply molecules belonging to new chemical classes that have the same mechanisms of action as older herbicides (e.g. the protoporphyrinogen-oxidase-inhibiting pyrimidinedione saflufenacil or the very-long-chain fatty acid elongase targeting sulfonylisoxazoline herbicide pyroxasulfone). Therefore, the number of tools to manage weeds, and in particular those that can control herbicide-resistant weeds, is diminishing rapidly. There is an imminent need for truly innovative classes of herbicides that explore chemical spaces and interact with target sites not previously exploited by older active ingredients. This review proposes a rationale for a natural-products-centered approach to herbicide discovery that capitalizes on the structural diversity and ingenuity afforded by these biologically active compounds. The natural process of extended-throughput screening (high number of compounds tested on many potential target sites over long periods of times) that has shaped the evolution of natural products tends to generate molecules tailored to interact with specific target sites. As this review shows, there is generally little overlap between the mode of action of natural and synthetic phytotoxins, and more emphasis should be placed on applying methods that have proved beneficial to the pharmaceutical industry to solve problems in the agrochemical industry.

  9. Novel fermentation processes for manufacturing plant natural products.

    PubMed

    Zhou, Jingwen; Du, Guocheng; Chen, Jian

    2014-02-01

    Microbial production of plant natural products (PNPs), such as terpenoids, flavonoids from renewable carbohydrate feedstocks offers sustainable and economically attractive alternatives to their petroleum-based production. Rapid development of metabolic engineering and synthetic biology of microorganisms shows many advantages to replace the current extraction of these useful high price chemicals from plants. Although few of them were actually applied on a large scale for PNPs production, continuous research on these high-price chemicals and the rapid growing global market of them, show the promising future for the production of these PNPs by microorganisms with a more economic and environmental friendly way. Introduction of novel pathways and optimization of the native cellular processes by metabolic engineering of microorganisms for PNPs production are rapidly expanding its range of cell-factory applications. Here we review recent progress in metabolic engineering of microorganisms for the production of PNPs. Besides, factors restricting the yield improvement and application of lab-scale achievements to industrial applications have also been discussed.

  10. Natural products and colon cancer: current status and future prospects

    PubMed Central

    Rajamanickam, Subapriya; Agarwal, Rajesh

    2008-01-01

    Carcinogenesis is a multistage process consisting of initiation, promotion and progression phases. Thus, the multistage sequence of events has many phases for prevention and intervention. Chemoprevention, a novel approach for controlling cancer, involves the use of specific natural products or synthetic chemical agents to reverse, suppress or prevent premalignancy before the development of invasive cancer. Several natural products, such as, grains, nuts, cereals, spices, fruits, vegetables, beverages, medicinal plants and herbs and their various phytochemical constituents including, phenolics, flavonoids, carotenoids, alkaloids, nitrogen containing as well as organosulfur compounds confer protective effects against wide range of cancers including colon cancer. Since diet has an important role in the etiology of colon cancer, dietary chemoprevention received attention for colon cancer prevention. However, identification of an agent with chemopreventive potential requires in vitro studies, efficacy and toxicity studies in animal models before embarking on human clinical trials. A brief introduction about colon cancer and the role of some recent natural products in colon cancer chemoprevention with respect to multiple molecular mechanisms in various in vitro, in vivo and clinical studies are described in this review. PMID:19884979

  11. Automated genome mining of ribosomal peptide natural products

    SciTech Connect

    Mohimani, Hosein; Kersten, Roland; Liu, Wei; Wang, Mingxun; Purvine, Samuel O.; Wu, Si; Brewer, Heather M.; Pasa-Tolic, Ljiljana; Bandeira, Nuno; Moore, Bradley S.; Pevzner, Pavel A.; Dorrestein, Pieter C.

    2014-07-31

    Ribosomally synthesized and posttranslationally modified peptides (RiPPs), especially from microbial sources, are a large group of bioactive natural products that are a promising source of new (bio)chemistry and bioactivity (1). In light of exponentially increasing microbial genome databases and improved mass spectrometry (MS)-based metabolomic platforms, there is a need for computational tools that connect natural product genotypes predicted from microbial genome sequences with their corresponding chemotypes from metabolomic datasets. Here, we introduce RiPPquest, a tandem mass spectrometry database search tool for identification of microbial RiPPs and apply it for lanthipeptide discovery. RiPPquest uses genomics to limit search space to the vicinity of RiPP biosynthetic genes and proteomics to analyze extensive peptide modifications and compute p-values of peptide-spectrum matches (PSMs). We highlight RiPPquest by connection of multiple RiPPs from extracts of Streptomyces to their gene clusters and by the discovery of a new class III lanthipeptide, informatipeptin, from Streptomyces viridochromogenes DSM 40736 as the first natural product to be identified in an automated fashion by genome mining. The presented tool is available at cy-clo.ucsd.edu.

  12. Bioactive natural products with anti-herpes simplex virus properties.

    PubMed

    Hassan, Sherif T S; Masarčíková, Radka; Berchová, Kateřina

    2015-10-01

    In this review, we highlight and summarise the most promising extracts, fractions and pure compounds as potential anti-herpes simplex virus (HSV) agents derived from microorganisms, marine organisms, fungi, animals and plants. The role of natural products in the development of anti-HSV drugs will be discussed. Herpes simplex viruses (HSV-1 and -2) are common human pathogens that remain a serious threat to human health. In recent years, a great interest has been devoted to the search for integrated management of HSV infections. Acyclovir and related nucleoside analogues have been licensed for the therapy that target viral DNA polymerase. Although these drugs are currently effective against HSV infections, the intensive use of these drugs has led to the problem of drug-resistant strains. Therefore, the search for new sources to develop new antiherpetic agents has gained major priority to overcome the problem. Natural products as potential, new anti-HSV drugs provide several advantages such as reduced side effects, less resistance, low toxicity and various mechanisms of action. This paper aims to provide an overview of natural products that possess antiviral activity against HSV. © 2015 Royal Pharmaceutical Society.

  13. Mining and engineering natural-product biosynthetic pathways.

    PubMed

    Wilkinson, Barrie; Micklefield, Jason

    2007-07-01

    Natural products continue to fulfill an important role in the development of therapeutic agents. In addition, with the advent of chemical genetics and high-throughput screening platforms, these molecules have become increasingly valuable as tools for interrogating fundamental aspects of biological systems. To access the vast portion of natural-product structural diversity that remains unexploited for these and other applications, genome mining and microbial metagenomic approaches are proving particularly powerful. When these are coupled with recombineering and related genetic tools, large biosynthetic gene clusters that remain intractable or cryptic in the native host can be more efficiently cloned and expressed in a suitable heterologous system. For lead optimization and the further structural diversification of natural-product libraries, combinatorial biosynthetic engineering has also become indispensable. However, our ability to rationally redesign biosynthetic pathways is often limited by our lack of understanding of the structure, dynamics and interplay between the many enzymes involved in complex biosynthetic pathways. Despite this, recent structures of fatty acid synthases should allow a more accurate prediction of the likely architecture of related polyketide synthase and nonribosomal peptide synthetase multienzymes.

  14. Xanthone biosynthesis in Hypericum perforatum cells provides antioxidant and antimicrobial protection upon biotic stress.

    PubMed

    Franklin, Gregory; Conceição, Luis F R; Kombrink, Erich; Dias, Alberto C P

    2009-01-01

    Xanthone production in Hypericum perforatum (HP) suspension cultures in response to elicitation by Agrobacterium tumefaciens co-cultivation has been studied. RNA blot analyses of HP cells co-cultivated with A. tumefaciens have shown a rapid up-regulation of genes encoding important enzymes of the general phenylpropanoid pathway (PAL, phenylalanine ammonia lyase and 4CL, 4-coumarate:CoA ligase) and xanthone biosynthesis (BPS, benzophenone synthase). Analyses of HPLC chromatograms of methanolic extracts of control and elicited cells (HP cells that were co-cultivated for 24h with A. tumefaciens) have revealed a 12-fold increase in total xanthone concentration and also the emergence of many xanthones after elicitation. Methanolic extract of elicited cells exhibited significantly higher antioxidant and antimicrobial competence than the equivalent extract of control HP cells indicating that these properties have been significantly increased in HP cells after elicitation. Four major de novo synthesized xanthones have been identified as 1,3,6,7-tetrahydroxy-8-prenyl xanthone, 1,3,6,7-tetrahydroxy-2-prenyl xanthone, 1,3,7-trihydroxy-6-methoxy-8-prenyl xanthone and paxanthone. Antioxidant and antimicrobial characterization of these de novo xanthones have revealed that xanthones play dual function in plant cells during biotic stress: (1) as antioxidants to protect the cells from oxidative damage and (2) as phytoalexins to impair the pathogen growth.

  15. Bioactive properties and functional constituents of Hypericum androsaemum L.: A focus on the phenolic profile.

    PubMed

    Jabeur, Inés; Tobaldini, Flávia; Martins, Natália; Barros, Lillian; Martins, Ivone; Calhelha, Ricardo C; Henriques, Mariana; Silva, Sónia; Achour, Lotfi; Santos-Buelga, Celestino; Ferreira, Isabel C F R

    2016-11-01

    Hypericum androsaemum L. ethanol:water extract acted as a lipid peroxidation inhibitor and free radical scavenger. A marked inhibition of the growth of breast, lung, cervical and hepatocellular human carcinoma cell lines was also observed, whereas no toxicity was shown against non-tumor porcine liver cells (>400μg/mL). The extract was also effective in inhibiting nitric oxide production, as an indicator of the anti-inflammatory potential. The anti-Candida effects varied among different strains of the same species, C. glabrata and C. tropicalis being the most sensible species with an effect directly related with the extract concentrations tested. A significant anti-biofilm formation potential was also observed, namely for C. glabrata and C. tropicalis (biofilm reduction >90%). 5-O-Caffeoylquinic and 3-O-caffeoylquinic acids were the most abundant phenolic compounds identified in the extract, and might be related with the observed bioactive effects. Nevertheless, future studies should be carried out to obtain dose-response curves of the isolated active compounds, in order to perform further pre-clinically testing to quantify the presence of the most active compounds in the extract. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Antibacterial and cytotoxic activity of prenylated bicyclic acylphloroglucinol derivatives from Hypericum amblycalyx.

    PubMed

    Winkelmann, Karin; San, Metin; Kypriotakis, Zacharias; Skaltsa, Helen; Bosilij, Blazenka; Heilmann, Jörg

    2003-01-01

    Two new bicyclic acylphloroglucinol derivatives, hypercalyxone A (1-[5,7-dihydroxy-2-methyl-3-(3-methyl-but-2-enyl)-2-(4-methyl-pent-3-enyl)-chroman-8-yl]-2-methyl-propan-1-one, 1) and B (1-[5,7-dihydroxy-2-methyl-3-(3-methyl-but-2-enyl)-2-(4-methyl-pent-3-enyl)-chroman-8-yl]-2-methyl-butan-1-one, 2), have been isolated from the petroleum ether extract of the aerial parts of Hypericum amblycalyx, together with two further compounds (1-[5,7-dihydroxy-2-methyl-2-(4-methyl-pent-3-enyl)-chroman-8-yl]-2-methyl-propan-1-one, 3 and 1-[5,7-dihydroxy-2-methyl-2-(4-methyl-pent-3-enyl)-chroman-8-yl]-2-methyl-butan-1-one, 4), which have been described only as semi-synthetic products. In addition, the known triterpene lup-20(29)-en-3-one was obtained. Structure elucidation was based on 1D and 2D NMR studies, as well as on data derived from mass spectrometry. The four acylphloroglucinol derivatives were evaluated for their cytotoxic and antibacterial activity. All compounds showed moderate cytotoxic activity against KB and Jurkat T cancer cells. Especially compounds 3 and 4 exhibited a strong antibacterial activity against different Gram-positive strains.

  17. Lanthanum rather than cadmium induces oxidative stress and metabolite changes in Hypericum perforatum.

    PubMed

    Babula, Petr; Klejdus, Bořivoj; Kovacik, Jozef; Hedbavny, Josef; Hlavna, Marián

    2015-04-09

    Physiology, oxidative stress and production of metabolites in Hypericum perforatum exposed to moderate Cd and/or La concentration (10 μM) were studied. La evoked increase in reactive oxygen species, malondialdehyde and proline but suppressed growth, tissue water content, glutathione, ascorbic acid and affected mineral nutrient contents more than Cd while the impact of Cd+La was not synergistic. Similar trend was observed at the level of superoxide dismutase gene expression. Shoot Cd amount increased in Cd+La while only root La increased in the same treatment. Extensive quantification of secondary metabolites revealed that La affected phenolic acids more pronouncedly than Cd in shoots and roots. Flavonols were suppressed by La that could contribute to the appearance of oxidative damage. Procyanidins increased in response to La in the shoots but decreased in the roots. Metabolic responses in Cd+La treatment resembled those of La treatment (almost identically in the roots). Phenylalanine ammonia-lyase activity was mainly suppressed by La. The presence of La also depleted amount of hypericin and expression of its putative gene (hyp-1) showed similar trend but accumulation of hyperforin increased under Cd or La excess. Clear differences in the stem and root anatomy in response to Cd or La were also found. Overall, H. perforatum is La-sensitive species and rather Cd ameliorated negative impact of La.

  18. Molecular Cloning and Characterization of a Xanthone Prenyltransferase from Hypericum calycinum Cell Cultures.

    PubMed

    Fiesel, Tobias; Gaid, Mariam; Müller, Andreas; Bartels, Joana; El-Awaad, Islam; Beuerle, Till; Ernst, Ludger; Behrends, Sönke; Beerhues, Ludger

    2015-08-27

    In plants, prenylation of metabolites is widely distributed to generate compounds with efficient defense potential and distinct pharmacological activities profitable to human health. Prenylated compounds are formed by members of the prenyltransferase (PT) superfamily, which catalyze the addition of prenyl moieties to a variety of acceptor molecules. Cell cultures of Hypericum calycinum respond to elicitor treatment with the accumulation of the prenylated xanthone hyperxanthone E. A cDNA encoding a membrane-bound PT (HcPT) was isolated from a subtracted cDNA library and transcript preparations of H. calycinum. An increase in the HcPT transcript level preceded hyperxanthone E accumulation in cell cultures of H. calycinum treated with elicitor. The HcPT cDNA was functionally characterized by expression in baculovirus-infected insect cells. The recombinant enzyme catalyzed biosynthesis of 1,3,6,7-tetrahydroxy-8-prenylxanthone through regiospecific C-8 prenylation of 1,3,6,7-tetrahydroxyxanthone, indicating its involvement in hyperxanthone E formation. The enzymatic product shared significant structural features with the previously reported cholinesterase inhibitor γ-mangostin. Thus, our findings may offer a chance for semisynthesis of new active agents to be involved in the treatment of Alzheimer's disease.

  19. Natural gas production problems : solutions, methodologies, and modeling.

    SciTech Connect

    Rautman, Christopher Arthur; Herrin, James M.; Cooper, Scott Patrick; Basinski, Paul M.; Olsson, William Arthur; Arnold, Bill Walter; Broadhead, Ronald F.; Knight, Connie D.; Keefe, Russell G.; McKinney, Curt; Holm, Gus; Holland, John F.; Larson, Rich; Engler, Thomas W.; Lorenz, John Clay

    2004-10-01

    Natural gas is a clean fuel that will be the most important domestic energy resource for the first half the 21st centtuy. Ensuring a stable supply is essential for our national energy security. The research we have undertaken will maximize the extractable volume of gas while minimizing the environmental impact of surface disturbances associated with drilling and production. This report describes a methodology for comprehensive evaluation and modeling of the total gas system within a basin focusing on problematic horizontal fluid flow variability. This has been accomplished through extensive use of geophysical, core (rock sample) and outcrop data to interpret and predict directional flow and production trends. Side benefits include reduced environmental impact of drilling due to reduced number of required wells for resource extraction. These results have been accomplished through a cooperative and integrated systems approach involving industry, government, academia and a multi-organizational team within Sandia National Laboratories. Industry has provided essential in-kind support to this project in the forms of extensive core data, production data, maps, seismic data, production analyses, engineering studies, plus equipment and staff for obtaining geophysical data. This approach provides innovative ideas and technologies to bring new resources to market and to reduce the overall environmental impact of drilling. More importantly, the products of this research are not be location specific but can be extended to other areas of gas production throughout the Rocky Mountain area. Thus this project is designed to solve problems associated with natural gas production at developing sites, or at old sites under redevelopment.

  20. Enhancement of dimethylsulfide production by anoxic stress in natural seawater

    NASA Astrophysics Data System (ADS)

    Omori, Yuko; Tanimoto, Hiroshi; Inomata, Satoshi; Wada, Shigeki; Thume, Kathleen; Pohnert, Georg

    2015-05-01

    Dimethylsulfide (DMS) is produced by phytoplankton in the ocean and plays an important role in biogeochemical cycles and climate system of the Earth. Previous field studies reported a possible relationship between DMS enhancement and anoxic condition, although the governing processes are still to be identified. Here we show the first direct evidence for the enhancement of DMS production by natural planktonic assemblages caused by anoxic stress. Under the anoxic condition, DMS production was considerably enhanced and DMS bacterial consumption was inhibited, resulting in an eightfold higher rate of gross DMS production than that under the oxic condition. Our results demonstrated that anoxic stress is one of important "environmental factors" in the marine DMS dynamics, suggesting the possible global importance due to ubiquity of anoxic conditions in the coastal oceans. This process would become more important in the future due to expansion of coastal hypoxic and anoxic zones by global warming.

  1. Cinnamate:CoA Ligase Initiates the Biosynthesis of a Benzoate-Derived Xanthone Phytoalexin in Hypericum calycinum Cell Cultures1[W][OA

    PubMed Central

    Gaid, Mariam M.; Sircar, Debabrata; Müller, Andreas; Beuerle, Till; Liu, Benye; Ernst, Ludger; Hänsch, Robert; Beerhues, Ludger

    2012-01-01

    Although a number of plant natural products are derived from benzoic acid, the biosynthesis of this structurally simple precursor is poorly understood. Hypericum calycinum cell cultures accumulate a benzoic acid-derived xanthone phytoalexin, hyperxanthone E, in response to elicitor treatment. Using a subtracted complementary DNA (cDNA) library and sequence information about conserved coenzyme A (CoA) ligase motifs, a cDNA encoding cinnamate:CoA ligase (CNL) was isolated. This enzyme channels metabolic flux from the general phenylpropanoid pathway into benzenoid metabolism. HcCNL preferred cinnamic acid as a substrate but failed to activate benzoic acid. Enzyme activity was strictly dependent on the presence of Mg2+ and K+ at optimum concentrations of 2.5 and 100 mm, respectively. Coordinated increases in the Phe ammonia-lyase and HcCNL transcript levels preceded the accumulation of hyperxanthone E in cell cultures of H. calycinum after the addition of the elicitor. HcCNL contained a carboxyl-terminal type 1 peroxisomal targeting signal made up by the tripeptide Ser-Arg-Leu, which directed an amino-terminal reporter fusion to the peroxisomes. Masking the targeting signal by carboxyl-terminal reporter fusion led to cytoplasmic localization. A phylogenetic tree consisted of two evolutionarily distinct clusters. One cluster was formed by CoA ligases related to benzenoid metabolism, including HcCNL. The other cluster comprised 4-coumarate:CoA ligases from spermatophytes, ferns, and mosses, indicating divergence of the two clades prior to the divergence of the higher plant lineages. PMID:22992510

  2. Anti-proliferative and anti-migration effects of Polish propolis combined with Hypericum perforatum L. on glioblastoma multiforme cell line U87MG.

    PubMed

    Borawska, Maria H; Naliwajko, Sylwia K; Moskwa, Justyna; Markiewicz-Żukowska, Renata; Puścion-Jakubik, Anna; Soroczyńska, Jolanta

    2016-09-20

    Propolis and Hypericum perforatum L. are natural products which contain many active compounds and have numerous beneficial effects, including an antitumor effect. Gliobmastoma multiforme (GBM) is a common primary brain tumor with poor prognosis and limited treatment options. In this study, the effect of propolis (EEP) combined with H. perforatum L. (HPE) on glioblastoma cell line U87MG was investigated for the first time. Anti-proliferative activity of EEP, HPE and their combination (EEP + HPE) was determined by a cytotoxicity test, DNA binding by [(3)H]-thymidine incorporation and cell migration assay. Anti-metastatic properties in U87MG treated with EEP, HPE and EEP + HPE were estimated on cells migration test (scratch assay) and metalloproteinases (MMP2 and MMP9) secretion (gelatin zymography). Combination of HPE and EEP extracts was found to have a time- and dose-dependent inhibitory effect on the viability of U87MG cells. This effect was significantly higher (p < 0.05) when compared to these two extracts applied separately, which was confirmed by the significant reduction of DNA synthesis and significantly higher mitochondrial membrane permeabilization. A significant decreasing in migration cells and in pro-MMP9 and pro-MMP2 secretion in U87MG cells were demonstrated after exposure to combination of EEP (30 μg/ml) with HPE (6.25 μg/ml). In this study, the combination of ethanolic extract from propolis and ethanolic extract of fresh-cut H. perforatum L. was proved the ability to reduce invasiveness of glioma cells through the inhibition of MMP2 and MMP9 secretion and suppression of cell migration. It has a more potent anti-proliferative effect on U87MG glioma cell line compared to using propolis and H. perforatum L. separately. Further studies are required to verify whether the examined extracts can activate apoptotic pathways.

  3. Acetic acid acts as an elicitor exerting a chitosan-like effect on xanthone biosynthesis in Hypericum perforatum L. root cultures.

    PubMed

    Valletta, Alessio; De Angelis, Giulia; Badiali, Camilla; Brasili, Elisa; Miccheli, Alfredo; Di Cocco, Maria Enrica; Pasqua, Gabriella

    2016-05-01

    Acetic acid acts as a signal molecule, strongly enhancing xanthone biosynthesis in Hypericum perforatum root cultures. This activity is specific, as demonstrated by the comparison with other short-chain monocarboxylic acids. We have recently demonstrated that Hypericum perforatum root cultures constitutively produce xanthones at higher levels than the root of the plant and that they respond to chitosan (CHIT) elicitation with a noteworthy increase in xanthone production. In the present study, CHIT was administered to H. perforatum root cultures using three different elicitation protocols, and the increase in xanthone production was evaluated. The best results (550 % xanthone increase) were obtained by subjecting the roots to a single elicitation with 200 mg l(-1) CHIT and maintaining the elicitor in the culture medium for 7 days. To discriminate the effect of CHIT from that of the solvent, control experiments were performed by administering AcOH alone at the same concentration used for CHIT solubilization. Unexpectedly, AcOH caused an increase in xanthone production comparable to that observed in response to CHIT. Feeding experiments with (13)C-labeled AcOH demonstrated that this compound was not incorporated into the xanthone skeleton. Other short-chain monocarboxylic acids (i.e., propionic and butyric acid) have little or no effect on the production of xanthones. These results indicate that AcOH acts as a specific signal molecule, able to greatly enhance xanthone biosynthesis in H. perforatum root cultures.

  4. The lipophilic extract of Hypericum perforatum exerts significant cytotoxic activity against T24 and NBT-II urinary bladder tumor cells.

    PubMed

    Skalkos, Dimitris; Stavropoulos, Nikolaos E; Tsimaris, Ioannis; Gioti, Eleni; Stalikas, Constantine D; Nseyo, Unyime O; Ioachim, Elli; Agnantis, Niki J

    2005-11-01

    Hypericum perforatum L. (St. John's wort) is a medicinal plant used for many pathologies, especially for the treatment of mild to moderate depression. In the present study we have investigated the cytotoxic activity of the locally collected (Epirus region) Hypericum perforatum L. against cultured T24 and NBT-II bladder cancer cell lines. The lipophilic extract of the herb, prepared using petroleum ether, induced apoptosis displaying LC(50) values at concentrations as low as 4 and 5 microg/mL. A fraction of this extract displayed 60 % cell growth inhibition at a concentration of 0.95 microg/mL. Evaluating the importance of various biologically active components of the extract, it was found that hypericins (hypericin, pseudohypericin, etc.) were identified only in the methanolic (lipophobic) extract of the herb, and not in the active lipophilic extract. In addition, hyperforin concentrations in the lipophilic extract and its most active fraction, were 0.94 microg/mL, and 0.17 microg/mL, respectively, while the active cytotoxic concentration of pure hyperforin appeared in the range of 1.8 microg/mL - 5.0 microg/mL. Therefore, pure hyperforin does not seem to contribute significantly to the cytotoxicity activity. Chlorophylls were identified in low, not significantly different, concentrations in all extracts and fractions and were not correlated to the biological activity. Owing to the combination of significant cytotoxic activity, natural abundance and low toxicity, the lipophilic extract of Hypericum perforatum holds the promise of being an interesting, new, antiproliferative agent against bladder cancer that deserves further investigation.

  5. Mimicking a natural pathway for de novo biosynthesis: natural vanillin production from accessible carbon sources.

    PubMed

    Ni, Jun; Tao, Fei; Du, Huaiqing; Xu, Ping

    2015-09-02

    Plant secondary metabolites have been attracting people's attention for centuries, due to their potentials; however, their production is still difficult and costly. The rich diversity of microbes and microbial genome sequence data provide unprecedented gene resources that enable to develop efficient artificial pathways in microorganisms. Here, by mimicking a natural pathway of plants using microbial genes, a new metabolic route was developed in E. coli for the synthesis of vanillin, the most widely used flavoring agent. A series of factors were systematically investigated for raising production, including efficiency and suitability of genes, gene dosage, and culture media. The metabolically engineered strain produced 97.2 mg/L vanillin from l-tyrosine, 19.3 mg/L from glucose, 13.3 mg/L from xylose and 24.7 mg/L from glycerol. These results show that the metabolic route enables production of natural vanillin from low-cost substrates, suggesting that it is a good strategy to mimick natural pathways for artificial pathway design.

  6. Mimicking a natural pathway for de novo biosynthesis: natural vanillin production from accessible carbon sources

    PubMed Central

    Ni, Jun; Tao, Fei; Du, Huaiqing; Xu, Ping

    2015-01-01

    Plant secondary metabolites have been attracting people’s attention for centuries, due to their potentials; however, their production is still difficult and costly. The rich diversity of microbes and microbial genome sequence data provide unprecedented gene resources that enable to develop efficient artificial pathways in microorganisms. Here, by mimicking a natural pathway of plants using microbial genes, a new metabolic route was developed in E. coli for the synthesis of vanillin, the most widely used flavoring agent. A series of factors were systematically investigated for raising production, including efficiency and suitability of genes, gene dosage, and culture media. The metabolically engineered strain produced 97.2 mg/L vanillin from l-tyrosine, 19.3 mg/L from glucose, 13.3 mg/L from xylose and 24.7 mg/L from glycerol. These results show that the metabolic route enables production of natural vanillin from low-cost substrates, suggesting that it is a good strategy to mimick natural pathways for artificial pathway design. PMID:26329726

  7. Elemental, nutritional, phytochemical and biological evaluation of Hypericum perforatum Linn.

    PubMed

    Dastagir, Ghulam; Ahmed, Rizwan; Shereen, Saima

    2016-03-01

    This study was carried out to study elemental, nutritional, phytochemical and biological evaluation of Hypericum perforatum collected from Swat in 2010. The elemental analysis showed that Ca was highest (5600 μg/g) in leaves and lowest (2500 μg/g) in flowers. The potassium was highest (840 μg/g) in fruit and lowest (80 μg/g) in leaves. Magnesium was highest (260 μg/g) in stem and lowest (200 μg/g) in flowers. Sodium was highest (4900 μg/g) in stem and lowest (4700 μg/g) in leaves and flowers. Copper was highest (26 μg/g) in stem and lowest (10 μg/g) in leaves. Iron was highest (5000 μg/g) in flowers lowest (1200 μg/g) in stem. Zinc was highest (80 μg/g) in flowers and lowest (46 μg/g) in stem. Nickle, cadmium and Cobalt were <5 μg/g for all plant parts. The nutritional analysis showed that the dry matter was in the range of (97.61%) in stem and (96.38%) in leaf, ash (5.43%) in flowers and (1.90%) in stem, crude protein (12.63%) in leaf and (6.15%) in stem, crude fibre (64.74%) in flowers and (13.0%) in leaf, ether extract (10.98%) in fruit and (1.88%) in stem and nitrogen free extract was (65.80%) in leaf and (10.98%) in flower, respectively. Hypericum perforatum did not show cytotoxic, insecticidal and antibacterial activity in vitro at different doses. The % activity was zero% in cytotoxic and insecticidal activities. However, H. perforatum plant parts revealed phytotoxic activity. The phytotoxic activity of leaf and fruit remained same (44.0%) at highest dose (500 μg/ml). The phytochemical screening showed the presence of mucilage, tannins, anthraquinones, saponins, fats and oils and proteins in all parts of the plant. Calcium oxalate was found in all parts except the fruit. Lignin and catechin was found in all parts except the leaf. Cutin was found only in stem and flower while chlorophyll was found only in stem and leaf. In various localities (Shartangaar, Panj Pali and Sharanko) of Swat fresh leaves were used while in Barani and Jaba fresh as

  8. Production of hydrogen by thermocatalytic cracking of natural gas

    SciTech Connect

    Muradov, N.

    1996-10-01

    The conventional methods of hydrogen production from natural gas (for example, steam reforming and partial oxidation) are complex, multi-step processes that produce large quantities of CO{sub 2}. The main goal of this project is to develop a technologically simple process for hydrogen production from natural gas (NG) and other hydrocarbon fuels via single-step decomposition of hydrocarbons. This approach eliminates or significantly reduces CO{sub 2} emission. Carbon is a valuable by-product of this process, whereas conventional methods of hydrogen production from NG produce no useful by-products. This approach is based on the use of special catalysts that reduce the maximum temperature of the process from 1400-1500{degrees}C (thermal non-catalytic decomposition of methane) to 500-900{degrees}C. Transition metal based catalysts and various forms of carbon are among the candidate catalysts for the process. This approach can advantageously be used for the development of compact NG reformers for on-site production of hydrogen-methane blends at refueling stations and, also, for the production of hydrogen-rich gas for fuel cell applications. The author extended the search for active methane decomposition catalysts to various modifications of Ni-, Fe-, Mo- and Co-based catalysts. Variation in the operational parameters makes it possible to produce H{sub 2}-CH{sub 4} blends with a wide range of hydrogen concentrations that vary from 15 to 98% by volume. The author found that Ni-based catalysts are more effective at temperatures below 750{degrees}C, whereas Fe-based catalysts are effective at temperatures above 800{degrees}C for the production of hydrogen with purity of 95% v. or higher. The catalytic pyrolysis of liquid hydrocarbons (pentane, gasoline) over Fe-based catalyst was conducted. The author observed the production of a hydrogen-rich gas (hydrogen concentration up to 97% by volume) at a rate of approximately 1L/min.mL of hydrocarbon fuel.

  9. Natural products as potential cancer therapy enhancers: A preclinical update

    PubMed Central

    Agbarya, Abed; Ruimi, Nili; Epelbaum, Ron; Ben-Arye, Eran

    2014-01-01

    Cancer is a multifactorial disease that arises as a consequence of alterations in many physiological processes. Recently, hallmarks of cancer were suggested that include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis, along with two emerging hallmarks including reprogramming energy metabolism and escaping immune destruction. Treating multifactorial diseases, such as cancer with agents targeting a single target, might provide partial treatment and, in many cases, disappointing cure rates. Epidemiological studies have consistently shown that the regular consumption of fruits and vegetables is strongly associated with a reduced risk of developing chronic diseases, such as cardiovascular diseases and cancer. Since ancient times, plants, herbs, and other natural products have been used as healing agents. Moreover, the majority of the medicinal substances available today have their origin in natural compounds. Traditionally, pharmaceuticals are used to cure diseases, and nutrition and herbs are used to prevent disease and to provide an optimal balance of macro- and micro-nutrients needed for good health. We explored the combination of natural products, dietary nutrition, and cancer chemotherapeutics for improving the efficacy of cancer chemotherapeutics and negating side effects. PMID:26770737

  10. Polyphenols-rich natural products for treatment of diabetes.

    PubMed

    Dragan, S; Andrica, F; Serban, Maria-Corina; Timar, R

    2015-01-01

    Currently, experimental and clinical evidences showed that polyphenols-rich natural products, like nutraceuticals and food supplements, may offer unique treatment modalities in type 2 diabetes mellitus (DM), due to their biological properties. Natural products modulate the carbohydrate metabolism by various mechanisms, such as restoring beta-cells integrity and physiology, enhancing insulin releasing activity, and the glucose using. Sea buckthorn berries, red grapes, bilberries, chokeberries and popular drinks like cocoa, coffee and green tea are all rich in polyphenols and may decrease the insulin response, offer in g a natural alternative of treatment in diabetes. Therefore, researches are now focused on potential efficacies of different types of polyphenols, including flavonoids, phenolic acids, lignans, anthocyans and stilbenes. Animal and human studies showed that polyphenols modulate carbohydrate and lipid metabolism, decrease glycemia and insulin resistance, increase lipid metabolism and optimize oxidative stress and inflammatory processes. It is important to understand the proper dose and duration of supplementation with polyphenols-rich extracts in order to guide effective therapeutic interventions in diabetic patients.

  11. Natural selection on testosterone production in a wild songbird population.

    PubMed

    McGlothlin, Joel W; Whittaker, Danielle J; Schrock, Sara E; Gerlach, Nicole M; Jawor, Jodie M; Snajdr, Eric A; Ketterson, Ellen D

    2010-06-01

    Because of their role in mediating life-history trade-offs, hormones are expected to be strongly associated with components of fitness; however, few studies have examined how natural selection acts on hormonal variation in the wild. In a songbird, the dark-eyed junco (Junco hyemalis), field experiments have shown that exogenous testosterone alters individuals' resolution of the survival-reproduction trade-off, enhancing reproduction at the expense of survival. Here we used standardized injections of gonadotropin-releasing hormone (GnRH) to assay variation in the testosterone production of males. Using measurements of annual survival and reproduction, we found evidence of strong natural selection acting on GnRH-induced increases in testosterone. Opposite to what would be predicted from the survival-reproduction trade-off, patterns of selection via survival and reproduction were remarkably similar. Males with GnRH-induced testosterone production levels that were slightly above the population mean were more likely to survive and also produced more offspring, leading to strong stabilizing selection. Partitioning reproduction into separate components revealed positive directional selection via within-pair siring success and stabilizing selection via extrapair mating success. Our data represent the most complete demonstration of natural selection on hormones via multiple fitness components, and they complement previous experiments to illuminate testosterone's role in the evolution of life-history trade-offs.

  12. Natural products as potential cancer therapy enhancers: A preclinical update.

    PubMed

    Agbarya, Abed; Ruimi, Nili; Epelbaum, Ron; Ben-Arye, Eran; Mahajna, Jamal

    2014-01-01

    Cancer is a multifactorial disease that arises as a consequence of alterations in many physiological processes. Recently, hallmarks of cancer were suggested that include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis, along with two emerging hallmarks including reprogramming energy metabolism and escaping immune destruction. Treating multifactorial diseases, such as cancer with agents targeting a single target, might provide partial treatment and, in many cases, disappointing cure rates. Epidemiological studies have consistently shown that the regular consumption of fruits and vegetables is strongly associated with a reduced risk of developing chronic diseases, such as cardiovascular diseases and cancer. Since ancient times, plants, herbs, and other natural products have been used as healing agents. Moreover, the majority of the medicinal substances available today have their origin in natural compounds. Traditionally, pharmaceuticals are used to cure diseases, and nutrition and herbs are used to prevent disease and to provide an optimal balance of macro- and micro-nutrients needed for good health. We explored the combination of natural products, dietary nutrition, and cancer chemotherapeutics for improving the efficacy of cancer chemotherapeutics and negating side effects.

  13. Overcome Cancer Cell Drug Resistance Using Natural Products

    PubMed Central

    Wang, Pu; Yang, Hua Li; Yang, Ying Juan; Wang, Lan; Lee, Shao Chin

    2015-01-01

    Chemotherapy is one of the major treatment methods for cancer. However, failure in chemotherapy is not uncommon, mainly due to dose-limiting toxicity associated with drug resistance. Management of drug resistance is important towards successful chemotherapy. There are many reports in the Chinese literature that natural products can overcome cancer cell drug resistance, which deserve sharing with scientific and industrial communities. We summarized the reports into four categories: (1) in vitro studies using cell line models; (2) serum pharmacology; (3) in vivo studies using animal models; and (4) clinical studies. Fourteen single compounds were reported to have antidrug resistance activity for the first time. In vitro, compounds were able to overcome drug resistance at nontoxic or subtoxic concentrations, in a dose-dependent manner, by inhibiting drug transporters, cell detoxification capacity, or cell apoptosis sensitivity. Studies in vivo showed that single compounds, herbal extract, and formulas had potent antidrug resistance activities. Importantly, many single compounds, herbal extracts, and formulas have been used clinically to treat various diseases including cancer. The review provides comprehensive data on use of natural compounds to overcome cancer cell drug resistance in China, which may facilitate the therapeutic development of natural products for clinical management of cancer drug resistance. PMID:26421052

  14. Production of bio-synthetic natural gas in Canada.

    PubMed

    Hacatoglu, Kevork; McLellan, P James; Layzell, David B

    2010-03-15

    Large-scale production of renewable synthetic natural gas from biomass (bioSNG) in Canada was assessed for its ability to mitigate energy security and climate change risks. The land area within 100 km of Canada's network of natural gas pipelines was estimated to be capable of producing 67-210 Mt of dry lignocellulosic biomass per year with minimal adverse impacts on food and fiber production. Biomass gasification and subsequent methanation and upgrading were estimated to yield 16,000-61,000 Mm(3) of pipeline-quality gas (equivalent to 16-63% of Canada's current gas use). Life-cycle greenhouse gas emissions of bioSNG-based electricity were calculated to be only 8.2-10% of the emissions from coal-fired power. Although predicted production costs ($17-21 GJ(-1)) were much higher than current energy prices, a value for low-carbon energy would narrow the price differential. A bioSNG sector could infuse Canada's rural economy with $41-130 billion of investments and create 410,000-1,300,000 jobs while developing a nation-wide low-carbon energy system.

  15. Natural Products from Marine Fungi—Still an Underrepresented Resource

    PubMed Central

    Imhoff, Johannes F.

    2016-01-01

    Marine fungi represent a huge potential for new natural products and an increased number of new metabolites have become known over the past years, while much of the hidden potential still needs to be uncovered. Representative examples of biodiversity studies of marine fungi and of natural products from a diverse selection of marine fungi from the author’s lab are highlighting important aspects of this research. If one considers the huge phylogenetic diversity of marine fungi and their almost ubiquitous distribution, and realizes that most of the published work on secondary metabolites of marine fungi has focused on just a few genera, strictly speaking Penicillium, Aspergillus and maybe also Fusarium and Cladosporium, the diversity of marine fungi is not adequately represented in investigations on their secondary metabolites and the less studied species deserve special attention. In addition to results on recently discovered new secondary metabolites of Penicillium species, the diversity of fungi in selected marine habitats is highlighted and examples of groups of secondary metabolites produced by representatives of a variety of different genera and their bioactivities are presented. Special focus is given to the production of groups of derivatives of metabolites by the fungi and to significant differences in biological activities due to small structural changes. PMID:26784209

  16. Water Resources and Natural Gas Production from the Marcellus Shale

    USGS Publications Warehouse

    Soeder, Daniel J.; Kappel, William M.

    2009-01-01

    The Marcellus Shale is a sedimentary rock formation deposited over 350 million years ago in a shallow inland sea located in the eastern United States where the present-day Appalachian Mountains now stand (de Witt and others, 1993). This shale contains significant quantities of natural gas. New developments in drilling technology, along with higher wellhead prices, have made the Marcellus Shale an important natural gas resource. The Marcellus Shale extends from southern New York across Pennsylvania, and into western Maryland, West Virginia, and eastern Ohio (fig. 1). The production of commercial quantities of gas from this shale requires large volumes of water to drill and hydraulically fracture the rock. This water must be recovered from the well and disposed of before the gas can flow. Concerns about the availability of water supplies needed for gas production, and questions about wastewater disposal have been raised by water-resource agencies and citizens throughout the Marcellus Shale gas development region. This Fact Sheet explains the basics of Marcellus Shale gas production, with the intent of helping the reader better understand the framework of the water-resource questions and concerns.

  17. Marine Natural Product Inhibitors of Neutrophil-Associated Inflammation

    PubMed Central

    Chen, Chun-Yu; Tsai, Yung-Fong; Chang, Wen-Yi; Yang, Shun-Chin; Hwang, Tsong-Long

    2016-01-01

    Neutrophils are widely recognized to play an important role in acute inflammatory responses, and recent evidence has expanded their role to modulating chronic inflammatory and autoimmune diseases. Reactive oxygen species (ROS) and microbicidal compounds released from neutrophils that are recruited to the site of inflammation contribute to the pathogenesis of multiple inflammation-associated diseases such as chronic obstructive pulmonary disease, atherosclerosis, and hepatitis. Marine organisms are a valuable source of bioactive compounds with potential for industrial and pharmaceutical application. Marine natural products that inhibit neutrophil activation could be used as drugs for the treatment of inflammatory diseases. Numerous studies investigating marine natural products have reported novel anti-inflammatory agents. Nevertheless, the detailed mechanisms underlying their actions, which could facilitate our understanding of the molecular events occurring in neutrophils, have not been reported in most of the associated research studies. Therefore, in this review, we will present marine products that inhibit neutrophil-associated inflammation. Furthermore, we will be limiting the detailed discussion to agents with well-investigated molecular targets. PMID:27472345

  18. Marine Natural Product Inhibitors of Neutrophil-Associated Inflammation.

    PubMed

    Chen, Chun-Yu; Tsai, Yung-Fong; Chang, Wen-Yi; Yang, Shun-Chin; Hwang, Tsong-Long

    2016-07-26

    Neutrophils are widely recognized to play an important role in acute inflammatory responses, and recent evidence has expanded their role to modulating chronic inflammatory and autoimmune diseases. Reactive oxygen species (ROS) and microbicidal compounds released from neutrophils that are recruited to the site of inflammation contribute to the pathogenesis of multiple inflammation-associated diseases such as chronic obstructive pulmonary disease, atherosclerosis, and hepatitis. Marine organisms are a valuable source of bioactive compounds with potential for industrial and pharmaceutical application. Marine natural products that inhibit neutrophil activation could be used as drugs for the treatment of inflammatory diseases. Numerous studies investigating marine natural products have reported novel anti-inflammatory agents. Nevertheless, the detailed mechanisms underlying their actions, which could facilitate our understanding of the molecular events occurring in neutrophils, have not been reported in most of the associated research studies. Therefore, in this review, we will present marine products that inhibit neutrophil-associated inflammation. Furthermore, we will be limiting the detailed discussion to agents with well-investigated molecular targets.

  19. Productivity of wet soils: Biomass of cultivated and natural vegetation

    SciTech Connect

    Johnston, C.A.

    1988-12-01

    Wet soils, soils which have agronomic limitations because of excess water, comprise 105 million acres of non-federal land in the conterminous United States. Wet soils which support hydrophytic plants are ''wetlands'', and are some of the most productive natural ecosystems in the world. When both above- and belowground productivity are considered, cattail (Typha latifolia) is the most productive temperate wetland species (26.4 Mg/ha/year). Both cattail and reed (Phragmites australis) have aboveground productivities of about 13 Mg/ha/year. Although average aboveground yields of reed canarygrass (Phalaris arundinacea) are lower (9.5 Mg/ha/year), techniques for its establishment and cultivation are well-developed. Other herbaceous wetland species which show promise as biomass crops include sedge (Carex spp.), river bulrush (Scirpus fluviatilis) and prairie cordgrass (Spartina pectinata). About 40% of wet soils in the conterminous US are currently cultivated, and they produce one-quarter of the major US crops. Most of this land is artificially drained for crops such as corn, soybeans, and vegetables. US wetlands are drained for agriculture at the rate of 223,000 ha/yr. Paddies flooded with water are used to grow rice, cranberries, and wild rice. Forage and live sphagnum moss are products of undrained wetlands. A number of federal and state regulations apply to the draining or irrigation of wetlands, but most do not seriously restrict their use for agriculture. 320 refs., 36 tabs.

  20. Entotheonella Bacteria as Source of Sponge-Derived Natural Products: Opportunities for Biotechnological Production.

    PubMed

    Bhushan, Agneya; Peters, Eike E; Piel, Jörn

    2017-01-01

    Marine sponges belong to the oldest animals existing today. Apart from their role in recycling of carbon and nitrogen in the ocean, they are also an important source of a wide variety of structurally diverse bioactive natural products. Over the past few decades, a multitude of compounds from sponges have been discovered exhibiting diverse, pharmacologically promising activities. However, in many cases the low substance quantities present in the sponge tissue would require the collection of large amounts of sponge material, thus impeding further drug development. Recent research has focused on understanding natural product biosynthesis in sponges and on investigating symbiotic bacteria as possible production sources in order to develop sustainable production systems. This chapter covers research efforts that have taken place over the past few years involving the identification of 'Entotheonella' symbionts responsible for production of sponge compounds, as well as the elucidation of their biosynthetic routes, highlighting future biotechnological applications.

  1. Molecules to Ecosystems: Actinomycete Natural Products In situ

    PubMed Central

    Behie, Scott W.; Bonet, Bailey; Zacharia, Vineetha M.; McClung, Dylan J.; Traxler, Matthew F.

    2017-01-01

    Actinomycetes, filamentous actinobacteria found in numerous ecosystems around the globe, produce a wide range of clinically useful natural products (NP). In natural environments, actinomycetes live in dynamic communities where environmental cues and ecological interactions likely influence NP biosynthesis. Our current understating of these cues, and the ecological roles of NP, is in its infancy. We postulate that understanding the ecological context in which actinomycete metabolites are made is fundamental to advancing the discovery of novel NP. In this review we explore the ecological relevance of actinomycetes and their secondary metabolites from varying ecosystems, and suggest that investigating the ecology of actinomycete interactions warrants particular attention with respect to metabolite discovery. Furthermore, we focus on the chemical ecology and in situ analysis of actinomycete NP and consider the implications for NP biosynthesis at ecosystem scales. PMID:28144233

  2. Marine Natural Products with P-Glycoprotein Inhibitor Properties

    PubMed Central

    Lopez, Dioxelis; Martinez-Luis, Sergio

    2014-01-01

    P-glycoprotein (P-gp) is a protein belonging to the ATP-binding cassette (ABC) transporters superfamily that has clinical relevance due to its role in drug metabolism and multi-drug resistance (MDR) in several human pathogens and diseases. P-gp is a major cause of drug resistance in cancer, parasitic diseases, epilepsy and other disorders. This review article aims to summarize the research findings on the marine natural products with P-glycoprotein inhibitor properties. Natural compounds that modulate P-gp offer great possibilities for semi-synthetic modification to create new drugs and are valuable research tools to understand the function of complex ABC transporters. PMID:24451193

  3. Natural milk cultures for the production of Argentinian cheeses.

    PubMed

    Reinheimer, J A; Binetti, A G; Quiberoni, A; Bailo, N B; Rubiolo, A C; Giraffa, G

    1997-01-01

    Samples (32) of natural milk cultures used in the Santa Fe, Argentina, area for soft and semihard cheese production were examined. The microbial composition (including lactic acid microflora characterization) and technological parameters (acidifying and proteolytic activities) were evaluated. The cultures contained mainly thermophilic lactic acid bacteria, identified as Streptococcus salivarius subsp. thermophilus (96.8% of the total strains) and Enterococcus spp. The strains showed a low proteolytic activity. The isolates of S. salivarius subsp. thermophilus exhibited a widespread phage resistance. The nonlactic microflora comprised coliforms, yeasts, spore-forming bacteria and lactate fermentative bacteria. The samples showed an acidity level from 0.38 to 0.69% lactic acid (pH from 4.25 to 5.75). The acidifying activity was optimal at 45 degrees C. The advantages and disadvantages of the employment of natural milk starters are discussed.

  4. Water for wood products versus nature, food or feed

    NASA Astrophysics Data System (ADS)

    Schyns, Joep; Booij, Martijn; Hoekstra, Arjen

    2017-04-01

    more water available for the generation of other ecosystem services. Our findings contribute to a more complete picture of the human appropriation of water and the understanding of the interlinkages between the SDGs, thus feeding the debate on water for wood products versus nature, food or feed.

  5. Advances in cancer therapy with plant based natural products.

    PubMed

    Mukherjee, A K; Basu, S; Sarkar, N; Ghosh, A C

    2001-10-01

    Natural Products have long been a fertile source of cure for cancer, which is projected to become the major causes of death in this century. However, there is a continuing need for development of new anticancer drugs, drug combinations and chemotherapy strategies, by methodical and scientific exploration of enormous pool of synthetic, biological and natural products. There are at least 250,000 species of plants out of which more than one thousand plants have been found to possess significant anticancer properties. While many molecules obtained from nature have shown wonders, there are a huge number of molecules that still either remains to be trapped or studied in details by the medicinal chemists. The article reviews many such structures and their related chemistry along with the recent advances in understanding mechanism of action and structure-function relationships of nature derived anti-cancer agents at the molecular, cellular and physiological levels. Taxol, one of the most outstanding agents, has been found beneficial in treatment of refractory ovarian, breast and other cancers. Another prominent molecule includes Podophyllotoxin. Synthetic modification of this molecule led to the development of Etoposide, known to be effective for small cell cancers of the lungs and testes. Camptothecin isolated from Camptotheca acuminata also have been extensively studied. Other important molecules discussed include Vincristine, Vinblastine, Colchicine, Ellipticine and Lepachol along with Flavopiridol, a semi-synthetic analogue of the chromone alkaloid Rohitukine from India, a pyridoindole alkaloid from leaves of Ochrosia species and many more. The review also deals with the lesser-known plants of sub-Himalayan region.

  6. Antiviral Natural Products Against Chronic Hepatitis B: Recent Developments.

    PubMed

    Parvez, Mohammad K; Arbab, Ahmed H; Al-Dosari, Mohammed S; Al-Rehaily, Adnan J

    2016-01-01

    Hepatitis B virus (HBV) is inherently a hepatotropic virus that causes acute and chronic hepatitis in about one-third of world population. Of the estimated 360 million chronically infected individuals, more than one million die of liver cirrhosis, fulminant liver failure or hepatocellular carcinoma (HCC) every year. Though there is an effective vaccine available, failure to protection because of vaccine-escape viral mutants in some population is also reported. Moreover, all the currently approved antiviral drugs have their limitations, too. Interferon (IFN-α) has limited efficacy and a high incidence of adverse side-effects in a proportion of chronic patients. Nucleos(t)ide analogs like, lamivudine, adefovir, tenofovir and entecavir are very effective in treating chronic hepatitis B (CHB), but long-term therapy eventually leads to drug-resistance. As an alternative approach, natural or plant products have provided promising therapeutics in modern pharma industry. Owing to their characteristics of high chemical diversity and biochemical specificity, natural products offer great promises as potentially effective antiviral drugs. A broad spectrum of phytochemicals including flavonoids (e.g., Vogonin), terpenes (e.g., Artemisinin), alkaloids (e.g., Oxymatrine), polyphenolics (e.g., geraniin), saponins (e.g., Astragaloside IV) and lignans (e.g., Helioxanthin) has been isolated and investigated for anti-HBV activities in vitro as well as in vivo. Nevertheless, these promising compounds have different and overlapping mechanisms of action by either inhibiting viral antigens secretion or suppression of DNA replication. The present article reviews the recent developments in anti-HBV natural products.

  7. The chemical versatility of natural-product assembly lines.

    PubMed

    Walsh, Christopher T

    2008-01-01

    Microbial natural products of both polyketide and nonribosomal peptide origin have been and continue to be important therapeutic agents as antibiotics, immunosupressants, and antitumor drugs. Because the biosynthetic genes for these metabolites are clustered for coordinate regulation, the sequencing of bacterial genomes continues to reveal unanticipated biosynthetic capacity for novel natural products. The re-engineering of pathways for such secondary metabolites to make novel molecular variants will be enabled by understanding of the chemical logic and protein machinery in the producer microbes. This Account analyzes the chemical principles and molecular logic that allows simple primary metabolite building blocks to be converted to complex architectural scaffolds of polyketides (PK), nonribosomal peptides (NRP), and NRP-PK hybrids. The first guiding principle is that PK and NRP chains are assembled as thioseters tethered to phosphopantetheinyl arms of carrier proteins that serve as thiotemplates for chain elongation. The second principle is that gate keeper protein domains select distinct monomers to be activated and incorporated with positional specificity into the growing natural product chains. Chain growth is via thioclaisen condensations for PK and via amide bond formation for elongating NRP chains. Release of the full length acyl/peptidyl chains is mediated by thioesterases, some of which catalyze hydrolysis while others catalyze regiospecific macrocyclization to build in conformational constraints. Tailoring of PK and NRP chains, by acylation, alkylation, glycosylation, and oxidoreduction, occurs both during tethered chain growth and after thioesterase-mediated release. Analysis of the types of protein domains that carry out chain initiation, elongation, tailoring, and termination steps gives insight into how NRP and PK biosynthetic assembly lines can be redirected to make novel molecules.

  8. Identification of light-independent inhibition of human immunodeficiency virus-1 infection through bioguided fractionation of Hypericum perforatum

    PubMed Central

    Maury, Wendy; Price, Jason P; Brindley, Melinda A; Oh, ChoonSeok; Neighbors, Jeffrey D; Wiemer, David F; Wills, Nickolas; Carpenter, Susan; Hauck, Cathy; Murphy, Patricia; Widrlechner, Mark P; Delate, Kathleen; Kumar, Ganesh; Kraus, George A; Rizshsky, Ludmila; Nikolau, Basil

    2009-01-01

    Background Light-dependent activities against enveloped viruses in St. John's Wort (Hypericum perforatum) extracts have been extensively studied. In contrast, light-independent antiviral activity from this species has not been investigated. Results Here, we identify the light-independent inhibition of human immunodeficiency virus-1 (HIV-1) by highly purified fractions of chloroform extracts of H. perforatum. Both cytotoxicity and antiviral activity were evident in initial chloroform extracts, but bioassay-guided fractionation produced fractions that inhibited HIV-1 with little to no cytotoxicity. Separation of these two biological activities has not been reported for constituents responsible for the light-dependent antiviral activities. Antiviral activity was associated with more polar subfractions. GC/MS analysis of the two most active subfractions identified 3-hydroxy lauric acid as predominant in one fraction and 3-hydroxy myristic acid as predominant in the other. Synthetic 3-hydroxy lauric acid inhibited HIV infectivity without cytotoxicity, suggesting that this modified fatty acid is likely responsible for observed antiviral activity present in that fraction. As production of 3-hydroxy fatty acids by plants remains controversial, H. perforatum seedlings were grown sterilely and evaluated for presence of 3-hydroxy fatty acids by GC/MS. Small quantities of some 3-hydroxy fatty acids were detected in sterile plants, whereas different 3-hydroxy fatty acids were detected in our chloroform extracts or field-grown material. Conclusion Through bioguided fractionation, we have identified that 3-hydroxy lauric acid found in field grown Hypericum perforatum has anti-HIV activity. This novel anti-HIV activity can be potentially developed into inexpensive therapies, expanding the current arsenal of anti-retroviral agents. PMID:19594941

  9. The Canadian Natural Health Products (NHP) Regulations: Industry Compliance Motivations

    PubMed Central

    Laeeque, Hina; Kachan, Natasha; Cohen, Jillian Clare; D'Cruz, Joseph

    2007-01-01

    This qualitative study explores corporations' motivations to comply with new natural health products (NHP) Regulations in Canada. Interviews were conducted with representatives from 20 Canadian NHP companies. Findings show that the rationale for compliance differs for large compared to small and medium-sized enterprises (SMEs). Large firms are motivated to comply with the regulations because of the deterrent fear of negative media coverage, social motivations, ability to comply and maintaining a competitive market advantage. In contrast, SMEs are motivated to comply due to the deterrent fear of legal prosecution and a sense of duty. PMID:17549245

  10. Natural Products as Inspiration for the Development of Asymmetric Catalysis

    PubMed Central

    Mohr, Justin T.; Krout, Michael R.; Stoltz, Brian M.

    2008-01-01

    Biologically active natural products often contain particularly challenging structural features and functionalities. Perhaps foremost among these difficulties are issues of stereochemistry. A useful strategy for synthesizing these molecules is to devise novel methods of bond-formation that provide new opportunities for enantioselective catalysis. In using this tactic, target structures define the problems to be solved and ultimately drive development of catalysis forward. New enantioselective methods discovered in the context of these total synthesis efforts then contribute to a greater understanding of fundamental bond construction and lead to valuable synthetic technologies useful for a variety of other applications. PMID:18800131

  11. Green Extraction of Natural Products: Concept and Principles

    PubMed Central

    Chemat, Farid; Vian, Maryline Abert; Cravotto, Giancarlo

    2012-01-01

    The design of green and sustainable extraction methods of natural products is currently a hot research topic in the multidisciplinary area of applied chemistry, biology and technology. Herein we aimed to introduce the six principles of green-extraction, describing a multifaceted strategy to apply this concept at research and industrial level. The mainstay of this working protocol are new and innovative technologies, process intensification, agro-solvents and energy saving. The concept, principles and examples of green extraction here discussed, offer an updated glimpse of the huge technological effort that is being made and the diverse applications that are being developed. PMID:22942724

  12. Xylochemistry--Making Natural Products Entirely from Wood.

    PubMed

    Stubba, Daniel; Lahm, Günther; Geffe, Mario; Runyon, Jason W; Arduengo, Anthony J; Opatz, Till

    2015-11-16

    The first total synthesis of the dimeric berberine alkaloid ilicifoline (ilicifoline B) is reported. Its carbon skeleton is constructed from ferulic acid, veratrole, and methanol. The synthesis reported herein employs starting materials solely derived from wood. The natural product is thus constructed entirely from renewable resources. The same strategy is applied to a formal total synthesis of morphinan alkaloids. The use of wood-derived building blocks (xylochemicals) instead of the conventional petrochemicals represents a sustainable alternative to classical synthetic approaches. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Competitive product inhibition of aromatase by natural estrogens.

    PubMed

    Shimizu, Y; Yarborough, C; Osawa, Y

    1993-03-01

    In order to better understand the function of aromatase, we carried out kinetic analyses to assess the ability of natural estrogens, estrone (E1), estradiol (E2), 16 alpha-OHE1, and estriol (E3), to inhibit aromatization. Human placental microsomes (50 micrograms protein) were incubated for 5 min at 37 degrees C with [1 beta-3H]testosterone (1.24 x 10(3) dpm 3H/ng, 35-150 nM) or [1 beta-3H,4-14C]androstenedione (3.05 x 10(3) dpm 3H/ng, 3H/14C = 19.3, 7-65 nM) as substrate in the presence of NADPH, with and without natural estrogens as putative inhibitors. Aromatase activity was assessed by tritium released to water from the 1 beta-position of the substrates. Natural estrogens showed competitive product inhibition against androgen aromatization. The Ki of E1, E2, 16 alpha-OHE1, and E3 for testosterone aromatization was 1.5, 2.2, 95, and 162 microM, respectively, where the Km of aromatase was 61.8 +/- 2.0 nM (n = 5) for testosterone. The Ki of E1, E2, 16 alpha-OHE1, and E3 for androstenedione aromatization was 10.6, 5.5, 252, and 1182 microM, respectively, where the Km of aromatase was 35.4 +/- 4.1 nM (n = 4) for androstenedione. These results show that estrogen inhibit the process of androgen aromatization and indicate that natural estrogens regulate their own synthesis by the product inhibition mechanism in vivo. Since natural estrogen binds to the active site of human placental aromatase P-450 complex as competitive inhibitors, natural estrogens might be further metabolized by aromatase. This suggests that human placental estrogen 2-hydroxylase activity is catalyzed by the active site of aromatase cytochrome P-450 and also agrees with the fact that the level of catecholestrogens in maternal plasma increases during pregnancy. The relative affinities and concentration of androgens and estrogens would control estrogen and catecholestrogen biosynthesis by aromatase.

  14. Natural Dietary and Herbal Products in Anti-Obesity Treatment.

    PubMed

    Sun, Nan-Nong; Wu, Tsung-Yen; Chau, Chi-Fai

    2016-10-11

    The prevalence of overweight and obesity is on the rise around the world. Common comorbidities associated with obesity, particularly diabetes, hypertension, and heart disease have an impact on social and financial systems. Appropriate lifestyle and behavior interventions are still the crucial cornerstone to weight loss success, but maintaining such a healthy lifestyle is extremely challenging. Abundant natural materials have been explored for their obesity treatment potential and widely used to promote the development of anti-obesity products. The weight loss segment is one of the major contributors to the overall revenue of the dietary supplements market. In this review, the anti-obesity effects of different dietary or herbal products, and their active ingredients and mechanisms of action against obesity will be discussed.

  15. Limitations and prospects of natural photosynthesis for bioenergy production.

    PubMed

    Larkum, A W D

    2010-06-01

    Solar energy is clearly a major future source of energy for humans. While solar photovoltaic and thermal harvesting are attractive there will be a need for biofuels to replace fossil fuels. Natural photosynthesis offers a means to do this, but photosynthesis is inherently inefficient. Terrestrial plants have already been used as a source of biofuels and this use will increase in the future, despite a number of attendant problems. Microalgae as a source of biofuels have to be technically proven and artificial photosynthesis/biohydrogen production lies further into the future. Consideration of these approaches must be weighed against (i) crop production in a hungry, as well as a fuel-hungry, world and (ii) the need to sustain biodiversity. Copyright 2010 Elsevier Ltd. All rights reserved.

  16. Neuroprotective Activity of Hypericum perforatum and Its Major Components

    PubMed Central

    Oliveira, Ana I.; Pinho, Cláudia; Sarmento, Bruno; Dias, Alberto C. P.

    2016-01-01

    Hypericum perforatum is a perennial plant, with worldwide distribution, commonly known as St. John’s wort. It has been used for centuries in traditional medicine for the treatment of several disorders, such as minor burns, anxiety, and mild to moderate depression. In the past years, its antidepressant properties have been extensively studied. Despite that, other H. perforatum biological activities, as its neuroprotective properties have also been evaluated. The present review aims to provide a comprehensive summary of the main biologically active compounds of H. perforatum, as for its chemistry, pharmacological activities, drug interactions and adverse reactions and gather scattered information about its neuroprotective abilities. As for this, it has been demonstrated that H. perforatum extracts and several of its major molecular components have the ability to protect against toxic insults, either directly, through neuroprotective mechanisms, or indirectly, through is antioxidant properties. H. perforatum has therefore the potential to become an effective neuroprotective therapeutic agent, despite further studies that need to be carried out. PMID:27462333

  17. St John's wort (Hypericum perforatum) in major depression.

    PubMed

    Shelton, Richard C

    2009-01-01

    The herb St John's wort (Hypericum perforatum) has been used for centuries to treat a variety of medical illnesses. In certain areas of Europe, St John's wort has been a commonly prescribed treatment for depression, but, in the United States, it is available for purchase over the counter as an herbal supplement. Some researchers believe that specific chemical constituents of St John's wort produce change in depression in a way similar to that of antidepressant medications, yet this hypothesis is problematic. In addition, studies that support the efficacy of St John's wort in patients with mild-to-moderate depression have limitations that may affect the accuracy of their conclusions. Studies measuring the effect of St John's wort in major depression have reported conflicting results and need to be reexamined. Because St John's wort is considered by some to be an alternative to conventional therapies, clinicians need to know whether it is an effective and safe treatment for different levels of severity of depression. Current evidence does not support its use, and, because of potential drug interactions, St John's wort is not a benign treatment.

  18. The snowmaker: nature identical snow production in the laboratory

    NASA Astrophysics Data System (ADS)

    Schleef, S.; Jaggi, M.; Loewe, H.; Schneebeli, M.

    2013-12-01

    Using natural snow for laboratory experiments can be tricky due to shortage of winter periods and snowfall, difficulties of sample casting and transport, and the great variability of natural snow due to the varying conditions of crystal growth in the clouds. This hinders repeatable laboratory experiments with reproducible specimen and microstructural characteristics. To minimize experimental uncertainties we designed an improved machine called snowmaker, which enables us to produce nature-identical snow in a cold laboratory under well defined conditions. The snowmaker is based on well-known principles: warm humid air from a heated water basin is advected into a cold nucleation chamber where the vapor resublimates on stretched Nylon wires. Crystals are automatically harvested by a motor driven brush rack and collected in a box, thereby several kilograms of snow can be produced per day with minimum maintenance. The excess vapor is collected in a moisture trap to avoid frost in the laboratory. The entire construction is designed as a rolling, modular assembly system which can easily carried out of the laboratory for defrosting. In addition to previous attempts we focus on the reproducibility of the samples and the comparison to natural snow down to the microscale. We show that the settings of water temperature and cold laboratory temperature facilitates the production of different crystal shapes like dendrites and needles in a reproducible way. Besides photography, we analyzed the microstructure of snowmaker crystals in aggregated specimen by X-ray microtomography. Depending on the settings we can create reproducible samples with density of 50-170 kg/m3 and specific surface areas of 50-80 mm-1. We briefly touch similarities between artificial and natural snow samples with respect to crystal habit, microstructural parameters and short-time metamorphism.

  19. Water extracts of tree Hypericum sps. protect DNA from oxidative and alkylating damage and enhance DNA repair in colon cells.

    PubMed

    Ramos, Alice A; Marques, Filipe; Fernandes-Ferreira, Manuel; Pereira-Wilson, Cristina

    2013-01-01

    Diet may induce colon carcinogenesis through oxidative or alkylating DNA damage. However, diet may also contain anticarcinogenic compounds that contribute to cancer prevention. DNA damage prevention and/or induction of repair are two important mechanisms involved in cancer chemoprevention by dietary compounds. Hypericum sps. are widely used in traditional medicine to prepare infusions due to their beneficial digestive and neurologic effects. In this study, we investigated the potential of water extracts from three Hypericum sps. and some of their main phenolic compounds to prevent and repair oxidative and alkylating DNA damage in colon cells. The results showed that water extracts of Hypericum perforatum, Hypericum androsaemum, Hypericum undulatum, quercetin and rutin have protective effect against oxidative DNA damage in HT29 cells. Protective effect was also observed against alkylating DNA damage induced by methyl-methanesulfonate, except for H. androsaemum. With regard to alkylating damage repair H. perforatum, H. androsaemum and chlorogenic acid increased repair of alkylating DNA damage by base excision repair pathway. No effect was observed on nucleotide excision repair pathway. Antigenotoxic effects of Hypericum sps. may contribute to colon cancer prevention and the high amount of phenolic compounds present in Hypericum sps. play an important role in DNA protective effects. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Hypericum perforatum L. extract - novel photosensitizer against human bladder cancer cells.

    PubMed

    Stavropoulos, N E; Kim, A; Nseyo, U U; Tsimaris, I; Chung, T D; Miller, T A; Redlak, M; Nseyo, U O; Skalkos, D

    2006-07-03

    The polar methanolic fraction (PMF) of the Hypericum perforatum L. extract has recently been developed and tested as a novel, natural photosensitizer for use in the photodynamic therapy (PDT), and photodynamic diagnosis (PDD). PMF has been tested on HL-60 leukemic cells and cord blood hemopoietic progenitors. In the present study, the efficacy of PMF as a phototoxic agent against urinary bladder carcinoma has been studied using the T24 (high grade metastatic cancer), and RT4 (primary low grade papillary transitional cell carcinoma) human bladder cancer cells. Following cell culture incubation, PMF was excited using 630 nm laser light. The photosensitizer exhibited significant photocytotoxicity in both cell lines at a concentration of 60microg/ml, with 4-8 J/cm(2) light dose, resulting in cell destruction from 80% to 86%. At the concentration of 20microg/ml PMF was not active in either cell line. These results were compared with the results obtained in the same cell lines, under the same conditions with a clinically approved photosensitizer, Photofrin. Photofrin was used in the maximum clinically tolerable dose of 4microg/ml, and it was also excited with 630 nm laser light. In the T24 cell Photofrin exhibited slightly less photocytotocixity, compared with PMF, resulting in 77% cell death with 8J/cm(2) light dose. However, against the RT4 cells Photofrin resulted in minimal cell death (9%) with even 8J/cm(2) light dose. Finally, the type of cell death induced by PMF photoactivation was studied using flow cytometry and DNA laddering. Cell death by PMF photodynamic action in these two bladder cell lines is caused predominently by apoptosis. The reported significant photocytotoxicity, selective localization, natural abundance, easy, and inexpensive preparation, underscore that the PMF extract hold the promise of being a novel, effective PDT photosensitizer.

  1. 30 CFR 260.116 - How do I measure natural gas production on my eligible lease?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false How do I measure natural gas production on my... do I measure natural gas production on my eligible lease? You must measure natural gas production on... natural gas, measured according to part 250, subpart L of this title, equals one barrel of oil equivalent...

  2. 76 FR 19996 - Cooperative Agreement With the University of Mississippi's National Center for Natural Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-11

    ... and dissemination of natural products research and science and the programs developed under the... National Center for Natural Products Research (U01) To Develop and Disseminate Botanical Natural Product... support of a cooperative agreement with the University of Mississippi's National Center for Natural...

  3. US production of natural gas from tight reservoirs

    SciTech Connect

    Not Available

    1993-10-18

    For the purposes of this report, tight gas reservoirs are defined as those that meet the Federal Energy Regulatory Commission`s (FERC) definition of tight. They are generally characterized by an average reservoir rock permeability to gas of 0.1 millidarcy or less and, absent artificial stimulation of production, by production rates that do not exceed 5 barrels of oil per day and certain specified daily volumes of gas which increase with the depth of the reservoir. All of the statistics presented in this report pertain to wells that have been classified, from 1978 through 1991, as tight according to the FERC; i.e., they are ``legally tight`` reservoirs. Additional production from ``geologically tight`` reservoirs that have not been classified tight according to the FERC rules has been excluded. This category includes all producing wells drilled into legally designated tight gas reservoirs prior to 1978 and all producing wells drilled into physically tight gas reservoirs that have not been designated legally tight. Therefore, all gas production referenced herein is eligible for the Section 29 tax credit. Although the qualification period for the credit expired at the end of 1992, wells that were spudded (began to be drilled) between 1978 and May 1988, and from November 5, 1990, through year end 1992, are eligible for the tax credit for a subsequent period of 10 years. This report updates the EIA`s tight gas production information through 1991 and considers further the history and effect on tight gas production of the Federal Government`s regulatory and tax policy actions. It also provides some high points of the geologic background needed to understand the nature and location of low-permeability reservoirs.

  4. Natural Products as Promising Therapeutics for Treatment of Influenza Disease.

    PubMed

    Sencanski, Milan; Radosevic, Draginja; Perovic, Vladimir; Gemovic, Branislava; Stanojevic, Maja; Veljkovic, Nevena; Glisic, Sanja

    2015-01-01

    The influenza virus represents a permanent global health threat because it circulates not only within but also between numerous host populations, thereby frequently causing unexpected outbreaks in animals and humans with a generally unpredictable course of disease and epidemiology. Conventional influenza therapy is directed against the viral neuraminidase protein, which promotes virus release from infected cells, and the viral ion channel M2, which facilitates viral uncoating. However, these drugs, albeit effective, have a major drawback: their targets are of a highly variable sequence. As a consequence, the virus can readily acquire resistance by mutating the drug targets. Indeed, most seasonal A/H1N1 viruses and the 2009 H1N1 virus are resistant to M2 inhibitors, and a significant proportion of the seasonal A/H1N1 viruses are resistant to the neuraminidase inhibitor oseltamivir. Development of new effective drugs for treatment of disease during the regular influenza seasons and the possible influenza pandemic represents an important goal. The results presented here point out natural products as a promising source of low toxic and widely accessible drug candidates for treatment of the influenza disease. Natural products combined with new therapeutic targets and drug repurposing techniques, which accelerate development of new drugs, serve as an important platform for development of new influenza therapeutics.

  5. Total Synthesis of Natural Products Using Hypervalent Iodine Reagents

    NASA Astrophysics Data System (ADS)

    Maertens, Gaetan; L'homme, Chloe; Canesi, Sylvain

    2014-12-01

    We present a review of natural product syntheses accomplished in our laboratory during the last five years. Each synthetic route features a phenol dearomatization promoted by an environmentally benign hypervalent iodine reagent. The dearomatizations demonstrate the “aromatic ring umpolung” concept, and involve stereoselective remodeling of the inert unsaturations of a phenol into a highly functionalized key intermediate that may contain a quaternary carbon center and a prochiral dienone system. Several new oxidative strategies were employed, including transpositions (1,3-alkyl shift and Prins-pinacol), a polycyclization, an ipso rearrangement, and direct nucleophilic additions at the phenol para position. Several alkaloids, heterocyclic compounds, and a polycyclic core have been achieved, including sceletenone (a serotonin reuptake inhibitor), acetylaspidoalbidine (an antitumor agent), fortucine (antiviral and antitumor), erysotramidine (curare-like effect), platensimycin (an antibiotic), and the main core of a kaurane diterpene (immunosuppressive agent and stimulator of apoptosis). These concise and in some cases enantioselective syntheses effectively demonstrate the importance of hypervalent iodine reagents in the total synthesis of bioactive natural products.

  6. Galanthamine, a natural product for the treatment of Alzheimer's disease.

    PubMed

    Marco, Luis; do Carmo Carreiras, Maria

    2006-01-01

    (-)-Galanthamine is a selective, reversible competitive acetylcholinesterase inhibitor that has been recently approved for the symptomatic treatment of Alzheimer's disease. Galanthamine is a natural product belonging to the Amaryllidaceae family of alkaloids. The pharmacological history of galanthamine shows that the bioactive compound was discovered accidentally in the early 1950s, and the plant extracts were initially used to treat nerve pain and poliomyelitis. In addition, galanthamine had since been tested for use in anesthesiology, from facial nerve paralysis to schizophrenia. Galanthamine is a long-acting, selective, reversible and competitive AChE inhibitor that has recently been tested in AD patients and found to be readily absorbed, to be a performance enhancer on memory tests in some patients, and to be well tolerated, although some cholinergic side effects were observed. A number of total synthetic approaches have been reported, and a method for the industrial scale-up preparation of galanthamine is now being developed and patented. A variety of galanthamine derivatives have also been synthesized aiming to develop an agent free from cholinergic adverse effects. Galanthamine is a natural product that complements other synthetic drugs for the management of AD. In this account we will review the recent patent literature showing the most important advance on the chemistry of galanthamine.

  7. A natural-product switch for a dynamic protein interface.

    PubMed

    Scheepstra, Marcel; Nieto, Lidia; Hirsch, Anna K H; Fuchs, Sascha; Leysen, Seppe; Lam, Chan Vinh; in het Panhuis, Leslie; van Boeckel, Constant A A; Wienk, Hans; Boelens, Rolf; Ottmann, Christian; Milroy, Lech-Gustav; Brunsveld, Luc

    2014-06-16

    Small ligands are a powerful way to control the function of protein complexes via dynamic binding interfaces. The classic example is found in gene transcription where small ligands regulate nuclear receptor binding to coactivator proteins via the dynamic activation function 2 (AF2) interface. Current ligands target the ligand-binding pocket side of the AF2. Few ligands are known, which selectively target the coactivator side of the AF2, or which can be selectively switched from one side of the interface to the other. We use NMR spectroscopy and modeling to identify a natural product, which targets the retinoid X receptor (RXR) at both sides of the AF2. We then use chemical synthesis, cellular screening and X-ray co-crystallography to split this dual activity, leading to a potent and molecularly efficient RXR agonist, and a first-of-kind inhibitor selective for the RXR/coactivator interaction. Our findings justify future exploration of natural products at dynamic protein interfaces. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Systems Biology Approaches to Understand Natural Products Biosynthesis

    PubMed Central

    Licona-Cassani, Cuauhtemoc; Cruz-Morales, Pablo; Manteca, Angel; Barona-Gomez, Francisco; Nielsen, Lars K.; Marcellin, Esteban

    2015-01-01

    Actinomycetes populate soils and aquatic sediments that impose biotic and abiotic challenges for their survival. As a result, actinomycetes metabolism and genomes have evolved to produce an overwhelming diversity of specialized molecules. Polyketides, non-ribosomal peptides, post-translationally modified peptides, lactams, and terpenes are well-known bioactive natural products with enormous industrial potential. Accessing such biological diversity has proven difficult due to the complex regulation of cellular metabolism in actinomycetes and to the sparse knowledge of their physiology. The past decade, however, has seen the development of omics technologies that have significantly contributed to our better understanding of their biology. Key observations have contributed toward a shift in the exploitation of actinomycete’s biology, such as using their full genomic potential, activating entire pathways through key metabolic elicitors and pathway engineering to improve biosynthesis. Here, we review recent efforts devoted to achieving enhanced discovery, activation, and manipulation of natural product biosynthetic pathways in model actinomycetes using genome-scale biological datasets. PMID:26697425

  9. Natural Vitamin D Content in Animal Products1

    PubMed Central

    Schmid, Alexandra; Walther, Barbara

    2013-01-01

    Humans derive most vitamin D from the action of sunlight in their skin. However, in view of the current Western lifestyle with most daily activities taking place indoors, sun exposure is often not sufficient for adequate vitamin D production. For this reason, dietary intake is also of great importance. Animal foodstuffs (e.g., fish, meat, offal, egg, dairy) are the main sources for naturally occurring cholecalciferol (vitamin D-3). This paper therefore aims to provide an up-to-date overview of vitamin D-3 content in various animal foods. The focus lies on the natural vitamin D-3 content because there are many countries in which foods are not regularly fortified with vitamin D. The published data show that the highest values of vitamin D are found in fish and especially in fish liver, but offal also provides considerable amounts of vitamin D. The content in muscle meat is generally much lower. Vitamin D concentrations in egg yolks range between the values for meat and offal. If milk and dairy products are not fortified, they are normally low in vitamin D, with the exception of butter because of its high fat content. However, as recommendations for vitamin D intake have recently been increased considerably, it is difficult to cover the requirements solely by foodstuffs. PMID:23858093

  10. Paraptosis in the anti-cancer arsenal of natural products.

    PubMed

    Lee, Dongjoo; Kim, In Young; Saha, Sharmistha; Choi, Kyeong Sook

    2016-06-01

    Given the problems with malignant cancer cells showing innate and acquired resistance to apoptosis, we need alternative means to induce cell death in cancer. Paraptosis is a type of programmed cell death that is characterized by dilation of the endoplasmic reticulum (ER) and/or mitochondria. Although relatively little is known regarding the molecular basis of paraptosis, the underlying mechanism clearly differs from that of apoptosis. Recent studies have shown that various natural products, including curcumin, celastrol, 15d-PGJ2, ophiobolin A, and paclitaxel, demonstrate anti-cancer effects by inducing the paraptosis-associated cell death, which was commonly characterized by vacuolation derived from the ER. Perturbation of cellular proteostasis due to proteasomal inhibition and disruption of sulfhydryl homeostasis, generation of reactive oxygen species, and/or imbalanced homeostasis of ions (e.g., Ca(2+) and K(+)) appear to contribute to the accumulation of misfolded protein and proteotoxicity in this process. Given the pathophysiological importance of paraptosis and the debate regarding the importance of apoptosis in solid tumor, we need to collect the available knowledge regarding paraptosis and suggest future directions in the field. Here, we review the morphological and biochemical features of paraptosis, the natural products that induce paraptosis-associated cell death, their proposed mechanisms, and the significance of paraptosis as a potential anti-cancer strategy. Such work and future clarifications should enable the development of new strategies for preventing cancer and/or combating malignant cancer.

  11. The Impending Renaissance in Discovery & Development of Natural Products.

    PubMed

    Pawar, Sandip V; Ho, Joe C H; Yadav, Ganapati D; Yadav, Vikramaditya G

    2017-01-01

    Antibiotics are wonder drugs. Unfortunately, owing to overuse, antibiotic resistance is now a serious problem. Society now finds itself in the post-antibiotic era, and the threat of infectious diseases is on the rise. New antibiotics are sorely needed. There is strong evidence that suggests natural products are an attractive source of new antimicrobials. They posses desirable structural and chemical properties that make them potent thearpeutics. However, steep tehnological challenges associated with screening and manufacturing these molecules has stifled the discovery, development and marketing of new antimicrobials. To this end, two recent scientific developments are poised to redress this situation. The recent development of metagenomics and ancillary high-throughput screening technologies has exponentiated the volume of useful genetic sequence information that can be screened for antimicrobial discovery. These approaches have been instrumental in the discovery of new antibiotics from soil and marine environments. Secondly, a new manufacturing paradigm employing metabolic engineering as its engine has greatly accelerated the path to market for these molecules, in addition to improving the atom and energy economy of antimicrobial manufacturing. We outine these developments in this review, and provide a perspective on integrating next-generation approaches such as metagenomics and metabolic engineering with traditional methodologies for discovering and manufacturing antimicrobial natural products in order to unleash a rennaissance in the discovery and development of antimicrobials.

  12. Drug development from natural products: exploiting synergistic effects.

    PubMed

    Ulrich-Merzenich, Gudrun; Panek, D; Zeitler, H; Vetter, H; Wagner, H

    2010-03-01

    Drug development in phytomedicine has been focused in the past on the discovery and analysis of new structures from natural products. The search aimed at the determination of the single "active principle" in plants, based on the assumption that a plant has one or a few ingredients which determine its therapeutic effects. But traditional systems of medicines like Ayurveda, traditional Chinese medicine or the European phytotherapy generally assume that a synergy of all ingredients of the plants will bring about the maximum of therapeutic efficacy. This approach has for long been impossible to investigate since adequate methods to standardize complex plant mixtures as well as to rationalize complex mode of actions were lacking. The introduction of high throughput technologies provides the opportunity to determine profiles of plants and to systematically explore the mode of action of combinatory drug regimes. The present review highlights the concept of synergy and gives examples of synergistic effects of plant constituents. It elaborates on how the high throughput technologies can be used in drug development from natural products with the aim of creating evidence-based plant medications in prevention and treatment of different diseases in the form of new single treatments or new combinatory drug regimes while exploiting synergy-effects.

  13. Natural products--antifungal agents derived from plants.

    PubMed

    Arif, Tasleem; Bhosale, J D; Kumar, Naresh; Mandal, T K; Bendre, R S; Lavekar, G S; Dabur, Rajesh

    2009-07-01

    A new spectrum of human fungal infections is increasing due to increased cancer, AIDS, and immunocompromised patients. The increased use of antifungal agents also resulted in the development of resistance to the present drugs. It makes necessary to discover new classes of antifungal compounds to cure fungal infections. Plants are rich source of bioactive secondary metabolites of wide variety such as tannins, terpenoids, saponins, alkaloids, flavonoids, and other compounds, reported to have in vitro antifungal properties. Since the plant kingdom provides a useful source of lead compounds of novel structure, a wide-scale investigation of species from the tropics has been considered. Therefore, the research on natural products and compounds derived from natural products has accelerated in recent years due to their importance in drug discovery. A series of molecules with antifungal activity against different strains of fungus have been found in plants, which are of great importance to humans. These molecules may be used directly or considered as a precursor for developing better molecules. This review attempts to summarize the current status of important antifungal compounds from plants.

  14. Prevention of microbial communities: novel approaches based natural products.

    PubMed

    Mogosanu, George D; Grumezescu, Alexandru M; Huang, Keng-Shiang; Bejenaru, Ludovic E; Bejenaru, Cornelia

    2015-01-01

    Firmly attached to different living or non-living, solid or fluid surfaces rich in nutrients and moisture, microbial biofilm is a matter of great interest due to its major importance for the healthcare community. Depending on common strategies such as mutual protection and hibernation (quiescent bacteria), the resistance, survival and virulence of microbial communities have large implications for human pathology, clinical environment and biomedical devices. The microbial biofilm is continuously changing, stimulating inflammation, increasing vascular permeability and preventing the action of macrophages. About 80% of human infections affecting the gastrointestinal, genitourinary and respiratory systems, oral mucosa and teeth, eyes, middle ear and skin are caused by biofilm-associated microorganisms. Therefore, the search for modern strategies is even more important as microbial biofilms resistant to conventional antibiotics, antiseptics and disinfectants are involved in the frequent treatment failures of some chronic inflammatory diseases and wounds. Natural products containing secondary metabolites, such as aromatic compounds, sulphurated derivatives, terpenoids (essential oils) and alkaloids as quorum-sensing inhibitors and biofilm disruptors, are promising alternatives for the prophylaxis and treatment of chronic infections. Surface modification of medical devices with non-polar functionalized nanoparticles stabilizes the natural compounds antibiofilm activity and inhibits microbial adhesion and biofilm formation and growth for a longer period of time. In this regard, an interdisciplinary approach is needed due to the large number of natural derivatives alone or in combination with biocompatible and biodegradable micro-/ nano-engineered materials.

  15. Probiotics Stimulate Production of Natural Antibodies in Chickens

    PubMed Central

    Haghighi, Hamid R.; Gong, Jianhua; Gyles, Carlton L.; Hayes, M. Anthony; Zhou, Huaijun; Sanei, Babak; Chambers, James R.; Sharif, Shayan

    2006-01-01

    Commensal bacteria in the intestine play an important role in the development of immune response. These bacteria interact with cells of the gut-associated lymphoid tissues (GALT). Among cells of the GALT, B-1 cells are of note. These cells are involved in the production of natural antibodies. In the present study, we determined whether manipulation of the intestinal microbiota by administration of probiotics, which we had previously shown to enhance specific systemic antibody response, could affect the development of natural antibodies in the intestines and sera of chickens. Our findings demonstrate that when 1-day-old chicks were treated with probiotics, serum and intestinal antibodies reactive to tetanus toxoid (TT) and Clostridium perfringens alpha-toxin in addition to intestinal immunoglobulin A (IgA) reactive to bovine serum albumin (BSA) were increased in unimmunized chickens. Moreover, IgG antibodies reactive to TT were increased in the intestines of probiotic-treated chickens compared to those of untreated controls. In serum, IgG and IgM reactive to TT and alpha-toxin were increased in probiotic-treated, unimmunized chickens compared to levels in untreated controls. However, no significant difference in serum levels of IgM or IgG response to BSA was observed. These results are suggestive of the induction of natural antibodies in probiotic-treated, unimmunized chickens. Elucidating the role of these antibodies in maintenance of the chicken immune system homeostasis and immune response to pathogens requires further investigation. PMID:16960107

  16. Cambial meristematic cells: a platform for the production of plant natural products.

    PubMed

    Ochoa-Villarreal, Marisol; Howat, Susan; Jang, Mi Ok; Kim, Il Suk; Jin, Young-Woo; Lee, Eun-Kyong; Loake, Gary J

    2015-12-25

    Plant cell culture constitutes a sustainable, controllable and environmentally friendly tool to produce natural products for the pharmaceutical, cosmetic and industrial biotechnology industries. However, there are significant obstacles to the commercial synthesis of high value chemicals from plant culture including low yields, performance instability, slow plant cell growth, industrial scale-up and downstream processing. Cambial meristematic cells constitute a platform to ameliorate many of these potential problems enabling the commercial production of high value chemicals.

  17. Lichen Symbiosis: Nature's High Yielding Machines for Induced Hydrogen Production

    PubMed Central

    Papazi, Aikaterini; Kastanaki, Elizabeth; Pirintsos, Stergios; Kotzabasis, Kiriakos

    2015-01-01

    Hydrogen is a promising future energy source. Although the ability of green algae to produce hydrogen has long been recognized (since 1939) and several biotechnological applications have been attempted, the greatest obstacle, being the O2-sensitivity of the hydrogenase enzyme, has not yet been overcome. In the present contribution, 75 years after the first report on algal hydrogen production, taking advantage of a natural mechanism of oxygen balance, we demonstrate high hydrogen yields by lichens. Lichens have been selected as the ideal organisms in nature for hydrogen production, since they consist of a mycobiont and a photobiont in symbiosis. It has been hypothesized that the mycobiont’s and photobiont’s consumption of oxygen (increase of COX and AOX proteins of mitochondrial respiratory pathways and PTOX protein of chrolorespiration) establishes the required anoxic conditions for the activation of the phycobiont’s hydrogenase in a closed system. Our results clearly supported the above hypothesis, showing that lichens have the ability to activate appropriate bioenergetic pathways depending on the specific incubation conditions. Under light conditions, they successfully use the PSII-dependent and the PSII-independent pathways (decrease of D1 protein and parallel increase of PSaA protein) to transfer electrons to hydrogenase, while under dark conditions, lichens use the PFOR enzyme and the dark fermentative pathway to supply electrons to hydrogenase. These advantages of lichen symbiosis in combination with their ability to survive in extreme environments (while in a dry state) constitute them as unique and valuable hydrogen producing natural factories and pave the way for future biotechnological applications. PMID:25826211

  18. Lichen symbiosis: nature's high yielding machines for induced hydrogen production.

    PubMed

    Papazi, Aikaterini; Kastanaki, Elizabeth; Pirintsos, Stergios; Kotzabasis, Kiriakos

    2015-01-01

    Hydrogen is a promising future energy source. Although the ability of green algae to produce hydrogen has long been recognized (since 1939) and several biotechnological applications have been attempted, the greatest obstacle, being the O2-sensitivity of the hydrogenase enzyme, has not yet been overcome. In the present contribution, 75 years after the first report on algal hydrogen production, taking advantage of a natural mechanism of oxygen balance, we demonstrate high hydrogen yields by lichens. Lichens have been selected as the ideal organisms in nature for hydrogen production, since they consist of a mycobiont and a photobiont in symbiosis. It has been hypothesized that the mycobiont's and photobiont's consumption of oxygen (increase of COX and AOX proteins of mitochondrial respiratory pathways and PTOX protein of chrolorespiration) establishes the required anoxic conditions for the activation of the phycobiont's hydrogenase in a closed system. Our results clearly supported the above hypothesis, showing that lichens have the ability to activate appropriate bioenergetic pathways depending on the specific incubation conditions. Under light conditions, they successfully use the PSII-dependent and the PSII-independent pathways (decrease of D1 protein and parallel increase of PSaA protein) to transfer electrons to hydrogenase, while under dark conditions, lichens use the PFOR enzyme and the dark fermentative pathway to supply electrons to hydrogenase. These advantages of lichen symbiosis in combination with their ability to survive in extreme environments (while in a dry state) constitute them as unique and valuable hydrogen producing natural factories and pave the way for future biotechnological applications.

  19. ACTIVITY OF NATURAL PRODUCTS AGAINST SOME PHYTOPATHOGENIC FUNGI.

    PubMed

    La Torre, A; Caradonia, F; Gianferro, M; Molinu, M G; Battaglia, V

    2014-01-01

    The requirement of environmental protection and food safety is perceived with always major interest by public opinion and it is consistent with European Union legislation on the sustainable use of pesticides (Directive 2009/128/EC). This directive requires member states to promote low pesticide-input, giving priority to non-chemical methods and low risk plant protection products. In order to contribute to the achievement of these objectives antifungal activity of natural substances, characterized by a good toxicological and ecotoxicological profile, was tested. Essential oil of Melaleuca alternifolia, essential oil of Syzygium aromaticum and extract from Mimosa tenuiflora were tested against Alternaria alternata, Botrytis cinerea and Fusarium oxysporum f. sp. lycopersici (races 1 and 2). In vitro tests involved determination of radial growth of the colonies of fungi in the presence of varying concentrations of tested products in agar media and determination of germination percentage in the presence of tested product at various concentrations. The products based on essential oil of M. alternifolia were also tested in vivo on tomato fruits wounded and artificially inoculated with A. alternata or with B. cinerea. The in vitro tests showed the antifungal activity of both essential oils instead the extract from M. tenuiflora exhibited poor antifungal activity and only against A. alternata and B. cinerea. The results on tomato fruits showed inhibition of grey mould and black mould by essential oil of M. alternifolia. The antifungal activity increased with increasing concentrations. In conclusion, the obtained results in the present study showed promising prospects for the utilisation of investigated products to reduce the using of antifungal chemicals and to achieve a more sustainable use of pesticides.

  20. Pharmacists and Natural Health Products: A systematic analysis of professional responsibilities in Canada.

    PubMed

    Farrell, Jennifer; Ries, Nola M; Boon, Heather

    2008-01-01

    PURPOSE: Natural health products (natural health products) such as herbs, vitamins and homeopathic medicines are widely available in Canadian pharmacies. The purpose of this paper was to conduct a systematic analysis of Canadian pharmacy policies and guidelines to explore pharmacists' professional responsibilities with respect to natural health products. METHODS: Legislation, codes of ethics, standards of practice and guidance documents that apply to the practice of pharmacy in each Canadian jurisdiction were systematically collected and examined to identify if, and how, these instruments establish professional duties in regard to natural health products. RESULTS: The majority of Canadian jurisdictions now include some explicit reference to natural health products in standards of practice policy or guideline documents. Often natural health products are simply assumed to be included in the over-the-counter (OTC) product category and thus professional responsibilities for OTCs are relevant for natural health products. A minority of provinces have specific policies on natural health products, herbals or homeopathy. In addition, the National Association of Pharmacy Regulatory Authorities' Model Standards of Practice specifically refers to natural health products. Most policy documents indicate that pharmacists should inquire about natural health product use when counselling patients and, when asked, should provide accurate information regarding the efficacy, toxicity, side effects or interactions of natural health products. Public messaging also indicates that pharmacists are knowledgeable professionals who can provide evidence-based information about natural health products. CONCLUSIONS: Explicit policies or guidelines regarding pharmacists' professional responsibilities with respect to natural health products currently exist in the majority of Canadian jurisdictions.