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Sample records for numerous norditerpenoid alkaloids

  1. 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...

  2. Constitutens of high altitude Himalayan herbs. Part XV: A new norditerpenoid alkaloid from the roots of Aconitum balfourii.

    PubMed

    Khetwal, K S; Pande, Sunita

    2004-04-01

    A new norditerpenoid alkaloid 9-hydroxysenbushine A has been isolated from the roots of high altitude Himalayan herb Aconitum balfourii by means of vacuum liquid chromatography and centrally accelerated radial thin layer chromatographic techniques and identified by means of MS, 1H and 13C NMR spectral methods. PMID:14984085

  3. 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...

  4. 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...

  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. The effect of 7, 8-Methylenedioxylycoctonine -Type Diterpenoid Alkaloids on the Toxicity of Methyllycaconitine in Mice

    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). The toxicity of many t...

  7. 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...

  8. 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...

  9. Vinca Alkaloids

    PubMed Central

    Moudi, Maryam; Go, Rusea; Yien, Christina Yong Seok; Nazre, Mohd.

    2013-01-01

    Vinca alkaloids are a subset of drugs obtained from the Madagascar periwinkle plant. They are naturally extracted from the pink periwinkle plant, Catharanthus roseus G. Don and have a hypoglycemic as well as cytotoxic effects. They have been used to treat diabetes, high blood pressure and have been used as disinfectants. The vinca alkaloids are also important for being cancer fighters. There are four major vinca alkaloids in clinical use: Vinblastine (VBL), vinorelbine (VRL), vincristine (VCR) and vindesine (VDS). VCR, VBL and VRL have been approved for use in the United States. Vinflunine is also a new synthetic vinca alkaloid, which has been approved in Europe for the treatment of second-line transitional cell carcinoma of the urothelium is being developed for other malignancies. Vinca alkaloids are the second-most-used class of cancer drugs and will stay among the original cancer therapies. Different researches and studies for new vinca alkaloid applications will be carried out in this regard. PMID:24404355

  10. Identification of Oxygenated Fatty Acid as a Side Chain of Lipo-Alkaloids in Aconitum carmichaelii by UHPLC-Q-TOF-MS and a Database.

    PubMed

    Liang, Ying; Wu, Jian-Lin; Leung, Elaine Lai-Han; Zhou, Hua; Liu, Zhongqiu; Yan, Guanyu; Liu, Ying; Liu, Liang; Li, Na

    2016-01-01

    Lipo-alkaloid is a kind of C19-norditerpenoid alkaloid usually found in Aconitum species. Structurally, they contain an aconitane skeleton and one or two fatty acid moieties of 3-25 carbon chains with 1-6 unsaturated degrees. Analysis of the lipo-alkaloids in roots of Aconitum carmichaelii resulted in the isolation of six known pure lipo-alkaloids (A1-A6) and a lipo-alkaloid mixture (A7). The mixture shared the same aconitane skeleton of 14-benzoylmesaconine, but their side chains were determined to be 9-hydroxy-octadecadienoic acid, 13-hydroxy-octadecadienoic acid and 10-hydroxy-octadecadienoic acid, respectively, by MS/MS analysis after alkaline hydrolysis. To our knowledge, this is the first time of the reporting of the oxygenated fatty acids as the side chains in naturally-occurring lipo-alkaloids. In order to identify more lipo-alkaloids, a compound database was established based on various combinations between the aconitane skeleton and the fatty acid chain, and then, the identification of lipo-alkaloids was conducted using the database, UHPLC-Q-TOF-MS and MS/MS. Finally, 148 lipo-alkaloids were identified from A. carmichaelii after intensive MS/MS analysis, including 93 potential new compounds and 38 compounds with oxygenated fatty acid moieties. PMID:27043515

  11. Exploiting plant alkaloids.

    PubMed

    Schläger, Sabrina; Dräger, Birgit

    2016-02-01

    Alkaloid-containing plants have been used for medicine since ancient times. Modern pharmaceuticals still rely on alkaloid extraction from plants, some of which grow slowly, are difficult to cultivate and produce low alkaloid yields. Microbial cells as alternative alkaloid production systems are emerging. Before industrial application of genetically engineered bacteria and yeasts, several steps have to be taken. Original alkaloid-forming enzymes have to be elucidated from plants. Their activity in the heterologous host cells, however, may be low. The exchange of individual plant enzymes for alternative catalysts with better performance and optimal fermentation parameters appear promising. The overall aim is enhancement and stabilization of alkaloid yields from microbes in order to replace the tedious extraction of low alkaloid concentrations from intact plants. PMID:26748036

  12. 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...

  13. New Perspectives in the Chemistry of Marine Pyridoacridine Alkaloids

    PubMed Central

    Plodek, Alois; Bracher, Franz

    2016-01-01

    Secondary metabolites from marine organisms are a rich source of novel leads for drug development. Among these natural products, polycyclic aromatic alkaloids of the pyridoacridine type have attracted the highest attention as lead compounds for the development of novel anti-cancer and anti-infective drugs. Numerous sophisticated total syntheses of pyridoacridine alkaloids have been worked out, and many of them have also been extended to the synthesis of libraries of analogues of the alkaloids. This review summarizes the progress in the chemistry of pyridoacridine alkaloids that was made in the last one-and-a-half decades. PMID:26821033

  14. Monoterpenoid Bisindole Alkaloids.

    PubMed

    Kitajima, Mariko; Takayama, Hiromitsu

    2016-01-01

    This chapter covers the literature on bisindole alkaloids consisting of monoterpenoid indoles, published up to June 2015. Bisindole alkaloids isolated from plants belonging to the families Apocynaceae and Loganiaceae, including Iboga-vobasine type, Aspidosperma-Aspidosperma type, eburnan-Aspidosperma type, Strychnos-Strychnos type, macroline-macroline type, and so on, are described. Some recent syntheses of monoterpenoid bisindole alkaloids are outlined as well. PMID:26827885

  15. 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.

  16. Amaryllidaceae and Sceletium alkaloids.

    PubMed

    Jin, Zhong

    2013-06-01

    Covering: July 2010 to June 2012. Previous review: Nat. Prod. Rep., 2011, 28, 1126-1142. Recent progress on the isolation, identification, biological activity and synthetic studies of structurally diverse alkaloids from plants of the family Amaryllidaceae is summarized in this review. In addition, the structurally related alkaloids isolated from Sceletium species are discussed as well. PMID:23644557

  17. Alkaloids of Ocotea brachybotra.

    PubMed

    Vecchietti, V; Casagrande, C; Ferrari, G

    1977-11-01

    Aporphine, proaporphine and morphinane alkaloids were isolated from the leaves of a Brazilian Lauracea, Ocotea brachybotra (Meiss.) Mez. The known alkaloids were identified through their physico-chemical properties as: (I) (+/-)-glaziovine, (II) dicentrine, (III) ocopodine, (IV) cassynthicine, (V) predicentrine, (VI) leucoxine, (IX) sinacutine and (X) pallidine. The structure of (VI) leucoxine was confirmed by a detailed analysis of the N.M.R. spectra recorded in various conditions. New morphinane alkaloids, (XI) ocobotrine and (XII) 14-espisinomenine, having the unusual B/C-trans configuration were also isolated. Their structures were determined using spectroscopic methods and chemical correlations. PMID:923790

  18. Dimeric Cinchona alkaloids.

    PubMed

    Boratyński, Przemysław J

    2015-05-01

    Nature is full of dimeric alkaloids of various types from many plant families, some of them with interesting biological properties. However, dimeric Cinchona alkaloids were not isolated from any species but were products of designed partial chemical synthesis. Although the Cinchona bark is amongst the sources of oldest efficient medicines, the synthetic dimers found most use in the field of asymmetric synthesis. Prominent examples include the Sharpless dihydroxylation and aminohydroxylation ligands, and dimeric phase transfer catalysts. In this article the syntheses of Cinchona alkaloid dimers and oligomers are reviewed, and their structure and applications are outlined. Various synthetic routes exploit reactivity of the alkaloids at the central 9-hydroxyl group, quinuclidine, and quinoline rings, as well as 3-vinyl group. This availability of reactive sites, in combination with a plethora of linker molecules, contributes to the diversity of the products obtained. PMID:25586655

  19. Occurrence of halogenated alkaloids.

    PubMed

    Gribble, Gordon W

    2012-01-01

    Once considered to be isolation artifacts or chemical "mistakes" of nature, the number of naturally occurring organohalogen compounds has grown from a dozen in 1954 to >5000 today. Of these, at least 25% are halogenated alkaloids. This is not surprising since nitrogen-containing pyrroles, indoles, carbolines, tryptamines, tyrosines, and tyramines are excellent platforms for biohalogenation, particularly in the marine environment where both chloride and bromide are plentiful for biooxidation and subsequent incorporation into these electron-rich substrates. This review presents the occurrence of all halogenated alkaloids, with the exception of marine bromotyrosines where coverage begins where it left off in volume 61 of The Alkaloids. Whereas the biological activity of these extraordinary compounds is briefly cited for some examples, a future volume of The Alkaloids will present full coverage of this topic and will also include selected syntheses of halogenated alkaloids. Natural organohalogens of all types, especially marine and terrestrial halogenated alkaloids, comprise a rapidly expanding class of natural products, in many cases expressing powerful biological activity. This enormous proliferation has several origins: (1) a revitalization of natural product research in a search for new drugs, (2) improved compound characterization methods (multidimensional NMR, high-resolution mass spectrometry), (3) specific enzyme-based and other biological assays, (4) sophisticated collection methods (SCUBA and remote submersibles for deep ocean marine collections), (5) new separation and purification techniques (HPLC and countercurrent separation), (6) a greater appreciation of traditional folk medicine and ethobotany, and (7) marine bacteria and fungi as novel sources of natural products. Halogenated alkaloids are truly omnipresent in the environment. Indeed, one compound, Q1 (234), is ubiquitous in the marine food web and is found in the Inuit from their diet of whale blubber. Given the fact that of the 500,000 estimated marine organisms--which are the source of most halogenated alkaloids--only a small percentage have been investigated for their chemical content, it is certain that myriad new halogenated alkaloids are awaiting discovery. For example, it is estimated that nearly 4000 species of bryozoans have not been examined for their chemical content. The few species that have been studied contain some extraordinary halogenated alkaloids, such as hinckdentine A (610) and the chartellines (611-613). Of the estimated 1.5 million species of fungi, secondary metabolites have been characterized from only 5000 species. The future seems bright for the collector of halogenated alkaloids! PMID:23189746

  20. 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

  1. Sarpagine and related alkaloids

    PubMed Central

    Namjoshi, Ojas A.; Cook, James M.

    2016-01-01

    The sarpagine-related macroline and ajmaline alkaloids share a common biosynthetic origin, and bear important structural similarities, as expected. These indole alkaloids are widely dispersed in 25 plant genera, principally in the Apocynaceae family. Very diverse and interesting biological properties have been reported for this group of natural products. Isolation of new sarpagine-related alkaloids as well as the asymmetric synthesis of these structurally complex molecules are of paramount importance to the synthetic and medicinal chemists. A total of 115 newly isolated sarpagine-related macroline and ajmaline alkaloids, along with their physicochemical properties have been included in this chapter. A general and efficient strategy for the synthesis of these monomeric alkaloids, as well as bisindoles has been presented, which involves application of the asymmetric Pictet–Spengler reaction (>98% ee) as a key step because of the ease of scale up of the tetracyclic template. Also included in this chapter are the syntheses of the sarpagine-related alkaloids, published since the year 2000. PMID:26827883

  2. Sarpagine and Related Alkaloids.

    PubMed

    Namjoshi, Ojas A; Cook, James M

    2016-01-01

    The sarpagine-related macroline and ajmaline alkaloids share a common biosynthetic origin, and bear important structural similarities, as expected. These indole alkaloids are widely dispersed in 25 plant genera, principally in the family Apocynaceae. Very diverse and interesting biological properties have been reported for this group of natural products. Isolation of new sarpagine-related alkaloids and the asymmetric synthesis of these structurally complex molecules are of paramount importance to the synthetic and medicinal chemists. A total of 115 newly isolated sarpagine-related macroline and ajmaline alkaloids, along with their physicochemical properties have been included in this chapter. A general and efficient strategy for the synthesis of these monomeric alkaloids, as well as bisindoles, has been presented, which involves application of the asymmetric Pictet-Spengler reaction (>98% ee) as a key step because of the ease of scale up of the tetracyclic template. Also included in this chapter are the syntheses of the sarpagine-related alkaloids, published since 2000. PMID:26827883

  3. 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

  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. 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 ...

  6. 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

  7. 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

  8. Identification and determination of ergot alkaloids in Morning Glory cultivars.

    PubMed

    Nowak, Julia; Woźniakiewicz, Michał; Klepacki, Piotr; Sowa, Anna; Kościelniak, Paweł

    2016-05-01

    Seeds of plants from Ipomoea genera contain numerous ergot alkaloids, including psychoactive ergine and ergometrine, and are often abused as so-called "legal highs." In this work, an analytical method for determination of ergine and ergometrine, and identification of other alkaloids was developed, optimized, and validated. Three extraction techniques, ultrasound-assisted extraction in bath, or with sonotrode, and microwave-assisted extraction were evaluated, and it was concluded that ultrasonic bath is the most suitable technique for extraction of ergot alkaloids. The extraction method was later optimized using a Doehlert experimental design with response surface methodology and used together with the optimized LC-Q-TOF-MS method. The analytical procedure was validated in terms of recovery and matrix effect, repeatability, and intermediate precision. Limits of detection and quantification were 1.0 and 3.0 ng mL(-1), respectively, and were sufficient for determination of ergot alkaloids in Ipomoea seeds. The analysis revealed that from five kinds of seeds purchased from different vendors, only three contained ergot alkaloids. Concentration of alkaloids and their relative abundance was similar in samples representative for whole seeds packs; however, when single seeds were analyzed, significant discrepancies in ergine and ergometrine concentrations were detected. Graphical Abstract Identification of six ergot alkaloids and determination of ergine and ergometrine in Morning glory seeds using the ultrasound-assisted extraction followed the LC-MS analysis. PMID:26873205

  9. [Alkaloids of plumula Nelumbinis].

    PubMed

    Wang, J; Hu, X; Yin, W; Cai, H

    1991-11-01

    Six alkaloids were isolated from the green seed embryo of Nelumbo nucifera growing in Ruichang, Jiangxi province. On the basis of physiochemical properties and spectroscopic methods (UV, IR, NMR, MS) they were identified as: lotusine, nuciferine, pronuciferine, liensinine, isoliensinine and neferine. PMID:1804171

  10. 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...

  11. Alkaloids from Balanites aegyptiaca.

    PubMed

    Sarker, S D; Bartholomew, B; Nash, R J

    2000-06-01

    High performance liquid chromatographic (HPLC) analysis of a dichloromethane extract of the stem-barks of Balanites aegyptiaca has yielded two known alkaloids, N-trans-feruloyltyramine (1) and N-cis-feruloyltyramine (2), and three common metabolites, vanillic acid, syringic acid and 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-1-propanone. PMID:10844174

  12. Immunoassay of alkaloids

    NASA Astrophysics Data System (ADS)

    Volkov, S. K.

    1993-08-01

    A survey is presented of literature data concerning the development and applications of the immunochemical methods for the assay of alkaloids — one of the classes of physiologically active compounds of plant origin most widely used in medical practice. The bibliography includes 141 references.

  13. 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

  14. Furoquinoline alkaloids from Teclea nobilis.

    PubMed

    Al-Rehaily, Adnan J; Ahmad, Mohammad S; Muhammad, Ilias; Al-Thukair, Assad A; Perzanowski, Herman P

    2003-12-01

    Five new furoquinoline alkaloids, namely tecleabine (1), tecleoxine (2), isotecleoxine (3), methylnkolbisine (4) and chlorodesnkolbisine (5) were isolated from the aerial parts of Teclea nobilis, together with seven known furoquinoline derivatives; one acridone alkaloid, and one known flavanone. The structures of the alkaloids 1-5 were established by 1D and 2D NMR spectral data, including COSY, HMQC and HMBC experiments, as well as HRMS. PMID:14630007

  15. 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-α- trans-cinnamoyloxylupanine ( 2), 13-α-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.

  16. Bisbenzylisoquinoline Alkaloids from Nelumbo nucifera.

    PubMed

    Itoh, Atsuko; Saitoh, Tomomi; Tani, Kaori; Uchigaki, Misaki; Sugimoto, Yumi; Yamada, Jun; Nakajima, Hiroshi; Ohshiro, Hideo; Sun, Schujian; Tanahashi, Takao

    2011-01-01

    From the embryos of the seeds of Nelumbo nucifera, three bisbenzylisoquinoline alkaloids, nelumboferine and nelumborines A and B, were isolated along with four known compounds, neferine, liensinine, isoliensinine and anisic acid. The structures of the new alkaloids were determined mainly by spectroscopic methods. PMID:21804237

  17. Diterpenoid alkaloids from Aconitum vilmorinianum.

    PubMed

    Yin, Tian-Peng; Cai, Le; Fang, Hai-Xian; Fang, Yun-Shan; Li, Zhen-Jie; Ding, Zhong-Tao

    2015-08-01

    Diterpenoid alkaloids, named vilmorines A-D, in addition to fifteen known alkaloids, were isolated from roots of Aconitum vilmorinianum. Their structures were established on the basis of extensive spectroscopic analyses. Antibacterial and antioxidant studies on isolated compounds were also carried out. PMID:26021734

  18. The Veratrum and Solanum alkaloids.

    PubMed

    Heretsch, Philipp; Giannis, Athanassios

    2015-01-01

    This survey on steroidal alkaloids of the Veratrum and Solanum family isolated between 1974 and 2014 includes 187 compounds and 197 references. New developments in the chemistry and biology of this family of natural products with a special focus on the medicinal relevance of the jervanine alkaloid cyclopamine are discussed. PMID:25845062

  19. Biosynthesis of the ergot alkaloids.

    PubMed

    Jakubczyk, Dorota; Cheng, Johnathan Z; O'Connor, Sarah E

    2014-10-01

    The ergots are a structurally diverse group of alkaloids derived from tryptophan and dimethylallyl pyrophosphate (DMAPP) . The potent bioactivity of ergot alkaloids have resulted in their use in many applications throughout human history. In this highlight, we recap some of the history of the ergot alkaloids, along with a brief description of the classifications of the different ergot structures and producing organisms. Finally we describe what the advancements that have been made in understanding the biosynthetic pathways, both at the genomic and the biochemical levels. We note that several excellent review on the ergot alkaloids, including one by Wallwey and Li in Nat. Prod. Rep., have been published recently. We provide a brief overview of the ergot alkaloids, and highlight the advances in biosynthetic pathway elucidation that have been made since 2011 in Section 4. PMID:25164781

  20. 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

  1. Ergot and Its Alkaloids

    PubMed Central

    Schiff, Paul L.

    2006-01-01

    This manuscript reviews the history and pharmacognosy of ergot, and describes the isolation/preparation, chemistry, pharmacodynamics, and pharmacotherapeutics of the major ergot alkaloids and their derivatives. A brief discussion of the hallucinogenic properties of lysergic acid diethylamide is also featured. An abbreviated form of the material found in this paper is presented in a 4-hour didactic format to third-professional year PharmD students as part of their study of vascular migraine headaches, Parkinson's disease, and naturally occurring hallucinogens/hallucinogen derivatives in the modular course offering Neurology/Psychiatry. PMID:17149427

  2. 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

  3. Dimeric pyrrole-imidazole alkaloids: Synthetic approaches and biosynthetic hypotheses

    PubMed Central

    Wang, Xiao; Ma, Zhiqiang; Wang, Xiaolei; De, Saptarshi; Ma, Yuyong

    2014-01-01

    The pyrrole-imidazole alkaloids are a group of structurally unique and biologically interesting marine sponge metabolites. Among them, the cyclic dimers have caught synthetic chemists’ attention particularly. Numerous synthetic strategies have been developed and various biosynthetic hypotheses have been proposed for these fascinating natural products. We discuss herein the synthetic approaches and the biosynthetic insights obtained from these studies. PMID:24828265

  4. Cyclopeptide Alkaloids from Ziziphus apetala.

    PubMed

    Han, Jing; Ji, Chang-Jiu; He, Wen-Jun; Shen, Yu; Leng, Ying; Xu, Wen-Yan; Fan, Jun-Ting; Zeng, Guang-Zhi; Kong, Ling-Dong; Tan, Ning-Hua

    2011-12-27

    Six novel Ia₃-type cyclopeptide alkaloids (1-6) were isolated from stems of Ziziphus apetala. Compound 5 and the known compounds mauritine A (7) and mauritine F (8) were isolated from the roots. Their structures were determined by spectroscopic analyses and chemical methods. The total alkaloids from the roots and the isolated cyclopeptide alkaloids were tested for antidepressant behavior on mice, cytotoxicity, and 11β-hydroxysteroid dehydrogenase (11β-HSD) inhibition in vitro. Only mauritine A (7) showed inhibitory activity on 11β-HSD1, with IC₅₀ values of 52.0 (human) and 31.2 μg/mL (mouse). PMID:22148241

  5. Biocatalysts from alkaloid producing plants.

    PubMed

    Kries, Hajo; O'Connor, Sarah E

    2016-04-01

    Metabolic pathways leading to benzylisoquinoline and monoterpene indole alkaloids in plants are revealing remarkable new reactions. Understanding of the enzymes involved in alkaloid biosynthesis provides access to a variety of applications in biocatalysis and bioengineering. In chemo-enzymatic settings, plant biocatalysts can transform medically important scaffolds. Additionally, synthetic biologists are taking alkaloid pathways as templates to assemble pathways in microorganisms that are tailored to the needs of medicinal chemistry. In light of these many recent discoveries, it is expected that plants will continue to be a source of novel biocatalysts for the foreseeable future. PMID:26773811

  6. Purine alkaloids in Paullinia.

    PubMed

    Weckerle, Caroline S; Stutz, Michael A; Baumann, Thomas W

    2003-10-01

    Among the few purine alkaloid-containing genera consumed as stimulants, Paullinia is the least investigated with respect to both chemotaxonomy and within-the-plant allocation of caffeine and its allies. Since purine alkaloids (PuA) have been proved to be valuable marker compounds in chemotaxonomy, 34 species of Paullinia and related genera were screened for them, but only one, P. pachycarpa, was positive in addition to the already known P. cupana and P. yoco. The PuA allocation in P. pachycarpa was examined and found to be restricted to theobromine in the stem, leaves and flowers. Moreover, the theobromine concentration in the stem cortex increased significantly towards the base of the plant. Since the stem cortex of P. yoco is traditionally used by the natives of Colombia and Ecuador to prepare a caffeine-rich beverage, we suspected that within the genus Paullinia the PuA are preferentially allocated to the older parts of the stem and not to young shoots like e.g., in the coffee plant (Coffea spp.). Indeed, the axis (greenhouse) of P. cupana (guaraná), known for its caffeine-rich seeds, exhibited a basipetal PuA gradient (0.005-0.145%). Moreover, the analysis of young cortex samples (herbarium) and of one piece of old stem (museum collection) revealed the same for P. yoco, even though we found much less (0.5 vs 2.5%) caffeine in the old cortex as compared to the only two analyses in 1926 of similar material. However, this discrepancy may be explained by the high variability of the PuA pattern we detected among yoco, the diversity of which the Indians take advantage. PMID:13679096

  7. Biosynthetic Pathways of Ergot Alkaloids

    PubMed Central

    Gerhards, Nina; Neubauer, Lisa; Tudzynski, Paul; Li, Shu-Ming

    2014-01-01

    Ergot alkaloids are nitrogen-containing natural products belonging to indole alkaloids. The best known producers are fungi of the phylum Ascomycota, e.g., Claviceps, Epichloë, Penicillium and Aspergillus species. According to their structures, ergot alkaloids can be divided into three groups: clavines, lysergic acid amides and peptides (ergopeptines). All of them share the first biosynthetic steps, which lead to the formation of the tetracyclic ergoline ring system (except the simplest, tricyclic compound: chanoclavine). Different modifications on the ergoline ring by specific enzymes result in an abundance of bioactive natural products, which are used as pharmaceutical drugs or precursors thereof. From the 1950s through to recent years, most of the biosynthetic pathways have been elucidated. Gene clusters from several ergot alkaloid producers have been identified by genome mining and the functions of many of those genes have been demonstrated by knock-out experiments or biochemical investigations of the overproduced enzymes. PMID:25513893

  8. Biosynthetic pathways of ergot alkaloids.

    PubMed

    Gerhards, Nina; Neubauer, Lisa; Tudzynski, Paul; Li, Shu-Ming

    2014-01-01

    Ergot alkaloids are nitrogen-containing natural products belonging to indole alkaloids. The best known producers are fungi of the phylum Ascomycota, e.g., Claviceps, Epichloë, Penicillium and Aspergillus species. According to their structures, ergot alkaloids can be divided into three groups: clavines, lysergic acid amides and peptides (ergopeptines). All of them share the first biosynthetic steps, which lead to the formation of the tetracyclic ergoline ring system (except the simplest, tricyclic compound: chanoclavine). Different modifications on the ergoline ring by specific enzymes result in an abundance of bioactive natural products, which are used as pharmaceutical drugs or precursors thereof. From the 1950s through to recent years, most of the biosynthetic pathways have been elucidated. Gene clusters from several ergot alkaloid producers have been identified by genome mining and the functions of many of those genes have been demonstrated by knock-out experiments or biochemical investigations of the overproduced enzymes. PMID:25513893

  9. Analysis of tropane and related alkaloids.

    PubMed

    Dräger, Birgit

    2002-11-29

    The current methods for tropane alkaloid chromatographic separation and determination are summarised. The alkaloids included are: the medicinally applied tropic acid esters hyoscyamine and scopolamine and their derivatives, cocaine and derivatives, the metabolites and degradation products of these compounds occurring in plant material, calystegines as nortropane alkaloids, anatoxins as homonortropane alkaloids, pelletierines and pseudopelletierines as alkaloids with isomeric structures. Developments in GC, HPLC, CE and TLC are presented and the advantages of each method for plant analysis are discussed. A summary for each chromatographic method lists the instrumentation and parameters applied for tropane alkaloids. PMID:12458942

  10. 27 CFR 21.99 - Brucine alkaloid.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Brucine alkaloid. 21.99... Brucine alkaloid. (a) Identification test. Add a few drops of concentrated nitric acid to about 10 mg of 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, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Brucine alkaloid. 21.99... Brucine alkaloid. (a) Identification test. Add a few drops of concentrated nitric acid to about 10 mg of 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, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Brucine alkaloid. 21.99... Brucine alkaloid. (a) Identification test. Add a few drops of concentrated nitric acid to about 10 mg of 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, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Brucine alkaloid. 21.99... Brucine alkaloid. (a) Identification test. Add a few drops of concentrated nitric acid to about 10 mg of brucine alkaloid. A vivid red color is produced. Dilute the red solution with a few drops of water and...

  14. 27 CFR 21.99 - Brucine alkaloid.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Brucine alkaloid. 21.99... Brucine alkaloid. (a) Identification test. Add a few drops of concentrated nitric acid to about 10 mg of brucine alkaloid. A vivid red color is produced. Dilute the red solution with a few drops of water and...

  15. Numerous Numerals.

    ERIC Educational Resources Information Center

    Henle, James M.

    This pamphlet consists of 17 brief chapters, each containing a discussion of a numeration system and a set of problems on the use of that system. The numeration systems used include Egyptian fractions, ordinary continued fractions and variants of that method, and systems using positive and negative bases. The book is informal and addressed to…

  16. The alkaloid profiles of Lupinus sulphureus.

    PubMed

    Cook, Daniel; Lee, Stephen T; Gardner, Dale R; Pfister, James A; Welch, Kevin D; Green, Benedict T; Davis, T Zane; Panter, Kip E

    2009-02-25

    Lupines are common plants on the rangelands in the western United States. Lupines 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 Columbia. Specimens of L. sulphureus from field collections and herbaria were evaluated taxonomically and by chemical means. A total of seven distinct alkaloid profiles and the individual alkaloids associated with each profile were identified. Each alkaloid profile was unique in its geographical distribution and its potential risk to livestock. In conclusion, taxonomic classification is not sufficient to determine risk, as chemical characterization of the alkaloids must also be performed. PMID:19182952

  17. Structural and quantitative analysis of Equisetum alkaloids.

    PubMed

    Cramer, Luise; Ernst, Ludger; Lubienski, Marcus; Papke, Uli; Schiebel, Hans-Martin; Jerz, Gerold; Beuerle, Till

    2015-08-01

    Equisetum palustre L. is known for its toxicity for livestock. Several studies in the past addressed the isolation and identification of the responsible alkaloids. So far, palustrine (1) and N(5)-formylpalustrine (2) are known alkaloids of E. palustre. A HPLC-ESI-MS/MS method in combination with simple sample work-up was developed to identify and quantitate Equisetum alkaloids. Besides the two known alkaloids six related alkaloids were detected in different Equisetum samples. The structure of the alkaloid palustridiene (3) was derived by comprehensive 1D and 2D NMR experiments. N(5)-Acetylpalustrine (4) was also thoroughly characterized by NMR for the first time. The structure of N(5)-formylpalustridiene (5) is proposed based on mass spectrometry results. Twenty-two E. palustre samples were screened by a HPLC-ESI-MS/MS method after development of a simple sample work-up and in most cases the set of all eight alkaloids were detected in all parts of the plant. A high variability of the alkaloid content and distribution was found depending on plant organ, plant origin and season ranging from 88 to 597mg/kg dried weight. However, palustrine (1) and the alkaloid palustridiene (3) always represented the main alkaloids. For the first time, a comprehensive identification, quantitation and distribution of Equisetum alkaloids was achieved. PMID:25823584

  18. Ergot alkaloid transport across ruminant gastric tissues.

    PubMed

    Hill, N S; Thompson, F N; Stuedemann, J A; Rottinghaus, G W; Ju, H J; Dawe, D L; Hiatt, E E

    2001-02-01

    Ergot alkaloids cause fescue toxicosis when livestock graze endophyte-infected tall fescue. It is generally accepted that ergovaline is the toxic component of endophyte-infected tall fescue, but there is no direct evidence to support this hypothesis. The objective of this study was to examine relative and potential transport of ergoline and ergopeptine alkaloids across isolated gastric tissues in vitro. Sheep ruminal and omasal tissues were surgically removed and placed in parabiotic chambers. Equimolar concentrations of lysergic acid, lysergol, ergonovine, ergotamine, and ergocryptine were added to a Kreb's Ringer phosphate (KRP) solution on the mucosal side of the tissue. Tissue was incubated in near-physiological conditions for 240 min. Samples were taken from KRP on the serosal side of the chambers at times 0, 30, 60, 120, 180, and 240 min and analyzed for ergot alkaloids by competitive ELISA. The serosal KRP remaining after incubation was freeze-dried and the alkaloid species quantified by HPLC. The area of ruminal and omasal tissues was measured and the potential transportable alkaloids calculated by multiplying the moles of transported alkaloids per square centimeter of each tissue type by the surface area of the tissue. Studies were conducted to compare alkaloid transport in reticular, ruminal, and omasal tissues and to determine whether transport was active or passive. Ruminal tissue had greater ergot alkaloid transport potential than omasal tissue (85 vs 60 mmol) because of a larger surface area. The ruminal posterior dorsal sac had the greatest potential for alkaloid transport, but the other ruminal tissues were not different from one another. Alkaloid transport was less among reticular tissues than among ruminal tissues. Transport of alkaloids seemed to be an active process. The alkaloids with greatest transport potential were lysergic acid and lysergol. Ergopeptine alkaloids tended to pass across omasal tissues in greater quantities than across ruminal tissues, but their transport was minimal compared to lysergic acid and lysergol. PMID:11219466

  19. 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...

  20. New aporphine alkaloids of Ocotea minarum.

    PubMed

    Vecchietti, V; Casagrande, C; Ferrari, G; Severini Ricca, G

    1979-10-01

    Fourteen aporphine alkaloids were isolated from the leaves of a Brazilian Lauracea, Ocotea minarum Nees (Mez). The known alkaloids were identified through their physico-chemical properties as: leucoxylonine (VII), dicentrine (IV), ocoteine (V), leucoxine (VI), ocopodine (VIII), predicentrine (IX), dicentrinone (XIV) and thalicminine (XV). Six new aporphine alkaloids were also isolated: ocotominarine (I), ocominarine (III), nor-leucoxylonine (XI), iso-oconovine (xii), 4-hydroxydicentrine (XIII) and ocominarone (XVI). Their structures were determined using spectroscopic methods and chemical correlations. PMID:510527

  1. Microbial metabolites of harman alkaloids.

    PubMed

    Herath, Wimal; Mikell, Julie Rakel; Ferreira, Daneel; Khan, Ikhlas Ahmad

    2003-06-01

    Several microorganisms showed the ability to transform the harman alkaloids, harmaline (1), harmalol (2) and harman (5). Harmaline (1) and harmalol (2) were converted by Rhodotorula rubra ATCC 20129 into the tryptamines, 2-acetyl-3-(2-acetamidoethyl)-7-methoxyindole (3) and 2-acetyl-3-(2-acetamidoethyl)-7-hydroxyindole (4), respectively. Harman (5) was biotransformed by Cunninghamella echinulata NRRL 3655 into 6-hydroxyharman (6) and harman-2-oxide (7). PMID:12808240

  2. Diterpenoid Alkaloids from Aconitum soongaricum var. pubescens.

    PubMed

    Chen, Lin; Shan, Lianhai; Zhang, Jifa; Xu, Wenliang; Wu, Mingyu; Huang, Shuai; Zhou, Xianli

    2015-12-01

    One new diterpenoid alkaloid, pubescensine (1), along with nine known diterpenoid alkaloids (2-10) were isolated from the roots of Aconitum soongaricum var. pubescens. Their structures were elucidated by spectroscopic analyses and comparison with previously reported data. All the compounds were evaluated for their antifeedant activities. The aconitine-type diterpenoid alkaloids (1-6) showed considerably potent antifeedant activity (EC50 < 1 mg/cm2), while the activities of napelline-type diterpenoid alkaloids (compds. 7, 9 and 10) were not significant (EC50 > 50 mg/cm2). PMID:26882665

  3. Cytotoxic aporphine alkaloids from Ocotea acutifolia.

    PubMed

    Garcez, Fernanda R; Francisca da Silva, Ana G; Garcez, Walmir S; Linck, Gabriela; de Fatima Matos, Maria C; Santos, Evelyn C S; Queiroz, Lyara M M

    2011-03-01

    Two new aporphinoid alkaloids, (+)-6 S-ocoteine N-oxide and (+)-norocoxylonine, were isolated from the leaves and trunk bark of OCOTEA ACUTIFOLIA (Lauraceae) along with thirteen aporphine analogues, one morphinan alkaloid, and one flavonoid. The aporphine alkaloids (+)-thalicsimidine and (+)-neolitsine are reported for the first time for the genus OCOTEA. The structures of all compounds were established on the basis of 1D- and 2D-NMR spectroscopic techniques, optical rotation and/or mass spectrometry data. The cytotoxic potential of eight of the aporphine alkaloids against four human cancer cell lines (Hep-2, MCF-7, B16-F10 and 786-0) was also evaluated. PMID:20922653

  4. An uptake system for dietary alkaloids in poison frogs (Dendrobatidae).

    PubMed

    Daly, J W; Secunda, S I; Garraffo, H M; Spande, T F; Wisnieski, A; Cover, J F

    1994-06-01

    The skin of poison frogs (Dendrobatidae) contains a wide variety of alkaloids that presumably serve a defensive role. These alkaloids persist for years in captivity, but are not present in captive-raised frogs. Alkaloids fed to poison frogs (Dendrobates, Phyllobates, Epipedobates) are readily accumulated into skin, where they remain for months. The process can be selective; an ant indolizidine is accumulated, while an ant pyrrolidine is not. Frogs (Colostethus) of the same family, which do not normally contain alkaloids, do not accumulate alkaloids. Such an alkaloid uptake system provides a means of maintaining skin alkaloids and suggests that some if not all such 'dendrobatid alkaloids' may have a dietary origin. PMID:7940573

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

    PubMed

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

    2015-03-17

    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

  6. Biosynthesis of benzylisoquinoline alkaloids in Corydalis bracteata: compartmentation and seasonal dynamics.

    PubMed

    Khodorova, Nadezda V; Shavarda, Alexey L; Lequart-Pillon, Michelle; Laberche, Jean-Claude; Voitsekhovskaja, Olga V; Boitel-Conti, Michèle

    2013-08-01

    Numerous species of the genus Corydalis (Papaveraceae) produce a large spectrum of benzylisoquinoline alkaloids (BIA), some of which are of potential therapeutic value, but no information on sites of their biosynthesis and compartmentation is available. This study focuses on the biosynthesis, compartmentation and seasonal dynamics of BIA in Corydalis bracteata (Steph. ex Willd) Pers., a geophyte with a very short spring vegetation period, which for the rest of the year is represented by underground tubers with buds. It was found that all organs of C. bracteata contained high levels of BIA, the highest concentrations being detected in underground tuber buds in early autumn. Neither xylem nor phloem sap contained alkaloids throughout the year but BIA were present in the apoplastic wash fluid of the tuber. The absence of long-distance transport of alkaloids was confirmed by the experiment using an isotopically labeled tracer, [ring-(13)C6]-tyramine: when whole plants were fed with the tracer with via the roots, the alkaloids became labeled in the roots only and not in other organs. However, when detached roots, leaves, tubers and stems were exposed to [ring-(13)C6]-tyramine, the label was incorporated into alkaloids in all organs. We conclude that no long-distance translocation of alkaloids occurs between organs of C. bracteata, while in the tuber the cell-to-cell transport of alkaloids could occur via the apoplast. In contrast to other BIA-producing species, every organ of C. bracteata was found to be capable of de novo biosynthesis of the full complement of alkaloids. PMID:23664175

  7. 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...

  8. Glycoalkaloids and calystegine alkaloids in potatoes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Potatoes contain two classes of alkaloids: the glycoalkaloids and the calystegines. The presence of glycoalkaloids in potatoes and their toxicity has been known for more than a century and much has been written about them. Discovery of the nortropane calystegine alkaloids is more recent, and the k...

  9. Halogenated Indole Alkaloids from Marine Invertebrates

    PubMed Central

    Pauletti, Patrícia Mendonça; Cintra, Lucas Silva; Braguine, Caio Guedes; da Silva Filho, Ademar Alves; Silva, Márcio Luís Andrade e; Cunha, Wilson Roberto; Januário, Ana Helena

    2010-01-01

    This review discusses the isolation, structural elucidation, and biological activities of halogenated indole alkaloids obtained from marine invertebrates. Meridianins and related compounds (variolins, psammopemmins, and aplicyanins), as well as aplysinopsins and leptoclinidamines, are focused on. A compilation of the 13C-NMR spectral data of these selected natural indole alkaloids is also provided. PMID:20559487

  10. Halogenated indole alkaloids from marine invertebrates.

    PubMed

    Pauletti, Patrícia Mendonça; Cintra, Lucas Silva; Braguine, Caio Guedes; da Silva Filho, Ademar Alves; Silva, Márcio Luís Andrade E; Cunha, Wilson Roberto; Januário, Ana Helena

    2010-01-01

    This review discusses the isolation, structural elucidation, and biological activities of halogenated indole alkaloids obtained from marine invertebrates. Meridianins and related compounds (variolins, psammopemmins, and aplicyanins), as well as aplysinopsins and leptoclinidamines, are focused on. A compilation of the (13)C-NMR spectral data of these selected natural indole alkaloids is also provided. PMID:20559487

  11. Plant alkaloids of the polymethyleneamine series

    NASA Astrophysics Data System (ADS)

    Rogoza, Ludmila N.; Salakhutdinov, Nariman F.; Tolstikov, Genrikh A.

    2005-04-01

    The published data on the structures and biological activities of the plant alkaloids of the biogenic polymethyleneamine series, viz., putrescine (1,4-diaminobutane), spermidine (1,8-diamino-4 -azaoctane), and spermine (1,12-diamino-4,9-diazadodecane), are considered and systematised. The structures and biological activities of some synthetic analogues of these alkaloids are also presented.

  12. Iboga-Type Alkaloids from Ervatamia officinalis.

    PubMed

    Tang, Ben-Qin; Wang, Wen-Jing; Huang, Xiao-Jun; Li, Guo-Qiang; Wang, Lei; Jiang, Ren-Wang; Yang, Ting-Ting; Shi, Lei; Zhang, Xiao-Qi; Ye, Wen-Cai

    2014-08-22

    Seven new iboga-type alkaloids, ervaoffines A-D (1-4), (7S)-3-oxoibogaine hydroxyindolenine (5), ibogaine-5,6-dione (6), and 19-epi-5-oxovoacristine (7), and 10 known alkaloids were isolated from Ervatamia officinalis. The absolute configurations of 1-7 were determined through X-ray diffraction and electronic circular dichroism (ECD) analyses. Ervaoffines A and B represent the first iboga-type pseudoindoxyl alkaloids in which the C-2 spiro carbon configuration is opposite to that of other members of this class, such as iboluteine (8). The relationship between the absolute configuration of the spiro carbons and the Cotton effect in the ECD spectrum is established for the first time for iboga-type pseudoindoxyl and oxindole alkaloids. Additionally, a plausible biogenetic pathway for these alkaloids is proposed. PMID:25093992

  13. 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

  14. Reproductive toxicity of ergot alkaloids in mink.

    PubMed

    Sharma, C; Aulerich, R J; Render, J A; Reimers, T; Rottinghaus, G E; Kizilkaya, K; Bursian, S J

    2002-12-01

    Ergot alkaloids are-synthesized by fungi of the Claviceps family that infect rye as well as other cereals and grains. Since a portion of the ranch mink diet is cereal, mink are at a risk of being exposed to ergot alkaloids. This study was performed to determine the reproductive toxicity of ergot alkaloids derived from ergot-contaminated oats in mink. Four groups of 12 female mink each were fed diets containing 0, 3, 6 or 12 ppm ergot alkaloids from 2w prior to the breeding season until the kits were approximately 33-d old (133 d). Females were mated with untreated males. Ergo talkaloids caused a transient decrease in feed consumption, but body weights were unaffected. The gestation period of the mink in the 6 ppm group was longer compared to controls. The number of mink whelping varied significantly with 9 mink whelping each in the control and 3 ppm groups compared to 4 mink in the 6 ppm group and 1 in the 12 ppm group. Ergot alkaloids had a significant effect on kit survivabilitywith no kits surviving in the 12 ppm group. Serum prolactin was significantly depressed in the 3 ergot alkaloid groups compared to the control group. This study indicated that ingestion of ergot alkaloids at 3 ppm or higher resulted in reproductive toxicity in mink. PMID:12458632

  15. Polycyclic Guanidine Alkaloids from Poecilosclerida Marine Sponges

    PubMed Central

    Sfecci, Estelle; Lacour, Thierry; Amade, Philippe; Mehiri, Mohamed

    2016-01-01

    Sessile marine sponges provide an abundance of unique and diversified scaffolds. In particular, marine guanidine alkaloids display a very wide range of biological applications. A large number of cyclic guanidine alkaloids, including crambines, crambescins, crambescidins, batzelladines or netamins have been isolated from Poecilosclerida marine sponges. In this review, we will explore the chemodiversity of tri- and pentacyclic guanidine alkaloids. NMR and MS data tools will also be provided, and an overview of the wide range of bioactivities of crambescidins and batzelladines derivatives will be given. PMID:27070629

  16. 4-Quinolone Alkaloids from Melochia odorata

    PubMed Central

    Jadulco, Raquel C.; Pond, Christopher D.; Van Wagoner, Ryan M.; Koch, Michael; Gideon, Osia G.; Matainaho, Teatulohi K.; Piskaut, Pius; Barrows, Louis R.

    2014-01-01

    The methanol extract of Melochia odorata yielded three 4-quinolone alkaloids including waltherione A (1) and two new alkaloids, waltherione C (2) and waltherione D (3). Waltheriones A and C showed significant activities in an in vitro anti-HIV cytoprotection assay at concentrations of 56.2 and 0.84 μM, and inhibition of HIV P24 formation of more than 50% at 1.7 and 0.95 μM, respectively. The structures of the alkaloids were established by spectroscopic data interpretation. PMID:24392742

  17. Marine Pyridoacridine Alkaloids: Biosynthesis and Biological Activities.

    PubMed

    Ibrahim, Sabrin R M; Mohamed, Gamal A

    2016-01-01

    Pyridoacridines are a class of strictly marine-derived alkaloids that constitute one of the largest chemical families of marine alkaloids. During the last few years, both natural pyridoacridines and their analogues have constituted excellent targets for synthetic works. They have been the subject of intense study due to their significant biological activities; cytotoxic, antibacterial, antifungal, antiviral, insecticidal, anti-HIV, and anti-parasitic activities. In the present review, 95 pyridoacridine alkaloids isolated from marine organisms are discussed in term of their occurrence, biosynthesis, biological activities, and structural assignment. PMID:26765351

  18. 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

  19. In vitro anticholinesterase activity of various alkaloids.

    PubMed

    Orhan, Ilkay; Naz, Qamar; Kartal, Murat; Tosun, Fatma; Sener, Bilge; Choudhary, M Iqbal

    2007-01-01

    In the current study, a number of alkaloids including retamine, cytisine, and sparteine (quinolizidine-type), yohimbine and vincamine (indole-type), scopolamine and atropine (tropane-type), colchicine (tropolone-type), allantoin (imidazolidine-type), trigonelline (pyridine-type) as well as octopamine, synephrine, and capsaicin (exocyclic amine-type) were tested in vitro for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) at 1 mg/ml concentration by the Ellman method using an ELISA microplate reader. Among the alkaloids tested, only capsaicin exerted a remarkable inhibitory effect towards both AChE and BChE [(62.7 +/- 0.79)% and (75.3 +/- 0.98)%, respectively]. While the rest of the alkaloids did not show any significant inhibition against AChE, three of the alkaloids, namely retamine, sparteine, and yohimbine, exerted a noteworthy anti-BChE effect as compared to galanthamine, the reference drug. PMID:18069241

  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. Cytotoxic indole alkaloids from Tabernaemontana divaricata.

    PubMed

    Bao, Mei-Fen; Yan, Ju-Ming; Cheng, Gui-Guang; Li, Xing-Yao; Liu, Ya-Ping; Li, Yan; Cai, Xiang-Hai; Luo, Xiao-Dong

    2013-08-23

    Five new vobasinyl-ibogan-type bisindole alkaloids, tabernaricatines A-E (1-5), two new monomers, tabernaricatines F and G (6 and 7), and 24 known indole alkaloids were isolated from the aerial parts of Tabernaemontana divaricata. Alkaloids 1 and 2 are the first vobasinyl-ibogan-type alkaloids possessing a six-membered ring via an ether linkage between C-17 and C-21. All compounds except for 3 were evaluated for their cytotoxicity against five human cancer cell lines; conophylline showed significant bioactivity against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cells with IC₅₀ values of 0.17, 0.35, 0.21, 1.02, and 1.49 μM, respectively. PMID:23944995

  2. Seco-tabersonine alkaloids from Tabernaemontana corymbosa.

    PubMed

    Lim, Kuan-Hon; Thomas, Noel F; Abdullah, Zanariah; Kam, Toh-Seok

    2009-02-01

    Two seco-tabersonine alkaloids, jerantiphyllines A and B, in addition to a tabersonine hydroxyindolenine, jerantinine H, and a recently reported vincamine alkaloid 7, were isolated from the leaf extract of the Malayan Tabernaemontana corymbosa and the structures were established using NMR and MS analysis. Biomimetic conversion of jerantinines A and E to their respective vincamine and 16-epivincamine derivatives were also carried out. PMID:19217125

  3. Two new indole alkaloids from Hunteria zeylanica.

    PubMed

    Liu, Quan; Chen, Chao-Jun; Zhang, Li; Gao, Kun

    2016-04-01

    Two new indole alkaloids, 14β-hydroperoxy-eburnamine (1) and 18α-hydroxy-eburnamine (2), together with three known indole alkaloids, (-)-eburnamonine (3), (-)-eburnamenine (4), and eburnamine (5) were isolated from Hunteria zeylanica collected in Hainan Province of China. Their structures were determined by spectroscopic analysis. The relative configuration of 2 was deduced by NOE experiment and evidenced by the calculations for energy minimization with the molecular modeling program Chem3D Ultra 10.0. PMID:26667775

  4. 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

  5. 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

  6. 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.

  7. 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...

  8. Monoterpenoid Indole Alkaloids from Catharanthus roseus Cultivated in Yunnan.

    PubMed

    Wang, Bei; Liu, Lu; Chen, Ying-ying; Li, Qiong; Li, Dan; Liu, Va-ping; Luo, Xiao-dong

    2015-12-01

    A new monoterpenoid indole alkaloid, 15,20-dehydro-3α-(2-oxopropyl) coronaridine (1), along with sixteen analogues (2-17) were isolated from the leaves of Catharanthus roseus cultivated in Yunnan. The new alkaloid was elucidated on the basis of extensive spectroscopic analysis, and the known alkaloids were identified by comparison with the reported spectroscopic data. Among them, alkaloid 16 was isolated from Catharanthus for the first time. PMID:26882670

  9. 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.

  10. The Double-Bond Configuration of Corynanthean Alkaloids and Its Impact on Monoterpenoid Indole Alkaloid Biosynthesis.

    PubMed

    Eckermann, Ruben; Gaich, Tanja

    2016-04-11

    Experimental evidence is provided for the coherence of the double-bond geometry and the occurrence of "secondary cyclizations" in the biosynthesis of monoterpenoid indole alkaloids. Biosynthetically, akuammiline, C-mavacurine, and Strychnos alkaloids are proposed to be derived from the corynanthean alkaloid geissoschizine, a key intermediate in the biosynthetic pathway of these monoterpenoid indole alkaloids. This process occurs by so-called "secondary cyclizations" from geissoschizine or its derivatives. Although corynanthean alkaloids like geissoschizine incorporate E or Z double bonds located at C19-C20, the alkaloids downstream in the biosynthesis exclusively exhibit the E double bond. This study shows that secondary cyclizations preferentially occur with the E isomer of geissoschizine or its derivatives. This is attributed to the flexibility of the quinolizidine system of the corynanthean alkaloids, which can adopt a cis or trans conformation. For the secondary cyclization to take place, the cis-quinolizidine conformation is required. Experimental evidence supports the hypothesis that the E double bond of geissoschizine induces the cis conformation, whereas the Z double bond induces the trans conformation, which prohibits secondary cyclization of the Z compounds. PMID:26933928

  11. Development of an Alkaloid-Pyrone Annulation: Synthesis of Pleiomaltinine**

    PubMed Central

    Ziegler, Robert E.; Tan, Shin-Jowl; Kam, Toh-Seok

    2012-01-01

    Odd Couple Methodology for the synthesis of alkaloid-pyrones using a novel pyrone annulation of β–carbolines and indoles with 3-siloxy-4-pyrones is reported. The approach has enabled semisynthesis of the unprecedented alkaloid-pyrone pleiomaltinine from the plant-derived indole-alkaloid pleiocarpamine. PMID:22893619

  12. Review of β-carboline alkaloids from the genus Aspidosperma.

    PubMed

    Layne, Tanya H; Roach, Joy S; Tinto, Winston F

    2015-01-01

    Plants belonging to the genus Aspidosperma, a member of the family Apocynaceae, provide a rich source of β-carboline alkaloids, which makes them potentially poisonous. However, some of these alkaloids possess antitumor and antimicrobial activity. The present review is a survey of the β-carboline alkaloids and shows that they comprise of a diverse array of structural modifications. PMID:25920243

  13. Production, detection, and purification of clavine-type ergot alkaloids.

    PubMed

    Wallwey, Christiane; Li, Shu-Ming

    2012-01-01

    Ergot alkaloids are indole derivatives with diverse structures and biological activities. This chapter describes the procedure from fungal cultivation to purified ergot alkaloids, as exemplified by fumigaclavine A in Penicillium commune. Furthermore, useful notes for working with purified ergot alkaloids are given. PMID:23065612

  14. 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...

  15. 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 ephedrine alkaloids present an unreasonable risk of illness or injury under conditions of use recommended...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. Ether bridge formation in loline alkaloid biosynthesis.

    PubMed

    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

    2014-02-01

    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 an 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

  1. Analysis of toxic alkaloids in body samples.

    PubMed

    Beyer, Jochen; Drummer, Olaf H; Maurer, Hans H

    2009-03-10

    Many plants contain toxic alkaloids which may be dangerous to humans. Despite the large number of poisonous plants, cases of fatal plant poisonings are relatively rare. The frequencies of poisonings and the plants involved are often regionally specific. Plant poisonings can be aggregated into three categories: unintended ingestions, intended ingestions, and poisoning due to abuse of plant material. Unintended ingestions often occur in children or from a mix-up of plants and mushrooms in adults. Intended ingestions are common in homicides and suicides. Increasingly common is the abuse of plants for hallucinogenic reasons. Toxicological analysis of such alkaloids may help in diagnosis of poisoning or abuse cases. This review describes the toxic alkaloids aconitine, atropine, coniine, colchicine, cytisine, dimethyltryptamine, harmine, harmaline, ibogaine, kawain, mescaline, scopolamine, and taxine, which are often involved in fatal and non-fatal poisonings. The paper summarizes the symptoms of the intoxications and reviews the methods of detection of their toxic constituents in biological fluids. PMID:19147309

  2. Antimicrobially active isoquinoline alkaloids from Litsea cubeba.

    PubMed

    Feng, Tao; Xu, Yan; Cai, Xiang-Hai; Du, Zhi-Zhi; Luo, Xiao-Dong

    2009-01-01

    Bioassay-guided fractionation of the alkaloidal extract of the aerial part of Litsea cubeba led to the isolation of two new isoquinoline alkaloids, (+)- N-(methoxycarbonyl)-N-norboldine (1) and (+)-isoboldine beta-N-oxide (2), together with 11 known analogues (3-13). Their structures were established by extensive spectroscopic techniques and by comparing spectroscopic data with those in the literature. Compounds 1 and 4 showed antimicrobial activities. This is the first report on the presence of compounds 1, 2, 6, 8, 9, 11, and 12 in this plant and on the antimicrobial activities of 1 and 4. The bioactivities of isoquinoline alkaloids are also at least partly responsible for the pharmacological function of the folk medicinal plant Litsea cubeba. PMID:18991207

  3. 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

  4. 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.

  5. 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

  6. Ephedra alkaloids inhibit platelet aggregation.

    PubMed

    Watson, Rex; Woodman, Ryan; Lockette, Warren

    2010-04-01

    Sympathomimetics, such as Ephedra alkaloids, are associated with an increased incidence of intracerebral hemorrhage believed to be secondary to concomitant elevations in blood pressure. We hypothesized that sympathomimetics decrease platelet aggregation. Reductions in epinephrine-mediated platelet aggregation by ephedrine, phenylpropanolamine, and racemic amphetamine were determined by measuring the changes that these sympathomimetics induced in the optical density of platelet-rich plasma from healthy individuals. Intracellular signal transduction was followed ex vivo by assaying the release of intracellular cyclic AMP and the ligand for the cytokine chemoreceptor 5 (RANTES) into platelet rich plasma. The effect of ephedrine on epinephrine-mediated increases in platelet selectin (CD62p) activation was assessed with flow cytometry. Data were analyzed with repeated-measures analyses of variance. Aggregation responses to epinephrine were greatly reduced in the presence of commonly used sympathomimetics such as ephedrine, phenylpropanolamine, and racemic amphetamine that have been found in cold remedies, appetite suppressants, or used in the treatment of attention-deficit hyperactivity disorder, respectively. Ephedrine diminished aggregation responses to ADP and gamma-thrombin, and this sympathomimetic reduced RANTES exocytosis, basal CD62p expression, and aggregation in platelets exposed to caffeine. Caffeine enhanced the effect of ephedrine on platelet function, and phenylpropanolamine amplified the inhibitory effect of aspirin on platelet aggregation. Sympathomimetics significantly alter platelet function, and they may increase the potential for bleeding independently of their effects on blood pressure. Despite restrictions imposed on their use, the consumption of sympathomimetics should be considered when any patient presents with findings of cerebral hemorrhage. PMID:20179577

  7. Dihydrofuro [2,3-b] quinolinium alkaloids in cultured cells of Ptelea trifoliata L. : Isolation of a new alkaloid, ptelecultinium.

    PubMed

    Petit-Paly, G; Montagu, M; Viel, C; Rideau, M; Chénieux, J C

    1987-07-01

    Two dihydrofuroquinoline alkaloids, ptelefolonium and another new alkaloid, ptelecultinium, have been isolated from callus strains of Ptelea trifoliata L.. Ptelecultinium was not known to occur in the mature plants. The structure of these two alkaloids were established by UV, MS and (1)H-NMR spectra. PMID:24248767

  8. Chemotaxonomy and geographical distribution of tropane alkaloids.

    PubMed

    Griffin, W J; Lin, G D

    2000-03-01

    This review illustrates the distribution of tropane alkaloids within the families Solanaceae, Erythroxylaceae, Proteaceae, Euphorbiaceae, Rhizophoraceae, Convolvulaceae and Cruciferae. Whereas tropane alkaloids are characteristic of the genera Datura, Brugmansia (tree datura) and Duboisia of the Solanaceae, the distribution is more widespread with novel tropane derivatives in families not traditionally associated with these bases. The chemical nature of more recently discovered water-soluble calystegines and the di- and trimeric forms from the Convolvulaceae (e.g. schizanthines from Schizanthus spp.), truxillines from Bolivian coca leaves and moonines of Erythroxylum moonii are highlighted. Where possible and appropriate, links between the phytochemistry and taxonomy are discussed. PMID:10746874

  9. 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 μg/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 μg/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 μM, 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 μM). The superoxide anion radical scavenging assay indicated that compounds 1-3, and 8 showed 14.8% (90.9 μM), 18.1% (90.9 μM), 51.5% (88.3 μM), and 30.4% (61.3 μM) superoxide anion radical scavenging capacity, respectively. PMID:26125976

  10. Pharmacokinetics of Hoasca alkaloids in healthy humans.

    PubMed

    Callaway, J C; McKenna, D J; Grob, C S; Brito, G S; Raymon, L P; Poland, R E; Andrade, E N; Andrade, E O; Mash, D C

    1999-06-01

    N,N-Dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine (THH) are the characteristic alkaloids found in Amazonian sacraments known as hoasca, ayahuasca, and yajè. Such beverages are characterized by the presence of these three harmala alkaloids, where harmine and harmaline reversibly inhibit monoamine oxidase A (MAO-A) while tetrahydroharmine weakly inhibits the uptake of serotonin. Together, both actions increase central and peripheral serotonergic activity while facilitating the psychoactivity of DMT. Though the use of such 'teas' has be known to western science for over 100 years, little is known of their pharmacokinetics. In this study, hoasca was prepared and administered in a ceremonial context. All four alkaloids were measured in the tea and in the plasma of 15 volunteers, subsequent to the ingestion of 2 ml hoasca/kg body weight, using gas (GC) and high pressure liquid chromatographic (HPLC) methods. Pharmacokinetic parameters were calculated and peak times of psychoactivity coincided with high alkaloid concentrations, particularly DMT which had an average Tmax of 107.5 +/- 32.5 min. While DMT parameters correlated with those of harmine, THH showed a pharmacokinetic profile relatively independent of harmine's. PMID:10404423

  11. Fluorescence lifetimes of some Rauwolfia alkaloids

    NASA Astrophysics Data System (ADS)

    Hidalgo, J.; Arjona, D. Gonzalez; Roldan, E.; Sanchez, M.

    1986-03-01

    The natural fluorescence lifetimes of the following Rauwolfia alkaloids, Reserpine, Rescinnamine, Corynanthine, Yohimbine, --- Ajmalicine, Serpentine and Ajmaline, have been calculated from a modified form of the Strickler-Berg equation. The actual lifetimes were derived from the quantum yields and the calculated natural lifetimes.

  12. Acetylcholinesterase-inhibiting alkaloids from Zephyranthes concolor.

    PubMed

    Reyes-Chilpa, Ricardo; Berkov, Strahil; Hernández-Ortega, Simón; Jankowski, Christopher K; Arseneau, Sebastien; Clotet-Codina, Imma; Esté, José A; Codina, Carles; Viladomat, Francesc; Bastida, Jaume

    2011-01-01

    The bulbs and aerial parts of Zephyranthes concolor (Lindl.) Benth. & Hook. f. (Amaryllidaceae), an endemic species to Mexico, were found to contain the alkaloids chlidanthine, galanthamine, galanthamine N-oxide, lycorine, galwesine, and epinorgalanthamine. Since currently only partial and low resolution (1)H-NMR data for chlidanthine acetate are available, and none for chlidanthine, its 1D and 2D high resolution (1)H- and (13)C-NMR spectra were recorded. Unambiguous assignations were achieved with HMBC, and HSQC experiments, and its structure was corroborated by X-ray diffraction. Minimum energy conformation for structures of chlidanthine, and its positional isomer galanthamine, were calculated by molecular modelling. Galanthamine is a well known acetylcholinesterase inhibitor; therefore, the isolated alkaloids were tested for this activity. Chlidanthine and galanthamine N-oxide inhibited electric eel acetylcholinesterase (2.4 and 2.6 × 10(-5) M, respectively), indicating they are about five times less potent than galanthamine, while galwesine was inactive at 10(-3) M. Inhibitory activity of HIV-1 replication, and cytotoxicity of the isolated alkaloids were evaluated in human MT-4 cells; however, the alkaloids showed poor activity as compared with standard anti-HIV drugs, but most of them were not cytotoxic. PMID:22086403

  13. A new indole alkaloid from Ervatamia yunnanensis.

    PubMed

    Jin, Yong-Sheng; Du, Jing-Ling; Chen, Hai-Sheng; Jin, Li; Liang, Shuang

    2010-01-01

    The stems of Ervatamia yunnanensis have afforded a new indole alkaloid, ervataine (1), whose structure was determined by spectroscopic analysis. Five known compounds, ibogaine (2) coronaridine (3), heyneanine (4), voacangine hydroxyindolenine (5) and coronaridine hydroxyindolenine (6), were also isolated. PMID:19647051

  14. 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...

  15. 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.

  16. 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, α-ergocryptin(in)e, β-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

  17. Determination and in-depth chromatographic analyses of alkaloids in South American and greenhouse-cultivated coca leaves.

    PubMed

    Moore, J M; Casale, J F; Klein, R F; Cooper, D A; Lydon, J

    1994-01-21

    Methodology is described for the detection and/or determination of cocaine and minor alkaloids in South American coca as well as in greenhouse- and tropical-cultivated field coca of known taxonomy. Coca leaf from Bolivia, Peru, Ecuador and Colombia were subjected to the determination of cocaine, cis- and trans-cinnamoylcocaine, tropacocaine, hygrine, cuscohygrine and the isomeric truxillines. The greenhouse samples were cocaine-bearing leaves of the genus Erythroxylum and included E. coca var. coca, E. novogranatense var. novogranatense and E. novogranatense var. truxillense, and the alkaloids determined were cocaine, ecgonine methyl ester, cuscohygrine, tropacocaine and the cinnamoylcocaines. The tropical-cultivated coca were E. novogranatense var. novogranatense and E. coca var. coca. Cocaine and minor alkaloids were isolated from basified powdered leaf samples using a toluene extractant, followed by acid-Celite column chromatography. The isolated alkaloids were determined by capillary gas chromatography with flame ionization or electron-capture detection. Methodology is also presented for the isolation and mass spectral analysis of numerous trace-level coca alkaloids of unknown structure. PMID:8118557

  18. 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

  19. 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 γ-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

  20. The epichloae: alkaloid diversity and roles in symbiosis with grasses

    PubMed Central

    Schardl, Christopher L; Florea, Simona; Pan, Juan; Nagabhyru, Padmaja; Bec, Sladana; Calie, Patrick J

    2013-01-01

    Epichloae (Epichlo and Neotyphodium species; Clavicipitaceae) are fungi that live in systemic symbioses with cool-season grasses, and many produce alkaloids that are deterrent or toxic to herbivores. The epichloae colonize much of the aerial plant tissues, and most benignly colonize host seeds to transmit vertically. Of their four chemical classes of alkaloids, the ergot alkaloids and indole-diterpenes are active against mammals and insects, whereas peramine and lolines specifically affect insects. Comparative genomic analysis of Clavicipitaceae reveals a distinctive feature of the epichloae, namely, large repeat blocks in their alkaloid biosynthesis gene loci. Such repeat blocks can facilitate gene losses, mutations, and duplications, thus enhancing diversity of alkaloid structures within each class. We suggest that alkaloid diversification is selected especially in the vertically transmissible epichloae. PMID:23850071

  1. 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

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

    PubMed

    Diaz, Gonzalo J

    2015-12-01

    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 γ-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

  3. Pyrrolizidine alkaloid profiles of some Senecio species from Egypt.

    PubMed

    El-Shazly, Assem

    2002-01-01

    Alkaloid profiles of two Egyptian Senecio species (Senecio aegyptius var. discoideus and S. desfontainei) in addition to a cultivated species (S. cineraria) were studied using capillary GLC and GLC-mass spectrometry with respect to pyrrolizidine alkaloids (PAs). Four alkaloids were identified in S. aegyptius var. discoideus, 8 in S. desfontainei and 13 in S. cineraria. Some of these alkaloids have not been reported from these plants. The alkaloidal pattern of different plant organs (flowers, leaves, stem, root) were also investigated. Senecionine has been found to be a one of the major alkaloid in all studied species, it was isolated and its structure was elucidated by 1H- and 13C-NMR. PMID:12132679

  4. Manzamine alkaloids as antileishmanial agents: A review.

    PubMed

    Ashok, Penta; Lathiya, Hiren; Murugesan, Sankaranarayanan

    2015-06-01

    Leishmaniasis is considered as one of the most Neglected Tropical Diseases (NTDs) in the world, caused by protozoan parasites of the genus Leishmania. Leishmaniasis control profoundly depends upon chemotherapy which includes pentavalent antimonials, paromomycin, pentamidine, amphotericin B and miltefosine. Miltefosine is the only oral drug used for the treatment of Visceral Leishmaniasis with high cure rate but decrease in susceptibility is observed in countries like India where it is extensively used. Hence, there is an urgent need to develop novel antileishmanial agents with good potency and better therapeutic profile. Manzamines are unique group of β-carboline alkaloids isolated from marine sponges and exhibited potent antileishmanial activity. In the present study, we described antileishmanial activity, cytotoxicity and structure activity relationship of natural manzamine alkaloids. PMID:25023608

  5. Total Synthesis of Dimeric HPI Alkaloids.

    PubMed

    Shen, Xianfu; Zhou, Yongyun; Xi, Yongkai; Zhao, Jingfeng; Zhang, Hongbin

    2016-04-01

    In this paper, we report a full account of the synthesis of dimeric hexahydropyrroloindole alkaloids and its analogues. The key feature of our new strategy is the novel catalytic copper (10 %) mediated intramolecular arylations of o-haloanilides followed by intermolecular oxidative dimerization of the resulting oxindoles in one pot. This sequential reaction leads to the key intermediates for the synthesis of (+)-chimonanthine, (+)-folicanthine, (-)-calycanthine and (-)-ditryptophenaline. In the presence of catalytic amount of cuprous iodide (10 %), an intramolecular arylation of o-haloanilides followed by an intermolecular oxidative dimerization of the resulting oxindoles leads to a common intermediate for the synthesis of (+)-chimonanthine, (+)-folicanthine and (-)-calycanthine. Based on this cascade sequence, we also developed a flexible strategy towards the asymmetric syntheses of dimeric HPI alkaloids (-)-ditryptophenaline and its analogues. PMID:26969313

  6. 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/6π-electrocyclization cascade followed by an oxidative aromatization process.

  7. 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

  8. Discovery of skin alkaloids in a miniaturized eleutherodactylid frog from Cuba

    PubMed Central

    Rodríguez, Ariel; Poth, Dennis; Schulz, Stefan; Vences, Miguel

    2011-01-01

    Four phylogenetically independent lineages of frogs are currently known to sequester lipid-soluble skin alkaloids for which a dietary source has been demonstrated. We report here a remarkable fifth such instance, in Eleutherodactylus iberia and Eleutherodactylus orientalis, two species of miniaturized frogs of the family Eleutherodactylidae from Cuba. Six pumiliotoxins and two indolizidines were found in E. iberia, one of the smallest frogs in the world and characterized by a contrasting colour pattern for which we hypothesize an aposematic function. Analyses of stomach content indicated a numerical prevalence of mites with an important proportion of oribatids—a group of arthropods known to contain one of the pumiliotoxins detected in E. iberia. This suggests that miniaturization and specialization to small prey may have favoured the acquisition of dietary skin alkaloids in these amphibians. PMID:21047848

  9. Two new alkaloids from Corydalis humosa.

    PubMed

    Zheng, Xiao-Ke; Li, Dan-Dan; Yan, Hui; Li, Meng; He, Jin-Li; Feng, Wei-Sheng

    2013-11-01

    Two new alkaloids, named 1,1-dimethyl-6-methoxy-7-hydroxyl-1,2,3,4-tetrahydroisoquinoline (1) and (1R)-(4-hydroxybenzyl)-7-hydroxyl-8-O-β-d-glucopyranosyl-1,2,3,4-tetrahydroisoquinoline (2), together with 11 known compounds (3-13), were isolated from the tubers of Corydalis humosa. Their structures were elucidated on the basis of their spectroscopic and chemical evidence. PMID:23919659

  10. A new alkaloid from Nodulisporium sp.

    PubMed

    Wang, Gao-qian; Zhao, Qin; Zheng, Qi-chang; Chen, Guo-dong; He, Rong-rong; Guo Liang-dong; Yao, Liang-dong; Gao, Haol

    2015-07-01

    The genus Nodulisporium, is known to produce secondary metabolites with structural diversity. A new alkaloid, 2-hy- droxy-1,1-dimethyl-1,2,3,9-tetrahydro-4H-carbazol-4-one(1), was isolated from the extract of a fungal strain Nodulisporium sp. fermented with rice, together with three known phenols, tyrosol(2), hydroxytyrosol(3), and hydroxytyrosol acetate(4). Their structures were identified by detailed spectroscopic analyses. PMID:26697685

  11. Aspidosperma-type Alkaloids from Melodinus suaveolens.

    PubMed

    Zhang, Jian; Song, Min; Liu, Zhi-Wen; Xiao, Hua; Fan, Chun-Lin; Zhang, Xiao-Qi; Ye, Wen-Cai

    2016-01-01

    Three new aspidosperma-type alkaloids, 3-oxo-11-hydroxytabersonine (2), 1 1-hydroxytabersonine N-oxide (3) and 11-methoxytabersonine N-oxide (4), along with three known ones were isolated from the twigs and leaves of Melodinus suaveolens. The structures of the new compounds were elucidated by using spectroscopic methods, and circular dichroism experiments. The known compounds were identified by comparing their spectroscopic data with those reported in the literature. PMID:26996019

  12. 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

  13. Alkaloids from the root of Isatis indigotica.

    PubMed

    Chen, Minghua; Gan, Lishe; Lin, Sheng; Wang, Xiaoliang; Li, Li; Li, Yuhuan; Zhu, Chenggen; Wang, Yanan; Jiang, Bingya; Jiang, Jiandong; Yang, Yongchun; Shi, Jiangong

    2012-06-22

    Seventeen new alkaloids (1-17) and 14 known analogues have been isolated from an aqueous extract of the root of Isatis indigotica. The structures and absolute configurations of these compounds were determined by extensive spectroscopic data analysis, including 2D NMR, single-crystal X-ray crystallography using anomalous scattering of Cu Kα radiation, and electronic circular dichroism spectra calculations based on the quantum-mechanical time-dependent density functional theory. Compounds 1, 2, and 3 are the first examples of natural products with unique linkages between a molecule of 2-(4-methoxy-1H-indol-3-yl)acetonitrile and 2-(1H-indol-3-yl)acetonitrile, 2-(4-methoxy-1H-indol-3-yl)acetonitrile, and 4-hydroxyphenylethane, respectively. Compounds (-)-4 and (+)-4 represent the first natural products with the pyrrolo[2,3-b]indolo[5,5a,6-b,a]quinazoline skeleton. Some structural assignments for the new alkaloids suggest that the assignments made for certain previously reported alkaloids require revision. Compounds 1-3 and arvelexin (18) show antiviral activity against the influenza virus A/Hanfang/359/95 (H3N2), with IC(50) values of 3.70-12.35 μM, and 17 inhibits Coxsackie virus B3 replication with an IC(50) of 6.87 μM. PMID:22694318

  14. Plant alkaloids as drug leads for Alzheimer's disease.

    PubMed

    Ng, Yu Pong; Or, Terry Cho Tsun; Ip, Nancy Y

    2015-10-01

    Alzheimer's disease (AD) is a neurodegenerative illness associated with dementia and is most prevalent among the elderly population. Current medications can only treat symptoms. Alkaloids are structurally diverse and have been an important source of therapeutics for various brain disorders. Two US Food and Drug Administration (FDA)-approved acetylcholinesterase inhibitors for AD, galantamine and rivastigmine, are in fact alkaloids. In addition, clinical trials of four other extensively studied alkaloids-huperzine A, caffeine, nicotine, and indomethacin-have been conducted but do not convincingly demonstrate their clinical efficacy for AD. Interestingly, rhynchophylline, a known neuroprotective alkaloid, was recently discovered by in silico screening as an inhibitor of EphA4, a novel target for AD. Here, we review the pathophysiological mechanisms underlying AD, current treatment strategies, and therapeutic potential of several selected plant alkaloids in AD, highlighting their various drug targets and the key supportive preclinical and clinical studies. Future research should include more rigorous clinical studies of the most promising alkaloids, the further development of recently discovered candidate alkaloids, and the continual search for new alkaloids for relevant drug targets. It remains promising that an alkaloid drug candidate could significantly affect the progression of AD in addition to providing symptomatic relief. PMID:26220901

  15. Pyrrolizidine alkaloid profiles of the Senecio cineraria group (Asteraceae).

    PubMed

    Tundis, Rosa; Loizzo, Monica R; Statti, Giancarlo A; Passalacqua, Nicodemo G; Peruzzi, Lorenzo; Menichini, Francesco

    2007-01-01

    Alkaloid profiles of five Senecio species (Asteraceae), including S. ambiguus subsp. ambiguus, S. ambiguus subsp. nebrodensis, S. gibbosus subsp. bicolor, S. gibbosus subsp. gibbosus, and S. gibbosus subsp. cineraria, were studied. Eleven pyrrolizidine alkaloids were identified and their content was evaluated by GLC-MS and GLC analysis. Otosenine and florosenine were found to be the major alkaloids in all studied species. It is interesting that only S. ambiguus subsp. nebrodensis was characterized by a high content of the alkaloids jacobine, jacoline, jaconine, and jacozine. PMID:17913058

  16. Biologically active indole and bisindole alkaloids from Tabernaemontana divaricata.

    PubMed

    Kam, Toh-Seok; Pang, Huey-Shen; Lim, Tuck-Meng

    2003-04-21

    The ethanol extract of the leaves of Tabernaemontana divaricata (double flower variety) provided a total of 23 alkaloids, including the new aspidosperma alkaloids, taberhanine, voafinine, N-methylvoafinine, voafinidine, voalenine and the new bisindole alkaloid, conophyllinine in addition to the previously known, biologically active bisindole, conophylline and its congener, conofoline. The structures of the new alkaloids were established by spectroscopic methods. The preparation and characterization of the corresponding quinones of the biologically active bisindoles are also described in relation to a structure-activity study of these compounds with respect to their action in stimulating insulin expression. PMID:12929658

  17. Reduction of venom alkaloids in Solenopsis richteri×Solenopsis invicta hybrid: an attempt to identify new alkaloidal components.

    PubMed

    Chen, Li; Hu, Qiong-Bo; Fadamiro, Henry Y

    2010-11-24

    The alkaloid chemistry of the venom of hybrid fire ant, Solenopsis richteri × Solenopsis invicta, was investigated using silica gel chromatography and GC-MS techniques. In addition to most cis alkaloids of parental species, S. richteri Forel and S. invicta Buren, the cis alkaloid fraction of the body extract of hybrid fire ants also contains five significant new alkaloids. Hydrogenation of the cis alkaloid fraction yielded only five piperidines, 4', 12', 12, 20', and 20. Sodium borohydride and lithium aluminum hydride selectively reduced C═N double bond in piperideine alkaloids to give a mixture of cis and trans piperidines. However, reduction of the five new components yielded several new peaks with much longer retention times and increasing molecular weights over 30. It is evident that the chemical identities of the five new peaks are quite different from those known piperidines or piperideines found in Solenopsis fire ants. PMID:20964344

  18. Dietary alkaloid sequestration in a poison frog: an experimental test of alkaloid uptake in Melanophryniscus stelzneri (Bufonidae).

    PubMed

    Hantak, Maggie M; Grant, Taran; Reinsch, Sherri; McGinnity, Dale; Loring, Marjorie; Toyooka, Naoki; Saporito, Ralph A

    2013-12-01

    Several lineages of brightly colored anurans independently evolved the ability to secrete alkaloid-containing defensive chemicals from granular glands in the skin. These species, collectively referred to as 'poison frogs,' form a polyphyletic assemblage that includes some species of Dendrobatidae, Mantellidae, Myobatrachidae, Bufonidae, and Eleutherodactylidae. The ability to sequester alkaloids from dietary arthropods has been demonstrated experimentally in most poison frog lineages but not in bufonid or eleutherodactylid poison frogs. As with other poison frogs, species of the genus Melanophryniscus (Bufonidae) consume large numbers of mites and ants, suggesting they might also sequester defensive alkaloids from dietary sources. To test this hypothesis, fruit flies dusted with alkaloid/nutritional supplement powder were fed to individual Melanophryniscus stelzneri in two experiments. In the first experiment, the alkaloids 5,8-disubstituted indolizidine 235B' and decahydroquinoline were administered to three individuals for 104 days. In the second experiment, the alkaloids 3,5-disubstituted indolizidine 239Q and decahydroquinoline were given to three frogs for 153 days. Control frogs were fed fruit flies dusted only with nutritional supplement. Gas chromatography/mass spectrometry analyses revealed that skin secretions of all experimental frogs contained alkaloids, whereas those of all control frogs lacked alkaloids. Uptake of decahydroquinoline was greater than uptake of 5,8-disubstituted indolizidine, and uptake of 3,5-disubstituted indolizidine was greater than uptake of decahydroquinoline, suggesting greater uptake efficiency of certain alkaloids. Frogs in the second experiment accumulated a greater amount of alkaloid, which corresponds to the longer duration and greater number of alkaloid-dusted fruit flies that were consumed. These findings provide the first experimental evidence that bufonid poison frogs sequester alkaloid-based defenses from dietary sources. PMID:24190023

  19. 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

  20. Two New C18-Diterpenoid Alkaloids from Delphinium anthriscifolium.

    PubMed

    Shan, Lianhai; Zhang, Jifa; Chen, Lin; Wang, Jiaxi; Huang, Shuai; Zhou, Xianli

    2015-12-01

    Two new C18-diterpenoid alkaloids, anthriscifoltine A (1) and anthriscifoltine B (2), along with three known diterpenoid alkaloids, deoxydelcorine (3), anthriscifolcine A (4) and anthriscifolcine G (5), were isolated from the whole herbs of Delphinium anthriscifolium var. majus. Their structures were elucidated by spectroscopic methods, including 1D, 2D NMR, and HR-ESI-MS. PMID:26882666

  1. 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...

  2. 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...

  3. 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...

  4. 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

  5. Heterologous expression of alkaloid biosynthetic genes--a review.

    PubMed

    Kutchan, T M

    1996-11-01

    Tetrahydrobenzylisoquinoline alkaloids comprise a diverse class of secondary metabolites with many pharmacologically active members. The biosynthesis at the enzyme level of at-least two tetrahydrobenzylisoquinoline alkaloids, the benzophenanthridine alkaloid sanguinarine in the California poppy, Eschscholtzia californica, and the bisbenzylisoquinoline alkaloid berbamunine in barberry, Berberis stolonifera, has been elucidated in detail starting from the aromatic amino acid (aa) L-tyrosine. In an initial attempt to develop alternate systems for the production of medicinally important alkaloids, one enzyme from each pathway (BBE, a covalently flavinylated enzyme of benzophenanthridine alkaloid biosynthesis and CYP80, a phenol coupling cytochrome P-450-dependent oxidase of bisbenzylisoquinoline alkaloid biosynthesis) has been purified to homogeneity, a partial aa sequence determined, and the corresponding cDNAs isolated with aid of synthetic oligos based on the aa sequences. The recombinant enzymes were actively expressed in Spotloptera frugiperda Sf9 cells using a baculovirus vector, purified and then characterized. Insect cell culture has proven to be a powerful system for the overexpression of alkaloid biosynthetic genes. PMID:8955631

  6. In vitro antibacterial screening of Cryptolepis sanguinolenta alkaloids.

    PubMed

    Paulo, A; Duarte, A; Gomes, E T

    1994-10-01

    The ethanol and aqueous crude extracts and five alkaloids isolated from the roots of Crytolepis sanguinolenta (Lindl.) Schlechter were screened for antibacterial activity against 7 reference strains by the twofold serial broth microdilution assay. The ethanol extract and the alkaloids cryptolepine and cryptoheptine inhibited the growth of all strains tested except that of Pseudomonas aeruginosa. PMID:7853864

  7. Dietary source for skin alkaloids of poison frogs (Dendrobatidae)?

    PubMed

    Daly, J W; Martin Garraffo, H; Spande, T F; Jaramillo, C; Stanley Rand, A

    1994-04-01

    A wide range of alkaloids, many of which are unknown elsewhere in nature, occur in skin of frogs. Major classes of such alkaloids in dendrobatid frogs are the batrachotoxins, pumiliotoxins, histrionicotoxins, gephyrotoxins, and decahydroquinolines. Such alkaloids are absent in skin of frogs (Dendrobates auratus) raised in Panama on wingless fruit flies in indoor terraria. Raised on leaf-litter arthropods that were collected in a mainland site, such terraria-raised frogs contain tricyclic alkaloids including the beetle alkaloid precoccinelline, 1,4-disubstituted quinolizidines, pyrrolizidine oximes, the millipede alkaloid nitropolyzonamine, a decahydroquinoline, a gephyrotoxin, and histrionicotoxins. The profiles of these alkaloids in the captive-raised frogs are closer to the mainland population ofDendrobates auratus at the leaf-litter site than to the parent population ofDendrobates auratus from a nearby island site. Extracts of a seven-month sampling of leaf-litter insects contained precoccinelline, pyrrolizidine oxime236 (major), and nitropolyzonamine (238). The results indicate a dietary origin for at least some "dendrobatid alkaloids," in particular the pyrrolizidine oximes, the tricyclic coccinellines, and perhaps the histrionicotoxins and gephyrotoxins. PMID:24242207

  8. Estimation of total alkaloid in Chitrakadivati by UV-Spectrophotometer

    PubMed Central

    Ajanal, Manjunath; Gundkalle, Mahadev B.; Nayak, Shradda U.

    2012-01-01

    Background: Herbal formulation standardization by adopting newer technique is need of the hour in the field of Ayurvedic pharmaceutical industry. As very few reports exist. These kind of studies would certainly widen the herbal research area. Chitrakadivati is one such popular herbal formulation used in Ayurveda. Many of its ingredients are known for presence of alkaloids. Methodology: Presence of alkaloid was tested qualitatively by Dragondroff's method then subjected to quantitative estimation by UV-Spectrophotometer. This method is based on the reaction between alkaloid and bromocresol green (BCG). Results and Conclusion: Study discloses that out of 16 ingredients, 9 contain alkaloid. Chitrakadivati has shown 0.16% of concentration of alkaloid and which is significantly higher than it's individual ingredients. PMID:23661869

  9. hERG Blockade by Iboga Alkaloids.

    PubMed

    Alper, Kenneth; Bai, Rong; Liu, Nian; Fowler, Steven J; Huang, Xi-Ping; Priori, Silvia G; Ruan, Yanfei

    2016-01-01

    The iboga alkaloids are a class of naturally occurring and synthetic compounds, some of which modify drug self-administration and withdrawal in humans and preclinical models. Ibogaine, the prototypic iboga alkaloid that is utilized clinically to treat addictions, has been associated with QT prolongation, torsades de pointes and fatalities. hERG blockade as IKr was measured using the whole-cell patch clamp technique in HEK 293 cells. This yielded the following IC50 values: ibogaine manufactured by semisynthesis via voacangine (4.09 ± 0.69 µM) or by extraction from T. iboga (3.53 ± 0.16 µM); ibogaine's principal metabolite noribogaine (2.86 ± 0.68 µM); and voacangine (2.25 ± 0.34 µM). In contrast, the IC50 of 18-methoxycoronaridine, a product of rational synthesis and current focus of drug development was >50 µM. hERG blockade was voltage dependent for all of the compounds, consistent with low-affinity blockade. hERG channel binding affinities (K i) for the entire set of compounds, including 18-MC, ranged from 0.71 to 3.89 µM, suggesting that 18-MC binds to the hERG channel with affinity similar to the other compounds, but the interaction produces substantially less hERG blockade. In view of the extended half-life of noribogaine, these results may relate to observations of persistent QT prolongation and cardiac arrhythmia at delayed intervals of days following ibogaine ingestion. The apparent structure-activity relationships regarding positions of substitutions on the ibogamine skeleton suggest that the iboga alkaloids might provide an informative paradigm for investigation of the structural biology of the hERG channel. PMID:25636206

  10. Concise synthesis of alkaloid (-)-205B.

    PubMed

    Rao, Nagavaram Narsimha; Cha, Jin Kun

    2015-02-18

    Described herein is a short total synthesis of alkaloid (-)-205B (1) by means of an anti-selective SN2' alkylation of an attractively functionalized cyclopropanol and diastereoselective cyclization of the resulting aminoallene adduct for bicyclic ring formation. The synthesis features a general route to cis- or trans-2,6-disubstituted piperidines by lithium aluminum hydride reduction of the imine intermediate by an appropriate choice of solvent and cis- or trans-2,5-disubstituted pyrrolidines by an exceptional level of chirality transfer from a pendant allene. Particularly noteworthy are the brevity and convergence made possible by a segment-coupling strategy. PMID:25635954

  11. Two toxic indole alkaloids from Penicillium islandicum.

    PubMed

    Cole, R J; Kirksey, J W; Cutler, H G; Wilson, D M; Morgan-Jones, G

    1976-05-01

    Two new isomeric metabolites, toxins A and B, were isolated from culture extracts of Penicillium islandicum. Both toxins had a molecular formula of C16H15O2N2Cl, and physical and chemical analyses indicated that they were indole alkaloids. LD50 of toxin A was about 75-125 mg/kg in day-old cockerels. Insufficient toxin B was available to determine accurate LD50 values. Toxin A moderately inhibited growth of wheat coleoptiles but did not inhibit growth of week-old intact corn and bean plants. Toxin B showed no plant-growth inhibition. PMID:1276998

  12. Muscarine, imidaozle, oxazole and thiazole alkaloids.

    PubMed

    Jin, Zhong

    2013-06-01

    Covering: July 2010 to June 2012. Previous review: Nat. Prod. Rep., 2011, 28, 1143-1191. Structurally diverse alkaloids containing five-membered heterocyclic subunits, such as imidazole, oxazole, thiazole, as well as their saturated congeners, are widely distributed in terrestrial and marine organisms and microorganisms. These naturally occurring secondary metabolites often exhibit extensive and pharmacologically important biological activities. The latest progress involving isolation, biological activities, chemical synthetic studies, and biosynthetic pathways of these natural products has been summarized in this review. PMID:23644572

  13. Leucophyllidine, a cytotoxic bisindole alkaloid constituted from the union of an eburnan and a new vinylquinoline alkaloid.

    PubMed

    Gan, Chew-Yan; Robinson, Ward T; Etoh, Tadahiro; Hayashi, Masahiko; Komiyama, Kanki; Kam, Toh-Seok

    2009-09-01

    A cytotoxic bisindole alkaloid possessing an unprecedented structure constituted from the union of an eburnan half and a novel vinylquinoline alkaloid has been isolated from Leuconotis griffithii. The structure was established by analysis of the spectroscopic data and confirmed by X-ray diffraction analysis. A possible biogenetic pathway to the novel quinolinic coupling partner is presented from an Aspidosperma precursor. PMID:19708704

  14. Cytotoxicity and accumulation of ergot alkaloids in human primary cells.

    PubMed

    Mulac, Dennis; Humpf, Hans-Ulrich

    2011-04-11

    Ergot alkaloids are secondary metabolites produced by fungi of the species Claviceps. Toxic effects after consumption of contaminated grains are described since mediaeval times. Of the more than 40 known ergot alkaloids six are found predominantly. These are ergotamine, ergocornine, ergocryptine, ergocristine, ergosine and ergometrine, along with their corresponding isomeric forms (-inine-forms). Toxic effects are known to be induced by an interaction of the ergot alkaloids as neurotransmitters, like dopamine or serotonin. Nevertheless data concerning cytotoxic effects are missing and therefore a screening of the six main ergot alkaloids was performed in human primary cells in order to evaluate the toxic potential. As it is well known that ergot alkaloids isomerize easily the stability was tested in the cell medium. Based on these results factors were calculated to correct the used concentration values to the biologically active lysergic (-ine) form. These factors range from 1.4 for the most stable compound ergometrine to 5.0 for the most unstable ergot alkaloid ergocristine. With these factors, reflecting the instability, several controverse literature data concerning the toxicity could be explained. To evaluate the cytotoxic effects of ergot alkaloids, human cells in primary culture were used. These cells remain unchanged in contrast to cell lines and the data allow a better comparison to the in vivo situation than using immortalized cell lines. To characterize the effects on primary cells, renal proximal tubule epithelial cells (RPTEC) and normal human astrocytes (NHA) were used. The parameters necrosis (LDH-release) and apoptosis (caspase-3-activation, DNA condensation and fragmentation) were distinguished. The results show that depending on the individual structure of the peptide ergot alkaloids the toxic properties change. While ergometrine as a lysergic acid amide did not show any effect, the peptide ergot alkaloids revealed a different toxic potential. Of all tested ergot alkaloids ergocristine was the most cytotoxic compound inducing apoptosis in human kidney cells starting at a concentration of 1μM in RPTEC. Uptake studies underline the cytotoxic properties, with an accumulation of peptide ergot alkaloids and no uptake of ergometrine. The results represent a new description of effects of ergot alkaloids regarding cytotoxicity and accumulation in human primary cells. For the first time apoptosis has been identified besides well described receptor effects. This gives a hint for a more complex mode of action of ergot alkaloids than described in literature so far. PMID:21295106

  15. Neurotoxic Alkaloids: Saxitoxin and Its Analogs

    PubMed Central

    Wiese, Maria; D’Agostino, Paul M.; Mihali, Troco K.; Moffitt, Michelle C.; Neilan, Brett A.

    2010-01-01

    Saxitoxin (STX) and its 57 analogs are a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs). PSTs are the causative agents of paralytic shellfish poisoning (PSP) and are mostly associated with marine dinoflagellates (eukaryotes) and freshwater cyanobacteria (prokaryotes), which form extensive blooms around the world. PST producing dinoflagellates belong to the genera Alexandrium, Gymnodinium and Pyrodinium whilst production has been identified in several cyanobacterial genera including Anabaena, Cylindrospermopsis, Aphanizomenon Planktothrix and Lyngbya. STX and its analogs can be structurally classified into several classes such as non-sulfated, mono-sulfated, di-sulfated, decarbamoylated and the recently discovered hydrophobic analogs—each with varying levels of toxicity. Biotransformation of the PSTs into other PST analogs has been identified within marine invertebrates, humans and bacteria. An improved understanding of PST transformation into less toxic analogs and degradation, both chemically or enzymatically, will be important for the development of methods for the detoxification of contaminated water supplies and of shellfish destined for consumption. Some PSTs also have demonstrated pharmaceutical potential as a long-term anesthetic in the treatment of anal fissures and for chronic tension-type headache. The recent elucidation of the saxitoxin biosynthetic gene cluster in cyanobacteria and the identification of new PST analogs will present opportunities to further explore the pharmaceutical potential of these intriguing alkaloids. PMID:20714432

  16. [Cytotoxic alkaloids from stems of Nelumbo nucifera].

    PubMed

    Duan, Xu-Hong; Pei, Lin; Jiang, Jian-Qin

    2013-12-01

    Chemical investigation was carried out to study the alkaloids from stems of Nelumbo nucifera and their cytotoxic activities. The constituents were separated by column chromatography, and their structures were elucidated by spectroscopic data analyses. The isolated compounds were evaluated for their cytotoxic activities by MTr method. Fifteen compounds were isolated from the total alkaloids extract and identified as asimilobine (1), isococlaurine (2), N-acetylnorarmepavine (3), crykonisine (4), velucryptine (5), pycnarrhine (6), liriodenine (7), nuciferine (8), nornuciferine (9), armepavine (10), N-methylasimilobine (11), coclaurine (12), N-norarmepavine (13), N-methylcoclaurine (14) and lysicamine (15). Compounds 1-7 and 12-15 were isolated from stems of this plant for the first time, and compounds 2-6 were firstly isolated from the family Nelumbonaceae. Compounds 7-10, 13 and 14 showed significant cytotoxic activities against HL-60 carcinoma cell line with inhibitory ratios of 51.36%, 59.09%, 52.51%, 53.93%, 51.43%, and 64.31% at concentration of 1 x 10(-5) mol x L(-1), respectively. PMID:24791498

  17. 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

  18. Chirality and numbering of substituted tropane alkaloids.

    PubMed

    Humam, Munir; Shoul, Tarik; Jeannerat, Damien; Muñoz, Orlando; Christen, Philippe

    2011-01-01

    The strict application of IUPAC rules for the numbering of tropane alkaloids is not always applied by authors and there is hence a lot of confusion in the literature. In most cases, the notation of 3, 6/7-disubstituted derivatives has been chosen arbitrarily, based on NMR and MS data, without taking into account the absolute configuration of these two carbons. This paper discusses the problem and the relevance of CD and NMR to determine molecular configurations. We report on the use of (1)H-NMR anisochrony (Δδ) induced by the Mosher's chiral auxiliary reagents (R)-(-)- and (S)-(+)-α-methoxy-α-trifluoromethyl-phenylacetyl chlorides (MTPA-Cl), to determine the absolute configuration of (3R,6R)-3α-hydroxy-6β-senecioyloxytropane, a disubstituted tropane alkaloid isolated from the aerial parts of Schizanthus grahamii (Solanaceae). These analytical tools should help future works in correctly assigning the configuration of additional 3, 6/7 disubstituted tropane derivatives. PMID:21869748

  19. Antifungal Quinoline Alkaloids from Waltheria indica.

    PubMed

    Cretton, Sylvian; Dorsaz, Stéphane; Azzollini, Antonio; Favre-Godal, Quentin; Marcourt, Laurence; Ebrahimi, Samad Nejad; Voinesco, Francine; Michellod, Emilie; Sanglard, Dominique; Gindro, Katia; Wolfender, Jean-Luc; Cuendet, Muriel; Christen, Philippe

    2016-02-26

    Chemical investigation of a dichloromethane extract of the aerial parts of Waltheria indica led to the isolation and characterization of five polyhydroxymethoxyflavonoids, namely, oxyanin A (1), vitexicarpin (3), chrysosplenol E (4), flindulatin (5), 5-hydroxy-3,7,4'-trimethoxyflavone (6), and six quinolone alkaloids, waltheriones M-Q (2, 7, 8, 10, 11) and 5(R)-vanessine (9). Among these, compounds 2, 7, 8, 10, and 11 have not yet been described in the literature. Their chemical structures were established by means of spectroscopic data interpretation including (1)H and (13)C, HSQC, HMBC, COSY, and NOESY NMR experiments and UV, IR, and HRESIMS. The absolute configurations of the compounds were established by ECD. The isolated constituents and 10 additional quinoline alkaloids previously isolated from the roots of the plant were evaluated for their in vitro antifungal activity against the human fungal pathogen Candida albicans, and 10 compounds (7, 9, 11-16, 18, 21) showed growth inhibitory activity on both planktonic cells and biofilms (MIC ≤ 32 μg/mL). Their spectrum of activity against other pathogenic Candida species and their cytotoxicity against human HeLa cells were also determined. In addition, the cytological effect of the antifungal isolated compounds on the ultrastructure of C. albicans was evaluated by transmission electron microscopy. PMID:26848627

  20. Determination of ergot alkaloids in feed by HPLC.

    PubMed

    Ruhland, M; Tischler, J

    2008-06-01

    A HPLC method for the determination of ergometrine, ergotamine, ergocristine, α-ergocryptine and ergocornine in cereals for animal feed and in mixed feed with high cereal content was developed. Samples were extracted under acidic conditions using a mixture of phosphoric acid and acetonitrile, the extract purified with solid phase extraction cartridges (strong cation exchange), and ergot alkaloids detected after gradient elution on a C18 column by HPLC with fluorescence detection. Detection and determination limits for each individual alkaloid were at 5 (μ/kg and 10 (μg/kg, respectively. With this method, high recovery (82-120%) and good reproducibility was achieved for wheat, rye and mixed feeds, at a sum of total determined alkaloids of < 500 (μg/kg. This method was used to analyse Bavarian feeds (n=124) over three years (2005-2007), and ergot alkaloids were detected in 91 % of the samples. The majority of positive samples had ergot alkaloid contents of < 250 μg/kg, the median alkaloid level was at 70 (μg/kg. The maximum sum of total determined alkaloids exceeded 1000 (μg/kg in wheat, triticale, rye, and mixed feeds, the highest result was obtained for mixed feed (4880 (μg/kg). PMID:23604683

  1. Antiplasmodial activity of Cryptolepis sanguinolenta alkaloids from leaves and roots.

    PubMed

    Paulo, A; Gomes, E T; Steele, J; Warhurst, D C; Houghton, P J

    2000-02-01

    The roots of Cryptolepis sanguinolenta have been investigated for their chemical composition since 1931 but so far no studies on the leaves have been reported although they are used in traditional medicine in Guinea-Bissau. Two new alkaloids identified as cryptolepinoic acid (1) and methyl cryptolepinoate (2) and the known alkaloids cryptolepine (4), hydroxycryptolepine (5/5a) and quindoline (6), were isolated from the ethanolic and chlorophormic leaf extracts. Aqueous and ethanolic extracts of the leaves and roots and seven alkaloids isolated from those extracts were tested in vitro against Plasmodium falciparum K1 (multidrug-resistant strain) and T996 (chloroquine-sensitive clone). All the extracts were shown to give 90% inhibition of P. falciparum K1 growth at concentrations < 23 micrograms/ml. Cryptolepine (4) was the most active alkaloid tested with IC50 values (0.23 microM to K1; 0.059 microM to T996) comparable with chloroquine (0.26 microM to K1; 0.019 microM to T996). The indolobenzazepine alkaloid cryptoheptine (7) was the second most active with IC50 values of 0.8 microM (K1) and 1.2 microM (T996). Cryptolepinoic acid (1) showed no significant activity while its ethyl ester derivative 3 was active against P. falciparum K1 (IC50 = 3.7 microM). All the indoloquinoline alkaloids showed cross-resistance with chloroquine but not the indolobenzazepine alkaloid 7. It was noticed that alkaloids with weakly basic characteristics were active whereas other structurally related alkaloids with different acid-base profiles were inactive. These observations are in agreement with the antimalarial mechanism of action for quinolines. PMID:10705730

  2. A Review of Bioinsecticidal Activity of Solanaceae Alkaloids

    PubMed Central

    Chowański, Szymon; Adamski, Zbigniew; Marciniak, Paweł; Rosiński, Grzegorz; Büyükgüzel, Ender; Büyükgüzel, Kemal; Falabella, Patrizia; Scrano, Laura; Ventrella, Emanuela; Lelario, Filomena; Bufo, Sabino A.

    2016-01-01

    Only a small percentage of insect species are pests. However, pest species cause significant losses in agricultural and forest crops, and many are vectors of diseases. Currently, many scientists are focused on developing new tools to control insect populations, including secondary plant metabolites, e.g., alkaloids, glycoalkaloids, terpenoids, organic acids and alcohols, which show promise for use in plant protection. These compounds can affect insects at all levels of biological organization, but their action generally disturbs cellular and physiological processes, e.g., by altering redox balance, hormonal regulation, neuronal signalization or reproduction in exposed individuals. Secondary plant metabolites cause toxic effects that can be observed at both lethal and sublethal levels, but the most important effect is repellence. Plants from the Solanaceae family, which contains numerous economically and ecologically important species, produce various substances that affect insects belonging to most orders, particularly herbivorous insects and other pests. Many compounds possess insecticidal properties, but they are also classified as molluscides, acaricides, nematocides, fungicides and bactericides. In this paper, we present data on the sublethal and lethal toxicity caused by pure metabolites and crude extracts obtained from Solanaceae plants. Pure substances as well as water and/or alcohol extracts cause lethal and sublethal effects in insects, which is important from the economical point of view. We discuss the results of our study and their relevance to plant protection and management. PMID:26938561

  3. A Review of Bioinsecticidal Activity of Solanaceae Alkaloids.

    PubMed

    Chowański, Szymon; Adamski, Zbigniew; Marciniak, Paweł; Rosiński, Grzegorz; Büyükgüzel, Ender; Büyükgüzel, Kemal; Falabella, Patrizia; Scrano, Laura; Ventrella, Emanuela; Lelario, Filomena; Bufo, Sabino A

    2016-01-01

    Only a small percentage of insect species are pests. However, pest species cause significant losses in agricultural and forest crops, and many are vectors of diseases. Currently, many scientists are focused on developing new tools to control insect populations, including secondary plant metabolites, e.g., alkaloids, glycoalkaloids, terpenoids, organic acids and alcohols, which show promise for use in plant protection. These compounds can affect insects at all levels of biological organization, but their action generally disturbs cellular and physiological processes, e.g., by altering redox balance, hormonal regulation, neuronal signalization or reproduction in exposed individuals. Secondary plant metabolites cause toxic effects that can be observed at both lethal and sublethal levels, but the most important effect is repellence. Plants from the Solanaceae family, which contains numerous economically and ecologically important species, produce various substances that affect insects belonging to most orders, particularly herbivorous insects and other pests. Many compounds possess insecticidal properties, but they are also classified as molluscides, acaricides, nematocides, fungicides and bactericides. In this paper, we present data on the sublethal and lethal toxicity caused by pure metabolites and crude extracts obtained from Solanaceae plants. Pure substances as well as water and/or alcohol extracts cause lethal and sublethal effects in insects, which is important from the economical point of view. We discuss the results of our study and their relevance to plant protection and management. PMID:26938561

  4. Daphmacromines A-J, alkaloids from Daphniphyllum macropodum.

    PubMed

    Cao, Mingming; Zhang, Yu; He, Hongping; Li, Shifei; Huang, Shengdian; Chen, Duozhi; Tang, Guihua; Li, Shunlin; Di, Yingtong; Hao, Xiaojiang

    2012-06-22

    Ten new yuzurine-type Daphniphyllum alkaloids, daphmacromines A-J (1-10), along with seven known alkaloids were isolated from the leaves and stems of Daphniphyllum macropodum. Their structures were elucidated by extensive spectroscopic techniques, including 2D NMR spectroscopy and mass spectrometry, and the structure of 1 was confirmed by single-crystal X-ray diffraction. The pesticidal and cytotoxic activities of the isolated alkaloids were evaluated in vitro against brine shrimp (Artemia salina) and five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480), respectively. This study also suggested structural revisions of oxodaphnigracine, oxodaphnigraciline, and epioxodaphnigraciline. PMID:22642560

  5. Cyclobutane-Containing Alkaloids: Origin, Synthesis, and Biological Activities

    PubMed Central

    Sergeiko, Anastasia; Poroikov, Vladimir V; Hanuš, Lumir O; Dembitsky, Valery M

    2008-01-01

    Present review describes research on novel natural cyclobutane-containing alkaloids isolated from terrestrial and marine species. More than 60 biological active compounds have been confirmed to have antimicrobial, antibacterial, antitumor, and other activities. The structures, synthesis, origins, and biological activities of a selection of cyclobutane-containing alkaloids are reviewed. With the computer program PASS some additional biological activities are also predicted, which point toward new possible applications of these compounds. This review emphasizes the role of cyclobutane-containing alkaloids as an important source of leads for drug discovery. PMID:19696873

  6. Semisynthetic derivatives of pyrrolizidine alkaloids of pharmacodynamic importance: a review.

    PubMed

    Atal, C K

    1978-01-01

    Pyrrolizidine alkaloids occur in more than 40 genera. Among these are two important genera, Senecio and Crotalaria, which have been responsible for heavy losses of livestock and poisoning in man due to their hepatotoxicity. Pyrrolizidine alkaloids are also reported to possess a number of other biological activities. Attempts have been made to convert the pyrrolizidine alkaloids to new structures by synthetic modifications. One hundred and twenty semisynthetic compounds were developed and investigated pharmacologically. The range of activity exhibited was hypotensive, local anesthetic, ganglion blocking, neuromuscular blocking and antispasmodic. The five most promising compounds of these series were subjected to detailed pharmacological investigations. PMID:27691

  7. Alkaloid 223A: the first trisubstituted indolizidine from dendrobatid frogs.

    PubMed

    Garraffo, H M; Jain, P; Spande, T F; Daly, J W

    1997-01-01

    The structure of alkaloid 223A (1), the first member of a new class of amphibian alkaloids, purified by HPLC from a skin extract of a Panamanian population of the frog Dendrobates pumilio Schmidt (Dendrobatidae) has been established as (5R,6S,8R,9S)- or (5S,6R,8S,9R)-6,8-diethyl-5-propylindolizidine, based on GC-MS, GC-FTIR, and 1H-NMR spectral studies. Three higher homologs of 223A, namely alkaloids 237L (2), 251M (3), and 267J (4), have been detected in other extracts, and tentative structures are proposed. PMID:9014346

  8. Ergot alkaloids--biology and molecular biology.

    PubMed

    Schardl, Christopher L; Panaccione, Daniel G; Tudzynski, Paul

    2006-01-01

    EA have been a major benefit, and a major detriment, to humans since early in recorded history. Their medicinal properties have been used, and continue to be used, to aid in childbirth, with new uses being found in the treatment of neurological and cardiovascular disorders. The surprisingly broad range of pharmaceutical uses for EA stems from their affinities for multiple receptors for three distinct neurotransmitters (serotonin, dopamine, and adrenaline), from the great structural diversity of natural EA, and from the application of chemical techniques that further expand that structural diversity. The dangers posed by EA to humans and their livestock stem from the ubiquity of ergot fungi (Claviceps species) as parasites of cereals, and of related grass endophytes (Epichloë, Neotyphodium, and Balansia species) that may inhabit pasture grasses and produce toxic levels of EA. Further concerns stem from saprophytic EA producers in the genera Aspergillus and Penicillium, especially A. fumigatus, an opportunistic pathogen of humans. Numerous fungal species produce EA with a wide variety of structures and properties. These alkaloids are associated with plants in the families Poaceae, Cyperaceae, and Convolvulaceae, apparently because these plants can have symbiotic fungi that produce EA. Pharmacological activities of EA relate to their specific structures. Known as potent vasoconstrictors, the ergopeptines include a lysergic acid substituent with an amide linkage to a complex cyclol-lactam ring structure generated from three amino acids. Simpler lysergyl amides and clavines are more apt to have oxytonic or psychotropic activities. One of the lysergyl amides is LSD (5), the most potent hallucinogen known. The EA biosynthetic pathway in Claviceps species has been studied extensively for many decades, and recent studies have also employed epichloës and A. fumigatus. The early pathway, shared among these fungi, begins with the action of an aromatic prenyl transferase, DMATrp synthase, which links a dimethylallyl chain to L-tryptophan. When the dmaW gene encoding DMATrp synthase was cloned and sequenced, the predicted product bore no identifiable resemblance to other known prenyl transferases. The dma W genes of Claviceps species are present in clusters of genes, several of which also have demonstrated roles in EA biosynthesis. In many other fungi, dma W homologues are identifiable in otherwise very different gene clusters. The roles of DMA Trp synthase homologues in these other fungi are probably quite variable. One of them is thought to prenylate the phenolic oxygen of L-tyrosine, and another catalyzes the unusual reverse prenylation reaction in the biosynthesis of fumigaclavine C(10), an EA characteristic of A. fumigatus. The second step of the EA pathway is N-methylation of DMATrp (12) to form 13, which is then subjected to a series of oxidation/oxygenation and reduction reactions to generate, in order, chanoclavine-I (16), agroclavine (19), and elymoclavine (6). Shunt reactions generate a wide variety of other clavines. Two epimerizations occur in this pathway: one from 12 to 16, the other from 16 to 19. Further oxidation of 6, catalyzed by the cytochrome-P450 CloA, generates lysergic acid (1). An unusual NRPS complex, lysergyl peptide synthetase (LPS), is responsible for linking 1 to three hydrophobic L-amino acids to generate the ergopeptide lactams. The LPS complex includes two polypeptides, one (LPS 2) possessing a single module for activation of 1, and the other (LPS 1) possessing three modules, each specifying one of the L-amino acids. Variations in LPS 1 sequences are associated with variations in the incorporated amino acids, leading to differences between strain chemotypes, and even multiple ergopeptines within strains. For example, C. purpurea P1 produces two distinct ergopeptines (ergotamine (4) and ergocryptine (Table I)), each of which is believed to be generated by multiple LPS 1 subunits encoded by separate, but related, genes (lpsA1 and lpsA2). The main ecological roles of EA in nature are probably to protect the fungi from consumption by vertebrate and invertebrate animals. The EA produced by plant-symbiotic fungi (such as epichloë endophytes) may protect the fungus by protecting the health and productivity of the host, which may otherwise suffer excessive grazing by animals. The EA, at levels typical of plants bearing these symbionts, can negatively affect the health of large mammals as well herbivorous insects. Some clavines have substantial anti-bacterial properties, which might protect the fungus and, in some cases, their host plants from infection. However, the fact that a large number of epichloë, and even several Claviceps species, produce no detectable EA indicates that the selection for their production is not universal. An unfortunate fact for many livestock producers is that some of the most popular forage grasses tend to possess EA-producing epichloë endophytes. Such endophytes are easily eliminated, but confer such fitness enhancements to their hosts that their presence is often preferred, despite the toxic EA. The future looks promising for continued interest in EA. Research continues into their pharmacological properties, medicinal uses, and structure-function relationships. New clavines and lysergic acid derivatives are identified regularly from new sources, such as marine animals. Also, programs are well underway to modify or replace epichloë endophytes of forage grasses in order to produce new grass cultivars that lack these toxins. PMID:17133714

  9. Ibogan, Aspidosperman, Vincamine, and Bisindole Alkaloids from a Malayan Tabernaemontana corymbosa: Iboga Alkaloids with C-20α Substitution.

    PubMed

    Nge, Choy-Eng; Chong, Kam-Weng; Thomas, Noel F; Lim, Siew-Huah; Low, Yun-Yee; Kam, Toh-Seok

    2016-05-27

    Ten new indole alkaloids (1-10) comprising five ibogan, two aspidosperman, one vincamine, and two bisindole alkaloids, in addition to 32 known alkaloids, were isolated from the stem-bark extract of a Malayan Tabernaemontana corymbosa. The structures of these alkaloids were determined based on analysis of the NMR and MS data and, in five instances (1, 3, 5, 6, 8), confirmed by X-ray diffraction analysis. Two of the iboga alkaloids, conodusines B (2) and C (3), and the iboga-containing bisindole tabernamidine B (10) are notable for the presence of an α-substituted acetyl group at C-20 of the iboga carbon skeleton. The iboga alkaloid (+)-conodusine E (5) had MS and NMR data that were identical to those of (-)-ervatamine I, recently isolated from Ervatamia hainanensis. Establishment of the absolute configuration of (+)-conodusine E (5) was based on analysis of the ECD data, correlation with (-)-heyneanine, and X-ray analysis, which showed that (+)-5 belongs to the same enantiomeric series as exemplified by (-)-coronaridine. The configuration at C-20' of the previously reported Tabernaemontana bisindole alkaloid 19'-oxotabernamine (renamed tabernamidine B) required revision based on the present results. Several of the bisindoles showed pronounced in vitro growth inhibitory activity against drug-sensitive and vincristine-resistant KB cells. PMID:27077800

  10. Total Synthesis of Alkaloid 205B

    PubMed Central

    2015-01-01

    Concise and highly stereocontrolled total syntheses of racemic and enantiopure frog alkaloid 205B (1) were accomplished in 11 steps from 4-methoxypyridines 6 and 7 in overall yields of 8 and 8%, respectively. The assembly of the core of the natural product relies on a stereoselective Tsuji–Trost allylic amination reaction and a ring-closing metathesis. The synthesis features the use of an N-acylpyridinium salt reaction to introduce the first stereocenter and an unprecedented trifluoroacetic anhydride-mediated addition of an allylstannane to a vinylogous amide with complete facial selectivity. Deoxygenation of the C4 ketone proved difficult but was accomplished via a modified Barton–McCombie reaction in the presence of a catalytic amount of diphenyl diselenide. PMID:25180567

  11. 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 structureactivity 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

  12. Anticancer Alkaloid Lamellarins Inhibit Protein Kinases

    PubMed Central

    Baunbæk, Dianne; Trinkler, Nolwenn; Ferandin, Yoan; Lozach, Olivier; Ploypradith, Poonsakdi; Rucirawat, Somsak; Ishibashi, Fumito; Iwao, Masatomo; Meijer, Laurent

    2008-01-01

    Lamellarins, a family of hexacyclic pyrrole alkaloids originally isolated from marine invertebrates, display promising anti-tumor activity. They induce apoptotic cell death through multi-target mechanisms, including inhibition of topoisomerase I, interaction with DNA and direct effects on mitochondria. We here report that lamellarins inhibit several protein kinases relevant to cancer such as cyclin-dependent kinases, dual-specificity tyrosine phosphorylation activated kinase 1A, casein kinase 1, glycogen synthase kinase-3 and PIM-1. A good correlation is observed between the effects of lamellarins on protein kinases and their action on cell death, suggesting that inhibition of specific kinases may contribute to the cytotoxicity of lamellarins. Structure/activity relationship suggests several paths for the optimization of lamellarins as kinase inhibitors. PMID:19172192

  13. Non-alkaloid constituents of Vinca major.

    PubMed

    Cheng, Gui-Guang; Zhao, Hai-Yun; Liu, Lu; Zhao, Yun-Li; Song, Chang-Wei; Gu, Ji; Sun, Wei-Bang; Liu, Ya-Ping; Luo, Xiao-Dong

    2016-01-01

    The present study was designed to investigate the non-alkaloid compounds from the leaves and stems of Vinca major cultivated in Yunnan Province, China. The compounds were isolated using chromatographic techniques. The structures were elucidated by 1D- and 2D-NMR spectroscopic methods in combination with UV, IR, and MS analyses. The 1, 1-diphenyl-2-picrylhydrazyl (DPPH)-scavenging activity of Compounds 1-7 were evaluated. One new iridoid glycoside (compound 1), together with 11 known compounds, were isolated from Vinca major. Compounds 1, 5, and 6 showed moderate DPPH-scavenging activity, with IC50 values being 70.6, 32.8, and 62.2 μmol·L(-1), respectively. In conclusion, compound 1 is a newly identified iridoid glycoside with moderate antioxidant activity. PMID:26850347

  14. Antiproliferative activity of arborescidine alkaloids and derivatives.

    PubMed

    Santos, Leonardo S; Theoduloz, Cristina; Pilli, Ronaldo A; Rodriguez, Jaime

    2009-09-01

    Current issues in cancer research involve searching for novel anticancer compounds that can be used to regulate the cell cycle and lead to more effective treatments of tumors. In this study, it was hypothesized that possessing a cyclic alkaloid similar to harmine, arborescidines can disrupt the proliferative state of cancer cells and block the activity of topoisomerases. The antiproliferative activity of arborescidines A-C and their derivatives was evaluated in vitro against four human tumor cell lines: gastric adenocarcinoma, lung cancer, bladder carcinoma and leukemia. Assuming the mechanism of action by topoisomerase II binding model, the compounds possessing the greatest activity had nonpolar side-chain into hydrophobic binding region on the DNA/topo II complex. PMID:19419803

  15. 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 α-erythroidine, β-erythroidine, and their oxo-derivatives 8-oxo-α-erythroidine and 8-oxo-β-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. α-Erythroidine and β-erythroidine showed binding affinity values for ERα of 0.015 ± 0.010% and 0.005 ± 0.010%, respectively, whereas only β-erythroidine bound to ERβ (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, α-erythroidine and β-erythroidine both induced the enhanced expression of the specific ERα-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 ERα, 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

  16. 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 (μ), peak-time (Tm), inhibitory ratio (I), and enhancement ratio (E) were calculated. The relationships between the concentration of Aconitum alkaloids and μ 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

  17. 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 (μ), peak-time (Tm), inhibitory ratio (I), and enhancement ratio (E) were calculated. The relationships between the concentration of Aconitum alkaloids and μ 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

  18. Ergot alkaloids induce vasoconstriction of bovine foregut vasculature

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Alkaloids produced by the Neotyphodium coenophialum endophyte in association with tall fescue (Lolium arundinaceum) are imputed to cause peripheral symptoms of fescue toxicosis. We hypothesized that theses compounds could correspondingly affect foregut vasculature. The objective of this study was to...

  19. Effects of Psychotria colorata alkaloids in brain opioid system.

    PubMed

    Amador, T A; Elisabetsky, E; Souza, D O

    1996-01-01

    An ethnopharmacological survey showed that home remedies prepared with flowers and fruits of Psychotria colorata are used by Amazonian peasants as pain killers. Psychopharmacological in vivo evaluation of alkaloids obtained from leaves and flowers of this species showed a marked dose-dependent naloxone-reversible analgesic activity, therefore suggesting an opioid-like pharmacological profile. This paper reports an inhibitory effect of P. colorata flower alkaloids on [3H]naloxone binding in rat striata as well as a decrease in adenylate cyclase basal activity. The alkaloids did not affect [3H] GMP-PNP binding. These findings provide a neurochemical basis for the opioid-like activity previously detected in vivo and point to Psychotria alkaloids as a potential source of new bioactive opiate derivatives. PMID:8833229

  20. Leishmanicidal evaluation of tetrahydroprotoberberine and spirocyclic erythrina-alkaloids.

    PubMed

    Callejon, Daniel R; Riul, Thalita B; Feitosa, Luis G P; Guaratini, Thais; Silva, Denise B; Adhikari, Achyut; Shrestha, Ram L S; Marques, Lucas M M; Baruffi, Marcelo D; Lopes, João L C; Lopes, Norberto P

    2014-01-01

    Leishmaniasis is one of the World's most problematic diseases in developing countries. Traditional medicines to treat leishmaniasis have serious side effects, as well as significant parasite resistance problems. In this work, two alkaloids 1 and 2 were obtained from Corydalis govaniana Wall and seven alkaloids 3-9, were obtained from Erythrina verna. The structures of the compounds were confirmed by mass spectrometry and 1D- and 2D-NMR spectroscopy. The leishmanicidal activity of compounds 1-9 against Leishmania amazonensis was tested on promastigote forms and cytotoxicity against J774 (macrophage cell line) was assessed in vitro. Compound 1 showed potent activity (IC50 = 0.18 µg/mL), compared with the standard amphotericin B (IC50 = 0.20 µg/mL). The spirocyclic erythrina-alkaloids showed lower leishmanicidal activity than dibenzoquinolizine type alkaloids. PMID:24802983

  1. Total synthesis of indole alkaloid (±)-subincanadine E.

    PubMed

    Tian, Jingjing; Du, Qiuchen; Guo, Rui; Li, Yun; Cheng, Bin; Zhai, Hongbin

    2014-06-20

    The first total synthesis of indole alkaloid (±)-subincanadine E has been accomplished. Ni(COD)2-mediated intramolecular Michael addition and zinc-mediated fragmentation reaction served as two key transformations. PMID:24869784

  2. Significance, chemistry and determination of ergot alkaloids: a review.

    PubMed

    Krska, R; Crews, C

    2008-06-01

    The purpose of this paper is to summarize the most relevant and recent information available on ergot alkaloids. This includes information about their occurrence, toxicity, chemistry, statutory limits, and their significance in feed and food. Recently, in 2005, the European Food Safety Authority (EFSA) concluded that validated analytical methods for the quantification of ergot alkaloids in feed materials are needed. For that reason, the major focus of the present paper is to report on the latest developments for the determination of major ergot alkaloids and their epimers in cereals and cereal-derived products. Information about the stability and the availability of calibrants, sampling issues, extraction and clean-up strategies, and a variety of final separation and detection techniques is provided. The recently developed liquid chromatography-tandem mass spectrometric methods (LC-MS/MS) for the simultaneous quantification and identification of ergot alkaloids are given special consideration. PMID:18484300

  3. [Monomeric indole alkaloids from the aerial parts of Catharanthus roseus].

    PubMed

    Zhong, Xiang-Zhang; Wang, Guo-Cai; Wang, Ying; Zhang, Xiao-Qi; Ye, Wen-Cai

    2010-04-01

    Catharanthus roseus (L.) G. Don is a plant of the Catharanthus genus of Apocynaceae which has been reported to have therapeutic effects of detoxication and anticancer. In order to further study the alkaloid constituents of C. roseus, the aerial parts of the plant were extracted with 95% EtOH, and then treated with 2% H2SO4 and NH3H2O to obtain total alkaloids. The total alkaloids were separated and purified by column chromatography over silica gel and prepared by high performance liquid chromatography (HPLC). Their structures were elucidated on the basis of physicochemical properties and spectral data. A new alkaloid together with five known compounds were isolated and identified as vindolinine B (1), lochnericine (2), horhammericine (3), vindorosine (4), vindoline (5), and coronaridine (6). Compound 1 is a new compound and named as vindolinine B. PMID:21355212

  4. A bacterial platform for fermentative production of plant alkaloids

    PubMed Central

    Nakagawa, Akira; Minami, Hiromichi; Kim, Ju-Sung; Koyanagi, Takashi; Katayama, Takane; Sato, Fumihiko; Kumagai, Hidehiko

    2011-01-01

    The secondary metabolites of higher plants include diverse chemicals, such as alkaloids, isoprenoids and phenolic compounds (phenylpropanoids and flavonoids). Although these compounds are widely used in human health and nutrition, at present they are mainly obtained by extraction from plants and extraction yields are low because most of these metabolites accumulate at low levels in plant cells. Recent advances in synthetic biology and metabolic engineering have enabled tailored production of plant secondary metabolites in microorganisms, but these methods often require the addition of expensive substrates. Here we develop an Escherichia coli fermentation system that yields plant alkaloids from simple carbon sources, using selected enzymes to construct a tailor-made biosynthetic pathway. In this system, engineered cells cultured in growth medium without additional substrates produce the plant benzylisoquinoline alkaloid, (S)-reticuline (yield, 46.0 mg l−1 culture medium). The fermentation platform described here offers opportunities for low-cost production of many diverse alkaloids. PMID:21610729

  5. 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.

  6. Bioinspired Collective Syntheses of Iboga-Type Indole Alkaloids.

    PubMed

    Zhao, Gaoyuan; Xie, Xingang; Sun, Haiyu; Yuan, Ziyun; Zhong, Zhuliang; Tang, Shouchu; She, Xuegong

    2016-05-20

    We present the application of a bioinspired collective synthesis strategy in the total syntheses of seven iboga-type indole alkaloids: (±)-tabertinggine, (±)-ibogamine, (±)-ibogaine, (±)-ibogaine hydroxyindolenine, (±)-3-oxoibogaine hydroxyindolenine, (±)-iboluteine, and (±)-ervaoffines D. In particular, tabertinggine and its congeners serve as iboga precursors for the subsequent biomimetic transformations into other iboga-type alkaloids. PMID:27160167

  7. Himalensines A and B, Alkaloids from Daphniphyllum himalense.

    PubMed

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

    2016-03-01

    Chemical investigation into the alkaloidal constituents of the Nepalese Daphniphyllum himalense has returned two new compounds, himalensines A (1) and B (2), with unprecedented carbon skeletons. Structures of the two alkaloids have been characterized on the basis of spectroscopic methods, especially via 2D NMR data analysis. Himalensine B (2) showed marginal inhibitory activities against two kinases, PTP1B and IKK-β. PMID:26914844

  8. Detection and quantification of pyrrolizidine alkaloids in antibacterial medical honeys.

    PubMed

    Cramer, Luise; Beuerle, Till

    2012-12-01

    In recent years, there has been an increasing interest in antibacterial honey for wound care ranging from minor abrasions and burns to leg ulcers and surgical wounds. On the other hand, several recent studies demonstrated that honey for human consumption was contaminated with natural occurring, plant derived pyrrolizidine alkaloids.1,2-Unsaturated pyrrolizidine alkaloids are a group of secondary plant metabolites that show developmental, hepato-, and geno-toxicity as well as carcinogenic effects in animal models and in in vitro test systems. Hence, it was of particular interest to analyze the pyrrolizidine alkaloid content of medical honeys intended for wound care.19 different medical honey samples and/or batches were analyzed by applying a recently established pyrrolizidine alkaloid sum parameter method. 1,2-Unsaturated pyrrolizidine alkaloids were converted into the common necin backbone structures and were analyzed and quantified by GC-MS in the selected ion monitoring mode.All but one medical honey analyzed were pyrrolizidine alkaloid positive. The results ranged from 10.6 µg retronecine equivalents per kg to 494.5 µg retronecine equivalents/kg medical honey. The average pyrrolizidine alkaloid content of all positive samples was 83.6 µg retronecine equivalents/kg medical honey (average of all samples was 79.3 µg retronecine equivalents/kg medical honey). The limit of detection was 2.0 µg retronecine equivalents/kg medical honey, while the limit of quantification was 6.0 µg retronecine equivalents/kg medical honey (S/N > 7/1).Based on the data presented here and considering the fact that medical honeys can be applied to open wounds, it seems reasonable to discuss the monitoring of 1,2-unsaturated pyrrolizidine alkaloids in honey intended for wound treatment. PMID:23161425

  9. Elaboration of simplified vinca alkaloids and phomopsin hybrids.

    PubMed

    Ngo, Quoc Anh; Roussi, Fanny; Thoret, Sylviane; Guéritte, Françoise

    2010-03-01

    Nine simplified vinca alkaloids and phomospin A hybrids, in which vindoline moiety has been replaced by a simpler scaffold, have been elaborated to evaluate their activity on the inhibition of tubulin polymerization. This article deals with the synthesis of various simplified vinca alkaloids, using a stereoselective coupling of catharantine with reactive aromatic compounds and methanol as well as their subsequent condensation with a large peptide chain mimicking those of phomopsin A. Biological evaluation and molecular modeling studies are also reported. PMID:20659111

  10. Jerantinines A-G, cytotoxic Aspidosperma alkaloids from Tabernaemontana corymbosa.

    PubMed

    Lim, Kuan-Hon; Hiraku, Osamu; Komiyama, Kanki; Kam, Toh-Seok

    2008-09-01

    Seven new indole alkaloids of the Aspidosperma type, jerantinines A-G (1-7), were isolated from a leaf extract of the Malayan Tabernaemontana corymbosa. The structures were established using NMR and MS analysis. Five of the alkaloids isolated and two derivatives (1-5, 8, 9) displayed pronounced in vitro cytotoxicity against human KB cells (IC50 < 1 microg/mL). PMID:18778099

  11. Cytotoxic indole alkaloids from the fruits of Melodinus cochinchinensis.

    PubMed

    Shao, Shun; Zhang, Hao; Yuan, Chun-Mao; Zhang, Yu; Cao, Ming-Ming; Zhang, Hai-Yuan; Feng, Yan; Ding, Xiao; Zhou, Qiang; Zhao, Qing; He, Hong-Ping; Hao, Xiao-Jiang

    2015-08-01

    Eight indole alkaloids, melosines A-H, together with 13 known alkaloids, were isolated from the fruits of Melodinus cochinchinensis. The structure elucidation of isolated secondary metabolites was based on comprehensive spectroscopic data analysis. Melosine B showed moderate cytotoxic activity against five human cancer cell lines, HL-60, SMMC-7721, A-549, MCF-7, and SW480 with IC50 values ranging from 1.6 to 8.1?M. PMID:25817833

  12. Genetics, genomics and evolution of ergot alkaloid diversity.

    PubMed

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

    2015-04-01

    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

  13. 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

  14. 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

  15. Over-expression of rate-limiting enzymes to improve alkaloid productivity.

    PubMed

    Takemura, Tomoya; Chow, Yit-lai; Todokoro, Takehiko; Okamoto, Takuya; Sato, Fumihiko

    2010-01-01

    Benzylisoquinoline alkaloids are one of the most important groups of secondary metabolites and include the economically important analgesic morphine and the antimicrobial agent berberine. To improve the productivity of these alkaloids, we investigated the effects of putative rate-limiting step enzymes in alkaloid biosynthesis. We constructed several over-expression vectors for biosynthetic enzymes and introduced them into cultured California poppy, a model isoquinoline alkaloid-producing plant. HPLC/LC-MS analysis of transgenic cells revealed that these enzymes varied in their ability to increase alkaloid production. We describe the use of a rate-limiting step gene to improve alkaloid productivity. PMID:20552446

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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 ...

  1. Alkaloids in bufonid toads (melanophryniscus): temporal and geographic determinants for two argentinian species.

    PubMed

    Daly, J W; Wilham, J M; Spande, T F; Garraffo, H M; Gil, R R; Silva, G L; Vaira, M

    2007-04-01

    Bufonid toads of the genus Melanophryniscus represent one of several lineages of anurans with the ability to sequester alkaloids from dietary arthropods for chemical defense. The alkaloid profile for Melanophryniscus stelzneri from a location in the province of Córdoba, Argentina, changed significantly over a 10-year period, probably indicating changes in availability of alkaloid-containing arthropods. A total of 29 alkaloids were identified in two collections of this population. Eight alkaloids were identified in M. stelzneri from another location in the province of Córdoba. The alkaloid profiles of Melanophryniscus rubriventris collected from four locations in the provinces of Salta and Jujuy, Argentina, contained 44 compounds and differed considerably between locations. Furthermore, alkaloid profiles of M. stelzneri and M. rubriventris strongly differed, probably reflecting differences in the ecosystem and hence in availability of alkaloid-containing arthropods. PMID:17333373

  2. 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

  3. Hydrachine A, a novel alkaloid from the roots of Hydrangea chinensis.

    PubMed

    Patnam, R; Chang, F R; Chen, C Y; Kuo, R Y; Lee, Y H; Wu, Y C

    2001-07-01

    A novel alkaloid, hydrachine A (3), has been isolated, along with 15 known compounds, from the roots of Hydrangea chinensis. The structure and stereochemistry of the new alkaloid 3 was determined using extensive 2D NMR data. PMID:11473431

  4. 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.

  5. Ornithine Decarboxylase, Polyamines, and Pyrrolizidine Alkaloids in Senecio and Crotalaria

    PubMed Central

    Birecka, Helena; Birecki, Mieczyslaw; Cohen, Eric J.; Bitonti, Alan J.; McCann, Peter P.

    1988-01-01

    When tested for ornithine and arginine decarboxylases, pyrrolizidine alkaloid-bearing Senecio riddellii, S. longilobus (Compositae), and Crotalaria retusa (Leguminosae) plants exhibited only ornithine decarboxylase activity. This contrasts with previous studies of four species of pyrrolizidine alkaloid-bearing Heliotropium (Boraginaceae) in which arginine decarboxylase activity was very high relative to that of ornithine decarboxylase. Unlike Heliotropium angiospermum and Heliotropium indicum, in which endogenous arginine was the only detectable precursor of putrescine channeled into pyrrolizidines, in the species studied here—using difluoromethylornithine and difluoromethylarginine as the enzyme inhibitors—endogenous ornithine was the main if not the only precursor of putrescine converted into the alkaloid aminoalcohol moiety. In S. riddellii and C. retusa at flowering, ornithine decarboxylase activity was present mainly in leaves, especially the young ones. However, other very young organs such as inflorescence and growing roots exhibited much lower or very low activities; the enzyme activity in stems was negligible. There was no correlation between the enzyme activity and polyamine or alkaloid content in either species. In both species only free polyamines were detected except for C. retusa roots and inflorescence—with relatively very high levels of these compounds—in which conjugated putrescine, spermidine, and spermine were also found; agmatine was not identified by HPLC in any plant organ except for C. retusa roots with rhizobial nodules. Organ- or age-dependent differences in the polyamine levels were small or insignificant. The highest alkaloid contents were found in young leaves and inflorescence. PMID:16665870

  6. Mutagenicity and recombinagenicity of Ocotea acutifolia (Lauraceae) aporphinoid alkaloids.

    PubMed

    Guterres, Zaira da Rosa; da Silva, Ana Francisca Gomes; Garcez, Walmir Silva; Garcez, Felipe Rodrigues; Fernandes, Carlos Alexandre; Garcez, Fernanda Rodrigues

    2013-09-18

    The somatic mutation and recombination test (SMART) in wing cells of Drosophila melanogaster was used to test the mutagenic and recombinogenic activities of five aporphinoid alkaloids isolated from Ocotea acutifolia: thalicminine (1), (+)-dicentrine (2), (+)-ocoteine (3), (+)-6S-ocoteine N-oxide (4), and (+)-leucoxine (5). Third-stage larvae derived from the standard cross with wing cell markers mwh and/or flr(3) were treated chronically. The frequencies of mutant spots observed in marked heterozygous descendants revealed significant dose-dependent genotoxicity for alkaloids 1-4; compounds 1 and 2 were the most active. Alkaloids 1-4 also induced mitotic recombination. The presence of a methoxyl group at C-3 (as in compound 3) lowers its genotoxic effect relative to that of unsubstituted analogue 2, and the introduction of an N-oxide functionality (3 vs. 4) further reduces genotoxicity. The very planar conformation of oxo-aporphine alkaloid 1 may account for its higher genotoxicity vs. its less-planar analogues 3 and 4. As previously reported for (+)-dicentrine (2), alkaloids 1, 3, and 4 may also be DNA intercalating agents, interfering with the catalytic activity of topoisomerases. PMID:23892138

  7. 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

  8. 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

  9. Analyses of alkaloids in different products by NACE-MS.

    PubMed

    Chiu, Chen-Wen; Liang, Hsin-Hui; Huang, Hsi-Ya

    2007-11-01

    A simple method for the separation and characterization of five nicotine-related alkaloids by NACE employing UV and MS detections is described here for the first time. Several factors, including NACE parameters (compositions of running solution) and MS parameters (such as nature and flow rate of sheath liquid, pressure of nebulization gas, and flow rate of dry gas), were optimized in order to obtain both an adequate CE separation and high MS signals for the alkaloid compounds used in this study. A reliable CE separation of five alkaloids was achieved in 50 mM ammonium formate that was dissolved in an ACN/methanol mixture (50:50, v/v) of pH* 4.0 (apparent pH 4.0). The optimal electrospray MS measurement was carried out in the positive ionization mode using a coaxial sheath liquid composed of isopropyl alcohol and water in the ratio of 80:20 v/v at a flow rate of 180 microL/h. In addition, the proposed NACE method was also applied in the analyses of alkaloids in several products including chewing gums, beverages, and tobaccos. This NACE-MS method was found to provide a better detection ability and separation resolution for the analysis of nicotine alkaloids when compared to other aqueous CE-MS reports. PMID:17955454

  10. 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...

  11. Recent investigations of ergot alkaloids incorporated into plant and/or animal systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ergot alkaloids produced by fungi have a basic chemical structure but different chemical moieties at substituent sites resulting in various forms of alkaloids that are distinguishable from one another. Since the ergoline ring structure found in ergot alkaloids is similar to that of biogenic amines (...

  12. Alkaloids from bufonid toads (Melanophryniscus): decahydroquinolines, pumiliotoxins and homopumiliotoxins, indolizidines, pyrrolizidines, and quinolizidines.

    PubMed

    Garraffo, H M; Spande, T F; Daly, J W; Baldessari, A; Gros, E G

    1993-03-01

    Skins of bufonid toads of the genus Melanophryniscus contain several classes of alkaloids: decahydroquinolines, pumiliotoxins, allopumiliotoxins, homopumiliotoxins, both 3,5- and 5,8-disubstituted indolizidines, 3,5-disubstituted pyrrolizidines, and a 1,4-disubstituted quinolizidine. Tricyclic alkaloids, including precoccinelline [193A] and alkaloid 236, an oxime methyl ether, are present in one population of Melanophryniscus stelzneri. PMID:8482947

  13. Pyrrolizidine alkaloid-derived DNA adducts as a common biological biomarker of pyrrolizidine alkaloid-induced tumorigenicity.

    PubMed

    Xia, Qingsu; Zhao, Yuewei; Von Tungeln, Linda S; Doerge, Daniel R; Lin, Ge; Cai, Lining; Fu, Peter P

    2013-09-16

    Pyrrolizidine alkaloid-containing plants are the most common poisonous plants affecting livestock, wildlife, and humans. The U.S. National Toxicology Program (NTP) classified riddelliine, a tumorigenic pyrrolizidine alkaloid, as "reasonably anticipated to be a human carcinogen" in the NTP 12th Report on Carcinogens in 2011. We previously determined that four DNA adducts were formed in rats dosed with riddelliine. The structures of the four DNA adducts were elucidated as (i) a pair of epimers of 7-hydroxy-9-(deoxyguanosin-N(2)-yl)dehydrosupinidine adducts (termed as DHP-dG-3 and DHP-dG-4) as the predominant adducts; and (ii) a pair of epimers of 7-hydroxy-9-(deoxyadenosin-N(6)-yl)dehydrosupinidine adducts (termed as DHP-dA-3 and DHP-dA-4 adducts). In this study, we selected a nontumorigenic pyrrolizidine alkaloid, platyphylliine, a pyrrolizidine alkaloid N-oxide, riddelliine N-oxide, and nine tumorigenic pyrrolizidine alkaloids (riddelliine, retrorsine, monocrotaline, lycopsamine, retronecine, lasiocarpine, heliotrine, clivorine, and senkirkine) for study in animals. Seven of the nine tumorigenic pyrrolizidine alkaloids, with the exception of lycopsamine and retronecine, are liver carcinogens. At 8-10 weeks of age, female F344 rats were orally gavaged for 3 consecutive days with 4.5 and 24 μmol/kg body weight test article in 0.5 mL of 10% DMSO in water. Twenty-four hours after the last dose, the rats were sacrificed, livers were removed, and liver DNA was isolated for DNA adduct analysis. DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4 adducts were formed in the liver of rats treated with the individual seven hepatocarcinogenic pyrrolizidine alkaloids and riddelliine N-oxide. These DNA adducts were not formed in the liver of rats administered retronecine, the nontumorigenic pyrrolizidine alkaloid, platyphylliine, or vehicle control. These results indicate that this set of DNA adducts, DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4, is a common biological biomarker of pyrrolizidine alkaloid-induced liver tumor formation. To date, this is the first finding that a set of exogenous DNA adducts are commonly formed from a series of tumorigenic xenobiotics. PMID:23937665

  14. 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

  15. Manzamine alkaloids: isolation, cytotoxicity, antimalarial activity and SAR studies.

    PubMed

    Ashok, Penta; Ganguly, Swastika; Murugesan, Sankaranarayanan

    2014-11-01

    The infectious disease Malaria is caused by different species of the genus Plasmodium. Resistance to quinoline antimalarial drugs and decreased susceptibility to artemisinin-based combination therapy have increased the need for novel antimalarial agents. Historically, natural products have been used for the treatment of infectious diseases. Identification of natural products and their semi-synthetic derivatives with potent antimalarial activity is an important method for developing novel antimalarial agents. Manzamine alkaloids are a unique group of β-carboline alkaloids isolated from various species of marine sponge displaying potent antimalarial activity against drug-sensitive and -resistant strains of Plasmodium. In this review, we demonstrate antimalarial potency, cytotoxicity and antimalarial SAR of manzamine alkaloids. PMID:24953707

  16. Cytotoxic and Anti-HIV Phenanthroindolizidine Alkaloids from Cryptocarya chinensis

    PubMed Central

    Wu, Tian-Shung; Su, Chung-Ren; Lee, Kuo-Hsiung

    2013-01-01

    Bioassay-guided fractionation of the cytotoxic ethanol extract of Cryptocarya chinensis has led to the isolation of 11 compounds, including two phenanthroindolizidine alkaloids [(−)-antofine (1) and dehydroantofine (2)], five pavine alkaloids (3–7), and four proaporphine alkaloids (8–11). The structures of the isolated compounds were determined by means of NMR spectroscopic methods, and supported by HRMS and optical rotation data. Compounds 1 and 2 showed cytotoxic activity against four cancer cell lines, L1210, P388, A549, and HCT-8, with 1 being the most potent against A549 and HCT-8 with EC50 values of 0.002 and 0.001 μg/mL, respectively. In addition, 2 is first reported to exhibit significant anti-HIV activity. PMID:22816292

  17. Alkaloid content of the seeds from Erythroxylum Coca var. Coca.

    PubMed

    Casale, John F; Toske, Steven G; Colley, Valerie L

    2005-11-01

    Alkaloid extracts from the seeds of Erythroxylum Coca var. Coca grown in the Chapare Valley of Bolivia were subjected to gas and liquid chromatographic-mass spectrometric analyses. Several alkaloids from these seeds were detected and characterized, including methylecgonidine, tropine, 3alpha-acetoxytropane, ecgonine methyl ester, cuscohygrine, N-norbenzoyltropine, benzoyltropine, hexanoylecgonine methyl ester, cocaine, cis-cinnamoylcocaine, and trans-cinnamoylcocaine. Methylecgonidine was determined to be the primary constituent and not an analytical artifact. Additionally, two significant new uncharacterized alkaloids were established as present. Recent evidence suggests that some cocaine processors are adding this seed extraction material to cocaine extracted from coca leaf and may impact cocaine impurity signature profiles. PMID:16382835

  18. A look inside an alkaloid multisite plant: the Catharanthus logistics.

    PubMed

    Courdavault, Vincent; Papon, Nicolas; Clastre, Marc; Giglioli-Guivarc'h, Nathalie; St-Pierre, Benoit; Burlat, Vincent

    2014-06-01

    Environmental pressures forced plants to diversify specialized metabolisms to accumulate noxious molecules such as alkaloids constituting one of the largest classes of defense metabolites. Catharanthus roseus produces monoterpene indole alkaloids via a highly elaborated biosynthetic pathway whose characterization greatly progressed with the recent expansion of transcriptomic resources. The complex architecture of this pathway, sequentially distributed in at least four cell types and further compartmentalized into several organelles, involves partially identified inter-cellular and intra-cellular translocation events acting as potential key-regulators of metabolic fluxes. The description of this spatial organization and the inherent secretion and sequestration of metabolites not only provide new insight into alkaloid cell biology and its involvement in plant defense processes but also present new biotechnological challenges for synthetic biology. PMID:24727073

  19. Activity of alkaloids on peptic ulcer: what's new?

    PubMed

    do Nascimento, Raphaela Francelino; de Sales, Igor Rafael Praxedes; de Oliveira Formiga, Rodrigo; Barbosa-Filho, José Maria; Sobral, Marianna Vieira; Tavares, Josean Fechine; Diniz, Margareth de Fátima Formiga Melo; Batista, Leônia Maria

    2015-01-01

    Peptic ulcer is a common disease characterized by lesions that affect the mucosa of the esophagus, stomach and/or duodenum, and may extend into the muscular layer of the mucosa. Natural products have played an important role in the process of development and discovery of new drugs, due to their wide structural diversity and present, mostly specific and selective biological activities. Among natural products the alkaloids, biologically active secondary metabolites, that can be found in plants, animals or microorganisms stand out. The alkaloids are compounds consisting of a basic nitrogen atom that may or may not be part of a heterocyclic ring. This review will describe 15 alkaloids with antiulcer activity in animal models and in vitro studies. PMID:25580688

  20. [A method for the determination of ergot alkaloids in food].

    PubMed

    Klug, C; Baltes, W; Krönert, W; Weber, R

    1988-02-01

    A suitable method has been developed for the routine analysis of the ergot alkaloids ergometrine, ergometrinine, ergosine, ergosinine, ergotamine, ergotaminine, ergocornine, ergocorninine, alpha-ergocryptine, alpha-ergocryptinine, beta-ergocryptine, beta-ergocryptinine, ergocristine and ergocristinine in cereal products. The method consists of food extraction, cleaning of the crude extract by a modified form of the Extrelut method, and identification and quantitative determination of the alkaloids by high pressure liquid chromatography (HPLC). The results are confirmed by thin layer chromatography (TLC) and gas-chromatography/mass spectrometry (GC/MS). Market investigations have shown contaminations in ecological as well as in conventional products, with rye products mainly being contaminated. Within the EEC, a maximum value of 0.05% ergot respectively a total alkaloid content of 1 mg/kg in cereals used for food production is prescribed. This value was not exceeded in any of the investigated samples. PMID:3354264

  1. 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

  2. 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.

  3. Carbazole alkaloids from the peels of Clausena lansium.

    PubMed

    Deng, Hui-Dong; Mei, Wen-Li; Wang, Hui; Guo, Zhi-Kai; Dong, Wen-Hua; Wang, Hao; Li, Shao-Peng; Dai, Hao-Fu

    2014-10-01

    A new carbazole alkaloid, claulansine K (1), together with six known carbazole alkaloids (2-7), was isolated from the peels of Clausena lansium (Lour.) Skeels. The new compound was elucidated using a combination of 1D and 2D NMR (HMQC, HMBC, COSY, and ROESY) techniques, and HR-EI-MS analyses. Compound 1 showed in vitro α-glucosidase inhibitory activity with the IC50 value of 0.11 mM. Compound 2 exhibited moderate antibacterial activity against Staphylococcus aureus with the diameter of inhibition zone of 14.2 mm. PMID:24993293

  4. Minor alkaloids from Guatteria dumetorum with antileishmanial activity.

    PubMed

    Correa, Jhonny Edmith; Ríos, Carlos Hernán; del Rosario Castillo, Amparo; Romero, Luz I; Ortega-Barría, Eduardo; Coley, Phyllis D; Kursar, Thomas A; Heller, Maria Verónica; Gerwick, William H; Rios, Luis Cubilla

    2006-02-01

    Nine known alkaloids [(+)-isodomesticine (1), (+)-norisodomesticine (2), (+)-nantenine ( 3), (+)-neolitsine (4), (+)-lirioferine (5), (+)-N-methyllaurotetanine (6), (+)-norlirioferine (7), (+)-isoboldine (8) and (+)-reticuline (9)] were isolated from young leaves of Guatteria dumetorum. Their structures were confirmed by NMR, mass and UV spectral analysis and by comparison to literature data. The growth inhibitory activity of each alkaloid was determined against the parasite Leishmania mexicana. Compounds 1-4 all showed significant activity whereby potency increased when a methylenedioxy functionality was present, especially at the 1,2-positions. PMID:16534735

  5. 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.

  6. New cyclopeptide alkaloid and lignan glycoside from Justicia procumbens.

    PubMed

    Jin, Hong; Chen, Li; Tian, Ying; Li, Bin; Dong, Jun-Xing

    2015-01-01

    This study reported a new cyclopeptide alkaloid, justicianene A (1), and a new lignan glycoside, procumbenoside H (2), isolated from Justicia procumbens. The structures of the new compounds were elucidated by means of spectroscopic analysis, including extensive 2D NMR studies and mass spectrometry. Cyclopeptide alkaloids were first observed from the genus Justicia. Compound 2 was cytotoxic against human LoVo colon carcinoma cells with an IC50 value of 17.908 ± 1.949 μM. PMID:25367562

  7. 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-(β-D-mannopyranosyloxy)-1H-indole-2-carboxylate (1), methyl 7-[(3-O-acetyl-β-D-mannopyranosyl)oxy]-1H-indole-2-carboxylate (2), and 2-methyl-1H-indol-7-yl β-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 μM. PMID:24934682

  8. Antifungal activity of the alkaloids from Eschscholzia californica.

    PubMed

    Singh, S; Jain, L; Pandey, M B; Singh, U P; Pandey, V B

    2009-01-01

    The isoquinoline alkaloids hunnemanine and norsanguinarine have been isolated from methanolic extract of the whole plant of Eschscholzia californica. These two alkaloids were checked for their antifungal activity against phytopathogenic fungi Alternaria melongenae, A. brassicola, A. brassicae, Curvularia lunata, C. maculans, Helminthosporium pennisetti, H. oryzae, H. turcicum, Fusarium undum and F. lini. Hunnemanine exhibited 100 % inhibition of spore germination of A. brassicae, H. pennisetti and F. lini at 1000 ppm whereas norsanguinarine exhibited 100 % inhibition of A. brassicicola and C. maculans at this concentration. PMID:19649736

  9. [Alkaloids from roots and stems of Litsea cubeba].

    PubMed

    Zhang, Shui-Ying; Guo, Qiang; Cao, Yuan; Zhang, Yuan; Gao, Xiao-Li; Tu, Peng-Fei; Chai, Xing-Yun

    2014-10-01

    A phytochemical investigation on the roots and stems of Litsea cubeba led to the isolation of seven isoquinolone alkaloids. By spectroscopic analysis and comparison of their 1H and 13C-NMR data with those in literatures, these alkaloids were identified as (+)-norboldine (1), (+)-boldine (2), (+)-reticuline (3), (+)-laurotetanine (4), (+)-isoboldine (5), (+)-N-methyl-laurotetanine (6), and berberine (7), respectively. Among them, 7 was isolated from the genus for the first time. The evaluation of these compounds showed weak anti-inflammatory activity against NO production in RAW 267.4 and BV-2 cells. PMID:25751947

  10. Budd-Chiari syndrome secondary to toxic pyrrolizidine alkaloid exposure.

    PubMed

    Wu, Janet S W; Poon, W T; Ma, C K; Chen, M L; Pang, K S; Mak, Tony W L; Chan, H B

    2013-12-01

    In this report, we describe a case of pyrrolizidine alkaloid-related Budd-Chiari syndrome in Hong Kong. A 10-month-old boy presented with ascites, right pleural effusion, and hepatomegaly after consumption of herbal drinks for 3 months. His clinical (including imaging) features were compatible with Budd-Chiari syndrome. Budd-Chiari syndrome is a rare disease entity in paediatric patients. In our case, extensive workup performed to look for the underlying cause of Budd-Chiari syndrome was unrevealing, except for toxic pyrrolizidine alkaloid exposure in his herbal drinks. PMID:24310665

  11. Microbial Factories for the Production of Benzylisoquinoline Alkaloids.

    PubMed

    Narcross, Lauren; Fossati, Elena; Bourgeois, Leanne; Dueber, John E; Martin, Vincent J J

    2016-03-01

    Benzylisoquinoline alkaloids (BIAs) are a family of ∼2500 alkaloids with both potential and realized pharmaceutical value, including most notably the opiates such as codeine and morphine. Only a few BIAs accumulate readily in plants, which limits the pharmaceutical potential of the family. Shifting BIA production to microbial sources could provide a scalable and flexible source of these compounds in the future. This review details the current status of microbial BIA synthesis and derivatization, including rapid developments in the past 6 months culminating in the synthesis of opioids from glucose in a microbial host. PMID:26775900

  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. In vitro inhibitory activities of Lauraceae aporphine alkaloids.

    PubMed

    Coy Barrera, Ericsson David; Cuca Suárez, Luis Enrique

    2010-03-01

    The in vitro anti-inflammatory effect of eight aporphine alkaloids isolated from the leaves of two Lauraceae plants (Pleurothyrium cinereum and Ocotea macrophylla) was evaluated through inhibition of two isozymes of cyclooxygenase (COX-1 and COX-2), 5-lipoxygenase (5-LOX), and platelet aggregation induced by PAF, AA and ADP. All alkaloids exhibited inhibitory activities against COX-2 (IC50 25.9-116 microM range) and PAF- and AA-induced platelet aggregation, while only four and three of them were good COX-1 and 5-LOX inhibitors, respectively. (+)-N-acetyl-nornantenine 6 was the most potent COX-2, 5-LOX, AA and PAF inhibitor. PMID:20420312

  14. ORCAnization of jasmonate-responsive gene expression in alkaloid metabolism.

    PubMed

    Memelink, J; Verpoorte, R; Kijne, J W

    2001-05-01

    Jasmonic acid is an important plant stress signalling molecule. It induces the biosynthesis of defence proteins and protective secondary metabolites. In alkaloid metabolism, jasmonate acts by coordinate activation of the expression of multiple biosynthesis genes. In terpenoid indole alkaloid metabolism and primary precursor pathways, jasmonate induces gene expression and metabolism via ORCAs, which are members of the AP2/ERF-domain family of plant transcription factors. Other jasmonate-regulated (secondary) metabolic pathways might also be controlled by ORCA-like AP2/ERF-domain transcription factors. If so, such regulators could be used to improve plant fitness or metabolite productivity of plants or cell cultures. PMID:11335174

  15. New 14-Membered Cyclopeptide Alkaloids from Zizyphus oxyphylla Edgew

    PubMed Central

    Kaleem, Waqar Ahmad; Nisar, Muhammad; Qayum, Mughal; Zia-Ul-Haq, Muhammad; Adhikari, Achyut; De Feo, Vincenzo

    2012-01-01

    Two new 14-membered cyclopeptide alkaloids, Oxyphylline B (4) and Oxyphylline C (5), along with three known 13-membered cyclopeptide alkaloids, were isolated from stem and roots of Zizyphus oxyphylla Edgew. The compounds were tested for antibacterial activity. Oxyphylline B (4) showed comparatively better antibacterial activities against Escherichia coli (MIC, 5 μg/mL) than other compounds. This compound also exhibited weak antimicrobial activities against Staphylococcus aureus (MIC, 25 μg/mL), Pseudomonas aeruginosa (MIC, 50 μg/mL) and Salmonella typhi (MIC, 50 μg/mL). PMID:23109868

  16. [Effects of steaming and baking on content of alkaloids in Aconite Lateralis Radix (Fuzi)].

    PubMed

    Yang, Chang-lin; Huang, Zhi-fang; Zhang, Yi-han; Liu, Yu-hong; Liu, Yun-huan; Chen, Yan; Yi, Jin-hai

    2014-12-01

    To study the effect of steaming and baking process on contents of alkaloids in Aconite Lateralis Radix (Fuzi), 13 alkaloids were analyzed by UPLC-MS/MS equipped with ESI ion source in MRM mode. In steaming process, the contents of diester-diterpenoid alkaloids decreased rapidly, the contents of monoester-diterpenoid alkaloids firstly increased, reached the peak at 40 min, and then deceased gradually. The contents of aconine alkaloids (mesaconine, aconine and hypaconine) increased all the time during processing, while the contents of fuziline, songorine, karacoline, salsolionl were stable or slightly decreased. In baking process, dynamic variations of alkaloids were different from that in the steaming process. Diester-diterpenoid alkaloids were degraded slightly slower than in steaming process. Monoester-diterpenoid alkaloids, aconine alkaloids and the total alkaloids had been destroyed at different degrees, their contents were significantly lower than the ones in steaming Fuzi at the same processing time. This experiment revealed the dynamic variations of alkaloids in the course of steaming and baking. Two processing methods which can both effectively remove the toxic ingredients and retain the active ingredients are simple and controllable, and are valuable for popularization and application. PMID:25898581

  17. Alkaloids from single skins of the Argentinian toad Melanophryniscus rubriventris (ANURA, BUFONIDAE): An unexpected variability in alkaloid profiles and a profusion of new structures.

    PubMed

    Garraffo, H Martin; Andriamaharavo, Nirina R; Vaira, Marcos; Quiroga, María F; Heit, Cecilia; Spande, Thomas F

    2012-12-01

    GC-MS analysis of single-skins of ten Melanophryniscus rubriventris toads (five collections of two toads each) captured during their breeding season in NW Argentina has revealed a total of 127 alkaloids of which 56 had not been previously detected in any frog or toad. Included among these new alkaloids are 23 new diastereomers of previously reported alkaloids. What is particularly distinguishing about the alkaloid profiles of these ten collections is the occurrence of many of the alkaloids, whether known or new to us, in only one of the ten skins sampled, despite two skins being obtained from each breeding site of the five populations. Many of the alkaloids are of classes known to have structures with branched-chains (e.g. pumiliotoxins and tricyclic structures) that are considered to derive from dietary mites. A large number of previously reported and new alkaloids are also of unclassified structures. Only a very few 3,5-disubstituted-indolizidine or -pyrrolizidine alkaloids are observed that have a straight-chain carbon skeleton and are likely derived from ant prey. The possible relationship of these collections made during the toad's brief breeding episodes to sequestration of dietary arthropods and individual alkaloid profiles is discussed. PMID:23596558

  18. Histochemical Investigation and Kinds of Alkaloids in Leaves of Different Developmental Stages in Thymus quinquecostatus

    PubMed Central

    Jing, Haiting; Liu, Jing; Liu, Hanzhu; Xin, Hua

    2014-01-01

    Thymus quinquecostatus, with more medical value, is a kind of wild plants. In order to exploit and utilize this plant, we studied the species and locations of alkaloids in its leaves. In this paper, histochemical study of leaves at different developing stages was taken to localize the alkaloids. Meanwhile, the kinds and content of alkaloids in leaves were identified using GC-MS technique. It was found that there were two kinds of glandular trichomes, namely, peltate trichomes and capitate trichomes, on the surface of leaves, and their secretory cells could secrete alkaloids. Results showed that trichomes could secrete alkaloids as soon as the first pair of leaves formed, and there were altogether 18 kinds of alkaloids identified by GC-MS. Nearly all of these alkaloids of leaves at different developing stages were distinct from each other, except one, 3-methoxy-a-methyl-benzeneethanamine, persists at different developing stages with high concentration. PMID:25101324

  19. EFFECT OF SHADE ON ALKALOID CONTENT OF LUPINUS LEUCOPHYLLUS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lupine-induced "crooked calf" syndrom is a significant problem for ranches in the semi-arid region of the channeled scablands of eastern Washington State. Rainfall and soil moisture has been proposed to affect the alkaloid content and/or palatability of L. leucophyllus. It is also possible that shad...

  20. Three New Isomeric Indole Alkaloids from Nauclea officinalis.

    PubMed

    Wang, Hai-Yang; Wang, Ru-Xia; Zhao, Yan-Xia; Liu, Ke; Wang, Feng-Ling; Sun, Jing-Yong

    2015-08-01

    Three new isomeric monoterpene indole alkaloids, naucleofficines I-III (1-3, resp.) were isolated from the stems (with bark) of Nauclea officinalis. Their structures were elucidated on the basis of spectroscopic methods and single-crystal diffraction analyses. The cytotoxic activities of 1-3 against human colon cancer, human gastric cancer, and human hepatoma cells were also investigated. PMID:26265577

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. LATE SEASON TOXIC ALKALOID CONCENTRATIONS IN TALL LARKSPUR (DELPHINIUM SPP.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tall larkspurs [Delphinium barbeyi, D. occidentale, D. glaucescens, D. glaucum] pose a serious poisoning threat to cattle on many summer ranges. Livestock producers often defer grazing until larkspur is mature, but specific information is lacking on toxic alkaloid concentrations in larkspur from th...

  6. 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...

  7. Ergot Alkaloids: Toxicokinetics and Vascular Effects in Grazing Animals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endophyte- (Neotyphodium coenophialum) infected tall fescue (Lolium arundinaceum) occupies nearly 14 million ha within the USA. Although the endophyte-forage association is beneficial to the plant’s survival and production, it is detrimental to grazing livestock as a consequence of ergot alkaloid p...

  8. 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...

  9. Synthesis of the Pentacyclic Skeleton of the Indole Alkaloid Arboflorine

    PubMed Central

    Leal, Raul A.; Beaudry, Danial R.; Alzghari, Saeed K.; Sarpong, Richmond

    2012-01-01

    An effective synthesis of the pentacyclic core of the unusual Kopsia alkaloid arboflorine is reported. The success of the synthetic route rested on the use of a borylative C–H functionalization reaction, a convergent Suzuki cross-coupling to a C(2) halogenated indole and an unprecedented transannular dehydrogenative C–N bond forming reaction. PMID:23020147

  10. A new alkaloid from the fruits of Celastrus orbiculatus.

    PubMed

    Guo, Yuanqiang; Li, Xian; Wang, Jinghui; Xu, Jing; Li, Ning

    2005-03-01

    From the fruits of Celastrus orbiculatus, a new alkaloid 3-oxo-4-benzyl-3, 4-dihydro-1H-pyrrolo [2, 1-c] oxazine-6-methylal (1), was isolated. The structure was elucidated on the basis of spectroscopic methods. PMID:15752648

  11. 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.

  12. 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.

  13. 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...

  14. Investigation of a betainic alkaloid from Punica granatum.

    PubMed

    Schmidt, Andreas; Mordhorst, Thorsten; Nieger, Martin

    2005-07-01

    Spectroscopic investigations reveal that a hydroquinone pyridinium alkaloid isolated from the leaves of pomegranates Punica granatum L. (X-ray) exists as a mixture of a conjugated and a cross-conjugated heterocyclic mesomeric betaine in aqueous and DMSO-d6 solution. Twofold deprotonation yields an anionic tripole. PMID:15938201

  15. 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

  16. 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...

  17. New cholinesterase inhibiting bisbenzylisoquinoline alkaloids from Abuta grandifolia.

    PubMed

    Cometa, Maria Francesca; Fortuna, Stefano; Palazzino, Giovanna; Volpe, Maria Teresa; Rengifo Salgado, Elsa; Nicoletti, Marcello; Tomassini, Lamberto

    2012-04-01

    The phytochemical study of the stem bark and wood of Abuta grandifolia (Mart.) Sandwith led to the identification of four bisbenzylisoquinoline alkaloids (BBIQs), namely (R,S)-2 N-norberbamunine (1), (R,R)-isochondodendrine (2), (S-S)-O4″-methyl, Nb-nor-O6'-demethyl-(+)-curine (3), and (S-S)-O4″-methyl, O6'-demethyl-(+)-curine (4), together with the aporphine alkaloid R-nornuciferine (5), all obtained by countercurrent distribution separation (CCD) and identified on the basis of their spectroscopic data. Alkaloids 3 and 4 were new. All the isolated compounds were tested for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. 1 was the most active against AChE, whereas 3 and 4 were the most potent against BChE. Interestingly, all tested alkaloids are more potent against BChE than against AChE. This selectivity of cholinesterase (ChE) inhibition could be important in order to speculate on their potential therapeutic relevance. PMID:22230193

  18. Two new C19-diterpenoid alkaloids from Aconitum straminiflorum.

    PubMed

    Qi, Yan; Zhao, Da-Ke; Zi, Shu-Hui; Zhang, Li-Mei; Guo, Cheng-Xing; Li, Gui-Qiong; Xun, Jun-Ju; Shen, Yong

    2016-04-01

    Two new C19-diterpenoid alkaloids, straconitines A (1) and B (2), were isolated from the roots of Aconitum straminiflorum. Their structures were elucidated as 14-benzoylducloudine D (1) and 6-hydroxy-14-benzoylducloudine D (2) based on spectroscopic analysis, including IR, ESI-MS, HR-ESI-MS, 1D, and 2D NMR. PMID:26558800

  19. Antimicrobial activities of indole alkaloids from Tabernaemontana catharinensis.

    PubMed

    Medeiros, Maria Rita Furquini; Prado, Luiz Afonso de Melo; Fernandes, Vanessa Colnaghi; Figueiredo, Sérgio Souza; Coppede, Juliana; Martins, Juliana; Fiori, Giovana Maria Lanchoti; Martinez-Rossi, Nilce Maria; Beleboni, Rene Oliveira; Contini, Silvia Helena Taleb; Pereira, Paulo Sérgio; Fachin, Ana Lúcia

    2011-02-01

    Tabernaemontana catharinensis root bark ethanol extract, EB2 fraction and the MMV alkaloid (12-methoxy-4-methylvoachalotine) were evaluated for their antimicrobial activities. T. catharinensis ethanol extract was effective against both strains of the dermatophyte Trichophyton rubrum at concentrations of 2.5 mg/mL (wild strain) and 1.25 mg/mL (mutant strain), while the EB2 fraction and MMV alkaloid showed a strong antifungal activity against wild and mutant strains with MIC values of <0.02 and 0.16 mg/mL, respectively. The EB2 fraction showed a strong antibacterial activity against ATCC strains of S. aureus, S. epidermidis, E. coli and P. aeruginosa with MICs from <0.02 to 0.04 mg/mL, as well as against resistant clinical isolates species of Enterococcus sp, Klebsiella oxytoca, Citrobacter, K. pneumoniae, P. mirabilis, S. aureus, S. epidermidis, E. coli and P. aeruginosa with MIC values ranging from 0.04 to 0.08 mg/mL. The MMV alkaloid presented a MIC of 0.16 mg/mL against the strains of S. aureus and E. coli ATCC. For the resistant clinical isolates Enterococcus sp, Citrobacter, S. aureus, S. epidermidis, E. coli and P. aeruginosa the MIC of MMV ranged from 0.08 to 0.31 mg/mL. The chromatography analysis of the EB2 fraction revealed the presence of indole alkaloids, including MMV, possibly responsible for the observed antimicrobial activity. PMID:21425672

  20. Two new aspidosperma indole alkaloids from Yunnan Kopsia arborea.

    PubMed

    Wu, Yuqiu; Kitajima, Mariko; Kogure, Noriyuki; Wang, Yunsong; Zhang, Rongping; Takayama, Hiromitsu

    2010-07-01

    Two new indole alkaloids, kopsiyunnanines G (1) and H (2), possessing the Aspidosperma skeleton were isolated from the aerial part of Yunnan Kopsia arborea BLUME (Apocynaceae). Their structures and stereochemistry were elucidated by means of MS and 2D NMR analyses. PMID:20606347

  1. Ergot alkaloids in some rye-based UK cereal products.

    PubMed

    Crews, C; Anderson, W A C; Rees, G; Krska, R

    2009-01-01

    UK rye-based cereal products were analysed for six major ergot alkaloids using an in-house-validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method that distinguished -ine and -inine epimers (isomers). Ergot alkaloids were detected in 25 of 28 samples subject to quantification limits of 1-3 µg kg(-1), including all of eleven rye crispbreads that had up to 340 µg kg(-1). Continental-style rye breads contained up to 121 µg kg(-1). Loaf breads, bread-mix flours, and crackers contained only low levels of alkaloids. Ergotamine, ergocristine, and ergosine were the predominant ergot alkaloids in terms of level and frequency of occurrence. There were no apparent differences in the ergot levels between the organic and non-organic products, although the numbers tested were low. Most rye breads had a ratio of -ines to -inines of about 1.5, and rye crispbreads had lower and more variable -ine to -inine ratios. PMID:24784971

  2. Electrophysiological comparison of insecticide and alkaloid agonists of Na channels.

    PubMed

    Leibowitz, M D; Schwarz, J R; Holan, G; Hille, B

    1987-07-01

    Macroscopic currents in Na channels were recorded from adult frog skeletal muscle under voltage clamp as various toxins were added to the bathing medium. Veratridine, cevadine, and 3-(4-ethoxybenzoyl)-veracevine modified the Na channels in a use-dependent manner during depolarizations and held them open for 3, 2.4, and 1.2 s, respectively, at -90 mV. The three alkaloids modified channels in the same way. Activation gating was shifted about -100 mV by the modification, and reversible closing of the channels by strong hyperpolarizations slowed reversal of the modification. The synthetic insecticides deltamethrin, EDO, GH739, and GH414 also modified channels during depolarizations that opened channels. The modification lasted 3 s with deltamethrin, but only 3-5 ms with the others. Hyperpolarization speeded the shutting off of current in insecticide-modified channels, but no reversible activation gating could be demonstrated. The ionic selectivity, PNa/PNH4, of channels was decreased by all of the toxins. This ratio was 0.11 in normal channels, 0.26 in insecticide-modified channels, and 0.7-1.6 in veratrum-alkaloid-modified channels. During use-dependent modification, the veratrum alkaloids reduced the total Na current markedly, while deltamethrin did not. Thus, alkaloid and insecticide modifications share many features but differ in how much the conducting properties of the pore are changed and whether the channel can close reversibly while the toxin remains bound. PMID:2442297

  3. Electrophysiological comparison of insecticide and alkaloid agonists of Na channels

    PubMed Central

    1987-01-01

    Macroscopic currents in Na channels were recorded from adult frog skeletal muscle under voltage clamp as various toxins were added to the bathing medium. Veratridine, cevadine, and 3-(4-ethoxybenzoyl)- veracevine modified the Na channels in a use-dependent manner during depolarizations and held them open for 3, 2.4, and 1.2 s, respectively, at -90 mV. The three alkaloids modified channels in the same way. Activation gating was shifted about -100 mV by the modification, and reversible closing of the channels by strong hyperpolarizations slowed reversal of the modification. The synthetic insecticides deltamethrin, EDO, GH739, and GH414 also modified channels during depolarizations that opened channels. The modification lasted 3 s with deltamethrin, but only 3-5 ms with the others. Hyperpolarization speeded the shutting off of current in insecticide-modified channels, but no reversible activation gating could be demonstrated. The ionic selectivity, PNa/PNH4, of channels was decreased by all of the toxins. This ratio was 0.11 in normal channels, 0.26 in insecticide-modified channels, and 0.7-1.6 in veratrum-alkaloid-modified channels. During use-dependent modification, the veratrum alkaloids reduced the total Na current markedly, while deltamethrin did not. Thus, alkaloid and insecticide modifications share many features but differ in how much the conducting properties of the pore are changed and whether the channel can close reversibly while the toxin remains bound. PMID:2442297

  4. Diversification of ergot alkaloids in natural and modified fungi.

    PubMed

    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

  5. Novel triterpenoid acyl esters and alkaloids from Anoectochilus roxburghii.

    PubMed

    Han, Mei-Hua; Yang, Xiu-Wei; Jin, Yan-Ping

    2008-01-01

    Two novel sorghumol acyl esters, sorghumol 3-O-Z-p-coumarate and sorghumol 3-O-E-p-coumarate, and a novel alkaloid, anoectochine, were isolated from the whole plants of Anoectochilus roxburghii along with one known triterpenoid, sorghumol. Their structures were established by their detailed spectral studies, including two-dimensional NMR ((1)H-(1)H COSY, HSQC and HMBC). PMID:18435530

  6. 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.

  7. Ibogan, tacaman, and cytotoxic bisindole alkaloids from tabernaemontana. Cononusine, an iboga alkaloid with unusual incorporation of a pyrrolidone moiety.

    PubMed

    Lim, Kuan-Hon; Raja, Vijay J; Bradshaw, Tracey D; Lim, Siew-Huah; Low, Yun-Yee; Kam, Toh-Seok

    2015-05-22

    Six new indole alkaloids, viz., cononusine (1, a rare example of an iboga-pyrrolidone conjugate), ervaluteine (2), vincamajicine (3), tacamonidine (4), 6-oxoibogaine (5), and N(4)-chloromethylnorfluorocurarine chloride (6), and two new vobasinyl-iboga bisindole alkaloids, ervatensines A (7) and B (8), in addition to other known alkaloids, were isolated from the stem-bark extract of the Malayan Tabernaemontana corymbosa. The structures of these alkaloids were established on the basis of NMR and MS analyses and, in one instance (7), confirmed by X-ray diffraction analysis. Vincamajicine (3) showed appreciable activity in reversing multidrug resistance in vincristine-resistant KB cells (IC50 2.62 ?M), while ervatensines A (7) and B (8) and two other known bisindoles displayed pronounced in vitro growth inhibitory activity against human KB cells (IC50 < 2 ?M). Compounds 7 and 8 also showed good growth inhibitory activity against A549, MCF-7, MDA-468, HCT-116, and HT-29 cells (IC50 0.70-4.19 ?M). Cell cycle and annexin V-FITC apoptosis assays indicated that compounds 7 and 8 inhibited proliferation of HCT-116 and MDA-468 cells, evoking apoptotic and necrotic cell death. PMID:25919190

  8. Eating chemically defended prey: alkaloid metabolism in an invasive ladybird predator of other ladybirds (Coleoptera: Coccinellidae).

    PubMed

    Sloggett, J J; Davis, A J

    2010-01-15

    By comparison with studies of herbivore physiological adaptation to plant allelochemicals, work on predator physiological adaptation to potentially toxic prey has been very limited. Such studies are important in understanding how evolution could shape predator diets. An interesting question is the specificity of predator adaptation to prey allelochemicals, given that many predators consume diverse prey with different chemical defences. The ladybird Harmonia axyridis, an invasive species in America, Europe and Africa, is considered a significant predatory threat to native invertebrates, particularly other aphid-eating ladybirds of which it is a strong intraguild predator. Although ladybirds possess species-specific alkaloid defences, H. axyridis exhibits high tolerance for allospecific ladybird prey alkaloids. Nonetheless, it performs poorly on species with novel alkaloids not commonly occurring within its natural range. We examined alkaloid fate in H. axyridis larvae after consumption of two other ladybird species, one containing an alkaloid historically occurring within the predator's native range (isopropyleine) and one containing a novel alkaloid that does not (adaline). Our results indicate that H. axyridis rapidly chemically modifies the alkaloid to which it has been historically exposed to render it less harmful: this probably occurs outside of the gut. The novel, more toxic alkaloid persists in the body unchanged for longer. Our results suggest metabolic alkaloid specialisation, in spite of the diversity of chemically defended prey that the predator consumes. Physiological adaptations appear to have made H. axyridis a successful predator of other ladybirds; however, limitations are imposed by its physiology when it eats prey with novel alkaloids. PMID:20038656

  9. 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

  10. Ergot alkaloids produced by endophytic fungi of the genus Epichloë.

    PubMed

    Guerre, Philippe

    2015-03-01

    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

  11. Formicine ants: An arthropod source for the pumiliotoxin alkaloids of dendrobatid poison frogs.

    PubMed

    Saporito, Ralph A; Garraffo, H Martin; Donnelly, Maureen A; Edwards, Adam L; Longino, John T; Daly, John W

    2004-05-25

    A remarkable diversity of bioactive lipophilic alkaloids is present in the skin of poison frogs and toads worldwide. Originally discovered in neotropical dendrobatid frogs, these alkaloids are now known from mantellid frogs of Madagascar, certain myobatrachid frogs of Australia, and certain bufonid toads of South America. Presumably serving as a passive chemical defense, these alkaloids appear to be sequestered from a variety of alkaloid-containing arthropods. The pumiliotoxins represent a major, widespread, group of alkaloids that are found in virtually all anurans that are chemically defended by the presence of lipophilic alkaloids. Identifying an arthropod source for these alkaloids has been a considerable challenge for chemical ecologists. However, an extensive collection of neotropical forest arthropods has now revealed a putative arthropod source of the pumiliotoxins. Here we report on the presence of pumiliotoxins in formicine ants of the genera Brachymyrmex and Paratrechina, as well as the presence of these ants in the stomach contents of the microsympatric pumiliotoxin-containing dendrobatid frog, Dendrobates pumilio. These pumiliotoxins are major alkaloids in D. pumilio, and Brachymyrmex and Paratrechina ants now represent the only known dietary sources of these toxic alkaloids. These findings further support the significance of ant-specialization and alkaloid sequestration in the evolution of bright warning coloration in poison frogs and toads. PMID:15128938

  12. Formicine ants: An arthropod source for the pumiliotoxin alkaloids of dendrobatid poison frogs

    PubMed Central

    Saporito, Ralph A.; Garraffo, H. Martin; Donnelly, Maureen A.; Edwards, Adam L.; Longino, John T.; Daly, John W.

    2004-01-01

    A remarkable diversity of bioactive lipophilic alkaloids is present in the skin of poison frogs and toads worldwide. Originally discovered in neotropical dendrobatid frogs, these alkaloids are now known from mantellid frogs of Madagascar, certain myobatrachid frogs of Australia, and certain bufonid toads of South America. Presumably serving as a passive chemical defense, these alkaloids appear to be sequestered from a variety of alkaloid-containing arthropods. The pumiliotoxins represent a major, widespread, group of alkaloids that are found in virtually all anurans that are chemically defended by the presence of lipophilic alkaloids. Identifying an arthropod source for these alkaloids has been a considerable challenge for chemical ecologists. However, an extensive collection of neotropical forest arthropods has now revealed a putative arthropod source of the pumiliotoxins. Here we report on the presence of pumiliotoxins in formicine ants of the genera Brachymyrmex and Paratrechina, as well as the presence of these ants in the stomach contents of the microsympatric pumiliotoxin-containing dendrobatid frog, Dendrobates pumilio. These pumiliotoxins are major alkaloids in D. pumilio, and Brachymyrmex and Paratrechina ants now represent the only known dietary sources of these toxic alkaloids. These findings further support the significance of ant-specialization and alkaloid sequestration in the evolution of bright warning coloration in poison frogs and toads. PMID:15128938

  13. Analysis of Isoquinoline Alkaloid Composition and Wound-Induced Variation in Nelumbo Using HPLC-MS/MS.

    PubMed

    Deng, Xianbao; Zhu, Lingping; Fang, Ting; Vimolmangkang, Sornkanok; Yang, Dong; Ogutu, Collins; Liu, Yanling; Han, Yuepeng

    2016-02-10

    Alkaloids are the most relevant bioactive components in lotus, a traditional herb in Asia, but little is known about their qualitative and quantitative distributions. Here, we report on the alkaloid composition in various lotus organs. Lotus laminae and embryos are rich in isoquinoline alkaloids, whereas petioles and rhizomes contain trace amounts of alkaloids. Wide variation of alkaloid accumulation in lamina and embryo was observed among screened genotypes. In laminae, alkaloid accumulation increases during early developmental stages, reaches the highest level at full size stage, and then decreases slightly during senescence. Vegetative and embryogenic tissues accumulate mainly aporphine-type and bisbenzylisoquinoline-type alkaloids, respectively. Bisbenzylisoquinoline-type alkaloids may be synthesized mainly in lamina and then transported into embryo via latex through phloem translocation. In addition, mechanical wounding was shown to induce significant accumulation of specific alkaloids in lotus leaves. PMID:26800445

  14. Indole Alkaloid Formation and Storage in Cell Suspension Cultures of Catharanthus roseus.

    PubMed

    Neumann, D; Krauss, G; Hieke, M; Gröger, D

    1983-05-01

    The localization and storage of alkaloids were investigated in a low producing cell suspension culture of CATHARANTHUS ROSEUS(L.) G. Don. (Apocynaceae). Fluorescence microscopy and electron microscopy indicate alkaloid accumulation to occur inside the vacuoles of particular cells. These alkaloid storage cells exhibit a vacuolar pH of 3, while "normal" cells of a suspension culture have a vacuolar pH of about 5. Alkaloids are taken up in their unprotonated forms, trapped by protonation inside the vacuole and are accumulated there. The differentiation of alkaloid storage cells depends both on the cell line and the growth conditions and seems to be a prerequisite for the accumulation of alkaloids in cell suspension cultures of CATHARANTHUS ROSEUS. PMID:17404935

  15. Selection of fungal elicitors to increase indole alkaloid accumulation in catharanthus roseus suspension cell culture.

    PubMed

    Zhao, J; Zhu, W -H.; Hu, Q

    2001-05-01

    Various fungal elicitors derived from 12 fungi were tested to improve indole alkaloid production in Catharanthus roseus cell suspension cultures. Results show that different fungal mycelium homogenates stimulate different kinds of indole alkaloid (ajmalicine, serpentine and catharanthine) accumulation, which ranged from 2- to 5-fold higher than the control. Some fungal culture filtrates also efficiently elicited the biosynthesis of different indole alkaloids. The optimal elicitor addition and exposure time for the maximal alkaloid production were on day 7 after subculture and for 3 days of treatment but different fungal elicitors showed the different optimal treatment dosages. Additions of elicitor at the doses ranging from 5 mg/l to 30 mg/l of carbon hydrate equivalent resulted in varieous amounts and kinds of indole alkaloid accumulation. Exposed to a same fungal elicitor, several different cell lines generated the different responses regarding as growth rate, culture color and alkaloid production. PMID:11339951

  16. 2,4-D and alkaloid accumulation in periwinkle cell suspensions.

    PubMed

    Arvy, M P; Imbault, N; Naudascher, F; Thiersault, M; Doireau, P

    1994-01-01

    Omission of 2,4-D from culture medium during one subculture of Catharanthus roseus cells, strain C20, resulted in an increased alkaloid accumulation, without effect on growth. Alkaloid accumulation, rather than growth, seemed to be more sensitive to 2,4-D. 2,4-D inhibited alkaloid accumulation essentially during growth phase, but its inhibitory effect during this period was partially reversible. As this reversibility was underlined only during the stationary phase, this suggested that this action could be situated upstream in a terpenoid non-specific pathway. 2,4-D feeding showed that inhibition is weaker and weaker as the alkaloid accumulation period proceeds. Auxin action during this period could take place downstream in specific alkaloid pathways. The lower alkaloid accumulation obtained after loganic acid feeding compared to that obtained with secologanin and loganin could indicate that loganic acid methylation should be one of the 2,4-D target(s). PMID:7849107

  17. 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

  18. 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

  19. Antileishmanial Activity of an Indole Alkaloid from Peschiera australis

    PubMed Central

    Delorenzi, Jan Carlo; Attias, Márcia; Gattass, Cerli R.; Andrade, Marcelo; Rezende, Cláudia; da Cunha Pinto, Ângelo; Henriques, Amélia T.; Bou-Habib, Dumith C.; Saraiva, Elvira M. B.

    2001-01-01

    In this study, we show the leishmanicidal effects of a chloroform fraction (CLF) and a purified indole alkaloid obtained from crude stem extract of Peschiera australis against Leishmania amazonensis, a causative agent of cutaneous leishmaniasis in the New World. In a bioassay-guided chemical fractionation, the leishmanicidal activity in CLF completely and irreversibly inhibited promastigote growth. This fraction was also active against amastigotes in infected murine macrophages. Chemical analysis of CLF identified an iboga-type indole alkaloid coronaridine as one of its major compounds. Coronaridine showed potent antileishmanial activity, inhibiting promastigote and amastigote growth. Promastigotes and amastigotes treated with CLF or coronaridine showed pronounced alterations in their mitochondria as assessed by transmission electron microscopy. PMID:11302794

  20. 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

  1. Stereoselective interaction of cinchona alkaloid isomers with bovine serum albumin.

    PubMed

    Liu, Yan; Chen, Mingmao; Jiang, Longguang; Song, Ling

    2015-08-15

    The dependence of the interaction between bovine serum albumin (BSA) and two cinchona alkaloids, quinine (QN) and quinidine (QD), on the absolute configuration of these stereoisomers has been comprehensively studied. The FTIR spectra showed that QN and QD interacted with both CO and C-N groups of BSA, resulting in changes to the secondary structure of the protein. Fluorescence quenching of BSA by the stereoisomers revealed lower efficiency for QD in quenching the Trp emission of BSA when compared to QN. Further analysis accurately described the different binding behaviors and recognition discrepancies of QN and QD towards BSA, which was reflected through binding affinities, driving forces, energy changes and conformational changes during the ligand-protein interactions. Synchronous fluorescence further proved that QD was farther from Trp and Tyr than that of QN. This work could provide basic data for clarifying the binding interaction, metabolism and distribution of cinchona alkaloid stereoisomers in vivo. PMID:25794736

  2. Previously Uncultured Marine Bacteria Linked to Novel Alkaloid Production.

    PubMed

    Choi, Eun Ju; Nam, Sang-Jip; Paul, Lauren; Beatty, Deanna; Kauffman, Christopher A; Jensen, Paul R; Fenical, William

    2015-09-17

    Low-nutrient media and long incubation times facilitated the cultivation of 20 taxonomically diverse Gram-negative marine bacteria within the phyla Bacteroidetes and Proteobacteria. These strains comprise as many as three new families and include members of clades that had only been observed using culture-independent techniques. Chemical studies of the type strains representing two new families within the order Cytophagales led to the isolation of nine new alkaloid secondary metabolites that can be grouped into four distinct structure classes, including azepinones, aziridines, quinolones, and pyrazinones. Several of these compounds possess antibacterial properties and appear, on structural grounds, to be produced by amino acid-based biosynthetic pathways. Our results demonstrate that relatively simple cultivation techniques can lead to the isolation of new bacterial taxa that are capable of the production of alkaloid secondary metabolites with antibacterial activities. These findings support continued investment in cultivation techniques as a method for natural product discovery. PMID:26299672

  3. Antiviral glycosidic bisindole alkaloids from the roots of Isatis indigotica.

    PubMed

    Liu, Yu-Feng; Chen, Ming-Hua; Guo, Qing-Lan; Lin, Sheng; Xu, Cheng-Bo; Jiang, Yue-Ping; Li, Yu-Huan; Jiang, Jian-Dong; Shi, Jian-Gong

    2015-01-01

    Seven new glycosidic bisindole alkaloids, isatindigobisindolosides A-G (1-7), were isolated from an aqueous extract of the Isatis indigotica roots. Their structures including absolute configurations were determined by spectroscopic and chemical methods, together with calculations of electronic circular dichroism (ECD) spectra based on the quantum-mechanical time-dependent density functional theory. In the NMR spectra of 1-3, it is found that integration of H-2 and intensity of C-2 are affected not only by a substitution group at C-2 but also by solvents. Influences of the glucopyranosyloxy on the calculated ECD spectra of the glycosidic bisindole alkaloids are discussed. Compounds 2, 5, and 6 showed antiviral activity against both the influenza virus A/Hanfang/359/95 (H3N2) and Coxsackie virus B3 with IC50 values of 8.4-100.0 μM. PMID:26123248

  4. 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.

  5. Various alkaloid profiles in decoctions of Banisteriopsis caapi.

    PubMed

    Callaway, J C

    2005-06-01

    Twenty nine decoctions of Banisteriopsis caapi from four different sources and one specimen of B. caapi paste were analyzed for N,N-dimethyltryptamine (DMT), tetrahydroharmine (THH), harmaline and harmine. Other plants were also used in the preparation of these products, typically Psychotria viridis, which provides DMT. There were considerable variations in alkaloid profiles, both within and between sample sources. DMT was not detected in all samples. Additional THH may be formed from both harmine and harmaline during the preparation of these products. The alkaloid composition of one decoction sample did not change significantly after standing at room temperature for 80 days, but the initial acidic pH was neutralized by natural fermentation after 50 days. PMID:16149328

  6. Antibacterial, antifungal and cytotoxic isoquinoline alkaloids from Litsea cubeba.

    PubMed

    Zhang, Wei; Hu, Jin-Feng; Lv, Wen-Wen; Zhao, Qing-Chun; Shi, Guo-Bing

    2012-01-01

    Five novel isoquinoline alkaloids (+)-N-(methoxylcarbonyl)-N-nordicentrin (1), (+)-N-(methoxylcarbonyl)-N-norpredicentrine (2), (+)-N-(methoxylcarbonyl)-N-norbulbodione (3), and (+)-N-(methoxylcarbonyl)-N-norisocorydione (4), and (+)-8-methoxyisolaurenine-N- oxide (5) were isolated, together with one known compound, (+)-N-(methoxylcarbonyl)- N-norglaucine (6), from a 70% EtOH extract of the barks of Litsea cubeba. Structural elucidation of all the compounds were performed by spectral methods such as 1D- and 2D-NMR, IR, UV, and HRESIMS. Alkaloids 1, 2 and 6 showed antimicrobial activity against the bacterium S. aureus and two fungi (A. alternata and C. nicotianae). Compounds 3,4 exhibited significant cytotoxicity against all of six tested tumor cell lines. PMID:23117434

  7. Isoneocryptolepine, a synthetic indoloquinoline alkaloid, as an antiplasmodial lead compound.

    PubMed

    Van Miert, Sabine; Hostyn, Steven; Maes, Bert U W; Cimanga, Kanyanga; Brun, Reto; Kaiser, Marcel; Mátyus, Péter; Dommisse, Roger; Lemière, Guy; Vlietinck, Arnold; Pieters, Luc

    2005-05-01

    The antiprotozoal activities of three naturally occurring isomeric indoloquinoline alkaloids, i.e., cryptolepine (1), neocryptolepine (2), and isocryptolepine (3), and two dimeric indoloquinoline alkaloids, cryptoquindoline (6) and biscryptolepine (7), originally obtained from the plant Cryptolepis sanguinolenta, were compared with those of a new synthetic indoloquinoline isomer, isoneocryptolepine (4), and a quaternary derivative, N-methyl-isocryptolepinium iodide (5). The latter compounds showed a high antiplasmodial activity against the chloroquine-resistant Plasmodium falciparum strain K1 (IC50 of 0.23 +/- 0.04 and 0.017 +/- 0.004 microM, respectively), while the cytotoxicity (L6 cells) was 4.32 +/- 0.04 and 12.7 +/- 2.0 microM, respectively. Isoneocryptolepine (4) was found to act as an inhibitor of beta-hematin formation and as a DNA-intercalating agent. PMID:15921407

  8. Recent progress in the total synthesis of indole alkaloids.

    PubMed

    Edwankar, Chitra R; Edwankar, Rahul V; Namjoshi, Ojas A; Rallapalli, Sundari K; Yang, Jie; Cook, James M

    2009-11-01

    This review describes the most recent synthetic routes directed toward the construction of structurally complex indole alkaloids, many syntheses of which contain the asymmetric Pictet-Spengler reaction as a key stereochemical step. A kinetic and conformational study of the epimerization of cis 1,2,3-trisubstituted tetrahydro-beta-carbolines into their trans counterparts is described, because this is key to complete asymmetric induction in the Pictet-Spengler reaction. A mechanistic study of the enzyme-catalyzed Pictet-Spengler reaction is also included. The total synthesis of the opioid agonist mitragynine, as well as corynantheidol and the oxindole alstonisine is presented. With regard to bisindole alkaloids, the total synthesis of the antileishmanial bisindoles accedinisine and N'-demethylaccedinisne is described. PMID:19894188

  9. Taichunamides: Prenylated Indole Alkaloids from Aspergillus taichungensis (IBT 19404).

    PubMed

    Kagiyama, Ippei; Kato, Hikaru; Nehira, Tatsuo; Frisvad, Jens C; Sherman, David H; Williams, Robert M; Tsukamoto, Sachiko

    2016-01-01

    Seven new prenylated indole alkaloids, taichunamides A-G, were isolated from the fungus Aspergillus taichungensis (IBT 19404). Taichunamides A and B contained an azetidine and 4-pyridone units, respectively, and are likely biosynthesized from notoamide S via (+)-6-epi-stephacidin A. Taichunamides C and D contain endoperoxide and methylsulfonyl units, respectively. This fungus produced indole alkaloids containing an anti-bicyclo[2.2.2]diazaoctane core, whereas A. protuberus and A. amoenus produced congeners with a syn-bicyclo[2.2.2]diazaoctane core. Plausible biosynthetic pathways to access these cores within the three species likely arise from an intramolecular hetero Diels-Alder reaction. PMID:26644336

  10. Five New Alkaloids from Cephalotaxus lanceolata and C. fortunei var. alpina.

    PubMed

    Ni, Ling; Zhong, Xiu-Hong; Cai, Jie; Bao, Mei-Fen; Zhang, Bing-Jie; Wu, Jing; Cai, Xiang-Hai

    2016-06-01

    Five new alkaloids (1-5) were isolated from the leaves and twigs of Cephalotaxus lanceolata and C. fortunei var. alpina along with 24 known alkaloids. The new structures were elucidated based on spectroscopic data including 1D and 2D NMR, FTIR, UV and MS. These new alkaloids showed no cytotoxicity to HeLa, SGC-7901 gastric cancer, and A-549 lung cancer cell lines. PMID:27016921

  11. 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 β-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

  12. Indole alkaloids from Aspidosperma rigidum and A. schultesii and their antiparasitic effects.

    PubMed

    Reina, Matías; Ruiz-Mesia, Wilfredo; Ruiz-Mesia, Lastenia; Martínez-Díaz, Rafael; González-Coloma, Azucena

    2011-01-01

    Five oxindole alkaloids, three plumerane-type alkaloids, subtype haplophitine, and one aspidospermatane-type alkaloid, subtype tubotaiwine, were isolated from the medicinal plants Aspidosperma rigidum and A. schultesii. One compound was identified as the transoid conformer of 18-oxo-O-methylaspidoalbine which was not previously described. The antiparasitic activity of all compounds against Trypanosoma cruzi and Leishmania infantum and their non-specific cytotoxicity against mammalian cells were also determined. PMID:21812339

  13. 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

  14. [Experimental study of radiation protective efficacy of Vinca alkaloid drugs].

    PubMed

    Krasil'nikov, I I; Zhakovko, E B; Chigareva, N G

    1994-01-01

    In experiments with rats and dogs exposed to whole-body nonlethal and lethal gamma-radiation (2; 2,9 or 7.5 Gy) the radioprotective efficacy Vinca alkaloids drugs was investigated. It has been shown that enterally administered Vincanor (10 mg/kg over a three-day period) increased the radioresistance of animals. The prolonged radioprotective effect of Vincanor are discussed with regard to the phenomenon of sequential partial DNA synthesis inhibition in radiosensitive tissues. PMID:8069381

  15. Zoaramine, a zoanthamine-like alkaloid with a new skeleton.

    PubMed

    Cen-Pacheco, Francisco; Norte, Manuel; Fernández, José J; Daranas, Antonio Hernández

    2014-06-01

    Chemical investigation of an Atlantic variety of Zoanthus sp. led to the isolation of two new metabolites, zoaramine and zoarenone. Their structures were deduced by the use of NMR spectroscopy and computational calculation of (1)H and (13)C chemical shifts. The core of these novel compounds resembles the structure of norzoanthamine alkaloids, and their isolation represents an important step toward a better understanding of the biogenetic origin of this group of antiosteoporotic molecules. PMID:24831410

  16. 2-substituted quinoline alkaloids as potential antileishmanial drugs.

    PubMed Central

    Fournet, A; Barrios, A A; Muñoz, V; Hocquemiller, R; Cavé, A; Bruneton, J

    1993-01-01

    Ten 2-substituted quinoline alkaloids isolated from a plant used for treatment of New World cutaneous leishmaniasis have antileishmanial in vitro activities against the extracellular forms of Leishmania spp. BALB/c mice infected with Leishmania amazonensis PH8 or H-142 or Leishmania venezuelensis were treated 1 day after the parasitic infection with a quinoline alkaloid (100 mg/kg of body weight per day) or with reference drug N-methylglucamine antimonate (Glucantime) (56 mg of pentavalent antimony [Sbv] per kg per day) for 14 days. Lesion development was the criterium used to assess disease severity. Two three-carbon chain quinolines [2-n-propylquinoline and 2-(1',2'-trans-epoxypropyl)quinoline (chimanine D)] were more potent than N-methylglucamine antimonate against L. amazonensis PH8, and five quinoline alkaloids [2-(3,4-methylenedioxyphenylethyl)quinoline, cusparine, 2-(3,4-dimethoxyphenylethyl)quinoline, 2-(E)-prop-1'-enylquinoline (chimanine B), and skimmianine] were as effective as the reference drug. Single treatment near the site of infection, 14 days after infection with L. amazonensis, with 2-n-propylquinoline or chimanine B reduced the severity of lesions but less notably than N-methylglucamine antimonate. 2-n-Propylquinoline exhibited significant activity against the virulent strain L. venezuelensis. The active products did not show any apparent toxicities during the experiment. This study is, to our knowledge, the first to show the activity of 2-substituted quinoline alkaloids for experimental treatment of New World cutaneous leishmaniasis. Further investigations of these compounds might yet prove helpful for the development of new antileishmanial drugs. PMID:8494383

  17. Antimalarial diterpene alkaloids from the seeds of Caesalpinia minax.

    PubMed

    Ma, Guoxu; Sun, Zhaocui; Sun, Zhonghao; Yuan, Jingquan; Wei, Hua; Yang, Junshan; Wu, Haifeng; Xu, Xudong

    2014-06-01

    Two new diterpene alkaloids, caesalminines A (1) and B (2), possessing a tetracyclic cassane-type furanoditerpenoid skeleton with γ-lactam ring, were isolated from the seeds of Caesalpinia minax. Their structures were determined by different spectroscopic methods and ECD calculation. The plausible biosynthetic pathway of caesalminines A and B was proposed. The anti-malarial activity of compounds 1 and 2 is presented with IC50 values of 0.42 and 0.79 μM, respectively. PMID:24727083

  18. General entry to aspidosperma alkaloids: enantioselective total synthesis of (-)-aspidophytine.

    PubMed

    Yang, Rongwen; Qiu, Fayang G

    2013-06-01

    A general approach toward the asymmetric total synthesis of various aspidosperma alkaloids includes the combination of a C-H bond activation with a Heck-type coupling, and the stereo-controlled formation of piperidine and pyrrolidine rings as key steps. The feasibility of this approach was demonstrated with the total synthesis of aspidophytine in 18 steps from 4,4-disubstituted cyclohexanedione and 2,3-dimethoxyaniline. PMID:23610074

  19. Ultrasonic extraction of steroidal alkaloids from potato peel waste.

    PubMed

    Hossain, Mohammad B; Tiwari, Brijesh K; Gangopadhyay, Nirupama; O'Donnell, Colm P; Brunton, Nigel P; Rai, Dilip K

    2014-07-01

    Potato processors produce large volumes of waste in the form of potato peel which is either discarded or sold at a low price. Potato peel waste is a potential source of steroidal alkaloids which are biologically active secondary metabolites which could serve as precursors to agents with apoptotic, chemopreventive and anti-inflammatory properties. The present study investigated the relative efficacy of ultrasound assisted extraction (UAE) and solid liquid extraction (SLE) both using methanol, to extract steroidal alkaloids from potato peel waste and identified optimal conditions for UAE of α-solanine, α-chaconine, solanidine and demissidine. Using response surface methodology optimal UAE conditions were identified as an amplitude of 61 μm and an extraction time of 17 min which resulted the recovery of 1102 μg steroidal alkaloids/g dried potato peel (DPP). In contrast, SLE yielded 710.51 glycoalkaloid μg/g DPP. Recoveries of individual glycoalkoids using UAE yielded 273, 542.7, 231 and 55.3 μg/g DPP for α-solanine, α-chaconine, solanidine and demissidine respectively. Whereas for SLE yields were 180.3, 337.6, 160.2 and 32.4 μg/g DPP for α-solanine, α-chaconine, solanidine and demissidine respectively. The predicted values from the developed second order quadratic polynomial equation were in close agreement with the experimental values with low average mean deviation (E<5%) values. Predicted models were highly significant (p<0.05) for all parameters studied. This study indicates that UAE has strong potential as an extraction method for steroidal alkaloids from potato peel waste. PMID:24582305

  20. Photoassisted Synthesis of Enantiopure Alkaloid Mimics Possessing Unprecedented Polyheterocyclic Cores

    PubMed Central

    Bhuvan Kumar, N.N.; Mukhina, Olga A.; Kutateladze, Andrei G.

    2013-01-01

    Enantiopure alkaloid mimics are synthesized via high yielding intramolecular cycloadditions of photogenerated azaxylylenes tethered to pyrroles, with further growth of molecular complexity via post-photochemical transformations of primary photoproducts. This expeditious access to structurally unprecedented polyheterocyclic cores is being developed in the context of diversity-oriented synthesis, as the modular design allows for rapid “pre-assembly” of diverse photoprecursors from simple building blocks/diversity inputs. PMID:23789841

  1. 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

  2. Aaptamine alkaloids from the Vietnamese sponge Aaptos sp.

    PubMed

    Shubina, Larisa K; Kalinovsky, Anatoly I; Fedorov, Sergey N; Radchenko, Oleg S; Denisenko, Vladimir A; Dmitrenok, Pavel S; Dyshlovoy, Sergey A; Krasokhin, Vladimir B; Stonik, Valentin A

    2009-08-01

    A series of aaptamines, including one new alkaloid (1), were isolated from the marine sponge Aaptos sp. collected in Vietnamese waters. The structure of 1 was elucidated using NMR and HRESIMS, as well as by chemical transformation of 1 to the previously known aaptamine and established as 3-N-morpholinyl-9-demethyl(oxy)aaptamine. The isolated compounds showed a potential cancer preventive activity. PMID:19768988

  3. The Daphniphyllum Alkaloids: Total Synthesis of (−)-Calyciphylline N

    PubMed Central

    2016-01-01

    Presented here is a full account on the development of a strategy culminating in the first total synthesis of the architecturally complex daphniphyllum alkaloid, (−)-calyciphylline N. Highlights of the approach include a highly diastereoselective, intramolecular Diels–Alder reaction of a silicon-tethered acrylate; an efficient Stille carbonylation of a sterically encumbered vinyl triflate; a one-pot Nazarov cyclization/proto-desilylation sequence; and the chemoselective hydrogenation of a fully substituted diene ester. PMID:25756504

  4. Metabolic engineering for the production of plant isoquinoline alkaloids.

    PubMed

    Diamond, Andrew; Desgagné-Penix, Isabel

    2016-06-01

    Several plant isoquinoline alkaloids (PIAs) possess powerful pharmaceutical and biotechnological properties. Thus, PIA metabolism and its fascinating molecules, including morphine, colchicine and galanthamine, have attracted the attention of both the industry and researchers involved in plant science, biochemistry, chemical bioengineering and medicine. Currently, access and availability of high-value PIAs [commercialized (e.g. galanthamine) or not (e.g. narciclasine)] is limited by low concentration in nature, lack of cultivation or geographic access, seasonal production and risk of overharvesting wild plant species. Nevertheless, most commercial PIAs are still extracted from plant sources. Efforts to improve the production of PIA have largely been impaired by the lack of knowledge on PIA metabolism. With the development and integration of next-generation sequencing technologies, high-throughput proteomics and metabolomics analyses and bioinformatics, systems biology was used to unravel metabolic pathways allowing the use of metabolic engineering and synthetic biology approaches to increase production of valuable PIAs. Metabolic engineering provides opportunity to overcome issues related to restricted availability, diversification and productivity of plant alkaloids. Engineered plant, plant cells and microbial cell cultures can act as biofactories by offering their metabolic machinery for the purpose of optimizing the conditions and increasing the productivity of a specific alkaloid. In this article, is presented an update on the production of PIA in engineered plant, plant cell cultures and heterologous micro-organisms. PMID:26503307

  5. The Alkaloid Alstonine: A Review of Its Pharmacological Properties

    PubMed Central

    Elisabetsky, E.; Costa-Campos, L.

    2006-01-01

    Indole compounds, related to the metabolism of tryptophan, constitute an extensive family, and are found in bacteria, plants and animals. Indolic compounds possess significant and complex physiological roles, and especially indole alkaloids have historically constituted a class of major importance in the development of new plant derived drugs. The indole alkaloid alstonine has been identified as the major component of a plant-based remedy, used in Nigeria to treat mental illnesses by traditional psychiatrists. Although it is certainly difficult to compare the very concept of mental disorders in different cultures, the traditional use of alstonine is remarkably compatible with its profile in experimental animals. Even though alstonine in mice models shows a psychopharmacological profile closer to the newer atypical antipsychotic agents, it also shows important differences and what seems to be an exclusive mechanism of action, not entirely clarified at this point. Considering the seemingly unique mode of action of alstonine and that its traditional use can be viewed as indicative of bioavailability and safety, this review focuses on the effects of alstonine in the central nervous system, particularly on its unique profile as an antipsychotic agent. We suggest that a thorough understanding of traditional medical concepts of health and disease in general and traditional medical practices in particular, can lead to true innovation in paradigms of drug action and development. Overall, the study of this unique indole alkaloid may be considered as another example of the richness of medicinal plants and traditional medical systems in the discovery of new prototypic drugs. PMID:16550222

  6. 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

  7. Absence of alkaloids in Psychotria carthagenensis Jacq. (Rubiaceae).

    PubMed

    Leal, M B; Elisabetsky, E

    1996-10-01

    Psychotria viridis and P. carthagenensis are often discussed in relation to the hallucinogenic beverage Ayahuasca, used for religious, medicinal and social purposes. The significance of including Psychotria species in this beverage has been understood on the basis of substantial amounts of tryptamine alkaloids detected on leaves of both P. viridis and P. carthagenensis. Nevertheless, there is a long lasting debate over the identification of which Psychotria species are actually traditionally employed. We here report that a P. carthagenensis leaf ethanol extract was found to be devoid of alkaloids. The extract significantly decreased mice body temperature (350 and 500 mg/kg). Toxicity assessment revealed that the extract induced sedation and slight ptoses (75% of animals treated with 1000 mg/kg). Lethality was not observed within 48 h. The data indicate that P. carthagenensis does have bioactive compound(s), possibly active at the central nervous system, but unlikely to be tryptamine alkaloids as in the case of P. viridis. Therefore, if P. carthagenensis is indeed used by ayahuasqueros, its chemical and pharmacological significance have yet to be elucidated. PMID:8941866

  8. Synthesis and Anticancer Activity of all known (?)-Agelastatin Alkaloids

    PubMed Central

    Han, Sunkyu; Siegel, Dustin S.; Morrison, Karen C.; Hergenrother, Paul J.

    2014-01-01

    The full details for our enantioselective total syntheses of (?)-agelastatins AF (16), the evolution of a new methodology for synthesis of substituted azaheterocycles, and the first side-by-side evaluation of all known (?)-agelastatin alkaloids against nine human cancer cell lines are described. Our concise synthesis of these alkaloids exploits the intrinsic chemistry of plausible biosynthetic precursors and capitalizes on a late-stage synthesis of the C-ring. The critical copper-mediated cross-coupling reaction was expanded to include guanidine-based systems, offering a versatile preparation of substituted imidazoles. The direct comparison of the anticancer activity of all naturally occurring (?)-agelastatins in addition to eight advanced synthetic intermediates enabled a systematic analysis of the structure activity relationship within the natural series. Significantly, (?)-agelastatin A (1) is highly potent against six blood cancer cell lines (20190 nM) without affecting normal red blood cells (>333 ?M). (?)-Agelastatin A (1) and (?)-agelastatin D (4), the two most potent members of this family, induce dose dependent apoptosis and arrest cells in the G2/M-phase of the cell cycle; however, using confocal microscopy we have determined that neither alkaloid affects tubulin dynamics within cells. PMID:24152243

  9. 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

    2015-01-01

    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

  10. Alkaloids from Australian frogs (Myobatrachidae): pseudophrynamines and pumiliotoxins.

    PubMed

    Daly, J W; Garraffo, H M; Pannell, L K; Spande, T F; Severini, C; Erspamer, V

    1990-01-01

    Australian frogs of the genus Pseudophryne contain two distinct classes of alkaloids. The pseudophrynamine class (3a-prenyl pyrrolo[2,3-b]indoles) are unique to this genus of frogs of the family Myobatrachidae, while the pumiliotoxin-A class (8-hydroxy-8-methyl-6-alkylidene-1-azabicyclo[4.3.0]nonanes) also occur in dendrobatid frogs of the genera Dendrobates, Epipedobates, and Minyobates, in ranid frogs of the genus Mantella, and in bufonid toads of the genus Melanophryniscus. All seven species of Pseudophryne examined contain both classes of alkaloids. The pseudophrynamines were the predominant class in both species (Pseudophryne guentheri and Pseudophryne occidentalis) from Western Australia, while all of the eastern species (Pseudophryne australis, Pseudophryne bibronii, Pseudophryne coriacea, Pseudophryne corroboree, and Pseudophryne semimarmorata) contained significant amounts of both pseudophrynamines and pumiliotoxins. Pumiliotoxins, in particular pumiliotoxin B, were predominant in two eastern species (P. australis and a southern population of P. corroboree), while pseudophrynamines were dominant in P. bibronii, four of six populations of P. coriacea, one population of P. semimarmorata, and a northern population of P. corroboree. Structures are proposed for several new alkaloids of the pseudophrynamine class. PMID:2380714

  11. Identification and developmental expression profiling of putative alkaloid biosynthetic genes in Corydalis yanhusuo bulbs

    PubMed Central

    Liao, Dengqun; Wang, Pengfei; Jia, Chan; Sun, Peng; Qi, Jianjun; Zhou, Lili; Li, Xian’en

    2016-01-01

    Alkaloids in bulbs of Corydalis (C.) yanhusuo are the major pharmacologically active compounds in treatment of blood vessel diseases, tumors and various pains. However, due to the absence of gene sequences in C. yanhusuo, the genes involved in alkaloid biosynthesis and their expression during bulb development remain unknown. We therefore established the first transcriptome database of C. yanhusuo via Illumina mRNA-Sequencing of a RNA composite sample collected at Bulb initiation (Day 0), early enlargement (Day 10) and maturation (Day 30). 25,013,630 clean 90 bp paired-end reads were de novo assembled into 47,081 unigenes with an average length of 489 bp, among which 30,868 unigenes (65.56%) were annotated in four protein databases. Of 526 putative unigenes involved in biosynthesis o f various alkaloids, 187 were identified as the candidate genes involved in the biosynthesis of benzylisoquinoline alkaloids (BIAs), the only alkaloid type reported in C. yanhusuo untill now. BIAs biosynthetic genes were highly upregulated in the overall pathway during bulb development. Identification of alkaloid biosynthetic genes in C. yanhusuo provide insights on pathways and molecular regulation of alkaloid biosynthesis, to initiate metabolic engineering in order to improve the yield of interesting alkaloids and to identify potentially new alkaloids predicted from the transcriptomic information. PMID:26777987

  12. Alkaloid variation in New Zealand kōwhai, 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

  13. Variability of alkaloids in the skin secretion of the European fire salamander (Salamandra salamadra terrestris).

    PubMed

    Mebs, Dietrich; Pogoda, Werner

    2005-04-01

    The two major alkaloids, samandarine and samandarone, were identified in the skin secretion of individual specimens from two populations of the European fire salamander (Salamandra salamandra terrestris) by gas chromatography/mass spectrometry. High intraspecific variability in the ratio of both alkaloids was observed, but also in individual specimens over a period of 4 months suggesting separate metabolic pathways of the compounds. Alkaloid synthesis appears to take place also in liver, testes and ovaries, whereas the larvae of the salamanders are entirely free of alkaloids. PMID:15777956

  14. Identification and developmental expression profiling of putative alkaloid biosynthetic genes in Corydalis yanhusuo bulbs.

    PubMed

    Liao, Dengqun; Wang, Pengfei; Jia, Chan; Sun, Peng; Qi, Jianjun; Zhou, Lili; Li, Xian'en

    2016-01-01

    Alkaloids in bulbs of Corydalis (C.) yanhusuo are the major pharmacologically active compounds in treatment of blood vessel diseases, tumors and various pains. However, due to the absence of gene sequences in C. yanhusuo, the genes involved in alkaloid biosynthesis and their expression during bulb development remain unknown. We therefore established the first transcriptome database of C. yanhusuo via Illumina mRNA-Sequencing of a RNA composite sample collected at Bulb initiation (Day 0), early enlargement (Day 10) and maturation (Day 30). 25,013,630 clean 90 bp paired-end reads were de novo assembled into 47,081 unigenes with an average length of 489 bp, among which 30,868 unigenes (65.56%) were annotated in four protein databases. Of 526 putative unigenes involved in biosynthesis o f various alkaloids, 187 were identified as the candidate genes involved in the biosynthesis of benzylisoquinoline alkaloids (BIAs), the only alkaloid type reported in C. yanhusuo untill now. BIAs biosynthetic genes were highly upregulated in the overall pathway during bulb development. Identification of alkaloid biosynthetic genes in C. yanhusuo provide insights on pathways and molecular regulation of alkaloid biosynthesis, to initiate metabolic engineering in order to improve the yield of interesting alkaloids and to identify potentially new alkaloids predicted from the transcriptomic information. PMID:26777987

  15. 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

  16. 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

  17. 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.

  18. Biscarpamontamines A and B, an aspidosperma-iboga bisindole alkaloid and an aspidosperma-aspidosperma bisindole alkaloid, from Tabernaemontana sphaerocarpa.

    PubMed

    Zaima, Kazumasa; Hirata, Tomoko; Hosoya, Takahiro; Hirasawa, Yusuke; Koyama, Koichiro; Rahman, Abdul; Kusumawati, Idha; Zaini, Noor Cholies; Shiro, Motoo; Morita, Hiroshi

    2009-09-01

    Two new bisindole alkaloids, biscarpamontamine A (1), possessing an aspidosperma-iboga-type skeleton, and biscarpamontamine B (2), having an aspidosperma-aspidosperma-type skeleton, were isolated from stems of Tabernaemontana sphaerocarpa, and their structures were elucidated on the basis of spectroscopic data analysis. The absolute configuration of biscarpamontamine B (2) was established by comparison of its CD spectrum and with that of vobtusine (3). Biscarpamontamine B (2) showed potent cytotoxicity against various human cancer cell lines. PMID:19711971

  19. Reaction of dehydropyrrolizidine alkaloids with valine and hemoglobin.

    PubMed

    Zhao, Yuewei; Wang, Shuguang; Xia, Qingsu; Gamboa da Costa, Gonçalo; Doerge, Daniel R; Cai, Lining; Fu, Peter P

    2014-10-20

    Pyrrolizidine alkaloid-containing plants are probably the most common poisonous plants affecting livestock, wildlife, and humans. Pyrrolizidine alkaloids exert toxicity through metabolism to dehydropyrrolizidine alkaloids that bind to cellular protein and DNA, leading to hepatotoxicity, genotoxicity, and tumorigenicity. To date, it is not clear how dehydropyrrolizidine alkaloids bind to cellular constituents, including amino acids and proteins, resulting in toxicity. Metabolism of carcinogenic monocrotaline, riddelliine, and heliotrine produces dehydromonocrotaline, dehyroriddelliine, and dehydroheliotrine, respectively, as primary reactive metabolites. In this study, we report that reaction of dehydromonocrotaline with valine generated four highly unstable 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived valine (DHP-valine) adducts. For structural elucidation, DHP-valine adducts were derivatized with phenyl isothiocyanate (PITC) to DHP-valine-PITC products. After HPLC separation, their structures were characterized by mass spectrometry, UV-visible spectrophotometry, (1)H NMR, and (1)H-(1)H COSY NMR spectral analysis. Two DHP-valine-PITC adducts, designated as DHP-valine-PITC-1 and DHP-valine-PITC-3, had the amino group of valine linked to the C7 position of the necine base, and the other two DHP-valine-PITC products, DHP-valine-PITC-2 and DHP-valine-PITC-4, linked to the C9 position of the necine base. DHP-valine-PITC-1 was interconvertible with DHP-valine-PITC-3, and DHP-valine-PITC-2 was interconvertible with DHP-valine-PITC-4. Reaction of dehydroriddelliine and dehydroheliotrine with valine provided similar results. However, reaction of valine and dehydroretronecine (DHR) under similar experimental conditions did not produce DHP-valine adducts. Reaction of dehydromonocrotaline with rat hemoglobin followed by derivatization with PITC also generated the same four DHP-valine-PITC adducts. This represents the first full structural elucidation of protein conjugated pyrrolic adducts formed from reaction of dehydropyrrolizidine alkaloids with an amino acid (valine). In addition, it was found that DHP-valine-2 and DHP-valine-4, with the valine amino group linked at the C7 position of the necine base, can lose the valine moiety to form DHP. PMID:25211425

  20. Lysine decarboxylase catalyzes the first step of quinolizidine alkaloid biosynthesis and coevolved with alkaloid production in leguminosae.

    PubMed

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

    2012-03-01

    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

  1. Genetics of Alkaloids in Papaver somniferum.

    PubMed

    Lal, R K; Sharma, J R

    1991-06-01

    Based on numerical and graphic analyses of 6 x 6 diallele cross progenies (n (2) = 36) over two environments, dominance was found to be most prevalent (in overdominance range without being inflated by non-allelic interactions) in parents for latex yield, and morphine, codeine, thebaine, and narcotine contents. However, the additive component was also significant for the former three traits. Dominant alleles mostly with positive effects were, by and large, asymmetrically distributed in parents except for narcotine content. Heritability estimates were moderate and corresponded with low genetic advance estimates for morphine, codeine, and thebaine contents. Ample genetic diversity among parents was reflected for all traits except narcotine content. On an overall basis, heterosis breeding was suggested to be a rewarding proposition for genetic improvement of the opium poppy ( PAPAVER SOMNIFERUM L.). PMID:17226158

  2. 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...

  3. 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 ...

  4. [Effect produced by the alkaloid fraction of Mimosa tenuiflora (tepescohuite) on the peristaltic reflex of the guinea pig ileum].

    PubMed

    Meckes-Lozoya, M; Lozoya, X; González, J L; Martínez, M

    1990-01-01

    An alkaloidal fraction was obtained from Mimosa tenuiflora (Willd.) Poir (tepescohuite) trunk bark. The product contained mainly an indolealkylamine and three minor alkaloids. This fraction inhibited the peristaltic reflex in the guinea-pig isolated ileum in vitro. PMID:2103706

  5. [Expression pattern of genes involved in tropane alkaloids biosynthesis and tropane alkaloids accumulation in Atropa belladonna].

    PubMed

    Qiang, Wei; Wang, Ya-Xiong; Zhang, Qiao-Zhuo; Li, Jin-Di; Xia, Ke; Wu, Neng-Biao; Liao, Zhi-Hua

    2014-01-01

    Atropa belladonna is a medicinal plant and main commercial source of tropane alkaloids (TAs) including scopolamine and hyoscyamine, which are anticholine drugs widely used clinically. Based on the high throughput transcriptome sequencing results, the digital expression patterns of UniGenes representing 9 structural genes (ODC, ADC, AIH, CPA, SPDS, PMT, CYP80F1, H6H, TRII) involved in TAs biosynthesis were constructed, and simultaneously expression analysis of 4 released genes in NCBI (PMT, CYP80F1, H6H, TRII) for verification was performed using qPCR, as well as the TAs contents detection in 8 different tissues. Digital expression patterns results suggested that the 4 genes including ODC, ADC, AIH and CPA involved in the upstream pathway of TAs, and the 2 branch pathway genes including SPDS and TRII were found to be expressed in all the detected tissues with high expression level in secondary root. While the 3 TAs-pathway-specific genes including PMT, CYP80F1, H6H were only expressed in secondary roots and primary roots, mainly in secondary roots. The qPCR detection results of PMT, CYP80F1 and H6H were consistent with the digital expression patterns, but their expression levels in primary root were too low to be detected. The highest content of hyoscyamine was found in tender stems (3.364 mg x g(-1)), followed by tender leaves (1.526 mg x g(-1)), roots (1.598 mg x g(-1)), young fruits (1.271 mg x g(-1)) and fruit sepals (1.413 mg x g(-1)). The highest content of scopolamine was detected in fruit sepals (1.003 mg x g(-1)), then followed by tender stems (0.600 mg x g(-1)) and tender leaves (0.601 mg x g(-1)). Both old stems and old leaves had the lowest content of hyoscyamine and scopolamine. The gene expression profile and TAs accumulation indicated that TAs in Atropa belladonna were mainly biosynthesized in secondary root, and then transported and deposited in tender aerial parts. Screening Atropa belladonna secondary root transcriptome database will facilitate unveiling the unknown enzymatic reactions and the mechanisms of transcriptional control. PMID:24754168

  6. 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...

  7. Synthesis and pharmacological activity of alkaloids from embryo of lotus, Nelumbo nucifera.

    PubMed

    Nishimura, Katsumi; Horii, Shinji; Tanahashi, Takao; Sugimoto, Yumi; Yamada, Jun

    2013-01-01

    Bisbenzylisoquinoline alkaloid, nelumboferine which was recently isolated from the embryo of Nelumbo nucifera, and stereoisomers of neferine, which is a major alkaloid of the embryo of N. nucifera, were stereoselectively synthesized. Pharmacological activity of nelumboferine, stereoisomers of neferine, liensinine, isoliensinine, and O-methylneferine were evaluated. PMID:23117579

  8. 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 ...

  9. 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 vasoactivity of these compounds. Objectives were to profile vasoactivity of ergot alkaloids in mesenteric artery and vein and determine if previous exposure to endophyte-infected tall fescue affec...

  10. 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

  11. Alkaloids from amphibian skin: a tabulation of over eight-hundred compounds.

    PubMed

    Daly, John W; Spande, Thomas F; Garraffo, H Martin

    2005-10-01

    A diverse array of biologically active, lipid-soluble alkaloids have been discovered in amphibian skin. Such alkaloids include the following: the steroidal samandarines from salamanders, the batrachotoxins, histrionicotoxins, gephyrotoxins, and epibatidine from neotropical poison frogs (Dendrobatidae), the pumiliotoxins, allopumiliotoxins, homopumiliotoxins, and decahydroquinolines from certain genera of anurans from four families (Dendrobatidae, Mantellidae, Bufonidae, and Myobatrachidae), a variety of izidines (pyrrolizidines, indolizidines, quinolizidines, lehmizidines), pyrrolidines, piperidines, various tricyclics (related in structures to the coccinellines), and spiropyrrolizidines from the first three of these four families, the pseudophrynamines from one genus of Australian frogs, and a variety of unclassified alkaloids as yet of undetermined structure. With the exception of the samandarines and the pseudophrynamines, all alkaloids appear to be derived from dietary sources. Although only a few of the over 800 amphibian skin alkaloids have been detected in arthropods, putative arthropod sources for the batrachotoxins and coccinelline-like tricyclics (beetles), the pumiliotoxins (ants, mites), the decahydroquinolines, izidines, pyrrolidines, and piperidines (ants), and the spiropyrrolizidines (millipedes) have been discovered. Ants are likely sources for histrionicotoxins, lehmizidines, and tricyclic gephyrotoxins. Epibatidines represent an important alkaloid class without a putative dietary source. The structures for many of these alkaloids have been rigorously established, while the structures of others represent tentative proposals, based only on mass spectral and FTIR spectral data, along with analogies to structures of well-defined alkaloids. PMID:16252926

  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. 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...

  14. 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...

  15. NATURAL FUNGICIDES FROM RUTA GRAVEOLENS L. LEAVES, INCLUDING A NEW QUINOLONE ALKALOID

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bioassay-directed isolation of antifungal compounds from Ruta graveolens leaves yielded seven compounds (two furanocoumarins, four quinolone alkaloids, including one novel compound (1-methyl-2- 4-[3,4-(methylenedioxy)phenyl]hexyl]-4-quinolone), and one quinoline alkaloid). We also report the 1H and ...

  16. 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...

  17. 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...

  18. Ambiguanine A-G, hexahydrobenzophenanthridine alkaloids from Corydalis ambigua var. amurensis.

    PubMed

    Yang, Zhi-You; Jiang, Bao-Hong; Teng, Fu-Kang; Han, Na; Liu, Zhi-Hui; Zhou, Jing-Jing; Wang, Yu; Guo, De-An; Yin, Jun

    2014-09-01

    Seven hexahydrobenzophenanthridine-type alkaloids, Ambiguanine A-G, along with eight known alkaloids, were isolated from tubers of Corydalis ambigua var. amurensis. Their structures were elucidated based on extensive spectroscopic analyses, with absolute configurations determined by CD experiments. PMID:24916320

  19. 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

  20. 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...

  1. Antimicrobial agents from higher plants. The quaternary alkaloids of Ptelea trifoliata.

    PubMed

    Mitscher, L A; Bathala, M S; Clark, G W; Beal, J L

    1975-01-01

    Quaternary alkaloid extracts of Ptelea trifoliata showed potentially interesting antimicrobial activity. Chromatographic examination showed the presence of six components. Of these, choline and O-4-methyl ptelefolinium were known compounds. Rational structures are proposed for the new alkaloids, O-4-methylhydroxyluninium, neohydroxylunine and pteleatinium salts. Pteleatinium salt is responsible for the antimicrobial activity of the extracts of the plant. PMID:1094214

  2. Chiral gas chromatographic determination of ephedrine-type alkaloids in dietary supplements containing M Hung.

    PubMed

    Betz, J M; Gay, M L; Mossoba, M M; Adams, S; Portz, B S

    1997-01-01

    M Hung is a traditional Chinese medicine derived from the aerial parts of several Ephedra species (Ephedraceae). These plants produce (-)-ephedrine, (+)-pseudoephedrine, (-)-norephedrine, (+)-norpseudoephedrine, (-)-N-methylephedrine, and (+)-N-methylpseudoephedrine. Racemic and (-)-ephedrine, (+)-pseudoephedrine, and (+/-)-norephedrine (phenylpropanolamine) are used clinically in the United States and are largely synthetic in origin. Current interest in M Hung is spurred by reports describing a "thermogenic" (calorie burning) effect provided by mixtures of ephedrine, caffeine, and aspirin. Products providing the key thermogenic compounds from natural sources are available as dietary supplements in retail outlets. Reports of potentially unsafe levels of the alkaloids, as well as possible fortification of M Hung-containing products with synthetic Ephedra alkaloids, prompted the development of a chiral gas chromatographic (GC) method that allows determination of alkaloid patterns and identification of isomerically impure synthetic alkaloids. Nine products were analyzed on a gamma-cyclodextrin capillary GC column. Identity of the alkaloids was verified by GC/mass spectrometry (MS) and GC/matrix isolation/Fourier transform infrared spectroscopy. No synthetic isomers were found in the dietary supplements analyzed. Three products contained only one of the ephedrine-type alkaloids. One product that listed M Hung as an ingredient contained no detectable ephedrine-type alkaloid. In products containing measurable quantities of these compounds, total alkaloid levels ranged from 0.3 to 56 mg/g. PMID:9086588

  3. Synthesis and antiproliferativeactivity of new vinca alkaloids containing an α,β-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 α,β-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 μM, thus comparable with vinblastine. PMID:26522953

  4. Separation and Quantitation of Seven Ergot Alkaloids in Bovine Vein Tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ergot alkaloid related toxicosis has been documented in forage animals for over thirty years, but few mass spectrometry analytical methods for the detection and quantitation of these compounds exist. A primary ergot alkaloid of interest was ergovaline, the predominant toxicant in endophyte-inf...

  5. Plant alkaloids that cause developmental defects through the disruption of cholinergic neurotransmission

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The exposure of a developing embryo or fetus to alkaloids from plants, plant products, or plant extracts has the potential to cause developmental defects in humans and animals. These defects may have multiple causes but those induced by piperidine and quinolizidine alkaloids arise from the inhibiti...

  6. 11-Isopropylcryptolepine: A novel alkaloid isolated from cryptolepis sanguinolenta characterized using submicro NMR techniques

    PubMed

    Hadden; Sharaf; Guido; Robins; Tackie; Phoebe; Schiff; Martin

    1999-02-01

    A new alkaloid has been isolated from extracts of the West African plant Cryptolepis sanguinolenta and identified by submicro NMR techniques as 11-isopropylcryptolepine (1). The unusual incorporation of the isopropyl group at the 11-position of the indolo[3,2-b]quinoline nucleus is suggestive of a mixed biosynthetic origin for the alkaloid. PMID:10075749

  7. Toxicity of ergovaline, the tall fescue ergot alkaloid, to Pratylenchus scribneri

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neotyphodium infected tall fescue produces a variety of secondary metabolites that are toxic and/or grazing deterrents. Alkaloid production has been related to defense against vertebrate and insect pests, in particular plant-parasitic nematodes. The ergot and pyrrollizidine (loline) alkaloids are ...

  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. 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...

  10. Construction of the [6-7-5-5] tetracyclic core of all the carbocyclic frameworks of yuzurimine-type alkaloids.

    PubMed

    Hayakawa, Ichiro; Niida, Keisuke; Kigoshi, Hideo

    2015-07-25

    Yuzurimine-type alkaloids make up a sub-family of Daphniphyllum alkaloids structurally featuring a [6-7-5-5] tetracarbocyclic core framework. In this manuscript, we describe our construction of the [6-7-5-5] tetracarbocyclic core of yuzurimine-type alkaloids by using a unique in situ intramolecular Wittig reaction and Sm-mediated cyclization as key steps. PMID:26097917

  11. 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

  12. Alkaloids induce programmed cell death in bloodstream forms of trypanosomes (Trypanosoma b. brucei).

    PubMed

    Rosenkranz, Vera; Wink, Michael

    2008-01-01

    The potential induction of a programmed cell death (PCD) in Trypanosoma b. brucei by 55 alkaloids of the quinoline, quinolizidine, isoquinoline, indole, terpene, tropane, steroid, and piperidine type was studied by measuring DNA fragmentation and changes in mitochondrial membrane potential. For comparison, the induction of apoptosis by the same alkaloids in human leukemia cells (Jurkat APO-S) was tested. Several alkaloids of the isoquinoline, quinoline, indole and steroidal type (berberine, chelerythrine, emetine, sanguinarine, quinine, ajmalicine, ergotamine, harmine, vinblastine, vincristine, colchicine, chaconine, demissidine and veratridine) induced programmed cell death, whereas quinolizidine, tropane, terpene and piperidine alkaloids were mostly inactive. Effective PCD induction (EC(50) below 10 microM) was caused in T. brucei by chelerythrine, emetine, sanguinarine, and chaconine. The active alkaloids can be characterized by their general property to inhibit protein biosynthesis, to intercalate DNA, to disturb membrane fluidity or to inhibit microtubule formation. PMID:18833031

  13. Differential alkaloid profile in Uncaria tomentosa micropropagated plantlets and root cultures.

    PubMed

    Luna-Palencia, Gabriela R; Huerta-Heredia, Ariana A; Cerda-García-Rojas, Carlos M; Ramos-Valdivia, Ana C

    2013-05-01

    The alkaloids of Uncaria tomentosa micropropagated plantlets and root cultures were isolated and identified by NMR and mass spectrometry. Plantlets yielded pteropodine (1), isopteropodine (2), mitraphylline (3), isomitraphylline (4), uncarine F (5), speciophylline (6), rhynchophylline (7) and isorhynchophylline (8). In plantlets growing under continuous light, tetracyclic alkaloids 7 and 8 decreased from 20 ± 1.8 at 2 months to 2.2 ± 0.33 mg/g dry wt at 6 months, while the pentacyclic alkaloids 1-4 increased from 7.7 ± 1.4 to 15 ± 0.05 mg/g dry wt, supporting their biogenetic conversion. Micropropagated plantlets produced four times more alkaloids (27.6 ± 3.1 mg/g dry wt) than greenhouse plants. Plantlet roots yielded 3, 4, 8 and the glucoindole alkaloids 3α-dihydrocadambine (9) and dolichantoside (10), the last one not previously found in Uncaria. PMID:23296316

  14. Detection and Characterization of Cocaine and Related Tropane Alkaloids in Coca Leaf, Cocaine, and Biological Specimens.

    PubMed

    Moore, J M; Moore, J F; Fodor, G; Jones, A B

    1995-12-01

    Cocaine, atropine and scopolamine are the three most important alkaloids in the tropane group. The detection of these alkaloids and their metabolites, at trace levels in biological matrices, is reviewed. These matrices include human and rat physiological fluids such as blood, urine, and saliva as well as human body tissue and hair. The detection, isolation, and determination of cocaine and related tropane alkaloids in cocaine-bearing leaf of South American and greenhouse-cultivated coca is discussed. The relationship between tropane alkaloids in coca leaf and their presence in illicit refined cocaine is addressed. A survey of modern methods for the detection of tropane alkaloids, including mass spectrometry, ultraviolet, infrared and Raman spectroscopy, gas and high-performance liquid chromatography and immunoassay techniques, is presented. PMID:26270476

  15. 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

  16. Antibacterial monoterpenoid indole alkaloids from Alstonia scholaris cultivated in temperate zone.

    PubMed

    Liu, Lu; Chen, Ying-Ying; Qin, Xu-Jie; Wang, Bei; Jin, Qiong; Liu, Ya-Ping; Luo, Xiao-Dong

    2015-09-01

    Three new monoterpenoid indole alkaloids, named normavacurine-21-one (1), 5-hydroxy-19, 20-E-alschomine (2), and 5-hydroxy-19, 20-Z-alschomine (3), together with thirteen known indole alkaloids (4-16) were isolated from the leaves of Alstonia scholaris cultivated in Kunming. Their structures were elucidated on the basis of extensive spectroscopic analysis, as well as by comparison with the reported spectroscopic data. The leaves of A. scholaris cultivated in Kunming, contained picrinine-type alkaloids, scholaricin-type alkaloids and nareline as major alkaloids. New compounds 1-3 might be derived from a common biogenetic precursor (5). Compounds 1, 5 and 10 exhibited significant antibacterial activity against Enterococcus faecalis, and 3, 9 and 14 against Pseudomonas aeruginosa with an MIC value of 0.781 μg/mL, while 14 showed moderate activity against Klepsiella pneumonia with an MIC value of 1.56 μg/mL. PMID:26136061

  17. (-)-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

  18. 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-α-l-rhamnopyranosyl-(1 → 6)-β-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 μmol/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

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

    PubMed Central

    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

  20. 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/Epichlo 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

  1. 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.

  2. The pharmacology of psychoactive alkaloids from ephedra and catha.

    PubMed

    Kalix, P

    1991-04-01

    Ever since the introduction of the alkaloid ephedrine as an anti-asthmatic, the CNS stimulatory effects of this sympathomimetic have been a problem in therapy. Indeed, the use of ephedrine is not only limited by its cardiovascular effects, but also by the occurrence of insomnia, restlessness and anxiety. Exceptionally, ephedrine may even induce toxic psychosis, and the possibility of this side effect has recently received renewed attention. Besides ephedrine, the ephedra plant contains some norpseudoephedrine. This substance is also called cathine, because it is a major alkaloid of Catha edulis or khat, a plant that is widely used as a stimulant in certain countries of East Africa and of the Arab Peninsula. The effects of khat have been explained formerly by those of cathine; some time ago, however, the labile alkaloid cathinone was discovered in khat. This substance is the keto-analog of cathine; it is therefore more lipophilic and penetrates easily to its sites of action in the central nervous system. Indeed, cathinone has been found to be a highly potent CNS stimulant and it is now known to be the main psychoactive constituent of khat; the results of various in vitro and in vivo studies indicate that cathinone must be considered a natural amphetamine. In confirmation of this view, it has recently been demonstrated that cathinone has in humans marked euphorigenic and psychostimulant effects. As the case may be, these findings may lead, together with epidemiological data, to a reconsideration of the use of khat as a stimulant and social drug. PMID:1881158

  3. Alkaloid production in Catharanthus roseus (L.) G. Don. : VI. Variation in alkaloid spectra of cell lines derived from one single leaf.

    PubMed

    Constabel, F; Rambold, S; Chatson, K B; Kurz, W G; Kutney, J P

    1981-08-01

    Analysis of 76 cell clones derived from one leaf of a periwinkle plant (Catharanthus roseus (L.) G. Don) showed the occurrence of Corynanthe-, Strychnos-, and Aspidosperma-type alkaloids. The majority of clones (62%) displayed compounds of all three types. Variation of the alkaloid spectra of the cell clones was low when compared to that found previously with serially subcultured callus and cell suspensions derived from different plants. PMID:24258743

  4. Iteamine, the first alkaloid isolated from Itea virginica L. inflorescence.

    PubMed

    Ayers, Benjamin J; Hollinshead, Jacqueline; Saville, Alexander W; Nakagawa, Shinpei; Adachi, Isao; Kato, Atsushi; Izumori, Ken; Bartholomew, Barbara; Fleet, George W J; Nash, Robert J

    2014-04-01

    Iteamine, o-aminobenzyl β-D-glucopyranoside, is the first alkaloid to be isolated from Itea virginica. Itea is the sole plant source of D-psicose, a rare sugar likely to be a major dietary supplement. The structure of iteamine was established by NMR and confirmed by total synthesis. Iteamine and its galacto-analog (which was not found in Itea plants) showed no strong inhibition of any of the 15 glycosidases tested; unnatural galacto-iteamine was a weak inhibitor of chicken liver α-N-acetylgalactosaminidase. PMID:24534106

  5. 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

  6. 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. PMID:26734082

  7. Biosynthesis and regulation of terpenoid indole alkaloids in Catharanthus roseus.

    PubMed

    Zhu, Jianhua; Wang, Mingxuan; Wen, Wei; Yu, Rongmin

    2015-01-01

    Catharanthus roseus produces a wide range of terpenoid indole alkaloids (TIA). Many of them, such as vinblastine and vincristine, have significant bioactivity. They are valuable chemotherapy drugs used in combination with other drugs to treat lymphoma and leukemia. The TIA biosynthetic pathway has been investigated for many years, for scientific interest and for their potential in manufacturing applications, to fulfill the market demand. In this review, the progress and perspective of C. roseus TIA biosynthesis and its regulating enzymes are described. In addition, the culture condition, hormones, signaling molecules, precursor feeding on the accumulation of TIA, and gene expression are also evaluated and discussed. PMID:26009689

  8. Efficacy of alkaloid (-)-corypalmine against spore germination of some fungi.

    PubMed

    Maurya, S; Srivastava, J S; Jha, R N; Pandey, V B; Singh, U P

    2002-01-01

    Inhibition activity of the alkaloid (-)-corypalmine on spore germination of plant pathogenic and saprophytic fungi (Alternaria solani, A brassicicola, A. brassicae, A. melongenae, Curvularia pallescens, C. lunata, C. maculans, Curvularisa sp., Colletotrichum sp., Helminthosporium speciferum, H. frumentacei, H. pennisetti, Heterosporium sp., Penicillum sp., Ustilago cynodontis) was determined. Spore germination of all the tested fungi was inhibited, Heterosporium sp. and Ustilago cynodontis being the most sensitive (complete inhibition of spore germination was observed at the very low concentration of 200 ppm). Curvularia palliscens, C. maculans and Curvularia sp. were less sensitive; complete inhibition of spore germination occurred at 400 ppm. PMID:12094740

  9. Biosynthesis and regulation of terpenoid indole alkaloids in Catharanthus roseus

    PubMed Central

    Zhu, Jianhua; Wang, Mingxuan; Wen, Wei; Yu, Rongmin

    2015-01-01

    Catharanthus roseus produces a wide range of terpenoid indole alkaloids (TIA). Many of them, such as vinblastine and vincristine, have significant bioactivity. They are valuable chemotherapy drugs used in combination with other drugs to treat lymphoma and leukemia. The TIA biosynthetic pathway has been investigated for many years, for scientific interest and for their potential in manufacturing applications, to fulfill the market demand. In this review, the progress and perspective of C. roseus TIA biosynthesis and its regulating enzymes are described. In addition, the culture condition, hormones, signaling molecules, precursor feeding on the accumulation of TIA, and gene expression are also evaluated and discussed. PMID:26009689

  10. Antifungal Activity of an Alkaloid Allosecurinine against Some Fungi

    PubMed Central

    Pandey, M. B.; Singh, U. P.

    2007-01-01

    An allosecurinine alkaloid was assayed against spore germination of some saprophytic and pathogenic fungi e.g., Alternaria alternata, A. solani, A. brassicicola, A. brassicae, Curvularia lunata, C. pallescens, C. maculans, Curvularia species, Colletotrichum species, C. musae, C. gloeosporioides, Erysiphe pisi, Fusarium udum, Helminthosporium echinoclova, H. pennisetti, H. spiciferum, and Heterosporium sp. It inhibited mild spore germination of all the fungi tested. Curvularia lunata, Curvularia sp., Collectotrichum sp., C. musae and Heterosporium sp. were most sensitive as complete inhibition of spore germination was observed at very low concentrations. PMID:24015071

  11. 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 μM, respectively. PMID:26197510

  12. The Effect of Polyhydroxylated Alkaloids on Maltase-Glucoamylase

    PubMed Central

    Shang, Qian; Xiang, Junfeng; Zhang, Hong; Li, Qian; Tang, Yalin

    2013-01-01

    One of the most important carbohydrate-splitting enzymes is themaltase-glucoamylase which catalyzes the hydrolysis of alpha-glucosidic linkages. Maltase-glucoamylase inhibitors during the last few years have aroused medical interests in the treatment of diabetes. They contribute to a better understanding of the mechanism of maltase-glucoamylase. At present there are many different classes of maltase-glucoamylase inhibitors. This paper focuses on alkaloidal inhibitors of maltase-glucoamylase and structure-activity relationship (SAR) studies between them in order to discover some drugs with better efficiency and lower toxicity for treating diabetes. PMID:23967118

  13. One-pot synthesis of vinca alkaloids-phomopsin hybrids.

    PubMed

    Gherbovet, Olga; Coderch, Claire; García Alvarez, María Concepción; Bignon, Jérôme; Thoret, Sylviane; Guéritte, Françoise; Gago, Federico; Roussi, Fanny

    2014-06-26

    Hybrids of vinca alkaloids and phomopsin A have been elaborated with the aim of interfering with the "vinca site" and the "peptide site" of the vinca domain in tubulin. They were synthesized by an efficient one-pot procedure that directly links the octahydrophomopsin lateral chain to the velbenamine moiety of 7'-homo-anhydrovinblastine. In their modeled complexes with tubulin, these hybrids were found to superimpose nicely on the tubulin-bound structures of vinblastine and phomopsin A. This good matching can account for the fact that two of them are very potent inhibitors of microtubules assembly and are cytotoxic against four cancer cell lines. PMID:24871162

  14. Alkaloid and sesquiterpenes from the root tuber of Curcuma longa.

    PubMed

    Wang, Li-yao; Zhang, Mian; Zhang, Chao-feng; Wang, Zheng-tao

    2008-07-01

    One new quinoline alkaloid and seven known bisabolane sesquiterpenes: 2-(2'-methyl-1'-propenyl)-4, 6-dimethyl-7-hydroxyquinoline (1), 2, 5-dihydroxybisabola-3, 10-diene (2), 4, 5-dihydroxybisabola-2,10-diene (3), turmeronol A (4), bisacurone (5), bisacurone A (6), bisacurone B (7) , bisacurone C (8), as well as dehydrozingerone (9) and zingerone (10) were isolated from the root tuber of Curcuma longa. Their structures were identified by spectral evidence. Compound 1 is a new compound, compounds 6 -8 were isolated from this plant for the first time and compounds 9 - 10 from Curcuma for the first time. PMID:18819476

  15. Three new monoterpenoid indole alkaloids from Vinca major.

    PubMed

    Zhang, Zhi-Jun; Du, Ru-Nan; He, Juan; Wu, Xing-De; Li, Yan; Li, Rong-Tao; Zhao, Qin-Shi

    2016-04-01

    Three new monoterpenoid indole alkaloids, 19-hydroxyl-10-methoxy-19, 20-dihydrovinorine (1), 19-O-acetyl-10-methoxy-19, 20-dihydrovinorine (2), and 19, 21α-dihydroxyl-10-methoxy-19, 20-dihydrovinorine (3), along with five known analogues (4-8), were isolated from the whole plants of Vinca major. The new structures were elucidated by extensive NMR and MS analysis and comparison with known compounds. In addition, compounds 1-3 were evaluated for their cytotoxicities against five human cancer cell lines. PMID:26700398

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

    PubMed

    Pesqueira, A; Harmon, D L; Branco, A F; Klotz, J L

    2014-03-01

    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 was to compare contractile-response patterns of single additions of the ergoline alkaloids lysergic acid, lysergol, and ergonovine and the ergopeptine alkaloids ergotamine, ergocristine, ergocryptine, ergocornine, and ergovaline (provided as tall fescue seed extract). Lateral saphenous veins were collected from 6 Holstein steers (BW = 397 ± 28 kg) immediately after slaughter, sliced into cross-sections, and suspended in myograph chambers containing oxygenated Krebs-Henseleit buffer (95% O2/5% CO2; pH = 7.4; 37°C). Treatments were added at 0 min and buffer was replaced in 15-min intervals for a 120-min incubation. In addition to maximum tension and time to reach maximum tension, percent relaxation and rate of relaxation were determined following maximum tension for each treatment. All compounds tested produced significant contractile responses (P < 0.05). All ergoline alkaloids reached maximum response in less time (P < 0.05) than the remaining compounds and began to relax immediately after first buffer change. Lysergic acid had the greatest (P < 0.05) percent relaxation and ergonovine had the greatest (P < 0.05) rate of relaxation. The ergopeptine alkaloids ergovaline, ergotamine, ergocristine, ergocryptine, and ergocornine had slower developing contractile responses with a longer (P < 0.05) interval until maximum tension was achieved compared to the ergoline alkaloids. Maximal responses to all the ergopeptine alkaloids, however, all persisted for the 120-min duration with negligible relaxation occurring. The different classes of alkaloids differed greatly in the type of contractile response generated in the lateral saphenous vein. Persistence of contractile response is thought to be the primary contributing factor to the vasoconstriction observed in animals demonstrating signs of fescue toxicosis, where different ergot alkaloids can contribute differently. PMID:24492541

  17. 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

  18. 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.

  19. Numerical Integration

    ERIC Educational Resources Information Center

    Sozio, Gerry

    2009-01-01

    Senior secondary students cover numerical integration techniques in their mathematics courses. In particular, students would be familiar with the "midpoint rule," the elementary "trapezoidal rule" and "Simpson's rule." This article derives these techniques by methods which secondary students may not be familiar with and an approach that…

  20. 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

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

    PubMed Central

    Fedurco, Milan; Gregorová, Jana; Šebrlová, Kristýna; Kantorová, Jana; Peš, Ondřej; 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 α1β2γ2 GABAA receptor showed no effect of N-methyllaurotetanine at concentrations lower than 30 μM. However, (S)-reticuline behaved as positive allosteric modulator at the α3, α5, and α6 isoforms of GABAA receptors. The depressant properties of aerial parts of E. californica are assigned to chloride-current modulation by (S)-reticuline at the α3β2γ2 and α5β2γ2 GABAA receptors. Interestingly, α1, α3, and α5 were not significantly affected by (R)-reticuline, 1,2-tetrahydroreticuline, codeine, and morphine—suspected (S)-reticuline metabolites in the rodent brain. PMID:26509084

  2. Biosynthetic pathway of terpenoid indole alkaloids in Catharanthus roseus.

    PubMed

    Zhu, Xiaoxuan; Zeng, Xinyi; Sun, Chao; Chen, Shilin

    2014-09-01

    Catharanthus roseus is one of the most extensively investigated medicinal plants, which can produce more than 130 alkaloids, including the powerful antitumor drugs vinblastine and vincristine. Here we review the recent advances in the biosynthetic pathway of terpenoid indole alkaloids (TIAs) in C. roseus, and the identification and characterization of the corresponding enzymes involved in this pathway. Strictosidine is the central intermediate in the biosynthesis of different TIAs, which is formed by the condensation of secologanin and tryptamine. Secologanin is derived from terpenoid (isoprenoid) biosynthetic pathway, while tryptamine is derived from indole biosynthetic pathway. Then various specific end products are produced by different routes during downstream process. Although many genes and corresponding enzymes have been characterized in this pathway, our knowledge on the whole TIA biosynthetic pathway still remains largely unknown up to date. Full elucidation of TIA biosynthetic pathway is an important prerequisite to understand the regulation of the TIA biosynthesis in the medicinal plant and to produce valuable TIAs by synthetic biological technology. PMID:25159992

  3. Antimicrobial, Antiparasitic and Cytotoxic Spermine Alkaloids from Albizia schimperiana

    PubMed Central

    Samoylenko, Volodymyr; Jacob, Melissa R.; Khan, Shabana I.; Zhao, Jianping; Tekwani, Babu L.; Midiwo, Jacob O.; Walker, Larry A.

    2013-01-01

    Albizia schimperianaOliv. (Leguminosae) is a tree distributed in the highland of Kenya, where it is used as a traditional medicine for the treatment of bacterial and parasitic infections, notably pneumonia and malaria, respectively. Bioassay guided isolation of the CH2Cl2–MeOH 1:1/MeOH-H2O 9:1 (mixed) extract of A. schimperiana afforded the new bioactive macrocyclic spermine alkaloid, namely 5,14-dimethylbudmunchiamine L1 1 and three known budmunchiamine analogs 2-4. The structures of the compounds 1-4 were determined by 1D and 2D NMR data, including COSY, HMQC, and HMBC experiments, and ESI-HRMS. Compounds 1 and 3 exhibited significant in vitro antimicrobial activity against a panel of microorganisms, including C. neoformans, methicillin-resistant S. aureus, E. coli, M. intracellulare, A. fumigatus. In addition, they demonstrated strong in vitro antimalarial activities against chloroquine-susceptible (D6) and -resistant (W2) strains of Plasmodium falciparum with IC50s ranging from 120–270 ng/mL. Compounds 1-4 were also evaluated for cytotoxic activity against selected human cancer cell lines and mammalian kidney fibroblasts (VERO cells). It was observed that hydroxyl substitution of the side chain of the budmunchiamines dramatically reduced the cytotoxicity and antimicrobial activity of the alkaloids 2 and 4 without decreasing antimalarial activity. PMID:19634324

  4. Plant-like biosynthesis of isoquinoline alkaloids in Aspergillus fumigatus.

    PubMed

    Baccile, Joshua A; Spraker, Joseph E; Le, Henry H; Brandenburger, Eileen; Gomez, Christian; Bok, Jin Woo; Macheleidt, Juliane; Brakhage, Axel A; Hoffmeister, Dirk; Keller, Nancy P; Schroeder, Frank C

    2016-06-01

    Natural product discovery efforts have focused primarily on microbial biosynthetic gene clusters (BGCs) containing large multimodular polyketide synthases and nonribosomal peptide synthetases; however, sequencing of fungal genomes has revealed a vast number of BGCs containing smaller NRPS-like genes of unknown biosynthetic function. Using comparative metabolomics, we show that a BGC in the human pathogen Aspergillus fumigatus named fsq, which contains an NRPS-like gene lacking a condensation domain, produces several new isoquinoline alkaloids known as the fumisoquins. These compounds derive from carbon-carbon bond formation between two amino acid-derived moieties followed by a sequence that is directly analogous to isoquinoline alkaloid biosynthesis in plants. Fumisoquin biosynthesis requires the N-methyltransferase FsqC and the FAD-dependent oxidase FsqB, which represent functional analogs of coclaurine N-methyltransferase and berberine bridge enzyme in plants. Our results show that BGCs containing incomplete NRPS modules may reveal new biosynthetic paradigms and suggest that plant-like isoquinoline biosynthesis occurs in diverse fungi. PMID:27065235

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

    PubMed

    Huybrechts, Bart; Callebaut, Alfons

    2015-01-01

    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

  6. The total synthesis of the Galbulimima alkaloid GB 13.

    PubMed

    Mander, Lewis N; McLachlan, Matthew M

    2003-03-01

    This contribution describes a synthetic approach to alkaloid GB 13, previously isolated from the North Australian and Papua New Guinean rain forest tree Galbulimima belgraveana. A Birch reductive alkylation of 2,5-dimethoxybenzoic acid by 3-methoxybenzyl bromide, followed by an acid-catalyzed cyclization was used to synthesize the [3.3.1]bicyclononane 8. A ring contraction performed on the diazo derivative 9 of the [3.3.1]bicyclononane led to [3.2.1]bicyclooctane 10. This [3.2.1]bicyclooctane was converted into a dienophile and subjected to a Diels-Alder reaction to generate a pentacyclic intermediate 13 with a carbon skeleton closely resembling the target alkaloid. The surplus substituent, required for activation and regioselectivity in the Diels-Alder reaction, was removed using Birch reductive conditions to effect a decyanation. It was discovered that a Birch reduction of the aromatic ring also present in the molecule could be performed at the same time to give the enone 15, which was cleaved by means of an Eschenmoser fragmentation. The piperidine ring found in the natural product was formed by reductive cyclization of the bis-oxime 18 derived from the alkynyl ketone 17 and the resulting material further elaborated to GB 13 (1) via ketone 20. PMID:12603121

  7. Alkaloid delta agonist BW373U86 increases hypoxic tolerance.

    PubMed

    Bofetiado, D M; Mayfield, K P; D'Alecy, L G

    1996-06-01

    Activation of delta opioid receptors increases survival time during acute, lethal hypoxia in mice. delta Agonists therefore present a promising avenue for therapeutic application to reduce the morbidity and mortality associated with clinical hypoxia in settings such as drowning, head injury apnea, and complicated childbirths. However, most delta agonists now available are peptides, and may have limited clinical utility. In the present study, we evaluate the neuroprotective ability of an alkaloid delta agonist, BW373U86. Alkaloid compounds, due to increased stability and increased systemic distribution, may be more favorable for clinical use. We found that BW373U86, like the peptide delta agonist, DPDPE ([D-Pen2, D-Pen5]-enkephalin), increases survival time of mice during lethal hypoxia. The mechanism of neuroprotection induced by delta receptor activation appears to involve decreasing body temperature. Further, using selective opioid receptor antagonists, it appears that BW373U86 exerts these neuroprotective effects by acting at delta-opioid receptors. PMID:8638797

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

    PubMed

    Fedurco, Milan; Gregorová, Jana; Šebrlová, Kristýna; Kantorová, Jana; Peš, Ondřej; 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 α 1 β 2 γ 2 GABAA receptor showed no effect of N-methyllaurotetanine at concentrations lower than 30 μM. However, (S)-reticuline behaved as positive allosteric modulator at the α 3, α 5, and α 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 α 3 β 2 γ 2 and α 5 β 2 γ 2 GABAA receptors. Interestingly, α 1, α 3, and α 5 were not significantly affected by (R)-reticuline, 1,2-tetrahydroreticuline, codeine, and morphine-suspected (S)-reticuline metabolites in the rodent brain. PMID:26509084

  9. Biogenetically inspired synthesis and skeletal diversification of indole alkaloids.

    PubMed

    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. PMID:24345948

  10. Indole alkaloids synthesis via a selective cyclization of aminocyclopropanes.

    PubMed

    De Simone, Filippo; Waser, Jérôme

    2012-01-01

    The continuous progress in medicinal chemistry requires more versatile synthetic strategies for the generation of large libraries of active compounds and their analogues. As a result, the research for new effective cyclization and cycloaddition reactions is an essential task in organic chemistry. In 2008 we developed the first catalytic formal homo-Nazarov reaction starting from activated cyclopropanes. Herein we report the extension of the catalytic formal homo-Nazarov cyclization to aminocyclopropanes. Highly diastereoselective cyclizations were obtained via an acyliminium intermediate generated through opening of the cyclopropane. An excellent control over the regioselectivity of either the C-C or C-N cyclization in the case of free indoles as nucleophilic partners was achieved. The utility of the developed methodology was demonstrated by the generation of the polycyclic scaffolds of Aspidosperma and Gonioma natural products starting from a common intermediate. Based on this method, a formal total synthesis of the alkaloid aspidospermidine and the total synthesis of the alkaloid goniomitine are presented. Finally, the scope and limitations of our methodology are discussed on an extended range of vinyl-cyclopropyl ketones with cyclic or acyclic carbamates, as well as ethers as donor groups on the cyclopropane. PMID:22613157

  11. 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 neoadjuvant 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

  12. Mass-spectrometry-directed analysis and purification of pyrrolizidine alkaloid cis/trans isomers in Gynura japonica.

    PubMed

    Fang, Lianxiang; Xiong, Aizhen; Yang, Xiao; Cheng, Wenzhi; Yang, Li; Wang, Zhengtao

    2014-08-01

    Pyrrolizidine alkaloids are highly hepatotoxic natural chemicals that produce irreversible chronic and acute hepatotoxic effects on human beings. Purification of large amounts of pyrrolizidine alkaloids is necessary for toxicity studies. In this study, an efficient method for targeted analysis and purification of pyrrolizidine alkaloid cis/trans isomers from herbal materials was developed for the first time. Targeted analysis of the hepatotoxic pyrrolizidine alkaloids was performed by liquid chromatography with tandem mass spectrometry (precursor ion scan and daughter ion scan), and the purification of pyrrolizidine alkaloids was achieved with a mass-directed auto purification system. The extraction and preparative liquid chromatography conditions were optimized. The developed method was applied to analysis of Gynura japonica (Thunb.) Juel., a herbal medicine traditionally used for detumescence and relieving pain but is potentially hepatotoxic as it contains pyrrolizidine alkaloids. Twelve pyrrolizidine alkaloids (six cis/trans isomer pairs) were identified with reference compounds or characterized by liquid chromatography with tandem mass spectrometry, and five individual pyrrolizidine alkaloids, including (E)-seneciphylline, seneciphylline, integerrimine, senecionine, and seneciphyllinine, were prepared from G. japonica roots with high efficiency. The results of this work provide a new technique for the preparation of large amounts of pyrrolizidine alkaloid reference substances, which will also benefit toxicological studies of pyrrolizidine alkaloids and treatments for pyrrolizidine alkaloid-induced toxicity. PMID:24840731

  13. 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

  14. Geographic and seasonal variation in alkaloid-based chemical defenses of Dendrobates pumilio from Bocas del Toro, Panama.

    PubMed

    Saporito, Ralph A; Donnelly, Maureen A; Garraffo, H Martin; Spande, Thomas F; Daly, John W

    2006-04-01

    Poison frogs contain an alkaloid-based chemical defense that is derived from a diet of certain alkaloid-containing arthropods, which include mites, ants, beetles, and millipedes. Variation in population-level alkaloid profiles among species has been documented, and more than 800 different alkaloids have been identified. In the present study, we examine individual alkaloid variation in the dendrobatid poison frog Dendrobates pumilio among seven populations and between two seasons on Isla Bastimentos, located in the Bocas del Toro archipelago of Panama. Alkaloid profiles vary among populations and between seasons, illustrating that chemical defense in this species can vary on a small spatial and temporal scale. Alkaloid variation among populations is marginally correlated with geographic distance, and close populations have profiles more similar to each other than to distant populations. Individuals within populations also vary in alkaloid profiles. Differences are attributed to both spatial and temporal variations in the availability of alkaloid-containing arthropods. Many of the alkaloids present in the skin of D. pumilio appear likely to be of ant origin, supporting the importance of myrmecophagy in chemical defense among poison frogs. However, a variety of frog skin alkaloids was recently detected in mites, suggesting that mites may also play an important role in chemical defense. PMID:16718571

  15. Identification of the cytochrome P450 monooxygenase that bridges the clavine and ergoline alkaloid pathways.

    PubMed

    Haarmann, Thomas; Ortel, Ingo; Tudzynski, Paul; Keller, Ullrich

    2006-04-01

    Clavines and D-lysergic acid-derived alkaloid amides and alkaloid peptides are two different families of compounds that have the indole-derived tetracyclic metergoline ring system in common. Previous work has shown that D-lysergic acid is biosynthetically derived from clavine alkaloids. Recent cloning and analysis of the ergot alkaloid biosynthesis gene cluster from the D-lysergic acid peptide (ergopeptines)-producing Claviceps purpurea, has shown that it most probably contains all genes necessary for D-lysergic acid synthesis as well as those that encode the assembly of D-lysergic acid peptides, such as ergotamine. To address the role of the oxygenase genes of alkaloid-gene clusters, the only cytochrome P450 monooxygenase gene of this cluster was inactivated by disruption. The resultant mutant accumulated agroclavine, elymoclavine, and chanoclavine in substantial amounts but not ergopeptines. Feeding the mutant with D-lysergic acid restored ergopeptine synthesis; this suggests a block in the conversion of elymoclavine to D-lysergic acid. The gene was designated cloA (for encoding a clavine oxidase, CLOA). Retransformation of the mutant with the intact cloA gene also restored ergopeptine synthesis. These data show that CLOA catalyses the conversion of clavines to D-lysergic acid, it acts as a critical enzyme in the ergot alkaloid gene cluster, and bridges the biosynthesis of the two different families of alkaloids. PMID:16538694

  16. Variability for the presence of pyrrolizidine alkaloids in Crotolaria juncea L.

    PubMed

    Ji, Xiuhong; Khan, I; Mosjidis, J A; Wang, Hui; Livant, P

    2005-08-01

    Sunn hemp (Crotalaria juncea L.) is the most widely grown legume used as green manure in the tropics where it is also grown as a fiber and animal fodder crop. It has been reported that sunn hemp seeds contain several pyrrolizidine alkaloids that when ingested in sufficient amount can be toxic to animals and birds. No information is available regarding variability for the presences of the different types of pyrrolizidine alkaloids in the seeds. The objective of this research was to analyze sunn hemp seeds of nine populations that originated in different parts of the world for several pyrrolizidine alkaloids to determine their level of variability for the presence of these compounds and to quantify the total amount of pyrrolizidine alkaloids in the seeds. Of the nine pyrrolizidine alkaloids tested, the sunn hemp populations only had junceine and trichodesmine. PI 207657 had very low levels of both alkaloids and PI 314239, PI 322377, PI 346297, and the US cultivar Tropic Sun had very low levels of trichodesmine. Although juncein was present in higher amounts than trichodesmine in the seeds of most accessions, its value was deemed to be small. The amount of pyrrolizidine alkaloids present in the sunn hemp populations studied was low. PMID:16124407

  17. DNA topoisomerase-directed anticancerous alkaloids: ADMET-based screening, molecular docking, and dynamics simulation.

    PubMed

    Singh, Swati; Das, Tamal; Awasthi, Manika; Pandey, Veda P; Pandey, Brijesh; Dwivedi, Upendra N

    2016-02-01

    Topoisomerases (Topo I and II) have been looked as crucial targets against various types of cancers. In the present paper, 100 anticancerous alkaloids were subjected to in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses to investigate their pharmacokinetic properties. Out of 100 alkaloids, only 18 were found to fulfill all the ADMET descriptors and obeyed the Lipinski's rule of five. All the 18 alkaloids were found to dock successfully within the active site of both Topo I and II. A comparison of the inhibitory potential of 18 screened alkaloids with those of selected drugs revealed that four alkaloids (oliveroline, coptisine, aristolactam, and piperine) inhibited Topo I, whereas six alkaloids (oliveroline, aristolactam, anonaine, piperine, coptisine, and liriodenine) inhibited Topo II more strongly than those of their corresponding drugs, topotecan and etoposide, respectively, with oliveroline being the outstanding. The stability of the complexes of Topo I and II with the best docked alkaloid, oliveroline, was further analyzed using 10 nSec molecular dynamics simulation and compared with those of the respective drugs, namely, topotecan and etoposide, which revealed stabilization of these complexes within 5 nSec of simulation with better stability of Topo II complex than that of Topo I. PMID:25594242

  18. 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.

  19. Alkaloids: an overview of their antibacterial, antibiotic-enhancing and antivirulence activities.

    PubMed

    Cushnie, T P Tim; Cushnie, Benjamart; Lamb, Andrew J

    2014-11-01

    With reports of pandrug-resistant bacteria causing untreatable infections, the need for new antibacterial therapies is more pressing than ever. Alkaloids are a large and structurally diverse group of compounds that have served as scaffolds for important antibacterial drugs such as metronidazole and the quinolones. In this review, we highlight other alkaloids with development potential. Natural, semisynthetic and synthetic alkaloids of all classes are considered, looking first at those with direct antibacterial activity and those with antibiotic-enhancing activity. Potent examples include CJ-13,136, a novel actinomycete-derived quinolone alkaloid with a minimum inhibitory concentration of 0.1 ng/mL against Helicobacter pylori, and squalamine, a polyamine alkaloid from the dogfish shark that renders Gram-negative pathogens 16- to >32-fold more susceptible to ciprofloxacin. Where available, information on toxicity, structure-activity relationships, mechanisms of action and in vivo activity is presented. The effects of alkaloids on virulence gene regulatory systems such as quorum sensing and virulence factors such as sortases, adhesins and secretion systems are also described. The synthetic isoquinoline alkaloid virstatin, for example, inhibits the transcriptional regulator ToxT in Vibrio cholerae, preventing expression of cholera toxin and fimbriae and conferring in vivo protection against intestinal colonisation. The review concludes with implications and limitations of the described research and directions for future research. PMID:25130096

  20. Anti-leishmanial activity of alkaloidal extracts obtained from different organs of Aspidosperma ramiflorum.

    PubMed

    Cunha, Ananda de Castro; Chierrito, Talita Perez Cantuaria; Machado, Gerzia Maria de Carvalho; Leon, Leonor Laura Pinto; da Silva, Cleuza Conceição; Tanaka, Julio Cesar; de Souza, Lauro Mera; Gonçalves, Regina Aparecida Correia; de Oliveira, Arildo José Braz

    2012-03-15

    The present study was designated to evaluate semi-quantitative antileishmanial activity of alkaloidal extracts that were obtained from 1g of different parts of Aspidosperma ramiflorum (leaves, roots, seeds, and stem barks). Alkaloidal extracts of barks and leaves presented a good activity against the extracellular form (promastigotes) of Leishmania (L.) amazonensis. It is known that compounds responsible for the antileishmanial activity in the alkaloidal extracts from A. ramiflorum are the monoterpenoid indole alkaloids ramiflorine A and ramiflorine B, therefore extracts obtained from different plant parts were analyzed by electrospray ionization mass spectrometry (ESI-MS) in order to evidence the presence of these bioactive alkaloids. Based on these findings, alkaloidal extract from leaves was fractionated on preparative thin-layer chromatography in a bioassay-guided fractionation affording individual purified ramiflorines A and B. Both ramiflorines A and B showed significant activity against Leishmania (L.) amazonensis (LD(50) values of 18.5±6.5μg/ml and 12.63±5.52μg/ml, respectively). Our results are showing that alkaloidal extract from leaves is a promising alternative to the use of stem barks from A. ramiflorum. PMID:22326547

  1. Rapid selective screening and determination of ephedrine alkaloids using GC-MS footnote mark.

    PubMed

    Ranieri, Tracy L; Ciolino, Laura A

    2008-01-01

    Ephedra (ma huang) has been widely used as an herb or herbal extract in both traditional Chinese medicine and Western world dietary supplements. The effects of Ephedra have been attributed to a series of six ephedrine alkaloids including ephedrine and pseudoephedrine. A GC-MS method for the ephedrine alkaloids is described which couples ammoniacal chloroform as the extraction solvent with a two-stage derivatisation scheme. This scheme produces the O-trimethylsilyl, N-trifluoracetyl derivatives (O-TMS, N-TFA) for the primary and secondary amine alkaloids, and the O-TMS derivatives for the tertiary amine alkaloids. Relatively clean extracts are obtained from complex matrices, and the six ephedrine alkaloids are effectively separated and identified. This approach was also evaluated for quantitative analysis, and was shown to provide quantitative results for ephedrine and pseudoephedrine, and good estimates for the four minor alkaloids. Figures of merit are presented for linearity, detection limits, precision and accuracy. We have applied this approach to the rapid screening and profiling of the ephedrine alkaloids in whole Ephedra plants, liquid plant extracts, dried powder plant extracts and a variety of Ephedra-containing dietary supplements. PMID:17879230

  2. Melyrid beetles (Choresine): a putative source for the batrachotoxin alkaloids found in poison-dart frogs and toxic passerine birds.

    PubMed

    Dumbacher, John P; Wako, Avit; Derrickson, Scott R; Samuelson, Allan; Spande, Thomas F; Daly, John W

    2004-11-01

    Batrachotoxins are neurotoxic steroidal alkaloids first isolated from a Colombian poison-dart frog and later found in certain passerine birds of New Guinea. Neither vertebrate group is thought to produce the toxins de novo, but instead they likely sequester them from dietary sources. Here we describe the presence of high levels of batrachotoxins in a little-studied group of beetles, genus Choresine (family Melyridae). These small beetles and their high toxin concentrations suggest that they might provide a toxin source for the New Guinea birds. Stomach content analyses of Pitohui birds revealed Choresine beetles in the diet, as well as numerous other small beetles and arthropods. The family Melyridae is cosmopolitan, and relatives in Colombian rain forests of South America could be the source of the batrachotoxins found in the highly toxic Phyllobates frogs of that region. PMID:15520388

  3. Structure-Activity Relationship of Benzophenanthridine Alkaloids from Zanthoxylum rhoifolium Having Antimicrobial Activity

    PubMed Central

    Tavares, Luciana de C.; Zanon, Graciane; Weber, Andréia D.; Neto, Alexandre T.; Mostardeiro, Clarice P.; Da Cruz, Ivana B. M.; Oliveira, Raul M.; Ilha, Vinicius; Dalcol, Ionara I.; Morel, Ademir F.

    2014-01-01

    Zanthoxylum rhoifolium (Rutaceae) is a plant alkaloid that grows in South America and has been used in Brazilian traditional medicine for the treatment of different health problems. The present study was designed to evaluate the antimicrobial activity of the steam bark crude methanol extract, fractions, and pure alkaloids of Z. rhoifolium. Its stem bark extracts exhibited a broad spectrum of antimicrobial activity, ranging from 12.5 to 100 µg/mL using bioautography method, and from 125 to 500 µg/mL in the microdilution bioassay. From the dichloromethane basic fraction, three furoquinoline alkaloids (1–3), and nine benzophenanthridine alkaloids (4–12) were isolated and the antimicrobial activity of the benzophenanthridine alkaloids is discussed in terms of structure-activity relationships. The alkaloid with the widest spectrum of activity was chelerythrine (10), followed by avicine (12) and dihydrochelerythrine (4). The minimal inhibitory concentrations of chelerythrine, of 1.50 µg/mL for all bacteria tested, and between 3.12 and 6.25 µg/mL for the yeast tested, show this compound to be a more powerful antimicrobial agent when compared with the other active alkaloids isolated from Z. rhoifolium. To verify the potential importance of the methylenedioxy group (ring A) of these alkaloids, chelerythrine was selected to represent the remainder of the benzophenanthridine alkaloids isolated in this work and was subjected to a demethylation reaction giving derivative 14. Compared to chelerythrine, the derivative (14) was less active against the tested bacteria and fungi. Kinetic measurements of the bacteriolytic activities of chelerythrine against the bacteria Bacillus subtilis (Gram-positive) and Escherichia coli (Gram-negative) were determined by optical density based on real time assay, suggesting that its mechanism of action is not bacteriolytic. The present study did not detect hemolytic effects of chelerythrine on erythrocytes and found a protective effect considering the decrease in TBARS and AOPP (advanced oxidized protein products) levels when compared to the control group. PMID:24824737

  4. Variability in alkaloid profiles in neotropical poison frogs (Dendrobatidae): genetic versus environmental determinants.

    PubMed

    Daly, J W; Secunda, S I; Garraffo, H M; Spande, T F; Wisnieski, A; Nishihira, C; Cover, J F

    1992-08-01

    Dendrobatid frogs produce a diverse set of alkaloids, whose profiles appear characteristic of frogs of each species or, in the case of variable species, of each population. In the case of one widespread species, Dendrobates auratus, alkaloid profiles in extracts of skin are markedly different in three populations, one from a Pacific island, Isla Taboga, Panama, one from central mountains in Panama, and the third from the Caribbean coast in Costa Rica. The first contains three major classes of dendrobatid alkaloids, the histrionicotoxins, the pumiliotoxin-A class and the decahydroquinolines. The second contains mainly histrionicotoxins, pumiliotoxin-A class alkaloids and one indolizidine. The third contains histrionicotoxins, a homopumiliotoxin, one decahydroquinoline, and a variety of indolizidines, quinolizidines and pyrrolizidines. Frogs from Isla Taboga or a nearby island were introduced into the Manoa Valley, Oahu, Hawaii, in 1932. Remarkably, although alkaloids of the pumiliotoxin-A class and one decahydroquinoline are still major constituents in skin extracts of Hawaiian frogs descended from the 1932 founding population, histrionicotoxins are absent and a novel tricyclic alkaloid is present. Offspring of wild-caught parents from Hawaii, Panama or Costa Rica raised in indoor terrariums on a diet of crickets and fruit flies do not contain detectable amounts of skin alkaloids. Offspring raised in large outside terrariums in Hawaii and fed mainly wild-caught termites and fruit flies do contain the same profile of alkaloids as their wild-caught parents in Hawaii, but at reduced levels. The genetic, environmental and dietary determinants of alkaloid profiles in dendrobatid frogs remain obscure, in particular the underlying cause for total absence in terrarium-reared frogs. PMID:1523680

  5. Genotoxicity of the boldine aporphine alkaloid in prokaryotic and eukaryotic organisms.

    PubMed

    Moreno, P R; Vargas, V M; Andrade, H H; Henriques, A T; Henriques, J A

    1991-06-01

    The aporphine alkaloid boldine, present in Peumus boldus (boldo-do-Chile) widely used all over the world, was tested for the presence of genotoxic, mutagenic and recombinogenic activities in microorganisms. This alkaloid did not show genotoxic activity with or without metabolic activation in the SOS chromotest and Ames tester strains TA100, TA98 and TA102. It was not able to induce point and frameshift mutations in haploid Saccharomyces cerevisiae cells. However, mitotic recombinational events such as crossing-over and gene conversion were weakly induced in diploid yeast cells by this alkaloid. Also, boldine was able to induce weakly cytoplasmic 'petite' mutation in haploid yeast cells. PMID:2046695

  6. 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

  7. Methods for regeneration and transformation in Eschscholzia californica: A model plant to investigate alkaloid biosynthesis.

    PubMed

    MacLeod, Benjamin P; Facchini, Peter J

    2006-01-01

    Eschscholzia californica Cham. (California poppy) is a plant species that accumulates pharmacologically active alkaloids biosynthetically related to the morphinan alkaloids of Papaver somniferum. This, in combination with the relative ease with which it is propagated in vitro, makes it a key model for benzylisoquinoline biosynthesis. Transformation techniques are an important tool for these studies and for metabolic engineering attempts. Agrobacterium mediated transformation techniques for this model species have been developed in our lab and used for modulation of transcript levels relevant to the biosynthesis of these alkaloids. Here we describe the techniques used in our lab for production of transgenic callus, hairy root cultures, and whole plants. PMID:16673930

  8. Lesions of potato sprout and extracted potato sprout alkaloid toxicity in Syrian hamsters.

    PubMed

    Baker, D; Keeler, R; Gaffield, W

    1987-01-01

    Hamsters were gavaged either dried potato sprout material, alkaloid extract of potato sprouts, or the marc from which the alkaloid fraction was extracted and then were examined for gross and microscopic lesions. Nine of 10 hamsters receiving dried potato sprout material and 3 of 5 hamsters receiving alkaloid extract had severe gastric and intestinal mucosal necrosis which was most severe in the glandular stomach, duodenum and proximal jejunum. All control hamsters gavaged with water and all hamsters gavaged with the potato sprout marc survived to the time of euthanasia and did not have gross or microscopic lesions. PMID:3612898

  9. Toxic alkaloids and their interaction with microsomal cytochrome P-450 in vitro.

    PubMed

    Peeples, A; Dalvi, R R

    1982-12-01

    Studies on the binding spectra of certain alkaloids with rat liver microsomes revealed that brucine, scopolamine and strychnine are type I compounds, whereas boldine, emetine, nicotine, reserpine and sanguinarine show type II binding. In contrast, colchicine and solanine failed to produce any measurable binding spectra. In vitro incubation of colchicine, nicotine or scopolamine with microsomal suspensions and NADPH resulted in demethylation of these alkaloids, while the incubation of boldine, brucine, emetine, reserpine, sanguinarine or solanine showed little or no dealkylation reaction. Furthermore, the effect of these alkaloids on the in vitro microsomal metabolism of a drug, benzphetamine, has also been studied. PMID:7185909

  10. Anti-inflammatory Activity of Pyrrolizidine Alkaloids from the Leaves of Madhuca pasquieri (Dubard).

    PubMed

    Hoang, Le Son; Tran, Manh Hung; Lee, Joo Sang; To, Dao Cuong; Nguyen, Van Thu; Kim, Jeong Ah; Lee, Jeong Hyung; Woo, Mi Hee; Min, Byung Sun

    2015-01-01

    A novel pyrrolizidine alkaloids, madhumidine A (1), and two known alkaloids, lindelofidine benzoic acid ester (2) and minalobine B (3) were isolated from the leaves of Madhuca pasquieri (Dubard) H. J. LAM. The chemical structures of these alkaloids were established mainly by NMR techniques and mass spectrometry. Their anti-inflammatory activity was evaluated against lipopolysaccharide-induced nitric oxide production in macrophage RAW264.7 cell. In addition, the cytotoxic activity of all isolated compounds was tested against a panel of cancer cell lines. PMID:26027474

  11. Ergot alkaloids in cereal products: results from the Bavarian Health and Food Safety Authority.

    PubMed

    Bürk, Gisela; Höbel, Werner; Richt, Anita

    2006-04-01

    The danger of ergot alkaloids has been well known for centuries. The origin and toxicology of these compounds have been clarified and flour mills assure us that they have mastered the problem technologically. Nevertheless, one can find food products with sometimes relatively high contents of these toxic alkaloids. Here we report on our experiences and results of an LC-MS/MS-method which we have developed to determine ergot alkaloids and which was applied to commercial products during the past two years. PMID:16548013

  12. Influence of Some Heavy Metals on Growth, Alkaloid Content and Composition in Catharanthus roseus L.

    PubMed Central

    Srivastava, N. K.; Srivastava, A. K.

    2010-01-01

    Shoot biomass production, alkaloid content and composition as influence by cadmium, manganese, nickel and lead at uniform dose of 5 mM were investigated in Catharanthus roseus plants grown in sand culture. Treatment with Mn, Ni, and Pb significantly enhanced total root alkaloid accumulation. Cd and Ni treatment resulted in two-fold where as Pb treatment resulted in three fold increase in serpentine content of roots. The non-significant affect on biomass suggests that plants can withstand metal stress at the level tested with positive affect on root alkaloid content. PMID:21969751

  13. Unified Total Syntheses of Fawcettimine Class Alkaloids: Fawcettimine, Fawcettidine, Lycoflexine, and Lycoposerramine B

    PubMed Central

    Pan, Guojun; Williams, Robert M.

    2012-01-01

    The total syntheses of the lycopodium alkaloids: fawcettimine, fawcettidine, lycoflexine, and lycoposerramine B have been accomplished through an efficient, unified, and stereocontrolled strategy, which relies on a Diels-Alder reaction to construct the cis-fused 6,5-carbocycles with one all-carbon quaternary center. Access to the enantioselective syntheses of both antipodes of those alkaloids can be achieved by kinetic resolution of the earliest intermediate via a Sharpless asymmetric dihydroxylation (Sharpless AD). Compared to existing approaches to these alkaloids, our synthetic route possesses superior stereocontrol over the C-4 and C-15 stereogenic centers as well as allowing for more functional variation on the 6-membered ring. PMID:22519642

  14. [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

  15. Alkaloids from an algicolous strain of Talaromyces sp.

    NASA Astrophysics Data System (ADS)

    Yang, Haibin; Li, Fang; Ji, Naiyun

    2016-03-01

    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.

  16. DNA binding studies of Vinca alkaloids: experimental and computational evidence.

    PubMed

    Pandya, Prateek; Gupta, Surendra P; Pandav, Kumud; Barthwal, Ritu; Jayaram, B; Kumar, Surat

    2012-03-01

    Fluorescence studies on the indole alkaloids vinblastine sulfate, vincristine sulfate, vincamine and catharanthine have demonstrated the DNA binding ability of these molecules. The binding mode of these molecules in the minor groove of DNA is non-specific. A new parameter of the purine-pyrimidine base sequence specificty was observed in order to define the non-specific DNA binding of ligands. Catharanthine had shown 'same' pattern of 'Pu-Py' specificity while evaluating its DNA binding profile. The proton resonances of a DNA decamer duplex were assigned. The models of the drug:DNA complexes were analyzed for DNA binding features. The effect of temperature on the DNA binding was also evaluated. PMID:22545401

  17. Antimalarial Oxoprotoberberine Alkaloids from the Leaves of Miliusa cuneata.

    PubMed

    Promchai, Thanika; Jaidee, Atchara; Cheenpracha, Sarot; Trisuwan, Kongkiat; Rattanajak, Roonglawan; Kamchonwongpaisan, Sumalee; Laphookhieo, Surat; Pyne, Stephen G; Ritthiwigrom, Thunwadee

    2016-04-22

    Five new oxoprotoberberine alkaloids, miliusacunines A-E (1-5), along with nine known compounds, 6-14, were isolated from an acetone extract of the leaves and twigs of Miliusa cuneata. Their structures were elucidated by spectroscopic analysis. All isolated compounds were evaluated for their cytotoxicities against the KB and Vero cell lines and for antimalarial activities against the Plasmodium falciparum strains TM4 and K1 (a sensitive and a multi-drug-resistant strain, respectively). Compound 1 showed in vitro antimalarial activity against the TM4 strain, with an IC50 value of 19.3 ± 3.4 μM, and compound 2 demonstrated significant activity against the K1 strain, with an IC50 value of 10.8 ± 4.1 μM. Both compounds showed no discernible cytotoxicity to the Vero cell line at the concentration levels evaluated. PMID:26928423

  18. Vitiquinolone--a quinolone alkaloid from Hibiscus vitifolius Linn.

    PubMed

    Ramasamy, D; Saraswathy, A

    2014-02-15

    Phytochemical investigations of the powdered root of Hibiscus vitifolius Linn. (Malvaceae) was extracted successively with n-hexane and chloroform. Analysis of the n-hexane extract by GC-MS led to the identification of twenty-six components by comparison of their mass spectra with GC-MS library data. A novel quinolone alkaloid, vitiquinolone (5) together with eight known compounds viz. β-Amyrin acetate (1), n-octacosanol (2), β-Amyrin (3), stigmasterol (4), xanthyletin (6), alloxanthoxyletin (7), xanthoxyletin (8) and betulinic acid (9) were isolated from chloroform extract by column chromatography over silica gel. The structure of vitiquinolone was established on the basis of spectroscopic methods including UV, IR, 1D, 2D NMR and ESI-MS. The known compounds were identified on the basis of their physical and spectroscopic data as reported in the literature. PMID:24128571

  19. Pyrrolizidine alkaloids in medicinal plants from North America.

    PubMed

    Roeder, E; Wiedenfeld, H; Edgar, J A

    2015-06-01

    Pyrrolizidine alkaloids (PAs) are mutagenic, carcinogenic, pneumotoxic, teratogenic and fetotoxic. Plants containing PAs commonly poison livestock in many countries, including the USA and Canada. In some regions of the world PA-producing plants sometimes grow in grain crops and items of food made with PA contaminated grain, such as bread baked using contaminated flour, have been, and continue to be, responsible for large incidents of acute, often fatal human poisoning. Herbal medicines and food supplements containing PAs are also recognized as a significant cause of human poisoning and it is desirable that such medications are identified and subjected to strict regulation. In this review we consider the PAs known to be, or likely to be, present in both the traditionally used medicinal plants of North America and also medicinal plants that have been introduced from other countries and are being recommended and used as phytopharmaceuticals in the USA and Canada. PMID:26189295

  20. 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

  1. Indole alkaloid glucosides from the roots of Isatis indigotica.

    PubMed

    Liu, Yu-Feng; Chen, Ming-Hua; Lin, Sheng; Li, Yu-Huan; Zhang, Dan; Jiang, Jian-Dong; Shi, Jian-Gong

    2016-01-01

    Five new indole alkaloid glucosides named isatindigotindolosides A-E (1-5), along with three known analogs (6-8), were isolated from an aqueous extract of the Isatis indigotica roots. Their structures including the absolute configurations were determined based on comprehensive spectroscopic data analysis, combined with chemical methods and electronic circular dichroism spectra calculations. In the preliminary assays, compounds 1, 6 and 7 showed antiviral activity against influenza virus A/Hanfang/359/95 (H3N2) with IC50 values of 14.6-33.3 μM. Compound 1 also exhibited inhibitory effect against nitric oxide (NO) production in microglial cell BV2 with an inhibition ratio of 93.0% at 10 μM. PMID:26651370

  2. 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 γ-alkylidene-α,β-unsaturated-γ-lactone or γ-alkylidene-α,β-unsaturated-γ-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

  3. Synthesis and biological evaluation of vinca alkaloids and phomopsin hybrids.

    PubMed

    Ngo, Quoc Anh; Roussi, Fanny; Cormier, Anthony; Thoret, Sylviane; Knossow, Marcel; Guénard, Daniel; Guéritte, Françoise

    2009-01-01

    Ten hybrids of vinca alkaloids and phomopsin A have been synthesized by linking the octahydrophomopsin lateral chain to the tertiary amine of the cleavamine moiety of anhydrovinblastine (AVLB) and vinorelbine. These compounds have been elaborated in order to obtain original products that may interfere with both binding sites of vinblastine (VLB) and phomopsin in tubulin. Although NMR and molecular modeling studies have shown that the orientation of the added peptide chains of these hybrids is not the same as those of phomopsin A, most of them are very potent inhibitors of microtubules assembly and they present good cytotoxicity against KB cell line. These interesting biological activities may eventually be explained by the fact that their lateral chain resides in a pocket distinct from that of the phomopsin A peptide, at the interface of tubulins beta and alpha. PMID:19072542

  4. Fumigaclavine I, a new alkaloid isolated from endophyte Aspergillus terreus.

    PubMed

    Shen, Li; Zhu, Li; Luo, Qian; Li, Xiao-Wen; Xi, Ju-Qun; Kong, Gui-Mei; Song, Yong-Chun

    2015-12-01

    The present study was designed to isolate and purify chemical constituents from solid culture of endophyte Aspergillus terreus LQ, using silica gel column chromatography, gel filtration with Sephadex LH-20, and HPLC. Fumigaclavine I (1), a new alkaloid, was obtained, along with seven known compounds, including fumigaclavine C (2), rhizoctonic acid (3), monomethylsulochrin (4), chaetominine (5), spirotryprostatin A (6), asperfumoid (7), and lumichrome (8). The structure of compound 1 was elucidated by various spectroscopic analyses (UV, MS, 1D and 2D NMR). The in vitro cytotoxicity of compound 1 was determined by MTT assay in human hepatocarcinoma cell line SMMC-7721, showing weaker cytotoxicity, compared with cisplatin, a clinically used cancer chemotherapeutic agent. PMID:26721713

  5. 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.

  6. Antileishmanial activity of indole alkaloids from Aspidosperma ramiflorum.

    PubMed

    Tanaka, J C A; da Silva, C C; Ferreira, I C P; Machado, G M C; Leon, L L; de Oliveira, A J B

    2007-06-01

    The present study was designated to evaluate the antileishmanial activity of acid and basic fractions that were obtained after acid-basic extraction, from ethanolic 70% crude extract and pure compounds from the stem bark of Aspidosperma ramiflorum. The basic alkaloidal fraction presented a good activity against the extracellular form (promastigotes) of Leishmania (L.) amazonensis (LD(50) value<47 microg/ml). Based on these findings, the basic fraction was fractionated on silica gel column chromatography in a bioassay-guided fractionation affording individual purified ramiflorines A and B. Both ramiflorines A and B showed significant activity against Leishmania (L.) amazonensis (LD(50) values of 16.3+/-1.6 microg/ml and 4.9+/-0.9 microg/ml, respectively). Our results are promising, showing that these compounds are biologically active against Gram-positive bacteria. PMID:17140782

  7. Determination of ephedrine alkaloids in dietary supplement standard reference materials.

    PubMed

    Sander, Lane C; Sharpless, Katherine E; Satterfield, Mary B; Ihara, Toshihide; Phinney, Karen W; Yen, James H; Wise, Stephen A; Gay, Martha L; Lam, Joseph W; McCooeye, Margaret; Gardner, Graeme; Fraser, Catharine; Sturgeon, Ralph; Roman, Mark

    2005-05-15

    A suite of five ephedra-containing dietary supplement Standard Reference Materials (SRMs) has been issued by the National Institute of Standards and Technology (NIST) with certified values for ephedrine alkaloids, synephrine, caffeine, and selected toxic trace elements. The materials represent a variety of natural, extracted, and processed sample matrixes that provide different analytical challenges. The constituents have been determined by multiple independent methods with measurements performed by NIST and by three collaborating laboratories. The methods utilized different sample extraction and cleanup steps in addition to different instrumental analytical techniques and approaches to quantification. In addition, food-matrix proximates were determined by National Food Processor Association laboratories for one of the ephedra-containing SRMs. The SRMs are primarily intended for method validation and for use as control materials to support the analysis of dietary supplements and related botanical materials. PMID:15889898

  8. Reviewing Colchicaceae Alkaloids – Perspectives of Evolution on Medicinal Chemistry

    PubMed Central

    Larsson, Sonny; Rønsted, Nina

    2014-01-01

    The subject of chemosystematics has provided insight to both botanical classification and drug development. However, degrees of subjectivity in botanical classifications and limited understanding of the evolution of chemical characters and their biosynthetic pathways has often hampered such studies. In this review an approach of taking phylogenetic classification into account in evaluating colchicine and related phenethylisoquinoline alkaloids from the family Colchicaceae will be applied. Following on the trends of utilizing evolutionary reasoning in inferring mechanisms in eg. drug resistance in cancer and infections, this will exemplify how thinking about evolution can influence selection of plant material in drug lead discovery, and how knowledge about phylogenetic relationships may be used to evaluate predicted biosynthetic pathways. PMID:24359194

  9. 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 FADH₂ dependent halogenase can be involved in the biosynthesis of the produced halocompounds. PMID:26404231

  10. Cryptolepine hydrochloride: a potent antimycobacterial alkaloid derived from Cryptolepis sanguinolenta.

    PubMed

    Gibbons, Simon; Fallah, Fatemeh; Wright, Colin W

    2003-04-01

    The activity of cryptolepine hydrochloride, a salt of the main indoloquinoline alkaloid from the West African medicinal plant Cryptolepis sanguinolenta, was assessed against the fast growing mycobacterial species Mycobacterium fortuitum, which has recently been shown to be of use in the evaluation of antitubercular drugs. The low minimum inhibitory concentration (MIC) of this compound (16 microg/mL) prompted further evaluation against other fast growing mycobacteria namely, M. phlei, M. aurum, M. smegmatis, M. bovis BCG and M. abcessus and the MICs ranged over 2-32 microg/mL for these species. The strong activity of this agent, the need for new antibiotics with activity against Mycobacterium tuberculosis, coupled with the ethnobotanical use of C. sanguinolenta extracts to treat infections, highlight the potential of the cryptolepine template for development of antimycobacterial agents. PMID:12722159

  11. The Biogeographical Distribution of Duncecap Larkspur (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...

  12. 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...

  13. 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...

  14. 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...

  15. Occurrence of skin alkaloids in non-dendrobatid frogs from Brazil (Bufonidae), Australia (Myobatrachidae) and Madagascar (Mantellinae).

    PubMed

    Daly, J W; Highet, R J; Myers, C W

    1984-01-01

    Several taxa of small frogs from the southern hemisphere contain alkaloids similar or identical to compounds previously known only from neotropical poison frogs of the family Dendrobatidae. Skin of the Brazilian toad Melanophryniscus moreirae (family Bufonidae) contains a new alkaloid 8-hydroxy-8-methyl-6-(5'-hydroxy-2'-methyl-hexylidene)-1-azabicycl o-[4.3.0] nonane (C16H29NO2), which is designated pumiliotoxin 267C. Such a structure is typical of the pumiliotoxin-A class of dendrobatid alkaloids. Melanophyryniscus moreirae contains smaller quantities of an alkaloid (C19H33NO3) identical in chromatographic and mass spectral properties to the dendrobatid alkaloid allopumiliotoxin 323B. Allopumiliotoxin 323B and an isomer of 267C occur with unidentified alkaloids in skin of the Australian frog Pseudophryne semimarmorata (family Myobatrachidae) and also in the skin of the Madagascan frog Mantella aurantiaca (family Ranidae, subfamily Mantellinae). In addition to new compounds, Mantella aurantiaca and M. madagascariensis also contain other alkaloids (e.g. histrionicotoxin and pumiliotoxin B) that were known previously only in dendrobatid frogs. Such alkaloids have not been detected in a phylogenetically wide array of other anuran amphibians, and the dendrobatid alkaloids thus become an evolutionary enigma. Certain of these compounds may have arisen convergently from new biosynthetic pathways in several families of frogs, or these alkaloids may represent parallel expression of shared-primitive pathways that are unexpressed or lost in related frogs. PMID:6523513

  16. 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

  17. Independent recruitment of a flavin-dependent monooxygenase for safe accumulation of sequestered pyrrolizidine alkaloids in grasshoppers and moths.

    PubMed

    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

  18. 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 7β-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).

  19. Studies of Genetic Variation of Essential Oil and Alkaloid Content in Boldo (Peumus boldus).

    PubMed

    Vogel, H; Razmilic, I; Muñoz, M; Doll, U; Martin, J S

    1999-02-01

    Boldo is a tree or shrub with medicinal properties native to Chile. The leaves contain alkaloids and essential oils. Variation of total alkaloid concentration, of the alkaloid boldine, and essential oil components were studied in different populations from northern, central, and southern parts of its geographic range and in their progenies (half-sib families). Total alkaloid concentration showed genetic variation between progenies of the central population but not between populations. Boldine content found in concentrations of 0.007 to 0.009% did not differ significantly between populations. Principal components of the essential oil were determined genetically, with highest values for ascaridole in the population of the north and for P-cymene in the south. Between half-sib families genetic variation was found in the central and northern populations for these components. The high heritability coefficients found indicate considerable potential for successful selection of individuals for these characters. PMID:17260243

  20. 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

  1. 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

  2. Apparent effects of glyphosate on alkaloid production in coca plants grown in Colombia.

    PubMed

    Casale, John; Lydon, John

    2007-05-01

    During the routine analysis of coca leaf material from South America, alkaloids in Erythroxylum coca var. ipadu (ECVI) leaf samples from fields suspected of being treated with glyphosate were compared with those from non-treated E. coca var. ipadu and Erythroxylum novogranatense var. novogranatense (ENVN) plants. Cocaine levels in leaf tissue from non-treated ECVI and ENVN were 0.53+/-0.08% and 0.64+/-0.08% (w/w), respectively, whereas leaves from treated plants were nearly devoid of cocaine. Further analysis demonstrated the presence of several previously undescribed N-nortropane alkaloids, several of which were tentatively identified. The results suggest that applications of glyphosate to coca plants can have dramatic effects on the quantity and quality of alkaloids produced by surviving or subsequent leaves. The analytical data presented will be of value to forensic chemists who encounter illicit cocaine preparations containing alkaloids produced from coca plants treated with glyphosate. PMID:17456084

  3. Effect of ergot alkaloids on contractility of bovine right ruminal artery and vein

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Alkaloids produced by the Neotyphodium coenophialum endophyte associated with tall fescue (Lolium arundinaceum) are imputed to cause symptoms of fescue toxicosis related to peripheral vasoconstriction. These compounds were hypothesized to correspondingly affect foregut vasculature. The objective of ...

  4. 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...

  5. Indolizidine 239Q and Quinolizidine 275I. Major alkaloids in two Argentinian bufonid toads (Melanophryniscus)

    PubMed Central

    Daly, John W.; Garraffo, H. Martin; Spande, Thomas F.; Yeh, Herman J. C.; Peltzer, Paola M.; Cacivio, Pedro; Baldo, J. Diego; Faivovich, Julián

    2008-01-01

    Alkaloid profiles in skin of poison frogs/toads (Dendrobatidae, Mantellidae, Bufonidae, and Myobatrachidae) are highly dependent on diet and hence on the nature of habitat. Extracts of the two species of toads (Melanophryniscus klappenbachi and M. cupreuscapularis) from similar habitats in the Corrientes/Chaco Provinces of Argentina have similar profiles of alkaloids, which differ considerably from profiles from other Melanophryniscus species from Brazil, Uruguay and Argentina. Structures of two major alkaloids 239Q (1) and 275I (2) were determined by mass, FTIR, and NMR spectral analysis as 5Z,9Z-3-(1-hydroxybutyl)-5-propylindolizidine and 6Z,10E-4,6-di(pent-4-enyl) quinolizidine, respectively. A third alkaloid, 249F (3), is postulated to be a homopumiliotoxin with an unprecedented conjugated exocyclic diene moiety. PMID:18848574

  6. The laser desorption/laser ionization mass spectra of some indole derivatives and alkaloids

    NASA Astrophysics Data System (ADS)

    Rogers, Kevin; Milnes, John; Gormally, John

    1992-06-01

    The laser desorption and laser ionization mass spectra of some indole derivatives and alkaloids are described with particular reference to their modes of fragmentation. Mass spectra of yohimbine, reserpine, quinine and quinidine are presented. Full experimental details are given.

  7. 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 μM caffeine, theophylline and paraxanthine, division of isolated protoplasts was significantly inhibited. Thirteen days treatment with > 250 μM 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

  8. Lucidimine A-D, four new alkaloids from the fruiting bodies of Ganoderma lucidum.

    PubMed

    Zhao, Zhen-Zhu; Chen, He-Ping; Feng, Tao; Li, Zheng-Hui; Dong, Ze-Jun; Liu, Ji-Kai

    2015-12-01

    Four new polycylic alkaloids, lucidimine A-D, were isolated from the fruiting bodies of Ganoderma lucidum. Their chemical structures were established based on 1D and 2D NMR data as well as HREIMS/HRESIMS analyses. PMID:26666338

  9. Indolizidine 239Q and quinolizidine 275I. Major alkaloids in two Argentinian bufonid toads (Melanophryniscus).

    PubMed

    Daly, John W; Garraffo, H Martin; Spande, Thomas F; Yeh, Herman J C; Peltzer, Paola M; Cacivio, Pedro M; Baldo, J Diego; Faivovich, Julián

    2008-12-15

    Alkaloid profiles in skin of poison frogs/toads (Dendrobatidae, Mantellidae, Bufonidae, and Myobatrachidae) are highly dependent on diet and hence on the nature of habitat. Extracts of the two species of toads (Melanophryniscus klappenbachi and Melanophryniscus cupreuscapularis) from similar habitats in the Corrientes/Chaco Provinces of Argentina have similar profiles of alkaloids, which differ considerably in profiles from other Melanophryniscus species from Brazil, Uruguay and Argentina. Structures of two major alkaloids 239Q (1) and 275I (2) were determined by mass, FTIR, and NMR spectral analysis as 5Z,9Z-3-(1-hydroxybutyl)-5-propylindolizidine and 6Z,10E-4,6-di(pent-4-enyl) quinolizidine, respectively. A third alkaloid, 249F (3), is postulated to be a homopumiliotoxin with an unprecedented conjugated exocyclic diene moiety. PMID:18848574

  10. Structural elucidation and NMR assignments of a new pyrrolizidine alkaloid from Crotalaria vitellina Ker Gawl.

    PubMed

    Casimiro Bezerra, Denise Aline; Fechine Tavares, Josean; dos Santos, Paula Ferreira; Castello Branco, Marianna Vieira Sobral; de Fátima Agra, Maria; Subrinho, Fernanda Lima; Braz-Filho, Raimundo; da Silva, Marcelo Sobral

    2013-08-01

    A new pyrrolizidine alkaloid, named crotavitelin, was isolated from fruits of Crotalaria vitellina, Fabaceae (Papilionoideae). The structure was established by spectroscopic techniques such as one-dimensional and two-dimensional NMR, IR, and MS. PMID:23716472

  11. Nine new tropane alkaloids from Datura stramonium L. identified by GC/MS.

    PubMed

    El Bazaoui, Ahmed; Bellimam, My Ahmed; Soulaymani, Abdelmajid

    2011-03-01

    Sixty seven tropane alkaloids were identified in the organs of Datura stramonium L. by GC/MS. Nine new tropane alkaloids, 3,7-dihydroxy-6-propionyloxytropane, 6,7-dehydro-3-tigloyloxytropane, 3-tigloyloxy-6,7-epoxytropane, 3,7-dihydroxy-6-(2'-methylbutyryloxy)tropane, 6,7-dehydroapoatropine, 3-(3'-methoxytropoyloxy)tropane, 3-tigloyloxy-6-isobutyryloxy-7-hydroxytropane, 3-tropoyloxy-6-isobutyryloxytropane, 3β-tropoyloxy-6β-isovaleroyloxytropane were tentatively identified. The alkaloids cyclotropine, dihydroaposcopolamine, 6,7-dehydrohyoscyamine and 4'-hydroxylittorine are reported for the first time for the genus Datura and 6,7-dehydrotropine for the family Solanaceae. Hyoscyamine and scopolamine figure as the major tropane alkaloids in the plant organs. PMID:20858536

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

    PubMed

    Guo, Zhifeng; 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

  13. 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...

  14. Sequestration of phenanthroindolizidine alkaloids by an Asclepiadaceae-feeding danaid butterfly, Ideopsis similis.

    PubMed

    Abe, F; Yamauchi, T; Honda, K; Omura, H; Hayashi, N

    2001-04-01

    3-Demethyl-14alpha-hydroxyisotylocrebrine N-oxide was isolated along with three homologous isotylocrebrine type alkaloids from the imagines and pupae of Ideopsis similis reared on the host plant, Tylophora tanakae. PMID:11314955

  15. Poor alkaloid sequestration by arrow poison frogs of the genus Phyllobates from Costa Rica.

    PubMed

    Mebs, Dietrich; Alvarez, Joseph Vargas; Pogoda, Werner; Toennes, Stefan W; Köhler, Gunther

    2014-03-01

    Frogs of the genus Phyllobates from Colombia are known to contain the highly toxic alkaloid batrachotoxin, but species from Central America exhibit only very low levels or are entirely free of this toxin. In the present study alcohol extracts from 101 specimens of Phyllobates lugubris and Phyllobates vittatus and 21 of three sympatric species (Dendrobates pumilio, Dendrobates auratus, Dendrobates granuliferus) from Costa Rica were analyzed by gas chromatography-mass spectrometry. Whereas the extracts of the Dendrobates species exhibited typical profiles of toxic alkaloids, those of the two Phyllobates species contained low levels of few alkaloids only, batrachotoxin was not detected. Although the feeding pattern of the Dendrobates and Phyllobates species are similar as revealed by examination of their stomach content (mainly ants and mites), the Phyllobates species are poorly sequestering alkaloids from their food source in contrast to the Dendrobates frogs. PMID:24467995

  16. Annonamine, a new aporphine alkaloid from the leaves of Annona muricata.

    PubMed

    Matsushige, Ayano; Kotake, Yaichiro; Matsunami, Katsuyoshi; Otsuka, Hideaki; Ohta, Shigeru; Takeda, Yoshio

    2012-01-01

    Atypical Parkinsonism in the Caribbean Island Guadeloupe is thought to be associated with the consumption of plants of the Annonaceae family, especially Annona muricata (soursop). In this study, a new aporphine alkaloid named annonamine (1) was isolated from the leaves of A. muricata L. together with four known benzylisoquinoline alkaloids (2-5). The structures of the isolated compounds were elucidated by the spectroscopic method. PMID:22293487

  17. Evaluation of Immunomodulatory Activity of the Alkaloid Fraction of Trichopus zeylanicus Gaertn on Experimental Animals

    PubMed Central

    Bachhav, R. S.; Sambathkumar, R.

    2016-01-01

    Trichopus zeylanicus Gaertn, (Trichopodaceae) is also known as “Arogyappacha” meaning the greener of health by tribal inhabitants (Kani tribes). This plant used as health tonic and rejuvenator. The whole plant material of Trichopus zeylanicus is defatted and successively extracted with methanol. The alkaloid fraction of Trichopus zeylanicus was obtained from methanol extract. Up to the dose of 2000 mg/kg b.w. per orally alkaloid fraction of Trichopus zeylanicus did not show any mortality or toxicity. Immunomodulatory activity of alkaloid fraction of Trichopus zeylanicus Gaertn was evaluated using various in vivo models including neutrophil adhesion test, delayed type hypersensitivity reaction, and effect on hematological parameter like, total white blood cell's, red blood cell's and hemoglobin and cyclophosphamide induce immunosupression. Sheep red blood cells were used to immunized the animals. The percentage of neutrophils adhesion to the nylon fiber was dose dependently increased in alkaloid fraction of Trichopus zeylanicus75, 150 and 300 mg/kg, p.o treated groups (50.57, 52.99 and 54.21%), respectively compared to control group. A dose dependent potentiating of delayed type hypersensitivity reaction induced by sheep red blood cells was also observed from the alkaloid fraction of Trichopus zeylanicus. On chronic administration of alkaloid fraction of Trichopus zeylanicus (75, 150 and 300 mg/kg. p.o.) caused significant (P<0.001) increased in hematological parameter like, total white blood cell's, red blood cell's and hemoglobin. Alkaloid fraction of Trichopus zeylanicus also prevented the myelosupression in mice treated cyclophosphamide (30 mg/kg, p.o.). The result of present investigation suggested that alkaloid fraction of Trichopus zeylanicus stimulate defense system by modulating several immunological parameters. PMID:27168696

  18. Pharmacological effects of ephedrine alkaloids on human alpha(1)- and alpha(2)-adrenergic receptor subtypes.

    PubMed

    Ma, Guoyi; Bavadekar, Supriya A; Davis, Yolande M; Lalchandani, Shilpa G; Nagmani, Rangaswamy; Schaneberg, Brian T; Khan, Ikhlas A; Feller, Dennis R

    2007-07-01

    Ephedra species of plants have both beneficial and adverse effects primarily associated with the presence of ephedrine alkaloids. Few reports have appeared that examine the direct actions of ephedrine alkaloids on human subtypes of adrenergic receptors (ARs). In the present study, ephedrine alkaloids were evaluated for their binding affinities on human alpha(1A)-, alpha(1B)-, alpha(1D)-, alpha(2A)-, alpha(2B)-, and alpha(2C)-AR subtypes expressed in HEK and Chinese hamster ovary cells. Cell-based reporter gene assays were used to establish functional activity of ephedrine alkaloids at alpha(1A)-, alpha(2A)-, and alpha(2C)-ARs. The data showed that ephedrine alkaloids did not activate alpha(1)- and alpha(2)-ARs and that they antagonized the agonist-mediated effects of phenylephrine and medetomidine on alpha(1)- and alpha(2)-ARs, respectively. As in the binding studies, 1R,2R- and 1R,2S-ephedrine showed greater functional antagonist activity than the 1S,2R- and 1S,2S-isomers. The rank order of affinity for the isomers was 1R,2R > 1R,2S > 1S,2R > 1S,2S. The rank order of potencies of alkaloids containing a 1R,2S-configuration was norephedrine > or = ephedrine > N-methylephedrine. These studies have demonstrated that orientation of the beta-hydroxyl group on the ethylamino side chain and the state of N-methyl substitution are important for alpha-AR binding and functional activity of the ephedrine alkaloids. In conclusion, the ephedrine isomers and analogs studied did not exhibit any direct agonist activity and were found to possess moderate antagonist activities on cloned human alpha-ARs. The blockade of presynaptic alpha(2A)- and alpha(2C)-ARs may have a pharmacological role in the direct actions of Ephedra alkaloids. PMID:17405867

  19. 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

  20. The Diaza[5.5.6.6]fenestrane Skeleton-Synthesis of Leuconoxine Alkaloids.

    PubMed

    Pfaffenbach, Magnus; Gaich, Tanja

    2016-03-01

    Among the Aspidosperma-derived monoterpene indole alkaloids, the leuconoxine subgroup has drawn significant attention from the synthetic community during the past few years. This Minireview summarizes the hitherto six completed total syntheses of leuconoxines emphasizing the different strategies for assembling the key structural motif, an unprecedented diaza[5.5.6.6]fenestrane skeleton. In addition, the proposed biogenetic relationships within the group of these alkaloids are described. PMID:26443970

  1. Cytochemical localization of polysaccharides in Claviceps paspali ultrastructure during submerged fermentation of alkaloids.

    PubMed

    Vorísek, J; Ludvík, J; Rehácek, Z

    1974-04-01

    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. PMID:4362461

  2. Complicated hypertension related to the abuse of ephedrine and caffeine alkaloids.

    PubMed

    Berman, Jeffrey A; Setty, Arathi; Steiner, Matthew J; Kaufman, Kenneth R; Skotzko, Christine

    2006-01-01

    Ephedra containing products (ECPs), which most often contain additional sources of caffeine alkaloids, may be an under-recognized cause of hypertension. ECPs, especially when used in combination or at higher than recommended doses, can cause life-threatening cardiovascular and neurological complications. We present a case of hypertensive encephalopathy with new onset generalized tonic-clonic seizure secondary to concomitant use of two OTC supplements containing a mixture of ephedrine and caffeine alkaloids. PMID:16956868

  3. Antisense RNA-mediated suppression of benzophenanthridine alkaloid biosynthesis in transgenic cell cultures of California poppy.

    PubMed

    Park, Sang-Un; Yu, Min; Facchini, Peter J

    2002-02-01

    California poppy (Eschscholzia californica Cham.) cell cultures produce several benzophenanthridine alkaloids, such as sanguinarine, chelirubine, and macarpine, with potent pharmacological activity. Antisense constructs of genes encoding two enzymes involved in benzophenanthridine alkaloid biosynthesis, the berberine bridge enzyme (BBE) and N-methylcoclaurine 3'-hydroxylase (CYP80B1), were introduced separately into California poppy cell cultures. Transformed cell lines expressing antisense BBE or antisense CYP80B1 constructs and displaying low levels of BBE or CYP80B1 mRNAs, respectively, showed reduced accumulation of benzophenanthridine alkaloids compared with control cultures transformed with a beta-glucuronidase gene. Pathway intermediates were not detected in any of the transformed cell lines. The suppression of benzophenanthridine alkaloid biosynthesis using BBE or CYP80B1 antisense RNA constructs also reduced the growth rate of the cultures. Two-dimensional (1)H-nuclear magnetic resonance and in vivo (15)N-nuclear magnetic resonance spectroscopy showed no difference in the abundance of carbohydrate metabolites in the various transgenic cell lines. However, transformed cells with reduced benzophenanthridine alkaloid levels contained larger cellular pools of several amino acids including alanine, leucine, phenylalanine, threonine, and valine compared with controls. The relative abundance of tyrosine, from which benzophenanthridine alkaloids are derived, was less than 2-fold higher in antisense-suppressed cells relative to controls. These results show that alterations in the metabolic flux through benzophenanthridine alkaloid biosynthesis can affect the regulation of amino acid pools. These data provide new insight into the metabolic engineering of benzophenanthridine alkaloid pathways. PMID:11842172

  4. Myritonines A-C, Alkaloids from Myrioneuron tonkinensis Based on a Novel Hexacyclic Skeleton.

    PubMed

    Li, Xiao-Hui; Zhang, Yu; Zhang, Jia-Hui; Li, Xiao-Nian; Cao, Ming-Ming; Di, Ying-Tong; Peng, Zong-Gen; Jiang, Jian-Dong; Hao, Xiao-Jiang

    2016-04-22

    Myritonines A-C (1-3), three new alkaloids bearing an unprecedented heterohexacyclic skeleton, were isolated from Myrioneuron tonkinensis. Their structures were determined by a combination of spectroscopic data and single-crystal X-ray diffraction analysis. Compound 3 represents the first Myrioneuron alkaloid featuring a unique trans-decahydroquinoline motif and was also found to possess a rare cyano functionality. Compounds 1 and 2 showed inhibition against the hepatitis C virus in vitro. PMID:26967892

  5. Cell type-specific localization of transcripts encoding nine consecutive enzymes involved in protoberberine alkaloid biosynthesis.

    PubMed

    Samanani, Nailish; Park, Sang-Un; Facchini, Peter J

    2005-03-01

    Molecular clones encoding nine consecutive biosynthetic enzymes that catalyze the conversion of l-dopa to the protoberberine alkaloid (S)-canadine were isolated from meadow rue (Thalictrum flavum ssp glaucum). The predicted proteins showed extensive sequence identity with corresponding enzymes involved in the biosynthesis of related benzylisoquinoline alkaloids in other species, such as opium poppy (Papaver somniferum). RNA gel blot hybridization analysis showed that gene transcripts for each enzyme were most abundant in rhizomes but were also detected at lower levels in roots and other organs. In situ RNA hybridization analysis revealed the cell type-specific expression of protoberberine alkaloid biosynthetic genes in roots and rhizomes. In roots, gene transcripts for all nine enzymes were localized to immature endodermis, pericycle, and, in some cases, adjacent cortical cells. In rhizomes, gene transcripts encoding all nine enzymes were restricted to the protoderm of leaf primordia. The localization of biosynthetic gene transcripts was in contrast with the tissue-specific accumulation of protoberberine alkaloids. In roots, protoberberine alkaloids were restricted to mature endodermal cells upon the initiation of secondary growth and were distributed throughout the pith and cortex in rhizomes. Thus, the cell type-specific localization of protoberberine alkaloid biosynthesis and accumulation are temporally and spatially separated in T. flavum roots and rhizomes, respectively. Despite the close phylogeny between corresponding biosynthetic enzymes, distinct and different cell types are involved in the biosynthesis and accumulation of benzylisoquinoline alkaloids in T. flavum and P. somniferum. Our results suggest that the evolution of alkaloid metabolism involves not only the recruitment of new biosynthetic enzymes, but also the migration of established pathways between cell types. PMID:15722473

  6. Indole alkaloids from cell suspension cultures of Tabernaemontana divaricata and Tabernanthe iboga.

    PubMed

    Pawelka, K H; Stöckigt, J

    1983-04-01

    From cell suspension cultures of Tabernaemontana divaricata and Tabernanthe iboga grown under standard conditions, six monoterpenoid indole alkaloids have been isolated and identified. T. divaricata synthesized apparicine, catharanthine, coronaridine, conoflorine, tubotaiwine and vinervine, whereas T. iboga produced tubotaiwine and conoflorine. Both cultures are a reasonable source for conoflorine, which is expected to be a good candidate for studying the mechanism of Aspidosperma type alkaloid formation at the cell-free level. PMID:24257961

  7. 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.

  8. 13,14-dihydrocoptisine--the genuine alkaloid from Chelidonium majus.

    PubMed

    Paulsen, Jana; Yahyazadeh, Mahdi; Hänsel, Sophie; Kleinwächter, Maik; Ibrom, Kerstin; Selmar, Dirk

    2015-03-01

    The genuine major benzylisoquinoline alkaloid occurring in the traditional medicinal plant greater celandine (Chelidonium majus L.) is 13,14-dihydrocoptisine and not - as described previously - coptisine. Structure of 13,14-dihydrocoptisine was elucidated. The discrepancy between the alkaloid pattern of the living plants and that of detached and dried leaves is due to the rapid and prompt conversion of 13,14-dihydrocoptisine to coptisine in the course of tissue injuries. Indeed, apart from the major alkaloid, some minor alkaloids might also be converted; this however is not in the centre of focus of this paper. This conversion is initiated by the change of pH. In vivo 13,14-dihydrocoptisine is localized in the acidic vacuoles, where it is stable. In contrast, in the neutral milieu, which results when vacuoles are destroyed in the course of tissue injuries, the genuine alkaloid is oxidized to yield coptisine. Accordingly, when alkaloids from C.majus should be analyzed, any postmortal conversion of 13,14-dihydrocoptisine has to be prevented. PMID:25666130

  9. Quantification of Aconitum alkaloids in aconite roots by a modified RP-HPLC method.

    PubMed

    Jiang, Zhi-Hong; Xie, Ying; Zhou, Hua; Wang, Jing-Rong; Liu, Zhong-Qiu; Wong, Yuen-Fan; Cai, Xiong; Xu, Hong-Xi; Liu, Liang

    2005-01-01

    The three Aconitum alkaloids, aconitine (1), mesaconitine (2) and hypaconitine (3), are pharmacologically active but also highly toxic. A standardised method is needed for assessing the levels of these alkaloids in aconite roots in order to ensure the safe use of these plant materials as medicinal herbs. By optimising extraction, separation and measurement conditions, a reliable, reproducible and accurate method for the quantitative determination of all three Aconitum alkaloids in unprocessed and processed aconite roots has been developed. This method should be appropriate for use in the quality control of Aconitum products. The three Aconitum alkaloids were separated by a modified HPLC method employing a C18 column gradient eluted with acetonitrile and ammonium bicarbonate buffer. Quantification of Aconitum alkaloids, detected at 240 nm, in different batches of samples showed that the content of 1, 2 and 3 varied significantly. In general, the alkaloid content of unprocessed roots was higher than that of processed roots. These variations were considered to be the result of differences in species, processing methods and places of origin of the samples. PMID:16315485

  10. 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

  11. Aptamer-Based Molecular Recognition of Lysergamine, Metergoline and Small Ergot Alkaloids

    PubMed Central

    Rouah-Martin, Elsa; Mehta, Jaytry; van Dorst, Bieke; de Saeger, Sarah; Dubruel, Peter; Maes, Bert U. W.; Lemiere, Filip; Goormaghtigh, Erik; Daems, Devin; Herrebout, Wouter; van Hove, François; Blust, Ronny; Robbens, Johan

    2012-01-01

    Ergot alkaloids are mycotoxins produced by fungi of the genus Claviceps, which infect cereal crops and grasses. The uptake of ergot alkaloid contaminated cereal products can be lethal to humans and animals. For food safety assessment, analytical techniques are currently used to determine the presence of ergot alkaloids in food and feed samples. However, the number of samples which can be analyzed is limited, due to the cost of the equipment and the need for skilled personnel. In order to compensate for the lack of rapid tests for the detection of ergot alkaloids, the aim of this study was to develop a specific recognition element for ergot alkaloids, which could be further applied to produce a colorimetric reaction in the presence of these toxins. As recognition elements, single-stranded DNA ligands were selected by using an iterative selection procedure named SELEX, i.e., Systematic Evolution of Ligands by EXponential enrichment. After several selection cycles, the resulting aptamers were cloned and sequenced. A surface plasmon resonance analysis enabled determination of the dissociation constants of the complexes of aptamers and lysergamine. Dissociation constants in the nanomolar range were obtained with three selected aptamers. One of the selected aptamers, having a dissociation constant of 44 nM, was linked to gold nanoparticles and it was possible to produce a colorimetric reaction in the presence of lysergamine. This system could also be applied to small ergot alkaloids in an ergot contaminated flour sample. PMID:23242153

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

    PubMed

    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

  13. 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

  14. Measurement of antiphotooxidative properties of isoquinoline alkaloids using transient thermal lens spectroscopy

    NASA Astrophysics Data System (ADS)

    Hung, J.; Castillo, J.; Laboren, I.; Rodríguez, M.; Hassegawa, M.

    2005-11-01

    The antiphotooxidative properties of boldine and chloride berberine were studied by time-resolved thermal lensing technique. These compounds belong to isoquinoline alkaloids possessing interesting biological activity (e.g. antibacterial, antimalarial, antitumor). Antiphotooxidative properties of the alkaloids were studied by mechanism of energy transference between powerful oxidizing agents such as singlet oxygen. Singlet oxygen was produced by energy transfer from chlorophyll-sensitized photooxidation of oil by exposure of high light intensities like laser. The lifetimes of singlet oxygen in dimethylsulfoxide, methanol and water were determined to confirm the assignment of the singlet molecular oxygen O II (1Δ g) in the experiments. In order to understand the effect of the alkaloids on active oxygen species, we carried out in detail an analysis of the thermal lensing signal. It was shown that the alkaloids can act as quenchers of singlet oxygen. To demonstrate the ability of the alkaloids to act efficient singlet oxygen acceptors, we have measured the fluorescence spectra of the studied alkaloids in the presence and in the absence of singlet oxygen. The antiphotooxidative activity of boldine and chloride berberine can be explained by the ability to quench singlet oxygen.

  15. Catharanthus roseus tissue culture: the effects of medium modifications on growth and alkaloid production.

    PubMed

    Carew, D P; Krueger, R J

    1977-01-01

    A number of nutritional factors as well as the growth factors 2,4-D and IAA were studied to determine their influence on growth and alkaloid formation in Catharanthus roseus suspension cultures. The optimal 2,4-D concentration for growth and alkaloid production was 1 mg/liter. With IAA, both 0.5 and 2.0 mg/liter in media produced tissue growth comparable to tissue receiving 1 mg/liter 2,4-D; however, qualitative and quantitative differences in alkaloid production were observed. Media formulations containing 2,4 and 6% sucrose showed proportionate increases in cell yield with increased sucrose, but concomitant decreases in alkaloid production. Suspension cultures in media containing 2, 5, and 10 times the normal level of phosphate exhibited little change in growth or alkaloid production. When thiamin HCl, yridoxine nicotinic acid and inositol were deleted from the medium, the tissue continued to grow well through the 24 month duration of the experiment; however, alkaloid production was altered quantitatively and qualitatively. PMID:895391

  16. 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 (Epichlo and Neotyphodium species), a monophyletic group of fungi in the family Clavicipitaceae, are systemic symbionts of cool-season grasses (Poaceae subfamily Poideae). 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 Epichlo 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 Epichlo 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

  17. Occurrence of Ergot and Ergot Alkaloids in Western Canadian Wheat and Other Cereals.

    PubMed

    Tittlemier, Sheryl A; Drul, Dainna; Roscoe, Mike; McKendry, Twylla

    2015-07-29

    A new method was developed to analyze 10 ergot alkaloids in cereal grains. Analytes included both "ine" and "inine" type ergot alkaloids. Validation of the method showed it performed with good accuracy and precision and that minor enhancement due to matrix effects was present during LC-MS/MS analysis, but was mitigated by use of an internal standard. The method was used to survey durum and wheat harvested in 2011, a year in which ergot infection was particularly widespread in western Canada. A strong linear relationship between the concentration of ergot alkaloids and the presence of ergot sclerotia was observed. In addition, shipments of cereals from 2010-2012 were also monitored for ergot alkaloids. Concentrations of total ergot alkaloids in shipments were lower than observed in harvest samples, and averaged from 0.065 mg/kg in barley to 1.14 mg/kg in rye. In shipments, the concentration of ergot alkaloids was significantly lower in wheat of higher grades. PMID:26134095

  18. Determination of Ephedra Alkaloids in Urine and Plasma by HPLC-UV: Collaborative Study

    PubMed Central

    Roman, Mark C.; Gray, D.; Laurensen, J.; Luo, G.; McClanahan, R.; Perez, R.; Roper, C.; Roscoe, V.; Shevchuk, C.; Suen, E.; Sullivan, D.

    2008-01-01

    Ten collaborating laboratories determined the ephedra alkaloid content (ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, methylephedrine, and methylpseudoephedrine) in 8 blind duplicates of human plasma and urine using high-performance liquid chromatography (HPLC) with UV detection. In addition to negative urine and plasma controls, urine samples were spiked with individual ephedra alkaloids ranging in concentration from about 1 to 5 μg/mL. Plasma samples were spiked with individual ephedra alkaloids ranging in concentration from about 100 to 400 ng/mL. Sample solutions were treated to solid-phase extraction using a strong-cation exchange column to help remove interferences. The HPLC analyses were performed on a polar-embedded phenyl column using UV detection at 210 nm. The ephedra alkaloids were not consistently detected in any of the spiked plasma samples. When ephedra alkaloids were detected in the plasma samples, reproducibility between blind replicate samples was very poor. Repeatability, reproducibility, and accuracy were also very poor for the spiked urine samples. On the basis of these re sults, the HPLC-UV method for the determination of ephedra alkaloids in human urine and plasma is not recommended for adoption as Official First Action. PMID:15084082

  19. Alkaloids as important scaffolds in therapeutic drugs for the treatments of cancer, tuberculosis, and smoking cessation.

    PubMed

    Kittakoop, Prasat; Mahidol, Chulabhorn; Ruchirawat, Somsak

    2014-01-01

    Alkaloid molecules can act, depending on a type of amine functionality present in alkalods, as either hydrogenacceptor or hydrogen-donor for hydrogen bonding that is critically important for the interaction (binding) between targets (enzymes, proteins and receptors) and drugs (ligands). Because of this unique property, alkaloid scaffolds are therefore present in several drugs and lead compounds. This review highlights alkaloid scaffolds in drugs, particularly those recently approved in 2012; it also covers the scaffolds in leads and drug candidates which are in clinical trials and preclinical pipeline. The review focuses on three therapeutic areas including treatments of cancer, tuberculosis, and tobacco cessation. Alkaloid scaffolds in drugs and leads are inspired by those of naturally occurring alkaloids, and these scaffolds include pyridine, piperidine, quinoline, quinolinone, quinazoline, isoquinoline, indole, indolinone, isoindole, isoxazole, imidazole, indazole, thiazole, pyrazole, oxazolidinone, oxadiazole, and benzazepine. In addition to medicinal chemistry aspects, natural products possessing an individual alkaloid scaffold, as well as the mechanism of action of drugs and leads, are also discussed in this review. PMID:24359196

  20. A stereoselective hydroxylation step of alkaloid biosynthesis by a unique cytochrome P450 in Catharanthus roseus.

    PubMed

    Giddings, Lesley-Ann; Liscombe, David K; Hamilton, John P; Childs, Kevin L; DellaPenna, Dean; Buell, C Robin; O'Connor, Sarah E

    2011-05-13

    Plant cytochrome P450s are involved in the production of over a hundred thousand metabolites such as alkaloids, terpenoids, and phenylpropanoids. Although cytochrome P450 genes constitute one of the largest superfamilies in plants, many of the catalytic functions of the enzymes they encode remain unknown. Here, we report the identification and functional characterization of a cytochrome P450 gene in a new subfamily of CYP71, CYP71BJ1, involved in alkaloid biosynthesis. Co-expression analysis of putative cytochrome P450 genes in the Catharanthus roseus transcriptome identified candidate genes with expression profiles similar to known terpene indole alkaloid biosynthetic genes. Screening of these candidate genes by functional expression in Saccharomyces cerevisiae yielded a unique P450-dependent enzyme that stereoselectively hydroxylates the alkaloids tabersonine and lochnericine at the 19-position of the aspidosperma-type alkaloid scaffold. Tabersonine, which can be converted to either vindoline or 19-O-acetylhörhammericine, represents a branch point in alkaloid biosynthesis. The discovery of CYP71BJ1, which forms part of the pathway leading to 19-O-acetylhörhammericine, will help illuminate how this branch point is controlled in C. roseus. PMID:21454651

  1. Variability in the content and composition of alkaloid found in Canadian ergot. III. Triticale and barley.

    PubMed

    Young, J C; Chen, Z J

    1982-01-01

    The total alkaloid content and individual alkaloid composition were determined by colorimetry and high performance liquid chromatography, respectively, for Canadian triticale and barley ergot (Claviceps purpurea). The total alkaloid content was highly variable between individual sclerotia from the same or different sources and ranged from 0.042 to 0.752% for triticale and from 0.082 to 1.04% for barley; average values were 0.239% for Ottawa triticale, 0.289% for Prairie triticale, and 0.264% for barley. Ergocristine and its isomer ergocristinine were the major constituents in both grains. On average, Canadian ergot pooled from rye, wheat, triticale, and barley consists of ergocristine (31%), ergocristinine (13%), ergocristinine (13%), ergotamine (17%), ergotaminine (8%), ergocryptine (5%), ergocryptinine (3%), ergometrine (5%), ergometrinine (2%), ergosine (4%), ergostinine (2%), ergocornine (4%), ergocorninine (2%), and unidentified alkaloids (3%), and an average total alkaloid content of 0.236%. With the exception of rye and barley ergot from the maritime regions, Canadian rye, wheat, triticale, and barley ergot is fairly uniform in individual alkaloid composition. PMID:7077057

  2. Aptamer-based molecular recognition of lysergamine, metergoline and small ergot alkaloids.

    PubMed

    Rouah-Martin, Elsa; Mehta, Jaytry; van Dorst, Bieke; de Saeger, Sarah; Dubruel, Peter; Maes, Bert U W; Lemiere, Filip; Goormaghtigh, Erik; Daems, Devin; Herrebout, Wouter; van Hove, François; Blust, Ronny; Robbens, Johan

    2012-01-01

    Ergot alkaloids are mycotoxins produced by fungi of the genus Claviceps, which infect cereal crops and grasses. The uptake of ergot alkaloid contaminated cereal products can be lethal to humans and animals. For food safety assessment, analytical techniques are currently used to determine the presence of ergot alkaloids in food and feed samples. However, the number of samples which can be analyzed is limited, due to the cost of the equipment and the need for skilled personnel. In order to compensate for the lack of rapid tests for the detection of ergot alkaloids, the aim of this study was to develop a specific recognition element for ergot alkaloids, which could be further applied to produce a colorimetric reaction in the presence of these toxins. As recognition elements, single-stranded DNA ligands were selected by using an iterative selection procedure named SELEX, i.e., Systematic Evolution of Ligands by EXponential enrichment. After several selection cycles, the resulting aptamers were cloned and sequenced. A surface plasmon resonance analysis enabled determination of the dissociation constants of the complexes of aptamers and lysergamine. Dissociation constants in the nanomolar range were obtained with three selected aptamers. One of the selected aptamers, having a dissociation constant of 44 nM, was linked to gold nanoparticles and it was possible to produce a colorimetric reaction in the presence of lysergamine. This system could also be applied to small ergot alkaloids in an ergot contaminated flour sample. PMID:23242153

  3. Variability in the content and composition of alkaloids found in Canadian ergot. I. Rye.

    PubMed

    Young, J C

    1981-01-01

    The total alkaloid content and individual alkaloid composition were determined by colorimetry and high performance liquid chromatography, respectively, for Canadian rye ergot sclerotia. The total alkaloid content was highly variable between sclerotia from the same head, field, or region and ranged from 0.011 to 0.452% (av. 0.249%). Levels were lowest in ergot from Prince Edward Island. The individual alkaloid composition was uniform throughout a single sclerotium or in different sclerotia from the same head, somewhat uniform for averages in different fields throughout a region, but highly variable from head to head in a given field. On a regional basis, ergotamine followed by ergocristine were the major alkaloids observed in the east whereas the order was reversed in the west. Ergometrine, ergosine, ergocornine, and ergocryptine were also observed to a lesser degree; ergostine was not observed. Isomerization of ergometrine increased from near 0% in the east to about 40% in the west, but was relatively constant (about 30%) for the peptide alkaloids in all regions. PMID:6894157

  4. 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

  5. Holistic approach based on high resolution and multiple stage mass spectrometry to investigate ergot alkaloids in cereals.

    PubMed

    Arroyo-Manzanares, Natalia; Malysheva, Svetlana V; Vanden Bussche, Julie; Vanhaecke, Lynn; Diana Di Mavungu, José; De Saeger, Sarah

    2014-01-01

    A holistic approach based on high resolution and multiple stage mass spectrometry was developed for identification of less studied or novel ergot alkaloid derivatives. Initially, the fragmentation of nine known ergot alkaloids was studied to establish a strategy for the identification of novel ergot alkaloids. Ions with m/z 223 and m/z 251 were found to be common for all ergopeptines, ergoamides and ergopeptams. Subsequently, parent scan experiments using these ions were performed to screen grain samples for the presence of possible ergot alkaloid derivatives. Besides the six most common ergot alkaloids and their corresponding epimers (for which reference standards were available), eleven other ergot alkaloid derivatives were identified following the proposed strategy. PMID:24274309

  6. 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

  7. Tandem Mass Spectrometry for Structural Identification of Sesquiterpene Alkaloids from the Stems of Dendrobium nobile Using LC-QToF.

    PubMed

    Wang, Yan-Hong; Avula, Bharathi; Abe, Naohito; Wei, Feng; Wang, Mei; Ma, Shuang-Cheng; Ali, Zulfiqar; Elsohly, Mahmoud A; Khan, Ikhlas A

    2016-05-01

    Dendrobium nobile is one of the fundamental herbs in traditional Chinese medicine. Sesquiterpene alkaloids are the main active components in this plant. Due to weak ultraviolet absorption and low content in D. nobile, these sesquiterpene alkaloids have not been extensively studied using chromatographic methods. Herein, tandem mass spectrometry combined with liquid chromatography separation provides a tool for the identification and characterization of the alkaloids from D. nobile. A total of nine sesquiterpene alkaloids were characterized by ultrahigh-performance liquid chromatography tandem mass spectrometry. These alkaloids can be classified into two subgroups that are represented by dendrobine and nobilonine. Tandem mass spectrometric studies revealed the fragmentation pathways of these two subgroup alkaloids that were used for the identification and characterization of other alkaloids in D. nobile. Characterization of these alkaloids using accurate mass and diagnostic fragments provided a reliable methodology for the analysis of D. nobile by ultrahigh-performance liquid chromatography tandem mass spectrometry. The limit of detection was defined as the signal-to-noise ratio equal to 3 : 1. Limits of detection of dendrobine and nobilonine were less than 30 ng/mL. The developed method was applied for the analysis of various Dendrobium species and related dietary supplements. Alkaloids were identified from D. nobile, but not detected from commercial samples including 13 other Dendrobium species and the 7 dietary supplements. PMID:27054915

  8. Identification and quantitation of alkaloids in coca tea

    PubMed Central

    Jenkins, Amanda J.; Llosa, Teobaldo; Montoya, Ivan

    2008-01-01

    The consumption of coca tea is a common occurrence in many South American countries. The tea is often packaged in individual servings as tea bags which contain approximately 1 g of plant material. The consumption of coca tea leads to ingestion of cocaine and other alkaloids: however, there is little information available regarding the pharmacological or toxicological effects that result from consumption of coca tea. We performed a series of studies with coca tea bags from two South American countries, Peru and Bolivia. The alkaloidal content of the ‘coca leaf’ in coca tea bags was determined by two different extraction methods: Soxhlet extraction with methanol (exhaustive extraction), and mechanical agitation with methanol. Extracts were purified by solid-phase extraction (SPE) followed by analysis by gas chromatography/mass spectrometry (GC/MS). Coca tea prepared from Peruvian and Bolivian coca tea bags was also analyzed by SPE-GC/MS assay. In addition, urine specimens were analyzed from an individual who consumed one cup of Peruvian coca tea and one cup of Bolivian coca tea on separate occasions. Urine samples were analyzed by immunoassay (TDxR) and SPE-GC/MS. Analysis of coca tea bags and coca tea indicated that cocaine, benzoylecgonine, ecgonine methyl ester and trans-cinnamoylcocaine were present in varying quantities. With exhaustive extraction, an average of 5.11 mg, and 4.86 mg of cocaine per tea bag were found in coca leaf from Peru and Bolivia, respectively. The average amounts of benzoylecgonine and ecgonine methyl ester in Peruvian coca leaf were 0.11 and 1.15 mg, and in Bolivian coca leaf were 0.12 and 2.93 mg per tea bag, respectively. trans-Cinnamoylcocaine was found in trace amounts in Peruvian tea bags and 0.16 mg/tea bag of Bolivian tea. When tea was prepared, an average of 4.14 mg of cocaine was present in a cup of Peruvian coca tea and 4.29 mg of cocaine was present in Bolivian tea. Following the consumption of a cup of Peruvian tea by one individual, a peak urine benzoylecgonine concentration of 3940 ng/ml occurred 10 h after ingestion. Consumption of Bolivian coca tea resulted in a peak benzoylecgonine concentration of 4979 ng/ml at 3.5 h. The cumulative urinary excretion of benzoylecgonine after approximately 48 h, determined by GC/MS, was 3.11 mg and 2.69 mg after consumption of Peruvian and Bolivian coca tea, respectively. This study demonstrated that coca tea bags and coca tea contain a significant amount of cocaine and cocaine-related alkaloids and the consumption of a single cup of Peruvian or Bolivian coca tea produces positive drug test results for cocaine metabolites. PMID:8819993

  9. Identification of cellular and molecular factors determining the response of cancer cells to six ergot alkaloids.

    PubMed

    Mrusek, Marco; Seo, Ean-Jeong; Greten, Henry Johannes; Simon, Michael; Efferth, Thomas

    2015-02-01

    Ergot alkaloids are psychoactive and vasoconstricting agents of the fungus Claviceps purpurea causing poisoning such as ergotism in medieval times (St. Anthony's Fire). This class of substances also inhibits tumor growth in vitro and in vivo, though the underlying mechanisms are unclear as yet. We investigated six ergot alkaloids (agroclavine, ergosterol, ergocornin E, ergotamine, dihydroergocristine, and 1-propylagroclavine tartrate) for their cytotoxicity towards tumor cell lines of the National Cancer Institute, USA. 1-Propylagroclavine tartrate (1-PAT) revealed the strongest cytotoxicity. Out of 76 clinically established anticancer drugs, cross-resistance was found between the ergot alkaloids and 6/7 anti-hormonal drugs (=85.7 %) and 5/15 DNA-alkylating drugs (=33.3 %). The IC50 values for the six alkaloids were not correlated to well-known determinants of drug resistance, such as proliferative activity (as measured by cell doubling times, PCNA expression, and cell cycle distribution), the multidrug resistance-mediating P-glycoprotein/MDR1 and expression or mutations of oncogenes and tumor suppressor genes (EGFR, RAS, TP53). While resistance of control drugs (daunorubicin, cisplatin, erlotinib) correlated with these classical resistance mechanisms, ergot alkaloids did not. Furthermore, COMPARE and hierarchical cluster analyses were performed of mRNA microarray data to identify genes correlating with sensitivity or resistance to 1-PAT. Twenty-three genes were found with different biological functions (signal transducers, RNA metabolism, ribosome constituents, cell cycle and apoptosis regulators etc.). The expression of only 3/66 neuroreceptor genes correlated with the IC50 values for 1-PAT, suggesting that the psychoactive effects of ergot alkaloids may not play a major role for the cytotoxic activity against cancer cells. In conclusion, the cytotoxicity of ergot alkaloids is not involved in classical mechanisms of drug resistance opening the possibility to bypass resistance and to treat otherwise drug-resistant and refractory tumors. The modes of action are multifactorial, which is a typical feature of many natural compounds. PMID:25342140

  10. 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

  11. 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.

  12. Full structure assignments of pyrrolizidine alkaloid DNA adducts and mechanism of tumor initiation.

    PubMed

    Zhao, Yuewei; Xia, Qingsu; Gamboa da Costa, Gonçalo; Yu, Hongtao; Cai, Lining; Fu, Peter P

    2012-09-17

    Pyrrolizidine alkaloid-containing plants are widespread in the world and are probably the most common poisonous plants affecting livestock, wildlife, and humans. Pyrrolizidine alkaloids are among the first chemical carcinogens identified in plants. Previously, we determined that metabolism of pyrrolizidine alkaloids in vivo and in vitro generated a common set of DNA adducts that are responsible for tumor induction. Using LC-ESI/MS/MS analysis, we previously determined that four DNA adducts (DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4) were formed in rats dosed with riddelliine, a tumorigenic pyrrolizidine alkaloid. Because of the lack of an adequate amount of authentic standards, the structures of DHP-dA-3 and DHP-dA-4 were not elucidated, and the structural assignment for DHP-dG-4 warranted further validation. In this study, we developed an improved synthetic methodology for these DNA adducts, enabling their full structural elucidation by mass spectrometry and NMR spectroscopy. We determined that DHP-dA-3 and DHP-dA-4 are a pair of epimers of 7-hydroxy-9-(deoxyadenosin-N(6)-yl) dehydrosupinidine, while DHP-dG-4 is 7-hydroxy-9-(deoxyguanosin-N(2)-yl)dehydrosupinidine, an epimer of DHP-dG-3. With the structures of these DNA adducts unequivocally elucidated, we conclude that cellular DNA preferentially binds dehydropyrrolizidine alkaloid, for example, dehydroriddelliine, at the C9 position of the necine base, rather than at the C7 position. We also determined that DHP-dA-3 and DHP-dA-4, as well as DHP-dG-3 and DHP-dG-4, are interconvertible. This study represents the first report with detailed structural assignments of the DNA adducts that are responsible for pyrrolizidine alkaloid tumor induction on the molecular level. A mechanism of tumor initiation by pyrrolizidine alkaloids is consequently fully determined. PMID:22857713

  13. Liquid chromatographic preparative method for isolating ergot alkaloids, using a particle-loaded membrane extracting disk.

    PubMed

    Ware, G M; Price, G; Carter, L; Eitenmiller, R R

    2000-01-01

    A liquid chromatographic method is described for the determination of ergot alkaloids in wheat. Ergonovine, ergotamine, ergocornine, alpha-ergocryptine, and ergocristine are extracted from wheat with methanol-0.25% concentrated H3PO4 (40 + 60) pH 2.2, cleaned up by using a solid-phase extraction (SPE) disk, and separated by reversed-phase liquid chromatography with fluorescence detection. Ergot alkaloids are basic compounds that form water-soluble salts in acidic aqueous solution. Because ergot alkaloid salts are positively charged, they can be easily and selectively trapped on a negatively charged strong cation-exchange SPE disk. A strong wash solvent, methanol-0.25% concentrated H3PO4 (40 + 60) was used to remove matrix interferences not bonded by ionic interactions with the cation-exchange column. The ergot alkaloids were eluted from the ion-exchange column by adjusting the pH of the elution solvents to slightly basic conditions (pH 9). The SPE disk concentrated and cleanly separated the ergot alkaloids from matrix interferences. Standard calibration curves for ergot alkaloids for the concentration range 0.1-2.0 microg/mL were linear. The SPE disk had a column capacity equivalent to about 1 g extracted wheat. At spiking levels of 2.3-46 ng/g for ergonovine and 20-400 ng/g for ergotamine, ergocornine, alpha-ergocryptine, and ergocristine, the mean recovery was 88.1% with a coefficient of variation (CV) of 5.33%. The recovery data ranged from 79.1 to 95.9%. Ergonovine had the lowest overall recovery and the largest CV. The method has an estimated reliable limit of detection and limit of quantitation of <5 and <20 ng/g, respectively, for each ergot alkaloid tested. PMID:11128143

  14. 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

  15. Identification and Quantification of the Main Active Anticancer Alkaloids from the Root of Glaucium flavum

    PubMed Central

    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

  16. 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

  17. Heterologous expression of lysergic acid and novel ergot alkaloids in Aspergillus fumigatus.

    PubMed

    Robinson, Sarah L; Panaccione, Daniel G

    2014-10-01

    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

  18. Effect of Drying Methods on the Steroidal Alkaloid Content of Potato Peels, Shoots and Berries.

    PubMed

    Hossain, Mohammad B; Brunton, Nigel P; Rai, Dilip K

    2016-01-01

    The present study has found that dried potato samples yielded significantly higher levels of steroidal alkaloids such as α-solanine and α-chaconine than the corresponding fresh samples, as determined by the UPLC-MS/MS technique. Among the drying techniques used, air drying had the highest effect on steroidal alkaloid contents, followed by freeze drying and vacuum oven drying. There was no significant difference between the freeze dried and vacuum oven dried samples in their α-chaconine contents. However, freeze dried potato shoots and berries had significantly higher α-solanine contents (825 µg/g dry weight (DW) in shoots and 2453 µg/g DW in berries) than the vacuum oven dried ones (325 µg/g dry weight (DW) in shoots and 2080 µg/g DW in berries). The kinetics of steroidal alkaloid contents of potato shoots during air drying were monitored over a period of 21 days. Both α-solanine and α-chaconine content increased to their maximum values, 875 µg/g DW and 3385 µg/g DW, respectively, after 7 days of drying. The steroidal alkaloid contents of the shoots decreased significantly at day 9, and then remained unchanged until day 21. In line with the potato shoots, air dried potato tuber peels also had higher steroidal alkaloid content than the freeze dried and vacuum oven dried samples. However, a significant decrease of steroidal alkaloid content was observed in air dried potato berries, possibly due to degradation during slicing of the whole berries prior to air drying. Remarkable variation in steroidal alkaloid contents among different tissue types of potato plants was observed with the potato flowers having the highest content. PMID:27023503

  19. 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 α-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 α-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

  20. Indole alkaloids from Muntafara sessilifolia with antiplasmodial and cytotoxic activities.

    PubMed

    Girardot, Marion; Deregnaucourt, Christiane; Deville, Alexandre; Dubost, Lionel; Joyeau, Roger; Allorge, Lucile; Rasoanaivo, Philippe; Mambu, Lengo

    2012-01-01

    Four vobasinyl-iboga bisindole and one 2-acyl monomeric indole alkaloids were isolated from the stem bark of Muntafara sessilifolia along with eleven known compounds. Their structures and relative stereochemistry were elucidated on the basis of spectroscopic data including 1D and 2D NMR and mass spectrometry (MS). All isolated compounds were evaluated in vitro for antiplasmodial activity against the chloroquine-resistant strain FcB1 of Plasmodium falciparum, and for cytotoxicity against the human lung cell line MRC-5 and the rat skeletal muscle cell line L-6. 3'-Oxo-tabernaelegantine A exhibited antiplasmodial activity (4.4 μM IC(50)) associated with non-significant cytotoxicity (selectivity index of 48). Tabernaelegantine B and D displayed the highest cytotoxicity with IC(50) values of 0.47 and 1.89 μM on MRC-5 cells, and 0.42 and 2.7 μM on L-6 cells, respectively. PMID:22033013