Science.gov

Sample records for numerous norditerpenoid alkaloids

  1. Norditerpenoid alkaloids from Delphinium nordhagenii.

    PubMed

    Shaheen, Farzana; Zeeshan, Muhammad; Ahmad, Manzoor; Anjum, Shazia; Ali, Shamshir; Fun, Hoong-Kun; Fun, Hong-Kun; Choudhary, Muhammad Iqbal; Atta-ur-Rahman

    2006-05-01

    Three new norditerpenoid alkaloids, nordhagenine A (1), nordhagenine B (2), and nordhagenine C (3), along with a known alkaloid, lycoctonine, were isolated from the aerial parts of Delphinium nordhagenii. The structures of the new compounds 1 and 2 were also deduced on the basis of single-crystal X-ray diffraction studies. PMID:16724850

  2. A new norditerpenoid alkaloid from Aconitum taipaicum.

    PubMed

    He, Yang-qing; Ma, Zhan-ying; Yang, Qian; Yao, Bing-hua; Gao, Li-ming

    2008-09-01

    To investigate the chemical constituents of the roots of Aconitum taipaicum, silica gel column chromatography was used for the isolation and purification of compounds. A new norditerpenoid alkaloid, isodelelatine (1), along with five known alkaloids, atisine (2), delfissinol (3), liangshanine (4), hypaconitine (5) and delelatine (6) were isolated and identified. The structure of the new compound was elucidated on the basis of spectral data. PMID:19048785

  3. Norditerpenoid alkaloids from the roots of Aconitum heterophyllum Wall with antibacterial activity.

    PubMed

    Ahmad, Manzoor; Ahmad, Waqar; Ahmad, Mansoor; Zeeshan, Muhammad; Obaidullah; Shaheen, Farzana

    2008-12-01

    Two new aconitine-type norditerpenoid alkaloids 6-dehydroacetylsepaconitine (1) and 13-hydroxylappaconitine (2), along with three known norditerpenoid alkaloids lycoctonine, delphatine and lappaconitine were isolated from the roots of the Aconitum heterophyllum Wall. These compounds exhibited significant antibacterial activity. The structure of compound 1 and 2 were deduced on the basis of their spectral data. PMID:18608773

  4. A toxicokinetic comparison of norditerpenoid alkaloids from Delphinium barbeyi and D. glaucescens in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cattle are poisoned by N-(methylsuccinimido) anthranoyllycoctonine type (MSAL-type) and 7,8-methylenedioxylycoctonine type (MDL-type) norditerpenoid alkaloids in Delphinium spp. Alkaloids in D. glaucescens are primarily of the MSAL-type, while D. barbeyi is a mixture of MSAL and MDL-types. The obj...

  5. Effect of MDL-type alkaloids on tall larkspur toxicosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Larkspur plants contain numerous norditerpenoid alkaloids which include the 7, 8-methylenedioxylycoctonine (MDL) -type alkaloids and the N-(methylsuccinimido) anthranoyllycoctonine (MSAL) -type alkaloids. The MSAL-type alkaloids are generally much more toxic (typically > 20x). Toxicity of many tal...

  6. Effect of MDL-Type alkaloids on tall larkspur toxicosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Larkspur plants contain numerous norditerpenoid alkaloids which include the 7, 8-methylenedioxylycoctonine (MDL) -type alkaloids and the N-(methylsuccinimido) anthranoyllycoctonine (MSAL) -type alkaloids. The MSAL-type alkaloids are generally much more toxic (typically > 20x) than the MDL-type alka...

  7. Toxicokinetics of norditerpenoid alkaloids from low larkspur (Delphinium andersonii) orally administered in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective- To better assess low larkspur toxicity and manage treatment of poisoned animals, more knowledge is needed about the serum toxicokinetics of toxic low larkspur alkaloids in cattle. Animals- Five black angus steers. Procedures- Low larkspur (Delphinium andersonii) in the flowering stage...

  8. The physiological effects and toxicokinetics of tall larkspur (Delphinium barbeyi) alkaloids in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Norditerpenoid alkaloids of larkspur (Delphinium spp.) have a range of pharmacological and physiological properties. For example, the norditerpenoid alkaloid methyllycaconitine (MLA) can act as competitive antagonist at nicotinic cholinergic receptors. In this study, both dose-response and toxicok...

  9. Diterpenoid alkaloids from Delphinium virgatum poiret.

    PubMed

    Meriçli, A H; Meriçli, F; Desai, H K; Ilarslan, R; Ulubelen, A; Pelletier, S W

    2001-05-01

    From the aerial parts of Delphinium virgatum Poiret, which is an endemic plant growing wildly in Turkey, a new norditerpenoid alkaloid, N-deethylperegrine alcohol, has been isolated along with the known alkaloids peregrine, peregrine alcohol, davisinol, hetisine, hetisinone and atisine. PMID:11400561

  10. Aspergiloid I, an unprecedented spirolactone norditerpenoid from the plant-derived endophytic fungus Aspergillus sp. YXf3

    PubMed Central

    Guo, Zhi Kai; Wang, Rong; Huang, Wei; Li, Xiao Nian; Jiang, Rong

    2014-01-01

    Summary An unusual C18 norditerpenoid, aspergiloid I (1), was isolated from the culture broth of Aspergillus sp. YXf3, an endophytic fungus derived from Ginkgo biloba. Its structure was unambiguously established by analysis of HRMS–ESI and spectroscopic data, and the absolute configuration was determined by low-temperature (100 K) single crystal X-ray diffraction with Cu K? radiation. This compound is structurally characterized by a new carbon skeleton with an unprecedented 6/5/6 tricyclic ring system bearing an ?,?-unsaturated spirolactone moiety in ring B, and represents a new subclass of norditerpenoid, the skeleton of which is named aspergilane. The hypothetical biosynthetic pathway for 1 was also proposed. The cytotoxic, antimicrobial, anti-oxidant and enzyme inhibitory activities of 1 were evaluated. PMID:25550731

  11. HPLC/MS analysis of toxic norditerpenoid alkaloids: Refinement of toxicity assessment of low larkspurs (Delphinium spp.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The low larkspurs (Delphinium nuttallianum and D. andersonii) are two toxic plant species that are often fatally ingested by cattle on western U.S. rangelands. To assess the potential toxicity of the plants, methods are needed to identify and quantify the toxic N-methylsuccinimidoanthranoyllycacont...

  12. Two Faces of Alkaloids

    NASA Astrophysics Data System (ADS)

    Dostál, Jirí

    2000-08-01

    Alkaloids can occur in two forms, denoted as ammonium salts and free bases. These forms differ substantially in their properties and in some cases in their structures. The article discusses and compares the salts and free bases of six well-known alkaloids: nicotine, morphine, cocaine, sanguinarine, allocryptopine, and magnoflorine. Relevance for the biological and medical uses of these compounds is emphasized.

  13. Effects of Larkspur (Delphinium barbeyi) on Heart Rate and Electrically Evoked Electromyographic Response of the External Anal Sphincter in Cattle.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Norditerpenoid alkaloids of larkspur (Delphinium spp.) are competitive antagonists of nicotinic cholinergic receptors and poison cattle with, high mortality. Of the norditerpenoids, the N-(methylsuccinimido) anthranoyllycoctonine type (MSAL-type) alkaloids are most toxic. This study tested the hyp...

  14. Heterokaryosis and Alkaloid Production in Claviceps purpurea

    PubMed Central

    Amici, Alba M.; Scotti, T.; Spalla, C.; Tognoli, L.

    1967-01-01

    Strain 275 FI of Claviceps purpurea, which produces large amounts of peptide alkaloids in submerged culture, is a heterokaryon; after several generations on agar media, it segregates the single components. These components (by us labeled V, C, and W) are stable and produce almost no alkaloids under described conditions of submerged culture. The mycelium of strain 275 FI consists of hyphae with multinucleate cells and does not produce conidia. Strains V, C, and W form numerous anastomoses when grown together on agar. By combining strains V and C, a heterokaryon similar to 275 FI in appearance has been obtained. This new strain produces amounts of alkaloids much larger than those produced by V and C separately or in associated submerged culture. We conclude, therefore, that in strain 275 FI the heterokaryotic condition is favorable to the production of alkaloids. Several conidiaproducing cultures of C. purpurea of various origins, as well as sclerotia of the same species, have been examined. The results demonstrated that the heterokaryotic condition is rare in the cultures, but it is frequent in the mycelium from sclerotia. Since it is known that the production of alkaloids is typical of the sclerotial phase in C. purpurea, it is suggested that this capacity is related to the heterokaryosis of the producing strains. Images Fig. 1 Fig. 2 PMID:6035054

  15. Marine Indole Alkaloids

    PubMed Central

    Netz, Natalie; Opatz, Till

    2015-01-01

    Marine indole alkaloids comprise a large and steadily growing group of secondary metabolites. Their diverse biological activities make many compounds of this class attractive starting points for pharmaceutical development. Several marine-derived indoles were found to possess cytotoxic, antineoplastic, antibacterial and antimicrobial activities, in addition to the action on human enzymes and receptors. The newly isolated indole alkaloids of marine origin since the last comprehensive review in 2003 are reported, and biological aspects will be discussed. PMID:26287214

  16. Understanding and manipulating alkaloid biosynthesis

    E-print Network

    Glenn, Weslee S. (Weslee Sinclair)

    2013-01-01

    Humans have exploited plant alkaloids as medicines since at least the Neolithic Era. Today, alkaloids such as vinblastine (isolated from Catharanthus roseus) and morphine (isolated from Papaver somniferum) are prescribed ...

  17. Biosynthesis of Fungal Indole Alkaloids

    PubMed Central

    Xu, Wei; Gavia, Diego J.; Tang, Yi

    2014-01-01

    This review provides a summary of recent research advances in elucidating the biosynthesis of fungal indole alkaloids. Different strategies used to incorporate and derivatize the indole/indoline moieties in various families of fungal indole alkaloids will be discussed, including tryptophan-containing nonribosomal peptides and polyketide-nonribosomal peptide hybrids; and alkaloids derived from other indole building blocks. This review also includes discussion regarding the downstream modifications that generate chemical and structural diversity among indole alkaloids. PMID:25180619

  18. Analysis of Ergot Alkaloids

    PubMed Central

    Crews, Colin

    2015-01-01

    The principles and application of established and newer methods for the quantitative and semi-quantitative determination of ergot alkaloids in food, feed, plant materials and animal tissues are reviewed. The techniques of sampling, extraction, clean-up, detection, quantification and validation are described. The major procedures for ergot alkaloid analysis comprise liquid chromatography with tandem mass spectrometry (LC-MS/MS) and liquid chromatography with fluorescence detection (LC-FLD). Other methods based on immunoassays are under development and variations of these and minor techniques are available for specific purposes. PMID:26046699

  19. Analysis of Ergot Alkaloids.

    PubMed

    Crews, Colin

    2015-06-01

    The principles and application of established and newer methods for the quantitative and semi-quantitative determination of ergot alkaloids in food, feed, plant materials and animal tissues are reviewed. The techniques of sampling, extraction, clean-up, detection, quantification and validation are described. The major procedures for ergot alkaloid analysis comprise liquid chromatography with tandem mass spectrometry (LC-MS/MS) and liquid chromatography with fluorescence detection (LC-FLD). Other methods based on immunoassays are under development and variations of these and minor techniques are available for specific purposes. PMID:26046699

  20. Alkaloids Toxic to Livestock

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Alkaloids are a specific group of nitrogen-containing natural metabolites that enable plants to overcome temporary or continuous threats integral to their environment, while also controlling essential functions of growth and reproduction. These compounds are probably produced primarily to control f...

  1. The Securinega alkaloids.

    PubMed

    Chirkin, Eqor; Atkatlian, William; Porée, François-Hugues

    2015-01-01

    Securinega alkaloids represent a family of plant secondary metabolites known for 50 years. Securinine (1), the most abundant and studied alkaloid of this series was isolated by Russian researchers in 1956. In the following years, French and Japanese scientists reported other Securinega compounds and extensive work was done to elucidate their intriguing structures. The homogeneity of this family relies mainly on its tetracyclic chemical backbone, which features a butenolide moiety (cycle D) and an azabicyclo[3.2.1]octane ring system (rings B and C). Interestingly, after a period of latency of 20 years, the Securinega topic reemerged as a prolific source of new natural structures and to date more than 50 compounds have been identified and characterized. The oligomeric subgroup gathering dimeric, trimeric, and tetrameric units is of particular interest. The unprecedented structure of the Securinega alkaloids was the subject of extensive synthetic efforts culminating in several efficient and elegant total syntheses. The botanical distribution of these alkaloids seems limited to the Securinega, Flueggea, Margaritaria, and Breynia genera (Phyllanthaceae). However, only a limited number of plant species have been considered for their alkaloid contents, and additional phytochemical as well as genetic studies are needed. Concerning the biosynthesis, experiments carried out with radiolabelled aminoacids allowed to identify lysine and tyrosine as the precursors of the piperidine ring A and the CD rings of securinine (1), respectively. Besides, plausible biosynthetic pathways were proposed for virosaine A (38) and B (39), flueggine A (46), and also the different oligomers flueggenine A-D (48-51), fluevirosinine A (56), and flueggedine (20). The case of nirurine (45) and secu'amamine (37) remains elusive and additional studies seem necessary to understand their mode of production. The scope of biological of activities of the Securinega alkaloids was mainly centered on the CNS activity of securinine (1), although the exact mechanism of action remained in part unknown. Nevertheless, for its stimulant and antispasmodic effects securinine nitrate was marketed as a drug in the USSR until the early 1990s. Moreover, securinine (1) and several other Securinega alkaloids recently demonstrated promising anticancer properties. In particular securinine (1) demonstrated markedly benefits in the treatment of acute myeloid leukemia. PMID:25845059

  2. Quinolizidine alkaloids from Lupinus lanatus

    NASA Astrophysics Data System (ADS)

    Neto, Alexandre T.; Oliveira, Carolina Q.; Ilha, Vinicius; Pedroso, Marcelo; Burrow, Robert A.; Dalcol, Ionara I.; Morel, Ademir F.

    2011-10-01

    In this study, one new quinolizidine alkaloid, lanatine A ( 1), together with three other known alkaloids, 13-?- trans-cinnamoyloxylupanine ( 2), 13-?-hydroxylupanine ( 3), and (-)-multiflorine ( 4) were isolated from the aerial parts of Lupinus lanatus (Fabaceae). The structures of alkaloids 1- 4 were elucidated by spectroscopic data analysis. The stereochemistry of 1 was determined by single crystal X-ray analysis. Bayesian statistical analysis of the Bijvoet differences suggests the absolute stereochemistry of 1. In addition, the antimicrobial potential of alkaloids 1- 4 is also reported.

  3. Adverse effects of larkspur (Delphinium spp.) on cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There are numerous species of larkspurs (Delphinium spp.) in North America. The larkspurs are a major cause of cattle losses on western ranges in the USA, especially on foothill and mountain rangelands. The toxicity of larkspur species is due to various norditerpenoid alkaloids. In this article, we ...

  4. The Effect of High Deltaline Concentration on the Toxicity of Methyllycaconitine in Mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Larkspurs (Delphinium) are one of the most serious toxic plant problems on foothill and mountain rangelands in the western U.S. Total costs to the livestock industry have been estimated at over $20 million annually. Larkspur plants contain numerous norditerpenoid alkaloids (>18) which occur as one...

  5. Automatic alkaloid removal system.

    PubMed

    Yahaya, Muhammad Rizuwan; Hj Razali, Mohd Hudzari; Abu Bakar, Che Abdullah; Ismail, Wan Ishak Wan; Muda, Wan Musa Wan; Mat, Nashriyah; Zakaria, Abd

    2014-01-01

    This alkaloid automated removal machine was developed at Instrumentation Laboratory, Universiti Sultan Zainal Abidin Malaysia that purposely for removing the alkaloid toxicity from Dioscorea hispida (DH) tuber. It is a poisonous plant where scientific study has shown that its tubers contain toxic alkaloid constituents, dioscorine. The tubers can only be consumed after it poisonous is removed. In this experiment, the tubers are needed to blend as powder form before inserting into machine basket. The user is need to push the START button on machine controller for switching the water pump ON by then creating turbulence wave of water in machine tank. The water will stop automatically by triggering the outlet solenoid valve. The powders of tubers are washed for 10 minutes while 1 liter of contaminated water due toxin mixture is flowing out. At this time, the controller will automatically triggered inlet solenoid valve and the new water will flow in machine tank until achieve the desire level that which determined by ultra sonic sensor. This process will repeated for 7 h and the positive result is achieved and shows it significant according to the several parameters of biological character ofpH, temperature, dissolve oxygen, turbidity, conductivity and fish survival rate or time. From that parameter, it also shows the positive result which is near or same with control water and assuming was made that the toxin is fully removed when the pH of DH powder is near with control water. For control water, the pH is about 5.3 while water from this experiment process is 6.0 and before run the machine the pH of contaminated water is about 3.8 which are too acid. This automated machine can save time for removing toxicity from DH compared with a traditional method while less observation of the user. PMID:24783795

  6. Cytotoxic indole alkaloids from Tabernaemontana officinalis.

    PubMed

    Zhang, Bing-Jie; Teng, Xi-Feng; Bao, Mei-Fen; Zhong, Xiu-Hong; Ni, Ling; Cai, Xiang-Hai

    2015-12-01

    Continued interest in cytotoxic alkaloids resulted in the isolation of 37 alkaloids including 29 known monoterpenoid indole alkaloids from the aerial parts of Tabernaemontana officinalis. Of the remaining 8 alkaloids, six were bisindole alkaloids named taberdivarines A-F (1-6) and the two were monomers named taberdivarines G and H (7-8). Alkaloids 1 and 2 are voaphylline-vobasinyl type bisindole alkaloids, a structural type previously unknown, while 3-6 exhibited cytotoxicity against three human cancer cell lines HeLa, MCF-7, and SW480 with IC50 values ranging from 1.42 to 11.35?M. PMID:25687604

  7. Example 1: Pyrrollizidine alkaloids (PAs) in Senecio Background

    E-print Network

    Constabel, Peter

    Example 1: Pyrrollizidine alkaloids (PAs) in Senecio Background - basic) NB: PAs protect eggs, and males contribute via sperm - alkaloid) iv) pharmacophagy (Danainae butterflies) - take in alkaloids from non

  8. Quinolizidine alkaloids from Genista ephedroides.

    PubMed

    Pistelli; Bertoli; Giachi; Morelli; Rubiolo; Bicchi

    2001-02-01

    Alkaloids retamine, anagyrine, lupanine, 17-oxoretamine, 12-alpha-hydroxylupanine were detected, along with four others unidentified compounds in the aerial parts of Genista ephedroides D.C. PMID:11106841

  9. Total synthesis and study of myrmicarin alkaloids

    E-print Network

    Ondrus, Alison Evelynn, 1981-

    2009-01-01

    I. Enantioselective Total Synthesis of Tricyclic Myrmicarin Alkaloids An enantioselective gram-scale synthesis of a key dihydroindolizine intermediate for the preparation of myrmicarin alkaloids is described. Key transformations ...

  10. 27 CFR 21.99 - Brucine alkaloid.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... temperature to 110° and dry to a constant weight before taking melting point. Note. Brucine alkaloid... brucine alkaloid. A vivid red color is produced. Dilute the red solution with a few drops of water and...

  11. 27 CFR 21.99 - Brucine alkaloid.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... temperature to 110° and dry to a constant weight before taking melting point. Note. Brucine alkaloid... brucine alkaloid. A vivid red color is produced. Dilute the red solution with a few drops of water and...

  12. 27 CFR 21.99 - Brucine alkaloid.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... temperature to 110° and dry to a constant weight before taking melting point. Note. Brucine alkaloid... brucine alkaloid. A vivid red color is produced. Dilute the red solution with a few drops of water and...

  13. 27 CFR 21.99 - Brucine alkaloid.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... temperature to 110° and dry to a constant weight before taking melting point. Note. Brucine alkaloid... brucine alkaloid. A vivid red color is produced. Dilute the red solution with a few drops of water and...

  14. Alkaloid synthesis using chiral secondary amine organocatalysts.

    PubMed

    Ishikawa, Hayato; Shiomi, Shinya

    2015-12-23

    Over the last decade, several excellent enantioselective total syntheses of important alkaloids using asymmetric reactions mediated by chiral secondary amine organocatalysts as a key step have been accomplished. This perspective article examines the full strategies of these alkaloid syntheses, especially the application of the organocatalytic reaction to construct the alkaloid scaffolds. PMID:26625722

  15. Synthesis and anticancer activity of epipolythiodiketopiperazine alkaloids

    E-print Network

    Hergenrother, Paul J.

    Synthesis and anticancer activity of epipolythiodiketopiperazine alkaloids Nicolas Boyer,a Karen C (ETP) alkaloids are a highly complex class of natural products with potent anticancer activity. Herein Epipolythiodiketopiperazine (ETP)1 alkaloids constitute a large (ca. 120 members) and diverse family of biologically active

  16. Ligand-exchange chromatography of alkaloids.

    PubMed

    Murgia, E; Walton, H F

    1975-02-12

    Alkaloids are separated by liquid chromatography on resins having functional carboxyl groups combined with copper (II) ions. The eluent is aqueous alcohol containing ammonia. Some resins retain alkaloids much better than others. Alkaloids studied included morphine, codeine, strychnine, atropine, papaverine, narcotine, cocaine, quinine, cinchonine and methadone. PMID:1150768

  17. 27 CFR 21.99 - Brucine alkaloid.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...2011-04-01 2011-04-01 false Brucine alkaloid. 21.99 Section 21.99 Alcohol...for Denaturants § 21.99 Brucine alkaloid. (a) Identification test. Add...nitric acid to about 10 mg of brucine alkaloid. A vivid red color is...

  18. 27 CFR 21.99 - Brucine alkaloid.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...2010-04-01 2010-04-01 false Brucine alkaloid. 21.99 Section 21.99 Alcohol...for Denaturants § 21.99 Brucine alkaloid. (a) Identification test. Add...nitric acid to about 10 mg of brucine alkaloid. A vivid red color is...

  19. 27 CFR 21.99 - Brucine alkaloid.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...2013-04-01 2013-04-01 false Brucine alkaloid. 21.99 Section 21.99 Alcohol...for Denaturants § 21.99 Brucine alkaloid. (a) Identification test. Add...nitric acid to about 10 mg of brucine alkaloid. A vivid red color is...

  20. 27 CFR 21.99 - Brucine alkaloid.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...2012-04-01 2012-04-01 false Brucine alkaloid. 21.99 Section 21.99 Alcohol...for Denaturants § 21.99 Brucine alkaloid. (a) Identification test. Add...nitric acid to about 10 mg of brucine alkaloid. A vivid red color is...

  1. 27 CFR 21.99 - Brucine alkaloid.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...2014-04-01 2014-04-01 false Brucine alkaloid. 21.99 Section 21.99 Alcohol...for Denaturants § 21.99 Brucine alkaloid. (a) Identification test. Add...nitric acid to about 10 mg of brucine alkaloid. A vivid red color is...

  2. [Diterpenoid alkaloids from Aconitum gymnandrum].

    PubMed

    Ding, L S; Wu, F E; Chen, Y Z

    1993-01-01

    Aconitum gymnandrum maxim. (ranunculaceae) is used as an herbal medicine in Tibet area. A new diterpenoid alkaloid, gymnandine (I) along with known alkaloids 14-acetyl-8-O-methyltalatisamine (II), acoforine (III), columbidine (IV), aconitine (V), ranaconitine (VI), talatizidine (VII), isotalatizidine (VIII), gymnanconitine (IX), talatisamine (X), and atisine HCI (XI) have been isolated from this unique species. The structure of I is determined on the basis of spectral evidences and comparison of the 13CNMR spectrum with that of denudatine. II has not been previously reported as a natural product and III-VII were isolated from this plant for the first time. PMID:8368077

  3. Alkaloid Ecology (continued) 2. Nicotine alkaloids, Nicotiana (tobacco)

    E-print Network

    Constabel, Peter

    : - nicotinic acid (as in NAD/NADH) - aspartate - pyrrole (furan ring) - arginine (ornithine) Enzymes induction by herbivores - topping plants by tobacco growers - PMT induction in root (systemic) - systemic) Other plant species containing these alkaloids: - accumulation in root parasitic plants (Indian Paint

  4. Biphenylquinolizidine alkaloids from Lagerstroemia indica.

    PubMed

    Kim, Hong Jin; Lee, Ik Soo; Youn, UiJoung; Chen, Quan Cheng; Ngoc, Tran Minh; Ha, Do Thi; Liu, Hongguang; Min, Byung Sun; Lee, Jin Yong; Seong, Rack Seon; Bae, KiHwan

    2009-04-01

    Two new biphenylquinolizidine alkaloids, 5-epi-dihydrolyfoline (1) and its stereoisomer, dihydrolyfoline (2), along with lagerine (3) were isolated from the aerial parts of Lagerstroemia indica. The structures of compounds 1-3 were elucidated by extensive spectroscopic techniques. PMID:19260657

  5. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...Dietary supplements containing ephedrine alkaloids. 119.1 Section 119.1 Food and...Dietary supplements containing ephedrine alkaloids. Dietary supplements containing ephedrine alkaloids present an unreasonable risk of...

  6. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...Dietary supplements containing ephedrine alkaloids. 119.1 Section 119.1 Food and...Dietary supplements containing ephedrine alkaloids. Dietary supplements containing ephedrine alkaloids present an unreasonable risk of...

  7. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...Dietary supplements containing ephedrine alkaloids. 119.1 Section 119.1 Food and...Dietary supplements containing ephedrine alkaloids. Dietary supplements containing ephedrine alkaloids present an unreasonable risk of...

  8. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...Dietary supplements containing ephedrine alkaloids. 119.1 Section 119.1 Food and...Dietary supplements containing ephedrine alkaloids. Dietary supplements containing ephedrine alkaloids present an unreasonable risk of...

  9. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...Dietary supplements containing ephedrine alkaloids. 119.1 Section 119.1 Food and...Dietary supplements containing ephedrine alkaloids. Dietary supplements containing ephedrine alkaloids present an unreasonable risk of...

  10. Alkaloid Changes in Tobacco Seeds during Germination.

    PubMed

    Weeks, W W; Bush, L P

    1974-01-01

    Nicotine, nornicotine, anabasine, and anatabine, normally found in growing and mature tobacco (Nicotiana tabacum L.) plants, were extracted and quantified from mature tobacco seeds and young tobacco seedlings. The rate of net alkaloid disappearance and accumulation in tobacco seedlings was related to phases of germination.In general, the increased rate of germination associated with higher temperatures also increased the rate of initial loss of alkaloids and the subsequent rate of accumulation of alkaloids. Maximum alkaloid accumulation in 144-hour-old seedlings cultured with 10-hour day occurred at 27 C. Following an 8-hour photoinduction period, seeds germinated in darkness accumulated greater amounts of alkaloids than seeds exposed to light each day. Seeds germinated in darkness for 96 hours, following the 8-hour photoinduction period, and then exposed to light each day accumulated the greatest amounts of alkaloids. PMID:16658655

  11. Total synthesis of Class II and Class III Galbulimima Alkaloids

    E-print Network

    Tjandra, Meiliana

    2010-01-01

    I. Total Synthesis of All Class III Galbulimima Alkaloids We describe the total synthesis of (+)- and (-)-galbulimima alkaloid 13, (-)-himgaline anad (-)-himbadine. The absolute stereochemistry of natural (-)-galbulimima ...

  12. De novo production of the plant-derived alkaloid strictosidine in yeast

    PubMed Central

    Brown, Stephanie; Clastre, Marc; Courdavault, Vincent; O’Connor, Sarah E.

    2015-01-01

    The monoterpene indole alkaloids are a large group of plant-derived specialized metabolites, many of which have valuable pharmaceutical or biological activity. There are ?3,000 monoterpene indole alkaloids produced by thousands of plant species in numerous families. The diverse chemical structures found in this metabolite class originate from strictosidine, which is the last common biosynthetic intermediate for all monoterpene indole alkaloid enzymatic pathways. Reconstitution of biosynthetic pathways in a heterologous host is a promising strategy for rapid and inexpensive production of complex molecules that are found in plants. Here, we demonstrate how strictosidine can be produced de novo in a Saccharomyces cerevisiae host from 14 known monoterpene indole alkaloid pathway genes, along with an additional seven genes and three gene deletions that enhance secondary metabolism. This system provides an important resource for developing the production of more complex plant-derived alkaloids, engineering of nonnatural derivatives, identification of bottlenecks in monoterpene indole alkaloid biosynthesis, and discovery of new pathway genes in a convenient yeast host. PMID:25675512

  13. Capillary gas chromatography of lupin alkaloids.

    PubMed

    Priddis, C R

    1983-05-20

    The resolution and identification of twelve lupin alkaloids are demonstrated using capillary gas chromatography and gas chromatography-mass spectrometry. The quantitative capabilities of capillary gas chromatography are illustrated by specific reference to the four major alkaloids of lupinus angustifolius, namely lupanine, 13-hydroxylupanine, augustifoline and alpha-isolupanine. PMID:6874800

  14. Ergot alkaloids: toxicokinetics and vascular effects

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endophyte (Neotyphodium coenophialum)-infected tall fescue (Lolium arundinaceum) occupies nearly 15 million ha in the USA. Although this symbiosis is beneficial to the plant, it produces ergot alkaloids that are detrimental to livestock production. Livestock consuming the alkaloids elicit adverse ph...

  15. Ecological context influences pollinator deterrence by alkaloids in floral nectar

    E-print Network

    Thomson, James D.

    LETTER Ecological context influences pollinator deterrence by alkaloids in floral nectar Robert J determined whether the pollinator-deterring effects of a nectar alkaloid found in the perennial vine. sempervirens in nature) to nectar alkaloids in several ecologically relevant scenarios. Although alkaloids

  16. Genetic variation in alkaloid accumulation in leaves of Nicotiana *

    PubMed Central

    Sun, Bo; Zhang, Fen; Zhou, Guo-jun; Chu, Guo-hai; Huang, Fang-fang; Wang, Qiao-mei; Jin, Li-feng; Lin, Fu-cheng; Yang, Jun

    2013-01-01

    Alkaloids are plant secondary metabolites that are widely distributed in Nicotiana species and contribute greatly to the quality of tobacco leaves. Some alkaloids, such as nornicotine and myosmine, have adverse effects on human health. To reduce the content of harmful alkaloids in tobacco leaves through conventional breeding, a genetic study of the alkaloid variation among different genotypes is required. In this study, alkaloid profiles in leaves of five Nicotiana tabacum cultivars and Nicotiana tomentosiformis were investigated. Six alkaloids were identified from all six genotypes via gas chromatograph-mass spectrometry (GC-MS). Significant differences in alkaloid content were observed both among different leaf positions and among cultivars. The contents of nornicotine and myosmine were positively and significantly correlated (R 2=0.881), and were also separated from those of other alkaloids by clustering. Thus, the genotype plays a major role in alkaloid accumulation, indicating a high potential for manipulation of alkaloid content through traditional breeding. PMID:24302710

  17. Potentiation of the actions of acetylcholine, epibatidine, and nicotine by methyllycaconitine at fetal muscle-type nicotinic acetylcholine receptors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Norditerpenoid alkaloids from Delphinium spp. (larkspur) have been described as possessing “curariform-like” activity in cattle and are of economic importance because of the poisonings they cause. Methyllycaconitine (MLA) is a norditerpenoid alkaloid found in high abundance in toxic larkspur, and i...

  18. Isoquinoline and isoindole alkaloids from Menispermum dauricum.

    PubMed

    Zhang, Xiaoqi; Ye, Wencai; Zhao, Shouxun; Che, Chun-Tao

    2004-04-01

    Three isoquinoline alkaloids and an isoindole alkaloid, along with eight known compounds, were isolated from the roots of Menispermum dauricum (Menispermacese). The alkaloids were characterized as 7-hydroxy-6-methoxy-1(2H)-isoquinolinone, 6,7-dimethoxy-N-methyl-3,4-dioxo-1(2H)-isoquinolinone, 1-(4-hydroxybenzoyl)-7-hydroxy-6-methoxy-isoquinoline and 6-hydroxy-5-methoxy-N-methylphthalimide, on the basis of spectral evidence including 1D- and 2D-NMR and MS analyses. PMID:15081297

  19. A case of beta-carboline alkaloid intoxication following ingestion of Peganum harmala seed extract.

    PubMed

    Frison, Giampietro; Favretto, Donata; Zancanaro, Flavio; Fazzin, Giorgio; Ferrara, Santo Davide

    2008-08-01

    Beta-carboline alkaloids harmine, harmaline, and tetrahydroharmine can stimulate the central nervous system by inhibiting the metabolism of amine neurotransmitters, or by direct interaction with specific receptors; they are found in numerous plants, including Peganum harmala, Passiflora incarnata and Banisteriopsis caapi, and in the entheogen preparation Ayahuasca, which is traditionally brewed using B. caapi to enhance the activity of amine hallucinogenic drugs. The ingestion of plant preparations containing beta-carboline alkaloids may result in toxic effects, namely visual and auditory hallucinations, locomotor ataxia, nausea, vomiting, confusion and agitation. We report a case of intoxication following intentional ingestion of P. harmala seed infusion; P. harmala seeds were bought over the Internet. The harmala alkaloids were identified by gas chromatography-mass spectrometry in the seed extract and the patient's urine. This is, to our knowledge, the first case of P. harmala intoxication corroborated by toxicological findings. PMID:18603389

  20. Piperidine alkaloids: Human and food animal teratogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Piperidine alkaloids are acutely toxic to adult livestock species and produce musculoskeletal deformities in neonatal animals. These teratogenic effects include multiple congenital contracture (MCC) deformities and cleft palate in cattle, pigs, sheep, and goats. Poisonous plants containing teratogen...

  1. Synthesis and anticancer activity of epipolythiodiketopiperazine alkaloids

    E-print Network

    Boyer, Nicolas Cedric

    The epipolythiodiketopiperazine (ETP) alkaloids are a highly complex class of natural products with potent anticancer activity. Herein, we report the application of a flexible and scalable synthesis, allowing the construction ...

  2. Total synthesis and study of myrmicarin alkaloids

    E-print Network

    Ondrus, Alison E.

    The myrmicarins are a family of air- and temperature-sensitive alkaloids that possess unique structural features. Our concise enantioselective synthesis of the tricyclic myrmicarins enabled evaluation of a potentially ...

  3. Total synthesis of all (?)-agelastatin alkaloids

    E-print Network

    Movassaghi, Mohammad

    The pyrrole-imidazole family of marine alkaloids, derived from linear clathrodin-like precursors, constitutes a diverse array of structurally complex natural products. The bioactive agelastatins are members of this family ...

  4. Total synthesis of cyclotryptamine and diketopiperazine alkaloids

    E-print Network

    Kim, Justin, Ph. D. Massachusetts Institute of Technology

    2013-01-01

    I. Total Synthesis of the (+)-12,12'-Dideoxyverticillin A The fungal metabolite (+)-12,12'-dideoxyverticillin A, a cytotoxic alkaloid isolated from a marine Penicillium sp., belongs to a fascinating family of densely ...

  5. Modified alkaloid pattern in developing tobacco callus.

    PubMed

    Tiburcio, A F; Ingersoll, R; Galston, A W

    1985-01-01

    Developing Nicotiana tabacum L. cv. Wisconsin-38 callus grown on modified Murashige-Skoog (MS) medium with Kao organic acids (pyruvic, citric, malic and fumaric acids) contains abnormally high levels of nornicotine and total alkaloids when compared with the leaves of the donor plant. Nornicotine/nicotine ratios observed during callus development suggest that nicotine is converted into nornicotine in the callus, with subsequent movement of alkaloids into roots formed on the callus and into the agar medium. Addition of Kao organic acids to the medium increases alkaloid levels, but cannot account for the abnormal increase in nicotine demethylation. This study thus reports two new findings: (a) that the total alkaloid content of tobacco callus can be greatly enhanced to 3.75% on a dry weight basis by exogenous organic acids, and (b) that endogenous nornicotine can accumulate in tobacco tissue cultures. PMID:11539700

  6. 27 CFR 21.99 - Brucine alkaloid.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... produced. (b) Melting point. 178 °±1 °C. Dry the alkaloid in an oven for one hour at 100 °C., increase the temperature to 110° and dry to a constant weight before taking melting point. Note. Brucine...

  7. New furocarbazole alkaloids from Lonicera quinquelocularis.

    PubMed

    Khan, Dilfaraz; Khan, Shafiullah; Badshah, Syed; Ali, Hazrat; Ullah, Hamid; Muhammad, Zia; Woodward, Simon

    2016-01-01

    Two new furocarbazole alkaloids, 3-formyl-6,7-dimethoxy-furo[1,2]carbazole (1) and methyl-6,7-dimethoxy-furo[1,2]carbazole-3-carboxylate (2), along with two known carbazole alkaloids, 3-formyl-2-hydroxy-7-methoxycarbazole (3) and methyl 2,7-dimethoxycarbazole-3-carboxylate (4) were isolated from the ethyl acetate soluble fraction of Lonicera quinquelocularis. Their structures were established on the basis of spectroscopic analysis. PMID:26168923

  8. Alkaloids from Lupinus argenteus var. stenophyllus.

    PubMed

    Keller, W J; Zelenski, S G

    1978-03-01

    TLC and GLC of an alkaloid extract of the aboveground portions of Lupinus argenteus Pursh. var. stenophyllus (Rydb.) Davis (Leguminosae) suggested the presence of sparteine, beta-isosparteine, delta5-dehydrolupanine, alpha-isolupanine, lupanine, thermopsine, and anagyrine. GLC-mass spectrometry confirmed these preliminary findings. Preparative TLC was used to isolate sparteine, and this alkaloid was further characterized by IR spectral analysis and derivatization. PMID:641742

  9. BIAdb: A curated database of benzylisoquinoline alkaloids

    PubMed Central

    2010-01-01

    Background Benzylisoquinoline is the structural backbone of many alkaloids with a wide variety of structures including papaverine, noscapine, codeine, morphine, apomorphine, berberine, protopine and tubocurarine. Many benzylisoquinoline alkaloids have been reported to show therapeutic properties and to act as novel medicines. Thus it is important to collect and compile benzylisoquinoline alkaloids in order to explore their usage in medicine. Description We extract information about benzylisoquinoline alkaloids from various sources like PubChem, KEGG, KNApSAcK and manual curation from literature. This information was processed and compiled in order to create a comprehensive database of benzylisoquinoline alkaloids, called BIAdb. The current version of BIAdb contains information about 846 unique benzylisoquinoline alkaloids, with multiple entries in term of source, function leads to total number of 2504 records. One of the major features of this database is that it provides data about 627 different plant species as a source of benzylisoquinoline and 114 different types of function performed by these compounds. A large number of online tools have been integrated, which facilitate user in exploring full potential of BIAdb. In order to provide additional information, we give external links to other resources/databases. One of the important features of this database is that it is tightly integrated with Drugpedia, which allows managing data in fixed/flexible format. Conclusions A database of benzylisoquinoline compounds has been created, which provides comprehensive information about benzylisoquinoline alkaloids. This database will be very useful for those who are working in the field of drug discovery based on natural products. This database will also serve researchers working in the field of synthetic biology, as developing medicinally important alkaloids using synthetic process are one of important challenges. This database is available from http://crdd.osdd.net/raghava/biadb/. PMID:20205728

  10. Lactam ergot alkaloids (ergopeptams) as predominant alkaloids in sclerotia of Claviceps purpurea from Norwegian wild grasses.

    PubMed

    Uhlig, Silvio; Petersen, Dirk

    2008-07-01

    Four major alkaloids in the extracts from sclerotia of Claviceps purpurea, picked from wild grasses, have been identified as lactam (non-cyclol) ergot alkaloids. The structural information was obtained from ion trap MS and NMR spectroscopy. The data for one of the lactam ergot alkaloids were coinciding with ergocristam [N-(lysergyl-valyl)-cyclo(phenylalanyl-prolyl)]. The structural information of two further lactam alkaloids was suggestive of either alpha- or beta-ergocryptam [N-(lysergyl-valyl)-cyclo(leucyl-prolyl) or N-(lysergyl-valyl)-cyclo(isoleucyl-prolyl)] and ergoannam [N-(lysergyl-leucyl)-cyclo(leucyl-prolyl) or N-(lysergyl-isoleucyl)-cyclo(isoleucyl-prolyl)]. The constitution of the fourth lactam ergot alkaloid corresponded to N-(lysergyl-isoleucyl)-cyclo(phenylalanyl-prolyl), a new ergopeptam, which has not been described before. Additionally, the cyclol-analogue of the new ergopeptam was detected in the extracts and has been identified on the basis of its product ion spectrum from fragmentation of [M+H](+). The study described in this paper shows that lactam ergot alkaloids may not only be minor products of ergopeptine biosynthesis, as has been suggested hitherto, but may be major biosynthetic endproducts for some ergot strains. This is also the first report demonstrating the production of an ergot alkaloid that contains isoleucine as the second amino acid, i.e. the N-(lysergyl-isoleucyl)-moiety, by parasitic, naturally growing C. purpurea. This unusual type of ergot alkaloid has so far only been found in saprophytic cultures of C. purpurea. PMID:18639312

  11. HELIOTROPIUM EUROPAEUM ALKALOIDS: A QUATERNARY PYRROLIZIDINE ALKALOID APPROACH TO ELISA DEVELOPMENT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Heliotropium europaeum has proven to be an agricultural pest capable of killing stock and severely reducing productivity due to its pyrrolizidine alkaloid content. Existing methods for the detection of pyrrolizidine alkaloids present in H. europaeum include an ELISA and HPLC-MS. The ELISA does not d...

  12. Determining important parameters related to cyanobacterial alkaloid toxin exposure

    SciTech Connect

    Love, A H

    2005-09-16

    Science-based decision making required robust and high-fidelity mechanistic data about the system dynamics and impacts of system changes. Alkaloid cyanotoxins have the characteristics to warrant consideration for their potential threat. Since insufficient information is available to construct a systems model for the alkaloid cyanotoxins, saxitoxins, anatoxins, and anatoxin-a(S), an accurate assessments of these toxins as a potential threat for use for intentional contamination is not possible. Alkaloid cyanotoxin research that contributed to such a model has numerous areas of overlap for natural and intentional health effects issues that generates dual improvements to the state of the science. The use of sensitivity analyses of systems models can identify parameters that, when determined, result in the greatest impact to the overall system and may help to direct the most efficient use of research funding. This type of modeling-assisted experimentation may allow rapid progress for overall system understanding compared to observational or disciplinary research agendas. Assessment and management of risk from intentional contamination can be performed with greater confidence when mechanisms are known and the relationships between different components are validated. This level of understanding allows high-fidelity assessments that do not hamper legitimate possession of these toxins for research purposes, while preventing intentional contamination that would affect public health. It also allows for appropriate response to an intentional contamination event, even if the specific contamination had not been previous considered. Development of science-based decision making tools will only improve our ability to address the new requirements addressing potential threats to our nation.

  13. Human alkaloid biosynthesis : chemical inducers of Parkinson's disease?

    E-print Network

    Hatzios, Stavroula K. (Stavroula-Artemis K.)

    2005-01-01

    The occurrence of certain alkaloids in the human brain appears to be associated with the onset of Parkinson's disease (PD). Recently, a human protein bearing homology to an alkaloid synthase in plants was identified. This ...

  14. Actions of Piperidine Alkaloid Teratogens at Fetal Nicotinic Acetylcholine Receptors.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Teratogenic alkaloids are found in many species of plants including Conium maculatum L., Nicotiana glauca, Nicotiana tabaccum, and multiple Lupinus spp. Fetal musculoskeletal defects produced by alkaloids from these plants include arthrogyropisis, scoliosis, torticollis, kyposis, lordosis, and clef...

  15. An Acetylenic Alkaloid from the Calcareous Sponge Leucetta sp.

    PubMed Central

    Hermawan, Idam; de Voogd, Nicole J.; Tanaka, Junichi

    2011-01-01

    A new acetylenic alkaloid was isolated from the sponge Leucetta sp. The structure was established by analyzing spectroscopic data. The alkaloid showed cytotoxicity IC50 2.5 ?g/mL against NBT-T2 cells. PMID:21556167

  16. Enantioselective total Synthesis of the agelastatin and trigonoliimine alkaloids

    E-print Network

    Han, Sunkyu, 1982-

    2012-01-01

    I. Total Synthesis of the (-)-Agelastatin Alkaloids The pyrrole-imidazole family of marine alkaloids, derived from linear clathrodin-like precursors, constitutes a diverse array of structurally complex natural products. ...

  17. Rotational Investigation of Tropane Alkaloids

    NASA Astrophysics Data System (ADS)

    Cocinero, Emilio J.; Lesarri, Alberto; Ecija, Patricia; Grabow, Jens-Uwe; Fernández, Jose A.; Castano, Fernando

    2010-06-01

    We report an investigation of the rotational spectrum of several tropane alkaloids using the new Balle-Flygare-type FT-MW spectrometer built at the University of the Basque Country. The initial work focused on the azabicycles of tropinone, scopine and scopoline, vaporized using heating methods. For tropinone the spectrum confirmed the presence of equatorial and axial conformers originated by the inversion of the N-methyl group, with the tropane motif adopting a distorted chair configuration. The determination of substitution and effective structures for the two conformers included the 13C, 15N and 18O isotopomers observed in natural abundance. The structures revealed the flexibility and structural changes associated to the N-methyl inversion, mostly a flattening at the nitrogen atom and a simultaneous rising of the carbonyl group in the axial form. The investigation of scopine gave an intense spectrum, but it was inconsistent with the structural models expected for this molecule. The carrier of the new spectrum was later identified as scopoline, generated in situ by an intramolecular reaction at the moderate temperatures of the nozzle. A single conformation was detected for scopoline, with an ether bridge seriously distorting the tropane motif. E. J. Cocinero, A. Lesarri, P. écija, J.-U. Grabow, J. A. Fernández, F. Castaño, in publication, 2010 E. J. Cocinero, A. Lesarri, P. Écija, J.-U. Grabow, J. A. Fernández, F. Castaño, Phys. Chem. Chem. Phys.,in press, 2010

  18. Multicomponent Therapeutics of Berberine Alkaloids

    PubMed Central

    Luo, Jiaoyang; Yan, Dan; Yang, Meihua; Dong, Xiaoping; Xiao, Xiaohe

    2013-01-01

    Although berberine alkaloids (BAs) are reported to be with broad-spectrum antibacterial and antiviral activities, the interactions among BAs have not been elucidated. In the present study, methicillin-resistant Staphylococcus aureus (MRSA) was chosen as a model organism, and modified broth microdilution was applied for the determination of the fluorescence absorption values to calculate the anti-MRSA activity of BAs. We have initiated four steps to seek the optimal combination of BAs that are (1) determining the anti-MRSA activity of single BA, (2) investigating the two-component combination to clarify the interactions among BAs by checkerboard assay, (3) investigating the multicomponent combination to determine the optimal ratio by quadratic rotation-orthogonal combination design, and (4) in vivo and in vitro validation of the optimal combination. The results showed that the interactions among BAs are related to their concentrations. The synergetic combinations included “berberine and epiberberine,” “jatrorrhizine and palmatine” and “jatrorrhizine and coptisine”; the antagonistic combinations included “coptisine and epiberberine”. The optimal combination was berberine?:?coptisine?:?jatrorrhizine?:?palmatine?:?epiberberine = 0.702?:?0.863?:?1?:?0.491?:?0.526, and the potency of the optimal combination on cyclophosphamide-immunocompromised mouse model was better than the natural combinations of herbs containing BAs. PMID:23634170

  19. Simulation of the type of coralin alkaloid-DNA binding

    NASA Astrophysics Data System (ADS)

    Kulikov, K. G.; Koshlan, T. V.

    2015-05-01

    Interaction between a synthesized coralin protoberberine alkaloid and the DNA double helix of the calf's thymus in a salt solution is studied by optical absorption spectroscopy and spectropolarimetry. The dependence of the spectral characteristics of the alkaloid on a ratio between the DNA base pair concentration and the alkaloid molecule concentration is considered. The parameters of bonds between the coralin alkaloid and the DNA double helix are determined using modified McGhee-von Hippel equations.

  20. Benzylisoquinoline alkaloid biosynthesis in opium poppy.

    PubMed

    Beaudoin, Guillaume A W; Facchini, Peter J

    2014-07-01

    Opium poppy (Papaver somniferum) is one of the world's oldest medicinal plants and remains the only commercial source for the narcotic analgesics morphine, codeine and semi-synthetic derivatives such as oxycodone and naltrexone. The plant also produces several other benzylisoquinoline alkaloids with potent pharmacological properties including the vasodilator papaverine, the cough suppressant and potential anticancer drug noscapine and the antimicrobial agent sanguinarine. Opium poppy has served as a model system to investigate the biosynthesis of benzylisoquinoline alkaloids in plants. The application of biochemical and functional genomics has resulted in a recent surge in the discovery of biosynthetic genes involved in the formation of major benzylisoquinoline alkaloids in opium poppy. The availability of extensive biochemical genetic tools and information pertaining to benzylisoquinoline alkaloid metabolism is facilitating the study of a wide range of phenomena including the structural biology of novel catalysts, the genomic organization of biosynthetic genes, the cellular and sub-cellular localization of biosynthetic enzymes and a variety of biotechnological applications. In this review, we highlight recent developments and summarize the frontiers of knowledge regarding the biochemistry, cellular biology and biotechnology of benzylisoquinoline alkaloid biosynthesis in opium poppy. PMID:24671624

  1. Localiza(on of Vinca alkaloid synthesis in Madagascar periwinkle

    E-print Network

    Constabel, Peter

    acids) Heldt, Fig 16.1 Non-protein amino acids: ­ not considered alkaloids but also(on - features and characterisi(cs #12;Alkaloid Families and Biosynthesis (mostly derived from amino;Quinolizidine Alkaloid-Containing Plants Cas:lleja miniata scarlet paintbrush, common

  2. Elisabethamine: a new diterpene alkaloid from Pseudopterogorgia elisabethae

    E-print Network

    Kerr, Russell G.

    Elisabethamine: a new diterpene alkaloid from Pseudopterogorgia elisabethae Athar Ata and Russell G from the Florida Keys, have resulted in the isolation of elisabethamine (1), a new diterpene alkaloid Ltd. All rights reserved. Keywords: alkaloids; anti-tumor compounds; anti-in¯ammatory compounds; NMR

  3. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Dietary supplements containing ephedrine alkaloids... UNREASONABLE RISK § 119.1 Dietary supplements containing ephedrine alkaloids. Dietary supplements containing ephedrine alkaloids present an unreasonable risk of illness or injury under conditions of use recommended...

  4. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Dietary supplements containing ephedrine alkaloids... UNREASONABLE RISK § 119.1 Dietary supplements containing ephedrine alkaloids. Dietary supplements containing ephedrine alkaloids present an unreasonable risk of illness or injury under conditions of use recommended...

  5. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Dietary supplements containing ephedrine alkaloids... UNREASONABLE RISK § 119.1 Dietary supplements containing ephedrine alkaloids. Dietary supplements containing ephedrine alkaloids present an unreasonable risk of illness or injury under conditions of use recommended...

  6. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Dietary supplements containing ephedrine alkaloids... UNREASONABLE RISK § 119.1 Dietary supplements containing ephedrine alkaloids. Dietary supplements containing ephedrine alkaloids present an unreasonable risk of illness or injury under conditions of use recommended...

  7. Alkaloid profiles of Mimosa tenuiflora and associated methods of analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The alkaloid contents of the leaves and seeds of M. tenuiflora collected from northeastern Brazil were studied. Alkaloids were isolated by classical acid/base extraction procedures and by cation exchange solid phase extraction. The crude alkaloid fractions were then analysed by thin layer chromatogr...

  8. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Dietary supplements containing ephedrine alkaloids... UNREASONABLE RISK § 119.1 Dietary supplements containing ephedrine alkaloids. Dietary supplements containing... ordinary conditions of use. Therefore, dietary supplements containing ephedrine alkaloids are...

  9. An efficient synthesis of loline alkaloids

    NASA Astrophysics Data System (ADS)

    Cakmak, Mesut; Mayer, Peter; Trauner, Dirk

    2011-07-01

    Loline (1) is a small alkaloid that, in spite of its simple-looking structure, has posed surprising challenges to synthetic chemists. It has been known for more than a century and has been the subject of extensive biological investigations, but only two total syntheses have been achieved to date. Here, we report an asymmetric total synthesis of loline that, with less then ten steps, is remarkably short. Our synthesis incorporates a Sharpless epoxidation, a Grubbs olefin metathesis and an unprecedented transannular aminobromination, which converts an eight-membered cyclic carbamate into a bromopyrrolizidine. The synthesis is marked by a high degree of chemo- and stereoselectivity and gives access to several members of the loline alkaloid family. It delivers sufficient material to support a programme aimed at studying the complex interactions between plants, fungi, insects and bacteria brokered by loline alkaloids.

  10. Ether bridge formation in loline alkaloid biosynthesis

    PubMed Central

    Pan, Juan; Bhardwaj, Minakshi; Faulkner, Jerome R.; Nagabhyru, Padmaja; Charlton, Nikki D.; Higashi, Richard M.; Miller, Anne-Frances; Young, Carolyn A.; Grossman, Robert B.; Schardl, Christopher L.

    2014-01-01

    Lolines are potent insecticidal agents produced by endophytic fungi of cool-season grasses. These alkaloids are composed of a pyrrolizidine ring system and an uncommon ether bridge linking carbons 2 and 7. Previous results indicated that 1-aminopyrrolizidine was a pathway intermediate. We used RNA interference to knock down expression of lolO, resulting in the accumulation of a novel alkaloid identified as exo-1-acetamidopyrrolizidine based on high-resolution MS and NMR. Genomes of endophytes differing in alkaloid profiles were sequenced, revealing that those with mutated lolO accumulated exo-1-acetamidopyrrolizidine but no lolines. Heterologous expression of wild-type lolO complemented a lolO mutant, resulting in the production of N-acetylnorloline. These results indicated that the non-heme iron oxygenase, LolO, is required for ether bridge formation, probably through oxidation of exo-1-acetamidopyrrolizidine. PMID:24374065

  11. Indole Alkaloids from Chaetomium globosum.

    PubMed

    Xu, Guo-Bo; He, Gu; Bai, Huan-Huan; Yang, Tao; Zhang, Guo-Lin; Wu, Lin-Wei; Li, Guo-You

    2015-07-24

    Two new indole alkaloids chaetocochin J (1) and chaetoglobinol A (8), along with chetomin (2), chetoseminudin A (3), cochliodinol (9), and semicochliodinol (10), were isolated from the rice culture of the fungus Chaetomium globosum. Their structures were elucidated by spectral analysis. Three new epipolythiodioxopiperazines, chaetocochins G-I (5-7), were identified by the combination of UPLC and mass spectrometric analysis. Chaetocochin I contained two sulfur bridges, one formed by three sulfur atoms between C-3 and C-11a, and the other formed by four sulfur atoms between C-3' and C-6'. Chaetocochin I was readily transformed into chetomin (2), chetoseminudin A (3), chaetocochin D (4), chaetocochin G (5), and chaetocochin H (6) by losing sulfur atoms. Compounds 1-3, and 8 exhibited antibacterial activities against Bacillus subtilis with MICs of 25, 0.78, 0.78, and 50 ?g/mL, respectively, but not against Gram-negative bacterium (Escherichia coli). Compounds 2 and 8 were inactive against Candida albicans, Fusarium graminearum, Fusarium vasinfectum, Saccharomyces cerevisiae, and Aspergillus niger even at the high concentrations of 200 and 100 ?g/mL, respectively. Compound 8 showed free radical scavenging capacity against the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical (ABTS(+•)), with IC50 values of 143.6 and 45.2 ?M, respectively. The free radical scavenging capacity rates of compounds 1-3 on the DPPH and ABTS(+•) were less than 20% at the test concentrations (89.9-108.3 ?M). The superoxide anion radical scavenging assay indicated that compounds 1-3, and 8 showed 14.8% (90.9 ?M), 18.1% (90.9 ?M), 51.5% (88.3 ?M), and 30.4% (61.3 ?M) superoxide anion radical scavenging capacity, respectively. PMID:26125976

  12. Hexacyclic monoterpenoid indole alkaloids from Rauvolfia verticillata.

    PubMed

    Gao, Yuan; Yu, Ai-Lin; Li, Gen-Tao; Hai, Ping; Li, Yan; Liu, Ji-Kai; Wang, Fei

    2015-12-01

    Five new hexacyclic monoterpenoid indole alkaloids, rauvovertine A (1), 17-epi-rauvovertine A (2), rauvovertine B (3), 17-epi-rauvovertine B (4), and rauvovertine C (5) together with 17 known analogues were isolated from the stems of Rauvolfia verticillata. Compounds 1/2 and 3/4 were obtained as C-17 epimeric mixtures due to rapid hemiacetal tautomerism in solution. The structures of 1-5 were established by spectroscopic analysis and with the aid of molecular modeling. The new alkaloids were evaluated for their cytotoxicity in vitro against human tumor HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cell lines. PMID:26474672

  13. Evaporative light scattering detection of pyrrolizidine alkaloids.

    PubMed

    Schaneberg, Brian T; Molyneux, Russell J; Khan, Ikhlas A

    2004-01-01

    A reverse-phase high-performance liquid chromatography method utilizing evaporative light scattering detection (ELSD) has been developed for the simultaneous detection of hepatotoxic pyrrolizidine alkaloids with and without chromophores, namely, riddelliine, riddelliine N-oxide, senecionine, senecionine N-oxide, seneciphylline, retrorsine, integerrimine, lasiocarpine and heliotrine. Pyrrolizidine alkaloids were detected in five plant extracts (Senecio spartioides, S. douglasii var. longilobus, S. jacobaea, S. intergerrimus var. exaltatus and Symphytum officinale). The detection of heliotrine (which does not contain a chromophore) was much improved by ELSD compared with photodiode array detection. PMID:14979525

  14. Recent pharmacological developments in ?-carboline alkaloid "harmaline".

    PubMed

    Khan, Farhan A; Maalik, Aneela; Iqbal, Zafar; Malik, Imran

    2013-12-01

    Peganum harmala (L) is a perennial plant which is native of eastern Iranian and west of India but also found in different regions of western USA. A number of ?-carboline compounds with therapeutic importance and different pharmacological effects, are present in this plant. Among other alkaloids, such as, harmine, harmalol and vasicine, isolated from various parts of the plant, harmaline is considered as most valuable with reference to its medicinal importance. Harmaline has been extensively studied in last decade and known to exert multiple pharmacological effects including antileishmanial, antimicrobial, antiplatelet, antiplasmodial, antitumoral, hypothermic and vasorelaxant activity. The proposed work is intended to highlight the recent pharmacological aspects of ?-carboline alkaloid "harmaline". PMID:23707188

  15. Therapeutic Potential of Steroidal Alkaloids in Cancer and Other Diseases.

    PubMed

    Jiang, Qi-Wei; Chen, Mei-Wan; Cheng, Ke-Jun; Yu, Pei-Zhong; Wei, Xing; Shi, Zhi

    2016-01-01

    Steroidal alkaloids are a class of secondary metabolites isolated from plants, amphibians, and marine invertebrates. Evidence accumulated in the recent two decades demonstrates that steroidal alkaloids have a wide range of bioactivities including anticancer, antimicrobial, anti-inflammatory, antinociceptive, etc., suggesting their great potential for application. It is therefore necessary to comprehensively summarize the bioactivities, especially anticancer activities and mechanisms of steroidal alkaloids. Here we systematically highlight the anticancer profiles both in vitro and in vivo of steroidal alkaloids such as dendrogenin, solanidine, solasodine, tomatidine, cyclopamine, and their derivatives. Furthermore, other bioactivities of steroidal alkaloids are also discussed. The integrated molecular mechanisms in this review can increase our understanding on the utilization of steroidal alkaloids and contribute to the development of new drug candidates. Although the therapeutic potentials of steroidal alkaloids look promising in the preclinical and clinical studies, further pharmacokinetic and clinical studies are mandated to define their efficacy and safety in cancer and other diseases. PMID:25820039

  16. Honatisine, a novel diterpenoid alkaloid, and six known alkaloids from Delphinium honanense and their cytotoxic activity.

    PubMed

    He, Yang Qing; Ma, Zhan Ying; Wei, Xiao Mei; Liu, Dong Jie; Du, Bao Zhong; Yao, Bing Hua; Gao, Li Ming

    2011-11-01

    A novel diterpene alkaloid named honatisine (1) has been isolated from the whole plants of Delphinium honanense, along with six known alkaloids, siwanine E (2), isoatisine (3), atisine (4), delcorinine (5), uraphine (6), and nordhagenine A (7). Their structures were deduced on the basis of their spectral data. All of them were evaluated by a SRB assay for their cytotoxicity, and compound 1 showed a significant cytotoxic activity (IC(50) =3.16 ?M) against the MCF-7 cell line. PMID:22083922

  17. The Alkaloid Profiles of Lupinus sulphureus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lupines are common plants found on the rangelands in the western United States. Lupines are known to contain alkaloids that can be toxic and teratogenic causing congenital birth defects (crooked calf disease). One such lupine, Lupinus sulphureus, occurs in parts of Oregon, Washington, and British ...

  18. Ergot alkaloids decrease rumen epithelial blood flow

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two experiments were conducted to determine if ergot alkaloids affect blood flow to the absorptive surface of the rumen of steers. Steers (n=8 total) were pair-fed alfalfa cubes at 1.5× NEM and received ground endophyte-infected tall fescue seed (E+) or endophyte-free tall fescue seed (E-) via rumen...

  19. Amides and an alkaloid from Portulaca oleracea.

    PubMed

    Kokubun, Tetsuo; Kite, Geoffrey C; Veitch, Nigel C; Simmonds, Monique S J

    2012-08-01

    A total of 16 phenolic compounds, including one new and five known N-cinnamoyl phenylethylamides, one new pyrrole alkaloid named portulacaldehyde, five phenylpropanoid acids and amides, and derivatives of benzaldehyde and benzoic acid, were isolated and identified from a polar fraction of an extract of Portulaca oleracea. Their structures were determined through spectroscopic analyses. PMID:22978226

  20. Probing chemical space with alkaloid-inspired libraries

    NASA Astrophysics Data System (ADS)

    McLeod, Michael C.; Singh, Gurpreet; Plampin, James N.; Rane, Digamber; Wang, Jenna L.; Day, Victor W.; Aubé, Jeffrey

    2014-02-01

    Screening of small-molecule libraries is an important aspect of probe and drug discovery science. Numerous authors have suggested that bioactive natural products are attractive starting points for such libraries because of their structural complexity and sp3-rich character. Here, we describe the construction of a screening library based on representative members of four families of biologically active alkaloids (Stemonaceae, the structurally related cyclindricine and lepadiformine families, lupin and Amaryllidaceae). In each case, scaffolds were based on structures of the naturally occurring compounds or a close derivative. Scaffold preparation was pursued following the development of appropriate enabling chemical methods. Diversification provided 686 new compounds suitable for screening. The libraries thus prepared had structural characteristics, including sp3 content, comparable to a basis set of representative natural products and were highly rule-of-five compliant.

  1. Ergot alkaloids: Quantitation and recognition challenges.

    PubMed

    Reinhard, H; Rupp, H; Zoller, O

    2008-03-01

    Bread, flour, infant formula and baby food samples (n=109, from which n=54 made of or containing rye), collected in 2001, 2003, and 2005, were analysed for ergot alkaloids. Samples were extracted using acidic conditions and the extracts subjected to an automated solid-phase clean up using combined cation exchange/reversed-phase sorbent cartridges (Oasis-MCX). Subsequent chromatographic separation and analysis was performed by liquid chromatography (LC) with fluorescence detection (FLD) and by LC with mass spectrometric detection (MS/MS). The ergot alkaloid (EAs) content of a sample was defined as the sum of the 16 alkaloids ergometrin(in)e, ergosin(in)e, ergotamin(in)e, ergostin(in)e, ergocornin(in)e, ?-ergocryptin(in)e, ?-ergocryptin(in)e and ergocristin(in)e. Comparability of results obtained by LC-FLD and LC-MS/MS was satisfactory, but varied for different alkaloids. The use of dihydro-ergocristine as an internal standard considerably improved the reliability of analytical data from LC-MS/MS. Compared with earlier data (Baumannet al., 1985) for median levels of ergot alkaloids in rye flour (140 ng/g) and bread (21.3 ng/g) from Switzerland, the median values for ergot alkaloids in rye flour collected in 2001 (n=13) and in 2005 (n=2) were 172 ng/g and 160 ng/g, respectively. The median values for bread (fresh weight) collected in 2001 (n=14), 2003 (n=7), and 2005 (n=2) were 87 ng/g, 120 ng/g, and 156 ng/g, respectively. Low levels of ergot alkaloids were also found in wheat products and in some infant formulae and baby foods containing rye. By additional LC-MS/MS experiments, the possible natural occurrence of ergot congeners containing the 9,10-unsaturated ergoline cation (m/z=223) was investigated. In a few samples, ergovalin(in)e was tentatively identified by these means. PMID:23606074

  2. Ergot Alkaloids Produced by Endophytic Fungi of the Genus Epichloë

    PubMed Central

    Guerre, Philippe

    2015-01-01

    The development of fungal endophytes of the genus Epichloë in grasses results in the production of different groups of alkaloids, whose mechanism and biological spectrum of toxicity can differ considerably. Ergot alkaloids, when present in endophyte-infected tall fescue, are responsible for “fescue toxicosis” in livestock, whereas indole-diterpene alkaloids, when present in endophyte-infected ryegrass, are responsible for “ryegrass staggers”. In contrast, peramine and loline alkaloids are deterrent and/or toxic to insects. Other toxic effects in livestock associated with the consumption of endophyte-infected grass that contain ergot alkaloids include the “sleepy grass” and “drunken horse grass” diseases. Although ergovaline is the main ergopeptine alkaloid produced in endophyte-infected tall fescue and is recognized as responsible for fescue toxicosis, a number of questions still exist concerning the profile of alkaloid production in tall fescue and the worldwide distribution of tall fescue toxicosis. The purpose of this review is to present ergot alkaloids produced in endophyte-infected grass, the factors of variation of their level in plants, and the diseases observed in the mammalian species as relate to the profiles of alkaloid production. In the final section, interactions between ergot alkaloids and drug-metabolizing enzymes are presented as mechanisms that could contribute to toxicity. PMID:25756954

  3. Comparison of methods for extraction of tobacco alkaloids.

    PubMed

    Jones, N M; Bernardo-Gil, M G; Lourenço, M G

    2001-01-01

    Ultrasound and microwave techniques were used to extract tobacco alkaloids, and response surface methodology was used to optimize extraction conditions. Ultrasonic technique factors were temperature, 30-85 degrees C; time, 3-45 min; solvent volume, 8-80 mL. Microwave extraction factors were pressure, 15-75 psi; time, 3-40 min; power, 30-90% of the maximum magnetron power of 650 W. Soxhlet and solvent AOAC-modified extraction methods were also applied after some improvements. Nicotine, nornicotine, anabasine, and anatabine were quantified by gas chromatography. A steam distillation International Standards Organization method for total alkaloid evaluation was used as reference. The results obtained by the different methods were compared using a least squares deviation test. The ultrasonic and the proposed modified-AOAC extraction method were the more convenient with regard to practicability and precision. The relative deviations (n = 5) were as follows: For the ultrasonic method in low-level alkaloid tobaccos, 0.7% nicotine and 1.4-14% minor alkaloids; in high-level alkaloid tobaccos, 2.4% nicotine and 4.5-5.1% minor alkaloids. For the modified AOAC method in low-level alkaloid tobaccos, 0.9% nicotine and 2.4-11.6% minor alkaloids; and in high-level alkaloid tobaccos, 1.7% nicotine and 2.0-2.4% minor alkaloids. PMID:11324592

  4. Synthesis and evaluation of Strychnos alkaloids as MDR reversal agents for cancer cell eradication

    E-print Network

    Synthesis and evaluation of Strychnos alkaloids as MDR reversal agents for cancer cell eradication: Total synthesis Strychnos alkaloids P-glycoprotein ABCB1 Multidrug resistance Resensitization Docking. We have developed an effective synthetic route to prepare various Strychnos alkaloids

  5. Enantioselective Synthesis of Tetrahydroprotoberberines and Bisbenzylisoquinoline Alkaloids from a Deprotonated -Aminonitrile

    E-print Network

    Lawson, Catherine L.

    Enantioselective Synthesis of Tetrahydroprotoberberines and Bisbenzylisoquinoline Alkaloids from for the preparation of various alkaloids. Here, the preparation of the benzylisoquinolines (+)-laudanidine and (-)-tetrahydropseudoepiberberine using Noyori's asymmetric transfer hydrogenation are described. The dimeric alkaloids (+)-O

  6. Regiocontrolled synthesis of the macrocyclic polyamine alkaloid ()-lunarine, a time-dependent inhibitor of trypanothione reductase

    E-print Network

    Schnaufer, Achim

    Regiocontrolled synthesis of the macrocyclic polyamine alkaloid (±)-lunarine, a time April 2002 A regiocontrolled synthesis of the macrocyclic polyamine alkaloid (±)-lunarine is described such study the macrocyclic polyamine alkaloid lunarine 1 was predicted to be a potential lead inhibitor (Fig

  7. Toxicosis by Plant Alkaloids in Humans and Animals in Colombia.

    PubMed

    Diaz, Gonzalo J

    2015-01-01

    Due to its tropical location, chains of mountains, inter-Andean valleys, Amazon basin area, eastern plains and shores on both the Atlantic and Pacific Oceans, Colombia has many ecosystems and the second largest plant biodiversity in the world. Many plant species, both native and naturalized, are currently recognized as toxic for both animals and humans, and some of them are known to cause their toxic effects due to their alkaloid content. Among these, there are plants containing the hepatotoxic pyrrolizidine alkaloids, neurotoxins such as the indolizidine alkaloid swainsonine and the piperidine alkaloids coniine and ?-coniceine and tropane alkaloids. Unfortunately, the research in toxic plants in Colombia is not nearly proportional to its plant biodiversity and the scientific information available is only very scarce. The present review aims at summarizing the scarce information about plant alkaloid toxicosis in animals and humans in Colombia. PMID:26690479

  8. Quinolizidine alkaloids from plants and their cell suspension cultures.

    PubMed

    Wink, M; Schiebel, H M; Witte, L; Hartmann, T

    1982-01-01

    The alkaloid composition of cell suspension cultures and differentiated plants of Lupinus polyphyllus was evaluated using quartz capillary gas-liquid chromatography, GLC-MS and FD-MS. Lupanine (97% of total alkaloids), sparteine, 13-angeloyloxylupanine and 13-tigloyloxylupanine were detected in alkaloid extracts of L. polyphyllus cell suspension cultures. Lupanine, 13-cis and 13-trans-cinnamoyloxylupanine were found in the spent cell culture medium. No significant difference was found in the alkaloid composition of photomixotrophic and heterotrophic cell strains although the alkaloid content was 5 to 10 times higher in photomixotrophic cell strains. In the respective plants we could identify 18 alkaloids which include the following esters of 13-hydroxylupanine: 13-tigloyloxylupanine, 13-angeloyloxylupanine, 13-cis-cinnamoyloxylupanine, 13-trans-cinnamoyloxylupanine, 13-benzoyloxylupanine, 13-(2-methylbutyryl)-oxylupanine; and 13-vanilloyloxylupanine. PMID:17402075

  9. Quinolizidine alkaloid biosynthesis: recent advances and future prospects

    PubMed Central

    Bunsupa, Somnuk; Yamazaki, Mami; Saito, Kazuki

    2012-01-01

    Lys-derived alkaloids, including piperidine, quinolizidine, indolizidine, and lycopodium alkaloids, are widely distributed throughout the plant kingdom. Several of these alkaloids have beneficial properties for humans and have been used in medicine. However, the molecular mechanisms underlying the biosynthesis of these alkaloids are not well understood. In the present article, we discuss recent advances in our understanding of Lys-derived alkaloids, especially the biochemistry, molecular biology, and biotechnology of quinolizidine alkaloid (QA) biosynthesis. We have also highlighted Lys decarboxylase (LDC), the enzyme that catalyzes the first committed step of QA biosynthesis and answers a longstanding question about the molecular entity of LDC activity in plants. Further prospects using current advanced technologies, such as next-generation sequencing, in medicinal plants have also been discussed. PMID:23112802

  10. Toxicosis by Plant Alkaloids in Humans and Animals in Colombia

    PubMed Central

    Diaz, Gonzalo J.

    2015-01-01

    Due to its tropical location, chains of mountains, inter-Andean valleys, Amazon basin area, eastern plains and shores on both the Atlantic and Pacific Oceans, Colombia has many ecosystems and the second largest plant biodiversity in the world. Many plant species, both native and naturalized, are currently recognized as toxic for both animals and humans, and some of them are known to cause their toxic effects due to their alkaloid content. Among these, there are plants containing the hepatotoxic pyrrolizidine alkaloids, neurotoxins such as the indolizidine alkaloid swainsonine and the piperidine alkaloids coniine and ?-coniceine and tropane alkaloids. Unfortunately, the research in toxic plants in Colombia is not nearly proportional to its plant biodiversity and the scientific information available is only very scarce. The present review aims at summarizing the scarce information about plant alkaloid toxicosis in animals and humans in Colombia. PMID:26690479

  11. Alkaloids Isolated from Natural Herbs as the Anticancer Agents

    PubMed Central

    Lu, Jin-Jian; Bao, Jiao-Lin; Chen, Xiu-Ping; Huang, Min; Wang, Yi-Tao

    2012-01-01

    Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery. Several alkaloids isolated from natural herbs exhibit antiproliferation and antimetastasis effects on various types of cancers both in vitro and in vivo. Alkaloids, such as camptothecin and vinblastine, have already been successfully developed into anticancer drugs. This paper focuses on the naturally derived alkaloids with prospective anticancer properties, such as berberine, evodiamine, matrine, piperine, sanguinarine, and tetrandrine, and summarizes the mechanisms of action of these compounds. Based on the information in the literature that is summarized in this paper, the use of alkaloids as anticancer agents is very promising, but more research and clinical trials are necessary before final recommendations on specific alkaloids can be made. PMID:22988474

  12. Rare bisindole alkaloids from the Amazonian tree Raputia simulans.

    PubMed

    Vougogiannopoulou, Konstantina; Travasarou, Aikaterini; Fokialakis, Nikolas; Skaltsounis, Alexios L

    2014-01-01

    The stem bark of Raputia simulans (Rutaceae) has been reported to contain simple and dimeric indole alkaloids. Further phytochemical investigation of R. simulans stem bark resulted in the isolation of three new alkaloids. These compounds represent a relatively new category of dimeric indole alkaloids with a cyclohexene moiety in their core. Their structure elucidations were based on NMR and HR-MS techniques, while structural aspects concerning their relative configuration were investigated using molecular mechanics calculations and NOESY experiments. PMID:24443432

  13. Tropane and pyrrolidine alkaloids from Convolvulus lanatus Vahl.

    PubMed

    el-Shazly, Assem; Wink, Michael

    2008-01-01

    The alkaloid composition of Convolvulus lanatus was investigated by GLC and GLC-MS. Altogether, thirteen tropane and pyrrolidine alkaloids were identified on the basis of mass spectral data and/or Kovats retention indices. Twelve of them have been recorded for the first time in this plant and some of these alkaloids were identified for the first time in the genus Convolvulus. Cuscohygrine is the major constituent. Qualitative and quantitative differences of root and aerial parts are discussed. PMID:18669014

  14. Analgesic activity of diterpene alkaloids from Aconitum baikalensis.

    PubMed

    Nesterova, Yu V; Povet'yeva, T N; Suslov, N I; Zyuz'kov, G N; Pushkarskii, S V; Aksinenko, S G; Schultz, E E; Kravtsova, S S; Krapivin, A V

    2014-08-01

    We compared analgesic activities of individual alkaloids extracted from Baikal aconite (Aconitum baikalensis): napelline, hypaconitine, songorine, mesaconitine, 12-epinapelline N-oxide. The detected analgesic activity was comparable to that of sodium metamizole. The mechanisms of analgesia were different in diterpene alkaloids of different structure. The antinociceptive effect of atisine alkaloids (12-epinapelline N-oxide, songorine) was naloxonedependent and realized via opioid receptor modulation. PMID:25110090

  15. Total synthesis of the Daphniphyllum alkaloid daphenylline

    NASA Astrophysics Data System (ADS)

    Lu, Zhaoyong; Li, Yong; Deng, Jun; Li, Ang

    2013-08-01

    The Daphniphyllum alkaloids are a large class of natural products isolated from a genus of evergreen plants widely used in Chinese herbal medicine. They display a remarkable range of biological activities, including anticancer, antioxidant, and vasorelaxation properties as well as elevation of nerve growth factor. Daphenylline is a structurally unique member among the predominately aliphatic Daphniphyllum alkaloids, and contains a tetrasubstituted arene moiety mounted on a sterically compact hexacyclic scaffold. Herein, we describe the first total synthesis of daphenylline. A gold-catalysed 6-exo-dig cyclization reaction and a subsequent intramolecular Michael addition reaction, inspired by Dixon's seminal work, were exploited to construct the bridged 6,6,5-tricyclic motif of the natural product at an early stage, and the aromatic moiety was forged through a photoinduced olefin isomerization/6?-electrocyclization cascade followed by an oxidative aromatization process.

  16. Two new alkaloids from Melodinus hemsleyanus Diels.

    PubMed

    Zhang, Pu-Zhao; Zhang, Ya-Mei; Gu, Jian; Zhang, Guo-Lin

    2016-01-01

    Two new monoterpenoid indole alkaloids, named 14,15-dihydro-14?,15?-epoxy-10-hydroxyscandine (1) and 15?-hydroxy-meloscandonine (2), together with 12 known compounds, were isolated from the aerial parts of Melodinus hemsleyanus Diels. The structures of 1 and 2 were elucidated on the bases of 1D and 2D NMR spectra and MS. Two new compounds were evaluated for their PTP1B and Drak2 inhibitory effects, and inactivity. PMID:26186199

  17. A chromanone alkaloid from Derris ovalifolia stem.

    PubMed

    Shankar, Thangaraj; Muthusubramanian, Shanmugam; Gandhidasan, Rathinasamy

    2009-01-01

    From the stem of Derris ovalifolia, a new chromanone alkaloid characterised as 7-methoxy-3-[1-(3-pyridyl)methylidene]-4-chromanone (1) was isolated along with four known compounds, dehydrotoxicarol (2), dehydrodeguelin (3), toxicarol isoflavone (4) and indole-3-carbaldehyde (5). Their structures were determined on the basis of spectral data interpretation. The structure of compound 1 has also been confirmed by synthesis. PMID:19851932

  18. Binding Parameters of Alkaloids Berberine and Sanguinarine with DNA

    E-print Network

    Gumenyuk, V G; Kutovyy, S Yu; Yashchuk, V M; Zaika, L A

    2012-01-01

    We study the interaction of berberine and sanguinarine (plant alkaloids) with DNA in aqueous solutions, by using optical spectroscopy methods (absorption and fluorescence). The dependencies of alkaloid spectral characteristics on the concentration ratio N/c between the DNA base pairs and alkaloid molecules in the solutions are considered, and the manifestations of the alkaloid-DNA binding are revealed. The character of binding is found to depend on N/c. The parameters of the binding of berberine and sanguinarine with DNA are determined, by using the modified Scatchard and McGhee-von Hippel equations

  19. Huperserines A-E, Lycopodium alkaloids from Huperzia serrata.

    PubMed

    Jiang, Wei-Wei; Liu, Fei; Gao, Xiu; He, Juan; Cheng, Xiao; Peng, Li-Yan; Wu, Xing-De; Zhao, Qin-Shi

    2014-12-01

    A phytochemical study on Huperzia serrata led to the isolation of four new 5-deoxyfawcettimine-related Lycopodium alkaloids, huperserines A-D (1-4), and one new lycodine-type alkaloid, huperserine E (5). Their structures were elucidated based on spectroscopic data, including 1D and 2D NMR techniques. 5-Carbonyl or 5-hydroxyl group is a typical characteristic of lycopodine- and fawcettimine-type alkaloids. This is the first report of the 5-deoxyfawcettimine type Lycopodium alkaloids. In vitro acetylcholinesterase (AChE) inhibitory activity assay showed that huperserine E exhibited moderate anti-AChE activity with an IC?? value of 6.71 ?M. PMID:25218968

  20. Koumine, Humantenine, and Yohimbane Alkaloids from Gelsemium elegans.

    PubMed

    Xu, You-Kai; Yang, Lin; Liao, Shang-Gao; Cao, Pei; Wu, Bin; Hu, Hua-Bin; Guo, Juan; Zhang, Ping

    2015-07-24

    Nine new alkaloids of the koumine (1-4), humantenine (5-7), and yohimbane (8, 9) types as well as 12 known analogues were isolated from the leaves and vine stems of Gelsemium elegans. Compound 1 is the first N-4-demethyl alkaloid of the koumine type, compound 7 is the first nor-humantenine alkaloid, and compounds 8 and 9 are the first N-1-oxide and the first seco-E-ring alkaloids, respectively, of the yohimbane type. Compounds 1 and 7 exhibited moderate cytotoxicity against five human tumor cell lines with IC50 values in the range 4.6-9.3 ?M. PMID:26103517

  1. Alkaloid variation in New Zealand k?whai, Sophora species.

    PubMed

    McDougal, Owen M; Heenan, Peter B; Jaksons, Peter; Sansom, Catherine E; Smallfield, Bruce M; Perry, Nigel B; van Klink, John W

    2015-10-01

    Alkaloid contents of leaf and seed samples of eight species of Sophora native to New Zealand, plus Sophora cassioides from Chile are reported. Fifty-six leaf and forty-two seed samples were analysed for alkaloid content by proton nuclear magnetic resonance spectroscopy, which showed major alkaloids as cytisine, N-methyl cytisine and matrine. GC analyses quantified these and identified further alkaloid components. The alkaloids identified were cytisine, sparteine, and matrine-types common to Sophora from other regions of the world. Cytisine, N-methyl cytisine, and matrine were generally the most abundant alkaloids across all species with seeds containing the highest concentrations of alkaloids. However, there was no clear taxonomic grouping based on alkaloid composition. A quantitative analysis of various parts of two Sophora microphylla trees showed that the seeds were the richest source of alkaloids (total 0.4-0.5% DM), followed by leaf and twig (0.1-0.3%) and then bark (0.04-0.06%), with only low amounts (<0.02%) found in the roots. This study represents the most comprehensive phytochemical investigation of New Zealand Sophora species to date and presents data for three species of Sophora for which no prior chemistry has been reported. PMID:26253652

  2. A homolog of tocopherol C-methyltransferases catalyzes N-methylation in anticancer alkaloid biosynthesis

    E-print Network

    Liscombe, David K.

    Madagascar periwinkle (Catharanthus roseus) is the sole source of the anticancer drugs vinblastine and vincristine, bisindole alkaloids derived from the dimerization of the terpenoid indole alkaloids vindoline and ...

  3. Exploiting alkaloid biosynthesis in Madagascar periwinkle to obtain natural product derivatives and new biocatalysts

    E-print Network

    Bernhardt, Peter, Ph. D. Massachusetts Institute of Technology

    2010-01-01

    Plant alkaloid biosynthesis produces many natural products with medicinal value. For example, vinblastine and vincristine from Catharanthus roseus monoterpene indole alkaloid biosynthesis, and camptothecin derivatives from ...

  4. Biparental defensive endowment of eggs with acquired plant alkaloid in the moth Utetheisa ornatrix.

    PubMed Central

    Dussourd, D E; Ubik, K; Harvis, C; Resch, J; Meinwald, J; Eisner, T

    1988-01-01

    The eggs of Utetheisa ornatrix contain pyrrolizidine alkaloids. These compounds are contributed by both parents, who sequester them as larvae from their food plants. Females receive alkaloid from the males at mating, apparently by seminal infusion, and transmit this alkaloid together with alkaloid of their own to the eggs. Field and laboratory tests showed that the alkaloids protect eggs from predators. The alkaloidal contribution of the male, although smaller than that of the female, itself provides significant egg protection. A previously identified pheromone, derived by the male from the alkaloid and emitted during precopulatory behavior, may announce the male alkaloidal worth to the female. PMID:3413071

  5. Identification of the quinolizidine alkaloids in Sophora leachiana

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sophora is a diverse genus representing herbs, shrubs, and trees that occurs throughout the world, primarily in the northern hemisphere. Sophora species contain a variety of quinolizidine alkaloids that are toxic and potentially teratogenic. However, there are no previous reports on the alkaloid c...

  6. Quinolizidine alkaloids in seeds of lupin genotypes of different origins.

    PubMed

    Boschin, Giovanna; Annicchiarico, Paolo; Resta, Donatella; D'Agostina, Alessandra; Arnoldi, Anna

    2008-05-28

    The intake of lupin-based foods could imply the exposure of consumers to quinolizidine alkaloids. The objectives of this study were to assess the genetic variation among and within 11 geographic regions of Lupinus albus ecotypes, verify the quinolizidine alkaloids amount of alkaloid-poor L. albus and Lupinus angustifolius varieties, and assess the effect of two climatically contrasting Italian environments on the alkaloid content. The quantitation was performed by GC-MS, and in all samples lupanine was the most abundant quinolizidine alkaloid, followed by albine and 13alpha-hydroxylupanine for L. albus and by 13alpha-hydroxylupanine and angustifoline for L. angustifolius. Some regions tended to have a high (Azores) or low (Egypt, Near East, Maghreb) total alkaloids content, but the variation among ecotypes within regions was larger than that among regions following the estimation of variance components. Alkaloid-poor varieties tended to have higher total alkaloid contents when grown in the subcontinental climate site, exceeding in some cases the limit of 0.200 mg/g. PMID:18433102

  7. Effects of Ergot Alkaloids on Bovine Sperm Motility In Vitro

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ergot alkaloids are synthesized by endophyte-infected (Neotyphodium coenophialum) tall fescue (Lolium arundinaceum (Schreb.) S.J. Darbyshire). Our objective was to determine direct effects of ergot alkaloids (ergotamine, dihydroergotamine and ergonovine) on the motility of bovine spermatozoa in vit...

  8. Monitoring the presence of ergot alkaloids in forage animal samples

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Novel Aspect Initial liquid chromatography tandem mass spectrometry method development for metabolite profiling of ergot alkaloids consumed by forage animals Introduction The presence of ergot alkaloids in forages has been reported to produce acute toxicity when consumed by forage animals. A meth...

  9. Tall fescue seed extraction and partial purification of ergot alkaloids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many substances in the tall fescue/endophyte association (Schedonorus arundinaceus/Epichloë coenophiala) have biological activity. Of these compounds only the ergot alkaloids are known to have significant mammalian toxicity and the predominant ergot alkaloids are ergovaline and ergovalinine. Because...

  10. Antiproliferative and Structure Activity Relationships of Amaryllidaceae Alkaloids.

    PubMed

    Cedrón, Juan C; Ravelo, Ángel G; León, Leticia G; Padrón, José M; Estévez-Braun, Ana

    2015-01-01

    The antiproliferative activity of a set of seven natural Amaryllidaceae alkaloids and 32 derivatives against four cancer cell lines (A2780, SW1573, T47-D and WiDr) was determined. The best antiproliferative activities were achieved with alkaloids derived from pancracine (2), haemanthamine (6) and haemantidine (7). For each skeleton, some structure-activity relationships were outlined. PMID:26263960

  11. Two new ?-carboline alkaloids from the roots of Gypsophila oldhamiana.

    PubMed

    Zhang, Yangmei; Wang, Gang; Lv, Huawei; Luo, Jianguang; Kong, Lingyi

    2015-01-01

    Phytochemical investigation of the roots of Gypsophila oldhamiana afforded two new ?-carboline alkaloids, oldhamiaines A and B (1 and 2), along with a known analogue (3). Their structures were elucidated by using spectroscopic and chemical methods. This is the first report of ?-carboline alkaloids in the genus Gypsophila. PMID:25554101

  12. Histological evaluation of brain damage caused by crude quinolizidine alkaloid extracts from lupines.

    PubMed

    Bañuelos Pineda, J; Nolasco Rodríguez, G; Monteon, J A; García López, P M; Ruiz Lopez, M A; García Estrada, J

    2005-10-01

    The effects of the intracerebroventricular (ICV) administration of crude extracts of lupin quinolizidine alkaloids (LQAs) were studied in adult rat brain tissue. Mature L. exaltatus and L. montanus seeds were collected in western Mexico, and the LQAs from these seeds were extracted and analyzed by capillary gas chromatography. This LQA extract was administered to the right lateral ventricle of adult rats through a stainless steel cannula on five consecutive days. While control animals received 10 microl of sesame oil daily (vehicle), the experimental rats (10 per group) received 20 ng of LQA from either L. exaltatus or from L. montanus. All the animals were sacrificed 40 h after receiving the last dose of alkaloids, and their brains were removed, fixed and coronal paraffin sections were stained with haematoxylin and eosin. Immediately after the administration of LQA the animals began grooming and suffered tachycardia, tachypnea, piloerection, tail erection, muscular contractions, loss of equilibrium, excitation, and unsteady walk. In the brains of the animals treated with LQA damaged neurons were identified. The most frequent abnormalities observed in this brain tissue were "red neurons" with shrunken eosinophilic cytoplasm, strongly stained pyknotic nuclei, neuronal swelling, spongiform neuropil, "ghost cells" (hypochromasia), and abundant neuronophagic figures in numerous brain areas. While some alterations in neurons were observed in control tissues, unlike those found in the animals treated with LQA these were not significant. Thus, the histopathological changes observed can be principally attributed to the administration of sparteine and lupanine present in the alkaloid extracts. PMID:16136497

  13. Do naïve ruminants degrade alkaloids in the rumen?

    PubMed

    Aguiar, Ramón; Wink, Michael

    2005-04-01

    Three different methods for the culture of rumen microorganisms (Hungate's technique, the Hohenheim in vitro gas production method, and the semicontinuous rumen simulation technique) were employed to study the influence of various alkaloids (sparteine, lupanine, cytisine, atropine, quinidine, lobeline, harmaline, arecoline, nicotine, caffeine, pilocarpine, gramine, senecionine, and monocrotaline) on rumen microorganisms. Rumen micro-organisms from naive ruminants (sheep, cattle) that had not been exposed to the alkaloids before were generally not able to degrade most of the alkaloids. Only the alkaloids pilocarpine, gramine, and monocrotaline appeared to be degradable. Rumen microorganisms from a sheep preconditioned to lupin alkaloids tolerated lupanine much better than nonadapted microorganisms, but no degradation occurred. The findings indicate that the main site of detoxification in naive ruminants is not the rumen but more likely the liver and kidneys as in nonruminants. PMID:16124250

  14. Biparental endowment of endogenous defensive alkaloids in Epilachna paenulata.

    PubMed

    Camarano, Soledad; González, Andrés; Rossini, Carmen

    2009-01-01

    Coccinellid beetles contain a variety of defensive alkaloids that render them unpalatable to predators. Epilachna paenulata (Coleoptera: Coccinellidae) is a South American ladybird beetle that feeds on plants of the Cucurbitaceae family. The defensive chemistry of E. paenulata has been characterized as a mixture of systemic piperidine, homotropane, and pyrrolidine alkaloids. Whole body extracts of adult beetles contain four major alkaloids: 2-(2'-oxopropyl)-6-methylpiperidine (1); 1-(6-methyl-2,3,4,5-tetrahydro-pyridin-2-yl)-propan-2-one (2); 1-methyl-9-azabicyclo[3.3.1]nonan-3-one (3); and 1-(2''-hydroxyethyl)-2-(12'-aminotridecyl)-pyrrolidine (4). Comparative studies of the defensive chemistry of eggs, larvae, pupae, and adults showed differences in alkaloid composition and concentration among life stages. While adults contained mainly the homotropane 1-methyl-9-azabicyclo[3.3.1]nonan-3-one (3), eggs showed the highest concentration of the piperidine 2-(2'-oxopropyl)-6-methylpiperidine (1). We studied the origin of this alkaloid in the eggs by feeding newly emerged, virgin adult beetles with [2-(13)C]-labeled acetate, and by performing crosses between (13)C-fed and unlabeled males and females. GC-MS analysis of alkaloids from (13)C-fed males and females showed high incorporation of (13)C into the alkaloids, as evidenced from a 20-30% increase of isotopic peaks in diagnostic fragment ions, confirming the expected endogenous origin of these alkaloids. In addition, analyses of eggs from different crosses showed that labeled alkaloids from both parents are incorporated into eggs, indicating that E. paenulata males transfer alkaloids to the females at mating. Biparental endowment of chemical defenses into eggs has been shown previously in insects that acquire defensive compounds from dietary sources. To our knowledge, this is the first report of biparental egg endowment of endogenous defenses. PMID:19052820

  15. Enantioselective Total Synthesis of Tricyclic Myrmicarin Alkaloids

    PubMed Central

    Movassaghi, Mohammad; Ondrus, Alison E.

    2010-01-01

    An enantioselective gram-scale synthesis of a key dihydroindolizine intermediate for the preparation of myrmicarin alkaloids is described. Key transformations in this convergent approach include a stereospecific palladium–catalyzed N-vinylation of a pyrrole with a vinyl triflate, a copper–catalyzed enantioselective conjugate reduction of a ?-pyrrolyl enoate, and a regioselective Friedel-Crafts reaction. The synthesis of optically active and isomerically pure samples of (4aR)-myrmicarins 215A, 215B, and 217 in addition to their respective C4a-epimers is presented. PMID:16178549

  16. A new pyrroloquinazoline alkaloid from Linaria vulgaris.

    PubMed

    Hua, Huiming; Cheng, Maosheng; Li, Xian; Pei, Yuehu

    2002-10-01

    A new alkaloid, 1,2,3,9-tetrahydropyrrolo(2,1-b)quinazolin-1-carboxylic acid (1), together with eight known compounds, 7-hydroxy vasicine (2), benzyl alcohol beta-D-(2'-O-beta-xylopyranosyl)glucopyranoside (3), benzyl alcohol O-beta-D-glucopyranoside (4), benzyl alcohol O-beta-D-primveroside (5), 3,5-dimethyl-4-hydroxy benzaldehyde (6), gluco-syringic acid (7), syringin (8), and liriodendrin (9), were isolated from the plants of Linaria vulgaris. Their structures were established by spectroscopic methods. PMID:12372872

  17. Plants containing pyrrolizidine alkaloids: toxicity and problems.

    PubMed

    Wiedenfeld, H

    2011-03-01

    Pyrrolizidine alkaloids (PA) are toxic for human and livestock. They undergo a metabolic toxication process in the liver which is the first target organ for PA poisoning. Worldwide many episodes of human PA intoxications are well reported. In many cases the reason for these intoxications has been PA contamination in food. The main tools for analysing food and fodder on PA content are based on GC and HPLC separation, followed by MS(-MS) detection. Actual incidents with toxic PA are the 'Jacobaea vulgaris (syn. Senecio jacobaea) problem' in Europe and the 'Ageratum conyzoides problem' in Ethiopia. PMID:21360374

  18. Hydroxylated Daphniphyllum Alkaloids from Daphniphyllum himalense.

    PubMed

    Zhang, Hua; Shyaula, Sajan L; Li, Jing-Ya; Li, Jia; Yue, Jian-Min

    2015-11-25

    Thirteen new hydroxylated calyciphylline A-type Daphniphyllum alkaloids (1-13) were isolated from an ethanolic extract of Daphniphyllum himalense. These structures were characterized on the basis of spectroscopic data analysis, especially from their 2D NMR spectra. Oxidation at the C-3, C-9, C-11, and C-12 positions is reported for the first time for this class of compounds. Selective compounds showed low inhibitory rates against three kinase enzymes, PTP1B, aurora A, and IKK-?, at a concentration of 20 ?g/mL. PMID:26486498

  19. Leaf herbivory and nutrients increase nectar alkaloids Lynn S. Adler,1

    E-print Network

    LETTER Leaf herbivory and nutrients increase nectar alkaloids Lynn S. Adler,1 * Michael Wink,2 on Nicotiana tabacum nectar and leaf alkaloids, floral traits and moth oviposition. We found a positive phenotypic correlation between nectar and leaf alkaloids. Herbivory induced alkaloids in nectar

  20. Biochemical Systematics and Ecology 29 (2001) 551561 Transfer of quinolizidine alkaloids from hosts

    E-print Network

    2001-01-01

    Biochemical Systematics and Ecology 29 (2001) 551­561 Transfer of quinolizidine alkaloids from have reduced herbivory when obtaining alkaloids from the hosts Lupinus argenteus and L. texensis alkaloid-containing hosts. To determine if alkaloids are present in all tissues of plants parasitizing

  1. Cardiovascular pharmacological effects of bisbenzylisoquinoline alkaloid derivatives.

    PubMed

    Qian, Jia-Qing

    2002-12-01

    Tetrandrine, dauricine, daurisoline and neferine are bisbenzylisoquinoline alkaloid derivatives isolated from Chinese traditional medicine and herbs. The cardiovascular pharmacological effects and the mechanism of actions of these compounds were reviewed. Tetrandrine isolated from Stephania tetrandra S Moore possesses antihypertensive and antiarrhythmic effects. The antihypertensive effects of tetrandrine have been demonstrated in experimental hypertensive animals and in hypertensive patients. Recent studies showed that in addition to its calcium antagonistic effect, tetrandrine interacted with M receptors. Modulation by M receptor is one of the pharmacological mechanisms of cardiovascular effects of tetrandrine. Dauricine and daurisoloine were isolated from Menispermum dauricum DC. The antiarrhythmic effects of dauricine have been verified in different experimental arrhythmic models and in cardiac arrhythmic patients. Dauricine blocked the cardiac transmembrane Na+,K+ and Ca2+ ion currents. Differing from quinidine and sotalol, which exhibited reverse use-dependent effect, dauricine prolonged APD in a normal use-dependent manner in experimental studies. The antiarrhythmic effect of daurisoline and neferine which is an alkaloid isolated from Nelumbo nucifera Gaertn, and their mechanisms of actions have also been studied. The antiarrhythmic effect of daurisoline is more potent than that of dauricine. PMID:12466045

  2. Ergot alkaloids produced by submerged cultures of Claviceps zizaniae.

    PubMed

    Kantorová, Michaela; Kolínská, Renata; Pazoutová, Sylvie; Honzátko, Ales; Havlícek, Vladimír; Flieger, Miroslav

    2002-07-01

    Two ergopeptine alkaloids, alpha-ergocryptine (1) and its C(8) epimer alpha-ergocryptinine, have been isolated from the mycelium and fermentation broth of submerged cultures of Claviceps zizaniae CCM 8240. The structure of 1 was determined by HPLC/positive ion APCI MS and NMR analysis. Alkaloid concentrations of 10 microg/mL in 14-day-old fermentation broth and 1 mg/g of dry mycelium mass were found. These results are of considerable biotechnological interest since these were the only detectable alkaloids produced. Toxicity of naturally occurring sclerotia of C. zizaniae cannot be excluded. PMID:12141870

  3. Quinolizidine alkaloid profiles of two taxa of Teline maderensis.

    PubMed

    Martins, Alice; Wink, Michael; Tei, Andreas; Rauter, Amélia P

    2003-01-01

    The alkaloid composition of the aerial parts of two taxa of Teline maderensis was studied by capillary GLC and GLC-MS. N-Methylcytisine was the major alkaloid found in both plants. Contents of cytisine and lupanine were higher in T. maderensis var. paivae while anagyrine content was more pronounced in T. maderensis var. maderensis. The alkaloids dehydrocytisine, N-acetylcytisine and epibaptifoline appeared only in T. maderensis var. maderensis and N-formylcytisine was identified as a minor constituent in T. maderensis var. paivae, and detected only in trace amounts in the other variety of the plant. PMID:14713148

  4. The role of biocatalysis in the asymmetric synthesis of alkaloids

    PubMed Central

    2013-01-01

    Alkaloids are not only one of the most intensively studied classes of natural products, their wide spectrum of pharmacological activities also makes them indispensable drug ingredients in both traditional and modern medicine. Among the methods for their production, biotechnological approaches are gaining importance, and biocatalysis has emerged as an essential tool in this context. A number of chemo-enzymatic strategies for alkaloid synthesis have been developed over the years, in which the biotransformations nowadays take an increasingly ‘central’ role. This review summarises different applications of biocatalysis in the asymmetric synthesis of alkaloids and discusses how recent developments and novel enzymes render innovative and efficient chemo-enzymatic production routes possible. PMID:25580241

  5. Total Synthesis and Study of Myrmicarin Alkaloids

    PubMed Central

    Ondrus, Alison E.

    2010-01-01

    The myrmicarins are a family of air and temperature sensitive alkaloids that possess unique structural features. Our concise enantioselective synthesis of the tricyclic myrmicarins enabled evaluation of a potentially biomimetic assembly of the complex members via direct dimerization of simpler structures. These studies revealed that myrmicarin 215B undergoes efficient and highly diastereoselective Brønsted acid-induced dimerization to generate a new heptacyclic structure, isomyrmicarin 430A. Mechanistic analysis demonstrated that heterodimerization between myrmicarin 215B and a conformationally restricted azafulvenium ion precursor afforded a functionalized isomyrmicarin 430A structure in a manner that was consistent with a highly efficient, non-concerted ionic process. Recent advancement in heterodimerization between tricyclic derivatives has enabled the preparation of strategically functionalized hexacyclic structures. The design and synthesis of structurally versatile dimeric compounds has greatly facilitated manipulation of these structures en route to more complex myrmicarin derivatives. PMID:19585010

  6. Synthesis and Anticancer Activity of Epipolythiodiketopiperazine Alkaloids

    PubMed Central

    Boyer, Nicolas; Morrison, Karen C.; Kim, Justin; Hergenrother, Paul J.; Movassaghi, Mohammad

    2013-01-01

    The epipolythiodiketopiperazine (ETP) alkaloids are a highly complex class of natural products with potent anticancer activity. Herein, we report the application of a flexible and scalable synthesis, allowing the construction of dozens of ETP derivatives. The evaluation of these compounds against cancer cell lines in culture allows for the first expansive structure–activity relationship (SAR) to be defined for monomeric and dimeric ETP-containing natural products and their synthetic cognates. Many ETP derivatives demonstrate potent anticancer activity across a broad range of cancer cell lines, and kill cancer cellsviainduction of apoptosis. Several traits thatbode well for the translational potential of the ETP class of natural products includeconcise and efficient synthetic access, potent induction of apoptotic cell death, activity against a wide range of cancer types, and a broad tolerance for modifications at multiple sitesthat should facilitate small-molecule drug development, mechanistic studies, and evaluation in vivo. PMID:23914293

  7. Microcalorimetry studies of the antimicrobial actions of Aconitum alkaloids.

    PubMed

    Shi, Yan-bin; Liu, Lian; Shao, Wei; Wei, Ting; Lin, Gui-mei

    2015-08-01

    The metabolic activity of organisms can be measured by recording the heat output using microcalorimetry. In this paper, the total alkaloids in the traditional Chinese medicine Radix Aconiti Lateralis were extracted and applied to Escherichia coli and Staphylococcus aureus. The effect of alkaloids on bacteria growth was studied by microcalorimetry. The power-time curves were plotted with a thermal activity monitor (TAM) air isothermal microcalorimeter and parameters such as growth rate constant (?), peak-time (Tm), inhibitory ratio (I), and enhancement ratio (E) were calculated. The relationships between the concentration of Aconitum alkaloids and ? of E. coli or S. aureus were discussed. The results showed that Aconitum alkaloids had little effect on E. coli and had a potentially inhibitory effect on the growth of S. aureus. PMID:26238544

  8. Aza-Tryptamine Substrates in Monoterpene Indole Alkaloid Biosynthesis

    E-print Network

    Lee, Hyang-Yeol

    Biosynthetic pathways can be hijacked to yield novel compounds by introduction of novel starting materials. Here we have altered tryptamine, which serves as the starting substrate for a variety of alkaloid biosynthetic ...

  9. New strategies for the synthesis of azepine-containing alkaloids 

    E-print Network

    Tallant, Matthew David

    2001-01-01

    The Stemona alkaloids are an important family of natural products which have received attention due to their unique chemical structure and important biological properties. The stemona family members contain the 4-azaazulene substructure (1...

  10. Microcalorimetry studies of the antimicrobial actions of Aconitum alkaloids*

    PubMed Central

    Shi, Yan-bin; Liu, Lian; Shao, Wei; Wei, Ting; Lin, Gui-mei

    2015-01-01

    The metabolic activity of organisms can be measured by recording the heat output using microcalorimetry. In this paper, the total alkaloids in the traditional Chinese medicine Radix Aconiti Lateralis were extracted and applied to Escherichia coli and Staphylococcus aureus. The effect of alkaloids on bacteria growth was studied by microcalorimetry. The power-time curves were plotted with a thermal activity monitor (TAM) air isothermal microcalorimeter and parameters such as growth rate constant (?), peak-time (Tm), inhibitory ratio (I), and enhancement ratio (E) were calculated. The relationships between the concentration of Aconitum alkaloids and ? of E. coli or S. aureus were discussed. The results showed that Aconitum alkaloids had little effect on E. coli and had a potentially inhibitory effect on the growth of S. aureus. PMID:26238544

  11. Substrate analogs to investigate alkaloid biosynthesis in Catharanthus roseus

    E-print Network

    McCoy, Elizabeth Ann, Ph. D. Massachusetts Institute of Technology

    2009-01-01

    Terpene indole alkaloids are a class of natural products produced by plants, many of which are used clinically for the treatment of human disease. Natural products, are not produced by the organism for the purpose of ...

  12. Alkaloids with Different Carbon Units from Myrioneuron faberi.

    PubMed

    Cao, Ming-Ming; Zhang, Yu; Huang, Sheng-Dian; Di, Ying-Tong; Peng, Zong-Gen; Jiang, Jian-Dong; Yuan, Chun-Mao; Chen, Duo-Zhi; Li, Shun-Lin; He, Hong-Ping; Hao, Xiao-Jiang

    2015-11-25

    Three new Myrioneuron alkaloids, myrifamines A-C (1-3), with unique skeletons were isolated from Myrioneuron faberi. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction analysis, and the stereochemistry of the other two alkaloids was determined using a combination of ROESY experiments and calculated and experimental electronic circular dichroism spectra. Myrifamine C (3) is the first example of a symmetric dimer among the Myrioneuron alkaloids. Known alkaloids myrionamide (4) and schoberine (5) were also isolated, and experimental NMR and X-ray diffraction data suggest their structural revision. Compound 2 showed significant inhibitory activity toward the hepatitis C virus in vitro, with a therapeutic index (CC50/EC50) greater than 108.7. PMID:26551513

  13. Crinine-type alkaloids from Hippeastrum aulicum and H. calyptratum.

    PubMed

    de Andrade, Jean Paulo; Guo, Ying; Font-Bardia, Mercè; Calvet, Teresa; Dutilh, Jullie; Viladomat, Francesc; Codina, Carles; Nair, Jerald J; Zuanazzi, Jose A Silveira; Bastida, Jaume

    2014-07-01

    An ongoing search for alkaloids in the Amaryllidaceae species using GC-MS resulted in the identification of two crinine-type alkaloids, aulicine (1) and 3-O-methyl-epimacowine, (2) from the indigenous Brazilian species Hippeastrum aulicum and Hippeastrum calyptratum, respectively. In addition, two alkaloids, 11-oxohaemanthamine (3) and 7-methoxy-O-methyllycorenine (4) were both isolated from H. aulicum. Furthermore, we provide here complete NMR spectroscopic data for the homolycorine analogues nerinine (5) and albomaculine (6). The absolute stereochemistry of the 5,10b-ethano bridge in the crinine variants was determined by circular dichroism and X-ray crystallographic analysis, thus presenting the first direct evidence for the presence of crinine-type alkaloids in the genus Hippeastrum. PMID:24768284

  14. Reprogramming alkaloid biosynthesis in Catharanthus roseus : synthetic biology in plants

    E-print Network

    Runguphan, Weerawat

    2011-01-01

    The medicinal plant Madagascar periwinkle (Catharanthus roseus) produces over 130 monoterpene indole alkaloid (MIA) natural products. Many of these compounds have pharmaceutical value, such as the anticancer agents vinblastine ...

  15. Arginine decarboxylase as the source of putrescine for tobacco alkaloids

    NASA Technical Reports Server (NTRS)

    Tiburcio, A. F.; Galston, A. W.

    1986-01-01

    The putrescine which forms a part of nicotine and other pyrrolidine alkaloids is generally assumed to arise through the action of ornithine decarboxylase (ODC). However, we have previously noted that changes in the activity of arginine decarboxylase (ADC), an alternate source of putrescine, parallel changes in tissue alkaloids, while changes in ODC activity do not. This led us to undertake experiments to permit discrimination between ADC and ODC as enzymatic sources of putrescine destined for alkaloids. Two kinds of evidence presented here support a major role for ADC in the generation of putrescine going into alkaloids: (a) A specific 'suicide inhibitor' of ADC effectively inhibits the biosynthesis of nicotine and nornicotine in tobacco callus, while the analogous inhibitor of ODC is less effective, and (b) the flow of 14C from uniformly labelled arginine into nicotine is much more efficient than that from ornithine.

  16. Erythroidine alkaloids: a novel class of phytoestrogens.

    PubMed

    Djiogue, Sefirin; Halabalaki, Maria; Njamen, Dieudonné; Kretzschmar, Georg; Lambrinidis, George; Hoepping, Josephine; Raffaelli, Francesca M; Mikros, Emmanuel; Skaltsounis, Alexios-Leandros; Vollmer, Günter

    2014-07-01

    Erythrina poeppigiana is a medicinal plant which is widely used in Asia, Latin America, and Africa in traditional remedies for gynecological complications and maladies. In continuation of studies for the discovery of novel phytoestrogens, four erythroidine alkaloids, namely ?-erythroidine, ?-erythroidine, and their oxo-derivatives 8-oxo-?-erythroidine and 8-oxo-?-erythroidine, were isolated and structurally characterized from the methanolic extract of the stem bark of E. poeppigiana. Due to the high amounts of erythroidines in the extract and considering the widespread utilization of Erythrina preparations in traditional medicine, the exploration of their estrogenic properties was performed. The estrogenicity of the isolated erythroidines was assayed in various estrogen receptor-(ER)-dependent test systems, including receptor binding affinity, cell culture based ER-dependent reporter gene assays, and gene expression studies in cultured cells using reverse transcription polymerase chain reaction techniques. ?-Erythroidine and ?-erythroidine showed binding affinity values for ER? of 0.015 ± 0.010% and 0.005 ± 0.010%, respectively, whereas only ?-erythroidine bound to ER? (0.006 ± 0.010%). In reporter gene assays, both erythroidines exhibited a significant dose-dependent estrogenic stimulation of ER-dependent reporter gene activity in osteosarcoma cells detectable already at 10 nM. Results were confirmed in the MVLN cells, a bioluminescent variant of MCF-7 breast cancer cells. Further, ?-erythroidine and ?-erythroidine both induced the enhanced expression of the specific ER?-dependent genes trefoil factor-1 and serum/glucocorticoid regulated kinase 3 in MCF-7 cells, confirming estrogenicity. Additionally, using molecular docking simulations, a potential mode of binding on ER?, is proposed, supporting the experimental evidences. This is the first time that an estrogenic profile is reported for erythroidine alkaloids, potentially a new class of phytoestrogens. PMID:25116117

  17. Pyrrolizidine alkaloids in pollen and pollen products.

    PubMed

    Kempf, Michael; Heil, Sandra; Hasslauer, Iris; Schmidt, Lukas; von der Ohe, Katharina; Theuring, Claudine; Reinhard, Annika; Schreier, Peter; Beuerle, Till

    2010-02-01

    Recently, 1,2-dehydropyrrolizidine alkaloid (PA) ester alkaloids, found predominantly as their N-oxides (PANOs, pyrrolizidine N-oxides), have been reported in both honey and in pollen obtained directly from PA plants and pollen loads collected by bees, raising the possibility of health risks for consumers of these products. We confirm these findings in regard to floral pollen, using pollen collected directly from flowers of the known PA plants Senecio jacobaea, S. vernalis, Echium vulgare and pollinia of Phalaenopsis hybrids, and we extend analyses of 1,2-unsaturated PAs and 1,2-unsaturated PANOs to include bee-pollen products currently being sold in supermarkets and on the Internet as food supplements. PA content of floral pollen ranged from 0.5 to 5 mg/g. The highest values were observed in pollen obtained from Senecio species. Up to 95% of the PAs are found as PANOs. Detailed studies with S. vernalis revealed unique PA patterns in pollen and flowers. While seneciphylline was the most prominent PA in S. vernalis pollen, the flowers were dominated by senecionine. To analyze trace amounts of 1,2-unsaturated PAs in pollen products, our previously elaborated method consisting of strong cation exchange-SPE, two reduction steps followed by silylation and subsequent capillary high-resolution GC-MS using SIM mode was applied. In total, 55 commercially available pollen products were analyzed. Seventeen (31%) samples contained 1,2-unsaturated PAs in the range from 1.08 to 16.35 microg/g, calculated as retronecine equivalents. The 1,2-unsaturated PA content of pollen products is expressed in terms of a single sum parameter and no background information such as foraged plants, pollen analysis, etc. was needed to analyze the samples. The detection limit of overall procedure and the reliable quantitation limit were 0.003 and 0.01 microg/g, respectively. PMID:20013884

  18. Evidence for an ergot alkaloid gene cluster in Claviceps purpurea.

    PubMed

    Tudzynski, P; Hölter, K; Correia, T; Arntz, C; Grammel, N; Keller, U

    1999-02-01

    A gene (cpd1) coding for the dimethylallyltryptophan synthase (DMATS) that catalyzes the first specific step in the biosynthesis of ergot alkaloids, was cloned from a strain of Claviceps purpurea that produces alkaloids in axenic culture. The derived gene product (CPD1) shows only 70% similarity to the corresponding gene previously isolated from Claviceps strain ATCC 26245, which is likely to be an isolate of C. fusiformis. Therefore, the related cpd1 most probably represents the first C. purpurea gene coding for an enzymatic step of the alkaloid biosynthetic pathway to be cloned. Analysis of the 3'-flanking region of cpd1 revealed a second, closely linked ergot alkaloid biosynthetic gene named cpps1, which codes for a 356-kDa polypeptide showing significant similarity to fungal modular peptide synthetases. The protein contains three amino acid-activating modules, and in the second module a sequence is found which matches that of an internal peptide (17 amino acids in length) obtained from a tryptic digest of lysergyl peptide synthetase 1 (LPS1) of C. purpurea, thus confirming that cpps1 encodes LPS1. LPS1 activates the three amino acids of the peptide portion of ergot peptide alkaloids during D-lysergyl peptide assembly. Chromosome walking revealed the presence of additional genes upstream of cpd1 which are probably also involved in ergot alkaloid biosynthesis: cpox1 probably codes for an FAD-dependent oxidoreductase (which could represent the chanoclavine cyclase), and a second putative oxidoreductase gene, cpox2, is closely linked to it in inverse orientation. RT-PCR experiments confirm that all four genes are expressed under conditions of peptide alkaloid biosynthesis. These results strongly suggest that at least some genes of ergot alkaloid biosynthesis in C. purpurea are clustered, opening the way for a detailed molecular genetic analysis of the pathway. PMID:10071219

  19. Carbazole and amide alkaloids from the stems of Clausena lansium.

    PubMed

    Du, Yi-Qian; Liu, Hang; Li, Chuang-Jun; Yang, Jing-Zhi; Ma, Jie; Zhang, Dan; Sun, Hua; Zhang, Dong-Ming

    2015-11-01

    Two new carbazole alkaloids, claulansine S (1) and claulansine T (2), and one new amide alkaloid, clauamide A (3), together with four known analogues (4-7) were isolated from the stems of Clausena lansium. Their structures were elucidated on the basis of spectroscopic analyses, including UV, IR, and NMR experiments (HSQC, HMBC, and NOE experiments). Compounds 4 and 6 showed moderate hepatoprotective activities. PMID:26095884

  20. Two novel minor alkaloids from Ethiopian Calpurnia aurea Ssp. aurea.

    PubMed

    Asres, K; Phillipson, J D; Mascagni, P

    1986-08-01

    Two novel minor quinolizidine alkaloids 4 beta-hydroxy-13alpha- O-(2'-pyrrolylcarbonyl)-lupanine (digittine) and its amino alcohol, 4 beta, 13alpha-dihydroxylupanine, have been isolated from Ethiopian Calpurnia aurea ssp. aurea. The structures of these alkaloids were determined by chemical transformation and by means of spectroscopic techniques (UV, IR, CD, MS, (1)H-NMR and (13)C-NMR) including two dimensional NMR. PMID:17345314

  1. Bioactive guanidine alkaloids from two Caribbean marine sponges.

    PubMed

    Laville, Rémi; Thomas, Olivier P; Berrué, Fabrice; Marquez, Diana; Vacelet, Jean; Amade, Philippe

    2009-09-01

    Seven new guanidine alkaloids (1-7) together with the known batzelladines A, F, H, and L, ptilomycalin A, and fromiamycalin were isolated from the Caribbean marine sponges Monanchora arbuscula and Clathria calla. Molecular structures were assigned on the basis of detailed analysis of 1D and 2D NMR spectra and mass spectrometry data, and bioactivities of the alkaloids were evaluated against human cancer cell lines and malaria protozoa. PMID:19743809

  2. Molecular genetics of alkaloid biosynthesis in Nicotiana tabacum.

    PubMed

    Dewey, Ralph E; Xie, Jiahua

    2013-10-01

    Alkaloids represent an extensive group of nitrogen-containing secondary metabolites that are widely distributed throughout the plant kingdom. The pyridine alkaloids of tobacco (Nicotiana tabacum L.) have been the subject of particularly intensive investigation, driven largely due to the widespread use of tobacco products by society and the role that nicotine (16) (see Fig. 1) plays as the primary compound responsible for making the consumption of these products both pleasurable and addictive. In a typical commercial tobacco plant, nicotine (16) comprises about 90% of the total alkaloid pool, with the alkaloids nornicotine (17) (a demethylated derivative of nicotine), anatabine (15) and anabasine (5) making up most of the remainder. Advances in molecular biology have led to the characterization of the majority of the genes encoding the enzymes directly responsible the biosynthesis of nicotine (16) and nornicotine (17), while notable gaps remain within the anatabine (15) and anabasine (5) biosynthetic pathways. Several of the genes involved in the transcriptional regulation and transport of nicotine (16) have also been elucidated. Investigations of the molecular genetics of tobacco alkaloids have not only provided plant biologists with insights into the mechanisms underlying the synthesis and accumulation of this important class of plant alkaloids, they have also yielded tools and strategies for modifying the tobacco alkaloid composition in a manner that can result in changing the levels of nicotine (16) within the leaf, or reducing the levels of a potent carcinogenic tobacco-specific nitrosamine (TSNA). This review summarizes recent advances in our understanding of the molecular genetics of alkaloid biosynthesis in tobacco, and discusses the potential for applying information accrued from these studies toward efforts designed to help mitigate some of the negative health consequences associated with the use of tobacco products. PMID:23953973

  3. Tropane alkaloids and calystegines as chemotaxonomic markers in the Solanaceae.

    PubMed

    Pigatto, Aline G S; Blanco, Carolina C; Mentz, Lilian A; Soares, Geraldo L G

    2015-12-01

    This study assessed the occurrence and distribution of tropane alkaloids and calystegines in genera of the family Solanaceae to identify patterns of distribution and make evolutionary inferences. A database of tropane alkaloids and calystegines occurrences was constructed from the results of a search of scientific websites and a hand search of periodicals. The terms "Solanaceae", "tropane alkaloids", and "calystegines" were used as index terms for a full-text article search unrestricted by date of publications. The number of occurrence and chemical diversity indices were calculated and cluster analysis and principal components analysis were performed. Overall, 996 occurrences were reported, 879 of tropane alkaloids (88.3%) and 117 of calystegines (11.7%). The calystegines were significantly more relevant than tropane alkaloids for characterization of distinct groups of genera on both analyses performed here. This corroborates the trend toward a chemical dichotomy observed on database analysis and somewhat reinforces the correlation between geographic distribution and occurrence of secondary metabolites, as the presence of calystegines alone (without tropane alkaloids) was only reported in genera that have South America as their center of diversity. PMID:26536852

  4. Genetics, Genomics and Evolution of Ergot Alkaloid Diversity

    PubMed Central

    Young, Carolyn A.; Schardl, Christopher L.; Panaccione, Daniel G.; Florea, Simona; Takach, Johanna E.; Charlton, Nikki D.; Moore, Neil; Webb, Jennifer S.; Jaromczyk, Jolanta

    2015-01-01

    The ergot alkaloid biosynthesis system has become an excellent model to study evolutionary diversification of specialized (secondary) metabolites. This is a very diverse class of alkaloids with various neurotropic activities, produced by fungi in several orders of the phylum Ascomycota, including plant pathogens and protective plant symbionts in the family Clavicipitaceae. Results of comparative genomics and phylogenomic analyses reveal multiple examples of three evolutionary processes that have generated ergot-alkaloid diversity: gene gains, gene losses, and gene sequence changes that have led to altered substrates or product specificities of the enzymes that they encode (neofunctionalization). The chromosome ends appear to be particularly effective engines for gene gains, losses and rearrangements, but not necessarily for neofunctionalization. Changes in gene expression could lead to accumulation of various pathway intermediates and affect levels of different ergot alkaloids. Genetic alterations associated with interspecific hybrids of Epichloë species suggest that such variation is also selectively favored. The huge structural diversity of ergot alkaloids probably represents adaptations to a wide variety of ecological situations by affecting the biological spectra and mechanisms of defense against herbivores, as evidenced by the diverse pharmacological effects of ergot alkaloids used in medicine. PMID:25875294

  5. Biosynthesis and Regulation of Bioprotective Alkaloids in the Gramineae Endophytic Fungi with Implications for Herbivores Deterrents.

    PubMed

    Luo, Hongping; Xie, Longxiang; Zeng, Jie; Xie, Jianping

    2015-12-01

    Four kinds of bioprotective alkaloids-peramine, loline, ergot alkaloid, indole-diterpenes, produced by grass-fungal endophyte symbioses, are deterrents or toxic to vertebrate and invertebrate herbivores. Ergot alkaloids have pharmacological properties and widely are used clinically. The regulation of alkaloids biosynthesis is under intensive study to improve the yield for better agricultural and medicinal application. In this paper, we summarize the structure, related genes, regulation, and toxicity of alkaloids. We focus on the biosynthesis and the regulation network of alkaloids. PMID:26349576

  6. Interactions in sheep between tall fescue ergot alkaloids and hepatotoxic carbon tetrachloride and Senecio pyrrolizidine alkaloids.

    PubMed

    Debessai, W T; Huan, J; Cheeke, P R

    1999-06-01

    The interaction between ergot alkaloids in endophyte-infected (E+) tall fescue (Festuca arundinacea) seed and pyrrolizidine alkaloids (PA) in tansy ragwort (TR; Senecio jacobaea) when simultaneously fed to sheep was investigated. Because of the hepatogenic effects of prolactin (PRL), it was hypothesized that low serum PRL induced by ergot alkaloids would increase the susceptibility of sheep to hepatotoxicity induced by PA. Sheep are normally resistant to PA-induced hepatotoxicity. Twenty-four wether lambs weighing 34.1 +/- 2.3 kg were used after being randomly assigned to 1 of 6 treatments of 4 wethers each. The diets offered were a control basal diet containing endophyte-free (E-) tall fescue seed, control + carbon tetrachloride (CCL4), E+ tall fescue basal diet, E+2CCl4, E(-)+TR, or E+2TR. The diets were composed of 50% alfalfa meal, 34.5% rolled barley, 5% soybean meal, 4% cane molasses, 0.5% trace mineralized salt and 6% tall fescue (E- or E+) seed. In the 2 TR treatments 25% of the alfalfa was replaced by TR. Interaction between ergot alkaloids in E+ tall fescue and PA in TR was assessed by gamma glutamyl transferase (GGTP) activity and/or sulfobromophthalein (BSP) clearance rate, both of which measure liver function. Serum GGTP activity was measured on days 14 and 28; plasma BSP clearance was monitored on days 28 and 70 by collection of blood at 4, 8 and 16 min after i.v. BSP injection. Serum PRL assays were performed on days 14, 70 and 84. Serum GGTP activity was elevated by CCl4 drenching on days 14 and 28. On day 28 TR feeding reduced GGTP activity, but there was no difference between the 2 TR treatments. There was no difference in the mean BSP half-times (t1/2) and % BSP retentions on day 28 among any of the 6 treatments. On day 70, there was no difference in the t1/2 or % BSP retention 4 min after BSP injection among any of the treatments. At 8 min after BSP injection, however, % BSP retention was significantly higher for the control +CCl4 than for the E+2CCl4 treatment. At 16 min after BSP injection, the E+ treatment had a higher mean % BSP retention value than the E+2CCl4 treatment; there were no differences among the other treatments. Serum PRL levels were reduced by E+ or CCl4 on all 3 dates of PRL evaluation. The lack of interaction between ergot alkaloids in E+ tall fescue seed and PA in TR as assessed by GGTP activity and/or BSP clearance in sheep may imply that the target sites o the 2 alkaloids are metabolically different. The low serum PRL with E+ did not increase susceptibility of sheep to CCl4 or PA. PMID:10349699

  7. Alkaloids and athlete immune function: caffeine, theophylline, gingerol, ephedrine, and their congeners.

    PubMed

    Senchina, David S; Hallam, Justus E; Kohut, Marian L; Nguyen, Norah A; Perera, M Ann d N

    2014-01-01

    Plant alkaloids are found in foods, beverages, and supplements consumed by athletes for daily nutrition, performance enhancement, and immune function improvement. This paper examined possible immunomodulatory roles of alkaloids in exercise contexts, with a focus on human studies. Four representative groups were scrutinized: (a) caffeine (guaranine, mateine); (b) theophylline and its isomers, theobromine and paraxanthine; (c) ginger alkaloids including gingerols and shogaol; and (d) ephedra alkaloids such as ephedrine and pseudoephedrine. Emerging or prospective alkaloid sources (Goji berry, Noni berry, and bloodroot) were also considered. Human in vitro and in vivo studies on alkaloids and immune function were often conflicting. Caffeine may be immunomodulatory in vivo depending on subject characteristics, exercise characteristics, and immune parameters measured. Caffeine may exhibit antioxidant capacities. Ginger may exert in vivo anti-inflammatory effects in certain populations, but it is unclear whether these effects are due to alkaloids or other biochemicals. Evidence for an immunomodulatory role of alkaloids in energy drinks, cocoa, or ephedra products in vivo is weak to nonexistent. For alkaloid sources derived from plants, variability in the reviewed studies may be due to the presence of unrecognized alkaloids or non-alkaloid compounds (which may themselves be immunomodulatory), and pre-experimental factors such as agricultural or manufacturing differences. Athletes should not look to alkaloids or alkaloid-rich sources as a means of improving immune function given their inconsistent activities, safety concerns, and lack of commercial regulation. PMID:24974722

  8. Transgenic and Mutation-Based Suppression of a Berberine Bridge Enzyme-Like (BBL) Gene Family Reduces Alkaloid Content in Field-Grown Tobacco

    PubMed Central

    Lewis, Ramsey S.; Lopez, Harry O.; Bowen, Steve W.; Andres, Karen R.; Steede, William T.; Dewey, Ralph E.

    2015-01-01

    Motivation exists to develop tobacco cultivars with reduced nicotine content for the purpose of facilitating compliance with expected tobacco product regulations that could mandate the lowering of nicotine levels per se, or the reduction of carcinogenic alkaloid-derived tobacco specific nitrosamines (TSNAs). A berberine bridge enzyme-like (BBL) gene family was recently characterized for N. tabacum and found to catalyze one of the final steps in pyridine alkaloid synthesis for this species. Because this gene family acts downstream in the nicotine biosynthetic pathway, it may represent an attractive target for genetic strategies with the objective of reducing alkaloid content in field-grown tobacco. In this research, we produced transgenic doubled haploid lines of tobacco cultivar K326 carrying an RNAi construct designed to reduce expression of the BBL gene family. Field-grown transgenic lines carrying functional RNAi constructs exhibited average cured leaf nicotine levels of 0.684%, in comparison to 2.454% for the untransformed control. Since numerous barriers would need to be overcome to commercialize transgenic tobacco cultivars, we subsequently pursued a mutation breeding approach to identify EMS-induced mutations in the three most highly expressed isoforms of the BBL gene family. Field evaluation of individuals possessing different homozygous combinations of truncation mutations in BBLa, BBLb, and BBLc indicated that a range of alkaloid phenotypes could be produced, with the triple homozygous knockout genotype exhibiting greater than a 13-fold reduction in percent total alkaloids. The novel source of genetic variability described here may be useful in future tobacco breeding for varied alkaloid levels. PMID:25688975

  9. Total synthesis of Galbulimima alkaloids. Resin-bound glycosyl phosphates as glycosyl donors.

    E-print Network

    Hunt, Diana Katharine

    2006-01-01

    I. Total Synthesis of Galbulimima Alkaloids. The total synthesis of enantiomerically enriched (+)- and (-)-galbulimima alkaloid 13 is outlined. Sequential use of catalytic cross-coupling and cross-metathesis reactions ...

  10. Nature's approach toward ring formation and structural diversity in ergot alkaloid biosynthesis

    E-print Network

    Cheng, Johnathan Zandrew

    2011-01-01

    Ergot alkaloids are fungal-derived secondary metabolites well known for a diverse array of pharmacological effects both beneficial and detrimental to human health. Historically, the ergot alkaloids have been known to cause ...

  11. Bovine lateral saphenous veins exposed to ergopeptine alkaloids do not relax

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ergot alkaloid, ergovaline has demonstrated a persistent binding and sustained contractile response in several vascular models. It was hypothesized that different alkaloids isolated from tall fescue (Lolium arundinaceum) will contribute to this response differently. The objective was to compare ...

  12. Bovine lateral saphenous veins exposed to ergopeptine alkaloids do not relax

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ergot alkaloid ergovaline has demonstrated a persistent and sustained contractile response in several different vascular models. It was hypothesized that different alkaloids isolated from tall fescue (Lolium arundinaceum) will contribute to this contractile response differently. The objective wa...

  13. Alkaloids of the Annonaceae: occurrence and a compilation of their biological activities.

    PubMed

    Lúcio, Ana Silvia Suassuna Carneiro; Almeida, Jackson Roberto Guedes da Silva; Da-Cunha, Emídio Vasconcelos Leitão; Tavares, Josean Fechine; Barbosa Filho, Jos Maria

    2015-01-01

    This chapter presents an overview of the chemistry and pharmacology of the alkaloids found in species of the Annonaceae family. The occurrence of alkaloids from Annonaceae species, as well as their chemical structures and pharmacological activities are summarized in informative and easy-to-understand tables. Within the Annonaceae family, the genera Annona, Duguetia, and Guatteria have led to many important publications. Valuable and comprehensive information about the structure of these alkaloids is provided. The alkaloids of the aporphine type represent the predominant group in this family. Many of the isolated alkaloids exhibit unique structures. In addition to the chemical structures, the pharmacological activities of some alkaloids are also presented in this chapter. Thus, the leishmanicidal, antimicrobial, antitumor, cytotoxic, and antimalarial activities observed for these alkaloids are highlighted. The chapter is presented as a contribution for the scientific community, mainly to enable the search for alkaloids in species belonging to the Annonaceae family. PMID:25845063

  14. Recognition of pyrrolizidine alkaloid esters in the invasive aquatic plant Gymnocoronis spilanthoides (Asteraceae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction – The freshwater aquatic plant Gymnocoronis spilanthoides (Senegal tea plant, jazmín del bañado, Falscher Wasserfreund) is an invasive plant in many countries. Behavioural observations of pyrrolizidine alkaloid-pharmacophagous butterflies suggested the presence of pyrrolizidine alkaloid...

  15. Synthesis of Morphinan Alkaloids in Saccharomyces cerevisiae.

    PubMed

    Fossati, Elena; Narcross, Lauren; Ekins, Andrew; Falgueyret, Jean-Pierre; Martin, Vincent J J

    2015-01-01

    Morphinan alkaloids are the most powerful narcotic analgesics currently used to treat moderate to severe and chronic pain. The feasibility of morphinan synthesis in recombinant Saccharomyces cerevisiae starting from the precursor (R,S)-norlaudanosoline was investigated. Chiral analysis of the reticuline produced by the expression of opium poppy methyltransferases showed strict enantioselectivity for (S)-reticuline starting from (R,S)-norlaudanosoline. In addition, the P. somniferum enzymes salutaridine synthase (PsSAS), salutaridine reductase (PsSAR) and salutaridinol acetyltransferase (PsSAT) were functionally co-expressed in S. cerevisiae and optimization of the pH conditions allowed for productive spontaneous rearrangement of salutaridinol-7-O-acetate and synthesis of thebaine from (R)-reticuline. Finally, we reconstituted a 7-gene pathway for the production of codeine and morphine from (R)-reticuline. Yeast cell feeding assays using (R)-reticuline, salutaridine or codeine as substrates showed that all enzymes were functionally co-expressed in yeast and that activity of salutaridine reductase and codeine-O-demethylase likely limit flux to morphine synthesis. The results of this study describe a significant advance for the synthesis of morphinans in S. cerevisiae and pave the way for their complete synthesis in recombinant microbes. PMID:25905794

  16. Pyrrolizidine alkaloids in honey and bee pollen.

    PubMed

    Dübecke, A; Beckh, G; Lüllmann, C

    2011-03-01

    A total of 3917 honey samples and 119 'bee pollen' samples (pollen collected by honeybees) were analysed for pyrrolizidine alkaloids (PAs). Some 0.05 M sulphuric acid was used for extraction followed by a clean-up step by means of solid-phase extraction. Separation and detection was achieved by target analysis using an LC-MS/MS system. PAs were found in 66% of the raw honeys (bulk honey not yet packaged in containers for sale in retail outlets) and in 94% of honeys available in supermarkets (retail honey). A total of 60% of the bee pollen samples were PA positive. The PA pattern was used to identify the potential origin of the PAs in honey, which was verified for the genus Echium by relative pollen analysis. The results give an estimate of the impact of PA-containing plants belonging to the genera Echium, Senecio and, to a certain extent, Eupatorium on PA levels in honey and can serve as a decision basis for beekeepers in order to find the most suitable location for the production of honey and bee pollen low in PAs. PMID:21360377

  17. Synthesis of Morphinan Alkaloids in Saccharomyces cerevisiae

    PubMed Central

    Fossati, Elena; Narcross, Lauren; Ekins, Andrew; Falgueyret, Jean-Pierre; Martin, Vincent J. J.

    2015-01-01

    Morphinan alkaloids are the most powerful narcotic analgesics currently used to treat moderate to severe and chronic pain. The feasibility of morphinan synthesis in recombinant Saccharomyces cerevisiae starting from the precursor (R,S)-norlaudanosoline was investigated. Chiral analysis of the reticuline produced by the expression of opium poppy methyltransferases showed strict enantioselectivity for (S)-reticuline starting from (R,S)-norlaudanosoline. In addition, the P. somniferum enzymes salutaridine synthase (PsSAS), salutaridine reductase (PsSAR) and salutaridinol acetyltransferase (PsSAT) were functionally co-expressed in S. cerevisiae and optimization of the pH conditions allowed for productive spontaneous rearrangement of salutaridinol-7-O-acetate and synthesis of thebaine from (R)-reticuline. Finally, we reconstituted a 7-gene pathway for the production of codeine and morphine from (R)-reticuline. Yeast cell feeding assays using (R)-reticuline, salutaridine or codeine as substrates showed that all enzymes were functionally co-expressed in yeast and that activity of salutaridine reductase and codeine-O-demethylase likely limit flux to morphine synthesis. The results of this study describe a significant advance for the synthesis of morphinans in S. cerevisiae and pave the way for their complete synthesis in recombinant microbes. PMID:25905794

  18. Effect of biotin on alkaloid production during submerged cultivation of Claviceps sp. strain SD-58.

    PubMed Central

    Desai, J D; Desai, A J; Patel, H C

    1983-01-01

    Addition of biotin to culture medium NL-406 significantly increased alkaloid yield during submerged cultivation of Claviceps sp. strain SD-58. Alkaloid yield was further enhanced by incorporating leucine in biotin-supplemented culture medium. Increased alkaloid production was associated with an increase in the lipid content of cells and in the number of chlamydospores. Biotin deficiency caused a reduction in alkaloid yield and a parallel decrease in lipid content and chlamydospore numbers. PMID:6870245

  19. Diterpene alkaloids with an aza-ent-kaurane skeleton from Isodon rubescens.

    PubMed

    Liu, Xu; Yang, Jing; Wang, Wei-Guang; Li, Yan; Wu, Ji-Zhou; Pu, Jian-Xin; Sun, Han-Dong

    2015-02-27

    Two compounds belonging to a new group of diterpene alkaloids, kaurines A and B (1 and 2), and an alkaloid bearing a succinimide moiety (3) were obtained from Isodon rubescens. Their structures and absolute configurations were determined by spectroscopy and quantum-chemical computational (13)C NMR and ECD data analysis. These alkaloids differ from known diterpene alkaloids and diterpenoids and are presumably biosynthesized from ent-kaurane diterpenoids. PMID:25590529

  20. Claviceps nigricans and Claviceps grohii: their alkaloids and phylogenetic placement.

    PubMed

    Pazoutová, Sylvie; Olsovská, Jana; Sulc, Miroslav; Chudícková, Milada; Flieger, Miroslav

    2008-06-01

    Claviceps purpurea, C. grohii, C. zizaniae, C. cyperi, and C. nigricans are closely related ergot fungi and form a monophyletic clade inside the genus Claviceps. Analysis of alkaloid content in C. nigricans sclerotia using UPLC detected ergocristine (1), ergosine (2), alpha-ergocryptine (3), and ergocristam (4). Alkaloids 1, 3, and 4 were found in the sclerotia of C. grohii. The content of 4 in the mixture of alkaloids from C. nigricans and C. grohii (over 8% and over 20%, respectively) was unusually high. Submerged shaken cultures of C. nigricans produced no alkaloids, whereas C. grohii culture formed small amounts (15 mg L (-1)) of extracellular clavines and 1. In the previously used HPLC method the ergocristam degradation product could have been obscured by the ergosine peak. Therefore sclerotia of a C. purpurea habitat-specific population G2 with the dominant production of 1 and 2 have been reanalyzed, but no 4 was detected. The phylogeny of the C. purpurea-related species group is discussed with regard to alkaloid-specific nonribosomal peptide synthetase duplication leading to the production of two main ergopeptines instead of a single product. PMID:18461998

  1. 6,7-diepicastanospermine, a tetrahydroxyindolizidine alkaloid inhibitor of amyloglucosidase

    SciTech Connect

    Molyneux, R.J.; Benson, M. ); Pan, Y.T.; Tropea, J.E.; Kaushal, G.P.; Elbein, A.D. )

    1991-10-15

    A tetrahydroxyindolizidine alkaloid, 6,7-diepicastanospermine, was isolated from the seeds of Castanospermum australe by extraction with methanol and purified to homogeneity using ion-exchange, preparative thin-layer, and radial chromatography. A very low yield of a pyrrolidine alkaloid, N-(hydroxyethyl)-2-(hydroxymethyl)-3-hydroxypyrrolidine, was also obtained by analogous methods. The purity of both alkaloids was established by gas chromatography of their trimethylsilyl (TMS) derivatives as better than 99%. The molecular weight of each alkaloid was established as 189 and 161, respectively, by mass spectrometry, and the structure of each was deduced from their {sup 1}H and {sup 13}C NMR spectra. The structure of the pyrrolidine alkaloids which co-occur in C. australe. 6,7-Diepicastanospermine was found to be a moderately good inhibitor of the fungal {alpha}-glucosidase, amyloglucosidase and a relatively weak inhibitor of {beta}-glucosidase. It failed to inhibit {alpha}-glucosidase. It failed to inhibit {alpha}- or {beta}-galactosidase, {alpha}- or {beta}-mannosidase, or {alpha}-L-fucosidase. Comparison of its inhibitory activity toward amyloglucosidase with those of its isomers, castanospermine and 6-epicastanospermine, demonstrated that epimerization of a single hydroxyl group can produce significant alteration of such inhibitory properties.

  2. Antiplatelet aggregation activity of diterpene alkaloids from Spiraea japonica.

    PubMed

    Li, Ling; Shen, Yue-Mao; Yang, Xiao-Sheng; Zuo, Guo-Ying; Shen, Zhi-Qiang; Chen, Zhi-He; Hao, Xiao-Jiang

    2002-08-01

    Six diterpene alkaloids with an atisine-type C(20)-skeleton isolated from the Chinese herbal medicines Spiraea japonica var. acuta and S. japonica var. ovalifolia, as well as eight derivatives of spiramine C and spiradine F were evaluated for the ability to inhibit aggregation of rabbit platelets induced by arachidonic acid, ADP, and platelet-activating factor (PAF) in vitro. The results showed that 12 of the 14 atisine-type diterpene alkaloids significantly inhibited PAF-induced platelet aggregation in a concentration-dependent manner, but had no effect on ADP- or arachidonic acid-induced aggregation, exhibiting a selective inhibition. It is the first report that C(20)-diterpene alkaloids inhibit PAF-induced platelet aggregation. However, spiramine C1 concentration-dependently inhibited platelet aggregation induced by PAF, ADP and arachidonic acid with IC(50) values of 30.5+/-2.7, 56.8+/-8.4 and 29.9+/-9.9 microM, respectively, suggesting a non-selective antiplatelet aggregation action. The inhibitory effect of spiramine C1 on arachidonic acid was as potent as that of aspirin. Primary studies of the structure-activity relationships for inhibition of PAF-induced aggregation showed that the oxygen substitution at the C-15 position and the presence of an oxazolidine ring in spiramine alkaloids were essential to their antiplatelet aggregation effects. These results suggest that the atisine-type alkaloids isolated from S. japonica are a class of novel antiplatelet aggregation agents. PMID:12163102

  3. Alkaloidal components in the poisonous plant, Ipomoea carnea (Convolvulaceae).

    PubMed

    Haraguchi, Mitsue; Gorniak, Silvana L; Ikeda, Kyoko; Minami, Yasuhiro; Kato, Atsushi; Watson, Alison A; Nash, Robert J; Molyneux, Russell J; Asano, Naoki

    2003-08-13

    Natural intoxication of livestock by the ingestion of Ipomoea carnea (Convolvulaceae) sometimes occurs in tropical regions of the world. Polyhydroxylated alkaloids were isolated from the leaves, flowers, and seeds of the poisonous plant and characterized. Chromatographic separation of the leaf extract resulted in the isolation of swainsonine (1), 2-epi-lentiginosine (2), calystegines B(1) (3), B(2) (4), B(3) (5), and C(1) (6), and N-methyl-trans-4-hydroxy-l-proline (7). The contents of 1 in the fresh leaves and flowers were 0.0029 and 0.0028%, respectively, whereas the contents of 1, 3, and 4 in the seeds were approximately 10 times higher than those in the leaves and flowers. Alkaloids 3, 4, and 6 showed a potent inhibitory activity toward rat lysosomal beta-glucosidase, with IC(50) values of 2.1, 0.75, and 0.84 microM, respectively, and alkaloid 5 was a moderate inhibitor of alpha- and beta-mannosidases. Although alkaloid 1 is known as a powerful inhibitor of lysosomal alpha-mannosidase (IC(50) = 0.02 microM), alkaloid 2, which has been thought to be an intermediate in the biosynthesis of 1, was also a potent inhibitor of alpha-mannosidase with an IC(50) value of 4.6 microM. PMID:12903959

  4. Ammonia chemical ionization tandem mass spectrometry in structural determination of alkaloids.

    E-print Network

    Ammonia chemical ionization tandem mass spectrometry in structural determination of alkaloids. II 7 June 2001 Chemical ionization tandem mass spectrometry (CI-MS/MS) of alkaloids with ammonia alkaloids in extracts from six pseudomyrmecine ants of the genus Tetraponera. The MS/MS techniques along

  5. The structural and synthetic implications of the biosynthesis of the calycanthaceous alkaloids, the communesins, and nomofungin

    E-print Network

    Stoltz, Brian M.

    The structural and synthetic implications of the biosynthesis of the calycanthaceous alkaloids Available online 11 April 2006 Abstract--A comparison is made between the calycanthaceous alkaloids for the communesins is presented that involves coupling of tryptamine with the ergot alkaloid aurantioclavine

  6. Synthetic studies toward the zoanthamine alkaloids: synthesis of the fully functionalized BC ring motif

    E-print Network

    Theodorakis, Emmanuel

    Synthetic studies toward the zoanthamine alkaloids: synthesis of the fully functionalized BC ring, collectively referred to as zoanthamine alkaloids.1 These natural products are distinguished by a densely the development of several synthetic routes toward the zoanthamine alkaloids7,8 that have recently culminated

  7. Asymmetric Total Synthesis of Dendrobatid Alkaloids: Preparation of Indolizidine 251F and Its 3-Desmethyl

    E-print Network

    Taber, Douglass

    Asymmetric Total Synthesis of Dendrobatid Alkaloids: Preparation of Indolizidine 251F and Its 3-mail: jaube@ku.edu Abstract: Total syntheses of alkaloid 251F (1), a natural product detected from the skin array of natural product targets, particularly alkaloids, unprecedented in other biological systems.1

  8. Alkaloid Profiles, Concentration and Pools in Velvet Lupine (Lupinus leucophyllus) Over the Growing Season

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lupinus leucophyllus is one of many lupine species known to contain toxic and/or teratogenic alkaloids that can cause congenital birth defects. The concentrations of total alkaloids and the individual major alkaloids were measured in three different years from different plant parts over the phenolog...

  9. Quinolizidine alkaloids from the curare adjuvant Clathrotropis glaucophylla.

    PubMed

    Sagen, Anne Lise; Gertsch, Jürg; Becker, Rita; Heilmann, Jörg; Sticher, Otto

    2002-12-01

    The bark of Clathrotropis glaucophylla (Fabaceae) is used as admixture of curare arrow poison by the Yanomami; Amerindians in Venezuela. A new quinolizidine alkaloid (QA), (-)-13alpha-hydroxy-15alpha-(1-hydroxyethyl)-anagyrine [(-)-clathrotropine], was isolated from the alkaloid extract of C. glaucophylla bark, together with eleven known QAs: (-)-anagyrine, (-)-thermopsine, (-)-baptifoline, (-)-epibaptifoline, (-)-rhombifoline, (-)-tinctorine, (-)-cytisine, (-)-N-methylcytisine, (-)-lupanine, (-)-6alpha-hydroxylupanine and (+)-5,6-dehydrolupanine. The isolation and structure elucidation were performed with the aid of chromatographic (TLC, HPLC and CC) and spectroscopic (UV and 1D/2D NMR) methods, and mass spectrometry. To our knowledge, this is the first time quinolizidine alkaloids have been isolated from an arrow poison ingredient. It is also the first report on Clathrotropis species being used for preparation of arrow poison. PMID:12453529

  10. In vitro production of alkaloids: Factors, approaches, challenges and prospects

    PubMed Central

    Ahmad, Sayeed; Garg, Madhukar; Tamboli, Ennus Tajuddin; Abdin, M. Z.; Ansari, S. H.

    2013-01-01

    The wide diversity of plant secondary metabolites is largely used for the production of various pharmaceutical compounds. In vitro cell tissue or organ culture has been employed as a possible alternative to produce such industrial compounds. Tissue culture techniques provide continuous, reliable, and renewable source of valuable plant pharmaceuticals and might be used for the large-scale culture of the plant cells from which these secondary metabolites can be extracted. Alkaloids are one of the most important secondary metabolites known to play a vital role in various pharmaceutical applications leading to an increased commercial importance in recent years. The tissue culture techniques may be utilized to improve their production of alkaloids via somaclonal variations and genetic transformations. The focus of this review is toward the application of different tissue culture methods/techniques employed for the in vitro production of alkaloids with a systematic approach to improve their production. PMID:23922453

  11. Hydrofocusing Bioreactor Produces Anti-Cancer Alkaloids

    NASA Technical Reports Server (NTRS)

    Gonda, Steve R.; Valluri, Jagan V.

    2011-01-01

    A methodology for growing three-dimensional plant tissue models in a hydrodynamic focusing bioreactor (HFB) has been developed. The methodology is expected to be widely applicable, both on Earth and in outer space, as a means of growing plant cells and aggregates thereof under controlled conditions for diverse purposes, including research on effects of gravitation and other environmental factors upon plant growth and utilization of plant tissue cultures to produce drugs in quantities greater and at costs lower than those of conventional methodologies. The HFB was described in Hydro focus - ing Bioreactor for Three-Dimensional Cell Culture (MSC-22358), NASA Tech Briefs, Vol. 27, No. 3 (March 2003), page 66. To recapitulate: The HFB offers a unique hydrofocusing capability that enables the creation of a low-shear liquid culture environment simultaneously with the herding of suspended cells and tissue assemblies and removal of unwanted air bubbles. The HFB includes a rotating cell-culture vessel with a centrally located sampling port and an internal rotating viscous spinner attached to a rotating base. The vessel and viscous spinner can be made to rotate at the same speed and direction or different speeds and directions to tailor the flow field and the associated hydrodynamic forces in the vessel in order to obtain low-shear suspension of cells and control of the locations of cells and air bubbles. For research and pharmaceutical-production applications, the HFB offers two major benefits: low shear stress, which promotes the assembly of cells into tissue-like three-dimensional constructs; and randomization of gravitational vectors relative to cells, which affects production of medicinal compounds. Presumably, apposition of plant cells in the absence of shear forces promotes cell-cell contacts, cell aggregation, and cell differentiation. Only gentle mixing is necessary for distributing nutrients and oxygen. It has been postulated that inasmuch as cells in the simulated microgravitation of an HFB do not need to maintain the same surface forces as in normal Earth gravitation, they can divert more energy sources to growth and differentiation and, perhaps, to biosynthesis of greater quantities of desired medicinal compounds. Because one can adjust the HFB to vary effective gravitation, one can also test the effects of intermediate levels of gravitation on biosynthesis of various products. The potential utility of this methodology for producing drugs was demonstrated in experiments in which sandalwood and Madagascar periwinkle cells were grown in an HFB. The conditions in the HFB were chosen to induce the cells to form into aggregate cultures that produced anti-cancer indole alkaloids in amounts greater than do comparable numbers of cells of the same species cultured according to previously known methodologies. The observations made in these experiments were interpreted as suggesting that the aggregation of the cells might be responsible for the enhancement of production of alkaloids.

  12. Alkaloid-derived molecules in low rank Argonne premium coals.

    SciTech Connect

    Winans, R. E.; Tomczyk, N. A.; Hunt, J. E.

    2000-11-30

    Molecules that are probably derived from alkaloids have been found in the extracts of the subbituminous and lignite Argonne Premium Coals. High resolution mass spectrometry (HRMS) and liquid chromatography mass spectrometry (LCMS) have been used to characterize pyridine and supercritical extracts. The supercritical extraction used an approach that has been successful for extracting alkaloids from natural products. The first indication that there might be these natural products in coals was the large number of molecules found containing multiple nitrogen and oxygen heteroatoms. These molecules are much less abundant in bituminous coals and absent in the higher rank coals.

  13. Anti-herpes virus activity of aporphine alkaloids.

    PubMed

    Montanha, J A; Amoros, M; Boustie, J; Girre, L

    1995-10-01

    We evaluated, in cell cultures, the action of a series of 19 aporphine alkaloids against Herpes simplex virus type 1 (HSV-1). On the basis of viral titre reduction, six alkaloids were found to be active. The mode of action of the three most potent inhibitors, oliverine HCl, pachystaudine, and oxostephanine, was studied. These compounds did not have any virucidal or prophylactic effect but they were shown to interfere with the viral replicative cycle. Although DNA synthesis was reduced, their exact target remains to be elucidated. In the discussion, some structure-activity relationships are considered. PMID:7480202

  14. Recent Advances in the Synthesis of Morphine and Related Alkaloids

    NASA Astrophysics Data System (ADS)

    Chida, Noritaka

    Morphine, an alkaloid isolated from the opium poppy, has been widely used as an analgesic, and has been a fascinating synthetic target of organic chemists. After the first total synthesis reported in 1952, a number of synthetic studies toward morphine have been reported, and findings obtained in such studies have greatly contributed to the progress of synthetic organic chemistry as well as medicinal chemistry. This review provides an overview of recent studies toward the total synthesis of morphine and related alkaloids. Work reported in the literature since 2004 will be reviewed.

  15. Cytotoxic mannopyranosides of indole alkaloids from Zanthoxylum nitidum.

    PubMed

    Hu, Jiang; Shi, Xiaodong; Mao, Xia; Chen, Jiangang; Li, Hui

    2014-06-01

    Three new mannopyranosides of indole alkaloids, methyl 7-(?-D-mannopyranosyloxy)-1H-indole-2-carboxylate (1), methyl 7-[(3-O-acetyl-?-D-mannopyranosyl)oxy]-1H-indole-2-carboxylate (2), and 2-methyl-1H-indol-7-yl ?-D-mannopyranoside (3), were isolated from an EtOH extract of the roots of Zanthoxylum nitidum. Their structures were identified as new compounds on the basis of the spectroscopic analyses. Bioactivity evaluation revealed that these alkaloids possess significant cytotoxicities against all the tested tumor cell lines with IC50 values of less than 30??M. PMID:24934682

  16. Adlumiceine methyl ester, a new alkaloid from Fumaria vaillantii.

    PubMed

    Iranshahy, Milad; Javidi-Shirazi, Hamideh; Pham, Ngoc B; Quinn, Ronald J; Sadeghian, Hamid; Iranshahi, Mehrdad

    2014-12-01

    A new alkaloid, adlumiceine methyl ester (1), together with two known alkaloids, parfumine (2) and N-methylhydrastine methyl ester (3), was isolated from aerial parts of Fumaria vaillantii. The structures of compounds were determined by 1D/2D NMR and MS data. All three compounds were tested for cytotoxic activity against PC3 and MCF7 cell lines using Alamar blue assay. The tested compounds showed no significant cytotoxic activity (IC50>50 ?M) against PC3 and MCF7 cell lines. PMID:25359679

  17. Our previous studies on G. dumetorum yielded several aporphine alkaloids that showed significant activity against Leishmania spp.

    E-print Network

    Coley, Phyllis

    Our previous studies on G. dumetorum yielded several aporphine alkaloids that showed significant conducted additional isolation efforts on the minor alkaloids of this species. A standard alkaloid on the identification of alkaloids 1±9 from G. dumetorum (Fig.1). All nine of these metabolites were tested against

  18. Inhibition of seed germination by quinolizidine alkaloids : Aspects of allelopathy in Lupinus albus L.

    PubMed

    Wink, M

    1983-08-01

    Germination of Lactuca sativa L. was inhibited by mixtures of quinolizidine alkaloids. The alkaloid esters resulted in the strongest inhibition: 6 mM 13-tigloyloxylupanine inhibited germination by 100%, whereas the other lupin alkaloids, such as lupanine and sparteine, gave a 45 and 20% inhibition, respectively. Seedlings of Lupinus albus L., which are not affected by quinolizidine alkaloids, excrete lupanine and 13-tigloyloxylupanine into the surrounding medium by their roots. It is assumed that lupin alkaloids are potential compounds of plant-plant interaction (i.e. allelopathy) besides their role in plant-herbivore interrelations. PMID:24264757

  19. Determination of Senecio alkaloids by thermospray liquid chromatography/mass spectrometry.

    PubMed

    Parker, C E; Verma, S; Tomer, K B; Reed, R L; Buhler, D R

    1990-01-01

    A series of Senecio alkaloid and alkaloid N-oxide standards has been analyzed using positive and negative ion thermospray liquid chromatography/mass spectrometry (LC/MS) with an ammonium acetate-containing mobile phase. On-line separations of pyrrolizidine alkaloids from extracts of Senecio jacobaea (tansy ragwort) and Senecio vulgaris (common groundsel) were done using an ammonium hydroxide-containing mobile phase. All of the alkaloids known to be present in the extracts were detected by ammonium hydroxide thermospray LC/MS, as well as many other components which may be as-yet-unidentified alkaloids. PMID:2306545

  20. The development of new synthetic strategies and methodologies for complex alkaloid total synthesis : a concise synthesis of (+)-chimonanthine, (+)-WIN 64821, (-)-ditryptophenaline and related alkaloids

    E-print Network

    Schmidt, Michael Anthony, 1980-

    2008-01-01

    I. The Development of a General Strategy Towards Dimeric Hexahydropyrroloindole Alkaloids. A Concise Total Synthesis of (+)-Chimonanthine, (+)-Folicanthine and (-)Calycanthine. An efficient and convergent strategy for the ...

  1. Biosynthesis of the defensive alkaloid cicindeloine in Stenus solutus beetles

    NASA Astrophysics Data System (ADS)

    Schierling, Andreas; Dettner, Konrad; Schmidt, Jürgen; Seifert, Karlheinz

    2012-08-01

    To protect themselves from predation and microorganismic infestation, rove beetles of the genus Stenus produce and store bioactive alkaloids like stenusine, 3-(2-methyl-1-butenyl)pyridine, and cicindeloine in their pygidial glands. The biosynthesis of stenusine and 3-(2-methyl-1-butenyl)pyridine was previously investigated in Stenus bimaculatus and Stenus similis, respectively. Both molecules follow the same biosynthetic pathway, where the N-heterocyclic ring is derived from l-lysine and the side chain from l-isoleucine. The different alkaloids are finally obtained by slight modifications of shared precursor molecules. The piperideine alkaloid cicindeloine occurs as a main compound additionally to ( E)-3-(2-methyl-1-butenyl)pyridine and traces of stenusine in the pygidial gland secretion of Stenus cicindeloides and Stenus solutus. Feeding of S. solutus beetles with [D,15N]-labeled amino acids followed by GC/MS analysis techniques showed that cicindeloine is synthesized via the identical pathway and precursor molecules as the other two defensive alkaloids.

  2. Australine, a pyrrolizidine alkaloid that inhibits amyloglucosidase and glycoprotein processing

    SciTech Connect

    Tropea, J.E.; Molyneux, R.J.; Kaushal, G.P.; Pan, Y.T.; Mitchell, M.; Elbein, A.D. )

    1989-03-07

    Australine is a polyhydroxylated pyrrolizidine alkaloid that was isolated from the seeds of the Australian tree Castanospermum australe and characterized by NMR and X-ray diffraction analysis. Since swainsonine and catanospermine are polyhydroxylated indolizidine alkaloids that inhibit specific glycosidases, the authors tested australine against a variety of exoglycosidases to determine whether it would inhibit any of these enzymes. This alkaloid proved to be a good inhibitor of the {alpha}-glucosidase amyloglucosidase (50% inhibition at 5.8 {mu}M), but it did not inhibit {beta}-glucosidase, {alpha}- or {beta}-mannosidase, or {alpha}- or {beta}-galactosidase. The inhibition of amyloglucosidase was of a competitive nature. Australine also inhibited the glycoprotein processing enzyme glucosidase I, but had only slight activity toward glucosidase II. When incubated with cultured cells, this alkaloid inhibited glycoprotein processing at the glucosidase I step and caused the accumulation of glycoproteins with Glc{sub 3}Man{sub 7-9}(GlcNAc){sub 2}-oligosaccharides.

  3. Diversification of Ergot Alkaloids in Natural and Modified Fungi

    PubMed Central

    Robinson, Sarah L.; Panaccione, Daniel G.

    2015-01-01

    Several fungi in two different families––the Clavicipitaceae and the Trichocomaceae––produce different profiles of ergot alkaloids, many of which are important in agriculture and medicine. All ergot alkaloid producers share early steps before their pathways diverge to produce different end products. EasA, an oxidoreductase of the old yellow enzyme class, has alternate activities in different fungi resulting in branching of the pathway. Enzymes beyond the branch point differ among lineages. In the Clavicipitaceae, diversity is generated by the presence or absence and activities of lysergyl peptide synthetases, which interact to make lysergic acid amides and ergopeptines. The range of ergopeptines in a fungus may be controlled by the presence of multiple peptide synthetases as well as by the specificity of individual peptide synthetase domains. In the Trichocomaceae, diversity is generated by the presence or absence of the prenyl transferase encoded by easL (also called fgaPT1). Moreover, relaxed specificity of EasL appears to contribute to ergot alkaloid diversification. The profile of ergot alkaloids observed within a fungus also is affected by a delayed flux of intermediates through the pathway, which results in an accumulation of intermediates or early pathway byproducts to concentrations comparable to that of the pathway end product. PMID:25609183

  4. The alkaloid profiles of Sophora nuttalliana and Sophora stenophylla

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sophora is a diverse genus in the family Fabaceae, comprised of herbs, shrubs, and trees that occurs throughout the world, primarily in the northern hemisphere. Species of Sophora are known to contain quinolizidine alkaloids that are toxic and potentially teratogenic. Two perennial herbaceous spec...

  5. Tall Fescue Alkaloids Bind Serotonin Receptors in Cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The serotonin (5HT) receptor 5HT2A is involved in the tall fescue alkaloid-induced vascular contraction in the bovine periphery. This was determined by evaluating the contractile responses of lateral saphenous veins biopsied from cattle grazing different tall fescue/endophyte combinations. The contr...

  6. Exactly which synephrine alkaloids does Citrus aurantium (bitter orange) contain?

    PubMed

    Allison, D B; Cutter, G; Poehlman, E T; Moore, D R; Barnes, S

    2005-04-01

    Following the withdrawal of ephedrine from the dietary supplement marketplace sales of products containing Citrus aurantium (CA) (bitter orange) for weight loss are believed to have increased dramatically. CA contains a number of constituents speculated to lead to weight loss, of which the most frequently cited constituent is synephrine. Concerns have been raised about the safety of products containing synephrine. To develop an adequate basis for clinical and public health recommendations, it is necessary to understand the nature of the synephrine alkaloids in CA. There are six possible isomers of synephrine (para, meta, ortho; and for each a d or l form). Some authors have stated that CA contains only p-synephrine, whereas other authors have stated that CA contains m-synephrine. This is an important distinction because the two molecules have different pharmacologic properties, which may differentially affect safety and efficacy. We are unable to identify published data that explicitly show whether CA contains p-synephrine, m-synephrine, or both. In this brief report, we show that at least one product purportedly containing synephrine alkaloids from CA contains both p-synephrine and m-synephrine. We believe this justifies further investigation into which synephrine alkaloids are present in CA and products purportedly containing synephrine alkaloids from CA and the relative quantities of each of the different isomers. PMID:15700046

  7. Pyrrolizidine alkaloids in food: A spectrum of potential health consequences

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Contamination of grain with 1,2-dehydropyrrolizidine ester alkaloids (dehydroPAs) and their N-oxides is responsible for large incidents of acute and subacute food poisoning, with high morbidity and mortality, in Africa and in central and south Asia. Herbal medicines and teas containing dehydroPAs ha...

  8. Two new Lycopodium alkaloids from Phlegmariurus phlegmaria (L.) Holub.

    PubMed

    Wang, Zhichong; Wu, Jichun; Zhao, Ningdong; Yang, Yiyu; Chen, Yegao

    2016-01-01

    Two new Lycopodium alkaloids, 4?-hydroxynankakurine B (1) and ?(13,N),N?-methylphlegmarine-N?-oxide (2), together with three known analogues, lycoposerramine E (3), nankakurine B (4) and lobscurinol (5), were isolated from Phlegmariurus phlegmaria. Their structures were established by mass spectrometry and 1D and 2D NMR techniques. PMID:26166258

  9. Pyrrolizidine alkaloid toxicity in livestock: A paradigm for human poisoning

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Livestock poisoning, primarily liver damage, caused by consumption of plants containing 1,2-dehydropyrro-lizidine ester alkaloids (dehydroPAs), and the corresponding N-oxides, is a relatively common occurrence worldwide. Because of the economic impact, extensive investigations...

  10. AUSTRALINE AND RELATED ALKALOIDS: EASY STRUCTURAL CONFIRMATION AND BIOLOGICAL ACTIVITIES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The first polyhydrroxylated pyrrolizidine alkaloid with a hydroxymethyl group at C-3 was isolated from pods of Alexa leiopetala (leguminosae) and designated alexine (1). The Australian legume Castanospermum australe is also known to produce the same structural type of pyrrolizidines. There are repor...

  11. Tobacco nicotine uptake permease (NUP1) affects alkaloid metabolism

    PubMed Central

    Hildreth, Sherry B.; Gehman, Elizabeth A.; Yang, Haibing; Lu, Rong-He; K C, Ritesh; Harich, Kim C.; Yu, Shi; Sandoe, Jackson L.; Okumoto, Sakiko; Murphy, Angus S.; Jelesko, John G.

    2011-01-01

    An effective plant alkaloid chemical defense requires a variety of transport processes, but few alkaloid transporters have been characterized at the molecular level. Previously, a gene fragment encoding a putative plasma membrane proton symporter was isolated, because it was coordinately regulated with several nicotine biosynthetic genes. Here, we show that this gene fragment corresponds to a Nicotiana tabacum gene encoding a nicotine uptake permease (NUP1). NUP1 belongs to a plant-specific class of purine uptake permease-like transporters that originated after the bryophytes but before or within the lycophytes. NUP1 expressed in yeast cells preferentially transported nicotine relative to other pyridine alkaloids, tropane alkaloids, kinetin, and adenine. NUP1-GFP primarily localized to the plasma membrane of tobacco Bright Yellow-2 protoplasts. WT NUP1 transcripts accumulated to high levels in the roots, particularly in root tips. NUP1-RNAi hairy roots had reduced NUP1 mRNA accumulation levels, reduced total nicotine levels, and increased nicotine accumulation in the hairy root culture media. Regenerated NUP1-RNAi plants showed reduced foliar and root nicotine levels as well as increased seedling root elongation rates. Thus, NUP1 affected nicotine metabolism, localization, and root growth. PMID:22006310

  12. The Raputindoles: Novel Cyclopentyl Bisindole Alkaloids from Raputia simulans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A novel class of bisindole alkaloids is established by the isolation and structural determination of Raputindoles A-D (1-4) from the Amazonian plant Raputia simulans Kallunki (Rutaceae). Complete spectroscopic characterization was accomplished by means of NMR spectroscopy and APCI (+) HRMS. Raputind...

  13. Effect of Ergot Alkaloids on Bovine Foregut Vasculature

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ergot alkaloids induce vasoconstriction of bovine foregut vasculature. Ergovaline induced the greatest response in ruminal artery while ergovaline and ergotamine induced the greatest response in ruminal vein. Lysergic acid did not stimulate a contractile response in either the ruminal artery or vein...

  14. THE TOXICITY AND KINETICS OF LARKSPUR ALKALOID, METHYLLYCACONITINE, IN MICE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Larkspur poisoning sporadically kills from 5-15% of the cattle on North American mountain rangelands. Of the 40 different diterpenoid larkspur alkaloids, one that is thought to be responsible for much of larkspur's toxicity has been identified as methyllycaconitine (MLA). Little is known of MLA to...

  15. Indole alkaloids of Rauwolfia reflexa. Carbon-13 nuclear magnetic resonance structural analysis of the bis(indole) alkaloid flexicorine

    SciTech Connect

    Chatterjee, A.; Ghosh, A.K.; Hagaman, E.W.

    1982-01-01

    The /sup 13/C NMR spectra analysis of the new bis(indole) alkaloid flexicorine and of its chemically modified derivatives were used to determine the structure of the natural base. Flexicorine is, apparently, the first 10'-hydroxy N'-unsubstituted indoline which preferentially exists in the original iminoquinone form. 2 tables.

  16. Simultaneous characterization of quaternary alkaloids, 8-oxoprotoberberine alkaloids, and a steroid compound in Coscinium fenestratum by liquid chromatography hybrid ion trap time-of-flight mass spectrometry.

    PubMed

    Deevanhxay, Phengxay; Suzuki, Makoto; Maeshibu, Nariaki; Li, He; Tanaka, Ken; Hirose, Sachio

    2009-10-15

    Simultaneous characterization of quaternary alkaloids, 8-oxoprotoberberine alkaloids, and a steroid compound in Coscinium fenestratum was successfully performed by liquid chromatography hybrid ion trap time-of-flight mass spectrometry (LC/IT-TOF MS). A total of 32 compounds, including 2 benzylisoquinoline alkaloids, 3 aporphine alkaloids, 12 quaternary protoberberine alkaloids, 10 8-oxoprotoberberine alkaloids, 3 tetrahydroprotoberberine alkaloids, and a steroid compound were simultaneously separated and characterized by matching the empirical molecular formulae with those published in literature and the multi-stage mass spectrometry (MS(n)) data obtained using structural information from IT, accurate mass measurement obtained from TOF MS, and HPLC separation. A total of 20 compounds, including 4 novel natural products were identified or tentatively identified for the first time from Coscinium fenestratum. In the positive-ion mode, 8-oxoprotoberberines produced [M+H](+) and [M+Na](+); the fragmentation of 8-oxodihydroprotoberberines produced [M+H-*CH(3)](+*), [M+H-*CH(3)-*CH(3)](+), and [M+H-*CH(3)-*CH(3)-CO](+), while 8-oxotetrahydroprotoberberines generated [M+H-*CH(3)](+*), [M+H-*CH(3)-*CH(3)](+), [M+H-*CH(3)-*H](+), and iminium ions from the cleavage of the protoberberine skeleton. The method can be applied for the analysis of 8-oxoberberine and other alkaloids in Coptis japonica, Phellodendron amurense, and other herbal medicines. PMID:19539442

  17. Accumulation of quinolizidine alkaloids in plants and cell suspension cultures: genera lupinus, cytisus, baptisia, genista, laburnum, and sophora.

    PubMed

    Wink, M; Witte, L; Hartmann, T; Theuring, C; Volz, V

    1983-08-01

    The patterns of quinolizidine alkaloids in cell cultures of 10 species of Fabaceae were analyzed by high-resolution GLC and GLC-MS and compared with the alkaloids present in the leaves of the respective plants. Lupanine was produced in all 10 cell suspension cultures as the main alkaloid. It was accompanied by sparteine, tetrahydrorhombifoline, 17-oxosparteine, 13-hydroxylupanine, 4-hydroxylupanine, 17-oxolupanine, and 13-hydroxylupanine esters as minor alkaloids in some species. The alkaloid patterns of the plants differed markedly in that alpha-pyridone alkaloids were the major alkaloids in the genera Cytisus, Genista, Laburnum and Sophora but were not accumulated in the cell cultures. These data further support the assumption that the pathway leading to lupanine is the basic pathway of quinolizidine alkaloids biosynthesis and that the other alkaloids are derived from lupanine. PMID:17404991

  18. Parasitic fungus Claviceps as a source for biotechnological production of ergot alkaloids.

    PubMed

    Hulvová, Helena; Galuszka, Petr; Frébortová, Jitka; Frébort, Ivo

    2013-01-01

    Ergot alkaloids produced by the fungus Claviceps parasitizing on cereals, include three major groups: clavine alkaloids, d-lysergic acid and its derivatives and ergopeptines. These alkaloids are important substances for the pharmatech industry, where they are used for production of anti-migraine drugs, uterotonics, prolactin inhibitors, anti-Parkinson agents, etc. Production of ergot alkaloids is based either on traditional field cultivation of ergot-infected rye or on submerged cultures of the fungus in industrial fermentation plants. In 2010, the total production of these alkaloids in the world was about 20,000 kg, of which field cultivation contributed about 50%. This review covers the recent advances in understanding of the genetics and regulation of biosynthesis of ergot alkaloids, focusing on possible applications of the new knowledge to improve the production yield. PMID:22261014

  19. Quinolizidine alkaloids and phomopsins in lupin seeds and lupin containing food.

    PubMed

    Reinhard, Hans; Rupp, Heinz; Sager, Fritz; Streule, Michael; Zoller, Otmar

    2006-04-21

    In recent years there has been growing interest in replacing (genetically modified) soya by lupin. Lupin seeds, flours and lupin containing food have been analyzed in order to assess the relevance of a potential health hazard given by mycotoxins and/or naturally occurring alkaloids. Since not all important alkaloids used for quantitation were commercially available, isolation of lupanine, 13alpha-hydroxylupanine and angustifoline from lupin flours of high alkaloid contents was performed. Alkaloids were analyzed by GC-MS/GC-FID in parallel, while the phomopsin mycotoxins were analyzed by ELISA, since chromatographic methods were not sensitive enough and required time-consuming sample cleanup. The analyzed lupin containing foods were free of phomopsins. In foods where lupin was only a minor constituent the alkaloid content was of no concern. However, roasted lupin beans intended as coffee surrogate had alkaloid contents close to the Australian intervention limit of 200 microg/g. PMID:16359686

  20. Genome mining of ascomycetous fungi reveals their genetic potential for ergot alkaloid production.

    PubMed

    Gerhards, Nina; Matuschek, Marco; Wallwey, Christiane; Li, Shu-Ming

    2015-06-01

    Ergot alkaloids are important as mycotoxins or as drugs. Naturally occurring ergot alkaloids as well as their semisynthetic derivatives have been used as pharmaceuticals in modern medicine for decades. We identified 196 putative ergot alkaloid biosynthetic genes belonging to at least 31 putative gene clusters in 31 fungal species by genome mining of the 360 available genome sequences of ascomycetous fungi with known proteins. Detailed analysis showed that these fungi belong to the families Aspergillaceae, Clavicipitaceae, Arthrodermataceae, Helotiaceae and Thermoascaceae. Within the identified families, only a small number of taxa are represented. Literature search revealed a large diversity of ergot alkaloid structures in different fungi of the phylum Ascomycota. However, ergot alkaloid accumulation was only observed in 15 of the sequenced species. Therefore, this study provides genetic basis for further study on ergot alkaloid production in the sequenced strains. PMID:25796201

  1. Correlation of Certain Alterations in Metabolic Activity with Alkaloid Production by Submerged Claviceps

    PubMed Central

    ?ehá?ek, Z.; Sajdl, P.; Kozová, J.; Malik, K. A.; ?i?icová, A.

    1971-01-01

    Alkaloid biosynthesis in Claviceps paspali MG-6 was favored by unbalanced growth. A positive correlation between the rate of protein turnover and alkaloid formation was noted. The pattern of the orthophosphate content in the mycelium resembled that in the ripening sclerotia of the parasitic strains. Alkaloids were revealed as potentially effective in energy metabolism. Reduced adenosine triphosphate (ATP) utilization and an increase in the ATP pool were found to be favorable for alkaloid production. Acetyl-coenzyme A carboxylase activity and the level of cell lipids were directly related to the intensity of alkaloid biosynthesis. An inverse relationship was observed between the activities of the tricarboxylic acid and glycoxylate cycles and the rate of alkaloid formation. PMID:4257780

  2. Metabolism of pyrrolizidine alkaloids by Peptostreptococcus heliotrinreducens and a mixed culture derived from ovine ruminal fluid.

    PubMed

    Hovermale, Jeannette T; Craig, A Morrie

    2002-12-10

    A mixed culture of ovine ruminal microbes metabolizes the macrocyclic pyrrolizidine alkaloids present in the plant Senecio jacobaea, including jacobine and seneciphylline. Previous attempts to identify metabolites of these alkaloids have not been successful. The objective of this study was to compare the metabolism of pyrrolizidine alkaloids by a mixed culture of ovine ruminal microbes to the metabolism of pyrrolizidine alkaloids by the known organism Peptostreptococcus heliotrinreducens. P. heliotrinreducens metabolizes the pyrrolizidine alkaloids heliotrine and lasiocarpine to 7alpha-hydroxy-1-methylene-8alpha-pyrrolizidine and 7alpha-angelyl-1-methylene-8alpha-pyrrolizidine, respectively. This organism does not metabolize the pyrrolizidine alkaloids jacobine or seneciphylline. A mixed culture of ovine ruminal microbes also metabolized heliotrine and lasiocarpine to identical methylene compounds. This mixed culture also metabolized jacobine and seneciphylline, with the production of very low levels of the corresponding 1-methylene compounds. Samples were analyzed by TLC and GC/MS. PMID:12488016

  3. Localization of the Enzymes of Quinolizidine Alkaloid Biosynthesis in Leaf Chloroplasts of Lupinus polyphyllus1

    PubMed Central

    Wink, Michael; Hartmann, Thomas

    1982-01-01

    Studies with purified chloroplasts of Lupinus polyphyllus LINDL. leaflets indicate that the first two enzymes of quinolizidine alkaloid biosynthesis, lysine decarboxylase and 17-oxosparteine synthase, are localized in the chloroplast stroma. Thus, both enzymes share the same subcellular compartment as the biosynthetic pathway of lysine, the precursor of quinolizidine alkaloids. The activity of diaminopimelate decarboxylase, the final enzyme in lysine biosynthesis, is about two to three orders of magnitude higher than that of the enzymes of alkaloid formation. PMID:16662483

  4. Tyrokeradines G and H, new bromotyrosine alkaloids from an Okinawan Verongid sponge.

    PubMed

    Kubota, Takaaki; Watase, Shinya; Sakai, Kanae; Fromont, Jane; Gonoi, Tohru; Kobayashi, Jun'ichi

    2015-11-15

    Two new bromotyrosine alkaloids, tyrokeradines G (1) and H (2), have been isolated from an Okinawan marine sponge of the order Verongida. The structures of 1 and 2 were elucidated on the basis of spectroscopic data. Tyrokeradine G (1) is the first bromotyrosine alkaloid possessing a ?-alanine unit, while tyrokeradine H (2) is a rare bromotyrosine alkaloid possessing a N-substituted pyridinium ring. Tyrokeradines G (1) and H (2) showed antifungal activity. PMID:26459215

  5. Flueggether A and Virosinine A, Anti-HIV Alkaloids from Flueggea virosa.

    PubMed

    Zhang, Hua; Zhu, Kong-Kai; Han, Ying-Shan; Luo, Cheng; Wainberg, Mark A; Yue, Jian-Min

    2015-12-18

    Two new alkaloids, flueggether A (1) and virosinine A (2), were isolated from a Chinese medicinal plant, Flueggea virosa. Their structures were assigned via spectroscopic methods with the absolute configurations of 1 and 2 being established by X-ray diffraction analysis and calculated electronic circular dichroism data, respectively. Compound 1 represents the first example with an ether bridge of Securinega alkaloid oligomers, and 2 bears a new heterocyclic backbone. Both alkaloids showed mild in vitro anti-HIV activity. PMID:26632657

  6. Two new diterpenoid alkaloids, beiwusines A and B, from Aconitum kusnezoffii.

    PubMed

    Li, Z B; Wang, F P

    1998-01-01

    Two new atisine-type diterpenoid alkaloids, beiwusine A (1) and B (2), have been isolated from the roots of Aconitum kusnezoffii Reichb. Their structures were established on the basis of spectroscopic data. Beiwusines A and B are the first examples of atisine-type diterpenoid alkaloids having a hydroxyl group at C-1. In addition, one known diterpenoid alkaloid spiramine H (3) has been isolated. PMID:11261218

  7. Taxonomic distribution of defensive alkaloids in Nearctic oribatid mites (Acari, Oribatida).

    PubMed

    Saporito, Ralph A; Norton, Roy A; Garraffo, Martin H; Spande, Thomas F

    2015-11-01

    The opisthonotal (oil) glands of oribatid mites are the source of a wide diversity of taxon-specific defensive chemicals, and are likely the location for the more than 90 alkaloids recently identified in oribatids. Although originally recognized in temperate oribatid species, alkaloids have also been detected in related lineages of tropical oribatids. Many of these alkaloids are also present in a worldwide radiation of poison frogs, which are known to sequester these defensive chemicals from dietary arthropods, including oribatid mites. To date, most alkaloid records involve members of the superfamily Oripodoidea (Brachypylina), although few species have been examined and sampling of other taxonomic groups has been highly limited. Herein, we examined adults of more than 60 species of Nearctic oribatid mites, representing 46 genera and 33 families, for the presence of alkaloids. GC-MS analyses of whole body extracts led to the detection of 15 alkaloids, but collectively they occur only in members of the genera Scheloribates (Scheloribatidae) and Protokalumma (Parakalummidae). Most of these alkaloids have also been detected previously in the skin of poison frogs. All examined members of the oripodoid families Haplozetidae and Oribatulidae were alkaloid-free, and no mites outside the Oripodoidea contained alkaloids. Including previous studies, all sampled species of the cosmopolitan oripodoid families Scheloribatidae and Parakalummidae, and the related, mostly tropical families Mochlozetidae and Drymobatidae contain alkaloids. Our findings are consistent with a generalization that alkaloid presence is widespread, but not universal in Oripodoidea. Alkaloid presence in tropical, but not temperate members of some non-oripodoid taxa (in particular Galumnidae) deserves further study. PMID:26264156

  8. Morphogenesis and Ultrastructure of Claviceps purpurea During Submerged Alkaloid Formation

    PubMed Central

    Vo?íšek, J.; Ludvík, J.; ?ehá?ek, Z.

    1974-01-01

    Criteria for morphogenetic and ultrastructural distinction between conidia and chlamydospores of a submerged culture of Claviceps purpurea (Fr.) Tul. are described. Both the hyphae of the sphacelia (asexual) stage and the conidia contained granular cytoplasm. Cytoplasmic invaginations in vacuoles were transformed to electron-opaque bodies and disintegrated prior to germination. The budding of conidia had basipetal succession. The chlamydospores were formed by rounding up the terminal cells of filamentous hyphae. Homogeneous nonvacuolized cytoplasm with lipid droplets and lipid-forming bodies was characteristic of young chlamydospores. Cristate mitochondria did not appear in the chlamydospores before the alkaloid production phase. Simultaneously a specific organelle in the chlamydospores, a dense body, appeared to absorb intracellular lipids and form large deposits of phospholipid material. No germination of chlamydospores was observed. The ultrastructural pattern described for chlamydospores was also observed in hyphae with reduced proliferation during the alkaloid production phase. Images PMID:4436258

  9. Biogenetically inspired synthesis and skeletal diversification of indole alkaloids

    NASA Astrophysics Data System (ADS)

    Mizoguchi, Haruki; Oikawa, Hideaki; Oguri, Hiroki

    2014-01-01

    To access architecturally complex natural products, chemists usually devise a customized synthetic strategy for constructing a single target skeleton. In contrast, biosynthetic assembly lines often employ divergent intramolecular cyclizations of a polyunsaturated common intermediate to produce diverse arrays of scaffolds. With the aim of integrating such biogenetic strategies, we show the development of an artificial divergent assembly line generating unprecedented numbers of scaffold variations of terpenoid indole alkaloids. This approach not only allows practical access to multipotent intermediates, but also enables systematic diversification of skeletal, stereochemical and functional group properties without structural simplification of naturally occurring alkaloids. Three distinct modes of [4+2] cyclizations and two types of redox-mediated annulations provided divergent access to five skeletally distinct scaffolds involving iboga-, aspidosperma-, andranginine- and ngouniensine-type skeletons and a non-natural variant within six to nine steps from tryptamine. The efficiency of our approach was demonstrated by successful total syntheses of (±)-vincadifformine, (±)-andranginine and (-)-catharanthine.

  10. Chemotaxonomy of Portuguese Ulex: quinolizidine alkaloids as taxonomical markers.

    PubMed

    Máximo, Patrícia; Lourenço, Ana; Tei, Andreas; Wink, Michael

    2006-09-01

    Six species of Portuguese Ulex L. in a total of nineteen populations were studied by GC-EIMS as to their content in quinolizidine alkaloids. Sparteine, beta-isosparteine, jussiaeiine A, N-methylcytisine, cytisine, 5,6-dehydrolupanine, rhombifoline, lupanine, jussiaeiine B, N-formylcytisine, N-acetylcytisine, anagyrine, jussiaeiine C, jussiaeiine D, pohakuline, baptifoline, and epibaptifoline were detected. Analysis of the chromatograms showed that the chemical profile of all species was mainly composed of N-methylcytisine, cytisine, anagyrine, and jussiaeiines A, B, C and D. Therefore a quantification study of these alkaloids in all the populations studied was done by GC. These data were then submitted to cluster analysis and principal component analysis, which allowed the definition of five chemotypes and the recognition of hybrids. N-methylcytisine, cytisine, and jussiaeiines A, C and D are recognized as markers of this genus in Portugal. PMID:16876210

  11. A Submarine Journey: The Pyrrole-Imidazole Alkaloids

    PubMed Central

    Forte, Barbara; Malgesini, Beatrice; Piutti, Claudia; Quartieri, Francesca; Scolaro, Alessandra; Papeo, Gianluca

    2009-01-01

    In his most celebrated tale “The Picture of Dorian Gray”, Oscar Wilde stated that “those who go beneath the surface do so at their peril”. This sentence could be a prophetical warning for the practitioner who voluntarily challenges himself with trying to synthesize marine sponge-deriving pyrrole-imidazole alkaloids. This now nearly triple-digit membered community has been growing exponentially in the last 20 years, both in terms of new representatives and topological complexity – from simple, achiral oroidin to the breathtaking 12-ring stylissadines A and B, each possessing 16 stereocenters. While the biosynthesis and the role in the sponge economy of most of these alkaloids still lies in the realm of speculations, significant biological activities for some of them have clearly emerged. This review will account for the progress in achieving the total synthesis of the more biologically enticing members of this class of natural products. PMID:20098608

  12. Antimalarial benzylisoquinoline alkaloid from the rainforest tree Doryphora sassafras.

    PubMed

    Buchanan, Malcolm S; Davis, Rohan A; Duffy, Sandra; Avery, Vicky M; Quinn, Ronald J

    2009-08-01

    Mass-directed isolation of the CH(2)Cl(2)/MeOH extract of Doryphora sassafras resulted in the purification of a new benzylisoquinoline alkaloid, 1-(4-hydroxybenzyl)-6,7-methylenedioxy-2-methylisoquinolinium trifluoroacetate (1), and the known aporphine alkaloid (S)-isocorydine (2). The structures of 1 and 2 were determined by 1D and 2D NMR and MS data analyses. The compounds were isolated during a drug discovery program aimed at identifying new antimalarial leads from a prefractionated natural product library. When tested against two different strains of the parasite Plasmodium falciparum (3D7 and Dd2), 1 displayed IC(50) values of 3.0 and 4.4 microM, respectively. Compound 1 was tested for cytotoxicity toward a human embryonic kidney cell line (HEK293) and displayed no activity at 120 microM. PMID:19637893

  13. Approach to the biosynthesis of atisine-type diterpenoid alkaloids.

    PubMed

    Zhao, Pei-Ji; Gao, Suo; Fan, Li-Ming; Nie, Jing-Lei; He, Hong-Ping; Zeng, Ying; Shen, Yue-Mao; Hao, Xiao-Jiang

    2009-04-01

    To determine the biosynthesis pathway of the atisine-type diterpenoid alkaloids spiramines A/B and C/D, feeding experiments in in vitro cultured plantlets and enzymatic transformations in cell-free extracts were performed in combination with LCMS and tandem MS analyses. L-[2-(13)C,(15)N]Serine was used in the feeding experiments and enzymatic transformations, and the diterpene spiraminol was identified as a biosynthetic precursor of spiramine alkaloids. The LCMS and tandem MS spectra of the extracts from these experiments indicated that L-[2-(13)C,(15)N]serine was incorporated into spiramines A/B and C/D. The labeled reaction products show that l-serine is the one possible nitrogen source involved in the biosynthesis of atisine-type DAs. PMID:19275222

  14. Total synthesis of a piperidine alkaloid, microcosamine A.

    PubMed

    Raji Reddy, Chada; Latha, Bellamkonda; Warudikar, Kamalkishor; Singarapu, Kiran Kumar

    2016-01-01

    The first asymmetric total synthesis of a new natural piperidine alkaloid, microcosamine A, has been accomplished from d-serine and d-methyl lactate as chiral pool starting materials. Key features of the strategy include the utility of Horner-Wadsworth-Emmons reaction, Luche reduction, intramolecular carbamate N-alkylation to form the piperidine framework and Julia-Kocienski olefination to install the triene side-chain. PMID:26565783

  15. Widespread Chemical Detoxification of Alkaloid Venom by Formicine Ants.

    PubMed

    LeBrun, Edward G; Diebold, Peter J; Orr, Matthew R; Gilbert, Lawrence E

    2015-10-01

    The ability to detoxify defensive compounds of competitors provides key ecological advantages that can influence community-level processes. Although common in plants and bacteria, this type of detoxification interaction is extremely rare in animals. Here, using laboratory behavioral assays and analyses of videotaped interactions in South America, we report widespread venom detoxification among ants in the subfamily Formicinae. Across both data sets, nine formicine species, representing all major clades, used a stereotyped grooming behavior to self-apply formic acid (acidopore grooming) in response to fire ant (Solenopsis invicta and S. saevissima) venom exposure. In laboratory assays, this behavior increased the survivorship of species following exposure to S. invicta venom. Species expressed the behavior when exposed to additional alkaloid venoms, including both compositionally similar piperidine venom of an additional fire ant species and the pyrrolidine/pyrroline alkaloid venom of a Monomorium species. In addition, species expressed the behavior following exposure to the uncharacterized venom of a Crematogaster species. However, species did not express acidopore grooming when confronted with protein-based ant venoms or when exposed to monoterpenoid-based venom. This pattern, combined with the specific chemistry of the reaction of formic acid with venom alkaloids, indicates that alkaloid venoms are targets of detoxification grooming. Solenopsis thief ants, and Monomorium species stand out as brood-predators of formicine ants that produce piperidine, pyrrolidine, and pyrroline venom, providing an important ecological context for the use of detoxification behavior. Detoxification behavior also represents a mechanism that can influence the order of assemblage dominance hierarchies surrounding food competition. Thus, this behavior likely influences ant-assemblages through a variety of ecological pathways. PMID:26385230

  16. Structure, Biosynthesis, and Occurrence of Bacterial Pyrrolizidine Alkaloids.

    PubMed

    Schimming, Olivia; Challinor, Victoria L; Tobias, Nicholas J; Adihou, Hélène; Grün, Peter; Pöschel, Laura; Richter, Christian; Schwalbe, Harald; Bode, Helge B

    2015-10-19

    Pyrrolizidine alkaloids (PAs) are widespread plant natural products with potent toxicity and bioactivity. Herein, the identification of bacterial PAs from entomopathogenic bacteria using differential analysis by 2D NMR spectroscopy (DANS) and mass spectrometry is described. Their biosynthesis was elucidated to involve a non-ribosomal peptide synthetase. The occurrence of these biosynthesis gene clusters in Gram-negative and Gram-positive bacteria indicates an important biological function in bacteria. PMID:26465655

  17. Development of Epipolythiodiketopiperazine syntheses and the total synthesis of diketopiperazine alkaloids

    E-print Network

    Adams, Timothy C. (Timothy Cho)

    2015-01-01

    I. The Development of Epipolythiodiketopiperazine (ETP) Syntheses Epipolythiodiketopiperazine (ETP) alkaloids represent a structurally complex and biologically potent class of secondary fungal metabolites and these molecules ...

  18. A new isoquinoline alkaloid with anti-microbial properties from Berberis jaeschkeana Schneid. var. jaeschkeana.

    PubMed

    Alamzeb, Muhammad; Khan, M Rafiullah; Mamoon-Ur-Rashid; Ali, Saqib; Khan, Ashfaq Ahmad

    2015-01-01

    One new isoquinoline alkaloid named berberidione (1) along with four new source alkaloids berberine (2), palmatine (3), jatrorrhizine (4) and chondrofoline (5) and three new source non-alkaloids syringic acid (6), ?-sitosterol (7) and stigmasterol (8) was isolated and characterised from different fractions of Berberis jaeschkeana Schneid var. jaeschkeana. All the structures were determined from 1D and 2D spectroscopic data. Crude extract, sub-fractions and isolated compounds showed excellent anti-microbial properties. The toxicity level for the alkaloids was found to be very low on THP-1 cells. PMID:25424893

  19. Recent Advances on the Total Syntheses of Communesin Alkaloids and Perophoramidine.

    PubMed

    Trost, Barry M; Osipov, Maksim

    2015-11-01

    The communesin alkaloids are a diverse family of Penicillium-derived alkaloids. Their caged-polycyclic structure and intriguing biological profiles have made these natural products attractive targets for total synthesis. Similarly, the ascidian-derived alkaloid, perophoramidine, is structurally related to the communesins and has also become a popular target for total synthesis. This review serves to summarize the many elegant approaches that have been developed to access the communesin alkaloids and perophoramidine. Likewise, strategies to access the communesin ring system are reviewed. PMID:26353936

  20. Feeding responses to selected alkaloids by gypsy moth larvae, Lymantria dispar (L.)

    NASA Astrophysics Data System (ADS)

    Shields, Vonnie D. C.; Rodgers, Erin J.; Arnold, Nicole S.; Williams, Denise

    2006-03-01

    Deterrent compounds are important in influencing the food selection of many phytophagous insects. Plants containing deterrents, such as alkaloids, are generally unfavored and typically avoided by many polyphagous lepidopteran species, including the gypsy moth Lymantria dispar (L.) (Lepidoptera: Lymantriidae). We tested the deterrent effects of eight alkaloids using two-choice feeding bioassays. Each alkaloid was applied at biologically relevant concentrations to glass fiber disks and leaf disks from red oak trees ( Quercus rubra) (L.), a plant species highly favored by these larvae. All eight alkaloids tested on glass fiber disks were deterrent to varying degrees. When these alkaloids were applied to leaf disks, only seven were still deterrent. Of these seven, five were less deterrent on leaf disks compared with glass fiber disks, indicating that their potency was dramatically reduced when they were applied to leaf disks. The reduction in deterrency may be attributed to the phagostimulatory effect of red oak leaves in suppressing the negative deterrent effect of these alkaloids, suggesting that individual alkaloids may confer context-dependent deterrent effects in plants in which they occur. This study provides novel insights into the feeding behavioral responses of insect larvae, such as L. dispar, to selected deterrent alkaloids when applied to natural vs artificial substrates and has the potential to suggest deterrent alkaloids as possible candidates for agricultural use.

  1. Elemental step thermodynamics of various analogues of indazolium alkaloids to obtaining hydride in acetonitrile.

    PubMed

    Lei, Nan-Ping; Fu, Yan-Hua; Zhu, Xiao-Qing

    2015-12-21

    A series of analogues of indazolium alkaloids were designed and synthesized. The thermodynamic driving forces of the 6 elemental steps for the analogues of indazolium alkaloids to obtain hydride in acetonitrile were determined using an isothermal titration calorimeter (ITC) and electrochemical methods, respectively. The effects of molecular structure and substituents on the thermodynamic driving forces of the 6 steps were examined. Meanwhile, the oxidation mechanism of NADH coenzyme by indazolium alkaloids was examined using the chemical mimic method. The result shows that the oxidation of NADH coenzyme by indazolium alkaloids in vivo takes place by one-step concerted hydride transfer mechanism. PMID:26451708

  2. Quinolizidine alkaloids isolated from Lupinus species enhance insulin secretion.

    PubMed

    García López, Pedro M; de la Mora, P Garzón; Wysocka, W; Maiztegui, Bárbara; Alzugaray, María E; Del Zotto, Héctor; Borelli, María I

    2004-11-01

    We have analyzed the effect of quinolizidine alkaloids from Lupinus species upon insulin secretion. Isolated normal rat islets were incubated with 3.3, 8.3, and 16.7 mM glucose, in the presence or absence of different concentrations of lupanine (0.05, 0.5, and 1.0 mM), 13-alpha-OH lupanine, 17-oxo-lupanine, and 2-thionosparteine. Insulin release was measured by radioimmunoassay. While 2-thionosparteine enhanced insulin secretion at all glucose concentrations, lupanine did at 8.3 and 16.7 mM, and 13-alpha-OH lupanine or 17-oxo-lupanine only at 16.7 mM glucose. Diazoxide (0.1 mM) decreased the effect of all alkaloids, without suppressing it completely. Consequently, blockage of beta-cell K(ATP)-sensitive channels is at least one of the mechanisms involved in the enhancing secretagogue effects of quinolizidine alkaloids. The fact that 13-alpha-OH lupanine and 17-oxo-lupanine only exert their secretagogue effect at high glucose concentrations could be of additional value when considering their potential use in the treatment of type 2 diabetes. PMID:15507230

  3. Ergot Alkaloids (Re)generate New Leads as Antiparasitics.

    PubMed

    Chan, John D; Agbedanu, Prince N; Grab, Thomas; Zamanian, Mostafa; Dosa, Peter I; Day, Timothy A; Marchant, Jonathan S

    2015-09-01

    Praziquantel (PZQ) is a key therapy for treatment of parasitic flatworm infections of humans and livestock, but the mechanism of action of this drug is unresolved. Resolving PZQ-engaged targets and effectors is important for identifying new druggable pathways that may yield novel antiparasitic agents. Here we use functional, genetic and pharmacological approaches to reveal that serotonergic signals antagonize PZQ action in vivo. Exogenous 5-hydroxytryptamine (5-HT) rescued PZQ-evoked polarity and mobility defects in free-living planarian flatworms. In contrast, knockdown of a prevalently expressed planarian 5-HT receptor potentiated or phenocopied PZQ action in different functional assays. Subsequent screening of serotonergic ligands revealed that several ergot alkaloids possessed broad efficacy at modulating regenerative outcomes and the mobility of both free living and parasitic flatworms. Ergot alkaloids that phenocopied PZQ in regenerative assays to cause bipolar regeneration exhibited structural modifications consistent with serotonergic blockade. These data suggest that serotonergic activation blocks PZQ action in vivo, while serotonergic antagonists phenocopy PZQ action. Importantly these studies identify the ergot alkaloid scaffold as a promising structural framework for designing potent agents targeting parasitic bioaminergic G protein coupled receptors. PMID:26367744

  4. Ergot Alkaloids (Re)generate New Leads as Antiparasitics

    PubMed Central

    Chan, John D.; Agbedanu, Prince N.; Grab, Thomas; Zamanian, Mostafa; Dosa, Peter I.; Day, Timothy A.; Marchant, Jonathan S.

    2015-01-01

    Abstract Praziquantel (PZQ) is a key therapy for treatment of parasitic flatworm infections of humans and livestock, but the mechanism of action of this drug is unresolved. Resolving PZQ-engaged targets and effectors is important for identifying new druggable pathways that may yield novel antiparasitic agents. Here we use functional, genetic and pharmacological approaches to reveal that serotonergic signals antagonize PZQ action in vivo. Exogenous 5-hydroxytryptamine (5-HT) rescued PZQ-evoked polarity and mobility defects in free-living planarian flatworms. In contrast, knockdown of a prevalently expressed planarian 5-HT receptor potentiated or phenocopied PZQ action in different functional assays. Subsequent screening of serotonergic ligands revealed that several ergot alkaloids possessed broad efficacy at modulating regenerative outcomes and the mobility of both free living and parasitic flatworms. Ergot alkaloids that phenocopied PZQ in regenerative assays to cause bipolar regeneration exhibited structural modifications consistent with serotonergic blockade. These data suggest that serotonergic activation blocks PZQ action in vivo, while serotonergic antagonists phenocopy PZQ action. Importantly these studies identify the ergot alkaloid scaffold as a promising structural framework for designing potent agents targeting parasitic bioaminergic G protein coupled receptors. PMID:26367744

  5. Activities of naphthylisoquinoline alkaloids and synthetic analogs against Leishmania major.

    PubMed

    Ponte-Sucre, Alicia; Faber, Johan H; Gulder, Tanja; Kajahn, Inga; Pedersen, Sarah E H; Schultheis, Martina; Bringmann, Gerhard; Moll, Heidrun

    2007-01-01

    The current treatments for leishmaniasis are unsatisfactory due to their toxic side effects, high costs, and increasing problems with drug resistance. Thus, there is an urgent need for alternative drugs against leishmaniasis. Different approaches have been used to identify novel pharmacophores against Leishmania sp. parasites, and one strategy has been the analysis of naturally occurring plant-derived compounds, including naphthylisoquinoline alkaloids. In the present study, we examined the abilities of these alkaloids to inhibit the growth of Leishmania major promastigotes and evaluated their effects on macrophages, dendritic cells, and fibroblasts. Furthermore, we determined the efficacy of selected compounds in decreasing the infection rate of macrophages and regulating their production of cytokines and nitric oxide. Our results demonstrate that the naphthylisoquinoline alkaloids ancistrocladiniums A and B (compounds 10 and 11) and the synthetic isoquinolinium salt (compound 14) were effective against intracellular amastigotes in the low submicromolar range, while toxicity against mammalian cells was observed at concentrations that were significantly higher than those needed to impair parasite replication. The activities of compounds 11 and 14 were mainly directed against the amastigote stage of L. major. This effect was not associated with the stimulation of host macrophages to produce nitric oxide or secrete cytokines relevant for the leishmanicidal function. In conclusion, our data suggest that ancistrocladiniums A and B (compounds 10 and 11) and the synthetically prepared isoquinolinium salt (compound 14) are promising candidates to be considered as lead compounds for leishmanicidal drugs. PMID:17088484

  6. Lysine Decarboxylase Catalyzes the First Step of Quinolizidine Alkaloid Biosynthesis and Coevolved with Alkaloid Production in Leguminosae[W][OA

    PubMed Central

    Bunsupa, Somnuk; Katayama, Kae; Ikeura, Emi; Oikawa, Akira; Toyooka, Kiminori; Saito, Kazuki; Yamazaki, Mami

    2012-01-01

    Lysine decarboxylase (LDC) catalyzes the first-step in the biosynthetic pathway of quinolizidine alkaloids (QAs), which form a distinct, large family of plant alkaloids. A cDNA of lysine/ornithine decarboxylase (L/ODC) was isolated by differential transcript screening in QA-producing and nonproducing cultivars of Lupinus angustifolius. We also obtained L/ODC cDNAs from four other QA-producing plants, Sophora flavescens, Echinosophora koreensis, Thermopsis chinensis, and Baptisia australis. These L/ODCs form a phylogenetically distinct subclade in the family of plant ornithine decarboxylases. Recombinant L/ODCs from QA-producing plants preferentially or equally catalyzed the decarboxylation of l-lysine and l-ornithine. L. angustifolius L/ODC (La-L/ODC) was found to be localized in chloroplasts, as suggested by the transient expression of a fusion protein of La-L/ODC fused to the N terminus of green fluorescent protein in Arabidopsis thaliana. Transgenic tobacco (Nicotiana tabacum) suspension cells and hairy roots produced enhanced levels of cadaverine-derived alkaloids, and transgenic Arabidopsis plants expressing (La-L/ODC) produced enhanced levels of cadaverine, indicating the involvement of this enzyme in lysine decarboxylation to form cadaverine. Site-directed mutagenesis and protein modeling studies revealed a structural basis for preferential LDC activity, suggesting an evolutionary implication of L/ODC in the QA-producing plants. PMID:22415272

  7. Dehydropyrrolizidine alkaloids in two Cryptantha species: Including two new open chain diesters one of which is amphoteric

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A livestock poisoning outbreak near Kingman, Arizona, USA, potentially linked to dehydropyrrolizidine alkaloids, prompted an evaluation of some local plants for the presence of these hepatotoxic alkaloids. Two species of Cryptantha, a Boraginaceous genus previously shown to produce potentially toxic...

  8. Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the Clavicipitaceae reveals dynamics of alkaloid loci

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The fungal family Clavicipitaceae includes plant symbionts and pathogens that produce neurotropic alkaloids with diverse effects on vertebrate and invertebrate animals. For example, ergot alkaloids are historically linked to mass poisonings (St. Anthony's fire) and sociological effects such as the ...

  9. Analysis of Alkaloids from Physalis peruviana by Capillary GC, Capillary GC-MS, and GC-FTIR.

    PubMed

    Kubwabo, C; Rollmann, B; Tilquin, B

    1993-04-01

    The alkaloid composition of the aerial parts and roots of PHYSALIS PERUVIANA was analysed by capillary GC (GC (2)), GC (2)-MS and GC (2)-FTIR. Eight alkaloids were identified, three of those alkaloids are 3beta-acetoxytropane and two N-methylpyrrolidinylhygrine isomers, which were not previously found in the genus PHYSALIS. A reproduction of the identification of alkaloids detected in the plant by the use of retention indices has been proposed. PMID:17230349

  10. YEAR TO YEAR VARIATION IN ALKALOID CONCENTRATION IN LUPINUS LEUCOPHYLLUS GROWING ON THE SCABLANDS OF CENTRAL WASHINGTON

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There was substantial year to year variation in total alkaloid concentration of lupines at all sites. Total alkaloid concentration over the 5 year period varied from two-fold to eight-fold at the individual sites. In any one year the change-trend in total alkaloid concentration was the same at eac...

  11. [Isolation of the ergot (Claviceps purpurea (Fr.) Tul., strain VKM-F-366D), producing the lactamic alkaloid ergocornam].

    PubMed

    Komarova, E L; Shain, S S; She?chenko, V I

    2002-01-01

    A new ergot strain VKM-F-3662D producing lactamic alkaloid ergocornam with concomitant alkaloids valinamide and ergometrine was isolated during selective works with sclerotium MS-462, which was obtained from ergocryptine ergot strain VKM-F-2642D. The structure of these alkaloids was determined by 1H and 13C NMR. PMID:12449796

  12. Time-dependent inhibitors of trypanothione reductase: Analogues of the spermidine alkaloid lunarine and related natural products

    E-print Network

    Schnaufer, Achim

    Time-dependent inhibitors of trypanothione reductase: Analogues of the spermidine alkaloid lunarine November 2005 Available online 21 November 2005 Abstract--The macrocyclic spermidine alkaloid lunarine 1 molecules related to 1 and the alkaloid itself have been synthesized in racemic form and evaluated against

  13. Very Short and Efficient Syntheses of the Spermine Alkaloid Kukoamine A and Analogs Using Isolable Succinimidyl Cinnamates

    E-print Network

    Schnaufer, Achim

    Very Short and Efficient Syntheses of the Spermine Alkaloid Kukoamine A and Analogs Using Isolable yields of the spermine alkaloid kukoamine A and analogs suita- ble for structure-activity relationship-hydroxysuccini- mide in the presence of N,N0 -dicyclohexylcarbodiimide. Kukoamine A (KukA, 1a), a spermine alkaloid

  14. Guanidine alkaloid analogs as inhibitors of HIV-1 Nef interactions with p53, actin, and p56lck

    E-print Network

    Weiss, Gregory A.

    Guanidine alkaloid analogs as inhibitors of HIV-1 Nef interactions with p53, actin, and p56lck-3 were used to identify a series of guanidine alkaloid-based inhibi- tors of Nef interactions with p53 efficacy of Nef inhibitors. Nef inhibition by the gua- nidine alkaloid congeners reported here could

  15. 1800 J. Org. Chem. 1995,60,1800-1805 Efficient Syntheses of the Marine Alkaloids Makaluvamine D and

    E-print Network

    Culpepper, J. Shane

    1800 J. Org. Chem. 1995,60,1800-1805 Efficient Syntheses of the Marine Alkaloids Makaluvamine D of the biologically active pyrrolo[4,3,2-del- quinoline marine alkaloids discorhabdin C (1)and makaluvamine D (3 is the structurally varied group of alkaloids containing the pyrrolo[4,3,2- delquinoline nucleus. These include

  16. Chapter 2--Progress toward the Total Synthesis of Scandine and the Melodinus Alkaloids 191 Progress toward the Total Synthesis of

    E-print Network

    Stoltz, Brian M.

    Chapter 2--Progress toward the Total Synthesis of Scandine and the Melodinus Alkaloids 191 CHAPTER 2 Progress toward the Total Synthesis of Scandine and the Melodinus Alkaloids 2.1 INTRODUCTION AND SYNTHETIC STRATEGY 2.1.1 INTRODUCTION The Melodinus alkaloids are a family of dihydroquinolinone natural

  17. Variation in pyrrolizidine alkaloid patterns of Senecio jacobaea Mirka Macel*, Klaas Vrieling, Peter G.L. Klinkhamer

    E-print Network

    Klinkhamer, Peter

    Variation in pyrrolizidine alkaloid patterns of Senecio jacobaea Mirka Macel*, Klaas Vrieling the variation in pyrrolizidine alkaloid (PA) patterns of lab-grown vegetative plants of 11 European Senecio alkaloids; Chemotypes; Jacobine; Erucifoline 1. Introduction Plants from the genus Senecio (Asteraceae

  18. Efficient strategy for the stereoselective synthesis of 2,3-disubstituted benzo[a]quinolizidine alkaloids: concise synthesis

    E-print Network

    Suh, Young-Ger

    [a]quinolizidine alkaloids: concise synthesis of (À)-protoemetinol Hyunyoung Moon a , Hongchan An a , Jaehoon Sim a , Kyeojin 2014 Keywords: (À)-Protoemetinol Benzo[a]quinolizidine alkaloid Cross metathesis Aza reserved. Benzo[a]quinolizidine alkaloids,1 which are mainly isolated from the two different families

  19. vol. 156, no. 1 the american naturalist july 2000 Alkaloid Uptake Increases Fitness in a Hemiparasitic Plant via

    E-print Network

    vol. 156, no. 1 the american naturalist july 2000 Alkaloid Uptake Increases Fitness on herbivores and pollinators in the field. Here, I show that the uptake of alkaloids in the annual hemiparasite, and increased lifetime seed production. These results indicate that resistance traits such as alkaloids can

  20. Transfer of quinolizidine alkaloids from hosts to hemiparasites in two Castilleja-Lupinus associations: analysis of floral and vegetative tissues.

    PubMed

    Adler, L S.; Wink, M

    2001-06-01

    Many hemiparasites, including several members of the Castilleja genus (Scrophulariaceae), obtain secondary compounds from their host plants. Both Castilleja miniata in subalpine Colorado and C. indivisa in central Texas have reduced herbivory when obtaining alkaloids from the hosts Lupinus argenteus and L. texensis (Fabaceae), respectively. However, pollinators were not deterred from visiting Castilleja parasitizing alkaloid-containing hosts. To determine if alkaloids are present in all tissues of plants parasitizing lupins, we analyzed floral tissue as well as leaves of both Castilleja species. Leaves, bracts, calices, corollas, gynoecium and nectar of both Castilleja species were examined for quinolizidine alkaloid presence using a Dragendorff reagent, and alkaloids were identified in vegetative tissue and nectar by capillary GLC and GLC-MS. Lupanine and alpha-isolupanine were the principal alkaloids in C. indivisa parasitizing L. texensis, while principal alkaloids of C. miniata parasitizing L. argenteus were 5,6-iso-dehydrolupanine, alpha-isolupanine, thermopsine, and 17-oxolupanine. Except for 17-oxolupanine, which was probably synthesized by biotransformation in the parasite, all other alkaloids correspond to those present in the host plants. Alkaloids were present in the leaves of both Castilleja species, and in the bracts, calices and gynoecium of some plants, but never in the corollas. Alkaloids from L. texensis and L. argenteus were not detected in nectar of either Castilleja species. The presence of alkaloids in leaves and outer floral tissue of both Castilleja species, but not nectar, may explain why alkaloid uptake and storage affected herbivores but not pollinators. PMID:11336806

  1. Dietary exposure to ergot alkaloids decreases contractility of bovine mesenteric vasculature

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ergot alkaloids are hypothesized to cause vasoconstriction in the midgut, and prior exposure may affect the vasoactivity of these compounds. The objectives of this study were to profile vasoactivity of ergot alkaloids in bovine mesenteric artery (MA) and vein (MV) and determine if previous exposure ...

  2. Toxic alkaloid concentrations in Delphinium nuttallianum, D. andersonii, and D. geyeri in the Intermountain region

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Low larkspurs (Delphinium nuttalliunum, D. andersonii) and plains larkspur (D. geyeri) are serious poisoning threats to cattle grazing on western North American rangelands. The dominant toxic alkaloid in low larkspurs and plains larkspur is methyllycaconitine (MLA); another very toxic alkaloid in lo...

  3. Identification of the Polyketide Biosynthetic Machinery for the Indolizidine Alkaloid Cyclizidine.

    PubMed

    Huang, Wei; Kim, Seong Jong; Liu, Joyce; Zhang, Wenjun

    2015-11-01

    The cyclizidine biosynthetic gene cluster was identified from Streptomyces NCIB 11649, which revealed the polyketide biosynthetic machinery for cyclizidine alkaloid biosynthesis. Both in vivo mutagenesis study and in vitro biochemical analysis provided insight into the timing and mechanism of the biosynthetic enzymes that produce cyclizidine-type indolizidine alkaloids. PMID:26473429

  4. DISTRIBUTION OF NORDITERPENE ALKALOIDS IN TALL LARKSPUR PLANT PARTS THROUGH THE GROWING SEASON

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous research showed toxic and total alkaloid pools in tall larkspur (Delphinium barbeyi) increased during early growth then declined precipitously during the late flower and pod stage of growth. The objective of this study was to measure the concentration and pools of toxic and total alkaloids...

  5. Synthesis and antiproliferativeactivity of new vinca alkaloids containing an ?,?-unsaturated aromatic side chain.

    PubMed

    Ngo, Quoc Anh; Nguyen, Le Anh; Vo, Ngoc Binh; Nguyen, Thuy Hang; Roussi, Fanny; Nguyen, The Hung; Nguyen, Van Tuyen

    2015-12-01

    A new series of vinca-alkaloids derivatives containing various ?,?-unsaturated aromatic side chains was synthesized. Four new vinca-alkaloids derivatives showed selective cytotoxicities against KB tumor cell lines with IC50 value below 0.1?M, thus comparable with vinblastine. PMID:26522953

  6. Cyclic enaminones. Part II: applications as versatile intermediates in alkaloid synthesis.

    PubMed

    Chattopadhyay, Amit Kumar; Hanessian, Stephen

    2015-11-01

    Among many other strategies, the enaminone approach is an important strategy to construct and diversify the azacyclic core in various alkaloids syntheses. In this brief review we discuss the application of cyclic enaminones as building blocks, as well as potential intermediates in the total synthesis of selected alkaloids. PMID:26490499

  7. Alkaloid profiles, concentration, and pools in velvet lupine (Lupinus leucophyllus) over the growing season.

    PubMed

    Lee, Stephen T; Ralphs, Michael H; Panter, Kip E; Cook, Daniel; Gardner, Dale R

    2007-01-01

    Lupinus leucophyllus is one of many lupine species known to contain toxic and/or teratogenic alkaloids that can cause congenital birth defects. The concentrations of total alkaloids and the individual major alkaloids were measured in three different years from different plant parts over the phenological development of the plant. All of the alkaloids were found in the different plant tissues throughout the growing season, although their levels varied in different tissues. Concentrations of total alkaloids and the individual alkaloids varied on an annual basis and in their distribution in the different tissues. Anagyrine levels were highest in the floral tissue, lupanine and unknown F accumulated to the greatest level in the vegetative tissue, and 5,6-dehydrolupanine accumulated to the highest level in the stem. These alkaloids appear to be in a metabolically active state with the teratogenic alkaloid anagyrine accumulating to its highest level in the developing seed. The latter is, thus, the phenological stage posing the greatest danger to grazing livestock. PMID:17146716

  8. Livestock Poisoning with Pyrrolizidine Alkaloid Containing Plants (Senecio, Crotalaria, Cynoglossum, Amsinckia, Heliotropium and Echium spp.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pyrrolizidine alkaloids (PAs) are potent liver toxins that have been identified in over 6,000 plants throughout the world. Alkaloids are nitrogen-based compounds with potent biological activity. About half of the identified PAs are toxic and several cause cancer (carcinogenic). PA-containing plants...

  9. Dimerization of (+)-Myrmicarin 215B. A Potential Biomimetic Approach to Complex Myrmicarin Alkaloids

    PubMed Central

    Ondrus, Alison E.; Movassaghi, Mohammad

    2009-01-01

    The acid promoted diastereoselective dimerization of myrmicarin 215B is described. The reactivity of these sensitive alkaloids, structural assignment, and a possible mechanism for the observed dimerization are discussed. These finding raise the intriguing possibility of the synthesis of the highly sensitive myrmicarin alkaloids based on a strategy involving the direct dimerization of functional tricyclic myrmicarin derivatives. PMID:20640170

  10. Heterozygous P53 knockout mouse model for dehydropyrrolizidine alkaloid-induced carcinogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dehydropyrrolizidine alkaloids are a large, structurally diverse group of plant-derived protoxins that are potentially carcinogenic. With worldwide significance, these alkaloids can contaminate or be naturally present in the human food supply. To develop a small animal model that may be used to com...

  11. THE DETECTION AND ESTIMATION OF PYRROLIZIDINE ALKALOIDS IN PLANTS AND FEEDS USING AN ELISA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pyrrolizidine alkaloid-containing plants are found throughout the world and are common in the genus Senecio. Many pyrrolizidine alkaloids are toxic and cause poisoning in livestock and in humans (Bull et al., 1968; Johnson et al., 1989; Mattocks, 1986; Prakash et al., 1999; Stegelmeier et al., 1999...

  12. The toxicity of Poison Dart Frog alkaloids against the Fire Ant (Solenopsis invicta)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hundreds of alkaloids, representing over 20 structural classes, have been identified from the skin of neotropical poison frogs (Dendrobatidae). These alkaloids are derived from arthropod prey of the frogs, and are generally are believed to deter vertebrate predators. We developed a method to put ind...

  13. Effect of Feeding Fescue Seed Containing Ergot Alkaloid Toxins on Stallion Spermatogenesis and Sperm Cells

    PubMed Central

    Fayrer-Hosken, R; Stanley, A; Hill, N; Heusner, G; Christian, M; Fuente, R De La; Baumann, C; Jones, L

    2012-01-01

    Contents The cellular effects of tall fescue grass–associated toxic ergot alkaloids on stallion sperm and colt testicular tissue were evaluated. This was a continuation of an initial experiment where the effects of toxic ergot alkaloids on the stallion spermiogram were investigated. The only spermiogram parameter in exposed stallions that was affected by the toxic ergot alkaloids was a decreased gel-free volume of the ejaculate. This study examined the effect of toxic ergot alkaloids on chilling and freezing of the stallion sperm cells. The effect of toxic ergot alkaloids on chilled extended sperm cells for 48 h at 5 °C was to make the sperm cells less likely to undergo a calcium ionophore–induced acrosome reaction. The toxic ergot alkaloids had no effect on the freezability of sperm cells. However, if yearling colts were fed toxic ergot alkaloids, then the cytological analysis of meiotic chromosome synapsis revealed a significant increase in the proportion of pachytene spermatocytes showing unpaired sex chromosomes compared to control spermatocytes. There was little effect of ergot alkaloids on adult stallions, but there might be a significant effect on yearling colts. PMID:22524585

  14. Cytotoxic effects of ?-carboline alkaloids on human gastric cancer SGC-7901 cells

    PubMed Central

    Fan, Yuxiang; Patima, Abulimiti; Chen, Yu; Zeng, Fanye; He, Wenting; Luo, Lingjuan; Jie, Yanghua; Zhu, Yanhua; Zhang, Liping; Lei, Jun; Xie, Xinmei; Zhang, Hongliang

    2015-01-01

    To investigate the cytotoxic effects of ?-carboline alkaloids on human gastric cancer SGC-7901 cells. Human gastric cancer SGC-790s1 cells were treated with ?-carboline alkaloids at the concentration of 0, 10, 20, 30 and 40 ?g/ml for 48 hr. Cell viability was measured by Cell Counting Kit-8 assay. Cell apoptosis was detected by Hoechst 33258 staining and DNA fragmentation analysis. The expression of phosphatase and tensin homolog (PTEN) and extracellular signal-regulated kinase (ERK) was examined by quantitative real-time PCR (qRT-PCR) assay and western blot analysis. ?-carboline alkaloids inhibited the growth of SGC-7901 cells concentration dependently. ?-carboline alkaloids treated SGC-7901 cells displayed apoptotic nuclei as detected using Hoechst 33258 staining. ?-carboline alkaloids also induced DNA ladder, indicative of apoptosis in SGC-7901 cells concentration-dependently. Furthermore, ?-carboline alkaloids increased PTEN and decreased ERK mRNA expression in SGC-7901 cells in a concentration dependent manner. They also increased PTEN and decreased ERK protein expression. ?-carboline alkaloids inhibit the growth and induce apoptosis of SGC-7901 cells. The cytotoxic effects of ?-carboline alkaloids might correlate with increased PTEN expression and decreased ERK expression in SGC-7901 cells. PMID:26550217

  15. Role of the LolP Cytochrome P450 Monooxygenase in Loline Alkaloid Biosynthesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The insecticidal loline alkaloids, produced by Neotyphodium uncinatum and related endophytes, are exo-1-aminopyrrolizidines with an ether bridge between C-2 and C-7. Loline alkaloids vary in methyl, acetyl, and formyl substituents on the 1-amine, which affect their biological activity. Enzymes for k...

  16. Poor permeability and absorption affect the activity of four alkaloids from Coptis.

    PubMed

    Cui, Han-Ming; Zhang, Qiu-Yan; Wang, Jia-Long; Chen, Jian-Long; Zhang, Yu-Ling; Tong, Xiao-Lin

    2015-11-01

    Coptidis rhizoma (Coptis) and its alkaloids exert various pharmacological functions in cells and tissues; however, the oral absorption of these alkaloids requires further elucidation. The present study aimed to examine the mechanism underlying the poor absorption of alkaloids, including berberine (BER), coptisine (COP), palmatine (PAL) and jatrorrhizine (JAT). An ultra?performance liquid chromatography (UPLC) method was validated for the determination of BER, COP, PAL and JAT in the above experimental medium. In addition, the apparent oil?water partition coefficient (Po/w); apparent permeability coefficient (Papp), determined using a parallel artificial membrane permeability assay (PAMPA) plate; membrane retention coefficient (R %); and effect of P?glycoprotein (P?gp) inhibitor on the Papp of the four alkaloids were investigated. The intestinal absorption rate constant (Ka) and absorption percentage (A %) of the four alkaloids were also determined. The results of the present study demonstrated that the Po/w of the four alkaloids in 0.1 mol·l?1 HCl medium was significantly higher (P<0.01), compared with those of the alkaloids in phosphate buffer (pH 7.4). The Papp of BER was 1.0?1.2x10?6 cm·s?1, determined using a PAMPA plate, and the Papp of BER, COP, PAL and JAT decreased sequentially. The concentrations of the four alkaloids on the apical?to?basolateral (AP?BL) surface and the basolateral?to?apical (BL?AP) surface increased in a linear manner, with increasing concentrations between 10 and 100 µmol. In addition, the transportation of BER on the BL?AP surface was significantly faster (P<0.01), compared with that on the AP?BL surface and, following the addition of verpamil (a P?gp inhibitor), the Papp (AP?BL) of the four alkaloids increased, whereas the Papp (BL?AP) was significantly decreased (P<0.01). The rat intestinal perfusion experiment demonstrated that the four alkaloids were poorly absorbed; however, the Ka of BER was significantly higher, compared with the three other alkaloids. Furthermore, the A % and Ka provided evidence that the absorption of BER was increased in the jejunum, compared with in the ileum. In conclusion, the four alkaloids from Coptis appeared to be poorly absorbed, determined using a shake flask, pre?coated PAMPA plates, a Caco?2 cell monolayer model and intestinal perfusion; however, absorption was higher in the jejunum than in the ileum. Among the four alkaloids, the permeability of BER was markedly higher than the others, and P?gp efflux had a significant effect on the absorption of those alkaloids. PMID:26352530

  17. Alteration of the alkaloid profile in genetically modified tobacco reveals a role of methylenetetrahydrofolate reductase in nicotine N-demethylation.

    PubMed

    Hung, Chiu-Yueh; Fan, Longjiang; Kittur, Farooqahmed S; Sun, Kehan; Qiu, Jie; Tang, She; Holliday, Bronwyn M; Xiao, Bingguang; Burkey, Kent O; Bush, Lowell P; Conkling, Mark A; Roje, Sanja; Xie, Jiahua

    2013-02-01

    Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of the tetrahydrofolate (THF)-mediated one-carbon (C1) metabolic network. This enzyme catalyzes the reduction of 5,10-methylene-THF to 5-methyl-THF. The latter donates its methyl group to homocysteine, forming methionine, which is then used for the synthesis of S-adenosyl-methionine, a universal methyl donor for numerous methylation reactions, to produce primary and secondary metabolites. Here, we demonstrate that manipulating tobacco (Nicotiana tabacum) MTHFR gene (NtMTHFR1) expression dramatically alters the alkaloid profile in transgenic tobacco plants by negatively regulating the expression of a secondary metabolic pathway nicotine N-demethylase gene, CYP82E4. Quantitative real-time polymerase chain reaction and alkaloid analyses revealed that reducing NtMTHFR expression by RNA interference dramatically induced CYP82E4 expression, resulting in higher nicotine-to-nornicotine conversion rates. Conversely, overexpressing NtMTHFR1 suppressed CYP82E4 expression, leading to lower nicotine-to-nornicotine conversion rates. However, the reduced expression of NtMTHFR did not affect the methionine and S-adenosyl-methionine levels in the knockdown lines. Our finding reveals a new regulatory role of NtMTHFR1 in nicotine N-demethylation and suggests that the negative regulation of CYP82E4 expression may serve to recruit methyl groups from nicotine into the C1 pool under C1-deficient conditions. PMID:23221678

  18. Effects of tryptophan derivatives and ?-carboline alkaloids on radiation- and peroxide-induced transformations of ethanol

    NASA Astrophysics Data System (ADS)

    Sverdlov, R. L.; Brinkevich, S. D.; Shadyro, O. I.

    2014-05-01

    The subject of this study was investigation of interactions of tryptophan and its derivatives, including structurally related ?-carboline alkaloids with oxygen- and carbon-centered radicals being formed during radiation- and peroxide-induced transformations of ethanol. It was shown that the above named compounds suppressed recombination and disproportionation reactions of ?-hydroxyethyl radicals. The inhibitory effects of tryptophan, 5-hydroxytryptophan and serotonin were mainly realized by means of reduction and addition reactions, while those of ?-carboline alkaloids - harmine, harmane and harmaline - were due to oxidation reactions. Melatonin displayed low reactivity towards ?-hydroxyethyl radicals. Tryptophan derivatives and ?-carboline alkaloids were found to inhibit radiation-induced oxidation of ethanol while being virtually not used up. The low transformation yields of tryptophan, 5-hydroxytryptophan and serotonin, as well as ?-carboline alkaloids, indicate their capability of regeneration, which could occur on interaction of tryptophan with ?-2 and ??2, or on oxidation of ?-hydroxyethyl radicals by ?-carboline alkaloids.

  19. Cytotoxic Indole Alkaloids against Human Leukemia Cell Lines from the Toxic Plant Peganum harmala.

    PubMed

    Wang, Chunhua; Zhang, Zhenxue; Wang, Yihai; He, Xiangjiu

    2015-01-01

    Bioactivity-guided fractionation was used to determine the cytotoxic alkaloids from the toxic plant Peganum harmala. Two novel indole alkaloids, together with ten known ones, were isolated and identified. The novel alkaloids were elucidated to be 2-(indol-3-yl)ethyl-?-L-rhamnopyranosyl-(1 ? 6)-?-D-glucopyranoside (2) and 3-hydroxy-3-(N-acetyl-2-aminoethyl)-6-methoxyindol-2-one (3). The cytotoxicity against human leukemia cells was assayed for the alkaloids and some of them showed potent activity. Harmalacidine (compound 8, HMC) exhibited the highest cytotoxicity against U-937 cells with IC50 value of 3.1 ± 0.2 ?mol/L. The cytotoxic mechanism of HMC was targeting the mitochondrial and protein tyrosine kinase signaling pathways (PTKs-Ras/Raf/ERK). The results strongly demonstrated that the alkaloids from Peganum harmala could be a promising candidate for the therapy of leukemia. PMID:26540074

  20. The serum concentrations of lupine alkaloids in orally-dosed Holstein cattle.

    PubMed

    Green, Benedict T; Lee, Stephen T; Welch, Kevin D; Gardner, Dale R; Stegelmeier, Bryan L; Davis, T Zane

    2015-06-01

    Teratogenic alkaloid-containing Lupinus spp. cause congenital defects known as crooked calf disease that is periodically economically devastating for the cattle industry. Previous research indicates that cattle breeds may eliminate plant toxins differently, potentially altering their susceptibility. The objective of this study was to describe the toxicokinetics in Holsteins of anagyrine, the teratogenic lupine alkaloid that produces crooked calf disease. Other alkaloids including lupanine, an unidentified alkaloid and 5,6-dehydrolupanine were also evaluated. Dried ground Lupinus leucophyllus was orally dosed to four Holstein steers and blood samples were collected for 96?h, analyzed for serum alkaloid concentrations and toxicokinetic parameters calculated. The serum elimination of anagyrine in Holstein steers was faster than those reported for beef breeds. This suggests that Holsteins may be less susceptible to lupine-induced crooked calf disease. Additional work is needed to confirm these findings and to verify if there is a breed difference in disease incidence or severity. PMID:25912242

  1. Antimicrobial activity of extracts and isoquinoline alkaloids of selected papaveraceae plants.

    PubMed

    Opletal, Lubomír; Lo?árek, Miroslav; Fra?ková, Adéla; Chlebek, Jakub; Smíd, Jakub; Hošt'álková, Anna; Safratová, Marcela; Hulcová, Daniela; Klou?ek, Pavel; Rozkot, Miroslav; Cahlíková, Lucie

    2014-12-01

    Alkaloidal extracts of seven selected plants of the family Papaveraceae were studied with respect to their activity against six strains of pathogenic bacteria and their alkaloidal fingerprint. Twenty-four alkaloids were determined by GC/MS, and twenty of them identified from their mass spectra, retention times and retention indexes. In the antibacterial assay, three Gram-positive (Enterorococcus faecalis, Staphylococcus aureus and S. hyicus), and three Gram-negative (Escherichia coli, Proteus mirabilis and Pseudomonas aeruginosa) strains were used. The most promising antimicrobial activity was shown by the alkaloidal extract of Macleaya cordata with MIC values of 16 ?g/mL for Staphylococcus aureus, 32 ?g/mL for Enterococcus faecalis and 64 ?g/mL for Staphylococcus hyicus and Escherichia coli. All the tested pure isoquinoline alkaloids were considered inactive within the tested concentrations. PMID:25632464

  2. (-)-Amarbellisine, a lycorine-type alkaloid from Amaryllis belladonna L. growing in Egypt.

    PubMed

    Evidente, Antonio; Andolfi, Anna; Abou-Donia, Amina H; Touema, Soad M; Hammoda, Hala M; Shawky, Eman; Motta, Andrea

    2004-07-01

    A new lycorine-type alkaloid, named (-)-amarbellisine, was isolated from the bulbs of Egyptian Amaryllis belladonna L. together with the well known alkaloids (-)-lycorine, (-)-pancracine, (+)-vittatine, (+)-11-hydroxyvittatine, and (+)-hippeastrine. The new alkaloid, containing the pyrrolo[de]phenanthridine ring system, was essentially characterised by spectroscopic and optical methods, and proved to be the 2-methoxy-3a,4,5,7,11b,11c-hexahydro-1H-[1,3]dioxolo[4,5-j]pyrrolo[3,2,1-de]phenanthridinol. By using HPTLC technique we also carried out a comparative study of the relative and total alkaloidal content at two different stages of plant growth. Finally, the antimicrobial activity of the isolated alkaloids was assayed. PMID:15279981

  3. Cytotoxic Indole Alkaloids against Human Leukemia Cell Lines from the Toxic Plant Peganum harmala

    PubMed Central

    Wang, Chunhua; Zhang, Zhenxue; Wang, Yihai; He, Xiangjiu

    2015-01-01

    Bioactivity-guided fractionation was used to determine the cytotoxic alkaloids from the toxic plant Peganum harmala. Two novel indole alkaloids, together with ten known ones, were isolated and identified. The novel alkaloids were elucidated to be 2-(indol-3-yl)ethyl-?-l-rhamnopyranosyl-(1 ? 6)-?-d-glucopyranoside (2) and 3-hydroxy-3-(N-acetyl-2-aminoethyl)-6-methoxyindol-2-one (3). The cytotoxicity against human leukemia cells was assayed for the alkaloids and some of them showed potent activity. Harmalacidine (compound 8, HMC) exhibited the highest cytotoxicity against U-937 cells with IC50 value of 3.1 ± 0.2 ?mol/L. The cytotoxic mechanism of HMC was targeting the mitochondrial and protein tyrosine kinase signaling pathways (PTKs-Ras/Raf/ERK). The results strongly demonstrated that the alkaloids from Peganum harmala could be a promising candidate for the therapy of leukemia. PMID:26540074

  4. Alkaloid profile of leaves and seeds of Lupinus hintonii C. P. Smith.

    PubMed

    Torres, Kalina Bermúdez; Quintos, Norma Robledo; Necha, Laura L Barrera; Wink, Michael

    2002-01-01

    L. hintonii C. P. Smith grows in the Central Highland forests of Mexico at altitudes between 2800 m to 3200 m above see level. Members of the genus Lupinus produce quinolizidine alkaloids as main chemical defensive compounds against herbivores. Surprisingly alkaloid profiles are rather constant within this species, while substantial variation was found when compared to morphologically closely related other taxa. As part of a phytochemical project on Mexican wild lupins, we report on the alkaloid profiles of seeds and leaves of L. hintonii. 19 alkaloids could be identified by capillary GLC-MS. Six major alkaloids occurred in leaves and seeds: 13-hydroxylupanine (28% and 45% respectively), tetrahydrorhombifoline (31% and 23% respectively), angustifoline (2% and 4% respectively), lupanine (7% and 5% respectively), 13alpha-tigloyloxylupanine (19% and 5% respectively) and 4alpha-angeloyl-3beta-hydroxylupanine (9% and 2%). This chemical pattern resembles that of the North American lupin L. floribundus. PMID:12064721

  5. Biogenetically-Inspired Total Synthesis of Epidithiodiketopiperazines and Related Alkaloids

    PubMed Central

    2015-01-01

    Conspectus Natural products chemistry has historically been the prime arena for the discovery of new chemical transformations and the fountain of insights into key biological processes. It remains a fervent incubator of progress in the fields of chemistry and biology and an exchange mediating the flow of ideas between these allied fields of science. It is with this ethos that our group has taken an interest in and pursued the synthesis of a complex family of natural products termed the dimeric epipolythiodiketopiperazine (ETP) alkaloids. We present here an Account of the highly complex target molecules to which we pegged our ambitions, our systematic and relentless efforts toward those goals, the chemistry we developed in their pursuit, and the insight we have gained for their translational potential as potent anticancer molecules. The dimeric ETP alkaloids are fungal metabolites that feature a highly complex molecular architecture comprising a densely functionalized core structure with many stereogenic centers, six of which are fully substituted, and a pair of vicinal quaternary carbon stereocenters, decorated on polycyclic architectures in addition to the unique ETP motif that has been recognized as acid-, base-, and redox-sensitive. A cyclo-dipeptide consisting of an essential tryptophan residue and a highly variable ancillary amino acid lies at the core of these structures; investigation of the transformations that take this simplistic core to the complex alkaloids lies at the heart of our research program. The dimeric epidithiodiketopiperazine alkaloids have largely resisted synthesis on account of their complexity since the 1970s when the founding members of this class, chaetocin A (HauserD. et al. Helv. Chim. Acta1970, 53, 10615448218) and verticillin A (KatagiriK. et al. J. Antibiot.1970, 23, 4205465723), were first isolated. This was despite their potent cytotoxic and bacteriostatic activities, which were well appreciated at the time of their discovery. In the past decade, an increasing number of studies have uncovered powerful new biological processes that these molecules can uniquely effect, such as the inhibition of histone methyltransferases by chaetocin A (GreinerD. et al. Nat. Chem. Biol.2005, 1, 14316408017). In fact, the complete collection of hexahydropyrroloindoline alkaloids features a diverse range of potent biological properties including cytotoxic, antitumor, antileukemic, antiviral, antibiotic, and antinematodal activities (JiangC.-S.; GuoY.-W.Mini-Rev. Med. Chem.2011, 11, 72821651467). This mélange of activities is reflective of their structural diversity. Under the precepts of retrobiosynthetic analysis, we have accomplished the syntheses of more than a dozen natural products, including members of the bionectin, calycanthaceous, chaetocin, gliocladin, naseseazine, and verticillin alkaloids. More importantly, these molecules have acted as venerable venues for the development of new strategies to address structural challenges including, but not limited to, C3–C3? vicinal quaternary centers, heterodimeric linkages, C3–Csp2 linkages, diketopiperazine oxidation, stereoselective thiolation, homologue-specific polysulfidation, and C12-hydroxyl incorporation. Synthesis of these natural products has resulted in the structural confirmation, and sometimes revision such as the case of (+)-naseseazines A and B, as well as access to many plausible biogenetically relevant intermediates and new synthetic ETP derivatives. Furthermore, our studies have paved the way for the formulation of a comprehensive SAR profile and the identification of lead compounds with in vitro subnanomolar IC50’s against a broad range of cancer types. PMID:25843276

  6. Tall fescue seed extraction and partial purification of ergot alkaloids

    NASA Astrophysics Data System (ADS)

    Bush, Lowell

    2014-12-01

    Many substances in the tall fescue/endophyte association (Schedonorus arundinaceus/Epichloë coenophiala) have biological activity. Of these compounds only the ergot alkaloids are known to have significant mammalian toxicity and the predominant ergot alkaloids are ergovaline and ergovalinine. Because synthetically produced ergovaline is difficult to obtain, we developed a seed extraction and partial purification protocol for ergovaline/ergovalinine that provided a biologically active product. Tall fescue seed was ground and packed into several different sized columns for liquid extraction. Smaller particle size and increased extraction time increased efficiency of extraction. Our largest column was a 114 × 52 × 61 cm (W×L×D) stainless steel tub. Approximately 150 kg of seed could be extracted in this tub. The extraction was done with 80% ethanol. When the solvent front migrated to bottom of the column, flow was stopped and seed was allowed to steep for at least 48 h. Light was excluded from the solvent from the beginning of this step to the end of the purification process. Following elution, ethanol was removed from the eluate by evaporation at room temperature. Resulting syrup was freeze-dried. About 80% recovery of alkaloids was achieved with 18-fold increase in concentration of ergovaline. Initial purification of the dried product was accomplished by extracting with hexane/water (6:1, v/v) and the hexane fraction was discarded. The aqueous fraction was extracted with chloroform, the aqueous layer discarded, after which the chloroform was removed with a resulting 20-fold increase of ergovaline. About 65% of the ergovaline was recovered from the chloroform residue for an overall recovery of 50%. The resultant partially purified ergovaline had biological activities in in vivo and in vitro bovine bioassays that approximate that of synthetic ergovaline.

  7. Tyrosine aminotransferase contributes to benzylisoquinoline alkaloid biosynthesis in opium poppy.

    PubMed

    Lee, Eun-Jeong; Facchini, Peter J

    2011-11-01

    Tyrosine aminotransferase (TyrAT) catalyzes the transamination of L-Tyr and ?-ketoglutarate, yielding 4-hydroxyphenylpyruvic acid and L-glutamate. The decarboxylation product of 4-hydroxyphenylpyruvic acid, 4-hydroxyphenylacetaldehyde, is a precursor to a large and diverse group of natural products known collectively as benzylisoquinoline alkaloids (BIAs). We have isolated and characterized a TyrAT cDNA from opium poppy (Papaver somniferum), which remains the only commercial source for several pharmaceutical BIAs, including codeine, morphine, and noscapine. TyrAT belongs to group I pyridoxal 5'-phosphate (PLP)-dependent enzymes wherein Schiff base formation occurs between PLP and a specific Lys residue. The amino acid sequence of TyrAT showed considerable homology to other putative plant TyrATs, although few of these have been functionally characterized. Purified, recombinant TyrAT displayed a molecular mass of approximately 46 kD and a substrate preference for L-Tyr and ?-ketoglutarate, with apparent K(m) values of 1.82 and 0.35 mm, respectively. No specific requirement for PLP was detected in vitro. Liquid chromatography-tandem mass spectrometry confirmed the conversion of L-Tyr to 4-hydroxyphenylpyruvate. TyrAT gene transcripts were most abundant in roots and stems of mature opium poppy plants. Virus-induced gene silencing was used to evaluate the contribution of TyrAT to BIA metabolism in opium poppy. TyrAT transcript levels were reduced by at least 80% in silenced plants compared with controls and showed a moderate reduction in total alkaloid content. The modest correlation between transcript levels and BIA accumulation in opium poppy supports a role for TyrAT in the generation of alkaloid precursors, but it also suggests the occurrence of other sources for 4-hydroxyphenylacetaldehyde. PMID:21949209

  8. Tall fescue seed extraction and partial purification of ergot alkaloids.

    PubMed

    Ji, Huihua; Fannin, F; Klotz, J; Bush, Lowell

    2014-01-01

    Many substances in the tall fescue/endophyte association (Schedonorus arundinaceus/Epichloë coenophiala) have biological activity. Of these compounds only the ergot alkaloids are known to have significant mammalian toxicity and the predominant ergot alkaloids are ergovaline and ergovalinine. Because synthetically produced ergovaline is difficult to obtain, we developed a seed extraction and partial purification protocol for ergovaline/ergovalinine that provided a biologically active product. Tall fescue seed was ground and packed into several different sized columns for liquid extraction. Smaller particle size and increased extraction time increased efficiency of extraction. Our largest column was a 114 × 52 × 61 cm (W × L × D) stainless steel tub. Approximately 150 kg of seed could be extracted in this tub. The extraction was done with 80% ethanol. When the solvent front migrated to bottom of the column, flow was stopped and seed was allowed to steep for at least 48 h. Light was excluded from the solvent from the beginning of this step to the end of the purification process. Following elution, ethanol was removed from the eluate by evaporation at room temperature and the resulting syrup was freeze-dried. About 80% recovery of alkaloids was achieved with 18-fold increase in concentration of ergovaline. Initial purification of the dried product was accomplished by extracting with hexane/water (6:1, v/v). The aqueous fraction was extracted with chloroform, the aqueous layer discarded, after which the chloroform was removed with a resulting 20-fold increase of ergovaline. About 65% of the ergovaline was recovered from the chloroform residue for an overall recovery of 50%. The resultant partially purified ergovaline had biological activities in in vivo and in vitro bovine bioassays that approximate that of synthetic ergovaline. PMID:25566528

  9. Unravelling the architecture and dynamics of tropane alkaloid biosynthesis pathways using metabolite correlation networks.

    PubMed

    Nguyen, Thi-Kieu-Oanh; Jamali, Arash; Lanoue, Arnaud; Gontier, Eric; Dauwe, Rebecca

    2015-08-01

    The tropane alkaloid spectrum in Solanaceae is highly variable within and between species. Little is known about the topology and the coordination of the biosynthetic pathways leading to the variety of tropine and pseudotropine derived esters in the alkaloid spectrum, or about the metabolic dynamics induced by tropane alkaloid biosynthesis stimulating conditions. A good understanding of the metabolism, including all ramifications, is however necessary for the development of strategies to increase the abundance of pharmacologically interesting compounds such as hyoscyamine and scopolamine. The present study explores the tropane alkaloid metabolic pathways in an untargeted approach involving a correlation-based network analysis. Using GC-MS metabolite profiling, the variation and co-variation among tropane alkaloids and primary metabolites was monitored in 60 Datura innoxia Mill. individuals, of which half were exposed to tropane alkaloid biosynthesis stimulating conditions by co-culture with Agrobacterium rhizogenes. Considerable variation was evident in the relative proportions of the tropane alkaloids. Remodeling of the tropane alkaloid spectrum under co-culture with A. rhizogenes involved a specific and strong increase of hyoscyamine production and revealed that the accumulation of hyoscyamine, 3-tigloyloxy-6,7-epoxytropane, and 3-methylbutyryloxytropane was controlled independently of the majority of tropane alkaloids. Based on correlations between metabolites, we propose a biosynthetic origin of hygrine, the order of esterification of certain di-oxygenated tropanes, and that the rate of acetoxylation contributes to control of hyoscyamine production. Overall, this study shows that the biosynthesis of tropane alkaloids may be far more complex and finely controlled than previously expected. PMID:25823585

  10. Curare Alkaloids: Constituents of a Matis Dart Poison.

    PubMed

    Malca Garcia, Gonzalo R; Hennig, Lothar; Shelukhina, Irina V; Kudryavtsev, Denis S; Bussmann, Rainer W; Tsetlin, Victor I; Giannis, Athanassios

    2015-11-25

    A phytochemical study of dart and arrow poison from the Matis tribe led to the identification of d-(-)-quinic acid, l-malic acid, ethyldimethylamine, magnoflorine, and five new bisbenzyltetrahydroisoquinoline alkaloids (BBIQAs), 1-5. d-Tubocurarine could not be identified among these products. BBIQA (3) contains a unique linkage at C-8 and C-11'. All structures were characterized by a combination of NMR and HRESIMS data. The effects of Matis poison and individual BBIQAs (1-3) on rat muscle nAChR expressed in Xenopus oocytes have been investigated using the two-electrode voltage clamp technique. PMID:26496427

  11. Bromotyrosine-derived alkaloids from the Caribbean sponge Aplysina lacunosa

    PubMed Central

    Göthel, Qun; Sirirak, Thanchanok

    2015-01-01

    Summary Three new bromotyrosine-derived alkaloids 14-debromo-11-deoxyfistularin-3 (1), aplysinin A (2), and aplysinin B (3), together with 15 known compounds (4–18) were isolated from the sponge Aplysina lacunosa collected from Stirrup Cay, Bahamas. The structures of the isolated compounds were identified on the basis of MS and NMR data analysis. The 13C NMR assignment of spirocyclohexadienylisoxazoline moieties of 1 and 2 were confirmed by an 1,1-ADEQUATE experiment. Compounds 1 and 2 showed a mild to moderate cytotoxic activities against KB-31 and FS4-LTM cell lines. Only aplysinin A (2) exhibited cytotoxicity against MCF-7 cells.

  12. Anti-Acetylcholinesterase Alkaloids from Annona glabra Leaf.

    PubMed

    Lee, Shoei-Sheng; Wu, Dong-Yi; Tsai, Sheng-Fa; Chen, Chien-Kuang

    2015-06-01

    Bioassay guided fractionation and separation of the EtOH extract of Annona glabra leaf against acetylcholinesterse led to the characterization of 15 alkaloids. Among them, (-)-actinodaphnine (2) and (-)-(6aS,7R)-7-hydroxyactinodaphnine (9) are new aporphines, although (+)-2 and (±)-2 have been found in several plants. Their structures were established by spectroscopic analysis. (-)-Anolobine (5) and (-)-roemeroline (8) showed moderate inhibitory activity against eel acetylcholinesterase with IC50 values of 22.4 and 26.3 ?M, respectively. PMID:26197510

  13. Tremorgenic indole alkaloids. The total synthesis of (-)-penitrem D.

    PubMed

    Smith, Amos B; Kanoh, Naoki; Ishiyama, Haruaki; Minakawa, Noriaki; Rainier, Jon D; Hartz, Richard A; Cho, Young Shin; Cui, Haifeng; Moser, William H

    2003-07-01

    A convergent, stereocontrolled total synthesis of the architecturally complex tremorgenic indole alkaloid (-)-penitrem D (4) has been achieved. Highlights of the synthesis include an efficient, asymmetric synthesis of the western hemisphere; the stereocontrolled assembly of the I-ring; discovery of a novel autoxidation to introduce the C(22) tertiary hydroxyl group, required for tremorgenic activity; union of fully elaborated eastern and western hemispheres, exploiting an indole synthetic protocol developed expressly for this purpose; and a late-stage, stereoselective construction of the A and F rings exploiting a Sc(OTf)(3-)promoted reaction cascade. The longest linear sequence leading to (-)-penitrem D (4) was 43 steps. PMID:12837093

  14. BILL E. KUNKLE INTERDISCIPLINARY BEEF SYMPOSIUM: Physiologic effects of ergot alkaloids: What happens when excretion does not equal consumption?

    PubMed

    Klotz, J L

    2015-12-01

    Increased persistence of tall fescue () infested with an endophytic fungus, (formerly ), in forage-based agriculture has led to increased effort in understanding the negative effects caused by consumption of ergot alkaloids by animals consuming this forage. Ergot alkaloids have been shown to have an extremely short plasma half-life, but this does not necessarily equate to total clearance. Studies that measured consumption and excretion of alkaloids have demonstrated that in the case of ergovaline, less is excreted than is consumed. The fate of ergot alkaloids that leave circulation but are not excreted is not well understood. Consequently, these "alkaloid balance studies" have led to speculation that ergovaline might bioaccumulate in the animal. Unfortunately, few data indisputably support this outcome. Progress has been slowed by the fact that the fungus produces a multitude of different ergot alkaloids that can bind to a variety of different receptors. Binding studies have shown that ergot alkaloids have unusually slow receptor dissociation rates that have been described as irreversible and contribute to a persistent signaling effect. In vitro analyses have revealed a potential for accumulation of ergot alkaloids through repetitive exposures to low concentrations creating a "depot" of alkaloids available to interact with receptors. The specific high binding affinity of ergot alkaloids combined with the potential turnover of alkaloids bound nonspecifically could extend residual effects of these compounds. Interestingly, cattle exposed to ergot alkaloids in vivo have a consistently lower vascular response to agonists that target receptors known to bind ergot alkaloids. If these same receptors are blocked with an antagonist, contractile response to ergopeptine alkaloids is also reduced significantly (>60% reduction). This observation that alkaloid exposure interrupts normal function of a receptor can persist 5 to 6 wk after animals have been removed from an ergot alkaloid source (and prolactin levels have long since returned to normal). Thus, clearance of ergot alkaloids from cattle grazing pasture with ergot alkaloid-producing endophytes may occur in a similar gradual manner. Studies that improve the understanding of how cattle process ergot alkaloids will help answer the question of whether ergot alkaloids bioaccumulate. PMID:26641161

  15. Individual and Geographic Variation of Skin Alkaloids in Three Swamp-Forest Species of Madagascan Poison Frogs (Mantella).

    PubMed

    Andriamaharavo, Nirina R; Garraffo, H Martin; Spande, Thomas F; Giddings, Lesley-Ann; Vieites, David R; Vences, Miguel; Saporito, Ralph A

    2015-09-01

    Seventy skins of three mantellid frog species from Madagascan swamp-forest habitats, Mantella aurantiaca, M. crocea, and M. milotympanum, were individually examined for skin alkaloids using GC/MS. These poison frogs were found to differ significantly in their alkaloid composition from species of Mantella originating from non-flooded rainforest in eastern Madagascar, which were examined in earlier work. Only 16 of the previously detected 106 alkaloids were represented among the 60 alkaloids from the swamp-forest frogs of the present study. We hypothesize this difference is related mainly to habitat but cannot exclude a phylogenetic component as the three swamp-forest species are a closely related monophyletic group. The paucity of alkaloids with unbranched-carbon skeletons (ant-derived) and the commonness of alkaloids with branched-carbon skeletons (mite-derived) indicate that oribatid mites are a major source of alkaloids in these species of mantellids. Furthermore, most of the alkaloids have an oxygen atom in their formulae. Differences in alkaloids were observed among species, populations of the same species, and habitats. In M. aurantiaca, small geographic distances among populations were associated with differences in alkaloid profiles, with a remote third site illustrating even greater differences. The present study and an earlier study of three other mantellid species suggest that oribatid mites, and not ants, are the major source of alkaloids in the species of mantellids examined thus far. PMID:26329921

  16. Vinca alkaloids in the therapeutic management of malignant pleural mesothelioma.

    PubMed

    Ceresoli, Giovanni Luca; Zucali, Paolo Andrea

    2015-12-01

    Therapeutic options for malignant pleural mesothelioma (MPM) are limited. Most patients are treated with chemotherapy during the course of their disease. The combination of pemetrexed with a platinum compound is the standard of care in the first-line setting, while no established treatment exists in the second and beyond-line setting. Vinca alkaloids are chemotherapeutic agents that have demonstrated clinical efficacy both as single agents and in combination in a broad spectrum of cancers, including MPM. Vinorelbine has shown activity in MPM patients as neoadiuvant therapy, first-line treatment, and in the second and third-line setting. Vinflunine is a derivative of vinorelbine that has been studied in MPM as first-line agent. While the role of vinca alkaloids in the first-line treatment of MPM seems marginal, treatment with vinorelbine remains a reasonable option for pemetrexed-pretreated patients in clinical practice, based on an acceptable rate of stable disease, confirmed by several trials. Ongoing studies on predictive biomarkers for vinorelbine will hopefully be able to individualize treatment, increasing response rates and survival outcomes. PMID:26526504

  17. Modulatory Effects of Eschscholzia californica Alkaloids on Recombinant GABAA Receptors

    PubMed Central

    Fedurco, Milan; Gregorová, Jana; Šebrlová, Kristýna; Kantorová, Jana; Peš, Ond?ej; Baur, Roland; Sigel, Erwin; Táborská, Eva

    2015-01-01

    The California poppy (Eschscholzia californica Cham.) contains a variety of natural compounds including several alkaloids found exclusively in this plant. Because of the sedative, anxiolytic, and analgesic effects, this herb is currently sold in pharmacies in many countries. However, our understanding of these biological effects at the molecular level is still lacking. Alkaloids detected in E. californica could be hypothesized to act at GABAA receptors, which are widely expressed in the brain mainly at the inhibitory interneurons. Electrophysiological studies on a recombinant ?1?2?2 GABAA receptor showed no effect of N-methyllaurotetanine at concentrations lower than 30??M. However, (S)-reticuline behaved as positive allosteric modulator at the ?3, ?5, and ?6 isoforms of GABAA receptors. The depressant properties of aerial parts of E. californica are assigned to chloride-current modulation by (S)-reticuline at the ?3?2?2 and ?5?2?2 GABAA receptors. Interestingly, ?1, ?3, and ?5 were not significantly affected by (R)-reticuline, 1,2-tetrahydroreticuline, codeine, and morphine—suspected (S)-reticuline metabolites in the rodent brain. PMID:26509084

  18. Isoquinoline alkaloid production by transformed cultures of Papaver somniferum.

    PubMed

    Yoshimatsu, K; Shimomura, K

    2001-01-01

    Three clones of transformed cultures of opium poppy (Papaver somniferum L.) were established by infection with Agrobacterium rhizogenes MAFF 03-01724. MAFF clone 1 being capable of forming somatic embryos was selected and its growth and isoquinoline alkaloid production was investigated. The illumination, temperature and nutrient medium composition greatly affected growth, cell morphology and alkaloid accumulation. The MAFF clone 1 cultured in Root Culture medium in the dark at 22 degrees C accumulated a high quantity of sanguinarine (652 micrograms/g dry weight) though the growth was poor (4.4 fold as fresh weight basis after 2 months of culture). The MAFF clone 1 cultured in a quarter macro salt strength Woody Plant medium under 14 h/day light at 22 degrees C developed into plantlets and accumulated significant quantity of codeine (648 micrograms/g dry wt) together with papaverine, noscapine, and sanguinarine. This clone was applied to a rotating drum fermenter (2 L working volume), and ca. 0.3 mg codeine and 0.06 mg sanguinarine were obtained after 4 weeks of culture. One quarter of the codeine produced was found in the culture medium. PMID:11915285

  19. Phenanthroindolizidines and Phenanthroquinolizidines: Promising Alkaloids for Anti-Cancer Therapy

    PubMed Central

    Chemler, Sherry R.

    2009-01-01

    The phenanthroindolizidine and phenanthroquinolizidine alkaloids, typified by tylophorine and cryptopleurine, are a family of plant-derived small molecules with significant therapeutic potential. The plant extracts have been used in herbal medicine and the isolated compounds have displayed a range of promising therapeutic activity such as anti-ameobicidal, anti-viral, anti-inflammatory and anti-cancer activity. Despite their therapeutic protential, no compounds in this class have fully passed clinical trials. Drawbacks include low in vivo anti-cancer activity, central nervous system toxicity and low natural availability. A number of biological effects of these compounds, such as protein and nucleic acid synthesis suppression, have been identified, but the specific biomolecular targets have not yet been identified. Significant effort has been expended in the synthesis and structure-activity-relationship (SAR) studies of these compounds with the hope that a new drug will emerge. This review will highlight important contributions to the isolation, synthesis, SAR and mechanism of action of the phenanthroindolizidine and pheanthroquinolizidine alkaloids. PMID:20160962

  20. Efficient enantiomeric synthesis of pyrrolidine and piperidine alkaloids from tobacco.

    PubMed

    Felpin, F X; Girard, S; Vo-Thanh, G; Robins, R J; Villiéras, J; Lebreton, J

    2001-09-21

    An enantiomeric synthesis of six piperidine and pyrrolidine alkaloids, (S)-nornicotine 1, (S)-nicotine 2, (S)-anatabine 3, (S)-N-methylanatabine 4, (S)-anabasine 5, and (S)-N-methylanabasine 6, known as natural products in tobacco, was established from a common chiral homoallylic (S)-3-(1-azido-but-3-enyl)-pyridine 15. An intramolecular hydroboration-cycloalkylation of the homoallylic azide intermediate 15 served as the key step in the pyrrolidine ring formation. A ring closing metathesis reaction (RCM) of a diethylenic amine intermediate (S)-allyl-(1-pyridin-3-yl-but-3-enyl)-carbamic acid benzyl ester 20 served as the key step in the piperidine ring formation. From the commercially available 3-pyridinecarboxaldehyde 13, a short and convenient enantiomeric synthesis of tobacco alkaloids is described: (S)-nornicotine 1 (5 steps, with an overall yield of 70%), (S)-nicotine 2 (6 steps, 65%), (S)-anatabine 3 (8 steps, 30%), (S)-N-methylanatabine 4 (8 steps, 25%), (S)-anabasine 5 (8 steps, 35%), and (S)-N-methylanabasine 6 (8 steps, 25%). PMID:11559179

  1. Pyrrolizidine alkaloids in food and feed on the Belgian market.

    PubMed

    Huybrechts, Bart; Callebaut, Alfons

    2015-11-01

    Pyrrolizidine alkaloids (PAs) are widely distributed plant toxins with species dependent hepatotoxic, carcinogenic, genotoxic and pneumotoxic risks. In a recent European Food Safety Authority (EFSA) opinion, only two data sets from one European country were received for honey, while one feed data set was included. No data are available for food or feed samples from the Belgian market. We developed an LC-MS/MS method, which allowed the detection and quantification of 16 PAs in a broad range of matrices in the sub ng g(-1) range. The method was validated in milk, honey and hay and applied to honey, tea (Camellia sinensis), scented tea, herbal tea, milk and feed samples bought on the Belgian market. The results confirmed that tea, scented tea, herbal tea and honey are important food sources of pyrrolizidine alkaloid contamination in Belgium. Furthermore, we detected PAs in 4 of 63 commercial milk samples. A high incidence rate of PAs in lucerne (alfalfa)-based horse feed and in rabbit feed was detected, while bird feed samples were less contaminated. We report for the first time the presence of monocrotaline, intermedine, lycopsamine, heliotrine and echimidine in cat food. PMID:26373269

  2. Effect of ergot alkaloids associated with fescue toxicosis on hepatic cytochrome P450 and antioxidant proteins

    SciTech Connect

    Settivari, Raja S.; Evans, Tim J.; Rucker, Ed; Rottinghaus, George E.; Spiers, Donald E.

    2008-03-15

    Intake of ergot alkaloids found in endophyte-infected tall fescue grass is associated with decreased feed intake and reduction in body weight gain. The liver is one of the target organs of fescue toxicosis with upregulation of genes involved in xenobiotic metabolism and downregulation of genes associated with antioxidant pathways. It was hypothesized that short-term exposure of rats to ergot alkaloids would change hepatic cytochrome P450 (CYP) and antioxidant expression, as well as reduce antioxidant enzyme activity and hepatocellular proliferation rates. Hepatic gene expression of various CYPs, selected nuclear receptors associated with the CYP induction, and antioxidant enzymes were measured using real-time PCR. Hepatic expression of CYP, antioxidant and proliferating cell nuclear antigen (PCNA) proteins were measured using Western blots. The CYP3A1 protein expression was evaluated using primary rat hepatocellular cultures treated with ergovaline, one of the major ergot alkaloids produced by fescue endophyte, in order to assess the direct role of ergot alkaloids in CYP induction. The enzyme activities of selected antioxidants were assayed spectrophotometrically. While hepatic CYP and nuclear receptor expression were increased in ergot alkaloid-exposed rats, the expression and activity of antioxidant enzymes were reduced. This could potentially lead to increased oxidative stress, which might be responsible for the decrease in hepatocellular proliferation after ergot alkaloid exposure. This study demonstrated that even short-term exposure to ergot alkaloids can potentially induce hepatic oxidative stress which can contribute to the pathogenesis of fescue toxicosis.

  3. Effects of antibacterial agents on in vitro ovine ruminal biotransformation of the hepatotoxic pyrrolizidine alkaloid jacobine.

    PubMed

    Wachenheim, D E; Blythe, L L; Craig, A M

    1992-08-01

    Ingestion of pyrrolizidine alkaloids, naturally occurring plant toxins, causes illness and death in a number of animal species. Senecio jacobaea pyrrolizidine alkaloids cause significant economic losses due to livestock poisoning, particularly in the Pacific Northwest. Some sheep are resistant to pyrrolizidine alkaloid poisoning, because ovine ruminal biotransformation detoxifies free pyrrolizidine alkaloids in digesta. Antibacterial agents modify ruminal fermentation. Pretreatment with antibacterial agents may account for some animal variability in resistance to pyrrolizidine alkaloid toxicosis, and antibacterial agents can also be used for characterizing ruminal pyrrolizidine alkaloid-biotransforming microflora. The objective of this study was to evaluate the effects of antibacterial agents on biotransformation of a predominant S. jacobaea pyrrolizidine alkaloid, jacobine, in ovine ruminal contents. Ovine ruminal jacobine biotransformation was tested in vitro with 20 independent antibacterial agents. Low amounts of rifampin and erythromycin prevented jacobine biotransformation. Chlortetracycline, lasalocid, monensin, penicillin G, and tetracycline were slightly less effective at inhibiting jacobine biotransformation. Bacitracin, crystal violet, kanamycin, and neomycin were moderately inhibitory against jacobine biotransformation. Brilliant green, chloramphenicol, gramicidin, nalidixic acid, polymyxin B SO4, sodium azide, streptomycin, sulfisoxazole, and vancomycin had little to no effect on jacobine biotransformation. The antibiotics that were most effective at inhibiting biotransformation were those that are active against gram-positive bacteria. Therefore, gram-positive bacteria are most likely critical members of the jacobine-biotransforming consortia. PMID:1514802

  4. Hepatotoxic pyrrolizidine alkaloids in pollen and drying-related implications for commercial processing of bee pollen.

    PubMed

    Boppré, Michael; Colegate, Steven M; Edgar, John A; Fischer, Ottmar W

    2008-07-23

    Using HPLC-ESI-MS, several saturated and 1,2-dehydropyrrolizidine alkaloids were detected, mainly as their N-oxides, in fresh pollen collected from flowers of the pyrrolizidine alkaloid-producing plants Echium vulgare, E. plantagineum, Senecio jacobaea, S. ovatus, and Eupatorium cannabinum, and/or pollen loads from bees (bee pollen) that foraged on those plants. A major alkaloidal metabolite in S. ovatus was tentatively identified, using its mass spectrometric data and biogenic considerations, as the previously unreported, saturated alkaloid, 2-hydroxysarracine. Heating had very little effect on the 1,2-dehydropyrrolizidine alkaloids and their N-oxides from a variety of sources. Considered in conjunction with international concerns about the adverse effects of these alkaloids, the results strongly indicate a need for monitoring pollen supplies intended for human consumption, at least until conditions for processing and/or selection are clearly defined such as to significantly reduce the hepatotoxic (and potentially carcinogenic and genotoxic) pyrrolizidine alkaloid content of bee pollen. PMID:18553916

  5. Naturally-occurring tetrahydro-?-carboline alkaloids derived from tryptophan are oxidized to bioactive ?-carboline alkaloids by heme peroxidases.

    PubMed

    Herraiz, Tomás; Galisteo, Juan

    2014-08-15

    ?-Carbolines are indole alkaloids that occur in plants, foods, and endogenously in mammals and humans, and which exhibit potent biological, psychopharmacological and toxicological activities. They form from naturally-occurring tetrahydro-?-carboline alkaloids arising from tryptophan by still unknown way and mechanism. Results in this research show that heme peroxidases catalyzed the oxidation of tetrahydro-?-carbolines (i.e. 1,2,3,4-tetrahydro-?-carboline-3-carboxylic acid and 1-methyl-1,2,3,4-tetrahydro-?-carboline-3-carboxylic acid) into aromatic ?-carbolines (i.e. norharman and harman, respectively). This oxidation followed a typical catalytic cycle of peroxidases through redox intermediates I, II, and ferric enzyme. Both, plant peroxidases (horseradish peroxidase, HRP) and mammalian peroxidases (myeloperoxidase, MPO and lactoperoxidase, LPO) catalyzed the oxidation in an efficient manner as determined by kinetic parameters (VMAX and KM). Oxidation of tetrahydro-?-carbolines was inhibited by peroxidase inhibitors such as sodium azide, ascorbic acid, hydroxylamine and excess of H2O2. The formation of aromatic ?-carbolines by heme peroxidases can help to explain the presence and activity of these compounds in biological systems. PMID:25035927

  6. Immunolocalization of alkaloids and X-ray microanalysis of elements in lupin seeds.

    PubMed

    Pozuelo, J M; Lucas, M M; de Lorenzo, C; Fernández-Pascual, M; Maldonado, S; de Felipe, M R

    2001-01-01

    Immunolocalization of alkaloids in lupin seeds (Lupinus spp.) has been performed by cryofixation and conventional methods. Alkaloids were localized in the protein bodies of the cotyledon cells. Some immunogold particles in the walls of these cells were also observed. There were no differences in the sites of localization between the two mentioned methods. X-ray microanalysis of elements showed the presence of P, Mg, S, and K in the protein bodies of cotyledon cells in lupin seeds. The role of K+ in alkaloids transport is discussed. PMID:11732315

  7. A phytochemical study of the quinolizidine alkaloids from Genista tenera by gas chromatography-mass spectrometry.

    PubMed

    Martins, Alice; Wink, Michael; Tei, Andreas; Brum-Bousquet, Michèle; Tillequin, François; Rauter, Amélia-Pilar

    2005-01-01

    Gas chromatography coupled with mass spectrometry has been used to analyse the alkaloids present in the aerial parts of Genista tenera. Anagyrine, cytisine, N-formylcytisine, N-methylcytisine and lupanine were the major compounds, the last two alkaloids being known for their hypoglycaemic activity. Dehydrocytisine, 5,6-dehydrolupanine, rhombifoline, aphylline and thermopsine were the minor alkaloids. The characterisation of the constituents was based on comparison of their Kovats retention indexes and electron impact-mass spectrometric data recorded on-line with those of reference compounds and literature data. PMID:16042152

  8. Pericolactines A-C, a New Class of Diterpenoid Alkaloids with Unusual Tetracyclic Skeleton.

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  10. Pelopuradazole, a new imidazole derivative alkaloid from the marine bacteria Pelomonas puraquae sp. nov.

    PubMed

    He, Xi-Xin; Chen, Xiao-Jie; Peng, Guang-Tian; Guan, Shan-Yue; Lei, Ling-Fang; Yao, Jun-Hua; Liu, Bing-Xin; Zhang, Cui-Xian

    2014-01-01

    One new imidazole derivative alkaloid pelopuradazole (1), together with three known alkaloids as in 3H-imidazole-4-carboxylic acid (2), 1H-pyrrole-2-carboxylic acid (3) and 2-methyl-3H-imidazole-4-carboxylic acid (4) and two known cyclo-dipeptides pelopurin A (5) and pelopurin B (6), has been isolated from the marine bacterium Pelomonas puraquae sp. nov. Pelopuradazole (1) was a new imidazole derivative alkaloid, while compounds 2, 3, 5 and 6 were firstly obtained as natural products. Compounds 1-6 were isolated from P. puraquae sp. nov. for the first time. PMID:24597911

  11. [Synthesis, physicochemical and pharmacological properties of pentacyclic alkaloid-analogues].

    PubMed

    Bubenyák, Máté

    2011-01-01

    Quinazolinocarboline rutaecarpine and evodiamine (Evodia rutaecarpa) are main alkaloid components of traditional Chinese folk-remedies. Evodiamine exhibited selective antitumor and antimetastatic effects on several cancer cell lines and became lead structure of anticancer agents. During our synthetic research we achieved to gain alkaloid hybrid derivatives by combining the structural elements of quinazolinocarbolines with analogous alkaloids or drug molecules having similar effects by bioisosteric replacements. 8-norrutaecarpine, a hybrid molecule of rutaecarpine and luotonin A containing the indolo-pyrroloquinazolinone ring system has been synthesized. The hybrids of rutaecarpine and piroxicam bearing the indolo-pyridobenzothiazine and the 12-azaindolo-pyridobenzothiazine structures were prepared on two alternative routes. Two new heterocondensed pentacyclic compounds, 5-sulfarutaecarpine and 5-sulfa-8-norrutaecarpine were reached via bioisosteric replacement on the structure of rutaecarpine and 8-norrutaecarpine. Two new tricyclic ring systems, pyrido-benzothiadiazine and pyrrolo-benzothiadiazine were produced as intermediaries of these pentacyclic molecules. Series of substituted derivatives were prepared for pharmacological studies by modification of the structures with various substituents and solubilizing groups. During our work alternative way for synthesis of nauclefine (Nauclea latifolia) was laboured, and we published the synthesis of indolylquinazolinone derivative bouchardatine (Bouchardata neurococca) for the first time. Some of the physicochemical attributes of the synthesized intermediaries were defined, such as the pKa constants of 2,3-poly-methylene-benzothiadiazines. Proton/deuteron exchange kinetic constants of active methylene-groups of five tricyclic compounds were measured by 1H NMR technique. Solvent-dependent ratio of the Z/E isomers of phenyhydrazone-derivatives in polar and apolar solvents were determined. In the case of 18 produced compounds our work was completed by in vitro pharmacological studies performed within co-operation with the Institute of Pharmacology. The viability of HeLa cells was inhibited by five of our compounds to similar extent as the effect of evodiamine. Eight of our compounds induced apoptosis on HeLa cells to similar extent as evodiamine. PMID:22329301

  12. Quinolizidine alkaloid composition of plants and of photomixotrophic cell suspension cultures of Sarothamnus scoparius and Orobanche rapum-genistae.

    PubMed

    Wink, M; Witte, L; Hartmann, T

    1981-12-01

    The alkaloid composition of Sarothamnus scoparius cell cultures, plants and of its root parasite Orobanche rapum-genistae were analyzed by capillary gas-liquid chromatography (GLC) and capillary GLC/mass spectrometry. S. scoparius plants were found to contain the already known isosparteine, sparteine, 17-oxosparteine, lupanine and other quinolizidine alkaloids such as ammodendrine, N-methylangustifoline, alpha-isolupanine, 5,6-dehydrolupanine, 4-hydroxylupanine, 17-oxolupanine and five 13-hydroxylupanine esters. Two new alkaloids could be identified, a dehydrosparteine (presumably the 11,12-dehydroderivative) and a dihydroxylupanine (presumably 4,13-dihydroxylupanine). The distribution of these alkaloids within the different plant organs is reported. Orobanche rapum-genistae plants contain the already known sparteine, lupanine and 13-hydroxylupanine and 12 other lupin alkaloids, which are present in the Sarothamnus host plant. Photomixotrophic cell suspension cultures of S. scoparius accumulate lupanine as the main alkaloid. On tissue differentiation (bud formation) the cultures accumulate sparteine as well as lupanine. Whereas sparteine is stored in the cells, lupanine is excreted into the medium. Alkaloid formation of the cell cultures is positively correlated with chlorophyll content of the cells. The alkaloid pattern found in S. scoparius supports the hypothesis that lupanine biosynthesis is the common route of quinolizidine alkaloid biosynthesis from which the other alkaloids such as sparteine are derived. PMID:17402058

  13. Biosynthesis and Accumulation of Ergoline Alkaloids in a Mutualistic Association between Ipomoea asarifolia (Convolvulaceae) and a Clavicipitalean Fungus1

    PubMed Central

    Markert, Anne; Steffan, Nicola; Ploss, Kerstin; Hellwig, Sabine; Steiner, Ulrike; Drewke, Christel; Li, Shu-Ming; Boland, Wilhelm; Leistner, Eckhard

    2008-01-01

    Ergoline alkaloids occur in taxonomically unrelated taxa, such as fungi, belonging to the phylum Ascomycetes and higher plants of the family Convolvulaceae. The disjointed occurrence can be explained by the observation that plant-associated epibiotic clavicipitalean fungi capable of synthesizing ergoline alkaloids colonize the adaxial leaf surface of certain Convolvulaceae plant species. The fungi are seed transmitted. Their capacity to synthesize ergoline alkaloids depends on the presence of an intact differentiated host plant (e.g. Ipomoea asarifolia or Turbina corymbosa [Convolvulaceae]). Here, we present independent proof that these fungi are equipped with genetic material responsible for ergoline alkaloid biosynthesis. The gene (dmaW) for the determinant step in ergoline alkaloid biosynthesis was shown to be part of a cluster involved in ergoline alkaloid formation. The dmaW gene was overexpressed in Saccharomyces cerevisiae, the encoded DmaW protein purified to homogeneity, and characterized. Neither the gene nor the biosynthetic capacity, however, was detectable in the intact I. asarifolia or the taxonomically related T. corymbosa host plants. Both plants, however, contained the ergoline alkaloids almost exclusively, whereas alkaloids are not detectable in the associated epibiotic fungi. This indicates that a transport system may exist translocating the alkaloids from the epibiotic fungus into the plant. The association between the fungus and the plant very likely is a symbiotum in which ergoline alkaloids play an essential role. PMID:18344419

  14. Independent Recruitment of a Flavin-Dependent Monooxygenase for Safe Accumulation of Sequestered Pyrrolizidine Alkaloids in Grasshoppers and Moths

    PubMed Central

    Wang, Linzhu; Beuerle, Till; Timbilla, James; Ober, Dietrich

    2012-01-01

    Several insect lineages have developed diverse strategies to sequester toxic pyrrolizidine alkaloids from food-plants for their own defense. Here, we show that in two highly divergent insect taxa, the hemimetabolous grasshoppers and the holometabolous butterflies, an almost identical strategy evolved independently for safe accumulation of pyrrolizidine alkaloids. This strategy involves a pyrrolizidine alkaloid N-oxygenase that transfers the pyrrolizidine alkaloids to their respective N-oxide, enabling the insects to avoid high concentrations of toxic pyrrolizidine alkaloids in the hemolymph. We have identified a pyrrolizidine alkaloid N-oxygenase, which is a flavin-dependent monooxygenase, of the grasshopper Zonocerus variegatus. After heterologous expression in E. coli, this enzyme shows high specificity for pyrrolizidine alkaloids of various structural types and for the tropane alkaloid atropine as substrates, a property that has been described previously for a pyrrolizidine alkaloid N-oxygenase of the arctiid moth Grammia geneura. Phylogenetic analyses of insect flavin-dependent monooxygenase sequences suggest that independent gene duplication events preceded the establishment of this specific enzyme in the lineages of the grasshoppers and of arctiid moths. Two further flavin-dependent monooxygenase sequences have been identified from Z. variegatus sharing amino acid identities of approximately 78% to the pyrrolizidine alkaloid N-oxygenase. After heterologous expression, both enzymes are also able to catalyze the N-oxygenation of pyrrolizidine alkaloids, albeit with a 400-fold lower specific activity. With respect to the high sequence identity between the three Z. variegatus sequences this ability to N-oxygenize pyrrolizidine alkaloids is interpreted as a relict of a former bifunctional ancestor gene of which one of the gene copies optimized this activity for the specific adaptation to pyrrolizidine alkaloid containing food plants. PMID:22363737

  15. Antiviral activity of natural and semi-synthetic chromone alkaloids.

    PubMed

    Houghton, P J; Woldemariam, T Z; Khan, A I; Burke, A; Mahmood, N

    1994-12-01

    The activity against human immunodeficiency virus (HIV) and herpes simplex virus (HSV), of the non-polar fraction of a methanolic extract of the rootbark of Schumanniophyton magnificum was found to be present in a fraction containing the chromone secondary amine schumannificine 1. Other chromone alkaloids present in the plant were isolated and tested for inhibition of HIV and HSV infections in C8166 and Vero cells, respectively. Acyl and methyl derivatives were prepared and tested. Of all the compounds tested, schumannificine 1 displayed the greatest activity against HIV, whereas potent anti-HSV activity was observed for a number of its derivatives. The presence of a piperidine ring and unsubstituted hydroxy groups on the molecules seems to favour the anti-HIV activity. The anti-HIV activity is considered to be due to irreversible binding to gp120 rather than inhibition of reverse transcriptase or protease. PMID:7535992

  16. Science in drug control: the alkaloid content of afghan opium.

    PubMed

    Remberg, Barbara; Sterrantino, Anna Freni; Artner, Robert; Janitsch, Christoph; Krenn, Liselotte

    2008-09-01

    Opium samples from Afghanistan were analyzed by HPLC for their content of morphine and three further alkaloids (codeine, thebaine, and papaverine). To our knowledge, this is the largest set of authentic opium samples analyzed in one study until now. The purpose was to assess possible correlations between samples and selected external factors, such as region of origin within Afghanistan, year of harvest, or intra-batch variation. In the investigated samples, a trend towards higher morphine concentrations in opium from the North-Eastern parts of Afghanistan was observed in the period from 2003 to 2005. More than 75% of the samples contained above 10% of morphine, the overall average was 14.4%. PMID:18816533

  17. Two new alkaloids from Portulaca oleracea and their cytotoxic activities.

    PubMed

    Tian, Jin-Long; Liang, Xiao; Gao, Pin-Yi; Li, Dan-Qi; Sun, Qian; Li, Ling-Zhi; Song, Shao-Jiang

    2014-01-01

    Two new alkaloids named (3R)-3,5-bis(3-methoxy-4-hydroxyphenyl)-2,3-dihydro-2(1H)-pyridinone (1) and 1,5-dimethyl-6-phenyl-1,2-dihydro-1,2,4-triazin-3(2H)-one (2), together with two known compounds (7'R)-N-feruloyl normetanephrine (3) and N-trans-feruloyl tyramine (4) were isolated from the air-dried aerial parts of Portulaca oleracea L. Their structures and configurations were elucidated by spectroscopic methods including 1D NMR, 2D NMR, and HR-MS techniques. In addition, compounds 1-4 were tested for in vitro cytotoxic activities against human lung (K562 and A549) and breast (MCF-7 and MDA-MB-435) cancer cell lines. PMID:24321009

  18. Biomimetic synthesis and studies toward enantioselective synthesis of flindersial alkaloids.

    PubMed

    Vallakati, Ravikrishna; Lundy, Brian J; Jansone-Popova, Santa; May, Jeremy A

    2015-01-01

    A strategy allowing both stereocontrol and control over structural isomer formation has been defined for the antimalarial flindersial alkaloids. The recently reported flinderoles were demonstrated to be derived from the natural product borrerine. The structural isomers of flinderoles, the borreverines, were also produced in vitro along with the flinderoles through the dimerization of borrerine in acidic conditions. This result is thought to replicate the biosynthesis of these compounds. Flinderoles A, B, and C, desmethylflinderole C, isoborreverine, and dimethylisoborreverine can each be synthesized in three steps from tryptamine. Furthermore, progress toward a concise enantioselective synthesis of flinderoles A, B, and C is described. This work includes enantioselective conjugate addition to an unprotected indole-appended enone. PMID:23529894

  19. Determination of pyrrolizidine alkaloids in tea, herbal drugs and honey.

    PubMed

    Bodi, Dorina; Ronczka, Stefan; Gottschalk, Christoph; Behr, Nastassja; Skibba, Anne; Wagner, Matthias; Lahrssen-Wiederholt, Monika; Preiss-Weigert, Angelika; These, Anja

    2014-01-01

    Honey was previously considered to be one of the main food sources of human pyrrolizidine alkaloid (PA) exposure in Europe. However, comprehensive analyses of honey and tea sampled in the Berlin retail market revealed unexpected high PA amounts in teas. This study comprised the analysis of 87 honey as well as 274 tea samples including black, green, rooibos, melissa, peppermint, chamomile, fennel, nettle, and mixed herbal tea or fruit tea. Total PA concentrations in tea ranged from < LOD to 5647 µg kg(-1), while a mean value of about 10 µg kg(-1) was found in honey samples. Additionally, herbal drugs were investigated to identify the source of PA in teas. Results suggest that PA in tea samples are most likely a contamination caused by co-harvesting of PA-producing plants. In some cases such as fennel, anise or caraway, it cannot be excluded that these plants are able to produce PA themselves. PMID:25222912

  20. Alkaloids from an algicolous strain of Talaromyces sp.

    NASA Astrophysics Data System (ADS)

    Yang, Haibin; Li, Fang; Ji, Naiyun

    2015-09-01

    Compounds isolated and identified in a culture of the alga-endophytic fungus Talaromyces sp. cf-16 included two naturally occurring alkaloids, 2-[(S)-hydroxy(phenyl)methyl]-3-methylquinazolin-4(3H)-one (1a) and 2-[(R)-hydroxy(phenyl)methyl]-3-methylquinazolin-4(3H)-one (1b), that were identified for the first time. In addition, seven known compounds (2-8) were obtained from the culture. Following chiral column chromatography, compounds 1a and 1b were identified as enantiomers by spectroscopic analyses and quantum chemical calculations. Bioassay results showed that 5 was more toxic to brine shrimp than the other compounds, and that 3-6 could inhibit Staphylococcus aureus.

  1. Dichlorinated and Brominated Rugulovasines, Ergot Alkaloids Produced by Talaromyces wortmannii.

    PubMed

    de Medeiros, Lívia Soman; da Silva, José Vinícius; Abreu, Lucas Magalhães; Pfenning, Ludwig Heinrich; Silva, Carolina Lúcia; Thomasi, Sérgio Secherrer; Venâncio, Tiago; van Pée, Karl-Heinz; Nielsen, Kristian Fog; Rodrigues-Filho, Edson

    2015-01-01

    UHPLC-DAD-HRMS based dereplication guided the detection of new halogenated alkaloids co-produced by Talaromyces wortmannii. From the fungal growth in large scale, the epimers 2,8-dichlororugulovasines A and B were purified and further identified by means of a HPLC-SPE/NMR hyphenated system. Brominated rugulovasines were also detected when the microbial incubation medium was supplemented with bromine sources. Studies from 1D/2D NMR and HRMS spectroscopy data allowed the structural elucidation of the dichlorinated compounds, while tandem MS/HRMS data analysis supported the rationalization of brominated congeners. Preliminary genetic studies revealed evidence that FADH? dependent halogenase can be involved in the biosynthesis of the produced halocompounds. PMID:26404231

  2. Variation in pyrrolizidine alkaloid patterns of Senecio jacobaea.

    PubMed

    Macel, Mirka; Vrieling, Klaas; Klinkhamer, Peter G L

    2004-04-01

    We studied the variation in pyrrolizidine alkaloid (PA) patterns of lab-grown vegetative plants of 11 European Senecio jacobaea populations. Plants were classified as jacobine, erucifoline, mixed or senecionine chemotypes based on presence and absence of the PAs jacobine or erucifoline. Due to the presence of jacobine, total PA concentration in jacobine chemotypes was higher than in erucifoline chemotypes. Both relative and absolute concentrations of individual PAs differed between half-sib and clonal families, which showed that variation in PA patterns had a genetic basis. Within most populations relative abundance of PAs varied considerably between individual plants. Most populations consisted either of the jacobine chemotype or of the erucifoline chemotype, sometimes in combination with mixed or senecionine chemotypes. PMID:15081286

  3. Pyrrolizidine alkaloids from Senecio jacobaea affect fungal growth.

    PubMed

    Hol, W H G; Van Veen, A

    2002-09-01

    We investigated the growth-reducing effects of pyrrolizidine alkaloids (PAs) from Senecio jacobaea on nine plant-associated fungi (five strains of Fusarium oxysporum, two of F. sambucinum, and two of Trichoderma sp). Fungal growth was monitored on water agar media containing different concentrations of monocrotaline, retrorsine, or a purified extract of PAs from S. jacobaea. The growth rate of six strains was inhibited by PAs at the highest test concentration (3.33 mM), with the magnitude of the inhibition (7-35%) being dependent upon the specific fungus-PA interaction. In general, the PA extract caused the largest inhibition. However, the fungi isolated from S. jacobaea were positively affected by the PA extract (7-9%). Retrorsine N oxide was as effective as retrorsine in its inhibition of mycelium growth. PMID:12449504

  4. Hydrolysis rates of pyrrolizidine alkaloids derived from Senecio jacobaea.

    PubMed

    Dueker, S R; Lamé, M W; Segall, H J

    1995-01-01

    Many of the commonly studied pyrrolizidine alkaloids (PAs) are built upon the subgroup retronecine (RET), which is released from the parent molecule by either base catalyzed or enzymatic hydrolysis of the ester linkages. The rate of appearance of RET in a hydrolytic study would thus reflect the rate of hydrolysis for the PA being tested. We have developed a gas chromatographic (GC) method to measure the release of RET from incubations of PAs with the guinea pig carboxylesterase, GPH1. The PAs tested were the following: jacobine (JAB), jacozine (JAZ), retrorsine (RES), and seneciphylline (SNP). The KmS for SNP and JAZ were determined to be 64.9 and 349.2 microM, respectively. In addition, a qualitative assessment of hydrolytic activity toward a radiolabelled mixture of retrorsine/riddelliine (RES/RIL) was performed with HPLC and radiometric detection. PMID:8572933

  5. Alkaloids from Pandanus amaryllifolius: Isolation and Their Plausible Biosynthetic Formation.

    PubMed

    Tsai, Yu-Chi; Yu, Meng-Lun; El-Shazly, Mohamed; Beerhues, Ludger; Cheng, Yuan-Bin; Chen, Lei-Chin; Hwang, Tsong-Long; Chen, Hui-Fen; Chung, Yu-Ming; Hou, Ming-Feng; Wu, Yang-Chang; Chang, Fang-Rong

    2015-10-23

    Pandanus amaryllifolius Roxb. (Pandanaceae) is used as a flavor and in folk medicine in Southeast Asia. The ethanolic crude extract of the aerial parts of P. amaryllifolius exhibited antioxidant, antibiofilm, and anti-inflammatory activities in previous studies. In the current investigation, the purification of the ethanolic extract yielded nine new compounds, including N-acetylnorpandamarilactonines A (1) and B (2); pandalizines A (3) and B (4); pandanmenyamine (5); pandamarilactones 2 (6) and 3 (7), and 5(E)-pandamarilactonine-32 (8); and pandalactonine (9). The isolated alkaloids, with either a ?-alkylidene-?,?-unsaturated-?-lactone or ?-alkylidene-?,?-unsaturated-?-lactam system, can be classified into five skeletons including norpandamarilactonine, indolizinone, pandanamine, pandamarilactone, and pandamarilactonine. A plausible biosynthetic route toward 1-5, 7, and 9 is proposed. PMID:26461164

  6. Dimerization of functional pyrroloindolizines for the synthesis of complex myrmicarin alkaloids

    E-print Network

    Ondrus, Alison E.

    The union of functionalized pyrroloindolizines for the synthesis of heterodimeric products relevant to myrmicarin alkaloids is described. Design and synthesis of tricyclic substrates and new methods for their union enable ...

  7. Facilitating Biomimetic Syntheses of Borrerine Derived Alkaloids by Means of Flow-Chemical Methods

    E-print Network

    Kamptmann, Sonja B.; Ley, Steven V.

    2014-11-05

    Flow chemistry, although now commonly used for general synthetic chemistry, has not been applied extensively in a biomimetic fashion. Here we show how the flow syntheses of borrerine derived alkaloids can use these principles to obtain complex...

  8. Development of Transcriptomic Resources for Interrogating the Biosynthesis of Monoterpene Indole Alkaloids in Medicinal Plant Species

    E-print Network

    Gongora-Castillo, Elsa

    The natural diversity of plant metabolism has long been a source for human medicines. One group of plant-derived compounds, the monoterpene indole alkaloids (MIAs), includes well-documented therapeutic agents used in the ...

  9. Quinolizidine alkaloids inGenista acanthoclada and its holoparasite,Cuscuta palaestina.

    PubMed

    Wink, M; Witte, L

    1993-03-01

    About 20 quinolizidine alkaloids were identified inGenista acanthoclada by capillary GLC and GLC-MS, such as sparteine, 11,12-dehy-drosparteine, retamine,N-methylcytisine, cytisine, 17-oxosparteine, lupanine,?-isolupanine, 5,6-dehydrolupanine, 10-oxosparteine,N-carbomethoxycytisine, 17-oxoretamine,N-formylcytisine,N-acetylcytisine, and anagyrine. Its phloem-feeding holoparasiteCuscuta palaestina contained alkaloids too, such as sparteine, 11,12-dehydrosparteine, retamine,N-methylcytisine, cytisine, 17-oxosparteine, lupanine,N-carbomethoxycytisine, and anagyrine. Whereas sparteine, retamine, 17-oxosparteine, and cytisine are the main alkaloids ofG. acanthoclada, lupanine, cytisine,N-methylcytisine, and anagyrine are abundant and enriched inC. palaestina. Since these alkaloids figure as antiherbivoral chemical defense compounds inGenista, it is assumed that the parasite can exploit the acquired allelochemicals for its own protection. PMID:24248948

  10. Acute toxicity of the major alkaloids of cultivated Lupinus angustifolius seed to rats.

    PubMed

    Petterson, D S; Ellis, Z L; Harris, D J; Spadek, Z E

    1987-02-01

    The seed of modern cultivars of Lupinus angustifolius normally contain less than 0.03% alkaloids. The acute oral LD50 to rats of a pro rata mixture of the alkaloids of L. angustifolius seed was found to be 2279 mg/kg. For lupanine the LD50 by oral administration was 1464 mg/kg and by intraperitoneal injection 177 mg/kg. For 13-hydroxylupanine the LD50 by intraperitoneal injection was 199 mg/kg. Since these two alkaloids comprise about 85% of the total and are known to be rapidly cleared from the body it is suggested that the alkaloids in this species do not pose a health problem for man. PMID:3611597

  11. Vasoconstrictive responses by the carotid and auricular arteries in goats to ergot alkaloid exposure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A fungal endophyte (Neotyphodium coenophialum) infects most plants of ‘Kentucky 31’ tall fescue (Lolium arundinaceum) and produces ergot alkaloids that cause persistent constriction of the vascular system in grazing livestock. Consequently, animals undergoing this toxicosis cannot regulate core body...

  12. Effect of purine alkaloids on the proliferation of lettuce cells derived from protoplasts.

    PubMed

    Sasamoto, Hamako; Fujii, Yoshiharu; Ashihara, Hiroshi

    2015-05-01

    To investigate the ecological role of caffeine, theobromine, theophylline and paraxanthine, which are released from purine alkaloid forming plants, the effects of these purine alkaloids on the division and colony formation of lettuce cells were assessed at concentrations up to 1 mM. Five days after treatment with 500 ?M caffeine, theophylline and paraxanthine, division of isolated protoplasts was significantly inhibited. Thirteen days treatment with > 250 ?M caffeine had a marked inhibitory effect on the colony formation of cells derived from the protoplasts. Other purine alkaloids also acted as inhibitors. The order of the inhibition was caffeine > theophylline > paraxanthine > theobromine. These observations suggest that a relatively low concentration of caffeine is toxic for proliferation of plant cells. In contrast, theobromine is a weak inhibitor of proliferation. Possible allelopathic roles of purine alkaloids in natural ecosystems are discussed. PMID:26058150

  13. Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids

    PubMed Central

    Moloudizargari, Milad; Mikaili, Peyman; Aghajanshakeri, Shahin; Asghari, Mohammad Hossein; Shayegh, Jalal

    2013-01-01

    Wild Syrian rue (Peganum harmala L. family Zygophyllaceae) is well-known in Iran and various parts of this plant including, its seeds, bark, and root have been used as folk medicine. Recent years of research has demonstrated different pharmacological and therapeutic effects of P. harmala and its active alkaloids, especially harmine and harmaline. Analytical studies on the chemical composition of the plant show that the most important constituents of this plant are beta-carboline alkaloids such as harmalol, harmaline, and harmine. Harmine is the most studied among these naturally occurring alkaloids. In addition to P. harmala (Syrian rue), these beta-carbolines are present in many other plants such as Banisteria caapi and are used for the treatment of different diseases. This article reviews the traditional uses and pharmacological effects of total extract and individual active alkaloids of P. harmala (Syrian rue). PMID:24347928

  14. A new indolopyridoquinazoline-type alkaloid from phellodendron amurense callus tissues

    PubMed

    Ikuta; Urabe; Nakamura

    1998-08-01

    Callus tissue from the stems of Phellodendron amurense (Rutaceae) produced a new indolopyridoquinazoline-type alkaloid, 7, 8-dihydroxyrutaecarpine (2), together with known 7-hydroxyrutaecarpine (1). Their structures were established using spectroscopic methods. PMID:9722486

  15. Alkaloids in Processed Rhizoma Corydalis and Crude Rhizoma Corydalis Analyzed by GC/MS

    PubMed Central

    Cai, Ru; Su, Huidan; Li, Yunlong

    2014-01-01

    The alkaloids in the processed Rhizoma Corydalis and the crude Rhizoma Corydalis were qualitatively and semiquantitatively analyzed using gas chromatography-mass spectrometry (GC/MS) method. The processing herb drug procedure was carried out according to the standard method of Chinese Pharmacopoeia. The samples were extracted using Soxhlet extractor with different solvents: methanol and acetone. The extraction effect on different solvents was investigated. The results showed that 11 kinds of alkaloids were identified from the crude Rhizoma Corydalis and only two were from the processed Rhizoma Corydalis. A total of 13 kinds of alkaloids were all based on two backbones. The alkaloids in the processed sample were less than those in the crude Rhizoma Corydalis significantly, while almost the corydaline has been changed in conformation after the sample had undergone processing, which provided support for the conclusion of reducing toxicity when the herbal medicine having been undergone a traditional drugs treatment process. PMID:25210643

  16. In vivo antimalarial efficacy of acetogenins, alkaloids and flavonoids enriched fractions from Annona crassiflora Mart.

    PubMed

    Pimenta, Lúcia Pinheiro Santos; Garcia, Giani Martins; Gonçalves, Samuel Geraldo do Vale; Dionísio, Bárbara Lana; Braga, Erika Martins; Mosqueira, Vanessa Carla Furtado

    2014-01-01

    Annona crassiflora and Annonaceae plants are known to be used to treat malaria by traditional healers. In this work, the antimalarial efficacy of different fractions of A. crassiflora, particularly acetogenin, alkaloids and flavonoid-rich fractions, was determined in vivo using Plasmodium berghei-infected mice model and toxicity was accessed by brine shrimp assay. The A. crassiflora fractions were administered at doses of 12.5 mg/kg/day in a 4-day test protocol. The results showed that some fractions from woods were rich in acetogenins, alkaloids and terpenes, and other fractions from leaves were rich in alkaloids and flavonoids. The parasitaemia was significantly (p < 0.05, p < 0.001) reduced (57-75%) with flavonoid and alkaloid-rich leaf fractions, which also increased mean survival time of mice after treatment. Our results confirm the usage of this plant in folk medicine as an antimalarial remedy. PMID:24678811

  17. Analyses of tobacco alkaloids by cation-selective exhaustive injection sweeping microemulsion electrokinetic chromatography.

    PubMed

    Huang, Hsi-Ya; Hsieh, Shih-Huan

    2007-09-14

    In this study, an on-line concentration method which coupled cation-selective exhaustive injection (CSEI) sweeping technology with microemulsion electrokinetic chromatography (MEEKC) was used to detect and analyze several tobacco alkaloids (nornicotine, anabasine, anatabine, nicotine, myosmine and cotinine) that are commonly found in various tobacco products. First, the effects of microemulsion compositions (oil, cosurfactant and solution pH) were examined in order to optimize the alkaloid separations in conventional MEEKC. The pH value and the injection length of basic plug were found to be the predominant influences on the alkaloid stacking. This optimal CSEI sweeping MEEKC method provided approximately 180- to 540-fold increase in detection sensitivity in terms of peak height without any loss in separation efficiency when compared to normal MEEKC separation. Furthermore, this proposed CSEI sweeping MEEKC method was applied successfully for the detection of the minor alkaloids nornicotine, anabasine and anatabine in tobacco products. PMID:17644105

  18. Terpenoid-Alkaloids: Their Biosynthetic Twist of Fate and Total Synthesis

    PubMed Central

    Cherney, Emily C.; Baran, Phil S.

    2015-01-01

    Terpenes and alkaloids are ever-growing classes of natural products that provide new molecular structures which inspire chemists and possess a broad range of biological activity. Terpenoid-alkaloids originate from the same prenyl units that construct terpene skeletons. However, during biosynthesis, a nitrogen atom (or atoms) is introduced in the form of ?-aminoethanol, ethylamine, or methylamine. Nitrogen incorporation can occur either before, during, or after the cyclase phase. The outcome of this unique biosynthesis is the formation of natural products containing unprecedented structures. These complex structural motifs expose current limitations in organic chemistry, thus providing opportunities for invention. This review focuses on total syntheses of terpenoid-alkaloids and unique issues presented by this class of natural products. More specifically, it examines how these syntheses relate to the way terpenoid-alkaloids are made in Nature. Developments in chemistry that have facilitated these syntheses are emphasized, as well as chemical technology needed to conquer those that evade synthesis. PMID:26207071

  19. N1,N10-ditigloylspermidine, a novel alkaloid from the seeds of Ipomoea nil.

    PubMed

    Schimming, T; Jenett-Siems, K; Siems, K; Witte, L; Eich, E

    2005-12-01

    A novel spermidine alkaloid, N1,N10-ditigloylspermidine (1), has been isolated from the seeds of Ipomoea nil (L.) Roth (Convolvulaceae). Structural elucidation was achieved by EIMS, HRMS, 1H NMR, and 13C NMR spectroscopy. PMID:16398277

  20. Safety concerns of herbal products and traditional Chinese herbal medicines: Dehydopyrrolizidine alkaloids and aristolochic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In many countries, including the United States, herbal supplements, tisanes and vegetable products including traditional Chinese medicines are largely unregulated and their content is not registered, monitored or verified. Consequently potent plant toxins including dehydopyrrolizidine alkaloids and...

  1. A multi-omics strategy resolves the elusive nature of alkaloids in Podophyllum species.

    PubMed

    Marques, Joaquim V; Dalisay, Doralyn S; Yang, Hong; Lee, Choonseok; Davin, Laurence B; Lewis, Norman G

    2014-11-01

    Podophyllum hexandrum and, to a much lesser extent P. peltatum, are sources of podophyllotoxin, extensively used as a chemical scaffold for various anti-cancer drugs. In this study, integrated omics technologies (including advanced mass spectrometry/metabolomics, transcriptome sequencing/gene assemblies, and bioinformatics) gave unequivocal evidence that both plant species possess a hitherto unknown aporphine alkaloid metabolic pathway. Specifically, RNA-seq transcriptome sequencing and bioinformatics guided gene assemblies/analyses in silico suggested presence of transcripts homologous to genes encoding all known steps in aporphine alkaloid biosynthesis. A comprehensive metabolomics analysis, including UPLC-TOF-MS and MALDI-MS imaging in situ, then enabled detection, identification, localization and quantification of the aporphine alkaloids, magnoflorine, corytuberine and muricinine, in the underground and aerial tissues. Interestingly, the purported presence of alkaloids in Podophyllum species has been enigmatic since the 19th century, remaining unresolved until now. The evolutionary and phylogenetic ramifications of this discovery are discussed. PMID:25166004

  2. Asexual endophytes in a native grass: Tradeoffs in mortality, growth, reproduction, and alkaloid production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neotyphodium endophytes are asexual, seed-borne fungal symbionts that are thought to interact mutualistically with their grass hosts. Benefits include increased growth, reproduction, and resistance of herbivores via endophytic alkaloids. Although these benefits are well established in infected int...

  3. Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids.

    PubMed

    Moloudizargari, Milad; Mikaili, Peyman; Aghajanshakeri, Shahin; Asghari, Mohammad Hossein; Shayegh, Jalal

    2013-07-01

    Wild Syrian rue (Peganum harmala L. family Zygophyllaceae) is well-known in Iran and various parts of this plant including, its seeds, bark, and root have been used as folk medicine. Recent years of research has demonstrated different pharmacological and therapeutic effects of P. harmala and its active alkaloids, especially harmine and harmaline. Analytical studies on the chemical composition of the plant show that the most important constituents of this plant are beta-carboline alkaloids such as harmalol, harmaline, and harmine. Harmine is the most studied among these naturally occurring alkaloids. In addition to P. harmala (Syrian rue), these beta-carbolines are present in many other plants such as Banisteria caapi and are used for the treatment of different diseases. This article reviews the traditional uses and pharmacological effects of total extract and individual active alkaloids of P. harmala (Syrian rue). PMID:24347928

  4. Patterns of indole alkaloids synthesis in response to heat shock, 5-azacytidine and Na-butyrate treatment of cultured catharanthus roseus mesophyll protoplasts

    SciTech Connect

    Saleem, M.; Cutler, A.J.

    1986-04-01

    Alkaloids of C. roseus are in high demand for therapeutic and other reasons. Cultured Catharanthus cells can produce limited quantities of these alkaloids. The authors have found that cultured mesophyll protoplasts in the presence of /sup 14/C-Tryptamine are capable of synthesizing alkaloids. The pattern of alkaloids synthesis changes when protoplasts are subjected to a heat shock at 37/sup 0/C. The heat shocked protoplasts incorporated 33% more /sup 14/C-Tryptamine and produced 3 new types of alkaloids. Treatment of protoplasts with 5-azacytidine, a DNA hypomethylating agent and Na-butyrate which induces hyperacetylation of histones produced qualitative and quantitative changes in the alkaloid pattern. Four new alkaloids following the above treatments were detected by TLC and HPLC of the extracts. It is suggested that the alkaloid pattern of the cultured protoplasts can be altered by treatment with compounds known as regulators of gene expression. Work is in progress to isolate and identify these new alkaloids.

  5. Mw Systematic Study of Alkaloids: the Distorted Tropane of Scopoline

    NASA Astrophysics Data System (ADS)

    Ecija, Patricia; Cocinero, Emilio J.; Basterretxea, Francisco J.; Fernandez, Jose A.; Castano, Fernando; Lesarri, Alberto

    2013-06-01

    Tropane alkaloids have diverse pharmacological uses and are well-known for their neurostimulant activity. Previous structure-activity-relationship established correlations between bioactivity and several aspects of ligand conformation and stereochemistry, including delicate intramolecular effects like nitrogen inversion^{a}. We have initiated a series of structural studies on tropane alkaloids^{b}, aimed to discerning their intrinsic stereochemical properties using rotational spectroscopy in supersonic jets^{c}. Here we extend these studies to the epoxytropanes, initially motivated to interrogate the influence of the epoxy group on nitrogen inversion and ring conformation. The rotational spectrum evidences a single structure in the gas phase, providing a first description of the (three ring) structurally-distorted tropane in scopoline. The determined rotational parameters of scopoline reveal the structural consequences of the intramolecular cyclation of scopine, which breaks the original epoxy group and creates a new ether bridge and a 7?-hydroxytropane configuration. The hydroxyl group further stabilizes the molecule by an O-H \\cdots N intramolecular hydrogen bond, which, in turn, forces the N-methyl group to the less stable axial form^{b}. The experimental work was supported by ab initio and DFT calculations. ^{a} i) S.Singh, Chem. Rev. 100, 925 (2000); ii) A. Krunic, D. Pan, W.J. Dunn III, S.V.S. Miariappan, Bioorg. & Med. Chem. 17, 811 (2009). ^{b} E.J. Cocinero, A. Lesarri, P. écija, J.-U. Grabow, J.A. Fernández, F. Castaño, Phys. Chem. Chem. Phys. 12, 6076 (2010). ^{c} E.J. Cocinero, A. Lesarri, P. écija, J.-U. Grabow, J.A. Fernández, F. Castaño, Phys. Chem. Chem. Phys. 12, 12486 (2010).

  6. Cytochemical Localization of Polysaccharides in Claviceps paspali Ultrastructure During Submerged Fermentation of Alkaloids

    PubMed Central

    Vo?íšek, J.; Ludvík, J.; ?ehá?ek, Z.

    1974-01-01

    Morphological characteristics of two types of elements in the submerged mycelium of Claviceps paspali are described. Distribution of polysaccharides in the cell wall and cytoplasm was cytochemically determined at the ultrastructural level. Polysaccharide deposition into the cell walls was proportional to the increase in the alkaloid yield. In the cytoplasm, on the other hand, the presence of polysaccharide grains indicated an absence of alkaloid synthesis. Images PMID:4362461

  7. Concise Total Syntheses of the Lycopodium Alkaloids (±)-Nankakurines A and B via Luciduline

    PubMed Central

    Cheng, Xiayun; Waters, Stephen P.

    2009-01-01

    Total syntheses of the Lycopodium alkaloids nankakurines A and B have been accomplished in 6 and 7 steps, respectively, via a sequence that passes through a third Lycopodium alkaloid, luciduline, and forgoes the use of protecting groups on nitrogen. Key features include a short preparation of luciduline followed by a concise and stereoselective aminoallylation/ring-closing metathesis protocol to fashion the spiropiperidine ring common to nankakurines A and B. PMID:20014779

  8. Pyrrolizidine alkaloids in and on the leaf surface of Senecio jacobaea L.

    PubMed

    Vrieling, Klaas; Derridj, Sylvie

    2003-12-01

    This is the first study showing that alkaloids are present on the leaf surface of plants. A concentration of 30-230 pmol/cm2 pyrrolizidine alkaloids (PA's) was detected in 8 different samples taken from Senecio jacobaea. PA concentration on the leaves was marginally correlated with PA concentration of the total leaf tissues. The PA spectrum on the leaf differed from the PA spectrum of the total leaf. PMID:14599520

  9. Biochemical studies on peptide alkaloids: induction of ion selective mitochondrial swelling.

    PubMed

    Kawai, K; Nozawa, Y; Ogihara, Y

    1977-11-15

    The effect of frangulanine, a cyclopeptide alkaloid isolated from Hovenia dulcis Thunb., on mitochondrial swelling was studied. Frangulanine induced mitochondrial swelling in 0.15 M KCl solution at the concentration of 6.5 muM. The alkaloid showed ion selectivity on the induction of mitochondrial swelling. Upon addition of frangulanine, mitochondria underwent swelling in 0.15 M KCl or RbCl solution but in neither NaCl nor LiCl solution. PMID:923705

  10. Currencies of mutualisms: sources of alkaloid genes in vertically transmitted epichloae.

    PubMed

    Schardl, Christopher L; Young, Carolyn A; Pan, Juan; Florea, Simona; Takach, Johanna E; Panaccione, Daniel G; Farman, Mark L; Webb, Jennifer S; Jaromczyk, Jolanta; Charlton, Nikki D; Nagabhyru, Padmaja; Chen, Li; Shi, Chong; Leuchtmann, Adrian

    2013-06-01

    The epichloae (Epichloë and Neotyphodium species), a monophyletic group of fungi in the family Clavicipitaceae, are systemic symbionts of cool-season grasses (Poaceae subfamily Poöideae). Most epichloae are vertically transmitted in seeds (endophytes), and most produce alkaloids that attack nervous systems of potential herbivores. These protective metabolites include ergot alkaloids and indole-diterpenes (tremorgens), which are active in vertebrate systems, and lolines and peramine, which are more specific against invertebrates. Several Epichloë species have been described which are sexual and capable of horizontal transmission, and most are vertically transmissible also. Asexual epichloae are mainly or exclusively vertically transmitted, and many are interspecific hybrids with genomic contributions from two or three ancestral Epichloë species. Here we employ genome-scale analyses to investigate the origins of biosynthesis gene clusters for ergot alkaloids (EAS), indole-diterpenes (IDT), and lolines (LOL) in 12 hybrid species. In each hybrid, the alkaloid-gene and housekeeping-gene relationships were congruent. Interestingly, hybrids frequently had alkaloid clusters that were rare in their sexual ancestors. Also, in those hybrids that had multiple EAS, IDT or LOL clusters, one cluster lacked some genes, usually for late pathway steps. Possible implications of these findings for the alkaloid profiles and endophyte ecology are discussed. PMID:23744053

  11. [Study on membrane injury mechanism of total alkaloids and berberine from Coptidis Rhizoma on Aeromonas hydrophila].

    PubMed

    Xue, Dong-fang; Zou, Zong-yao; Chen, Biao; Wang, Yan-zhi; Wu, Hao; Ye, Xiao-li; Li, Xue-gang

    2015-05-01

    To explore the antibacterial activity and mechanism of total alkaloids and berberine from Coptidis Rhizoma on Aeromonas hydrophila, and determine the effect of total alkaloids and berberine from Coptidis Rhizoma on minimum inhibitory concentrations, permeability and fluidity of cell membrane, conformation of membrane proteins and virulence factors of A. hydrophila. The results showed that both total alkaloids and berberine from Coptidis Rhizoma had antibacterial activities on A. hydrophila, with minimum inhibitory concentrations of 62.5 and 125 mg · L(-1), respectively. Total alkaloids and berberine from Coptidis Rhizoma could increase the fluidity of membrane, change the conformation of membrane porteins and increase the permeability of bacteria membrane by 24.52% and 19.66%, respectively. Besides, total alkaloids and berberine from Coptidis Rhizoma significantly decreased the hemolysis of exotoxin and the mRNA expressions of aerA and hlyA (P < 0.05, P < 0.01), the secretion of endotoxin and the mRNA expression of LpxC (P < 0.05, P < 0.01). The results suggested that the antibacterial activity of total alkaloids and berberine from Coptidis Rhizoma on A. hydrophila may be related to the bacteria membrane injury. They inhibited the bacterial growth by increasing membrane lipid fluidity and changing conformation of membrane proteins, and reduced the secretion of virulence factors of A. hydrophila to weaken the pathogenicity. PMID:26323149

  12. Determination of quinolizidine alkaloids in different Lupinus species by NACE using UV and MS detection.

    PubMed

    Ganzera, Markus; Krüger, Anja; Wink, Michael

    2010-12-15

    Lupin seeds are important for animal and human nutrition. However, they may contain toxic quinolizidine alkaloids (QA). Analytical methods for a reliable alkaloid determination are therefore of importance. Here the presented study reports on the first CE method for the analysis of QA in Lupinus species. A buffer system consisting of 100mM ammonium formate in methanol, acetonitrile, and small amounts of water and acetic acid enabled the baseline separation of sparteine, lupanine, angustifoline and 13alpha-hydroxylupanine in less than 10min. Applied voltage, temperature and detection wavelength were 25kV, 30 degrees C and 210nm, respectively. Additional compounds were identified in CE-MS experiments, in which all alkaloids could be assigned in positive ESI mode at corresponding [M+H](+) values. The CE method was validated for linearity, sensitivity, accuracy and precision, and then used to assess the seeds of seven different Lupinus species for their alkaloid content. Lupanine was present in all of them within a range from 0.02% (L. densiflorus, L. microcarpus) to 1.47% (L. albus). The highest percentage of an individual alkaloid was found in L. polyphyllus (3.28% of angustifoline), the content of total alkaloids ranged from 0.43% (L. microcarpus) to 5.13% in L. polyphyllus. The quantitative results were in good agreement with literature data. PMID:20580181

  13. Currencies of Mutualisms: Sources of Alkaloid Genes in Vertically Transmitted Epichloae

    PubMed Central

    Schardl, Christopher L.; Young, Carolyn A.; Pan, Juan; Florea, Simona; Takach, Johanna E.; Panaccione, Daniel G.; Farman, Mark L.; Webb, Jennifer S.; Jaromczyk, Jolanta; Charlton, Nikki D.; Nagabhyru, Padmaja; Chen, Li; Shi, Chong; Leuchtmann, Adrian

    2013-01-01

    The epichloae (Epichloë and Neotyphodium species), a monophyletic group of fungi in the family Clavicipitaceae, are systemic symbionts of cool-season grasses (Poaceae subfamily Poöideae). Most epichloae are vertically transmitted in seeds (endophytes), and most produce alkaloids that attack nervous systems of potential herbivores. These protective metabolites include ergot alkaloids and indole-diterpenes (tremorgens), which are active in vertebrate systems, and lolines and peramine, which are more specific against invertebrates. Several Epichloë species have been described which are sexual and capable of horizontal transmission, and most are vertically transmissible also. Asexual epichloae are mainly or exclusively vertically transmitted, and many are interspecific hybrids with genomic contributions from two or three ancestral Epichloë species. Here we employ genome-scale analyses to investigate the origins of biosynthesis gene clusters for ergot alkaloids (EAS), indole-diterpenes (IDT), and lolines (LOL) in 12 hybrid species. In each hybrid, the alkaloid-gene and housekeeping-gene relationships were congruent. Interestingly, hybrids frequently had alkaloid clusters that were rare in their sexual ancestors. Also, in those hybrids that had multiple EAS, IDT or LOL clusters, one cluster lacked some genes, usually for late pathway steps. Possible implications of these findings for the alkaloid profiles and endophyte ecology are discussed. PMID:23744053

  14. Variation in the expression of ergot alkaloids between individual tillers of perennial ryegrass

    NASA Astrophysics Data System (ADS)

    Mace, Wade; Lunn, Kristy; Lloyd-West, Catherine

    2014-11-01

    Epichloë fungal endophytes of cool season grasses are well known to produce a range of alkaloids of benefit to the host. Some of these compounds are advantageous to agriculture due to qualities that promote pasture persistence (e.g. the loline class of alkaloids confer insect protection) while others are detrimental to the wellbeing of grazing livestock. The ergot alkaloids (e.g. ergovaline), produced in ryegrass and tall fescue associations, causes poor animal health in farming regions in many countries around the world and further study is required to improve our knowledge on this class of compounds. Here we present the application of a quantitative LC-MS/MS (liquid chromatography coupled to mass spectrometry) method measuring eight ergot alkaloids (chanoclavine, agroclavine, elymoclavine, lysergol, lysergic acid, ergine, lysergyl alanine, ergovaline) produced by endophyte infected grasses, to monitor levels in individual tillers from multiple plants of a single cultivar of perennial ryegrass (Lolium perenne cv. ‘Grasslands Samson’) infected with a common toxic endophyte strain (Epichloë festucae var. lolii). Monitoring the expression in individual tillers allows an estimation of the variability within a plant (between tillers) as well as between plants. The study showed that there is significant variation in the concentration of the ergot alkaloids between tillers of a single plant, at or exceeding the level of variation observed between individual plants of a population. This result emphasizes the fundamental importance of robust experimental design and sampling procedures when alkaloid expression assessment is required and these need to be rigorously tailored to the hypothesis being tested.

  15. Binary stress induces an increase in indole alkaloid biosynthesis in Catharanthus roseus

    PubMed Central

    Zhu, Wei; Yang, Bingxian; Komatsu, Setsuko; Lu, Xiaoping; Li, Ximin; Tian, Jingkui

    2015-01-01

    Catharanthus roseus is an important medicinal plant, which produces a variety of indole alkaloids of significant pharmaceutical relevance. In the present study, we aimed to investigate the potential stress-induced increase of indole alkaloid biosynthesis in C. roseus using proteomic technique. The contents of the detectable alkaloids ajmalicine, vindoline, catharanthine, and strictosidine in C. roseus were significantly increased under binary stress. Proteomic analysis revealed that the abundance of proteins related to tricarboxylic acid cycle and cell wall was largely increased; while, that of proteins related to tetrapyrrole synthesis and photosynthesis was decreased. Of note, 10-hydroxygeraniol oxidoreductase, which is involved in the biosynthesis of indole alkaloid was two-fold more abundant in treated group compared to the control. In addition, mRNA expression levels of genes involved in the indole alkaloid biosynthetic pathway indicated an up-regulation in their transcription in C. roseus under UV-B irradiation. These results suggest that binary stress might negatively affect the process of photosynthesis in C. roseus. In addition, the induction of alkaloid biosynthesis appears to be responsive to binary stress. PMID:26284098

  16. Variation in Alkaloid Production from Genetically Diverse Lolium Accessions Infected with Epichloë Species.

    PubMed

    Moore, Joseph R; Pratley, James E; Mace, Wade J; Weston, Leslie A

    2015-12-01

    Widespread infection of Epichloë occultans in annual ryegrass in Australia suggests that infection provides its weedy host, Lolium rigidum, some ecological advantage. Initial studies determined the distribution and profiles of known Epichloë alkaloids (epoxy-janthitrems, ergovaline, lolines, lolitrem B, and peramine) in plant extracts using a combination of GC-FID and HPLC techniques utilizing a single accession of Australian L. rigidum. However, the lolines N-acetylnorloline (NANL) and N-formylloline (NFL) were the only alkaloids detected and were highly concentrated in the immature inflorescences of mature plants. Additional glasshouse studies subjected a wide range of Australian L. rigidum haplotypes and international annual Lolium accessions to a suite of analyses to determine alkaloid levels and profiles. Again, NFL and NANL were the key lolines produced, with NFL consistently predominating. Considerable variation in alkaloid production was found both within and between biotypes and accessions evaluated under identical conditions, at the same maturation stage and on the same tissue type. The pyrrolopyrazine alkaloid peramine was also present in 8 out of 17 Australian biotypes of L. rigidum and 7 out of 33 international accessions infected with Epichloë spp.; the highest peramine concentrations were observed in seed extracts from L. rigidum collected from Australia. This study represents the first report of alkaloids from a geographically diverse collection of annual ryegrass germplasm infected with Epichloë spp. when grown under identical controlled conditions. PMID:26550846

  17. [Pyrrolizidine alkaloids and seneciosis in farm animals. Part 1: occurrence, chemistry and toxicology].

    PubMed

    Petzinger, E

    2011-01-01

    Pyrrolizidine alkaloids belong to a class of phytotoxins which are present in more than 6000 plant species. The disease seneciosis in farm animals represents the severe poisoning by pyrrolizidine alkaloids from plants of the genus Senecio. This form of poisoning has been known since the end of the 19th century in Germany, the USA, Canada and New Zealand, and is mainly caused by Senecio jacobaea and related Senecio spp. in farm animals, including poultry. Animal poisoning by pyrrolizidine alkaloids is of worldwide importance. In Germany poisoning of horses and cattle by Senecio jacobaea, which was earlier named Schweinsberg disease, is of renewed relevance for veterinary medicine. The disease occurs almost entirely as a consequence of chronic poisoning and in general ends fatally. The ultimate cause is the formation of toxic metabolites of pyrrolizidine alkaloids in the liver, and their covalent binding to nucleic acids and proteins leading to liver cirrhosis. Because many pyrrolizidine alkaloids possess mutagenic, and a few also carcinogenic properties, European and international authorities are concerned about possible residue levels in food of animal origin. The review addresses in its first part several aspects, being the occurrence, the chemistry, and the toxicology of pyrrolizidine alkaloids as well as animal intoxications by poisonous plants. In the second part (46) clinical characteristics of animal seneciosis, the therapeutic interventions, the significant species differences and a critical assessment of so-called nontoxic amounts of Senecio plants in animal fodder with reference to cumulative lethal toxin doses are presented. PMID:22138830

  18. Transfer of bipiperidyl and quinolizidine alkaloids toViscum cruciatum Sieber (Loranthaceae) hemiparasitic onRetama sphaerocarpa boissier (Leguminosae).

    PubMed

    Martin Cordero, C; Gil Serrano, A M; Ayuso Gonzalez, M J

    1993-10-01

    Plant material ofViscum cruciatum Sieber contains bipiperidyl (ammodendrine) and quinolizidine alkaloids (lupanine, 5,6-dehydrolupanine, retamine, cytisine,N-methylcytisine). This plant obtains the alkaloids by root parasitism onRetama sphaerocarpa Boissier (host plant). These results have important implications forViscum ecology, for the study of herbivores that areViscum specialists, and in the development of systems for the investigation of the role of alkaloids as plant defenses. PMID:24248584

  19. Evidence of maternal provisioning of alkaloid-based chemical defenses in the strawberry poison frog Oophaga pumilio.

    PubMed

    Stynoski, Jennifer L; Torres-Mendoza, Yaritbel; Sasa-Marin, Mahmood; Saporito, Ralph A

    2014-03-01

    Many organisms use chemical defenses to reduce predation risk. Aposematic dendrobatid frogs sequester alkaloid-based chemical defenses from a diet of arthropods, but research on these defenses has been limited to adults. Herein, we investigate chemical defense across development in a dendrobatid frog, Oophaga pumilio. This species displays complex parental care: at hatching, mothers transport tadpoles to phytotelmata, and then return to supply them with an obligate diet of nutritive eggs for about six weeks. We collected eggs, tadpoles, juveniles, and adults of O. pumilio, and detected alkaloids in all life stages. The quantity and number of alkaloids increased with frog and tadpole size. We did not detect alkaloids in the earliest stage of tadpoles, but alkaloids were detected as trace quantities in nutritive eggs and as small quantities in ovarian eggs. Tadpoles hand-reared with eggs of an alkaloid-free heterospecific frog did not contain alkaloids. Alkaloids that are sequestered from terrestrial arthropods were detected in both adults and phytotelm-dwelling tadpoles that feed solely on nutritive eggs, suggesting that this frog may be the first animal known to actively provision post-hatch offspring with chemical defenses. Finally, we provide experimental evidence that maternally derived alkaloids deter predation of tadpoles by a predatory arthropod. PMID:24804437

  20. Changes in plant defense chemistry (pyrrolizidine alkaloids) revealed through high-resolution spectroscopy

    NASA Astrophysics Data System (ADS)

    Carvalho, Sabrina; Macel, Mirka; Schlerf, Martin; Moghaddam, Fatemeh Eghbali; Mulder, Patrick P. J.; Skidmore, Andrew K.; van der Putten, Wim H.

    2013-06-01

    Plant toxic biochemicals play an important role in defense against natural enemies and often are toxic to humans and livestock. Hyperspectral reflectance is an established method for primary chemical detection and could be further used to determine plant toxicity in the field. In order to make a first step for pyrrolizidine alkaloids detection (toxic defense compound against mammals and many insects) we studied how such spectral data can estimate plant defense chemistry under controlled conditions. In a greenhouse, we grew three related plant species that defend against generalist herbivores through pyrrolizidine alkaloids: Jacobaea vulgaris, Jacobaea erucifolia and Senecio inaequidens, and analyzed the relation between spectral measurements and chemical concentrations using multivariate statistics. Nutrient addition enhanced tertiary-amine pyrrolizidine alkaloids contents of J. vulgaris and J. erucifolia and decreased N-oxide contents in S. inaequidens and J. vulgaris. Pyrrolizidine alkaloids could be predicted with a moderate accuracy. Pyrrolizidine alkaloid forms tertiary-amines and epoxides were predicted with 63% and 56% of the variation explained, respectively. The most relevant spectral regions selected for prediction were associated with electron transitions and Csbnd H, Osbnd H, and Nsbnd H bonds in the 1530 and 2100 nm regions. Given the relatively low concentration in pyrrolizidine alkaloids concentration (in the order of mg g-1) and resultant predictions, it is promising that pyrrolizidine alkaloids interact with incident light. Further studies should be considered to determine if such a non-destructive method may predict changes in PA concentration in relation to plant natural enemies. Spectroscopy may be used to study plant defenses in intact plant tissues, and may provide managers of toxic plants, food industry and multitrophic-interaction researchers with faster and larger monitoring possibilities.

  1. Heterologous Expression of Lysergic Acid and Novel Ergot Alkaloids in Aspergillus fumigatus

    PubMed Central

    Robinson, Sarah L.

    2014-01-01

    Different lineages of fungi produce distinct classes of ergot alkaloids. Lysergic acid-derived ergot alkaloids produced by fungi in the Clavicipitaceae are particularly important in agriculture and medicine. The pathway to lysergic acid is partly elucidated, but the gene encoding the enzyme that oxidizes the intermediate agroclavine is unknown. We investigated two candidate agroclavine oxidase genes from the fungus Epichloë festucae var. lolii × Epichloë typhina isolate Lp1 (henceforth referred to as Epichloë sp. Lp1), which produces lysergic acid-derived ergot alkaloids. Candidate genes easH and cloA were expressed in a mutant strain of the mold Aspergillus fumigatus, which typically produces a subclass of ergot alkaloids not derived from agroclavine or lysergic acid. Candidate genes were coexpressed with the Epichloë sp. Lp1 allele of easA, which encodes an enzyme that catalyzed the synthesis of agroclavine from an A. fumigatus intermediate; the agroclavine then served as the substrate for the candidate agroclavine oxidases. Strains expressing easA and cloA from Epichloë sp. Lp1 produced lysergic acid from agroclavine, a process requiring a cumulative six-electron oxidation and a double-bond isomerization. Strains that accumulated excess agroclavine (as a result of Epichloë sp. Lp1 easA expression in the absence of cloA) metabolized it into two novel ergot alkaloids for which provisional structures were proposed on the basis of mass spectra and precursor feeding studies. Our data indicate that CloA catalyzes multiple reactions to produce lysergic acid from agroclavine and that combining genes from different ergot alkaloid pathways provides an effective strategy to engineer important pathway molecules and novel ergot alkaloids. PMID:25107976

  2. Identification and quantification of the main active anticancer alkaloids from the root of Glaucium flavum.

    PubMed

    Bournine, Lamine; Bensalem, Sihem; Wauters, Jean-Noël; Iguer-Ouada, Mokrane; Maiza-Benabdesselam, Fadila; Bedjou, Fatiha; Castronovo, Vincent; Bellahcène, Akeila; Tits, Monique; Frédérich, Michel

    2013-01-01

    Glaucium flavum is used in Algerian folk medicine to remove warts (benign tumors). Its local appellations are Cheqiq el-asfar and Qarn el-djedyane. We have recently reported the anti-tumoral activity of Glaucium flavum root alkaloid extract against human cancer cells, in vitro and in vivo. The principal identified alkaloid in the extract was protopine. This study aims to determine which component(s) of Glaucium flavum root extract might possess potent antitumor activity on human cancer cells. Quantitative estimation of Glaucium flavum alkaloids was realized by HPLC-DAD. Glaucium flavum effect on human normal and cancer cell viability was determined using WST-1 assay. Quantification of alkaloids in Glaucium flavum revealed that the dried root part contained 0.84% of protopine and 0.07% of bocconoline (w/w), while the dried aerial part contained only 0.08% of protopine, glaucine as the main alkaloid, and no bocconoline. In vitro evaluation of the growth inhibitory activity on breast cancer and normal cells demonstrated that purified protopine did not reproduce the full cytotoxic activity of the alkaloid root extract on cancer cell lines. On the other hand, bocconoline inhibited strongly the viability of cancer cells with an IC50 of 7.8 µM and only a low cytotoxic effect was observed against normal human cells. Our results showed for the first time that protopine is the major root alkaloid of Glaucium flavum. Finally, we are the first to demonstrate a specific anticancer effect of Glaucium flavum root extract against breast cancer cells, which can be attributed, at least in part, to bocconoline. PMID:24317429

  3. Differences in Tolerance to Host Cactus Alkaloids in Drosophila koepferae and D. buzzatii

    PubMed Central

    Soto, Ignacio M.; Carreira, Valeria P.; Corio, Cristian; Padró, Julián; Soto, Eduardo M.; Hasson, Esteban

    2014-01-01

    The evolution of cactophily in the genus Drosophila was a major ecological transition involving over a hundred species in the Americas that acquired the capacity to cope with a variety of toxic metabolites evolved as feeding deterrents in Cactaceae. D. buzzatii and D. koepferae are sibling cactophilic species in the D. repleta group. The former is mainly associated with the relatively toxic-free habitat offered by prickly pears (Opuntia sulphurea) and the latter has evolved the ability to use columnar cacti of the genera Trichocereus and Cereus that contain an array of alkaloid secondary compounds. We assessed the effects of cactus alkaloids on fitness-related traits and evaluated the ability of D. buzzatii and D. koepferae to exploit an artificial novel toxic host. Larvae of both species were raised in laboratory culture media to which we added increasing doses of an alkaloid fraction extracted from the columnar cactus T. terschekii. In addition, we evaluated performance on an artificial novel host by rearing larvae in a seminatural medium that combined the nutritional quality of O. sulphurea plus amounts of alkaloids found in fresh T. terschekii. Performance scores in each rearing treatment were calculated using an index that took into account viability, developmental time, and adult body size. Only D. buzzatii suffered the effects of increasing doses of alkaloids and the artificial host impaired viability in D. koepferae, but did not affect performance in D. buzzatii. These results provide the first direct evidence that alkaloids are key determinants of host plant use in these species. However, the results regarding the artificial novel host suggest that the effects of alkaloids on performance are not straightforward as D. koepferae was heavily affected. We discuss these results in the light of patterns of host plan evolution in the Drosophila repleta group. PMID:24520377

  4. Differences in tolerance to host cactus alkaloids in Drosophila koepferae and D. buzzatii.

    PubMed

    Soto, Ignacio M; Carreira, Valeria P; Corio, Cristian; Padró, Julián; Soto, Eduardo M; Hasson, Esteban

    2014-01-01

    The evolution of cactophily in the genus Drosophila was a major ecological transition involving over a hundred species in the Americas that acquired the capacity to cope with a variety of toxic metabolites evolved as feeding deterrents in Cactaceae. D. buzzatii and D. koepferae are sibling cactophilic species in the D. repleta group. The former is mainly associated with the relatively toxic-free habitat offered by prickly pears (Opuntia sulphurea) and the latter has evolved the ability to use columnar cacti of the genera Trichocereus and Cereus that contain an array of alkaloid secondary compounds. We assessed the effects of cactus alkaloids on fitness-related traits and evaluated the ability of D. buzzatii and D. koepferae to exploit an artificial novel toxic host. Larvae of both species were raised in laboratory culture media to which we added increasing doses of an alkaloid fraction extracted from the columnar cactus T. terschekii. In addition, we evaluated performance on an artificial novel host by rearing larvae in a seminatural medium that combined the nutritional quality of O. sulphurea plus amounts of alkaloids found in fresh T. terschekii. Performance scores in each rearing treatment were calculated using an index that took into account viability, developmental time, and adult body size. Only D. buzzatii suffered the effects of increasing doses of alkaloids and the artificial host impaired viability in D. koepferae, but did not affect performance in D. buzzatii. These results provide the first direct evidence that alkaloids are key determinants of host plant use in these species. However, the results regarding the artificial novel host suggest that the effects of alkaloids on performance are not straightforward as D. koepferae was heavily affected. We discuss these results in the light of patterns of host plan evolution in the Drosophila repleta group. PMID:24520377

  5. The Only African Wild Tobacco, Nicotiana africana: Alkaloid Content and the Effect of Herbivory

    PubMed Central

    Marlin, Danica; Nicolson, Susan W.; Yusuf, Abdullahi A.; Stevenson, Philip C.; Heyman, Heino M.; Krüger, Kerstin

    2014-01-01

    Herbivory in some Nicotiana species is known to induce alkaloid production. This study examined herbivore-induced defenses in the nornicotine-rich African tobacco N. africana, the only Nicotiana species indigenous to Africa. We tested the predictions that: 1) N. africana will have high constitutive levels of leaf, flower and nectar alkaloids; 2) leaf herbivory by the African bollworm Helicoverpa armigera will induce increased alkaloid levels in leaves, flowers and nectar; and 3) increased alkaloid concentrations in herbivore-damaged plants will negatively affect larval growth. We grew N. africana in large pots in a greenhouse and exposed flowering plants to densities of one, three and six fourth-instar larvae of H. armigera, for four days. Leaves, flowers and nectar were analyzed for nicotine, nornicotine and anabasine. The principal leaf alkaloid was nornicotine (mean: 28 µg/g dry mass) followed by anabasine (4.9 µg/g) and nicotine (0.6 µg/g). Nornicotine was found in low quantities in the flowers, but no nicotine or anabasine were recorded. The nectar contained none of the alkaloids measured. Larval growth was reduced when leaves of flowering plants were exposed to six larvae. As predicted by the optimal defense theory, herbivory had a localized effect and caused an increase in nornicotine concentrations in both undamaged top leaves of herbivore damaged plants and herbivore damaged leaves exposed to one and three larvae. The nicotine concentration increased in damaged compared to undamaged middle leaves. The nornicotine concentration was lower in damaged leaves of plants exposed to six compared to three larvae, suggesting that N. africana rather invests in new growth as opposed to protecting older leaves under severe attack. The results indicate that the nornicotine-rich N. africana will be unattractive to herbivores and more so when damaged, but that potential pollinators will be unaffected because the nectar remains alkaloid-free even after herbivory. PMID:25025217

  6. The only African wild tobacco, Nicotiana africana: alkaloid content and the effect of herbivory.

    PubMed

    Marlin, Danica; Nicolson, Susan W; Yusuf, Abdullahi A; Stevenson, Philip C; Heyman, Heino M; Krüger, Kerstin

    2014-01-01

    Herbivory in some Nicotiana species is known to induce alkaloid production. This study examined herbivore-induced defenses in the nornicotine-rich African tobacco N. africana, the only Nicotiana species indigenous to Africa. We tested the predictions that: 1) N. africana will have high constitutive levels of leaf, flower and nectar alkaloids; 2) leaf herbivory by the African bollworm Helicoverpa armigera will induce increased alkaloid levels in leaves, flowers and nectar; and 3) increased alkaloid concentrations in herbivore-damaged plants will negatively affect larval growth. We grew N. africana in large pots in a greenhouse and exposed flowering plants to densities of one, three and six fourth-instar larvae of H. armigera, for four days. Leaves, flowers and nectar were analyzed for nicotine, nornicotine and anabasine. The principal leaf alkaloid was nornicotine (mean: 28 µg/g dry mass) followed by anabasine (4.9 µg/g) and nicotine (0.6 µg/g). Nornicotine was found in low quantities in the flowers, but no nicotine or anabasine were recorded. The nectar contained none of the alkaloids measured. Larval growth was reduced when leaves of flowering plants were exposed to six larvae. As predicted by the optimal defense theory, herbivory had a localized effect and caused an increase in nornicotine concentrations in both undamaged top leaves of herbivore damaged plants and herbivore damaged leaves exposed to one and three larvae. The nicotine concentration increased in damaged compared to undamaged middle leaves. The nornicotine concentration was lower in damaged leaves of plants exposed to six compared to three larvae, suggesting that N. africana rather invests in new growth as opposed to protecting older leaves under severe attack. The results indicate that the nornicotine-rich N. africana will be unattractive to herbivores and more so when damaged, but that potential pollinators will be unaffected because the nectar remains alkaloid-free even after herbivory. PMID:25025217

  7. Antiplasmodial and antioxidant isoquinoline alkaloids from Dehaasia longipedicellata.

    PubMed

    Zahari, Azeana; Cheah, Foo Kit; Mohamad, Jamaludin; Sulaiman, Syazreen Nadia; Litaudon, Marc; Leong, Kok Hoong; Awang, Khalijah

    2014-05-01

    The crude extract of the bark of Dehaasia longipedicellata exhibited antiplasmodial activity against the growth of Plasmodium falciparum K1 isolate (resistant strain). Phytochemical studies of the extract led to the isolation of six alkaloids: two morphinandienones, (+)-sebiferine (1) and (-)-milonine (2); two aporphines, (-)-boldine (3) and (-)-norboldine (4); one benzlyisoquinoline, (-)-reticuline (5); and one bisbenzylisoquinoline, (-)-O-O-dimethylgrisabine (6). Their structures were determined on the basis of 1D and 2D?NMR, IR, UV, and LCMS spectroscopic techniques and upon comparison with literature values. Antiplasmodial activity was determined for all of the isolated compounds. They showed potent to moderate activity with IC50 values ranging from 0.031 to 30.40?µM. (-)-O-O-dimethylgrisabine (6) and (-)-milonine (2) were the two most potent compounds, with IC50 values of 0.031 and 0.097?µM, respectively, that were comparable to the standard, chloroquine (0.090?µM). The compounds were also assessed for their antioxidant activities with di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (IC50?=?18.40-107.31?µg/mL), reducing power (27.40-87.40?%), and metal chelating (IC50?=?64.30 to 257.22?µg/mL) having good to low activity. (-)-O-O-dimethylgrisabine (6) exhibited a potent antioxidant activity of 44.3?% reducing power, while di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium and metal chelating activities had IC50 values of 18.38 and 64.30?µg/mL, respectively. Thus it may be considered as a good reductant with the ability to chelate metal and prevent pro-oxidant activity. In addition to the antiplasmodial and antioxidant activities, the isolated compounds were also tested for their cytotoxicity against a few cancer and normal cell lines. (-)-Norboldine (4) exhibited potent cytotoxicity towards pancreatic cancer cell line BxPC-3 with an IC50 value of 27.060?±?1.037?µM, and all alkaloids showed no toxicity towards the normal pancreatic cell line (hTERT-HPNE). PMID:24723007

  8. Cyclolization of D-lysergic acid alkaloid peptides.

    PubMed

    Havemann, Judith; Vogel, Dominik; Loll, Bernhard; Keller, Ullrich

    2014-01-16

    The tripeptide chains of the ergopeptines, a class of pharmacologically important D-lysergic acid alkaloid peptides, are arranged in a unique bicyclic cyclol based on an amino-terminal ?-hydroxyamino acid and a terminal orthostructure. D-lysergyl-tripeptides are assembled by the nonribosomal peptide synthetases LPS1 and LPS2 of the ergot fungus Claviceps purpurea and released as N-(D-lysergyl-aminoacyl)-lactams. We show total enzymatic synthesis of ergopeptines catalyzed by a Fe²?/2-ketoglutarate-dependent dioxygenase (EasH) in conjunction with LPS1/LPS2. Analysis of the reaction indicated that EasH introduces a hydroxyl group into N-(D-lysergyl-aminoacyl)-lactam at ?-C of the aminoacyl residue followed by spontaneous condensation with the terminal lactam carbonyl group. Sequence analysis revealed that EasH belongs to the wide and diverse family of the phytanoyl coenzyme A hydroxylases. We provide a high-resolution crystal structure of EasH that is most similar to that of phytanoyl coenzyme A hydroxylase, PhyH, from human. PMID:24361048

  9. Anti-inflammatory sesquiterpene pyridine alkaloids from Tripterygium wilfordii.

    PubMed

    Gao, Chang; Huang, Xiao-Xiao; Bai, Ming; Wu, Jie; Li, Jian-You; Liu, Qing-Bo; Li, Ling-Zhi; Song, Shao-Jiang

    2015-09-01

    During a screening procedure involving higher plants to find novel candidates for use as anti-inflammatory agents, Tripterygium wilfordii Hook. f. was shown to exhibit considerable inhibitory activity. Five new sesquiterpene pyridine alkaloids, tripterygiumines S-W (1-4,15), along with 14 known dihydroagarofuran derivatives, were isolated from the roots of the T. wilfordii Hook. f. Their structures were established by extensive use of spectroscopic techniques, including 1D and 2D NMR spectroscopy and high-resolution mass spectrometry. All compounds were evaluated for their anti-inflammatory activity by measuring the nitric oxide production by the LPS-induced murine macrophage cell line RAW264.7. It was found that 1, 5, and 19 possessed potent nitric oxide inhibitory activity with IC50 values ranging from 2.99 to 28.80 ?M, without any effect on the cell viability of RAW264.7 cells. Accordingly, compounds 1, 5, and 19, especially 5, were identified as promising candidates for further scientific investigation of their potential use as anti-inflammatory agents. PMID:26071072

  10. Microwave Spectroscopy of Alkaloids: the Conformational Shapes of Nicotine

    NASA Astrophysics Data System (ADS)

    Grabow, Jens-Uwe; Mata, S.; López, J. C.; Pe?a, I.; Cabezas, C.; Blanco, S.; Alonso, J. L.

    2010-06-01

    Nicotinoid alkaloids consist of two ring systems connected via a C-C ?-bond: Joining pyridine either with a (substituted) pyrrolidine or piperidine ring system, pyrrolidinic or piperidinic nicotinoids are formed. Nicotine itself, consisting of pyridine and N-methylpyrrolidine, is the prototype pyrrolidinic nicotinoid. Its coupled heteoaromatic and heteroaliphatic ring systems exhibit three sites that allow for conformational flexibility: (I) puckering of the pyrrolidine ring (Eq./Ax. positions of the pyridine), (II) inversion of the N-methyl group (Eq./Ax. positions of the hydrogen), and (III) relative orientation of the two rings (Syn-Anti). Two conformations of nicotine have been observed using the In-phase/quadrature-phase-Modulation Passage-Acquired-Coherence Technique (IMPACT) Fourier Transform Microwave (FTMW) spectrometer in Valladolid. The preferred conformations are characterized by an equatorial (Eq.) pyridine moiety and equatorial (Eq.) N-CH_3 stereochemistry. The planes of two rings are almost perpendicular with respect to each other while exhibiting two low energy conformations, Syn and Anti, that differ by a 180° rotation about the C-C ?-bond. The Eq.-Eq. conformational preference is likely due to a weak hydrogen bond interaction between the nitrogen lone pair at the N-methylpyrroline and the closest hydrogen in pyridine. Supporting quantum-chemical calculations are also provided. Lavrich, R. J.; Suenram, R. D.; Plusquellic, D. F.; Davis, S. 58th International Symposium on Molecular Spectroscopy, Columbus, OH 2003, RH13.

  11. Antinociceptive profile of (-)-spectaline: a piperidine alkaloid from Cassia leptophylla.

    PubMed

    Alexandre-Moreira, Magna Suzana; Viegas, Claudio; Palhares de Miranda, Ana Luisa; Bolzani, Vanderlan da Silva; Barreiro, Eliezer J

    2003-09-01

    The antinociceptive activity of (-)-spectaline (1), a piperidine alkaloid isolated from Cassia leptophylla Vog. (Leguminosae), was investigated. We have also studied the acute oral toxicity of 1 in mice and it did not show any signals of toxicity in doses lower than 400 micromol/kg. The antinociceptive effect of 1 was evaluated on chemical (acetic acid, formalin and capsaicin) and thermal (hot plate and tail flick) pain models in mice, using classical standard drugs. Dipyrone ID (50) = 14.68 micromol/kg (4.8 mg/kg), indomethacin ID (50) = 0.78 micromol/kg (0.28 mg/kg) and (-)-spectaline ID (50) = 48.49 micromol/kg (15.75 mg/kg), all produced a significant inhibition of acetic acid-induced abdominal writhing in mice. (-)-Spectaline was inactive in the hyperalgesic model of formalin and did not show any central analgesic activity (hot plate and tail flick models). In the capsaicin-induced neurogenic pain model, (-)-spectaline presented an important inhibitory effect with an ID (50) = 20.81 microg/paw and dipyrone ID (50) = 19.89 microg/paw. The ensemble of results permitted us to identify 1 as an antinociceptive compound. The mechanism underlying this antinociceptive effect of 1 remains unknown, but the results suggest that such an effect could be related to pathways associated to vanilloid receptor systems. PMID:14598202

  12. Identification of genes induced in alkaloid-producing cultures of Claviceps sp.

    PubMed

    Arntz, C; Tudzynski, P

    1997-04-01

    In order to identify genes which are expressed during alkaloid synthesis in an axenic culture of Claviceps sp. (strain ATCC 26245), a cDNA library from a producing culture was differentially screened with cDNA from producing (cDNA+) and non-producing (cDNA-) cultures, respectively. Altogether, ten cDNA clones were obtained, the alkaloid-synthesis-correlated expression of which was confirmed by Northern analyses. Evaluation of their nucleotide and derived amino-acid sequences identified one gene unequivocally, coding for dimethylallyltryptophan-synthase (DMAT-S), the initial enzyme of the specific alkaloid pathway. For two other genes significant homologies to known fungal genes were detected: one clone showed homology to the Neurospora crassa ccg1 gene, coding for a clock-regulated putative general stress protein; seven cDNA clones, derived from the same gene, which is highly expressed under these conditions, contained typical hydrophobin domains and long stretches of asparagine/glycine repeats (like QID3 from Trichoderma harzianum), thus probably representing a cell-wall constituent. These data show that this is not only a successful approach to clone genes specific for the alkaloid-pathway of C. purpurea, but also of genes which might be involved in the differentiation of sclerotial hyphae, the prerequisite for alkaloid synthesis. PMID:9108144

  13. N-methyldecahydroquinolines: an unexpected class of alkaloids from Amazonian poison frogs (Dendrobatidae).

    PubMed

    Daly, John W; Ware, Nathaniel; Saporito, Ralph A; Spande, Thomas F; Garraffo, H Martin

    2009-06-01

    The dominant alkaloids previously identified in skin extracts of Amazonian dendrobatid frogs of the genus Ameerega are histrionicotoxins and 2,5-disubstituted decahydroquinolines. Analysis of alkaloids in skin extracts of Ameerega picta from Bolivia revealed that the alkaloid 257A, previously reported as a 2,5-disubstituted decahydroquinoline, is an N-methyl-2,5-disubstituted decahydroquinoline. We characterized alkaloids of another 12 of the more than 25 species recently assigned to the genus Ameerega, and five additional N-methyldecahydroquinolines were identified. In some cases, the relative configuration of the N-methyldecahydroquinolines was determined by comparison with the N-methylated products prepared from the corresponding 2,5-disubstituted decahydroquinolines of known relative configuration. A dietary source for N-methyldecahydroquinolines is unknown; however, myrmicine ants are the likely source for the 2,5-disubstituted decahydroquinolines. The alkaloids in skin extracts of three species of another genus of Amazonian poison frog, Adelphobates, were also characterized, but N-methyldecahydroquinolines were not detected. PMID:19432407

  14. Alkaloid metabolism in thrips-Papaveraceae interaction: recognition and mutual response.

    PubMed

    Schütz, Ingeborg; Moritz, Gerald B; Roos, Werner

    2014-01-15

    Frankliniella occidentalis (Pergande), the Western Flower Thrips (WFT), is a polyphagous and highly adaptable insect of the order Thysanoptera. It has a broad host range but is rarely found on Papaveraceae, which might be due to deterrent effects of alkaloids present in most species of this family. In order to test the adaptive potential of WFT, we investigated its interaction with two Papaveraceae offered as sole feeding source. We found that WFT are able to live and feed on leaves of Eschscholzia californica and Chelidonium majus. Both plants respond to thrips feeding by the enhanced production of benzophenanthridine alkaloids. Furthermore, cell cultures of E. californica react to water insoluble compounds prepared from adult thrips with enhanced alkaloid production. During feeding, WFT take up benzophenanthridine alkaloids from either plant and from an artificial feeding medium and convert them to their less toxic dihydroderivatives. This was shown in detail with sanguinarine, the most cytotoxic benzophenanthridine. A similar conversion is used in plants to prevent self-intoxication by their own toxins. We conclude that WFT causes a phytoalexin-like response in Papaveraceae, but is able to adapt to such host plants by detoxification of toxic alkaloids. PMID:24331426

  15. Luminescence and binding properties of two isoquinoline alkaloids chelerythrine and sanguinarine with ctDNA

    NASA Astrophysics Data System (ADS)

    Li, Junfen; Li, Baohong; Wu, Yanbo; Shuang, Shaomin; Dong, Chuan; Choi, Martin M. F.

    2012-09-01

    The binding mode and mechanism of the interactions between two planar cationic alkaloids chelerythrine (Che) and sanguinarine (San) with calf thymus DNA (ctDNA) were systematically investigated at pH 5.40 using UV-vis absorption spectroscopy, fluorescence spectroscopy and cyclic voltammetry. Che and San show strong fluorescence at 570 and 589 nm, respectively. Che displays fluorescence enhancement with ctDNA whereas the fluorescence of San is quenched on interaction with ctDNA. In addition, UV-vis spectra of both alkaloids show apparent hypochromicity and are bathochromic shifted, indicating that they could intercalate into ctDNA bases. The fluorescence polarization of Che and San increases in the presence of ctDNA, again implying the intercalation of two alkaloids with ctDNA. This conclusion was also supported by the results obtained from anion quenching and cyclic voltammetry. The binding constants of both alkaloids with ctDNA were calculated in the order of 105 L/mol. San binds with ctDNA 3-fold stronger than Che. The stoichiometric bindings are five nucleotides per Che or San. Electrostatic binding also exists between the alkaloids and DNA helix. Finally, theoretical calculations show that only certain parts of Che and San molecules intercalate into the DNA helix.

  16. Screening of Alkaloidal Fraction of Conium maculatum L. Aerial Parts for Analgesic and Antiinflammatory Activity

    PubMed Central

    Madaan, Reecha; Kumar, S.

    2012-01-01

    Conium maculatum Linn. (Umbelliferae) has been traditionally used in the treatment of spasmodic disorders, and to relieve nervous excitation, rheumatic pains in the old and feeble, pain in stomach, pain of gastric ulcer, nervousness and restlessness. Alkaloids have long been considered as bioactive group of constituents present in C. maculatum. Despite a long tradition of use, C. maculatum has not been evaluated pharmacologically to validate its traditional claims for analgesic and antiinflammatory activities. Thus, the present investigations were undertaken with an objective to evaluate alkaloidal fraction of C. maculatum aerial parts for analgesic and antiinflammatory activities. Test doses (100 or 200 mg/kg, p.o.) of alkaloidal fraction were evaluated for analgesic activity using tail flick test and antiinflammatory activity using carrageenan-induced paw oedema test in rats. Morphine (5 mg/kg, p.o.) and indomethacin (5 mg/kg, p.o.) were used as standard analgesic and antiinflammatory drugs, respectively. Alkaloidal fraction of the plant exhibited significant analgesic activity at a dose of 200 mg/kg as it showed significant increase in tail flicking reaction time with respect to the control during 2 h intervals of observation. It also exhibited significant antiinflammatory activity at a dose of 200 mg/kg as it inhibited paw oedema in rats to 71% and reduced the paw volume one-fourth to the control during 1st h of the study. The present investigations suggest that alkaloids are responsible for analgesic and antiinflammatory activities of C. maculatum. PMID:23716876

  17. Effects of dietary protein and lupine alkaloids on growth and survivorship ofSpodoptera eridania.

    PubMed

    Johnson, N D; Bentley, B L

    1988-05-01

    Toxic chemicals and nutrients are often positively correlated within and among plants. We studied how such correlations affect the suitability of plants as food for herbivores by assessing the growth and survivorship ofSpodoptera eridania (army worm) on artificial diets containing lupine alkaloids and casein. We found that (1) the effects of casein were determined by other dietary components: increased dietary casein led to increased larval growth only when the diet was also high in wheat germ. (2) Dietary alkaloids were effective at very low concentrations, reducing both growth and survivorship. The alkaloids lupanine and sparteine were not synergistic in their effects, and the interaction between alkaloids and casein was significant only in the low-wheat-germ diets. (3) The effects of casein and alkaloids were generally apparent only in the first instar, and the growth of fifth-instar larvae was unaffected by diet. (4) Using these artificial diet experiments, we can make simple predictions about the food quality of plants grown under various nutrient regimes. These predictions are consistant with recent ideas about optimal plant defenses. PMID:24276288

  18. Protein and alkaloid patterns of the floral nectar in some solanaceous species.

    PubMed

    Kerchner, András; Darók, Judit; Bacskay, Ivett; Felinger, Attila; Jakab, Gábor; Farkas, Ágnes

    2015-09-01

    The family Solanaceae includes several melliferous plants, which tend to produce copious amounts of nectar. Floral nectar is a chemically complex aqueous solution, dominated by sugars, but minor components such as amino acids, proteins, flavonoids and alkaloids are present as well. This study aimed at analysing the protein and alkaloid profile of the nectar in seven solanaceous species. Proteins were examined with SDS-PAGE and alkaloids were analyzed with HPLC. The investigation of protein profile revealed significant differences in nectar-protein patterns not only between different plant genera, but also between the three Nicotiana species investigated. SDS-PAGE suggested the presence of several Nectarin proteins with antimicrobial activity in Nicotiana species. The nectar of all tobacco species contained the alkaloid nicotine, N. tabacum having the highest nicotine content. The nectar of Brugmansia suaveolens, Datura stramonium, Hyoscyamus niger and Lycium barbarum contained scopolamine, the highest content of which was measured in B. suaveolens. The alkaloid concentrations in the nectars of most solanaceous species investigated can cause deterrence in honeybees, and the nectar of N. rustica and N. tabacum can be considered toxic for honeybees. PMID:26344026

  19. Alkaloid defenses of co-mimics in a putative Müllerian mimetic radiation

    PubMed Central

    2014-01-01

    Background Polytypism in aposematic species is unlikely according to theory, but commonly seen in nature. Ranitomeya imitator is a poison frog species exhibiting polytypic mimicry of three congeneric model species (R. fantastica, R. summersi, and two morphs of R. variabilis) across four allopatric populations (a "mimetic radiation"). In order to investigate chemical defenses in this system, a key prediction of Müllerian mimicry, we analyzed the alkaloids of both models and mimics from four allopatric populations. Results In this study we demonstrate distinct differences in alkaloid profiles between co-mimetic species within allopatric populations. We further demonstrate that R. imitator has a greater number of distinct alkaloid types than the model species and more total alkaloids in all but one population. Conclusions Given that R. imitator is the more abundant species in these populations, R. imitator is likely driving the majority of predator-learned avoidance in these complexes. The success of Ranitomeya imitator as a putative advergent mimic may be a direct result of differences in alkaloid sequestration. Furthermore, we propose that automimicry within co-mimetic species is an important avenue of research. PMID:24707851

  20. A general procedure for the enantioselective synthesis of the minor tobacco alkaloids nornicotine, anabasine, and anatabine.

    PubMed

    Ayers, Joshua T; Xu, Rui; Dwoskin, Linda P; Crooks, Peter A

    2005-01-01

    The minor tobacco alkaloids nornicotine, anabasine, and anatabine from Nicotiana tobacum are known to possess nicotinic receptor agonist activity, although they are relatively less potent than S-(-)-nicotine, the principal tobacco alkaloid. Previous pharmacological investigations and structure-activity studies have been limited owing to the lack of availability of the optically pure forms of these minor alkaloids. We now report a 2-step synthetic procedure for the enantioselective synthesis of the optical isomers of nornicotine and anabasine, and a modified procedure for the synthesis of anatabine enantiomers. These procedures involve initial formation of the chiral ketimine resulting from the condensation of either 1R, 2R, 5R-(+)- or 1S, 2S, 5S-(-)-2-hydroxy-3-pinanone with 3-(aminomethyl)pyridine followed by enantioselective C-alkylation with an appropriate halogenoalkane or halogenoalkene species, N-deprotection, and base-catalyzed intramolecular ring closure, to form the appropriate, chirally pure minor tobacco alkaloid. Using this approach, the R-(+)- and S-(-)-enantiomers of the above minor tobacco alkaloids were obtained in good overall chemical yield and excellent enantomeric excess. PMID:16353951

  1. Nicotine alkaloids as antioxidant and potential protective agents against in vitro oxidative haemolysis.

    PubMed

    Malczewska-Jaskó?a, Karolina; Jasiewicz, Beata; Mrówczy?ska, Lucyna

    2016-01-01

    The capacity of eleven nicotine alkaloids to reduce oxidative stress was investigated. In order to provide a structure-activity relationships analysis, new nicotine derivatives with a substituent introduced into the pyrrolidine ring were synthesized and investigated together with nicotine and its known analogs. All newly synthesized compounds were characterized by (1)H, (13)C NMR and EI-MS technique. The antioxidant properties of nicotine, its known analogs and newly produced derivatives, were evaluated by various antioxidant assays such 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH(•)) scavenging, ferrous ions (Fe(2+)) chelating activity and total reducing ability determination by Fe(3+) ? Fe(2+) transformation assay. The protective effects of all compounds tested against 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH) and tert-butyl hydroperoxide (t-BuOOH)-induced oxidative haemolysis and morphological injury of human erythrocytes, were estimated in vitro. The results showed that nicotine alkaloids exhibited various antiradical efficacy and antioxidant activity in a structure- and a dose-dependent manner. In addition, the capacity of nicotine alkaloids to protect erythrocytes from AAPH- and t-BuOOH-induced oxidative haemolysis, was dependent on its incubation time with cells. Our findings showed that chemical and biological investigations conducted simultaneously can provide comprehensive knowledge concerning the antioxidant potential of nicotine alkaloids. This knowledge can be helpful in better understanding the properties of nicotine alkaloids under oxidative stress conditions. PMID:26658032

  2. Alkaloid variation among epichloid endophytes of sleepygrass (Achnatherum robustum) and consequences for resistance to insect herbivores.

    PubMed

    Shymanovich, Tatsiana; Saari, Susanna; Lovin, Mary E; Jarmusch, Alan K; Jarmusch, Scott A; Musso, Ashleigh M; Charlton, Nikki D; Young, Carolyn A; Cech, Nadja B; Faeth, Stanley H

    2015-01-01

    Epichloid endophytes are well known symbionts of many cool-season grasses that may alleviate environmental stresses for their hosts. For example, endophytes produce alkaloid compounds that may be toxic to invertebrate or vertebrate herbivores. Achnatherum robustum, commonly called sleepygrass, was aptly named due to the presence of an endophyte that causes toxic effects to livestock and wildlife. Variation in alkaloid production observed in two A. robustum populations located near Weed and Cloudcroft in the Lincoln National Forest, New Mexico, suggests two different endophyte species are present in these populations. Genetic analyses of endophyte-infected samples revealed major differences in the endophyte alkaloid genetic profiles from the two populations, which were supported with chemical analyses. The endophyte present in the Weed population was shown to produce chanoclavine I, paspaline, and terpendoles, so thus resembles the previously described Epichloë funkii. The endophyte present in the Cloudcroft population produces chanoclavineI, ergonovine, lysergic acid amide, and paspaline, and is an undescribed endophyte species. We observed very low survival rates for aphids feeding on plants infected with the Cloudcroft endophyte, while aphid survival was better on endophyte infected plants in the Weed population. This observation led to the hypothesis that the alkaloid ergonovine is responsible for aphid mortality. Direct testing of aphid survival on oat leaves supplemented with ergonovine provided supporting evidence for this hypothesis. The results of this study suggest that alkaloids produced by the Cloudcroft endophyte, specifically ergonovine, have insecticidal properties. PMID:25501262

  3. Phyrochemrsiry, 1978. Vol 17. p 172 Pergamon Press Pnnted m England ISOLATION OF THE PYRROLIZIDINE ALKALOID EUROPINE N-OXIDE FROM

    E-print Network

    Keinan, Ehud

    ALKALOID EUROPINE N-OXIDE FROM HELIOTROPIUM MARIS-MORTUI AND H. ROTUNDIFOLIUM L. H. ZALKOW*, L. GELBAUM-HeLiotropium maris-mortui; H. rotundifolium; Boraginaceae; pyrrolizidine alkaloid. europine N-oxide. Heliotropium,-H,O. The organic layer contained almost no material and gave no Mattocks test [I] for pyrrolizidine alkaloids

  4. Ergopeptine Alkaloid Production by Endophytes in a Common Tall Fescue Genotype iN. s. Hill,* W.A. Parrott, and D. D. Pope

    E-print Network

    Parrott, Wayne

    Ergopeptine Alkaloid Production by Endophytes in a Common Tall Fescue Genotype iN. s. Hill,* W Battista, 1990); however, the endophyte also pro- duces ergopeptine alkaloids, which are responsible consuming tall rescue herbage. Recent investi- .gations in which ergopeptine alkaloids were infused

  5. Synthesis and Anticancer Activity of all Known (-)-Agelastatin Alkaloids Page S1/ S35 Sunkyu Han, Dustin S. Siegel, Karen C. Morrison, Paul J. Hergenrother, and Mohammad Movassaghi

    E-print Network

    Hergenrother, Paul J.

    Synthesis and Anticancer Activity of all Known (-)-Agelastatin Alkaloids Page S1/ S35 Sunkyu Han and Anticancer Activity of All Known (­)-Agelastatin Alkaloids Sunkyu Han, Dustin S. Siegel, Karen C. Morrison Spectra S16 #12;Synthesis and Anticancer Activity of all Known (-)-Agelastatin Alkaloids Page S2/ S35

  6. The effects of methyllycaconitine on the response of TE-671 cells to acetylcholine and epibatidine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methyllycaconitine (MLA) is a norditerpenoid alkaloid found in Delphinium spp., and is a potent and selective antagonist of a7-nicotinic acetylcholine receptors. Plants with high concentrations of MLA are responsible for many livestock poisonings in the Intermountain West of the United States of Am...

  7. Serum Elimination Profiles of Methyllycaconitine and Deltaline in Cattle Following Oral Administration of Larkspur (Delphinium barbeyi)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objectives of this study were to describe the simple elimination kinetics of two abundant norditerpenoid alkaloids in larkspur, MLA and deltaline, and measure the heart rate response of intoxicated cattle over 96 hours. Five Angus steers halter broke, gentled, and habituated to metabolism crate...

  8. Distribution of Delphinium occidentale chemotypes and their potential toxicity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Larkspurs (Delphinium spp.) are poisonous plants found on rangelands in Western North America. Larkspur’s toxicity has been attributed to the norditerpenoid alkaloids which are divided into two main structural groups; the highly toxic (N-methylsuccinimido) anthranoyllycoctonine type (MSAL-type) and...

  9. Effects of the ergot alkaloids dihydroergotamine, ergonovine, and ergotamine on growth of Escherichia coli O157:H7 in vitro

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A series of experiments were conducted to evaluate the effects of ergot alkaloids (dihydroergotamine, ergonovine, and ergotamine) on E. coli O157:H7 in both pure and mixed ruminal fluid culture. Alkaloids were added to solutions of E. coli O157:H7 strains 933 (pure and ruminal cultures) and 6058 (r...

  10. Vasoconstrictive responses of the testicular and caudal arteries in bulls exposed to ergot alkaloids from tall fescue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Color Doppler ultasonography was used to evaluate vasoconstrictive responses of the testicular artery in yearling bulls to ergot alkaloids. Ergot alkaloid-induced constriction of the testicular artery could disrupt thermoregulation of the testes and reduce bull fertility. Luminal areas of the test...

  11. The Actions of Piperidine Alkaloids at Fetal Muscle-Type and Autonomic-Type Nicotinic Acetylcholine Receptors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Piperidine alkaloids are found in many species of plants including Conium maculatum, Nicotiana spp., and Lupinus spp. A pharmacodynamic comparison was made of the alkaloids ammodendrine, anabasine, anabaseine, and coniine in; SH-SY5Y cells which express autonomic-type nicotinic acetylcholine recept...

  12. The effect of varying alkaloid concentrations on the feeding behavior of gypsy moth larvae, Lymantria dispar (L.) (Lepidoptera: Lymantriidae)

    PubMed Central

    Shields, Vonnie D.C.; Smith, Kristen P.; Arnold, Nicole S.; Gordon, Ineta M.; Shaw, Taharah E.; Waranch, Danielle

    2010-01-01

    Nine alkaloids (acridine, aristolochic acid, atropine, berberine, caffeine, nicotine, scopolamine, sparteine, and strychnine) were evaluated as feeding deterrents for gypsy moth larvae (Lymantria dispar (L.); Lepidoptera: Lymantriidae). Our aim was to determine and compare the taste threshold concentrations, as well as the ED50 values, of the nine alkaloids to determine their potency as feeding deterrents. The alkaloids were applied to disks cut from red oak leaves (Quercus rubra) (L.), a plant species highly favored by larvae of this polyphagous insect species. We used two-choice feeding bioassays to test a broad range of biologically relevant alkaloid concentrations spanning five logarithmetic steps. We observed increasing feeding deterrent responses for all the alkaloids tested and found that the alkaloids tested exhibited different deterrency threshold concentrations ranging from 0.1 mM to 10 mM. In conclusion, it appears that this generalist insect species bears a relatively high sensitivity to these alkaloids, which confirms behavioral observations that it avoids foliage containing alkaloids. Berberine and aristolochic acid were found to have the lowest ED50 values and were the most potent antifeedants. PMID:21278814

  13. A reversed-phase HPLC-UV method developed and validated for simultaneous quantification of six alkaloids from Nicotiana spp.

    PubMed

    Moghbel, Nahid; Ryu, BoMi; Steadman, Kathryn J

    2015-08-01

    A reversed-phase HPLC-UV method was developed, optimized, and validated for the separation and quantitation of six target alkaloids from leaves of Nicotiana species (nicotine, nornicotine, anatabine, anabasine, myosmine, and cotinine). A bidentate reversed-phase C18 column was used as stationary phase and an alkaline ammonium formate buffer and acetonitrile as mobile phase. The alkaloids were well separated in a short run time of 13min with mobile phase pH 10.5 and a small gradient of 9-13% acetonitrile, and detected using UV at 260nm. Peak parameters were acceptable for all six closely related alkaloids. The proposed method has enough linearity with correlation coefficient >0.999 within the investigated range for all tested alkaloids. Satisfactory precision was achieved for both intra- and inter-day assay, with RSD less than 2% for all alkaloid standards. Reproducibility was also within the acceptable range of RSD <2%. Limit of detection was 1.6?g/mL for nicotine and below 1?g/mL for all other alkaloids. The limit of quantification was 2.8 and 4.8?g/mL for nornicotine and nicotine respectively, and below 2?g/mL for all other alkaloids. The method was successfully applied for simultaneous analysis of alkaloids in leaves of Nicotiana benthamiana. PMID:26114650

  14. The effect of body condition on disposition of alkaloids from silvery lupine (Lupinus argenteus pursh) in sheep.

    PubMed

    Lopez-Ortiz, S; Panter, K E; Pfister, J A; Launchbaugh, K L

    2004-09-01

    Several species of lupine (Lupinus spp.) are poisonous to livestock, producing death in sheep and "crooked calf disease" in cattle. Range livestock cope with poisonous plants through learned foraging strategies or mechanisms affecting toxicant disposition. When a toxic plant is eaten, toxicant clearance may be influenced by the animal's nutritional and/or physiological status. This research was conducted to determine whether differences in body condition or short-term nutritional supplementation of sheep altered the disposition of lupine alkaloids given as a single oral dose of ground silvery lupine (Lupinus argenteus) seed. Ewes in average body condition (ABC, n = 9) and low body condition (LBC, n = 10) received a single dose of ground lupine seeds including pods (8.5 g/kg BW) via gavage on the first day of the experiment, and were then randomly assigned to one of two nutritional supplement treatments. Blood samples were taken 0 to 60 h after dosing to compare blood alkaloid concentration and to evaluate alkaloid absorption and elimination profiles. Concentrations of total alkaloid and anagyrine, 5,6 dehydrolupanine, lupanine, and alkaloid E were measured in serum. These four alkaloids constituted 78 and 75% of the total alkaloid concentration in serum for LBC vs. ABC groups, respectively. Initial analysis indicated that short-term supplementation had no effect on alkaloid disposition, and supplementation was removed from the statistical model. The highest concentration of total alkaloids was observed 2 h after dosing. Overall, serum total alkaloid and anagyrine levels (area under the curve) were higher (P < 0.01) for sheep in the LBC group. Serum peak concentrations of total alkaloid and anagyrine were higher in LBC vs. ABC groups (P < 0.05). Serum elimination of anagyrine, unknown alkaloid E, and lupanine was decreased in LBC vs. ABC treatments (P < 0.05). These results demonstrate that body condition is important in the disposition of lupine alkaloids; however, further research is needed to determine the potential benefit, if any, that short-term nutritional supplementation might have on alkaloid disposition. PMID:15446497

  15. The orientation of protoberberine alkaloids and their binding activities to human serum albumin by surface-enhanced Raman scattering

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Zhao, Yu; Bai, Xueyuan; Wang, Yingping; Zhao, Daqing

    2011-03-01

    Raman and surface-enhanced Raman scattering (SERS) technique are reliably used to compare relative intensity shifts and to investigate the adsorption geometry of protoberberine alkaloids on Ag nanoparticles. We report joint application of fluorescence and SERS spectroscopy to study the interaction between protoberberine alkaloids and human serum albumin (HSA). We propose SERS technique to improve the quenching interaction caused by protoberberine alkaloids which are used to be applied in recognition process of fluorescent drugs with large biomolecules. The fluorescence results show that the fluorescence intensity of HSA is significantly decreased in presence of protoberberine alkaloids. The SERS technique demonstrates obvious advantages over direct measurements in discriminating and identifying pharmaceutical molecules. By means of this method, we are able to detect important information concerning the orientation of protoberberine alkaloids when interacting with HSA. We also show that the nitrogen atom is free, but a benzene ring and two adjacent methoxy groups are involved in the spontaneously electrostatic inducement and subsequently binding with HSA.

  16. Application of GC-MS/MS for the Analysis of Tobacco Alkaloids in Cigarette Filler and Various Tobacco Species

    PubMed Central

    Lisko, Joseph G.; Stanfill, Stephen B.; Duncan, Bryce W.; Watson, Clifford H.

    2015-01-01

    This publication reports the first known use of gas chromatography-tandem mass spectrometry for the quantitation of five minor tobacco alkaloids (nornicotine, myosmine, anabasine, anatabine and isonicoteine) in various tobacco samples. A summary of the concentrations of these minor alkaloid levels in the filler from 50 popular cigarette brands were found to be 659 – 986 ?g/g nornicotine, 8.64 – 17.3 ?g/g myosmine, 127 – 185 ?g/g anabasine, 927 – 1390 ?g/g anatabine, and 23.4 – 45.5 ?g/g isonicoteine. Levels of minor alkaloids found in reference cigarettes (1R5F, 2R4F, 3R4F, CM4 and CM6) as well as burley, flue-cured, oriental, reconstituted, Nicotiana rustica and Nicotiana glauca tobacco types are also reported. Quantitation of the minor tobacco alkaloids is important because the alkaloids have been shown to be precursors of carcinogenic tobacco specific N?-nitrosamines. PMID:23394466

  17. [Plant alkaloid from Ammopiptantus mongolia--an inhibitor of nitrogen oxide synthesis in animals].

    PubMed

    Burgedbazar, B; Kubrina, L N; Egorov, V Iu; Vanin, A F

    1991-01-01

    A decrease of the formation in the mouse liver of nitrogen oxide incorporated into ferrum mononitrozyl complexes (FMNC) with diethyldithiocarbamate (DETC) recorded by ESR method was discovered. This decrease was induced by one of the alkaloids isolated from Ammopiptantus mongolica which grows in the Gobi desert. This effect seems to be due to the antioxidant properties of the alkaloid under study. Alkaloid lessened the formation of FMNC with DETC both in the control animals and in those treated with lipopolysaccharide from E. coli initiating inflammation processes and intensification of NO synthesis. Proceeding from the data obtained it is suggested that free radicals reacting with the antioxidant affect NO formation by increasing the level of free calcium in the cell. PMID:1665346

  18. Exposure to Ergot Alkaloids During Gestation Reduces Fetal Growth in Sheep

    NASA Astrophysics Data System (ADS)

    Duckett, Susan; Pratt, Scott; Andrae, John

    2014-08-01

    Tall fescue [Lolium arundinaceum (Schreb.) Darbysh; Schedonorus phoenix (Scop.) Holub] is the primary cool season perennial grass in the eastern U.S. Most tall fescue contains an endophyte (Neotyphodium coenophialum), which produces ergot alkaloids that cause vasoconstriction and could restrict blood flow to the fetus in pregnant animals. The objective of this study was to examine fetal growth during maternal exposure to ergot alkaloids during gestation. Pregnant ewes (n = 16) were randomly assigned to one of two dietary treatments: 1) endophyte-infected (Neotyphodium coenophialum) tall fescue seed (E+; 0.8 ug of ergovaline /g diet DM) and 2) endophyte-free tall fescue seed (E-; 0.0 ug of ergovaline/g diet DM). Birth weight of lambs was reduced by 37% for E+ compared to E-. Organ and muscle weights were also lighter for E+ than E-. Exposure to ergot alkaloids in utero reduces fetal growth and muscle development.

  19. Cases of ergotism in livestock and associated ergot alkaloid concentrations in feed

    NASA Astrophysics Data System (ADS)

    Craig, A.; Klotz, James; Duringer, Jennifer

    2015-02-01

    Ergot-induced disease was known long before Biblical times and has been the root cause for countless human epidemics spanning from the early fourteenth century to the late sixteenth century. In contrast, many of these same ergot alkaloids have been utilized for their medicinal properties to mitigate migraine headaches and have had indications as anticarcinogens. Although ergot alkaloids have been used for centuries, basic pharmacokinetic data has not been documented for clinical disease. Consequently, a threshold dose and accurate dose-response data have yet to be established. Throughout the past several years, new detection techniques have emerged to detect these alkaloids at the parts per billion which have allowed for new efforts to be made with respect to determining threshold levels and making accurate clinical diagnoses. This perspectives article provides a critical initial step for establishing a uniform interpretation of ergot toxicosis from limited existing data.

  20. Differential effects of alkaloids on sodium currents of isolated single skeletal muscle fibers.

    PubMed

    Körper, S; Wink, M; Fink, R H

    1998-10-01

    The effects of the alkaloids ajmaline, lupanine, sparteine, serpentine, strychnine, and yohimbine were studied with the loose patch clamp technique on sodium currents of isolated single skeletal muscle fibers. The IC50 values for half-maximal blocking of the sodium currents were 6.6 microM for ajmaline, 55.7 microM for quinidine, 168.8 microM for sparteine, and 1.2 mM for lupanine. The observed Na+ channel inhibition is in accordance with the use of ajmaline, quinidine and sparteine as antiarrhythmic drugs. The interference of alkaloids with Na+ channels can also be interpreted as a means to strongly interfere with neuronal transmission in herbivores. Alkaloids thus serve as chemical defense compounds for the plants producing them. PMID:9781689

  1. Alkaloid-Containing Plants Poisonous to Cattle and Horses in Europe

    PubMed Central

    Cortinovis, Cristina; Caloni, Francesca

    2015-01-01

    Alkaloids, nitrogen-containing secondary plant metabolites, are of major interest to veterinary toxicology because of their occurrence in plant species commonly involved in animal poisoning. Based on epidemiological data, the poisoning of cattle and horses by alkaloid-containing plants is a relatively common occurrence in Europe. Poisoning may occur when the plants contaminate hay or silage or when forage alternatives are unavailable. Cattle and horses are particularly at risk of poisoning by Colchicum autumnale (meadow saffron), Conium maculatum (poison hemlock), Datura stramonium (jimson weed), Equisetum palustre (marsh horsetail), Senecio spp. (ragwort and groundsel) and Taxus baccata (European yew). This review of poisonous alkaloid-containing plants describes the distribution of these plants, conditions under which poisoning occurs, active toxic principles involved and subsequent clinical signs observed. PMID:26670251

  2. Total Syntheses of the Monoterpene Indole Alkaloids (±)-Alstilobanine A and E, and (±)-Angustilodine

    PubMed Central

    Feng, Yiqing; Majireck, Max M.

    2014-01-01

    A synthetic strategy has been developed culminating in stereoselective total syntheses of the small class of unusual monoterpenoid indole alkaloids exemplified by alstilobanine A (3) and E (2) and angustilodine (1). A pivotal step includes a novel intermolecular Michael-type addition of an indole ester dianion to a piperidine-derived nitrosoalkene to form the C15, C16 bond of the alkaloids. In addition, an application of the Romo protocol for effecting a stereoselective intramolecular nucleophile-assisted aldol-lactonization was employed, leading to a ?-lactone incorporating the requisite cis-fused 2-azadecalin moiety and also setting the C15, C19, C20 relative stereochemistry of the metabolites. It was then possible to stereoselectively effect an aldolization of a dianion derived from this indole ester ?-lactone intermediate with formaldehyde to introduce the requisite C16 hydroxymethyl group. Further manipulations of the system ultimately led to the three alkaloids in racemic form. PMID:24319990

  3. Host alkaloids differentially affect developmental stability and wing vein canalization in cactophilic Drosophila buzzatii.

    PubMed

    Padró, J; Carreira, V; Corio, C; Hasson, E; Soto, I M

    2014-12-01

    Host shifts cause drastic consequences on fitness in cactophilic species of Drosophila. It has been argued that changes in the nutritional values accompanying host shifts may elicit these fitness responses, but they may also reflect the presence of potentially toxic secondary compounds that affect resource quality. Recent studies reported that alkaloids extracted from the columnar cactus Trichocereus terscheckii are toxic for the developing larvae of Drosophila buzzatii. In this study, we tested the effect of artificial diets including increasing doses of host alkaloids on developmental stability and wing morphology in D. buzzatii. We found that alkaloids disrupt normal wing venation patterning and affect viability, wing size and fluctuating asymmetry, suggesting the involvement of stress-response mechanisms. Theoretical implications are discussed in the context of developmental stability, stress, fitness and their relationship with robustness, canalization and phenotypic plasticity. PMID:25366093

  4. Elucidating steroid alkaloid biosynthesis in Veratrum californicum: production of verazine in Sf9 cells.

    PubMed

    Augustin, Megan M; Ruzicka, Dan R; Shukla, Ashutosh K; Augustin, Jörg M; Starks, Courtney M; O'Neil-Johnson, Mark; McKain, Michael R; Evans, Bradley S; Barrett, Matt D; Smithson, Ann; Wong, Gane Ka-Shu; Deyholos, Michael K; Edger, Patrick P; Pires, J Chris; Leebens-Mack, James H; Mann, David A; Kutchan, Toni M

    2015-06-01

    Steroid alkaloids have been shown to elicit a wide range of pharmacological effects that include anticancer and antifungal activities. Understanding the biosynthesis of these molecules is essential to bioengineering for sustainable production. Herein, we investigate the biosynthetic pathway to cyclopamine, a steroid alkaloid that shows promising antineoplastic activities. Supply of cyclopamine is limited, as the current source is solely derived from wild collection of the plant Veratrum californicum. To elucidate the early stages of the pathway to cyclopamine, we interrogated a V. californicum RNA-seq dataset using the cyclopamine accumulation profile as a predefined model for gene expression with the pattern-matching algorithm Haystack. Refactoring candidate genes in Sf9 insect cells led to discovery of four enzymes that catalyze the first six steps in steroid alkaloid biosynthesis to produce verazine, a predicted precursor to cyclopamine. Three of the enzymes are cytochromes P450 while the fourth is a ?-aminobutyrate transaminase; together they produce verazine from cholesterol. PMID:25939370

  5. Cytotoxic esterified diterpenoid alkaloid derivatives with increased selectivity against a drug-resistant cancer cell line

    PubMed Central

    Wada, Koji; Ohkoshi, Emika; Morris-Natschke, Susan L.; Bastow, Kenneth F.; Lee, Kuo-Hsiung

    2011-01-01

    C-6 Esterifications of delpheline (1) were carried out to provide 20 new diterpenoid alkaloid derivatives (4–22, 24). Three natural alkaloids (1–3) and all synthesized compounds (4–25) were evaluated for cytotoxic activity against lung (A549), prostate (DU145), nasopharyngeal (KB), and vincristine-resistant nasopharyngeal (KB-VIN) cancer cell lines and interestingly, showed an improved drug resistance profile compared to paclitaxel. Particularly, 6-(4-fluoro-3-methylbenzoyl)delpheline (22) displayed 2.6-fold greater potency against KB-VIN cells compared with the parental non-drug resistant KB cells. 6-Acylation of 1 appears to be critical for producing cytotoxic activity in this alkaloid class and a means to provide promising new leads for further development into antitumor agents. PMID:22142543

  6. Enantiospecific Synthesis and Biological Investigations of a Nuphar Alkaloid: Proposed Structure of a Castoreum Component

    PubMed Central

    Seki, Hajime; Georg, Gunda I.

    2014-01-01

    An enantiospecific synthesis of a Nuphar alkaloid was achieved in 9 steps from N-Boc-(L)-proline. The alkaloid is a minor component of castoreum, the dried scent glands of the beaver. During the course of our study, the stereochemistry of three synthetic intermediates was verified by X-ray analysis, which contributes to resolving existing discrepancies among the literature reports regarding the synthesis of this particular compound. Based on our synthesis, we propose the structure of the natural product. Also, intrigued by castoreum’s therapeutic effect, which was used in ancient Greece and Rome for gynecological and other purposes, biological screening was conducted. We found that the alkaloid has affinity for the oxytocin receptor. PMID:25395879

  7. Alkaloid-Containing Plants Poisonous to Cattle and Horses in Europe.

    PubMed

    Cortinovis, Cristina; Caloni, Francesca

    2015-01-01

    Alkaloids, nitrogen-containing secondary plant metabolites, are of major interest to veterinary toxicology because of their occurrence in plant species commonly involved in animal poisoning. Based on epidemiological data, the poisoning of cattle and horses by alkaloid-containing plants is a relatively common occurrence in Europe. Poisoning may occur when the plants contaminate hay or silage or when forage alternatives are unavailable. Cattle and horses are particularly at risk of poisoning by Colchicum autumnale (meadow saffron), Conium maculatum (poison hemlock), Datura stramonium (jimson weed), Equisetum palustre (marsh horsetail), Senecio spp. (ragwort and groundsel) and Taxus baccata (European yew). This review of poisonous alkaloid-containing plants describes the distribution of these plants, conditions under which poisoning occurs, active toxic principles involved and subsequent clinical signs observed. PMID:26670251

  8. Large scale extraction of pyrrolizidine alkaloids from tansy ragwort (Senecio jacobaea).

    PubMed

    Craig, A M; Sheggeby, G; Wicks, C e

    1984-04-01

    A new technique of large-scale pyrrolizidine alkaloid (PA) extraction was developed in response to toxicity studies on food animals. Results of toxicity experiments on cattle vary from those on rodents (2); therefore, dose/response studies need to be germaine to the appropriate species. This new technique for extraction utilizes protonation of the ring nitrogen and partition of solvent to preferentially extract the alkaloid. The primary equipment used in the system we developed includes a large stainless-steel extraction/separation tank, holding tanks, and a 100-liter vacuum distillation system. From 23 kg of plant material of Senecio jacobaea , our system was able to produce 8-10 g of alkaloid per run, compared to the 3 g which we achieved using other extraction methods (2,4). Additional advantages of our system include a lower labor cost and the ability to recycle the organic solvent. PMID:6730295

  9. Enantiospecific Synthesis and Biological Investigations of a Nuphar Alkaloid: Proposed Structure of a Castoreum Component.

    PubMed

    Seki, Hajime; Georg, Gunda I

    2014-06-01

    An enantiospecific synthesis of a Nuphar alkaloid was achieved in 9 steps from N-Boc-(L)-proline. The alkaloid is a minor component of castoreum, the dried scent glands of the beaver. During the course of our study, the stereochemistry of three synthetic intermediates was verified by X-ray analysis, which contributes to resolving existing discrepancies among the literature reports regarding the synthesis of this particular compound. Based on our synthesis, we propose the structure of the natural product. Also, intrigued by castoreum's therapeutic effect, which was used in ancient Greece and Rome for gynecological and other purposes, biological screening was conducted. We found that the alkaloid has affinity for the oxytocin receptor. PMID:25395879

  10. Role of Glycols and Tweens in the Production of Ergot Alkaloids by Claviceps paspali

    PubMed Central

    Mizrahi, A.; Miller, G.

    1969-01-01

    Several glycols and Tweens markedly stimulated the production of ergot alkaloids in submerged cultures of Claviceps paspali. The role of these compounds was investigated in shake flasks and bench-scale fermentors. 2,3-Butanediol was not utilized by the fungus, and 1,2-propanediol-1-14C was not incorporated into the alkaloids. Glycols and Tweens lowered the surface tension of the basal medium and promoted the utilization of metabolites. In the presence of glycols and Tweens, an increased uptake of labeled sorbitol and succinic acid took place, whereas the specific radioactivity of the alkaloids was not affected. These results indicated that glycols and Tweens are not involved directly in the biosynthetic process; they apparently acted as surface-active agents, facilitating transport of metabolites into the cells. PMID:5776521

  11. The inhibition activity of selected beta-carboline alkaloids on enzymes of acetylcholinesterase and butyrylcholinesterase.

    PubMed

    Krsková, Zuzana; Martin, Jan; Dusek, Jaroslav

    2011-06-01

    This thesis deals with testing of inhibition activity beta-carboline alkaloids on activity of enzymes acetylcholinesterase (ACHE) and butyrylcholinesterase (BUCHE) using test "Fast Blue B salt" at TLC desk and Ellman's test using spectrophotometer. It was also investigated how dimethylsulfoxide used as a solvent in combination with water affects activity of enzymes and alkaloids. Results show harmine in form of base and salt in water and in mixture of DMSO and water has the hightest inhibition activity on ACHE using eserine as reference substance. Harmalol in form of salt in water and harmine in form of base and salt in mixture of DMSO and water has the hightest activity on BUCHE. It was find out that DMSO considerably affects activity of enzymes and alkaloids. PMID:21838142

  12. Main alkaloids of Peganum harmala L. and their different effects on dicot and monocot crops.

    PubMed

    Shao, Hua; Huang, Xiaoli; Zhang, Yuanming; Zhang, Chi

    2013-01-01

    Alkaloids with allelopathic activity are not as well-known as other allelochemicals. Our study revealed that total alkaloids from seeds of the medicinal plant Peganum harmala L. possessed significant growth inhibitory effect on four treated plants, with dicot plants (lettuce and amaranth) being more sensitive than the tested monocot plants (wheat and ryegrass). Further investigation led to the isolation of harmaline and harmine as the main active ingredients in the total alkaloids of P. harmala seeds. Harmaline exerted potent inhibitory effects on seedling growth of treated plants, especially dicots, inhibiting root elongation of lettuce and amaranth by 31% and 47% at a very low concentration (5 µg/mL), whereas harmine exhibited much weaker non-selective inhibitory effect on the plants. Considering the high yield and poor utilization of P. harmala in China, we anticipate that this plant could be exploited as an alternative weed management tool in the future. PMID:23446919

  13. Thin-Layer Chromatography/Desorption Electrospray Ionization Mass Spectrometry: Investigation of Goldenseal Alkaloids

    SciTech Connect

    Van Berkel, Gary J; Tomkins, Bruce A; Kertesz, Vilmos

    2007-01-01

    Desorption electrospray ionization mass spectrometry was investigated as a means to qualitatively identify and to quantify analytes directly from developed normal-phase thin layer chromatography plates. The atmospheric sampling capillary of a commercial ion trap mass spectrometer was extended to permit sampling and ionization of analytes in bands separated on intact TLC plates (up to 10 cm x 10 cm). A surface positioning software package and the appropriate hardware enabled computer-controlled surface scanning along the length of development lanes or at fixed RF value across the plates versus the stationary desorption electrospray emitter. Goldenseal (Hydrastis canadensis) and related alkaloids and commercial dietary supplements were used as standards and samples. Alkaloid standards and samples were spotted and separated on aluminum- or glass-backed plates using established literature methods. The mass spectral signal levels as a function of desorption spray solvent were investigated with acetonitrile proving superior to methanol. The detection levels (ca. 5 ng each or 14 -28 pmol) in mass spectral full scan mode were determined statistically from the calibration curves (2.5 - 100 pmol) for the standards berberine, palmatine and hydrastinine spotted as a mixture and separated on the plates. Qualitative screening of the major alkaloids present in six different over-the-counter "goldenseal" dietary supplements was accomplished by obtaining full scan mass spectra during surface scans along the development lane in the direction of increasing RF value. In one sample, alkaloids were detected that strongly suggested the presence of at least one additional herb undeclared on the product label. These same data indicated the misidentification of one of the alkaloids in the TLC literature. Quantities of the alkaloids present in two of the samples determined using the mass spectral data were in reasonable agreement with the label values indicating the quantitative ability of the method. The advantage of mass spectral measurements in identifying and quantifying materials within overlapping bands and in providing positive identification for even minor species in a mixture was also demonstrated.

  14. The interaction of telomere DNA G-quadruplex with three bis-benzyltetrahydroisoquinoline alkaloids.

    PubMed

    Ji, Xiaohui; Chen, Jiejun; Sun, Hongxia; Zhou, Huaxi; Xiang, Junfeng; Peng, An; Tang, Yalin; Zhao, Changqi

    2011-12-01

    Telomeres are important multifunctional nucleoprotein structures located at the ends of eukaryotic chromosomes. Telomerase regulates telomere elongation, and its activity is associated with tumorigenesis. Because the activity of telomerase can be inhibited by G-quadruplex (G4) formation (a four-stranded DNA with stacks of G-quartets formed by four guanines in a planar structure), the role of G4 in cancer therapy has attracted many research interests. We studied the effects of three natural alkaloids-tetrandrine, fangchinoline, and berbamine-on the stability and formation of telomere DNA G4 with circular dichroism melting spectroscopy (melting-CD), variable temperature ultraviolet (melting-UV), proton nuclear magnetic resonance spectroscopy ((1)H NMR), and molecular docking, and examined the relationships among the alkaloid structure and their activities. We further investigated their cytotoxicity with the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) and flow cytometry (FCM). The results demonstrated that alkaloids increased G4 stability and induced its formation, which added structure diversity of G4-ligands. The results showed that -OH at R(1), -OCH(3) at R(2), and [Formula: see text] at R(3) had higher stability than other substituent groups for these alkaloids. We also found a transition of antiparallel to parallel G4 as the temperature increased. The result indicated the possible advantage of parallel G4 in adversity. In addition, the alkaloids demonstrated a moderate cytotoxicity and proved to be cell cycle blocker in the G(1) phase. These alkaloids have revealed promising potentials to be the agents for antitumor therapy. PMID:22017543

  15. Plant-Symbiotic Fungi as Chemical Engineers: Multi-Genome Analysis of the Clavicipitaceae Reveals Dynamics of Alkaloid Loci

    PubMed Central

    Schardl, Christopher L.; Young, Carolyn A.; Hesse, Uljana; Amyotte, Stefan G.; Andreeva, Kalina; Calie, Patrick J.; Fleetwood, Damien J.; Haws, David C.; Moore, Neil; Oeser, Birgitt; Panaccione, Daniel G.; Schweri, Kathryn K.; Voisey, Christine R.; Farman, Mark L.; Jaromczyk, Jerzy W.; Roe, Bruce A.; O'Sullivan, Donal M.; Scott, Barry; Tudzynski, Paul; An, Zhiqiang; Arnaoudova, Elissaveta G.; Bullock, Charles T.; Charlton, Nikki D.; Chen, Li; Cox, Murray; Dinkins, Randy D.; Florea, Simona; Glenn, Anthony E.; Gordon, Anna; Güldener, Ulrich; Harris, Daniel R.; Hollin, Walter; Jaromczyk, Jolanta; Johnson, Richard D.; Khan, Anar K.; Leistner, Eckhard; Leuchtmann, Adrian; Li, Chunjie; Liu, JinGe; Liu, Jinze; Liu, Miao; Mace, Wade; Machado, Caroline; Nagabhyru, Padmaja; Pan, Juan; Schmid, Jan; Sugawara, Koya; Steiner, Ulrike; Takach, Johanna E.; Tanaka, Eiji; Webb, Jennifer S.; Wilson, Ella V.; Wiseman, Jennifer L.; Yoshida, Ruriko; Zeng, Zheng

    2013-01-01

    The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloë and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some—including the infamous ergot alkaloids—have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses. PMID:23468653

  16. Determination of pyrrolizidine alkaloids in honey from selected sites by solid phase extraction and HPLC-MS.

    PubMed

    Crews, C; Startin, J R; Clarke, P A

    1997-07-01

    A method was developed for the determination in honey of the Ragwort (Senecio jacobaea) derived pyrrolizidine alkaloids jacoline, jacozine, jacobine, seneciphylline and senecionine, combining solid-phase extraction with high performance liquid chromatography and atmospheric pressure chemical ionization mass spectrometric detection. The method allowed determination of individual alkaloids and offered a considerable improvement in terms of speed, sensitivity and specificity over previous approaches, but was not suitable for determination of jaconine, a minor alkaloid in Ragwort. Instrument calibrations were linear over the range 0.005 to 100 micrograms/ml, equivalent to approximately 0.001 to 2.0 mg/kg in honey with the extraction method used and allowing for observed recoveries. Detection limits in honey were 0.002 mg/kg. Recoveries for most of the alkaloids were between 57 and 70%. The alkaloids have been determined in a number of samples of honey selected after pollen identification and counting. The alkaloids were not detectable in samples containing two grains or less of Ragwort pollen per gram of honey. Samples collected in late July and August contained Ragwort pollen at 15-21 grains/g and total alkaloid concentrations of 0.011-0.056 mg/kg. Similar contributions to the total were made by jacozine, seneciophylline and senecionine, with jacobine making a larger and jacoline a smaller contribution. Two samples of honey containing Ragwort pollen at 24 and 16 grains/g had total alkaloid concentrations of 0.42 and 1.48 mg/kg respectively (not corrected for recovery). The alkaloid profile in these samples was dominated by seneciphylline and senecionine which together comprised 90-95% of the total. Alkaloids were not detected in retail honeys. PMID:9328525

  17. Alkaloids of the South African Amaryllidaceae: a review.

    PubMed

    Nair, Jerald J; Bastida, Jaume; Codina, Caries; Viladomat, Francesc; van Staden, Johannes

    2013-09-01

    The plant family Amaryllidaceae is known for its horticultural and ornamental appeal as well as its medicinal value. In relation to these characteristics, trade in Amaryllid flower varieties (especially daffodils) is a multi-million dollar revenue generator for the floriculture industry. Of greater significance are the medicinal attributes of the family, which has already spawned the Alzheimer's prescription drug galanthamine, a potent and selective inhibitor of the enzyme acetylcholinesterase, of significance in the progression of neurodegeneration associated with motor neuron diseases, with annual global sales of around $150 million. Furthermore, it is anticipated that an anticancer drug target related to the Amaryllidaceae alkaloid pancratistatin, presently under advanced clinical evaluation, will enter commercial circulation within the next decade. Members of the Amaryllidaceae are distributed through both tropical and subtropical regions of the globe, but are of prominence within three distinct geographical locations, including Andean South America, the Mediterranean basin, and southern Africa. The southern African zone is known to harbor at least a third of the worldwide complement of around 1000 species, many of which are widely utilized in the traditional medicinal practices of the indigenous people of the region. Given its therapeutic and economic value, its natural abundance in the southern African region, coupled to its widespread usage in ethnic medicine, the family Amaryllidaceae provides a diverse and accessible platform for phytochemical based drug discovery. A consolidation of its traditional usage as well as its chemical and pharmacological profiles will thus guide efforts aimed at maximizing this potential. In undertaking this survey of the Amaryllidaceae of southern African, we aimed to achieve these goals. PMID:24273880

  18. Comparative Analysis of Amaryllidaceae Alkaloids from Three Lycoris Species.

    PubMed

    Tian, Yongqiang; Zhang, Chunyun; Guo, Mingquan

    2015-01-01

    The major active constituents from Amaryllidaceae family were reported to be Amaryllidaceae alkaloids (AAs), which exhibited a wide spectrum of biological activities, such as anti-tumor, anti-viral, and acetyl-cholinesterase-inhibitory activities. In order to better understand their potential as a source of bioactive AAs and the phytochemical variations among three different species of Lycoris herbs, the HPLC fingerprint profiles of Lycoris aurea (L. aurea), L. radiata, and L. guangxiensis were firstly determined and compared using LC-UV and LC-MS/MS. As a result, 39 peaks were resolved and identified as AAs, of which nine peaks were found in common for all these three species, while the other 30 peaks could be revealed as characteristic AAs for L. aurea, L. radiata and L. guangxiensis, respectively. Thus, these AAs can be used as chemical markers for the identification and quality control of these plant species. To further reveal correlations between chemical components and their pharmaceutical activities of these species at the molecular level, the bioactivities of the total AAs from the three plant species were also tested against HepG2 cells with the inhibitory rate at 78.02%, 84.91% and 66.81% for L. aurea, L. radiata and L. guangxiensis, respectively. This study firstly revealed that the three species under investigation were different not only in the types of AAs, but also in their contents, and both contributed to their pharmacological distinctions. To the best of our knowledge, the current research provides the most detailed phytochemical profiles of AAs in these species, and offers valuable information for future valuation and exploitation of these medicinal plants. PMID:26690108

  19. Production of Peptide Ergot Alkaloids in Submerged Culture by Three Isolates of Claviceps purpurea

    PubMed Central

    Amici, A. M.; Minghetti, A.; ScottI, T.; Spalla, C.; Tognoli, L.

    1969-01-01

    Three strains of Claviceps purpurea (Fr.) Tul., isolated from sclerotia grown on rye, produce under submerged conditions ergocryptine and ergotamine, ergocornine and ergosine, and ergocristine, respectively. All of the strains either lacked the ability to produce conidia or formed them sparingly, but they accumulated large quantities of lipids and sterols. The fermentations are typically divided into two phases. The first is characterized by the rapid utilization and exhaustion of the phosphate contained in the medium, rapid uptake of ammonium nitrogen and of citric acid, rapid growth, and low alkaloid production; the second phase is characterized by slower growth and by a marked accumulation of lipids, sterols, and alkaloids. PMID:5373678

  20. Three new alkaloids and three new phenolic glycosides from Liparis odorata.

    PubMed

    Jiang, Piao; Liu, Hongdong; Xu, Xianghong; Liu, Bo; Zhang, Dongming; Lai, Xuewen; Zhu, Genghua; Xu, Peng; Li, Bin

    2015-12-01

    Three new alkaloids, liparis alkaloid A (1), B (2), C (3), and three new phenolic glycosides, liparis glycoside H (4), I (5), J (6), together with three known phenolic glycosides (7-9) were isolated from the whole plant of Liparis odorata. Their structures were characterized on the basis of extensive 1D-, 2D-NMR and HR-ESI-MS experiments. In addition, compounds 1-3 revealed hypolipidemic effects in the in vitro bioassays, and the ability to inhibit LPS-induced NO production of these isolated phenolic glycosides (4-9) was also evaluated. PMID:26481137

  1. Relationships among Ergot Alkaloids, Cytochrome P450 Activity, and Beef Steer Growth

    NASA Astrophysics Data System (ADS)

    Rosenkrans, Charles; Ezell, Nicholas

    2015-03-01

    Determining a grazing animal’s susceptibility to ergot alkaloids has been a research topic for decades. Our objective was to determine if the Promega™ P450-Glo assay could be used to indirectly detect ergot alkaloids or their metabolites in urine of steers. The first experiment validated the effects of ergot alkaloids [0, 20, and 40 ?M of ergotamine (ET), dihydroergotamine (DHET), and ergonovine (EN)] on human CYP3A4 using the P450-Glo assay (Promega™ V9800). With this assay, luminescence is directly proportional to CYP450 activity. Relative inhibition of in vitro cytochrome P450 activity was affected (P < 0.001) by an interaction between alkaloids and concentration. That interaction resulted in no concentration effect of EN, but within ET and DHET 20 and 40 µM concentrations inhibited CYP450 activity when compared with controls. In experiment 2, urine was collected from Angus-sired crossbred steers (n = 39; 216 ± 2.6 d of age; 203 ± 1.7 kg) after grazing tall fescue pastures for 105 d. Non-diluted urine was added to the Promega™ P450-Glo assay, and observed inhibition (3.7 % ± 2.7 of control). Urine content of total ergot alkaloids (331.1 ng/mg of creatinine ± 325.7) was determined using enzyme linked immunosorbent assay. Urine inhibition of CYP450 activity and total alkaloids were correlated (r = -0.31; P < 0.05). Steers were genotyped at CYP450 single nucleotide polymorphism, C994G. Steer genotype affected (P < 0.03) inhibition of CYP450 activity by urine; heterozygous steers had the least amount of CYP450 inhibition suggesting that genotyping cattle may be a method of identifying animals that are susceptible to ergot alkaloids. Although, additional research is needed, we demonstrate that the Promega™ P450-Glo assay is sensitive to ergot alkaloids and urine from steers grazing tall fescue. With some refinement the P450-Glo assay has potential as a tool for screening cattle for their exposure to fescue toxins.

  2. Detecting potential teratogenic alkaloids from blue cohosh rhizomes using an in vitro rat embryo culture.

    PubMed

    Kennelly, E J; Flynn, T J; Mazzola, E P; Roach, J A; McCloud, T G; Danford, D E; Betz, J M

    1999-10-01

    The novel alkaloid thalictroidine (1), as well as the known alkaloids taspine (2), magnoflorine (3), anagyrine (4), baptifoline (5), 5,6-dehydro-alpha-isolupanine (6), alpha-isolupanine (7), lupanine (8), N-methylcytisine (9), and sparteine (10), were identified from an extract of Caulophyllum thalictroides rhizomes. N-Methylcytisine exhibited teratogenic activity in the rat embryo culture (REC), an in vitro method to detect potential teratogens. The structure of 1 was elucidated using various spectroscopic methods, primarily by NMR techniques. Thalictroidine, anagyrine, and alpha-isolupanine were not teratogenic in the REC at tested concentrations. Taspine (2) showed high embryotoxicity, but no teratogenic activity, in the REC. PMID:10543898

  3. Relationships among ergot alkaloids, cytochrome P450 activity, and beef steer growth.

    PubMed

    Rosenkrans, Charles F; Ezell, Nicholas S

    2015-01-01

    Determining a grazing animal's susceptibility to ergot alkaloids has been a research topic for decades. Our objective was to determine if the Promega™ P450-Glo assay could be used to indirectly detect ergot alkaloids or their metabolites in urine of steers. The first experiment validated the effects of ergot alkaloids [0, 20, and 40 ?M of ergotamine (ET), dihydroergotamine (DHET), and ergonovine (EN)] on human CYP3A4 using the P450-Glo assay (Promega™ V9800). With this assay, luminescence is directly proportional to CYP450 activity. Relative inhibition of in vitro cytochrome P450 activity was affected (P < 0.001) by an interaction between alkaloids and concentration. That interaction resulted in no concentration effect of EN, but within ET and DHET 20 and 40 ?M concentrations inhibited CYP450 activity when compared with controls. In experiment 2, urine was collected from Angus-sired crossbred steers (n = 39; 216 ± 2.6 days of age; 203 ± 1.7 kg) after grazing tall fescue pastures for 105 days. Non-diluted urine was added to the Promega™ P450-Glo assay, and observed inhibition (3.7 % ± 2.7 of control). Urine content of total ergot alkaloids (331.1 ng/mg of creatinine ± 325.7) was determined using enzyme linked immunosorbent assay. Urine inhibition of CYP450 activity and total alkaloids were correlated (r = -0.31; P < 0.05). Steers were genotyped at CYP450 single nucleotide polymorphism, C994G. Steer genotype affected (P < 0.03) inhibition of CYP450 activity by urine; heterozygous steers had the least amount of CYP450 inhibition suggesting that genotyping cattle may be a method of identifying animals that are susceptible to ergot alkaloids. Although, additional research is needed, we demonstrate that the Promega™ P450-Glo assay is sensitive to ergot alkaloids and urine from steers grazing tall fescue. With some refinement the P450-Glo assay has potential as a tool for screening cattle for their exposure to fescue toxins. PMID:25815288

  4. Benzylisoquinoline alkaloids from the papaveraceae: the heritage of Johannes Gadamer (1867-1928).

    PubMed

    Meyer, Achim; Imming, Peter

    2011-11-28

    The substance archive of the laboratory of Johannes Gadamer (1867-1928), Marburg, Germany, was analyzed thoroughly with modern instrumental methods, with the samples purified when necessary, and the authenticity of the samples confirmed by historical and analytical evidence. Eight formerly unknown alkaloids of the benzylisoquinoline type were identified in the archive originally isolated from Corydalis cava or Fumaria vaillantii. This finding underscores the importance of the work of Johannes Gadamer and his group in stimulating overall progress in natural product chemistry. Several alkaloids were isolated by the group long before they were officially reported. PMID:22029392

  5. Relationships among ergot alkaloids, cytochrome P450 activity, and beef steer growth

    PubMed Central

    Rosenkrans, Charles F.; Ezell, Nicholas S.

    2015-01-01

    Determining a grazing animal's susceptibility to ergot alkaloids has been a research topic for decades. Our objective was to determine if the Promega™ P450-Glo assay could be used to indirectly detect ergot alkaloids or their metabolites in urine of steers. The first experiment validated the effects of ergot alkaloids [0, 20, and 40 ?M of ergotamine (ET), dihydroergotamine (DHET), and ergonovine (EN)] on human CYP3A4 using the P450-Glo assay (Promega™ V9800). With this assay, luminescence is directly proportional to CYP450 activity. Relative inhibition of in vitro cytochrome P450 activity was affected (P < 0.001) by an interaction between alkaloids and concentration. That interaction resulted in no concentration effect of EN, but within ET and DHET 20 and 40 ?M concentrations inhibited CYP450 activity when compared with controls. In experiment 2, urine was collected from Angus-sired crossbred steers (n = 39; 216 ± 2.6 days of age; 203 ± 1.7 kg) after grazing tall fescue pastures for 105 days. Non-diluted urine was added to the Promega™ P450-Glo assay, and observed inhibition (3.7 % ± 2.7 of control). Urine content of total ergot alkaloids (331.1 ng/mg of creatinine ± 325.7) was determined using enzyme linked immunosorbent assay. Urine inhibition of CYP450 activity and total alkaloids were correlated (r = ?0.31; P < 0.05). Steers were genotyped at CYP450 single nucleotide polymorphism, C994G. Steer genotype affected (P < 0.03) inhibition of CYP450 activity by urine; heterozygous steers had the least amount of CYP450 inhibition suggesting that genotyping cattle may be a method of identifying animals that are susceptible to ergot alkaloids. Although, additional research is needed, we demonstrate that the Promega™ P450-Glo assay is sensitive to ergot alkaloids and urine from steers grazing tall fescue. With some refinement the P450-Glo assay has potential as a tool for screening cattle for their exposure to fescue toxins. PMID:25815288

  6. Ergot alkaloid intoxication in perennial ryegrass (Lolium perenne): an emerging animal health concern in Ireland?

    PubMed

    Canty, Mary J; Fogarty, Ursula; Sheridan, Michael K; Ensley, Steve M; Schrunk, Dwayne E; More, Simon J

    2014-01-01

    Four primary mycotoxicosis have been reported in livestock caused by fungal infections of grasses or cereals by members of the Clavicipitaceae family. Ergotism (generally associated with grasses, rye, triticale and other grains) and fescue toxicosis (associated with tall fescue grass, Festuca arundinacea) are both caused by ergot alkaloids, and referred to as 'ergot alkaloid intoxication'. Ryegrass staggers (associated with perennial ryegrass Lolium perenne) is due to intoxication with an indole-diperpene, Lolitrem B, and metabolites. Fescue-associated oedema, recently described in Australia, may be associated with a pyrrolizidine alkaloid, N-acetyl norloline. Ergotism, caused by the fungus Claviceps purpurea, is visible and infects the outside of the plant seed. Fescue toxicosis and ryegrass staggers are caused by Neotyphodium coenophalium and N. lolii, respectively. Fescue-associated oedema has been associated with tall fescue varieties infected with a specific strain of N. coenophialum (AR542, Max P or Max Q). The name Neotyphodium refers to asexual derivatives of Epichloë spp., which have collectively been termed the epichloë fungi. These fungi exist symbiotically within the grass and are invisible to the naked eye. The primary toxicological effect of ergot alkaloid involves vasoconstriction and/or hypoprolactinaemia. Ingestion of ergot alkaloid by livestock can cause a range of effects, including poor weight gain, reduced fertility, hyperthermia, convulsions, gangrene of the extremities, and death. To date there are no published reports, either internationally or nationally, reporting ergot alkaloid intoxication specifically associated with perennial ryegrass endophytes. However, unpublished reports from the Irish Equine Centre have identified a potential emerging problem of ergot alkaloid intoxication with respect to equines and bovines, on primarily perennial ryegrass-based diets. Ergovaline has been isolated in varying concentrations in the herbage of a small number of equine and bovine farms where poor animal health and performance had been reported. Additionally, in some circumstances changes to the diet, where animals were fed primarily herbage, were sufficient to reverse adverse effects. Pending additional information, these results suggest that Irish farm advisors and veterinarians should be aware of the potential adverse role on animal health and performance of ergot alkaloids from perennial ryegrass infected with endophytic fungi. PMID:25295161

  7. Concise and Enantioselective Total Synthesis of (?)-Mehranine, (?)-Methylenebismehranine, and Related Aspidosperma Alkaloids**

    PubMed Central

    Mewald, Marius; Medley, Jonathan William; Movassaghi, Mohammad

    2014-01-01

    We report an efficient and highly stereoselective synthetic strategy for the synthesis of aspidosperma alkaloids based on the transannular cyclization of a chiral lactam precursor. Three new stereocenters are formed in this key step with excellent level of diastereoselection due to the conformational bias of the cyclization precursor, leading to a versatile pentacyclic intermediate. A subsequent stereoselective epoxidation followed by a mild formamide reduction enabled the first total synthesis of the aspidosperma alkaloids (?)-mehranine and (+)-(6S,7S)-dihydroxy-N-methylaspidospermidine. A late-stage scandium trifluoromethanesulfonate-mediated dimerization of (?)-mehranine enabled the first total synthesis of (?)-methylenebismehranine. PMID:25196158

  8. Ergot alkaloid intoxication in perennial ryegrass (Lolium perenne): an emerging animal health concern in Ireland?

    PubMed Central

    2014-01-01

    Four primary mycotoxicosis have been reported in livestock caused by fungal infections of grasses or cereals by members of the Clavicipitaceae family. Ergotism (generally associated with grasses, rye, triticale and other grains) and fescue toxicosis (associated with tall fescue grass, Festuca arundinacea) are both caused by ergot alkaloids, and referred to as ‘ergot alkaloid intoxication’. Ryegrass staggers (associated with perennial ryegrass Lolium perenne) is due to intoxication with an indole-diperpene, Lolitrem B, and metabolites. Fescue-associated oedema, recently described in Australia, may be associated with a pyrrolizidine alkaloid, N-acetyl norloline. Ergotism, caused by the fungus Claviceps purpurea, is visible and infects the outside of the plant seed. Fescue toxicosis and ryegrass staggers are caused by Neotyphodium coenophalium and N. lolii, respectively. Fescue-associated oedema has been associated with tall fescue varieties infected with a specific strain of N. coenophialum (AR542, Max P or Max Q). The name Neotyphodium refers to asexual derivatives of Epichloë spp., which have collectively been termed the epichloë fungi. These fungi exist symbiotically within the grass and are invisible to the naked eye. The primary toxicological effect of ergot alkaloid involves vasoconstriction and/or hypoprolactinaemia. Ingestion of ergot alkaloid by livestock can cause a range of effects, including poor weight gain, reduced fertility, hyperthermia, convulsions, gangrene of the extremities, and death. To date there are no published reports, either internationally or nationally, reporting ergot alkaloid intoxication specifically associated with perennial ryegrass endophytes. However, unpublished reports from the Irish Equine Centre have identified a potential emerging problem of ergot alkaloid intoxication with respect to equines and bovines, on primarily perennial ryegrass-based diets. Ergovaline has been isolated in varying concentrations in the herbage of a small number of equine and bovine farms where poor animal health and performance had been reported. Additionally, in some circumstances changes to the diet, where animals were fed primarily herbage, were sufficient to reverse adverse effects. Pending additional information, these results suggest that Irish farm advisors and veterinarians should be aware of the potential adverse role on animal health and performance of ergot alkaloids from perennial ryegrass infected with endophytic fungi. PMID:25295161

  9. Activities and Effects of Ergot Alkaloids on Livestock Physiology and Production

    PubMed Central

    Klotz, James L.

    2015-01-01

    Consumption of feedstuffs contaminated with ergot alkaloids has a broad impact on many different physiological mechanisms that alters the homeostasis of livestock. This change in homeostasis causes an increased sensitivity in livestock to perturbations in the ambient environment, resulting in an increased sensitivity to such stressors. This ultimately results in large financial losses in the form of production losses to livestock producers around the world. This review will focus on the underlying physiological mechanisms that are affected by ergot alkaloids that lead to decreases in livestock production. PMID:26226000

  10. Dispacamide E and other bioactive bromopyrrole alkaloids from two Indonesian marine sponges of the genus Stylissa.

    PubMed

    Ebada, Sherif S; Linh, Mai Hoang; Longeon, Arlette; de Voogd, Nicole J; Durieu, Emilie; Meijer, Laurent; Bourguet-Kondracki, Marie-Lise; Singab, Abdel Nasser B; Müller, Werner E G; Proksch, Peter

    2015-02-01

    Chemical investigation of methanolic extracts of the two Indonesian marine sponges Stylissa massa and Stylissa flabelliformis yielded 25 bromopyrrole alkaloids including 2 new metabolites. The structures of all isolated compounds were unambiguously elucidated based on extensive 1D and 2D NMR, LR-MS and HR-MS analyses. All isolated compounds were assayed for their antiproliferative and protein kinase inhibitory activities. Several of the tested compounds revealed selective activity(ies) which suggested preliminary SARs of the isolated bromopyrrole alkaloids. PMID:25116895

  11. Concise and enantioselective total synthesis of (-)-mehranine, (-)-methylenebismehranine, and related Aspidosperma alkaloids.

    PubMed

    Mewald, Marius; Medley, Jonathan William; Movassaghi, Mohammad

    2014-10-20

    We report an efficient and highly stereoselective strategy for the synthesis of Aspidosperma alkaloids based on the transannular cyclization of a chiral lactam precursor. Three new stereocenters are formed in this key step with excellent diastereoselectivity due to the conformational bias of the cyclization precursor, leading to a versatile pentacyclic intermediate. A subsequent stereoselective epoxidation followed by a mild formamide reduction enabled the first total synthesis of the Aspidosperma alkaloids (-)-mehranine and (+)-(6S,7S)-dihydroxy-N-methylaspidospermidine. A late-stage dimerization of (-)-mehranine mediated by scandium trifluoromethanesulfonate completed the first total synthesis of (-)-methylenebismehranine. PMID:25196158

  12. Evolution of a Strategy for Total Synthesis of the Marine Fungal Alkaloid (±)-Communesin F

    PubMed Central

    Seo, Jae Hong; Liu, Peng; Weinreb, Steven M.

    2010-01-01

    A new synthetic strategy for construction of the heptacyclic marine fungal alkaloid (±)-communesin F has been devised. Key reactions include an intramolecular Heck cyclization of a tetrasubstituted alkene to generate a tetracyclic enamide bearing one of the quaternary carbon centers (C7) of the alkaloid, an intramolecular reductive cyclization of an N-Boc aniline onto the oxindole moiety to form a pentacyclic framework containing the southern aminal, a stereoselective N-Boc-lactam enolate C-allylation to introduce the second quaternary carbon center (C8), and an azide reduction/N-Boc-lactam-opening cascade leading to the northern aminal. PMID:20334369

  13. Unlocking the Diversity of Alkaloids in Catharanthus roseus: Nuclear Localization Suggests Metabolic Channeling in Secondary Metabolism

    PubMed Central

    Stavrinides, Anna; Tatsis, Evangelos C.; Foureau, Emilien; Caputi, Lorenzo; Kellner, Franziska; Courdavault, Vincent; O’Connor, Sarah E.

    2015-01-01

    Summary The extraordinary chemical diversity of the plant-derived monoterpene indole alkaloids, which include vinblastine, quinine, and strychnine, originates from a single biosynthetic intermediate, strictosidine aglycone. Here we report for the first time the cloning of a biosynthetic gene and characterization of the corresponding enzyme that acts at this crucial branchpoint. This enzyme, an alcohol dehydrogenase homolog, converts strictosidine aglycone to the heteroyohimbine-type alkaloid tetrahydroalstonine. We also demonstrate how this enzyme, which uses a highly reactive substrate, may interact with the upstream enzyme of the pathway. PMID:25772467

  14. Biotransformation of nicotine alkaloids by tobacco shooty teratomas induced by a Ti plasmid mutant.

    PubMed

    Saito, K; Murakoshi, I; Inzé, D; Van Montagu, M

    1989-03-01

    Tobacco shooty or rooty teratomas and hairy roots were induced by Agrobacterium tumefaciens (pGV 3845), A. tumefaciens (pGV 3304) and A. rhizogenes (pRi 8196), respectively. The tobacco alkaloids, nicotine, nornicotine and anatabine, were produced in hairy roots and in rooty teratomas but not in shooty teratomas. However, the shooty teratomas have the ability to accumulate the alkaloids and to biotransform nicotine to nornicotine. These were established by co-culture experiments incubating hairy roots and shooty teratomas in a same dish and by biotransformation experiments with shooty teratomas. PMID:24240441

  15. Evaluation of micellar electrokinetic capillary chromatography for the analysis of selected tobacco alkaloids.

    PubMed

    Yang, S S; Smetena, I; Goldsmith, A I

    1996-10-01

    Micellar electrokinetic capillary chromatography was evaluated for simultaneous determination of several tobacco alkaloids with similar molecular structure. Satisfactory separation of nicotine, nornicotine, myosmine, anatabine and anabasine extracted from tobacco was achieved by introducing an ionic surfactant, sodium dodecyl sulfate, into the buffer system at a concentration of 100 mM. Sample preparation involved a single extraction with water containing 1% triethanolamine. Separation was performed on a 72 cm long, uncoated fused-silica capillary. Experimental parameters such as applied voltage, pH value, buffer composition and surfactant concentration were optimized. Enhancement of UV absorption of alkaloids in the presence of micelles was also studied. PMID:8885385

  16. Asymmetric Synthetic Access to the Hetisine Alkaloids: Total Synthesis of (+)-Nominine

    PubMed Central

    Peese, Kevin M.

    2008-01-01

    A dual cycloaddition strategy for the synthesis of the hetisine alkaloids has been developed, illustrated by a concise asymmetric total synthesis of (+)-nominine (7). The approach relies on an early-stage intramolecular 1,3-dipolar cycloaddition of a 4-oxido-isoquinolinium betaine dipole with an ene–nitrile dipolarophile. Subsequent late-stage pyrrolidine-induced dienamine isomerization/Diels–Alder cascade allows for rapid construction of the carbon–nitrogen polycyclic skeleton within this class of C20-diterpenoid alkaloids. PMID:18046691

  17. Indole Alkaloids from the Sea Anemone Heteractis aurora and Homarine from Octopus cyanea.

    PubMed

    Shaker, Kamel H; Göhl, Matthias; Müller, Tobias; Seifert, Karlheinz

    2015-11-01

    The two new indole alkaloids 2-amino-1,5-dihydro-5-(1H-indol-3-ylmethyl)-4H-imidazol-4-one (1), 2-amino-5-[(6-bromo-1H-indol-3-yl)methyl]-3,5-dihydro-3-methyl-4H-imidazol-4-one (2), and auramine (3) have been isolated from the sea anemone Heteractis aurora. Both indole alkaloids were synthesized for the confirmation of the structures. Homarine (4), along with uracil (5), hypoxanthine (6), and inosine (7) have been obtained from Octopus cyanea. PMID:26567952

  18. Monoterpene pyridine alkaloids and phenolics from Scrophularia ningpoensis and their cardioprotective effect.

    PubMed

    Zhu, Ling-Juan; Hou, Yun-Long; Shen, Xiu-Yu; Pan, Xiao-Dong; Zhang, Xue; Yao, Xin-Sheng

    2013-07-01

    Scrophularianines A-C (1-3), three new unusual monoterpene pyridine alkaloids with cyclopenta [c] pyridine skeleton reported from the genus Scrophularia for the first time, together with 15 known compounds (4-18), were isolated from the extract of Scrophularia ningpoensis. Their structures were elucidated on the basis of extensive analyses of spectroscopic evidences. The biogenetic relationship between monoterpene pyridine alkaloids and iridoids was proposed preliminarily. The myocardial protective bioassay indicated that compounds 13 and 14 with a concentration of 10(-4)M exhibited significantly protective effect against H2O2-induced apoptosis in cardiomyocytes. PMID:23602903

  19. Evolutionary recruitment of a flavin-dependent monooxygenase for the detoxification of host plant-acquired pyrrolizidine alkaloids in the alkaloid-defended arctiid moth Tyria jacobaeae.

    PubMed

    Naumann, Claudia; Hartmann, Thomas; Ober, Dietrich

    2002-04-30

    Larvae of Tyria jacobaeae feed solely upon the pyrrolizidine alkaloid-containing plant Senecio jacobaea. Ingested pyrrolizidine alkaloids (PAs), which are toxic to unspecialized insects and vertebrates, are efficiently N-oxidized in the hemolymph of T. jacobaeae by senecionine N-oxygenase (SNO), a flavin-dependent monooxygenase (FMO) with a high substrate specificity for PAs. Peptide microsequences obtained from purified T. jacobaeae SNO were used to clone the corresponding cDNA, which was expressed in active form in Escherichia coli. T. jacobaeae SNO possesses a signal peptide characteristic of extracellular proteins, and it belongs to a large family of mainly FMO-like sequences of mostly unknown function, including two predicted Drosophila melanogaster gene products. The data indicate that the gene for T. jacobaeae SNO, highly specific for toxic pyrrolizidine alkaloids, was recruited from a preexisting insect-specific FMO gene family of hitherto unknown function. The enzyme allows the larvae to feed on PA-containing plants and to accumulate predation-deterrent PAs in the hemolymph. PMID:11972041

  20. Numerical Relativity

    NASA Technical Reports Server (NTRS)

    Baker, John G.

    2009-01-01

    Recent advances in numerical relativity have fueled an explosion of progress in understanding the predictions of Einstein's theory of gravity, General Relativity, for the strong field dynamics, the gravitational radiation wave forms, and consequently the state of the remnant produced from the merger of compact binary objects. I will review recent results from the field, focusing on mergers of two black holes.

  1. Towards a Molecular Understanding of the Biosynthesis of Amaryllidaceae Alkaloids in Support of Their Expanding Medical Use

    PubMed Central

    Takos, Adam M.; Rook, Fred

    2013-01-01

    The alkaloids characteristically produced by the subfamily Amaryllidoideae of the Amaryllidaceae, bulbous plant species that include well know genera such as Narcissus (daffodils) and Galanthus (snowdrops), are a source of new pharmaceutical compounds. Presently, only the Amaryllidaceae alkaloid galanthamine, an acetylcholinesterase inhibitor used to treat symptoms of Alzheimer’s disease, is produced commercially as a drug from cultivated plants. However, several Amaryllidaceae alkaloids have shown great promise as anti-cancer drugs, but their further clinical development is restricted by their limited commercial availability. Amaryllidaceae species have a long history of cultivation and breeding as ornamental bulbs, and phytochemical research has focussed on the diversity in alkaloid content and composition. In contrast to the available pharmacological and phytochemical data, ecological, physiological and molecular aspects of the Amaryllidaceae and their alkaloids are much less explored and the identity of the alkaloid biosynthetic genes is presently unknown. An improved molecular understanding of Amaryllidaceae alkaloid biosynthesis would greatly benefit the rational design of breeding programs to produce cultivars optimised for the production of pharmaceutical compounds and enable biotechnology based approaches. PMID:23727937

  2. Single cell subtractive transcriptomics for identification of cell-specifically expressed candidate genes of pyrrolizidine alkaloid biosynthesis.

    PubMed

    Sievert, Christian; Beuerle, Till; Hollmann, Julien; Ober, Dietrich

    2015-09-01

    Progress has recently been made in the elucidation of pathways of secondary metabolism. However, because of its diversity, genetic information concerning biosynthetic details is still missing for many natural products. This is also the case for the biosynthesis of pyrrolizidine alkaloids. To close this gap, we tested strategies using tissues that express this pathway in comparison to tissues in which this pathway is not expressed. As many pathways of secondary metabolism are known to be induced by jasmonates, the pyrrolizidine alkaloid-producing species Heliotropium indicum, Symphytum officinale, and Cynoglossum officinale of the Boraginales order were treated with methyl jasmonate. An effect on pyrrolizidine alkaloid levels and on transcript levels of homospermidine synthase, the first specific enzyme of pyrrolizidine alkaloid biosynthesis, was not detectable. Therefore, a method was developed by making use of the often observed cell-specific production of secondary compounds. H. indicum produces pyrrolizidine alkaloids exclusively in the shoot. Homospermidine synthase is expressed only in the cells of the lower leaf epidermis and the epidermis of the stem. Suggesting that the whole pathway of pyrrolizidine alkaloid biosynthesis might be localized in these cells, we have isolated single cells of the upper and lower epidermis by laser-capture microdissection. The resulting cDNA preparations have been used in a subtractive transcriptomic approach. Quantitative real-time polymerase chain reaction has shown that the resulting library is significantly enriched for homospermidine-synthase-coding transcripts providing a valuable source for the identification of further genes involved in pyrrolizidine alkaloid biosynthesis. PMID:26057225

  3. Alkaloids from the Mangrove-Derived Actinomycete Jishengella endophytica 161111

    PubMed Central

    Wang, Pei; Kong, Fandong; Wei, Jingjing; Wang, Yi; Wang, Wei; Hong, Kui; Zhu, Weiming

    2014-01-01

    A new alkaloid, 2-(furan-2-yl)-6-(2S,3S,4-trihydroxybutyl)pyrazine (1), along with 12 known compounds, 2-(furan-2-yl)-5-(2S,3S,4-trihydroxybutyl)pyrazine (2), (S)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (3), (S)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (4), (4S)-4-(2-methylbutyl)-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (5), (S)-4-benzyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (6), flazin (7), perlolyrine (8), 1-hydroxy-?-carboline (9), lumichrome (10), 1H-indole-3-carboxaldehyde (11), 2-hydroxy-1-(1H-indol-3-yl)ethanone (12), and 5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde (13), were isolated and identified from the fermentation broth of an endophytic actinomycetes, Jishengella endophytica 161111. The new structure 1 and the absolute configurations of 2–6 were determined by spectroscopic methods, J-based configuration analysis (JBCA) method, lactone sector rule, and electronic circular dichroism (ECD) calculations. Compounds 8–11 were active against the influenza A virus subtype H1N1 with IC50 and selectivity index (SI) values of 38.3(±1.2)/25.0(±3.6)/39.7(±5.6)/45.9(±2.1) ?g/mL and 3.0/16.1/3.1/11.4, respectively. The IC50 and SI values of positive control, ribavirin, were 23.1(±1.7) ?g/mL and 32.2, respectively. The results showed that compound 9 could be a promising new hit for anti-H1N1 drugs. The absolute configurations of 2–5, 13C nuclear magnetic resonance (NMR) data and the specific rotations of 3–6 were also reported here for the first time. PMID:24451190

  4. Alkaloid profiling as an approach to differentiate Lupinus garfieldensis, Lupinus sabinianus, and Lupinus sericeus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction – Many species in the Lupinus genus are poorly defined resulting in improper taxonomic identification. Lupine species may contain quinolizidine and/or piperidine alkaloids that can be acutely toxic and/or teratogenic resulting in crooked calf disease. Objective – To identify any char...

  5. CATTLE GRAZEing VELVET LUPINE (Lupinus leucophyllus): INFLUENCE OF ASSOCIATED FORAGES, ALKALOID LEVELS AND POPULATION CYCLEs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Certain lupines (Lupinus spp.) contain alkaloids that cause contracture-type skeletal birth defects and cleft palate (“Crooked calf syndrome”) if the pregnant cow consumes them during the 40 – 70th day of gestation. The objective of this study was to determine when cattle graze velvet lupine (Lupi...

  6. Are loline alkaloid levels regulated in grass endophytes by gene expression or substrate availability

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many cool-season grasses (Poaceae, subfam. Pooideae) possess seedborne fungal symbionts, the epichloae, known for their bioprotective properties, and especially for production of anti-insect alkaloids such as lolines. Asexual epichloae (Neotyphodium species) are primarily or entirely transmitted ver...

  7. Bioactive 1 4-Dihydroxy-5-phenyl-2-pyridinone alkaloids from Septoria pistaciarum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Four new 1,4-dihydroxy-5-phenyl-2-pyridinone alkaloids (1-4) were isolated from an EtOAc extract of a culture medium of Septoria pistaciarum. The structures of these compounds were determined by spectroscopic methods, and the absolute configuration of the major compound 1 by X-ray crystallographic a...

  8. Contact toxicities of Anuran Skin Alkaloids against the Red Imported Fire Ant (Solenopsis invicta)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nearly 500 alkaloids, representing over 20 structural classes, have been identified from the skin of poison frogs (Dendrobatidae). These cutaneous compounds, which are derived from leaf-litter arthropods eaten by the frogs, generally are believed to deter predators. We tested the red imported fire a...

  9. Total Synthesis of Sedum Alkaloids via Catalyst Controlled aza-Cope Rearrangement and Hydroformylation with Formaldehyde

    PubMed Central

    Ren, Hong; Wulff, William D.

    2013-01-01

    The catalytic asymmetric aminoallylation of chiral aldehydes is developed as a new method for the catalyst controlled synthesis of syn- and anti-1,3-aminoalcohols. This methodology is highlighted in the synthesis of the sedum alkaloids (+)-sedridine and (+)-allosedridine both of which have their final carbon incorporated during closure of the piperidine ring via a hydroformylation with formaldehyde. PMID:23259754

  10. Total synthesis of sedum alkaloids via catalyst controlled aza-Cope rearrangement and hydroformylation with formaldehyde.

    PubMed

    Ren, Hong; Wulff, William D

    2013-01-18

    The catalytic asymmetric aminoallylation of chiral aldehydes is developed as a new method for the catalyst controlled synthesis of syn- and anti-1,3-aminoalcohols. This methodology is highlighted in the synthesis of the sedum alkaloids (+)-sedridine and (+)-allosedridine both of which have their final carbon incorporated during closure of the piperidine ring via a hydroformylation with formaldehyde. PMID:23259754

  11. (Received, August 2004; Accepted, November 2004) ANTI-MICROBIAL ACTIVITY OF THE ALKALOID EXTRACT OF Genista

    E-print Network

    Paré, Paul W.

    OF LUPANINE AND S-CALYCOTOMINE AMAR ZELLAGUI1 , SALAH RHOUATI1 , JOEL CRECHE2 ,GÀBOR TÓTH3 , AHMED A. AHMED4, afforded two alkaloids, identified as lupanine (2-oxosparteine) 1 and S-calycotomine 2. The complete 1 H and 13 C chemical shifts assignments of Lupanine and S- Calycotomine were determined using 1D and 2D NMR

  12. Cellular localization of quinolizidine alkaloids by laser desorption mass spectrometry (LAMMA 1000).

    PubMed

    Wink, M; Heinen, H J; Vogt, H; Schiebel, H M

    1984-12-01

    Stem sections of Lupinus polyphyllus and Cytisus scoparius have been analyzed for the distribution of quinolizidine alkaloids by laser desorption mass spectrometry, employing a LAMMA 1000 instrument. Sparteine and lupanine could be recorded and were found to be restricted to the epidermis and probably also to the neighbouring 1 or 2 subepidermal cell layers. PMID:24253573

  13. Signaling Pathways Used by Ergot Alkaloids to Inhibit Bovine Sperm Motility

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ergot alkaloids exert their toxic or pharmaceutical effects through membrane receptor-mediated activities. This study investigated the signaling pathways involved in the in vitro inhibitory effects of both ergotamine (ET) and dihydroergotamine (DEHT) on bovine sperm motility using specific inhibitor...

  14. Ergot alkaloids produced by endophyte-infected tall fescue decrease rumen epithelial blood flow of cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ergot alkaloids have been shown to induce vasoconstriction of both peripheral and ruminal vessels. Constriction of ruminal vessels could lead to a reduction in epithelial blood flow thereby reducing nutrient absorption. The objectives of this experiment were to determine if steers receiving endophyt...

  15. Evaluation of the Vasoconstrictive Capacity of Tall Fescue Alkaloids Using Fescue Naive Bovine Lateral Saphenous Veins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vasoconstriction is associated with consumption of toxic endophyte-infected tall fescue. Because it is not known if endophyte-produced alkaloids act alone or in concert, the objective of this study was to examine the vasoconstrictive potentials of D-lysergic acid (LSA) and ergovaline (ERV) individua...

  16. Piperidine, pyridine alkaloid inhibition of fetal movement in a day 40 pregnant goat model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The inhibition of fetal movement is one mechanism behind the development of multiple congenital contracture-type defects and cleft palate in developing fetuses of humans and animals. In this study, we tested the alkaloids anabasine, lobeline, and myosmine for agonist actions, and sensitivity to alp...

  17. Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

    PubMed Central

    Kuete, Victor; Biavatti, Maique W

    2015-01-01

    Summary This review focuses on pyridoacridine-related metabolites as one biologically interesting group of alkaloids identified from marine sources. They are produced by marine sponges, ascidians and tunicates, and they are structurally comprised of four to eight fused rings including heterocycles. Acridine, acridone, dihydroacridine, and quinolone cores are features regularly found in these alkaloid skeletons. The lack of hydrogen atoms next to quaternary carbon atoms for two or three rings makes the chemical shift assignment a difficult task. In this regard, one of the aims of this review is the compilation of previously reported, pyridoacridine 13C NMR data. Observations have been made on the delocalization of electrons and the presence of some functional groups that lead to changes in the chemical shift of some carbon resonances. The lack of mass spectra information for these alkaloids due to the compactness of their structures is further discussed. Moreover, the biosynthetic pathways of some of these metabolites have been shown since they could inspire biomimetic synthesis. The synthesis routes used to prepare members of these marine alkaloids (as well as their analogues), which are synthesized for biological purposes are also discussed. Pyridoacridines were found to have a large spectrum of bioactivity and this review highlights and compares the pharmacophores that are responsible for the observed bioactivity. PMID:26664587

  18. Coregulated Expression of Loline Alkaloid-Biosynthesis Genes in Neotyphodium Uncinatum Cultures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epichloë endophytes (holomorphic Epichloë spp. and anamorphic Neotyphodium spp.) are systemic, often heritable symbionts of cool-season grasses (subfamily Pooideae). Many epichloae provide protection to their hosts by producing anti-insect compounds. Among these are the loline alkaloids (LA), which ...

  19. Physiologic effects of ergot alkaloids: What happens when excretion does not equal consumption?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increased persistence of tall fescue (Lolium arundinaceum) infested with an endophytic fungus Epichloë coenophiala (formerly Neotyphodium coenophialum) in forage-based agriculture has led to increased effort in understanding the negative effects caused by consumption of ergot alkaloids by animals co...

  20. Crotalaria medicaginea associated with horse deaths in northern Australia: new pyrrolizidine alkaloids.

    PubMed

    Fletcher, Mary T; Hayes, Patricia Y; Somerville, Michael J; De Voss, James J

    2011-11-01

    Crotalaria medicaginea has been implicated in horse poisoning in grazing regions of central-west Queensland, which resulted in the deaths of more than 35 horses from hepatotoxicosis in 2010. Liver pathology was suggestive of pyrrolizidine alkaloidosis, and we report here the isolation of two previously uncharacterized pyrrolizidine alkaloids from C. medicaginea plant specimens collected from pastures where the horses died. The first alkaloid was shown by mass spectometric and NMR analyses to be 1?,2?-epoxy-7?-hydroxy-1?-methoxymethyl-8?-pyrrolizidine, which, like other alkaloids previously isolated from C. medicaginea, lacks the requisite functionality for hepatotoxcity. The second alkaloid isolated in this investigation was a new macrocyclic diester of otonecine, which we have named cromedine. The (1)H and (13)C NMR spectra of cromedine were fully assigned by 2D NMR techniques and allowed the constitution of the macrocyclic diester to be assigned unambiguously. C. medicaginea specimens implicated in this investigation do not belong to any of the three recognized Australian varieties (C. medicaginea var. neglecta, C. medicaginea var. medicaginea, and C. medicaginea var. linearis) and appear to be a local variant or form, referred to here as C. medicaginea (chemotype cromedine). PMID:21899365

  1. Effects of solar UV radiation on alkaloid production in Erythroxylum novogranatense var. novogranatense

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cocaine-producing species of Erythroxylum have been cultivated in South America for centuries, yet little is know of environmental effects on alkaloid production in these species. Given the high incidence of UV radiation in the equatorial and high altitude environments in which cocaine-producing sp...

  2. Doppler ultrasonography for evaluating vascular responses to ergopeptine alkaloids in livestock

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ergot alkaloids are produced by non-spore producing fungal endophytes that infect certain species of grasses, most notably tall fescue [Lolium arundinaceum (Schreb.) Darbysh.] and perennial ryegrass (Lolium perenne L.), and the spore producing Claviceps spp. that infect seed heads of certain grasses...

  3. Pyrrolizidine alkaloids: Potential role in the etiology of cancers, pulmonary hypertension, congenital anomalies, and liver disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Large outbreaks of acute food-related poisoning, characterized by hepatic sinusoidal obstruction syndrome, hemorrhagic necrosis, and rapid liver failure, occur on a regular basis in some countries. They are caused by 1,2-dehydropyrrolizidine alkaloids contaminating locally grown grain. Similar acute...

  4. Pyrrolizidine alkaloid-containing toxic plants (Scenecio, Crotalaria, Cynoglossum, Amsinckia, Heliotropium, and Echium spp.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pyrrolizidine alkaloid (PA) containing plants are found throughout the world and are probably the most common plant cause of poisoning of livestock, wildlife and humans. PAs are potent liver toxins that under some conditions can be carcinogenic. The objective of this paper is to briefly introduce hi...

  5. Extraction Optimization of Tinospora cordifolia and Assessment of the Anticancer Activity of Its Alkaloid Palmatine

    PubMed Central

    Ali, Huma; Dixit, Savita

    2013-01-01

    Objective. To optimize the conditions for the extraction of alkaloid palmatine from Tinospora cordifolia by using response surface methodology (RSM) and study its anticancerous property against 7,12-dimethylbenz(a)anthracene (DMBA) induced skin carcinogenesis in Swiss albino mice. Methods. The effect of three independent variables, namely, extraction temperature, time, and cycles was investigated by using central composite design. A single topical application of DMBA (100??g/100??L of acetone), followed 2 weeks later by repeated application of croton oil (1% in acetone three times a week) for 16 weeks, exhibited 100 percent tumor incidence (Group 2). Results. The highest yield of alkaloid from Tinospora cordifolia could be achieved at 16 hours of extraction time under 40°C with 4 extraction cycles. Alkaloid administration significantly decreases tumor size, number, and the activity of serum enzyme when compared with the control (Group 2). In addition, depleted levels of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase and increased DNA damage were restored in palmatine treated groups. Conclusion. The data of the present study clearly indicate the anticancer potential of palmatine alkaloid in DMBA induced skin cancer model in mice. PMID:24379740

  6. Determination of tobacco alkaloids by gas chromatography with nitrogen-phosphorus detection.

    PubMed

    Yang, S S; Smetena, I; Huang, C B

    2002-04-01

    An improved method, gas chromatography (GC) with nitrogen-phosphorus detection (NPD), has been used for determination of alkaloids in green and cured tobacco. Tobacco alkaloids of interest included nicotine, nornicotine, myosmine, anabasine, and anatabine. Tobacco samples were treated with a small quantity of aqueous ammonia solution to "loosen" tobacco tissue and to adjust pH, then extracted with solvent. The composition of the extraction solvent solution affected recoveries of the alkaloids, particularly nornicotine, and also contributed to other phenomena such as carry-over in the injection liner and "quenching" of the nitrogen-phosphorus detector. Use of a packed injection liner (e.g. with Carbowax-KOH on Chromosorb) to reduce carry-over was studied. Quenching of the nitrogen-phosphorus detector was eliminated by reducing the injection volume (i.e. increasing the split ratio), by use of a packed injection liner, and by reducing the amount of pretreatment with aqueous ammonia. A narrow bore capillary column (i.e. 0.18 mm id) was used to improve sensitivity and resolution and to increase the speed of GC analysis. An internal standard, 2,4'-dipyridyl, was used for quantitative measurement of these tobacco alkaloids. PMID:12194047

  7. Cerebroprotective and regenerative effects of alkaloid Z77 under conditions of brain ischemia.

    PubMed

    Zyuz'kov, G N; Suslov, N I; Losev, E A; Ermolaeva, L A; Zhdanov, V V; Udut, E V; Miroshnichenko, L A; Simanina, E V; Demkin, V P; Povet'eva, T N; Nesterova, Yu V; Udut, V V; Minakova, M Yu; Dygai, A M

    2015-01-01

    We studied the psychopharmacological effects of atisine-type diterpene alkaloid Z77 in a rat model of cerebral ischemia. Pronounced cerebroprotective effect was found consisting in normalization of the orienting and exploratory activity and conditioned behavior associated with significant correction of morphological changes in the brain. The direct stimulatory effect of Z77 on neural stem cells was shown in vitro. PMID:25573368

  8. Synthesis of the ester side chains of some potently antileukemic harringtonia alkaloids from chiral citrates.

    PubMed

    Ancliff, Rachael A; Russell, Andrew T; Sanderson, Adam J

    2006-08-14

    The selective reduction of one of the three carboxyl groups of two chiral citric acid derivatives to the corresponding aldehydes, under Rosenmund conditions, are reported together with the application of these aldehydes to the syntheses of the ester side chains of some potently antileukemic Cephalotaxus alkaloids e.g. anhydroharringtonine. PMID:17028757

  9. Gene Clusters for Insecticidal Loline Alkaloids in the Grass-Endophytic Fungus Neotyphodium uncinatum

    PubMed Central

    Spiering, Martin J.; Moon, Christina D.; Wilkinson, Heather H.; Schardl, Christopher L.

    2005-01-01

    Loline alkaloids are produced by mutualistic fungi symbiotic with grasses, and they protect the host plants from insects. Here we identify in the fungal symbiont, Neotyphodium uncinatum, two homologous gene clusters (LOL-1 and LOL-2) associated with loline-alkaloid production. Nine genes were identified in a 25-kb region of LOL-1 and designated (in order) lolF-1, lolC-1, lolD-1, lolO-1, lolA-1, lolU-1, lolP-1, lolT-1, and lolE-1. LOL-2 contained the homologs lolC-2 through lolE-2 in the same order and orientation. Also identified was lolF-2, but its possible linkage with either cluster was undetermined. Most lol genes were regulated in N. uncinatum and N. coenophialum, and all were expressed concomitantly with loline-alkaloid biosynthesis. A lolC-2 RNA-interference (RNAi) construct was introduced into N. uncinatum, and in two independent transformants, RNAi significantly decreased lolC expression (P < 0.01) and loline-alkaloid accumulation in culture (P < 0.001) compared to vector-only controls, indicating involvement of lolC in biosynthesis of lolines. The predicted LolU protein has a DNA-binding site signature, and the relationships of other lol-gene products indicate that the pathway has evolved from various different primary and secondary biosynthesis pathways. PMID:15654104

  10. Indole Alkaloids from Fischerella Inhibit Vertebrate Development in the Zebrafish (Danio rerio) Embryo Model

    PubMed Central

    Walton, Katherine; Gantar, Miroslav; Gibbs, Patrick D. L.; Schmale, Michael C.; Berry, John P.

    2014-01-01

    Cyanobacteria are recognized producers of toxic or otherwise bioactive metabolite associated, in particular, with so-called “harmful algal blooms” (HABs) and eutrophication of freshwater systems. In the present study, two apparently teratogenic indole alkaloids from a freshwater strain of the widespread cyanobacterial genus, Fischerella (Stigonemataceae), were isolated by bioassay-guided fractionation, specifically using the zebrafish (Danio rerio) embryo, as a model of vertebrate development. The two alkaloids include the previously known 12-epi-hapalindole H isonitrile (1), and a new nitrile-containing variant, 12-epi-ambiguine B nitrile (2). Although both compounds were toxic to developing embryos, the former compound was shown to be relatively more potent, and to correlate best with the observed embryo toxicity. Related indole alkaloids from Fischerella, and other genera in the Stigonemataceae, have been widely reported as antimicrobial compounds, specifically in association with apparent allelopathy. However, this is the first report of their vertebrate toxicity, and the observed teratogenicity of these alkaloids supports a possible contribution to the toxicity of this widespread cyanobacterial family, particularly in relation to freshwater HABs and eutrophication. PMID:25533520

  11. Polymorphic Nucleic Acid Binding of Bioactive Isoquinoline Alkaloids and Their Role in Cancer

    PubMed Central

    Maiti, Motilal; Kumar, Gopinatha Suresh

    2010-01-01

    Bioactive alkaloids occupy an important position in applied chemistry and play an indispensable role in medicinal chemistry. Amongst them, isoquinoline alkaloids like berberine, palmatine and coralyne of protoberberine group, sanguinarine of the benzophenanthridine group, and their derivatives represent an important class of molecules for their broad range of clinical and pharmacological utility. In view of their extensive occurrence in various plant species and significantly low toxicities, prospective development and use of these alkaloids as effective anticancer agents are matters of great current interest. This review has focused on the interaction of these alkaloids with polymorphic nucleic acid structures (B-form, A-form, Z-form, HL-form, triple helical form, quadruplex form) and their topoisomerase inhibitory activity reported by several research groups using various biophysical techniques like spectrophotometry, spectrofluorimetry, thermal melting, circular dichroism, NMR spectroscopy, electrospray ionization mass spectroscopy, viscosity, isothermal titration calorimetry, differential scanning calorimetry, molecular modeling studies, and so forth, to elucidate their mode and mechanism of action for structure-activity relationships. The DNA binding of the planar sanguinarine and coralyne are found to be stronger and thermodynamically more favoured compared to the buckled structure of berberine and palmatine and correlate well with the intercalative mechanism of sanguinarine and coralyne and the partial intercalation by berberine and palmatine. Nucleic acid binding properties are also interpreted in relation to their anticancer activity. PMID:20814427

  12. Seasonal variation in pyrrolizidine alkaloid concentration and plant development in Senecio madagascariensis poir. (Asteraceae) in Brazil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This chapter presents the results of studies conducted in the municipality of Eldorado do Sul, State of Rio Grande do Sul, Brazil, in July and October 2007 and January and May 2008 to measure the pyrrolizidine alkaloid (PA) concentrations of S. madagascariensis plant material (including leaves, flow...

  13. Separation and purification of five alkaloids from Aconitum duclouxii by counter-current chromatography.

    PubMed

    Wang, Yarong; Cai, Shining; Chen, Yang; Deng, Liang; Zhou, Xumei; Liu, Jia; Xu, Xin; Xia, Qiang; Lin, Mao; Zhang, Jili; Huang, Weili; Wang, Wenjun; Xiang, Canhui; Cui, Guozhen; Du, Lianfeng; He, Huan; Qi, Baohui

    2015-07-01

    C19 -diterpenoid alkaloids are the main components of Aconitum duclouxii Levl. The process of separation and purification of these compounds in previous studies was tedious and time consuming, requiring multiple chromatographic steps, thus resulted in low recovery and high cost. In the present work, five C19 -diterpenoid alkaloids, namely, benzoylaconine (1), N-deethylaconitine (2), aconitine (3), deoxyaconitine (4), and ducloudine A (5), were efficiently prepared from A. duclouxii Levl (Aconitum L.) by ethyl acetate extraction followed with counter-current chromatography. In the process of separation, the critical conditions of counter-current chromatography were optimized. The two-phase solvent system composed of n-hexane/ethyl acetate/methanol/water/NH3 ·H2 O (25%) (1:1:1:1:0.1, v/v) was selected and 148.2 mg of 1, 24.1 mg of 2, 250.6 mg of 3, 73.9 mg of 4, and 31.4 mg of 5 were obtained from 1 g total Aconitum alkaloids extract, respectively, in a single run within 4 h. Their purities were found to be 98.4, 97.2, 98.2, 96.8, and 96.6%, respectively, by ultra-high performance liquid chromatography analysis. The presented separation and purification method was simple, fast, and efficient, and the obtained highly pure alkaloids are suitable for biochemical and toxicological investigation. PMID:25907585

  14. Characterization of rumen bacterial pyrrolizidine alkaloid biotransformation in ruminants of various species.

    PubMed

    Wachenheim, D E; Blythe, L L; Craig, A M

    1992-12-01

    An in vitro assay was used to examine biotransformation of toxic Senecio jacobaea pyrrolizidine alkaloids (PA) in ovine, bovine, and caprine rumen contents. Pyrrolizidine alkaloids were analysed by high performance liquid chromatography, and the rates of the alkaloid biotransformation were determined. The microbiological "Most Probable Numbers" technique was also used, in combination with thin-layer chromatography, to estimate relative numbers of rumen PA-biotransforming bacteria in the same samples. Pyrrolizidine alkaloids were biotransformed at average rates of 2.9 micrograms/ml/h (bovine), 25.6 micrograms/ml/h (caprine), and 19.2 micrograms/ml/h (ovine). Estimates of numbers of PA-biotransforming bacteria were 1.1 x 10(7) bacteria/ml rumen contents (bovine), 2.4 x 10(7) bacteria/ml (caprine), and 3.0 x 10(7) bacteria/ml (ovine). This project is among the first to quantitate rates of PA biotransformation in rumen contents and to identify caprine and bovine, in addition to ovine, rumen PA-biotransforming activity, as well as to estimate the actual numbers of PA-biotransforming bacteria in rumen contents. PMID:1287970

  15. Currencies of mutualisms: Sources of alkaloid genes in vertically transmitted epichloae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The epichloae (Epichloë and Neotyphodium species), a monophyletic group of fungi in the family Clavicipitaceae, are systemic symbionts of cool-season grasses (Poaceae subfamily Poöideae). Most epichloae are vertically transmitted in seeds (endophytes), and most produce alkaloids that attack nervous ...

  16. Ergot alkaloids reduce rumen epithelial blood flow and volatile fatty acid absorption

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ergot alkaloids have been shown to induce vasoconstriction of both peripheral and ruminal vessels. Constriction of ruminal vessels could lead to a reduction in epithelial blood flow thereby reducing nutrient absorption. The objectives of this experiment were to determine if steers receiving endophyt...

  17. Effect of alkaloids of Solanum melongena on the central nervous system.

    PubMed

    Vohora, S B; Kumar, I; Khan, M S

    1984-08-01

    Crude alkaloidal fraction isolated from the leaves of Solanum melongena was screened for its effects on the central nervous system. It exhibited significant analgesic effect and some CNS depression but no anticonvulsant action. The analgesic effects were of non-narcotic type. LD50 was estimated to be higher than 1 g/kg i.p. in mice. PMID:6482482

  18. Nitrogen supplementation does not affect level of an Alkaloid swainsonine in four locoweeds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Locoweeds are legumes that can be highly poisonous to livestock and wild animals. Locoweed toxicity depends on the association of a plant and a fungal endophyte which produces the alkaloid swainsonine (SWA); however, environmental factors affecting SWA synthesis are unknown. Additionally, locoweeds ...

  19. Opportunities in metabolic engineering to facilitate scalable alkaloid production

    E-print Network

    Leonard, Effendi

    Numerous drugs and drug precursors in the current pharmacopoeia originate from plant sources. The limited yield of some bioactive compounds in plant tissues, however, presents a significant challenge for large-scale drug ...

  20. Staphylococcal enterotoxin A gene-carrying Staphylococcus aureus isolated from foods and its control by crude alkaloid from papaya leaves.

    PubMed

    Handayani, Lita; Faridah, Didah Nur; Kusumaningrum, Harsi D

    2014-11-01

    Staphylococcus aureus is a known pathogen causing intoxication by producing enterotoxins in food. Staphylococcal enterotoxin A is one of the enterotoxins commonly implicated in staphylococcal food poisoning. The ability of crude alkaloid extract from papaya leaves to inhibit the growth of S. aureus and staphylococcal enterotoxin A synthesis was investigated. Staphylococcal enterotoxin A gene-carrying S. aureus was isolated from raw milk and ready-to-eat foods. Crude alkaloid was extracted from ground, dried papaya leaves using ultrasonic-assisted extraction, and a MIC of the alkaloid was determined by the broth macrodilution method. Furthermore, S. aureus isolate was exposed to the crude alkaloid extract at one- and twofold MIC, and the expression of sea was subsequently analyzed using a quantitative reverse transcription real-time PCR. Ten isolates of S. aureus were obtained, and nine of those isolates were sea carriers. The yield of crude alkaloid extract was 0.48 to 1.82% per dry weight of papaya leaves. A MIC of crude alkaloid to S. aureus was 0.25 mg/ml. After exposure to the alkaloid at 0.25 and 0.5 mg/ml for 2 h, a significant increase in cycle threshold values of sea was observed. The sea was expressed 29 and 41 times less when S. aureus was exposed to crude alkaloid at one- and twofold MIC, respectively. This study revealed that crude alkaloid of papaya leaves could control staphylococcal enterotoxin A gene-carrying S. aureus by suppressing the expression of sea, in addition to the ability to inhibit the growth of S. aureus. The expression of sea was successfully quantified. PMID:25364936

  1. Effects of the ergot alkaloids dihydroergotamine, ergonovine, and ergotamine on growth of Escherichia coli O157:H7 in vitro.

    PubMed

    Looper, M L; Edrington, T S; Moubarak, A S; Callaway, T R; Rosenkrans, C F

    2008-10-01

    A series of experiments were conducted to evaluate the effects of ergot alkaloids (dihydroergotamine, ergonovine, and ergotamine) on E. coli O157:H7 in both pure and mixed ruminal fluid culture. Alkaloids were added to solutions of E. coli O157:H7 strains 933 (pure and ruminal cultures) and 6058 (ruminal culture only), and growth rates and colony-forming units (CFU) of E. coli O157:H7 were measured. Two mixtures of all three alkaloids at either 2 or 500 microM for each alkaloid decreased (p < 0.001) the growth rate of E. coli O157:H7 in pure culture compared to the individual alkaloids. Dihydroergotamine tended (p = 0.07) to reduce growth rate of E. coli O157:H7 in pure culture compared with ergonovine or ergotamine alone. Increased concentrations of dihydroergotamine and ergotamine decreased (p < 0.003) growth rate of E. coli O157:H7 but increasing concentrations of ergonovine did not influence (p > 0.10) E. coli O157:H7 growth rate. Similar to results in pure culture, a mixture of all three alkaloids at various concentrations for each alkaloid decreased (p < 0.001) the CFU of E. coli O157:H7 strain 6058 in mixed ruminal culture compared to the individual ergot alkaloids. Dihydroergotamine decreased (p = 0.04) CFU of E. coli O157:H7 strain 6058 when compared to ergonovine but CFU were similar (p > 0.10) between dihydroergotamine and ergotamine. Ruminal and (or) intestinal populations of E. coli O157:H7 may be influenced in livestock consuming endophyte-infected tall fescue, and these alterations could be due to the presence of ergot alkaloids in fescue plants. PMID:18681792

  2. Visualizing a plant defense and insect counterploy: alkaloid distribution in Lobelia leaves trenched by a plusiine caterpillar.

    PubMed

    Oppel, Craig B; Dussourd, David E; Garimella, Umadevi

    2009-06-01

    Insects that feed on plants protected by latex canals often sever leaf veins or cut trenches across leaves before feeding distal to the cuts. The insects thereby depressurize the canals and reduce latex exudation at their prospective feeding site. How the cuts affect the distribution and concentration of latex chemicals was not known. We modified a microwave-assisted extraction technique to analyze the spatial distribution of alkaloids in leaves of Lobelia cardinalis (Campanulaceae) that have been trenched by a plusiine caterpillar, Enigmogramma basigera (Lepidoptera: Noctuidae). We produced sharp two dimensional maps of alkaloid distribution by microwaving leaves to transfer alkaloids to TLC plates that were then sprayed with Dragendorff's reagent to visualize the alkaloids. The leaf prints were photographed and analyzed with image processing software for quantifying alkaloid levels. A comparison of control and trenched leaves documented that trenching reduces alkaloid levels by approximately 50% both distal and proximal to the trench. The trench becomes greatly enriched in alkaloids due to latex draining from surrounding areas. Measurements of exudation from trenched leaves demonstrate that latex pressures are rapidly restored proximal, but not distal to the trench. Thus, the trench serves not only to drain latex with alkaloids from the caterpillar's prospective feeding site, but also to isolate this section, thereby preventing an influx of latex from an extensive area that likely extends beyond the leaf. Microwave-assisted extraction of leaves has potential for diverse applications that include visualizing the impact of pathogens, leaf miners, sap-sucking insects, and other herbivores on the distribution and abundance of alkaloids and other important defensive compounds. PMID:19468794

  3. The addition of five minor tobacco alkaloids increases nicotine-induced hyperactivity, sensitization and intravenous self-administration in rats.

    PubMed

    Clemens, Kelly J; Caillé, Stephanie; Stinus, Luis; Cador, Martine

    2009-11-01

    Several minor tobacco alkaloids have been found to exhibit properties pharmacologically relevant to the addictive profile of tobacco; however, little is known of their effects on a behavioural model of drug addiction. In this study we compared the locomotor and reinforcing effects of intravenous nicotine (30 microg/kg per infusion) vs. a cocktail of nicotine plus five minor alkaloids found in tobacco smoke (anabasine, nornicotine, anatabine, cotinine and myosmine). Rats were initially tested for their locomotor response to nicotine or nicotine plus the minor alkaloids with six intravenous injections over 1 h. We then assessed the spontaneous acquisition of intravenous self-administration with nicotine or nicotine plus the minor alkaloids, under a fixed-ratio 1 schedule followed by responding on a fixed-ratio 5 schedule, progressive-ratio schedule and a single within-session ascending dose-response test. The activity test was repeated following the progressive-ratio phase to assess locomotor sensitization. A second group of rats were then tested on the locomotor procedure to better clarify the role of each individual minor alkaloid in nicotine-induced locomotor activity. Compared to nicotine alone, addition of the minor tobacco alkaloids increased locomotor activity and increased locomotor sensitization following self-administration. During fixed-ratio 5, progressive ratio and the dose-response test, rats receiving nicotine plus the minor alkaloids responded significantly more than those receiving nicotine alone. Testing of each minor alkaloid in the second experiment indicated that anatabine, cotinine and myosmine individually increased nicotine-induced locomotor activity. These results suggest that the minor tobacco alkaloids, particularly anatabine, cotinine and myosmine, may increase the motivation for nicotine and thus facilitate smoking behaviour. PMID:19366487

  4. Integration of Transcriptome, Proteome and Metabolism Data Reveals the Alkaloids Biosynthesis in Macleaya cordata and Macleaya microcarpa

    PubMed Central

    Liu, Fuqing; Huang, Peng; Zhu, Pengcheng; Chen, Jinjun; Shi, Mingming; Guo, Fang; Cheng, Pi; Zeng, Jing; Liao, Yifang; Gong, Jing; Zhang, Hong-Mei; Wang, Depeng; Guo, An-Yuan; Xiong, Xingyao

    2013-01-01

    Background The Macleaya spp., including Macleaya cordata and Macleaya microcarpa, are traditional anti-virus, inflammation eliminating, and insecticide herb medicines for their isoquinoline alkaloids. They are also known as the basis of the popular natural animal food addictive in Europe. However, few studies especially at genomics level were conducted on them. Hence, we performed the Macleaya spp. transcriptome and integrated it with iTRAQ proteome analysis in order to identify potential genes involved in alkaloids biosynthesis. Methodology and Principal Findings We elaborately designed the transcriptome, proteome and metabolism profiling for 10 samples of both species to explore their alkaloids biosynthesis. From the transcriptome data, we obtained 69367 and 78255 unigenes for M. cordata and M. microcarpa, in which about two thirds of them were similar to sequences in public databases. By metabolism profiling, reverse patterns for alkaloids sanguinarine, chelerythrine, protopine, and allocryptopine were observed in different organs of two species. We characterized the expressions of enzymes in alkaloid biosynthesis pathways. We also identified more than 1000 proteins from iTRAQ proteome data. Our results strongly suggest that the root maybe the organ for major alkaloids biosynthesis of Macleaya spp. Except for biosynthesis, the alkaloids storage and transport were also important for their accumulation. The ultrastructure of laticifers by SEM helps us to prove the alkaloids maybe accumulated in the mature roots. Conclusions/Significance To our knowledge this is the first study to elucidate the genetic makeup of Macleaya spp. This work provides clues to the identification of the potential modulate genes involved in alkaloids biosynthesis in Macleaya spp., and sheds light on researches for non-model medicinal plants by integrating different high-throughput technologies. PMID:23326424

  5. Enzymatic and Chemo-Enzymatic Approaches Towards Natural and Non-Natural Alkaloids: Indoles, Isoquinolines, and Others

    NASA Astrophysics Data System (ADS)

    Stöckigt, Joachim; Chen, Zhong; Ruppert, Martin

    The multi-step enzyme catalysed biosyntheses of monoterpenoid indole and isoquinoline alkaloids are described. Special emphasis is placed on those pathways leading to alkaloids of pharmacological and medicinal significance which have been fully elucidated at the enzyme level. The successful identification and cloning of cDNAs of single enzymes and their application provides great opportunities to develop novel strategies for both in vitro and in vivo alkaloid production in whole plants or tissue cultures, as well as in microbial systems such as Escherichia coli and yeast.

  6. Metabolic Profiling of Pyrrolizidine Alkaloids in Foliage of Two Echium spp. Invaders in Australia-A Case of Novel Weapons?

    PubMed

    Skoneczny, Dominik; Weston, Paul A; Zhu, Xiaocheng; Gurr, Geoff M; Callaway, Ragan M; Weston, Leslie A

    2015-01-01

    Metabolic profiling allows for simultaneous and rapid annotation of biochemically similar organismal metabolites. An effective platform for profiling of toxic pyrrolizidine alkaloids (PAs) and their N-oxides (PANOs) was developed using ultra high pressure liquid chromatography quadrupole time-of-flight (UHPLC-QTOF) mass spectrometry. Field-collected populations of invasive Australian weeds, Echium plantagineum and E. vulgare were raised under controlled glasshouse conditions and surveyed for the presence of related PAs and PANOs in leaf tissues at various growth stages. Echium plantagineum possessed numerous related and abundant PANOs (>17) by seven days following seed germination, and these were also observed in rosette and flowering growth stages. In contrast, the less invasive E. vulgare accumulated significantly lower levels of most PANOs under identical glasshouse conditions. Several previously unreported PAs were also found at trace levels. Field-grown populations of both species were also evaluated for PA production and highly toxic echimidine N-oxide was amongst the most abundant PANOs in foliage of both species. PAs in field and glasshouse plants were more abundant in the more widely invasive species, E. plantagineum, and may provide competitive advantage by increasing the plant's capacity to deter natural enemies in its invaded range through production of novel weapons. PMID:26561809

  7. Metabolic Profiling of Pyrrolizidine Alkaloids in Foliage of Two Echium spp. Invaders in Australia—A Case of Novel Weapons?

    PubMed Central

    Skoneczny, Dominik; Weston, Paul A.; Zhu, Xiaocheng; Gurr, Geoff M.; Callaway, Ragan M.; Weston, Leslie A.

    2015-01-01

    Metabolic profiling allows for simultaneous and rapid annotation of biochemically similar organismal metabolites. An effective platform for profiling of toxic pyrrolizidine alkaloids (PAs) and their N-oxides (PANOs) was developed using ultra high pressure liquid chromatography quadrupole time-of-flight (UHPLC-QTOF) mass spectrometry. Field-collected populations of invasive Australian weeds, Echium plantagineum and E. vulgare were raised under controlled glasshouse conditions and surveyed for the presence of related PAs and PANOs in leaf tissues at various growth stages. Echium plantagineum possessed numerous related and abundant PANOs (>17) by seven days following seed germination, and these were also observed in rosette and flowering growth stages. In contrast, the less invasive E. vulgare accumulated significantly lower levels of most PANOs under identical glasshouse conditions. Several previously unreported PAs were also found at trace levels. Field-grown populations of both species were also evaluated for PA production and highly toxic echimidine N-oxide was amongst the most abundant PANOs in foliage of both species. PAs in field and glasshouse plants were more abundant in the more widely invasive species, E. plantagineum, and may provide competitive advantage by increasing the plant’s capacity to deter natural enemies in its invaded range through production of novel weapons. PMID:26561809

  8. Simultaneous quantification and pharmacokinetics of alkaloids in Herba Ephedrae-Radix Aconiti Lateralis extracts.

    PubMed

    Song, Shuai; Tang, Qingfa; Huo, Huiling; Li, Hancheng; Xing, Xuefeng; Luo, Jiabo

    2015-01-01

    The combination of Herba Ephedrae (Mahuang in Chinese) and Radix Aconiti Lateralis (Fuzi in Chinese) is a classical preparation in traditional Chinese medicine and used for treating colds and rheumatic arthralgia. However, herbal medicines containing ephedrines and Aconitum alkaloids are strictly regulated because of the potential for adverse effects on the cardiovascular system and the central nervous system. We aimed to investigate the pharmacokinetics of 11 alkaloids in the Mahuang-Fuzi combination and single-herb extracts after oral administration in rats. The alkaloids were norephedrine, norpseudoephedrine, ephedrine, pseudoephedrine, methylephedrine, aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine. Simultaneous determination of the alkaloids, including two pairs of diastereomers, was achieved in 14.5 min by a simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method. The separation was performed on a Zorbax SB-Aq column (100 mm × 2.1 mm, 3.5 ?m) at a flow rate of 0.3 mL/min using acetonitrile-0.1% formic acid aqueous solution as the mobile phase. The validated method demonstrated adequate sensitivity, selectivity and process efficiency for the quantitative analysis of complex herbal components. Compared with single-herb extracts, alkaloids in plasma (except methylephedrine, benzoylmesaconine and benzoylhypaconine) showed slower elimination (the mean residence time or half-life was longer), although the maximum plasma concentration and area under the plasma concentration curve values decreased. Accumulation may occur with continuous drug intake. These results suggest that drug monitoring may be essential for the safe use of the Mahuang-Fuzi combination. PMID:25324527

  9. Pterin-Dependent Mono-oxidation for the Microbial Synthesis of a Modified Monoterpene Indole Alkaloid.

    PubMed

    Ehrenworth, A M; Sarria, S; Peralta-Yahya, P

    2015-12-18

    Monoterpene indole alkaloids (MIAs) have important therapeutic value, including as anticancer and antimalarial agents. Because of their chemical complexity, therapeutic MIAs, or advanced intermediates thereof, are often isolated from the native plants. The microbial synthesis of MIAs would allow for the rapid and scalable production of complex MIAs and MIA analogues for therapeutic use. Here, we produce the modified MIA hydroxystrictosidine from glucose and the monoterpene secologanin via a pterin-dependent mono-oxidation strategy. Specifically, we engineered the yeast Saccharomyces cerevisiae for the high-level synthesis of tetrahydrobiopterin to mono-oxidize tryptophan to 5-hydroxytryptophan, which, after decarboxylation to serotonin, is coupled to exogenously fed secologanin to produce 10-hydroxystrictosidine in an eight-enzyme pathway. We selected hydroxystrictosidine as our synthetic target because hydroxylation at the 10' position of the alkaloid core strictosidine provides a chemical handle for the future chemical semisynthesis of therapeutics. We show the generality of the pterin-dependent mono-oxidation strategy for alkaloid synthesis by hydroxylating tyrosine to L-DOPA-a key intermediate in benzylisoquinoline alkaloid (BIA) biosynthesis-and, thereafter, further converting it to dopamine. Together, these results present the first microbial synthesis of a modified alkaloid, the first production of tetrahydrobiopterin in yeast, and the first use of a pterin-dependent mono-oxidation strategy for the synthesis of L-DOPA. This work opens the door to the scalable production of MIAs as well as the production of modified MIAs to serve as late intermediates in the semisynthesis of known and novel therapeutics. Further, the microbial strains in this work can be used as plant pathway discovery tools to elucidate known MIA biosynthetic pathways or to identify pathways leading to novel MIAs. PMID:26214239

  10. Identification of legal highs--ergot alkaloid patterns in two Argyreia nervosa products.

    PubMed

    Paulke, Alexander; Kremer, Christian; Wunder, Cora; Wurglics, Mario; Schubert-Zsilavecz, Manfred; Toennes, Stefan W

    2014-09-01

    Nowadays psychoactive plants marketed as "legal highs" or "herbal highs" increase in popularity. One popular "legal high" are the seeds of the Hawaiian baby woodrose Argyreia nervosa (Synonym: Argyreia speciosa, Convolvolus speciosus). At present there exists no study on A. nervosa seeds or products, which are used by consumers. The quality of commercial available A. nervosa seeds or products is completely unknown. In the present study, a commercial available seed collection (five seeds labeled "flash of inspiration", FOI) was analyzed for ergot alkaloids together with an A. nervosa product (two preparations in capsule form, "druids fantasy", DF). For this purpose high performance liquid chromatography high resolution tandem mass spectrometry (HPLC-HRMS/MS) technique was employed. Besides the major ingredients such as lysergic acid amide (LSA) and ergometrine the well known A. nervosa compounds lysergol/elymoclavine/setoclavine, chanoclavine and the respective stereoisomers were detected in DF, while only LSA and ergometrine could be found in FOI. In addition, in DF lysergic acid was found, which has not been reported yet as ingredient of A. nervosa. In both products, DF as well as in FOI, LSA/LSA-isomers were dominant with 83-84% followed by ergometrine/ergometrinine with 10-17%. Therefore, LSA, followed by ergometrine/ergometrinine, could be confirmed to be the main ergot alkaloids present in A. nervosa seeds/products whereas the other ergot alkaloids seemed to be of minor importance (less than 6.1% in DF). The total ergot alkaloid amounts varied considerably between DF and FOI by a factor of 8.6 as well as the LSA concentration ranging from 3 ?g (lowest amount in one FOI seed) to approximately 34 ?g (highest amount in one DF capsule). Among the FOI seeds, the LSA concentration varied from approximately 3-15 ?g per seed. Thus, the quality/potency of seeds/preparations depends on the amount of ergot alkaloids and the intensity of an expected trip is totally unpredictable. PMID:25036782

  11. Folate-vinca alkaloid conjugates for cancer therapy: a structure-activity relationship.

    PubMed

    Leamon, Christopher P; Vlahov, Iontcho R; Reddy, Joseph A; Vetzel, Marilynn; Santhapuram, Hari Krishna R; You, Fei; Bloomfield, Alicia; Dorton, Ryan; Nelson, Melissa; Kleindl, Paul; Vaughn, Jeremy F; Westrick, Elaine

    2014-03-19

    Vintafolide is a potent folate-targeted vinca alkaloid small molecule drug conjugate (SMDC) that has shown promising results in multiple clinical oncology studies. Structurally, vintafolide consists of 4 essential modules: (1) folic acid, (2) a hydrophilic peptide spacer, (3) a disulfide-containing, self-immolative linker, and (4) the cytotoxic drug, desacetylvinblastine hydrazide (DAVLBH). Here, we report a structure-activity study evaluating the biological impact of (i) substituting DAVLBH within the vintafolide molecule with other vinca alkaloid analogues such as vincristine, vindesine, vinflunine, or vinorelbine; (ii) substituting the naturally (S)-configured Asp-Arg-Asp-Asp-Cys peptide with alternative hydrophilic spacers of varied composition; and (iii) varying the composition of the linker module. A series of vinca alkaloid-containing SMDCs were synthesized and purified by HPLC and LCMS. The SMDCs were screened in vitro against folate receptor (FR)-positive cells, and anti-tumor activity was tested against well-established subcutaneous FR-positive tumor xenografts. The cytotoxic and anti-tumor activity was directly compared to that produced by vintafolide. Among all the folate vinca alkaloid SMDCs tested, DAVLBH-containing SMDCs were active, while those constructed with vincristine, vindesine, or vinorelbine analogues failed to produce meaningful biological activity. Within the DAVLBH series, having a bioreleasable, self-immolative linker system was found to be critical for activity since multiple analogues constructed with thioether-based linkers all failed to produce meaningful activity both in vitro and in vivo. Substitutions of some or all of the natural amino acids within vintafolide's hydrophilic spacer module did not significantly change the in vitro or in vivo potency of the SMDCs. Vintafolide remains one of the most potent folate-vinca alkaloid SMDCs produced to date, and continued clinical development is warranted. PMID:24564229

  12. Pyrrolizidine alkaloids in honey: comparison of analytical methods.

    PubMed

    Kempf, M; Wittig, M; Reinhard, A; von der Ohe, K; Blacquière, T; Raezke, K-P; Michel, R; Schreier, P; Beuerle, T

    2011-03-01

    Pyrrolizidine alkaloids (PAs) are a structurally diverse group of toxicologically relevant secondary plant metabolites. Currently, two analytical methods are used to determine PA content in honey. To achieve reasonably high sensitivity and selectivity, mass spectrometry detection is demanded. One method is an HPLC-ESI-MS-MS approach, the other a sum parameter method utilising HRGC-EI-MS operated in the selected ion monitoring mode (SIM). To date, no fully validated or standardised method exists to measure the PA content in honey. To establish an LC-MS method, several hundred standard pollen analysis results of raw honey were analysed. Possible PA plants were identified and typical commercially available marker PA-N-oxides (PANOs). Three distinct honey sets were analysed with both methods. Set A consisted of pure Echium honey (61-80% Echium pollen). Echium is an attractive bee plant. It is quite common in all temperate zones worldwide and is one of the major reasons for PA contamination in honey. Although only echimidine/echimidine-N-oxide were available as reference for the LC-MS target approach, the results for both analytical techniques matched very well (n = 8; PA content ranging from 311 to 520 µg kg(-1)). The second batch (B) consisted of a set of randomly picked raw honeys, mostly originating from Eupatorium spp. (0-15%), another common PA plant, usually characterised by the occurrence of lycopsamine-type PA. Again, the results showed good consistency in terms of PA-positive samples and quantification results (n = 8; ranging from 0 to 625 µg kg(-1) retronecine equivalents). The last set (C) was obtained by consciously placing beehives in areas with a high abundance of Jacobaea vulgaris (ragwort) from the Veluwe region (the Netherlands). J. vulgaris increasingly invades countrysides in Central Europe, especially areas with reduced farming or sites with natural restorations. Honey from two seasons (2007 and 2008) was sampled. While only trace amounts of ragwort pollen were detected (0-6.3%), in some cases extremely high PA values were detected (n = 31; ranging from 0 to 13019 µg kg(-1), average = 1261 or 76 µg kg(-1) for GC-MS and LC-MS, respectively). Here the results showed significantly different quantification results. The GC-MS sum parameter showed in average higher values (on average differing by a factor 17). The main reason for the discrepancy is most likely the incomplete coverage of the J. vulgaris PA pattern. Major J. vulgaris PAs like jacobine-type PAs or erucifoline/acetylerucifoline were not available as reference compounds for the LC-MS target approach. Based on the direct comparison, both methods are considered from various perspectives and the respective individual strengths and weaknesses for each method are presented in detail. PMID:21082464

  13. Analysis of Indole Alkaloids from Rhazya stricta Hairy Roots by Ultra-Performance Liquid Chromatography-Mass Spectrometry.

    PubMed

    Akhgari, Amir; Laakso, Into; Seppänen-Laakso, Tuulikki; Yrjönen, Teijo; Vuorela, Heikki; Oksman-Caldentey, Kirsi-Marja; Rischer, Heiko

    2015-01-01

    Rhazya stricta Decne. (Apocynaceae) contains a large number of terpenoid indole alkaloids (TIAs). This study focused on the composition of alkaloids obtained from transformed hairy root cultures of R. stricta employing ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). In the UPLC-MS analyses, a total of 20 TIAs were identified from crude extracts. Eburenine and vincanine were the main alkaloids followed by polar glucoalkaloids, strictosidine lactam and strictosidine. Secodine-type alkaloids, tetrahydrosecodinol, tetrahydro- and dihydrosecodine were detected too. The occurrence of tetrahydrosecodinol was confirmed for the first time for R. stricta. Furthermore, two isomers of yohimbine, serpentine and vallesiachotamine were identified. The study shows that a characteristic pattern of biosynthetically related TIAs can be monitored in Rhazya hairy root crude extract by this chromatographic method. PMID:26694342

  14. A Concise and Versatile Double-Cyclization Strategy for the Highly Stereoselective Synthesis and Arylative Dimerization of Aspidosperma Alkaloids

    E-print Network

    Medley, Jonathan William

    Building cycles: A strategy for the concise, stereoselective synthesis of aspidosperma alkaloids and related structures via a common putative diiminium ion intermediate is reported. The approach enables the dimerization ...

  15. Development and validation of a reversed-phase HPLC method for determination of alkaloids from Papaver somniferum L. (Papaveraceae).

    PubMed

    Acevska, Jelena; Dimitrovska, Aneta; Stefkov, Gjoshe; Brezovska, Katerina; Karapandzova, Marija; Kulevanova, Svetlana

    2012-01-01

    An HPLC method for the separation of six target alkaloids from Papaver somniferum L. (morphine, codeine, oripavine, thebaine, papaverine, and noscapine) was developed, optimized, and validated. The chromatographic behavior of these alkaloids was investigated using a reversed-phase chromatography at acidic and alkaline pH. The effects of ion-pairing agents, pH value of the mobile phase, concentration of the buffer components, mobile phase organic modifier, and column temperature were studied. Regardless of the large differences in their pKa values, all alkaloids were separated within a close retention window, and good peak shape was achieved for each of the six alkaloids. The proposed method has adequate selectivity, linearity, accuracy, precision, and reproducibility and is applicable for poppy straw. PMID:22649926

  16. Hydroxylic solvent-induced ring opening of the dehydropyrrolizidine alkaloids riddelliine and seneciphylline: implications for toxicity and analytical studies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    etabolites that can also cause various cancers in animal models. Riddelliine and seneciphylline are closely-related, macrocyclic diester dehydropyrrolizidine alkaloids produced by various species in the Asteraceae. Despite the evidence of carcinogenicity in animal models, and the increasing concerns...

  17. Synthetic Studies Toward Selected Members of the Pyrrole-imidazole Alkaloids: Axinellamine, Konbu’acidin and Palau' amine 

    E-print Network

    Zancanella, Manuel

    2011-10-21

    The pyrrole imidazole alkaloids (PIA) is an ever-growing family of structurally related natural products isolated from several species of sponges which now features more than one hundred memebrs. Their complex molecular ...

  18. Blood pyrrole-protein adducts as a diagnostic and prognostic index in pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome

    PubMed Central

    Gao, Hong; Ruan, Jianqing Q; Chen, Jie; Li, Na; Ke, Changqiang Q; Ye, Yang; Lin, Ge; Wang, Jiyao Y

    2015-01-01

    Background The diagnosis of hepatic sinusoidal obstruction syndrome (HSOS) induced by pyrrolizidine alkaloids is mainly based on clinical investigation. There is currently no prognostic index. This study evaluated the quantitative measurement of blood pyrrole-protein adducts (PPAs) as a diagnostic and prognostic index for pyrrolizidine alkaloid-induced HSOS. Methods Suspected drug-induced liver injury patients were prospectively recruited. Blood PPAs were quantitatively measured using ultra-performance liquid chromatography-tandem mass spectrometry. Patients’ age, sex, biochemistry test results, and a detailed drug history were recorded. The patients were divided into two groups, ie, those with HSOS induced by pyrrolizidine alkaloid-containing drugs and those with liver injury induced by drugs without pyrrolizidine alkaloids. The relationship between herb administration, clinical outcomes, blood sampling time, and blood PPA concentration in pyrrolizidine alkaloid-associated HSOS patients was analyzed using multiple linear regression analysis. Results Forty patients met the entry criteria, among whom 23 had pyrrolizidine alkaloid-associated HSOS and 17 had liver injury caused by drugs without pyrrolizidine alkaloids. Among the 23 patients with pyrrolizidine alkaloid-associated HSOS, ten recovered, four developed chronic disease, eight died, and one underwent liver transplantation within 6 months after onset. Blood PPAs were detectable in 24 of 40 patients with concentrations from 0.05 to 74.4 nM. Sensitivity and specificity of the test for diagnosis of pyrrolizidine alkaloid-associated HSOS were 100% (23/23) and 94.1% (23/24), respectively. The positive predictive value was 95.8% and the negative predictive value was 100%, whereas the positive likelihood ratio was 23.81. The level of blood PPAs in the severe group (died or received liver transplantation) was significantly higher than that in the recovery/chronicity group (P=0.004). Conclusion Blood PPAs measured by ultra-performance liquid chromatography-tandem mass spectrometry are highly sensitive and specific for pyrrolizidine alkaloid-associated HSOS. The blood PPA concentration is related to the severity and clinical outcome of pyrrolizidine alkaloid-associated HSOS. PMID:26346783

  19. Efficient and Stereoselective Dimerization of Pyrroloindolizine Derivatives Inspired by a Hypothesis for the Biosynthesis of Complex Myrmicarin Alkaloids

    PubMed Central

    Movassaghi, Mohammad; Ondrus, Alison E.; Chen, Bin

    2010-01-01

    Pyrroloindolizine derivatives participate in efficient and stereoselective homo- and heterodimerization reactions upon treatment with Brønsted or Lewis acids. The distinctive ability of pyrroloindolizines to act as azafulvenium ion precursors provides direct access to both heptacyclic and hexacyclic dimeric products. The inherent reactivity of these structures suggests a concise synthesis of complex myrmicarin alkaloids via dimerization of pyrroloindolizines, and may have implications for the biosynthesis of these intriguing alkaloids. PMID:18020368

  20. An old yellow enzyme gene controls the branch point between Aspergillus fumigatus and Claviceps purpurea ergot alkaloid pathways.

    PubMed

    Coyle, Christine M; Cheng, Johnathan Z; O'Connor, Sarah E; Panaccione, Daniel G

    2010-06-01

    Ergot fungi in the genus Claviceps and several related fungal groups in the family Clavicipitaceae produce toxic ergot alkaloids. These fungi produce a variety of ergot alkaloids, including clavines as well as lysergic acid derivatives. Ergot alkaloids are also produced by the distantly related, opportunistic human pathogen Aspergillus fumigatus. However, this fungus produces festuclavine and fumigaclavines A, B, and C, which collectively differ from clavines of clavicipitaceous fungi in saturation of the last assembled of four rings in the ergoline ring structure. The two lineages are hypothesized to share early steps of the ergot alkaloid pathway before diverging at some point after the synthesis of the tricyclic intermediate chanoclavine-I. Disruption of easA, a gene predicted to encode a flavin-dependent oxidoreductase of the old yellow enzyme class, in A. fumigatus led to accumulation of chanoclavine-I and chanoclavine-I-aldehyde. Complementation of the A. fumigatus easA mutant with a wild-type allele from the same fungus restored the wild-type profile of ergot alkaloids. These data demonstrate that the product of A. fumigatus easA is required for incorporation of chanoclavine-I-aldehyde into more-complex ergot alkaloids, presumably by reducing the double bond conjugated to the aldehyde group, thus facilitating ring closure. Augmentation of the A. fumigatus easA mutant with a homologue of easA from Claviceps purpurea resulted in accumulation of ergot alkaloids typical of clavicipitaceous fungi (agroclavine, setoclavine, and its diastereoisomer isosetoclavine). These data indicate that functional differences in the easA-encoded old yellow enzymes of A. fumigatus and C. purpurea result in divergence of their respective ergot alkaloid pathways. PMID:20435769