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Sample records for hypericum natural products

  1. New Synthetic Methods for Hypericum Natural Products

    SciTech Connect

    Insik Jeon

    2006-12-12

    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. 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. PMID:26876610

  3. Inhibition of Bacterial Growth and Biofilm Production by Constituents from Hypericum spp

    PubMed Central

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

    2011-01-01

    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, Hypericumellipticum, Hypericum prolificum and Hypericum punctatum as inhibitors of bacterial growth and biofilm production. Assays were conducted against Staphylococcus epidermidis, Staphylococcusaureus, 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. PMID:22170780

  4. 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

  5. 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

  6. 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. PMID:25096393

  7. The production of hypericins in two selected Hypericum perforatum shoot cultures is related to differences in black gland structure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In vitro shoot cultures of Hypericum perforatum derived from wild populations grown in Armenia have a wide variation of hypericin and pseudohypericin metabolite content. We found that a germ line denoted as HP3 produces six times more hypericin and fourteen times more pseudohypericin than a second l...

  8. 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

  9. Inhibition of prostaglandin E(2) production by anti-inflammatory hypericum perforatum extracts and constituents in RAW264.7 Mouse Macrophage Cells.

    PubMed

    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

    2007-09-01

    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 E(2) (PGE(2)) 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

  10. 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

  11. Polycyclic Polyprenylated Acylphloroglucinol Congeners Possessing Diverse Structures from Hypericum henryi.

    PubMed

    Yang, Xing-Wei; Li, Ming-Ming; Liu, Xia; Ferreira, Daneel; Ding, Yuanqing; Zhang, Jing-Jing; Liao, Yang; Qin, Hong-Bo; Xu, Gang

    2015-04-24

    Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a class of hybrid natural products sharing the mevalonate/methylerythritol phosphate and polyketide biosynthetic pathways and showing considerable structural and bioactive diversity. In a systematic phytochemical investigation of Hypericum henryi, 40 PPAP-type derivatives, including the new compounds hyphenrones G-Q, were obtained. These compounds represent 12 different structural types, including four unusual skeletons exemplified by 5, 8, 10, and 17. The 12 different core structures found are explicable in terms of their biosynthetic origin. The structure of a known PPAP, perforatumone, was revised to hyphenrone A (5) by NMR spectroscopic and biomimetic synthesis methods. Several compounds exhibited inhibitory activities against acetylcholinesterase and human tumor cell lines. This study deals with the structural diversity, function, and biogenesis of natural PPAPs. PMID:25871261

  12. Constituents of Hypericum laricifolium and their cyclooxygenase (COX) enzyme activities.

    PubMed

    El-Seedi, Hesham Rushdey; Ringbom, Therese; Torssell, Kurt; Bohlin, Lars

    2003-12-01

    Investigation of the aerial parts of the medicinal plant Hypericum laricifolium led to the isolation of two new natural products, hentriacontanyl caffeate (1a), nonacosanyl caffeate (1b). In addition, stigmasterol, beta-sitosterol, 3-epi-betulinic acid (2), caffeic acid (3), ferulic acid, docosanol, p-hydroxybenzoic acid, 3,4-dimethoxy benzoic acid, quercetin (4), quercetin-3-O-galactoside (5), quercetin-3-O-rutinoside (6), quercetin-3-O-rhamnoside (7), quercetin-3-O-glucuronide (8) and shikimic acid were also isolated. The structures were determined by 1D- and 2D-NMR, mass spectrometry, and chemical transformations. The anti-inflammatory effects of the isolated compounds were discussed briefly. PMID:14646327

  13. 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

  14. Impact of hypericum (St.-John's-wort) given prenatally on cognition of mice offspring.

    PubMed

    Rayburn, W F; Gonzalez, C L; Christensen, H D; Harkins, T L; Kupiec, T C

    2001-01-01

    This study investigated the cognitive impact of prenatal exposure to the herbal antidepressant hypericum in CD-1 mice. Hypericum (182 mg/kg/day) or a placebo was consumed in food bars for 2 weeks before mating and throughout gestation. The hypericin content in our hypericum formulation was in the middle range of standardized hypericum products. One offspring per gender from each litter (hypericum 13, placebo 12) was tested on each of the following tasks: juvenile runway with adult memory, adult Morris maze, adult passive avoidance, or adult straight water runway followed by a dry Cincinnati maze. Learning occurred in both genders in all tasks (P<.003) with no significant differences between treatments at the final trial. Female offspring exposed to hypericum, rather than to a placebo, required more time to learn the Morris maze task (P<.05). Postlearning sessions did not show any significant differences. In conclusion, prenatal exposure to a therapeutic dose of hypericum did not have a major impact on certain cognitive tasks in mice offspring. PMID:11792531

  15. 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. PMID:27200032

  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. 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

  18. 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. PMID:26950610

  19. Immunomudulatory effects of hydroalcoholic extract of Hypericum perforatum

    PubMed Central

    Abtahi Froushani, Seyyed Meysam; Esmaili gouvarchin Galee, Hadi; Khamisabadi, Mahsa; Lotfallahzade, Bita

    2015-01-01

    Objective: Hypericum perforatum (St. John's Wort) has long been used in traditional medicine to treat a variety of internal and external ailments. The present study was done to evaluate the immumodulatory potentials of the hydroalcoholic extract of H. perforatum. Materials and Methods: Twenty male BALB/c-mice were randomly allocated in two equal groups and immunized with sheep red blood cells (SRBCs) and complete Freund’s adjuvant. Mice in the treatment group orally received hydroalcoholic extract of H. perforatum (110 mg/Kg daily) from the beginning of the study which continued for 2 weeks. Results: The data indicated a significant increase in the level of anti-SRBC antibody and simultaneously a significant decrease in the level of cellular immunity, an enhancement in foot pad thickness, in treatment group compared to control group. The level of the respiratory burst in phagocytic cells and the level of lymphocyte proliferation in splenocytes were significantly decreased in the treatment group compared to control group. Moreover, extract caused a significant reduction in the production of pro-inflammatory IL-17 as well as IFN-γ, parallel to increasing the level of IL-6. Conclusions: The hydroalcoholic extract of H. perforatum may be used as a natural source for treatment of immunopathologic conditions. PMID:25767758

  20. The cytohistological basis of apospory in Hypericum perforatum L.

    PubMed

    Galla, G; Barcaccia, G; Schallau, A; Puente Molins, M; Bäumlein, H; Sharbel, T F

    2011-03-01

    St. John's wort (Hypericum perforatum L., 2n = 4x = 32) is a medicinal plant that produces pharmaceutically important metabolites with antidepressive, anticancer and antiviral activities. It is also regarded as a serious weed in many countries. H. perforatum is furthermore an attractive model system for the study of apomixis. Natural populations of H. perforatum are predominantly composed of tetraploid individuals, although diploids and hexaploids are known to occur. It has been demonstrated that while diploids are sexual, polyploids are facultative apomictic whereby a single individual can produce both sexual and apomictic seeds. Despite our increasing understanding of gamete formation in sexually reproducing species, relatively little is known regarding the cytological basis of reproduction in H. perforatum. Here, we have studied embryo sac formation and the genetic constitution of seeds by means of staining-clearing of ovules/ovaries, DIC microscopy and flow cytometric seed screening (FCSS) of embryo and endosperm DNA contents. Comparisons of female sporogenesis and gametogenesis between sexual and apomictic accessions have enabled the identification of major phenotypic differences in embryo sac formation, in addition to complex fertilization scenarios entailing reduced and unreduced male and female gametes. These data provide new insights into the production of aposporous seeds in H. perforatum, and complement ongoing population genetic, genomic and transcriptomic studies. PMID:20596730

  1. St. John's Wort (Hypericum Perforatum) and Pregnancy

    MedlinePlus

    ... live chat Live Help Fact Sheets Share St. John’s Wort (Hypericum perforatum) Friday, 01 May 2015 In ... This sheet talks about whether exposure to St. John’s Wort may increase the risk for birth defects ...

  2. 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

  3. Natural products as photoprotection.

    PubMed

    Saewan, Nisakorn; Jimtaisong, Ampa

    2015-03-01

    The rise in solar ultraviolet radiation on the earth's surface has led to a depletion of stratospheric ozone over recent decades, thus accelerating the need to protect human skin against the harmful effects of UV radiation such as erythema, edema, hyperpigmentation, photoaging, and skin cancer. There are many different ways to protect skin against UV radiation's harmful effects. The most popular way to reduce the amount of UV radiation penetrating the skin is topical application of sunscreen products that contain UV absorbing or reflecting active molecules. Based on their protection mechanism, the active molecules in sunscreens are broadly divided into inorganic and organic agents. Inorganic sunscreens reflect and scatter UV and visible radiation, while organic sunscreens absorb UV radiation and then re-emit energy as heat or light. These synthetic molecules have limited concentration according to regulation concern. Several natural compounds with UV absorption property have been used to substitute for or to reduce the quantity of synthetic sunscreen agents. In addition to UV absorption property, most natural compounds were found to act as antioxidants, anti-inflammatory, and immunomodulatory agents, which provide further protection against the damaging effects of UV radiation exposure. Compounds derived from natural sources have gained considerable attention for use in sunscreen products and have bolstered the market trend toward natural cosmetics. This adds to the importance of there being a wide selection of active molecules in sunscreen formulations. This paper summarizes a number of natural products derived from propolis, plants, algae, and lichens that have shown potential photoprotection properties against UV radiation exposure-induced skin damage. PMID:25582033

  4. NATURAL PRODUCTS FOR PEST MANAGEMENT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The topic of natural products as pesticides is reviewed, with a discussion of the advantages and disadvantages of adopting a natural product-based strategy for pesticide discovery. Current and past natural product and natural product-based herbicides, insecticides, fungicides, molluscicides, rodent...

  5. 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

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

    PubMed

    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 E(2) 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  8. 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

  9. Marine natural products.

    PubMed

    Blunt, John W; Copp, Brent R; Keyzers, Robert A; Munro, Murray H G; Prinsep, Michèle R

    2013-02-01

    This review covers the literature published in 2011 for marine natural products, with 870 citations (558 for the period January to December 2011) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1152 for 2011), together with the relevant biological activities, source organisms and country of origin. Biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included. PMID:23263727

  10. Marine natural products.

    PubMed

    Blunt, John W; Copp, Brent R; Keyzers, Robert A; Munro, Murray H G; Prinsep, Michèle R

    2016-03-01

    This review covers the literature published in 2014 for marine natural products (MNPs), with 1116 citations (753 for the period January to December 2014) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1378 in 456 papers for 2014), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included. PMID:26837534

  11. Marine natural products.

    PubMed

    Blunt, John W; Copp, Brent R; Keyzers, Robert A; Munro, Murray H G; Prinsep, Michèle R

    2014-01-17

    This review covers the literature published in 2012 for marine natural products, with 1035 citations (673 for the period January to December 2012) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1241 for 2012), together with the relevant biological activities, source organisms and country of origin. Biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included. PMID:24389707

  12. Marine natural products.

    PubMed

    Blunt, John W; Copp, Brent R; Keyzers, Robert A; Munro, Murray H G; Prinsep, Michèle R

    2015-02-01

    This review covers the literature published in 2013 for marine natural products (MNPs), with 982 citations (644 for the period January to December 2013) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1163 for 2013), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included. PMID:25620233

  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. PMID:24946147

  14. Natural products: Emulation illuminates biosynthesis

    NASA Astrophysics Data System (ADS)

    Mercer, Jaron A. M.; Burns, Noah Z.

    2015-11-01

    A concise synthesis of the fungal natural product epicolactone suggests that this highly stereochemically complex yet racemic natural product may come from a cascade reaction between two polyhydroxylated arenes.

  15. Pest management with natural products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The 2012 Philadelphia ACS Symposium on Natural Products for Pest Management introduced recent discoveries and applications of natural products from insect, terrestrial plant, microbial, and synthetic sources for the management of insects, weeds, plant pathogenic microbes, and nematodes. The symposiu...

  16. 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

  17. 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

  18. Hypericum for fatigue - a pilot study.

    PubMed

    Stevinson, C; Dixon, M; Ernst, E

    1998-12-01

    Fatigue is a common reason for consulting a doctor but there is no definitive treatment. Hypericum perforatum has been shown to reduce symptoms of fatigue in depressed patients. It therefore may have potential value as a remedy for fatigue of unexplained origin. This pilot study aimed to investigate the effect of Hypericum on fatigue in a small group of patients in order to formulate a hypothesis upon which a randomized controlled trial could be subsequently based. The study protocol followed an uncontrolled, open design. Twenty patients consulting their doctors complaining of fatigue were treated with Hypericum extract (3×1 tablet daily) for six weeks. Compared to baseline values, perceived fatigue was significantly lower after 2 weeks of treatment and reduced significantly further after 6 weeks. Symptoms of depression and anxiety were also reduced. Baseline scores suggested that nearly half the sample may have been depressed at the start of the trial which was possibly related to fatigue. These results suggest there is scope for conducting a randomized placebo-controlled trial to investigate the specific effect of Hypericum on fatigue and that the study design must take account of the role of depression in fatigue. PMID:23196027

  19. Supramolecular complexations of natural products.

    PubMed

    Schneider, Hans-Jörg; Agrawal, Pawan; Yatsimirsky, Anatoly K

    2013-08-21

    Complexations of natural products with synthetic receptors as well as the use of natural products as host compounds are reviewed, with an emphasis on possible practical uses or on biomedical significance. Applications such as separation, sensing, enzyme monitoring, and protection of natural drugs are first outlined. We then discuss examples of complexes with all important classes of natural compounds, such as amino acids, peptides, nucleosides/nucleotides, carbohydrates, catecholamines, flavonoids, terpenoids/steroids, alkaloids, antibiotics and toxins. PMID:23703643

  20. Natural products and caries prevention.

    PubMed

    Cheng, Lei; Li, Jiyao; He, Libang; Zhou, Xuedong

    2015-01-01

    Dental caries is considered as the most common polymicrobial oral disease in the world. With the aim of developing alternative approaches to reduce or prevent the decay, numerous papers showed the potential anticaries activity of a number of natural products. The natural products with anticaries effects are selected from e.g. food, beverages, flowers or traditional herbs. Most of the effective components are proven to be polyphenol compounds. Many of the natural products are studied as antibacterial agents, while some of them are found to be effective in shifting the de-/remineralization balance. However, the mechanisms of the anticaries effects are still unclear for most of the natural products. In the future, more efforts need to be made to seek novel effective natural products via in vitro experiment, animal study and in situ investigations, as well as to enhance their anticaries effects with the help of novel technology like nanotechnology. PMID:25871417

  1. Xanthones from aerial parts of Hypericum laricifolium Juss.

    PubMed

    Ramírez-Gonzáilez, Irama; Amaro-Luis, Juan Manuel; Bahsas, Alí

    2013-12-01

    From the aerial parts of Hypericum laricifolium Juss., twelve compounds were isolated and identified. They were the xanthones: 1-hydroxy-7-methoxy-xanthone (1), 1,7-dihydroxy-xanthone (2), 2-hydroxy-xanthone (3), 6-deoxyisojacareubin (4), 1,3-dihydroxy-6-methoxy-xanthone (6), and 1,5,6-trihydroxy-7-methoxy-xanthone (7), together with beta-sitosterol, betulinic acid, vanillic acid, isoquercitrin and a mixture of quercetin and isorhamnetin. All the compounds were characterized by spectroscopic and mass spectrometric methods, and by comparison with literature data. Thisis the first report on the presence of xanthones in H.laricifolium. 1,3-Dihydroxy-6-methoxy-xanthone has been previously synthesized, but this is the first report of its isolation from a natural source. PMID:24555284

  2. Natural Products as Molecular Messengers*

    PubMed Central

    Meinwald, Jerrold

    2011-01-01

    The chemistry of naturally-occurring compounds has long been pursued in the search for medicines, dyes, pesticides, flavors, and fragrances. In addition, the deeper aim of understanding life itself as a chemical phenomenon has motivated generations of scientists. One consequence of such studies has been the realization that natural products often serve central roles as biological signaling agents. We consider natural products from the viewpoint of the organisms that produce and/or respond to them, and suggest how a naturally-occurring compound may acquire its role in chemical communication. PMID:21190370

  3. 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

  4. 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

  5. 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

  6. 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. PMID:12494339

  7. The efficiency of Viscum album ssp. album and Hypericum perforatum on human immune cells in vitro.

    PubMed

    Fidan, Isil; Ozkan, Semiha; Gurbuz, Ilhan; Yesilyurt, Emine; Erdal, Berna; Yolbakan, Sultan; Imir, Turgut

    2008-01-01

    Viscum album L. ssp. album and Hypericum perforatum L. are used for the treatment of different diseases. In this study, the effects of these herbals on immune cells were assessed in vitro. The phagocytosis, candidacidal activity of neutrophils and adhesion function of epithelial cells were investigated. Also, the expression of the surface markers of lymphocytes was analyzed by flow cytometry. It was observed that V. album ssp. album increased phagocytic activity and candidacidal activity of neutrophils and decreased adhesion function of epithelial cells. We also observed that in human peripheral blood mononuclear cells stimulated by Viscum album L. ssp. album the levels of CD4(+)CD25(+) and CD8(+)CD25(+) T cells, CD69 expressions in the activated T lymphocytes and CD3(-)CD16(+)CD56(+) NK cells increased compared to the cells that were not stimulated by this herbal. Whereas CD4(+)CD25(+), CD8(+)CD25(+) T cells, CD 69 expression and CD3(-)CD16(+)CD56(+) Natural killer cells did not show any significant differences with the presence of Hypericum perforatum L. compared to the control group. Hypericum perforatum L. increased candidacidal activity of neutrophils and decreased adhesion function of epithelial cells. In the light of these findings, it is considered that these extracts may be used as an adjuvant treatment option for immune activation in immunosuppressed patients. PMID:18668395

  8. 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). PMID:21338993

  9. 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. PMID:24603092

  10. Synthesis of Polycyclic Natural Products

    SciTech Connect

    Tuan Hoang Nguyen

    2003-05-31

    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.

  11. 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

  12. 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. PMID:27525351

  13. 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).

  14. 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

  15. Bacterial symbionts and natural products

    PubMed Central

    Crawford, Jason M.; Clardy, Jon

    2011-01-01

    The study of bacterial symbionts of eukaryotic hosts has become a powerful discovery engine for chemistry. This highlight looks at four case studies that exemplify the range of chemistry and biology involved in these symbioses: a bacterial symbiont of a fungus and a marine invertebrate that produce compounds with significant anticancer activity, and bacterial symbionts of insects and nematodes that produce compounds that regulate multilateral symbioses. In the last ten years, a series of shocking revelations – the molecular equivalents of a reality TV show’s uncovering the true parents of a well known individual or a deeply hidden family secret – altered the study of genetically encoded small molecules, natural products for short. These revelations all involved natural products produced by bacterial symbionts, and while details differed, two main plot lines emerged: parentage, in which the real producers of well known natural products with medical potential were not the organisms from which they were originally discovered, and hidden relationships, in which bacterially produced small molecules turned out to be the unsuspected regulators of complex interactions. For chemists, these studies led to new molecules, new biosynthetic pathways, and an understanding of the biological functions these molecules fulfill. PMID:21594283

  16. Antiplatelet properties of natural products.

    PubMed

    Vilahur, Gemma; Badimon, Lina

    2013-01-01

    Cardiovascular diseases (CVD) and its main underlying cause, atherothrombosis, are the major culprits of morbidity and mortality worldwide. Apart from the treatment of cardiovascular risk factors and the use of antithrombotic agents there is considerable interest in the role of natural food products and their bioactive components in the prevention and treatment of cardiovascular disorders. The consumption of healthy diets rich in functional foods, such as the Mediterranean diet, has shown to exert profound cardioprotective effects in the primary and secondary prevention of CVD. Moreover, accumulating data have attributed these beneficial effects, at least in part, to the modulation of key players in the pathogenesis of atherosclerosis, including amelioration in the lipid profile and vascular function and a decrease in oxidative stress and inflammation. Although with a much less clear picture, natural dietary compounds have also demonstrated to exert antiplatelet activities, further contributing to reduce the thrombotic risk. This article provides a brief overview of the atherothrombotic process to further provide an up-to-date review of the antiplatelet properties exerted by natural products and/or food-derived bioactive constituents - including ω-3 PUFA, olive oil, garlic and onions, tomatoes, mushrooms, polyphenol-rich beverages, and flavonol-rich cocoa - as well as to describe the mechanisms underlying these antiplatelet activities. PMID:23994642

  17. 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

  18. Antimalarial natural products: a review

    PubMed Central

    Mojab, Faraz

    2012-01-01

    Objective: Malaria is an infectious disease commonplace in tropical countries. For many years, major antimalarial drugs consisted of natural products, but since 1930s these drugs have been largely replaced with a series of synthetic drugs. This article tries to briefly indicate that some plants which previously were used to treat malaria, as a result of deficiencies of synthetic drugs, have revived into useful products once more. It also attempts to describe some tests which can be used to evaluate plant extracts for antimalarial activity. Materials and Methods: By referring to some recent literatures, data were collected about plants used for the treatment of malaria, evaluation of plant extracts for antimalarial activity, modes of action of natural antimalarial agents, and recent research on antimalarial plants in Iran and other countries. Results and Conclusion: There is an urgent need for the development of new treatments for malaria. Many countries have a vast precedence in the use of medicinal plants and the required knowledge spans many centuries. Although malaria is controlled in Iran, some researchers tend to study malaria and related subjects. In vitro biological tests for the detection of antimalarial activities in plant extracts are currently available. It is vital that the efficacy and safety of traditional medicines be validated and their active constituents be identified in order to establish reliable quality control measures. PMID:25050231

  19. 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

  20. Natural products as sources for new pesticides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Natural products as pesticides have been reviewed from several perspectives in the past; however, no review has examined the impact of natural product and natural product-based pesticides, as a function of new active ingredient registrations with the Environmental Protection Agency (EPA), on the U.S...

  1. 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

  2. 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. PMID:26310208

  3. Natural products and anti-inflammatory activity.

    PubMed

    Yuan, Gaofeng; Wahlqvist, Mark L; He, Guoqing; Yang, Min; Li, Duo

    2006-01-01

    The aim of this review paper was to summarise some commonly available natural products and their anti-inflammatory activity. We have collected data from MEDLINE, Current Contents and scientific journals, which included 92 publications. There are numerous natural products detailed in this literature; however we have summarized a few of the most commonly available and potent ones. In this paper, the natural products with anti-inflammatory activity including curcumin, parthenolide, cucurbitacins, 1,8-cineole, pseudopterosins, lyprinol, bromelain, flavonoids, saponins, marine sponge natural products and Boswellia serrata gum resin were reviewed. Natural products play a significant role in human health in relation to the prevention and treatment of inflammatory conditions. Further studies are being conducted to investigate the mechanism of action, metabolism, safety and long term side effect of these natural products, as well as interactions between these natural products with food and drug components. PMID:16672197

  4. Hypericum for depression. An update of the clinical evidence.

    PubMed

    Stevinson, C; Ernst, E

    1999-12-01

    This review is aimed at providing an updated evaluation of the clinical evidence regarding Hypericum perforatum (St. John's wort) as an antidepressant, based on recently published randomised controlled trials. Computerised literature searches revealed six trials published since the metaanalysis by Linde et al. (1996) [Linde, K., Ramirez, G., Mulrow, C.D., Pauls, A., Weidenhammer, W., Melchart, D., 1996. St. John's wort for depression--an overview and meta-analysis of randomised clinical trials. Br. Med. J. 313, 253-258]. The results of these studies provide further evidence that hypericum is superior to placebo in treating mild or moderate depression. However, there is still insufficient evidence to assess the efficacy of hypericum in comparison with conventional, particularly modern, antidepressants. Furthermore, there remains a lack of trials assessing long-term effects, other types of depression and different preparations and doses. It is concluded that recent clinical trials strengthen the case for hypericum as an antidepressant, but more work needs to be done to answer the remaining questions. PMID:10625118

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  6. 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

  7. Recent Advances in Natural Product Discovery

    PubMed Central

    Luo, Yunzi; Cobb, Ryan E.; Zhao, Huimin

    2014-01-01

    Natural products have been and continue to be the source and inspiration for a substantial fraction of human therapeutics. Although the pharmaceutical industry has largely turned its back on natural product discovery efforts, such efforts continue to flourish in academia with promising results. Natural products have traditionally been identified from a top-down perspective, but more recently genomics- and bioinformatics-guided bottom-up approaches have provided powerful alternative strategies. Here we review recent advances in natural product discovery from both angles, including diverse sampling and innovative culturing and screening approaches, as well as genomics-driven discovery and genetic manipulation techniques for both native and heterologous expression. PMID:25260043

  8. 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.

  9. 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. PMID:25300487

  10. 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

  11. 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. PMID:26509922

  12. Natural Products for Pest Management

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most organisms synthesize secondary products with biological activity that is useful in their defense. Defense can be against vertebrates, arthropods, mollusks, plants (both algal and higher plants), and microbes. Many of these compounds have been used from ancient times to the present as pharmace...

  13. 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.

  14. 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

  15. 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. PMID:7857511

  16. 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. PMID:22700239

  17. 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. PMID:23600727

  18. 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.

  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. PMID:23501254

  20. 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

  1. 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.

  2. Engineering microbial hosts for production of bacterial natural products.

    PubMed

    Zhang, Mingzi M; Wang, Yajie; Ang, Ee Lui; Zhao, Huimin

    2016-08-27

    Covering up to end 2015Microbial fermentation provides an attractive alternative to chemical synthesis for the production of structurally complex natural products. In most cases, however, production titers are low and need to be improved for compound characterization and/or commercial production. Owing to advances in functional genomics and genetic engineering technologies, microbial hosts can be engineered to overproduce a desired natural product, greatly accelerating the traditionally time-consuming strain improvement process. This review covers recent developments and challenges in the engineering of native and heterologous microbial hosts for the production of bacterial natural products, focusing on the genetic tools and strategies for strain improvement. Special emphasis is placed on bioactive secondary metabolites from actinomycetes. The considerations for the choice of host systems will also be discussed in this review. PMID:27072804

  3. An introduction to natural products isolation.

    PubMed

    Sarker, Satyajit D; Nahar, Lutfun

    2012-01-01

    Natural products, well known for unique chemical diversity and bioactivity, have continued to offer templates for the development of novel scaffolds of drugs. With the remarkable developments in the areas of separation science, spectroscopic techniques, microplate-based ultrasensitive in vitro assays and high-throughput screening (HTS) technologies, natural products research has gained momentum in recent years. The pre-isolation analyses of crude extracts or fraction from different natural matrices, isolation, online detection and dereplication of natural products, studies on chemotaxonomy and biosynthesis, chemical finger-printing, quality control of herbal products, and metabolomic studies have now become much easier than ever before because of the availability of a number of modern sophisticated hyphenated techniques, e.g., GC-MS, LC-PDA, LC-MS, LC-FTIR, LC-NMR, LC-NMR-MS, and CE-MS. This introductory chapter presents a general overview of the processes involved in natural products research, starting from extraction and isolation to elucidation of the structures of purified natural products and their bioactivity. PMID:22367891

  4. 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.

  5. Characterizing the metabolic fingerprint and anti-inflammatory activity of Hypericum gentianoides.

    PubMed

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

    2008-06-25

    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 E 2 synthesis in mammalian macrophages. PMID:18512936

  6. 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

  7. Hypermongones A-J, Rare Methylated Polycyclic Polyprenylated Acylphloroglucinols from the Flowers of Hypericum monogynum.

    PubMed

    Xu, Wen-Jun; Zhu, Meng-Di; Wang, Xiao-Bing; Yang, Ming-Hua; Luo, Jun; Kong, Ling-Yi

    2015-05-22

    Hypermongones A-J (1-10), rare methylated polycyclic polyprenylated acylphloroglucinol derivatives, together with three known simple acylphloroglucinols (11-13) as their plausible biogenetic precursors, were identified from the flowers of Hypericum monogynum. The structures of 1-10 were elucidated by analysis of their 1D and 2D NMR spectroscopic data; the absolute configuration of their polycyclic skeleton was determined by the electronic circular dichroism exciton chirality method and was subsequently confirmed by an X-ray diffraction study of 1. The evaluation of their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide-induced RAW264.7 cells revealed that compound 7 exhibited significant NO inhibition activity, with an IC50 value of 9.5 μM. PMID:25924023

  8. 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

  9. 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. PMID:26739136

  10. 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. PMID:26456468

  11. Mechanistic Advances in Plant Natural Product Enzymes

    PubMed Central

    Usera, Aimee R.; O’Connor, Sarah E.

    2009-01-01

    Summary of Recent Advances The biosynthetic pathways of plant natural products offer an abundance of knowledge to scientists in many fields. Synthetic chemists can be inspired by the synthetic strategies that nature uses to construct these compounds. Chemical and biological engineers are working to reprogram these biosynthetic pathways to more efficiently produce valuable products. Finally, biochemists and enzymologists are interested in the detailed mechanisms of the complex transformations involved in construction of these natural products. Study of biosynthetic enzymes and pathways therefore has a wide-ranging impact. In recent years, many plant biosynthetic pathways have been characterized, particularly the pathways that are responsible for alkaloid biosynthesis. Here we highlight recently studied alkaloid biosynthetic enzymes that catalyze production of numerous complex medicinal compounds, as well as the specifier proteins in glucosinosolate biosynthesis, whose structure and mechanism of action are just beginning to be unraveled. PMID:19632140

  12. 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

  13. 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

  14. Psychoactive natural products: overview of recent developments.

    PubMed

    Ujváry, István

    2014-01-01

    Natural psychoactive substances have fascinated the curious mind of shamans, artists, scholars and laymen since antiquity. During the twentieth century, the chemical composition of the most important psychoactive drugs, that is opium, cannabis, coca and "magic mushrooms", has been fully elucidated. The mode of action of the principal ingredients has also been deciphered at the molecular level. In the past two decades, the use of herbal drugs, such as kava, kratom and Salvia divinorum, began to spread beyond their traditional geographical and cultural boundaries. The aim of the present paper is to briefly summarize recent findings on the psychopharmacology of the most prominent psychoactive natural products. Current knowledge on a few lesser-known drugs, including bufotenine, glaucine, kava, betel, pituri, lettuce opium and kanna is also reviewed. In addition, selected cases of alleged natural (or semi-natural) products are also mentioned. PMID:24695249

  15. 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

  16. Supercritical fluid extraction in natural products analyses.

    PubMed

    Nahar, Lutfun; Sarker, Satyajit D

    2012-01-01

    Supercritical fluids (SCFs) are increasingly replacing the organic solvents, e.g., n-hexane, chloroform, dichloromethane, or methanol, that are conventionally used in industrial extraction, purification, and recrystallization operations because of regulatory and environmental pressures on hydrocarbon and ozone-depleting emissions. In natural products extraction and isolation, supercritical fluid extraction (SFE), especially employing supercritical CO(2), has become a popular choice. Sophisticated modern technologies allow precise regulation of changes in temperature and pressure, and thus manipulation of solvating property of the SCF, which helps the extraction of natural products of a wide range of polarities. This chapter deals mainly with the application of the SFE technology in the natural products extraction and isolation, and outlines various methodologies with specific examples. PMID:22367893

  17. 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

    2014-01-01

    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. PMID:24609016

  18. Current natural products with antihypertensive activity.

    PubMed

    Bai, Ren-Ren; Wu, Xiao-Ming; Xu, Jin-Yi

    2015-10-01

    Natural products have been an important source of new drugs, which also played a dominant role in the discovery and research of new drugs for the treatment of hypertension. This review article reviews the recent progress in the research and development of natural lead compounds with antihypertensive activity, including alkaloids, diterpenes, coumarins, flavonoids, and peptides. We summarized their structures, sources, as well as the antihypertensive mechanisms. These information provides instructive reference for the following structural modifications and optimization. PMID:26481372

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. Coal or natural gas for ecofuel production

    SciTech Connect

    Geertsema, A.

    1998-07-01

    The paper reviews the technology of the Fischer-Tropsch synthesis used in the Sasal plant in South Africa. It discusses environmental aspects and economics of new FT facilities for the production of diesel fuels. Several projects are briefly described which use this technology for natural gas conversion.

  8. 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

  9. 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. PMID:25266458

  10. 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

  11. 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

  12. 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

  13. European Directive fragrances in natural products.

    PubMed

    Scheman, Andrew; Scheman, Nicole; Rakowski, Ella-Marie

    2014-01-01

    Information on the presence of European Directive fragrance (EUF) allergens in plants and foods is important for numerous reasons. If an individual is allergic to an EUF and is avoiding fragrance, it is possible that they may still be exposed to the allergen in a natural product. In addition, because many of these allergens are also found in foods, it is possible that ingestion of a food containing the allergen may induce systemic contact allergy. Finally, individuals with lip dermatitis may react to contact with foods that contain the allergen. In this article, we have used the data available to identify which plants and foods contain EUF. When available, concentrations of EUF in natural products are provided. The goal of this article is to narrow down the list of botanicals to avoid for specific EUF allergies. PMID:24603515

  14. 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

  15. Advanced biomaterials development from "natural products".

    PubMed

    Baier, R E

    1988-04-01

    Natural substances and structures can serve increasingly well as biomedical products, given recent advances in understanding of requirements for biocompatibility and of methods for their preservation and surface tailoring. A successful example is the derivation of limb salvaging vessels, used in arterial reconstructive surgery, from human umbilical cords. There are numerous opportunities for additional product development from the umbilical cords' main ingredient, Wharton's gel, ranging from biolubricants to wound-healing aids. Major problems yet to be overcome with natural starting materials are their propensity for calcification and eventual biodeterioration. Surface modification of biomaterials to exhibit desired degrees of interaction with contacting viable tissues promises the greatest beneficial results. General principles of bioadhesion have broad applicability, predicting material behavior in environments as diverse as blood, saliva, and seawater. PMID:3058928

  16. Accelerated solvent extraction for natural products isolation.

    PubMed

    Mottaleb, Mohammad A; Sarker, Satyajit D

    2012-01-01

    Accelerated solvent extraction (ASE(®)), first introduced in 1995, is an automated rapid extraction technique that utilizes common solvents at elevated temperature and pressure, and thereby increases the efficiency of extraction of organic compounds from solid and semisolid matrices. ASE(®) allows extractions for sample sizes 1-100 g in minutes, reduces solvent uses dramatically, and can be applied to a wide range of matrices, including natural products. PMID:22367894

  17. Standardization for natural product synthetic biology.

    PubMed

    Zhao, Huimin; Medema, Marnix H

    2016-08-27

    Standardization is one of the foundational features of modern-day engineering, and the use of standardized parts and processes is a key element that distinguishes bona fide synthetic biology from traditional genetic engineering. Here, we discuss the role of standardization in natural product synthetic biology, focusing on standardization of data on biosynthetic pathways and gene clusters, as well as the role of standardization in the process of biosynthetic gene cluster engineering. PMID:27313083

  18. Mass spectrometry in natural product chemistry.

    PubMed

    Clayton, E; Hill, H C; Reed, R I

    1966-01-01

    Some mass spectrometric techniques are described which seem applicable to investigating problems in natural product chemistry. One example is of a sample of 5 mcg of a compound being identified by comparison with an authentic sample of prostaglandin derivative. Compared were mass, ion content, and structure. In the prostaglandin/unknown substance comparison, high-resolution mass spectrometry resolved a quandary: apparent additional ions present in the unknown substance were shown to be an impurity. PMID:12262324

  19. 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

  20. 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. PMID:9204773

  1. 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. PMID:25544013

  2. 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

  3. Targeting Mycobacterial Enzymes with Natural Products.

    PubMed

    Sieniawska, Elwira

    2015-10-22

    Tuberculosis (TB) is a recurring threat to contemporary civilization. It affects not only those within developing countries, but has also appeared again in places where it was once considered eradicated. TB co-infection in patients infected by HIV is, at the time of writing, the most common cause of death. In the field of searching for new antimycobacterial drug leads, compounds of natural origin still remain a promising source. The review is intended to gather information about natural products (metabolites of plants, fungi, bacteria, and marine sponges) that show activity against mycobacterial enzymes. Here, natural metabolites are presented as being inhibitors/activators of the mycobacterial enzymes involved in mycobacterial growth in vitro (ClpC1, ClpP, MurE ligase, mycothiol S-conjugate amidase, β-ketoacyl-ACP synthase, InhA) and in vivo, as regards the host cell (PtpB). Each enzyme is briefly described so as to generate an understanding of its role in mycobacterial growth and engender a perception of the mechanism of action of the studied natural compounds. Furthermore, after the introduction of the enzyme, its inhibitors are listed and exactly characterized. PMID:26441042

  4. 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. PMID:17722151

  5. Phylogenetic Approaches to Natural Product Structure Prediction

    PubMed Central

    Ziemert, Nadine; Jensen, Paul R.

    2015-01-01

    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. PMID:23084938

  6. Dithiolopyrrolone Natural Products: Isolation, Synthesis and Biosynthesis

    PubMed Central

    Qin, Zhiwei; Huang, Sheng; Yu, Yi; Deng, Hai

    2013-01-01

    Dithiolopyrrolones are a class of antibiotics that possess the unique pyrrolinonodithiole (4H-[1,2] dithiolo [4,3-b] pyrrol-5-one) skeleton linked to two variable acyl groups. To date, there are approximately 30 naturally occurring dithiolopyrrolone compounds, including holomycin, thiolutin, and aureothricin, and more recently thiomarinols, a unique class of hybrid marine bacterial natural products containing a dithiolopyrrolone framework linked by an amide bridge with an 8-hydroxyoctanoyl chain linked to a monic acid. Generally, dithiolopyrrolone antibiotics have broad-spectrum antibacterial activity against various microorganisms, including Gram-positive and Gram-negative bacteria, and even parasites. Holomycin appeared to be active against rifamycin-resistant bacteria and also inhibit the growth of the clinical pathogen methicillin-resistant Staphylococcus aureus N315. Its mode of action is believed to inhibit RNA synthesis although the exact mechanism has yet to be established in vitro. A recent work demonstrated that the fish pathogen Yersinia ruckeri employs an RNA methyltransferase for self-resistance during the holomycin production. Moreover, some dithiolopyrrolone derivatives have demonstrated promising antitumor activities. The biosynthetic gene clusters of holomycin have recently been identified in S. clavuligerus and characterized biochemically and genetically. The biosynthetic gene cluster of thiomarinol was also identified from the marine bacterium Pseudoalteromonas sp. SANK 73390, which was uniquely encoded by two independent pathways for pseudomonic acid and pyrrothine in a novel plasmid. The aim of this review is to give an overview about the isolations, characterizations, synthesis, biosynthesis, bioactivities and mode of action of this unique family of dithiolopyrrolone natural products, focusing on the period from 1940s until now. PMID:24141227

  7. 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

  8. Natural products from microbes associated with insects.

    PubMed

    Beemelmanns, Christine; Guo, Huijuan; Rischer, Maja; Poulsen, Michael

    2016-01-01

    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

  9. 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

  10. 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

  11. Secondary metabolites of Hypericum leptophyllum Hochst., an endemic Turkish species.

    PubMed

    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

  12. Volatile constituents of two Hypericum species from Tunisia.

    PubMed

    Hosni, Karim; Msaâda, Kamel; Ben Taârit, Mouna; Chahed, Thouraya; Marzouk, Brahim

    2011-11-01

    The chemical composition of the essential oils obtained by hydrodistillation from the aerial parts of the Tunisian Hypericum perforatum and H. ericoides ssp. roberti was elucidated by a combination of GC and GC-MS analyses. The main constituents of the oil of H. perforatum were alpha-pinene (11.8%), alpha-ylangene (10.4%), germacrene-D (9.5%), n-octane (6.5%) and alpha-selinene (5.9%). The oil of H. ericoides ssp. roberti exhibited a higher amount of aliphatic and branched hydrocarbons and the main constituents were n-octane (29.1%), alpha-pinene (10.9%), pulegone (7.7%) and acetophenone (7%). Both qualitative and quantitative differences were observed between the studied oils. This chemical variability seems likely to result from the genetic variability, since samples of both species were collected at the same location and processed under the same conditions. PMID:22224299

  13. Hypericum treatment of mild depressions with somatic symptoms.

    PubMed

    Hübner, W D; Lande, S; Podzuweit, H

    1994-10-01

    In a randomized, placebo-controlled, double-blind study, 39 patients with depression with somatic symptoms were treated with hypericum extract LI 160. The therapy lasted for 4 weeks; the dosage was 300 mg three times daily. At the onset of the study as well as after 2 and 4 weeks, the following criteria were analyzed: HAMD, B-L, CGI, and vegetative symptoms. The results show a significant improvement in the active treatment group at the 5% level as compared to placebo. Seventy percent of the patients treated with LI 160 were free of symptoms after 4 weeks. Typical symptoms of the depression such as lack of activity, tiredness, fatigue, and disturbed sleep, were especially responsive. In no case were any undesirable side effects observed. PMID:7857500

  14. 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.

  15. 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. PMID:25122538

  16. Synthetic biology of fungal natural products

    PubMed Central

    Mattern, Derek J.; Valiante, Vito; Unkles, Shiela E.; Brakhage, Axel A.

    2015-01-01

    Synthetic biology is an ever-expanding field in science, also encompassing the research area of fungal natural product (NP) discovery and production. Until now, different aspects of synthetic biology have been covered in fungal NP studies from the manipulation of different regulatory elements and heterologous expression of biosynthetic pathways to the engineering of different multidomain biosynthetic enzymes such as polyketide synthases or non-ribosomal peptide synthetases. The following review will cover some of the exemplary studies of synthetic biology in filamentous fungi showing the capacity of these eukaryotes to be used as model organisms in the field. From the vast array of different NPs produced to the ease for genetic manipulation, filamentous fungi have proven to be an invaluable source for the further development of synthetic biology tools. PMID:26284053

  17. 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

  18. 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

  19. 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

  20. 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

    2012-05-01

    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

  1. 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

  2. Historical variation of structural novelty in a natural product library.

    PubMed

    Kong, De-Xin; Guo, Ming-Yue; Xiao, Zhi-Hong; Chen, Ling-Ling; Zhang, Hong-Yu

    2011-11-01

    To evaluate the potential of natural products as novel structure suppliers, a historical analysis was performed on the structural novelty of a natural product library, viz., the Chapman & Hall/CRC Dictionary of Natural Products. The results show that although the unexplored natural product universe is still ample, it is more and more difficult to find novel agents from nature, with the discovery probability of novel structures and scaffolds being lower than 50% in the near future, which mainly results from the intrinsic redundancy of natural products and, thus, is unlikely to be reversed merely through technical progresses. PMID:22083910

  3. Natural product derived immune-regulatory agents.

    PubMed

    Talmadge, James E

    2016-08-01

    We can now declare that the clinical goal of immune intervention as a therapeutic strategy for neoplastic, infectious, autoimmune and inflammatory diseases, has been achieved and in many instances obtained regulatory approval. Although, interest in and optimism for this approach has fluctuated, in the last 20years, immunotherapy has progressed from trials with crude microbial mixtures and extracts to the sophisticated use of pure cultured bacterial, synthetized active moieties identified from crude extracts, analogues therefrom and agonists and antagonists identified during screening resulting in reproducible pharmacologically active compounds with multiple mechanisms of action. Our current understanding of the mechanism of action for immunoregulatory agents contributes to the future discovery of improved strategies to use these and future immunotherapies. In this review we have identified and discussed, those drugs that have been approved and or are in clinical development as immunoregulatory agents, emphasizing those derived from or associated with natural product. PMID:26968760

  4. 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. PMID:22821661

  5. 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

  6. 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).

  7. CO Methanation for Synthetic Natural Gas Production.

    PubMed

    Kambolis, Anastasios; Schildhauer, Tilman J; Kröcher, Oliver

    2015-01-01

    Energy from woody biomass could supplement renewable energy production towards the replacement of fossil fuels. A multi-stage process involving gasification of wood and then catalytic transformation of the producer gas to synthetic natural gas (SNG) represents progress in this direction. SNG can be transported and distributed through the existing pipeline grid, which is advantageous from an economical point of view. Therefore, CO methanation is attracting a great deal of attention and much research effort is focusing on the understanding of the process steps and its further development. This short review summarizes recent efforts at Paul Scherrer Institute on the understanding of the reaction mechanism, the catalyst deactivation, and the development of catalytic materials with benign properties for CO methanation. PMID:26598405

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

    2015-01-01

    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. PMID:26343621

  13. 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

  14. 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

  15. Natural products of relevance in the prevention and supportive treatment of depression.

    PubMed

    Muszyńska, Bożena; Łojewski, Maciej; Rojowski, Jacek; Opoka, Włodzimierz; Sułkowska-Ziaja, Katarzyna

    2015-01-01

    The use of herbs or their parts: leaves, roots, rhizomes, flowers, seeds, natural strains, as well as extracts or isolated metabolites is becoming more and more popular. Natural remedies not only act prophylactically, but also help to alleviate symptoms of many diseases and enhance the overall functioning of the internal organs. Many raw materials of natural origin plays a role in treatment of health problems, and also in case of serious diseases such as depression. Depression (affective disorder) now affects about 10% of the population, but in next few years due to the development of civilization and increasing pace of life, the probable number of people suffering from this disease can grow rapidly. Natural raw materials such as Bacopa monnieri, Crocus sativus, Eleutherococcus senticosus, Griffonia simplicifolia, Hypericum perforatum, Sceletium tortuosum, Piper methysticum, Rhodiola rosea, Aspalathus linearis, Camellia sinensis, Ficus carica, Lycium chinense, Cuminum cyminum, Panax Ginseng can effectively assist the prevention and treatment of depression. Daily diet may also have positive effect in prevention of this disease. It was found that 5-hydroxy-L-tryptophan, L-tryptophan (which are precursors of serotonin in the CNS), omega-3 fatty acids and anthranilic acid (vitamin L1) are able to improve mood. L-Tryptophan, 5-hydroxy-L-tryptophan are present in the largest quantities in the fruiting bodies of edible mushrooms. Omega-3 fatty acids are found in the flesh of fish, walnuts, soybeans, beans and chicken egg protein, while the anthranilic acid is commonly found in plants. PMID:26276913

  16. Marine Natural Products as Novel Antioxidant Prototypes

    PubMed Central

    Takamatsu, Satoshi; Hodges, Tyler W.; Rajbhandari, Ira; Gerwick, William H.; Hamann, Mark T.; Nagle, Dale G.

    2016-01-01

    Pure natural products isolated from marine sponges, algae, and cyanobacteria were examined for antioxidant activity using a 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) solution-based chemical assay and a 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) cellular-based assay. The DCFH system detects only antioxidants that penetrate cellular membranes. Potent antioxidants were identified and the results from each system compared. The algal metabolites cymopol (1), avrainvilleol (3), and fragilamide (4), and the invertebrate constituent puupehenone (5) showed strong antioxidant activity in both systems. Several compounds were active in the DPPH assay but significantly less active in the DCFH system. The green algal metabolite 7-hydroxycymopol (2) was isolated from Cymopolia barbata and its structure determined. Compound 2 was significantly less active in the DCFH system than cymopol (1). The sponge metabolites (1S)-(+)-curcuphenol (6), aaptamine (7), isoaaptamine (8), and curcudiol (9) and the cyanobacterial pigment scytonemin (10) showed strong antioxidant activity in the DPPH assay, but were relatively inactive in the DCFH system. Thus, cellular uptake dramatically affects the potential significance of antioxidants discovered using only the DPPH assay. The apparent “proantioxidants” hormothamnione A diacetate (11) and Laurencia monomer diacetate (12) require metabolic activation for antioxidant activity. Significant advantages are achieved using both a solution- and cellular-based assay to discover new antioxidants. PMID:12762791

  17. Natural Products That Target Cancer Stem Cells.

    PubMed

    Moselhy, Jim; Srinivasan, Sowmyalakshmi; Ankem, Murali K; Damodaran, Chendil

    2015-11-01

    The cancer stem cell model suggests that tumor initiation is governed by a small subset of distinct cells with stem-like character termed cancer stem cells (CSCs). CSCs possess properties of self-renewal and intrinsic survival mechanisms that contribute to resistance of tumors to most chemotherapeutic drugs. The failure to eradicate CSCs during the course of therapy is postulated to be the driving force for tumor recurrence and metastasis. Recent studies have focused on understanding the unique phenotypic properties of CSCs from various tumor types, as well as the signaling pathways that underlie self-renewal and drug resistance. Natural products (NPs) such as those derived from botanicals and food sources may modulate vital signaling pathways involved in the maintenance of CSC phenotype. The Wingless/Integrated (WNT), Hedgehog, Notch and PI3K/AKT/mTOR pathways have all been associated with quiescence and self-renewal of CSCs, as well as execution of CSC function including differentiation, multidrug resistance and metastasis. Recent studies evaluating NPs against CSC support the epidemiological evidence linking plant-based diets with reduced malignancy rates. This review covers the key aspects of NPs as modulators of CSC fate. PMID:26503998

  18. Structure and Function of Macroalgal Natural Products.

    PubMed

    Young, Ryan M; Schoenrock, Kathryn M; von Salm, Jacqueline L; Amsler, Charles D; Baker, Bill J

    2015-01-01

    Since the initial discovery of marine phyco-derived secondary metabolites in the 1950s there has been a rapid increase in the description of new algal natural products. These metabolites have multiple ecological roles as well as commercial value as potential drugs or lead compounds. With the emergence of resistance to our current arsenal of drugs as well as the development of new chemotherapies for currently untreatable diseases, new compounds must be sourced. As outlined in this chapter algae produce a diverse range of chemicals many of which have potential for the treatment of human afflictions.In this chapter we outline the classes of metabolites produced by this chemically rich group of organisms as well as their respective ecological roles in the environment. Algae are found in nearly every environment on earth, with many of these organisms possessing the ability to shape the ecosystem they inhabit. With current challenges to climate stability, understanding how these important organisms interact with their environment as well as one another might afford better insight into how they respond to a changing climate. PMID:26108497

  19. Natural products and the aging process.

    PubMed

    Ergin, Volkan; Bali, Elif Burcu; Hariry, Reza Ebrahimi; Karasu, Cimen

    2013-12-01

    Abstract Literature surveys show that the most of the research that have been conducted on the effect of herbal remedies on many tissue pathologies, including metabolic disturbances, cardiovascular decline, neurodegeneration, cataract, diabetic retinopathy and skin inflammation, all lead to an accelerated aging process. The increased carbonylation of proteins (carbonyl stress) disturbing their function has been indicated as an underlying mechanism of cellular senescence and age-related diseases. Because it is also linked to the carbonyl stress, aging chronic disease and inflammation plays an important role in understanding the clinical implications of cellular stress response and relevant markers. Greater knowledge of the molecular and cellular mechanisms involved in several pathologies associated with aging would provide a better understanding to help us to develop suitable strategies, use specific targets to mitigate the effect of human aging, prevent particularly chronic degenerative diseases and improve quality of life. However, research is lacking on the herbal compounds affecting cellular aging signaling as well as studies regarding the action mechanism(s) of natural products in prevention of the age-related disease. This review provides leads for identifying new medicinal agents or potential phytochemical drugs from plant sources for the prevention or delaying cellular aging processes and the treatment of some disorders related with accelerated body aging. PMID:25436747

  20. 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

  1. The impact of enzyme engineering upon natural product glycodiversification

    PubMed Central

    Williams, Gavin J; Gantt, Richard W; Thorson, Jon S

    2015-01-01

    Glycodiversification of natural products is an effective strategy for small molecule drug development. Recently, improved methods for chemo-enzymatic synthesis of glycosyl donors has spurred the characterization of natural product glycosyltransferases (GTs), revealing that the substrate specificity of many naturally occurring GTs as too stringent for use in glycodiversification. Protein engineering of natural product GTs has emerged as an attractive approach to overcome this limitation. This review highlights recent progress in the engineering/evolution of enzymes relevant to natural product glycodiversification with a particular focus upon GTs. PMID:18678278

  2. 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

  3. 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. PMID:27462333

  4. STRATEGIES FOR THE USE OF NATURAL PRODUCTS FOR WEED MANAGEMENT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Natural products have not been utilized as extensively for weed management as they have been for insect and plant pathogen management, but there are several notable successes such as glufosinate and the natural product-derived triketone herbicides. The two fundamental approaches to the use of natur...

  5. AGROCHEMICAL DISCOVERY: FINDING NEW FUNGICIDES FROM NATURAL PRODUCTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The continuing development of fungicide resistance in plant and human pathogens necessitates the discovery and development of new fungicides. Discovery and evaluation of natural product fungicides is largely dependent upon the availability of miniaturized antifungal bioassays. Essentials for natur...

  6. Developing a drug-like natural product library.

    PubMed

    Quinn, Ronald J; Carroll, Anthony R; Pham, Ngoc B; Baron, Paul; Palframan, Meredith E; Suraweera, Lekha; Pierens, Gregory K; Muresan, Sorel

    2008-03-01

    Addressing drug-like/lead-like properties of biologically active small molecules early in a lead generation program is the current paradigm within the drug discovery community. Lipinski's "rule of five" has become the most commonly used tool to assess the relationship between structures and drug-like properties. Sixty percent of the 126 140 unique compounds in The Dictionary of Natural Products had no violations of Lipinski's "rule of five". We have isolated 814 natural products based on their expected drug-like/lead-like properties to generate a natural product library (NPL) in which 85% of the isolated compounds had no Lipinski violations. The library demonstrates the feasibility of obtaining natural products known for rich chemical diversity with the required physicochemical properties for drug discovery. The knowledge generated in creation of the library of structurally characterized pure natural products may provide opportunities to front-load lead-like property space in natural product drug discovery programs. PMID:18257534

  7. 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

  8. 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

  9. Secondary metabolomics: natural products mass spectrometry goes global.

    PubMed

    Kersten, Roland D; Dorrestein, Pieter C

    2009-08-21

    A global LC-MS metabolite analysis of wild-type Pseudomonas auerigunosa and mutants targeting the natural product pyochelin revealed the production of previously unknown metabolites, the 2-alkyl-4,5-dihydrothiazole-4-carboxylates. PMID:19817465

  10. Hypericum in Infection: Identification of Anti-viral and Anti-inflammatory Constituents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Iowa Center for Research on Botanical Dietary Supplements seeks to optimize Echinacea, Hypericum and Prunella supplements for human-health benefit, focusing on anti-viral, anti-inflammatory and anti-pain effects. This paper reports on ongoing anti-viral and anti-inflammatory studies on Hypericu...

  11. Bioactive xanthones from the roots of Hypericum perforatum (common St John's Wort)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In contemporary western alternative medicine, extracts of the inflorescences and upper stem leaves of Hypericum perforatum L. (common St. John’s Wort; Clusiaceae) are taken orally for the treatment of mild to moderate depression and applied topically to promote wound-healing. Numerous researchers h...

  12. Analysis of Breeding Systems, Ploidy, and the Role of Hexaploids in Three Hypericum perforatum L. Populations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hexaploid seeds are produced by predominantly tetraploid populations of Hypericum perforatum, but the fate of hexaploid seedlings and their reproductive behavior have not been closely examined. We used flow cytometry to analyze single seeds and individual plant samples of three accessions of H. per...

  13. 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

  14. Lavandulyl flavanones from the stems of Hypericum calycinum L.

    PubMed

    Win, Thida; Htwe, Thant Thant; Shwe, Htay Htay; Heilmann, Jörg

    2012-06-01

    One novel lavandulyl flavanone (=2,3-dihydro-2-phenyl-4H-1-benzopyran-4-one) with an unusual 5,2',4',6'-tetrahydroxy substitution, calycinigin A (1), was isolated from the stems of Hypericum calycinum L. (Hypericaceae). The structure was elucidated on the basis of 1D- and 2D-NMR analysis, as well as mass spectrometry (LR-EI- and HR-EI-MS) and circular dichroism. Three known lavandulyl flavanones with 5,7,2',4',6'-pentahydroxy substitution, i.e., 2-4, were also isolated. Chemosystematically, this is the first report on the occurrence of prenylated flavanones in the family Hypericaceae. Reduction of cell viability by all compounds was evaluated in a MTT (=3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay using HeLa cells. Compound 1 showed moderate activity with an IC₅₀ value of 9.7±1.8 μM, whereas compounds 2-4 were less active exhibiting IC₅₀ values of 11.6±0.9, 19.3±1.5, and 40.7±2.4 μM, respectively. The antioxidant activity was evaluated by an ORAC (Oxygen Radical Absorbance Capacity) assay, and calycinigin A (1) was again the most active compound with a Trolox equivalent of 2.3±0.2. None of the compounds was able to reduce the TNF-α induced ICAM-1 expression in vitro using human microvascular endothelial cells (HMEC-1). PMID:22700237

  15. Explosive radiation in high Andean Hypericum-rates of diversification among New World lineages.

    PubMed

    Nürk, Nicolai M; Scheriau, Charlotte; Madriñán, Santiago

    2013-01-01

    The páramos, high-elevation Andean grasslands ranging from ca. 2800 m to the snow line, harbor one of the fastest evolving biomes worldwide since their appearance in the northern Andes 3-5 million years (Ma) ago. Hypericum (St. John's wort), with over 65% of its Neotropical species, has a center of diversity in these high Mountain ecosystems. Using nuclear rDNA internal transcribed spacer (ITS) sequences of a broad sample of New World Hypericum species we investigate phylogenetic patterns, estimate divergence times, and provide the first insights into diversification rates within the genus in the Neotropics. Two lineages appear to have independently dispersed into South America around 3.5 Ma ago, one of which has radiated in the páramos (Brathys). We find strong support for the polyphyly of section Trigynobrathys, several species of which group within Brathys, while others are found in temperate lowland South America (Trigynobrathys s.str.). All páramo species of Hypericum group in one clade. Within these páramo Hypericum species enormous phenotypic evolution has taken place (life forms from arborescent to prostrate shrubs) evidently in a short time frame. We hypothesize multiple mechanisms to be responsible for the low differentiation in the ITS region contrary to the high morphological diversity found in Hypericum in the páramos. Amongst these may be ongoing hybridization and incomplete lineage sorting, as well as the putative adaptive radiation, which can explain the contrast between phenotypic diversity and the close phylogenetic relationships. PMID:24062764

  16. 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. PMID:24388805

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

    PubMed

    Ladner, Christopher C; Williams, Gavin J

    2016-03-01

    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 has been developed that enables 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 non-ribosomal peptide analogues. PMID:26527577

  18. Natural Products and Dietary Prevention of Cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The concept of cancer prevention was first introduced in studies using the natural form of vitamin A in the prevention of epithelial cancers. Ever since, research on cancer prevention has grown and become a rather specialized field study. Cancer is a multistage process, and takes several years for...

  19. 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

  20. 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. PMID:26332654

  1. 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

  2. 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. PMID:23081914

  3. The use of an extract of Hypericum perforatum and Azadirachta indica in advanced diabetic foot: an unexpected outcome.

    PubMed

    Iabichella, Maria Letizia

    2013-01-01

    This is the first case reporting the results of using an extract of Hypericum flowers (Hypericum perforatum) and neem oil (Azadirachta indica) in foot wounds with exposed bone in a patient with bilateral advanced diabetic ulcers. The effective use of this cheap treatment in patients with diabetic lesions on the feet, if confirmed in a wide controlled study, might allow the caregivers to take care of patients at home. PMID:23413284

  4. The Structural Biology of Enzymes Involved in Natural Product Glycosylation

    PubMed Central

    Singh, Shanteri; Phillips, George N.

    2012-01-01

    The glycosylation of microbial natural products often dramatically influences the biological and/or pharmacological activities of the parental metabolite. Over the past decade, crystal structures of several enzymes involved in the biosynthesis and attachment of novel sugars found appended to natural products have emerged. In many cases, these studies have paved the way to a better understanding of the corresponding enzyme mechanism of action and have served as a starting point for engineering variant enzymes to facilitate to production of differentially-glycosylated natural products. This review specifically summarizes the structural studies of bacterial enzymes involved in biosynthesis of novel sugar nucleotides. PMID:22688446

  5. 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

  6. 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

  7. Using Video Production in Teaching Natural History.

    ERIC Educational Resources Information Center

    Fink, Linda S.

    1997-01-01

    Describes a course that uses video production projects to entice lower level students into independent field investigation, reinforce their scientific curiosity, and build their confidence in the value of their own observations. Discusses the rationale behind using video, the lab structure, the success of this approach, and logistics and…

  8. Coal or natural gas for ecofuel production

    SciTech Connect

    Geertsema, A.

    1998-04-01

    Given the extensive available resources of coal and, to a lesser extent, natural gas, the challenge to access these resources in a way that balances growth and conservation in a responsible way, is a tough technological task. On the one hand there is the inadverterable and undesirable liberation of CO{sub 2} when carbon is used and on the other hand it is reasonable to assume that hydrocarbon liquids will, for the foreseeable future, remain the backbone of the supply of energy to automotive vehicles. It is therefore necessary that options for improved environmental performance of such fuels are developed and considered for application where the economics would permit it.

  9. 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. PMID:27364626

  10. Plant Natural Products Targeting Bacterial Virulence Factors.

    PubMed

    Silva, Laura Nunes; Zimmer, Karine Rigon; Macedo, Alexandre José; Trentin, Danielle Silva

    2016-08-24

    Decreased antimicrobial efficiency has become a global public health issue. The paucity of new antibacterial drugs is evident, and the arsenal against infectious diseases needs to be improved urgently. The selection of plants as a source of prototype compounds is appropriate, since plant species naturally produce a wide range of secondary metabolites that act as a chemical line of defense against microorganisms in the environment. Although traditional approaches to combat microbial infections remain effective, targeting microbial virulence rather than survival seems to be an exciting strategy, since the modulation of virulence factors might lead to a milder evolutionary pressure for the development of resistance. Additionally, anti-infective chemotherapies may be successfully achieved by combining antivirulence and conventional antimicrobials, extending the lifespan of these drugs. This review presents an updated discussion of natural compounds isolated from plants with chemically characterized structures and activity against the major bacterial virulence factors: quorum sensing, bacterial biofilms, bacterial motility, bacterial toxins, bacterial pigments, bacterial enzymes, and bacterial surfactants. Moreover, a critical analysis of the most promising virulence factors is presented, highlighting their potential as targets to attenuate bacterial virulence. The ongoing progress in the field of antivirulence therapy may therefore help to translate this promising concept into real intervention strategies in clinical areas. PMID:27437994

  11. Genomic mining for Aspergillus natural products.

    PubMed

    Bok, Jin Woo; Hoffmeister, Dirk; Maggio-Hall, Lori A; Murillo, Renato; Glasner, Jeremy D; Keller, Nancy P

    2006-01-01

    The genus Aspergillus is renowned for its ability to produce a myriad of bioactive secondary metabolites. Although the propensity of biosynthetic genes to form contiguous clusters greatly facilitates assignment of putative secondary metabolite genes in the completed Aspergillus genomes, such analysis cannot predict gene expression and, ultimately, product formation. To circumvent this deficiency, we have examined Aspergillus nidulans microarrays for expressed secondary metabolite gene clusters by using the transcriptional regulator LaeA. Deletion or overexpression of laeA clearly identified numerous secondary metabolite clusters. A gene deletion in one of the clusters eliminated the production of the antitumor compound terrequinone A, a metabolite not described, from A. nidulans. In this paper, we highlight that LaeA-based genome mining helps decipher the secondary metabolome of Aspergilli and provides an unparalleled view to assess secondary metabolism gene regulation. PMID:16426969

  12. Native and engineered promoters in natural product discovery.

    PubMed

    Myronovskyi, Maksym; Luzhetskyy, Andriy

    2016-08-27

    Covers the period up to 2016Bacterial-based natural products have long represented a promising resource for the development of commercially relevant therapeutics, and more than two thirds of these products have been developed from members of the genus Streptomyces. The extensive sequencing of bacterial genomes suggests that the majority of gene clusters encoding natural products are silent and not expressed under standard laboratory conditions. However, these clusters can be activated through systematic exchanges between native transcriptionally silent promoters and transcriptionally active promoters. Therefore, the availability of well-studied constitutive and inducible promoters is of the utmost importance for identifying natural products encoded by silent gene clusters. This manuscript provides an overview of the promoter control elements for streptomycetes and examples of their successful application in refactoring the biosynthetic pathways of natural products. PMID:27438486

  13. 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

  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. PMID:26609051

  16. Natural products-friends or foes?

    PubMed

    Margină, Denisa; Ilie, Mihaela; Grădinaru, Daniela; Androutsopoulos, Vasilis P; Kouretas, Demetrios; Tsatsakis, Aristidis M

    2015-08-01

    A trend in the general population has been observed in recent years regarding the orientation toward preventive measures in health; in this context the increased interest from the users and researchers concerning the active effect of food supplements on the health state and on longevity, is noticeable. All over the world, the consumption of natural foods and of vegetal supplements has increased spectacularly over the last 5-10 years. The decreased prevalence of cardio-vascular diseases associated with Mediterranean diet, as well as the French paradox convinced researchers to scientifically document the beneficial outcomes pointed out by traditional use of plants, and to try to develop supplements that would have the same positive effects as these noticed for diet components. The intense research dedicated to this topic revealed the fact that food supplements are linked to some problematic aspects, such as toxicological side effects when associated with classical synthetic drugs. The food supplement-drug interactions are submitted to complex issues regarding pharmacokinetic interactions leading to changes in absorption, distribution, metabolism and excretion processes with direct impact on effect and toxicological potential. The present review based on recent literature aims at discussing the food-drug interactions with direct impact on efficacy and toxicity of drugs. PMID:25980574

  17. 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. PMID:21244594

  18. 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

  19. 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)

  20. Brevetoxin Degradation and By-Product Formation via Natural Sunlight

    PubMed Central

    Hardman, Ron C.; Cooper, William J.; Bourdelais, Andrea J.; Gardinali, Piero; Baden, Daniel G.

    2010-01-01

    We investigated the effects of solar radiation on brevetoxin (PbTx2). Our findings suggest that natural sunlight mediates brevetoxin (PbTx2) degradation and results in brevetoxin by-product formation via photochemical processes. PMID:26436141

  1. 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

  2. Raman spectra of carotenoids in natural products.

    PubMed

    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 nu1 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 nu1 band at 1537 cm(-1) which can be assigned to crocetin, having seven conjugated carbon-carbon double bonds. A correlation between nu1 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 nu1 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 nu1 bands at 1504 and 1496 cm(-1), respectively. On the basis of the correlation between nu1 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. PMID:12909134

  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. 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. PMID:27155563

  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. Anti-Enterovirus 71 Agents of Natural Products.

    PubMed

    Wang, Liyan; Wang, Junfeng; Wang, Lishu; Ma, Shurong; Liu, Yonghong

    2015-01-01

    This review, with 42 references, presents the fascinating area of anti-enterovirus 71 natural products over the last three decades for the first time. It covers literature published from 2005-2015 and refers to compounds isolated from biogenic sources. In total, 58 naturally-occurring anti-EV71 compounds are recorded. PMID:26370955

  7. Bioactive activities of natural products against herpesvirus infection.

    PubMed

    Son, Myoungki; Lee, Minjung; Sung, Gi-Ho; Lee, Taeho; Shin, Yu Su; Cho, Hyosun; Lieberman, Paul M; Kang, Hyojeung

    2013-10-01

    More than 90% of adults have been infected with at least one human herpesvirus, which establish long-term latent infection for the life of the host. While anti-viral drugs exist that limit herpesvirus replication, many of these are ineffective against latent infection. Moreover, drug-resistant strains of herpesvirus emerge following chemotherapeutic treatment. For example, resistance to acyclovir and related nucleoside analogues can occur when mutations arise in either HSV thymidine kinase or DNA polymerases. Thus, there exists an unmet medical need to develop new anti-herpesvirus agents with different mechanisms of action. In this Review, we discuss the promise of anti-herpetic substances derived from natural products including extracts and pure compounds from potential herbal medicines. One example is Glycyrrhizic acid isolated from licorice that shows promising antiviral activity towards human gammaherpesviruses. Secondly, we discuss anti-herpetic mechanisms utilized by several natural products in molecular level. While nucleoside analogues inhibit replicating herpesviruses in lytic replication, some natural products can disrupt the herpesvirus latent infection in the host cell. In addition, natural products can stimulate immune responses against herpesviral infection. These findings suggest that natural products could be one of the best choices for development of new treatments for latent herpesvirus infection, and may provide synergistic anti-viral activity when supplemented with nucleoside analogues. Therefore, it is important to identify which natural products are more efficacious anti-herpetic agents, and to understand the molecular mechanism in detail for further advance in the anti-viral therapies. PMID:24173639

  8. 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. PMID:27417932

  9. 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. PMID:24503452

  10. Spillover of a biological control agent (Chrysolina quadrigemina) onto native St. Johnswort (Hypericum punctatum)

    PubMed Central

    Cook-Patton, Susan C.; Agrawal, Anurag A.

    2016-01-01

    Biological control agents may have unintended effects on native biota, particularly species that are closely related to the target invader. Here, we explored how Chrysolina quadrigemina, a beetle introduced to control the invasive weed Hypericum perforatum, impacts native H. punctatum in Tompkins County, New York, USA. Using a suite of complementary field surveys and experimental manipulations, we examined beetle preference for native and exotic Hypericum species and whether beetle herbivory influences the spatial distribution of H. punctatum. We found that the introduced beetle readily consumes native H. punctatum in addition to its intended target, and that H. punctatum at our field sites generally occurs along forest edges despite higher performance of experimental plants in more open habitats. However, we found no evidence that the beetle limits H. punctatum to forest edge habitats. PMID:27069816

  11. Morphological and Phytochemical Diversity among Hypericum Species of the Mediterranean Basin

    PubMed Central

    Nürk, Nicolai M.; Crockett, Sara L.

    2012-01-01

    The genus Hypericum L. (St. John’s wort, Hypericaceae) includes more than 450 species that occur in temperature or tropical mountain regions of the world. 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. The Mediterranean Basin has been recognized as a hot spot of diversity for the genus Hypericum, and as such is a region in which many endemic species occur. Species belonging to sections distributed in this area of the world display considerable morphological and phytochemical diversity. Results of a cladistic analysis, based on 89 morphological characters that were considered phylogenetically informative, are given here. In addition, a brief overview of morphological characteristics and the distribution of pharmaceutically relevant secondary metabolites for species native to this region of the world are presented. PMID:22662020

  12. Spillover of a biological control agent (Chrysolina quadrigemina) onto native St. Johnswort (Hypericum punctatum).

    PubMed

    Tingle, Jessica L; Cook-Patton, Susan C; Agrawal, Anurag A

    2016-01-01

    Biological control agents may have unintended effects on native biota, particularly species that are closely related to the target invader. Here, we explored how Chrysolina quadrigemina, a beetle introduced to control the invasive weed Hypericum perforatum, impacts native H. punctatum in Tompkins County, New York, USA. Using a suite of complementary field surveys and experimental manipulations, we examined beetle preference for native and exotic Hypericum species and whether beetle herbivory influences the spatial distribution of H. punctatum. We found that the introduced beetle readily consumes native H. punctatum in addition to its intended target, and that H. punctatum at our field sites generally occurs along forest edges despite higher performance of experimental plants in more open habitats. However, we found no evidence that the beetle limits H. punctatum to forest edge habitats. PMID:27069816

  13. Antidepressant-like activity of adhyperforin, a novel constituent of Hypericum perforatum L.

    PubMed Central

    Tian, Jingwei; Zhang, Fangxi; Cheng, Jucan; Guo, Shuren; Liu, Pinglan; Wang, Hongbo

    2014-01-01

    Adhyperforin is a novel constituent of Hypericum perforatum L., but its antidepressant-like activity remains unclear. To explore that, several well-validated animal models of depression as well as neurotransmitter reuptake and transporter binding assays were conducted. The results showed adhyperforin could reduce the immobility time of mice in the forced swimming test and tail suspension assay, antagonize the behaviors induced by reserpine, and have no effect on locomotor activity. Furthermore, following establishment of a chronic unpredictable mild stress model, adhyperforin increased the number of crossings and rearings in rats in the open field test and increased the sucrose consumption. Finally, adhyperforin inhibited uptake of serotonin, norepinephrine, and dopamine, and displayed robust binding affinities for the serotonin and norepinephrine transporters. Overall, the current study provides the first evidence that adhyperforin is a novel, active ingredient of Hypericum perforatum L. with robust antidepressant-like activity. PMID:25005489

  14. 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. PMID:22059469

  15. 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 Central

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

    2011-01-01

    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. PMID:22059469

  16. Norsampsones A-D, four new decarbonyl polycyclic polyprenylated acylphloroglucinols from Hypericum sampsonii.

    PubMed

    Tian, Wen-Jing; Yu, Yang; Yao, Xiao-Jun; Chen, Hai-Feng; Dai, Yi; Zhang, Xiao-Kun; Yao, Xin-Sheng

    2014-07-01

    Norsampsones A-D (1-4), four new decarbonyl polycyclic polyprenylated acylphloroglucinols, together with a new biogenetically related compound hypersampsone M (5), were isolated from the aerial parts of Hypericum sampsonii. Norsampsones A-D featured an unprecedented carbon skeleton with the loss of C-2 carbonyl in the phloroglucinol ring. All structures were determined by extensive NMR spectroscopic methods, ECD calculation, and single-crystal X-ray diffraction. PMID:24932990

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  18. Composition and Antimicrobial Activity of the Essential Oil and Extract of Hypericum elongatum

    NASA Astrophysics Data System (ADS)

    Ghasemi, Younes; Khalaj, Amir; Mohagheghzadeh, Abdolali; Khosravi, Ahmad Reza; Morowvat, Mohammad Hossein

    HOFARIGHUN, RAEE flower, thousand eyes wort are popular names for Hypericum sp in Persian language mostly called H. perforatum. It has been used as antispasmodic, diuretic, antimigraine, antiepileptic and cholagouge. Tisane of these plants in red wine was used as snake bite and burning remedy. The volatile constituents, obtained from air-dried aerial parts of fruiting Hypericum elongatum were analyzed by GC/MS method. Thirty four components of about 96.50% of total oil were identified. Pinene <α> (80.43%), Terpinene <γ> (4.23%) and Pinene <ß>(2.59%) were the principal components (87.16%). The essential oil and hydroalcoholic extract were evaluated for antibacterial, antifungal and anti-yeast activities by using disc diffusion method. Screening of the antimicrobials was investigated on Gram positive bacteria (Staphylococcus aureus PTCC 1112, Staphylococcus epidermidis PTCC 1114, Bacillus subtilis PTCC 1023, Enterococcus faecalis ATCC 8043), Gram negative bacteria (Escherichia coli PTCC 1338, Pseudomonas aeruginosa PTCC 1047, Salmonella typhi PTCC 1609), yeasts (Candida albicans ATCC 14053, Candida kefyr ATCC 3826) and fungi (Aspergillus niger PLM 1140, Aspergillus fumigatus PLM 712). The MIC of essential oil also was identified. Antimicrobial activity of essential oil against all of the microorganisms was observed, except Aspergillus niger and Aspergillus fumigatus. In spite of antimicrobial activity of hydroalcoholic extract against bacteria, there was no antimicrobial activity against fungi and yeasts. A survey of the literature revealed no reports dealing with chemical composition of essential oil and antimicrobial activity of Hypericum elongatum.

  19. 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. PMID:26451111

  20. 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

  1. Environmental policy and regulatory constraints to natural gas production.

    SciTech Connect

    Elcock, D.

    2004-12-17

    For the foreseeable future, most of the demand for natural gas in the United States will be met with domestic resources. Impediments, or constraints, to developing, producing, and delivering these resources can lead to price increases or supply disruptions. Previous analyses have identified lack of access to natural gas resources on federal lands as such an impediment. However, various other environmental constraints, including laws, regulations, and implementation procedures, can limit natural gas development and production on both federal and private lands. This report identifies and describes more than 30 environmental policy and regulatory impediments to domestic natural gas production. For each constraint, the source and type of impact are presented, and when the data exist, the amount of gas affected is also presented. This information can help decision makers develop and support policies that eliminate or reduce the impacts of such constraints, help set priorities for regulatory reviews, and target research and development efforts to help the nation meet its natural gas demands.

  2. Opportunities and Challenges for Natural Products as Novel Antituberculosis Agents.

    PubMed

    Farah, Shrouq I; Abdelrahman, Abd Almonem; North, E Jeffrey; Chauhan, Harsh

    2016-01-01

    Current tuberculosis (TB) treatment suffers from complexity of the dosage regimens, length of treatment, and toxicity risks. Many natural products have shown activity against drug-susceptible, drug-resistant, and latent/dormant Mycobacterium tuberculosis, the pathogen responsible for TB infections. Natural sources, including plants, fungi, and bacteria, provide a rich source of chemically diverse compounds equipped with unique pharmacological, pharmacokinetic, and pharmacodynamic properties. This review focuses on natural products as starting points for the discovery and development of novel anti-TB chemotherapy and classifies them based on their chemical nature. The classes discussed are divided into alkaloids, chalcones, flavonoids, peptides, polyketides, steroids, and terpenes. This review also highlights the importance of collaboration between phytochemistry, medicinal chemistry, and physical chemistry, which is very important for the development of these natural compounds. PMID:26565779

  3. Biosynthesis of Phosphonic and Phosphinic Acid Natural Products

    PubMed Central

    Metcalf, William W.; van der Donk, Wilfred A.

    2009-01-01

    Natural products containing carbon-phosphorus bonds (phosphonic and phosphinic acids) have found widespread use in medicine and agriculture. Recent years have seen a renewed interest in the biochemistry and biology of these compounds with the cloning of the biosynthetic gene clusters for several family members. This review discusses the commonalities and differences in the molecular logic that lies behind the biosynthesis of these compounds. The current knowledge regarding the metabolic pathways and enzymes involved in the production of a number of natural products, including the approved antibiotic fosfomycin, the widely used herbicide phosphinothricin, and the clinical candidate for treatment of malaria FR900098, is presented. Many of the enzymes involved in the biosynthesis of these compounds catalyze chemically and biologically unprecedented transformations and a wealth of new biochemistry has been revealed through their study. These studies have also suggested new strategies for natural product discovery. PMID:19489722

  4. 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.

  5. 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. PMID:25961523

  6. 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. PMID:26586404

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

    PubMed

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

    2016-01-01

    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. PMID:27136524

  8. 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

  9. Engineered Biosynthesis of Medicinally Important Plant Natural Products in Microorganisms.

    PubMed

    Zhang, Shuwei; Wang, Siyuan; Zhan, Jixun

    2016-01-01

    Plants produce structurally and functionally diverse natural products. Some of these compounds possess promising health-benefiting properties, such as resveratrol (antioxidant) curcumin (anti-inflammatory, anti-allergic and anticancer), paclitaxel (anticancer) and artemisinin (antimalarial). These compounds are produced through particular biosynthetic pathways in the plants. While supply of these medicinally important molecules relies on extraction from the producing species, recent years have seen significant advances in metabolic engineering of microorganisms for the production of plant natural products. Escherichia coli and Saccharomyces cerevisiae are the two most widely used heterologous hosts for expression of enzymes and reconstitution of plant natural product biosynthetic pathways. Total biosynthesis of many plant polyketide natural products such as curcumin and piceatannol in microorganisms has been achieved. While the late biosynthetic steps of more complex molecules such as paclitaxel and artemisinin remain to be understood, reconstitution of their partial biosynthetic pathways and microbial production of key intermediates have been successful. This review covers recent advances in understanding and engineering the biosynthesis of plant polyketides and terpenoids in microbial hosts. PMID:26456465

  10. 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. PMID:25482899

  11. Elemental fingerprinting of Hypericum perforatum (St John's Wort) herb and preparations using ICP-OES and chemometrics.

    PubMed

    Owen, Jade D; Kirton, Stewart B; Evans, Sara J; Stair, Jacqueline L

    2016-06-01

    St. John's wort (SJW) (Hypericum perforatum) is a herbal remedy commonly used to treat mild depression. The elemental profiles of 54 samples (i.e., dry herbs, tablets and capsules) were evaluated by monitoring 25 elements using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). The major elemental constituents in the SJW samples were Ca (300-199,000μg/g), Mg (410-3,530μg/g), Al (4.4-900μg/g), Fe (1.154-760μg/g), Mn (2.4-261μg/g), Sr (0.88-83.6μg/g), and Zn (7-64μg/g). For the sixteen elements that could be reliably quantified, principal component analysis (PCA) was used to investigate underlying patterns in the data. PCA models identified 7 key elements (i.e., Ba, Ca, Cd, Mg, Mo, Ni and Y), which described 85% of the variance in the dataset in the first three principal components. The PCA approach resulted in a general delineation between the three different formulations and provides a basis for monitoring product quality in this manner. PMID:26994552

  12. 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. PMID:25004127

  13. Perylenequinone Natural Products: Enantioselective Synthesis of the Oxidized Pentacyclic Core‡

    PubMed Central

    Mulrooney, Carol A.; Morgan, Barbara J.; Li, Xiaolin; Kozlowski, Marisa C.

    2009-01-01

    An enantioselective approach to the perylenequinone core found in the mold perylenequinone natural products is outlined. Specifically, the first asymmetric syntheses of helical chiral perylenequinones absent any additional stereogenic centers are described. Key elements of the synthetic venture include a catalytic enantioselective biaryl coupling, a PIFA-induced naphthalene hydroxylation, and a palladium-mediated aromatic decarboxylation. Transfer of the binaphthalene axial stereochemistry to the perylenequinone helical stereochemistry proceeded with good fidelity. Furthermore, the resultant perylenequinones were shown to possess sufficient atropisomeric stability to be viable intermediates in the biogenesis of the perylenequinone natural products. This stability supports the use of the helical axis as a stereochemical relay in synthesis of the natural products containing additional stereochemical centers. PMID:19894746

  14. 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

  15. In Situ Natural Product Discovery via an Artificial Marine Sponge

    PubMed Central

    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. PMID:25004127

  16. 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

  17. Chemoenzymatic and Bioenzymatic Synthesis of Carbohydrate Containing Natural Products

    NASA Astrophysics Data System (ADS)

    Ostash, Bohdan; Yan, Xiaohui; Fedorenko, Victor; Bechthold, Andreas

    The domain of bioactive natural products contains many oligosaccharides and aglycones decorated with various sugars. Glycan moieties influence essential aspects of biology of small molecules, such as mode of action, target recognition, pharmacokinetics, stability, and others. Methods of generation of novel glycosylated natural products are therefore of great value, as they, for example, may help fight human diseases more efficiently or provide healthier diet. This review covers the existing literature published mainly over the last decade that deals with biology-based approaches to novel glycoforms. Both genetic manipulations of biosynthesis of glycoconjugates and chemoenzymatic synthesis of novel "sweet" molecules are reviewed here. Wherever available, relationships between carbohydrate portions of the natural products and their biological activities are highlighted.

  18. Recent advances in deep-sea natural products.

    PubMed

    Skropeta, Danielle; Wei, Liangqian

    2014-08-01

    Covering: 2009 to 2013. This review covers the 188 novel marine natural products described since 2008, from deep-water (50->5000 m) marine fauna including bryozoa, chordata, cnidaria, echinodermata, microorganisms, mollusca and porifera. The structures of the new compounds and details of the source organism, depth of collection and country of origin are presented, along with any relevant biological activities of the metabolites. Where reported, synthetic studies on the deep-sea natural products have also been included. Most strikingly, 75% of the compounds were reported to possess bioactivity, with almost half exhibiting low micromolar cytotoxicity towards a range of human cancer cell lines, along with a significant increase in the number of microbial deep-sea natural products reported. PMID:24871201

  19. Covalent interaction of ascorbic acid with natural products

    PubMed Central

    Kesinger, Nicholas G.; Stevens, Jan F.

    2009-01-01

    While ascorbic acid (Vitamin C) is mostly known as a cofactor for proline hydroxylase and as a biological antioxidant, it also forms covalent bonds with natural products which we here refer to as ‘ascorbylation’. A number of natural products containing an ascorbate moiety has been isolated and characterized from a variety of biological sources, ranging from marine algae to flowering plants. Most of these compounds are formed as a result of nucleophilic substitution or addition by ascorbate, e.g. the ascorbigens from Brassica species are ascorbylated indole derivatives. Some ascorbylated tannins appear to be formed from electrophilic addition to dehydroascorbic acid. There are also examples of annulations of ascorbate with dietary polyphenols, e.g., epigallocatechin gallate (EGCG) and resveratrol derivatives. Herein is a survey of thirty-three ascorbylated natural products and their reported biological activities. PMID:19875138

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

    PubMed

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

    2016-03-01

    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

  1. 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. PMID:24824531

  2. 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

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

    PubMed

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

    2016-01-01

    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. PMID:27399665

  4. Exploiting the reversibility of natural product glycosyltransferase-catalyzed reactions.

    PubMed

    Zhang, Changsheng; Griffith, Byron R; Fu, Qiang; Albermann, Christoph; Fu, Xun; Lee, In-Kyoung; Li, Lingjun; Thorson, Jon S

    2006-09-01

    Glycosyltransferases (GTs), an essential class of ubiquitous enzymes, are generally perceived as unidirectional catalysts. In contrast, we report that four glycosyltransferases from two distinct natural product biosynthetic pathways-calicheamicin and vancomycin-readily catalyze reversible reactions, allowing sugars and aglycons to be exchanged with ease. As proof of the broader applicability of these new reactions, more than 70 differentially glycosylated calicheamicin and vancomycin variants are reported. This study suggests the reversibility of GT-catalyzed reactions may be general and useful for generating exotic nucleotide sugars, establishing in vitro GT activity in complex systems, and enhancing natural product diversity. PMID:16946071

  5. Structure, Chemical Synthesis, and Biosynthesis of Prodiginine Natural Products.

    PubMed

    Hu, Dennis X; Withall, David M; Challis, Gregory L; Thomson, Regan J

    2016-07-27

    The prodiginine family of bacterial alkaloids is a diverse set of heterocyclic natural products that have likely been known to man since antiquity. In more recent times, these alkaloids have been discovered to span a wide range of chemical structures that possess a number of interesting biological activities. This review provides a comprehensive overview of research undertaken toward the isolation and structural elucidation of the prodiginine family of natural products. Additionally, research toward chemical synthesis of the prodiginine alkaloids over the last several decades is extensively reviewed. Finally, the current, evidence-based understanding of the various biosynthetic pathways employed by bacteria to produce prodiginine alkaloids is summarized. PMID:27314508

  6. Microscale Methodology for Structure Elucidation of Natural Products

    PubMed Central

    Molinski, Tadeusz F.

    2010-01-01

    1. Summary of Recent Advances Advances in microscale spectroscopic techniques, particularly microcryoprobe NMR, allow discovery and structure elucidation of new molecules down to only a few nanomole. Newer methods for utilizing circular dichroism (CD) have pushed the limits of detection to picomole levels. NMR and CD methods are complementary to the task of elucidation of complete stereostructures of complex natural products. Together, integrated microprobe NMR spectroscopy, microscale degradation and synthesis, are synergistic tools for discovery of bioactive natural products and have opened new realm for discovery among extreme sources including compounds from uncultured microbes, rare invertebrates and environmental samples. PMID:20880694

  7. Complexity Generation during Natural Product Biosynthesis using Redox Enzymes

    PubMed Central

    Wang, Peng; Gao, Xue; Tang, Yi

    2012-01-01

    Redox enzymes such as FAD-dependent and cytochrome P450 oxygenases play indispensible roles in generating structural complexity during natural product biosynthesis. In the pre-assembly steps, redox enzymes can convert garden variety primary metabolites into unique starter and extender building blocks. In the post-assembly tailoring steps, redox cascades can transform nascent scaffolds into structurally complex final products. In this review, we will discuss several recently characterized redox enzymes in the biosynthesis of polyketides and nonribosomal peptides. PMID:22564679

  8. Using singlet oxygen to synthesize polyoxygenated natural products from furans.

    PubMed

    Montagnon, Tamsyn; Tofi, Maria; Vassilikogiannakis, Georgios

    2008-08-01

    [Reaction: see text]. Singlet oxygen is a powerful tool in the armament of the synthetic organic chemist and possibly in that of nature itself. In this Account, we illustrate a small selection of the many ways singlet oxygen can be harnessed in the laboratory to aid in the construction of the complex molecular motifs found in natural products. A more philosophical question is also addressed: namely, how much do singlet oxygen oxidations influence the biogenesis of these natural products? All the synthetic examples surveyed in this Account can be characterized as belonging to the same class because they all involve the oxidation of a substituted furan nucleus by singlet oxygen. Readily accessible and relatively simple furans can be transformed into a host of complex motifs present in a diverse range of natural products by the action of singlet-oxygen-mediated reaction sequences. These reactions are highly advantageous because they frequently deliver a rapid and dramatic increase in molecular complexity in high yield. Furthermore, an unusually wide structural diversity is exhibited by the molecular motifs obtained from these reaction sequences. For example, relatively minor modifications to the starting substrate and to the reaction conditions may lead to products as variable as spiroketal lactones, 3-keto-tetrahydrofurans, various types of bis-spiroketals, 4-hydroxy cyclopentenones, or spiroperoxylactones. In addition, two more specialized examples are discussed in this Account. The core of the prunolide molecules and the chinensine family of natural products were rapidly synthesized using effective and short singlet oxygen mediated strategies; this adds weight to the assertion that singlet oxygen is a very effective moderator of complex cascade reaction sequences. We also show how our synthetic investigations have provided evidence that these same strategies might be used in the biogenesis of these molecules. In the cases of the chinensines and the

  9. 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.

  10. 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.