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Sample records for numerous norditerpenoid alkaloids

  1. Synthesis of the C(18) -norditerpenoid alkaloid neofinaconitine: a lesson in convergent synthesis planning.

    PubMed

    Liu, Xiao-Yu; Chen, David Y-K

    2014-01-20

    Hexacyclic framework: The total synthesis of the complex C18 -norditerpenoid alkaloid neofinaconitine has been achieved by a convergent approach. This remarkable synthesis featured two Diels-Alder cycloadditions and subsequent Mannich-type N-acyliminium and radical cyclizations to establish the unique hexacyclic core structure of the target molecule.

  2. Structural diversity and defensive properties of norditerpenoid alkaloids.

    PubMed

    González-Coloma, Azucena; Reina, Matías; Medinaveitia, Alberto; Guadaño, Ana; Santana, Omar; Martínez-Díaz, Rafael; Ruiz-Mesía, Lastenia; Alva, Allenger; Grandez, Maritza; Díaz, Rafael; Gavín, José A; De la Fuente, Gabriel

    2004-07-01

    We have tested the insect antifeedant and toxic activity of 43 norditerpenoid alkaloids on Spodoptera littoralis and Leptinotarsa decemlineata including eserine (physostigmine), anabasine, and atropine. Antifeedant effects of the test compounds were structure- and species-dependent. The most active antifeedants to L. decemlineata were 1,14-diacetylcardiopetaline (9) and 18-hydroxy- 14-O-methylgadesine (33), followed by 8-O-methylconsolarine (12), 14-O-acetyldelectinine (27), karakoline (7), cardiopetaline (8), 18-O-demethylpubescenine (13), 14-O-acetyldeltatsine (18), takaosamine (21), ajadine (24), and 8-O-methylcolumbianine (6) (EC50 < 1 microg/cm2). This insect showed a moderate response to atropine. S. littoralis had the strongest antifeedant response to 24, 18, 14-O-acetyldelcosine (19), and delphatine (29) (EC50 < 3 microg/cm2). None of the model substances affected the feeding behavior of this insect. The most toxic compound to L. decemlineata was aconitine (1), followed by cardiopetalidine (10) (% mortality > 60), 14-deacetylpubescenine (14), 18-O-benzoyl-18-O-demethyl-14-O-deacetylpubescenine (17), 14-O-acetyldelcosine (19), 14-deacetylajadine (25) and methyllycaconitine (30) (% mortality > 45). Orally injected S. littoralis larvae were negatively affected by 1, cardiopetaline (8), 10, 1,14-O-acetylcardiopetalidina (11), 12, 14, 1,18-O-diacetyl-19-oxo-gigactonine (41), olivimine (43), and eserine in varying degrees. Their antifeedant or insecticidal potencies did not parallel their reported nAChR binding activity, but did correlate with the agonist/antagonist insecticidal/antifeedant model proposed for nicotininc insecticides. A few compounds [14, tuguaconitine (38), 14-demethyldelboxine (40), 19, dehydrodelsoline (36), 18-O-demethylpubescenine (13), 41, 9, and delcosine (23)] had selective cytotoxic effects to ward insect-derived Sf9 cells. None were cytotoxic to mammalian CHO cells and none increased Trypanosoma cruzi mortality. The selective cytotoxic

  3. C19-Norditerpenoid Alkaloids from Aconitum szechenyianum and Their Effects on LPS-Activated NO Production.

    PubMed

    Wang, Fei; Yue, Zhenggang; Xie, Pei; Zhang, Li; Li, Zhen; Song, Bei; Tang, Zhishu; Song, Xiaomei

    2016-01-01

    Three new C19-norditerpenoid alkaloids (1-3), along with two known C19-norditerpenoid alkaloids (4-5) have been isolated from Aconitum szechenyianum. Their structures were established by extensive spectroscopic techniques and chemical methods as szechenyianine A (1), szechenyianine B (2), szechenyianine C (3), N-deethyl-3-acetylaconitine (4), and N-deethyldeoxyaconitine (5). Additionally, compounds 1-5 were tested for the inhibition of NO production on LPS-activated RAW264.7 cells with IC50 values of 36.62 ± 6.86, 3.30 ± 0.11, 7.46 ± 0.89, 8.09 ± 1.31, and 11.73 ± 1.94 μM, respectively, while the positive control drug dexamethasone showed inhibitory activity with IC50 value of 8.32 ± 1.45 μM. The structure-activity relationship of aconitine alkaloids were discussed. PMID:27598121

  4. 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

  5. Actinomadurol, an Antibacterial Norditerpenoid from a Rare Actinomycete, Actinomadura sp. KC 191.

    PubMed

    Shin, Bora; Kim, Byung-Yong; Cho, Eunji; Oh, Ki-Bong; Shin, Jongheon; Goodfellow, Michael; Oh, Dong-Chan

    2016-07-22

    A new secondary metabolite, actinomadurol (1), was isolated along with the known compound JBIR-65 (2) from a rare actinomycete, Actinomadura strain KC 191. The structure of 1 was established as a rare member of the bacterial C-19 norditerpenoid class by NMR data and ECD calculations. The absolute configuration of 2, which was previously reported without stereochemical analysis, was determined by using the modified Mosher's method and ECD calculations. Actinomadurol (1) exhibited potent antibacterial activity against pathogenic strains, such as Staphylococcus aureus, Kocuria rhizophila, and Proteus hauseri (MIC = 0.39-0.78 μg/mL), whereas JBIR-65 (2) showed no antibacterial activity.

  6. Eight new diterpenoids and two new nor-diterpenoids from the stems of Croton cascarilloides.

    PubMed

    Kawakami, Susumu; Toyoda, Hiroki; Harinantenaina, Liva; Matsunami, Katsuyoshi; Otsuka, Hideaki; Shinzato, Takakazu; Takeda, Yoshio; Kawahata, Masatoshi; Yamaguchi, Kentaro

    2013-01-01

    From the stems of Croton cascarilloides, eight new diterpenoids, named crotocascarins A-H (1-8), having a crotofolane skeleton were isolated along with two new nor-diterpenoids (9 and 10), named crotocascarins α and β, derived through rearrangement of the crotofolane skeleton. The structures of these compounds were elucidated by means of extensive one- and two-dimensional NMR spectroscopic analyses. The absolute structures of the diterpene moiety were determined by application of the circular dichroism (CD) rule for the γ-lactone ring. The relative structures of the two crotofolanes (1 and 2) and one rearranged compound (9) were confirmed by X-ray crystallographic analyses. Compounds 1, 2 and 9 possessed 2-methylbutyric acid in their molecules, the absolute configuration of which was found to be 2S by comparison of its HPLC behavior with that of an authentic sample. Therefore, the absolute structures of these crotocascarins (1, 2 and 9) were unambiguously determined. The absolute structures of crotofolanes are reported for the first time in this paper.

  7. Alkaloids from Delphinium pentagynum.

    PubMed

    Díaz, Jesús G; Ruiz, Juan García; Herz, Werner

    2004-07-01

    Aerial parts of a collection of Delphinium pentagynum Lam. from Niebla, Southern Spain, furnished one diterpene alkaloid, 2-dehydrodeacetylheterophylloidine, two norditerpene alkaloids, 14-demethyl-14-isobutyrylanhweidelphinine and 14-demethyl-14-acetylanhweidelphinine, the known alkaloids 14-deacetylnudicauline, methyllycaconitine, 14-deacetyl-14-isobutyrylnudicauline, 14-acetylbrowniine, browniine, delcosine, lycoctonine, 18-methoxygadesine, neoline, karakoline and the aporphine alkaloid magnoflorine. Structures of the alkaloids were established by MS, 1D and 2-D NMR techniques.

  8. In vivo Cytotoxicity Studies of Amaryllidaceae Alkaloids.

    PubMed

    Nair, Jerald J; Bastida, Jaume; van Staden, Johannes

    2016-01-01

    The plant family Amaryllidaceae is recognizable for its esthetic floral characteristics, its widespread usage in traditional medicine as well as its unique alkaloid principles. Few alkaloid-producing families rival the Amaryllidaceae in terms of the diversity of its structures as well as their wide applicability on the biological landscape. In particular, cytotoxic effects have come to be a dominant theme in the biological properties of Amaryllidacea alkaloids. To this extent, a significant number of structures have been subjected to in vitro studies in numerous cell lines from which several targets have been identified as promising chemotherapeutics. By contrast, in vivo models of study involving these alkaloids have been carried out to a lesser extent and should prove crucial in the continued development of a clinical target such as pancratistatin. This survey examines the cytotoxic effects of Amaryllidaceae alkaloids in vivo and contrasts these against the corresponding in vitro effects.

  9. In vitro ruminal metabolism of larkspur alkaloids.

    PubMed

    Siemion, R S; Raisbeck, M F; Waggoner, J W; Tidwell, M A; Sanchez, D A

    1992-06-01

    Larkspur (Delphinium sp) poisoning of range cattle is a serious, recurring problem in the western United States. Numerous stratagems have been recommended to ameliorate larkspur intoxication, but none are completely effective. Previous studies in this laboratory indicated bovine ruminal microflora are capable of chemically modifying Delphinium alkaloids. Research reported herein was undertaken to further evaluate whether differences in ovine and bovine rumen metabolism might explain differences in susceptibility to larkspur intoxication and whether existing metabolic activity can be enhanced by sustained exposure to Delphinium alkaloids. Comparison of ovine and bovine rumen metabolism of Delphinium geyeri alkaloids in vitro failed to demonstrate differences in the rate of alkaloid metabolism. Rumen liquor collected sequentially from a fistulated cow dosed with dried Delphinium geyeri did not vary in ability to metabolize larkspur alkaloids.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  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.

  12. 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

  13. New Perspectives in the Chemistry of Marine Pyridoacridine Alkaloids

    PubMed Central

    Plodek, Alois; Bracher, Franz

    2016-01-01

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

  14. 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.

  15. The discovery of alkaloids.

    PubMed

    Hosztafi, S

    1997-07-01

    This paper presents the history of the discovery of the first alkaloids. Isolation of alkaloids is connected with the study of the active principles of medicines of plant origin, for example opium and cinchona bark. Sertürner described morphine as a plant alkali and claimed that it was capable of neutralizing free acids yielding salts. The recognition of alkaloids as a new class of compounds was an important step at that time because of the dogmatic denial of the possible existence of plant bases. Isolation of alkaloids is a significant event from the point of view of chemistry, physiology and medicine. The discovery caused essential conceptual changes in chemistry. Priority claims with reference to the discovery of the alkaloids are also reviewed.

  16. [Alkaloids of Annonaceae. XXIX. Alkaloids of Annona muricata].

    PubMed

    Leboeuf, M; Legueut, C; Cavé, A; Desconclois, J F; Forgacs, P; Jacquemin, H

    1981-05-01

    From leaves, root - and stem - barks of Annona muricata L., seven isoquinoline alkaloids have been isolated: reticuline (main alkaloid), coclaurine, coreximine, atherosperminine, stepharine. Anomurine and anomuricine, two minor alkaloids, are new tetrahydrobenzylisoquinolines, with 5, 6, 7 substituted ring A. The phytochemical significance of these alkaloids is discussed.

  17. Dimeric Cinchona alkaloids.

    PubMed

    Boratyński, Przemysław J

    2015-05-01

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

  18. 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

  19. 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

  20. Sarpagine and related alkaloids

    PubMed Central

    Namjoshi, Ojas A.; Cook, James M.

    2016-01-01

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

  1. 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

  2. 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 ...

  3. Biosynthesis of Fungal Indole Alkaloids

    PubMed Central

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

    2014-01-01

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

  4. 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

  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

  6. 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

  7. Simple Indolizidine and Quinolizidine Alkaloids.

    PubMed

    Michael, Joseph P

    2016-01-01

    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

  8. Simple Indolizidine and Quinolizidine Alkaloids.

    PubMed

    Michael, Joseph P

    2016-01-01

    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

  9. Quinolizidine alkaloids from Lupinus lanatus

    NASA Astrophysics Data System (ADS)

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

    2011-10-01

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

  10. 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

  11. 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

  12. Alkaloids from Galanthus nivalis.

    PubMed

    Berkov, Strahil; Codina, Carles; Viladomat, Francesc; Bastida, Jaume

    2007-07-01

    Phytochemical studies on Galanthus nivalis of Bulgarian origin resulted in the isolation of five compounds: 11-O-(3'-hydroxybutanoyl)hamayne, 3,11-O-(3',3''-dihydroxybutanoyl)hamayne, 3-O-(2''-butenoyl)-11-O-(3'-hydroxybutanoyl)hamayne, 3,11,3''-O-(3',3'',3'''-trihydroxybutanoyl)hamayne, and 2-O-(3'-acetoxybutanoyl)lycorine, together with five known alkaloids: ungeremine, lycorine, tazettine, hamayne, and ismine. Their structures were determined by (1)H and (13)C NMR spectroscopy and two-dimensional (1)H-(1)H and (1)H-(13)C chemical shift correlation experiments.

  13. Bioactive montanine derivatives from halide-induced rearrangements of haemanthamine-type alkaloids. Absolute configuration by VCD.

    PubMed

    Cedrón, Juan C; Estévez-Braun, Ana; Ravelo, Angel G; Gutiérrez, David; Flores, Ninoska; Bucio, María A; Pérez-Hernández, Nury; Joseph-Nathan, Pedro

    2009-04-01

    An unexpected rearrangement of haemanthamine-type alkaloids in the presence of halogenating agents has been found. Rearranged compounds present the 5,11-methanomorphantridine framework characteristic of montanine-type alkaloids. These compounds are difficult to obtain because of their scarcity in natural sources and because the synthetic approaches developed so far require numerous steps. Vibrational circular dichroism (VCD) spectroscopy was used to determine the absolute configuration of one of the rearranged compounds. Several rearranged alkaloids showed antimalarial activity.

  14. Accumulation of ergot alkaloids during conidiophore development in Aspergillus fumigatus.

    PubMed

    Mulinti, Prashanthi; Allen, Natalie A; Coyle, Christine M; Gravelat, Fabrice N; Sheppard, Donald C; Panaccione, Daniel G

    2014-01-01

    Production of ergot alkaloids in the opportunistic fungal pathogen Aspergillus fumigatus is restricted to conidiating cultures. These cultures typically accumulate several pathway intermediates at concentrations comparable to that of the pathway end product. We investigated the contribution of different cell types that constitute the multicellular conidiophore of A. fumigatus to the production of ergot alkaloid pathway intermediates versus the pathway end product, fumigaclavine C. A relatively minor share (11 %) of the ergot alkaloid yield on a molar basis was secreted into the medium, whereas the remainder was associated with the conidiating colonies. Entire conidiating cultures (containing hyphae, vesicle of conidiophore, phialides of conidiophore, and conidia) accumulated higher levels of the pathway intermediate festuclavine and lower levels of the pathway end product fumigaclavine C than did isolated, abscised conidia, indicating that conidiophores and/or hyphae have a quantitatively different ergot alkaloid profile compared to that of conidia. Differences in alkaloid accumulation among cell types also were indicated by studies with conidiophore development mutants. A ∆medA mutant, in which conidiophores are numerous but develop poorly, accumulated higher levels of pathway intermediates than did the wildtype or a complemented ∆medA mutant. A ∆stuA mutant, which grows mainly as hyphae and produces very few, abnormal conidiophores, produced no detectable ergot alkaloids. The data indicated heterogeneous spatial distribution of ergot alkaloid pathway intermediates versus pathway end product in conidiating cultures of A. fumigatus. This skewed distribution may reflect differences in abundance or activity of pathway enzymes among cell types of those conidiating cultures. PMID:23925951

  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.

  16. Biosynthetic Pathways of Ergot Alkaloids

    PubMed Central

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

    2014-01-01

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

  17. The Chemistry of the Akuammiline Alkaloids.

    PubMed

    Adams, Gregory L; Smith, Amos B

    2016-01-01

    An update on the literature covering the akuammiline family of alkaloids is presented. This chapter begins with a summary of new akuammiline alkaloids reported since 2000 and is followed by an overview of new reported bioactivities of akuammiline alkaloids since 2000. The remainder of the chapter comprises a comprehensive review of the synthetic chemistry that has been reported in the last 50 years concerning akuammiline alkaloids and their structural motifs.

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. The alkaloid profiles of Lupinus sulphureus.

    PubMed

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

    2009-02-25

    Lupines are common plants on the rangelands in the western United States. Lupines contain alkaloids that can be toxic and teratogenic causing congenital birth defects (crooked calf disease). One such lupine, Lupinus sulphureus, occurs in parts of Oregon, Washington, and British Columbia. Specimens of L. sulphureus from field collections and herbaria were evaluated taxonomically and by chemical means. A total of seven distinct alkaloid profiles and the individual alkaloids associated with each profile were identified. Each alkaloid profile was unique in its geographical distribution and its potential risk to livestock. In conclusion, taxonomic classification is not sufficient to determine risk, as chemical characterization of the alkaloids must also be performed.

  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.

  4. Monoterpene alkaloids from Argylia radiata.

    PubMed

    Bianco, Armandodoriano; Bonadies, Francesco; Cianciolo, Valeria; Melchioni, Cristiana; Ramunno, Alessia; Dezzi, Sandro; Nicoletti, Marcello; Serafini, Mauro; Ballero, Mauro

    2002-04-01

    Argylia radiata (L.) D. Don (Bignoniaceae) represents an important source of secondary metabolites, largely unexplored. The paper presents the isolation from the plant root of two new monoterpene alkaloids, 10-acetoxy-actinidine and 4-nor-7,8-dehydro-10-hydroxy-skytanthine, whose structures were elucidated by Mass spectrometry and 1H-NMR data.

  5. Indole alkaloids from Antirhea lucida.

    PubMed

    Weniger, B; Rafik, W; Bastida, J; Quirion, J C; Anton, R

    1995-12-01

    A new indole alkaloid, N,N-methyl-3'-indolylmethyl-5-methoxytryptamine, as well as the known gramine, N,N-dimethyltryptamine and 6-methoxy-2-methyl-1,2,3,4-tetrahydro-beta-carboline were isolated from the roots of Antirhea lucida (Sw.) Hook (Rubiaceae). Their structures were established by spectroscopic methods.

  6. Quaternary alkaloids of tinospora species.

    PubMed

    Bisset, N G; Nwaiwu, J

    1983-08-01

    The occurrence of quaternary alkaloids in TINOSPORA (and PARABAENA) species (Menispermaceae) has been studied. The main components were generally the protoberberine bases berberine and palmatine, with jatrorrhizine an occasional minor constituent, and the aporphine base magnoflorine. Choline was also often present. Only magnoflorine was detected in the PARABAENA material examined. PMID:17404996

  7. 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...

  8. Numerous Numerals.

    ERIC Educational Resources Information Center

    Henle, James M.

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

  9. Antifeedant C20 diterpene alkaloids.

    PubMed

    González-Coloma, Azucena; Reina, Matías; Guadaño, Ana; Martínez-Díaz, Rafael; Díaz, Jesús G; García-Rodriguez, Juan; Alva, Allenger; Grandez, Maritza

    2004-09-01

    We have tested the insect antifeedant and toxic activity of 21 C20 diterpenoid alkaloids on Spodoptera littoralis and Leptinotarsa decemlineata. The antifeedant effects of the test compounds were structure- and species-dependent. The most active antifeedants to L. decemlineata and S. littoralis were the rearranged form of hetisine (20; EC50 = 1.7 microg/cm2) and 19-oxodihydroatisine (9; EC50 = 0.1 microg/cm2), resp. Glandulosine (8) moderately affected orally injected S. littoralis larvae. A few compounds (13-oxocardiopetamine (4), 9, and atisinium chloride (13)) had cytotoxic effects to insect-derived Sf9 cells with varying degrees of selectivity with respect to mammalian CHO cells. Compounds 4 and 15,22-O-diacetyl-19-oxodihydroatisine (10) increased Trypanosoma cruzi mortality. Our results support the plant protective role of C20 diterpenoid alkaloids and open a new field for parasite control strategies.

  10. 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.

  11. Six new alkaloids from Melodinus henryi.

    PubMed

    Ma, Ke; Wang, Jun-Song; Luo, Jun; Kong, Ling-Yi

    2015-01-01

    A total of six new alkaloids, melodinhenines A-F (1-6), were isolated from Melodinus henryi. Melodinhenines A and B are new eburnan-vindolinine-type bisindole alkaloids and melodinhenines C-F are new quinolinic melodinus alkaloids. Their structures were elucidated through extensive spectroscopic methods including 2D NMR and HRESIMS analyses. The absolute configuration of 1 and 2 was determined using ECD exciton chirality method. To the best of our knowledge, this is the first report on the determination of the absolute configuration of eburnan-vindolinine-type bisindole alkaloid using this method.

  12. Intraspecific variability in the alkaloid metabolism of Galanthus elwesii.

    PubMed

    Berkov, Strahil; Sidjimova, Borjana; Evstatieva, Luba; Popov, Simeon

    2004-03-01

    Alkaloid pattern of individuals from 16 Bulgarian Galanthus elwesii populations was investigated by GC/MS and TLC. Twenty-one Amaryllidaceae alkaloids were detected and 14 of them were identified. Crinane type alkaloids, haemanthamine or crinine, dominated alkaloid metabolism in most of the populations. With exception of one population, where the separate individuals showed variable alkaloid profiles (dominated by crinine or haemanthamine) the individuals of the rest of populations have identical and characteristic alkaloid profiles. Some populations showed remarkable differences in respect to their alkaloid pattern-type of biosynthesis, main alkaloids and number of alkaloids. Populations dominated by galanthamine type alkaloids were found as well. These data demonstrate that like the morphological features, the alkaloid metabolism of G. elwesii is also variable.

  13. Alkaloids of Nelumbo lutea (Wild.) pers. (Nymphaeaceae)

    PubMed

    Zelenski, S G

    1977-11-01

    A phytochemical investigation of an alcoholic extract of the petioles of Nelumbo lutea resulted in the identification of the alkaloids N-methylasimilobine, anonaine, and roemerine. The alkaloids nuciferine, armepavine, N-nornuciferine, and N-norarmepavine, previously previously reported in the whole plant, were also identified.

  14. 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

  15. Phenylalkylamine alkaloids from Stapelia hirsuta L.

    PubMed

    Shabana, Marwan; Gonaid, Mariam; Salama, Maha Mahmoud; Abdel-Sattar, Essam

    2006-07-10

    Four alkaloids of the phenethylamine derivatives have been isolated from the n-butanol fraction of the aerial parts of Stapelia hirsuta L. The structures of the isolated alkaloids were determined as N-acetyl hordenine (a new natural compound), hordenine, candicine and hordenine-1-O-beta-D-glucoside, in addition to luteolin-7-O-beta-D-glucopyranoside. PMID:16753902

  16. Polycyclic Guanidine Alkaloids from Poecilosclerida Marine Sponges

    PubMed Central

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

    2016-01-01

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

  17. Marine Pyridoacridine Alkaloids: Biosynthesis and Biological Activities.

    PubMed

    Ibrahim, Sabrin R M; Mohamed, Gamal A

    2016-01-01

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

  18. 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...

  19. Anxiolytic Activity of Diterpene Alkaloid Songorine.

    PubMed

    Nesterova, Yu V; Povet'eva, T N; Suslov, N I; Shults, E E; Ziuz'kov, G N; Aksinenko, S G; Afanas'eva, O G; Krapivin, A V; Kharina, T G

    2015-09-01

    Antianxiety action of diterpene alkaloid songorine was studied using Vogel conflict test. Songorine in a dose of 0.25 mg/kg demonstrated high anxiolytic activity comparable to that of phenazepam and produced no sedative effect.

  20. Anxiolytic Activity of Diterpene Alkaloid Songorine.

    PubMed

    Nesterova, Yu V; Povet'eva, T N; Suslov, N I; Shults, E E; Ziuz'kov, G N; Aksinenko, S G; Afanas'eva, O G; Krapivin, A V; Kharina, T G

    2015-09-01

    Antianxiety action of diterpene alkaloid songorine was studied using Vogel conflict test. Songorine in a dose of 0.25 mg/kg demonstrated high anxiolytic activity comparable to that of phenazepam and produced no sedative effect. PMID:26468026

  1. 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.

  2. Total Synthesis of the Akuammiline Alkaloid Picrinine

    PubMed Central

    2015-01-01

    We report the first total synthesis of the complex akuammiline alkaloid picrinine, which was first isolated nearly five decades ago. Our synthetic approach features a concise assembly of the [3.3.1]-azabicyclic core, a key Fischer indolization reaction to forge the natural product’s carbon framework, and a series of delicate late-stage transformations to complete the synthesis. Our synthesis of picrinine also constitutes a formal synthesis of the related polycyclic alkaloid strictamine. PMID:24597784

  3. Bioactive indole alkaloids isolated from Alstonia angustifolia

    PubMed Central

    Pan, Li; Terrazas, César; Muñoz Acuña, Ulyana; Ninh, Tran Ngoc; Chai, Heebyung; Carcache de Blanco, Esperanza J.; Soejarto, Djaja D.; Satoskar, Abhay R.

    2014-01-01

    Bioassay-guided fractionation was conducted on a CHCl3-soluble extract of the stem bark of Alstonia angustifolia (Apocynaceae) collected in Vietnam using the HT-29 human colon cancer cell line, and led to the isolation of a new sarpagine-type indole alkaloid (1), together with nine known alkaloids, including four macroline-derived alkaloids (2–5), a sarpagine-type alkaloid (6), and four macroline-pleiocarpamine bisindole alkaloids (7–10). The structure of the new compound (1) was determined on the basis of spectroscopic data interpretation. Compounds 1–10 were evaluated in vitro for their NF-κB (p65) inhibitory activity against the Hela cells in an ELISA assay. The new sarpagine alkaloid, N(4)-methyltalpinine (1), was found to show significant NF-κB inhibitory activity (ED50 = 1.2 µM). Furthermore, all the isolates (1–10) were evaluated in vitro for their antileishmanial activity, and compounds (1–4, 6 and 8–10) exhibited leishmaniacidal activity against promastigotes of Leishmania mexicana. PMID:25584095

  4. 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.

  5. Hemlock alkaloids from Socrates to poison aloes.

    PubMed

    Reynolds, Tom

    2005-06-01

    Hemlock (Conium maculatum L. Umbelliferae) has long been known as a poisonous plant. Toxicity is due to a group of piperidine alkaloids of which the representative members are coniine and gamma-coniceine. The latter is the more toxic and is the first formed biosynthetically. Its levels in relation to coniine vary widely according to environmental conditions and to provenance of the plants. Surprisingly, these piperidine alkaloids have turned up in quite unrelated species in the monocotyledons as well as the dicotyledons. Aloes, for instance, important medicinal plants, are not regarded as poisonous although some species are very bitter. Nevertheless a small number of mostly local species contain the alkaloids, especially gamma-coniceine and there have been records of human poisoning. The compounds are recognized by their characteristic mousy smell. Both acute and chronic symptoms have been described. The compounds are neurotoxins and death results from respiratory failure, recalling the effects of curare. Chronic non-lethal ingestion by pregnant livestock leads to foetal malformation. Both acute and chronic toxicity are seen with stock in damp meadows and have been recorded as problems especially in North America. The alkaloids derive biosynthetically from acetate units via the polyketide pathway in contrast to other piperidine alkaloids which derive from lysine.

  6. 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.

  7. The alkaloids of the madangamine group.

    PubMed

    Amat, Mercedes; Pérez, Maria; Ballette, Roberto; Proto, Stefano; Bosch, Joan

    2015-01-01

    This chapter is focused on madangamines, a small group of complex diamine alkaloids isolated from marine sponges of the order Haplosclerida, and covers their isolation, characterization, biogenesis, biological activity, and synthesis. Structurally, madangamines are pentacyclic alkaloids with an unprecedented skeletal type, characterized by a common diazatricyclic core and two peripheral macrocyclic rings. The isolation of these alkaloids from Xestospongia ingens (madangamines A-E) and Pachychalina alcaloidifera (madangamine F) is described in detail. Physical and complete spectroscopic 1H and 13C NMR data are included. The proposed biogenesis of madangamines from ammonia, a functionalized three-carbon unit, and saturated or unsaturated linear long-chain dialdehydes, via partially reduced bis-alkylpyridine macrocycles, is discussed. The synthesis of alkaloids of the madangamine group has been little explored, with only one total synthesis reported so far, that of (+)-madangamine D. This review also describes several model synthetic approaches to the diazatricyclic ABC core of these alkaloids, as well as model studies on the construction of the (Z,Z)-unsaturated 11-membered E macrocycle common to madangamines A-E, the 13- and 14-membered D rings of madangamines C-E, and the all-cis-triunsaturated 15-membered D ring of madangamine A. Some members of this group have shown significant in vitro cytotoxicity against a number of cancer cell lines.

  8. 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

  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. Biological activity of alkaloids from Solanum dulcamara L.

    PubMed

    Kumar, Padma; Sharma, Bindu; Bakshi, Nidhi

    2009-01-01

    Alkaloids are well known for their antimicrobial activity. Though all natural alkaloids come from plants, not all plants produce alkaloids. Plants of the Solanaceae family are known for their high alkaloid content. Alkaloids are found in all plant parts like roots, stems, leaves, flowers, fruits and seeds. In the present study, those plant parts of Solanum dulcamara were selected which have been reported to produce a high content of a specific alkaloid: solanine (from unripe fruits), solasodine (from flowers) and beta-solamarine (from roots). These alkaloids were extracted from various parts of S. dulcamara by well-established methods and were screened for their antibacterial activity. Human pathogenic bacteria, viz., Enterobacter aerogenes, Escherichia coli, Staphylococcus aureus, were selected for the study. All three alkaloids inhibited the growth of E. coli and S. aureus. However, no significant activity was observed against E. aerogenes. Minimum inhibitory concentration and minimum bactericidal concentration were also evaluated.

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

    PubMed

    Eckermann, Ruben; Gaich, Tanja

    2016-04-11

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

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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...

  17. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  18. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Dietary supplements containing ephedrine alkaloids... UNREASONABLE RISK § 119.1 Dietary supplements containing ephedrine alkaloids. Dietary supplements containing ephedrine alkaloids present an unreasonable risk of illness or injury under conditions of use recommended...

  19. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  20. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  1. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

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

    PubMed

    Wallwey, Christiane; Li, Shu-Ming

    2012-01-01

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

  3. Pancratium canariense as an important source of amaryllidaceae alkaloids.

    PubMed

    Cedrón, Juan C; Oberti, Juan C; Estévez-Braun, Ana; Ravelo, Angel G; Del Arco-Aguilar, Marcelino; López, Matías

    2009-01-01

    Four new alkaloids (1-4) have been isolated from a methanolic extract of bulbs of Pancratium canariense, together with 12 known alkaloids (5-16). The structures of the new alkaloids were determined by extensive 1D and 2D NMR spectroscopic studies and X-ray diffraction.

  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. Antitussive indole alkaloids from Kopsia hainanensis.

    PubMed

    Tan, Min-Jia; Yin, Chun; Tang, Chun-Ping; Ke, Chang-Qiang; Lin, Ge; Ye, Yang

    2011-06-01

    Three new indole alkaloids, named kopsihainins A-C (1-3), and two known compounds, kopsinine (4) and methyl demethoxycarbonylchanofruticosinate (5), were isolated from the stems of Kopsia hainanensis. Their structures were determined using extensive spectroscopic methods. The two main constituents 4 and 5 exhibited significant antitussive activity in a citric acid induced guinea pig cough model. The antitussive effect of 4 was demonstrated to interact with the δ-opioid receptor. This is the first report of antitussive effects of aspidofractinine type and chanofruticosinate type alkaloids.

  6. The expanding universe of alkaloid biosynthesis.

    PubMed

    De Luca, V; Laflamme, P

    2001-06-01

    Characterization of many of the major gene families responsible for the generation of central intermediates and for their decoration, together with the development of large genomics and proteomics databases, has revolutionized our capability to identify exotic and interesting natural-product pathways. Over the next few years, these tools will facilitate dramatic advances in our knowledge of the biosynthesis of alkaloids, which will far surpass that which we have learned in the past 50 years. These tools will also be exploited for the rapid characterization of regulatory genes, which control the development of specialized cell factories for alkaloid biosynthesis.

  7. Antimicrobial hasubanalactam alkaloid from Stephania glabra.

    PubMed

    Semwal, Deepak Kumar; Rawat, Usha

    2009-03-01

    A novel hasubanalactam alkaloid, named glabradine, has been isolated from the tubers of Stephania glabra, together with three known quaternary protoberberine alkaloids, palmatine, dehydrocorydalmine and stepharanine. The structure of glabradine was assigned as 7-O-demethyl-N,O-dimethyloxostephinine, by means of rigorous spectroscopic analysis including 2 D NMR measurements. It was evaluated for antimicrobial activity against Staphylococcus aureus, S. mutans, Microsporum gypseum, M. canis and Trichophyton rubrum and displayed potent antimicrobial activity superior to those of novobiocin and erythromycin used as positive controls. PMID:19148860

  8. 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.

  9. Alkaloid diversity in Galanthus elwesii and Galanthus nivalis.

    PubMed

    Berkov, Strahil; Bastida, Jaume; Sidjimova, Borjana; Viladomat, Francesc; Codina, Carles

    2011-01-01

    Seventy alkaloids of galanthamine, lycorine, homolycorine, tazettine, haemanthamine, narciclasine, and tyramine types were detected by GC/MS in 25 Galanthus elwesii and seven Galanthus nivalis populations, collected from different locations in Bulgaria. Intraspecies diversity in the alkaloid profiles regarding the main alkaloid types (chemotypes) was observed. Tyramine-type protoalkaloids (namely, hordenine and its derivatives) were dominant in 19 populations of G. elwesii. In other populations of G. elwesii, the plants accumulated mainly homolycorine-, lycorine-, and galanthamine-type alkaloids. The alkaloid profiles of G. nivalis were dominated by narciclasine-, galanthamine-, lycorine-, haemanthamine-, or tazettine-type compounds. Geographical distribution of chemotypes indicated a relationship between populations, since adjacent populations often displayed similar alkaloid profiles. The results from year-to-year sampling and transplantation experiments imply genetic determination of alkaloid synthesis in the two studied species of Galanthus.

  10. Apoptosis-Inducing Effects of Amaryllidaceae Alkaloids.

    PubMed

    Nair, Jerald J; van Staden, Johannes; Bastida, Jaume

    2016-01-01

    The Amaryllidaceae occupies a privileged status amongst medicinal plants in having delivered the Alzheimer's drug galanthamine to the clinical market. Following its resounding success, there have been several positive indicators for the emergence of an anticancer drug from the family due to the potent antiproliferative activities manifested by several of its alkaloid constituents. Of these, the phenanthridones such as pancratistatin hold most promise as potential chemotherapeutics having succumbed to various phases of clinical trials. Other cytotoxic targets of the Amaryllidaceae are to be found within the lycorane and crinane groups, as exemplified by crinine and lycorine. Although the molecular targets of these alkaloids still remain elusive, much effort has gone into understanding their mode of action in cancer cells. Recent findings have shown that the apoptotic pathway may be a key factor in cancer cell death instigated by Amaryllidaceae alkaloids. As such, this review seeks to: (a) examine the apoptotic effects of Amaryllidaceae alkaloids in cancer cells; (b) explore the molecular basis to these effects; and (c) provide a pharmacophoric rationale in support of these activities.

  11. Highly selective hydroformylation of the cinchona alkaloids.

    PubMed

    Lambers, Marielle; Beijer, Felix H; Padron, José M; Toth, Imre; de Vries, Johannes G

    2002-07-12

    The four naturally occurring cinchona alkaloids were subjected to hydroformylation to create an extra functional group that allows immobilization. Cinchonidine, quinine, and quinidine, could be hydroformylated with virtually complete terminal selectivity, using a rhodium/tetraphosphite catalyst. The cinchonidine aldehyde was reduced to the alcohol and subjected to reductive amination with benzylamine.

  12. Chinchona alkaloid from Dendrosenecio kilimanjari subsp. cottonii.

    PubMed

    Were, O; Benn, M; Munavu, R

    1997-02-01

    Investigation of the Tanzanian Dendrosenecio kilimanjari subsp. cottonii resulted in the isolation of the cinchona alkaloid, cinchonidine. Conversion of cinchonidine to deoxy-cinchonidine was achieved in high yield using zinc dust in aqueous sulphuric acid. This illustrates the first reduction of a quinoline system using these reagents.

  13. 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.

  14. Probing Chemical Space with Alkaloid-Inspired Libraries

    PubMed Central

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

    2014-01-01

    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, due to 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. PMID:24451589

  15. Probing chemical space with alkaloid-inspired libraries.

    PubMed

    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 sp(3)-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 sp(3) content, comparable to a basis set of representative natural products and were highly rule-of-five compliant.

  16. Insecticidal Constituents and Activity of Alkaloids from Cynanchum mongolicum.

    PubMed

    Ge, Yang; Liu, Pingping; Yang, Rui; Zhang, Liu; Chen, Hongxing; Camara, Ibrahima; Liu, Yiqing; Shi, Wangpeng

    2015-09-21

    Based on MS and NMR data and bioassay-guided tracing, three insecticidal alkaloids I, II and III from Cynanchum mongolicum were identified to be antofine N-oxide, antofine and tylophorine. Alkaloid I was more toxic than alkaloids II and III, but they were less active against Spodoptera litura than total alkaloids. The contact toxicity from these alkaloids against the aphid Lipaphis erysimi was significant, as the 24 h-LC50 values of alkaloids I, II, III and total alkaloids were 292.48, 367.21, 487.791 and 163.52 mg/L, respectively. The development disruption of S. litura larvae was tested, the pupation and emergence rates of S. litura decreased and the acute mortality of S. litura increased significantly by day 3 after being injected in their body cavity with 10-40 mg/L of total alkaloid. The ecdysone titer of treated S. litura larvae and prepupae declined with increasing alkaloid concentration. The alkaloids of Cynanchum mongolicum are potential insect growth inhibitors.

  17. Aconitum lipo-alkaloids--semisynthetic products of the traditional medicine.

    PubMed

    Borcsa, Botond; Csupor, Dezso; Forgo, Peter; Widowitz, Ute; Bauer, Rudolf; Hohmann, Judit

    2011-04-01

    The term lipo-alkaloid is used for C19 aconitane alkaloids containing one or two long-chain fatty acid residues. Lipo-alkaloids are transesterified derivatives of the most toxic and highly effective diester-type diterpene alkaloids, such as aconitine, hypaconitine, mesaconitine. Lipo-alkaloids are native minor compounds of aconite drugs, but their amount significantly increases after traditional processing, which is a general method in the Far Eastern traditional medicinal systems. Analytical works demonstrated that cautious processing (usually boiling) of crude aconite roots decreases the amount of normal diterpene alkaloids and increases the concentration of lipo-alkaloids resulting in the reduction of toxicity of the drugs. Many papers reported that lipo-alkaloids occur as a complex mixture in the drugs, and the isolation of the individual components is extremely difficult. These compounds have been identified using highly sensitive analytical methods (HPLC-MS, NMR), and semisynthetic approaches have been developed to ensure lipo-alkaloids in pure form for pharmacological studies. This review summarizes the structure, chemistry, semisynthesis, analytics and bioactivities of lipo-alkaloids. On the basis of 32 references this is the first comprehensive study on this topic, covering the data of 173 compounds.

  18. Total synthesis of the Daphniphyllum alkaloid daphenylline

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

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

  19. 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

  20. Recent developments in the chemistry of quinazolinone alkaloids.

    PubMed

    Kshirsagar, U A

    2015-09-28

    Quinazolinones, an important class of fused heterocyclic alkaloids has attracted high attention in organic and medicinal chemistry due to their significant and wide range of biological activities. There are approximately 150 naturally occurring quinazolinone alkaloids known till 2005. Several new quinazolinone alkaloids (∼55) have been isolated in the last decade. Natural quinazolinones with exotic structural features and remarkable biological activities have incited a lot of activities in the synthetic community towards the development of new synthetic strategies and approaches for the total synthesis of quinazolinone alkaloids. This review is focused on these advances in the chemistry of quinazolinone alkaloids in the last decade. This article covers the newly isolated quinazolinone natural products with their biological activities and the recently reported total syntheses of quinazolinone alkaloids from 2006 to 2015.

  1. Natural alkaloids: basic aspects, biological roles, and future perspectives.

    PubMed

    Qiu, Shi; Sun, Hui; Zhang, Ai-Hua; Xu, Hong-Ying; Yan, Guang-Li; Han, Ying; Wang, Xi-Jun

    2014-06-01

    Natural products have gained popularity worldwide for promoting healthcare, as well as disease prevention. Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery. Several alkaloids isolated from natural herbs exhibit antiproliferation, antibacterial, antiviral, insecticidal, and antimetastatic effects on various types of cancers both in vitro and in vivo. This paper focuses on the naturally-derived alkaloids such as berberine, matrine, piperine, fritillarine, and rhynchophylline, etc., and summarizes the action mechanisms of these compounds. Based on the information in the literature that is summarized in this paper, the use of alkaloids as drugs is very promising, but more research and clinical trials are necessary before final recommendations on specific alkaloids can be made. Following this, it is hoped that as a result of this review, there will be a greater awareness of the excellent promise that natural alkaloids show for use in the therapy of diseases.

  2. 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

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

    PubMed

    Diaz, Gonzalo J

    2015-12-11

    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.

  4. 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

  5. Histamine release inhibition activity of bisbenzylisoquinoline alkaloids.

    PubMed

    Nakamura, K; Tsuchiya, S; Sugimoto, Y; Sugimura, Y; Yamada, Y

    1992-12-01

    Eleven examples of bisbenzylisoquinoline alkaloids (head-to-head; 10, head-to-tail; 1) and one half molecule type (N-methylcoclaurine), were tested by in vitro histamine release inhibition assay. The order of the potency of the inhibitory effect was ranked thus: homoaromoline, aromoline, isotetrandrine, cepharanthine, fangchinoline, obaberine, and tetrandrine. The following substances, cepharanoline, berbamine, oxyacanthine, and cycleanine (head-to-tail structure) had no inhibitory effect. N-Methylcoclaurine showed an inhibitory effect comparable to that of fangchinoline. PMID:1484888

  6. Synthesis studies on the Melodinus alkaloid meloscine

    PubMed Central

    Feldman, Ken S.; Antoline, Joshua F.

    2012-01-01

    The pentacyclic Melodinus alkaloid (±)-meloscine was synthesized in 19 chemical steps from 2-bromobenzaldehyde through a route featuring an allenyl azide cyclization cascade to deliver the core azabicyclo[3.3.0]octane substructure. Peripheral functionalization of this core included a Tollens-type aldol condensation to set the quaternary center at C(20) and a diastereoselective ring closing metathesis to forge the tetrahydropyridine ring. PMID:23316092

  7. A new diketopiperazine alkaloid from Aspergillus oryzae.

    PubMed

    Shaaban, Mohamed; El-Metwally, Mohammad Magdy; Nasr, Hamdi

    2014-01-01

    Investigation of bioactive secondary metabolites from terrestrial Aspergillus oryzae sp. MMAO1 using M2 medium afforded a new diketopiperazine alkaloid, 7,9-dihydroxy-3-(1H-indol-3-ylmethyl)-8-methoxy-2,3,11,11a-tetrahydro-6H-pyrazino[1,2-b]isoquinoline-1,4-dione (1a), containing the unusual amino acid L-6,8-dihydroxy-7-methoxyphenylalanine. This was co-isolated with ditryptophenaline (2), cyclo-(Tryp,Tyr) (4), cyclo-(Pro,Val), α-cyclopiazonic acid (3), kojic acid and uridine. Re-cultivation of the fungal strain on Dox medium led to the production of bisdethio(bismethylthio)gliotoxin (5), pseurotin A (6) along with linoleic acid, α-cyclopiazonic acid (3) and kojic acid. The chemical structure of the new diketopiperazine alkaloid including the relative configuration was determined by 1D and 2D NMR spectroscopy and HR-ESI-MS spectrometry, and by comparison with the related literature. The new alkaloid (1a) showed no antimicrobial activity or cytotoxicity against brine shrimps.

  8. A new monoterpenoid oxindole alkaloid from Hamelia patens micropropagated plantlets.

    PubMed

    Paniagua-Vega, David; Cerda-García-Rojas, Carlos M; Ponce-Noyola, Teresa; Ramos-Valdivia, Ana C

    2012-11-01

    Chemical studies on Hamelia patens (Rubiaceae) micropropagated plantlets allowed production of a new monoterpenoid oxindole alkaloid, named (-)-hameline (7), together with eight known alkaloids, tetrahydroalstonine (1), aricine (2), pteropodine (3), isopteropodine (4), uncarine F (5), speciophylline (6), palmirine (8), and rumberine (9). The structure of the new alkaloid was assigned on the basis of 1D and 2D NMR spectroscopy, mass spectrometry, and molecular modeling.

  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.

  11. Evaluation of Biosynthetic Pathway and Engineered Biosynthesis of Alkaloids.

    PubMed

    Kishimoto, Shinji; Sato, Michio; Tsunematsu, Yuta; Watanabe, Kenji

    2016-01-01

    Varieties of alkaloids are known to be produced by various organisms, including bacteria, fungi and plants, as secondary metabolites that exhibit useful bioactivities. However, understanding of how those metabolites are biosynthesized still remains limited, because most of these compounds are isolated from plants and at a trace level of production. In this review, we focus on recent efforts in identifying the genes responsible for the biosynthesis of those nitrogen-containing natural products and elucidating the mechanisms involved in the biosynthetic processes. The alkaloids discussed in this review are ditryptophenaline (dimeric diketopiperazine alkaloid), saframycin (tetrahydroisoquinoline alkaloid), strictosidine (monoterpene indole alkaloid), ergotamine (ergot alkaloid) and opiates (benzylisoquinoline and morphinan alkaloid). This review also discusses the engineered biosynthesis of these compounds, primarily through heterologous reconstitution of target biosynthetic pathways in suitable hosts, such as Escherichia coli, Saccharomyces cerevisiae and Aspergillus nidulans. Those heterologous biosynthetic systems can be used to confirm the functions of the isolated genes, economically scale up the production of the alkaloids for commercial distributions and engineer the biosynthetic pathways to produce valuable analogs of the alkaloids. In particular, extensive involvement of oxidation reactions catalyzed by oxidoreductases, such as cytochrome P450s, during the secondary metabolite biosynthesis is discussed in details. PMID:27548127

  12. 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

  13. Drug Delivery Systems and Combination Therapy by Using Vinca Alkaloids

    PubMed Central

    Lee, Chun-Ting; Huang, Yen-Wei; Yang, Chih-Hui; Huang, Keng-Shiang

    2015-01-01

    Developing new methods for chemotherapy drug delivery has become a topic of great concern. Vinca alkaloids are among the most widely used chemotherapy reagents for tumor therapy; however, their side effects are particularly problematic for many medical doctors. To reduce the toxicity and enhance the therapeutic efficiency of vinca alkaloids, many researchers have developed strategies such as using liposome-entrapped drugs, chemical- or peptide-modified drugs, polymeric packaging drugs, and chemotherapy drug combinations. This review mainly focuses on the development of a vinca alkaloid drug delivery system and the combination therapy. Five vinca alkaloids (eg, vincristine, vinblastine, vinorelbine, vindesine, and vinflunine) are reviewed. PMID:25877096

  14. 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.

  15. 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

  16. 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...

  17. Cinchona alkaloids from Cinchona succirubra and Cinchona ledgeriana.

    PubMed

    Cheng, Gui-Guang; Cai, Xiang-Hai; Zhang, Bao-Hong; Li, Yan; Gu, Ji; Bao, Mei-Fen; Liu, Ya-Ping; Luo, Xiao-Dong

    2014-02-01

    Seven new cinchona alkaloids, cinchonanines A-G (1-7), and 29 known alkaloids were isolated from the barks of Cinchona surrirubra and C. ledgeriana collected from Yunnan Province in China. The new structures were elucidated by extensive spectroscopic analysis. All compounds were evaluated for their cytotoxicity against five human cancer cell lines. Compounds 2, 13, 14, and 15 showed moderate cytotoxicity.

  18. 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...

  19. A new alkaloid isolated from Abies webbiana leaf

    PubMed Central

    Ghosh, Ashoke K.; Sen, Debanjan; Bhattacharya, Sanjib

    2010-01-01

    A new alkaloid namely 1-(4’-methoxyphenyl)-aziridine was isolated from the leaf of Abies webbiana Lindl. (Pinaceae), grown in Sikkim Himalayan region of India. Its chemical structure was elucidated on the basis of elemental and spectral analyses. This is the first experimental report of the isolation of any alkaloid from A. webbiana. PMID:21808564

  20. Galanthindole: a new indole alkaloid from Galanthus plicatus ssp. byzantinus.

    PubMed

    Unver, Nehir; Kaya, G Irem; Werner, Christa; Verpoorte, Robert; Gözler, Belkis

    2003-09-01

    A new indole alkaloid, galanthindole, was isolated from Galanthus plicatus ssp. byzantinus (Amaryllidaceae), a plant native to northwestern Turkey. Incorporating a non-fused indole ring, galanthindole may represent the prototype of a new subgroup of the Amaryllidaceae alkaloids. Two other bases, (+)-11-hydroxyvittatine and hordenine, are also reported from the same plant.

  1. 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...

  2. Antiproliferative and Structure Activity Relationships of Amaryllidaceae Alkaloids.

    PubMed

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

    2015-07-30

    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.

  3. 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.

  4. 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

  5. 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.

  6. Chirality and numbering of substituted tropane alkaloids.

    PubMed

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

    2011-08-25

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

  7. Pyrrolizidine alkaloids of Echium vulgare honey found in pure pollen.

    PubMed

    Boppré, Michael; Colegate, Steven M; Edgar, John A

    2005-02-01

    The pyrrolizidine alkaloids previously identified in floral honey attributed to Echium vulgare (Boraginaceae) have been detected (8000-14 000 ppm) in pure pollen collected from the anthers of Echium vulgare. Pyrrolizidine alkaloids and/or their N-oxides were isolated from the aqueous acid extracts of pollen by use of strong cation-exchange, solid-phase extraction and identified by liquid chromatographic/mass spectrometric (LCMS) analysis. The pyrrolizidine alkaloids in the pollen are present mainly as the N-oxides. In addition to seven previously described pyrrolizidine alkaloids and/or their N-oxides (echimidine, acetylechimidine, uplandicine, 9-O-angelylretronecine, echiuplatine, leptanthine, and echimiplatine), one unidentified (echivulgarine), but previously found in honey, and two previously undescribed (vulgarine and 7-O-acetylvulgarine) pyrrolizidine alkaloids and/or their N-oxides were identified in the pollen. Tentative structures for these unidentified pyrrolizidine alkaloids are proposed on the basis of the mass spectrometric data and biogenetic considerations. The implications of these results for identifying the source and subsequent concentrations of pyrrolizidine alkaloids in honeys and commercial bee pollen are briefly discussed. PMID:15686407

  8. A Review of Bioinsecticidal Activity of Solanaceae Alkaloids

    PubMed Central

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

    2016-01-01

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

  9. 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

    2016-03-01

    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

  10. Ergot alkaloids--biology and molecular biology.

    PubMed

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

    2006-01-01

    EA have been a major benefit, and a major detriment, to humans since early in recorded history. Their medicinal properties have been used, and continue to be used, to aid in childbirth, with new uses being found in the treatment of neurological and cardiovascular disorders. The surprisingly broad range of pharmaceutical uses for EA stems from their affinities for multiple receptors for three distinct neurotransmitters (serotonin, dopamine, and adrenaline), from the great structural diversity of natural EA, and from the application of chemical techniques that further expand that structural diversity. The dangers posed by EA to humans and their livestock stem from the ubiquity of ergot fungi (Claviceps species) as parasites of cereals, and of related grass endophytes (Epichloë, Neotyphodium, and Balansia species) that may inhabit pasture grasses and produce toxic levels of EA. Further concerns stem from saprophytic EA producers in the genera Aspergillus and Penicillium, especially A. fumigatus, an opportunistic pathogen of humans. Numerous fungal species produce EA with a wide variety of structures and properties. These alkaloids are associated with plants in the families Poaceae, Cyperaceae, and Convolvulaceae, apparently because these plants can have symbiotic fungi that produce EA. Pharmacological activities of EA relate to their specific structures. Known as potent vasoconstrictors, the ergopeptines include a lysergic acid substituent with an amide linkage to a complex cyclol-lactam ring structure generated from three amino acids. Simpler lysergyl amides and clavines are more apt to have oxytonic or psychotropic activities. One of the lysergyl amides is LSD (5), the most potent hallucinogen known. The EA biosynthetic pathway in Claviceps species has been studied extensively for many decades, and recent studies have also employed epichloës and A. fumigatus. The early pathway, shared among these fungi, begins with the action of an aromatic prenyl transferase

  11. Cytotoxic and antimalarial bisbenzylisoquinoline alkaloids from Stephania erecta.

    PubMed

    Likhitwitayawuid, K; Angerhofer, C K; Cordell, G A; Pezzuto, J M; Ruangrungsi, N

    1993-01-01

    (+)-2-N-Methyltelobine [1], a new alkaloid, together with twelve known bisbenzylisoquinolines, was isolated from the tubers of Stephania erecta. The structure determination and the complete 1H- and unambiguous 13C-nmr assignments of 1 were obtained through extensive use of several 1D and 2D nmr techniques. All alkaloids inhibited the growth of cultured Plasmodium falciparum strains D-6 and W-2 and displayed nonselective cytotoxicity with a battery of cultured mammalian cells. These data were used for the calculation of selectivity indices. Relative to known antimalarial agents, these bisbenzylisoquinoline alkaloids do not appear to be promising clinical candidates at the present time. PMID:8450319

  12. γ-Lactam alkaloids from the flower buds of daylily.

    PubMed

    Matsumoto, Takahiro; Nakamura, Seikou; Nakashima, Souichi; Ohta, Tomoe; Yano, Mamiko; Tsujihata, Junichiro; Tsukioka, Junko; Ogawa, Keiko; Fukaya, Masashi; Yoshikawa, Masayuki; Matsuda, Hisashi

    2016-07-01

    Four new alkaloids, hemerocallisamines IV-VII, were isolated from the methanol extract of flower buds of daylily. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. The absolute stereochemistry of the hemerocallisamines IV-VI was elucidated by the application of the modified Mosher's method, HPLC analysis, and optical rotation. In the present study, the isolated alkaloids significantly inhibited the aggregation of Aβ42 in vitro. This is the first report about bioactive alkaloids with a γ-lactam ring from daylily. In addition, isolated nucleosides showed accelerative effects on neurite outgrowth under the non-fasting condition. PMID:26849229

  13. γ-Lactam alkaloids from the flower buds of daylily.

    PubMed

    Matsumoto, Takahiro; Nakamura, Seikou; Nakashima, Souichi; Ohta, Tomoe; Yano, Mamiko; Tsujihata, Junichiro; Tsukioka, Junko; Ogawa, Keiko; Fukaya, Masashi; Yoshikawa, Masayuki; Matsuda, Hisashi

    2016-07-01

    Four new alkaloids, hemerocallisamines IV-VII, were isolated from the methanol extract of flower buds of daylily. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. The absolute stereochemistry of the hemerocallisamines IV-VI was elucidated by the application of the modified Mosher's method, HPLC analysis, and optical rotation. In the present study, the isolated alkaloids significantly inhibited the aggregation of Aβ42 in vitro. This is the first report about bioactive alkaloids with a γ-lactam ring from daylily. In addition, isolated nucleosides showed accelerative effects on neurite outgrowth under the non-fasting condition.

  14. Indole Alkaloids from the Leaves of Nauclea officinalis.

    PubMed

    Fan, Long; Liao, Cheng-Hui; Kang, Qiang-Rong; Zheng, Kai; Jiang, Ying-Chun; He, Zhen-Dan

    2016-07-23

    Three new indole alkaloids, named naucleamide G (1), and nauclealomide B and C (5 and 6), were isolated from the n-BuOH-soluble fraction of an EtOH extract of the leaves of Nauclea officinalis, together with three known alkaloids, paratunamide C (2), paratunamide D (3) and paratunamide A (4). The structures with absolute configurations of the new compounds were identified on the basis of 1D and 2D NMR, HRESIMS, acid hydrolysis and quantum chemical circular dichroism (CD) calculation. According to the structures of isolated indole alkaloids, their plausible biosynthetic pathway was deduced.

  15. 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

  16. Photofragmentation mechanisms in protonated chiral cinchona alkaloids.

    PubMed

    Kumar, Sunil; Lucas, Bruno; Fayeton, Jacqueline; Scuderi, Debora; Alata, Ivan; Broquier, Michel; Barbu-Debus, Katia Le; Lepère, Valeria; Zehnacker, Anne

    2016-08-10

    The photo-stability of protonated cinchona alkaloids is studied in the gas phase by a multi-technique approach. A multi-coincidence technique is used to demonstrate that the dissociation is a direct process. Two dissociation channels are observed. They result from the C8-C9 cleavage, accompanied or not by hydrogen migration. The branching ratio between the two photo-fragments is different for the two pseudo-enantiomers quinine and quinidine. Mass spectrometry experiments coupling UV photo-dissociation of the reactants and structural characterization of the ionic photo-products by Infra-Red Multiple Photo-Dissociation (IRMPD) spectroscopy provide unambiguous information on their structure. In addition, quantum chemical calculations allow proposing a reactive scheme and discussing it in terms of the ground-state geometry of the reactant.

  17. Benhamycin, novel alkaloid from terrestrial Streptomyces sp.

    PubMed

    Shaaban, Mohamed; Abdel-Aziz, Mohamed S

    2007-11-01

    During our screening for bioactive natural compounds from microorganisms, a novel alkaloid has been isolated from a terrestrial Streptomyces sp. isolate NR12, and named as benhamycin (1). This was along with the known metabolites, uracil, thymine, p-hydroxybenzoic acid, 2'-deoxyuridin, tryptophol, indolyl-3-carboxylic acid, and indolyl-3-carbaldehyde. Chemical structure of the novel compound was determined by detailed analysis of its spectroscopic data (extensive NMR experiments, 1 & 2D, MS spectroscopy, and MS high resolution). Structurally, Benhamycin (1) is a pentacyclic aromatic compound bearing an acridine moiety lactamized with benzene. Biological studies showed that the strain extract was moderately active against Gram-positive, Gram-negative bacteria and fungi.

  18. 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

  19. Pyrrolidonyl and pyridyl alkaloids in Lymantria dispar.

    PubMed

    Deml, Reinhold

    2003-01-01

    The occurrence and metabolism of nicotine and related N-containing compounds in body fluids of the gipsy moth were addressed. Thin layer chromatographic studies clearly showed the simultaneous presence of GABA and 2-pyrrolidone but not of GABamide in the larval haemolymph and osmeterial secretion of Lymantria dispar as well as in the corresponding body fluids of the saturniids, Saturnia pavonia and Attacus atlas. Furthermore, feeding and injection experiments using alkylated precursors and combined gas chromatography/mass spectrometry gave evidence of the transformation of 2-pyrrolidone to nicotine and of nicotinic acid to nicotinamide in caterpillars of L. dispar. Based on these results, on the earlier described variation of the secondary-compound patterns of L. dispar during its development, and on literature data, metabolic pathways for the hitherto detected pyridyl and pyrrolidonyl alkaloids in Lymantriidae (and possibly Saturniidae) are proposed.

  20. Alkaloids from Spathelia excelsa: their chemosystematic significance.

    PubMed

    Lima, M da Paz; Rosas, Lisandra Vieira; da Silva, M Fátima das G F; Ferreira, A Gilberto; Fernandes, João B; Vieira, Paulo C

    2005-07-01

    The methanol extract from the leaves of Spathelia excelsa yielded six alkaloids: 2-(12-oxo-tridecanyl)-3-methoxy-4-quinolone, 2-(10-hydroxy-10-methyldodecanyl)-3-methoxy-4-quinolone, 2-(11-hydroxy-11-methyldodecanyl)-3-methoxy-4-quinolone, 2-(12-hydroxytridecanyl)-3-methoxy-4-quinolone, 7-hydroxy-2-(3-hydroxy-3-methylbutyl)-4-quinolone and 6-hydroxy-2-(3-hydroxy-3-methylbutyl)-4-quinolone, in addition to the known 3-O-beta-d-glucopiranosylsitosterol and (-)-epicatechin. The 2-alkyl-4(1H)-quinolones in S. excelsa display strong similarities with those in Dictyolomatoideae, which contains several 2-alkyl-4-quinolones. The data reported herein thus provide firm support for placing Spathelioideae close to or within the Dictyolomatoideae. PMID:16002107

  1. Erythroidine alkaloids: a novel class of phytoestrogens.

    PubMed

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

    2014-07-01

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

  2. Activity of pyrrolizidine alkaloids against biofilm formation and Trichomonas vaginalis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Crotalaria genus belongs to the subfamily Papilionoideae comprising about 600 species spread throughout tropical, neotropical and subtropical regions. In this study, seeds of Crolatalaria pallida were used to the isolation of usaramine, a pyrrolizidine alkaloid. Thus, Pseudomonas aeruginosa and Stap...

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

    PubMed

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

    2015-08-01

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

  4. 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.

  5. A new pyrrole alkaloid from seeds of Castanea sativa.

    PubMed

    Hiermann, Alois; Kedwani, Samir; Schramm, Hans Wolfgang; Seger, Christoph

    2002-02-01

    A new pyrrole alkaloid, methyl-(5-formyl-1H-pyrrole-2-yl)-4-hydroxybutyrate (1), was isolated from sweet chestnut seeds and its structure elucidated on the basis of data from NMR spectroscopy and by comparison with synthetic analogues.

  6. 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

  7. 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.

  8. 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.

  9. Marine bromopyrrole alkaloids: synthesis and diverse medicinal applications.

    PubMed

    Rane, Rajesh; Sahu, Niteshkumar; Shah, Chetan; Karpoormath, Rajshekhar

    2014-01-01

    Marine organisms have been found to be a very rich source of bioactive molecules. Among marine organisms, sponges have been proven to be excellent producers of secondary metabolites. More than 5,300 compounds have been isolated from sponges with around 200 new molecules reported each year. Bromopyrrole alkaloids constitute a family of exclusively marine alkaloids and represent a fascinating example of the large variety of compounds formed by marine sponges which exhibit different biological activities such as antifeedent, anti-biofilm, anticancer, antiinflammatory, antimicrobial, immunomodulatory, analgesic, antiserotonergic, antiangiogenic, antihistaminic, chitinase inhibitor and actimyosin ATPase activator. More than 140 derivatives with different structures and biological activities, have been isolated from more than 20 different sponges. Most of these alkaloids share a key building block, pyrrole-imidazole with oroidin being their underlying structural motif. In this review detailed account of isolation and medicinal application of marine bromopyrrole alkaloids and their synthetic derivatives are discussed. PMID:24359195

  10. Two new alkaloids from marine sponge Callyspongia sp.

    PubMed

    Yang, Bin; Tao, Huaming; Zhou, Xuefeng; Lin, Xiu-Ping; Liu, Yonghong

    2013-03-01

    Two new alkaloids, callylactam A (1) and callyimine A (4), along with three known ones (2, 3 and 5), were isolated from the marine sponge Callyspongia sp. The structures were determined on the basis of NMR and MS analysis.

  11. Computational Studies on Cinchona Alkaloid-Catalyzed Asymmetric Organic Reactions.

    PubMed

    Tanriver, Gamze; Dedeoglu, Burcu; Catak, Saron; Aviyente, Viktorya

    2016-06-21

    Remarkable progress in the area of asymmetric organocatalysis has been achieved in the last decades. Cinchona alkaloids and their derivatives have emerged as powerful organocatalysts owing to their reactivities leading to high enantioselectivities. The widespread usage of cinchona alkaloids has been attributed to their nontoxicity, ease of use, stability, cost effectiveness, recyclability, and practical utilization in industry. The presence of tunable functional groups enables cinchona alkaloids to catalyze a broad range of reactions. Excellent experimental studies have extensively contributed to this field, and highly selective reactions were catalyzed by cinchona alkaloids and their derivatives. Computational modeling has helped elucidate the mechanistic aspects of cinchona alkaloid catalyzed reactions as well as the origins of the selectivity they induce. These studies have complemented experimental work for the design of more efficient catalysts. This Account presents recent computational studies on cinchona alkaloid catalyzed organic reactions and the theoretical rationalizations behind their effectiveness and ability to induce selectivity. Valuable efforts to investigate the mechanisms of reactions catalyzed by cinchona alkaloids and the key aspects of the catalytic activity of cinchona alkaloids in reactions ranging from pharmaceutical to industrial applications are summarized. Quantum mechanics, particularly density functional theory (DFT), and molecular mechanics, including ONIOM, were used to rationalize experimental findings by providing mechanistic insights into reaction mechanisms. B3LYP with modest basis sets has been used in most of the studies; nonetheless, the energetics have been corrected with higher basis sets as well as functionals parametrized to include dispersion M05-2X, M06-2X, and M06-L and functionals with dispersion corrections. Since cinchona alkaloids catalyze reactions by forming complexes with substrates via hydrogen bonds and long

  12. The effects of Aconitum alkaloids on the central nervous system.

    PubMed

    Ameri, A

    1998-10-01

    Preparations of Aconitum roots are employed in Chinese and Japanese medicine for analgesic, antirheumatic and neurological indications. The recent surge in use of phytomedicine derived from traditional Chinese medicine as well as increasing concerns about possible toxic effects of these compounds have inspired a great deal of research into the mechanisms by which certain Aconitum alkaloids may act on the central nervous system. The pharmacological effects of preparations of Aconitum roots are attributed to several diterpenoid alkaloids. The main alkaloid of these plants is aconitine, a highly toxic diterpenoid alkaloid which is known to suppress the inactivation of voltage-dependent Na+ channels by binding to neurotoxin binding site 2 of the alpha-subunit of the channel protein. In this article the pharmacology of several structurally related Aconitum alkaloids is highlighted and their therapeutic vs toxic potential is discussed. Neurochemical and neurophysiological studies will be reviewed with emphasis on the effects of the alkaloids in regions of the brain that have been implicated in pain transmission and generation of epileptic activity. Considering the chemical structure of the Aconitum alkaloids as well as their mechanism of action, a subdivision in three groups becomes obvious: the first group comprises such alkaloids which possess high toxicity due to two ester boundings at the diterpene skeleton. The members of this group activate voltage-dependent sodium channels already at resting potential and inhibit noradrenaline reuptake. Activation of sodium channels and in consequence excessive depolarization with final inexcitability and suppression of pain transmission account for their antinociceptive properties. The second group comprises less toxic monoesters which have been shown to possess strong antinociceptive, antiarrhythmic and antiepileptiform properties due to a blockade of the voltage-dependent sodium channel. Electrophysiological studies have

  13. Computational Studies on Cinchona Alkaloid-Catalyzed Asymmetric Organic Reactions.

    PubMed

    Tanriver, Gamze; Dedeoglu, Burcu; Catak, Saron; Aviyente, Viktorya

    2016-06-21

    Remarkable progress in the area of asymmetric organocatalysis has been achieved in the last decades. Cinchona alkaloids and their derivatives have emerged as powerful organocatalysts owing to their reactivities leading to high enantioselectivities. The widespread usage of cinchona alkaloids has been attributed to their nontoxicity, ease of use, stability, cost effectiveness, recyclability, and practical utilization in industry. The presence of tunable functional groups enables cinchona alkaloids to catalyze a broad range of reactions. Excellent experimental studies have extensively contributed to this field, and highly selective reactions were catalyzed by cinchona alkaloids and their derivatives. Computational modeling has helped elucidate the mechanistic aspects of cinchona alkaloid catalyzed reactions as well as the origins of the selectivity they induce. These studies have complemented experimental work for the design of more efficient catalysts. This Account presents recent computational studies on cinchona alkaloid catalyzed organic reactions and the theoretical rationalizations behind their effectiveness and ability to induce selectivity. Valuable efforts to investigate the mechanisms of reactions catalyzed by cinchona alkaloids and the key aspects of the catalytic activity of cinchona alkaloids in reactions ranging from pharmaceutical to industrial applications are summarized. Quantum mechanics, particularly density functional theory (DFT), and molecular mechanics, including ONIOM, were used to rationalize experimental findings by providing mechanistic insights into reaction mechanisms. B3LYP with modest basis sets has been used in most of the studies; nonetheless, the energetics have been corrected with higher basis sets as well as functionals parametrized to include dispersion M05-2X, M06-2X, and M06-L and functionals with dispersion corrections. Since cinchona alkaloids catalyze reactions by forming complexes with substrates via hydrogen bonds and long

  14. Cytotoxic and antimalarial bisbenzylisoquinoline alkaloids from Cyclea barbata.

    PubMed

    Lin, L Z; Shieh, H L; Angerhofer, C K; Pezzuto, J M; Cordell, G A; Xue, L; Johnson, M E; Ruangrungsi, N

    1993-01-01

    An alkaloid extract derived from the roots of Cyclea barbata demonstrated cytotoxic and antimalarial activities, and five bisbenzylisoquinoline alkaloids, (+)-tetrandrine [1], (-)-limacine [2], (+)-thalrugosine [3], (+)-homoaromoline [4], and (-)-cycleapeltine [5], were isolated as the active principles. The complete and unambiguous assignments of the 1H- and 13C-nmr data of these substances were made by 1D and 2D nmr techniques (COSY, phase-sensitive ROESY, HETCOR, and FLOCK). PMID:8450318

  15. Alkaloids from roots of Stemona sessilifolia and their antitussive activities.

    PubMed

    Yang, Xin-Zhou; Zhu, Jian-Yu; Tang, Chun-Ping; Ke, Chang-Qiang; Lin, Ge; Cheng, Tin-Yan; Rudd, John A; Ye, Yang

    2009-02-01

    Protostemonamide ( 1), a new protostemonine-type alkaloid, and 12 known compounds were isolated from the roots of Stemona sessilifolia. Their structures were elucidated by 1 D and 2 D NMR spectral and other spectroscopic studies. The main alkaloidal constituents, protostemonine ( 2), stemospironine ( 4), and maistemonine ( 7), showed significant antitussive activity in a citric acid-induced guinea pig cough model following peripheral administration; stemonamine ( 11) had antitussive activity following i. c. v. administration.

  16. 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 α-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.

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

    PubMed

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

    2015-01-01

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

  18. 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

  19. [ALKALOIDS OF PEGANUM HARMALA L. AND THEIR BIOLOGICAL ACTIVITY].

    PubMed

    Vachnadze, V; Suladze, T; Vachnadze, N; Kintsurashvili, L; Novikova, J

    2015-06-01

    Peganum Harmala L., Peganасеае widely distributed in Georgia. On the basis of chemical analysis of the composition of alkaloids it was found out that the plant contains quinazoline derivatives, among which dominats alkaloid d, 1 peganine: С11Н12NО2, m.p. 198-99ºC (СН3ОН). UV, λmax 275 (lgε 3,95). In IR-spectrum (KBr) 1625 cm- (-N=C) 3200-370 (OH)cm-1 . Mass- spectrum: М+ 171(100%). It was studied the dynamics of accumulation for total alkaloids and d, l - peganine: in the budding phase the amount of alkaloids was - 3,71%, d, l - peganine 0,07÷0,09%; in the phase of mass flowering the sum of alkaloids - 4,51% ,d, l - peganine - 0,1÷0,13%; in the phase of ripeness total alkaloids - 3.92%; d,l - peganine - 0,08÷0,1. The study of specific pharmacological activity showed that the d,l - peganine similar to peganine at a dose of 30 mg/kg causes a decrease in heart rate by 30÷40 beats/min, which is characteristic for anticholinesterases, in parallel with this, a decrease in cholinesterase activity in blood serum has been observed.

  20. 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

    2015-01-01

    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.

  1. Evaluation of Aconitum diterpenoid alkaloids as antiproliferative agents.

    PubMed

    Wada, Koji; Ohkoshi, Emika; Zhao, Yu; Goto, Masuo; Morris-Natschke, Susan L; Lee, Kuo-Hsiung

    2015-04-01

    Little information has been reported on the antitumor effects of the diterpenoid alkaloid constituents of Aconitum plants, used in the herbal drug 'bushi'. This study was aimed at determining the antitumor activities of Aconitum C19-and C20-diterpenoid alkaloids and synthetic derivatives against lung (A549), prostate (DU145), nasopharyngeal (KB), and vincristine-resistant nasopharyngeal (KB-VIN) cancer cell lines. Newly synthesized C20-diterpenoid alkaloid derivatives showed substantial suppressive effects against all human tumor cell lines tested. In contrast, natural and derivatized C19-diterpenoid alkaloids showed only a slight or no effect. Most of the active compounds were hetisine-type C20-diterpenoid alkaloids, specifically kobusine and pseudokobusine analogs with two different substitution patterns, C-11 and C-11,15. Notably, several C20-diterpenoid alkaloids were more potent against multidrug-resistant KB subline KB-VIN cells. Pseudokobusine 11-3'-trifluoromethylbenzoate (94) is a possible promising new lead meriting additional evaluation against multidrug-resistant tumors.

  2. Anticholinesterase inhibitory activity of quaternary alkaloids from Tinospora crispa.

    PubMed

    Yusoff, Mashitah; Hamid, Hazrulrizawati; Houghton, Peter

    2014-01-01

    Quaternary alkaloids are the major alkaloids isolated from Tinospora species. A previous study pointed to the necessary presence of quaternary nitrogens for strong acetylcholinesterase (AChE) inhibitory activity in such alkaloids. Repeated column chromatography of the vine of Tinospora crispa extract led to the isolation of one new protoberberine alkaloid, 4,13-dihydroxy-2,8,9-trimethoxydibenzo[a,g]quinolizinium (1), along with six known alkaloids-dihydrodiscretamine (2), columbamine (3), magnoflorine (4), N-formylannonaine (5), N-formylnornuciferine (6), and N-trans-feruloyltyramine (7). The seven compounds were isolated and structurally elucidated by spectroscopic analysis. Two known alkaloids, namely, dihydrodiscretamine and columbamine are reported for the first time for this plant. The compounds were tested for AChE inhibitory activity using Ellman's method. In the AChE inhibition assay, only columbamine (3) showed strong activity with IC50 48.1 µM. The structure-activity relationships derived from these results suggest that the quaternary nitrogen in the skeleton has some effect, but that a high degree of methoxylation is more important for acetylcholinesterase inhibition. PMID:24448061

  3. A comparison of the antimalarial activity of the cinchona alkaloids against Plasmodium falciparum in vitro.

    PubMed

    Wesche, D L; Black, J

    1990-06-01

    The effects of four major cinchona alkaloids: (-) quinine, (+) quinidine, (-)cinchonidine, and (+)cinchonine against Plasmodium falciparum FCQ-27/PNG were studied. The alkaloids were tested in vitro as either single alkaloids, racemic mixtures of stereoisomers, or as an equimolar combination of all four alkaloids. Results indicate (+)quinidine to be most effective and both (+)stereoisomers were more potent than the (-)stereoisomers. Inhibitory concentrations 50% (Ki) of racemic mixtures of stereoisomers were similar to those of the (+)stereoisomers alone. The Ki of four alkaloids in equimolar combination were similar to that of the (-) cinchonidine/(+)cinchonine racemic mixture. A total alkaloidal extract of Cinchona sp. was tested and compared with the pure alkaloids. HPLC analysis indicated that (+)cinchonine, (-)cinchonidine and (-)quinine were present in a ratio of approximately 1:1:2, respectively. The total alkaloid extract, with (-)stereoisomers predominating, was less effective than the four alkaloids in combination. The nature of the interaction between stereoisomers was investigated and appears to be one of addition.

  4. Rapid determination of Papaver somniferum alkaloids in process streams using monolithic column high-performance liquid chromatography with chemiluminescence detection.

    PubMed

    Costin, Jason W; Lewis, Simon W; Purcell, Stuart D; Waddell, Lucy R; Francis, Paul S; Barnett, Neil W

    2007-07-30

    We have combined high-performance liquid chromatography (HPLC) separations using a monolithic column with acidic potassium permanganate and tris(2,2'-bipyridyl)ruthenium(II) chemiluminescence detection in a rapid and highly sensitive method to monitor the process of extracting opiate alkaloids from Papaver somniferum. Due to the high flow rates allowed with the monolithic column and the inherent selectivity of the chemiluminescence reactions, the four predominant alkaloids--morphine, codeine, oripavine and thebaine--were determined in less than 2 min. The results obtained with numerous process samples compared favourable with those of the standard HPLC methodology. Limits of detection were 1x10(-10) M, 5x10(-10) M, 5x10(-10) M and 1x10(-9) M, for morphine, codeine, oripavine and thebaine, respectively.

  5. 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

  6. 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

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

    PubMed

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

    2014-01-01

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

  8. 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

  9. Micelle assisted structural conversion with fluorescence modulation of benzophenanthridine alkaloids.

    PubMed

    Pradhan, Ankur Bikash; Bhuiya, Sutanwi; Haque, Lucy; Tiwari, Richa; Das, Suman

    2017-01-01

    In this study we have reported the anionic surfactant (Sodium dodecyl sulfate, SDS) driven structural conversion of two benzophenanthridine plant alkaloids namely Chelerythrine (herein after CHL) and Sanguinarine (herein after SANG). Both the alkaloids exist in two forms: the charged iminium and the neutral alkanolamine form. The iminium form is stable at low pH (<6.5) and the alkanolamine form exists at higher pH (>10.1). The fluorescence intensity of the alkanolamine form is much stronger than the iminium form. The iminium form of both the alkaloids remains stable whereas the alkanolamine form gets converted to the iminium form in the SDS micelle environment. The iminium form possesses positive charge and it seems that electrostatic interaction between the positively charged iminium and negatively charged surfactant leads to the stabilization of the iminium form in the Stern layer of the anionic micelle. Whereas the conversion of the alkanolamine form into the iminium form takes place and that can be monitored in naked eye since the iminium form is orange in colour and the alkanolamine form has blue violet emission. Such a detail insight about the photophysical properties of the benzophenanthridine alkaloids would be a valuable addition in the field of alkaloid-surfactant interaction. PMID:27419642

  10. Post-genome research on the biosynthesis of ergot alkaloids.

    PubMed

    Li, Shu-Ming; Unsöld, Inge A

    2006-10-01

    Genome sequencing provides new opportunities and challenges for identifying genes for the biosynthesis of secondary metabolites. A putative biosynthetic gene cluster of fumigaclavine C, an ergot alkaloid of the clavine type, was identified in the genome sequence of ASPERGILLUS FUMIGATUS by a bioinformatic approach. This cluster spans 22 kb of genomic DNA and comprises at least 11 open reading frames (ORFs). Seven of them are orthologous to genes from the biosynthetic gene cluster of ergot alkaloids in CLAVICEPS PURPUREA. Experimental evidence of the identified cluster was provided by heterologous expression and biochemical characterization of two ORFs, FgaPT1 and FgaPT2, in the cluster of A. FUMIGATUS, which show remarkable similarities to dimethylallyltryptophan synthase from C. PURPUREA and function as prenyltransferases. FgaPT2 converts L-tryptophan to dimethylallyltryptophan and thereby catalyzes the first step of ergot alkaloid biosynthesis, whilst FgaPT1 catalyzes the last step of the fumigaclavine C biosynthesis, i. e., the prenylation of fumigaclavine A at C-2 position of the indole nucleus. In addition to information obtained from the gene cluster of ergot alkaloids from C. PURPUREA, the identification of the biosynthetic gene cluster of fumigaclavine C in A. FUMIGATUS opens an alternative way to study the biosynthesis of ergot alkaloids in fungi. PMID:16902860

  11. 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

  12. Geographic distribution of three alkaloid chemotypes of Croton lechleri.

    PubMed

    Milanowski, Dennis J; Winter, Rudolph E K; Elvin-Lewis, Memory P F; Lewis, Walter H

    2002-06-01

    Three known alkaloids, isoboldine (2), norisoboldine (1), and magnoflorine (8), have been isolated for the first time from Croton lechleri, a source of the wound healing latex "sangre de grado". An HPLC system was developed, and a large number of latex and leaf samples of C. lechleri from 22 sites in northern Peru and Ecuador were analyzed to gain an understanding of the natural variation in alkaloid content for the species. Up to six alkaloids were found to occur in the leaves including, in addition to those listed above, thaliporphine (3), glaucine (4), and taspine (9), whereas the latex contained only 9. Taspine (9) is the component that has been previously found to be responsible for the wound healing activity of C. lechleri latex, and its mean concentration throughout the range examined was found to be 9% of the latex by dry weight. In addition, three chemotypes are defined based on the alkaloid content of the leaves, and the geographic distribution of these chemotypes is discussed along with a quantitative analysis of the alkaloid content as a function of chemotype.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  14. 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...

  15. 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.

  16. Transgenic and mutation-based suppression of a berberine bridge enzyme-like (BBL) gene family reduces alkaloid content in field-grown tobacco.

    PubMed

    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.

  17. 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

  18. Comparative qualitative and quantitative determination of alkaloids in narcotic and condiment Papaver somniferum cultivars.

    PubMed

    Frick, Susanne; Kramell, Robert; Schmidt, Jürgen; Fist, Anthony J; Kutchan, Toni M

    2005-05-01

    In the present study morphinan, tetrahydrobenzylisoquinoline, benzo[c]phenanthridine, and phthalideisoquinoline alkaloids were determined qualitatively and quantitatively by HPLC and LC-MS analysis in tissues of the Tasmanian Papaver somniferum L. elite cultivar C048-6-14-64. The data were compared with the results from the low-morphine cultivar "Marianne". In the elite cultivar, 91.2% of the latex alkaloids consist of the three pharmaceutically most valuable alkaloids: morphine, codeine, and thebaine. In the root system, the major alkaloids are sanguinarine/10-hydroxysanguinarine and dihydrosanguinarine/10-hydroxydihydrosanguinarine. In the stems and leaves of C048-6-14-64, the same alkaloids were measured as in the latex. In the stems, a gradient in relative total alkaloid content from the top downward toward the roots was observed. The concentration of morphine was decreasing toward the roots, whereas an increasing gradient from the upper to the lower stem parts was detected for codeine. The relative total alkaloid concentration in leaves remained constant; no gradient was observed. The cultivar "Marianne" displayed a shifted pattern of alkaloid accumulation and reduced levels of total alkaloid. In the condiment cultivar, 80.5% of the alkaloids of the latex consisted of the two phthalideisoquinoline alkaloids narcotoline and noscapine. Only 18.8% of the relative total alkaloid content were morphinan alkaloids. In contrast to the narcotic cultivar, in which the benzo[c]phenanthridines in roots dominated over the morphinan and tetrahydrobenzylisoquinoline alkaloids, the concentration of benzo[c]phenanthridines in "Marianne" was similar to that of morphinan and tetrahydrobenzylisoquinoline alkaloids. These data suggest a differential alkaloid regulation in each cultivar of P. somniferum.

  19. (+)-Chenabinol (Revised NMR Data) and Two New Alkaloids from Berberis vulgaris and their Biological Activity.

    PubMed

    Novák, Zdenĕk; Hošt'álková, Anna; Opletal, Lubomír; Nováková, Lucie; Hrabinová, Martina; Kuneš, Jiří; Cahlíková, Lucie

    2015-10-01

    A known alkaloid (+)-chenabinol (1) and two new secobisbenzylisoquinoline alkaloids were isolated by standard chromatographic methods from the root bark of Berberis vulgaris L. The structures of the new alkaloids, named berkristine (2) and verfilline (3), were established by spectroscopic (including 2D NMR), and HRMS (ESI) methods. The alkaloids were tested for their inhibition activity of human cholinesterases and prolyl oligopeptidase. Compound 1 inhibited human butyrylcholinesterase with an IC50 value of 44.8 ± 5.4 μM.

  20. Hydrofocusing Bioreactor Produces Anti-Cancer Alkaloids

    NASA Technical Reports Server (NTRS)

    Gonda, Steve R.; Valluri, Jagan V.

    2011-01-01

    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.

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

    PubMed Central

    2013-01-01

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

  2. [Occurrence of indole alkaloids among secondary metabolites of soil Aspergillus].

    PubMed

    Vinokurova, N G; Khmel'nitskaia, I I; Baskunov, B P; Arinbasarov, M U

    2003-01-01

    The occurrence of indole alkaloids among secondary fungal metabolites was studied in species of the genus Aspergillus, isolated from soils that were sampled in various regions of Russia (a total of 102 isolates of the species A. niger, A. phoenicis, A. fumigatus, A. flavus, A. versicolor, A. ustus, A. clavatus, and A. ochraceus). Clavine alkaloids were represented by fumigaclavine, which was formed by A. fumigatus. alpha-Cyclopiazonic acid was formed by isolates of A. fumigatus, A. flavus, A. versicolor, A. phoenicis, and A. clavatus. The occurrence of indole-containing diketopiperazine alkaloids was documented for isolates of A. flavus, A. fumigatus, A. clavatus, and A. ochraceus. No indole-containing metabolites were found among the metabolites of A. ustus or A. niger. PMID:12722658

  3. 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

  4. HPTLC and GC/MS Study of Amaryllidaceae Alkaloids of Two Narcissus Species.

    PubMed

    Shawky, Eman; Abou-Donia, Amina H; Darwish, Fikria A; Toaima, Soad M; Takla, Sarah S; Pigni, Natalia B; Bastida, Jaume

    2015-08-01

    In this article, we report on the alkaloid profile and dynamic of alkaloid content and diversity in two Narcissus plants at different stages of development. The alkaloid profile of the two Narcissus species was investigated by GC/MS and HPTLC. Fifty eight Amaryllidaceae alkaloids were detected, and 25 of them were identified in the different organs of N. tazetta and N. papyraceus. The alkaloid 3-O-methyl-9-O-demethylmaritidine is tentatively identified here for the first time from the Amaryllidaceae family, and four alkaloids (tazettamide, sternbergine, 1-O-acetyllycorine, 2,11-didehydro-2-dehydroxylycorine) are tentatively identified for the first time in the genus Narcissus. The different organs of the two species analyzed showed remarkable differences in their alkaloid pattern, type of biosynthesis, main alkaloid and number of alkaloids. Lycorine-type alkaloids dominated the alkaloid, metabolism in N. papyraceus, while alkaloids of narciclasine-, galanthamine- and homolycorine-types were found only in the species N. tazetta L.

  5. [Clavine alkaloid biosynthesis by the fungus Penicillium palitans westling 1911 isolated from ancient permafrost deposits].

    PubMed

    Kozlovskiĭ, A G; Zhelifonova, V P; Antipova, T V

    2009-01-01

    The relic strain of Penicillium palitans isolated from the ancient permafrost deposits produces clavine alkaloids such as festuclavine, fumigaclavine A, and fumigaclavine B. Alkaloid biosynthesis is concurrent with the growth. Tryptophan and zinc ion additives to the culture medium stimulate the synthesis of alkaloids. PMID:19382708

  6. Engineering strategies for the fermentative production of plant alkaloids in yeast

    PubMed Central

    Trenchard, Isis J.; Smolke, Christina D.

    2015-01-01

    Microbial hosts engineered for the biosynthesis of plant natural products offer enormous potential as powerful discovery and production platforms. However, the reconstruction of these complex biosynthetic schemes faces numerous challenges due to the number of enzymatic steps and challenging enzyme classes associated with these pathways, which can lead to issues in metabolic load, pathway specificity, and maintaining flux to desired products. Cytochrome P450 enzymes are prevalent in plant specialized metabolism and are particularly difficult to express heterologously. Here, we describe the reconstruction of the sanguinarine branch of the benzylisoquinoline alkaloid pathway in Saccharomyces cerevisiae, resulting in microbial biosynthesis of protoberberine, protopine, and benzophenanthridine alkaloids through to the end-product sanguinarine, which we demonstrate can be efficiently produced in yeast in the absence of the associated biosynthetic enzyme. We achieved titers of 676 µg/L stylopine, 548 µg/L cis-N-methylstylopine, 252 µg/L protopine, and 80 µg/L sanguinarine from the engineered yeast strains. Through our optimization efforts, we describe genetic and culture strategies supporting the functional expression of multiple plant cytochrome P450 enzymes in the context of a large multi-step pathway. Our results also provided insight into relationships between cytochrome P450 activity and yeast ER physiology. We were able to improve the production of critical intermediates by 32-fold through genetic techniques and an additional 45-fold through culture optimization. PMID:25981946

  7. Cytotoxicity of Naturally Occurring Isoquinoline Alkaloids of Different Structural Types.

    PubMed

    Chlebek, Jakub; Doskocil, Ivo; Hulcová, Daniela; Breiterová, Katerina; Šafratová, Marcela; Havelek, Radim; Habartová, Klára; Hošt'álková, Anna; Volštátová, Tereza; Cahlíková, Lucie

    2016-06-01

    Forty-six isoquinoline alkaloids, of eleven structural types isolated in our laboratory, have been evaluated for their cytotoxicity against two cancer cell lines (Caco-2 and Hep-G2 cancer cells), as well as against normal human lung fibroblast cells. Only scoulerine, aromoline, berbamine and parfumidine showed significant cytotoxic effects, but only scoulerine was active against both Caco-2 and Hep-G2 cells (IC50 values 6.44 ± 0.87 and 4.57 ± 0.42, respectively). Unfortunately, except for parfumidine, the other active alkaloids were also cytotoxic to the normal human lung fibroblast cells.

  8. Antitussive stemoninine alkaloids from the roots of Stemona tuberosa.

    PubMed

    Lin, Li-Gen; Li, Kan Man; Tang, Chun-Ping; Ke, Chang-Qiang; Rudd, John A; Lin, Ge; Ye, Yang

    2008-06-01

    Investigation of the roots of Stemona tuberosa afforded five minor constituents, stemoenonine (1), 9a- O-methylstemoenonine (2), oxystemoenonine (3), 1,9a- seco-stemoenonine (4), and oxystemoninine (5), along with the known compound stemoninoamide (6). Their structures were elucidated by 1D and 2D NMR spectra and other spectroscopic studies. Alkaloids 1, 2, and 6, as well as the representative stemoninine-type alkaloid, stemoninine (7), were screened for antitussive activity in the citric acid-induced guinea pig cough model. Compounds 6 and 7 exhibited strong antitussive activity after oral and intraperitoneal administrations.

  9. Cytotoxicity of Naturally Occurring Isoquinoline Alkaloids of Different Structural Types.

    PubMed

    Chlebek, Jakub; Doskocil, Ivo; Hulcová, Daniela; Breiterová, Katerina; Šafratová, Marcela; Havelek, Radim; Habartová, Klára; Hošt'álková, Anna; Volštátová, Tereza; Cahlíková, Lucie

    2016-06-01

    Forty-six isoquinoline alkaloids, of eleven structural types isolated in our laboratory, have been evaluated for their cytotoxicity against two cancer cell lines (Caco-2 and Hep-G2 cancer cells), as well as against normal human lung fibroblast cells. Only scoulerine, aromoline, berbamine and parfumidine showed significant cytotoxic effects, but only scoulerine was active against both Caco-2 and Hep-G2 cells (IC50 values 6.44 ± 0.87 and 4.57 ± 0.42, respectively). Unfortunately, except for parfumidine, the other active alkaloids were also cytotoxic to the normal human lung fibroblast cells. PMID:27534109

  10. Chemiluminescence detection of opium poppy (Papaver somniferum) alkaloids.

    PubMed

    Francis, Paul S; Adcock, Jacqui L; Costin, Jason W; Purcell, Stuart D; Pfeffer, Frederick M; Barnett, Neil W

    2008-11-01

    A review with 98 references. The determination of the opium poppy (Papaver somniferum) alkaloids and their semi-synthetic derivatives has important applications in industrial process monitoring, clinical analysis and forensic science. Liquid-phase chemiluminescence reagents such as tris(2,2'-bipyridyl)ruthenium(II) and acidic potassium permanganate exhibit remarkable sensitivity and complementary selectivity for many P. somniferum alkaloids, which has been exploited in the development of a range of analytical procedures using flow analysis, high-performance liquid chromatography, capillary electrophoresis and microfluidic instrumentation.

  11. 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.

  12. 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.

  13. The cell and developmental biology of alkaloid biosynthesis.

    PubMed

    De Luca, V; St Pierre, B

    2000-04-01

    Plants produce unique natural products as a result of gene mutation and subsequent adaptation of metabolic pathways to create new secondary metabolites. However, their biosynthesis and accumulation remains remarkably under the control of the biotic and abiotic environments. Alkaloid biosynthesis, which requires the adaptation of cellular activities to perform specialized metabolism without compromising general homeostasis, is accomplished by restricting product biosynthesis and accumulation to particular cells and to defined times of plant development. The cell and developmental biology of alkaloid biosynthesis, which is remarkably complex, evolved in part by recruiting pre-existing enzymes to perform new functions.

  14. 3-Methoxysampangine, a novel antifungal copyrine alkaloid from Cleistopholis patens.

    PubMed Central

    Liu, S C; Oguntimein, B; Hufford, C D; Clark, A M

    1990-01-01

    Further examination of the active ethanolic extract of the root bark of Cleistopholis patens by using bioassay-directed fractionation resulted in the isolation of a new alkaloid, 3-methoxysampangine (compound I), together with three known alkaloids, eupolauridine (compound II), liriodenine (compound III), and eupolauridine N-oxide (compound IV). The proposed structure of compound I was based on its physicochemical properties and spectral data. 3-Methoxysampangine exhibited significant antifungal activity against Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans. This is the first report of the isolation of liriodenine (compound III) from the root bark of C. patens. PMID:2188584

  15. Antifouling indole alkaloids from two marine derived fungi.

    PubMed

    He, Fei; Han, Zhuang; Peng, Jiang; Qian, Pei-Yuan; Qi, Shu-Hua

    2013-03-01

    In order to find non-toxic antifouling natural products from marine microorganisms, the chemical constituents of two marine derived fungi Penicillium sp. and Aspergillus sydowii have been investigated under bio-guided fractionation. A new indolyl diketopiperazine compound, penilloid A (1), together with 15 known ones were isolated from these two strains. The structure of 1 was elucidated on the basis of NMR and mass spectra. Some alkaloids showed significant antifouling and antibacterial activities. The results indicate that indole alkaloids could be a potential antifouling agent resource.

  16. Alkaloids from the South China Sea Black Coral Antipathes dichotoma.

    PubMed

    Qi, Shu-Hua; Su, Guo-Chen; Wang, Yi-Fei; Liu, Qiu-Ying; Gao, Cheng-Hai

    2009-01-01

    A new carbazole alkaloid, antipathine A (1), together with three known zoanthoxanthin alkaloids (2--4) was isolated from the EtOH/CH2Cl2 extracts of the South China Sea black coral Antipathes dichotoma. The structure of 1 was determined on the bases of extensive spectroscopic analysis, including 1D and 2D NMR data. Compounds 1 and 2 showed moderate cytotoxicity against human stomach carcinoma SGC-7901 cell line with IC50 of 67.38 and 86.40 microg/ml, respectively, and 1 and 2 also showed weak cytotoxicity toward human liver carcinoma Hep_G2 cell line.

  17. Indole alkaloids from Vinca major and V. minor growing in Turkey.

    PubMed

    Bahadori, Fatemeh; Topçu, Gülaçti; Boğa, Mehmet; Türkekul, Ayla; Kolak, Ufuk; Kartal, Murat

    2012-06-01

    A new indole alkaloid, 11-hydroxypolyneuridine, was isolated from Vinca major subsp. major L. and the known indole alkaloids vallesiachotamine and isovallesiachotamine from Vinca minor L. This is the first report on the alkaloids of both Vinca species growing in Turkey; vallesiachotamine and isovallesiachotamine were isolated from a Vinca species for the first time. V. minor may be considered as a new source for these two alkaloids due to their occurrence in high amount in the aerial parts of the plant. The alkaloid extracts of the two Vinca species were found to have high lipid peroxidation inhibitory and DPPH radical scavenging activities. Anticholinesterase activity of the extracts was also very strong.

  18. [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.

  19. Alkaloids in the human food chain--natural occurrence and possible adverse effects.

    PubMed

    Koleva, Irina I; van Beek, Teris A; Soffers, Ans E M F; Dusemund, Birgit; Rietjens, Ivonne M C M

    2012-01-01

    Alkaloid-containing plants are an intrinsic part of the regular Western diet. The present paper summarizes the occurrence of alkaloids in the food chain, their mode of action and possible adverse effects including a safety assessment. Pyrrolizidine alkaloids are a reason for concern because of their bioactivation to reactive alkylating intermediates. Several quinolizidine alkaloids, β-carboline alkaloids, ergot alkaloids and steroid alkaloids are active without bioactivation and mostly act as neurotoxins. Regulatory agencies are aware of the risks and have taken or are considering appropriate regulatory actions for most alkaloids. These vary from setting limits for the presence of a compound in feed, foods and beverages, trying to define safe upper limits, advising on a strategy aiming at restrictions in use, informing the public to be cautious or taking specific plant varieties from the market. For some alkaloids known to be present in the modern food chain, e.g., piperine, nicotine, theobromine, theophylline and tropane alkaloids risks coming from the human food chain are considered to be low if not negligible. Remarkably, for many alkaloids that are known constituents of the modern food chain and of possible concern, tolerable daily intake values have so far not been defined.

  20. 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.

  1. Pyrrolizidine alkaloids from Symphytum officinale L. and their percutaneous absorption in rats.

    PubMed

    Brauchli, J; Lüthy, J; Zweifel, U; Schlatter, C

    1982-09-15

    An analysis of a commercial sample of Symphyti radix originating from Poland with a total alkaloid content of 0.07% revealed the presence of 7 pyrrolizidine alkaloid-N-oxides: 7-acetyl intermedine, 7-acetyl lycopsamine as the main constituents and lycopsamine, intermedine, symphytine and traces of 2 further not yet identified alkaloids. The percutaneous absorption of these alkaloids was investigated in rats, using a crude alcoholic extract of the plant corresponding to a dose of 194 mg alkaloid-N-oxides/kg b.wt. The excretion of N-oxides in the urine during 2 days was in the range of 0.1-0.4% of the dose. The dermally absorbed N-oxides are not or only to a small extent converted to the free alkaloids in the organism. The oral application led to a 20-50 times higher excretion of N-oxides and free alkaloids in the urine. PMID:7128756

  2. Analysis, separation, and bioassay of pyrrolizidine alkaloids from comfrey (Symphytum officinale).

    PubMed

    Couet, C E; Crews, C; Hanley, A B

    1996-01-01

    Pyrrolizidine alkaloids have been linked to liver and lung cancers and a range of other deleterious effects. As with many natural toxicants, major problems arise in determining the effects of the different members of the class and the importance of various forms of ingestion. In this study we have investigated the levels of pyrrolizidine alkaloids in comfrey (Symphytum officinale), determined the levels in different parts of the plant and in herbal remedies, separated the alkaloids into two main groups--the principal parent alkaloids and the corresponding N-oxides--and, finally, carried out a simple bioassay based upon the mutagenic capability of the separated compounds in a human cell line. We conclude that the part of the plant ingested is important in terms of alkaloid challenge and that the effect of two of the major groups of alkaloids individually is different from that of alkaloids in the whole plant extract. PMID:8887946

  3. 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

  4. 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

  5. Ergovaline, an endophytic alkaloid. 1. Animal physiology and metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ergovaline is an ergot alkaloid found in some endophyte-infected ryegrasses and has been implicated in the expression of ergotism-like symptoms of grazing livestock, as well as in the protection of the plant against invertebrate predation and abiotic stresses. These selection pressures have resulted...

  6. 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...

  7. 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, 4β-hydroxynankakurine B (1) and Δ(13,N),N(α)-methylphlegmarine-N(β)-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.

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

    PubMed

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

    2016-01-01

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

  9. Effect of Ergot Alkaloids on Bovine Foregut Vasculature

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  10. Alkaloid profiling and anticholinesterase activity of South American Lycopodiaceae species.

    PubMed

    Konrath, Eduardo Luis; Ortega, María Gabriela; de Loreto Bordignon, Sérgio; Apel, Miriam Anders; Henriques, Amélia Teresinha; Cabrera, José Luis

    2013-02-01

    The alkaloid extracts of four Huperzia and one Lycopodiella species, from Brazilian habitats, were tested for their in vitro anticholinesterase activities. IC(50) values showed a potent acetylcholinesterase inhibition for H. reflexa (0.11 ± 0.05 μg/mL), followed by H. quadrifariata (2.0 ± 0.3 μg/mL), H. acerosa (5.5 ± 0.9 μg/mL), H. heterocarpon (25.6 ± 2.7 μg/mL) and L. cernua (42.6 ± 1.5 μg/mL). A lower inhibition of butyrylcholinesterase was observed for all species with the exception of H. heterocarpon (8.3 ± 0.9 μg/mL), whose alkaloid extract presented a selectivity for pseudocholinesterase. Moreover, the chemical study of the bioactive extracts performed by GC-MS, revealed the presence of a number of Lycopodium alkaloids belonging to the lycopodane, flabellidane and cernuane groups. Surprisingly, the potent acetylcholinesterase inhibitors huperzines A and B were not detected in the extracts, suggesting that other alkaloids may be responsible for such an effect. PMID:22117191

  11. 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...

  12. 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...

  13. Revised NMR data for incartine: an alkaloid from Galanthus elwesii.

    PubMed

    Berkov, Strahil; Reyes-Chilpa, Ricardo; Codina, Carles; Viladomat, Francesc; Bastida, Jaume

    2007-07-12

    Phytochemical studies on Galanthus elwesii resulted in the isolation of five alkaloids: incartine, hordenine, hippeastrine, 8-O-demethylhomolycorine and lycorine. The NMR data given previously for incartine were revised and completed by two-dimensional 1H-1H and 1H-13C chemical shift correlation experiments. In vitro studies on the bioactivity of incartine were carried out.

  14. 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.

  15. Two new antifungal alkaloids produced by Streptoverticillium morookaense.

    PubMed

    Feng, Na; Ye, Wanhui; Wu, Ping; Huang, Yicun; Xie, Haihui; Wei, Xiaoyi

    2007-03-01

    A new carbazole alkaloid, streptoverticillin, and a new 2-azetidinone, streptoverticillinone, along with three known cyclodipeptides were isolated from the mycelial solid culture of Streptoverticillium morookaense. Their structures were elucidated by analysis of 1D and 2D NMR, mass spectra and optical rotation data. Two new compounds exhibited antifungal activity against Peronophythora litchii. PMID:17446689

  16. In vitro cytotoxicity of various dehydropyrrolizidine ester alkaloids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dehydropyrrolizidine alkaloids (DHPAs) are plant-derived hepato-, pneumo- and geno-toxins that are carcinogenic in several species. Because of the difficulty in isolating sufficient DHPA for toxicological studies, there are few direct comparisons of toxicity. The objectives of this study was to de...

  17. Genetic variation of piperidine alkaloids in Pinus ponderosa: a common garden study

    PubMed Central

    Gerson, Elizabeth A.; Kelsey, Rick G.; St Clair, J. Bradley

    2009-01-01

    Background and Aims Previous measurements of conifer alkaloids have revealed significant variation attributable to many sources, environmental and genetic. The present study takes a complementary and intensive, common garden approach to examine genetic variation in Pinus ponderosa var. ponderosa alkaloid production. Additionally, this study investigates the potential trade-off between seedling growth and alkaloid production, and associations between topographic/climatic variables and alkaloid production. Methods Piperidine alkaloids were quantified in foliage of 501 nursery seedlings grown from seed sources in west-central Washington, Oregon and California, roughly covering the western half of the native range of ponderosa pine. A nested mixed model was used to test differences among broad-scale regions and among families within regions. Alkaloid concentrations were regressed on seedling growth measurements to test metabolite allocation theory. Likewise, climate characteristics at the seed sources were also considered as explanatory variables. Key Results Quantitative variation from seedling to seedling was high, and regional variation exceeded variation among families. Regions along the western margin of the species range exhibited the highest alkaloid concentrations, while those further east had relatively low alkaloid levels. Qualitative variation in alkaloid profiles was low. All measures of seedling growth related negatively to alkaloid concentrations on a natural log scale; however, coefficients of determination were low. At best, annual height increment explained 19·4 % of the variation in ln(total alkaloids). Among the climate variables, temperature range showed a negative, linear association that explained 41·8 % of the variation. Conclusions Given the wide geographic scope of the seed sources and the uniformity of resources in the seedlings' environment, observed differences in alkaloid concentrations are evidence for genetic regulation of alkaloid

  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. 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.

  20. Complement-mediated antiinflammatory effect of bisbenzylisoquinoline alkaloid fangchinoline.

    PubMed

    Hristova, M; Istatkova, R

    1999-11-01

    Complement-mediated mode of action of bisbenzylisoquinoline alkaloid fangchinoline was investigated in vivo and in vitro. The application of fangchinoline intraperitoneally (i.p.) to complement normal mice, strain ICR, inhibited the complement activity in serum and peritoneal exudate. The substance activated serum complement of C5-deficient DBA/2 mice. Fangchinoline was able to provoke local inflammatory reaction in both strains after subcutaneous (s.c.) injection. The alkaloid suppressed paw swelling induced by live Candida albicans in ICR and DBA/2 mice. Its effect depended on the dose and time of injection prior to inflammatory reaction. The in vitro experiments proved the interference of fangchinoline action with post-C5 reactions. The substance augmented C5-convertase formation and functional activity. These results are in correspondence with our previous investigations, proving the complement-mediated action of fangchinoline. The antiinflammatory effect could be a consequence of the caused complement exhaustion. PMID:11962544

  1. 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.

  2. A submarine journey: the pyrrole-imidazole alkaloids.

    PubMed

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

    2009-11-27

    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.

  3. 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

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

    PubMed

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

    2015-08-15

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

  5. Synthesis and Antimicrobial Characterization of Half-Calycanthaceous Alkaloid Derivatives.

    PubMed

    Zheng, Shaojun; Zhou, Xinping; Xu, Shixun; Zhu, Rui; Bai, Hongjin; Zhang, Jiwen

    2016-01-01

    A total of 29 novel tetrahydropyrroloindol-based calycanthaceous alkaloid derivatives were synthesized from indole-3-acetonitrile in good yields. The synthesized compounds were evaluated against nine strains of bacteria and a wide range of plant pathogen fungi. Bioassay results revealed that majority of the compounds displayed similar or higher in vitro antimicrobial activities than the positive control. The biological activities also indicated that substituents at R₄ and R₅ significantly affect the activities. Notably, compound c4 was found to be most active among the tested calycanthaceous analogues and might be a novel potential leading compound for further development as an antifungal agent. The results could pave the way for further design and structural modification of calycanthaceous alkaloids as antimicrobial agents. PMID:27618003

  6. 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.

  7. Synthesis and Antimicrobial Characterization of Half-Calycanthaceous Alkaloid Derivatives.

    PubMed

    Zheng, Shaojun; Zhou, Xinping; Xu, Shixun; Zhu, Rui; Bai, Hongjin; Zhang, Jiwen

    2016-09-09

    A total of 29 novel tetrahydropyrroloindol-based calycanthaceous alkaloid derivatives were synthesized from indole-3-acetonitrile in good yields. The synthesized compounds were evaluated against nine strains of bacteria and a wide range of plant pathogen fungi. Bioassay results revealed that majority of the compounds displayed similar or higher in vitro antimicrobial activities than the positive control. The biological activities also indicated that substituents at R₄ and R₅ significantly affect the activities. Notably, compound c4 was found to be most active among the tested calycanthaceous analogues and might be a novel potential leading compound for further development as an antifungal agent. The results could pave the way for further design and structural modification of calycanthaceous alkaloids as antimicrobial agents.

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

    PubMed

    Mizoguchi, Haruki; Oikawa, Hideaki; Oguri, Hiroki

    2014-01-01

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

  9. Alkaloids from the stem bark of Micromelum falcatum.

    PubMed

    Luo, Xiong Ming; Qi, Shu Hua; Yin, Hao; Gao, Cheng Hai; Zhang, Si

    2009-06-01

    Two new quinoldione alkaloids, methyl 2-(3-hydroxy-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl)acetate (1) and 3-hydroxy-1-methyl-3-(2-oxopropyl)quinoline-2,4(1H,3H)-dione (2), and two quinolinone alkaloids previously synthesized but first isolated as natural products, N-methylflindersine (3) and 4-hydroxy-3-methoxy-1-methyl-2(1H)-quinolinone (4), were isolated from the stem bark of Micromelum falcatum, together with the known N-methylswietenidine-B (5). Their structures were established mainly on the basis of 1D- and 2D-NMR techniques. All compounds were evaluated for toxicity towards brine shrimp larvae, and 3 showed strong toxicity with an LD(50) value of 1.39 microg/ml.

  10. Procedure for isolating the endophyte from tall fescue and screening isolates for ergot alkaloids.

    PubMed

    Bacon, C W

    1988-11-01

    A procedure was developed to isolate and determine ergot alkaloid production by Acremonium coenophialum, the endophytic fungus of tall fescue. The procedure established that macerated leaf sheath or pith from inflorescence stem placed either in a liquid medium or on a corn meal-malt extract agar medium produced isolated mycelium and characteristic conidia within a 3- to 3.5-week period. Once isolated, each fungus was placed in another liquid medium, M104T, where competent strains produced total ergot alkaloids ranging from 38 to 797 mg/liter. Several isolates were negative for ergot alkaloid synthesis. The production of ergot alkaloids by individual isolates was unstable; isolates rapidly degenerated in their ability to produce ergot alkaloids during subculture. However, the procedure as presented allows the assessment of an isolate for ergot alkaloid synthesis during its initial isolation.

  11. 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.

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

    PubMed

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

    2014-07-01

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

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

    PubMed Central

    2016-01-01

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

  14. Prenatal exposure to arecoline (areca nut alkaloid) and birth outcomes.

    PubMed

    García-Algar, O; Vall, O; Alameda, F; Puig, C; Pellegrini, M; Pacifici, R; Pichini, S

    2005-05-01

    The betel nut is commonly used as a drug by Asian populations. A high prevalence of adverse pregnancy outcomes has been reported in women who chewed betel quid during gestation. The hypothesis that chronic exposure of the fetus to arecoline (the principal alkaloid of the areca nut) is the cause was investigated in a clinical observational study on six newborns from Asian mothers who chewed betel nut during pregnancy.

  15. Amaryllidaceae Isocarbostyril Alkaloids and Their Derivatives as Promising Antitumor Agents

    PubMed Central

    Ingrassia, Laurent; Lefranc, Florence; Mathieu, Véronique; Darro, Francis; Kiss, Robert

    2008-01-01

    This review covers the isolation, total synthesis, biologic activity, and more particularly the in vitro and in vivo antitumor activities of naturally occurring isocarbostyril alkaloids from the Amaryllidaceae family. Starting from these natural products, new derivatives have been synthesized to explore structure-activity relationships within the chemical class and to obtain potential candidates for preclinical development. This approach appears to be capable of providing novel promising anticancer agents. PMID:18607503

  16. 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.

  17. Enantioselective Nazarov Cyclization Catalyzed by a Cinchona Alkaloid Derivative

    PubMed Central

    Huang, Yu-Wen; Frontier, Alison J.

    2015-01-01

    Nucleophilic catalysts for a 1,6 addition/Nazarov cyclization/elimination sequence were evaluated for their ability to induce enantioselectivity in the electrocyclization step. Of the tertiary amines examined, it was found that a cinchona alkaloid derivative was able to generate substituted 5-hydroxy γ-methylene cyclopentenones with excellent enantioselectivity. The study results suggest that successful cyclization depends upon the ability of the dienyl diketone substrate to readily adopt an s-cis conformation. PMID:26085696

  18. 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

  19. An improved synthesis of 10,11-didehydro Cinchona alkaloids.

    PubMed

    Kacprzak, Karol M; Lindner, Wolfgang; Maier, Norbert M

    2008-03-01

    A revised procedure for the conversion of the four major Cinchona alkaloids (quinine, quinidine, cinchonidine, and cinchonine) into their respective 10,11-didehydro derivatives is described. The reported protocol offers several advantages over a recently published synthetic route. These include (i) enhanced robustness (ii) ready scalability (iii) reduced operational complexity and number of steps (iv) chromatography-free work-up. In addition, toxic solvents were replaced by environmentally less problematic alternatives.

  20. Bioactive carbazole alkaloids from the stems of Clausena lansium.

    PubMed

    Du, Yi-Qian; Liu, Hang; Li, Chuang-Jun; Ma, Jie; Zhang, Dan; Li, Li; Sun, Hua; Bao, Xiu-Qi; Zhang, Dong-Ming

    2015-06-01

    Seven new carbazole alkaloids, claulansines L-R (1-7), and six known analogues (8-13) were isolated from the stems of Clausena lansium. Their structures were elucidated on the basis of spectroscopic analyses, including UV, IR, and NMR experiments (HSQC, HMBC, and NOE experiment). Compound 7 showed moderate anti-inflammatory activities. Compounds 3, 5, 6, 8, and 12 exhibited moderate hepatoprotective activities. PMID:25804252

  1. Lodopyridone, a Structurally Unprecedented Alkaloid from a Marine Actinomycete

    PubMed Central

    Maloney, Katherine N.; MacMillan, John B.; Kauffman, Christopher A.; Jensen, Paul R.; DiPasquale, Antonio G.; Rheingold, Arnold L.; Fenical, William

    2010-01-01

    Chemical examination of the secondary metabolites of a marine Saccharomonospora sp., isolated from marine sediments collected at the mouth of the La Jolla Submarine Canyon, yielded the unprecedented alkaloid lodopyridone (1). The low proton-to-carbon ratio of 1 precluded structure elucidation by NMR spectroscopic methods, thus the structure was defined by X-ray crystallography. Lodopyridone is cytotoxic to HCT-116 human colon cancer cells with IC50 = 3.6 μM. PMID:19883103

  2. Distribution of opiate alkaloids in brain tissue of experimental animals

    PubMed Central

    Pilija, Vladimir; Mimica-Dukic, Neda; Budakov, Branislav; Cvjeticanin, Stanko

    2012-01-01

    The present study examined regional distribution of opiate alkaloids from seized heroin in brain regions of experimental animals in order to select parts with the highest content of opiates. Their analysis should contribute to resolve causes of death due to heroin intake. The tests were performed at different time periods (5, 15, 45 and 120 min) after male and female Wistar rats were treated with seized heroin. Opiate alkaloids (codeine, morphine, acetylcodeine, 6-acetylmorphine and 3,6-diacetylmorphine) were quantitatively determined in brain regions known for their high concentration of µ-opiate receptors: cortex, brainstem, amygdala and basal ganglia, by using gas chromatography–mass spectrometry (GC–MS). The highest content of opiate alkaloids in the brain tissue of female animals was found 15 min and in male animals 45 min after treatment. The highest content of opiates was determined in the basal ganglia of the animals of both genders, indicating that this part of brain tissue presents a reliable sample for identifying and assessing contents of opiates after heroin intake. PMID:23554560

  3. Cactus alkaloids. XXXVI. Mescaline and related compounds from Trichocereus peruvianus.

    PubMed

    Pardanani, J H; McLaughlin, J L; Kondrat, R W; Cooks, R G

    1977-01-01

    Agurell has previously detected (tlc, glc-ms) tyramine, 3-methoxytyramine, and two unknown alkaloids in the Peruvian cactus, Trichocereus peruvianus Br. and R. The presence of mescaline in other similar Trichocereus species prompted us to reinvestigate this species, which is commercially available in the United States. The nonphenolic alkaloid extracts yielded an abundance of crystalline mescaline hydrochloride (0.82% yield) and a trace of 3,4-dimethoxyphenethylamine (tlc-ms). Crystalline tyramine hydrochloride, 3-methoxytyramine hydrochloride, and 3,5 dimethoxy-4-hydroxphenethylamine hydrochloride were isolated from the phenolic alkaloid extracts; the last compound has not been previously crystallized from nature, although it is the immediate biosynthetic precursor of mescaline. Crystalline 2-chloromescaline hydrochloride was isolated drom the nonphenolic extracts; but, as determined by mass-analyzed ion kinetic energy spectrometry, this new compound is an extraction artifact. Both 2-chloromescaline and 2.6-dichloromescaline hydrochlorides were prepared synthetically from mescaline. This cactus species has a mescaline content equal or superior to peyote and should be legally controlled as an item of drug abuse.

  4. Determination of alkaloids in onion nectar by micellar electrokinetic chromatography.

    PubMed

    Carolina Soto, Verónica; Jofré, Viviana Patricia; Galmarini, Claudio Romulo; Silva, María Fernanda

    2016-07-01

    Nectar is the most important floral reward offered by plants to insects. Minor components such as alkaloid compounds in nectar affect bee foraging, with great influence in seed production. CE is an advantageous tool for the analysis of unexplored samples such as onion nectar due to the limited amounts of samples. Considering the importance of these compounds, a simultaneous determination of nicotine, theophylline, theobromine, caffeine, harmaline, piperine in onion nectar by MEKC-UV is herein reported. The extraction of alkaloid compounds in nectar was performed by SPE using a homemade miniaturized column (C18 ). Effects of several important factors affecting extraction efficiency as well as electrophoretic performance were investigated to acquire optimum conditions. Under the proposed conditions, the analytes can be separated within 15 min in a 50 cm effective length capillary (75 μm id) at a separation voltage of 20 kV in 20 mmol/L sodium tretraborate, 100 mmol/L SDS. The amount of sample requirement was reduced up to 2000 times, when compared to traditional methods, reaching limits of detection as low as 0.0153 ng/L. For the first time, this study demonstrates that there are marked qualitative and quantitative differences in nectar alkaloids between open pollinated and male sterile lines (MSLs) and also within MSLs.

  5. Determination of alkaloids in onion nectar by micellar electrokinetic chromatography.

    PubMed

    Carolina Soto, Verónica; Jofré, Viviana Patricia; Galmarini, Claudio Romulo; Silva, María Fernanda

    2016-07-01

    Nectar is the most important floral reward offered by plants to insects. Minor components such as alkaloid compounds in nectar affect bee foraging, with great influence in seed production. CE is an advantageous tool for the analysis of unexplored samples such as onion nectar due to the limited amounts of samples. Considering the importance of these compounds, a simultaneous determination of nicotine, theophylline, theobromine, caffeine, harmaline, piperine in onion nectar by MEKC-UV is herein reported. The extraction of alkaloid compounds in nectar was performed by SPE using a homemade miniaturized column (C18 ). Effects of several important factors affecting extraction efficiency as well as electrophoretic performance were investigated to acquire optimum conditions. Under the proposed conditions, the analytes can be separated within 15 min in a 50 cm effective length capillary (75 μm id) at a separation voltage of 20 kV in 20 mmol/L sodium tretraborate, 100 mmol/L SDS. The amount of sample requirement was reduced up to 2000 times, when compared to traditional methods, reaching limits of detection as low as 0.0153 ng/L. For the first time, this study demonstrates that there are marked qualitative and quantitative differences in nectar alkaloids between open pollinated and male sterile lines (MSLs) and also within MSLs. PMID:27005835

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

    PubMed

    Diamond, Andrew; Desgagné-Penix, Isabel

    2016-06-01

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

  7. 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

  8. Monoterpene indole alkaloids from the twigs of Kopsia arborea.

    PubMed

    Cheenpracha, Sarot; Raksat, Achara; Ritthiwigrom, Thunwadee; Laphookhieo, Surat

    2014-10-01

    The phytochemistry of Kopsia arborea Blume has received considerable attention, which has resulted in the isolation of a number of new unusual indole alkaloids with intriguing structures. In this study, a new eburnane-type alkaloid, phutdonginin (1), together with eight known alkaloids: 19-OH-(-)- eburnamonine (2), melodinine E (3), kopsinine (4), kopsilongine (5), kopsamine (6), (-)-methylenedioxy-1 1,12-kopsinaline (7), decarbomethoxykopsiline (8), and vincadifformine (9), were isolated from the twigs of K. arborea. Their structures were characterized extensively by 1D and 2D NMR spectroscopy and HR-ESI-MS. All compounds were submitted to TLC screening for acetylcholinesterase inhibitory activities. Only kopsamine and decarbomethoxykopsiline showed AChE inhibition with MIR values of 12.5 and 6.25 μg, respectively, compared with galanthamine (positive control, 0.004 μg). In addition, compounds 1 and 2 inhibited moderate antibacterial activity against E. coli TISTR 780 with the MIC value of 32 .g/mL. PMID:25522533

  9. Isoquinoline alkaloids from Tinospora cordifolia inhibit rat lens aldose reductase.

    PubMed

    Patel, Mayurkumar B; Mishra, Shrihari

    2012-09-01

    The inhibitory activity of Tinospora cordifolia stem-derived alkaloids was evaluated against lens aldose reductase (AR) isolated from male Wistar rats. Anticataract potential of the alkaloids of T. cordifolia was evaluated in vitro in rat lenses, considering the activity of normal rat lenses as 100%. The biologically active constituents of T. cordifolia extract were characterized as the isoquinoline alkaloids, jatrorrhizine, palmatine and magnoflorine, by spectral analysis. The inhibitory effects varied with all chemicals and concentrations used. The inhibitory concentration (IC₅₀) values of jatrorrhizine, palmatine and magnoflorine are 3.23, 3.45 and 1.25 µg/mL respectively. The concentration of maximum activity was selected for its effect on galactose-induced polyol accumulation in vitro. The percentage inhibition of galactose-induced polyol accumulation was 62.6, 58.8 and 27.7% in the presence of jatrorrhizine, palmatine and magnoflorine, respectively. Magnoflorine may be useful as lead compounds and new agents for AR inhibition. PMID:22294283

  10. Short-term toxicity studies of loline alkaloids in mice.

    PubMed

    Finch, S C; Munday, J S; Munday, R; Kerby, J W F

    2016-08-01

    Epichloë endophytes have been used successfully in pastoral systems to reduce the impact of insect pests through the expression of secondary metabolites. The use of endophytes could be extended to other plant species, such as cereal crops, where the production of bioactive secondary metabolites would reduce the reliance on pesticides for insect control. The success of this approach is dependent on the selection of an appropriate secondary metabolite target which must not only be effective against insect pests but also be safe for grazing and monogastric animals. The loline alkaloids have been identified as possible target metabolites as they are associated with potent effects on insects and low toxicity to grazing animals. The purpose of the current study was to generate toxicological data on the loline alkaloids in a monogastric system using mice. Male and female mice were fed 415 mg/kg/day total lolines for a 3-week period. The loline treatment caused no statistically significant effect on gross pathology, histology, haematology, blood chemistry, heart rate, blood pressure or motor coordination. Reduced weight gain and food consumption were noted in the loline groups during the initial stages of the experiment. This experiment raises no food safety concerns for the loline alkaloids. PMID:27276360

  11. 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

  12. β-Carboline alkaloids from Galianthe ramosa inhibit malate synthase from Paracoccidioides spp.

    PubMed

    de Freitas, Carla S; Kato, Lucilia; de Oliveira, Cecília M A; Queiroz, Luiz H K; Santana, Mábio J; Schuquel, Ivânia T; Delprete, Piero G; da Silva, Roosevelt A; Quintino, Guilherme O; da Silva Neto, Benedito R; Soares, Célia M A; Pereira, Maristela

    2014-12-01

    As part of our continuing chemical and biological analyses of Rubiaceae species from Cerrado, we isolated novel alkaloids 1 and 2, along with known compounds epicatechin, ursolic acid, and oleanolic acid, from Galianthe ramosa. Alkaloid 2 inhibited malate synthase from the pathogenic fungus Paracoccidioides spp. This enzyme is considered an important molecular target because it is not found in humans. Molecular docking simulations were used to describe the interactions between the alkaloids and malate synthase.

  13. 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.

  14. 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.

  15. 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

  16. Alkaloids from the deep-sea-derived fungus Aspergillus westerdijkiae DFFSCS013.

    PubMed

    Peng, Jiang; Zhang, Xiao-Yong; Tu, Zheng-Chao; Xu, Xin-Ya; Qi, Shu-Hua

    2013-05-24

    Two new benzodiazepine alkaloids, circumdatins K and L (1, 2), two new prenylated indole alkaloids, 5-chlorosclerotiamide (3) and 10-epi-sclerotiamide (4), and one novel amide, aspergilliamide B (5), together with six known alkaloids were isolated from the deep-sea-derived fungus Aspergillus westerdijkiae DFFSCS013. Their structures were elucidated by extensive spectroscopic analysis. All of the compounds were tested for cytotoxicity toward human carcinoma A549, HL-60, K562, and MCF-7 cell lines.

  17. Plug-and-Play Benzylisoquinoline Alkaloid Biosynthetic Gene Discovery in Engineered Yeast.

    PubMed

    Morris, J S; Dastmalchi, M; Li, J; Chang, L; Chen, X; Hagel, J M; Facchini, P J

    2016-01-01

    Benzylisoquinoline alkaloid (BIA) metabolism has been the focus of a considerable research effort over the past half-century, primarily because of the pharmaceutical importance of several compounds produced by opium poppy (Papaver somniferum). Advancements in genomics technologies have substantially accelerated the rate of gene discovery over the past decade, such that most biosynthetic enzymes involved in the formation of the major alkaloids of opium poppy have now been isolated and partially characterized. Not unexpectedly, the availability of all perceived biosynthetic genes has facilitated the reconstitution of several BIA pathways in microbial hosts, including yeast (Saccharomyces cerevisiae). Product yields are currently insufficient to consider the commercial production of high-value BIAs, such as morphine. However, the rudimentary success demonstrated by the uncomplicated and routine assembly of a multitude of characterized BIA biosynthetic genes provides a valuable gene discovery tool for the rapid functional identification of the plethora of gene candidates available through increasingly accessible genomic, transcriptomic, and proteomic databases. BIA biosynthetic gene discovery represents a substantial research opportunity largely owing to the wealth of existing enzyme data mostly obtained from a single plant species. Functionally novel enzymes and variants with potential metabolic engineering applications can be considered the primary targets. Selection of candidates from sequence repositories is facilitated by the monophyletic relationship among biosynthetic genes belonging to a wide range of enzyme families, such as the numerous cytochromes P450 and AdoMet-dependent O- and N-methyltransferases that operate in BIA metabolism. We describe methods for the rapid functional screening of uncharacterized gene candidates encoding potential BIA biosynthetic enzymes using yeast strains engineered to perform selected metabolic conversions. As an initial

  18. [Studies on the effect of an alkaloid extract of Symphytum officinale on human lymphocyte cultures].

    PubMed

    Behninger, C; Abel, G; Röder, E; Neuberger, V; Göggelmann, W

    1989-12-01

    An alkaloid extract of Symphytum officinale was investigated for its chromosome-damaging effect in human lymphocytes in vitro. In concentrations of 1.4 micrograms/ml and 14 micrograms/ml the alkaloids had no effect, in concentrations of 140 micrograms/ml and 1400 micrograms/ml the alkaloids induced sister chromatid exchanges (SCE) as well as chromosome aberrations. Additionally, the influence of rat liver enzymes (S9) was tested. The SCE-inducing capacity and the clastogenic effect of Symphytum alkaloids was increased by simultaneous application of S9-Mix. PMID:2616671

  19. Selective uptake of pyrrolizidine N-oxides by cell suspension cultures from pyrrolizidine alkaloid producing plants.

    PubMed

    von Borstel, K; Hartmann, T

    1986-02-01

    The N-oxides of pyrrolizidine alkaloids such as senecionine or monocrotaline are rapidly taken up and accumulated by cell suspension cultures obtained from plants known to produce pyrrolizidines, i.e. Senecio vernalis, vulgaris, viscosus (Asteraceae) and Symphytum officinale (Boraginaceae). The transport of the N-oxides into the cells is a specific and selective process. Other alkaloid N-oxides such as sparteine N-oxide are not taken up. Cell cultures from plant species which do not synthesize pyrrolizidine alkaloids are unable to accumulate pyrrolizidine N-oxides. The suitability of the pyrrolizidine N-oxides in alkaloid storage and accumulation is emphasized. PMID:24247963

  20. 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

  1. Naturally occurring bioactive Cyclobutane-containing (CBC) alkaloids in fungi, fungal endophytes, and plants.

    PubMed

    Dembitsky, Valery M

    2014-10-15

    This article focuses on the occurrence and biological activities of cyclobutane-containing (CBC) alkaloids obtained from fungi, fungal endophytes, and plants. Naturally occurring CBC alkaloids are of particular interest because many of these compounds display important biological activities and possess antitumour, antibacterial, antimicrobial, antifungal, and immunosuppressive properties. Therefore, these compounds are of great interest in the fields of medicine, pharmacology, medicinal chemistry, and the pharmaceutical industry. Fermentation and production of CBC alkaloids by fungi and/or fungal endophytes is also discussed. This review presents the structures and describes the activities of 98 CBC alkaloids.

  2. 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.

  3. 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.

  4. Structural Diversity and Biological Activities of Indole Diketopiperazine Alkaloids from Fungi.

    PubMed

    Ma, Yang-Min; Liang, Xi-Ai; Kong, Yang; Jia, Bin

    2016-09-01

    Indole diketopiperazine alkaloids are secondary metabolites of microorganisms that are widely distributed in filamentous fungi, especially in the genera Aspergillus and Penicillium of the phylum Ascomycota or sac fungi. These alkaloids represent a group of natural products characterized by diversity in both chemical structures and biological activities. This review aims to summarize 166 indole diketopiperazine alkaloids from fungi published from 1944 to mid-2015. The emphasis is on diverse chemical structures within these alkaloids and their relevant biological activities. The aim is to assess which of these compounds merit further study for purposes of drug development. PMID:27538469

  5. 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.

  6. 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

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

    PubMed

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

    2015-01-01

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

  8. Alkaloid variation in New Zealand kōwhai, Sophora species.

    PubMed

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

    2015-10-01

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

  9. Toxicity study of the main alkaloids of Datura ferox in broilers.

    PubMed

    Kovatsis, A; Flaskos, J; Nikolaidis, E; Kotsaki-Kovatsi, V P; Papaioannou, N; Tsafaris, F

    1993-11-01

    Seeds of the weed Datura ferox are frequent contaminants of raw materials used for animal feed. These seeds produce various toxic effects and contain mainly the alkaloids scopolamine and hyoscyamine. In this 3-month toxicity study, a mixture of scopolamine and hyoscyamine (98:2) was incorporated at four total alkaloid levels (1.5, 15, 75 or 150 mg/kg feed) into a control diet fed to 100 broilers. Alkaloid feeding caused significant reductions in the body weight gain of birds, especially of those fed a dose of 150 mg alkaloid/kg feed. Growth-retarding effects, however, were transient, as no changes in body weight gain were noted after 52 days of alkaloid feeding. Alkaloid-treated broilers showed no significant differences from controls with respect to the cardiac rate and breathing frequency nor in relation to plasma aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase activities. In contrast, plasma leucine aminopeptidase activity was significantly reduced after 3 months in all alkaloid-fed birds. Autopsy and histological examination of tissues by light and electron microscopy revealed no pathological changes associated with alkaloid feeding. Broilers appeared generally healthy and behaved normally throughout. These data should be considered in the formulation of new, improved regulations defining the maximum allowable alkaloid content of D. ferox seeds contaminating raw materials destined for use as broiler feed. PMID:8258413

  10. Chemotypic and genotypic diversity in the ergot alkaloid pathway of Aspergillus fumigatus.

    PubMed

    Robinson, Sarah L; Panaccione, Daniel G

    2012-01-01

    Aspergillus fumigatus is an opportunistic human pathogen that synthesizes a group of mycotoxins via a branch of the ergot alkaloid pathway. This fungus is globally distributed, and genetic data indicate that isolates recombine freely over that range; however, previous work on ergot alkaloids has focused on a limited number of isolates. We hypothesized that A. fumigatus harbors variation in the chemotype of ergot alkaloids and genotype of the ergot alkaloid gene cluster. Analysis of 13 isolates by high performance liquid chromatography revealed four distinct ergot alkaloid profiles or chemotypes. Five isolates completed the A. fumigatus branch of the ergot alkaloid pathway to fumigaclavine C. Six independent isolates accumulated fumigaclavine A, the pathway intermediate immediately before fumigaclavine C. One isolate accumulated only the early pathway intermediates chanoclavine-i and chanocla-vine-i aldehyde, and one isolate lacked ergot alkaloids altogether. A genetic basis for each of the observed chemotypes was obtained either by PCR analysis of the ergot alkaloid gene cluster or through sequencing of easL, the gene encoding the prenyl transferase that reverse prenylates fumigaclavine A to fumigaclavine C. Isolates also exhibited differences in pigmentation and sporulation. The ergot alkaloid chemotypes were widely distributed geographically and among substrate of origin. PMID:22453123

  11. 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.

  12. 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

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

    PubMed

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

    2014-01-01

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

  14. An Ergot Alkaloid Biosynthesis Gene and Clustered Hypothetical Genes from Aspergillus fumigatus†

    PubMed Central

    Coyle, Christine M.; Panaccione, Daniel G.

    2005-01-01

    The ergot alkaloids are a family of indole-derived mycotoxins with a variety of significant biological activities. Aspergillus fumigatus, a common airborne fungus and opportunistic human pathogen, and several fungi in the relatively distant taxon Clavicipitaceae (clavicipitaceous fungi) produce different sets of ergot alkaloids. The ergot alkaloids of these divergent fungi share a four-member ergoline ring but differ in the number, type, and position of the side chains. Several genes required for ergot alkaloid production are known in the clavicipitaceous fungi, and these genes are clustered in the genome of the ergot fungus Claviceps purpurea. We investigated whether the ergot alkaloids of A. fumigatus have a common biosynthetic and genetic origin with those of the clavicipitaceous fungi. A homolog of dmaW, the gene controlling the determinant step in the ergot alkaloid pathway of clavicipitaceous fungi, was identified in the A. fumigatus genome. Knockout of dmaW eliminated all known ergot alkaloids from A. fumigatus, and complementation of the mutation restored ergot alkaloid production. Clustered with dmaW in the A. fumigatus genome are sequences corresponding to five genes previously proposed to encode steps in the ergot alkaloid pathway of C. purpurea, as well as additional sequences whose deduced protein products are consistent with their involvement in the ergot alkaloid pathway. The corresponding genes have similarities in their nucleotide sequences, but the orientations and positions within the cluster of several of these genes differ. The data indicate that the ergot alkaloid biosynthetic capabilities in A. fumigatus and the clavicipitaceous fungi had a common origin. PMID:15933009

  15. Aporphine alkaloid contents increase with moderate nitrogen supply in Annona diversifolia Saff. (Annonaceae) seedlings during diurnal periods.

    PubMed

    Orozco-Castillo, José Agustín; Cruz-Ortega, Rocío; Martinez-Vázquez, Mariano; González-Esquinca, Alma Rosa

    2016-10-01

    Aporphine alkaloids are secondary metabolites that are obtained in low levels from species of the Annonaceae family. Nitrogen addition may increase the alkaloid content in plants. However, previous studies published did not consider that nitrogen could change the alkaloid content throughout the day. We conducted this short-term study to determine the effects of nitrogen applied throughout the diurnal period on the aporphine alkaloids via measurements conducted on the roots, stems and leaves of Annona diversifolia seedlings. The 60-day-old seedlings were cultured with the addition of three levels of nitrogen (0, 30 and 60 mM), and alkaloid extracts were analysed using high-performance liquid chromatography. The highest total alkaloid content was measured in the treatment with moderate nitrogen supply. Further, the levels of aporphine alkaloids changed significantly in the first few hours of the diurnal period. We conclude that aporphine alkaloid content increased with moderate nitrogen supply and exhibited diurnal variation.

  16. 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...

  17. 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 ...

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

    PubMed

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

    1990-01-01

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

  19. Numerical Development

    ERIC Educational Resources Information Center

    Siegler, Robert S.; Braithwaite, David W.

    2016-01-01

    In this review, we attempt to integrate two crucial aspects of numerical development: learning the magnitudes of individual numbers and learning arithmetic. Numerical magnitude development involves gaining increasingly precise knowledge of increasing ranges and types of numbers: from non-symbolic to small symbolic numbers, from smaller to larger…

  20. A divergent approach to benzylisoquinoline-type and oxoaporphine alkaloids via regioselective direct ring metalation of alkoxy isoquinolines.

    PubMed

    Melzer, Benedikt; Bracher, Franz

    2015-07-28

    Methoxy- and benzyloxy-substituted isoquinolines are regioselectively metalated at C-1 with the Knochel-Hauser base, subsequent trapping with aromatic aldehydes gives aryl(isoquinolin-1-yl)carbinols as building blocks for divergent syntheses of different types of benzylisoquinoline alkaloids. Photochemical cyclization of ortho-bromo analogues under reductive conditions gives oxoaporphine alkaloids. Nine benzylisoquinoline alkaloids and two oxoaporphine alkaloids were obtained in two or three steps from appropriate isoquinolines.

  1. Biogenetically-inspired total synthesis of epidithiodiketopiperazines and related alkaloids.

    PubMed

    Kim, Justin; Movassaghi, Mohammad

    2015-04-21

    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 ( Hauser , D. et al. Helv. Chim. Acta 1970 , 53 , 1061 ) and verticillin A ( Katagiri , K. et al. J. Antibiot. 1970 , 23 , 420 ), 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

  2. 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

  3. 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...

  4. 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 ...

  5. 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...

  6. Ability of endophytic filamentous fungi associated with Cinchona ledgeriana to produce Cinchona alkaloids.

    PubMed

    Maehara, Shoji; Simanjuntak, Partomuan; Maetani, Yoshihide; Kitamura, Chinami; Ohashi, Kazuyoshi; Shibuya, Hirotaka

    2013-04-01

    We have investigated the ability of endophytic filamentous fungi associated with Cinchona ledgeriana (Rubiaceae) to produce Cinchona alkaloids on potato dextrose agar medium and in a synthetic liquid medium. It was found that all twenty-one endophytic fungi produce Cinchona alkaloids, despite their genetic differences.

  7. Abundant Respirable Ergot Alkaloids from the Common Airborne Fungus Aspergillus fumigatus†

    PubMed Central

    Panaccione, Daniel G.; Coyle, Christine M.

    2005-01-01

    Ergot alkaloids are mycotoxins that interact with several monoamine receptors, negatively affecting cardiovascular, nervous, reproductive, and immune systems of exposed humans and animals. Aspergillus fumigatus, a common airborne fungus and opportunistic human pathogen, can produce ergot alkaloids in broth culture. The objectives of this study were to determine if A. fumigatus accumulates ergot alkaloids in a respirable form in or on its conidia, to quantify ergot alkaloids associated with conidia produced on several different substrates, and to measure relevant physical properties of the conidia. We found at least four ergot alkaloids, fumigaclavine C, festuclavine, fumigaclavine A, and fumigaclavine B (in order of abundance), associated with conidia of A. fumigatus. Under environmentally relevant conditions, the total mass of ergot alkaloids often constituted >1% of the mass of the conidium. Ergot alkaloids were extracted from conidia produced on all media tested, and the greatest quantities were observed when the fungus was cultured on latex paint or cultured maize seedlings. The values for physical properties of conidia likely to affect their respirability (i.e., diameter, mass, and specific gravity) were significantly lower for A. fumigatus than for Aspergillus nidulans, Aspergillus niger, and Stachybotrys chartarum. The demonstration of relatively high concentrations of ergot alkaloids associated with conidia of A. fumigatus presents opportunities for investigations of potential contributions of the toxins to adverse health effects associated with the fungus and to aspects of the biology of the fungus that contribute to its success. PMID:15933008

  8. Conformational, IR spectroscopic and electronic properties of conium alkaloids and their adducts with C60 fullerene

    NASA Astrophysics Data System (ADS)

    Zabolotnyi, M. A.; Prylutskyy, Yu I.; Poluyan, N. A.; Evstigneev, M. P.; Dovbeshko, G. I.

    2016-08-01

    Conformational, IR spectroscopic and electronic properties of the components of Conium alkaloids (Conium maculatum) in aqueous environment were determined by model calculations and experiment. With the help of FT-IR spectroscopy the possibility of formation of an adduct between γ-coniceine alkaloid and C60 fullerene was demonstrated, which is important for further application of conium analogues in biomedical purposes.

  9. Abundant respirable ergot alkaloids from the common airborne fungus Aspergillus fumigatus.

    PubMed

    Panaccione, Daniel G; Coyle, Christine M

    2005-06-01

    Ergot alkaloids are mycotoxins that interact with several monoamine receptors, negatively affecting cardiovascular, nervous, reproductive, and immune systems of exposed humans and animals. Aspergillus fumigatus, a common airborne fungus and opportunistic human pathogen, can produce ergot alkaloids in broth culture. The objectives of this study were to determine if A. fumigatus accumulates ergot alkaloids in a respirable form in or on its conidia, to quantify ergot alkaloids associated with conidia produced on several different substrates, and to measure relevant physical properties of the conidia. We found at least four ergot alkaloids, fumigaclavine C, festuclavine, fumigaclavine A, and fumigaclavine B (in order of abundance), associated with conidia of A. fumigatus. Under environmentally relevant conditions, the total mass of ergot alkaloids often constituted >1% of the mass of the conidium. Ergot alkaloids were extracted from conidia produced on all media tested, and the greatest quantities were observed when the fungus was cultured on latex paint or cultured maize seedlings. The values for physical properties of conidia likely to affect their respirability (i.e., diameter, mass, and specific gravity) were significantly lower for A. fumigatus than for Aspergillus nidulans, Aspergillus niger, and Stachybotrys chartarum. The demonstration of relatively high concentrations of ergot alkaloids associated with conidia of A. fumigatus presents opportunities for investigations of potential contributions of the toxins to adverse health effects associated with the fungus and to aspects of the biology of the fungus that contribute to its success.

  10. 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...

  11. 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...

  12. 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...

  13. Abundant respirable ergot alkaloids from the common airborne fungus Aspergillus fumigatus.

    PubMed

    Panaccione, Daniel G; Coyle, Christine M

    2005-06-01

    Ergot alkaloids are mycotoxins that interact with several monoamine receptors, negatively affecting cardiovascular, nervous, reproductive, and immune systems of exposed humans and animals. Aspergillus fumigatus, a common airborne fungus and opportunistic human pathogen, can produce ergot alkaloids in broth culture. The objectives of this study were to determine if A. fumigatus accumulates ergot alkaloids in a respirable form in or on its conidia, to quantify ergot alkaloids associated with conidia produced on several different substrates, and to measure relevant physical properties of the conidia. We found at least four ergot alkaloids, fumigaclavine C, festuclavine, fumigaclavine A, and fumigaclavine B (in order of abundance), associated with conidia of A. fumigatus. Under environmentally relevant conditions, the total mass of ergot alkaloids often constituted >1% of the mass of the conidium. Ergot alkaloids were extracted from conidia produced on all media tested, and the greatest quantities were observed when the fungus was cultured on latex paint or cultured maize seedlings. The values for physical properties of conidia likely to affect their respirability (i.e., diameter, mass, and specific gravity) were significantly lower for A. fumigatus than for Aspergillus nidulans, Aspergillus niger, and Stachybotrys chartarum. The demonstration of relatively high concentrations of ergot alkaloids associated with conidia of A. fumigatus presents opportunities for investigations of potential contributions of the toxins to adverse health effects associated with the fungus and to aspects of the biology of the fungus that contribute to its success. PMID:15933008

  14. Isolation of a minor nitro-alkaloid from the aerial parts of Duguetia furfuracea--Annonaceae.

    PubMed

    Carollo, Carlos Alexandre; de Siqueira, Joao Maximo

    2009-01-01

    The refractionation of an alkaloidal extract of the leaves and twigs of Duguetia furfuracea has provided a minor aporphinoid alkaloid, named (+)-8-nitrous-isocorydine or (+)-1,2,3-trymethoxy-11-hydroxy-8-nitrous- aporphine. The structure of the new compound was elucidated by spectroscopic methods, notably 2D NMR and HRESIMS.

  15. 7,7-Dimethylaporphine and Other Alkaloids from the Bark of Guatteria friesiana.

    PubMed

    Costa, Emmanoel V; Pinheiro, Maria Lúcia B; Maia, Beatriz Helena L N S; Marques, Francisco A; Ruiz, Ana Lúcia T G; Marchetti, Gabriela M; Carvalho, João Ernesto de; Soares, Milena B P; Costa, Cinara O S; Galvão, Alexandre F C; Lopes, Norberto P; Koolen, Hector H F; Bezerra, Daniel P; Barison, Andersson

    2016-06-24

    Phytochemical investigation of the bark of Guatteria friesiana afforded 12 new aporphines (1-12), along with nine known alkaloids (13-21). The structures of the new alkaloids were determined on the basis of spectroscopic data interpretation. The cytotoxic activity of the isolated compounds against a small panel of tumor cell lines was assessed using the Alamar blue assay. PMID:27300257

  16. Two new cytotoxic indole alkaloids from a deep-sea sediment derived metagenomic clone.

    PubMed

    Yan, Xia; Tang, Xi-Xiang; Chen, Lin; Yi, Zhi-Wei; Fang, Mei-Juan; Wu, Zhen; Qiu, Ying-Kun

    2014-04-01

    Two new indole alkaloids, metagenetriindole A (1) and metagenebiindole A (2), were identified from deep-sea sediment metagenomic clone derived Escherichia coli fermentation broth. The structures of new compounds were elucidated by spectroscopic methods. The two new indole alkaloids demonstrated moderately cytotoxic activity against CNE2, Bel7402 and HT1080 cancer cell lines in vitro.

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

    PubMed

    Lee, Eun-Jeong; Facchini, Peter J

    2011-11-01

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

  18. 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

  19. 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.

  20. The comparative toxicity of a reduced, crude comfrey (Symphytum officinale) alkaloid extract and the pure, comfrey-derived pyrrolizidine alkaloids, lycopsamine and intermedine in chicks (Gallus gallus domesticus)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Comfrey (Symphytum officinale), a commonly used herb, contains dehydropyrrolizidine alkaloids (DHPAs) that, as a group of bioactive metabolites, are potentially hepatotoxic, pneumotoxic, genotoxic and carcinogenic. Consequently, regulatory agencies and international health organizations have recomm...

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

    PubMed

    Komarova, E L; Shain, S S; Sheĭchenko, V I

    2002-01-01

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

  2. 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

  3. Monoterpenoid glucoindole alkaloids and iridoids from Pterocephalus pinardii.

    PubMed

    Gülcemal, Derya; Masullo, Milena; Alankuş-Calişkan, Ozgen; Karayildirim, Tamer; Senol, Serdar G; Piacente, Sonia; Bedir, Erdal

    2010-03-01

    A new secondary metabolite, pterocephaline, along with the known cantleyoside, 7alpha-morroniside, 3beta,5alpha-tetrahydrodesoxycordifoline lactam, 5S-5-carboxyvincoside, sweroside, and loganin have been isolated from the aerial parts of P. pinardii (Dipsacaceae). Moreover, cantleyoside-methyl-hemiacetal and cantleyoside-dimethyl-acetal were obtained as seco-iridoid artifacts. The structures were elucidated by extensive spectroscopic methods including 1D-((1)H, (13)C and TOCSY) and 2D-NMR (DQF-COSY, HSQC and HMBC). Monoterpenoid glucoindole alkaloids were encountered for the first time in Dipsacaceae family.

  4. 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.

  5. Dimacrolide Sesquiterpene Pyridine Alkaloids from the Stems of Tripterygium regelii.

    PubMed

    Fan, Dongsheng; Zhu, Guo-Yuan; Li, Ting; Jiang, Zhi-Hong; Bai, Li-Ping

    2016-01-01

    Two new dimacrolide sesquiterpene pyridine alkaloids (DMSPAs), dimacroregelines A (1) and B (2), were isolated from the stems of Tripterygium regelii. The structures of both compounds were characterized by extensive 1D and 2D NMR spectroscopic analyses, as well as HRESIMS data. Compounds 1 and 2 are two rare DMSPAs possessing unique 2-(3'-carboxybutyl)-3-furanoic acid units forming the second macrocyclic ring, representing the first example of DMSPAs bearing an extra furan ring in their second macrocyclic ring system. Compound 2 showed inhibitory effects on the proliferation of human rheumatoid arthritis synovial fibroblast cell (MH7A) at a concentration of 20 μM. PMID:27589701

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

    PubMed

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

    2015-11-25

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

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

    PubMed

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

    2014-04-01

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

  8. Microdetermination of cinchona alkaloids by atomic absorption spectroscopy

    NASA Astrophysics Data System (ADS)

    Ayad, Magda M.; Khayyal, S. E.; Farrag, N. M.

    A sensitive and rapid microdetermination method has been developed for the determination of cinchona alkaloids via their mercury complex. Different parameters of the procedure have been thoroughly studied. The percentage recoveries for quinine, quinidine, cinchonine and cinchonidine were found to be 98.97 ±0.62, 99.06 ± 0.62, 98.90 ± 0.74, respectively. The results obtained are favourably compared to the official ones. The method is characterised by its specificity, accuracy and good precision.

  9. Hybrid Pyrrole-Imidazole Alkaloids from the Sponge Agelas sceptrum.

    PubMed

    Muñoz, Julie; Köck, Matthias

    2016-02-26

    A chemical investigation of the tropical sponge Agelas sceptrum from Plana Cays (Bahamas) led to the isolation of two hybrid pyrrole-imidazole alkaloids (PIAs), 15'-oxoadenosceptrin (1) and decarboxyagelamadin C (2). Herein, we report their challenging structure elucidation established by NMR and ECD spectroscopy. 15'-Oxoadenosceptrin (1) shows sceptrin merged with an adenine moiety, not yet encountered in the PIA family, whereas decarboxyagelamadin C (2) is a close derivative of agelamadins C to E recently isolated from an Agelas sp. from Okinawa. PMID:26872204

  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.

  11. A new prenylated indole diketopiperazine alkaloid from Eurotium cristatum.

    PubMed

    Zou, Xianwei; Li, Ying; Zhang, Xiaona; Li, Qian; Liu, Xuan; Huang, Yun; Tang, Tao; Zheng, Saijing; Wang, Weimiao; Tang, Jintian

    2014-11-03

    A new prenylated indole diketopiperazine alkaloid, cristatumin F (1), and four known metabolites, echinulin (2), dehydroechinulin (3), neoechinulin A (4) and variecolorin O (5), were isolated from the crude extract of the fungus Eurotium cristatum. The structure of 1 was elucidated primarily by NMR and MS methods. The absolute configuration of 1 was assigned using Marfey's method applied to its acid hydrolyzate. Cristatumin F (1) showed modest radical scavenging activity against DPPH radicals, and exhibited marginal attenuation of 3T3L1 pre-adipocytes.

  12. (+)-Angchibangkine, a new type of bisbenzylisoquinoline alkaloid, and other dimers from Pachygone dasycarpa.

    PubMed

    Guinaudeau, H; Böhlke, M; Lin, L Z; Angerhofer, C K; Cordell, G A; RuangrungsiN

    1997-03-01

    Analysis of the alkaloidal fraction of the stem bark extract of Pachygone dasycarpa (Menispermaceae) resulted in the isolation of 10 known bisbenzylisoquinolines, (+)-tetrandrine, (+)-penduline, (+)-fangchinoline, (+)-atherospermoline, (+)-N-methyl-7-O-demethylpeinamine, (+)-daphnoline, (4-)-isotrilobine (1), (+)-cocsuline (2), (+)-tricordatine (3), (+)-2'-norcocsuline, and the new alkaloid (+)-12-O-methyltricordatine (4). The last bisbenzylisoquinoline alkaloid isolated, (+)-angchibangkine (5), is the first member of this alkaloid class found to possess three diphenyl ether bridges in the 7-6',8-7', and 11-12' positions. Structure elucidation of these alkaloids and of (+)-O-methylangchibangkine (6) was achieved by analysis of spectral data. Compounds 4-6 show antiplasmodial activity against Plasmodium falciparum. PMID:9157192

  13. In vitro antiplasmodial, antiamoebic, and cytotoxic activities of a series of bisbenzylisoquinoline alkaloids.

    PubMed Central

    Marshall, S J; Russell, P F; Wright, C W; Anderson, M M; Phillipson, J D; Kirby, G C; Warhurst, D C; Schiff, P L

    1994-01-01

    Twenty-four bisbenzylisoquinoline alkaloids were screened for antiplasmoidal, antiamoebic, and cytotoxic activities by use of in vitro microtests. Eight of the alkaloids had antiplasmodial activity, with a 50% inhibitory concentration (IC50) of less than 1 microM against a multidrug-resistant strain of Plasmodium falciparum (chloroquine had an IC50 of 0.2 microM). The three alkaloids most active against Entamoeba histolytica, aromoline, isotrilobine, and insularine, had IC50s of 5 to 11.1 microM (metronidazole had an IC50 of 1.87 microM). None of the 24 bisbenzylisoquinoline alkaloids exhibited significant cytotoxicity against the KB cell line, the most toxic being berbamine, with an IC50 of 17.8 microM (the IC50 of podophyllotoxin was 0.008 microM). Bisbenzylisoquinoline alkaloids merit further investigation as potential novel antimalarial agents. PMID:8141587

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

    PubMed

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

    2013-05-01

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

  15. Elevational variation of quinolizidine alkaloid contents in a lupine (Lupinus argenteus) of the Rocky Mountains.

    PubMed

    Carey, D B; Wink, M

    1994-04-01

    Quinolizidine alkaloid contents of leaves and seeds ofLupinus argenteus (Fabaceae) collected from seven different localities near Gothic, Colorado were determined by capillary GLC. Differences in alkaloid levels between sites are substantial and alkaloid quantity decreases as elevation increases. Leaves at the lowest elevation, for example, contain six times the alkaloid levels of leaves at the highest elevation. Seeds from plants of low-and high-elevation sites were grown under identical conditions in the green-house. Alkaloid levels of leaves of seedlings were significantly higher in those seedlings derived from populations of low elevations than those of high elevations, indicating that the observed differences in the field are at least partly genetic and not environmental. To determine whether predation rates were responsible for these genetic differences, data on seed predation rates and observations on herbivory were collected. PMID:24242200

  16. Bioactive heterocyclic alkaloids with diterpene structure isolated from traditional Chinese medicines.

    PubMed

    Xu, Tengfei; Liu, Shu; Meng, Lulu; Pi, Zifeng; Song, Fengrui; Liu, Zhiqiang

    2016-07-15

    The diterpenoid alkaloids as one type of heterocyclic alkaloids have been found in many traditional herbal medicines, such as genus Consolida, Aconitum, and Delphinium (Ranunculaceae). Pharmacological researches have indicated that many diterpenoid alkaloids are the main bioactive components which have analgesic, anti-inflammatory, anti-microbial, anti-tumor, cardiotonic, and anti-arrhythmic activities. Studies focused on the determination, quantitation and pharmacological properties of these alkaloids have dramatically increased during the past few years. Up to now, newly discovered diterpenoid alkaloids with important biological activities have been isolated and synthesized. Considering their significant role and diffusely used in many disease treatments, we summarized the information of their analysis methods, bioactivity, metabolism and biotransformation in vivo as well as the pharmacological mechanisms. Based on above review, the further researches are suggested.

  17. 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

  18. 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

  19. 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.

  20. 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.

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

    PubMed Central

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

    2016-01-01

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

  2. Excretion of alkaloids by malpighian tubules of insects.

    PubMed

    Maddrell, S H; Gardiner, B O

    1976-04-01

    Nicotine is transported at high rates by Malpighian tubules of larvae of Manduca sexta, Pieris brassicae and Rhodnius prolixus and the transport persists in the absence of alkaloid from the diet. In the fluid-secreting portion of Rhodnius tubules this transport is not coupled to ion transport, nor is it dependent on the physiological state of the animal. The transport, which can occur against a steep electrochemical gradient, shows saturation kinetics with a maximal rate of 700 pmol. min-1 per tubule and is half saturated at 2-3 mM. Nicotine transport independent of ion movements also occurs in the lower resorptive parts of Rhodnius tubules. Both portions of Rhodnius tubules can transport morphine and atropine. These alkaloids and nicotine compete with one naother and are presumed to be carried by the smae transport system. Nicotine transport in Rhodnius was unaffected by organic anions, such as amaranth and benzyl penicillin, or by the organic anion transport inhibitor, probenecid. Fluid secretion in 5-HT-stimulated tubules was reduced by atropine and nicotine, probably by blocking the 5-HT receptors. The Malpighian tubules of adult Calliphora erythrocephala and Musca domestica remove nicotine from bathing solutions, an unknown metabolic accumulating in the tubules. Adult P. brassicae and M. sexta do not exhibit transport of nicotine by their Malpighian tubules.

  3. Bioactive pyridoacridine alkaloids from the micronesian sponge Oceanapia sp.

    PubMed

    Eder, C; Schupp, P; Proksch, P; Wray, V; Steube, K; Müller, C E; Frobenius, W; Herderich, M; van Soest, R W

    1998-02-01

    The Micronesian sponge Oceanapia sp. afforded three pyridoacridine alkaloids: the known compounds kuanoniamine C (1) and kuanoniamine D (2), as well as the new N-deacyl derivative (3) of the kuanoniamines. Compounds 1 and 2 exhibited insecticidal activity toward neonate larvae of the polyphagous pest insect Spodoptera littoralis (LC50 of 156 and 59 ppm, respectively), when incorporated into artificial diet. Both compounds also showed toxicity in the brine shrimp lethality test with a LC50 of 37 micrograms/mL (compound 1) and 19 micrograms/mL (compound 2), respectively. The N-deacyl derivative did not show any remarkable effect in both bioassays. Cytotoxcity of the alkaloids was studied in vitro, using two human cell lines. The new derivative (3) appeared to be active in the same range of concentrations as kuanoniamine C (1) and D (2). The IC50 of 3 was 1.2 micrograms/mL toward HeLa cells and 2.0 micrograms/mL toward MONO-MAC 6 cells. In receptor binding assays compound 2 showed affinity to A1- and A2A-adenosine receptors with Ki values of 2.94 and 13.7 microM, respectively. Compound 1 was less active than compound 2, whereas compound 3 showed no affinity toward adenosine receptors. In addition, compounds 1-3 exhibited moderate affinity to benzodiazepine binding sites of GABAA receptors. PMID:9514015

  4. New cycloartane saponin and monoterpenoid glucoindole alkaloids from Mussaenda luteola.

    PubMed

    Mohamed, Shaymaa M; Backheet, Enaam Y; Bayoumi, Soad A; Ross, Samir A

    2016-04-01

    A new cycloartane-type saponin with unusual hydroxylation at C-17 and a unique side chain, 9 (R), 19, 22 (S), 24 (R) bicyclolanost-3β, 12α, 16β, 17α tetrol-25-one 3-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranoside (1) and two new monoterpenoid glucoindole alkaloids, 10-methoxy pumiloside (2) and the previously chemically synthesized, 10-methoxy strictosidine (3) along with other five known compounds, 7α-morroniside (4), 7-epi-loganin (5), (7β)-7-O-methylmorroniside (6), 5(S)-5-carboxystrictisidine (7) and apigenin-7-O-neohesperidoside (8) were isolated from the aerial parts of Mussaenda luteola (Rubiaceae). The structural elucidation of the isolates was accomplished by extensive (1D and 2D NMR) spectroscopic data analysis and HR-ESI-MS. Compounds 4-8 were reported for the first time from the genus Mussaenda. Interestingly, this is the first report for the occurrence of the monoterpenoid glucoindole-type alkaloids in the genus which might be useful for the chemotaxonomic evaluation of the genus Mussaenda. All isolates were evaluated for their antiprotozoal activities. Compound 7 showed good antitrypanosomal activity with IC50 and IC90 values of 13.7 and 16.6 μM compared to IC50 and IC90 values of 13.06 and 28.99 μM for the positive control DFMO, difluoromethylornithine.

  5. 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

  6. New cycloartane saponin and monoterpenoid glucoindole alkaloids from Mussaenda luteola.

    PubMed

    Mohamed, Shaymaa M; Backheet, Enaam Y; Bayoumi, Soad A; Ross, Samir A

    2016-04-01

    A new cycloartane-type saponin with unusual hydroxylation at C-17 and a unique side chain, 9 (R), 19, 22 (S), 24 (R) bicyclolanost-3β, 12α, 16β, 17α tetrol-25-one 3-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranoside (1) and two new monoterpenoid glucoindole alkaloids, 10-methoxy pumiloside (2) and the previously chemically synthesized, 10-methoxy strictosidine (3) along with other five known compounds, 7α-morroniside (4), 7-epi-loganin (5), (7β)-7-O-methylmorroniside (6), 5(S)-5-carboxystrictisidine (7) and apigenin-7-O-neohesperidoside (8) were isolated from the aerial parts of Mussaenda luteola (Rubiaceae). The structural elucidation of the isolates was accomplished by extensive (1D and 2D NMR) spectroscopic data analysis and HR-ESI-MS. Compounds 4-8 were reported for the first time from the genus Mussaenda. Interestingly, this is the first report for the occurrence of the monoterpenoid glucoindole-type alkaloids in the genus which might be useful for the chemotaxonomic evaluation of the genus Mussaenda. All isolates were evaluated for their antiprotozoal activities. Compound 7 showed good antitrypanosomal activity with IC50 and IC90 values of 13.7 and 16.6 μM compared to IC50 and IC90 values of 13.06 and 28.99 μM for the positive control DFMO, difluoromethylornithine. PMID:26969788

  7. New cycloartane saponin and monoterpenoid glucoindole alkaloids from Mussaenda luteola

    PubMed Central

    Mohamed, Shaymaa M.; Backheet, Enaam Y.; Bayoumi, Soad A.; Ross, Samir A.

    2016-01-01

    A new cycloartane-type saponin with unusual hydroxylation at C-17 and a unique side chain, 9 (R), 19, 22 (S), 24 (R) bicyclolanost-3β, 12α, 16β, 17α tetrol-25-one 3-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranoside (1) and two new monoterpenoid glucoindole alkaloids, 10-methoxy pumiloside (2) and the previously chemically synthesized, 10-methoxy strictosidine (3) along with other five known compounds, 7α-morroniside (4), 7-epi-loganin (5), (7β)-7-O-methylmorroniside (6), 5(S)-5-carboxystrictisidine (7) and apigenin-7-O-neohesperidoside (8) were isolated from the aerial parts of Mussaenda luteola (Rubiaceae). The structural elucidation of the isolates was accomplished by extensive (1D and 2D NMR) spectroscopic data analysis and HR-ESI-MS. Compounds 4–8 were reported for the first time from the genus Mussaenda. Interestingly, this is the first report for the occurrence of the monoterpenoid glucoindole-type alkaloids in the genus which might be useful for the chemotaxonomic evaluation of the genus Mussaenda. All isolates were evaluated for their antiprotozoal activities. Compound 7 showed good antitrypanosomal activity with IC50 and IC90 values of 13.7 and 16.6 µM compared to IC50 and IC90 values of 13.06 and 28.99 µM for the positive control DFMO, difluoromethylornithine. PMID:26969788

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

    PubMed

    Yoshimatsu, K; Shimomura, K

    2001-01-01

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

  9. 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.

  10. Antiparasitic hybrids of Cinchona alkaloids and bile acids.

    PubMed

    Leverrier, Aurélie; Bero, Joanne; Frédérich, Michel; Quetin-Leclercq, Joëlle; Palermo, Jorge

    2013-08-01

    A series of 16 hybrids of Cinchona alkaloids and bile acids (4a-h, 5a-h) was prepared by means of a Barton-Zard decarboxylation reaction. Quinine, quinidine, cinchonine and cinchonidine were functionalized at position C-2 of the quinoline nucleus by radical attack of a norcholane substituent. The newly synthesized hybrids were evaluated in vitro for their antitrypanosomal, antileishmanial and antiplasmodial activities, along with their cytotoxicity against WI38, a normal human fibroblast cell line. Seven compounds (4d, 4f, 4h, 5b, 5d, 5f, 5h) showed promising trypanocidal activity with IC₅₀ values in the same range as the commercial drug suramine. Moreover all the 16 hybrids showed antiplasmodial activity (IC₅₀ ≤ 6 μg/ml), particularly those containing a nor-chenodeoxycholane moiety (4b, 4d, 4f, 4h, 5b, 5d, 5f, 5h) with IC₅₀ values comparable to those of the natural alkaloids, and selectivity indices in the range of 5.6-15.7.

  11. Cytotoxic Alkaloids from the Stem of Xylopia laevigata.

    PubMed

    Menezes, Leociley R A; Costa, Cinara O D Sousa; Rodrigues, Ana Carolina B da C; Santo, Felipe R do E; Nepel, Angelita; Dutra, Lívia M; Silva, Felipe M A; Soares, Milena B P; Barison, Andersson; Costa, Emmanoel V; Bezerra, Daniel P

    2016-01-01

    Xylopia laevigata (Annonaceae), known locally as "meiú" or "pindaíba", is widely used in folk medicine in Northeastern Brazil. In the present work, we performed phytochemical analyses of the stem of X. laevigata, which led to the isolation of 19 alkaloids: (-)-roemerine, (+)-anonaine, lanuginosine, (+)-glaucine, (+)-xylopine, oxoglaucine, (+)-norglaucine, asimilobine, (-)-xylopinine, (+)-norpurpureine, (+)-N-methyllaurotetanine, (+)-norpredicentrine, (+)-discretine, (+)-calycinine, (+)-laurotetanine, (+)-reticuline, (-)-corytenchine, (+)-discretamine and (+)-flavinantine. The in vitro cytotoxic activity toward the tumor cell lines B16-F10 (mouse melanoma), HepG2 (human hepatocellular carcinoma), K562 (human chronic myelocytic leukemia) and HL-60 (human promyelocytic leukemia) and non-tumor peripheral blood mononuclear cells (PBMCs) was tested using the Alamar Blue assay. Lanuginosine, (+)-xylopine and (+)-norglaucine had the highest cytotoxic activity. Additionally, the pro-apoptotic effects of lanuginosine and (+)-xylopine were investigated in HepG2 cells using light and fluorescence microscopies and flow cytometry-based assays. Cell morphology consistent with apoptosis and a marked phosphatidylserine externalization were observed in lanuginosine- and (+)-xylopine-treated cells, suggesting induction of apoptotic cell death. In addition, (+)-xylopine treatment caused G₂/M cell cycle arrest in HepG2 cells. These data suggest that X. laevigata is a potential source for cytotoxic alkaloids. PMID:27399666

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

    PubMed

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

    2015-01-01

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

  13. Pro-toxic dehydropyrrolizidine alkaloids in the traditional Andean herbal medicine “asmachilca”

    PubMed Central

    Colegate, Steven M.; Boppré, Michael; Monzón, Julio; Betz, Joseph M.

    2015-01-01

    Ethnopharmacological relevance Asmachilca is a Peruvian medicinal herb preparation ostensibly derived from Eupatorium gayanum Wedd. = Aristeguietia gayana (Wedd.) R.M. King & H. Rob. (Asteraceae: Eupatorieae). Decoctions of the plant have a reported bronchodilation effect that is purported to be useful in the treatment of respiratory allergies, common cold and bronchial asthma. However, its attractiveness to pyrrolizidine alkaloid-pharmacophagous insects indicated a potential for toxicity for human consumers. Aim of the study To determine if commercial asmachilca samples, including fully processed herbal teas, contain potentially toxic 1,2-dehydropyrrolizidine alkaloids. Materials and methods Two brands of “Asmachilca” herbal tea bags and four other commercial samples of botanical materials for preparing asmachilca medicine were extracted and analyzed using HPLC-esi(+)MS and MS/MS for the characteristic retention times and mass spectra of known dehydropyrrolizidine alkaloids. Other suspected dehydropyrrolizidine alkaloids were tentatively identified based on MS/MS profiles and high resolution molecular weight determinations. Further structure elucidation of isolated alkaloids was based on 1D and 2D NMR spectroscopy. Results Asmachilca attracted many species of moths which are known to pharmacophagously gather dehydropyrrolizidine alkaloids. Analysis of 5 of the asmachilca samples revealed the major presence of the dehydropyrrolizidine alkaloid monoesters rinderine and supinine, and their N-oxides. The 6th sample was very similar but did not contain supinine or its N-oxide. Small quantities of other dehydropyrrolizidine alkaloid monoesters, including echinatine and intermedine, were also detected. In addition, two major metabolites, previously undescribed, were isolated and identified as dehydropyrrolizidine alkaloid monoesters with two “head-to-tail” linked viridifloric and/or trachelanthic acids. Estimates of total pyrrolizidine alkaloid and N

  14. Numerical nebulae

    NASA Astrophysics Data System (ADS)

    Rijkhorst, Erik-Jan

    2005-12-01

    The late stages of evolution of stars like our Sun are dominated by several episodes of violent mass loss. Space based observations of the resulting objects, known as Planetary Nebulae, show a bewildering array of highly symmetric shapes. The interplay between gasdynamics and radiative processes determines the morphological outcome of these objects, and numerical models for astrophysical gasdynamics have to incorporate these effects. This thesis presents new numerical techniques for carrying out high-resolution three-dimensional radiation hydrodynamical simulations. Such calculations require parallelization of computer codes, and the use of state-of-the-art supercomputer technology. Numerical models in the context of the shaping of Planetary Nebulae are presented, providing insight into their origin and fate.

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

    PubMed

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

    2015-09-01

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

  16. An atypical pattern of accumulation of scopolamine and other tropane alkaloids and expression of alkaloid pathway genes in Hyoscyamus senecionis.

    PubMed

    Dehghan, Esmail; Shahriari Ahmadi, Farajollah; Ghotbi Ravandi, Elnaz; Reed, Darwin W; Covello, Patrick S; Bahrami, Ahmad Reza

    2013-09-01

    A cDNA encoding hyoscyamine 6β-hydroxylase (H6H, EC 1.14.11.11), a bifunctional enzyme catalyzing the last two steps in the scopolamine biosynthetic pathway, was isolated from Hyoscyamus senecionis, a medicinal plant endemic to the Iranian plateau. Expression analysis indicates that Hsh6h is expressed in all tested organs of H. senecionis including roots, rhizomes, leaves, stems and flowers unlike the other tropane alkaloid producing species. In parallel to this, in leaves, levels of scopolamine, the product of H6H, were higher than the substrate hyoscyamine. These data suggest that not only does the conversion of hyoscyamine to scopolamine take place in the root, followed by translocation to aerial parts, but also accumulated hyoscyamine in the aerial parts may be converted to scopolamine by activity of HsH6H. Analysis of expression profiles of putrescine N-methyltransferase and tropinone reductase I and II genes also indicates the organ-independent expression of these genes. Here we also introduce H. senecionis as an important tropane alkaloid producing species with its thick underground parts as a source of hyoscyamine, while its leaves can be considered as a source of scopolamine.

  17. 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.

  18. [Study on change rule of 6 ester-type alkaloids in process of Heishunpian].

    PubMed

    Wang, Yun-wei; Zhong, Lian; Li, Xin-yi; Xu, Min; Yang, Shi-long; Li, Lang; Wu, Chun-jie; Huang, Qin-wan

    2015-04-01

    To study the variation of six ester-type alkaloids and characteristic fingerprints in the process from Radix Aconite Lateralis to Heishunpian and lay a foundation for the study of the processing principle of Heishunpian, HPLC. analysis was performed on a Phenomenex Gemini C18 (4.6 mm x 250 mm, 5 microm) with acetonitrile and 40 mmol x L(-1) ammonium acetate (adjusted to pH 10 with concentrated ammonia water) as mobile phase. The detection wavelength was set at 235 nm. The flow rate was set at 0.8 mL x min(-1) and the injection volume was 10-20 microL. Six ester-type alkaloids were determined and characteristic fingerprints of the process were established. As the process continues, the contents of diester diterpene alkaloids were decreased step by step, while the contents varia tion of monoester diterpene alkaloids were not obvious. Each sample showed significant difference in characteristic fingerprints. With the exception of 6 known monoester diterpene alkaloids and diester diterpene alkaloids, 13 peaks were marked in the characteristic fingerprints, of which the total change rule of the other 7 unknown peaks were similar with 3 diester diterpene alkaloids. The established method is accurate, reliable and repeatable, and can provide reference for revealing change rule of index components and illuminating processing principle in the process of Heishunpian.

  19. Induction of tropane alkaloid formation in transformed root cultures of Brugmansia suaveolens (Solanaceae).

    PubMed

    Zayed, Rawia; Wink, Michael

    2004-01-01

    Hairy root cultures of Brugmansia suaveolens were set up by infection of root tips with Agrobacterium rhizogenes. The successful transformation was confirmed by analysing rolC and virC genes using polymerase chain reaction (PCR). Hairy root cultures were employed to study the formation of tropane alkaloids, such as hyoscyamine. The transformed cultures were incubated with potential elicitors, such as methyljasmonate, quercetin and salicylic acid in order to stimulate the biosynthesis of tropane alkaloids. Profile and amounts of tropane alkaloids were analysed using capillary GLC-MS. At least 18 different tropane alkaloids could be identified. Treatment of the cultures with 200 microM methyljasmonate increased the alkaloid accumulation 25-fold up to a level of 1 mg/g fresh weight as compared to untreated controls. Quercetin enhanced the alkaloid production 10 fold (0.4 mg/g fresh weight) within 24 h. In contrast 100 microM salicylic acid decreased alkaloids to a level of 1 microg/g fresh weight. PMID:15666547

  20. Alkaloid biosynthesis in Papaver sp. cells in culture and during organogenesis.

    PubMed

    Alkhimova, O G; Kyrylenko, T K; Vagyn, Y V; Heslop-Harrison, J S

    2001-01-01

    In vitro cell cultures of two Papaver species, P. somniferum and P. bracteatum initiated from mature seeds were screened for their ability to produce alkaloids. Protocols for callus induction, somatic embryogenesis and organogenesis were established. The alkaloid contents were analysed by high-performance-liquid chromatography, thin-layer chromatography and spectrophotometric assays. Undifferentiated callus produced small amounts of sanguinarine, which increased with the degree of tissue differentiation. Embryogenic calli were maintained in culture for more than 2 years, retaining a high regeneration capability. Thin-layer chromatography analysis revealed variations in alkaloid spectrum between parallel cell lines. The morphinan alkaloid, thebaine, was found to be accumulated exclusively in morphogenous strains of P. bracteatum, and morphine was the major alkaloid in the spectrum of P. somniferum dedifferentiated callus. Regenerant plants synthesized thebaine and sanguinarine at the same level as juvenile plants grown from P. bracteatum seeds. We revealed differences in the ability to produce different types of alkaloids: seed-derived plants were able to accumulate thebaine while undifferentiated primary cell cultures produced only sanguinarine. The production of either sanguinarine and morphinan alkaloids are found in regenerants showing that both metabolic pathways were active in young plantlets.

  1. 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.

  2. 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.

  3. Effect of polyamine biosynthetic inhibitors on alkaloids and organogenesis in tobacco callus cultures.

    PubMed

    Tiburcio, A F; Kaur-Sawhney, R; Galston, A W

    1987-01-01

    We studied the effects of inhibitors of ornithine decarboxylase (ODC), arginine decarboxylase (ADC) and spermidine synthase (Spd synthase) on organogenesis and the titers of polyamines (PA) and alkaloids in tobacco calli. DL-alpha-diffluromethylarginine (DFMA) and D-arginine (D-Arg), both inhibitors of ADC activity, were more effective than DL-alpha-difluromethylorinithine (DFMO), an inhibitor of ODC, in reducing titers of PA and the putrescine (Put)-derived alkaloids (nornicotine and nicotine). Dicyclohexylammonium sulfate (DCHA), an inhibitor of Spd synthase, was also more efficient than DFMO in reducing PA and alkaloid levels. Root organogenesis is inversely related to the titers of Put and alkaloids. Thus, DFMA and D-Arg, which strongly inhibit Put and alkaloid biosynthesis, markedly promote root organogenesis, while control callus with high Put and alkaloid content showed poor root organization. These results suggest that morphological differentiation is not required for activation of secondary metabolic pathways and support the view that ADC has a major role in the generation of Put going to the pyrrolidine ring of tobacco alkaloids.

  4. 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

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

    PubMed Central

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

    2004-01-01

    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

  6. 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

  7. Pyrrolizidine Alkaloids: Potential Role in the Etiology of Cancers, Pulmonary Hypertension, Congenital Anomalies, and Liver Disease.

    PubMed

    Edgar, John A; Molyneux, Russell J; Colegate, Steven M

    2015-01-20

    Large outbreaks of acute food-related poisoning, characterized by hepatic sinusoidal obstruction syndrome, hemorrhagic necrosis, and rapid liver failure, occur on a regular basis in some countries. They are caused by 1,2-dehydropyrrolizidine alkaloids contaminating locally grown grain. Similar acute poisoning can also result from deliberate or accidental consumption of 1,2-dehydropyrrolizidine alkaloid-containing herbal medicines, teas, and spices. In recent years, it has been confirmed that there is also significant, low-level dietary exposure to 1,2-dehydropyrrolizidine alkaloids in many countries due to consumption of common foods such as honey, milk, eggs, salads, and meat. The level of 1,2-dehydropyrrolizidine alkaloids in these foods is generally too low and too intermittent to cause acute toxicity. However, these alkaloids are genotoxic and can cause slowly developing chronic diseases such as pulmonary arterial hypertension, cancers, cirrhosis, and congenital anomalies, conditions unlikely to be easily linked with dietary exposure to 1,2-dehydropyrrolizidine alkaloids, especially if clinicians are unaware that such dietary exposure is occurring. This Perspective provides a comprehensive review of the acute and chronic toxicity of 1,2-dehydropyrrolizidine alkaloids and their potential to initiate certain chronic diseases, and suggests some associative considerations or indicators to assist in recognizing specific cases of diseases that may have resulted from dietary exposure to these hazardous natural substances. If it can be established that low-level dietary exposure to 1,2-dehydropyrrolizidine alkaloids is a significant cause of some of these costly and debilitating diseases, then this should lead to initiatives to reduce the level of these alkaloids in the food chain.

  8. 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.

  9. [Effects of alkaloids from Coptidis Rhizoma on mouse peritoneal macrophages in vitro].

    PubMed

    Zhou, Xia; Peng, Yao-zong; Huang, Tao; Li, Ling; Mou, Shao-xia; Kou, Shu-ming; Li, Xue-gang

    2015-12-01

    This work was mainly studied the effects of the four alkaloids from Coptidis Rhizoma on the mouse peritoneal macrophages in vitro and preliminarily discussed the regulating mechanisms. The effect of alkaloids from Coptidis Rhizoma on the vitality of macrophages was measured by the MTT assay. The effect of alkaloids on the phagocytosis of macrophages was determined by neutral red trial and respiratory burst activity was tested by NBT. The expressions of respiratory-burst-associated genes influenced by alkaloids were detected by qRT-PCR. The conformation change of membrane protein in macrophages by the impact of alkaloids was studied by fluorospectro-photometer. Results showed that the four alkaloids from Coptidis Rhizoma could increase the phagocytosis of macrophages in different level and berberine had the best effect. Berberine, coptisine and palmatine had up-regulation effects on respiratory burst activity of mouse peritoneal macrophages stimulated by PMA and regulatory activity on the mRNA expression of PKC, p40phox or p47phox, whereas the epiberberine had no significant influence on respiratory burst. Moreover, alkaloids from Coptidis Rhizoma could change the conformation of membrane protein and the berberine showed the strongest activity. The results suggested that the four alkaloids from Coptidis Rhizoma might activate macrophages through changing the conformation of membrane protein of macrophages and then enhanced the phagocytosis and respiratory burst activity of macrophages. Furthermore, the regulatory mechanism of alkaloids on the respiratory burst activity of macrophages may be also related to the expression level of PKC, p40phox and p47phox.

  10. [Effects of alkaloids from Coptidis Rhizoma on mouse peritoneal macrophages in vitro].

    PubMed

    Zhou, Xia; Peng, Yao-zong; Huang, Tao; Li, Ling; Mou, Shao-xia; Kou, Shu-ming; Li, Xue-gang

    2015-12-01

    This work was mainly studied the effects of the four alkaloids from Coptidis Rhizoma on the mouse peritoneal macrophages in vitro and preliminarily discussed the regulating mechanisms. The effect of alkaloids from Coptidis Rhizoma on the vitality of macrophages was measured by the MTT assay. The effect of alkaloids on the phagocytosis of macrophages was determined by neutral red trial and respiratory burst activity was tested by NBT. The expressions of respiratory-burst-associated genes influenced by alkaloids were detected by qRT-PCR. The conformation change of membrane protein in macrophages by the impact of alkaloids was studied by fluorospectro-photometer. Results showed that the four alkaloids from Coptidis Rhizoma could increase the phagocytosis of macrophages in different level and berberine had the best effect. Berberine, coptisine and palmatine had up-regulation effects on respiratory burst activity of mouse peritoneal macrophages stimulated by PMA and regulatory activity on the mRNA expression of PKC, p40phox or p47phox, whereas the epiberberine had no significant influence on respiratory burst. Moreover, alkaloids from Coptidis Rhizoma could change the conformation of membrane protein and the berberine showed the strongest activity. The results suggested that the four alkaloids from Coptidis Rhizoma might activate macrophages through changing the conformation of membrane protein of macrophages and then enhanced the phagocytosis and respiratory burst activity of macrophages. Furthermore, the regulatory mechanism of alkaloids on the respiratory burst activity of macrophages may be also related to the expression level of PKC, p40phox and p47phox. PMID:27141680

  11. Asexual endophytes in a native grass: tradeoffs in mortality, growth, reproduction, and alkaloid production.

    PubMed

    Faeth, Stanley H; Hayes, Cinnamon J; Gardner, Dale R

    2010-10-01

    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 to herbivores via endophytic alkaloids. Although these benefits are well established in infected introduced, agronomic grasses, little is known about the cost and benefits of endophyte infection in native grass populations. These populations exist as mosaics of uninfected and infected plants, with the latter often comprised of plants that vary widely in alkaloid content. We tested the costs and benefits of endophyte infections with varying alkaloids in the native grass Achnatherum robustum (sleepygrass). We conducted a 4-year field experiment, where herbivory and water availability were controlled and survival, growth, and reproduction of three maternal plant genotypes [uninfected plants (E-), infected plants with high levels of ergot alkaloids (E+A+), and infected plants with no alkaloids (E+A-)] were monitored over three growing seasons. Generally, E+A+ plants had reduced growth over the three growing seasons and lower seed production than E- or E+A- plants, suggesting a cost of alkaloid production. The reduction in vegetative biomass in E+A+ plants was most pronounced under supplemented water, contrary to the prediction that additional resources would offset the cost of alkaloid production. Also, E+A+ plants showed no advantage in growth, seed production, or reproductive effort under full herbivory relative to E- or E+A- grasses, contrary to the predictions of the defensive mutualism hypothesis. However, E+A+ plants had higher overwintering survival than E+A- plants in early plant ontogeny, suggesting that alkaloids associated with infection may protect against below ground herbivory or harsh winter conditions. Our results suggest that the mosaic of E-, E+A+, and E+A- plants observed in nature may result from varying biotic and abiotic selective factors that maintain

  12. 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.

  13. 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…

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

    PubMed

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

    1991-06-01

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

  15. 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

  16. 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

  17. [Research progress on alkaloids constituents from Zanthoxylum and their pharmacological activities].

    PubMed

    Yuan, Hai-mei; Qiu, Lu; Xie, Zhen-jian; Zou, Liang; Zheng, Jin; Fu, Qiang

    2015-12-01

    There are 250 species of Zanthoxylum (Rutaceae) in the world. This genus distributed in tropical and subtropical regions. Alkaloids are the major and representative ingredients in these plants including quinolines, isoquinolines, and amide alkaloids, with such biological activities as anti-tumor, anti-inflammatory, analgesic, anti-virus, anti-platelet aggregation, anti-bacteria and anti- oxidant. These species have been used for a long time to treat toothache, urinary and venereal diseases, lumbago and rheumatism. This review summarizes the chemical constituents and pharmacological activities from the Z. sppplants, in an effort to the systematic research and application of the alkaloids of this genus.

  18. Alkaloids from marine invertebrates as important leads for anticancer drugs discovery and development.

    PubMed

    Imperatore, Concetta; Aiello, Anna; D'Aniello, Filomena; Senese, Maria; Menna, Marialuisa

    2014-12-05

    The present review describes research on novel natural antitumor alkaloids isolated from marine invertebrates. The structure, origin, and confirmed cytotoxic activity of more than 130 novel alkaloids belonging to several structural families (indoles, pyrroles, pyrazines, quinolines, and pyridoacridines), together with some of their synthetic analogs, are illustrated. Recent discoveries concerning the current state of the potential and/or development of some of them as new drugs, as well as the current knowledge regarding their modes of action, are also summarized. A special emphasis is given to the role of marine invertebrate alkaloids as an important source of leads for anticancer drug discovery.

  19. [Research progress on alkaloids constituents from Zanthoxylum and their pharmacological activities].

    PubMed

    Yuan, Hai-mei; Qiu, Lu; Xie, Zhen-jian; Zou, Liang; Zheng, Jin; Fu, Qiang

    2015-12-01

    There are 250 species of Zanthoxylum (Rutaceae) in the world. This genus distributed in tropical and subtropical regions. Alkaloids are the major and representative ingredients in these plants including quinolines, isoquinolines, and amide alkaloids, with such biological activities as anti-tumor, anti-inflammatory, analgesic, anti-virus, anti-platelet aggregation, anti-bacteria and anti- oxidant. These species have been used for a long time to treat toothache, urinary and venereal diseases, lumbago and rheumatism. This review summarizes the chemical constituents and pharmacological activities from the Z. sppplants, in an effort to the systematic research and application of the alkaloids of this genus. PMID:27141666

  20. Naturally occurring plant isoquinoline N-oxide alkaloids: their pharmacological and SAR activities.

    PubMed

    Dembitsky, Valery M; Gloriozova, Tatyana A; Poroikov, Vladimir V

    2015-01-15

    The present review describes research on novel natural isoquinoline alkaloids and their N-oxides isolated from different plant species. More than 200 biological active compounds have shown confirmed antimicrobial, antibacterial, antitumor, and other activities. The structures, origins, and reported biological activities of a selection of isoquinoline N-oxides alkaloids are reviewed. With the computer program PASS some additional SAR (structure-activity relationship) activities are also predicted, which point toward new possible applications of these compounds. This review emphasizes the role of isoquinoline N-oxides alkaloids as an important source of leads for drug discovery.

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

    PubMed

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

    2015-11-27

    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.

  2. 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

  3. [Ergotism due to simultaneous use of ergot alkaloids and high activity antiretroviral therapy].

    PubMed

    Cifuentes M, Daniel; Blanco L, Sergio; Ramírez F, Camila

    2016-06-01

    High activity antiretroviral therapy may exacerbate the activity of ergot alkaloids due to an inhibition of cytochrome P450. We report a 57 years old female with AIDS treated with lamivudine, zidovudine, atazanavir, ritonavir and cotrimoxazole presenting with ischemic signs in the four limbs. There was acrocyanosis and weak radial and ulnar pulses. A family member referred that the patient used ergot alkaloids for headaches. An ergotism due to the simultaneous use of ergot alkaloids and antiretroviral therapy was suspected. The latter was discontinued and intravenous nitroglycerin, nifedipine and pentoxifyline were started with good results. PMID:27598502

  4. GC-MS investigation of Amaryllidaceae alkaloids in Galanthus xvalentinei nothosubsp. subplicatus.

    PubMed

    Sarikaya, Buket Bozkurt; Berkov, Strahil; Bastida, Jaume; Kaya, Gulen Irem; Onur, Mustafa Ali; Somer, Nehir Unver

    2013-03-01

    A GC-MS analysis of alkaloids in the aerial parts and bulbs of Galanthus xvalentinei nothosubsp. subplicatus was performed for the first time. Totally, twenty-six alkaloids were identified, of which tazettine and galanthindole were the major ones. Acetylcholinesterase inhibitory activity of the alkaloidal extracts was determined using modified in vitro Ellman's method. Significant anticholinesterase activity was observed in the tested samples (bulbs: IC50 = 21.3 microg/mL, aerial parts: IC50 = 16.3 microg/mL).

  5. Neopetrosiamine A, biologically active bis-piperidine alkaloid from the Caribbean sea sponge Neopetrosia proxima.

    PubMed

    Wei, Xiaomei; Nieves, Karinel; Rodríguez, Abimael D

    2010-10-01

    A new tetracyclic bis-piperidine alkaloid, neopetrosiamine A (1), has been extracted from the marine sponge Neopetrosiaproxima collected off the west coast of Puerto Rico. The structure of compound 1 was elucidated by analysis of spectroscopic data coupled with careful comparisons of its (1)H and (13)C NMR data with those of a well-known 3-alkylbis-piperidine alkaloid model. The new alkaloid displayed strong in vitro cytotoxic activity against a panel of cancer cell lines as well as in vitro inhibitory activity against the pathogenic microbes Mycobacterium tuberculosis and Plasmodium falciparum.

  6. 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.

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

    PubMed

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

    2008-09-01

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

  8. Mammalian opiate alkaloid synthesis: lessons derived from plant biochemistry.

    PubMed

    Meijerink, W J; Molina, P E; Abumrad, N N

    1999-09-01

    The presence of opiate receptors in mammalian tissues has stimulated the search for endogenous ligands to these receptors and has led to the discovery and characterization of endogenous opioid peptides. However, recent studies have provided evidence for the presence of opiate alkaloids in mammalian tissues and for their endogenous synthesis. The study of their origin and synthetic pathway has been significantly influenced by the early classical biochemical studies performed in plants. This review is a historical account of the use and abuse of opiates, the elucidation of morphine's synthetic pathway in the poppy plant, and the subsequent characterization of its presence in mammalian tissues. Clearly, our understanding of its synthetic pathway and regulation is a reflection of observations originally made in plant biochemistry.

  9. 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.

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

    PubMed

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

    2016-04-22

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

  11. Engineering biosynthesis of the anticancer alkaloid noscapine in yeast

    PubMed Central

    Li, Yanran; Smolke, Christina D.

    2016-01-01

    Noscapine is a potential anticancer drug isolated from the opium poppy Papaver somniferum, and genes encoding enzymes responsible for the synthesis of noscapine have been recently discovered to be clustered on the genome of P. somniferum. Here, we reconstitute the noscapine gene cluster in Saccharomyces cerevisiae to achieve the microbial production of noscapine and related pathway intermediates, complementing and extending previous in planta and in vitro investigations. Our work provides structural validation of the secoberberine intermediates and the description of the narcotoline-4′-O-methyltransferase, suggesting this activity is catalysed by a unique heterodimer. We also reconstitute a 14-step biosynthetic pathway of noscapine from the simple alkaloid norlaudanosoline by engineering a yeast strain expressing 16 heterologous plant enzymes, achieving reconstitution of a complex plant pathway in a microbial host. Other engineered yeasts produce previously inaccessible pathway intermediates and a novel derivative, thereby advancing protoberberine and noscapine related drug discovery. PMID:27378283

  12. Acridone alkaloids from Glycosmis chlorosperma as DYRK1A inhibitors.

    PubMed

    Beniddir, Mehdi A; Le Borgne, Erell; Iorga, Bogdan I; Loaëc, Nadège; Lozach, Olivier; Meijer, Laurent; Awang, Khalijah; Litaudon, Marc

    2014-05-23

    Two new acridone alkaloids, chlorospermines A and B (1 and 2), were isolated from the stem bark of Glycosmis chlorosperma, together with the known atalaphyllidine (3) and acrifoline (4), by means of bioguided isolation using an in vitro enzyme assay against DYRK1A. Acrifoline (4) and to a lesser extent chlorospermine B (2) and atalaphyllidine (3) showed significant inhibiting activity on DYRK1A with IC50's of 0.075, 5.7, and 2.2 μM, respectively. Their selectivity profile was evaluated against a panel of various kinases, and molecular docking calculations provided structural details for the interaction between these compounds and DYRK1A. PMID:24798019

  13. 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

  14. 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

  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. 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

  17. Engineering biosynthesis of the anticancer alkaloid noscapine in yeast.

    PubMed

    Li, Yanran; Smolke, Christina D

    2016-01-01

    Noscapine is a potential anticancer drug isolated from the opium poppy Papaver somniferum, and genes encoding enzymes responsible for the synthesis of noscapine have been recently discovered to be clustered on the genome of P. somniferum. Here, we reconstitute the noscapine gene cluster in Saccharomyces cerevisiae to achieve the microbial production of noscapine and related pathway intermediates, complementing and extending previous in planta and in vitro investigations. Our work provides structural validation of the secoberberine intermediates and the description of the narcotoline-4'-O-methyltransferase, suggesting this activity is catalysed by a unique heterodimer. We also reconstitute a 14-step biosynthetic pathway of noscapine from the simple alkaloid norlaudanosoline by engineering a yeast strain expressing 16 heterologous plant enzymes, achieving reconstitution of a complex plant pathway in a microbial host. Other engineered yeasts produce previously inaccessible pathway intermediates and a novel derivative, thereby advancing protoberberine and noscapine related drug discovery. PMID:27378283

  18. 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 8α-polyveolinone (1), N-acetyl-8α-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.

  19. Purine alkaloids from the South China Sea gorgonian Subergorgia suberosa.

    PubMed

    Qi, Shu-Hua; Zhang, Si; Huang, Hui

    2008-04-01

    Four new purine alkaloids, namely, 6-(1'-purine-6',8'-dionyl)suberosanone ( 1), 3,9-(2-imino-1-methyl-4-imidazolidinone-5-yl)isopropenylpurine-6,8-dione ( 2), 1-(3'-carbonylbutyl)purine-6,8-dione ( 3), and 9-(3'-carbonylbutyl)purine-6,8-dione ( 4), together with three known compounds, guanosine ( 5), thymidine ( 6), and adenosine ( 7), were isolated from the EtOH/CH 2Cl 2 extracts of the South China Sea gorgonian Subergorgia suberosa. The structures of 1- 4 were determined on the basis of extensive spectroscopic analysis, including 1D and 2D NMR data. Compounds 1- 4 all showed weak cytotoxicity toward human cancer cell lines MDA-MB-231 and A435.

  20. Cytochrome P450 as dimerization catalyst in diketopiperazine alkaloid biosynthesis.

    PubMed

    Saruwatari, Takayoshi; Yagishita, Fumitoshi; Mino, Takashi; Noguchi, Hiroshi; Hotta, Kinya; Watanabe, Kenji

    2014-03-21

    As dimeric natural products frequently exhibit useful biological activities, identifying and understanding their mechanisms of dimerization is of great interest. One such compound is (−)-ditryptophenaline, isolated from Aspergillus flavus, which inhibits substance P receptor for potential analgesic and anti-inflammatory activity. Through targeted gene knockout in A. flavus and heterologous yeast gene expression, we determined for the first time the gene cluster and pathway for the biosynthesis of a dimeric diketopiperazine alkaloid. We also determined that a single cytochrome P450, DtpC, is responsible not only for pyrroloindole ring formation but also for concurrent dimerization of N-methylphenylalanyltryptophanyl diketopiperazine monomers into a homodimeric product. Furthermore, DtpC exhibits relaxed substrate specificity, allowing the formation of two new dimeric compounds from a non-native monomeric precursor, brevianamide F. A radical-mediated mechanism of dimerization is proposed.

  1. Degradation of quinolizidine alkaloids of lupin by Rhizopus oligosporus.

    PubMed

    Ortega-David, Eduar; Rodríguez-Stouvenel, Aida

    2013-06-01

    Rhizopus oligosporus has proven beneficial in the detoxification of lupin seeds. The fermentation process is mainly affected by the initial pH in the medium. In the range of growth of mold, there are maximum enzymatic activities in pH of 3.5 and 5.5. Metabolism change occurs at these pH levels; therefore, we studied the growth, pH changes, dry matter intake, and alkaloid degradation within 48 h of fermentation. Cultures of lupin agar (LA) with pH of 3.5 and 5.5 were made in Petri dishes with lupin flour. Results showed pH directly affects the degradation of alkaloids and fungal growth. Detoxification levels achieved were 16.58 and 63.23 % in treatments LA 3.5 and LA 5.5, respectively. Fungal growth was 0.919 mg/cm(2) in LA 3.5 and 1.081 mg/cm(2) in LA 5.5. Maximum degradation rate in LA 5.5 was given between 16 and 20 h, which coincided with maximum fungal growth. Despite having similar dry matter intake in both treatments, a pH of 3.5 did not show the same degree of detoxification. The analysis with exponential, yield of growth, yield of dry matter intake and luedeking and piret equations, confirm the relation between intake and growth with detoxification. Dry matter intake equation predicts with R (2) of 0.94 the detoxification in LA 5.5. A pH of 5.5 is directly related with detoxification and fungal development. PMID:23435939

  2. 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).

  3. Capillary electrophoretic study of the synergistic biological effects of alkaloids from Chelidonium majus L. in normal and cancer cells.

    PubMed

    Kulp, Maria; Bragina, Olga

    2013-04-01

    In this study, the synergistic biological action of five celandine alkaloids in normal and cancer cells was investigated by capillary electrophoresis with light-emitting diode-induced native fluorescence detection. The specific capacity of each alkaloid to penetrate into the cells was estimated by monitoring alkaloid concentration decreases in the cell medium during incubation with murine fibroblast NIH/3T3, mouse melanoma B16F10, and human breast cancer MCF7 cell lines. Mixtures of isoquinoline alkaloids containing protopine, chelidonine, sanguinarine, allocryptopine, and stylopine were applied to cell cultures for 20 and 40 min, and the content of alkaloids in the cell media was measured by capillary electrophoresis (CE). CE separation of isoquinoline alkaloids was performed in 30 mM phosphate buffer (pH 2.5). As these alkaloids have native fluorescence, they were directly detected using the commercially available UV light-emitting diode without troublesome fluorescent derivatization. The results showed a differential ability of celandine alkaloids to penetrate into the normal and cancer cell interior, which was inversely proportional to their cytotoxic activity. While the most effective transport of celandine alkaloids from the cell medium to the cell interior was observed for normal murine fibroblast NIH/3T3 cells (about 55% of total content), cytotoxicity tests demonstrated selective and profound apoptotic effects of a five-alkaloid combination in the mouse melanoma B16F10 cell line.

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

    PubMed

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

    1999-02-01

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

  5. [Determination of 7 bio-active alkaloids in Stephania plants by RP-HPLC].

    PubMed

    Huang, J; Guo, J; Duan, G

    1998-07-01

    Seven bio-active alkaloids (stepholidine, sinoacutine, isocorydine, l-tetrahydropalmatine, crebanine, fanchinoline and tetrandrine) in Stephania plants were determined by RP-HPLC, using UV detection (282 nm) and gradient elution. The reversed phase system consisted of ODS column and methanol-water-triethylamine as mobile phase. The flow rate was 1.0 ml.min-1. Good linearity between peak heights and concentrations of the alkaloids was obtained in the concentration range. The HPLC method proved accurate, precise and sensitive. The results showed that there were some differences in the occurrence and content of the alkaloids between various species and between the same species from different habitats and collecting time. Based on the results, some species with high content of the 7 bio-active alkaloids were selected. The study provided some useful information for the utilization of medicinal plant resources in the genus Stephania. PMID:12016887

  6. 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

  7. 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.

  8. 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

  9. 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...

  10. Safety concerns of herbal products and traditional Chinese herbal medicines: Dehydropyrrolizidine 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 dehydropyrrolizidine alkaloids ...

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

    PubMed

    Casale, John; Lydon, John

    2007-05-01

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

  12. A journey under the sea: the quest for marine anti-cancer alkaloids.

    PubMed

    Tohme, Rita; Darwiche, Nadine; Gali-Muhtasib, Hala

    2011-01-01

    The alarming increase in the global cancer death toll has fueled the quest for new effective anti-tumor drugs thorough biological screening of both terrestrial and marine organisms. Several plant-derived alkaloids are leading drugs in the treatment of different types of cancer and many are now being tested in various phases of clinical trials. Recently, marine-derived alkaloids, isolated from aquatic fungi, cyanobacteria, sponges, algae, and tunicates, have been found to also exhibit various anti-cancer activities including anti-angiogenic, anti-proliferative, inhibition of topoisomerase activities and tubulin polymerization, and induction of apoptosis and cytotoxicity. Two tunicate-derived alkaloids, aplidin and trabectedin, offer promising drug profiles, and are currently in phase II clinical trials against several solid and hematologic tumors. This review sheds light on the rich array of anti-cancer alkaloids in the marine ecosystem and introduces the most investigated compounds and their mechanisms of action. PMID:22113577

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

    NASA Astrophysics Data System (ADS)

    Rogers, Kevin; Milnes, John; Gormally, John

    1992-06-01

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

  14. Thesinine-4'-O-beta-D-glucoside the first glycosylated plant pyrrolizidine alkaloid from Borago officinalis.

    PubMed

    Herrmann, Martina; Joppe, Holger; Schmaus, Gerhard

    2002-06-01

    The glycosylated pyrrolizidine alkaloid, thesinine-4'-O-beta-D-glucoside, has been isolated from the aqueous methanol extract of dried, defatted seeds of Borago officinalis (Boraginaceae). The structure was established by means of spectroscopic and chemical analysis. PMID:12031432

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

    PubMed

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

    2015-01-01

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

  16. Antitussive, expectorant and anti-inflammatory alkaloids from Bulbus Fritillariae Cirrhosae.

    PubMed

    Wang, Dongdong; Zhu, Jingyi; Wang, Shu; Wang, Xiaoxia; Ou, Yang; Wei, Dandan; Li, Xueping

    2011-12-01

    The primary objective of this study is to evaluate the antitussive, expectorant and anti-inflammatory effects of alkaloids imperialine (I), chuanbeinone (II), verticinone (III), and verticine (IV), which were isolated from the Bulbus Fritillariae Cirrhosae (BFC) using phytochemical method. The results showed that all the alkaloids significantly inhibited cough frequency and increased latent period of cough in mice induced by ammonia. Besides, imperialine(I), verticinone(III) and verticine(IV) markedly enhanced mice's tracheal phenol red output in expectorant evaluation, and imperialine(I), chuanbeinone(II) significantly inhibited the development of ear edema in a dose-dependent manner in anti-inflammatory assessment. Moreover, important differences were found among the structure-activity relationships for the four alkaloids. These results confirmed that the four alkaloids imperialine, chuanbeinone, verticinone and verticine may be the active ingredients of the Bulbus F. Cirrhosae (BFC).

  17. 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

  18. 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.

  19. Melokhanines A-J, Bioactive Monoterpenoid Indole Alkaloids with Diverse Skeletons from Melodinus khasianus.

    PubMed

    Cheng, Gui-Guang; Li, Dan; Hou, Bo; Li, Xiao-Nian; Liu, Lu; Chen, Ying-Ying; Lunga, Paul-Keilah; Khan, Afsar; Liu, Ya-Ping; Zuo, Zhi-Li; Luo, Xiao-Dong

    2016-09-23

    The new melokhanines A-J (1-10) and 22 known (11-32) alkaloids were isolated from the twigs and leaves of Melodinus khasianus. The new compounds and their absolute configurations were elucidated by extensive analysis of spectroscopic, X-ray diffraction, and computational data. Melokhanine A (1), composed of a hydroxyindolinone linked to an octahydrofuro[2,3-b]pyridine moiety, is an unprecedented monoterpenoid indole alkaloid. Melokhanines B-H (2-8) possess a new 6/5/5/6/6 pentacyclic indole alkaloid skeleton. Alkaloids 1-16, 25-27, 31, and 32 showed the best antibacterial activity against Pseudomonas aeruginosa (MIC range 2-22 μM). Among the seven dermatophytes tested, compound 1 showed significant inhibitory activity against Microsporum canis, M. ferrugineum, and Trichophyton ajelloi (MIC range 38-150 μM), i.e., half the efficacy of the positive control, griseofulvin. PMID:27584856

  20. Plant Alkaloids as Antiplatelet Agent: Drugs of the Future in the Light of Recent Developments

    PubMed Central

    Ain, Qurrat-Ul-; Khan, Haroon; Mubarak, Mohammad S.; Pervaiz, Aini

    2016-01-01

    An alkaloid is a class of naturally occurring organic nitrogen-containing compounds that are frequently found in the plant kingdom. Many alkaloids are valuable medicinal agents that can be utilized to treat various diseases including malaria, diabetics, cancer, cardiac dysfunction etc. Similarly, platelet aggregation beyond the purpose of homeostasis is the underlying cause of blood clotting related diseases. This review presents a thorough understanding of alkaloids as antiplatelet agents with a possible mechanism of action based on the literature of the last decade. In addition, this review will address the antiplatelet activity of alkaloids and their medicinal usage as potent antiplatelet agents with a description of structural relationship activity and possible lead compounds for future drug discovery. PMID:27713699

  1. 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...

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

    PubMed

    Sasamoto, Hamako; Fujii, Yoshiharu; Ashihara, Hiroshi

    2015-05-01

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

  3. A new view on the codonocarpine type alkaloids of Capparis decidua.

    PubMed

    Forster, Yvonne; Ghaffar, Abdul; Bienz, Stefan

    2016-08-01

    Several spermidine alkaloids are described in literature as constituents of the root bark of Capparis decidua. Since some of the proposed structures, however, are in conflict with the expected biosynthetic paths, an extract of the root bark of the plant was re-investigated. Four major spermidine alkaloids of the codonocarpine type were identified and their structures elucidated: of the four compounds, isocodonocarpine was described previously for C. decidua and cadabicine was proposed as a possible constituent as well. Codonocarpine was found for the first time in an extract of C. decidua but was previously isolated from a closely related plant. Capparidisinine, finally, is an alkaloid with a structure that has never been described before. The structures of the four alkaloids are substantiated by NMR and MS data, and the four compounds are in logical agreement with biosynthetic considerations: they would arise from α,ω-bis-adducts of spermidine with coumaric and/or ferulic acids, followed by phenol oxidation.

  4. 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.

  5. Thesinine-4'-O-beta-D-glucoside the first glycosylated plant pyrrolizidine alkaloid from Borago officinalis.

    PubMed

    Herrmann, Martina; Joppe, Holger; Schmaus, Gerhard

    2002-06-01

    The glycosylated pyrrolizidine alkaloid, thesinine-4'-O-beta-D-glucoside, has been isolated from the aqueous methanol extract of dried, defatted seeds of Borago officinalis (Boraginaceae). The structure was established by means of spectroscopic and chemical analysis.

  6. 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

  7. Antiplasmodial activity of three bisbenzylisoquinoline alkaloids from the tuber of Stephania rotunda.

    PubMed

    Chea, Aun; Bun, Sok-Siya; Azas, Nadine; Gasquet, Monique; Bory, Sothavireak; Ollivier, Evelyne; Elias, Riad

    2010-11-01

    Three bisbenzylisoquinoline alkaloids were isolated for the first time from Stephania rotunda tuber. Their structures were elucidated by spectroscopic methods and their antiplasmodial activity was investigated in vitro on chloroquine resistant Plasmodium falciparum strain W2. These alkaloids were identified as 2-norcepharanthine (1), cepharanoline (2) and fangchinoline (3). In vitro, they displayed significant antiplasmodial activity with inhibitory concentration 50 values of 0.3, 0.2 and 0.3 µM. PMID:20981617

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

    PubMed

    Bachhav, R S; Sambathkumar, R

    2016-01-01

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

  9. Hyrtinadines C and D, New Azepinoindole-Type Alkaloids from a Marine Sponge Hyrtios sp.

    PubMed

    Kubota, Takaaki; Nakamura, Kenta; Sakai, Kanae; Fromont, Jane; Gonoi, Tohru; Kobayashi, Jun'ichi

    2016-01-01

    New bisindole alkaloids, hyrtinadines C (1) and D (2), have been isolated from an Okinawan marine sponge Hyrtios sp. The structures of hyrtinadines C (1) and D (2) were elucidated based on analyses of the spectral data. Hyrtinadines C (1) and D (2) were the relatively rare alkaloids possessing a 3,4-fused azepinoindole skeleton. Hyrtinadines C (1) and D (2) showed antimicrobial activity. PMID:27373657

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

    PubMed Central

    Bachhav, R. S.; Sambathkumar, R.

    2016-01-01

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

  11. 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.

  12. 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.

  13. Bioproduction of Cinchona alkaloids by the endophytic fungus Diaporthe sp. associated with Cinchona ledgeriana.

    PubMed

    Maehara, Shoji; Simanjuntak, Partomuan; Kitamura, Chinami; Ohashi, Kazuyoshi; Shibuya, Hirotaka

    2012-01-01

    We report that an endophytic filamentous fungus species of the genus Diaporthe isolated from Cinchona ledgeriana (Rubiaceae) produces Cinchona alkaloids (quinine, quinidine, cinchonidine, and cinchonine) upon cultivation in a synthetic liquid medium. This study provides evidence that Cinchona alkaloids are produced not only in Cinchona plant cells, but also in the endophytic microbe cells, and will help to elucidate the relationship between endophytic microbes and their host plants.

  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. Rapid Screening of Ergot Alkaloids in Sclerotia by MALDI-TOF Mass Spectrometry.

    PubMed

    Sivagnanam, Kumaran; Komatsu, Emy; Patrick, Susan; Rampitsch, Christoph; Perreault, Hélène; Gräfenhan, Tom

    2016-07-01

    Ergot is a common disease of wheat and other cereal grains that is predominantly caused by Claviceps purpurea in the field, often affecting crop yield in addition to the environment. Infected grain can be contaminated with dark sclerotia, which contain fungal metabolites such as ergot alkaloids. The occurrence of ergot alkaloids in cereal grain is a major health concern for humans and livestock. Effective and rapid screening of these mycotoxins is crucial for producers, processors, and consumers of cereal-based food and feed grain. Established methods of ergot alkaloid screening based on LC-MS or GC-MS require laborious processes. A novel method using matrix-assisted laser desorption ionization (MALDI)-time-of-flight (TOF) MS was developed to identify four ergot alkaloids. Using dihydroxybenzoic acid as the matrix, ergosine, ergocornine, ergocryptine, and ergocristine were readily detected in individual sclerotia of C. purpurea. The accuracy of the identified ergot alkaloids was further confirmed by tandem MS analysis. MALDI-TOF MS is suitable for high-throughput screening of ergot alkaloids because it permits rapid and accurate identification, simple sample preparation, and no derivatization or chromatographic separation. PMID:27455930

  16. Structural and mechanistic bases of the anticancer activity of natural aporphinoid alkaloids.

    PubMed

    Liu, Yanjuan; Liu, Junxi; Di, Duolong; Li, Min; Fen, Yan

    2013-01-01

    Aporphinoid alkaloids, which encompass a large number of complicated structures, are an important group of natural products. The anticancer activity of aporphinoid alkaloids has become a hot pharmaceutical research area in recent years. Recent studies on the anticancer activity of these compounds are reviewed. The structure activity relationships (SARs) and anticancer mechanisms of aporphinoid alkaloids, as well as simple aporphine, oxoaporphine, dehydroaporphine and dimeric aporphine, have been summarized. The presence of a 1,2-methylenedioxy group and methylation of nitrogen are key features to the cytotoxicity of aporphinoid alkaloids. Oxidation and dehydrogenation of C7 could improve the anticancer activity. The contributions of chirality of hydrogen at C6a and the substitution pattern of other positions about aporphinoid alkaloids for anticancer activity remain unknown. Induced cancer cells apoptosis, prevention of cell proliferation, DNA topoisomerase inhibition, reducing the drug-resistant cellular side population (SP) or cancer stem cells (CSCs) and inhibition of epidermal growth factor receptor (EGFR) tyrosine kinase seem to play important roles in the molecular mechanisms of anticancer activity about aporphinoid alkaloids. PMID:23978138

  17. [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.

  18. 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

  19. 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.

  20. Comparative analysis of Papaver somniferum genotypes having contrasting latex and alkaloid profiles.

    PubMed

    Chaturvedi, Nidarshana; Singh, Mridula; Shukla, Ashutosh K; Shasany, Ajit K; Shanker, Karuna; Lal, Raj K; Khanuja, Suman P S

    2014-07-01

    Papaver somniferum produces therapeutically useful benzylisoquinoline alkaloids (BIAs) like papaverine, thebaine, codeine, and morphine that accumulate in its capsular latex. Morphine is a potent analgesic but is also abused as a narcotic, which has increased the demand for non-narcotic thebaine that can be converted into various analgesics. To curtail the narcotic menace, many distinct genotypes of the plant have been developed that are deficient in morphine and/or latex. Sujata is one such latex-less low alkaloid-producing variety developed from the alkaloid-rich gum harvest variety Sampada. Its utility for gene prospecting and studying differential gene regulation responsible for its low alkaloid, nutritive seed oil, and latex-less phenotype has been exploited in this study. BIA profiling of Sujata and Sampada capsules at the early and late stages indicated that except for thebaine, Sujata had a depressed alkaloid phenotype as compared to Sampada. Comparative transcript-based analysis of the two genotypes was carried out in the early stage capsule (higher thebaine) using subtractive hybridization and microarray. Interrogation of a P. somniferum array yielded many differentially expressing transcripts. Their homology-based annotation classified them into categories--latex related, oil/lipid related, alkaloid related, cell wall related, and others. These leads will be useful to characterize the highly sought after Sujata phenotype.

  1. 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) 1α-OMe or 1α-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 3α-OH is beneficial to the cardiac activity; iii) the effect on the cardiac action of 6α-OMe, 13-OH, 15α-OH, and 16-demethoxy or a double bond between C-15 and C-16 depends on the substituent pattern on the nitrogen atom.

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

    NASA Astrophysics Data System (ADS)

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

    2005-11-01

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

  3. 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

  4. 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

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

    PubMed

    Young, J C

    1981-01-01

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

  6. 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.

  7. Arborisidine and Arbornamine, Two Monoterpenoid Indole Alkaloids with New Polycyclic Carbon-Nitrogen Skeletons Derived from a Common Pericine Precursor.

    PubMed

    Wong, Suet-Pick; Chong, Kam-Weng; Lim, Kuan-Hon; Lim, Siew-Huah; Low, Yun-Yee; Kam, Toh-Seok

    2016-04-01

    Two new monoterpene indole alkaloids, characterized by previously unencountered natural product skeletons, viz., arborisidine (1), incorporating indolizidine and cyclohexanone moieties fused to an indole unit, and arbornamine (2), incorporating an unprecedented 6/5/6/5/6 "arbornane" skeleton (distinct from the eburnan or tacaman skeleton), were isolated from a Malayan Kopsia arborea. The structures of the alkaloids were determined based on analysis of the NMR and MS data. Possible biogenetic pathways to these alkaloids from a common pericine precursor (3) are presented.

  8. Quantitative 1H nuclear magnetic resonance metabolite profiling as a functional genomics platform to investigate alkaloid biosynthesis in opium poppy.

    PubMed

    Hagel, Jillian M; Weljie, Aalim M; Vogel, Hans J; Facchini, Peter J

    2008-08-01

    Opium poppy (Papaver somniferum) produces a diverse array of bioactive benzylisoquinoline alkaloids and has emerged as a versatile model system to study plant alkaloid metabolism. The plant is widely cultivated as the only commercial source of the narcotic analgesics morphine and codeine. Variations in plant secondary metabolism as a result of genetic diversity are often associated with perturbations in other metabolic pathways. As part of a functional genomics platform, we used (1)H nuclear magnetic resonance (NMR) metabolite profiling for the analysis of primary and secondary metabolism in opium poppy. Aqueous and chloroform extracts of six different opium poppy cultivars were subjected to chemometric analysis. Principle component analysis of the (1)H NMR spectra for latex extracts clearly distinguished two varieties, including a low-alkaloid variety and a high-thebaine, low-morphine cultivar. Distinction was also made between pharmaceutical-grade opium poppy cultivars and a condiment variety. Such phenotypic differences were not observed in root extracts. Loading plots confirmed that morphinan alkaloids contributed predominantly to the variance in latex extracts. Quantification of 34 root and 21 latex metabolites, performed using Chenomx NMR Suite version 4.6, showed major differences in the accumulation of specific alkaloids in the latex of the low-alkaloid and high-thebaine, low-morphine varieties. Relatively few differences were found in the levels of other metabolites, indicating that the variation was specific for alkaloid metabolism. Exceptions in the low-alkaloid cultivar included an increased accumulation of the alkaloid precursor tyramine and reduced levels of sucrose, some amino acids, and malate. Real-time polymerase chain reaction analysis of 42 genes involved in primary and secondary metabolism showed differential gene expression mainly associated with alkaloid biosynthesis. Reduced alkaloid levels in the condiment variety were associated with the

  9. Interaction of benzo[c]phenanthridine and protoberberine alkaloids with animal and yeast cells.

    PubMed

    Slaninová, I; Táborská, E; Bochoráková, H; Slanina, J

    2001-01-01

    We compared the effects of four quaternary benzo[c]phenanthridine alkaloids--chelerythrine, chelilutine, sanguinarine, and sanguilutine--and two quaternary protoberberine alkaloids-berberine and coptisine--on the human cell line HeLa (cervix carcinoma cells) and the yeasts Saccharomyces cerevisiae and Schizosaccharomyces japonicus var. versatilis. The ability of alkaloids to display primary fluorescence, allowed us to record their dynamics and localization in cells. Cytotoxic, anti-microtubular, and anti-actin effects in living cells were studied. In the yeasts, neither microtubules nor cell growth was seriously affected even at the alkaloid concentration of 100 microg/ml. The HeLa cells, however, responded to the toxic effect of alkaloids at concentrations ranging from 1 to 50 microg/ml. IC50 values for individual alkaloids were: sanguinarine IC50 = 0.8 microg/ml, sanguilutine IC50 = 8.3 microg/ml, chelerythrine IC50 = 6.2 microg/ml, chelilutine IC50 = 5.2 microg/ml, coptisine IC50 = 2.6 microg/ml and berberine IC50 > 10.0 microg/ml. In living cells, sanguinarine produced a decrease in microtubule numbers, particularly at the cell periphery, at a concentration of 0.1 microg/ml. The other alkaloids showed a similar effect but at higher concentrations (5-50 microg/ml). The strongest effects of sanguinarine were explained as a consequence of its easy penetration through the cell membrane owing to nonpolar pseudobase formation and to a high degree of molecular planarity.

  10. Anxiolytic-like effect of ethanolic extract of Argemone mexicana and its alkaloids in Wistar rats

    PubMed Central

    Arcos-Martínez, Aideé Itzel; Muñoz-Muñiz, Omar David; Domínguez-Ortiz, Miguel Ángel; Saavedra-Vélez, Margarita Virginia; Vázquez-Hernández, Maribel; Alcántara-López, María Gabriela

    2016-01-01

    Objective: Argemone mexicana is a Papaveracea plant; some reports have shown their antibacterial, anti-cancer, sedative and probably anti-anxiety properties. From their aerial parts, flavonoids and alkaloids have been isolated, which are intrinsically related to some actions on the central nervous system. The aim of this study was to evaluate the anxiolytic-like effects of the plant, using its ethanolic extract and alkaloid-enriched extract obtained from fresh leaves. Material and Methods: Phytochemical screening was carried out together with evaluation of antioxidant capacity and the enrichment of alkaloids present in the extract. Subsequently, 100 and 200 mg/kg doses of ethanolic extract and alkaloid-enriched extract (200 µg/kg) were intraperitoneally administered to female Wistar rats, which were exposed to elevated plus maze (EPM) test. Picrotoxin (1 mg/kg), a non-competitive gamma-aminobutyric acid A (GABAA) chloride channel antagonist, was used in experimental procedures to evaluate if this receptor is involved in the anxiolytic-like effects of A. mexicana. To discard motor effects associated with the treatments, the rats were evaluated by the locomotor activity test. Results: Only the ethanolic extract at 200 mg/kg and alkaloid-enriched extract (200 µg/kg) produced anxiolytic-like effects similarly to diazepam 2 mg/kg on EPM test, without affecting locomotor activity. Meanwhile, the administration of picrotoxin blocked anti-anxiety effect of alkaloid-enriched extract of the plant. Conclusion: These results showed that A. mexicana is a potential anxiolytic agent and we suggest that this effect is mediated by the GABAA receptor. These effects are related to the presence of alkaloids. PMID:27516989

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

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

  12. 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.

  13. Mutation in the Plasmodium falciparum CRT protein determines the stereospecific activity of antimalarial cinchona alkaloids.

    PubMed

    Griffin, Carol E; Hoke, Jonathan M; Samarakoon, Upeka; Duan, Junhui; Mu, Jianbing; Ferdig, Michael T; Warhurst, David C; Cooper, Roland A

    2012-10-01

    The Cinchona alkaloids are quinoline aminoalcohols that occur as diastereomer pairs, typified by (-)-quinine and (+)-quinidine. The potency of (+)-isomers is greater than the (-)-isomers in vitro and in vivo against Plasmodium falciparum malaria parasites. They may act by the inhibition of heme crystallization within the parasite digestive vacuole in a manner similar to chloroquine. Earlier studies showed that a K76I mutation in the digestive vacuole-associated protein, PfCRT (P. falciparum chloroquine resistance transporter), reversed the normal potency order of quinine and quinidine toward P. falciparum. To further explore PfCRT-alkaloid interactions in the malaria parasite, we measured the in vitro susceptibility of eight clonal lines of P. falciparum derived from the 106/1 strain, each containing a unique pfcrt allele, to four Cinchona stereoisomer pairs: quinine and quinidine; cinchonidine and cinchonine; hydroquinine and hydroquinidine; 9-epiquinine and 9-epiquinidine. Stereospecific potency of the Cinchona alkaloids was associated with changes in charge and hydrophobicity of mutable PfCRT amino acids. In isogenic chloroquine-resistant lines, the IC(50) ratio of (-)/(+) CA pairs correlated with side chain hydrophobicity of the position 76 residue. Second-site PfCRT mutations negated the K76I stereospecific effects: charge-change mutations C72R or Q352K/R restored potency patterns similar to the parent K76 line, while V369F increased susceptibility to the alkaloids and nullified stereospecific differences between alkaloid pairs. Interactions between key residues of the PfCRT channel/transporter with (-) and (+) alkaloids are stereospecifically determined, suggesting that PfCRT binding plays an important role in the antimalarial activity of quinine and other Cinchona alkaloids.

  14. Mutation in the Plasmodium falciparum CRT Protein Determines the Stereospecific Activity of Antimalarial Cinchona Alkaloids

    PubMed Central

    Griffin, Carol E.; Hoke, Jonathan M.; Samarakoon, Upeka; Duan, Junhui; Mu, Jianbing; Ferdig, Michael T.; Warhurst, David C.

    2012-01-01

    The Cinchona alkaloids are quinoline aminoalcohols that occur as diastereomer pairs, typified by (−)-quinine and (+)-quinidine. The potency of (+)-isomers is greater than the (−)-isomers in vitro and in vivo against Plasmodium falciparum malaria parasites. They may act by the inhibition of heme crystallization within the parasite digestive vacuole in a manner similar to chloroquine. Earlier studies showed that a K76I mutation in the digestive vacuole-associated protein, PfCRT (P. falciparum chloroquine resistance transporter), reversed the normal potency order of quinine and quinidine toward P. falciparum. To further explore PfCRT-alkaloid interactions in the malaria parasite, we measured the in vitro susceptibility of eight clonal lines of P. falciparum derived from the 106/1 strain, each containing a unique pfcrt allele, to four Cinchona stereoisomer pairs: quinine and quinidine; cinchonidine and cinchonine; hydroquinine and hydroquinidine; 9-epiquinine and 9-epiquinidine. Stereospecific potency of the Cinchona alkaloids was associated with changes in charge and hydrophobicity of mutable PfCRT amino acids. In isogenic chloroquine-resistant lines, the IC50 ratio of (−)/(+) CA pairs correlated with side chain hydrophobicity of the position 76 residue. Second-site PfCRT mutations negated the K76I stereospecific effects: charge-change mutations C72R or Q352K/R restored potency patterns similar to the parent K76 line, while V369F increased susceptibility to the alkaloids and nullified stereospecific differences between alkaloid pairs. Interactions between key residues of the PfCRT channel/transporter with (−) and (+) alkaloids are stereospecifically determined, suggesting that PfCRT binding plays an important role in the antimalarial activity of quinine and other Cinchona alkaloids. PMID:22869567

  15. Comparative disposition kinetics of two diastereomeric pairs of cinchona alkaloids in the dog.

    PubMed

    Abraham, I; Ueda, C T

    1984-04-01

    The comparative disposition kinetics of quinidine, quinine, cinchonine , and cinchonidine were investigated in five male, mongrel dogs after intravenous bolus injections of a 9.2-mmol/kg dose of each alkaloid base. Blood and plasma specimens were obtained at various times up to 6 h postdose and assayed for quinidine and quinine with a TLC-fluorometric procedure and for cinchonine and cinchonidine by HPLC. The plasma alkaloid concentration-time data were analyzed by weighted, nonlinear least-squares regression analysis to obtain the central compartment volume (Vc), disposition rate constants (alpha and beta), and corresponding half-life values (t1/2). Total body clearance (CL) and apparent volume of distribution (Vd) were estimated by nonparametric analysis. In this study, the highest plasma alkaloid concentrations were reached with quinidine and the lowest concentrations with the quinidine congener, cinchonine . The other congeneric pair, quinine and cinchonidine , exhibited plasma alkaloid concentrations that were comparable and intermediate to those of quinidine and cinchonine . With cinchonine and cinchonidine , the plasma and blood concentration-time curves were virtually superimposable. However, with quinidine and quinine, the plasma alkaloid concentrations of these diastereomers were approximately twice the corresponding blood concentrations. The total body clearance rate of quinidine was significantly slower than quinine and cinchonine clearance. No difference in clearance was observed between cinchonine and cinchonidine . The beta and t1/2 beta for quinidine were significantly smaller and larger, respectively, than the corresponding values obtained with the other alkaloids. No significant differences in alpha or Vc and Vd were found between and within the two diastereomeric pairs of alkaloids. The differences in disposition kinetics observed in this study were attributable to an interaction of stereochemical and 6'-methoxy group substitution effects.

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

    PubMed Central

    Robinson, Sarah L.

    2014-01-01

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

  17. 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. [Effect of precursor on growth and accumulation of alkaloids of Lycoris radiata suspension cells].

    PubMed

    Zhang, Yuqiong; Li, Yong; Zhou, Jianhui; Chen, Na; Wang, Meifang; Dong, Zhaorong; Gao, Cuiyun; Zhong, Yanlong

    2014-02-01

    In order to investigate the effects of phenylalanine, tyrosine and tyramine on the growth of Lycoris radiata suspension cells and the accumulation of alkaloids, the growth quantity of the cells as well as the content of alkaloids in cells were determined, which were treated with above three kinds of precursors alone and phenylalanine combined with tyrosine respectively. The results indicate that the addition of phenylalanine alone and addition of phenylalanine on the basis of tyrosine at high concentration (200 micromol/L) had no significant effect on the growth of Lycoris radiata suspension cells and the content of alkaloids in cells; whereas tyrosine and tyramine promoted the growth of the cells and alkaloids accumulation. Treated with tyrosine at high concentration (200 micromol/L), the content of alkaloids of the cells was 2.56-fold higher than that of the control group, the amounts of lycoramine (3.77 mg/g) and galanthamine (4.46 mg/g) were 6.61-fold and 6.97-fold higher than that of the control group, respectively. When treated with tyramine (200 micromol/L), the amount of alkaloids in Lycoris radiata suspension cells was 2.63-fold higher than that of the control group, and the amounts of lycoramine (4.45 mg/g) and galanthamine (5.14 mg/g) were 9.08-fold and 9.18-fold higher than that of the control group, respectively. The above results demonstrate that adding tyrosine and tyramine in the media significantly promoted the growth of the Lycoris radiata suspension cells and alkaloids accumulation in the cells. PMID:24945053

  19. Elimination of alkaloids from plant-derived human monoclonal antibody.

    PubMed

    Ko, Kisung; Wei, Xiaochen; Crooks, Peter A; Koprowski, Hilary

    2004-03-01

    A human antiviral monoclonal antibody (mAb) expressed in transgenic tobacco plants was purified from the tobacco leaf by two different methods. In one method, total protein precipitated with ammonium sulfate was applied to a Hi-Trap protein A column (column method). In the second method, leaf supernatant obtained after liquid nitrogen leaf grinding was directly immunoprecipitated using protein A-agarose beads (immunoprecipitation method). The column and immunoprecipitation methods yielded 0.52 and 0.45 microg of plant-derived mAb (mAb(P))/g, respectively, from fresh leaf tissue. The product derived using the column method exhibited higher binding activity compared to immunoprecipitation-derived product against rabies virus strain CVS-11 in ELISA. Gas chromatography/mass spectrometry analysis, which has a detection limit of 5 pg revealed no detectable levels of nicotine or other related plant alkaloids in the purified mAb(P) from either purification procedure. Thus, both purification methodologies yield mAb(P) uncontaminated with nicotine from the tobacco leaves.

  20. 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

  1. 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.

  2. 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.

  3. Cytotoxic Epipolythiodioxopiperazine Alkaloids from Filamentous Fungi of the Bionectriaceae

    PubMed Central

    Figueroa, Mario; Graf, Tyler N.; Ayers, Sloan; Adcock, Audrey F.; Kroll, David J.; Yang, Jilai; Swanson, Steven M.; Munoz-Acuna, Ulyana; Carcache de Blanco, Esperanza J.; Agrawal, Rajesh; Wani, Mansukh C.; Darveaux, Blaise A.; Pearce, Cedric J.; Oberlies, Nicholas H.

    2013-01-01

    Bioactivity-directed fractionation of the organic extracts of two filamentous fungi of the Bionectriaceae, strains MSX 64546 and MSX 59553 from the Mycosynthetix library, led to the isolation of a new dimeric epipolythiodioxopiperazine alkaloid, verticillin H (1), along with six related analogues, Sch 52900 (2), verticillin A (3), gliocladicillin C (4), Sch 52901 (5), 11′-deoxyverticillin A (6), and gliocladicillin A (7). The structures of compounds 1–7 were determined by extensive NMR and HRMS analyses, as well as by comparisons to the literature. All compounds (1–7) were evaluated for cytotoxicity against a panel of human cancer cell lines, displaying IC50 values ranging from 1.2 µM to 10 nM. Compounds 1–5 were examined for activity in the NF-κB assay, where compounds 2 and 3 revealed activity in the sub-micromolar range. Additionally, compounds 1, 3, and 4 were tested for EGFR inhibition using an enzymatic assay, while compound 3 was examined against an overexpressing EGFR+ve cancer cell line. PMID:22968289

  4. 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

  5. N-alkenyl indoles as useful intermediates for alkaloid synthesis.

    PubMed

    Li, Hao; Boonnak, Nawong; Padwa, Albert

    2011-11-18

    A mild cross-coupling reaction to access several N-alkenyl-substituted indoles has been developed. The coupling procedure involves treating a NH-indole with various alkenyl bromides using a combination of 10 mol % of copper(I) iodide and 20 mol % of ethylenediamine as the catalyst in dioxane at 110 °C in the presence of K(3)PO(4) as the base. When treated with acid, these unique enamines produce a dimeric product derived from a preferred protonation reaction at the enamine π-bond. A cationic cyclization reaction of the readily available 2-(2-(1H-indol-1-yl)allyl)cyclopentanol was utilized to construct tetracyclic indole derivatives with a quaternary stereocenter attached to the C(2)-position of the indole ring. An alternative strategy for selective functionalization at the C(2)-position of a N-alkenyl-substituted indole derivative that was also studied involves a radical cyclization of a xanthate derivative. The work described provides an attractive route to the tetracyclic core of some vinca alkaloids, including the tetrahydroisoquinocarbazole RS-2135. PMID:22007631

  6. Metabolic studies of the Amaryllidaceous alkaloids galantamine and lycorine based on electrochemical simulation in addition to in vivo and in vitro models.

    PubMed

    Jahn, Sandra; Seiwert, Bettina; Kretzing, Sascha; Abraham, Getu; Regenthal, Ralf; Karst, Uwe

    2012-12-01

    Alkaloids from the plant family of Amaryllidaceae, such as galantamine (GAL) and lycorine (LYC), are known to exhibit numerous promising biological and pharmacological activities like antibacterial, antiviral or anti-inflammatory effects. Nonetheless, studies on the biotransformation pathway are rare for this substance class, unless approval for use as medication exists. While GAL has become a prescription drug used to alleviate and delay the symptoms of Alzheimer's disease, LYC exhibits potential antitumor properties. However, it has also been linked to toxic effects resulting in nausea and emesis. Whereas there are few publications available describing the metabolic pathway of GAL in animals and humans, the metabolism of LYC is unknown. Therefore, this study is concerned with the investigation of the oxidative metabolism of GAL and LYC, which was achieved by means of three different approaches: electrochemical (EC) simulation coupled on-line to liquid chromatography (LC) with electrospray mass spectrometric (ESI-MS) detection was applied in addition to in vivo experiments in beagle dog analyzing plasma (BP) and in vitro incubations with rat liver microsomes (RLM). This way, it should be investigated if electrochemistry can be used to predict the oxidative metabolism of alkaloids. For GAL, the EC model was capable of predicting most metabolites observed during microsomal and plasma studies, including N-demethylated, dehydrogenated and oxygenated products or a combination of these. LYC was found to be metabolized far less than GAL in the animal-based approaches, but several EC oxidation products were generated. Some principal metabolic routes could successfully be correlated for this alkaloid as well, comprising dehydrogenation, dehydration to ungeremine and oxygenation reactions. PMID:23176740

  7. Pyrrolizidine Alkaloid-Protein Adducts: Potential Non-invasive Biomarkers of Pyrrolizidine Alkaloid-Induced Liver Toxicity and Exposure.

    PubMed

    Xia, Qingsu; Zhao, Yuewei; Lin, Ge; Beland, Frederick A; Cai, Lining; Fu, Peter P

    2016-08-15

    Pyrrolizidine alkaloids (PAs) are phytochemicals present in hundreds of plant species from different families widely distributed in many geographical regions around the world. PA-containing plants are probably the most common type of poisonous plants affecting livestock, wildlife, and humans. There have been many large-scale human poisonings caused by the consumption of food contaminated with toxic PAs. PAs require metabolic activation to generate pyrrolic metabolites to exert their toxicity. In this study, we developed a novel method to quantify pyrrole-protein adducts present in the blood. This method involves the use of AgNO3 in acidic ethanol to cleave the thiol linkage of pyrrole-protein (DHP-protein) adducts, and the resulting 7,9-di-C2H5O-DHP is quantified by HPLC-ES-MS/MS multiple reaction monitoring analysis in the presence of a known quantity of isotopically labeled 7,9-di-C2D5O-DHP internal standard. Using this method, we determined that diester-type PAs administered to rats produced higher levels of DHP-protein adducts than other types of PAs. The results suggest that DHP-protein adducts can potentially serve as minimally invasive biomarkers of PA exposure. PMID:27388689

  8. 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

  9. 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

  10. Hydroxyl radical scavenging activities of isoquinoline alkaloids isolated from Coptis chinensis.

    PubMed

    Jang, Moon Hee; Kim, Hyun Young; Kang, Ki Sung; Yokozawa, Takako; Park, Jeong Hill

    2009-03-01

    The hydroxyl radical (*OH) scavenging and ferrous ion chelating activities of four isoquinoline alkaloids isolated from Coptis chinensis Franch were studied for the identification of their structural characteristics to scavenge *OH. The *OH was generated via Fe(II)-catalazed Fenton reaction in this study and the reliable measurement of *OH scavenging activities of isoquinoline alkaloids were achieved using electron spin resonance (ESR) spectrometry method. At the 1 mM concentration, berberrubine (85%) showed the strongest *OH scavenging activity and the next were in the decreasing order of coptisine (79%), berberine (23%), and palmatine (22%). The ferrous ion chelating effects of the alkaloids showed similar pattern with their *OH scavenging effects. These results suggest that *OH scavenging effects of the alkaloids were closely related to their ferrous ion chelating activities. In addition, metal chelating functional groups such as hydroxy group at C-9 and methylenedioxy group at C-9 and C-10 were thought to contribute to the *OH scavenging activities of the isoquinoline alkaloids.

  11. 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.

  12. Recent advances in isolation, synthesis, and evaluation of bioactivities of bispyrroloquinone alkaloids of marine origin.

    PubMed

    Nijampatnam, Bhavitavya; Dutta, Shilpa; Velu, Sadanandan E

    2015-08-01

    The ocean continues to provide a plethora of unique scaffolds capable of remarkable biological applications. A large number of pyrroloiminoquinone alkaloids, including discorhabdins, epinardins, batzellines, makaluvamines, and veiutamine, have been isolated from various marine organisms. A class of pyrroloiminoquinone-related alkaloids, known as bispyrroloquinones, is the focus of this review article. This family of marine alkaloids, which contain an aryl substituted bispyrroloquinone ring system, includes three subclasses of alkaloids namely, wakayin, tsitsikammamines A-B, and zyzzyanones A-D. Both wakayin and the tsitsikammamines contain a tetracyclic fused bispyrroloiminoquinone ring system, while zyzzyanones contain a fused tricyclic bispyrroloquinone ring system. The unique chemical structures of these marine natural products and their diverse biological properties, including antifungal and antimicrobial activity, as well as the potent, albeit generally nonspecific and universal cytotoxicities, have attracted great interest of synthetic chemists over the past three decades. Tsitsikammamines, wakayin, and several of their analogs show inhibition of topoisomerases. One additional possible mechanism of anticancer activity of tsitsikammamines analogs that has been discovered recently is through the inhibition of indoleamine 2, 3-dioxygenase, an enzyme involved in tumoral immune resistance. This review discusses the isolation, synthesis, and evaluation of bioactivities of bispyrroloquinone alkaloids and their analogs.

  13. Piperidine, pyridine alkaloid inhibition of fetal movement in a day 40 pregnant goat model.

    PubMed

    Green, Benedict T; Lee, Stephen T; Welch, Kevin D; Pfister, James A; Panter, Kip E

    2013-08-01

    Inhibition of fetal movement is one mechanism behind the development of multiple congenital contracture-type defects in developing fetuses of humans and animals. We tested the alkaloids anabasine, lobeline, and myosmine for agonist actions, and sensitivity to alpha conotoxins EI and GI blockade at fetal muscle-type nicotinic acetylcholine receptors (nAChR) expressed by TE-671 cells. We also determined if the alkaloids decreased fetal movement in an IV dosed, day 40 pregnant goat model. In TE-671 cells, all three alkaloids elicited concentration-dependent changes in membrane potential sensing dye fluorescence. 1.0 μM alpha conotoxin GI shifted the concentration-effect curves of anabasine and myosmine to the right, and decreased maximal responses. Neither of the conotoxins blocked the actions of lobeline in TE-671 cells. In the day 40 pregnant goats, 0.8 mg/kg anabasine abolished fetal movement at 30 and 60 min after dosing and fetal movement was reduced by lobeline and myosmine. The blockade of anabasine and myosmine actions in TE-671 cells by alpha conotoxin GI indicates that they are agonists at fetal muscle-type nAChR. All three alkaloids did significantly decrease fetal movement in the day 40 pregnant goat model suggesting a potential for these alkaloids to cause multiple congenital contracture-type defects in developing fetuses.

  14. Loganin and secologanin derived tryptamine-iridoid alkaloids from Palicourea crocea and Palicourea padifolia (Rubiaceae).

    PubMed

    Berger, Andreas; Kostyan, Maria Katharina; Klose, Simon Immo; Gastegger, Michael; Lorbeer, Eberhard; Brecker, Lothar; Schinnerl, Johann

    2015-08-01

    During comparative analysis on Palicourea species from Costa Rica, two unusual loganin derived tryptamine-iridoid alkaloids were isolated from an accession of Palicourea crocea. Besides the already known brachycerine (2), palicroceaine (1) features a novel hexacyclic backbone. A second provenance, however, yielded strictosidinic acid (3), belonging to the more common secologanin derived tryptamine-iridoid alkaloids, such as those found in Palicourea padifolia. From this species, strictosidine (4), lyaloside (5) and its derivative (E)-O-(6')-(4″-hydroxy-3″,5″-dimethoxy)-cinnamoyl lyaloside (6) could be isolated. A herbarium specimen-based screening was performed, indicating some degree of regional differentiation in alkaloid content and biosynthetic pathways within the widespread and variable Pal. crocea. It further shows its differentiation from the related strictosidine containing Palicourea croceoides. The occurrence of loganin derived tryptamine-iridoid alkaloids in Pal. crocea, Psychotria brachyceras and Psychotria brachypoda, all putatively unrelated members of the Palicourea s.l. clade, is a noteworthy exception within the genus, otherwise largely characterized by secologanin-derived tryptamine-iridoid alkaloids. PMID:26043882

  15. 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.

  16. Identification of QTLs for resistant starch and total alkaloid content in brown and polished rice.

    PubMed

    Zeng, Y W; Sun, D; Du, J; Pu, X Y; Yang, S M; Yang, X M; Yang, T; Yang, J Z

    2016-01-01

    An F3 population consisting of 117 F2:3 families derived from a cross between two varieties of rice, Gongmi No. 3 and Diantun 502, with a large difference in their resistant starch and total alkaloid content, was used for quantitative trait locus (QTL) mapping. Two QTLs of resistant starch for rice (qRS7-1, qRS7-2) were identified in a linkage group on chromosome 7, which could explain phenotypic variance from 7.6 to 17.3%, due to additive effects for resistant starch from Gongmi No. 3 or over-dominance effects for qRS7-2 of the marker interval (RM3404-RM478) on chromosome 7 from Gongmi No. 3, accounting for 13.8-17.3% of the phenotypic variance. Two QTLs of total alkaloids for brown rice (qALb7-1, qALb7-2) were identified in the same linkage group, which could explain phenotypic variance from 7.7 and 19.3%, respectively, due to dominance or over-dominance effects for total alkaloids on chromosome 7 from Diantun 502. To our knowledge, these are the first QTLs to be identified, which are related to resistant starch and total alkaloid content in rice. These results are beneficial for understanding the genetic basis of, as well as for developing markers linked with, resistant starch and total alkaloids of functional components for marker-assisted selection breeding in rice. PMID:27525873

  17. 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

  18. Bioactive alkaloids of frog skin: Combinatorial bioprospecting reveals that pumiliotoxins have an arthropod source

    PubMed Central

    Daly, John W.; Kaneko, Tetsuo; Wilham, Jason; Garraffo, H. Martin; Spande, Thomas F.; Espinosa, Alex; Donnelly, Maureen A.

    2002-01-01

    Nearly 500 alkaloids have been detected in skin extracts from frogs of the family Dendrobatidae. All seem to have been sequestered unchanged into skin glands from alkaloid-containing arthropods. Ants, beetles, and millipedes seem to be the source of decahydroquinolines, certain izidines, coccinellines, and spiropyrrolizidine oximes. But the dietary source for a major group of frog-skin alkaloids, namely the pumiliotoxins (PTXs), alloPTXs, and homoPTXs, remained a mystery. In hopes of revealing an arthropod source for the PTX group, small arthropods were collected from eight different sites on a Panamanian island, where the dendrobatid frog (Dendrobates pumilio) was known to contain high levels of two PTXs. The mixed arthropod collections from several sites, each representing up to 20 arthropod taxa, contained PTX 307A and/or alloPTX 323B. In addition, the mixed arthropod collections from several sites contained a 5,8-disubstituted indolizidine (205A or 235B), representing another class of alkaloids previously unknown from an arthropod. An ant alkaloid, decahydroquinoline 195A, was detected in the mixed arthropod collections from several sites. Thus, “combinatorial bioprospecting” demonstrates that further collection and analysis of individual taxa of leaf-litter arthropods should reveal the taxa from which PTXs, alloPTXs, and 5,8-disubstituted indolizidines are derived. PMID:12381780

  19. Systematic silencing of benzylisoquinoline alkaloid biosynthetic genes reveals the major route to papaverine in opium poppy.

    PubMed

    Desgagné-Penix, Isabel; Facchini, Peter J

    2012-10-01

    Papaverine, a major benzylisoquinoline alkaloid in opium poppy (Papaver somniferum), is used as a vasodilator and antispasmodic. Conversion of the initial intermediate (S)-norcoclaurine to papaverine involves 3'-hydroxylation, four O-methylations and dehydrogenation. However, our understanding of papaverine biosynthesis remains controversial more than a century after an initial scheme was proposed. In vitro assays and in vivo labeling studies have been insufficient to establish the sequence of conversions, the potential role of the intermediate (S)-reticuline, and the enzymes involved. We used virus-induced gene silencing in opium poppy to individually suppress the expression of six genes with putative roles in papaverine biosynthesis. Suppression of the gene encoding coclaurine N-methyltransferase dramatically increased papaverine levels at the expense of N-methylated alkaloids, indicating that the main biosynthetic route to papaverine proceeds via N-desmethylated compounds rather than through (S)-reticuline. Suppression of genes encoding (S)-3'-hydroxy-N-methylcoclaurine 4-O-methyltransferase and norreticuline 7-O-methyltransferase, which accept certain N-desmethylated alkaloids, reduced papaverine content. In contrast, suppression of genes encoding N-methylcoclaurine 3'-hydroxylase or reticuline 7-O-methyltransferase, which are specific for N-methylated alkaloids, did not affect papaverine levels. Suppression of norcoclaurine 6-O-methyltransferase transcript levels significantly suppressed total alkaloid accumulation, implicating (S)-coclaurine as a key branch-point intermediate. The differential detection of N-desmethylated compounds in response to suppression of specific genes highlights the primary route to papaverine.

  20. Increasing morphinan alkaloid production by over-expressing codeinone reductase in transgenic Papaver somniferum.

    PubMed

    Larkin, Philip J; Miller, James A C; Allen, Robert S; Chitty, Julie A; Gerlach, Wayne L; Frick, Susanne; Kutchan, Toni M; Fist, Anthony J

    2007-01-01

    Only plants of the Papaver genus (poppies) are able to synthesize morphinan alkaloids, and cultivation of P. somniferum, opium poppy, remains critical for the production and supply of morphine, codeine and various semi-synthetic analgesics. Opium poppy was transformed with constitutively expressed cDNA of codeinone reductase (PsCor1.1), the penultimate step in morphine synthesis. Most transgenic lines showed significant increases in capsule alkaloid content in replicated glasshouse and field trials over 4 years. The morphinan alkaloid contents on a dry weight basis were between 15% and 30% greater than those in control high-yielding genotypes and control non-transgenic segregants. Transgenic leaves had approximately 10-fold greater levels of Cor transcript compared with non-transgenic controls. Two cycles of crossing of the best transgenic line into an elite high-morphine genotype resulted in significant increases in morphine and total alkaloids relative to the elite recurrent parent. No significant changes in alkaloid profiles or quantities were observed in leaf, roots, pollen and seed.

  1. Human ABCB1 confers cells resistance to cytotoxic guanidine alkaloids from Pterogyne nitens.

    PubMed

    Satake, Kazuhiro; Tsukamoto, Megumi; Mitani, Yuji; Regasini, Luis Octavio; da Silva Bolzani, Vanderlan; Efferth, Thomas; Nakagawa, Hiroshi

    2015-01-01

    Multidrug resistance (MDR) caused by human ABCB1 (P-glycoprotein/MDR1) is one of the major obstacles in chemotherapy. To understand the mechanism of MDR by ABCB1 and circumvent the MDR, in the present study, we established human ABCB1-expressing cells (Flp-In-293/ABCB1 cells) and examined the cytotoxic effects of four guanidine alkaloids from Pterogyne nitens (galegine, nitensidine A, pterogynidine and pterogynine) using Flp-In-293/Mock and Flp-In-293/ABCB1 cells. The activity of ABCB1 in Flp-In-293/ABCB1 cells were confirmed by typical substrates for ABCB1 (taxol and vinblastine) in MTT assay. Flp-In-293/ABCB1 cells were also resistant to the four guanidine alkaloids as well as taxol and vinblastine compared to Flp-In-293/Mock cells although the four guanidine alkaloids exhibited cytotoxicity against the two Flp-In-293 cells. Furthermore, the four guanidine alkaloids were also found to stimulate the ATPase activity of ABCB1 in ATPase assays. These results suggest that ABCB1 can confer the resistance to the cytotoxic guanidine alkaloids by transporting them.

  2. Enhancement of alkaloid production in opium and California poppy by transactivation using heterologous regulatory factors.

    PubMed

    Apuya, Nestor R; Park, Joon-Hyun; Zhang, Liping; Ahyow, Maurice; Davidow, Patricia; Van Fleet, Jennifer; Rarang, Joel C; Hippley, Matthew; Johnson, Thomas W; Yoo, Hye-Dong; Trieu, Anthony; Krueger, Shannon; Wu, Chuan-yin; Lu, Yu-ping; Flavell, Richard B; Bobzin, Steven C

    2008-02-01

    Genes encoding regulatory factors isolated from Arabidopsis, soybean and corn have been screened to identify those that modulate the expression of genes encoding for enzymes involved in the biosynthesis of morphinan alkaloids in opium poppy (Papaver somniferum) and benzophenanthridine alkaloids in California poppy (Eschscholzia californica). In opium poppy, the over-expression of selected regulatory factors increased the levels of PsCOR (codeinone reductase), Ps4'OMT (S-adenosyl-l-methionine:3'-hydroxy-N-methylcoclaurine 4'-O-methyltransferase) and Ps6OMT [(R,S)-norcoclaurine 6-O-methyltransferase] transcripts by 10- to more than 100-fold. These transcriptional activations translated into an enhancement of alkaloid production in opium poppy of up to at least 10-fold. In California poppy, the transactivation effect of regulatory factor WRKY1 resulted in an increase of up to 60-fold in the level of EcCYP80B1 [(S)-N-methylcoclaurine 3'-hydroxylase] and EcBBE (berberine bridge enzyme) transcripts. As a result, the accumulations of selected alkaloid intermediates were enhanced up to 30-fold. The transactivation effects of other regulatory factors led to the accumulation of the same intermediates. These regulatory factors also led to the production of new alkaloids in California poppy callus culture.

  3. 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.

  4. 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

  5. Screening of Alkaloidal Fraction of Conium maculatum L. Aerial Parts for Analgesic and Antiinflammatory Activity

    PubMed Central

    Madaan, Reecha; Kumar, S.

    2012-01-01

    Conium maculatum Linn. (Umbelliferae) has been traditionally used in the treatment of spasmodic disorders, and to relieve nervous excitation, rheumatic pains in the old and feeble, pain in stomach, pain of gastric ulcer, nervousness and restlessness. Alkaloids have long been considered as bioactive group of constituents present in C. maculatum. Despite a long tradition of use, C. maculatum has not been evaluated pharmacologically to validate its traditional claims for analgesic and antiinflammatory activities. Thus, the present investigations were undertaken with an objective to evaluate alkaloidal fraction of C. maculatum aerial parts for analgesic and antiinflammatory activities. Test doses (100 or 200 mg/kg, p.o.) of alkaloidal fraction were evaluated for analgesic activity using tail flick test and antiinflammatory activity using carrageenan-induced paw oedema test in rats. Morphine (5 mg/kg, p.o.) and indomethacin (5 mg/kg, p.o.) were used as standard analgesic and antiinflammatory drugs, respectively. Alkaloidal fraction of the plant exhibited significant analgesic activity at a dose of 200 mg/kg as it showed significant increase in tail flicking reaction time with respect to the control during 2 h intervals of observation. It also exhibited significant antiinflammatory activity at a dose of 200 mg/kg as it inhibited paw oedema in rats to 71% and reduced the paw volume one-fourth to the control during 1st h of the study. The present investigations suggest that alkaloids are responsible for analgesic and antiinflammatory activities of C. maculatum. PMID:23716876

  6. Recent Developments in the Isolation, Synthesis, and Bioactivities of Bispyrroloquinone Alkaloids of Marine Origin

    PubMed Central

    Nijampatnam, Bhavitavya; Dutta, Shilpa; Velu, Sadanandan E.

    2016-01-01

    The ocean continues to provide a plethora of unique scaffolds capable of remarkable biological applications. A large number of pyrroloiminoquinone alkaloids, including discorhabdins, epinardins, batzellines, makaluvamines, and veiutamine have already been isolated from marine organisms. A class of pyrroloiminoquinone-related alkaloids known as bispyrroloquinones is the focus of this review. This family of marine alkaloids, which contain an aryl substituted bispyrroloquinone ring system, includes three subclasses of alkaloids namely, wakayin, tsitsikammamines A-B and zyzzyanones A-D. Both wakayin and the tsitsikammamines contain a tetracyclic fused bispyrroloiminoquinone ring system, while zyzzyanones contain a fused tricyclic bispyrroloquinone ring system. The unique chemical structures of these marine natural products and their diverse biological properties, including antifungal and antimicrobial activity, as well as the potent, albeit generally nonspecific and universal cytotoxicities, have attracted great interest of synthetic chemists over the past three decades. Tsitsikammamines, wakayin, and several of their analogues show inhibition of topoisomerases. One additional possible mechanism of anticancer activity of tsitsikammamines analogues that was discovered recently is through the inhibition of indoleamine 2,3-dioxygenase, an enzyme involved in tumoral immune resistance. This review discusses the isolation, synthesis, and bioactivities of bispyrroloquinone alkaloids and their analogues. PMID:26253489

  7. The influence of Datura ferox alkaloids on egg-laying hens.

    PubMed

    Kovatsis, A; Kotsaki-Kovatsi, V P; Nikolaidis, E; Flaskos, J; Tzika, S; Tzotzas, G

    1994-04-01

    Seeds of the weed Datura ferox are frequent contaminants of raw materials used for animal feed. In this study a mixture of scopolamine and hyoscyamine (98:2), the 2 main alkaloids of Datura ferox seeds, was incorporated at 4 total alkaloid levels (1.5, 15, 75 or 150 mg/kg feed) into a control diet fed to 100 egg-laying hens for 3 mo. Alkaloid doses of 150 mg/kg feed reduced egg production for the first 5-6 w of feeding, whereas lower doses had no effect. Egg weight, eggshell thickness and body weight of hens were unaffected at all doses. Doses of 150 mg/kg feed produced significant increases in the cardiac rate of hens after 5 w. Breathing frequency at all doses was unaffected. Determination of plasma aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and leucine aminopeptidase activities, as well as autopsy and histological examinations, revealed no obvious alkaloid-related toxic effects. It was concluded that a total alkaloid dose as high as 75 mg/kg feed can be safely administered to egg-laying hens. PMID:8197722

  8. Wild Argentinian Amaryllidaceae, a new renewable source of the acetylcholinesterase inhibitor galanthamine and other alkaloids.

    PubMed

    Ortiz, Javier E; Berkov, Strahil; Pigni, Natalia B; Theoduloz, Cristina; Roitman, German; Tapia, Alejandro; Bastida, Jaume; Feresin, Gabriela E

    2012-11-13

    The Amaryllidaceae family is well known for its pharmacologically active alkaloids. An important approach to treat Alzheimer’s disease involves the inhibition of the enzyme acetylcholinesterase (AChE). Galanthamine, an Amaryllidaceae alkaloid, is an effective, selective, reversible, and competitive AchE inhibitor. This work was aimed at studying the alkaloid composition of four wild Argentinian Amarillydaceae species for the first time, as well as analyzing their inhibitory activity on acetylcholinesterase. Alkaloid content was characterized by means of GC-MS analysis. Chloroform basic extracts from Habranthus jamesonii, Phycella herbertiana, Rhodophiala mendocina and Zephyranthes filifolia collected in the Argentinian Andean region all contained galanthamine, and showed a strong AChE inhibitory activity (IC50 between 1.2 and 2 µg/mL). To our knowledge, no previous reports on alkaloid profiles and AChEIs activity of wild Argentinian Amarillydaceae species have been publisihed. The demand for renewable sources of industrial products like galanthamine and the need to protect plant biodiversity creates an opportunity for Argentinian farmers to produce such crops.

  9. Phylogenetic Analyses Reveal Monophyletic Origin of the Ergot Alkaloid Gene dmaW in Fungi

    PubMed Central

    Liu, Miao; Panaccione, Daniel G.; Schardl, Christopher L.

    2009-01-01

    Ergot alkaloids are indole-derived mycotoxins that are important in agriculture and medicine. Ergot alkaloids are produced by a few representatives of two distantly related fungal lineages, the Clavicipitaceae and the Trichocomaceae. Comparison of the ergot alkaloid gene clusters from these two lineages revealed differences in the relative positions and orientations of several genes. The question arose: is ergot alkaloid biosynthetic capability from a common origin? We used a molecular phylogenetic approach to gain insights into the evolution of ergot alkaloid biosynthesis. The 4-γ,γ-dimethylallyltryptophan synthase gene, dmaW, encodes the first step in the pathway. Amino acid sequences deduced from dmaW and homologs were submitted to phylogenetic analysis, and the results indicated that dmaW of Aspergillus fumigatus (mitosporic Trichocomaceae) has the same origin as corresponding genes from clavicipitaceous fungi. Relationships of authentic dmaW genes suggest that they originated from multiple gene duplications with subsequent losses of original or duplicate versions in some lineages. PMID:19812724

  10. 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

  11. Identification of QTLs for resistant starch and total alkaloid content in brown and polished rice.

    PubMed

    Zeng, Y W; Sun, D; Du, J; Pu, X Y; Yang, S M; Yang, X M; Yang, T; Yang, J Z

    2016-07-29

    An F3 population consisting of 117 F2:3 families derived from a cross between two varieties of rice, Gongmi No. 3 and Diantun 502, with a large difference in their resistant starch and total alkaloid content, was used for quantitative trait locus (QTL) mapping. Two QTLs of resistant starch for rice (qRS7-1, qRS7-2) were identified in a linkage group on chromosome 7, which could explain phenotypic variance from 7.6 to 17.3%, due to additive effects for resistant starch from Gongmi No. 3 or over-dominance effects for qRS7-2 of the marker interval (RM3404-RM478) on chromosome 7 from Gongmi No. 3, accounting for 13.8-17.3% of the phenotypic variance. Two QTLs of total alkaloids for brown rice (qALb7-1, qALb7-2) were identified in the same linkage group, which could explain phenotypic variance from 7.7 and 19.3%, respectively, due to dominance or over-dominance effects for total alkaloids on chromosome 7 from Diantun 502. To our knowledge, these are the first QTLs to be identified, which are related to resistant starch and total alkaloid content in rice. These results are beneficial for understanding the genetic basis of, as well as for developing markers linked with, resistant starch and total alkaloids of functional components for marker-assisted selection breeding in rice.

  12. Enhancement of alkaloid production in opium and California poppy by transactivation using heterologous regulatory factors.

    PubMed

    Apuya, Nestor R; Park, Joon-Hyun; Zhang, Liping; Ahyow, Maurice; Davidow, Patricia; Van Fleet, Jennifer; Rarang, Joel C; Hippley, Matthew; Johnson, Thomas W; Yoo, Hye-Dong; Trieu, Anthony; Krueger, Shannon; Wu, Chuan-yin; Lu, Yu-ping; Flavell, Richard B; Bobzin, Steven C

    2008-02-01

    Genes encoding regulatory factors isolated from Arabidopsis, soybean and corn have been screened to identify those that modulate the expression of genes encoding for enzymes involved in the biosynthesis of morphinan alkaloids in opium poppy (Papaver somniferum) and benzophenanthridine alkaloids in California poppy (Eschscholzia californica). In opium poppy, the over-expression of selected regulatory factors increased the levels of PsCOR (codeinone reductase), Ps4'OMT (S-adenosyl-l-methionine:3'-hydroxy-N-methylcoclaurine 4'-O-methyltransferase) and Ps6OMT [(R,S)-norcoclaurine 6-O-methyltransferase] transcripts by 10- to more than 100-fold. These transcriptional activations translated into an enhancement of alkaloid production in opium poppy of up to at least 10-fold. In California poppy, the transactivation effect of regulatory factor WRKY1 resulted in an increase of up to 60-fold in the level of EcCYP80B1 [(S)-N-methylcoclaurine 3'-hydroxylase] and EcBBE (berberine bridge enzyme) transcripts. As a result, the accumulations of selected alkaloid intermediates were enhanced up to 30-fold. The transactivation effects of other regulatory factors led to the accumulation of the same intermediates. These regulatory factors also led to the production of new alkaloids in California poppy callus culture. PMID:17961129

  13. 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.

  14. 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.

  15. Comparative Analysis of Amaryllidaceae Alkaloids from Three Lycoris Species.

    PubMed

    Tian, Yongqiang; Zhang, Chunyun; Guo, Mingquan

    2015-12-07

    The major active constituents from Amaryllidaceae family were reported to be Amaryllidaceae alkaloids (AAs), which exhibited a wide spectrum of biological activities, such as anti-tumor, anti-viral, and acetyl-cholinesterase-inhibitory activities. In order to better understand their potential as a source of bioactive AAs and the phytochemical variations among three different species of Lycoris herbs, the HPLC fingerprint profiles of Lycoris aurea (L. aurea), L. radiata, and L. guangxiensis were firstly determined and compared using LC-UV and LC-MS/MS. As a result, 39 peaks were resolved and identified as AAs, of which nine peaks were found in common for all these three species, while the other 30 peaks could be revealed as characteristic AAs for L. aurea, L. radiata and L. guangxiensis, respectively. Thus, these AAs can be used as chemical markers for the identification and quality control of these plant species. To further reveal correlations between chemical components and their pharmaceutical activities of these species at the molecular level, the bioactivities of the total AAs from the three plant species were also tested against HepG2 cells with the inhibitory rate at 78.02%, 84.91% and 66.81% for L. aurea, L. radiata and L. guangxiensis, respectively. This study firstly revealed that the three species under investigation were different not only in the types of AAs, but also in their contents, and both contributed to their pharmacological distinctions. To the best of our knowledge, the current research provides the most detailed phytochemical profiles of AAs in these species, and offers valuable information for future valuation and exploitation of these medicinal plants.

  16. Calcium antagonist properties of the bisbenzylisoquinoline alkaloid cycleanine.

    PubMed

    Martínez, J A; Bello, A; Rubio, L L; Rodríguez, C; Galán, L; Caudales, E; Alvarez, J L

    1998-01-01

    The alkaloid cycleanine ([12aR-(12aR,24aR)]-2,3,12a,13,14,15,24,24a-octa hydro-5,6,17,18- tetramethoxy-1,13-dimethyl-8, 11:20,23-dietheno-1H,12H [1,10]dioxacyclooctadecino[2,3,4-ij:11,12,13-i'j']diisoquinolin e) was extracted from the bulbs of Stephania glabra (Roxb) Miers and its effects on cardiac and smooth muscle preparations were studied and compared to those of nifedipine (1,4-dihydro-2, 6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine dicarboxylic acid dimethylesther). Cycleanine inhibited the KCl-induced contraction of rabbit aortic rings with higher potency than nifedipine. IC50s for cycleanine and nifedipine were 0.8 and 7.10(-9) M respectively. Cycleanine had minor effects on the norepinephrine-induced contraction of rabbit aortic rings. Cycleanine and nifedipine also depressed the contraction of rat ventricular preparations but with lower potency (IC50 = 3 and 0.03.10(-6) M respectively). Action potential duration of rat right ventricular strips was decreased by both compounds. L-type Ca-current (ICaL) of single rat ventricular cardiomyocytes was inhibited by cycleanine in a voltage- and frequency-dependent manner. With a higher potency nifedipine inhibited ICaL in a tonic and almost frequency-independent manner. The results suggest that cycleanine can act as a potent vascular selective Ca-antagonist. PMID:9565772

  17. In Vitro and In Vivo Characterization of the Alkaloid Nuciferine

    PubMed Central

    Farrell, Martilias S.; McCorvy, John D.; Huang, Xi-Ping; Urban, Daniel J.; White, Kate L.; Giguere, Patrick M.; Doak, Allison K.; Bernstein, Alison I.; Stout, Kristen A.; Park, Su Mi; Rodriguiz, Ramona M.; Gray, Bradley W.; Hyatt, William S.; Norwood, Andrew P.; Webster, Kevin A.; Gannon, Brenda M.; Miller, Gary W.; Porter, Joseph H.; Shoichet, Brian K.; Fantegrossi, William E.; Wetsel, William C.; Roth, Bryan L.

    2016-01-01

    Rationale The sacred lotus (Nelumbo nucifera) contains many phytochemicals and has a history of human use. To determine which compounds may be responsible for reported psychotropic effects, we used in silico predictions of the identified phytochemicals. Nuciferine, an alkaloid component of Nelumbo nucifera and Nymphaea caerulea, had a predicted molecular profile similar to antipsychotic compounds. Our study characterizes nuciferine using in vitro and in vivo pharmacological assays. Methods Nuciferine was first characterized in silico using the similarity ensemble approach, and was followed by further characterization and validation using the Psychoactive Drug Screening Program of the National Institute of Mental Health. Nuciferine was then tested in vivo in the head-twitch response, pre-pulse inhibition, hyperlocomotor activity, and drug discrimination paradigms. Results Nuciferine shares a receptor profile similar to aripiprazole-like antipsychotic drugs. Nuciferine was an antagonist at 5-HT2A, 5-HT2C, and 5-HT2B, an inverse agonist at 5-HT7, a partial agonist at D2, D5 and 5-HT6, an agonist at 5-HT1A and D4 receptors, and inhibited the dopamine transporter. In rodent models relevant to antipsychotic drug action, nuciferine blocked head-twitch responses and discriminative stimulus effects of a 5-HT2A agonist, substituted for clozapine discriminative stimulus, enhanced amphetamine induced locomotor activity, inhibited phencyclidine (PCP)-induced locomotor activity, and rescued PCP-induced disruption of prepulse inhibition without induction of catalepsy. Conclusions The molecular profile of nuciferine was similar but not identical to that shared with several approved antipsychotic drugs suggesting that nuciferine has atypical antipsychotic-like actions. PMID:26963248

  18. 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

  19. 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...

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

    PubMed

    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

  1. [Biosynthesis of poppy isoquinoline alkaloids in nature and in vitro culture. 1. Opium poppy (Papaver somniferum L.)].

    PubMed

    Kunakh, V A; Katsan, V A

    2003-01-01

    The analysis of literature data on production of isoquinoline alkaloids by Papaver somniferum L. plants and cell cultures has been made. The relationship of morphinane alkaloids biosynthesis with the processes of tissue and cell differentiation are discussed. The information on enzymes and pathways of regulation of morphine and sanguinarine biosynthesis are presented. The data on sanguinarine and morphine physiological role are analyzed.

  2. A reversed-phase HPLC-UV method developed and validated for simultaneous quantification of six alkaloids from Nicotiana spp.

    PubMed

    Moghbel, Nahid; Ryu, BoMi; Steadman, Kathryn J

    2015-08-01

    A reversed-phase HPLC-UV method was developed, optimized, and validated for the separation and quantitation of six target alkaloids from leaves of Nicotiana species (nicotine, nornicotine, anatabine, anabasine, myosmine, and cotinine). A bidentate reversed-phase C18 column was used as stationary phase and an alkaline ammonium formate buffer and acetonitrile as mobile phase. The alkaloids were well separated in a short run time of 13min with mobile phase pH 10.5 and a small gradient of 9-13% acetonitrile, and detected using UV at 260nm. Peak parameters were acceptable for all six closely related alkaloids. The proposed method has enough linearity with correlation coefficient >0.999 within the investigated range for all tested alkaloids. Satisfactory precision was achieved for both intra- and inter-day assay, with RSD less than 2% for all alkaloid standards. Reproducibility was also within the acceptable range of RSD <2%. Limit of detection was 1.6μg/mL for nicotine and below 1μg/mL for all other alkaloids. The limit of quantification was 2.8 and 4.8μg/mL for nornicotine and nicotine respectively, and below 2μg/mL for all other alkaloids. The method was successfully applied for simultaneous analysis of alkaloids in leaves of Nicotiana benthamiana.

  3. Alkaloid and phenolic compounds of Galanthus caucasicus, Magnolia obovata, Cocculus laurifolius, and Veratrum lobelianum grown in Georgia.

    PubMed

    Tsakadze, Dali M; Samsoniya, Shota A; Ziaev, Richsivoi; Abdusamatov, Abdulatip

    2005-01-01

    A collection of plants from the country of Georgia (Galanthus caucasicus, Magnolia obovata, Cocculus laurifolius, and Veratrum lobelianum) has been studied for their alkaloid content. Our studies led to the isolation and identification of 24 alkaloids, three of which are being identified and reported for the first time.

  4. Vasoconstrictive responses of the testicular and caudal arteries in bulls exposed to ergot alkaloids from tall fescue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Color Doppler ultasonography was used to evaluate vasoconstrictive responses of the testicular artery in yearling bulls to ergot alkaloids. Ergot alkaloid-induced constriction of the testicular artery could disrupt thermoregulation of the testes and reduce bull fertility. Luminal areas of the test...

  5. Cases of ergotism in livestock and associated ergot alkaloid concentrations in feed

    NASA Astrophysics Data System (ADS)

    Craig, A.; Klotz, James; Duringer, Jennifer

    2015-02-01

    Ergot-induced disease was known long before Biblical times and has been the root cause for countless human epidemics spanning from the early fourteenth century to the late sixteenth century. In contrast, many of these same ergot alkaloids have been utilized for their medicinal properties to mitigate migraine headaches and have had indications as anticarcinogens. Although ergot alkaloids have been used for centuries, basic pharmacokinetic data has not been documented for clinical disease. Consequently, a threshold dose and accurate dose-response data have yet to be established. Throughout the past several years, new detection techniques have emerged to detect these alkaloids at the parts per billion which have allowed for new efforts to be made with respect to determining threshold levels and making accurate clinical diagnoses. This perspectives article provides a critical initial step for establishing a uniform interpretation of ergot toxicosis from limited existing data.

  6. Alkaloid-Containing Plants Poisonous to Cattle and Horses in Europe

    PubMed Central

    Cortinovis, Cristina; Caloni, Francesca

    2015-01-01

    Alkaloids, nitrogen-containing secondary plant metabolites, are of major interest to veterinary toxicology because of their occurrence in plant species commonly involved in animal poisoning. Based on epidemiological data, the poisoning of cattle and horses by alkaloid-containing plants is a relatively common occurrence in Europe. Poisoning may occur when the plants contaminate hay or silage or when forage alternatives are unavailable. Cattle and horses are particularly at risk of poisoning by Colchicum autumnale (meadow saffron), Conium maculatum (poison hemlock), Datura stramonium (jimson weed), Equisetum palustre (marsh horsetail), Senecio spp. (ragwort and groundsel) and Taxus baccata (European yew). This review of poisonous alkaloid-containing plants describes the distribution of these plants, conditions under which poisoning occurs, active toxic principles involved and subsequent clinical signs observed. PMID:26670251

  7. Cytotoxic Guanidine Alkaloids from a French Polynesian Monanchora n. sp. Sponge.

    PubMed

    El-Demerdash, Amr; Moriou, Céline; Martin, Marie-Thérèse; Rodrigues-Stien, Alice de Souza; Petek, Sylvain; Demoy-Schneider, Marina; Hall, Kathryn; Hooper, John N A; Debitus, Cécile; Al-Mourabit, Ali

    2016-08-26

    Four bicyclic and three pentacyclic guanidine alkaloids (1-7) were isolated from a French Polynesian Monanchora n. sp. sponge, along with the known alkaloids monalidine A (8), enantiomers 9-11 of known natural product crambescins, and the known crambescidins 12-15. Structures were assigned by spectroscopic data interpretation. The relative and absolute configurations of the alkaloids were established by analysis of (1)H NMR and NOESY spectra and by circular dichroism analysis. The new norcrambescidic acid (7) corresponds to interesting biosynthetic variation within the pentacyclic core. All compounds exhibited antiproliferative and cytotoxic efficacy against KB, HCT116, HL60, MRC5, and B16F10 cancer cells, with IC50 values ranging from 4 nM to 10 μM. PMID:27419263

  8. Elucidating steroid alkaloid biosynthesis in Veratrum californicum: production of verazine in Sf9 cells.

    PubMed

    Augustin, Megan M; Ruzicka, Dan R; Shukla, Ashutosh K; Augustin, Jörg M; Starks, Courtney M; O'Neil-Johnson, Mark; McKain, Michael R; Evans, Bradley S; Barrett, Matt D; Smithson, Ann; Wong, Gane Ka-Shu; Deyholos, Michael K; Edger, Patrick P; Pires, J Chris; Leebens-Mack, James H; Mann, David A; Kutchan, Toni M

    2015-06-01

    Steroid alkaloids have been shown to elicit a wide range of pharmacological effects that include anticancer and antifungal activities. Understanding the biosynthesis of these molecules is essential to bioengineering for sustainable production. Herein, we investigate the biosynthetic pathway to cyclopamine, a steroid alkaloid that shows promising antineoplastic activities. Supply of cyclopamine is limited, as the current source is solely derived from wild collection of the plant Veratrum californicum. To elucidate the early stages of the pathway to cyclopamine, we interrogated a V. californicum RNA-seq dataset using the cyclopamine accumulation profile as a predefined model for gene expression with the pattern-matching algorithm Haystack. Refactoring candidate genes in Sf9 insect cells led to discovery of four enzymes that catalyze the first six steps in steroid alkaloid biosynthesis to produce verazine, a predicted precursor to cyclopamine. Three of the enzymes are cytochromes P450 while the fourth is a γ-aminobutyrate transaminase; together they produce verazine from cholesterol.

  9. Improved method for the determination of oxindole alkaloids in Uncaria tomentosa by high performance liquid chromatography.

    PubMed

    Ganzera, M; Muhammad, I; Khan, R A; Khan, I A

    2001-07-01

    This Paper describes an improved HPLC method for the determination of pentacyclic oxindole alkaloids in Uncaria tomentosa (Cat's Claw). Six of the isomeric compounds could be baseline separated at room temperature within less than 30 min by using 3 microm C-18 column material and a mobile phase consisting of 10 mM phosphate buffer at pH 7.0 and acetonitrile. At a wavelength of 245 nm all standard compounds could be detected at concentrations as low as 0.63 microg/ml. Different samples of U. tomentosa bark and market products containing Cat's Claw were extracted with a modified procedure ensuring the integrity of the alkaloids and analyzed successfully. The results indicated accuracy and consistency of the new method, and showed variations in the total alkaloid content in products from 0.156 to 0.962%.

  10. Pelianthinarubins A and B, Red Pyrroloquinoline Alkaloids from the Fruiting Bodies of the Mushroom Mycena pelianthina.

    PubMed

    Pulte, Anna; Wagner, Silke; Kogler, Herbert; Spiteller, Peter

    2016-04-22

    Pelianthinarubin A (1) and pelianthinarubin B (2), two previously unknown pyrroloquinoline alkaloids, have been isolated from fruiting bodies of Mycena pelianthina. The structures of these alkaloids have been deduced from their HR-(+)-ESIMS and 2D NMR data. The absolute configurations of the pelianthinarubins A (1) and B (2) were assigned by analysis of the NOE correlations and coupling constants and by comparison of the CD spectra of 1 and 2 and of hercynine obtained by degradation of 1 with suitable compounds of known absolute configuration. The pelianthinarubins A (1) and B (2), which contain an S-hercynine moiety, differ considerably from the known pyrroloquinoline alkaloids from marine organisms and other Mycena species, such as the mycenarubins, the haematopodins, and the sanguinones.

  11. Exposure to ergot alkaloids during gestation reduces fetal growth in sheep

    PubMed Central

    Duckett, Susan K.; Andrae, John G.; Pratt, Scott L.

    2014-01-01

    Tall fescue [Lolium arundinaceum (Schreb.) Darbysh; Schedonorus phoenix (Scop.) Holub] is the primary cool season perennial grass in the eastern U.S. Most tall fescue contains an endophyte (Neotyphodium coenophialum), which produces ergot alkaloids that cause vasoconstriction and could restrict blood flow to the fetus in pregnant animals. The objective of this study was to examine fetal growth during maternal exposure to ergot alkaloids during gestation. Pregnant ewes (n = 16) were randomly assigned to one of two dietary treatments: (1) endophyte-infected (N. coenophialum) tall fescue seed (E+; 0.8 ug of ergovaline /g diet DM) and (2) endophyte-free tall fescue seed (E−; 0.0 ug of ergovaline/g diet DM). Birth weight of lambs was reduced by 37% for E+ compared to E−. Organ and muscle weights were also lighter for E+ than E−. Exposure to ergot alkaloids in utero reduces fetal growth and muscle development. PMID:25191653

  12. Cases of ergotism in livestock and associated ergot alkaloid concentrations in feed

    PubMed Central

    Craig, A. Morrie; Klotz, James L.; Duringer, Jennifer M.

    2015-01-01

    Ergot-induced disease in humans was known long before Biblical times and has been the root cause for countless human epidemics spanning from the early fourteenth century to the late sixteenth century. In contrast, many of these same ergot alkaloids have been utilized for their medicinal properties to mitigate migraine headaches and have had indications as anti-carcinogens. Although ergot alkaloids have been used for centuries by humans, basic pharmacokinetic data has not been documented for clinical disease in livestock. Consequently, a threshold dose and accurate dose-response data have yet to be established. Throughout the past several years, new detection techniques have emerged to detect these alkaloids at the parts per billion (ppb) level which has allowed for new efforts to be made with respect to determining threshold levels and making accurate clinical diagnoses in affected animals. This perspectives article provides a critical initial step for establishing a uniform interpretation of ergot toxicosis from limited existing data. PMID:25741505

  13. Enantiospecific Synthesis and Biological Investigations of a Nuphar Alkaloid: Proposed Structure of a Castoreum Component

    PubMed Central

    Seki, Hajime; Georg, Gunda I.

    2014-01-01

    An enantiospecific synthesis of a Nuphar alkaloid was achieved in 9 steps from N-Boc-(L)-proline. The alkaloid is a minor component of castoreum, the dried scent glands of the beaver. During the course of our study, the stereochemistry of three synthetic intermediates was verified by X-ray analysis, which contributes to resolving existing discrepancies among the literature reports regarding the synthesis of this particular compound. Based on our synthesis, we propose the structure of the natural product. Also, intrigued by castoreum’s therapeutic effect, which was used in ancient Greece and Rome for gynecological and other purposes, biological screening was conducted. We found that the alkaloid has affinity for the oxytocin receptor. PMID:25395879

  14. Short-term toxicity studies of sanguinarine and of two alkaloid extracts of Sanguinaria canadensis L.

    PubMed

    Becci, P J; Schwartz, H; Barnes, H H; Southard, G L

    1987-01-01

    The short-term toxicity of sanguinarine, a benzophenanthridine alkaloid, and of two alkaloid extracts of Sanguinaria canadensis L. are presented. The acute oral LD50 in rats of sanguinarine was calculated to be 1658 mg/kg, and of the two alkaloid extracts, 1440 and 1250 mg/kg. The acute iv LD50 in rats of sanguinarine was found to be 29 mg/kg. No toxic effects were observed in rats fed up to 150 ppm sanguinarine in the diet for 14 d and in rats treated by gavage with up to 0.6 mg/kg body weight for 30 d. The acute dermal LD50 in rabbits was found to be greater than 200 mg/kg.

  15. Alkaloid-Containing Plants Poisonous to Cattle and Horses in Europe.

    PubMed

    Cortinovis, Cristina; Caloni, Francesca

    2015-12-01

    Alkaloids, nitrogen-containing secondary plant metabolites, are of major interest to veterinary toxicology because of their occurrence in plant species commonly involved in animal poisoning. Based on epidemiological data, the poisoning of cattle and horses by alkaloid-containing plants is a relatively common occurrence in Europe. Poisoning may occur when the plants contaminate hay or silage or when forage alternatives are unavailable. Cattle and horses are particularly at risk of poisoning by Colchicum autumnale (meadow saffron), Conium maculatum (poison hemlock), Datura stramonium (jimson weed), Equisetum palustre (marsh horsetail), Senecio spp. (ragwort and groundsel) and Taxus baccata (European yew). This review of poisonous alkaloid-containing plants describes the distribution of these plants, conditions under which poisoning occurs, active toxic principles involved and subsequent clinical signs observed. PMID:26670251

  16. Isolation of Cells Specialized in Anticancer Alkaloid Metabolism by Fluorescence-Activated Cell Sorting.

    PubMed

    Carqueijeiro, Inês; Guimarães, Ana Luísa; Bettencourt, Sara; Martínez-Cortés, Teresa; Guedes, Joana G; Gardner, Rui; Lopes, Telma; Andrade, Cláudia; Bispo, Cláudia; Martins, Nuno Pimpão; Andrade, Paula; Valentão, Patrícia; Valente, Inês M; Rodrigues, José A; Duarte, Patrícia; Sottomayor, Mariana

    2016-08-01

    Plant specialized metabolism often presents a complex cell-specific compartmentation essential to accomplish the biosynthesis of valuable plant natural products. Hence, the disclosure and potential manipulation of such pathways may depend on the capacity to isolate and characterize specific cell types. Catharanthus roseus is the source of several medicinal terpenoid indole alkaloids, including the low-level anticancer vinblastine and vincristine, for which the late biosynthetic steps occur in specialized mesophyll cells called idioblasts. Here, the optical, fluorescence, and alkaloid-accumulating properties of C. roseus leaf idioblasts are characterized, and a methodology for the isolation of idioblast protoplasts by fluorescence-activated cell sorting is established, taking advantage of the distinctive autofluorescence of these cells. This achievement represents a crucial step for the development of differential omic strategies leading to the identification of candidate genes putatively involved in the biosynthesis, pathway regulation, and transmembrane transport leading to the anticancer alkaloids from C. roseus. PMID:27356972

  17. Alkaloid-Containing Plants Poisonous to Cattle and Horses in Europe.

    PubMed

    Cortinovis, Cristina; Caloni, Francesca

    2015-12-08

    Alkaloids, nitrogen-containing secondary plant metabolites, are of major interest to veterinary toxicology because of their occurrence in plant species commonly involved in animal poisoning. Based on epidemiological data, the poisoning of cattle and horses by alkaloid-containing plants is a relatively common occurrence in Europe. Poisoning may occur when the plants contaminate hay or silage or when forage alternatives are unavailable. Cattle and horses are particularly at risk of poisoning by Colchicum autumnale (meadow saffron), Conium maculatum (poison hemlock), Datura stramonium (jimson weed), Equisetum palustre (marsh horsetail), Senecio spp. (ragwort and groundsel) and Taxus baccata (European yew). This review of poisonous alkaloid-containing plants describes the distribution of these plants, conditions under which poisoning occurs, active toxic principles involved and subsequent clinical signs observed.

  18. Exposure to Ergot Alkaloids During Gestation Reduces Fetal Growth in Sheep

    NASA Astrophysics Data System (ADS)

    Duckett, Susan; Pratt, Scott; Andrae, John

    2014-08-01

    Tall fescue [Lolium arundinaceum (Schreb.) Darbysh; Schedonorus phoenix (Scop.) Holub] is the primary cool season perennial grass in the eastern U.S. Most tall fescue contains an endophyte (Neotyphodium coenophialum), which produces ergot alkaloids that cause vasoconstriction and could restrict blood flow to the fetus in pregnant animals. The objective of this study was to examine fetal growth during maternal exposure to ergot alkaloids during gestation. Pregnant ewes (n = 16) were randomly assigned to one of two dietary treatments: 1) endophyte-infected (Neotyphodium coenophialum) tall fescue seed (E+; 0.8 ug of ergovaline /g diet DM) and 2) endophyte-free tall fescue seed (E-; 0.0 ug of ergovaline/g diet DM). Birth weight of lambs was reduced by 37% for E+ compared to E-. Organ and muscle weights were also lighter for E+ than E-. Exposure to ergot alkaloids in utero reduces fetal growth and muscle development.

  19. Study on the Alkaloids in Tibetan Medicine Aconitum pendulum Busch by HPLC-MSn Combined with Column Chromatography.

    PubMed

    Wang, Beibei; Dong, Jie; Ji, Jiaojiao; Yuan, Jiang; Wang, Jiali; Wu, Jiarui; Tan, Peng; Liu, Yonggang

    2016-01-01

    A rapid, convenient and effective identification method of alkaloids was established and an attempt on isolating and analyzing the alkaloids in Aconitum pendulum Busch was conducted successfully. In this article, four high-content components including deoxyaconitine, benzoylaconine, aconine and neoline were isolated by using column chromatography. HPLC-MS(n)was employed to deduce the regulations of fragmentation of diterpenoid alkaloids which displayed a characteristic behavior of loss of CO(28u), CH3COOH(60u), CH3OH(32u), H2O(18u) and C6H5COOH(122u). Then, according to fragmentation regulation of mass spectrometry, 42 alkaloids were found inA. pendulum Among them, 38 compounds were identified and 29 alkaloids were reported for the first time for this herb. Therefore, this means that HPLC-MS(n)combined with column chromatography could work as an effective and reliable tool for rapid identification of the chemical components of herbal medicine.

  20. The orientation of protoberberine alkaloids and their binding activities to human serum albumin by surface-enhanced Raman scattering

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Zhao, Yu; Bai, Xueyuan; Wang, Yingping; Zhao, Daqing

    2011-03-01

    Raman and surface-enhanced Raman scattering (SERS) technique are reliably used to compare relative intensity shifts and to investigate the adsorption geometry of protoberberine alkaloids on Ag nanoparticles. We report joint application of fluorescence and SERS spectroscopy to study the interaction between protoberberine alkaloids and human serum albumin (HSA). We propose SERS technique to improve the quenching interaction caused by protoberberine alkaloids which are used to be applied in recognition process of fluorescent drugs with large biomolecules. The fluorescence results show that the fluorescence intensity of HSA is significantly decreased in presence of protoberberine alkaloids. The SERS technique demonstrates obvious advantages over direct measurements in discriminating and identifying pharmaceutical molecules. By means of this method, we are able to detect important information concerning the orientation of protoberberine alkaloids when interacting with HSA. We also show that the nitrogen atom is free, but a benzene ring and two adjacent methoxy groups are involved in the spontaneously electrostatic inducement and subsequently binding with HSA.