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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. Total Synthesis, Relay Synthesis, and Structural Confirmation of the C18-Norditerpenoid Alkaloid Neofinaconitine

    PubMed Central

    Shi, Yuan; Wilmot, Jeremy T.; Nordstrøm, Lars Ulrik; Tan, Derek S.; Gin, David Y.

    2013-01-01

    The first total synthesis of the C18-norditerpenoid aconitine alkaloid neofinaconitine and relay syntheses of neofinaconitine and 9-deoxylappaconitine from condelphine are reported. A modular, convergent synthetic approach involves initial Diels–Alder cycloaddition between two unstable components, cyclopropene 10 and cyclopentadiene 11. A second Diels–Alder reaction features the first use of an azepinone dienophile 8, with high diastereofacial selectivity achieved via rational design of the siloxydiene component 36 with a sterically-demanding bromine substituent. Subsequent Mannich-type N-acyliminium and radical cyclizations provide the complete hexacyclic skeleton 33 of the aconitine alkaloids. Key endgame transformations include installation of the C8-hydroxyl group via conjugate addition of water to a putative strained bridghead enone intermediate 45, and one-carbon oxidative truncation of the C4 sidechain to afford racemic neofinaconitine. Complete structural confirmation was provided by a concise relay synthesis of (+)-neofinaconitine and (+)-9-deoxylappaconitine from condelphine, with X-ray crystallographic analysis of the former clarifying the NMR spectral discrepancy between neofinaconitine and delphicrispuline, which were previously assigned identical structures. PMID:24040959

  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. 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...

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

    PubMed Central

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

    2014-01-01

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

  7. 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

  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. Pyrrolizidine alkaloids.

    PubMed

    Robertson, Jeremy; Stevens, Kiri

    2014-12-01

    This review covers pyrrolizidine alkaloids isolated from natural sources. Topics include: aspects of structure, isolation, and biological/pharmacological studies; total syntheses of necic acids, necine bases and closely-related non-natural analogues. PMID:25158215

  10. Alkaloids in Marine Algae

    PubMed Central

    Güven, Kas?m Cemal; Percot, Aline; Sezik, Ekrem

    2010-01-01

    This paper presents the alkaloids found in green, brown and red marine algae. Algal chemistry has interested many researchers in order to develop new drugs, as algae include compounds with functional groups which are characteristic from this particular source. Among these compounds, alkaloids present special interest because of their pharmacological activities. Alkaloid chemistry has been widely studied in terrestrial plants, but the number of studies in algae is insignificant. In this review, a detailed account of macro algae alkaloids with their structure and pharmacological activities is presented. The alkaloids found in marine algae may be divided into three groups: 1. Phenylethylamine alkaloids, 2. Indole and halogenated indole alkaloids, 3. Other alkaloids. PMID:20390105

  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. 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

  13. New Perspectives in the Chemistry of Marine Pyridoacridine Alkaloids.

    PubMed

    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. Dimeric Cinchona alkaloids.

    PubMed

    Boraty?ski, Przemys?aw 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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...

  4. Simple Indolizidine and Quinolizidine Alkaloids.

    PubMed

    Michael, Joseph P

    2015-01-01

    This review of simple indolizidine and quinolizidine alkaloids (i.e., those in which the parent bicyclic systems are in general not embedded in polycyclic arrays) is an update of the previous coverage in Volume 55 of this series (2001). The present survey covers the literature from mid-1999 to the end of 2013; and in addition to aspects of the isolation, characterization, and biological activity of the alkaloids, much emphasis is placed on their total synthesis. A brief introduction to the topic is followed by an overview of relevant alkaloids from fungal and microbial sources, among them slaframine, cyclizidine, Steptomyces metabolites, and the pantocins. The important iminosugar alkaloids lentiginosine, steviamine, swainsonine, castanospermine, and related hydroxyindolizidines are dealt with in the subsequent section. The fourth and fifth sections cover metabolites from terrestrial plants. Pertinent plant alkaloids bearing alkyl, functionalized alkyl or alkenyl substituents include dendroprimine, anibamine, simple alkaloids belonging to the genera Prosopis, Elaeocarpus, Lycopodium, and Poranthera, and bicyclic alkaloids of the lupin family. Plant alkaloids bearing aryl or heteroaryl substituents include ipalbidine and analogs, secophenanthroindolizidine and secophenanthroquinolizidine alkaloids (among them septicine, julandine, and analogs), ficuseptine, lasubines, and other simple quinolizidines of the Lythraceae, the simple furyl-substituted Nuphar alkaloids, and a mixed quinolizidine-quinazoline alkaloid. The penultimate section of the review deals with the sizable group of simple indolizidine and quinolizidine alkaloids isolated from, or detected in, ants, mites, and terrestrial amphibians, and includes an overview of the "dietary hypothesis" for the origin of the amphibian metabolites. The final section surveys relevant alkaloids from marine sources, and includes clathryimines and analogs, stellettamides, the clavepictines and pictamine, and bis(quinolizidine) alkaloids. PMID:26777309

  5. 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

  6. 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...

  7. 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 ...

  8. Quinolizidine alkaloids from Lupinus lanatus

    NASA Astrophysics Data System (ADS)

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

    2011-10-01

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

  9. 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

  10. 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

  11. 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

  12. 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

  13. [Alkaloids from Annonaceae XLVII*: Alkaloides of Guatteria ouregou**].

    PubMed

    Lebœuf, M; Cortes, D; Hocquemiller, R; Cavé, A

    1983-08-01

    The Guianese Annonaceous plant GUATTERIA OUREGOU D UN. has yielded fourteen isoquinoline alkaloids, five of which are novel. They belong to several structural types; attention is specially drawn to three original skeletons, namely 7-hydoxy-7-methyl aporphinoids, 7- GEM-dimethyl aporphinoids and alpha- GEM-dimethyl cularinoids. The results concerning solvent shift in (1)H NMR spectra of some of these alkaloids are emphasized. Finally the phytochemical significance of the isolated alkaloids is discussed considering their chemotaxonomic and biogenetic interest. PMID:17404989

  14. 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

  15. 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

  16. Quinolizidine alkaloids from Genista ephedroides.

    PubMed

    Pistelli; Bertoli; Giachi; Morelli; Rubiolo; Bicchi

    2001-02-01

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

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. Alkaloid synthesis using chiral secondary amine organocatalysts.

    PubMed

    Ishikawa, Hayato; Shiomi, Shinya

    2015-12-23

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

  3. 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

  4. Endophyte-associated ergot alkaloids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fescue toxicosis is a very costly (greater than $600 million/annually) for the cattle, horse and small ruminant industries. The tall fescue forage responsible for this intoxication is infected with an endophytic fungus (Neotyphodium coenophialum) that produces ergot alkaloids, which are toxic to th...

  5. Alkaloid Changes in Tobacco Seeds during Germination.

    PubMed

    Weeks, W W; Bush, L P

    1974-01-01

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

  6. 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

  7. Stereoselective synthesis of (+)-loline alkaloid skeleton.

    PubMed

    Miller, Kelsey E; Wright, Anthony J; Olesen, Margaret K; Hovey, M Todd; Scheerer, Jonathan R

    2015-02-01

    The loline alkaloids present a compact polycyclic pyrrolizidine skeleton and contain a strained five-membered ethereal bridge, structural features that have proven challenging for synthetic chemists to incorporate since the discovery of this natural product family more than 100 years ago. These alkaloids are produced by mutualistic fungal symbionts (endophytes) living on certain species of pasture grasses and protect the host plant from insect herbivory. The asymmetric total synthesis of loline alkaloids is reported and extends our first-generation (racemic) synthesis of this alkaloid family. Key to the synthesis is a diastereoselective tethered aminohydroxylation of a homoallylic carbamate function and a Petasis Borono-Mannich addition. PMID:25611615

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

    PubMed Central

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

    2015-01-01

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

  9. 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...

  10. Capillary gas chromatography of lupin alkaloids.

    PubMed

    Priddis, C R

    1983-05-20

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

  11. 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

  12. 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...

  13. 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

  14. 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

  15. 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

  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 ?M, and inhibition of HIV P24 formation of more than 50% at 1.7 and 0.95 ?M, respectively. The structures of the alkaloids were established by spectroscopic data interpretation. PMID:24392742

  17. Isoquinoline and isoindole alkaloids from Menispermum dauricum.

    PubMed

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

    2004-04-01

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

  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. Loline alkaloids: Currencies of mutualism.

    PubMed

    Schardl, Christopher L; Grossman, Robert B; Nagabhyru, Padmaja; Faulkner, Jerome R; Mallik, Uma P

    2007-04-01

    Several species of Lolium and other cool-season grasses (Poaceae subfamily Pooideae) tend to harbor symbiotic, seed-transmitted, fungi that enhance their fitness by various means. These fungal endophytes--species of Neotyphodium or Epichloë (Clavicipitaceae)--are known for production of antiherbivore metabolites such as the bioprotective loline alkaloids. Lolines are saturated pyrrolizidines with an exo-1-amine and an ether bridge between C-2 and C-7. The ether bridge is an unusual feature for a biogenic compound in that it links two bridgehead carbon atoms. Much of the loline-biosynthetic pathway has been elucidated by administering isotopically labeled precursors to fungal cultures and by comparisons of loline biosynthesis genes to known gene families. The first step appears to be an unusual gamma-substitution reaction involving an enzyme related to O-acetylhomoserine (thiol) lyase, but which uses the secondary amine of L-proline rather than a sulfhydryl group as the nucleophile. The strained ether bridge is added after formation of the pyrrolizidine rings. Lolines with dimethylated or acylated 1-amines have insect antifeedant and insecticidal activities comparable to nicotine, but little or no toxicity to mammals. Considering the surprising abundance of lolines in some grass-endophyte symbiota, possible additional effects on plant stress tolerance and physiology are worth future consideration. In this review, we discuss the history of loline discovery, methods of analysis, biological activities and distribution in nature, as well as progress on the genetics and biochemistry of their biosynthesis, and on the chemical synthesis of these alkaloids. PMID:17346759

  20. Modified alkaloid pattern in developing tobacco callus.

    PubMed

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

    1985-01-01

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

  1. 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...

  2. Alkaloids from Lupinus argenteus var. stenophyllus.

    PubMed

    Keller, W J; Zelenski, S G

    1978-03-01

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

  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 pyrrole alkaloids from Solanum sodomaeum.

    PubMed

    El Sayed, K A; Hamann, M T; Abd El-Rahman, H A; Zaghloul, A M

    1998-06-26

    Two new pyrrole alkaloids, solsodomine A and B, were isolated from the fresh berries of Solanum sodomaeum L., collected from the Libyan desert. The structures of these compounds were established by 2D-NMR, including 15N NMR spectroscopy and chemical degradation. Solsodomine A (1) shows activity against Mycobacterium intracellulare. This is the first report of pyrrole alkaloids from the genus Solanum. PMID:9644084

  5. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  7. 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.

  8. Multicomponent Therapeutics of Berberine Alkaloids

    PubMed Central

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

    2013-01-01

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

  9. 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...

  10. Benzylisoquinoline alkaloid biosynthesis in opium poppy.

    PubMed

    Beaudoin, Guillaume A W; Facchini, Peter J

    2014-07-01

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

  11. 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.

  12. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  13. 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...

  14. 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

  15. 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.

  16. 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

  17. Diterpenoid alkaloids and flavonoids from Delphinium trichophorum.

    PubMed

    Lin, Chao-Zhan; Zhao, Zhong-Xiang; Xie, Si-Min; Mao, Ju-Hua; Zhu, Chen-Chen; Li, Xiao-Hui; Zeren-dawa, Bairi; Suolang-qimei, Kangsa; Zhu, Dun; Xiong, Tian-Qin; Wu, Ai-Zhi

    2014-01-01

    Five hetisane-type C20-diterpenoid alkaloids, trichodelphinines A-E, one delnudine-type C20-diterpenoid alkaloid, trichodelphinine F and three known flavonoids, quercetin, quercetin 3-O-?-D-glucopyranoside, and quercetin 3-O-?-D-glucopyranoside-7-O-?-L-arabinopyranoside, were isolated from whole plants of Delphinium trichophorum Franch. Their structures were elucidated on the basis of extensive spectroscopic analysis, including HSQC, HMBC, (1)H-(1)H COSY, NOESY and X-ray crystallographic analysis, and from chemical evidence. The cytotoxic activities of the diterpenoid alkaloids were evaluated using the MTT method, and the IC50 values of their cytotoxicity against A549 cancer cells ranged from 12.03 to 52.79 ?M. PMID:24256579

  18. 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

  19. 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

  20. 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

  1. 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

  2. Indole Alkaloids from Chaetomium globosum.

    PubMed

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

    2015-07-24

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

  3. Hexacyclic monoterpenoid indole alkaloids from Rauvolfia verticillata.

    PubMed

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

    2015-12-01

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

  4. Evaporative light scattering detection of pyrrolizidine alkaloids.

    PubMed

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

    2004-01-01

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

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

    PubMed

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

    2016-01-01

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

  6. 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

  7. Amides and an alkaloid from Portulaca oleracea.

    PubMed

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

    2012-08-01

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

  8. 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

  9. The Alkaloid Profiles of Lupinus sulphureus

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  10. 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.

  11. 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

  12. 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

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

    PubMed

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

    1982-01-01

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

  14. Quinolizidine alkaloid biosynthesis: recent advances and future prospects

    PubMed Central

    Bunsupa, Somnuk; Yamazaki, Mami; Saito, Kazuki

    2012-01-01

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

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

    PubMed

    Diaz, Gonzalo J

    2015-01-01

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

  16. 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

  17. 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

  18. Chlorinated alkaloids in Menispermum dauricum DC: root culture.

    PubMed

    Sugimoto, Y; Babiker, H A; Saisho, T; Furumoto, T; Inanaga, S; Kato, M

    2001-05-18

    Feeding experiments using (36)Cl showed that Menispermum dauricum root culture produces four alkaloids containing chlorine. They included the novel alkaloids dauricumine and dauricumidine as well as the known alkaloids acutumine and acutumidine. The structures of novel alkaloids were established by spectroscopic, crystallographic, and chemical methods. These four alkaloids were labeled with (36)Cl, isolated, and fed independently to root cultures. Mutual conversion between acutumine and acutumidine, and between dauricumine and dauricumidine by N-methylation and N-demethylation, was demonstrated. Moreover, dauricumine was converted to acutumine and acutumidine. Epimerization of acutumidine to dauricumidine or vice versa was not observed. These results suggest that dauricumine is the first chlorinated alkaloid formed in cultured M. dauricum roots. Skewed distribution of radioactivity derived from labeled dauricumine is proof that epimerization at C-1 proceeds at a lower rate than N-demethylation. PMID:11348110

  19. 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 (Epichloë 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

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

    PubMed

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

    2013-08-01

    Epichloae (Epichloë 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. 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

  2. Total synthesis of the Daphniphyllum alkaloid daphenylline

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

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

  3. Total synthesis of all (–)-Agelastatin alkaloids

    PubMed Central

    Siegel, Dustin S.; Han, Sunkyu

    2010-01-01

    The pyrrole-imidazole family of marine alkaloids, derived from linear clathrodin-like precursors, constitutes a diverse array of structurally complex natural products. The bioactive agelastatins are members of this family that possess a tetracyclic molecular framework incorporating C4–C8 and C7–N12 bond connectivities. We provide a hypothesis for the formation of the unique agelastatin architecture that maximally exploits the intrinsic chemistry of plausible biosynthetic precursors. We report the concise enantioselective total syntheses of all known agelastatin alkaloids including the first total syntheses of agelastatins C, D, E, and F. Our gram-scale chemical synthesis of agelastatin A was inspired by our hypothesis for the biogenesis of the cyclopentane C-ring and required the development of new transformations including an imidazolone-forming annulation reaction and a carbohydroxylative trapping of imidazolones. PMID:21218186

  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. 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

  6. 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

  7. A chromanone alkaloid from Derris ovalifolia stem.

    PubMed

    Shankar, Thangaraj; Muthusubramanian, Shanmugam; Gandhidasan, Rathinasamy

    2009-01-01

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

  8. 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

  9. 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

  10. 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

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

    PubMed

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

    2015-07-24

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

  12. 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

  13. 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

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

    PubMed

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

    2008-05-28

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

  15. 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...

  16. 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-?. PMID:26914844

  17. 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...

  18. 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

  19. 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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  1. 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... SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION DIETARY SUPPLEMENTS THAT PRESENT A SIGNIFICANT OR UNREASONABLE RISK § 119.1 Dietary supplements containing ephedrine alkaloids. Dietary supplements...

  2. 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... SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION DIETARY SUPPLEMENTS THAT PRESENT A SIGNIFICANT OR UNREASONABLE RISK § 119.1 Dietary supplements containing ephedrine alkaloids. Dietary supplements...

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Dietary supplements containing ephedrine alkaloids... SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION DIETARY SUPPLEMENTS THAT PRESENT A SIGNIFICANT OR UNREASONABLE RISK § 119.1 Dietary supplements containing ephedrine alkaloids. Dietary supplements...

  4. 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... SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION DIETARY SUPPLEMENTS THAT PRESENT A SIGNIFICANT OR UNREASONABLE RISK § 119.1 Dietary supplements containing ephedrine alkaloids. Dietary supplements...

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

    PubMed

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

    2005-10-01

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

  6. Do naïve ruminants degrade alkaloids in the rumen?

    PubMed

    Aguiar, Ramón; Wink, Michael

    2005-04-01

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

  7. 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

  8. 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

  9. Alkaloids from Piper sarmentosum and Piper nigrum.

    PubMed

    Ee, G C L; Lim, C M; Lim, C K; Rahmani, M; Shaari, K; Bong, C F J

    2009-01-01

    Detailed chemical studies on the roots of Piper sarmentosum and Piper nigrum have resulted in several alkaloids. The roots of P. sarmentosum gave a new aromatic compound, 1-nitrosoimino-2,4,5-trimethoxybenzene (1). Piper nigrum roots gave pellitorine (2), (E)-1-[3',4'-(methylenedioxy)cinnamoyl]piperidine (3), 2,4-tetradecadienoic acid isobutyl amide (4), piperine (5), sylvamide (6), cepharadione A (7), piperolactam D (8) and paprazine (9). Structural elucidation of these compounds was achieved through NMR and MS techniques. Cytotoxic activity screening of the plant extracts indicated some activity. PMID:19809914

  10. 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

  11. Hydroxylated Daphniphyllum Alkaloids from Daphniphyllum himalense.

    PubMed

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

    2015-11-25

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

  12. Plants containing pyrrolizidine alkaloids: toxicity and problems.

    PubMed

    Wiedenfeld, H

    2011-03-01

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

  13. Aspidofractinine and Eburnane Alkaloids from a North Borneo Kopsia. Ring-Contracted, Additional Ring-Fused, and Paucidactine-Type Aspidofractinine Alkaloids from K. pauciflora.

    PubMed

    Yap, Wai-Sum; Gan, Chew-Yan; Sim, Kae-Shin; Lim, Siew-Huah; Low, Yun-Yee; Kam, Toh-Seok

    2016-01-22

    Eleven new indole alkaloids (1-11) comprising seven aspidofractinine and four eburnane alkaloids, were isolated from the stem-bark extract of Kopsia pauciflora occurring in Malaysian Borneo. The aspidofractinine alkaloids include a ring-contracted, an additional ring-fused, a paucidactine regioisomer, two paucidactine, and one kopsine alkaloid. The structures of several of these alkaloids were also confirmed by X-ray diffraction analyses. The bisindole alkaloids isolated, norpleiomutine and kopsoffinol, showed in vitro growth inhibitory activity against human PC-3, HCT-116, MCF-7, and A549 cells and moderate effects in reversing multidrug-resistance in vincristine-resistant human KB cells. PMID:26717050

  14. A new alkaloid from Salsola collina.

    PubMed

    Xiang, Yu; Li, You-Bin; Zhang, Jian; Li, Ping; Yao, Yuan-Zhang

    2007-06-01

    Salsola collina is widely distributed in droughty and semi-droughty area, which is used as a kind of folk remedy in traditional Chinese medicine for treatment of hypertension. The study is on the chemical constituents of this herb from its aerial parts to obtain its active constituents. Dried and crushed aerial parts of this herb were extracted three times with 95% EtOH at reflux. The ethanol extracts were combined and concentrated under reduced pressure at 70 degrees C to yield residue, which was suspended in water and successively partitioned with light petroleum, chloroform and n-butanol. The chloroform and n-butanol fractions were treated by various chromatographic techniques, such as silica gel, C18 reversed-phase silica gel and macroporous resin column chromatography. Compounds were elucidated by their physicochemical properties and spectroscopic analysis. In the course of our study on searching biological active components from this herb, a new alkaloid together with three known alkaloids were isolated and identified as N-transferuloyl-3-methyldopamine (1), 3-[4-(beta-D-glucopyranosyloxy)-3-methoxyphenyl]-N-[2-(4-hydroxyl-3-methoxyphenyl) ethyl]-2-propenamide (2), salsoline A (3), salsoline B (4). Compound 4 is a new compound and named as salsoline B, while compound 2 was obtained in Salsola collina for the first time. PMID:17702398

  15. 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

  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. 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, ?-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 (?/kg and 10 (?g/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 (?g/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 ?g/kg, the median alkaloid level was at 70 (?g/kg. The maximum sum of total determined alkaloids exceeded 1000 (?g/kg in wheat, triticale, rye, and mixed feeds, the highest result was obtained for mixed feed (4880 (?g/kg). PMID:23604683

  19. Fungal endophyte-infected grasses: Alkaloid accumulation and aphid response.

    PubMed

    Siegel, M R; Latch, G C; Bush, L P; Fannin, F F; Rowan, D D; Tapper, B A; Bacon, C W; Johnson, M C

    1990-12-01

    The occurrence of the alkaloidsN-formyl andN-acetyl loline, peramine, lolitrem B, and ergovaline and the response of aphids to plants containing these compounds were determined in species and cultivars ofFestuca,Lolium, and other grass genera infected with fungal endophytes (Acremonium spp., andEpichloe typhina). Twenty-nine of 34 host-fungus associations produced one or more of the alkaloids, most frequently peramine or ergovaline. Three alkaloids (lolines, peramine, and ergovaline) were found in tall fescue and in perennial ryegrass infected withA. coenophialum, while peramine, lolitrem B, and ergovaline were present in perennial ryegrass and in tall fescue infected withA. lolii and inF. longifolia infected withE. typhina. WhileA. coenophialum andA. lolii produced similar patterns of alkaloids regardless of the species or cultivar of grass they infected, isolates ofE. typhina produced either no alkaloids or only one or two different alkaloids in the grasses tested. Aphid bioassays indicated thatRhopalosiphum padi andSchizaphis graminum did not survive on grasses containing loline alkaloids and thatS. graminum did not survive on peramine-containing grasses. Ergovaline-containing grasses did not affect either aphid. PMID:24263431

  20. 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

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

    PubMed

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

    2003-01-01

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

  2. Two new N-oxide alkaloids from Stemona cochinchinensis.

    PubMed

    Lin, Ligen; Bao, Han; Wang, Anqi; Tang, Chunping; Dien, Pham-Huu; Ye, Yang

    2014-01-01

    Two new N-oxide alkaloids with pyrrolo[1,2-?]azepine skeleton, namely isoneostemocochinine-N-oxide (1) and neostemocochinine-N-oxide (2), as well as three known alkaloids with pyrido[1,2-?]azepine skeletons, were isolated and identified from the roots of Stemona cochinchinensis (Stemonaceae). The structures of these compounds were elucidated by 1D- and 2D-NMR spectra and other spectroscopic studies. Additionally, the 1H- and 13C-NMR characteristic of N-oxide Stemona alkaloids was summarized. Stemokerrin showed potent anti-tussive activity on citric acid-induced guinea pig model. PMID:25479189

  3. 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

  4. 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

  5. Total Synthesis and Study of Myrmicarin Alkaloids

    PubMed Central

    Ondrus, Alison E.

    2010-01-01

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

  6. Synthesis and Anticancer Activity of Epipolythiodiketopiperazine Alkaloids

    PubMed Central

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

    2013-01-01

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

  7. 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

  8. Erythroidine alkaloids: a novel class of phytoestrogens.

    PubMed

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

    2014-07-01

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

  9. Pyrrolizidine alkaloids in pollen and pollen products.

    PubMed

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

    2010-02-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. 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...

  12. Alkaloids with Different Carbon Units from Myrioneuron faberi.

    PubMed

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

    2015-11-25

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

  13. [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

  14. 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

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

    NASA Technical Reports Server (NTRS)

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

    1986-01-01

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

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

    PubMed

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

    2014-07-01

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

  17. On the sequence of bond formation in loline alkaloid biosynthesis.

    PubMed

    Faulkner, Jerome R; Hussaini, Syed R; Blankenship, Jimmy D; Pal, Sitaram; Branan, Bruce M; Grossman, Robert B; Schardl, Christopher L

    2006-07-01

    Loline alkaloids are saturated pyrrolizidines with an oxygen bridge between carbon atoms C-2 and C-7 and an amino group on C-1. They are bioprotective alkaloids produced by Epichloë and Neotyphodium species, mutualistic fungal endophytes that are symbiotic with cool-season grasses. The sequence of bond formation in loline alkaloid biosynthesis was determined by synthesizing deuterated forms of potential intermediates and feeding them to cultures of the endophyte Neotyphodium uncinatum. These cultures incorporated deuterium from labeled N-(3-amino-3-carboxypropyl)proline and exo-1-aminopyrrolizidine into N-formylloline. The first result suggests that N-(3-amino-3-carboxypropyl)proline is the first committed intermediate in loline biosynthesis, and the second result demonstrates that the pyrrolizidine rings form before the ether bridge. The incorporation of these two compounds into lolines and the lack of incorporation of several related compounds clarify the order of bond formation in loline alkaloid biosynthesis. PMID:16755627

  18. 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

  19. 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 ?M. PMID:25367562

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

    PubMed

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

    1986-08-01

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

  1. Synthesis of the Common Core Structure of the Stemofoline Alkaloids.

    PubMed

    Ideue, Eiji; Shimokawa, Jun; Fukuyama, Tohru

    2015-10-16

    A novel synthetic route to the common core structural motif of the stemofoline alkaloids has been developed. The key transformations include (1) an intramolecular 1,3-dipolar cycloaddition reaction of a highly functionalized nitrone, (2) the subsequent formation of a caged structure via lithiated allylic sulfoxide, and (3) the concomitant sila-Pummerer reaction of ?-silylalkenyl sulfoxide to prepare a thioester precursor. A series of stereochemistries on the highly caged core structure characteristic of the stemofoline alkaloids was successfully assembled. PMID:26376282

  2. Bioactive guanidine alkaloids from two Caribbean marine sponges.

    PubMed

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

    2009-09-01

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

  3. Molecular genetics of alkaloid biosynthesis in Nicotiana tabacum.

    PubMed

    Dewey, Ralph E; Xie, Jiahua

    2013-10-01

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

  4. Concentrations of ephedra alkaloids and caffeine in commercial dietary supplements.

    PubMed

    Haller, Christine A; Duan, Minjing; Benowitz, Neal L; Jacob, Peyton

    2004-04-01

    Dietary supplements that contain Ma Huang (ephedra alkaloids) and guarana (caffeine) are widely marketed and used in the U.S. for weight loss and athletic performance enhancement, despite a lack of adequate research on the pharmacology of these botanical stimulants. We developed and applied a novel liquid chromatography-tandem mass spectrometry (LC-MS-MS) method to quantitate the various ephedra alkaloids found in dietary supplements that contain Ephedra species. The quantities of ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, methylephedine, methylpseudoephedrine, and caffeine were determined for 35 commercial dietary supplements and compared with the amounts listed on the product labels. The total ephedra alkaloid content ranged from 5.97 mg to 29.3 mg per serving. Two supplement brands did not list the quantity of ephedra alkaloids on the label, and four did not list the amount of caffeine per serving. Of the products tested, 31% contained > 110% of the total ephedra alkaloids listed on the label, and 6% of the supplements contained < 90% of the listed amount. For caffeine, 86% of the product lots that listed the caffeine amount contained less than 90% of the labeled quantity. No products contained > 110% of the declared caffeine content. The total ephedra alkaloid content varied significantly from lot to lot in 5 of 9 products. Three product brands contained proportions of alkaloids that exceeded amounts reported for E. sinica, including one that was 98% ephedrine, one that had 10% norpseudoephedrine, and one that contained an average of 13% methylephedrine. We conclude that product inconsistency is common among some commercially available dietary supplements that contain ephedra alkaloids and caffeine. PMID:15107143

  5. Pyrrole alkaloids from the fruits of Morus alba.

    PubMed

    Kim, Seon Beom; Chang, Bo Yoon; Hwang, Bang Yeon; Kim, Sung Yeon; Lee, Mi Kyeong

    2014-12-15

    Phytochemical investigation of the fruits of Morus alba afforded seventeen pyrrole alkaloids including five new compounds. The structures of five new pyrrole alkaloids, named morroles B-F (4, 5, 7, 16 and 17), were determined on the basis of spectroscopic interpretations. 4-[Formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]butanoate (2) was synthesized by chemical reaction but first isolated from nature. Among isolated compounds, compounds 6 and 14 significantly inhibited pancreatic lipase activity. PMID:25467154

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

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

    PubMed

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

    1999-06-01

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

  12. 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

  13. Synthesis of Morphinan Alkaloids in Saccharomyces cerevisiae.

    PubMed

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

    2015-01-01

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

  14. Pyrrolizidine alkaloids in honey and bee pollen.

    PubMed

    Dübecke, A; Beckh, G; Lüllmann, C

    2011-03-01

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

  15. 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

  16. 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

  17. 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

  18. Pyrrolizidine alkaloids in Senecio madagascariensis from Australia and Hawaii and assessment of possible livestock poisoning

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The alkaloid content of Senecio madagascariensis collected from Australia, and from Hawaii, was examined. Alkaloids were identified by GC-MS analysis and included: senecivernine, senecionine, integerrimine, senkirkine, mucronatinine, retrorsine, usaramine, otosenine, acetylsenkirkine, desacetyldoro...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

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

    PubMed

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

    2015-02-27

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

  7. 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

  8. 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 (...

  9. 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...

  10. 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

  11. Quinolizidine alkaloids from the curare adjuvant Clathrotropis glaucophylla.

    PubMed

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

    2002-12-01

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

  12. 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

  13. Physicochemical characterization of the Strychnos alkaloids by capillary zone electrophoresis.

    PubMed

    Fu, Shaoping; Zhang, Feng; Zhang, Xiaozhe; Xu, Qing; Xiao, Hongbin; Liang, Xinmiao

    2005-11-01

    A capillary zone electrophoresis (CZE) method has been developed for investigating the physicochemical characteristics of five Strychnos alkaloids in Strychnos nux-vomica L. Firstly, the dissociation constants of the five Strychnos alkaloids were determined, based on the relation between the effective mobility of the solutes and the buffer pH. The mathematical relationship was strictly deduced from the fundamental electrophoretic theory and the dissociation equilibrium. Secondly, an equation describing the relation between the migration time of alkaloids of similar structure and their molecular weights was developed and used to predict the migration order and to calculate the electrosomotic velocity. The results predicted by the theory agreed with those from experiments. PMID:16317898

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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

  20. Aporphine and bisaporphine alkaloids from Aristolochia lagesiana var. intermedia.

    PubMed

    Ferreira, Marcia L R; de Pascoli, Inara C; Nascimento, Isabele R; Zukerman-Schpector, Julio; Lopes, Lucia M X

    2010-03-01

    Corydines, isocorydines, and analogous aporphine alkaloids were isolated from the leaves of Aristolochia lagesiana var. intermedia, together with three bisaporphine salts (lagesianines B-D). Their structures were determined by chemical derivatizations and spectroscopic analyses. Lagesianines B and C are the first examples of N-CH(2)-N' and C-2-O-C-1' linked dimeric aporphine alkaloids, respectively, while the monomeric units of lagesianine D, which has a carbon skeleton, are linked through C-7-C-5'via an ethane-1,2-diol group (C-7-CHOHCHOH-C-5'). PMID:20036405

  1. 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.

  2. Anti-herpes virus activity of aporphine alkaloids.

    PubMed

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

    1995-10-01

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

  3. Synthesis of the 1-phenethyltetrahydroisoquinoline alkaloids (+)-dysoxyline, (+)-colchiethanamine, and (+)-colchiethine.

    PubMed

    Reddy, Raju Jannapu; Kawai, Nobuyuki; Uenishi, Jun'ichi

    2012-12-21

    Asymmetric total syntheses of the 1-phenethyl-1,2,3,4-tetrahydroisoquinoline alkaloids (+)-dysoxyline (1), (+)-colchiethanamine (2), and (+)-colchiethine (3) are described. In the synthetic routes, coupling of a key, enatiomerically pure 1-(sulfonylmethyl)tetrahydroisoquinoline with aromatic aldehydes, performed by using the Julia-Kocienski reaction, afforded the corresponding 1-(?-styryl)-substituted tetrahydroisoquinolines with complete retention of the absolute configuration at the C1 carbon atom. Functionalization of the products generated in these processes by using four- or five-step sequences gave the target alkaloids 1-3. PMID:23176065

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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

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

    PubMed

    Wink, M

    1983-08-01

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

  10. Pyrrolizidine Alkaloids in Adenostyles alliariae and A. glabra from the Austrian Alps.

    PubMed

    Chizzola, Remigius

    2015-07-01

    The alkaloid content of Adenostyles alliariae and A. glabra (Asteraceae) has been evaluated. Both species contain toxic macrocyclic unsaturated pyrrolizidine alkaloids with seneciphylline as the main compound accounting for more than 90% of the alkaloid fraction in all above ground plant parts. Further alkaloids were spartioidine, acetyl-senciphylline and senecionine. Inflorescences showed the highest alkaloid contents with 21.1 and 13.4 mg/g in A. alliariae and A. glabra, respectively. Stems and leaves had 2-3 times lower contents. Therefore, these Adenostyles species must be considered as highly toxic plants. PMID:26411004

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

    PubMed

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

    1990-01-01

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

  12. [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

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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...

  18. 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

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

    PubMed

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

    2005-04-01

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

  20. Tropane alkaloid analysis by chromatographic and electrophoretic techniques: an update.

    PubMed

    Aehle, Elke; Dräger, Birgit

    2010-05-15

    Tropane alkaloids like atropine are antidotes applied against organophosphorus intoxications. Atropine is toxic itself and should be closely monitored during treatment. Hence, simple, fast, and sensitive determination methods for tropane alkaloids in serum are desirable. Mostly adopted methods of analysis are gas chromatography (GC); high performance liquid chromatography (HPLC), and capillary electrophoresis (CE). Various liquid and solid capillary fillings used in micellar electrokinetic chromatography, microemulsion electrokinetic chromatography, capillary electrochromatography, and enantioseparation provide high versatility to CE applications. In HPLC, specialised columns enhance separation efficacy. Ultraviolet light detection is common practise, but recently sensitivity and analyte identification were enhanced by coupling GC, HPLC, and CE to mass spectrometry. Apart from medical treatment, tropane alkaloids, cocaine in particular, are abused with various intentions. Forensic analysis of tropane alkaloids and their metabolites comprises the additional difficulty of unequivocal drug identification. Because of severe legal consequences, sophisticated analytical methods were developed and may provide additional techniques for therapeutic drug monitoring. Examples from forensic cocaine analysis and from doping analysis are included in this review. PMID:20381435

  1. 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...

  2. 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

  3. 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

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

    PubMed Central

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

    2011-01-01

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

  5. 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...

  6. 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...

  7. Synthesis of alkaloid 223A and a structural revision.

    PubMed

    Toyooka, Naoki; Fukutome, Ayako; Nemoto, Hideo; Daly, John W; Spande, Thomas F; Garraffo, H Martin; Kaneko, Tetsuo

    2002-05-16

    [structure: see text] Synthesis of alkaloid 223A has been achieved by sequential use of our original conjugate addition reaction to enaminoesters as the key step. The proposed structure for natural 223A (A, absolute configuration unknown) was revised to B, and the relative stereostructure was determined to be 5R*,6R*,8R*,9S* by the present synthesis. PMID:12000281

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

    PubMed

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

    2016-01-01

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

  9. 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...

  10. 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...

  11. 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...

  12. 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

  13. 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...

  14. 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...

  15. 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

  16. 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.

  17. 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

  18. 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

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

    PubMed

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

    2009-10-15

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

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

    PubMed

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

    1983-08-01

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

  1. 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

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

    PubMed

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

    2006-04-21

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

  3. 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

  4. 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

  5. 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

  6. 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

  7. Experience influences gustatory responsiveness to pyrrolizidine alkaloids in the polyphagous caterpillar, Estigmene acrea.

    PubMed

    Chapman, R F; Bernays, E A; Singer, M S; Hartmann, T

    2003-11-01

    Electrophysiological recordings from taste sensilla of the caterpillar Estigmene acrea with the pyrrolizidine alkaloid, seneciphylline N-oxide, demonstrated that prior feeding on plants with pyrrolizidine alkaloids caused an increase in responsiveness of the PA-sensitive cells in two sensilla, relative to feeding on plants without such chemicals. Rearing on synthetic diet without pyrrolizidine alkaloids for up to seven generations caused a continuous decline in responsiveness, that could be reversed by experience with powdered Crotalaria pumila in the diet or by pure pyrrolizidine alkaloid, monocrotaline, in the diet. Response to the cardiac glycoside, ouabain, that stimulates one of the two pyrrolizidine alkaloid-sensitive cells, showed a similar decline. Pyrrolizidine alkaloids had no measurable effect on growth and development. Responses in all other taste cells were unaffected. The data are discussed in relation to the possible adaptive significance and the possible mechanisms involved. PMID:14520497

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

    PubMed Central

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

    1971-01-01

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

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

    PubMed

    Hovermale, Jeannette T; Craig, A Morrie

    2002-12-10

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

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

    PubMed

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

    2006-09-01

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

  11. 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

  12. 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

  13. 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.

  14. A Submarine Journey: The Pyrrole-Imidazole Alkaloids †

    PubMed Central

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

    2009-01-01

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

  15. 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 ?M. PMID:26123248

  16. 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

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

    PubMed

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

    2015-11-15

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

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

    PubMed Central

    Wink, Michael; Hartmann, Thomas

    1982-01-01

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

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

    PubMed

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

    2015-12-18

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

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

    PubMed

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

    2015-11-01

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

  1. ?-Agarofurans and Sesquiterpene Pyridine Alkaloids from Maytenus spinosa.

    PubMed

    Gutiérrez-Nicolás, Fátima; Oberti, Juan C; Ravelo, Ángel G; Estévez-Braun, Ana

    2014-08-22

    Nine new ?-dihydroagarofurans (1-9) and four new sesquiterpene pyridine alkaloids (10-13) were isolated from the leaves of Maytenus spinosa. Their structures were determined mainly by 1D- and 2D-NMR spectroscopic studies. The absolute configuration of compound 6 was established using CD spectroscopy. Several derivatives (14-20) were prepared from the sesquiterpene 13. Most of the sesquiterpenoids were tested for anti-HIV activity, but only compound 1 was found to be active. PMID:25057904

  2. 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

  3. 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

  4. 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

  5. Interrupted Fischer Indolization Approach toward the Communesin Alkaloids and Perophoramidine

    PubMed Central

    Schammel, Alex W.; Chiou, Grace; Garg, Neil K.

    2012-01-01

    A concise approach toward the total synthesis of the communesin alkaloids and perophoramidine is reported. The strategy relies on the use of the interrupted Fischer indolization to build the tetracyclic indoline core of the natural products. Studies to probe the scope and limitations of this plan are presented. Although the methodology does not tolerate a C8-allyl substituent en route to the challenging vicinal quaternary stereocenters, variation at C7 and on the C ring is permitted. PMID:22905746

  6. 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

  7. 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

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

    PubMed

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

    2015-10-19

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

  9. 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

  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. Quinolizidine alkaloids isolated from Lupinus species enhance insulin secretion.

    PubMed

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

    2004-11-01

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

  12. 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

  13. 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 A–F (1–6), 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 (20–190 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

  14. 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

  15. 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

  16. 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

  17. Environmental and genotypic influences on isoquinoline alkaloid content in Sanguinaria canadensis.

    PubMed

    Salmore, A K; Hunter, M D

    2001-09-01

    In a common garden, we investigated genetic and environmental influences on alkaloid production using Sanguinaria canadensis as a model. Nutrient and shade regimes were applied to replicated clones over one growing season, and induction of alkaloid production in bloodroot was tested on a whole-plant basis using jasmonic acid as an elicitor. Alkaloid concentrations increased with decreasing light intensity and fertilizer levels. Induction was not achieved by foliar application of jasmonic acid. Genetic influences represented by clone effects may be indicated by variation in alkaloid concentration by clone, but this experimental design did not allow us to distinguish genetic from pre-experiment environmental influences on the rhizomes. PMID:11545367

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

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

    PubMed Central

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

    2012-01-01

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

  4. 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

  5. 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...

  6. 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 ...

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

    PubMed

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

    2007-01-01

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

  8. 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...

  9. 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

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

    PubMed

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

    2015-12-01

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

  11. 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...

  12. Chiral gas chromatographic determination of ephedrine-type alkaloids in dietary supplements containing Má Huáng.

    PubMed

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

    1997-01-01

    Má Huáng 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 Má Huáng 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 Má Huáng-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 Má Huáng 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

  13. 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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  15. 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...

  16. 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...

  17. 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...

  18. 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

  19. 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 ...

  20. 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 ...

  1. 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 ...

  2. 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...

  3. 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...

  4. 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...

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

    PubMed

    Adler, L S.; Wink, M

    2001-06-01

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

  6. 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

  7. 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...

  8. 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

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

    PubMed

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

    2015-11-01

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

  10. Anthranilate synthase from Ruta graveolens. Duplicated AS alpha genes encode tryptophan-sensitive and tryptophan-insensitive isoenzymes specific to amino acid and alkaloid biosynthesis.

    PubMed Central

    Bohlmann, J; Lins, T; Martin, W; Eilert, U

    1996-01-01

    Anthranilate synthase (AS, EC 4.1.3.27) catalyzes the conversion of chorismate into anthranilate, the biosynthetic precursor of both tryptophan and numerous secondary metabolites, including inducible plant defense compounds. The higher plant Ruta graveolens produces tryptophan and elicitor-inducible, anthranilate-derived alkaloids by means of two differentially expressed nuclear genes for chloroplast-localized AS alpha subunits, AS alpha 1 and AS alpha 2. Mechanisms that partition chorismate between tryptophan and inducible alkaloids thus do not entail chloroplast/cytosol separation of AS isoenzymes and yet might involve differential feedback regulation of pathway-specific AS alpha subunits. The two AS alpha isoenzymes of R. graveolens were expressed as glutathione S-transferase fusion proteins in Escherichia coli deletion mutants defective in AS activity and were purified to homogeneity. Differential sensitivity of the transformed E. coli strains toward 5-methyltryptophan, a false-feedback inhibitor of AS, was demonstrated. Characterization of affinity-purified AS alpha isoenzymes revealed that the noninducible AS alpha 2 of R. graveolens is strongly feedback inhibited by 10 microns tryptophan. In contrast, the elicitor-inducible AS alpha 1 isoenzyme is only slightly affected even by tryptophan concentrations 10-fold higher than those observed in planta. These results are consistent with the hypothesis that chorismate flux into biosynthesis of tryptophan and defense-related alkaloid biosynthesis in R. graveolens is regulated at the site of AS alpha isoenzymes at both genetic and enzymatic levels. PMID:8787026

  11. 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 ?g/mL, while 14 showed moderate activity against Klepsiella pneumonia with an MIC value of 1.56 ?g/mL. PMID:26136061

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

    PubMed

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

    2014-12-01

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

  13. 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

  14. 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

  15. 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 3?-dihydrocadambine (9) and dolichantoside (10), the last one not previously found in Uncaria. PMID:23296316

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

    PubMed

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

    2015-01-01

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

  17. Occurrence of peptide and clavine ergot alkaloids in tall fescue grass.

    PubMed

    Lyons, P C; Plattner, R D; Bacon, C W

    1986-04-25

    Evidence is presented that ergot alkaloids are ubiquitous in tall fescue pastures infected with the clavicipitaceous fungal endophyte Sphacelia typhina (or Acremonium coenophialum). Ergopeptide alkaloids, predominantly ergovaline, constituted 10 to 50 percent of the total ergot alkaloid concentration, which was as high as 14 milligrams per kilogram in sheaths and 1.5 milligrams per kilogram in blades. Ergot alkaloid concentrations were substantially increased by application of large amounts (10 millimoles per liter) of potassium nitrate or ammonium chloride to infected plants in the greenhouse. The results indicate that ergot alkaloids are probably responsible for the toxicity to cattle of this common pasture and lawn grass and that ergotism-like toxicoses may be caused by clavicipitaceous fungi other than Claviceps. PMID:3008328

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

    PubMed

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

    2002-01-01

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

  19. 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

  20. Bromopyrrole Alkaloids as Lead Compounds against Protozoan Parasites

    PubMed Central

    Scala, Fernando; Fattorusso, Ernesto; Menna, Marialuisa; Taglialatela-Scafati, Orazio; Tierney, Michelle; Kaiser, Marcel; Tasdemir, Deniz

    2010-01-01

    In the present study, 13 bromopyrrole alkaloids, including the oroidin analogs hymenidin (2), dispacamide B (3) and dispacamide D (4), stevensine (5) and spongiacidin B (6), their derivatives lacking the imidazole ring bromoaldisin (7), longamide B (8) and longamide A (9), the dimeric oroidin derivatives sceptrin (10) and dibromopalau’amine (11), and the non-oroidin bromopyrrolohomoarginin (12), manzacidin A (13), and agelongine (14), obtained from marine sponges belonging to Axinella and Agelas genera have been screened in vitro against four parasitic protozoa, i.e., two Trypanosoma species (T. brucei rhodesiense and T. cruzi), Leishmania donovani and Plasmodium falciparum (K1 strain, a chloroquine resistant strain), responsible of human diseases with high morbidity and, in the case of malaria, high mortality. Our results indicate longamide B (8) and dibromopalau’amine (11) to be promising trypanocidal and antileishmanial agents, while dispacamide B (3) and spongiacidin B (6) emerge as antimalarial lead compounds. In addition, evaluation of the activity of the test alkaloids (2–14) against three different enzymes (PfFabI, PfFabG, PfFabZ) involved in the de novo fatty acid biosynthesis pathway of P. falciparum (PfFAS-II) identified bromopyrrolohomoarginin (12) as a potent inhibitor of PfFabZ. The structural similarity within the series of tested molecules allowed us to draw some preliminary structure-activity relationships. Tests against the mammalian L6 cells revealed important clues on therapeutic index of the metabolites. This is the first detailed study on the antiprotozoal potential of marine bromopyrrole alkaloids. PMID:20714430

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

    PubMed

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

    2014-01-01

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

  3. 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

  4. 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

  5. A new alkaloid glycoside from the rhizomes of Aristolochia fordiana.

    PubMed

    Zhou, Zhongbo; Luo, Jianguang; Pan, Ke; Kong, Lingyi

    2014-01-01

    A new alkaloid glycoside named fordianoside (1), together with three known compounds arabinothalictoside (2), 6-O-p-coumaroyl-?-fructofuranosyl-(2 ? 1)-?-d-glucopyranoside (3) and 4-[formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl] butanoic acid (4), was isolated from the rhizomes of Aristolochia fordiana. The structure of 1 was established as (1S)-1,2,3,4-tetrahydro-7-hydroxy-1-[(4-hydroxybenzyl) methyl]-2,2-dimethyl-8-O-isoquinolinyl ?-d-glucopyranoside by using chemical and spectroscopic methods including HR-ESI-MS, 1D and 2D NMR. PMID:24716548

  6. [Long QRS tachycardia secondary to Aconitum napellus alkaloid ingestion].

    PubMed

    Gaibazzi, Nicola; Gelmini, Gian Paolo; Montresor, Graziano; Canel, Daniela; Comini, Teresa; Fracalossi, Claudio; Martinetti, Claudio; Poeta, Maria Luisa; Ziacchi, Vigilio

    2002-08-01

    The roots and seeds of the aconite (Aconitum napellus) contain alkaloids with modulatory activity on the sodium voltage-dependent channels; most fatal cases have been determined by ventricular tachycardia and respiratory paralysis. The only established treatment is supportive. We report a case of poisoning from Aconitum napellus, ingested by a husband and wife who thought the plant was "mountain chicory". They both had tachyarrhythmias, but the husband had more malignant episodes of hemodynamically unstable wide QRS tachycardia and respiratory paralysis requiring mechanical ventilation. PMID:12407844

  7. 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

  8. 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

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

    PubMed

    Göthel, Qun; Sirirak, Thanchanok; Köck, Matthias

    2015-01-01

    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 (13)C 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

  10. 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

  11. 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

  12. Antifungal Activity of an Alkaloid Allosecurinine against Some Fungi.

    PubMed

    Singh, A K; Pandey, M B; Singh, U P

    2007-06-01

    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

  13. 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

  14. 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

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

    PubMed

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

    2015-08-01

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

  16. 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

  17. 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

  18. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Ceresoli, Giovanni Luca; Zucali, Paolo Andrea

    2015-12-01

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

  1. 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

  2. The thermodynamics of vinca alkaloid-induced tubulin spirals formation.

    PubMed

    Lobert, Sharon; Ingram, Jeffrey W; Correia, John J

    2007-03-01

    Vinca alkaloids are antimitotic, anticancer agents that induce tubulin to form spiral polymers at physiological protein concentrations. We used sedimentation velocity to investigate the effects of six vinca alkaloids on tubulin spiraling. Fitting to a Wyman linkage model reveals a drug dependent change of over two orders of magnitude in spiraling potential, K(1)K(2). Thermodynamic analysis of LnK(1)K(2) data demonstrates large and positive DeltaS values, indicating that tubulin spiral formation is entropically-driven. From the curvature in van't Hoff plots of vinblastine data, we estimate DeltaC(p) for GTP and GDP conditions to be -439 and -396 cal/mol K. Partitioning of DeltaS into the hydrophobic effect, DeltaS(HE), change in rotational/translational freedom, DeltaS(RT) and change in protein conformation, DeltaS(other), demonstrates that the major driving force for tubulin spiral formation is burial of hydrophobic surfaces and that protein conformational changes do not make a significant contribution. Spiraling potential is an indicator of antimitotic activity in vivo, although turbidity studies indicate that there is no correlation between spiraling potential and microtubule inhibition in vitro. Mechanisms that explain this discrepancy are discussed. PMID:16757093

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

    PubMed

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

    2001-09-21

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

  4. 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

  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. 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

  7. 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

  8. 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

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

    PubMed Central

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

    1992-01-01

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

  10. 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.

  11. 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

  12. 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

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

    PubMed

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

    1992-08-01

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

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

    PubMed

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

    2008-07-23

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

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

    PubMed

    Herraiz, Tomás; Galisteo, Juan

    2014-08-15

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

  16. 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

  17. 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

  18. Specific recognition, detoxification and metabolism of pyrrolizidine alkaloids by the polyphagous arctiid Estigmene acrea.

    PubMed

    Hartmann, T; Theuring, C; Beuerle, T; Klewer, N; Schulz, S; Singer, M S; Bernays, E A

    2005-05-01

    Evidence is presented that the polyphagous arctiid Estigmene acrea is well adapted to sequester and specifically handle pyrrolizidine alkaloids of almost all known structural types representative of the major plant families with pyrrolizidine alkaloid-containing species, i.e. Asteraceae with the tribes Senecioneae and Eupatorieae, Boraginaceae, Fabaceae, Apocynaceae and Orchidaceae. The adaptation of E. acrea to pyrrolizidine alkaloids includes a number of specialized characters: (i) highly sensitive recognition of alkaloid sources by pyrrolizidine alkaloid-specific taste receptors; (ii) detoxification of pyrrolizidine alkaloids by N-oxidation catalyzed by a specific flavin-dependent monooxygenase; (iii) transfer and maintenance of all types of pyrrolizidine N-oxides through all developmental stages; (iv) conversion of the various structures into the male courtship pheromone hydroxydanaidal most probably through retronecine and insect specific retronecine esters (creatonotines) as common intermediates; (v) specific integration into mating behavior and defense strategies. Toxic otonecine derivatives, e.g. the senecionine analogue senkirkine, which often accompany the common retronecine derivatives and which cannot be detoxified by N-oxidation do not affect the development of E. acrea larvae. Senkirkine is not sequestered at all. Non-toxic 1,2-saturated platynecine derivatives that frequently occur together with toxic retronecine esters are sequestered and metabolized to hydroxydanaidal, indicating the ability of E. acrea to aromatize saturated pyrrolizidines. Although pyrrolizidine alkaloids, even if they are offered continuously at a high level (2%) in the larval diet, are non-toxic, E. acrea larvae are not able to develop exclusively on a pyrrolizidine alkaloid-containing plant like Crotalaria. Therefore, E. acrea appears to be specifically adapted to exploit pyrrolizidine alkaloid-containing plants as "drug source" but not as a food source. PMID:15804574

  19. 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

  20. Diversity-oriented synthesis of Lycopodium alkaloids inspired by the hidden functional group pairing pattern.

    PubMed

    Zhang, Jing; Wu, Jinbao; Hong, Benke; Ai, Wenying; Wang, Xiaoming; Li, Houhua; Lei, Xiaoguang

    2014-01-01

    Natural products continue to provide a rich source of inspiration for both chemists and biologists. The efficient synthesis of bioactive natural products or natural product-like molecules has offered tremendous opportunities for complex biological processes exploration and drug discovery. However, because natural products usually contain numerous stereogenic centres and polycyclic ring systems, significant synthetic challenges remain. Here we employ the build/couple/pair strategy that is frequently used in diversity-oriented synthesis to obtain skeletally diverse compounds with complexities comparable to natural products. Inspired by the functional group pairing patterns hidden in Lycopodium alkaloids, we efficiently and in parallel construct four natural products, (+)-Serratezomine A, (-)-Serratinine, (+)-8?-Hydroxyfawcettimine and (-)-Lycoposerramine-U, as well as six different unnatural scaffolds, following the advanced build/couple/pair algorithm. This newly developed strategy is expected to be applied to the efficient synthesis of other complex natural products possessing functional group pairing patterns as well as skeletally diverse natural product-like molecules. PMID:25082077

  1. Use of cyclodextrins for the enantioselective separation of ergot alkaloids by capillary zone electrophoresis.

    PubMed

    Fanali, S; Flieger, M; Steinerova, N; Nardi, A

    1992-01-01

    Ergot alkaloid enantiomer derivatives were resolved using capillary zone electrophoresis. The effect of cyclodextrins, added to the background electrolyte, on the migration time and the resolution was studied. Good separation for epimeric ergot alkaloid derivatives was also obtained using phosphate buffer at pH 2.5. Separation was improved by supplementing the background electrolyte with 30 mM of gamma-cyclodextrin. Good resolution of racemic ergot alkaloid derivatives in their enantiomers was achieved in a background electrolyte containing either beta-cyclodextrin or its derivative, or gamma-cyclodextrin. PMID:1587252

  2. 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

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

    PubMed

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

    2001-01-01

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

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

    PubMed

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

    2005-01-01

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

  5. [Polymethyleneamine alkaloids of animal origin. I. Metabolites of marine and microbial organisms].

    PubMed

    Rogoza, L N; Salakhutdinov, N F; Tolstikov, G A

    2005-01-01

    This review, issued in two parts, describes the information on the structure and biological activity of animal alkaloids derived from polymethyleneamines and produced by marine organisms, wasps, spiders, and microorganisms. Animal alkaloids are outstanding models for developing methods and drugs for the treatment of many human diseases. In the first part, we consider compounds produced by marine and microbial organisms. Some promising synthetic analogues of these alkaloids are used in developing modem preparations for the chelate therapy of excessive blood iron content and antituberculosis, antiproliferative, and immunosuppressive drugs. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2005, vol. 31, no. 6; see also http://www.maik.ru. PMID:16363128

  6. Acquisition, transformation and maintenance of plant pyrrolizidine alkaloids by the polyphagous arctiid Grammia geneura.

    PubMed

    Hartmann, T; Theuring, C; Beuerle, T; Bernays, E A; Singer, M S

    2005-10-01

    The polyphagous arctiid Grammia geneura appears well adapted to utilize for its protection plant pyrrolizidine alkaloids of almost all known structural types. Plant-acquired alkaloids that are maintained through all life-stages include various classes of macrocyclic diesters (typically occurring in the Asteraceae tribe Senecioneae and Fabaceae), macrocyclic triesters (Apocynaceae) and open-chain esters of the lycopsamine type (Asteraceae tribe Eupatorieae, Boraginaceae and Apocynaceae). As in other arctiids, all sequestered and processed pyrrolizidine alkaloids are maintained as non-toxic N-oxides. The only type of pyrrolizidine alkaloids that is neither sequestered nor metabolized are the pro-toxic otonecine-derivatives, e.g. the senecionine analog senkirkine that cannot be detoxified by N-oxidation. In its sequestration behavior, G. geneura resembles the previously studied highly polyphagous Estigmene acrea. Both arctiids are adapted to exploit pyrrolizidine alkaloid-containing plants as "drug sources". However, unlike E. acrea, G. geneura is not known to synthesize the pyrrolizidine-derived male courtship pheromone, hydroxydanaidal, and differs distinctly in its metabolic processing of the plant-acquired alkaloids. Necine bases obtained from plant acquired pyrrolizidine alkaloids are re-esterified yielding two distinct classes of insect-specific ester alkaloids, the creatonotines, also present in E. acrea, and the callimorphines, missing in E. acrea. The creatonotines are preferentially found in pupae; in adults they are largely replaced by the callimorphines. Before eclosion the creatonotines are apparently converted into the callimorphines by trans-esterification. Open-chain ester alkaloids such as the platynecine ester sarracine and the orchid alkaloid phalaenopsine, that do not possess the unique necic acid moiety of the lycopsamine type, are sequestered by larvae but they need to be converted into the respective creatonotines and callimorphines by trans-esterification in order to be transferred to the adult stage. In the case of the orchid alkaloids, evidence is presented that during this processing the necine base (trachelanthamidine) is converted into its 7-(R)-hydroxy derivative (turneforcidine), indicating the ability of G. geneura to introduce a hydroxyl group at C-7 of a necine base. The creatonotines and callimorphines display a striking similarity to plant necine monoesters of the lycopsamine type to which G. geneura is well adapted. The possible function of insect-specific trans-esterification in the acquisition of necine bases derived from plant acquired alkaloids, especially from those that cannot be maintained through all life-stages, is discussed. PMID:16102415

  7. 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

  8. 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

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

    PubMed

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

    2014-01-01

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

  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. 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.

  12. 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…

  13. [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

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

    PubMed

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

    2015-01-01

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

  15. 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

  16. Indolosesquiterpene alkaloids from the Cameroonian medicinal plant Polyalthia oliveri (Annonaceae).

    PubMed

    Kouam, Simeon Fogue; Ngouonpe, Alain Wembe; Lamshöft, Marc; Talontsi, Ferdinand Mouafo; Bauer, Jonathan O; Strohmann, Carsten; Ngadjui, Bonaventure Tchaleu; Laatsch, Hartmut; Spiteller, Michael

    2014-09-01

    The stem bark of Polyalthia oliveri was screened for its chemical constituents using liquid chromatography high resolution mass spectrometry resulting in the isolation of three indolosesquiterpene alkaloids named 8?-polyveolinone (1), N-acetyl-8?-polyveolinone (2) and N-acetyl-polyveoline (3), together with three known compounds, dehydro-O-methylisopiline (4), N-methylurabaine (5) and polycarpol (6). The structures of the compounds were elucidated by means of high resolution mass spectrometry and different NMR techniques and chemical transformations. Their absolute configurations were assigned by ab-initio calculation of CD and ORD data (for 2 and 3) and X-ray diffraction analysis (for 2). Compounds 2 and 3 exhibited moderate antiplasmodial activity against erythrocytic stages of chloroquine-sensitive Plasmodium falciparum NF54 strain and low cytotoxicity on rat skeletal myoblast (L6) cell line. PMID:25039009

  17. 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

  18. 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

  19. 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.

  20. 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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    1994-12-01

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

  3. 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

  4. Dibromopyrrole alkaloids from the marine sponge Acanthostylotella sp.

    PubMed

    Ebada, Sherif Saeed; Edrada-Ebel, RuAngelie; de Voogd, Nicole J; Wray, Victor; Proksch, Peter

    2009-01-01

    Fourteen dibromopyrrole alkaloids were isolated from the marine sponge Acanthostylotella sp. collected in Indonesia. In addition to the known compounds 4,5-dibromo-N-(methoxy-methyl)-1H-pyrrole-2-carboxamide (7), 4,5-dibromo-1H-pyrrole-2-carboxamide (8), mukanadin D (9), (+/-)-longamide B methyl ester (10), (+/-)-longamide B (11), (+/-)-longamide (12), 3,4-dibromo-lH-pyrrole-2-carboxamide (13), 2-cyano-4,5-dibromo-1H-pyrrole (14), six compounds were isolated that proved to be new natural products including acanthamides A-D (1-4), methyl 3,4-dibromo-1H-pyrrole-2-carboxylate (5) and 3,5-dibromo-1H-pyrrole-2-carboxylic acid (6). The structures of the new compounds were unequivocally identified based on one and two dimensional NMR and on HRFTMS as well as by comparison with the literature. PMID:19370874

  5. The interaction of plant alkaloids with DNA. II. Berberinium chloride.

    PubMed Central

    Davidson, M W; Lopp, i; Alexander, S; Wilson, W D

    1977-01-01

    The interaction of berberinium chloride with DNA has been investigated using spectrophotometry, viscometric titrations with sonicated and closed circular superhelical DNA, and flow polarized fluorescence. The binding results for berberinium were found to fit the neighbor exclusion model. The two viscometric titrations and flow polarized fluorescence results exclusion model. The two viscometric titrations and flow polarized fluorescence results also indicated that berberinium binds to DNA by intercalation. Titration of sonicated DNA with berberinium produced viscosity increases which were less than those obtained with quinacrine and the titration of superhelical DNA indicated a significantly smaller unwinding angle for intercalation of berberinium than for quinacrine. These results can be interpreted in terms of a model in which (i) berberinium is partially intercalated into the double helix, or (ii) the alkaloid is more completely intercalated into the double helix, but causes bending of the helix due to the slight nonplanarity of the berberinium ring system, or (iii) a combination of (i) and (22). PMID:909789

  6. Polar alkaloids from the Caribbean marine sponge Niphates digitalis.

    PubMed

    Regalado, Erik L; Mendiola, Judith; Laguna, Abilio; Nogueiras, Clara; Thomas, Olivier P

    2010-08-01

    A method involving flash chromatography, semi-preparative phenylhexyl RP HPLC-DAD-ELSD combined with analytic polar-RP HPLC-DAD, was applied to separate and purify six highly nitrogenated bases and a bicyclic amidine alkaloid, the major components of the marine sponge Niphates digitalis. Their structures were identified as 1,8-diazabicyclo[5.4.0]undec-7-ene (1), deoxycytidine (2), phenylalanine (3), adenosine (4), deoxyguanosine (5), adenine (6) and thymidine (7) on the basis of spectroscopic data analyses. This is the first report of these compounds in a marine sponge belonging to the Niphates genus and the first evidence of the presence of 1 from a natural source. PMID:20839615

  7. 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.

  8. Synthesis and Fungicidal Activity of ?-Carboline Alkaloids and Their Derivatives.

    PubMed

    Li, Zhibin; Chen, Shaohua; Zhu, Shaowen; Luo, Jianjun; Zhang, Yaomou; Weng, Qunfang

    2015-01-01

    A series of ?-Carboline derivatives were designed, synthesized, and evaluated for their fungicidal activities in this study. Several derivatives electively exhibited fungicidal activities against some fungi. Especially, compound F5 exhibited higher fungicidal activity against Rhizoctonia solani (53.35%) than commercial antiviral agent validamycin (36.4%); compound F16 exhibited high fungicidal activity against Oospora citriaurantii ex Persoon (43.28%). Some of the alkaloids and their derivatives (compounds F4 and F25) exhibited broad-spectrum fungicidal activity. Specifically, compound F4 exhibited excellent high broad-spectrum fungicidal activity in vitro, and the curative and protection activities against P. litchi in vivo reached 92.59% and 59.26%, respectively. The new derivative, F4, with optimized physicochemical properties, obviously exhibited higher activities both in vitro and in vivo; therefore, F4 may be used as a new lead structure for the development of fungicidal drugs. PMID:26263966

  9. 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 ?M 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 ?M on MRC-5 cells, and 0.42 and 2.7 ?M on L-6 cells, respectively. PMID:22033013

  10. Variation in pyrrolizidine alkaloid patterns of Senecio jacobaea.

    PubMed

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

    2004-04-01

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

  11. Pyrrolizidine alkaloids from Senecio jacobaea affect fungal growth.

    PubMed

    Hol, W H G; Van Veen, A

    2002-09-01

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

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

    PubMed

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

    1995-01-01

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

  13. 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

  14. 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

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

    PubMed

    Wink, M; Witte, L; Hartmann, T

    1981-12-01

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

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

    PubMed Central

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

    2012-01-01

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

  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. 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

  20. 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

  1. 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 ...

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

    PubMed

    Wink, M; Witte, L

    1993-03-01

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

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

    PubMed

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

    1987-02-01

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

  4. RNA targeting by small molecules: Binding of protoberberine, benzophenanthridine and aristolochia alkaloids to various RNA structures.

    PubMed

    Kumar, Gopinatha Suresh

    2012-07-01

    Studies on RNA targeting by small molecules to specifically control certain cellular functions is an area of remarkable current interest. For this purpose, a basic understanding of the molecular aspects of the interaction of small molecules with various RNA structures is essential. Alkaloids are a group of natural products with potential therapeutic utility, and very recently, their interaction with many RNA structures have been reported. Especially noteworthy are the protoberberines and aristolochia alkaloids distributed widely in many botanical families. Many of the alkaloids of these group exhibit excellent binding affinity to many RNA structures that may be exploited to develop RNA targeted therapeutics. This review attempts to present the current status on the understanding of the interaction of these alkaloids with various RNA structures, mainly highlighting the biophysical aspects. PMID:22750990

  5. 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

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

    PubMed Central

    Cherney, Emily C.; Baran, Phil S.

    2015-01-01

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

  7. 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

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

    PubMed

    Ikuta; Urabe; Nakamura

    1998-08-01

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

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

    PubMed

    Sasamoto, Hamako; Fujii, Yoshiharu; Ashihara, Hiroshi

    2015-05-01

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

  10. 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...

  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. Variability in the yield of benzophenanthridine alkaloids in wildcrafted vs cultivated bloodroot (Sanguinaria canadensis L.).

    PubMed

    Graf, Tyler N; Levine, Keith E; Andrews, Margaret E; Perlmutter, Jason M; Nielsen, Samara Joy; Davis, Jeanine M; Wani, Mansukh C; Oberlies, Nicholas H

    2007-02-21

    Populations of bloodroot [Sanguinaria canadensis L. (Papaveraceae)] are found throughout the eastern forests of North America, with particular abundance in the southern Appalachian Mountains. Increasingly, it is finding use in Europe as a nonantibiotic animal feed supplement to promote weight gain. As efforts to cultivate this herb are underway, there is a need to understand the effect of agronomic permutations on both the dry mass rhizome yield and the yield of benzophenanthridine alkaloids. Month-to-month variability of the concentration of the alkaloids sanguinarine and chelerythrine in both cultivated and wildcrafted bloodroot was examined. The alkaloid yield was consistently higher, but more variable, in wildcrafted plants. On average, cultivated rhizomes were both larger and more consistently sized than those that were wildcrafted. The concentration of a suite of trace elements was measured in soil that was collected concomitantly with each plant accession. Differences in element profiles were compared against alkaloid yields. PMID:17253712

  13. 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

  14. Quantitative analysis of alkaloidal constituents in imported fire ants by gas chromatography.

    PubMed

    Yu, Yu-Ting; Wei, Hong-Yi; Fadamiro, Henry Y; Chen, Li

    2014-06-25

    A method based on silica gel chromatography and GC-MS/GC-FID analyses was developed for the quantitation of alkaloidal compounds in imported fire ants, Solenopsis richteri, S. invicta, and their hybrid found in the southern United States. The cis and trans alkaloids from fire ant body extracts were successfully separated by silica gel chromatography, identified by GC-MS, and quantitated by GC-FID. Piperideine compounds were eluted together with the cis and trans piperidines, but were well-resolved on a nonpolar GC column. Eight pairs of piperidine isomers and 12 piperideines were quantitated. The ratios of trans alkaloids to corresponding cis isomers ranged from 87 to 378:1 in S. invicta and were significantly higher than in S. richteri and hybrid ants. The results were discussed in relation to the evolution of fire ant venom alkaloids and their role as host location cues for parasitic Pseudacteon phorid flies. PMID:24873743

  15. 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...

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

    PubMed Central

    Cai, Ru; Su, Huidan; Li, Yunlong

    2014-01-01

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

  17. 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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2014-11-01

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

  20. 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

  1. Phosphorylated Derivatives of Alkaloids and Nitrogen-containing Heterocycles — Cholinesterase Inhibitors

    NASA Astrophysics Data System (ADS)

    Sadykov, Abid S.; Dalimov, D. N.; Godovikov, Nikolai N.

    1983-10-01

    The review deals with the synthesis and anticholinesterase activities of phosphorylated derivatives of certain alkaloids and nitrogen-containing heterocycles. It is shown that the conformational properties of the alkaloid and nitrogen-containing heterocycle residues in the composition of the organophosphorus inhibitor (OPI) molecule play an important role in the inhibition of the catalytic activity of cholinesterases. The type of inhibition of cholinesterases also varies as a function of chemical structure. The bibliography includes 45 references.

  2. Identification of metabolites of selected benzophenanthridine alkaloids and their toxicity evaluation.

    PubMed

    Sandor, Roman; Midlik, Adam; Sebrlova, Kristyna; Dovrtelova, Gabriela; Noskova, Kristyna; Jurica, Jan; Slaninova, Iva; Taborska, Eva; Pes, Ondrej

    2016-03-20

    Selected benzo[c]phenathridine alkaloids were biotransformed using rat liver microsomes and identified by liquid chromatography and mass spectrometry. While the metabolites of commercially available sanguinarine and chelerythrine have been studied in detail, data about the metabolism of the minor alkaloids remained unknown. Reactions involved in transformation include single and/or double O-demethylation, demethylenation, reduction, and hydroxylation. Two metabolites, when isolated, purified and tested for toxicity, were found to be less toxic than the original compounds. PMID:26808066

  3. 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

  4. Enantioselective Total Syntheses of Akuammiline Alkaloids (+)-Strictamine, (-)-2(S)-Cathafoline, and (-)-Aspidophylline A.

    PubMed

    Moreno, Jesus; Picazo, Elias; Morrill, Lucas A; Smith, Joel M; Garg, Neil K

    2016-02-01

    The akuammiline alkaloids are a family of natural products that have been widely studied for decades. Although notable synthetic achievements have been made recently, akuammilines that possess a methanoquinolizidine core have evaded synthetic efforts. We report an asymmetric approach to these alkaloids, which has culminated in the first total syntheses of (-)-2(S)-cathafoline and the long-standing target (+)-strictamine. Moreover, the first enantioselective total synthesis of aspidophylline A is described. PMID:26783944

  5. 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

  6. Total synthesis of the neotropical poison-frog alkaloid (-)-205B.

    PubMed

    Smith, Amos B; Kim, Dae-Shik

    2005-07-21

    [reaction: see text]. A stereocontrolled total synthesis of the neotropical poison-frog alkaloid (-)-205B (1) has been achieved, employing a dithiane three-component linchpin coupling, a one-pot sequential construction of the embedded indolizidine ring, and ring-closing metathesis (RCM) to arrive at the novel 8b-azaacenaphthylene ring system comprising the alkaloid. The synthesis proceeded with a longest linear sequence of 19 steps, affording (-)-1 in 5.6% overall yield. PMID:16018632

  7. 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

  8. Idiospermuline, a trimeric pyrrolidinoindoline alkaloid from the seed of Idiospermum australiense.

    PubMed

    Kuke, R K; Allan, R D; Johnston, G A; Mewett, K N; Mitrovic, A D; Duke, C C; Hambley, T W

    1995-08-01

    Purification of a methanol extract from the seed of Idiospermum australiense, guided by bioactivity on a rat brain cortical wedge preparation has afforded two known dimeric alkaloids, the piperidinoindoline (+)-calycanthine [1] and the pyrrolidinoindoline, (-)-chimonanthine [2] along with a new trimeric pyrrolidinoindoline alkaloid, (-)-idiospermuline [3]. Te structure of idiospermuline [3] was determined by spectroscopic methods and the absolute configuration by an X-ray crystallographic study of idiospermuline trimethiodide [4]. PMID:7595588

  9. 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

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

    PubMed

    Kawai, K; Nozawa, Y; Ogihara, Y

    1977-11-15

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

  11. 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

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

    PubMed

    Vrieling, Klaas; Derridj, Sylvie

    2003-12-01

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

  13. 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.

  14. 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

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

    PubMed

    Ganzera, Markus; Krüger, Anja; Wink, Michael

    2010-12-15

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

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

    PubMed

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

    2015-12-01

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

  17. 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

  18. 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

  19. Dimeric bisindole alkaloids from the stem bark of Strychnos nux-vomica L.

    PubMed

    Jonville, Marie-Caroline; Dive, Georges; Angenot, Luc; Bero, Joanne; Tits, Monique; Ollivier, Evelyne; Frédérich, Michel

    2013-03-01

    Strychnos nux-vomica L. (Loganiaceae) is famous for its monomeric alkaloid content, such as strychnine, a convulsant poison. The stem bark of the tree is traditionally used to treat intermittent fever in South East Asia. In various studies, it appeared that dimeric indolo-monoterpenic alkaloids possess a promising activity on Plasmodium falciparum. Three bisindolomonoterpenic alkaloids together with strychnochrysine, previously identified in the root bark of S. nux-vomica, were isolated from the stem bark. The structures of these compounds were established using NMR spectroscopy and mass spectrometry. Stereochemistry of the compounds was confirmed by molecular modelling. This then allowed the structural determination of strychnoflavine, a coloured bisindole alkaloid previously isolated from the root bark of the tree. Moreover, the conformational inversion in alkaloids possessing an ether bond in the strychnane moiety could be easily predicted by specific ? (13)C NMR values. These longicaudatine-type alkaloids were found to display in vitro antiplasmodial activity against a chloroquine resistant strain and a chloroquine sensitive strain. The most interesting was strychnochrysine showing an IC(50) value at around 10 ?M. PMID:23219610

  20. 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

  1. Growth characteristics of Sanguinaria canadensis L. cell suspensions and immobilized cultures for production of benzophenanthridine alkaloids.

    PubMed

    Rho, D; Chauret, N; Laberge, N; Archambault, J

    1992-02-01

    Sanguinaria canadensis L. plants were harvested from a local forest and calli were initiated from leaf explants. The production of benzophenanthridine alkaloids (i.e. sanguinarine, sanguilutine, sanguirubine, chelerythrine, chelilutine and chelirubine) by S. canadensis cell grown in modified B5 and IM2 media was compared to the alkaloid content of rhizomes. Sanguinarine accounted for approximately 80% of the total alkaloid content of cultured cells (1.3%, g g-1) while sanguinarine and sanguirubine accounted for 70% of rhizome alkaloids (9.0%, g g-1). Sanguinarine, chelirubine and chelerythrine were the only known alkaloids detected in cultured S. canadensis cells. Maximum alkaloid production of cultures performed using B5 medium, containing half the original nitrate concentration, was observed following extracellular nitrate and sugar depletion. The scale-up of this culture was successfully performed in a 2-1 immobilization bioreactor. The consumption of sugar and nitrate as well as the oxygen (OTR) and carbon dioxide (CTR) transfer rates of the immobilized cell culture were monitored for 15 days. The maximum sugar and nitrate consumption rates were 1.8 g l-1 per day and 2.3 mM per day respectively. The maximum OTR and CTR of the immobilized cell culture were 0.8 mmol O2 l-1 h-1 and 0.95 mmol CO2 l-1 h-1 respectively. The sanguinarine yield of this culture reached 1.0% based on biomass dry weight (g g-1 dw) by day 15. PMID:1368065

  2. 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

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

    PubMed

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

    2015-05-01

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

  4. Acaricidal activity of alkaloid fractions of Leucas indica Spreng against Rhipicephalus (Boophilus) annulatus tick.

    PubMed

    Divya, T M; Soorya, V C; Amithamol, K K; Juliet, S; Ravindran, R; Nair, S N; Ajithkumar, K G

    2014-03-01

    The acaricidal activity from alkaloid and non-alkaloid fractions of Leucas indica were studied against Rhipicephalus (Boophilus) annulatus tick using adult immersion test under laboratory conditions. For this purpose, the engorged female R.(B.) annulatus tick were exposed to two fold serial dilutions of alkaloid extract (50 mg/ml, 25 mg/ml, 12.5 mg/ml, 6 mg/ml and 3 mg/ml) using 'dipping method' in vitro. The efficacy was assessed by measuring the percentage of adult mortality, inhibition of fecundity and hatching rate. The alkaloid fraction of the extract produced concentration dependent delayed adult tick mortality. The extract at a concentration of 50 mg/ml demonstrated 66.67 per cent mortality and 55.16 per cent inhibition of fecundity. Nicotine was identified as one of the compounds of alkaloid fraction. However, it did not reveal any acaricidal activity when tested in vitro at concentrations ranging from 62.5-1000 ?g/mL. Hence, the acaricidal action of L. indica is not due to nicotine. Non alkaloid fraction also did not reveal any acaricidal effects against R. (B.) annulatus tick. PMID:24862044

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

    PubMed Central

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

    2013-01-01

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

  6. 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

  7. Contribution of fungal loline alkaloids to protection from aphids in a grass-endophyte mutualism.

    PubMed

    Wilkinson, H H; Siegel, M R; Blankenship, J D; Mallory, A C; Bush, L P; Schardl, C L

    2000-10-01

    Fungal endophytes provide grasses with enhanced protection from herbivory, drought, and pathogens. The loline alkaloids (saturated 1-aminopyrrolizidines with an oxygen bridge) are fungal metabolites often present in grasses with fungal endophytes of the genera Epichloë or Neotyphodium. We conducted a Mendelian genetic analysis to test for activity of lolines produced in plants against aphids feeding on those plants. Though most loline-producing endophytes are asexual, we found that a recently described sexual endophyte, Epichloë festucae, had heritable variation for loline alkaloid expression (Lol+) or nonexpression (Lol-). By analyzing segregation of these phenotypes and of linked DNA polymorphisms in crosses, we identified a single genetic locus controlling loline alkaloid expression in those E. festucae parents. We then tested segregating Lol+ and Lol- full-sibling fungal progeny for their ability to protect host plants from two aphid species, and observed that alkaloid expression cosegregated with activity against these insects. The in planta loline alkaloid levels correlated with levels of anti-aphid activity. These results suggested a key role of the loline alkaloids in protection of host plants from certain aphids, and represent, to our knowledge, the first Mendelian analysis demonstrating how a fungal factor contributes protection to plant-fungus mutualism. PMID:11043464

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

    PubMed

    Petzinger, E

    2011-01-01

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

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

    PubMed

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

    1993-10-01

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

  10. 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

  11. 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...

  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. 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...

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

    PubMed

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

    2013-01-01

    Glaucium flavum is used in Algerian folk medicine to remove warts (benign tumors). Its local appellations are Cheqiq el-asfar and Qarn el-djedyane. We have recently reported the anti-tumoral activity of Glaucium flavum root alkaloid extract against human cancer cells, in vitro and in vivo. The principal identified alkaloid in the extract was protopine. This study aims to determine which component(s) of Glaucium flavum root extract might possess potent antitumor activity on human cancer cells. Quantitative estimation of Glaucium flavum alkaloids was realized by HPLC-DAD. Glaucium flavum effect on human normal and cancer cell viability was determined using WST-1 assay. Quantification of alkaloids in Glaucium flavum revealed that the dried root part contained 0.84% of protopine and 0.07% of bocconoline (w/w), while the dried aerial part contained only 0.08% of protopine, glaucine as the main alkaloid, and no bocconoline. In vitro evaluation of the growth inhibitory activity on breast cancer and normal cells demonstrated that purified protopine did not reproduce the full cytotoxic activity of the alkaloid root extract on cancer cell lines. On the other hand, bocconoline inhibited strongly the viability of cancer cells with an IC50 of 7.8 µM and only a low cytotoxic effect was observed against normal human cells. Our results showed for the first time that protopine is the major root alkaloid of Glaucium flavum. Finally, we are the first to demonstrate a specific anticancer effect of Glaucium flavum root extract against breast cancer cells, which can be attributed, at least in part, to bocconoline. PMID:24317429

  16. 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.

  17. 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

  18. 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

  19. 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

  20. The Only African Wild Tobacco, Nicotiana africana: Alkaloid Content and the Effect of Herbivory

    PubMed Central

    Marlin, Danica; Nicolson, Susan W.; Yusuf, Abdullahi A.; Stevenson, Philip C.; Heyman, Heino M.; Krüger, Kerstin

    2014-01-01

    Herbivory in some Nicotiana species is known to induce alkaloid production. This study examined herbivore-induced defenses in the nornicotine-rich African tobacco N. africana, the only Nicotiana species indigenous to Africa. We tested the predictions that: 1) N. africana will have high constitutive levels of leaf, flower and nectar alkaloids; 2) leaf herbivory by the African bollworm Helicoverpa armigera will induce increased alkaloid levels in leaves, flowers and nectar; and 3) increased alkaloid concentrations in herbivore-damaged plants will negatively affect larval growth. We grew N. africana in large pots in a greenhouse and exposed flowering plants to densities of one, three and six fourth-instar larvae of H. armigera, for four days. Leaves, flowers and nectar were analyzed for nicotine, nornicotine and anabasine. The principal leaf alkaloid was nornicotine (mean: 28 µg/g dry mass) followed by anabasine (4.9 µg/g) and nicotine (0.6 µg/g). Nornicotine was found in low quantities in the flowers, but no nicotine or anabasine were recorded. The nectar contained none of the alkaloids measured. Larval growth was reduced when leaves of flowering plants were exposed to six larvae. As predicted by the optimal defense theory, herbivory had a localized effect and caused an increase in nornicotine concentrations in both undamaged top leaves of herbivore damaged plants and herbivore damaged leaves exposed to one and three larvae. The nicotine concentration increased in damaged compared to undamaged middle leaves. The nornicotine concentration was lower in damaged leaves of plants exposed to six compared to three larvae, suggesting that N. africana rather invests in new growth as opposed to protecting older leaves under severe attack. The results indicate that the nornicotine-rich N. africana will be unattractive to herbivores and more so when damaged, but that potential pollinators will be unaffected because the nectar remains alkaloid-free even after herbivory. PMID:25025217

  1. 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

  2. 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

  3. Metabolic fate of depsides and alkaloid constituents in aqueous extracts from Mercurialis perennis L. during fermentation.

    PubMed

    Lorenz, Peter; Conrad, Jürgen; Stintzing, Florian C

    2013-09-01

    Dog's mercury (Mercurialis perennis L.) is an old medicinal plant, nowadays used in complementary medicine. Aqueous fermented extracts of the plant are being mainly applied in remedies to treat external inflammations, but a thorough phytochemical characterization is still lacking. Therefore, the conversion of characteristic compound classes from M. perennis extracts during fermentation and storage was investigated. The microbial transformation of the two main depsides phaselic acid (=(2R)-O-[(E)-caffeoyl]malic acid; 1) and mercurialis acid (=(2R)-[(E)-caffeoyloxy]glutaric acid; 2) was monitored by HPLC-DAD. The degradation followed a second-order kinetic, and the calculated half-life periods of both constituents were 67 and 30?months, respectively. Several depside metabolites were detected by GC/MS in AcOEt extracts as (t) BuMe2 Si (TBDMS) derivatives after derivatization, mainly dihydrocinnamic acids. Moreover, numerous ?-hydroxy acids were found, allegedly as degradation products from amino acids or peptides. The microbial alteration of the main alkaloid hermidin was also examined. After three days of fermentation, three novel N-metabolites were formed and thoroughly assigned in CH2 Cl2 extracts as a mixture of 3-ethylhermidin, 3-ethylhermidin quinone, and (E/Z)-3-ethylidenehermidin by GC/MS and NMR methods, as well as by means of total synthesis. A mechanism for the formation of these N-metabolites starting from dimeric hermidin oxidation products is proposed. The obtained results reveal the complex pathways plant constituents may undergo during the fermentation of the extracts. PMID:24078603

  4. Anti-inflammatory sesquiterpene pyridine alkaloids from Tripterygium wilfordii.

    PubMed

    Gao, Chang; Huang, Xiao-Xiao; Bai, Ming; Wu, Jie; Li, Jian-You; Liu, Qing-Bo; Li, Ling-Zhi; Song, Shao-Jiang

    2015-09-01

    During a screening procedure involving higher plants to find novel candidates for use as anti-inflammatory agents, Tripterygium wilfordii Hook. f. was shown to exhibit considerable inhibitory activity. Five new sesquiterpene pyridine alkaloids, tripterygiumines S-W (1-4,15), along with 14 known dihydroagarofuran derivatives, were isolated from the roots of the T. wilfordii Hook. f. Their structures were established by extensive use of spectroscopic techniques, including 1D and 2D NMR spectroscopy and high-resolution mass spectrometry. All compounds were evaluated for their anti-inflammatory activity by measuring the nitric oxide production by the LPS-induced murine macrophage cell line RAW264.7. It was found that 1, 5, and 19 possessed potent nitric oxide inhibitory activity with IC50 values ranging from 2.99 to 28.80 ?M, without any effect on the cell viability of RAW264.7 cells. Accordingly, compounds 1, 5, and 19, especially 5, were identified as promising candidates for further scientific investigation of their potential use as anti-inflammatory agents. PMID:26071072

  5. Cyclolization of D-lysergic acid alkaloid peptides.

    PubMed

    Havemann, Judith; Vogel, Dominik; Loll, Bernhard; Keller, Ullrich

    2014-01-16

    The tripeptide chains of the ergopeptines, a class of pharmacologically important D-lysergic acid alkaloid peptides, are arranged in a unique bicyclic cyclol based on an amino-terminal ?-hydroxyamino acid and a terminal orthostructure. D-lysergyl-tripeptides are assembled by the nonribosomal peptide synthetases LPS1 and LPS2 of the ergot fungus Claviceps purpurea and released as N-(D-lysergyl-aminoacyl)-lactams. We show total enzymatic synthesis of ergopeptines catalyzed by a Fe²?/2-ketoglutarate-dependent dioxygenase (EasH) in conjunction with LPS1/LPS2. Analysis of the reaction indicated that EasH introduces a hydroxyl group into N-(D-lysergyl-aminoacyl)-lactam at ?-C of the aminoacyl residue followed by spontaneous condensation with the terminal lactam carbonyl group. Sequence analysis revealed that EasH belongs to the wide and diverse family of the phytanoyl coenzyme A hydroxylases. We provide a high-resolution crystal structure of EasH that is most similar to that of phytanoyl coenzyme A hydroxylase, PhyH, from human. PMID:24361048

  6. Antitumor effects of the benzophenanthridine alkaloid sanguinarine: Evidence and perspectives.

    PubMed

    Gaziano, Roberta; Moroni, Gabriella; Buè, Cristina; Miele, Martino Tony; Sinibaldi-Vallebona, Paola; Pica, Francesca

    2016-01-15

    Historically, natural products have represented a significant source of anticancer agents, with plant-derived drugs becoming increasingly explored. In particular, sanguinarine is a benzophenanthridine alkaloid obtained from the root of Sanguinaria canadensis, and from other poppy Fumaria species, with recognized anti-microbial, anti-oxidant and anti-inflammatory properties. Recently, increasing evidence that sanguinarine exibits anticancer potential through its capability of inducing apoptosis and/or antiproliferative effects on tumor cells, has been proved. Moreover, its antitumor seems to be due not only to its pro-apoptotic and inhibitory effects on tumor growth, but also to its antiangiogenic and anti-invasive properties. Although the precise mechanisms underlying the antitumor activity of this compound remain not fully understood, in this review we will focus on the most recent findings about the cellular and molecular pathways affected by sanguinarine, together with the rationale of its potential application in clinic. The complex of data currently available suggest the potential application of sanguinarine as an adjuvant in the therapy of cancer, but further pre-clinical studies are needed before such an antitumor strategy can be effectively translated in the clinical practice. PMID:26798435

  7. Cardiovascular effects of ephedra alkaloids: a comprehensive review.

    PubMed

    Andraws, Richard; Chawla, Preety; Brown, David L

    2005-01-01

    The Ephedra alkaloids have received much press lately secondary to reported adverse events in those using whole extracts as "dietary supplements" for weight loss or athletic performance enhancement. These reports are troubling given the increasing use of these supplements by the general public. We reviewed the available literature as well as online material on these compounds, including information on their pharmacology, regulation, effects on weight loss and athletic performance, and adverse events. Extracts of Ephedra shrubs contain highly active alpha- and beta-adrenergic agonists that have profound effects on the heart and vasculature. Evidence for their effectiveness is limited. Adverse cardiovascular and cerebrovascular effects, including stroke, myocardial infarction, and sudden death, temporally related to their use are well described. The recent Food and Drug Administration ban on these compounds is not broad enough. Ephedra supplements contain a highly bioactive class of compounds that pose a significant risk to the public under the current regulatory framework. More stringent oversight by regulatory authorities is required to minimize the incidence of adverse events. PMID:15991150

  8. Taste receptors for pyrrolizidine alkaloids in a monophagous caterpillar.

    PubMed

    Bernays, E A; Chapman, R F; Lamunyon, C W; Hartmann, T

    2003-07-01

    Caterpillars of Utetheisa ornatrix are monophagous on species of Crotalaria which they obtain pyrrolizidine alkaloids (PAs) for defense and which the males convert to a pheromone. We show that a taste receptor neuron in each of the lateral and medial galeal styloconic sensilla responds to PAs of three different types. Monocrotaline, commonly present in Crotalaria species, is the most strongly stimulating with thresholds of response below 10(-11) and 10(-9) M in the two sensilla. These are among the lowest known taste thresholds in any insect and are similar to the thresholds for PAs in a polyphagous arctiid caterpillar that also sequesters PAs and uses them as the source of male pheromone. The receptors also respond to heliotrine, a type of PA that is probably never encountered by the insects. Monocrotaline and senecionine N-oxide are shown in behavioral assays to be phagostimulants. The data show that there is no tight link between taste receptor sensitivity to specific PAs and hostplant selection in these caterpillars. Perhaps the adults are primarily responsible for hostplant selection. PMID:12921447

  9. Antitumor effects of the benzophenanthridine alkaloid sanguinarine: Evidence and perspectives

    PubMed Central

    Gaziano, Roberta; Moroni, Gabriella; Buè, Cristina; Miele, Martino Tony; Sinibaldi-Vallebona, Paola; Pica, Francesca

    2016-01-01

    Historically, natural products have represented a significant source of anticancer agents, with plant-derived drugs becoming increasingly explored. In particular, sanguinarine is a benzophenanthridine alkaloid obtained from the root of Sanguinaria canadensis, and from other poppy Fumaria species, with recognized anti-microbial, anti-oxidant and anti-inflammatory properties. Recently, increasing evidence that sanguinarine exibits anticancer potential through its capability of inducing apoptosis and/or antiproliferative effects on tumor cells, has been proved. Moreover, its antitumor seems to be due not only to its pro-apoptotic and inhibitory effects on tumor growth, but also to its antiangiogenic and anti-invasive properties. Although the precise mechanisms underlying the antitumor activity of this compound remain not fully understood, in this review we will focus on the most recent findings about the cellular and molecular pathways affected by sanguinarine, together with the rationale of its potential application in clinic. The complex of data currently available suggest the potential application of sanguinarine as an adjuvant in the therapy of cancer, but further pre-clinical studies are needed before such an antitumor strategy can be effectively translated in the clinical practice. PMID:26798435

  10. Suppression of angiogenesis by the plant alkaloid, sanguinarine.

    PubMed

    Eun, Jong-Pil; Koh, Gou Young

    2004-04-30

    Sanguinarine is a benzophenanthridine alkaloid derived from the root of Sanguinaria canadensis. Its principal pharmacologic use is in dental products where it has antibacterial, antifungal, and anti-inflammatory activities that reduce gingival inflammation and supragingival plaque formation. Angiogenesis is indispensable for inflammation, and most angiogenesis is dependent on vascular endothelial growth factor (VEGF). However, the effect of sanguinarine on angiogenesis is not known. In the present study, we examined the effect of sanguinarine on VEGF-induced angiogenesis in vitro and in vivo. Interestingly, sanguinarine markedly suppressed VEGF-induced endothelial cell migration, sprouting, and survival in vitro in a dose-dependent manner at nanomolar concentrations. Furthermore, sanguinarine potently suppressed blood vessel formation in vivo in mouse Matrigel plugs and the chorioallantoic membrane of chick embryos. Our biochemical assays indicated that sanguinarine strongly suppressed basal and VEGF-induced Akt phosphorylation, while it did not produce any changes in VEGF-induced activation of ERK1/2 and PLCgamma1. Therefore, we conclude that sanguinarine is a potent antiangiogenic natural product, and its mode of action could involve the blocking of VEGF-induced Akt activation. Thus, in addition to antibacterial, antifungal, and anti-inflammatory activities, sanguinarine has a novel antiangiogenic role. PMID:15063803

  11. Hobartine: a tetracyclic indole alkaloid extracted from Aristotelia chilensis (maqui).

    PubMed

    Paz Robles, Cristian; Badilla Vidal, Natalia; Suarez, Sebastián; Baggio, Ricardo

    2014-11-01

    The natural compound hobartine {systematic name: (1R)-3-[(1S,5S)-(4,4,8-trimethylbicyclo[3.3.1]non-7-en-2-yl)methyl]-2,3-dihydro-1H-indole}, C20H26N2, (I), is an indole alkaloid isolated from Aristotelia chilensis as part of a study of secondary metabolites from Chilean flora. The colourless compound has a tetracyclic structure closely related to the strongly coloured polymorphic structures discussed in Paz et al. [Acta Cryst. (2013), C69, 1509-1512] and Watson et al. [Acta Cryst. (1989), C45, 1322-1324]. The main differences reside in the absence of a keto group in (I) compared with the previous structures, as well as an endo double bond in (I) contrasting with the exo double bond found in the previous structures. The supramolecular structure of (I) in strongly related to the twofold screw axis, around which isolated chains build up, internally linked by an N-H···N hydrogen bond which is the only significant intermolecular interaction present in the structure. PMID:25370110

  12. Glucuronidation, a new metabolic pathway for pyrrolizidine alkaloids.

    PubMed

    He, Yu-Qi; Yang, Li; Liu, Hui-Xin; Zhang, Jiang-Wei; Liu, Yong; Fong, Alan; Xiong, Ai-Zhen; Lu, Yan-Liu; Yang, Ling; Wang, Chang-Hong; Wang, Zheng-Tao

    2010-03-15

    Pyrrolizidine alkaloids (PAs) possess significant hepatotoxicity to humans and animals after metabolic activation by liver P450 enzymes. Metabolism pathways of PAs have been studied for several decades, including metabolic activation, hydroxylation, N-oxidation, and hydrolysis. However, the glucuronidation of intact PAs has not been investigated, although glucuronidation plays an important role in the elimination and detoxication of xenobiotics. In this study, PAs glucuronidation was investigated, and three important points were found. First, we demonstrated that senecionine (SEN)-a representative hepatotoxic PA-could be conjugated by glucuronic acid via an N-glucuronidation reaction catalyzed by uridine diphosphate glucuronosyl transferase in human liver microsomes. Second, glucuronidation of SEN was catalyzed not only by human but also other animal species and showed significant species differences. Rabbits, cattle, sheep, pigs, and humans showed the significantly higher glucuronidation activity than mice, rats, dogs, and guinea pigs on SEN. Kinetics of SEN glucuronidation in humans, pigs, and rabbits followed the one-site binding model of the Michaelis-Menten equation, while cattle and sheep followed the two-sites binding model of the Michaelis-Menten equation. Third, besides SEN, other hepatotoxic PAs including monocrotaline, adonifoline, and isoline also underwent N-glucuronidation in humans and several animal species such as rabbits, cattle, sheep, and pigs. PMID:20092275

  13. Microwave Spectroscopy of Alkaloids: the Conformational Shapes of Nicotine

    NASA Astrophysics Data System (ADS)

    Grabow, Jens-Uwe; Mata, S.; López, J. C.; Peńa, I.; Cabezas, C.; Blanco, S.; Alonso, J. L.

    2010-06-01

    Nicotinoid alkaloids consist of two ring systems connected via a C-C σ-bond: Joining pyridine either with a (substituted) pyrrolidine or piperidine ring system, pyrrolidinic or piperidinic nicotinoids are formed. Nicotine itself, consisting of pyridine and N-methylpyrrolidine, is the prototype pyrrolidinic nicotinoid. Its coupled heteoaromatic and heteroaliphatic ring systems exhibit three sites that allow for conformational flexibility: (I) puckering of the pyrrolidine ring (Eq./Ax. positions of the pyridine), (II) inversion of the N-methyl group (Eq./Ax. positions of the hydrogen), and (III) relative orientation of the two rings (Syn-Anti). Two conformations of nicotine have been observed using the In-phase/quadrature-phase-Modulation Passage-Acquired-Coherence Technique (IMPACT) Fourier Transform Microwave (FTMW) spectrometer in Valladolid. The preferred conformations are characterized by an equatorial (Eq.) pyridine moiety and equatorial (Eq.) N-CH_3 stereochemistry. The planes of two rings are almost perpendicular with respect to each other while exhibiting two low energy conformations, Syn and Anti, that differ by a 180° rotation about the C-C σ-bond. The Eq.-Eq. conformational preference is likely due to a weak hydrogen bond interaction between the nitrogen lone pair at the N-methylpyrroline and the closest hydrogen in pyridine. Supporting quantum-chemical calculations are also provided. Lavrich, R. J.; Suenram, R. D.; Plusquellic, D. F.; Davis, S. 58th International Symposium on Molecular Spectroscopy, Columbus, OH 2003, RH13.

  14. Pyrrolizidine alkaloid toxicity in livestock: a paradigm for human poisoning?

    PubMed

    Molyneux, R J; Gardner, D L; Colegate, S M; Edgar, J A

    2011-03-01

    Livestock poisoning, primarily liver damage, caused by consumption of plants containing 1,2-dehydropyrrolizidine ester alkaloids (dehydroPAs), and the corresponding N-oxides, is a relatively common occurrence worldwide. Because of the economic impact, extensive investigations of such episodes have been performed, particularly in Australia, South Africa the United States and, more recently, South America. Plant species most commonly involved are members of the families Boraginaceae, Asteraceae and Leguminosae. These may be native species that periodically flourish under particular climatic conditions or introduced species that thrive in the absence of natural control factors such as herbivory and competition. Contamination of grain crops with dehydroPA-producing plants has resulted in large-scale incidents of food poisoning in humans, with high morbidity and mortality, especially in Africa and in central and south Asia, with recent episodes in Afghanistan and possibly Ethiopia. Attention has recently focused on the potential for low levels of dehydroPAs to contaminate many food products in developed countries, possibly leading to progressive, chronic diseases that may not include overt hepatotoxicity. This overview examines the potential for better control of exposure and means of monitoring dehydroPA intake by extrapolation of knowledge gained from animal studies to the human situation. PMID:21360375

  15. Biologically active vallesamine, strychnan, and rhazinilam alkaloids from Alstonia: Pneumatophorine, a nor-secovallesamine with unusual incorporation of a 3-ethylpyridine moiety.

    PubMed

    Lim, Jun-Lee; Sim, Kae-Shin; Yong, Kien-Thai; Loong, Bi-Juin; Ting, Kang-Nee; Lim, Siew-Huah; Low, Yun-Yee; Kam, Toh-Seok

    2015-09-01

    Four alkaloids comprising two vallesamine, one strychnan, and one pyranopyridine alkaloid, in addition to 32 other known alkaloids were isolated from two Malayan Alstonia species, Alstonia pneumatophora and Alstonia rostrata. The structures of these alkaloids were determined using NMR and MS analyses, and in one instance, confirmed by X-ray diffraction analysis. The nor-6,7-secovallesamine alkaloid, pneumatophorine, is notable for an unusual incorporation of a 3-ethylpyridine moiety in a monoterpenoid indole. The rhazinilam-type alkaloids (rhazinicine, nor-rhazinicine, rhazinal, and rhazinilam) showed strong cytotoxicity toward human KB, HCT-116, MDA-MB-231, and MRC-5 cells, while pneumatophorine, the uleine alkaloid undulifoline, and the strychnan alkaloids, N4-demethylalstogustine and echitamidine, induced concentration dependent relaxation in phenylephrine-precontracted rat aortic rings. PMID:26125941

  16. Effect of culture process on alkaloid production by Catharanthus roseus cells. II. Immobilized cultures.

    PubMed

    Tom, R; Jardin, B; Chavarie, C; Rho, D; Archambault, J

    1991-11-01

    Two processes for the production of indole alkaloids 2 l surface-immobilized bioreactor cultures of Catharanthus roseus cells using Zenk's Alkaloid Production Medium (APM) were evaluated. The 1-stage process consisted of inoculating APM containing bioreactors and incubating for 15 d. The 2-stage process involved inoculating growth medium-containing bioreactors, growing the immobilized cultures for a certain period of time and subsequently replacing this medium with APM. The production stage which lasted for 15 d. High production in 2-stage cultures required the replacement of the growth regulator 2,4-dichlorophenoxyacetic acid by indole-3-acetic acid in the growth medium and a growth stage of 6 d (late exponential phase) before production initiation. Growth, main nutrient consumption and alkaloid production were monitored. Both culture regimes resulted in similar biomass production, dw (10-13 g l-1). The 2-stage cultures yielded biomass richer in organic nutrients (200-300%) and with higher respiratory activity (approximately 250%), indicated by their lower biomass-to-carbohydrate yields (31% and 26%), as compared to 1-stage cultures (41%). Two-stage cultures produced more known products (10 as compared to 6) at yields (5 to 4800 micrograms g-1) 3 to 5 times higher than 1-stage cultures. More alkaloids were alkaloids released in the medium of 2-stage cultures, under non-lysing conditions, (20 to 4700 micrograms l-1) than in 1-stage cultures (20 to 460 micrograms l-1). These results were compared to those obtained from shake flask cultures performed at the same time, with the same C. roseus cell line and under similar regimes and reported previously. Suspension and immobilized cultures performed according to the 1-stage regime showed similar total production. However, release of known alkaloids was 2 to 3 times higher in immobilized than in suspension cultures. Total alkaloid production of 2-stage suspension cultures was 3.8-fold higher than 2-stage immobilized cultures. Two stage immobilized cultures released 4 more known alkaloids than the 2-stage suspensions. Lower oxygen availability in the 2 l immobilized cultures may explain lower specific growth rates (0.15-0.22 d-1) and total alkaloid production levels, compared to 200 ml suspension cultures (0.2-0.4 d-1) reported in our previous paper. PMID:1367689

  17. Involvement of protein kinase and G proteins in the signal transduction of benzophenanthridine alkaloid biosynthesis.

    PubMed

    Mahady, G B; Liu, C; Beecher, C W

    1998-05-01

    We have previously reported that elicitor-induced benzophenanthridine alkaloid biosynthesis in suspension-cell cultures of Sanguinaria canadensis L. (SCP-GM) is mediated by a signal transduction system that involves calcium and possibly protein kinase(s). In this work, a number of exogenous agents were employed to further investigate the components of the signal transduction pathway involved in the induction of alkaloid biosynthesis by a fungal elicitor and abscisic acid (ABA). SCP-GM suspension-cells were treated with compounds that modify protein kinase activity, including phorbol esters, and 1-oleoyl-2-acetyl-rac-glycerol (OAG), a synthetic diacylglycerol analogue. Phorbol-12-myristate-13-acetate induced alkaloid accumulation by as much as 65-fold over control values, while the negative control, phorbol-13-monoacetate, had no effect. OAG also increased alkaloid production by approximately 25-fold as compared to controls. Likewise, pretreatment of the suspension-cell cultures with H-7 or staurosporine, significantly suppressed ABA- or fungal-induction of benzophenanthridine alkaloid biosynthesis. Modulators of GTP-binding protein activity were also active in this system. Treatment of the suspension-cells with cholera toxin (CHX) induced alkaloid accumulation by 25-fold, which increased to 34-fold when CHX was combined with a fungal elicitor derived from Penicillium expansum (PE), and 32-fold when CHX was combined with ABA. Treatment of SCP-GM cells with CHX also enhanced the activities of two N-methyltransferases in the benzophenanthridine biosynthetic pathway namely, tetrahydroberberine-N-methyltransferase and tetrahydrocoptisine-N-methyltransferase, by six and seven fold, respectively. Furthermore, benzophenanthridine alkaloid biosynthesis was induced by treating the suspension-cells with the G-protein activators, mastoparan, mas-7 or melittin, while the inactive homologue, mas-17, did not. Suppression of alkaloid accumulation occurred when the suspension-cells were treated with GDP beta S or pertussis toxin prior to treatment of the SCP-GM cells with either PE or ABA. The results support the hypothesis that one or more protein kinases, and putative G proteins are involved in the signal transduction pathway that mediates ABA and fungal-induced benzophenanthridine alkaloid biosynthesis. PMID:9621455

  18. Luminescence and binding properties of two isoquinoline alkaloids chelerythrine and sanguinarine with ctDNA

    NASA Astrophysics Data System (ADS)

    Li, Junfen; Li, Baohong; Wu, Yanbo; Shuang, Shaomin; Dong, Chuan; Choi, Martin M. F.

    2012-09-01

    The binding mode and mechanism of the interactions between two planar cationic alkaloids chelerythrine (Che) and sanguinarine (San) with calf thymus DNA (ctDNA) were systematically investigated at pH 5.40 using UV-vis absorption spectroscopy, fluorescence spectroscopy and cyclic voltammetry. Che and San show strong fluorescence at 570 and 589 nm, respectively. Che displays fluorescence enhancement with ctDNA whereas the fluorescence of San is quenched on interaction with ctDNA. In addition, UV-vis spectra of both alkaloids show apparent hypochromicity and are bathochromic shifted, indicating that they could intercalate into ctDNA bases. The fluorescence polarization of Che and San increases in the presence of ctDNA, again implying the intercalation of two alkaloids with ctDNA. This conclusion was also supported by the results obtained from anion quenching and cyclic voltammetry. The binding constants of both alkaloids with ctDNA were calculated in the order of 105 L/mol. San binds with ctDNA 3-fold stronger than Che. The stoichiometric bindings are five nucleotides per Che or San. Electrostatic binding also exists between the alkaloids and DNA helix. Finally, theoretical calculations show that only certain parts of Che and San molecules intercalate into the DNA helix.

  19. Effects of dietary protein and lupine alkaloids on growth and survivorship ofSpodoptera eridania.

    PubMed

    Johnson, N D; Bentley, B L

    1988-05-01

    Toxic chemicals and nutrients are often positively correlated within and among plants. We studied how such correlations affect the suitability of plants as food for herbivores by assessing the growth and survivorship ofSpodoptera eridania (army worm) on artificial diets containing lupine alkaloids and casein. We found that (1) the effects of casein were determined by other dietary components: increased dietary casein led to increased larval growth only when the diet was also high in wheat germ. (2) Dietary alkaloids were effective at very low concentrations, reducing both growth and survivorship. The alkaloids lupanine and sparteine were not synergistic in their effects, and the interaction between alkaloids and casein was significant only in the low-wheat-germ diets. (3) The effects of casein and alkaloids were generally apparent only in the first instar, and the growth of fifth-instar larvae was unaffected by diet. (4) Using these artificial diet experiments, we can make simple predictions about the food quality of plants grown under various nutrient regimes. These predictions are consistant with recent ideas about optimal plant defenses. PMID:24276288

  20. N-methyldecahydroquinolines: an unexpected class of alkaloids from Amazonian poison frogs (Dendrobatidae).

    PubMed

    Daly, John W; Ware, Nathaniel; Saporito, Ralph A; Spande, Thomas F; Garraffo, H Martin

    2009-06-01

    The dominant alkaloids previously identified in skin extracts of Amazonian dendrobatid frogs of the genus Ameerega are histrionicotoxins and 2,5-disubstituted decahydroquinolines. Analysis of alkaloids in skin extracts of Ameerega picta from Bolivia revealed that the alkaloid 257A, previously reported as a 2,5-disubstituted decahydroquinoline, is an N-methyl-2,5-disubstituted decahydroquinoline. We characterized alkaloids of another 12 of the more than 25 species recently assigned to the genus Ameerega, and five additional N-methyldecahydroquinolines were identified. In some cases, the relative configuration of the N-methyldecahydroquinolines was determined by comparison with the N-methylated products prepared from the corresponding 2,5-disubstituted decahydroquinolines of known relative configuration. A dietary source for N-methyldecahydroquinolines is unknown; however, myrmicine ants are the likely source for the 2,5-disubstituted decahydroquinolines. The alkaloids in skin extracts of three species of another genus of Amazonian poison frog, Adelphobates, were also characterized, but N-methyldecahydroquinolines were not detected. PMID:19432407

  1. How polyamine synthesis inhibitors and cinnamic acid affect tropane alkaloid production.

    PubMed

    Marconi, Patricia L; Alvarez, María A; Pitta-Alvarez, Sandra I

    2007-01-01

    Hairy roots of Brugmansia candida produce the tropane alkaloids scopolamine and hyoscyamine. In an attempt to divert the carbon flux from competing pathways and thus enhance productivity, the polyamine biosynthesis inhibitors cyclohexylamine (CHA) and methylglyoxal-bis-guanylhydrazone (MGBG) and the phenylalanine-ammonia-lyase inhibitor cinnamic acid were used. CHA decreased the specific productivity of both alkaloids but increased significantly the release of scopolamine (approx 500%) when it was added in the mid-exponential phase. However, when CHA was added for only 48 h during the exponential phase, the specific productivity of both alkaloids increased (approx 200%), favoring scopolamine. Treatment with MGBG was detrimental to growth but promoted release into the medium of both alkaloids. However, when it was added for 48 h during the exponential phase, MGBG increased the specific productivity (approx 200%) and release (250- 1800%) of both alkaloids. Cinnamic acid alone also favored release but not specific productivity. When a combination of CHA or MGBG with cinnamic acid was used, the results obtained were approximately the same as with each polyamine biosynthesis inhibitor alone, although to a lesser extent. Regarding root morphology, CHA inhibited growth of primary roots and ramification. However, it had a positive effect on elongation of lateral roots. PMID:17416978

  2. Simultaneous quantification of 11 isoquinoline alkaloids in Corydalis impatiens (Pall.) Fisch by HPLC.

    PubMed

    Niu, Xiaofeng; Li, Weifeng; Xu, Hongbo; Liu, Xia; Qi, Lin

    2013-07-01

    Isoquinoline alkaloids are the primary active ingredients of Corydalis, but an analytical method for quality assessment of the active ingredients in Corydalis impatiens (Pall). Fisch has not been reported. A new, simple, and multiple-component quantification method was developed for the simultaneous quantification of 11 isoquinoline alkaloids including capnoidine, chelianthifoline, bicuculline, protopine, isoapocavidine, apocavidine, cavidine, tetrahydroepiberberine, ochotensimine, tetrahydrocoptisine, and tetrahydrocorysamine in C. impatiens. Separation of the isoquinoline alkaloids was performed on a RP C18 column (150 × 4.6 mm, 5 ?m) with potassium dihydrogen phosphate buffer (pH 2.5, adjusted by phosphoric acid)/acetonitrile (53:47, v/v) containing 0.3% sodium dodecyl sulfonate. The flow rate and detection wavelength were set at 1 mL/min and 295 nm, respectively. Full validation of the assay was carried out including linearity, precision, accuracy, stability, LOD, and limit of quantitation. All calibration curves showed a good linear relationship (r > 0.999) in test range. The results demonstrated that the developed method was reliable, rapid, and specific. Six batches of C. impatiens samples from different sources were determined using the established method. The contents of alkaloids ranged from 11.68 to 351.83 ?g/g. This method can be applied for quality evaluation and control of C. impatiens. Eleven isoquinoline alkaloids were first reported on simultaneous determination with HPLC. PMID:23610009

  3. Effect of culture process on alkaloid production by Catharanthus roseus cells. I. Suspension cultures.

    PubMed

    Tom, R; Jardin, B; Chavarie, C; Archambault, J

    1991-11-01

    The processes for production of indole alkaloids in shake flask suspension cultures of Catharanthus roseus cells using Zenk's alkaloid production medium (APM) were evaluated. The 1-stage process consisted of inoculating APM and incubating for 15 days. The 2-stage process involved 6 d of cultivation in growth medium followed by 15 d of incubation in APM. Growth, main nutrient consumption and alkaloid production were monitored. Both culture processes produced approximately 20 g dw per 1 biomass. However, 2-stage cultures yielded an inorganic nutrient richer and more active plant cell biomass, richer in inorganic nutrients, as indicated by higher (greater than 70%) nutrient availability and consumption. Total and individual indole alkaloid production were 10 times higher (740 mg l-1 and 25 to 4000 micrograms per g dw, respectively) for 2-stage than for 1-stage cultures. For both processes, highest alkaloid productivity coincided with complete extracellular consumption of major inorganic nutrients, especially nitrate, by the cells. Complete carbohydrate consumption in 2-stage cultures resulted in a 40% decline in production. Small but significant (approximately 10%) product release was observed for both culture regimes, which seemed not to be related to cell lysis. PMID:1367684

  4. Alkaloid metabolism in thrips-Papaveraceae interaction: recognition and mutual response.

    PubMed

    Schütz, Ingeborg; Moritz, Gerald B; Roos, Werner

    2014-01-15

    Frankliniella occidentalis (Pergande), the Western Flower Thrips (WFT), is a polyphagous and highly adaptable insect of the order Thysanoptera. It has a broad host range but is rarely found on Papaveraceae, which might be due to deterrent effects of alkaloids present in most species of this family. In order to test the adaptive potential of WFT, we investigated its interaction with two Papaveraceae offered as sole feeding source. We found that WFT are able to live and feed on leaves of Eschscholzia californica and Chelidonium majus. Both plants respond to thrips feeding by the enhanced production of benzophenanthridine alkaloids. Furthermore, cell cultures of E. californica react to water insoluble compounds prepared from adult thrips with enhanced alkaloid production. During feeding, WFT take up benzophenanthridine alkaloids from either plant and from an artificial feeding medium and convert them to their less toxic dihydroderivatives. This was shown in detail with sanguinarine, the most cytotoxic benzophenanthridine. A similar conversion is used in plants to prevent self-intoxication by their own toxins. We conclude that WFT causes a phytoalexin-like response in Papaveraceae, but is able to adapt to such host plants by detoxification of toxic alkaloids. PMID:24331426

  5. Simultaneous determination of Ephedra sinica and Citrus aurantium var. amara alkaloids by ion-pair chromatography.

    PubMed

    Ganzera, M; Lanser, C; Stuppner, H

    2005-05-15

    Ephedra sinica (Ma Huang) preparations have recently gained a lot of attention because of serious side effects associated with their prolonged consumption. Citrus aurantium var. amara is now used as an alternative, despite the fact that similar side effects are suspected. We have developed and validated the first analytical procedure for the simultaneous determination of all major alkaloids from both species. Using the ion-pairing reagent SDS, a C-18 stationary phase (3mum material) and a pH-gradient for elution enabled the baseline separation of six alkaloids ((+/-)-octopamine, (+/-)-synephrine, tyramine, (-)-norephedrine, (+)-pseudoephedrine and (-)-ephedrine) within less than 30min. The method is sensitive (LODalkaloid content. Dominant alkaloids were (-)-ephedrine (0.9-1.6%) and/or (+/-)-synephrine (0.1-3.0%). Whether a product contained Ephedra-alkaloids or not could be determined in all investigated samples unambiguously. PMID:18970068

  6. Influence of genetic factors on the ephedrine alkaloid composition ratio of Ephedra plants.

    PubMed

    Matsumoto, Masashi; Hirayama, Manabu; Ohtomi, Norihiro; Ohno, Takeshi; Nomura, Yukihiro; Iida, Osamu; Sugimura, Koji; Kawahara, Nobuo; Tsuchida, Takashi; Mikage, Masayuki

    2015-01-01

    We investigated the ephedrine alkaloid [(-)-ephedrine and (+)-pseudoephedrine] composition ratio of a crude Chinese herbal drug described in the Japanese Pharmacopoeia 'Ephedra herb (Chinese name: Mahuang)'. There were marked changes in the alkaloid composition ratio of wild plants in areas where both male and female clusters coexisted. However, in genetically homogeneous areas with the growth of male or female clusters alone, all of the coefficients of the regression lines were positive, but each gradient varied. This suggests that the alkaloid composition ratio has a clear tendency in each individual. Based on this, we cultivated individuals for vegetative propagation, and evaluated the alkaloid content ratio. Those propagated by separating the roots showed a specific tendency regardless of the cultivation area (Wakayama, Tanegashima). Those propagated by separating the herbaceous stem showed a specific tendency regardless of the soil or harvest time. In addition, we surveyed the (-)-ephedrine content ratio of 3- to 6-year-old strains. There was a high positive correlation coefficient between the previous and subsequent years. These findings suggest that the ephedrine alkaloid composition ratio of Ephedra herb depends on genetic factors, but not on environmental factors or the growth period. PMID:25115226

  7. Determination of caffeine and sympathomimetic alkaloids in weight loss supplements by high-performance liquid chromatography.

    PubMed

    Evans, Ronald L; Siitonen, Paul H

    2008-01-01

    Reversed-phase high-performance liquid chromatography utilizing photodiode array detection is used for the simultaneous determination of caffeine and nine alkaloids from Citrus aurantium (CA) and ephedra (EA) contained in dietary weight loss products. Since the Food and Drug Administration (FDA) ban of EA, manufacturers have substituted CA in their weight loss formulations, usually combined with high levels of caffeine. The alkaloids contained in CA have some physiological effects similar to those of the EA alkaloids and are, therefore, cause for concern. Caffeine has been shown to potentiate the toxicity of the EA alkaloids. Recently, a federal judge overturned the absolute ban and allowed marketing of low levels (<10 mg/day) of total EA alkaloids. To support an absolute ban, the FDA is now compelled to perform dose-dependent toxicology studies to determine the toxic dose(s) of EA. The toxicity of the CA compounds is largely unknown, especially in combination with caffeine. The described method enables quantitation over a wide range of product formulations. Recoveries range from 91% to 100% from a variety of fortified plant matrices. PMID:18218190

  8. Protein and alkaloid patterns of the floral nectar in some solanaceous species.

    PubMed

    Kerchner, András; Darók, Judit; Bacskay, Ivett; Felinger, Attila; Jakab, Gábor; Farkas, Ágnes

    2015-09-01

    The family Solanaceae includes several melliferous plants, which tend to produce copious amounts of nectar. Floral nectar is a chemically complex aqueous solution, dominated by sugars, but minor components such as amino acids, proteins, flavonoids and alkaloids are present as well. This study aimed at analysing the protein and alkaloid profile of the nectar in seven solanaceous species. Proteins were examined with SDS-PAGE and alkaloids were analyzed with HPLC. The investigation of protein profile revealed significant differences in nectar-protein patterns not only between different plant genera, but also between the three Nicotiana species investigated. SDS-PAGE suggested the presence of several Nectarin proteins with antimicrobial activity in Nicotiana species. The nectar of all tobacco species contained the alkaloid nicotine, N. tabacum having the highest nicotine content. The nectar of Brugmansia suaveolens, Datura stramonium, Hyoscyamus niger and Lycium barbarum contained scopolamine, the highest content of which was measured in B. suaveolens. The alkaloid concentrations in the nectars of most solanaceous species investigated can cause deterrence in honeybees, and the nectar of N. rustica and N. tabacum can be considered toxic for honeybees. PMID:26344026

  9. Alkaloid variation among epichloid endophytes of sleepygrass (Achnatherum robustum) and consequences for resistance to insect herbivores.

    PubMed

    Shymanovich, Tatsiana; Saari, Susanna; Lovin, Mary E; Jarmusch, Alan K; Jarmusch, Scott A; Musso, Ashleigh M; Charlton, Nikki D; Young, Carolyn A; Cech, Nadja B; Faeth, Stanley H

    2015-01-01

    Epichloid endophytes are well known symbionts of many cool-season grasses that may alleviate environmental stresses for their hosts. For example, endophytes produce alkaloid compounds that may be toxic to invertebrate or vertebrate herbivores. Achnatherum robustum, commonly called sleepygrass, was aptly named due to the presence of an endophyte that causes toxic effects to livestock and wildlife. Variation in alkaloid production observed in two A. robustum populations located near Weed and Cloudcroft in the Lincoln National Forest, New Mexico, suggests two different endophyte species are present in these populations. Genetic analyses of endophyte-infected samples revealed major differences in the endophyte alkaloid genetic profiles from the two populations, which were supported with chemical analyses. The endophyte present in the Weed population was shown to produce chanoclavine I, paspaline, and terpendoles, so thus resembles the previously described Epichloë funkii. The endophyte present in the Cloudcroft population produces chanoclavineI, ergonovine, lysergic acid amide, and paspaline, and is an undescribed endophyte species. We observed very low survival rates for aphids feeding on plants infected with the Cloudcroft endophyte, while aphid survival was better on endophyte infected plants in the Weed population. This observation led to the hypothesis that the alkaloid ergonovine is responsible for aphid mortality. Direct testing of aphid survival on oat leaves supplemented with ergonovine provided supporting evidence for this hypothesis. The results of this study suggest that alkaloids produced by the Cloudcroft endophyte, specifically ergonovine, have insecticidal properties. PMID:25501262

  10. Nicotine alkaloids as antioxidant and potential protective agents against in vitro oxidative haemolysis.

    PubMed

    Malczewska-Jaskóła, Karolina; Jasiewicz, Beata; Mrówczyńska, Lucyna

    2016-01-01

    The capacity of eleven nicotine alkaloids to reduce oxidative stress was investigated. In order to provide a structure-activity relationships analysis, new nicotine derivatives with a substituent introduced into the pyrrolidine ring were synthesized and investigated together with nicotine and its known analogs. All newly synthesized compounds were characterized by (1)H, (13)C NMR and EI-MS technique. The antioxidant properties of nicotine, its known analogs and newly produced derivatives, were evaluated by various antioxidant assays such 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH(•)) scavenging, ferrous ions (Fe(2+)) chelating activity and total reducing ability determination by Fe(3+) → Fe(2+) transformation assay. The protective effects of all compounds tested against 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH) and tert-butyl hydroperoxide (t-BuOOH)-induced oxidative haemolysis and morphological injury of human erythrocytes, were estimated in vitro. The results showed that nicotine alkaloids exhibited various antiradical efficacy and antioxidant activity in a structure- and a dose-dependent manner. In addition, the capacity of nicotine alkaloids to protect erythrocytes from AAPH- and t-BuOOH-induced oxidative haemolysis, was dependent on its incubation time with cells. Our findings showed that chemical and biological investigations conducted simultaneously can provide comprehensive knowledge concerning the antioxidant potential of nicotine alkaloids. This knowledge can be helpful in better understanding the properties of nicotine alkaloids under oxidative stress conditions. PMID:26658032

  11. Alkaloid defenses of co-mimics in a putative Müllerian mimetic radiation

    PubMed Central

    2014-01-01

    Background Polytypism in aposematic species is unlikely according to theory, but commonly seen in nature. Ranitomeya imitator is a poison frog species exhibiting polytypic mimicry of three congeneric model species (R. fantastica, R. summersi, and two morphs of R. variabilis) across four allopatric populations (a "mimetic radiation"). In order to investigate chemical defenses in this system, a key prediction of Müllerian mimicry, we analyzed the alkaloids of both models and mimics from four allopatric populations. Results In this study we demonstrate distinct differences in alkaloid profiles between co-mimetic species within allopatric populations. We further demonstrate that R. imitator has a greater number of distinct alkaloid types than the model species and more total alkaloids in all but one population. Conclusions Given that R. imitator is the more abundant species in these populations, R. imitator is likely driving the majority of predator-learned avoidance in these complexes. The success of Ranitomeya imitator as a putative advergent mimic may be a direct result of differences in alkaloid sequestration. Furthermore, we propose that automimicry within co-mimetic species is an important avenue of research. PMID:24707851

  12. A general procedure for the enantioselective synthesis of the minor tobacco alkaloids nornicotine, anabasine, and anatabine.

    PubMed

    Ayers, Joshua T; Xu, Rui; Dwoskin, Linda P; Crooks, Peter A

    2005-01-01

    The minor tobacco alkaloids nornicotine, anabasine, and anatabine from Nicotiana tobacum are known to possess nicotinic receptor agonist activity, although they are relatively less potent than S-(-)-nicotine, the principal tobacco alkaloid. Previous pharmacological investigations and structure-activity studies have been limited owing to the lack of availability of the optically pure forms of these minor alkaloids. We now report a 2-step synthetic procedure for the enantioselective synthesis of the optical isomers of nornicotine and anabasine, and a modified procedure for the synthesis of anatabine enantiomers. These procedures involve initial formation of the chiral ketimine resulting from the condensation of either 1R, 2R, 5R-(+)- or 1S, 2S, 5S-(-)-2-hydroxy-3-pinanone with 3-(aminomethyl)pyridine followed by enantioselective C-alkylation with an appropriate halogenoalkane or halogenoalkene species, N-deprotection, and base-catalyzed intramolecular ring closure, to form the appropriate, chirally pure minor tobacco alkaloid. Using this approach, the R-(+)- and S-(-)-enantiomers of the above minor tobacco alkaloids were obtained in good overall chemical yield and excellent enantomeric excess. PMID:16353951

  13. Dietary alkaloids and the development of androconial organs in Estigmene acrea

    PubMed Central

    Davenport, Jason W.; Conner, William E.

    2003-01-01

    Male salt marsh moths, Estigmene acrea (Lepidoptera: Arctiidae), possess inflatable androconial organs called coremata. Prior to mating males form aggregations and inflate their coremata en masse. The communal display attracts additional males and females for the purpose of mating. The coremata are known to carry the plant-derived dihydropyrrolizine, hydroxydanaidal. This pheromonal substance is derived from secondary plant chemicals called pyrrolizidine alkaloids found in the larval diet. When E. acrea larvae were raised on semi-synthetic diets containing different levels of the pyrrolizidine alkaloid precursors the alkaloids triggered a pronounced morphogenetic effect. Adult males that fed on high levels of the pyrrolizidine alkaloid monocrotaline N-oxide (2500 µg) developed the largest coremata. Males that fed on lower levels of monocrotaline N-oxide (500 µg) or no alkaloid, while normal in body weight, had coremata that were progressively smaller and less robust. The size of the coremata and their commensurate pheromonal charge may have behavioral consequences in the unusual mating system of this species. PMID:15841220

  14. Antifungal and Antibacterial Activity of Extracts and Alkaloids of Selected Amaryllidaceae Species.

    PubMed

    Lo?árek, Miroslav; Nováková, Jitka; Klou?ek, Pavel; Hošt'álkoviá, Anna; Kokoška, Ladislav; Lucie Gábrlová; Šafratová, Marcela; Opletal, Lubomír; Cahliková, Lucie

    2015-09-01

    Alkaloidal extracts of six selected species of Amaryllidaceae were studied with respect to their antibacterial and anti-yeast activity and their alkaloidal fingerprint. Twenty-five alkaloids were determined by GC/MS, and sixteen of them identified from their mass spectra, retention times and retention indexes. In the antimicrobial assay, Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus were used, along with isolates of the human pathogenic yeasts Candida albicans, C. glabrata, C. dubliniensis and Lodderomyces elongiosporus. The six extracts, together with 19 Amaryllidaceae alkaloids isolated in our laboratory, showed almost no inhibitory activity against the bacteria tested. However, promising anti-yeast properties were detected; the most potent activity was shown by lycorine, which inhibited C. dubliniensis with a MIC of 32 µg/mL, C. albicans and L. elongiosporus, both with MICs of 64 µg/mL, followed by caranine inhibiting C. dubliniensis with a MIC of 128 µg/mL. Among the alkaloidal extracts, Narcissus jonquilla cv. Baby Moon showed the most potent anti-yeast activity, with minimal and average MIC values of 128 and 192 µg/mL, respectively, followed by Leucojum aestivum, Narcissus poeticus var. recurvus and N. canaliculatus (average MICs 256, 267 and 299 µg/mL, respectively). The lowest MIC value among extracts was obtained for N. canaliculatus against L. elongiosporus (MIC 64 µg/mL). PMID:26594752

  15. Optimization of Extraction and Enrichment of Steroidal Alkaloids from Bulbs of Cultivated Fritillaria cirrhosa

    PubMed Central

    Wang, Shu; Du, Qingdan; Wang, Nanyi; Liu, Simei; Wang, Xiaoxia; Jiang, Jinghui

    2014-01-01

    The bulbs of cultivated Fritillaria cirrhosa (BCFC) are used in China both for food and folk medicine due to its powerful biological activities. The aim of this study is to optimize the extraction and enrichment conditions of alkaloids from BCFC. Firstly, the orthogonal experimental design was used to optimize and evaluate four variables (ethanol concentration, solid-liquid ratio, extraction time, and temperature). Thereafter, resin adsorption was as a means to enrich alkaloids. Among 16 tested resins, H-103 resin presented higher adsorption capacity and desorption ratio. The equilibrium experimental data of the adsorption of total alkaloids, imperialine, and peimisine were well-fitted to the pseudo-first-order kinetics model, Langmuir and Freundlich isotherms models. Finally, in order to optimize the parameters for purifying alkaloids, dynamic adsorption and desorption tests were carried out. After one run treatment with H-103 resin, the contents of total alkaloids, imperialine, and peimisine in the product were 21.40-, 18.31-, and 22.88-fold increased with recovery yields of 94.43%, 90.57%, and 96.16%, respectively. PMID:24804207

  16. Tobacco alkaloids reduction by casings added/enzymatic hydrolysis treatments assessed through PLSR analysis.

    PubMed

    Lin, Shunshun; Zhang, Xiaoming; Song, Shiqing; Hayat, Khizar; Eric, Karangwa; Majeed, Hamid

    2016-03-01

    Based on encouraged development of potential reduced-exposure products (PREPs) by the US Institute of Medicine, casings (glucose and peptides) added treatments (CAT) and enzymatic (protease and xylanase) hydrolysis treatments (EHT) were developed to study their effect on alkaloids reduction in tobacco and cigarette mainstream smoke (MS) and further investigate the correlation between sensory attributes and alkaloids. Results showed that the developed treatments reduced nicotine by 14.5% and 24.4% in tobacco and cigarette MS, respectively, indicating that both CAT and EHT are potentially effective for developing lower-risk cigarettes. Sensory and electronic nose analysis confirmed the significant influence of treatments on sensory and cigarette MS components. PLSR analysis demonstrated that tobacco alkaloids were positively correlated to the off-taste, irritation and impact attributes, and negatively correlated to the aroma and softness attributes. Additionally, nicotine and anabasine from tobacco leaves positively contributed to the impact attribute, while they negatively contributed to the aroma attribute (P<0.05). Meanwhile, most alkaloids in cigarette MS positively contributed to the impact and irritation attributes (P<0.05). Hence, this study paved a way to better understand the correlation between tobacco alkaloids and sensory attributes. PMID:26739812

  17. Evolutionary recruitment of a flavin-dependent monooxygenase for stabilization of sequestered pyrrolizidine alkaloids in arctiids.

    PubMed

    Langel, Dorothee; Ober, Dietrich

    2011-09-01

    Pyrrolizidine alkaloids are secondary metabolites that are produced by certain plants as a chemical defense against herbivores. They represent a promising system to study the evolution of pathways in plant secondary metabolism. Recently, a specific gene of this pathway has been shown to have originated by duplication of a gene involved in primary metabolism followed by diversification and optimization for its specific function in the defense machinery of these plants. Furthermore, pyrrolizidine alkaloids are one of the best-studied examples of a plant defense system that has been recruited by several insect lineages for their own chemical defense. In each case, this recruitment requires sophisticated mechanisms of adaptations, e.g., efficient excretion, transport, suppression of toxification, or detoxification. In this review, we briefly summarize detoxification mechanism known for pyrrolizidine alkaloids and focus on pyrrolizidine alkaloid N-oxidation as one of the mechanisms allowing insects to accumulate the sequestered toxins in an inactivated protoxic form. Recent research into the evolution of pyrrolizidine alkaloid N-oxygenases of adapted arctiid moths (Lepidoptera) has shown that this enzyme originated by the duplication of a gene encoding a flavin-dependent monooxygenase of unknown function early in the arctiid lineage. The available data suggest several similarities in the molecular evolution of this adaptation strategy of insects to the mechanisms described previously for the evolution of the respective pathway in plants. PMID:21288541

  18. Simultaneous determination of the content of isoquinoline alkaloids in Dicranostigma leptopodum (Maxim) Fedde and the effective fractionation of the alkaloids by high-performance liquid chromatography with diode array detection.

    PubMed

    Chen, Yali; Li, Min; Liu, Jianjun; Yan, Qian; Zhong, Mei; Liu, Junxi; Di, Duolong; Liu, Jinxia

    2015-01-01

    A simple and efficient method was developed for the simultaneous determination of eight isoquinoline alkaloids in methanol extracts of Dicranostigma leptopodum (Maxim) Fedde and the effective fractionation of the alkaloids of D. leptopodum by high-performance liquid chromatography with diode array detection. The chromatographic conditions were optimized on a SinoChrom ODS-BP column to obtain a good separation of the four types of alkaloid analytes, including two aporphines (isocorydine, corydine), two protopines (protopine and allocryptopine), a morphine (sinoacutine), and three quaternary protoberberine alkaloids (berberrubine, 5-hydroxycoptisine, and berberine). The separation of these alkaloids was significantly affected by the composition of the mobile phase, and particularly by its pH value. Acetonitrile (A) and 0.2% phosphoric acid solution adjusted to pH 6.32 with triethylamine (B) were selected as the mobile phase with a gradient elution. With this method, a new quaternary protoberberine alkaloid was isolated and the two structural isomers (isocorydine and corydine) were baseline separated. The appropriate harvest period for D. leptopodum was also recommended based on our analysis. The method for the effective fraction of the alkaloids of D. leptopodum was optimized under this method with regard to the varying significant pharmacological activities of the alkaloids. PMID:25330407

  19. Antibacterial Properties of Alkaloid Extracts from Callistemon citrinus and Vernonia adoensis against Staphylococcus aureus and Pseudomonas aeruginosa

    PubMed Central

    Mabhiza, Donald; Chitemerere, Tariro; Mukanganyama, Stanley

    2016-01-01

    The development of new antibiotics from new chemical entities is becoming more and more expensive, time-consuming, and compounded by emerging strains that are drug resistant. Alkaloids are plant secondary metabolites which have been shown to have potent pharmacological activities. The effect of alkaloids from Callistemon citrinus and Vernonia adoensis leaves on bacterial growth and efflux pump activity was evaluated on Staphylococcus aureus and Pseudomonas aeruginosa. At a concentration of 1.67 mg/mL, the alkaloids inhibited bacterial growth with comparable effects to ampicillin, a standard antibiotic. The alkaloids from C. citrinus were the most potent against S. aureus with an MIC of 0.0025 mg/mL and MBC of 0.835 mg/mL. It was shown that effects on P. aeruginosa by both plant alkaloids were bacteriostatic. P. aeruginosa was most susceptible to drug efflux pump inhibition by C. citrinus alkaloids which caused an accumulation of Rhodamine 6G of 121% compared to the control. Thus, C. citrinus alkaloids showed antibacterial activity as well as inhibiting ATP-dependent transport of compounds across the cell membrane. These alkaloids may serve as potential courses of compounds that can act as lead compounds for the development of plant-based antibacterials and/or their adjunct compounds. PMID:26904285

  20. Effects of the ergot alkaloids dihydroergotamine, ergonovine, and ergotamine on growth of Escherichia coli O157:H7 in vitro

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A series of experiments were conducted to evaluate the effects of ergot alkaloids (dihydroergotamine, ergonovine, and ergotamine) on E. coli O157:H7 in both pure and mixed ruminal fluid culture. Alkaloids were added to solutions of E. coli O157:H7 strains 933 (pure and ruminal cultures) and 6058 (r...