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Sample records for 275i major alkaloids

  1. 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

  2. UPLC Separation and QTof–MS Identification of Major Alkaloids in Plumula Nelumbinis

    PubMed Central

    Lin, Zongtao; Yang, Ruinan; Guan, Zheng; Chen, Ailiang; Li, Wei

    2016-01-01

    Introduction As an essential medicine and tea source in many countries, Plumula Nelumbinis potentially exerts its major biological activities through its alkaloids. However, its activities are not fully understood due to the lack of studies on its chemical components. Objective To establish an Ultra Performance Liquid Chromatography–Diode-Array Detector (UPLC–DAD) method, combined with an Electrospray Ionization–Quadrupole Time-of-flight Mass Spectrometry (ESI–QTof MS), for the separation and identification of Plumula Nelumbinis alkaloids. Methods The eluant from an UPLC separation of an ethanol extract of Plumula Nelumbinis was directly infused into an ESI–QTof MS system. Both positive and negative ion modes of ESI with low and high Collision Energy (CE) were used to obtain sufficient MS information. Results 21 alkaloids were tentatively identified based on their chromatographic characteristics, UV spectra, exact mass, MS fragments, and literature reports. They consist of 6 bis-1-benzyltetrahydroisoquinoline, 11 benzyltetrahydroisoquinoline (containing 2 glycoalkaloids and 2 quaternary ammoniums), 2 aporphine, one proaporphine, and one indole alkaloids. Eleven were identified in Plumula Nelumbinis for the first time and 7 were firstly reported in Nelumbo nucifera Gaertn. Five compounds, namely norcoclaurine-4′-O-glucoside, norcoclaurine-6-O-glucoside, isolotusine, 6-demethyl-4′-methyl-N-methylcoclaurine and N-norisoliensinine, were characterized and proposed as new compounds. Conclusion The established UPLC–DAD–ESI–QTof–MS method is efficient for systematic identification of the alkaloids in Plumula Nelumbinis extract. PMID:24733684

  3. 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.

  4. [Alkaloids of Pausinystalia macroceras].

    PubMed

    Leboef, M; Cavé, A; Mangeney, P; Bouquet, A

    1981-04-01

    A study of the alkaloidal content of trunk-barks of Pausinystalia macroceras (K. Schum.) Pierre, Rubiaceae, resulted in the isolation of six alkaloids, five of which are indole alkaloids that belong to the yohimbane and heteroyohimbane groups; among them, yohimbine was found in major amount. Moreover, the levorotatory isomer of calycanthine, a quinoline dimeric tryptophane derived base, has been isolated for the first time. The phytochemical significance of calycanthine and related alkaloids is discussed.

  5. Relationship between the endophyte embellisia spp. and the toxic alkaloid swainsonine in major locoweed species (Astragalus and Oxytropis)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Locoweeds (Astragalus and Oxytropis spp. which contain the toxic alkaloid swainsonine) cause widespread poisoning of livestock on western rangelands. There are 354 species of Astragalus and 22 species of Oxytropis in the US and Canada. Recently a fungal endophyte, Embellisia spp., was isolated fro...

  6. Rapid quantification of four major bioactive alkaloids in Corydalis decumbens (Thunb.) Pers. by pressurised liquid extraction combined with liquid chromatography-triple quadrupole linear ion trap mass spectrometry.

    PubMed

    Shen, Yan; Han, Chao; Jiang, Yongxiang; Zhou, Xiujin; Zhu, Zhenou; Lei, Xinxiang

    2011-05-30

    A new method based on pressurised liquid extraction (PLE) followed by liquid chromatography-triple quadrupole linear ion trap mass spectrometry (LC-QTrap-MS) analysis has been developed for the identification and quantification of four major alkaloids in extracts of Corydalis decumbens (Thunb.) Pers. PLE extractions were performed using 90% ethanol; temperature was set at 100°C and pressure at 1500 psi. HPLC analysis was performed on a Waters XBridge™ C(18) column (150 mm × 2.1mm i.d., 3.5 μm) eluted by a mobile phase of acetonitrile and 0.2% acetic acid. Data acquisition was carried out in multiple reaction monitoring transitions (MRMs) mode, monitoring two MRM transitions to ensure an accurate identification of target compounds in the samples. Additional identification and confirmation of target compounds were performed using the enhanced product ion modus (EPI) of the linear ion trap. The novel LC-QTrap-MS platform offers the best sensitivity and specificity for characterization and quantitative determination of the four alkaloids in C. decumbens (Thunb.) Pers. and fulfils the quality criteria for routine laboratory application.

  7. Inhibition of Na(+),K(+)-ATPase by the extract of Stephania cephararantha HAYATA and bisbenzylisoquinoline alkaloid cycleanine, a major constituent.

    PubMed

    Satoh, Kanako; Nagai, Fumiko; Ono, Minoru; Aoki, Naoto

    2003-08-01

    The Stephania cephararantha HAYATA extract, and its constituent bisbenzylisoquinoline alkaloids, such as cycleanine, cepharanthine, isotetrandrine, berbamine, homoaromoline, and cepharanoline were studied for effects on Na(+),K(+)-ATPase activity. The S. cephararantha HAYATA extract inhibited Na(+),K(+)-ATPase activity with an apparent IC(50) value of 540 microg/mL. Cycleanine markedly inhibited Na(+),K(+)-ATPase activity with an IC(50) value of 6.2 x 10(-4)M. It slightly inhibited Mg(2+)-ATPase, H(+)-ATPase, and Ca(2+)-ATPase. No effects on alkaline and acid phosphatase activities were observed. The inhibition by isotetrandrine, homoaromoline, cepharanthine, and berbamine was less marked, and cepharanoline showed no effect. Five synthetic analogues of cepharanthine slightly inhibited the activity. The mechanism of inhibition by cycleanine on Na(+),K(+)-ATPase activity was examined in detail, and the following results were obtained in the overall reaction: (1) the mode of inhibition was noncompetitive with respect to ATP; (2) the degree of inhibition was decreased with a decrease of K(+) concentration; (3) it was not affected by Na(+) concentration; (4) the inhibition mechanism was different from that of ouabain. The activity of K(+)-dependent p-nitrophenyl phosphatase, a partial reaction of Na(+),K(+)-ATPase, did not appear to have been inhibited by cycleanine in the reaction mixture containing 15 mM K(+) (optimum condition). However, cycleanine increased the K(0.5) value for K(+) and reduced the K(i) values for Na(+) and ATP, in K(+)-dependent p-nitrophenyl phosphatase. Cycleanine might interact with the enzyme in Na.E(1)-P form and prevents the reaction step from Na.E(1)-P to E(2)-P.

  8. 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

  9. Analysis of Ergot Alkaloids.

    PubMed

    Crews, Colin

    2015-06-03

    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.

  10. Genetic variation in alkaloid accumulation in leaves of Nicotiana.

    PubMed

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

    2013-12-01

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

  11. Arecoline, a major alkaloid of areca nut, inhibits p53, represses DNA repair, and triggers DNA damage response in human epithelial cells.

    PubMed

    Tsai, Yi-Shan; Lee, Ka-Wo; Huang, Jau-Ling; Liu, Yu-Sen; Juo, Suh-Hang Hank; Kuo, Wen-Rei; Chang, Jan-Gowth; Lin, Chang-Shen; Jong, Yuh-Jyh

    2008-07-30

    The International Agency for Research on Cancer declared that areca nut was carcinogenic to human. Areca nut is the main component of betel quid (BQ), which is commonly consumed in Asia. Epidemiological studies have shown that BQ chewing is a predominant risk factor for oral and pharyngeal cancers. It has been known that areca nut is genotoxic to human epithelial cells. However, the molecular and cellular mechanisms underlying areca nut-associated genotoxicity are not fully understood. Here we showed that arecoline, a major alkaloid of areca nut, might contribute to oral carcinogenesis through inhibiting p53 and DNA repair. We found, on the biological aspect, that arecoline could induce gamma-H2AX phosphorylation, a sensitive DNA damage marker, in KB, HEp-2, and 293 cells, suggesting that DNA damages were elicited by arecoline. This phenomenon was supported by the observations of arecoline-induced hyperphosphorylation of ATM, Nbs1, Chk1/2, p53, and Cdc25C, as well as G2/M cell cycle arrest, indicating that a cellular DNA damage response was activated. To explore the possible mechanism accounting for arecoline-elicited DNA damages, we found that arecoline could inhibit p53 by its expression and transactivation function. As a result, the expression of p53-regulated p21(WAF1) and the p53-activated DNA repair were repressed by arecoline. Finally, we showed that p53 mRNA transcripts were frequently down-regulated in BQ-associated oral cancer, suggesting that arecoline-mediated p53 inhibition might play a role in BQ-associated tumorigenesis.

  12. Alkaloids in Marine Algae

    PubMed Central

    Güven, Kasım Cemal; Percot, Aline; Sezik, Ekrem

    2010-01-01

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

  13. 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.

  14. Amaryllidaceae and Sceletium alkaloids.

    PubMed

    Jin, Zhong

    2009-03-01

    Alkaloids from the plants of Amaryllidaceae family consists of an unique class of nitrogen-containing compounds showing diverse and significant biological activities, including anticancer and acetylcholinesterase (AChE) inhibitory activities. This review summarizes the research into the isolation, structure elucidation, biological activity, and chemical aspects of the Amaryllidaceae alkaloids over the last two years. In addition, structurally closely related Sceletium alkaloids are also discussed.

  15. 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.

  16. Alkaloids from Menispermum dauricum.

    PubMed

    Yu, Bing-Wu; Chen, Jian-Yong; Wang, Yan-Ping; Cheng, Kin-Fin; Li, Xiao-Yu; Qin, Guo-Wei

    2002-10-01

    The alkaloids, dechloroacutumidine and 1-epidechloroacutumine, together with three known alkaloids, acutumidine, acutumine, and dechloroacutumine, were isolated from the rhizomes of Menispermum dauricum and their structures established by spectral and chemical methods. The cytotoxicity of each compound against the growth of human cell lines was studied, and acutumine selectively inhibited T-cell growth.

  17. 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.

  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. Alkaloids from Esenbeckia pilocarpoides.

    PubMed

    Bevalot, F; Fournet, A; Moretti, C; Vaquette, J

    1984-12-01

    A preliminary screening showed the occurrence of alkaloids only in root bark and roots of ESENBECKIA PILOCARPOIDES H. B. K., (Rutaceae). Six alkaloids have been isolated and identified from root bark: one acridone, 1-hydroxy-3-methoxy- N-methyl-acridone; four furoquinolines, maculine, flindersiamine, kokusaginine, kokusagine; the sixth, isomaculine, a furo-4-quinolone, known as a synthetic product, has been isolated for the first time from a natural source.

  20. Marine Indole Alkaloids

    PubMed Central

    Netz, Natalie; Opatz, Till

    2015-01-01

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

  1. 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.

  2. 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.

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

    PubMed

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

    1983-08-01

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

  4. Cytotoxicity of Hymenocallis expansa alkaloids.

    PubMed

    Antoun, M D; Mendoza, N T; Ríos, Y R; Proctor, G R; Wickramaratne, D B; Pezzuto, J M; Kinghorn, A D

    1993-08-01

    From the bulbs and leaves of Hymenocallis expansa (Amaryllidaceae), three alkaloid constituents were identified: (+)-tazettine, (+)-hippeastrine, and (-)-haemanthidine. These alkaloids demonstrated significant cytotoxicity when tested against a panel of human and murine tumor cell lines.

  5. Alkaloids from Hippeastrum papilio.

    PubMed

    de Andrade, Jean Paulo; Berkov, Strahil; Viladomat, Francesc; Codina, Carles; Zuanazzi, José Angelo S; Bastida, Jaume

    2011-08-18

    Galanthamine, an acetylcholinesterase inhibitor marketed as a hydrobromide salt (Razadyne®, Reminyl®) for the treatment of Alzheimer's disease (AD), is obtained from Amaryllidaceae plants, especially those belonging to the genera Leucojum, Narcissus, Lycoris and Ungernia. The growing demand for galanthamine has prompted searches for new sources of this compound, as well as other bioactive alkaloids for the treatment of AD. In this paper we report the isolation of the new alkaloid 11β-hydroxygalanthamine, an epimer of the previously isolated alkaloid habranthine, which was identified using NMR techniques. It has been shown that 11β-hydroxygalanthamine has an important in vitro acetylcholinesterase inhibitory activity. Additionally, Hippeastrum papilio yielded substantial quantities of galanthamine.

  6. [A new alkaloid from Menispermum dauricum DC--N-desmethyldauricine].

    PubMed

    Pan, X P

    1992-01-01

    A new phenolic dauricine-type alkaloid together with the know dauricine were isolated from the rhizoma of Menispermum dauricum DC cultivated in Xianning district, Hubei province. Dauricine was obtained as the major alkaloid and was confirmed by comparison with authentic sample. The new alkaloid is an unstable white powder: Based on spectrometric analysis (UV, IR, FAB-MS and 1HNMR) and N-methylation which offered dauricine dimethiodide (V), the structure was elucidated as RR, N-desmethyldauricine (II), which was isolated for the first time from nature.

  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. 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

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

    PubMed Central

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

    2004-01-01

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

  10. Indole alkaloids from Geissospermum reticulatum.

    PubMed

    Reina, M; Ruiz-Mesia, W; López-Rodríguez, M; Ruiz-Mesia, L; González-Coloma, A; Martínez-Díaz, R

    2012-05-25

    Ten indole alkaloids were isolated from Geissospermum reticulatum, seven (1-7) from the leaves and three (8-10) from the bark. Seven were aspidospermatan-type alkaloids (1-3, 5-9), including four (5-8) with a 1-oxa-3-cyclopentene group in their molecule, which we named geissospermidine subtype. Compounds 1-3, 5-8, and 10 had not been reported previously as natural products, while 4 and 9 were the known alkaloids O-demethylaspidospermine and flavopereirine. Their structures were determined by spectroscopic techniques including 1D and 2D NMR experiments (COSY, NOESY, HSQC, HMBC). Additionally, X-ray crystallographic analyses of 1, 2, and 6 were performed. Antiparasitic activities of the ethanolic and alkaloidal extracts and of the pure alkaloids were tested against Trypanosoma cruzi and Leishmania infantum. In general, the extracts exhibited selective action and were more active against Leishmania than against Trypanosoma. Alkaloid 4 was also very active against L. infantum.

  11. 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.

  12. Quinoline alkaloids from Acronychia laurifolia.

    PubMed

    Cui, B; Chai, H; Dong, Y; Horgen, F D; Hansen, B; Madulid, D A; Soejarto, D D; Farnsworth, N R; Cordell, G A; Pezzuto, J M; Kinghorn, A D

    1999-09-01

    Bioassay-directed fractionation of a root extract of Acronychia laurifolia (Rutaceae) using the KB-V1+ human tumor cell line led to the isolation of six quinoline alkaloids. One of these alkaloids is novel, namely, 2,3-methylenedioxy-4,7-dimethoxyquinoline and the other five were identified as the known compounds, evolitrine, gamma-fagarine, skimmianine, kokusaginine and maculosidine. Two known bis-tetrahydrofuran lignans, sesamolin and yangambin, were also identified. The structure of the new alkaloid was determined by spectroscopic methods. All of the isolates were evaluated against a panel of human cancer cell lines; four of the alkaloids showed weak cytotoxic activity.

  13. 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.

  14. Comparative study of fourteen alkaloids from Uncaria rhynchophylla hooks and leaves using HPLC-diode array detection-atmospheric pressure chemical ionization/MS method.

    PubMed

    Qu, Jialin; Gong, Tianxing; Ma, Bin; Zhang, Lin; Kano, Yoshihiro; Yuan, Dan

    2012-01-01

    The purpose of the study is to compare alkaloid profile of Uncaria rhynchophylla hooks and leaves. Ten oxindole alkaloids and four glycosidic indole alkaloids were identified using HPLC-diode array detection (DAD) or LC-atmospheric pressure chemical ionization (APCI)-MS method, and a HPLC-UV method for simultaneous quantification of major alkaloids was validated. The hooks are characterized by high levels of four oxindole alkaloids rhynchophylline (R), isorhynchophylline (IR), corynoxeine (C) and isocorynoxeine (IC), while the leaves contained high level of two glycosidic indole alkaloids vincoside lactam (VL) and strictosidine (S). The presented methods have proven its usefulness in chemical characterization of U. rhynchophylla hooks and leaves.

  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. Identification, occurrence and activity of quinazoline alkaloids in Peganum harmala.

    PubMed

    Herraiz, Tomás; Guillén, Hugo; Arán, Vicente J; Salgado, Antonio

    2017-05-01

    Peganum harmala L. is a medicinal plant from the Mediterranean region and Asia currently used for recreative psychoactive purposes (Ayahuasca analogue), and increasingly involved in toxic cases. Its psychopharmacological and toxicological properties are attributed to quinazoline and β-carboline alkaloids. In this work three major quinazoline alkaloids were isolated from P. harmala extracts and characterized as peganine (vasicine), deoxypeganine (deoxyvasicine) and a novel compound identified by HPLC-DAD-MS and NMR as peganine β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranoside (peganine glycoside). Peganine appeared in flowers and leaves in high levels; high amounts of deoxypeganine and peganine were found in immature and green fruits whereas peganine and peganine glycoside accumulated in high amount in dry seeds reaching up to 1 and 3.9% (w/w), respectively. Roots and stems contained low amount of quinazolines. Seeds extracts containing both quinazoline and β-carboline alkaloids potently inhibited human monoamine oxidase (MAO)-A. However, quinazoline alkaloids did not contribute to MAO inhibition that was due to β-carbolines, suggesting that MAO-related psychoactive or toxic actions do not arise from quinazolines. Quinazoline alkaloids were poor radical scavengers in the ABTS assay whereas seed extracts had good activity. Quinazoline alkaloids are known to exert bronchodilator and abortifacient actions, and could contribute to such effects reported in P. harmala.

  17. Molecular genetics of alkaloid biosynthesis in Nicotiana tabacum.

    PubMed

    Dewey, Ralph E; Xie, Jiahua

    2013-10-01

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

  18. Cellular distribution of alkaloids and their translocation via phloem and xylem: the importance of compartment pH.

    PubMed

    Nowak, M; Selmar, D

    2016-11-01

    The physico-chemical background of alkaloid allocation within plants is outlined and discussed exemplarily for pyrrolizidine alkaloids (PAs) and nicotine. The trigger for this discourse is the finding that, for example, PAs, which are taken up from the soil, are translocated in the xylem, whereas - when genuinely present in plants - they are allocated as N-oxides via phloem. Special emphasis is put on the impact of different pH values in certain compartments, as this entails significant changes in the relative lipophilic character of alkaloids: tertiary alkaloids diffuse readily through biomembranes, while the corresponding protonated alkaloids are retained in acidic compartments, i.e. vacuoles or xylem. Therefore, this phenomenon, well known as the 'ion trap mechanism', is also relevant for long-distance transport of alkaloids. Any efficient allocation of typical tertiary alkaloids within the phloem can thus be excluded. In contrast, due to their strongly increased hydrophilic properties, alkaloid-N-oxides or quarternary alkaloids cannot diffuse through biomembranes and, consequently, would be retained in the acidic xylem during translocation. The major aim of this paper is to sharpen the mind for the chemical peculiarities of alkaloids and to consider them adequately in forthcoming investigations on allocation of alkaloids.

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

    PubMed

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

    2016-01-18

    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.

  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. 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.

  2. Transcription factors in alkaloid biosynthesis.

    PubMed

    Yamada, Yasuyuki; Sato, Fumihiko

    2013-01-01

    Higher plants produce a large variety of low-molecular weight secondary compounds. Among them, nitrogen-containing alkaloids are the most biologically active and are often used pharmaceutically. Whereas alkaloid chemistry has been intensively investigated, alkaloid biosynthesis, including the relevant biosynthetic enzymes, genes and their regulation, and especially transcription factors, is largely unknown, as only a limited number of plant species produce certain types of alkaloids and they are difficult to study. Recently, however, several groups have succeeded in isolating the transcription factors that are involved in the biosynthesis of several types of alkaloids, including bHLH, ERF, and WRKY. Most of them show Jasmonate (JA) responsiveness, which suggests that the JA signaling cascade plays an important role in alkaloid biosynthesis. Here, we summarize the types and functions of transcription factors that have been isolated in alkaloid biosynthesis, and characterize their similarities and differences compared to those in other secondary metabolite pathways, such as phenylpropanoid and terpenoid biosyntheses. The evolution of this biosynthetic pathway and regulatory network, as well as the application of these transcription factors to metabolic engineering, is discussed.

  3. 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

  4. 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.

  5. Nonaqueous CE ESI-IT-MS analysis of Amaryllidaceae alkaloids.

    PubMed

    Zhang, Yulin; Chen, Zilin

    2013-03-01

    The Amaryllidaceae are widely distributed medical plants. Lycorine, lycoramine, lycoremine, and lycobetaine are the major active alkaloids in Amaryllidaceae plants. A nonaqueous CE ESI-IT-MS method for separation, identification, and quantification of the Amaryllidaceae alkaloids has been developed. The MS(1-3) behavior has been studied and the fragmentation pathways of main fragment ions have been proposed. The effects of several factors such as composition and concentration of buffer, applied voltage, composition, and flow rate of the sheath liquid, nebulizing gas pressure, flow rate, and temperature of drying gas were investigated. Under the optimal conditions, the linear concentration range of these compounds was wide with the correlation coefficient (R(2) ) >0.99. RSDs of migration time and peak areas were <10%. The LODs were <240 ng/mL. The proposed method can be successfully applied to the determination of the related alkaloids in the Lycoris radiata roots.

  6. Newly discovered ergot alkaloids in Sorghum ergot Claviceps africana occurring for the first time in Israel.

    PubMed

    Shimshoni, J A; Cuneah, O; Sulyok, M; Krska, R; Sionov, E; Barel, S; Meller Harel, Y

    2017-03-15

    Sorghum ergot is a disease caused commonly by C. africana. In 2015, ergot was identified for the first time in sorghum fields in Israel, leading to measures of eradication and quarantine. The aims of the study were to identify the ergot species by molecular and ergot alkaloid profile analysis, to determine the ergot alkaloid profile in pure honeydew and in infected sorghum silages and to estimate the safety of sorghum silages as a feed source. C. africana was rapidly and reliably identified by microscopical and molecular analysis. Dihydroergosine was identified as the major ergot alkaloid. Dihydrolysergol and dihydroergotamine were identified for the first time as significant ergot alkaloid components within the C. africana sclerotia, thereby providing for the first time a proof for the natural occurrence of dihydroergotamine. The sorghum silages were found to be safe for feed consumption, since the ergot alkaloids and the regulated mycotoxins were below their regulated limits.

  7. The use of genomics and metabolomics methods to quantify fungal endosymbionts and alkaloids in grasses.

    PubMed

    Rasmussen, Susanne; Lane, Geoffrey A; Mace, Wade; Parsons, Anthony J; Fraser, Karl; Xue, Hong

    2012-01-01

    The association of plants with endosymbiotic micro-organisms poses a particular challenge to metabolomics studies. The presence of endosymbionts can alter metabolic profiles of plant tissues by introducing non-plant metabolites such as fungal specific alkaloids, and by metabolic interactions between the two organisms. An accurate quantification of the endosymbiont and its metabolites is therefore critical for studies of interactions between the two symbionts and the environment.Here, we describe methods that allow the quantification of the ryegrass Neotyphodium lolii fungal endosymbiont and major alkaloids in its host plant Lolium perenne. Fungal concentrations were quantified in total genomic DNA (gDNA) isolated from infected plant tissues by quantitative PCR (qPCR) using primers specific for chitinase A from N. lolii. To quantify the fungal alkaloids, we describe LC-MS based methods which provide coverage of a wide range of alkaloids of the indolediterpene and ergot alkaloid classes, together with peramine.

  8. 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.

  9. 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...

  10. 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...

  11. 27 CFR 21.99 - Brucine alkaloid.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Brucine alkaloid. 21.99... Brucine alkaloid. (a) Identification test. Add a few drops of concentrated nitric acid to about 10 mg of brucine alkaloid. A vivid red color is produced. Dilute the red solution with a few drops of water and...

  12. 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...

  13. 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...

  14. Tissue distribution and biosynthesis of 1,2-saturated pyrrolizidine alkaloids in Phalaenopsis hybrids (Orchidaceae).

    PubMed

    Frölich, Cordula; Hartmann, Thomas; Ober, Dietrich

    2006-07-01

    Phalaenopsis hybrids contain two 1,2-saturated pyrrolizidine monoesters, T-phalaenopsine (necine base trachelanthamidine) and its stereoisomer Is-phalaenopsine (necine base isoretronecanol). T-Phalaenopsine is the major alkaloid accounting for more than 90% of total alkaloid. About equal amounts of alkaloid were genuinely present as free base and its N-oxide. The structures were confirmed by GC-MS. The quantitative distribution of phalaenopsine in various organs and tissues of vegetative rosette plants and flowering plants revealed alkaloid in all tissues. The highest concentrations were found in young and developing tissues (e.g., root tips and young leaves), peripheral tissues (e.g., of flower stalks) and reproductive organs (flower buds and flowers). Within flowers, parts that usually attract insect visitors (e.g., labellum with colorful crests as well as column and pollinia) show the highest alkaloid levels. Tracer feeding experiments with (14)C-labeled putrecine revealed that in rosette plants the aerial roots were the sites of phalaenopsine biosynthesis. However active biosynthesis was only observed in roots still attached to the plant but not in excised roots. There is a slow but substantial translocation of newly synthesized alkaloid from the roots to other plant organs. A long-term tracer experiment revealed that phalaenopsine shows neither turnover nor degradation. The results are discussed in the context of a polyphyletic molecular origin of the biosynthetic pathways of pyrrolizidine alkaloids in various scattered angiosperm taxa. The ecological role of the so called non-toxic 1,2-saturated pyrrolizidine alkaloids is discussed in comparison to the pro-toxic 1,2-unsaturated pyrrolizidine alkaloids. Evidence from the plant-insect interphase is presented indicating a substantial role of the 1,2-saturated alkaloids in plant and insect defense.

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

    PubMed

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

    2015-08-01

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

  16. Hypolipidemic Effects of Alkaloids from Rhizoma Coptidis in Diet-Induced Hyperlipidemic Hamsters.

    PubMed

    He, Kai; Kou, Shuming; Zou, Zongyao; Hu, Yinran; Feng, Min; Han, Bing; Li, Xuegang; Ye, Xiaoli

    2016-05-01

    This study was conducted to evaluate the antihyperlipidemic activity of five major alkaloids in Rhizoma Coptidis using high-fat- and high-cholesterol-induced hyperlipidemic hamsters. Hyperlipidemic hamsters were treated with coptisine, berberine, jatrorrhizine, palmatine, epiberberine, and total Rhizoma Coptidis alkaloids with a dose of 46.7 mg/kg × day for 140 days. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids were examined after alkaloid treatment. The results showed that all therapy agents prevented body weight gain, reduced the serum total cholesterol, and increased the high-density lipoprotein cholesterol of hamsters. Berberine, jatrorrhizine, and total Rhizoma Coptidis alkaloids decreased the triglyceride level in hyperlipidemic hamsters, while coptisine, jatrorrhizine, palmatine, and total Rhizoma Coptidis alkaloids significantly suppressed the elevation of the low-density lipoprotein cholesterol level. The fecal excretion of bile acids was significantly elevated by berberine, coptisine, jatrorrhizine, palmatine, total Rhizoma Coptidis alkaloids, and orlistat. Notably, total Rhizoma Coptidis alkaloids possess a much stronger lipid-lowering effect than the pure Rhizoma Coptidis alkaloids. Quantitative reverse transcription-polymerase chain reaction analyses revealed that Rhizoma Coptidis alkaloids could retard the synthesis of cholesterol by downregulating the mRNA expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase and accelerate the clearance of lipids by upregulating the low-density lipoprotein receptor, cholesterol 7α-hydroxylase, and uncoupling protein-2 expression. These findings highlight the critical role of Rhizoma Coptidis alkaloids in hyperlipidemia treatment. Thus, they need to be considered in future therapeutic approaches.

  17. 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

  18. 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).

  19. Alkaloids with antioxidant activities from Aconitum handelianum.

    PubMed

    Yin, Tian-Peng; Cai, Le; Xing, Yun; Yu, Jing; Li, Xue-Jiao; Mei, Rui-Feng; Ding, Zhong-Tao

    2016-06-01

    A new C20-diterpenoid alkaloid handelidine (1) and twenty-seven known alkaloids (2-28) were isolated from the roots of Aconitum handelianum. Their structures were established on the basis of extensive spectroscopic analyses. The study indicated that denudatine-type C20-diterpenoid alkaloids with vicinal-triol system and benzyltetrahydroisoquinoline alkaloids exhibited significant antioxidant activities measured by three antioxidant test systems. The aconitine-type C19-diterpenoid alkaloids could serve as potential secondary antioxidants for their strong binding effects to metal ions.

  20. 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.

  1. 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.

  2. The Catharanthus alkaloids: pharmacognosy and biotechnology.

    PubMed

    van Der Heijden, Robert; Jacobs, Denise I; Snoeijer, Wim; Hallard, Didier; Verpoorte, Robert

    2004-03-01

    The Catharanthus (or Vinca) alkaloids comprise a group of about 130 terpenoid indole alkaloids. Vinblastine is now marketed for more than 40 years as an anticancer drug and became a true lead compound for drug development. Due to the pharmaceutical importance and the low content in the plant of vinblastine and the related alkaloid vincristine, Catharanthus roseus became one of the best-studied medicinal plants. Consequently it developed as a model system for biotechnological studies on plant secondary metabolism. The aim of this review is to acquaint a broader audience with the recent progress in this research and with its exciting perspectives. The pharmacognostical aspects of the Catharanthus alkaloids cover botanical (including some historical), phytochemical and analytical data. An up-to-date view on the biosynthesis of the alkaloids is given. The pharmacological aspects of these alkaloids and their semi-synthetic derivatives are only discussed briefly. The biotechnological part focuses on alternative production systems for these alkaloids, for example by in vitro culture of C. roseus cells. Subsequently it will be discussed to what extent the alkaloid biosynthetic pathway can be manipulated genetically ("metabolic engineering"), aiming at higher production levels of the alkaloids. Another approach is to produce the alkaloids (or their precursors) in other organisms such as yeast. Despite the availability of only a limited number of biosynthetic genes, the research on C. roseus has already led to a broad scientific spin-off. It is clear that many interesting results can be expected when more genes become available.

  3. Ergot alkaloid transport across ruminant gastric tissues.

    PubMed

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

    2001-02-01

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

  4. Alkaloids from Hippeastrum equestre. Part I. Phamine, a new phenanthridone alkaloid.

    PubMed

    Döpke, W; Pham, L H; Gründemann, E; Bartoszek, M; Flatau, S

    1995-12-01

    From the bulbs of Vietnamese Hippeastrum equestre Herb. (Amaryllidaceae), besides the well known alkaloids lycorine, tazettine, and hippeastrine, a new alkaloid, phamine, has been isolated. Its structure was established by spectroscopic methods.

  5. Progress of pharmacological studies on alkaloids from Apocynaceae.

    PubMed

    Liu, Lu; Cao, Jian-Xin; Yao, Yuan-Cheng; Xu, Sheng-Ping

    2013-01-01

    Alkaloid was a kind of biological active ingredient. There were various types of alkaloids in Apocynaceae. This paper reviewed the progress on alkaloids from Apocynaceae, which contained origin, structure, and pharmacological activity.

  6. Angustilobine and andranginine type indole alkaloids and an uleine-secovallesamine bisindole alkaloid from Alstonia angustiloba.

    PubMed

    Ku, Wai-Foong; Tan, Shin-Jowl; Low, Yun-Yee; Komiyama, Kanki; Kam, Toh-Seok

    2011-12-01

    A total of 20 alkaloids were isolated from the leaf and stem-bark extracts of Alstonia angustiloba, of which two are hitherto unknown. One is an alkaloid of the angustilobine type (angustilobine C), while the other is a bisindole alkaloid angustiphylline, derived from the union of uleine and secovallesamine moieties. The structures of these alkaloids were established using NMR and MS analysis. Angustilobine C showed moderate cytotoxicity towards KB cells.

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

    PubMed

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

    2011-03-01

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

  8. 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.

  9. [Recent results on the pharmacodynamics of Strychnos malgaches alkaloids].

    PubMed

    Rasoanaivo, P; Ratsimamanga-Urverg, S; Frappier, F

    1996-01-01

    Investigation of Strychnos (Loganiaceae) shrubs and trees was initiated by their traditional uses of their inherent poisons on arrows: this led to the discovery of strychnine and curare alkaloids. Subsequently, phytochemical investigation of several Strychnos species has shown great structural diversity of the alkaloid constituent which also display various biological effects, i.e. convulsive and relaxant effects on muscles, and antimicrobial, antitumor and antihypertensive properties. Ethnobotanical field work conducted in different regions of Madagascar revealed that infusion of three Strychnos species, S. mostueoides, S. myrtoides and S. diplotricha, is used in association with subcurative doses of chloroquine to treat chronic malaria. Bioassayfractionation led to the isolation of two major bioactive components, strychnobrasiline and malagashanine. Whereas strychnobrasiline is a previously known chemical compound, malagashanine is the first in a series of a new subtype of Strychnos alkaloids. These two alkaloids are devoid of intrinsic antimalarial effects, both in vitro (IC50 = 73.0 micrograms/ml for strychnobrasiline and 69.1 micrograms/ml for malagashanine) and in vivo (10 mg/kg conferred a 5% suppression of parasitemia). When these alkaloids are combined with chloroquine at doses much lower than required for antiplasmodial effects, they greatly enhance the chloroquine action in a dose dependent manner as seen by the isobologram method. Several minor alkaloids structurally related to malagashanine were also isolated from Madagascan Strychnos. They all enhance, to greater or lesser degrees, the chloroquine effectiveness. Interestingly, there is a positive correlation between the ethnomedical use of the three Strychnos species as chloroquine adjuvants and the chloroquine-potentiating effects of malagashanine and strychnobrasiline isolated from them. After preliminary toxicological studies, infusion of stem barks of S. myrtoides in association with chloroquine

  10. 13,14-dihydrocoptisine--the genuine alkaloid from Chelidonium majus.

    PubMed

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

    2015-03-01

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

  11. Four new fluorenone alkaloids and one new dihydroazafluoranthene alkaloid from Caulophyllum robustum Maxim.

    PubMed

    Wang, Xiao-Ling; Liu, Bing-Rui; Chen, Chien-Kuang; Wang, Jun-Ru; Lee, Shoei-Sheng

    2011-09-01

    Four new fluorenone alkaloids, caulophylline A-D (1-4), and one new dihydroazafluoranthene alkaloid, caulophylline E (5) were isolated from the roots of Caulophyllum robustum Maxim. Their structures were elucidated by spectroscopic analysis. Among the isolated alkaloids, Caulophylline E showed good scavenging effects against DPPH radical with IC(50) of 39 μM.

  12. The alkaloids of Delphinium cashmirianum.

    PubMed

    Shamma, M; Chinnasamy, P; Miana, G A; Khan, A; Bashir, M; Salazar, M; Patil, P; Beal, J L

    1979-01-01

    Dephinium cashmirianum Royle (Ranunculaceae) has yielded the new base cashmiradelphine (12), together with the known alkaloids anthranoyllycoctonine (9), lycaconitine (15), avadharidine (17), lappaconitine (4), and N-deacetyllappaconitine (7). Pyridinium chlorochromate oxidation of lycoctonine furnished the new aldehyde lycoctonal (11). The arrhythmogenic and heart rate effects of several of these diterpenoidal alkaloids have been measured on the isolated guinea atria. Lappaconitine was arrhythmogenic at 10(-4)M concentrations. But in contrast to the reference drug aconitine, lappaconitine did not increase the heart rate. In anesthetized rabbits injected with lappaconitine, N-deacetyllappaconitine, and lappaconine up to 1 mg/kg, cardiac arrhythmia was quickly observed. Even up to 5 mg/kg, the other substances were non-arrhythmogenic.

  13. Alkaloids from Boophone haemanthoides (Amaryllidaceae).

    PubMed

    Nair, Jerald J; Rárová, Lucie; Strnad, Miroslav; Bastidad, Jaume; van Staden, Johannes

    2013-12-01

    In this study, the South African Amaryllid Boophone haemanthoides was examined for its phytochemical composition and cytotoxicity. In the process eight alkaloid structures, including the new compound distichaminol, were identified in bulb ethanolic extracts. Of the isolates, lycorine and distichamine exhibited strong activities against human acute lymphoblastic leukemia (CEM), breast adenocarcinoma (MCF7) and cervical adenocarcinoma (HeLa) cells with IC50S ranging from 1.8 to 9.2 microM.

  14. Morphinane alkaloid dimers from Sinomenium acutum.

    PubMed

    Jin, Hui-Zi; Wang, Xiao-Ling; Wang, Hong-Bing; Wang, Yu-Bo; Lin, Li-Ping; Ding, Jian; Qin, Guo-Wei

    2008-01-01

    Two new morphinane alkaloid dimers, 2,2'-disinomenine (1) and 7',8'-dihydro-1,1'-disinomenine (2), and known 1, 1'-disinomenine (3), were isolated from ethanol extracts of stems of Sinomenium acutum. Their structures were elucidated on the basis of spectroscopic methods. The absolute configuration of alkaloids 1-3 was determined by direct comparison of their CD spectra with the known alkaloid sinomenine. The isolated alkaloids were tested for cytotoxicity against A549, P388, and HeLa cell lines, and 1 and 3 showed weak inhibition against A549 and Hela cells.

  15. 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.

  16. The alkaloid alstonine: a review of its pharmacological properties.

    PubMed

    Elisabetsky, E; Costa-Campos, L

    2006-03-01

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

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

    PubMed Central

    Elisabetsky, E.; Costa-Campos, L.

    2006-01-01

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

  18. Opioid peptides and opiate alkaloids in immunoregulatory processes.

    PubMed

    Stefano, George B; Kream, Richard M

    2010-06-30

    Among the various non-neuronal cell types known to express and utilize neuropeptides, those of the immune system have received much attention in recent years. In particular, comparative studies in vertebrates and invertebrates have shown that endogenous opioid peptides are engaged in receptor mediated autoregulatory immune and neuroendocrine processes. The majority of these immune processes are stimulatory, as determined by their effects on conformational changes indicative of immunocyte activation, cellular motility, and phagocytosis. Endogenous opioid peptides form an effective network of messenger molecules in cooperation with cytokines, opiate alkaloids, and certain regulatory enzymes (neutral endopeptidase 24.11). Peptide-mediated immunostimulatory effects observed in this system are operationally counteracted by the inhibitory effects of morphine and related opiates. Opioid/opiate signaling processes are mediated by several types of receptors with different degrees of selectivity. Among them the recently identified, opioid insensitive µ(3) receptor deserves attention on account of its specificity for opiate alkaloids.

  19. Photoreduction and ketone-sensitized reduction of alkaloids.

    PubMed

    Görner, Helmut; Miskolczy, Zsombor; Megyesi, Mónika; Biczók, László

    2011-01-01

    The photoprocesses of berberine, palmatine, coralyne, sanguinarine, flavopereirine and ellipticine were studied in several solvents. The quantum yields Φ(Δ) of singlet molecular oxygen formation of berberine, palmatine and sanguinarine are moderate in dichloromethane (0.2-0.6) and much smaller in acetonitrile or trifluoroethanol. For the other alkaloids examined, Φ(Δ) is rather independent of solvent polarity. The direct and ketone-sensitized photolysis, using steady-state irradiation at 313 nm or 248/308 nm laser pulses, was studied by absorption and fluorescence spectroscopy. Thereby, radicals were observed yielding eventually dihydro derivatives as major products, which are thermally back-converted on admission of oxygen. The quantum yield of conversion of alkaloids to dihydroalkaloids is enhanced in the presence of triethylamine. The reaction in the presence of ketones and electron or H-atom donors has a quantum yield of close to unity.

  20. 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.

  1. Cytotoxic oxoisoaporphine alkaloids from Menispermum dauricum.

    PubMed

    Yu, B W; Meng, L H; Chen, J Y; Zhou, T X; Cheng, K F; Ding, J; Qin, G W

    2001-07-01

    Four new oxoisoaporphine alkaloids, daurioxoisoporphines A-D (1-4), were isolated from the rhizomes of Menispermum dauricum. The structures of these alkaloids were established by spectroscopic methods. The cytotoxic evaluation of 1 and 2 is reported against four cancer cell lines.

  2. Plant alkaloids of the polymethyleneamine series

    NASA Astrophysics Data System (ADS)

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

    2005-04-01

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

  3. Glycoalkaloids and calystegine alkaloids in potatoes

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  4. The effect of body condition on serum concentrations of two teratogenic alkaloids (anagyrine and ammodendrine) from Lupines (Lupinus spp.) that cause crooked calf disease.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several species of lupine (Lupinus spp.) are toxic to livestock, causing death losses in sheep and cattle but more commonly “crooked calf disease” in pregnant range cows. The major toxic alkaloids in lupine are of the quinolizidine alkaloid group and include the teratogen anagyrine, which is primari...

  5. Identification and characterization of indole and oxindole alkaloids from leaves of mitragyna speciosa korth using liquid chromatography-accurate QToF mass spectrometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Alkaloids have been reported to be the major physiologically active constituents in Mitragyna. An analytical method was developed to provide an alternative, fast method for characterization of alkaloids from various Mitragyna speciosa samples. The separation was achieved using a reversed phase (C-8)...

  6. 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.

  7. Indole Alkaloids from Alocasia macrorrhiza.

    PubMed

    Zhu, Ling-Hua; Chen, Cheng; Wang, Hui; Ye, Wen-Cai; Zhou, Guang-Xiong

    2012-01-01

    Five new indole alkaloids, alocasins A-E (3-7), together with known hyrtiosin B (1) and hyrtiosulawesin (2) were isolated from Alocasia macrorrhiza (L.) SCHOTT; their structures were elucidated on the basis of spectroscopic data. Compounds 1-7 were in vitro tested for cytostatic activity on human throat cancer (Hep-2), human hepatocarcinoma (Hep-G2), and human nasopharyngeal carcinoma epithelial (CNE) cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method; compounds 2, 3, 6 and 7 showed mild antiproliferative activity against Hep-2 and Hep-G2 whereas compounds 2 and 4 showed gentle antiproliferative activity against CNE.

  8. Enantioselective synthesis of alkaloids from phenylglycinol-derived lactams.

    PubMed

    Amat, Mercedes; Llor, Núria; Griera, Rosa; Pérez, Maria; Bosch, Joan

    2011-04-01

    This review is focused on recent synthetic achievements and ongoing work in our laboratory using phenylglycinol-derived oxazolopiperidone lactams as starting materials for the enantioselective synthesis of piperidine-containing alkaloids: madangamines, 2,5-disubstituted decahydroquinoline and 1-substituted tetrahydroisoquinoline alkaloids, the indole alkaloids 20S- and 20R-dihydrocleavamine and quebrachamine, and indole alkaloids of the uleine and silicine groups.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  11. Comparative Study of Alkaloid Pattern of Four Bulgarian Fumaria species.

    PubMed

    Doncheva, Tsvetelina; Yordanova, Gabriela; Vutov, Vassil; Kostova, Nadezhda; Philipov, Stefan

    2016-02-01

    The alkaloid pattern of four Fumaria species (Fumaria kralikii, Fumaria rostellata, Fumaria schleicherii, Fumaria thureii) growing in Bulgaria was investigated by GC-MS and twenty isoquinoline alkaloids were determined. Phytochemical investigation of the alkaloid composition on Fumaria thuretii Boiss was made for the first time. The alkaloid profile of the species was compared at two levels, between different species and within two species from different habitats. Two chemotypical groups, based on the types of isoquinoline alkaloids were suggested. To group A belong species F. kralikii, F. rostellata (F. r. 1) and F. thuretii containing more than 50% spirobenzylisoquinoline alkaloids of the crude alkaloid mixtures. To group B belong species F. rostellata (F. r. 2) and F. schleicherii containing more than 40% protopine alkaloids and relatively high percentage phthaldeisoquinoline alkaloids (11-19%). In group A phthaldeisoquinoline alkaloids were not detected.

  12. Quantitative 1H Nuclear Magnetic Resonance Metabolite Profiling as a Functional Genomics Platform to Investigate Alkaloid Biosynthesis in Opium Poppy1[W

    PubMed Central

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

    2008-01-01

    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 1H 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 1H 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

  13. Bromopyrrole Alkaloids from Okinawan Marine Sponges Agelas spp.

    PubMed

    Tanaka, Naonobu; Kusama, Taishi; Kashiwada, Yoshiki; Kobayashi, Jun'ichi

    2016-01-01

    In our continuing study for structurally and biogenetically interesting natural products from marine organisms, Okinawan marine sponges Agelas spp. were investigated, resulting in the isolation of 18 unique alkaloids including five dimeric bromopyrrole alkaloids (1-5), ten monomeric bromopyrrole alkaloids (6-15), and three conjugates of monomeric bromopyrrole alkaloid and hydroxykynurenine (16-18). In this mini-review, the isolation, structure elucidation, and antimicrobial activities of these alkaloids are summarized.

  14. 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.

  15. Quantitative analysis of bioactive carbazole alkaloids in Murraya koenigii.

    PubMed

    Joshi, Trapti; Mahar, Rohit; Singh, Sumit K; Srivastava, Piush; Shukla, Sanjeev K; Mishra, Dipak K; Bhatta, R S; Kanojiya, Sanjeev

    2015-02-01

    Carbazole alkaloids induce apoptosis in HL-60 cells through activation of the caspase-9/caspase-3 pathway and they are targeted as potential anticancer agents. Thus, the naturally occurring carbazole alkaloids become important as precursors for lead optimization in drug development. A method based on ultra performance liquid chromatography coupled with photodiode-array detection was developed using reverse phase isocratic elution with 85:15 acetonitrile and ammonium acetate buffer (5 mM). Seven samples of Murrya koenigii (L.) Spreng. from north-central India (Uttar Pradesh) were analyzed. All three targeted analytes, koenimbidine (mk1), koenimbine (mk2) and mahanimbine (mk3), were well separated within 4.0 min with linearity of the calibration curves (r2 > 0.999). The limits of detection and quantification of mk1, mk2 and mk3 were 0.7, 0.4, 0.04 μg/mL and 2.14, 1.21, 0.12 μg/mL, respectively. The natural abundance of mk1, mk2 and mk3 was 0.06-0.20, 0.04-0.69 and 0.13-0.42%, w/w, respectively, in the dried powdered leaves, whereas, the tissue specific distribution of carbazole alkaloids was observed in the order of predominance, mk1 leaf>root>fruit>stem, mk2 fruit>leaf >stem>root, and mk3 fruit>leaf>root>stem. The developed method was validated for limits of detection and quantification, repeatability, accuracy, precision and stability. This is the first report on the natural abundance of the major carbazole alkaloids in M. koenigii and the method developed can be used in HPLC/UPLC systems.

  16. Application of Liquid Chromatography/Ion Trap Mass Spectrometry Technique to Determine Ergot Alkaloids in Grain Products

    PubMed Central

    Szymczyk, Krystyna; Jędrzejczak, Renata; Roszko, Marek

    2015-01-01

    Summary A liquid chromatography/ion trap mass spectrometry-based method to determine six ergot alkaloids and their isomers is presented. The samples were cleaned on neutral alumina-based solid-phase extraction cartridges. The following method parameters were obtained (depending on the analyte and spiking level): method recovery from 63.0 to 104.6%, relative standard deviation below 18%, linear range from 1 to 325 µg/kg, linear correlation coefficient not less than 0.98. The developed analytical procedure was applied to determine the levels of ergot alkaloids in 65 samples of selected rye-based food products (flour – 34 samples, bran – 12 samples, rye – 18 samples, flakes – 1 sample). Measurable levels of alkaloids were found in majority of the analysed samples, particularly in rye flour. Additionally, alkaloids were determined in ergot sclerotia isolated from rye grains. Total content was nearly 0.01% (97.9 mg/kg). However, the alkaloid profile was dominated by ergocristine at 45.6% (44.7 mg/kg), an alkaloid not commonly found in the tested food products. Ergocorninine at 0.2% (0.2 mg/kg) was the least abundant alkaloid. PMID:27904328

  17. The Genus Diphasiastrum and Its Lycopodium Alkaloids.

    PubMed

    Halldorsdottir, Elsa Steinunn; Kowal, Natalia Magdalena; Olafsdottir, Elin Soffia

    2015-08-01

    The genus Diphasiastrum includes at least 23 species distributed primarily across the northern temperate and subarctic areas of the world. These plants produce an array of lycopodium alkaloids, and some species such as Diphasiastrum complanatum have been used in traditional medicine for ages for various conditions. Hybridization is common in this group of plants and they have always been a challenge for taxonomists and other scientists studying them. To date, 11 Diphasiastrum species have been reported to produce lycopodium alkaloids. In this review, reported alkaloids and their distribution patterns across these species along with taxonomical and bioactivity considerations are reviewed and discussed.

  18. 4-Quinolone alkaloids from Melochia odorata.

    PubMed

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

    2014-01-24

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

  19. 4-Quinolone Alkaloids from Melochia odorata

    PubMed Central

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

    2014-01-01

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

  20. Synthesis of morphine alkaloids and derivatives.

    PubMed

    Rinner, Uwe; Hudlicky, Tomas

    2012-01-01

    This review summarizes recent developments in the total synthesis of morphine alkaloids and some of the semisynthetic derivatives. The literature is covered for the period of 5 years after the publication of the last review in 2005. The syntheses that appeared in this period are covered in detail and are placed in the context of all syntheses of opiate alkaloids since the original one published by Gates in 1952. The introduction covers the historical aspects of total synthesis of these alkaloids. The synthesis of some of the medicinally useful derivatives is reviewed in the last section along with some of the methodology required for their preparation.

  1. Isoquinoline and isoindole alkaloids from Menispermum dauricum.

    PubMed

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

    2004-04-01

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

  2. Gelsemium alkaloids, immunosuppressive agents from Gelsemium elegans.

    PubMed

    Xu, You-Kai; Liao, Shang-Gao; Na, Zhi; Hu, Hua-Bin; Li, Yan; Luo, Huai-Rong

    2012-09-01

    Bioassay-guided isolation of the stems of Gelsemium elegans has led to the isolation of two new Gelsemium alkaloids, 21-(2-oxopropyl)-koumine (1) and 11-methoxygelselegine (2), and two known alkaloids, koumine (3) and gelselegine (4). The structures of 1-2 were determined by spectroscopic (for both) and single-crystal X-ray diffraction (for 1) analysis. All compounds isolated were evaluated for their potential as immunosuppressive agents and the data suggested that Gelsemium alkaloids of different structural types possibly have potential as immunosuppressive agents.

  3. Racemic alkaloids from the fungus Ganoderma cochlear.

    PubMed

    Wang, Xin-Long; Dou, Man; Luo, Qi; Cheng, Li-Zhi; Yan, Yong-Ming; Li, Rong-Tao; Cheng, Yong-Xian

    2017-01-01

    Seven pairs of new alkaloid enantiomers, ganocochlearines C-I (1, 3-8), and three pairs of known alkaloids were isolated from the fruiting bodies of Ganoderma cochlear. The chemical structures of new compounds were elucidated on the basis of 1D and 2D NMR data. The absolute configurations of compounds 1, 3-10 were assigned by ECD calculations. Biological activities of these isolates against renal fibrosis were accessed in rat normal or diseased renal interstitial fibroblast cells. Importantly, the plausible biosynthetic pathway for this class of alkaloids was originally proposed.

  4. Polycyclic Guanidine Alkaloids from Poecilosclerida Marine Sponges.

    PubMed

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

    2016-04-09

    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.

  5. 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.

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

    PubMed

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

    2013-12-02

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

  7. 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.

  8. 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

  9. 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...

  10. Steroidal alkaloid toxicity to fish embryos.

    PubMed

    Crawford, L; Kocan, R M

    1993-02-01

    Embryos of two species of fish were evaluated for their suitability as model systems for steroidal alkaloid toxicity, the Japanese rice fish, medaka (Oryzius latipes) and the rainbow trout (Oncorhynchus mykiss). Additionally, the equine neurotoxic sesquiterpene lactone repin, was also tested. A PROBIT program was used to evaluate the EC1, EC50 and EC99 as well as the associated confidence limits. The steroidal alkaloids tested were the Solanum potato glycoalkaloids alpha-chaconine, alpha-solanine, the aglyclones solanidine and solasodine and the Veratrum alkaloid, jervine. Embryo mortality, likely due to structural or functional abnormalities in the early development stages of the embryo, were the only response observed in both species. The rainbow trout exhibited a toxic response to chaconine, solasidine, repin and solanine but the medaka embryos were only affected by the compounds, chaconine and solanine. Rainbow trout may indeed serve as a good lower vertebrate model for studying the toxicity of steroidal alkaloids.

  11. 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.

  12. Antiprotozoal and antioxidant alkaloids from Alternanthera littoralis.

    PubMed

    Koolen, Hector H F; Pral, Elizabeth M F; Alfieri, Silvia C; Marinho, Jane V N; Serain, Alessandra F; Hernández-Tasco, Alvaro J; Andreazza, Nathalia L; Salvador, Marcos J

    2017-02-01

    Five alkaloids, in addition to hydroxytyrosol and uridine, were isolated from aerial parts of Alternanthera littoralis P. Beauv. Among the isolated compounds, alternamide A was an unusual tricyclic alkaloid with a bridged benzoazepine core. All isolated alkaloids have a catechol moiety, indicating a possible common biosynthetic route. Their structures were established by 1D and 2D NMR spectroscopy in combination with extensive tandem MS experiments by collisional induced dissociation (CID). The antiprotozoal activity of the isolated compounds was assayed against trypomastigote forms of Trypanosoma cruzi and amastigotes of Leishmania amazonensis. Alternamine A was the most active compound, reducing markedly the viability of both parasites. Antioxidant capacities evaluated by ORACFL assay showed that the isolated alkaloids (mainly alternamide B) contributed to the high activity recorded for the ethanolic crude extract; possibly, the catechol moiety present in all structures plays a central role in this result.

  13. Opiate alkaloids in Ascaris suum.

    PubMed

    Pryor, S C; Putnam, Jennifer; Hoo, Nanyamka

    2004-01-01

    The parasitic worm Ascaris suum contains the opiate alkaloids morphine and morphine-6-glucuronide as determined by HPLC coupled to electrochemical detection and by gas chromatography/mass spectrometry. The level of morphine in muscle tissue of female and male is 252 +/- 32.68, 1168 +/- 278 and 180 +/- 23.47 (ng/g of wet tissue), respectively. The level of M6G in muscle tissue of female and male is 167 +/- 28.37 and 92 +/- 11.45 (ng/g of wet tissue), respectively. Furthermore, Ascaris maintained for 5 days contained a significant amount of morphine, as did their medium, demonstrating their ability to synthesize the opiate alkaloid. The anatomic distribution of morphine was examined by indirect immunofluorescent staining and HPLC of various tissues dissected from male and female adult worms. Immunofluorescence revealed morphine in the subcuticle layers, in the animals' nerve chords and in the female reproductive organs. Morphine was found to be most prevalent in the muscle tissue and there is significantly more morphine in females than males, probably due to the large amounts in the female uterus. Morphine (10(-9) M) and morphine-6-glucuronide (10(-9) M) stimulated the release of NO from Ascaris muscle tissue. Naloxone (10(-7) M), and L-NAME (10(-6) M) blocked (P < 0.005) morphine-stimulated NO release from A. suum muscle. CTOP (10(-7) M) did not block morphine's NO release. However, naloxone could not block M6G stimulated NO release by muscle tissue, whereas CTOP (10(-7) M) blocked its release. These findings were in seeming contradiction to our inability to isolate a mu opiate receptor messenger RNA by RT-PCR using a human mu primer. This suggests that a novel mu opiate receptor was present and selective toward M6G.

  14. Alkaloids from Fissistigma latifolium (Dunal) Merr.

    PubMed

    Alias, Asmah; Hazni, Hazrina; Jaafar, Faridahanim Mohd; Awang, Khalijah; Ismail, Nor Hadiani

    2010-06-24

    A phytochemical study of the bark of Fissistigma latifolium (Annonaceae) yielded a new aporphine alkaloid, (-)-N-methylguattescidine (1), and eight known alkaloids: liriodenine (2), oxoxylopine (3), (-)-asimilobine (4), dimethyltryptamine (5), (-)-remerine (6), (-)-anonaine (7), columbamine (8) and lysicamine (9). The compounds were isolated using various chromatographic methods and structural elucidation was accomplished by means of spectroscopic methods, notably 1D-NMR ((1)H, (13)C, DEPT), 2D-NMR (COSY, HMQC, HMBC), UV, IR and MS.

  15. 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.

  16. Indole Alkaloids from Marine Sources as Potential Leads against Infectious Diseases

    PubMed Central

    França, Paulo H. B.; Barbosa, Daniel P.; da Silva, Daniel L.; Ribeiro, Êurica A. N.; Santana, Antônio E. G.; Santos, Bárbara V. O.; Barbosa-Filho, José M.; Quintans, Jullyana S. S.; Barreto, Rosana S. S.; Quintans-Júnior, Lucindo J.; de Araújo-Júnior, João X.

    2014-01-01

    Indole alkaloids comprise a large and complex class of natural products found in a variety of marine sources. Infectious diseases remain a major threat to public health, and in the absence of long-term protective vaccines, the control of these infectious diseases is based on a small number of chemotherapeutic agents. Furthermore, the emerging resistance against these drugs makes it urgently necessary to discover and develop new, safe and, effective anti-infective agents. In this regard, the aim of this review is to highlight indole alkaloids from marine sources which have been shown to demonstrate activity against infectious diseases. PMID:24995289

  17. 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.

  18. 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.

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

    PubMed Central

    2014-01-01

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

  20. [Isolation and identification of alkaloids form Menispermum dauricum growing in Xianning].

    PubMed

    Pan, X; Hu, C; Zeng, F; Zhang, S; Xu, J

    1998-09-01

    The alkaloids of rhizoma of Menispermum dauricum DC growing in Xianning have been subjected to isolation and identification. The results showed that its two major constituents, which are only next of dauricine in content, are dauricinoline and daurinoline, instead of the commonly found daurisoline in the same plant materials from North China.

  1. Bioactive 1 4-Dihydroxy-5-phenyl-2-pyridinone alkaloids from Septoria pistaciarum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Four new 1,4-dihydroxy-5-phenyl-2-pyridinone alkaloids (1-4) were isolated from an EtOAc extract of a culture medium of Septoria pistaciarum. The structures of these compounds were determined by spectroscopic methods, and the absolute configuration of the major compound 1 by X-ray crystallographic a...

  2. 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

  3. Sophora alopecuroides L. var. alopecuroides alleviates morphine withdrawal syndrome in mice: involvement of alkaloid fraction and matrine

    PubMed Central

    Kianbakht, Saeed; Hashem Dabaghian, Fataneh

    2016-01-01

    Objective(s): Evaluation of the Sophora alopecuroides var. alopecuroides seed effects on morphine withdrawal syndrome in mice and determination of the alkaloid composition of the seed total extract. Materials and Methods: The effects of the seed total extract, alkaloid fraction and major compound matrine on the mice morphine withdrawal syndrome were compared to saline and methadone. Mice were made dependent on morphine by morphine sulfate injection 3 times a day for 3 days. The withdrawal jumping and diarrhea were induced by administration of naloxone 2 hr after the 10th injection of morphine sulfate on the day 4. The total extract (100, 200, 300 mg/kg), alkaloid fraction (5, 10, 20 mg/kg), matrine (5, 15, 30 mg/kg), methadone (10 mg/kg) or saline were injected 30 min before naloxone. All drugs were administered by subcutaneous injection. The total extract alkaloid composition was also determined by gas chromatography (GC) and GC-MS analysis. Results: All doses of the total extract, alkaloid fraction and matrine as well as methadone decreased jumping and diarrhea significantly compared to the saline. The effects of the total extract and alkaloid fraction were not significantly different from methadone. But, there were significant differences between the effects of matrine and methadone. Matrine, cytisine, sophoridine, n-methyl cytisine, sophocarpine and sophoramine were the major alkaloids. There was no nicotine in the total extract. Conclusion: S. alopecuroides var. alopecuroides suppresses opioid withdrawal with efficacy comparable to methadone. Matrine may be one of the alkaloids responsible for the effect of the plant. PMID:27872705

  4. 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...

  5. 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.

  6. Multicomponent Therapeutics of Berberine Alkaloids

    PubMed Central

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

    2013-01-01

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

  7. 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.

  8. [Study on optimum extraction conditions of alkaloids from Pinellia ternate].

    PubMed

    Zeng, Jianhong; Peng, Zhengsong; Mao, Zicheng; Wei, Shuhong

    2003-05-01

    The optimum extraction conditions of alkaloids from Pinellia ternate (Thunb.) Breit were studied by orthogonal test. The results showed that the highest extraction rate of the alkaloids could be obtained by smashing the material in 60 (sieve number) of fragmentation and socking the material in 2.575 mol/L ammonia water, extracting alkaloids with 18 times as much chlorolform at room temperature for 25 hours. The highest extraction rate of alkaloids was 0.0817%.

  9. 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.

  10. Mitochondria: a promising target for anticancer alkaloids.

    PubMed

    Urra, Félix A; Cordova-Delgado, Miguel; Pessoa-Mahana, Hernan; Ramírez-Rodríguez, Oney; Weiss-Lopez, Boris; Ferreira, Jorge; Araya-Maturana, Ramiro

    2013-01-01

    A great number of alkaloids exhibit high potential in cancer research. Some of them are anticancer drugs with well-defined clinical uses, exerting their action on microtubules dynamics or DNA replication and topology. On the other hand, mitochondria have been recognized as an essential organelle in the establishment of tumor characteristics, especially the resistance to cell death, high proliferative capacity and adaptation to unfavorable cellular environment. Interestingly, many alkaloids exert their anticancer activities affecting selectively some functions of the tumor mitochondria by 1) modulating OXPHOS and ADP/ATP transport, 2) increasing ROS levels and mitochondrial potential dissipation by crosstalk between endoplasmic reticulum (ER) and mitochondria, 3) inducing mitochondria-dependent apoptosis and autophagy, 4) inhibiting mitochondrial metabolic pathways and 5) by alteration of the morphology and biogenesis of this organelle. These antecedents show the relevance of developing research about the effects of alkaloids on functions controlled by tumor mitochondria, offering an attractive target for the design of new alkaloid derivatives, considering organelle- specific delivery strategies. This review describes mitochondria as a central component in the anticancer action of a set of alkaloids, in a way to illustrate the importance of this organelle in medicinal chemistry.

  11. 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.

  12. 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.

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

    PubMed Central

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

    2012-01-01

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

  14. 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...

  15. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  16. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Code of Federal Regulations, 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...

  17. 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...

  18. 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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  20. Two new amaryllidaceae alkaloids from the bulbs of Lycoris radiata.

    PubMed

    Wang, Lei; Zhang, Xiao-Qi; Yin, Zhi-Qi; Wang, Ying; Ye, Wen-Cai

    2009-06-01

    Two new Amaryllidaceae alkaloids, named lycoranines A (1) and B (2), were isolated from the bulbs of Lycoris radiata. Their structures were elucidated on the basis of extensive spectroscopic analysis. Compound 2 was a new-type alkaloid, which provided a new insight into the biosynthesis of alkaloids in Amaryllidaceae plants.

  1. Linkage analysis of a rare alkaloid present in a tetraploid potato with Solanum chacoense background.

    PubMed

    Sagredo, B; Lorenzen, J; Casper, H; Lafta, A

    2011-02-01

    The potato genotype ND4382-19 has Solanum chacoense Bitt. in its genetic background. Foliar alkaloid analysis of it and its progeny ND5873 (ND4382-19 × Chipeta) by gas chromatography-mass spectrometry (GC-MS) showed that, in addition to the expected alkaloids (solanidine, leptinidine, and acetyl-leptinidine), there was an aglycone of another rare alkaloid. Its molecular mass and some of the m/z fragment ions were similar to leptinidine, but the major fragment ion was the m/z 150 peak of solanidine. This fragmentation pattern suggested that this alkaloid is a solanidine-based compound with mass equal to leptinidine. Leptinidine differs from solanidine by an extra -OH group, but the GC-MS fragmentation pattern of the rare compound indicated hydroxylation at a different position than the C-23 of leptinidine. The exact chemical structure is still unknown, and further analysis, such as NMR will be necessary to determine the structure. Segregation analysis of ND5873 (ND4382-19 × Chipeta) showed that presence of this rare compound segregated in a 1:1 ratio, indicating that a single gene controlled its synthesis and/or accumulation in foliar tissue. Analysis with AFLP and microsatellite markers indicated that the locus-controlling presence of this alkaloid resided on potato chromosome I, with the nearest flanking AFLP markers 0.6 and 9.4 cM apart. This rare alkaloid was present in the foliage and not detected in potato tubers. Its presence in leaves did not affect resistance/susceptibility to Colorado potato beetle.

  2. Thin-Layer Chromatography/Desorption Electrospray Ionization Mass Spectrometry: Investigation of Goldenseal Alkaloids

    SciTech Connect

    Van Berkel, Gary J; Tomkins, Bruce A; Kertesz, Vilmos

    2007-01-01

    Desorption electrospray ionization mass spectrometry was investigated as a means to qualitatively identify and to quantify analytes directly from developed normal-phase thin layer chromatography plates. The atmospheric sampling capillary of a commercial ion trap mass spectrometer was extended to permit sampling and ionization of analytes in bands separated on intact TLC plates (up to 10 cm x 10 cm). A surface positioning software package and the appropriate hardware enabled computer-controlled surface scanning along the length of development lanes or at fixed RF value across the plates versus the stationary desorption electrospray emitter. Goldenseal (Hydrastis canadensis) and related alkaloids and commercial dietary supplements were used as standards and samples. Alkaloid standards and samples were spotted and separated on aluminum- or glass-backed plates using established literature methods. The mass spectral signal levels as a function of desorption spray solvent were investigated with acetonitrile proving superior to methanol. The detection levels (ca. 5 ng each or 14 -28 pmol) in mass spectral full scan mode were determined statistically from the calibration curves (2.5 - 100 pmol) for the standards berberine, palmatine and hydrastinine spotted as a mixture and separated on the plates. Qualitative screening of the major alkaloids present in six different over-the-counter "goldenseal" dietary supplements was accomplished by obtaining full scan mass spectra during surface scans along the development lane in the direction of increasing RF value. In one sample, alkaloids were detected that strongly suggested the presence of at least one additional herb undeclared on the product label. These same data indicated the misidentification of one of the alkaloids in the TLC literature. Quantities of the alkaloids present in two of the samples determined using the mass spectral data were in reasonable agreement with the label values indicating the quantitative ability of

  3. Ether bridge formation in loline alkaloid biosynthesis

    PubMed Central

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

    2014-01-01

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

  4. An efficient synthesis of loline alkaloids

    NASA Astrophysics Data System (ADS)

    Cakmak, Mesut; Mayer, Peter; Trauner, Dirk

    2011-07-01

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

  5. Two new alkaloids from Narcissus serotinus L.

    PubMed

    Pigni, Natalia B; Berkov, Strahil; Elamrani, Abdelaziz; Benaissa, Mohammed; Viladomat, Francesc; Codina, Carles; Bastida, Jaume

    2010-10-14

    The Amaryllidaceae family is well known for the presence of an exclusive group of alkaloids with a wide range of biological activities. Narcissus serotinus L. is a plant belonging to this family and its geographical distribution is mainly located along the Mediterranean coast. In the present work, specimens collected near Casablanca (Morocco) were used to study the alkaloid content of this species. Starting with 350 g of the whole plant we used standard extraction and purification procedures to obtain fractions and compounds for GC-MS and NMR analysis. As well as five known alkaloids, we isolated two new compounds: 1-O-(3´-acetoxybutanoyl)lycorine and narseronine. The latter has been previously published, but with an erroneous structure.

  6. [Evaluation of antimicrobial activity of indol alkaloids].

    PubMed

    Rojas Hernández, N M

    1979-01-01

    In pursuing the study of the antimicrobial properties of alkaloids prepared from Cuban plants the activity of 10 indol alkaloids and 4 semisynthetic variables obtained from three plants--Catharanthus roseus G. Don., Vallesia antillana Wood and Ervatamia coronaria Staph, of the family Apocynaceae--growing in Cuba was assessed in vitro. The alkaloids and the variables used were catharantine, vindoline, vindolinine, perivine, reserpine, tabernaemontanine, tetrahydroalstonine, aparicine, vindolinic acid, reserpic acid and vindolininol. These were faced to 40 bacterial strains from the genera Salmonella, Shigella, Proteus, Escherichia, Pseudomonas, Staphylococcus and Corynebacterium as well as to fungi and yeasts from the genera Aspergillus, kCunnighamella, kCandida and Saccharomyces. The method involving cylindric sections in a double agar layer was applied and lectures were obtained at 24-48 hours of incubation at 25 degrees C for fungi and yeasts and 37 degrees C for bacteria. Inhibition zones are reported in millimeters.

  7. Diterpenoid alkaloids and flavonoids from Delphinium trichophorum.

    PubMed

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

    2014-01-01

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

  8. 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

  9. Leucovernine and acetylleucovernine, alkaloids from Leucojum vernum.

    PubMed

    Forgo, Peter; Hohmann, Judit

    2005-11-01

    The fresh bulbs of Leucojum vernum provided seven tyrosine-derived alkaloids; two of them have not been reported before and are named leucovernine and acetylleucovernine. The five known alkaloids were N-demethylgalanthamine, hippeastrine, 9-O-demethylhomolycorine, 5alpha-hydroxyhomolycorine, and 11-hydroxyvittatine. These compounds have been isolated from this species for the first time. The structure determination was carried out by the combination of liquid-phase one- and two-dimensional NMR spectroscopy and high-resolution mass spectrometry.

  10. 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.

  11. Alkaloids from Hippeastrum morelianum Lem. (Amaryllidaceae).

    PubMed

    Giordani, Raquel B; de Andrade, Jean P; Verli, Hugo; Dutilh, Julie H; Henriques, Amélia T; Berkov, Strahil; Bastida, Jaume; Zuanazzi, José Angelo S

    2011-10-01

    The Amaryllidaceae family has proven to be a rich source of active molecules. As part of an ongoing project, we report a phytochemical study of Hippeastrum morelianum (Amaryllidaceae), from which we have isolated two homolycorine-type alkaloids, the new 2α,7-dimethoxyhomolycorine (1) and the poorly described candimine (2), as well as six known alkaloids: tazettine, pretazettine, 3-epimacronine, haemanthamine, hamayne and trisphaeridine. For reference purposes, the NMR of the isolated compounds was unequivocally described, based on 2D NMR measurements including (1)H-(1)H COSY, (1)H-(1)H NOESY, HSQC and HMBC.

  12. Differential effects of sugar-mimic alkaloids in mulberry latex on sugar metabolism and disaccharidases of Eri and domesticated silkworms: enzymatic adaptation of Bombyx mori to mulberry defense.

    PubMed

    Hirayama, Chikara; Konno, Kotaro; Wasano, Naoya; Nakamura, Masatoshi

    2007-12-01

    Mulberry leaves (Morus spp.) exude latex rich in sugar-mimic alkaloids, 1,4-dideoxy-1,4-imino-d-arabinitol (d-AB1) and 1-deoxynojirimycin (DNJ), as a defense against herbivorous insects. Sugar-mimic alkaloids are inhibitors of sugar-metabolizing enzymes, and are toxic to the Eri silkworm, Samia ricini, a generalist herbivore, but not at all to the domesticated silkworm, Bombyx mori, a mulberry specialist. To address the phenomena, we fed both larvae diets containing different sugar sources (sucrose, glucose or none) with or without sugar-mimic alkaloids from mulberry latex. In S. ricini, addition of sugar-mimic alkaloids to the sucrose (the major sugar in mulberry leaves) diet reduced both growth and the absorption ratio of sugar, but it reduced neither in B. mori. The midgut soluble sucrase activity of S. ricini was low and inhibited by very low concentrations of sugar-mimic alkaloids (IC(50)=0.9-8.2microM), but that of B. mori was high and not inhibited even by very high concentrations (IC(50)>1000microM) of sugar-mimic alkaloids. In S. ricini, the addition of sugar-mimic alkaloids to the glucose diet still had considerable negative effects on growth, although it did not reduce the absorption ratio of glucose. The hemolymph of S. ricini fed sugar-mimic alkaloids contained sugar-mimic alkaloids. The trehalose concentration in the hemolymph increased significantly in S. ricini fed sugar-mimic alkaloids, but not in B. mori. The trehalase activities of S. ricini were lower and inhibited by lower concentrations of sugar-mimic alkaloids than those of B. mori. These results suggest that sugar-mimic alkaloids in mulberry latex exert toxicity to S. ricini larvae first by inhibiting midgut sucrase and digestion of sucrose, and secondly, after being absorbed into hemolymph, by inhibiting trehalase and utilization of trehalose, the major blood sugar. Further, our results reveal that B. mori larvae evolved enzymatic adaptation to mulberry defense by developing sucrase and

  13. Hydrofocusing Bioreactor Produces Anti-Cancer Alkaloids

    NASA Technical Reports Server (NTRS)

    Gonda, Steve R.; Valluri, Jagan V.

    2011-01-01

    A methodology for growing three-dimensional plant tissue models in a hydrodynamic focusing bioreactor (HFB) has been developed. The methodology is expected to be widely applicable, both on Earth and in outer space, as a means of growing plant cells and aggregates thereof under controlled conditions for diverse purposes, including research on effects of gravitation and other environmental factors upon plant growth and utilization of plant tissue cultures to produce drugs in quantities greater and at costs lower than those of conventional methodologies. The HFB was described in Hydro focus - ing Bioreactor for Three-Dimensional Cell Culture (MSC-22358), NASA Tech Briefs, Vol. 27, No. 3 (March 2003), page 66. To recapitulate: The HFB offers a unique hydrofocusing capability that enables the creation of a low-shear liquid culture environment simultaneously with the herding of suspended cells and tissue assemblies and removal of unwanted air bubbles. The HFB includes a rotating cell-culture vessel with a centrally located sampling port and an internal rotating viscous spinner attached to a rotating base. The vessel and viscous spinner can be made to rotate at the same speed and direction or different speeds and directions to tailor the flow field and the associated hydrodynamic forces in the vessel in order to obtain low-shear suspension of cells and control of the locations of cells and air bubbles. For research and pharmaceutical-production applications, the HFB offers two major benefits: low shear stress, which promotes the assembly of cells into tissue-like three-dimensional constructs; and randomization of gravitational vectors relative to cells, which affects production of medicinal compounds. Presumably, apposition of plant cells in the absence of shear forces promotes cell-cell contacts, cell aggregation, and cell differentiation. Only gentle mixing is necessary for distributing nutrients and oxygen. It has been postulated that inasmuch as cells in the simulated

  14. Alkaloid production by callous tissue cultures of Cereus peruvianus (Cactaceae).

    PubMed

    de Oliveira, Arildo José Braz; Machado, Maria Fátima Pires da Silva

    2003-02-01

    The morphologically undifferentiated cells of nonregenerant callous tissue of Cereus peruvianus cultured in the original medium and in medium supplemented with tyrosine were used as an alkaloid source. Comparison of alkaloid production by C. peruvianus plants and by callous tissues indicated that alkaloid levels were almost twice as high in callous tissues as in shoots of C. peruvianus plants. The ratio of alkaloid concentration between mature plant and morphologically undifferentiated cells of callous tissue was 1:1.7. A relationship between culture medium containing tyrosine and alkaloid production was also observed in the callous tissues of C. peruvianus. Since increased alkaloid production may be induced by additional factors such as tyrosine, increasing levels of tyrosine or other conditions of the culture medium may be considered factors for inducing higher alkaloid production by C. peruvianus callous tissues.

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2011-11-01

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

  17. The Alkaloid Profiles of Lupinus sulphureus

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  18. Ergot alkaloids decrease rumen epithelial blood flow

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  19. Photochemical N-demethylation of alkaloids.

    PubMed

    Ripper, J A; Tiekink, E R; Scammells, P J

    2001-02-26

    Certain alkaloids were observed to undergo N-demethylation processes under photochemical conditions. Tropine, acetyltropine, tropinone, and atropine were cleanly N-demethylated upon treatment with tetraphenylporphin, oxygen, and light. Dextromethorphan also underwent a N-demethylation reaction, but reacted further to afford an imine. In contrast, 14-acyloxycodeinones underwent a photochemically induced tandem N-demethylation acyl migration.

  20. Dehydropyrrolizidine alkaloid toxicity, cytotoxicity, and carcinogenicity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dehyro-pyrrolizidine alkaloid (PA)-containing plants compose about 5% of the world’s flowering plants and they commonly poison livestock, wildlife and humans. Previous work has produced considerable understanding of PA toxicity, species susceptibility, conditions and routes of exposure, toxin metab...

  1. 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.

  2. New indole alkaloid from Peschiera affinis (Apocynaceae).

    PubMed

    Santos, Allana Kellen L; Machado, Luciana L; Bizerra, Ayla Marcia C; Monte, Francisco José Q; Santiago, Gilvandete M P; Braz-Filho, Raimundo; Lemos, Telma L G

    2012-06-01

    A new indole alkaloid of the pyridocarbazole type, named 6N-hydroxy-olivacine, and two known compounds, 2N-oxide-olivacine and olivacine, were isolated from roots of Peschiera affinis. The structures of the compounds were determined by spectroscopic {IR and extensive NMR (COSY, HMQC, HMBCand NOESY)} and EIMS analysis.

  3. Four new Amaryllidaceae alkaloids from Zephyranthes candida.

    PubMed

    Shitara, Nanase; Hirasawa, Yusuke; Hasumi, Shunsuke; Sasaki, Tadahiro; Matsumoto, Misaki; Wong, Chin Piow; Kaneda, Toshio; Asakawa, Yoshinori; Morita, Hiroshi

    2014-07-01

    Four new Amaryllidaceae alkaloids (1-4) possessing a homolycorine-type or a crinine-type skeleton have been isolated from the aerial part of Zephyranthes candida, and their structures were elucidated on the basis of spectroscopic data. The stereochemistry was elucidated by combination of NOESY correlations and CD analyses.

  4. Modulation of CYPs, P-gp, and PXR by Eschscholzia californica (California Poppy) and Its Alkaloids.

    PubMed

    Manda, Vamshi K; Ibrahim, Mohamed A; Dale, Olivia R; Kumarihamy, Mallika; Cutler, Stephen J; Khan, Ikhlas A; Walker, Larry A; Muhammad, Ilias; Khan, Shabana I

    2016-04-01

    Eschscholzia californica, a native US plant, is traditionally used as a sedative, analgesic, and anxiolytic herb. With the rapid rise in the use of herbal supplements together with over-the-counter and prescription drugs, the risk for potential herb-drug interactions is also increasing. Most of the clinically relevant pharmacokinetic drug interactions occur due to modulation of cytochrome P450 enzymes (CYPs), P-glycoprotein, and the pregnane X receptor by concomitantly used herbs. This study aimed to determine the effects of an EtOH extract, aqueous extract (tea), basic CHCl3 fractions, and isolated major alkaloids, namely protopine (1), escholtzine (2), allocryptopine (3), and californidine (4), of E. californica on the activity of cytochrome P450s, P-glycoprotein and the pregnane X receptor. The EtOH extract and fractions showed strong time-dependent inhibition of CYP 3A4, CYP 2C9, and CYP 2C19, and reversible inhibition of CYP 2D6. Among the alkaloids, escholtzine (2) and allocryptopine (3) exhibited time-dependent inhibition of CYP 3A4, CYP 2C9, and CYP 2C19 (IC50 shift ratio > 2), while protopine (1) and allocryptopine (3) showed reversible inhibition of CYP 2D6 enzyme. A significant activation of the pregnane X receptor (> 2-fold) was observed with the EtOH extract, basic CHCl3 fraction, and alkaloids (except protopine), which resulted into an increased expression of mRNA and the activity of CYP 3A4 and CYP 1A2. The expression of P-glycoprotein was unaffected. However, aqueous extract (tea) and its main alkaloid californidine (4) did not affect cytochrome P450s, P-glycoprotein, or the pregnane X receptor. This data suggests that EtOH extract of E. californica and its major alkaloids have a potential of causing interactions with drugs that are metabolized by cytochrome P450s, while the tea seems to be safer.

  5. Phylogeny Predicts the Quantity of Antimalarial Alkaloids within the Iconic Yellow Cinchona Bark (Rubiaceae: Cinchona calisaya)

    PubMed Central

    Maldonado, Carla; Barnes, Christopher J.; Cornett, Claus; Holmfred, Else; Hansen, Steen H.; Persson, Claes; Antonelli, Alexandre; Rønsted, Nina

    2017-01-01

    Considerable inter- and intraspecific variation with respect to the quantity and composition of plant natural products exists. The processes that drive this variation remain largely unknown. Understanding which factors determine chemical diversity has the potential to shed light on plant defenses against herbivores and diseases and accelerate drug discovery. For centuries, Cinchona alkaloids were the primary treatment of malaria. Using Cinchona calisaya as a model, we generated genetic profiles of leaf samples from four plastid (trnL-F, matK, rps16, and ndhF) and one nuclear (ITS) DNA regions from twenty-two C. calisaya stands sampled in the Yungas region of Bolivia. Climatic and soil parameters were characterized and bark samples were analyzed for content of the four major alkaloids using HPLC-UV to explore the utility of evolutionary history (phylogeny) in determining variation within species of these compounds under natural conditions. A significant phylogenetic signal was found for the content of two out of four major Cinchona alkaloids (quinine and cinchonidine) and their total content. Climatic parameters, primarily driven by changing altitude, predicted 20.2% of the overall alkaloid variation, and geographical separation accounted for a further 9.7%. A clade of high alkaloid producing trees was identified that spanned a narrow range of altitudes, from 1,100 to 1,350 m. However, climate expressed by altitude was not a significant driver when accounting for phylogeny, suggesting that the chemical diversity is primarily driven by phylogeny. Comparisons of the relative effects of both environmental and genetic variability in determining plant chemical diversity have scarcely been performed at the genotypic level. In this study we demonstrate there is an essential need to do so if the extensive genotypic variation in plant biochemistry is to be fully understood. PMID:28382048

  6. Inhibitory effect of steroidal alkaloids on drug transport and multidrug resistance in human cancer cells.

    PubMed

    Lavie, Y; Harel-Orbital, T; Gaffield, W; Liscovitch, M

    2001-01-01

    Intrinsic or acquired resistance of tumor cells to multiple cytotoxic drugs (multidrug resistance MDR) is a major cause of failure of cancer chemotherapy. MDR is often caused by elevated expression of drug transporters such as P-glycoprotein (P-gp) or multidrug resistance protein (MRP). A number of compounds, termed chemosensitizers, have little or no cytotoxic action of their own, but inhibit (P-gp) or MRP-mediated drug export and are capable of sensitizing MDR cells to the cytotoxic effects of chemotherapeutic drugs. Here we examined the ability of steroidal alkaloids of plant origin, namely the Veratrum sp. alkaloid cyclopamine and the Lycopersicon sp. alkaloid tomatidine, to act as potent and effective chemosensitizers in multidrug resistant tumor cells. Drug uptake was determined by measuring accumulation of tetramethylrosamine in multidrug resistant NCI AdrR human adenocarcinoma cells. Resistance to adriamycin and vinblastine was determined by utilizing the MTT cell survival assay. Cyclopamine and tomatidine elevate tetramethylrosamine uptake by NCI AdrR cells and sensitize the cells to the cytotoxic action of adriamycin and vinblastine. In both cases these agents are comparable in patency and efficacy to verapamil, a reversal agent commonly used in MDR research. It is concluded that steroidal alkaloids of plant origin act as inhibitors of P-gp-mediated drug transport and multidrug resistance and therefore may serve as chemosensitizers in combination chemotherapy with conventional cytotoxic drugs for treating multidrug resistant cancer.

  7. High performance liquid chromatography analysis of canthinone alkaloids from Eurycoma longifolia.

    PubMed

    Choo, Chee-Yan; Chan, Kit-Lam

    2002-04-01

    A reversed phase-high performance liquid chromatography method with a photodiode array detector was developed for the simultaneous determination of three major alkaloids, 9-methoxycanthin-6-one (1), 3-methylcanthin-5,6-dione (2) and its 9-methoxy analogue (3) in Eurycoma longifolia Jack. These alkaloids were easily separated by a gradient elution protocol of 20 - 42 % acetonitrile in 0.1 % acetic acid. Compound 1 showed characteristic absorption at 350 nm only whereas its dione analogues, 2 and 3 displayed strong absorptions at both 350 and 451 nm. The linear calibration ranges were 0.7 - 50 microg x mL(-1) for 1, 1.5-50 microg x mL(-1) for 2 and 3.1 -100 microg x mL(-1) for 3. The recoveries of the three alkaloids were 90.8-101.0% with relative standard deviations from 0.35 to 6.31 % (n = 3). The limits of detection for all the alkaloids were within the range of 0.35 - 0.7 microg x mL(-1). This method was successfully applied to the phytochemical analysis of E. longifolia roots obtained from different sources.

  8. Detection of a new piperideine alkaloid in the pygidial glands of some Stenus beetles.

    PubMed

    Wittmann, Isabel; Schierling, Andreas; Dettner, Konrad; Göhl, Matthias; Schmidt, Jürgen; Seifert, Karlheinz

    2015-09-01

    Rove beetles of the genus Stenus produce and store bioactive alkaloids like stenusine (3), 3-(2-methylbut-1-enyl)pyridine (4), and cicindeloine (5) in their pygidial glands to protect themselves from predation and microorganismic infestation. The biosynthesis of stenusine (3), 3-(2-methylbut-1-enyl)pyridine (4), and cicindeloine (5) was previously investigated in Stenus bimaculatus, Stenus similis, and Stenus solutus, respectively. The piperideine alkaloid cicindeloine (5) occurs also as a major compound in the pygidial gland secretion of Stenus cicindeloides. The three metabolites 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 few modifications of shared precursor molecules, such as 2,3,4,5-tetrahydro-5-(2-methylbutylidene)pyridine (1). This piperideine alkaloid was synthesized and detected by GC/MS and GC at a chiral phase in the pygidial glands of Stenus similis, Stenus tarsalis, and Stenus cicindeloides.

  9. Prehistoric peyote use: alkaloid analysis and radiocarbon dating of archaeological specimens of Lophophora from Texas.

    PubMed

    El-Seedi, Hesham R; De Smet, Peter A G M; Beck, Olof; Possnert, Göran; Bruhn, Jan G

    2005-10-03

    Two archaeological specimens of peyote buttons, i.e. dried tops of the cactus Lophophora williamsii (Lem.) Coulter, from the collection of the Witte Museum in San Antonio, was subjected to radiocarbon dating and alkaloid analysis. The samples were presumably found in Shumla Cave No. 5 on the Rio Grande, Texas. Radiocarbon dating shows that the calibrated 14C age of the weighted mean of the two individual dated samples corresponds to the calendric time interval 3780-3660 BC (one sigma significance). Alkaloid extraction yielded approximately 2% of alkaloids. Analysis with thin-layer chromatography (TLC) and gas chromatography-mass spectrometry (GC-MS) led to the identification of mescaline in both samples. No other peyote alkaloids could be identified. The two peyote samples appear to be the oldest plant drug ever to yield a major bioactive compound upon chemical analysis. The identification of mescaline strengthens the evidence that native North Americans recognized the psychotropic properties of peyote as long as 5700 years ago.

  10. Evaluation of the analgesic effect of alkaloid extract of Peganum harmala L.: possible mechanisms involved.

    PubMed

    Farouk, Loubna; Laroubi, Amine; Aboufatima, Rachida; Benharref, Ahmed; Chait, Abderrahman

    2008-02-12

    The seeds of Peganum harmala L. (Pgh) (Zygophyllaceae) have been used in Moroccan traditional medicine for treatment of a various diseases and to relieve dolorous process. The major objective of this paper was to investigate the mechanism of the analgesia induced by alkaloid extract of Peganum harmala. In the present work, the antinociceptive action was assayed in several experimental models in mice: writhing, formalin, and hot plate tests. The alkaloid extract (12.5 and 25mg/kg) and in a dose-dependent manner significantly reduced the nociception by acetic acid intraperitoneal injection (p<0.001). In the formalin test, the extract also significantly reduced the painful stimulus in both phases of the test (p<0.001). Treatment with the extract when given by (i.p. or i.c.v.) or with morphine (10mg/kg, i.p.) produced a significant increase of the reaction time in hot plate test. These result showed that the alkaloid extract of Pgh contains active analgesic principles acting both centrally and peripherally. Furthermore, this antinociceptive effect has been avoided by naloxone at a dose of 1mg/kg in the first phase of formalin and hot plate tests indicating that this extract act partly through an opioid-mediated mechanism. In conclusion, the alkaloid extract of Peganum harmala seems to have both central and peripheral antinociceptive activities which may be mediated by opioid receptors.

  11. 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.

  12. Carbazole alkaloids from Murraya koenigii trigger apoptosis and autophagic flux inhibition in human oral squamous cell carcinoma cells.

    PubMed

    Utaipan, Tanyarath; Athipornchai, Anan; Suksamrarn, Apichart; Jirachotikoon, Canussanun; Yuan, Xiaohong; Lertcanawanichakul, Monthon; Chunglok, Warangkana

    2017-01-01

    Carbazole alkaloids, a major constituent of Murraya koenigii (L.) Sprengel (Rutaceae), exhibit biological effects such as anticancer activity via the induction of apoptosis, and they represent candidate chemotherapeutic agents. Oral squamous cell carcinoma (OSCC) is the most prevalent cancer of the oral cavity and a growing and serious health problem worldwide. In this study, we investigated the anticancer properties and mechanisms of action of two carbazole alkaloids derived from M. koenigii leaves, mahanine and isomahanine, in the OSCC cell line CLS-354. At 15 μM, mahanine and isomahanine were cytotoxic to CLS-354 cells, triggering apoptosis via caspase-dependent and -independent mechanisms. Autophagosomes, visualised using monodansylcadaverine (MDC) labelling, were numerous in carbazole alkaloid-treated cells. Mahanine and isomahanine markedly induced the expression of the autophagosome marker microtubule-associated protein 1 light chain 3, type II (LC3B-II). Genetic and chemical inhibition of autophagy via silencing of the Autophagy protein 5 gene and exposure to bafilomycin A1 (BafA1), respectively, did not arrest carbazole alkaloid-induced apoptosis, indicating that it occurs independently of autophagic activation. Surprisingly, both carbazole alkaloids caused increased accumulation of p62/sequestosome1 (p62/SQSTM1), with coordinated expression of LC3B-II and cleaved caspase-3, suggesting inhibition of autophagic flux. Our results suggest that inhibition of autophagic flux is associated with carbazole alkaloid-induced apoptosis. Our findings provide evidence of a novel cytotoxic action of natural carbazole alkaloids and support their use as candidate chemotherapeutic agents for the treatment of OSCC.

  13. The biology and chemistry of the zoanthamine alkaloids.

    PubMed

    Behenna, Douglas C; Stockdill, Jennifer L; Stoltz, Brian M

    2008-01-01

    Marine natural products have long played an important role in natural products chemistry and drug discovery. Mirroring the rich variety and complicated interactions of the marine environment, the substances isolated from sea creatures tend to be incredibly diverse in both molecular structure and biological activity. The natural products isolated from the polyps of marine zoanthids are no exception. The zoanthamine alkaloids, the first of which were isolated over 20 years ago, are of particular interest to the synthetic community because they feature a novel structural framework and exhibit a broad range of biological activities. In this Review, we summarize the major contributions to understanding the zoanthamine natural products with regard to their isolation and structure determination, as well as studies on their biological activity and total synthesis.

  14. 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.

  15. 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

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

    PubMed

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

    2001-05-18

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

  17. 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

  18. 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

  19. 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.

  20. Determination of Ephedrine Alkaloids in Botanicals and Dietary Supplements by HPLC-UV

    PubMed Central

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

    2008-01-01

    An international collaborative study was conducted of a high-performance liquid chromatography (HPLC)-UV method for the determination of the major (ephedrine [EP] and pseudoephedrine [PS]) and minor (norephedrine [NE], norpseudoephedrine [NP], methylephedrine [ME], and methylpseudoephedrine [MP]) alkaloids in selected dietary supplements representative of the commercially available products. Ten collaborating laboratories determined the ephedrine-type alkaloid content in 8 blind replicate samples. Five products contained ephedra ground herb or ephedra extract. These 5 products included ground botanical raw material of Ephedra sinica, a common powdered extract of Ephedra sinica, a finished product containing only Ephedra sinica ground botanical raw material, a complex multicomponent dietary supplement containing Ma Huang, and a high-protein chocolate flavored drink mix containing Ma Huang extract. In addition, collaborating laboratories received a negative control and negative control spiked with ephedrine alkaloids at high and low levels for recovery studies. Test extracts were treated to solid-phase extraction using a strong-cation exchange column to help remove interferences. The HPLC analyses were performed on a polar-embedded phenyl column using UV detection at 210 nm. Repeatability relative standard deviations (RSDr) ranged from 0.64–3.0% for EP and 2.0–6.6% for PS, excluding the high protein drink mix. Reproducibility relative standard deviations (RSDR) ranged from 2.1–6.6% for EP and 9.0–11.4% for PS, excluding the high protein drink mix. Recoveries ranged from 84.7–87.2% for EP and 84.6–98.2% for PS. The data developed for the minor alkaloids are more variable with generally unsatisfactory HORRATS(i.e., >2). However, since these alkaloids generally add little to the total alkaloid content of the products, the method gives satisfactory results in measuring total alkaloid content (RSDr 0.85–3.13%; RSDR 2.03–10.97%, HORRAT 0.69–3

  1. Direct and comprehensive analysis of ginsenosides and diterpene alkaloids in Shenfu injection by combinatory liquid chromatography-mass spectrometric techniques.

    PubMed

    Yang, Hua; Liu, Lei; Gao, Wen; Liu, Ke; Qi, Lian-Wen; Li, Ping

    2014-04-01

    Shenfu injection (SFI) is a widely used Chinese herbal formulation for cardiac diseases prepared from red ginseng and processed aconite root. Clinical observations and pharmacological effects on SFI have been well investigated. Chemical analysis and quality control studies of this formulation, however, are relatively limited, especially regarding toxic aconite alkaloids. In this work, a high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-QTOF MS) method was applied to comprehensive analysis of constituents in SFI. Highly sensitive MS allows direct analysis of injections without additional sample pretreatment required. Using diagnostic ions and fragmentation rules, we identified 23 trace diterpene alkaloids, nineteen ginseng saponins, one panaxytriol, and one 5-hydroxymethylfurfural in SFI. A LC-MS method with selected ion monitoring was then used to quantify 24 major alkaloids and ginsenosides. The method was validated in terms of linearity, accuracy and precision. Especially, the limits of quantification were low to 0.4-18ng/mL for diterpene alkaloids. The total concentrations of saponins and alkaloids were about 676-742μg/mL and 3-7μg/mL in five batches of SFI samples, respectively. Finally, cosine ratio and euclidean distance were introduced to evaluate the batch-to-batch reproducibility of SFI samples, and the results demonstrated high quality consistency. Global identification and quantification of complex constituents based on LC-MS promises wide applications in quality control and batch monitoring for herbal products.

  2. [Identification of aminoalcohol-diterpenoid alkaloids in Aconiti Lateralis Radix Praeparata and study of their cardiac effects].

    PubMed

    Wang, Lu; Ding, Jia-Yu; Liu, Xiu-Xiu; Tang, Ming-Hai; Chao, Ruo-Bing; Wang, Feng-Peng

    2014-12-01

    In order to affirm the cardioactive components in Fuzi, we identified a group of aminoalcohol- diterpenoid alkaloids in Fuzi using ultra high-performance liquid chromatography coupled with electrospray ionization mass spectrometer (UPLC-ESI-MS) method. Among a total of forty-one isolated ingredients, thirteen major aminoalcohol-diterpenoid alkaloids were identified by comparing their retention times and MS spectra with those of the reference substances. Moreover, Fuzi samples from different places of origin and with different processing methods were examined and their components displayed a pattern of high similarity, though the relative abundance varies probably due to their different processing methods. Furthermore, the cardiac effect of each identified alkaloid was individually evaluated using the isolated bullfrog heart perfusion experiment. Among the thirteen aminoalcohol diterpenoid alkaloids tested, six of them significantly enhanced the amplitude rates. Taken together, we affirm that the cardioactive components in Fuzi are aminoalcohol-diterpenoid alkaloids, shedding light on future studies of the mechanisms and development of these cardioactive compounds.

  3. Analytical methods for determination of alkaloids and saponins from roots of Caulophyllum thalictroids (L) Michx using UPLC HPLC and HPTLC

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A comparison study of analytical methods including HPLC, UPLC and HPTLC are presented in this paper for the determination of major alkaloid and triterpene saponins from the roots of Caulophyllum thalictroides (L.) Michx. (blue cohosh) and dietary supplements claiming to contain blue cohosh. The meth...

  4. GC-MS investigation of tropane alkaloids in Datura stramonium.

    PubMed

    Philipov, Stefan; Berkov, Strahil

    2002-01-01

    Alkaloids, GS-MS, Datura stramonium The alkaloid spectrum in roots, leaves and seeds of Datura stramonium L. was investigated by GC-MS. Twenty-nine tropane alkaloids are detected. Twelve of them are new constituents for the species and the two tropane esters 3-(3'-acetoxytropoyloxy)tropane (21) and 3-(2'-hydroxytropoyloxy)tropane (26) are described for the first time.

  5. Two new morphinane alkaloids from Sinomenium acutum.

    PubMed

    Wang, Xiao-Ling; Liu, Bing-Rui; Wang, Jun-Ru; Chen, Chien-Kuang; Qin, Guo-Wei; Lee, Shoei-Sheng

    2011-06-01

    Two new morphinane alkaloids, 1-hydroxy-10-oxo-sinomenine (1) and 4,5-epoxy-14-hydroxy sinomenine N-oxide (2), have been isolated from the stems of Sinomenium acutum. Their structures were established by various spectral analyses, especially 2D NMR experiments. The structure of 2 was confirmed by single crystal X-ray diffraction. The absolute configurations of 1 and 2 were deduced by comparison of CD spectra with the known alkaloid sinomenine (3). Compound 1 was tested for DPPH inhibition and gave IC(50) of 27.9 μM. Compound 2 was tested for neuroprotective effect and showed significant activity against β-amyloid(25-35)-induced oxidative injury (*P < 0.05) at 10 μM in PC-12 cells.

  6. Total synthesis of the Daphniphyllum alkaloid daphenylline

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

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

  7. 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.

  8. Two new alkaloids from Capparis himalayensis.

    PubMed

    Li, Yun-Qiu; Yang, Shi-Lin; Li, He-Ran; Xu, Li-Zhen

    2008-02-01

    Two new alkaloids, Capparin A (1) and B (2), along with seven known compounds 6-methoxyindoline-2,3-dione (3), wogonin (4), oroxylin A (5), kaempferol (6), apigenin (7), quercetin (8) and luteolin (9), were isolated from the whole plant of Capparis himalayensis. Their structures have been established on the basis of spectral methods and the structure of 1 was confirmed by X-ray crystallographic analysis.

  9. Muscarine, imidaozle, oxazole and thiazole alkaloids.

    PubMed

    Jin, Zhong

    2013-06-01

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

  10. 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

  11. 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

  12. Alkaloid patterns in some varieties of Datura stramonium.

    PubMed

    Berkov, Strahil; Zayed, Rawia; Doncheva, Tsvetelina

    2006-04-01

    A comparative GC-MS investigation of the alkaloid patterns of three varieties of Datura stramonium vars. stramonium, tatula and godronii, was carried out. Twenty-five tropane alkaloids were identified in the plant organs. Alkaloid patterns of the roots, leaves and seeds of the varieties grown at equal conditions in Bulgaria were very similar. In contrast, alkaloid pattern of D. stramonium var. stramonium, grown in Egypt, showed significant differences indicating that it is influenced more strongly by the environmental factors than genetic ones.

  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. 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.

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

    PubMed

    Plodek, Alois; Bracher, Franz

    2016-01-26

    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.

  16. Indole alkaloids from the leaves of Philippine Alstonia scholaris.

    PubMed

    Macabeo, Allan Patrick G; Krohn, Karsten; Gehle, Dietmar; Read, Roger W; Brophy, Joseph J; Cordell, Geoffrey A; Franzblau, Scott G; Aguinaldo, Alicia M

    2005-05-01

    The first seco-uleine alkaloids, manilamine (1) (18-hydroxy-19,20-dehydro-7,21-seco-uleine) and N4-methyl angustilobine B (2), were isolated from the (pH 5) alkaloid extract of Philippine Alstonia scholaris leaves together with the known indole alkaloids 19,20-(E)-vallesamine (3), angustilobine B N4-oxide (4), 20(S)-tubotaiwine (5), and 6,7-seco-angustilobine B (6). The structure of the alkaloids was established from MS and NMR experiments.

  17. Anticancer Alkaloids from Trees: Development into Drugs

    PubMed Central

    Isah, Tasiu

    2016-01-01

    Trees have made an enormous phytochemical contribution in anticancer drugs' development more than any other life form. The contributions include alkaloids that are biosynthesized in various ways and yield. Lead alkaloids isolated from the trees are taxol and camptothecins that currently have annual sales in billion dollars. Other important alkaloids isolated from these life forms include rohitukine, harringtonine, acronycine, thalicarpine, usambarensine, ellipticine, and matrines. Studies on their mechanism of action and target on the DNA and protein of cancerous cells aided the development of potent hemisynthesized congeners. The molecules and their congeners passed/are passing a long period of historical development before approved as antineoplastic drugs for cancer chemotherapy. Some of them did not find the application as anticancer drugs due to ineffectiveness in clinical trials; others are generating research interest in the antineoplastic activity at the present and have reached clinical trial stages. Potentials in antineoplastic molecules from trees are high and are hoped to be commensurate with cancer types afflicting human society in the future. PMID:28082790

  18. 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).

    PubMed

    Brown, Ammon W; Stegelmeier, Bryan L; Colegate, Steven M; Gardner, Dale R; Panter, Kip E; Knoppel, Edward L; Hall, Jeffery O

    2016-05-01

    Comfrey (Symphytum officinale), a commonly used herb, contains dehydropyrrolizidine alkaloids that, as a group of bioactive metabolites, are potentially hepatotoxic, pneumotoxic, genotoxic and carcinogenic. Consequently, regulatory agencies and international health organizations have recommended comfrey be used for external use only. However, in many locations comfrey continues to be ingested as a tisane or as a leafy vegetable. The objective of this work was to compare the toxicity of a crude, reduced comfrey alkaloid extract to purified lycopsamine and intermedine that are major constituents of S. officinale. Male, California White chicks were orally exposed to daily doses of 0.04, 0.13, 0.26, 0.52 and 1.04 mmol lycopsamine, intermedine or reduced comfrey extract per kg bodyweight (BW) for 10 days. After another 7 days chicks were euthanized. Based on clinical signs of poisoning, serum biochemistry, and histopathological analysis the reduced comfrey extract was more toxic than lycopsamine and intermedine. This work suggests a greater than additive effect of the individual alkaloids and/or a more potent toxicity of the acetylated derivatives in the reduced comfrey extract. It also suggests that safety recommendations based on purified compounds may underestimate the potential toxicity of comfrey.

  19. 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

  20. Monoterpene Indole Alkaloids from the Fruit of Tabernaemontana litoralis and Differential Alkaloid Composition in Various Fruit Components.

    PubMed

    Qu, Yang; Simonescu, Razvan; De Luca, Vincenzo

    2016-12-23

    Two new monoterpene indole alkaloids, isoakuammiline (1) and 18-hydroxypseudovincadifformine (2), and five known alkaloids, coronaridine (3), heyneanine (4), 3,19-oxidocoronaridine (5), tabersonine, and strictosidine, were identified from the fruit of Tabernaemontana litoralis. The structures of the alkaloids were determined using NMR and MS data analyses. While 18-hydroxypseudovincadifformine (2) showed a new hydroxylation pattern, isoakuammiline (1) revealed a novel skeleton for monoterpene indole alkaloids. In spite of the isolation of stemmadenine from the fruit tissues in other Tabernaemontana species, this vital biosynthetic precursor of iboga, aspidosperma, and pseudoaspidosperma skeletons was not found in T. litoralis.

  1. [A new alkaloid of Menispermum dauricum DC--dauriciline].

    PubMed

    Pang, X P; Chen, Y W; Li, X J; Long, J G

    1991-01-01

    A new phenolic dauricine-type alkaloid, named "dauriciline", was isolated from the rhizome of Menispermum dauricum DC. It is a pale yellow powder. Based on spectrometric analysis (UV.FAB-MS and 1HNMR) and chemical reaction the structure of the new alkaloid was elucidated as RR,7,7'-demethyldauricine (VI).

  2. Identification of the quinolizidine alkaloids in Sophora leachiana

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  3. 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...

  4. Leptopyrine, new alkaloid from Leptopyrum fumarioides L. (Ranunculaceae).

    PubMed

    Doncheva, Tsvetelina; Solongo, Amgalan; Kostova, Nadezhda; Gerelt-Od, Yadamsuren; Selenge, Dangaa; Philipov, Stefan

    2015-01-01

    A new type of isoquinoline alkaloid leptopyrine was isolated from the aerial parts of Leptopyrum fumarioides L. (Ranunculaceae) of Mongolian origin. The known alkaloids protopine and thalifoline were isolated for the first time from this the species. All structures were established by physical and spectral analyses.

  5. Evolution of alkaloid biosynthesis in the genus Narcissus.

    PubMed

    Berkov, Strahil; Martínez-Francés, Vanessa; Bastida, Jaume; Codina, Carles; Ríos, Segundo

    2014-03-01

    In an attempt to reveal the relationships between alkaloid biosynthesis and phylogeny, we investigated by GC-MS the alkaloid patterns of 22 species and 3 hybrids (from 45 locations) from seven main sections of the genus Narcissus (Amaryllidaceae). The results indicate that the first alkaloids to evolve in the genus Narcissus were of the lycorine- and homolycorine-type. The alkaloid pattern of the Nevadensis section supports its recent separation from the Pseudonarcissus section. The plants of Narcissus pallidulus (Ganymedes section) show a predominance of Sceletium-type compounds, which are quite rare in the Amaryllidaceae family. Two successful evolutionary strategies involving alkaloid biosynthesis and leading to an expansion in taxa and occupied area were determined. Firstly, a diversification of alkaloid patterns and a high alkaloid concentration in the organs of the large Narcissus species (in the Pseudonarcissus section) resulted in an improved chemical defence in diverse habitats. Secondly, both plant size and alkaloid biosynthesis were reduced (in the Bulbocodium and Apodanthi sections) relegated to dry pastures and rocky places.

  6. MULTICOMPONENT REACTIONS IN ALKALOID-BASED DRUG DISCOVERY

    PubMed Central

    Magedov, I. V.; Kornienko, A.

    2016-01-01

    Multicomponent reactions are emerging as a powerful tool in alkaloid-based drug discovery. This Highlight describes several recent (all published in 2011) examples of the employment of multicomponent reactions for the synthesis of biologically active alkaloids and their medicinally relevant analogues. PMID:27917001

  7. Binding of quinolizidine alkaloids to nicotinic and muscarinic acetylcholine receptors.

    PubMed

    Schmeller, T; Sauerwein, M; Sporer, F; Wink, M; Müller, W E

    1994-09-01

    Fourteen quinolizidine alkaloids, isolated from Lupinus albus, L. mutabilis, and Anagyris foetida, were analyzed for their affinity for nicotinic and/or muscarinic acetylcholine receptors. Of the compounds tested, the alpha-pyridones, N-methylcytisine and cytisine, showed the highest affinities at the nicotinic receptor, while several quinolizidine alkaloid types were especially active at the muscarinic receptor.

  8. 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.

  9. 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...

  10. Accumulation of Ergopeptide Alkaloids in Symbiotic Tall Fescue Grown under Deficits of Soil Water and Nitrogen Fertilizer

    PubMed Central

    Arechavaleta, M.; Bacon, C. W.; Plattner, R. D.; Hoveland, C. S.; Radcliffe, D. E.

    1992-01-01

    The fungus Acremonium coenophialum is endophytically associated with tall fescue (Festuca arundinacea Schreber). Within this symbiotum the fungus produces ergopeptide alkaloids, which are associated with livestock toxicoses. Environmental effects on the production of ergot alkaloids within the symbiotum are unknown. We conducted a greenhouse study of the effects of flooding, nitrogen rate during fertilization (11, 73, and 220 mg of N per pot weekly), nitrogen form (3.4 and 34 mg of N as NH4+ or NO3- per pot), and drought stress (-0.03, -0.05, and -0.50 MPa) on ergopeptide alkaloid concentrations in one genotype of nonsymbiotic and symbiotic tall fescue grown in plastic pots. It was determined that the concentration of ergovaline, the major type of ergopeptide alkaloid, was increased but was not as high as that in nonflooded controls. Total ergopeptide and ergovaline concentrations in plants receiving high (220 mg of N per pot) and low (11 mg of N per pot) levels of NH4NO3 fertilization were not affected by flooding. The form of nitrogen was important since all concentrations of NO3--N increased ergopeptide alkaloid content, as opposed to the effects of NH4+-N, which was effective only at high concentrations (34 mg of N per pot). Ergopeptide concentrations were highest in drought-stressed plants grown at -0.50 MPa and fertilized at the moderate or high N rate. The results suggest that within this genotype, ergopeptide alkaloid biosynthesis by the fungus is not appreciably affected by flooding but is greatly increased by high rates of N fertilization and moderate water deficit. PMID:16348675

  11. 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.

  12. A new pyrroloquinazoline alkaloid from Linaria vulgaris.

    PubMed

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

    2002-10-01

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

  13. Enantioselective Total Synthesis of Tricyclic Myrmicarin Alkaloids

    PubMed Central

    Movassaghi, Mohammad; Ondrus, Alison E.

    2010-01-01

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

  14. New ester alkaloids from lupins (genus lupinus).

    PubMed

    Mühlbauer, P; Witte, L; Wink, M

    1988-06-01

    Esters of 13-hydroxylupanine and 4-hydroxylupanine with acetic, propionic, butyric, isobutyric, valeric, isovaleric, tiglic, benzoic, and TRANS-cinnamic acid have been synthesized and characterized by capillary gas-liquid chromatography and mass spectrometry (EI-MS, CI-MS). In LUPINUS POLYPHYLLUS, L. ALBUS, L. ANGUSTIFOLIUS, and L. MUTABILIS we could identify new ester alkaloids (e.g. 13-propyloxylupanine, 13-butyryloxylupanine, 13-isobutyryloxylupanine, and 4-tigloyloxylupanine) besides the known esters, i.e. 13-acetoxylupanine, 13-isovaleroyloxylupanine, 13-angeloyloxylupanine, 13-tigloyloxylupanine, 13-benzoyloxylupanine, 13- CIS-cinnamoyloxylupanine nine, and 13- TRANS-cinnamoyloxylupanine.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  16. Cardiovascular pharmacological effects of bisbenzylisoquinoline alkaloid derivatives.

    PubMed

    Qian, Jia-Qing

    2002-12-01

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

  17. Antifungal Indole Alkaloids from Winchia calophylla.

    PubMed

    Yang, Mei-Li; Chen, Jia; Sun, Meng; Zhang, Dong-Bo; Gao, Kun

    2016-05-01

    Ten indole alkaloids (1-10) were obtained from an antifungal extract of Winchia calophylla, of which two (2 and 4) were new. N(4)-Methyl-10-hydroxyl-desacetylakuammilin (2) was an akuammiline-type indole alkaloid. N(1)-Methyl-echitaminic acid (4) was an unusual zwitterion with a basic vincorine-type skeleton. This is the first report of 10 in W. calophylla. The structures of all of the compounds were determined based on spectroscopic data, and their bioactivities were assessed. Compound 1 showed potent activity against the plant pathogenic fungi of Penicillium italicum and Fusarium oxysporum f.sp cubens with IC50 s of 10.4 and 11.5 µM, respectively, and 3 inhibited Rhizoctonia solani with an IC50 of 11.7 µM. Compounds 2 and 4 showed weak cytotoxicity against the human leukemic cell line HL-60 in vitro with IC50 s of 51.4 and 75.3 µM, respectively. Compounds 1 and 2 displayed weak activity against acetylcholinesterase with IC50 s around 61.3 and 52.6 µM, respectively.

  18. Measurement of some Benzylisoquinoline Alkaloids in Different Organs of Persian Poppy during Ontogenetical Stages.

    PubMed

    Rezaei, Mahdi; Naghavi, Mohammad Reza; Hosseinzadeh, Abdol Hadi; Abbasi, Alireza

    2016-05-01

    Papaver bracteatum, a perennial species, has been known as a rich source of thebaine and a potential alternative to Papaver somniferum for the production of codeine and some semisynthetic antagonist drugs. In this study, ion mobility spectrum (IMS) of the root, leaf, bottom part of stem, upper part of stem, capsule wall, petal, and capsule content during developmental stages of P. bracteatum including annual rosette, perennial rosette, bud initiation, pendulous bud, preflowering, and lancing were investigated. The IMS revealed thebaine, papaverine, and noscapine as the major components of the extracted alkaloids. Based on the results of the study it appears that, at least in part, there is a competition among the biosynthesis pathways of papaverine, noscapine, and morphinan alkaloids from a common source. Root and capsule wall were the most potent organs for extraction of thebaine, while lancing stage was the best developmental stage for thebaine exploitation. However, it seems that total biomass of root and capsule wall plays a key role in the final selection of favorite organ. Although papaverine and noscapine in the stem at preflowering stage had the most quantity, significant amounts were found in the capsule wall. In general, total alkaloid content of leaf was lower than the other plant parts.

  19. The effect of isoquinoline alkaloids on opiate withdrawal.

    PubMed

    Capasso, A; Piacente, S; De Tommasi, N; Rastrelli, L; Pizza, C

    2006-01-01

    Our interest has been centered on isoquinoline alkaloids obtained from Argemone mexicana (Papaveraceae), Aristolochia constricta (Aristolochiaceae) and the opium alkaloid, papaverine. In this respect, the effect of these isoquinoline alkaloids was investigated on contractions induced by naloxone of isolated guinea pig ileum acutely exposed to morphine in vitro. The activity of these alkaloids was compared to the control compound, papaverine. Furthermore, the effect of these isoquinoline alkaloids was also determined on naloxone-precipitated withdrawal in isolated guinea pig ileum exposed to DAMGO (highly selective mu opioid receptor agonist) and U50-488H (highly selective kappa opioid receptor agonist) to test whether the possible interaction of isoquinoline alkaloids on opioid withdrawal involves mu- and/or kappa-opioid receptors. Isoquinoline alkaloids from A. mexicana (from 5 x 10(-6) to 1 x 10(-4) M), from A. constricta (1 x 10(-5) x 10(-5)-1 x 10(-4) M) as well as papaverine treatment (1 x 10(-7)-5 x 10(-6)-1 x 10(-6) M) before or after the opioid agonists were able of both preventing and reversing the naloxone-induced contraction after exposure to mu (morphine and DAMGO) or kappa (U50-488H) opiate receptor agonists in a concentration-dependent manner. Both acetylcholine response and electrical stimulation were also reduced by isoquinoline alkaloids and papaverine treatment as well as the final opiate withdrawal was still reduced. The results of the present study indicate that isoquinoline alkaloids as well as papaverine were able to produce significant influence on the opiate withdrawal in vitro and these compounds were able to exert their effects both at mu and kappa opioid agonists.

  20. Spatial and temporal patterns of alkaloid variation in the poison frog Oophaga pumilio in Costa Rica and Panama over 30 years.

    PubMed

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

    2007-11-01

    A total of 232 alkaloids, representing 21 structural classes were detected in skin extracts from the dendrobatid poison frog Oophaga pumilio, collected from 53 different populations from over 30 years of research. The highly toxic pumiliotoxins and allopumiliotoxins, along with 5,8-disubstitiuted and 5,6,8-trisubstituted indolizidines, all of which are proposed to be of dietary mite origin, were common constituents in most extracts. One decahydroquinoline (DHQ), previously shown be of ant origin, occurred in many extracts often as a major alkaloid, while other DHQs occurred rather infrequently. Histrionicotoxins, thought to be of ant origin, did not appear to possess a specific pattern of occurrence among the populations, but when present, were usually found as major components. Certain 3,5-disubstituted pyrrolizidines and indolizidines, known to be of ant origin, did occur in extracts, but infrequently. Alkaloid composition differed with regard to geographic location of frog populations, and for populations that were sampled two or more times during the 30-year period significant changes in alkaloid profiles sometimes occurred. The results of this study indicate that chemical defense in a dendrobatid poison frog is dependent on geographic location and habitat type, which presumably controls the abundance and nature of alkaloid-containing arthropods.

  1. Morphinane alkaloids with cell protective effects from Sinomenium acutum.

    PubMed

    Bao, Guan-Hu; Qin, Guo-Wei; Wang, Rui; Tang, Xi-Can

    2005-07-01

    One new morphinane alkaloid, sinomenine N-oxide (1), and one new natural occurring morphinane alkaloid, N-demethylsinomenine (2), together with six known alkaloids, 7,8-didehydro-4-hydroxy-3,7-dimethoxymorphinan-6-ol (3), sinomenine (4), sinoacutine (5), N-norsinoacutine, acutumine, and acutumidine, were isolated from the stems of Sinomenium acutum. Their structures were elucidated on the basis of spectroscopic analysis and chemical methods. Compounds 2, 3, and 5 have protective effects against hydrogen peroxide-induced cell injury.

  2. Cytotoxic alkaloids from stems, leaves and twigs of Dasymaschalon blumei.

    PubMed

    Chanakul, Waraporn; Tuchinda, Patoomratana; Anantachoke, Natthinee; Pohmakotr, Manat; Piyachaturawat, Pawinee; Jariyawat, Surawat; Suksen, Kanoknetr; Jaipetch, Tharworn; Nuntasaen, Narong; Reutrakul, Vichai

    2011-10-01

    Bioassay-guided fractionation of the cytotoxic ethyl acetate extract from the stems of Dasymaschalon blumei (Annonaceae) led to the isolation of four aristololactam alkaloids, including the hitherto unknown 3,5-dihydroxy-2,4-dimethoxyaristolactam (1), as well as the three known compounds, aristolactam BI, goniopedaline, and griffithinam. Additionally, the cytotoxic extract from the combined leaves and twigs of the same plant yielded three known oxoaporphine alkaloids, oxodiscoguattine, dicentrinone, and duguevalline. The structures of aristolactams and oxoaporphine alkaloids were elucidated on the basis of spectroscopic methods. All isolates were evaluated for cytotoxicity against a panel of mammalian cancer cell lines and a noncancerous human embryonic kidney cell Hek 293.

  3. 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.

  4. The Amaryllidaceae alkaloids: biosynthesis and methods for enzyme discovery.

    PubMed

    Kilgore, Matthew B; Kutchan, Toni M

    2016-06-01

    Amaryllidaceae alkaloids are an example of the vast diversity of secondary metabolites with great therapeutic promise. The identification of novel compounds in this group with over 300 known structures continues to be an area of active study. The recent identification of norbelladine 4'-O-methyltransferase (N4OMT), an Amaryllidaceae alkaloid biosynthetic enzyme, and the assembly of transcriptomes for Narcissus sp. aff. pseudonarcissus and Lycoris aurea highlight the potential for discovery of Amaryllidaceae alkaloid biosynthetic genes with new technologies. Recent technical advances of interest include those in enzymology, next generation sequencing, genetic modification, nuclear magnetic resonance spectroscopy (NMR), and mass spectrometry (MS).

  5. A new cytotoxic carbazole alkaloid and two new other alkaloids from Clausena excavata.

    PubMed

    Peng, Wen-Wen; Zeng, Guang-Zhi; Song, Wei-Wu; Tan, Ning-Hua

    2013-07-01

    One new carbazole alkaloid, excavatine A (1), and two additional new alkaloids, excavatine B (2) and excavatine C (3), were isolated from the stems and leaves of Clausena excavata Burm.f. (Rutaceae). Their structures were determined on the basis of detailed spectroscopic analyses, especially 2D-NMR and HR-EI-MS data. Compounds 1-3 were tested for their cytotoxic activities against A549, HeLa, and BGC-823 cancer cell lines, and for their antimicrobial activities against Candida albicans and Staphylococcus aureus. Only 1 exhibited cytotoxicity against A549 and HeLa cell lines with the IC50 values of 5.25 and 1.91 μg/ml, respectively.

  6. Transcriptomic insight into terpenoid and carbazole alkaloid biosynthesis, and functional characterization of two terpene synthases in curry tree (Murraya koenigii)

    PubMed Central

    Meena, Seema; Rajeev Kumar, Sarma; Dwivedi, Varun; Kumar Singh, Anup; Chanotiya, Chandan S.; Akhtar, Md. Qussen; Kumar, Krishna; Kumar Shasany, Ajit; Nagegowda, Dinesh A.

    2017-01-01

    Curry tree (Murraya koenigii L.) is a rich source of aromatic terpenes and pharmacologically important carbazole alkaloids. Here, M. koenigii leaf transcriptome was generated to gain insight into terpenoid and alkaloid biosynthesis. Analysis of de novo assembled contigs yielded genes for terpene backbone biosynthesis and terpene synthases. Also, gene families possibly involved in carbazole alkaloid formation were identified that included polyketide synthases, prenyltransferases, methyltransferases and cytochrome P450s. Further, two genes encoding terpene synthases (MkTPS1 and MkTPS2) with highest in silico transcript abundance were cloned and functionally characterized to determine their involvement in leaf volatile formation. Subcellular localization using GFP fusions revealed the plastidial and cytosolic localization of MkTPS1 and MkTPS2, respectively. Enzymatic characterization demonstrated the monoterpene synthase activity of recombinant MkTPS1, which produced primarily (−)-sabinene from geranyl diphosphate (GPP). Recombinant MkTPS2 exhibited sesquiterpene synthase activity and formed (E,E)-α-farnesene as the major product from farnesyl diphosphate (FPP). Moreover, mRNA expression and leaf volatile analyses indicated that MkTPS1 accounts for (−)-sabinene emitted by M. koenigii leaves. Overall, the transcriptome data generated in this study will be a great resource and the start point for characterizing genes involved in the biosynthetic pathway of medicinally important carbazole alkaloids. PMID:28272514

  7. 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.

  8. Total Synthesis and Study of Myrmicarin Alkaloids

    PubMed Central

    Ondrus, Alison E.

    2010-01-01

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

  9. Tetrahydroberberine, a pharmacologically active naturally occurring alkaloid.

    PubMed

    Pingali, Subramanya; Donahue, James P; Payton-Stewart, Florastina

    2015-04-01

    Tetrahydroberberine (systematic name: 9,10-dimethoxy-5,8,13,13a-tetrahydro-6H-benzo[g][1,3]benzodioxolo[5,6-a]quinolizine), C20H21NO4, a widely distributed naturally occurring alkaloid, has been crystallized as a racemic mixture about an inversion center. A bent conformation of the molecule is observed, with an angle of 24.72 (5)° between the arene rings at the two ends of the reduced quinolizinium core. The intermolecular hydrogen bonds that play an apparent role in crystal packing are 1,3-benzodioxole -CH2···OCH3 and -OCH3···OCH3 interactions between neighboring molecules.

  10. Synthesis and Anticancer Activity of Epipolythiodiketopiperazine Alkaloids

    PubMed Central

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

    2013-01-01

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

  11. Heterocyclic Amaryllidaceae Alkaloids: Biosynthesis and Pharmacological Applications.

    PubMed

    Hotchandani, Tarun; Desgagne-Penix, Isabel

    2017-01-01

    Amaryllidaceae alkaloids (AAs), which are natural heterocyclic compounds, are isolated from Amaryllidaceae plants such as narcissus, snowdrop and spider lily. AAs have been extensively studied due to their multiple pharmacological properties. Nevertheless, knowledge of AA synthesis in plants is lacking and most genes encoding enzymes involved in their production remain unknown. AAs are structurally complex compounds which are challenging for total chemical synthesis that is economically viable. Therefore the understanding of AA biosynthesis could allow for the development of biotechnologies for the production of natural AAs or analogues, maintaining or improving their pharmacological properties. In this review, we describe the progress regarding the biosynthesis and pharmacological properties of AAs. The most recent developments in neurological, anti-cancer and anti-microbial bioactivities of heterocyclic AAs are covered.

  12. Coptis chinensis alkaloids exert anti-adipogenic activity on 3T3-L1 adipocytes by downregulating C/EBP-α and PPAR-γ.

    PubMed

    Choi, Jae Sue; Kim, Ji-Hye; Ali, Md Yousof; Min, Byung-Sun; Kim, Gun-Do; Jung, Hyun Ah

    2014-10-01

    Obesity is a complex, multifactorial, and chronic disease that increases the risk for type 2 diabetes, coronary heart disease and hypertension, and has become a major worldwide health problem. Developing novel anti-obesity drugs from natural products is a promising solution to the global health problem of obesity. While screening anti-obesity potentials of natural products, the methanol extract of the rhizome of Coptis chinensis (Coptidis Rhizoma) was found to significantly inhibit adipocyte differentiation and lipid contents in 3T3-L1 cells, as assessed by Oil-Red O staining. Five known alkaloids, berberine, epiberberine, coptisine, palmatine, and magnoflorine, were isolated from the n-BuOH fraction of the methanol extract of Coptidis Rhizoma. We determined the chemical structure of these alkaloids through comparisons of published nuclear magnetic resonance (NMR) spectral data. Furthermore, we screened these alkaloids for their ability to inhibit adipogenesis over a range of concentrations (12.5-50 μM). All five Coptidis Rhizoma alkaloids significantly inhibited lipid accumulation in 3T3-L1 cells without affecting cell viability in a concentration dependent manner. In addition, the five alkaloids significantly reduced the expression levels of several adipocyte marker genes including proliferator activated receptor-γ (PPAR-γ) and CCAAT/enhancer-binding protein-α (C/EBP-α). In the present study, we found that the isolated alkaloids inhibited adipogenesis in a dose-dependent manner in 3T3-L1 cells; this inhibition was attributed to their abilities to downregulate the protein levels of the adipocyte marker proteins PPAR-γ and C/EBP-α. Thus, these results suggest that Coptidis Rhizoma extract and its isolated alkaloids may be of therapeutic interest with respect to the treatment of obesity.

  13. Quantitative determination of ergot alkaloids in biological fluids by radioimmunoassay.

    PubMed Central

    Kleimola, T T

    1978-01-01

    1 Cross-reactivity of ergot alkaloids with an antiserum produced against lysergic acid conjugated with human serum, albumin was utilized to develop a radioimmunoassay for ergotamine, dihydroergotamine, dihydroergotoxine, ergometrine and methylergometrine in biological fluids. The antisera showed no cross-reactivity with simpler indole structures. 2 A procedure for extraction and concentration of alkaloids in biological fluids was developed. 3 The assay is sensitive for 1.8 ng/ml ergotamine, 1.5 ng/ml dihydroergotamine, 2.2 ng/ml dihydroergotoxine, 0.7 ng/ml ergotmetrine and 0.5 ng/ml methylergometrine. 4 The assay is sufficiently sensitive to permit the measurement of urine and plasma ergot alkaloid levels and it is suitable for determination in cases where a known ergot alkaloid is used. PMID:687503

  14. 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...

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

    PubMed

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

    1996-01-01

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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. Indole and beta-carboline alkaloids from Geissospermum sericeum.

    PubMed

    Steele, Jonathan C P; Veitch, Nigel C; Kite, Geoffrey C; Simmonds, Monique S J; Warhurst, David C

    2002-01-01

    The indole alkaloid geissoschizoline (1) and two new derivatives, geissoschizoline N(4)-oxide (2) and 1,2-dehydrogeissoschizoline (3), were obtained from the bark of Geissospermum sericeum together with the beta-carboline alkaloid flavopereirine (4). The in vitro antiplasmodial activity of these compounds was evaluated in chloroquine-resistant (K1) and chloroquine-sensitive (T9-96) Plasmodium falciparum. Their cytotoxicity was determined in a human (KB) cell line.

  2. Recent Progress in the Chemistry of Daphniphyllum Alkaloids †.

    PubMed

    Chattopadhyay, Amit Kumar; Hanessian, Stephen

    2017-03-08

    Daphniphyllum is an evergreen species known since 1826. After initial systematic investigations, more than 320 members of this family have been isolated, which comprise complex and fascinating structures. Unique azapolycyclic architectures containing one or more quaternary stereocenters render these alkaloids synthetically challenging. This review covers efforts toward the synthesis of Daphniphyllum alkaloids spanning the period from 2005 to the beginning of 2016, including reported biological activities as well as the isolation of new members of this genus.

  3. Unusual alkaloids of the highland species Astragalus cryptanthus Wedd. (Fabaceae).

    PubMed

    Echeverría, Javier; Espinoza, Sergio M; Niemeyer, Hermann M

    2017-01-01

    Two unusual caprolactam alkaloids, 3-(dimethylamino)hexahydro-2H-azepin-2-one and 3-(methylamino)-hexahydro-2H-azepin-2-one, were isolated from the aerial parts of Astragalus cryptanthus Wedd.; their structures were unambiguously determined based on data from extensive 1D and 2D NMR, GC-MS and FT-IR spectroscopic analyses. This is the first report of this alkaloid type in the genus Astragalus.

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

    PubMed

    Cramer, Luise; Beuerle, Till

    2012-12-01

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

  5. 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.

  6. Furoquinoline alkaloids from the southern African Rutaceae Teclea natalensis.

    PubMed

    Tarus, Paul K; Coombes, Philip H; Crouch, Neil R; Mulholland, Dulcie A; Moodley, B

    2005-03-01

    The chloroform and ethyl acetate extracts of the leaves of Teclea natalensis have yielded two furoquinoline alkaloids, 6-[(2,3-epoxy-3-methylbutyl)oxy]-4,7-dimethoxyfuro[2,3-b]quinoline and 4,7-dimethoxy-6-[(3-methyl-2-butenyl)oxy]furo[2,3-b]quinoline, and the known alkaloids 4,7-dimethoxy-8-[(3-methyl-2-butenyl)oxy]furo[2,3-b]quinoline, flindersiamine and dictamnine.

  7. Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism

    PubMed Central

    Yan, Xinmiao; Kang, Hong; Feng, Jun; Yang, Yiyan; Tang, Kailin; Zhu, Ruixin; Yang, Li; Wang, Zhengtao; Cao, Zhiwei

    2016-01-01

    Pyrrolizidine Alkaloids (PAs) are currently one of the most important botanical hepatotoxic ingredients. Glutathion (GSH) metabolism is the most reported pathway involved in hepatotoxicity mechanism of PAs. We speculate that, for different PAs, there should be a common mechanism underlying their hepatotoxicity in GSH metabolism. Computational methods were adopted to test our hypothesis in consideration of the limitations of current experimental approaches. Firstly, the potential targets of 22 PAs (from three major PA types) in GSH metabolism were identified by reverse docking; Secondly, glutathione S-transferase A1 (GSTA1) and glutathione peroxidase 1 (GPX1) targets pattern was found to be a special characteristic of toxic PAs with stepwise multiple linear regressions; Furthermore, the molecular mechanism underlying the interactions within toxic PAs and these two targets was demonstrated with the ligand-protein interaction analysis; Finally, GSTA1 and GPX1 were proved to be significant nodes in GSH metabolism. Overall, toxic PAs could be identified by GSTA1 and GPX1 targets pattern, which suggests their common hepatotoxicity mechanism: the interfering of detoxication in GSH metabolism. In addition, all the strategies developed here could be extended to studies on toxicity mechanism of other toxins. PMID:26959016

  8. Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism.

    PubMed

    Yan, Xinmiao; Kang, Hong; Feng, Jun; Yang, Yiyan; Tang, Kailin; Zhu, Ruixin; Yang, Li; Wang, Zhengtao; Cao, Zhiwei

    2016-03-07

    Pyrrolizidine Alkaloids (PAs) are currently one of the most important botanical hepatotoxic ingredients. Glutathion (GSH) metabolism is the most reported pathway involved in hepatotoxicity mechanism of PAs. We speculate that, for different PAs, there should be a common mechanism underlying their hepatotoxicity in GSH metabolism. Computational methods were adopted to test our hypothesis in consideration of the limitations of current experimental approaches. Firstly, the potential targets of 22 PAs (from three major PA types) in GSH metabolism were identified by reverse docking; Secondly, glutathione S-transferase A1 (GSTA1) and glutathione peroxidase 1 (GPX1) targets pattern was found to be a special characteristic of toxic PAs with stepwise multiple linear regressions; Furthermore, the molecular mechanism underlying the interactions within toxic PAs and these two targets was demonstrated with the ligand-protein interaction analysis; Finally, GSTA1 and GPX1 were proved to be significant nodes in GSH metabolism. Overall, toxic PAs could be identified by GSTA1 and GPX1 targets pattern, which suggests their common hepatotoxicity mechanism: the interfering of detoxication in GSH metabolism. In addition, all the strategies developed here could be extended to studies on toxicity mechanism of other toxins.

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

    PubMed

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

    2016-05-01

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

  10. Chemistry and Biology of the Pyrrole-Imidazole Alkaloids.

    PubMed

    Lindel, Thomas

    2017-01-01

    More than a decade after our last review on the chemistry of the pyrrole-imidazole alkaloids, it was time to analyze once more the developments in that field. The comprehensive article focusses on the total syntheses of pyrrole-imidazole alkaloids that have appeared since 2005. The classic monomeric pyrrole-imidazole alkaloids have all been synthesized, sometimes primarily to demonstrate the usefulness of a new method, as in the case of the related molecules agelastatin A and cyclooroidin with more than 15 syntheses altogether. The phakellin skeleton has been made more than 10 times, too, with a focus on the target structure itself. Thus, some of the pyrrole-imidazole alkaloids are now available in gram amounts, and the supply problem has been solved. The total synthesis of the dimeric pyrrole-imidazole alkaloids is still mostly in its pioneering phase with two routes to palau'amine and massadine discovered and three routes to the axinellamines and ageliferin. In addition, the review summarizes recent discoveries regarding the biological activity of the pyrrole-imidazole alkaloids. Regarding the biosynthesis of sceptrin, a pathway is proposed that starts from nagelamide I and proceeds via two electrocyclizations and reduction.

  11. 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.

  12. 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.

  13. Genetics, Genomics and Evolution of Ergot Alkaloid Diversity

    PubMed Central

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

    2015-01-01

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

  14. Cytotoxicity studies of lycorine alkaloids of the Amaryllidaceae.

    PubMed

    Nair, Jerald J; van Staden, Johannes

    2014-08-01

    The plant family Amaryllidaceae is renowned for its unique alkaloid constituents which possess a significant array of structural diversity. Several of these alkaloids are known for their interesting biological properties, of which galanthamine and pancratistatin have acquired a privileged status due to their relevance in the pharmaceutical arena. In particular, galanthamine represents the first prescription drug emanating from the Amaryllidaceae after its approval by the FDA in 2001 for the treatment of Alzheimer's disease. Following on this commercial success there have been sustained projections for the emergence of an anticancer agent related to pancratistatin due to the potency, selectivity, low toxicity and high tolerability typifying targets of this series of alkaloids. The lycorine series of alkaloids have also garnered widespread interest as cytotoxic agents and were amongst the earliest of the Amaryllidaceae constituents to exhibit such activity. To date over 100 of such naturally-occurring or synthetically-derived alkaloids have been screened for cytotoxic effects against a number of cancer cell lines. This survey examines the cytotoxic properties of lycorine alkaloids, highlights the outcomes of structure-activity relationship orientated studies and affords plausible insights to the mechanistic rationale behind these effects.

  15. [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.

  16. Effect of Iboga Alkaloids on µ-Opioid Receptor-Coupled G Protein Activation

    PubMed Central

    Antonio, Tamara; Childers, Steven R.; Rothman, Richard B.; Dersch, Christina M.; King, Christine; Kuehne, Martin; Bornmann, William G.; Eshleman, Amy J.; Janowsky, Aaron; Simon, Eric R.; Reith, Maarten E. A.; Alper, Kenneth

    2013-01-01

    Objective The iboga alkaloids are a class of small molecules defined structurally on the basis of a common ibogamine skeleton, some of which modify opioid withdrawal and drug self-administration in humans and preclinical models. These compounds may represent an innovative approach to neurobiological investigation and development of addiction pharmacotherapy. In particular, the use of the prototypic iboga alkaloid ibogaine for opioid detoxification in humans raises the question of whether its effect is mediated by an opioid agonist action, or if it represents alternative and possibly novel mechanism of action. The aim of this study was to independently replicate and extend evidence regarding the activation of μ-opioid receptor (MOR)-related G proteins by iboga alkaloids. Methods Ibogaine, its major metabolite noribogaine, and 18-methoxycoronaridine (18-MC), a synthetic congener, were evaluated by agonist-stimulated guanosine-5´-O-(γ-thio)-triphosphate ([35S]GTPγS) binding in cells overexpressing the recombinant MOR, in rat thalamic membranes, and autoradiography in rat brain slices. Results And Significance In rat thalamic membranes ibogaine, noribogaine and 18-MC were MOR antagonists with functional Ke values ranging from 3 uM (ibogaine) to 13 uM (noribogaine and 18MC). Noribogaine and 18-MC did not stimulate [35S]GTPγS binding in Chinese hamster ovary cells expressing human or rat MORs, and had only limited partial agonist effects in human embryonic kidney cells expressing mouse MORs. Ibogaine did not did not stimulate [35S]GTPγS binding in any MOR expressing cells. Noribogaine did not stimulate [35S]GTPγS binding in brain slices using autoradiography. An MOR agonist action does not appear to account for the effect of these iboga alkaloids on opioid withdrawal. Taken together with existing evidence that their mechanism of action also differs from that of other non-opioids with clinical effects on opioid tolerance and withdrawal, these findings suggest a

  17. Beta-carboline and quinoline alkaloids in root cultures and intact plants of Peganum harmala.

    PubMed

    Zayed, Rawin; Wink, Michael

    2005-01-01

    Alkaloid profiles of root and shoot cultures, seedlings and mature plants were analysed by capillary GLC and GLC-MS. beta-Carboline alkaloids, such as harmine, harmaline dominate in normal and root cultures transformed by Agrobacterium rhizogenes, as well as in roots and fruits of the plant. In shoots, flowers and shoot cultures quinoline alkaloids such as peganine, deoxypeganine, vasicinone and deoxyvasicinone widely replace the beta-carboline alkaloids. In root cultures, the formation of beta-carboline alkaloids can be induced by methyljasmonate and several other elicitors indicating that these alkaloids are part of the reactive chemical defence system of Peganum harmala.

  18. Application of high-performance capillary electrophoresis to the quantitative analysis of nicotine and profiling of other alkaloids in ATF-regulated tobacco products.

    PubMed

    Lu, G H; Ralapati, S

    1998-01-01

    Tobacco products regulated by the Bureau of Alcohol, Tobacco and Firearms (ATF), are classified at different excise tax rates according to the Code of Federal Regulations. These include the smoking (cigars, cigarettes, pipe tobacco and roll-your-own) and smokeless (chewing tobacco and snuff) tobacco products. The active principal components in all tobacco products belong to a class of compounds known as alkaloids. Nicotine is the major tobacco alkaloid, comprising about 98% of the total alkaloids. It is also the primary determinant of what constitutes a tobacco product from a regulatory standpoint. Nornicotine, anabasine and anatabine constitute the minor tobacco alkaloids of importance and interest to ATF. We have previously shown capillary electrophoresis (CE) to be a powerful analytical tool for monitoring nicotine in ATF-regulated products. Here we have extended those CE studies to (i) quantitate nicotine in ATF-regulated tobacco products and (ii) to characterize these different tobacco products according to their alkaloid profiles. Results from these studies will be presented.

  19. Major depression

    MedlinePlus

    Depression - major; Depression - clinical; Clinical depression; Unipolar depression; Major depressive disorder ... providers do not know the exact causes of depression. It is believed that chemical changes in the ...

  20. 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.

  1. Liquid chromatographic analysis of cinchona alkaloids in beverages.

    PubMed

    Horie, Masao; Oishi, Mitsuo; Ishikawa, Fusako; Shindo, Tetsuya; Yasui, Akiko; Ogino, Shuzo; Ito, Koichi

    2006-01-01

    A method for the determination of Cinchona extract (whose main components are the alkaloids cinchonine, cinchonidine, quinidine, and quinine) in beverages by liquid chromatography was developed. A beverage with an alcohol content of more than 10% was loaded onto an OASIS HLB solid-phase extraction cartridge, after it was adjusted to pH 10 with 28% ammonium hydroxide. Other beverages were centrifuged at 4000 rpm for 5 min, and the supernatant was loaded onto the cartridge. The cartridge was washed with water followed by 15% methanol, and the Cinchona alkaloids were eluted with methanol. The Cinchona alkaloids in the eluate were chromatographed on an L-column ODS (4.6 mm id x 150 mm) with methanol and 20 mmol/L potassium dihydrogen phosphate (3 + 7) as the mobile phase. Cinchona alkaloids were monitored with an ultraviolet (UV) detector at 230 nm, and with a fluorescence detector at 405 nm for cinchonine and cinchonidine and 450 nm for quinidine and quinine (excitation at 235 nm). The calibration curves for Cinchona alkaloids with the UV detector showed good linearity in the range of 2-400 microg/mL. The detection limit of each Cinchona alkaloid, taken to be the concentration at which the absorption spectrum could be identified, was 2 microg/mL. The recovery of Cinchona alkaloids added at a level of 100 microg/g to various kinds of beverages was 87.6-96.5%, and the coefficients of variation were less than 3.3%. A number of beverage samples, some labeled to contain bitter substances, were analyzed by the proposed method. Quinine was detected in 2 samples of carbonated beverage.

  2. 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...

  3. 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 ...

  4. 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.

  5. Dehydropyrrolizidine Alkaloid Toxicity, Cytotoxicity, and Carcinogenicity

    PubMed Central

    Stegelmeier, Bryan L.; Colegate, Steven M.; Brown, Ammon W.

    2016-01-01

    Dehydropyrrolizidine alkaloid (DHPA)-producing plants have a worldwide distribution amongst flowering plants and commonly cause poisoning of livestock, wildlife, and humans. Previous work has produced considerable understanding of DHPA metabolism, toxicity, species susceptibility, conditions, and routes of exposure, and pathogenesis of acute poisoning. Intoxication is generally caused by contaminated grains, feed, flour, and breads that result in acute, high-dose, short-duration poisoning. Acute poisoning produces hepatic necrosis that is usually confirmed histologically, epidemiologically, and chemically. Less is known about chronic poisoning that may result when plant populations are sporadic, used as tisanes or herbal preparations, or when DHPAs contaminate milk, honey, pollen, or other animal-derived products. Such subclinical exposures may contribute to the development of chronic disease in humans or may be cumulative and probably slowly progress until liver failure. Recent work using rodent models suggest increased neoplastic incidence even with very low DHPA doses of short durations. These concerns have moved some governments to prohibit or limit human exposure to DHPAs. The purpose of this review is to summarize some recent DHPA research, including in vitro and in vivo DHPA toxicity and carcinogenicity reports, and the implications of these findings with respect to diagnosis and prognosis for human and animal health. PMID:27916846

  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.

  7. 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

  8. 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.

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

    NASA Astrophysics Data System (ADS)

    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.

  10. 6,7-diepicastanospermine, a tetrahydroxyindolizidine alkaloid inhibitor of amyloglucosidase

    SciTech Connect

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

    1991-10-15

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

  11. Epidihydropinidine, the main piperidine alkaloid compound of Norway spruce (Picea abies) shows promising antibacterial and anti-Candida activity.

    PubMed

    Fyhrquist, Pia; Virjamo, Virpi; Hiltunen, Eveliina; Julkunen-Tiitto, Riitta

    2017-03-01

    This study reports for the first time promising antibacterial and antifungal effects of epidihydropinidine, the major piperidine alkaloid in the needles and bark of Norway spruce, Picea abies (L.) Karsten. Epidihydropinidine was growth inhibitory against all bacterial and fungal strains used in our investigation, showing the lowest MIC value of 5.37μg/mL against Pseudomonas aeruginosa, Enterococcus faecalis, Candida glabrata and C. albicans. Epidihydropinidine was nearly three times more active than tetracycline against P. aeruginosa and E. faecalis. Promising antibacterial effects were also recorded against Staphylococcus aureus and Bacillus cereus (MIC 10.75μg/mL) as well as against Salmonella enterica (MIC and MBC 43μg/mL). Our preliminary results suggest that epidihydropinidine as well related alkaloids of Norway spruce could be powerful candidates for new antibiotics and for preventing food spoilage.

  12. Identification and quantification of isoquinoline alkaloids in the genus Sarcocapnos by GC-MS.

    PubMed

    Suau, R; Cabezudo, B; Valpuesta, M; Posadas, N; Diaz, A; Torres, G

    2005-01-01

    Six cularine alkaloids, cularicine, O-methylcularicine, celtisine, cularidine, cularine and celtine, three isocularine alkaloids, sarcophylline, sarcocapnine and sarcocapnidine, and five non-cularine alkaloids, glaucine, protopine, ribasine, dihydrosanguinarine and chelidonine, were identified and quantified by GC-MS in nine taxa of the genus Sarcocapnos (Fumariaceae). The chemotaxonomic significance of the results is discussed.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Teratogenic alkaloid-containing Lupinus spp. cause significant losses to the cattle industry. Previous research has suggested that Holstein cattle clear toxic Delphinium alkaloids from their serum at a greater rate than beef cattle. The toxicokinetics of lupine alkaloids in Holsteins are not known...

  14. 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.

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

    PubMed

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

    2013-09-16

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

  16. Quantitative determination of Amaryllidaceae alkaloids from Galanthus reginae-olgae subsp. vernalis and in vitro activities relevant for neurodegenerative diseases.

    PubMed

    Conforti, Filomena; Loizzo, Monica Rosa; Marrelli, Mariangela; Menichini, Federica; Statti, Giancarlo A; Uzunov, Dimitar; Menichini, Francesco

    2010-01-01

    In the present work the qualitative and quantitative analysis of Amaryllidaceae-type alkaloids in the aerial parts and bulbs of Galanthus reginae-olgae Orph. subsp. vernalis Kamari is presented for the first time using GC-MS analysis. The alkaloids galanthamine, lycorine, and tazettine were identified in both extracts while crinine and neronine were found only in the bulbs. The yield of alkaloid fraction from bulbs (36.8%) is very high compared to the yield from aerial parts (9.34%). Lycorine was the major component in both fractions. The antioxidant potential was determined by three complementary methods. The preparations to reduce the stable free radical DPPH to the yellow-colored 1,1-diphenyl-2-picrylhydrazyl with IC(50) values of 39 and 29 mug/mL for MeOH extracts from aerial parts and bulbs, respectively. The higher activity was given by EtOAc fraction of aerial parts with IC(50) of 10 mug/mL. This activity is probably due to the presence in EtOAc fraction of polar compounds such as polyphenols. The fraction exhibited a significant antioxidant capacity also in the beta-carotene-linoleic acid test system. A higher level of antioxidant activity was observed for EtOAc fraction from bulbs with IC(50) of 10 mug/mL after 30 min and 9 mug/mL after 60 min of incubation. In contrast, the fraction from bulbs performed poorly in the lipid peroxidation liposomes assay. Significant activity was obtained for dichloromethane fraction from aerial parts (IC(50) of 74 mug/mL). The major abundance of alkaloid in dichloromethane fraction may be responsible of the bulbs anti-cholinesterase highest activity (38.5%) at 0.5 mg/mL.

  17. Characterization of chemical constituents and rats metabolites of an alkaloidal extract of Alstonia scholaris leaves by liquid chromatography coupled with mass spectrometry.

    PubMed

    Cao, Jing; Shen, Hong-Mei; Wang, Qi; Qian, Yi; Guo, Hong-Cheng; Li, Kai; Qiao, Xue; Guo, De-An; Luo, Xiao-Dong; Ye, Min

    2016-07-15

    Alstonia scholaris has been used in "Dai" ethnic medicine to treat chronic respiratory diseases for a long history, and the major bioactive constituents are alkaloids. An alkaloidal extract of A. scholaris leaves (AAS) has been developed into an investigational new drug, and has been approved for phase I/II clinical trials by China Food and Drug Administration. However, little is known on the chemical composition and in vivo metabolism of AAS, thus far. In this study, an ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC/qTOF-MS) method was established to characterize the chemical constituents of AAS. Samples were separated on an ACQUITY UPLC CSH column (2.1×100mm, 1.7μm) with acetonitrile and water containing 0.3% formic acid as the mobile phase. On the basis of high-accuracy mass spectral analysis, a total of 35 alkaloids were characterized from AAS, including 11 scholaricine-type, 9 vallesamine-type, 12 picrinine-type, and 3 tubotaiwine-type alkaloids. Furthermore, the metabolic pathways of 4 representative alkaloids in rats were studied. They mainly undertook hydroxylation and glucuronidation reactions. Based on the above metabolic pathways, the metabolism of AAS (10mg/kg) in rats after oral administration was studied by LC/MS. A total of 33 compounds in plasma, 40 compounds in urine, and 38 compounds in feces were characterized. The results indicated that scholaricine-type alkaloids could get into circulation more readily than the other types. This is the first systematic study on chemical profiling and metabolites identification of AAS.

  18. Effect of alkaloids isolated from Amaryllidaceae on herpes simplex virus.

    PubMed

    Renard-Nozaki, J; Kim, T; Imakura, Y; Kihara, M; Kobayashi, S

    1989-01-01

    Studies were carried out on the effects of Amaryllidaceae alkaloids and their derivatives upon herpes simplex virus (type 1), the relationship between their structure and antiviral activity and the mechanism of this activity. All alkaloids used in these experiments were biosynthesized from N-benzylphenethylamine; the apogalanthamine group was synthesized in our laboratory; those which may eventually prove to be antiviral agents had a hexahydroindole ring with two functional hydroxyl groups. Benzazepine compounds were neither cytotoxic nor antiviral, but many structures containing dibenzazocine were toxic at low concentrations. It was established that the antiviral activity of alkaloids is due to the inhibition of multiplication and not to the direct inactivation of extracellular viruses. The mechanism of the antiviral effect could be partly explained as a blocking of viral DNA polymerase activity.

  19. Quinolizidine alkaloids from the curare adjuvant Clathrotropis glaucophylla.

    PubMed

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

    2002-12-01

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

  20. 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

  1. beta-Carboline alkaloids: biochemical and pharmacological functions.

    PubMed

    Cao, Rihui; Peng, Wenlie; Wang, Zihou; Xu, Anlong

    2007-01-01

    beta-Carboline alkaloids are a large group of natural and synthetic indole alkaloids with different degrees of aromaticity, some of which are widely distributed in nature, including various plants, foodstuffs, marine creatures, insects, mammalians as well as human tissues and body fluids. These compounds are of great interest due to their diverse biological activities. Particularly, these compounds have been shown to intercalate into DNA, to inhibit CDK, Topisomerase, and monoamine oxidase, and to interact with benzodiazepine receptors and 5-hydroxy serotonin receptors. Furthermore, these chemicals also demonstrated a broad spectrum of pharmacological properties including sedative, anxiolytic, hypnotic, anticonvulsant, antitumor, antiviral, antiparasitic as well as antimicrobial activities. In this review, we summerized the biochemical and pharmacological functions of beta-carboline alkaloids.

  2. 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

  3. Phytochemical and biological investigations of Amaryllidaceae alkaloids: a review.

    PubMed

    Ding, Yan; Qu, Dan; Zhang, Kai-Mei; Cang, Xiao-Xin; Kou, Zi-Nong; Xiao, Wei; Zhu, Jing-Bo

    2017-01-01

    Amaryllidaceae is a family that includes 75 genera and about 1100 species, which have a long history of medicinal use. Many plants have been proven to possess efficacy for neurological injury and inflammatory conditions. This article summarizes 357 Amaryllidaceae alkaloids, and cites 166 174 references over the last three decades. These alkaloids are classified into 14 skeleton types, and their abundant sources are also included. Modern pharmacology studies demonstrate that alkaloids that exclusively occur in Amaryllidaceae plant possess wide-ranging pharmacological actions, especially effects on the central nervous system, as well as antitumor, antimicrobial, and anti-inflammatory activities. Effective monomeric compounds from Amaryllidaceae screened for pharmacological activity in vivo and in vitro are also summarized.

  4. Mechanistic insights to the cytotoxicity of Amaryllidaceae alkaloids.

    PubMed

    Nair, Jerald J; Rárová, Lucie; Strnad, Miroslav; Bastida, Jaume; van Staden, Johannes

    2015-01-01

    With over 500 individual compounds, the Amaryllidaceae alkaloids represent a large and structurally diverse group of phytochemicals. Coupled to this structural diversity is the significant array of biological properties manifested by many of its members, of which their relevance in motor neuron disease and cancer chemotherapy has attracted considerable attention. To this extent, galanthamine has evolved into a successful commercial drug for Alzheimer's disease since its approval by the FDA in 2001. Concurrently, there have been several positive indicators for the emergence of an anticancer drug from the Amaryllidaceae due to the potency of several of its representatives as cell line specific antiproliferative agents. In this regard, the phenanthridones such as pancratistatin and narciclasine have offered most promise since their advancement into clinical trials, following which there has been renewed interest in the cytotoxic properties of these alkaloids. Given this background, this review seeks to highlight the various mechanisms which have been invoked to corroborate the cytotoxic effects of Amaryllidaceae alkaloids.

  5. Aza-tryptamine substrates in monoterpene indole alkaloid biosynthesis

    PubMed Central

    Lee, Hyang-Yeol; Yerkes, Nancy; O’Connor, Sarah E.

    2009-01-01

    Biosynthetic pathways can be hijacked to yield novel compounds by introduction of novel starting materials. Here we have altered tryptamine, which serves as the starting substrate for a variety of alkaloid biosynthetic pathways, by replacing the indole with one of four aza-indole isomers. We show that two aza-tryptamine substrates can be successfully incorporated into the products of the monoterpene indole alkaloid pathway in Catharanthus roseus. Use of unnatural heterocycles in precursor directed biosynthesis, in both microbial and plant natural product pathways, has not been widely demonstrated, and successful incorporation of starting substrate analogs containing the aza-indole functionality has not been previously reported. This work serves as a starting point to explore fermentation of aza-alkaloids from other tryptophan and tryptamine derived natural product pathways. PMID:20064432

  6. Aza-tryptamine substrates in monoterpene indole alkaloid biosynthesis.

    PubMed

    Lee, Hyang-Yeol; Yerkes, Nancy; O'Connor, Sarah E

    2009-12-24

    Biosynthetic pathways can be hijacked to yield novel compounds by introduction of novel starting materials. Here we have altered tryptamine, which serves as the starting substrate for a variety of alkaloid biosynthetic pathways, by replacing the indole with one of four aza-indole isomers. We show that two aza-tryptamine substrates can be successfully incorporated into the products of the monoterpene indole alkaloid pathway in Catharanthus roseus. Use of unnatural heterocycles in precursor-directed biosynthesis, in both microbial and plant natural product pathways, has not been widely demonstrated, and successful incorporation of starting substrate analogs containing the aza-indole functionality has not been previously reported. This work serves as a starting point to explore fermentation of aza-alkaloids from other tryptophan- and tryptamine-derived natural product pathways.

  7. 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.

  8. CYP96T1 of Narcissus sp. aff. pseudonarcissus Catalyzes Formation of the Para-Para' C-C Phenol Couple in the Amaryllidaceae Alkaloids

    PubMed Central

    Kilgore, Matthew B.; Augustin, Megan M.; May, Gregory D.; Crow, John A.; Kutchan, Toni M.

    2016-01-01

    The Amaryllidaceae alkaloids are a family of amino acid derived alkaloids with many biological activities; examples include haemanthamine, haemanthidine, galanthamine, lycorine, and maritidine. Central to the biosynthesis of the majority of these alkaloids is a C-C phenol-coupling reaction that can have para-para', para-ortho', or ortho-para' regiospecificity. Through comparative transcriptomics of Narcissus sp. aff. pseudonarcissus, Galanthus sp., and Galanthus elwesii we have identified a para-para' C-C phenol coupling cytochrome P450, CYP96T1, capable of forming the products (10bR,4aS)-noroxomaritidine and (10bS,4aR)-noroxomaritidine from 4′-O-methylnorbelladine. CYP96T1 was also shown to catalyzed formation of the para-ortho' phenol coupled product, N-demethylnarwedine, as less than 1% of the total product. CYP96T1 co-expresses with the previously characterized norbelladine 4′-O-methyltransferase. The discovery of CYP96T1 is of special interest because it catalyzes the first major branch in Amaryllidaceae alkaloid biosynthesis. CYP96T1 is also the first phenol-coupling enzyme characterized from a monocot. PMID:26941773

  9. CYP96T1 of Narcissus sp. aff. pseudonarcissus Catalyzes Formation of the Para-Para' C-C Phenol Couple in the Amaryllidaceae Alkaloids.

    PubMed

    Kilgore, Matthew B; Augustin, Megan M; May, Gregory D; Crow, John A; Kutchan, Toni M

    2016-01-01

    The Amaryllidaceae alkaloids are a family of amino acid derived alkaloids with many biological activities; examples include haemanthamine, haemanthidine, galanthamine, lycorine, and maritidine. Central to the biosynthesis of the majority of these alkaloids is a C-C phenol-coupling reaction that can have para-para', para-ortho', or ortho-para' regiospecificity. Through comparative transcriptomics of Narcissus sp. aff. pseudonarcissus, Galanthus sp., and Galanthus elwesii we have identified a para-para' C-C phenol coupling cytochrome P450, CYP96T1, capable of forming the products (10bR,4aS)-noroxomaritidine and (10bS,4aR)-noroxomaritidine from 4'-O-methylnorbelladine. CYP96T1 was also shown to catalyzed formation of the para-ortho' phenol coupled product, N-demethylnarwedine, as less than 1% of the total product. CYP96T1 co-expresses with the previously characterized norbelladine 4'-O-methyltransferase. The discovery of CYP96T1 is of special interest because it catalyzes the first major branch in Amaryllidaceae alkaloid biosynthesis. CYP96T1 is also the first phenol-coupling enzyme characterized from a monocot.

  10. Dracunculus medinensis and Schistosoma mansoni contain opiate alkaloids.

    PubMed

    Zhu, W; Baggerman, G; Secor, W Evan; Casares, F; Pryor, S C; Fricchione, G L; Ruiz-Tiben, E; Eberhard, M L; Bimi, L; Stefano, G B

    2002-04-01

    The results of analysis, by high-performance liquid chromatography coupled with electrochemical detection and by nano-electrospray-ionization, double quadrupole/orthogonal-acceleration, time-of-flight mass spectrometry, indicate that adult Dracunculus medinensis and Schistosoma mansoni both contain the opiate alkaloid morphine and that D. medinesis also contains the active metabolite of morphine, morphine 6-glucuronide. From these and previous observations, it would appear that many helminths are probably using opiate alkaloids as potent immunosuppressive and antinociceptive signal molecules, to down-regulate immunosurveillance responsiveness and pain signalling in their hosts.

  11. Microbial Factories for the Production of Benzylisoquinoline Alkaloids.

    PubMed

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

    2016-03-01

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

  12. 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

    2008-11-04

    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.

  13. 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.

  14. 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.

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

    PubMed

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

    2015-01-01

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

  16. 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.

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

    PubMed Central

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

    2012-01-01

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

  18. New 14-membered cyclopeptide alkaloids from Zizyphus oxyphylla Edgew.

    PubMed

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

    2012-01-01

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

  19. Alkaloids and Phenolic Compounds from Sida rhombifolia L. (Malvaceae) and Vasorelaxant Activity of Two Indoquinoline Alkaloids.

    PubMed

    Chaves, Otemberg Souza; Teles, Yanna Carolina Ferreira; Monteiro, Matheus Morais de Oliveira; Mendes Junior, Leônidas das Graças; Agra, Maria de Fátima; Braga, Valdir de Andrade; Silva, Tânia Maria Sarmento; Souza, Maria de Fátima Vanderlei de

    2017-01-06

    The follow-up of phytochemical and pharmacological studies of Sida rhombifolia L. (Malvaceae) aims to strengthen the chemosystematics and pharmacology of Sida genera and support the ethnopharmacological use of this species as hypotensive herb. The present work reports phytoconstituents isolated and identified from aerial parts of S. rhombifolia by using chromatographic and spectroscopic methods. The study led to the isolation of scopoletin (1), scoporone (2), ethoxy-ferulate (3), kaempferol (4), kaempferol-3-O-β-d-glycosyl-6''-α-d-rhamnose (5), quindolinone (6), 11-methoxy-quindoline (7), quindoline (8), and the cryptolepine salt (9). The alkaloids quindolinone (6) and cryptolepine salt (9) showed vasorelaxant activity in rodent isolated mesenteric arteries.

  20. 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.

  1. [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.

  2. Histochemical investigation and kinds of alkaloids in leaves of different developmental stages in Thymus quinquecostatus.

    PubMed

    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.

  3. 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.

  4. The nuclear genome of Rhazya stricta and the evolution of alkaloid diversity in a medically relevant clade of Apocynaceae

    PubMed Central

    Sabir, Jamal S. M.; Jansen, Robert K.; Arasappan, Dhivya; Calderon, Virginie; Noutahi, Emmanuel; Zheng, Chunfang; Park, Seongjun; Sabir, Meshaal J.; Baeshen, Mohammed N.; Hajrah, Nahid H.; Khiyami, Mohammad A.; Baeshen, Nabih A.; Obaid, Abdullah Y.; Al-Malki, Abdulrahman L.; Sankoff, David; El-Mabrouk, Nadia; Ruhlman, Tracey A.

    2016-01-01

    Alkaloid accumulation in plants is activated in response to stress, is limited in distribution and specific alkaloid repertoires are variable across taxa. Rauvolfioideae (Apocynaceae, Gentianales) represents a major center of structural expansion in the monoterpenoid indole alkaloids (MIAs) yielding thousands of unique molecules including highly valuable chemotherapeutics. The paucity of genome-level data for Apocynaceae precludes a deeper understanding of MIA pathway evolution hindering the elucidation of remaining pathway enzymes and the improvement of MIA availability in planta or in vitro. We sequenced the nuclear genome of Rhazya stricta (Apocynaceae, Rauvolfioideae) and present this high quality assembly in comparison with that of coffee (Rubiaceae, Coffea canephora, Gentianales) and others to investigate the evolution of genome-scale features. The annotated Rhazya genome was used to develop the community resource, RhaCyc, a metabolic pathway database. Gene family trees were constructed to identify homologs of MIA pathway genes and to examine their evolutionary history. We found that, unlike Coffea, the Rhazya lineage has experienced many structural rearrangements. Gene tree analyses suggest recent, lineage-specific expansion and diversification among homologs encoding MIA pathway genes in Gentianales and provide candidate sequences with the potential to close gaps in characterized pathways and support prospecting for new MIA production avenues. PMID:27653669

  5. Profiles of phenolic compounds and purine alkaloids during the development of seeds of Theobroma cacao cv. Trinitario.

    PubMed

    Pereira-Caro, Gema; Borges, Gina; Nagai, Chifumi; Jackson, Mel C; Yokota, Takao; Crozier, Alan; Ashihara, Hiroshi

    2013-01-16

    Changes occurring in phenolic compounds and purine alkaloids, during the growth of seeds of cacao (Theobroma cacao) cv. Trinitario, were investigated using HPLC-MS/MS. Extracts of seeds with a fresh weight of 125, 700, 1550, and 2050 mg (stages 1-4, respectively) were analyzed. The phenolic compounds present in highest concentrations in developing and mature seeds (stages 3 and 4) were flavonols and flavan-3-ols. Flavan-3-ols existed as monomers of epicatechin and catechin and as procyanidins. Type B procyanidins were major components and varied from dimers to pentadecamer. Two anthocyanins, cyanidin-3-O-arabinoside and cyanidin-3-O-galactoside, along with the N-phenylpropernoyl-l-amino acids, N-caffeoyl-l-aspartate, N-coumaroyl-l-aspartate, N-coumaroyl-3-hydroxytyrosine (clovamide), and N-coumaroyltyrosine (deoxyclovamide), and the purine alkaloids theobromine and caffeine, were present in stage 3 and 4 seeds. Other purine alkaloids, such as theophylline and additional methylxanthines, did not occur in detectable quantities. Flavan-3-ols were the only components to accumulate in detectable quantities in young seeds at developmental stages 1 and 2.

  6. Genetic and Phenotypic Analyses of a Papaver somniferum T-DNA Insertional Mutant with Altered Alkaloid Composition

    PubMed Central

    Kawano, Noriaki; Kiuchi, Fumiyuki; Kawahara, Nobuo; Yoshimatsu, Kayo

    2012-01-01

    The in vitro shoot culture of a T-DNA insertional mutant of Papaver somniferum L. established by the infection of Agrobacterium rhizogenes MAFF03-01724 accumulated thebaine instead of morphine as a major opium alkaloid. To develop a non-narcotic opium poppy and to gain insight into its genetic background, we have transplanted this mutant to soil, and analyzed its alkaloid content along with the manner of inheritance of T-DNA insertion loci among its selfed progenies. In the transplanted T0 primary mutant, the opium (latex) was found to be rich in thebaine (16.3% of dried opium) by HPLC analysis. The analyses on T-DNA insertion loci by inverse PCR, adaptor-ligation PCR, and quantitative real-time PCR revealed that as many as 18 copies of T-DNAs were integrated into a poppy genome in a highly complicated manner. The number of copies of T-DNAs was decreased to seven in the selected T3 progenies, in which the average thebaine content was 2.4-fold that of the wild type plant. This may indicate that the high thebaine phenotype was increasingly stabilized as the number of T-DNA copies was decreased. In addition, by reverse transcription PCR analysis on selected morphine biosynthetic genes, the expression of codeine 6-O-demethylase was clearly shown to be diminished in the T0 in vitro shoot culture, which can be considered as one of the key factors of altered alkaloid composition. PMID:24288085

  7. Genomic and metabolic characterisation of alkaloid biosynthesis by asexual Epichloë fungal endophytes of tall fescue pasture grasses.

    PubMed

    Ekanayake, Piyumi N; Kaur, Jatinder; Tian, Pei; Rochfort, Simone J; Guthridge, Kathryn M; Sawbridge, Timothy I; Spangenberg, German C; Forster, John W

    2017-01-04

    Symbiotic associations between tall fescue grasses and asexual Epichloë fungal endophytes exhibit biosynthesis of alkaloid compounds causing both beneficial and detrimental effects. Candidate novel endophytes with favourable chemotypic profiles have been identified in germplasm collections by screening for genetic diversity, followed by metabolite profile analysis in endogenous genetic backgrounds. A subset of candidates was subjected to genome survey sequencing to detect the presence or absence and structural status of known genes for biosynthesis of the major alkaloid classes. The capacity to produce specific metabolites was directly predictable from metabolic data. In addition, study of duplicated gene structure in heteroploid genomic constitutions provided further evidence for the origin of such endophytes. Selected strains were inoculated into meristem-derived callus cultures from specific tall fescue genotypes to perform isogenic comparisons of alkaloid profile in different host backgrounds, revealing evidence for host-specific quantitative control of metabolite production, consistent with previous studies. Certain strains were capable of both inoculation and formation of longer-term associations with a nonhost species, perennial ryegrass (Lolium perenne L.). Discovery and primary characterisation of novel endophytes by DNA analysis, followed by confirmatory metabolic studies, offers improvements of speed and efficiency and hence accelerated deployment in pasture grass improvement programs.

  8. Cinchona Alkaloid Catalyzed Sulfa-Michael Addition Reactions Leading to Enantiopure β-Functionalized Cysteines.

    PubMed

    Breman, Arjen C; Telderman, Suze E M; van Santen, Roy P M; Scott, Jamie I; van Maarseveen, Jan H; Ingemann, Steen; Hiemstra, Henk

    2015-11-06

    Sulfa-Michael additions to α,β-unsaturated N-acylated oxazolidin-2-ones and related α,β-unsaturated α-amino acid derivatives have been enantioselectively catalyzed by Cinchona alkaloids functionalized with a hydrogen bond donating group at the C6' position. The series of Cinchona alkaloids includes known C6' (thio)urea and sulfonamide derivatives and several novel species with a benzimidazole, squaramide or a benzamide group at the C6' position. The sulfonamides were especially suited as bifunctional organocatalysts as they gave the products in very good diastereoselectivity and high enantioselectivity. In particular, the C6' sulfonamides catalyzed the reaction with the α,β-unsaturated α-amino acid derivatives to afford the products in a diastereomeric ratio as good as 93:7, with the major isomer being formed in an ee of up to 99%. The products of the organocatalytic sulfa-Michael addition to α,β-unsaturated α-amino acid derivatives were subsequently converted in high yields to enantiopure β-functionalized cysteines suitable for native chemical ligation.

  9. The role of phloem sieve elements and laticifers in the biosynthesis and accumulation of alkaloids in opium poppy.

    PubMed

    Samanani, Nailish; Alcantara, Joenel; Bourgault, Richard; Zulak, Katherine G; Facchini, Peter J

    2006-08-01

    The benzylisoquinoline alkaloids of opium poppy, including the narcotic analgesics morphine and codeine, accumulate in the multinucleate cytoplasm of specialized laticifers that accompany vascular tissues throughout the plant. In mature opium poppy plants, immunofluorescence labeling using specific antibodies showed that four alkaloid biosynthetic enzymes, (S)-norcoclaurine 6-O-methyltransferase (6OMT), (S)-coclaurine N-methyltransferase (CNMT), (S)-3'-hydroxy-N-methylcoclaurine-4'-O-methyltransferase (4'OMT) and salutaridinol-7-O-acetyltransferase (SAT) were restricted to sieve elements of the phloem adjacent or proximal to laticifers. The identity of sieve elements was confirmed by (i) the specific immunogold labeling of the characteristic cytoplasm of this cell type, (ii) the co-localization of a sieve element-specific H(+)-ATPase with all biosynthetic enzymes and (iii) the strict association of sieve plates with immunofluorescent cells. The localization of laticifers was demonstrated antibodies specific to major latex protein (MLP), which is characteristic of this cell type. In situ hybridization using antisense RNA probes for 6OMT, CNMT, 4'OMT and SAT showed that the corresponding gene transcripts were found in the companion cell paired with each sieve element. Seven benzylisoquinoline alkaloid biosynthetic enzymes, (S)-N-methylcoclaurine 3'-hydroxylase (CYP80B1), berberine bridge enzyme, codeinone reductase, 6OMT, CNMT, 4'OMT and SAT were localized by immunofluorescence labeling to the sieve elements in the root and hypocotyl of opium poppy seedlings. The abundance of these enzymes increased rapidly between 1 and 3 days after seed germination. The localization of seven biosynthetic enzymes to the sieve elements provides strong support for the unique, cell type-specific biosynthesis of benzylisoquinoline alkaloids in the opium poppy.

  10. 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

  11. Two new indolopyridoquinazoline alkaloidal glycosides from Ranunculus ternatus.

    PubMed

    Zhang, Lin; Yang, Zhuang; Tian, Jing-Kui

    2007-08-01

    Two new indolopyridoquinazoline alkaloidal glycosides, 11-O-beta-D-glucopyranosyl rutaecarpine (ternatoside C) and 11-O-alpha-L-rhamnosyl-(1-->6)-beta-D-glucopyranosyl rutaecarpine (ternatoside D) were isolated from the roots of Ranunculus ternatus. Their structures were determined on the basis of spectroscopic and chemical methods.

  12. 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.

  13. Diterpenoid alkaloid toxicosis in cattle in the Swiss Alps.

    PubMed

    Puschner, Birgit; Booth, Marcia C; Tor, Elizabeth R; Odermatt, Arnold

    2002-02-01

    Between 1995 and 1999, several cattle of a group of 80 heifers died acutely on a pasture in the Swiss Alps. The animals were Found dead between July 9th and 15th eachyear. Only 1 animal was examined on post-mortem, and no significant lesions were found. Aconitum vulpera, A napellus, and Delphinium elatum were identified in the pasture. The presence of diterpenoid alkaloid-containing plants in the pasture, the rapid death of the animals, and the lack of pathologic lesions suggested diterpenoid alkaloid toxicosis as a cause of death. A multiresidue alkaloid screen using gas chromatography with a mass spectrometric detector was employed on rumen, abomasal, small intestine, and cecal contents from the I heifer. Deltaline, deltamine, and lycoctonine were identified. Aconitine was found in all gastrointestinal samples using a sensitive and highly specific liquid chromatography/mass spectrometry methodology for aconitine analysis. The findings ofditerpenoid alkaloids in the gastrointestinal contents confirmed exposure to Delphinium and Aconitum spp, possibly resulting in sudden death.

  14. 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...

  15. Ochrocephalamine A, a new quinolizidine alkaloid from Oxytropis ochrocephala Bunge.

    PubMed

    Liu, Li-Na; Ran, Jian-Qiang; Li, Li-Jun; Zhao, Yu; Goto, Masuo; Morris-Natschke, Susan L; Lee, Kuo-Hsiung; Zhao, Bao-Yu; Tan, Cheng-Jian

    2016-11-16

    One dimeric matrine-type alkaloid, ochrocephalamine A (1), was isolated from the poisonous plant Oxytropis ochrocephala Bunge. Its structure was elucidated by spectroscopic data and single-crystal X-ray diffraction. The insecticidal and cytotoxic activities of 1 were evaluated.

  16. 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...

  17. Isolation of a new carboline alkaloid from Trigonostemon lii.

    PubMed

    Yang, Hongmei; Luo, Yanping; Zhao, Hongmei; Wu, Jichun; Chen, Yegao

    2016-01-01

    A new carboline alkaloid, 1-(7-methoxy-quinolinyl-4'-yl)-3,4-dihydro-β-carboline (1), was isolated from the leaves and twigs of Trigonostemon lii Y.T. Chang, together with three known ones, trigonostemonines C and D (2 and 3), and trigonoliimine A (4). Their structures were elucidated by spectroscopic analyses, including 2D-NMR techniques.

  18. 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.

  19. Dimeric pyrrole-imidazole alkaloids: synthetic approaches and biosynthetic hypotheses.

    PubMed

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

    2014-08-14

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

  20. Indole alkaloids from the seeds of Centaurea cyanus (Asteraceae).

    PubMed

    Sarker, S D; Laird, A; Nahar, L; Kumarasamy, Y; Jaspars, M

    2001-08-01

    Preparative RP-HPLC analysis of a methanol extract of the seeds of Centaurea cyanus afforded four indole alkaloids: moschamine, cis-moschamine, centcyamine and cis-centcyamine, the latter two being new natural products. Structures of these compounds were elucidated by comprehensive spectroscopic analyses. General toxicity of the isolates was determined by Brine Shrimp Lethality bioassay.

  1. Tall Fescue Alkaloids Bind Serotonin Receptors in Cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  2. 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...

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

    SciTech Connect

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

    1989-03-07

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

  4. 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...

  5. 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...

  6. 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...

  7. 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

  8. Cytotoxic agents of the crinane series of amaryllidaceae alkaloids.

    PubMed

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

    2012-12-01

    In the alkaloid galanthamine, the plant family Amaryllidaceae has endowed the pharmaceutical community with a potent and selective inhibitor of the enzyme acetylcholinestersae (AChE), of prominence in the chemotherapeutic approach towards motor neuron diseases. Following on the commercial success of this prescription drug in the treatment of Alzheimer's disease, it is anticipated that other drug candidates will in future emerge from the family. In this regard, the phenanthridones, exemplified by narciclasine and pancratistatin, of the lycorine series of Amaryllidaceae alkaloids have shown much promise as remarkably potent and selective anticancer agents, with a drug target of the series destined for the clinical market within the next decade. Given these interesting biological properties and their natural abundance, plants of the Amaryllidaceae have provided a diverse and accessible platform for phytochemical-based drug discovery. The crinane series of Amaryllidaceae alkaloids are also enriched with a significant array of biological properties. As a consequence of their close structural similarity to the anticancer agents of the lycorine series, the cytotoxic potential of crinane alkaloids has been realized through structure-activity relationship (SAR) studies involving targets of both semi-synthetic and natural origin, which has identified several members as leads with promising antiproliferative profiles. As the first of its kind, this review seeks to collate such information from the past few decades in advancing the crinane group as a viable platform for anticancer drug discovery.

  9. Alkaloid synthesis and accumulation in Leucojum aestivum in vitro cultures.

    PubMed

    Berkov, Strahil; Pavlov, Atanas; Georgiev, Vasil; Bastida, Jaume; Burrus, Monique; Ilieva, Mladenka; Codina, Carles

    2009-03-01

    The alkaloids of intact plants, calli and shoot-clump cultures of L. aestivum were analyzed by GC-MS. Twenty-four alkaloids were detected. Calli appeared to produce sparse alkaloid profiles in stark contrast to shoot-clumps that had similar profiles to those of the intact plant. Seven shoot-clump strains produced galanthamine predominantly whereas another three were dominated by lycorine. Shoot-clump strains cultivated under light accumulated about two-times more galanthamine (an average of 74 microg/g of dry weight) than those cultivated in darkness (an average of 39 microg/g of dry weight). In comparison to intact plants, the shoot-clumps accumulated 5-times less galanthamine. The high variability of both the galanthamine content (67% and 75% of coefficient of variation under light and darkness conditions, respectively) and alkaloid patterns indicates that the shoot-clump cultures initiated from callus could be used as a tool for improvement of the in vitro cultures.

  10. Major Links.

    ERIC Educational Resources Information Center

    Henderson, Tona

    1995-01-01

    Provides electronic mail addresses for resources and discussion groups related to the following academic majors: art, biology, business, chemistry, computer science, economics, health sciences, history, literature, math, music, philosophy, political science, psychology, sociology, and theater. (AEF)

  11. Optimisation of supercritical fluid extraction of indole alkaloids from Catharanthus roseus using experimental design methodology--comparison with other extraction techniques.

    PubMed

    Verma, Arvind; Hartonen, Kari; Riekkola, Marja-Liisa

    2008-01-01

    Response surface modelling, using MODDE 6 software for Design of Experiments and Optimisation, was applied to optimise supercritical fluid extraction (SFE) conditions for the extraction of indole alkaloids from the dried leaves of Catharanthus roseus. The effects of pressure (200-400 bar), temperature (40-80 degrees C), modifier concentration (2.2-6.6 vol%) and dynamic extraction time (20-60 min) on the yield of alkaloids were evaluated. The extracts were analysed by high-performance liquid chromatography and the analytes were identified using ion trap-electrospray ionisation-mass spectrometry. The method was linear for alkaloid concentration in the range 0.18-31 microg/mL. The limits of detection and quantification for catharanthine, vindoline, vinblastine and vincristine were 0.2, 0.15, 0.1 and 0.08 microg/mL and 2.7, 2.0, 1.3 and 1.1 microg/g, respectively. The dry weight content of major alkaloids in the plants were compared using different extraction methods, i.e. SFE, Soxhlet extraction, solid-liquid extraction with sonication and hot water extraction at various temperatures. The extraction techniques were also compared in terms of reproducibility, selectivity and analyte recoveries. Relative standard deviations for the major alkaloids varied from 4.1 to 17.5% in different extraction methods. The best recoveries (100%) for catharanthine were obtained by SFE at 250 bar and 80 degrees C using 6.6 vol% methanol as modifier for 40 min, for vindoline by Soxhlet extraction using dichloromethane in a reflux for 16 h, and for 3',4'-anhydrovinblastine by solid-liquid extraction using a solution of 0.5 m sulphuric acid and methanol (3:1 v/v) in an ultrasonic bath for 3 h.

  12. Molecular Cloning and Characterization of a Vacuolar Class III Peroxidase Involved in the Metabolism of Anticancer Alkaloids in Catharanthus roseus1[C

    PubMed Central

    Costa, Maria Manuela R.; Hilliou, Frederique; Duarte, Patrícia; Pereira, Luís Gustavo; Almeida, Iolanda; Leech, Mark; Memelink, Johan; Barceló, Alfonso Ros; Sottomayor, Mariana

    2008-01-01

    Catharanthus roseus produces low levels of two dimeric terpenoid indole alkaloids, vinblastine and vincristine, which are widely used in cancer chemotherapy. The dimerization reaction leading to α-3′,4′-anhydrovinblastine is a key regulatory step for the production of the anticancer alkaloids in planta and has potential application in the industrial production of two semisynthetic derivatives also used as anticancer drugs. In this work, we report the cloning, characterization, and subcellular localization of an enzyme with anhydrovinblastine synthase activity identified as the major class III peroxidase present in C. roseus leaves and named CrPrx1. The deduced amino acid sequence corresponds to a polypeptide of 363 amino acids including an N-terminal signal peptide showing the secretory nature of CrPrx1. CrPrx1 has a two-intron structure and is present as a single gene copy. Phylogenetic analysis indicates that CrPrx1 belongs to an evolutionary branch of vacuolar class III peroxidases whose members seem to have been recruited for different functions during evolution. Expression of a green fluorescent protein-CrPrx1 fusion confirmed the vacuolar localization of this peroxidase, the exact subcellular localization of the alkaloid monomeric precursors and dimeric products. Expression data further supports the role of CrPrx1 in α-3′,4′-anhydrovinblastine biosynthesis, indicating the potential of CrPrx1 as a target to increase alkaloid levels in the plant. PMID:18065566

  13. Antagonistic effect of alkaloids and saponins on bioactivity in the quinine tree (Rauvolfia caffra sond.): further evidence to support biotechnology in traditional medicinal plants

    PubMed Central

    2013-01-01

    Background The Quinine tree (Rauvolfia caffra) is used as a medicinal plant among traditional communities in many countries to manage tumors and other diseases associated with oxidative stress. To validate indigenous knowledge and possibly position this herb for technology uptake and utilization, we established the level of antioxidant activity in R. caffra, and probed for the presence of associated phytochemicals. Methods Antioxidant activity was determined on 1,1-diphenyl-2-picrylhydrazyl (DPPH) while major phytochemicals were identified by multiple tests on methanol fractions. Results R. caffra showed promise as a cure, with antioxidant activity comparable to the commercially used drug quercetin (R. caffra = 79.7% ±1.9; quercetin = 82.6% ± 2.0). However, we found two phytochemicals with possible antagonistic effect: co-occurrence of alkaloids and saponins significantly reduced antioxidant activity (alkaloids only = 63%; alkaloids plus saponins = 15%; steroids, terpenoids and cardiac glycosides = 82%), thus alkaloids and saponins should be exclusive to each other in drug formulations. Conclusions Antagonistic relationship among phytochemicals would affect the efficacy of crude extracts as used in traditional medicine. Unlike in herbal medicine, use of modern biotechnology in extraction, purification and design of optimal combinations will ensure efficient drug formulations with optimum bioactivity and minimum toxicity. Metabolic pathway engineering under a controlled environment may optimize availability of desired compounds. PMID:24160735

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

    PubMed

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

    2015-05-22

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

  15. Major depression.

    PubMed

    Bentley, Susan M; Pagalilauan, Genevieve L; Simpson, Scott A

    2014-09-01

    Major depression is a common, disabling condition seen frequently in primary care practices. Non-psychiatrist ambulatory providers are increasingly responsible for diagnosing, and primarily managing patients suffering from major depressive disorder (MDD). The goal of this review is to help primary care providers to understand the natural history of MDD, identify practical tools for screening, and a thoughtful approach to management. Clinically challenging topics like co-morbid conditions, treatment resistant depression and pharmacotherapy selection with consideration to side effects and medication interactions, are also covered.

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

    PubMed

    Guerre, Philippe

    2015-03-06

    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.

  17. 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

  18. Does mowing height influence alkaloid production in endophytic tall fescue and perennial ryegrass?

    PubMed

    Salminen, Seppo O; Grewal, Parwinder S; Quigley, Martin F

    2003-06-01

    The mutualistic symbiosis following infection of tall fescue, Festuca arundinacea, and perennial ryegrass, Lolium perenne, by fungal endophyte (Neotyphodium spp.) results in the production of alkaloids that are feeding deterrents or toxic to insects and livestock. If the levels of the alkaloids can be manipulated by cultural practices in the grasses that are used for home lawns and golf courses, this could alleviate the need for pesticide applications in urban environments. We evaluated the influence of mowing height on the levels of some alkaloids in a greenhouse experiment for two consecutive months. In tall fescue, levels of four of the nine alkaloids, including one presumptive alkaloid, showed increased levels with increasing the mowing height from 2.5 to 7.5 cm. The alkaloids were ergonovine, ergocryptine, perloline methyl ether, and an unidentified alkaloid designated as unknown C. In perennial ryegrass, three out of six alkaloids, perloline methyl ether, chanoclavine, and unknown A, showed similar increases. The alkaloid levels in perennial ryegrass showed more variability than those in tall fescue between the two sampling dates. It was clear in both grasses that the relative levels of the alkaloids varied with mowing height, as well as over time.

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

    PubMed

    Sloggett, J J; Davis, A J

    2010-01-15

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

  20. Major Andre

    ERIC Educational Resources Information Center

    Henisch, B. A.; Henisch, H. K.

    1976-01-01

    If most Revolutionary era people seem two-dimensional their lives simpler to understand than ours, it may be only that history, with the benefit of hindsight, clarifies. Examines a profile of Major John Andre, the British liaison officer in Benedict Arnold's plan to surrender West Point, as both hero and villain to show the complexity of early…

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

    PubMed

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

    2016-02-10

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

  2. Epiberberine, a natural protoberberine alkaloid, inhibits urease of Helicobacter pylori and jack bean: Susceptibility and mechanism.

    PubMed

    Tan, Lihua; Li, Cailan; Chen, Hanbin; Mo, Zhizhun; Zhou, Jiangtao; Liu, Yuhong; Ma, Zhilin; Xu, Yuyao; Yang, Xiaobo; Xie, Jianhui; Su, Ziren

    2017-02-04

    In our previous study, Rhizoma Coptidis extract was found to exert more potent inhibitory effect than its major component berberine towards urease from Helicobacter pylori (HPU) and jack bean (JBU). In continuation of our work, the present study was designed to further comparatively investigate the urease inhibitory activities of five major protoberberine alkaloids in Rhizoma Coptidis, namely berberine, palmatine, coptisine, epiberberine, jateorhizine to identify the bioactive constituent, and illuminate the potential mechanism of action. Results indicated that the five protoberberine alkaloids acted as concentration-dependent inactivators of urease with IC50 values ranging between 3.0 and 5087μM for HPU and 2.3->10,000μM for JBU, respectively. Notably, epiberberine (EB) was found to be the most potent inhibitor against both ureases with IC50 values of 3.0±0.01μM for HPU and 2.3±0.01μM for JBU, which was more effective than the standard urease inhibitor, acetohydroxamic acid (83±0.01μM for HPU and 22±0.01μM for JBU, respectively). Further kinetic analysis revealed that the type of EB inhibition against HPU was slow-binding and uncompetitive, with Ki of 10.6±0.01μM, while slow-binding and competitive against JBU with Ki of 4.6±0.01μM. Addition of thiol reagents, such as l-cysteine, glutathione and dithiothreitol, significantly abolished the inhibition, while Ni(2+) competitive inhibitors, boric acid and sodium fluoride, synergetically inhibited urease with EB, indicating the obligatory role of the active site sulfhydryl group for the inhibition. In addition, binding of EB with the urease proved to be reversible, as about 65% and 90% enzymatic activity of HPU and JBU, respectively, could be restored by dithiothreitol application. These findings highlighted the potential role of Rhizoma Coptidis protoberberine alkaloids, especially EB, as a lead urease inhibitor in the treatment of diseases associated with ureolytic bacteria. Thus, EB had good potential

  3. Exploring Cancer Therapeutics with Natural Products from African Medicinal Plants, Part II: Alkaloids, Terpenoids and Flavonoids.

    PubMed

    Nwodo, Justina N; Ibezim, Akachukwu; Simoben, Conrad V; Ntie-Kang, Fidele

    2016-01-01

    Cancer stands as second most common cause of disease-related deaths in humans. Resistance of cancer to chemotherapy remains challenging to both scientists and physicians. Medicinal plants are known to contribute significantly to a large population of Africa, which is to a very large extent linked to folkloric claims which is part of their livelihood. In this review paper, the potential of naturally occurring anti-cancer agents from African flora has been explored, with suggested modes of action, where such data is available. Literature search revealed plant-derived compounds from African flora showing anti-cancer and/or cytotoxic activities, which have been tested in vitro and in vivo. This corresponds to 400 compounds (from mildly active to very active) covering various compound classes. However, in this part II, we only discussed the three major compound classes which are: flavonoids, alkaloids and terpenoids.

  4. Analysis of bioactive Amaryllidaceae alkaloid profiles in Lycoris species by GC-MS.

    PubMed

    Guo, Ying; Pigni, Natalia B; Zheng, Yuhong; de Andrade, Jean Paulo; Torras-Claveria, Laura; Borges, Warley de Souza; Viladomat, Frances; Codina, Carles; Bastida, Jaume

    2014-08-01

    The genus Lycoris, a group of Amaryllidaceae plants distributed in temperate regions of Eastern Asia, is already known for containing representative alkaloids typical of this botanical family with a wide range of biological activities (for example, lycorine and galanthamine). In the present work, the alkaloid profiles of nine species, L. albiflora, L. aurea, L. chinensis, L. haywardii, L. incarnata, L. longituba, L. radiata, L. sprengeri, and L. squamigera, and one variety (L. radiata var. pumila) have been evaluated by GC-MS. Structures belonging to the lycorine-, homolycorine-, haemanthamine-, narciclasine-, tazettine-, montanine- and galanthamine-series were identified and quantified, with galanthamine- and lycorine-type alkaloids predominating and usually showing a high relative abundance in comparison with other alkaloids of the extracts. Interestingly, L. longituba revealed itself to be a potential commercial source of bioactive alkaloids. In general terms, our results are consistent with the alkaloid profiles reported in the literature for previously studied species.

  5. Characterization and simultaneous quantification of biological aporphine alkaloids in Litsea cubeba by HPLC with hybrid ion trap time-of-flight mass spectrometry and HPLC with diode array detection.

    PubMed

    Zhang, Shuiying; Zhang, Qian; Guo, Qiang; Zhao, Yunfang; Gao, Xiaoli; Chai, Xingyun; Tu, Pengfei

    2015-08-01

    The root and rhizome of Litsea cubeba (Lour) Pers., named 'Dou-chi-jiang' in Chinese, has been traditionally used for treatment of cardiovascular and cerebrovascular diseases, rheumatic arthralgia, and other diseases in China. Aporphine alkaloids are its characteristic ingredients and responsible for its bioactivities, especially anti-inflammatory and analgesic effects. A sensitive and reliable high-performance liquid chromatography with diode array detection-tandem mass spectrometry method was developed for characterization and simultaneous determination of biological aporphine alkaloids in 'Dou-chi-jiang'. The optimized chromatographic conditions were performed on an Eclipse XDB C18 column with a gradient of acetonitrile/water containing 0.1% formic acid as the mass spectrometry mobile phase and acetonitrile/water containing 0.2% diethylamine (pH 3.10, adjusted by acetic acid) as the liquid chromatography mobile phase. The fragmentation pathways by loss of CO, ·CH3 , ·NH3 , and ·NH2 CH3 were detected as characteristic for aporphine alkaloids. Based on these characteristics, total 12 analogues were identified. The quantification method was validated in terms of linearity, precision, and accuracy for six major aporphine alkaloids, which was successfully applied for simultaneous determination in ten batches of samples. The established method is simple, rapid, and specific for characterization and quantitation of aporphine alkaloids in 'Dou-chi-jiang' and other traditional Chinese medicines rich in this kind of ingredient.

  6. (13)C-NMR Spectral Data of Alkaloids Isolated from Psychotria Species (Rubiaceae).

    PubMed

    Carvalho Junior, Almir Ribeiro de; Vieira, Ivo Jose Curcino; Carvalho, Mario Geraldo de; Braz-Filho, Raimundo; S Lima, Mary Anne; Ferreira, Rafaela Oliveira; José Maria, Edmilson; Oliveira, Daniela Barros de

    2017-01-11

    The genus Psychotria (Rubiaceae) comprises more than 2000 species, mainly found in tropical and subtropical forests. Several studies have been conducted concerning their chemical compositions, showing that this genus is a potential source of alkaloids. At least 70 indole alkaloids have been identified from this genus so far. This review aimed to compile (13)C-NMR data of alkaloids isolated from the genus Psychotria as well as describe the main spectral features of different skeletons.

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

    PubMed

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

    2015-11-01

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

  8. Determination of opiate alkaloids in process liquors using capillary electrophoresis.

    PubMed

    Hindson, Benjamin J; Francis, Paul S; Purcell, Stuart D; Barnett, Neil W

    2007-02-19

    This paper describes the determination of opiate alkaloids (morphine, codeine, oripavine and thebaine) in industrial process liquors using capillary zone electrophoresis with UV-absorption detection at 214 nm. A study of cyclodextrin type and concentration revealed that the addition of 30 mM hydroxypropyl-beta-cyclodextrin to the electrolyte solution (100mM Tris adjusted to pH 2.8) was suitable to resolve the four analytes of interest. Typical analysis time was 12 min and the limit of detection for each alkaloid was 2.5 x 10(-6) M. The results for the proposed methodology were in good agreement with those of a conventional HPLC procedure. Under the same conditions, short-end injection was used to reduce the effective separation length from 41.5 to 8.5 cm, which allowed the determination of morphine and thebaine in process liquors within 2.5 min.

  9. 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.

  10. Nantenine alkaloid presents anticonvulsant effect on two classical animal models.

    PubMed

    Ribeiro, R A; Leite, J R

    2003-01-01

    The present study investigated the anticonvulsant and convulsant profiles of nantenine, an aporphine alkaloid found in several vegetal species. At lower doses (20-50 mg/kg, i.p.) the alkaloid proved to be effective in inhibiting pentylenotetrazol- (PTZ 100 mg/kg, s.c.) and maximal electroshock-induced seizures (80 mA, 50 pulses/s, 0.2 s), suggesting its potential as an anticonvulsant drug. However, at higher doses (> or = 75 mg/kg, i.p.) a convulsant activity was observed. Comparing the present in vivo nantenine effects on seizures with previous in vitro biphasic action on Na+, K+-ATPase activity, the convulsant effect appears to be related to inhibition of these phosphatase at high doses whereas anticonvulsant effect, observed at low doses, seems attributable to its stimulation and the resultant decrease of Ca2+-influx into the cell.

  11. Alkaloidal metabolites from a marine-derived Aspergillus sp. fungus.

    PubMed

    Liao, Lijuan; You, Minjung; Chung, Beom Koo; Oh, Dong-Chan; Oh, Ki-Bong; Shin, Jongheon

    2015-03-27

    Fumiquinazoline S (1), a new quinazoline-containing alkaloid, and the known fumiquinazolines F (6) and L (7) of the same structural class were isolated from the solid-substrate culture of an Aspergillus sp. fungus collected from marine-submerged wood. In addition, isochaetominines A-C (2-4) and 14-epi-isochaetominine C (5), new alkaloids possessing an unusual amino acid-based tetracyclic core framework related to the fumiquinazolines, were isolated from the same fungal strain. The structures of these compounds were determined by combined spectroscopic methods, and the absolute configurations were assigned by NOESY, ROESY, and advanced Marfey's analyses along with biogenetic considerations. The new compounds exhibited weak inhibition against Na(+)/K(+)-ATPase.

  12. 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

  13. Separation of bisbenzylisoquinoline alkaloids by micellar electrokinetic chromatography.

    PubMed

    Kuo, Ching-Hua; Sun, Shao-Wen

    2002-01-01

    The micellar electrokinetic chromatographic (MEKC) separation of seven bisbenzylisoquinoline alkaloids has been developed. The effects of various separating factors were studied. Optimum separation was achieved using a buffer (pH 9.2) of 20 mM sodium borate and 20 mM sodium dihydrogen phosphate buffer containing 55 mM sodium cholate; the optimum voltage and injection time were 21 kV and 0.05 min, respectively. Highest peak efficiency was obtained when the analytes were dissolved in 10 mM sodium dodecyl sulphate as sample matrix for injection. The elution order of the bisbenzylisoquinoline alkaloids was related to their lipophilicity. The resolution, run time and detection limits of the MEKC method were compared with those of an HPLC method developed previously.

  14. 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.

  15. Extractions of isoquinoline alkaloids with butanol and octanol.

    PubMed

    Gregorová, Jana; Babica, Jan; Marek, Radek; Paulová, Hana; Táborská, Eva; Dostál, Jirí

    2010-09-01

    Six different isoquinoline alkaloids (sanguinarine, chelerythrine, berberine, coptisine, allocryptopine, and protopine) were extracted by butanol and octanol from aqueous solution, pH 4.5. The samples were analyzed by HPLC. Butanol extraction was non-selective, alkaloids passed into organic phase in 83-98%. Octanol extraction provided more selective yields: sanguinarine 99%, chelerythrine 94%, berberine 18%, coptisine 16%, allocryptopine 7.5%, protopine 7%. Further, we tested octanol treatment of extract from Dicranostigma lactucoides. The octanol extraction yields were also selective: sanguinarine 98%, chelerythrine 92%, chelirubine 92.5%, protopine 6% and allocryptopine 3.5%. 6-Butoxy-5,6-dihydrosanguinarine and 6-butoxy-5,6-dihydrochelerythrine were prepared and their NMR and MS data are reported and discussed.

  16. Various alkaloid profiles in decoctions of Banisteriopsis caapi.

    PubMed

    Callaway, J C

    2005-06-01

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

  17. Antitumor quinazoline alkaloids from the seeds of Peganum harmala.

    PubMed

    Wang, Chun-Hua; Zeng, Hong; Wang, Yi-Hai; Li, Chuan; Cheng, Jun; Ye, Zhi-Jun; He, Xiang-Jiu

    2015-05-01

    A phytochemical study on the methanol extracts from the seeds of Peganum harmala L. led to a new quizonaline alkaloid (S)-vasicinone-1-O-β-d-glucopyranoside (1) and four known ones, (R)-vasicinone-1-O-β-d-glucopyranoside (2), (S)-vasicinone (3), vasicine (4), and deoxyvasicinone (5). Their structures were elucidated by spectroscopic analysis including IR, HR-ESI-MS, 1D and 2D NMR, and specific rotation as well as by comparison of the data with those in the literature. All of the alkaloids were screened for antiproliferative activity against human gastric cancer cells MCG-803 with MTT method. Compounds 1 and 3 exhibited moderate inhibitory activity.

  18. A new microbial degradation pathway of steroid alkaloids.

    PubMed

    Gaberc-Porekar, V; Gottlieb, H E; Mervic, M

    1983-10-01

    In the degradation pathway of the steroid alkaloid tomatidine by Gymnoascus reesii the A-ring of tomatidine is opened with the formation of the 4-hydroxy-3,4-secotomatidine-3-oic acid, which was identified in the form of N-acetyl-3,4-tomatidine-carbolactone by mass, IR and 1H NMR spectra. Cleavage of the A-ring in the starting reaction indicates that an alternative pathway must be operating, instead of the general oxidative one.

  19. Mechanism of inhibition of cell proliferation by Vinca alkaloids.

    PubMed

    Jordan, M A; Thrower, D; Wilson, L

    1991-04-15

    We have used a structure-activity approach to investigate whether the Vinca alkaloids inhibit cell proliferation primarily by means of their effects on mitotic spindle microtubules or by another mechanism or by a combination of mechanisms. Five Vinca alkaloids were used to investigate the relationship in HeLa cells between inhibition of cell proliferation and blockage of mitosis, alteration of spindle organization, and depolymerization of microtubules. Indirect immunofluorescence staining of microtubules and 4,6-diamidino-2-phenylindole staining of chromatin were used to characterize the effects of the drugs on the distributions of cells in stages of the cell cycle and on the organization of microtubules and chromosomes in metaphase spindles. The microtubule polymer was isolated from cells and quantified using a competitive enzyme-linked immunoadsorbent assay for tubulin. We observed a nearly perfect coincidence between the concentration of each Vinca derivative that inhibited cell proliferation and the concentration that caused 50% accumulation of cells at metaphase, despite the fact that the antiproliferative potencies of the drugs varied over a broad concentration range. Inhibition of cell proliferation and blockage of cells at metaphase at the lowest effective concentrations of all Vinca derivatives occurred with little or no microtubule depolymerization or spindle disorganization. With increasing drug concentrations, the organization of microtubules and chromosomes in arrested mitotic spindles deteriorated in a manner that was common to all five congeners. These results indicate that the antiproliferative activity of the Vinca alkaloids at their lowest effective concentrations in HeLa cells is due to inhibition of mitotic spindle function. The results suggest further that the Vinca alkaloids inhibit cell proliferation by altering the dynamics of tubulin addition and loss at the ends of mitotic spindle microtubules rather than by depolymerizing the microtubules

  20. Antiplasmodial activities of furoquinoline alkaloids from Teclea afzelii.

    PubMed

    Wansi, Jean Duplex; Hussain, Hidayat; Tcho, Alain Tadjong; Kouam, Simeon F; Specht, Sabine; Sarite, Salem Ramadan; Hoerauf, Achim; Krohn, Karsten

    2010-05-01

    The study of the chemical constituents of the stem bark of Teclea afzelii (Rutaceae) has resulted in the isolation and characterization of four furoquinoline alkaloids, namely kokusaginine (1), tecleaverdoornine (2), maculine (3) and montrifoline (4) together with lupeol (5) and beta-sitosterol glucopyranoside (6). The structures of the isolated compounds were elucidated based on spectroscopic studies. The antimalarial activity of compounds 1-4 against Plasmodium falciparum in vitro shows partial suppression of parasitic growth.

  1. 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

  2. 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

  3. Stereoselective synthesis of enantiomerically pure nupharamine alkaloids from castoreum.

    PubMed

    Stoye, Alexander; Quandt, Gabriele; Brunnhöfer, Björn; Kapatsina, Elissavet; Baron, Julia; Fischer, André; Weymann, Markus; Kunz, Horst

    2009-01-01

    An animalic note: The first total synthesis of the all-cis nupharamine 2, an alkaloid from beaver castoreum, is based on the stereoselective domino Mannich-Michael reaction of N-galactosylfurylaldimine to give 1 (Piv = pivaloyl), subsequent conjugate cuprate addition, and stereoselective protonation of the enolate. These reactions are all controlled by the carbohydrate. Protonation of the enolate after cleavage of the auxiliary leads to epimer 3.

  4. Acetylcholinesterase inhibitory activity of pyrrolizidine alkaloids from Echium confusum Coincy.

    PubMed

    Benamar, Houari; Tomassini, Lamberto; Venditti, Alessandro; Marouf, Abderrazak; Bennaceur, Malika; Serafini, Mauro; Nicoletti, Marcello

    2017-06-01

    Four pyrrolizidine alkaloids, namely 7-O-angeloyllycopsamine N-oxide 1, echimidine N-oxide 2, echimidine 3 and 7-O-angeloylretronecine 4, were isolated for the first time from the whole plant ethanolic extract of Echium confusum Coincy, through bioassay-guided approach. Their structures were determined by spectroscopic means. All the isolates compounds showed moderate activities in inhibiting AChE, with IC50 0.276-0.769.

  5. In vitro cytotoxicity of the protoberberine-type alkaloids.

    PubMed

    Iwasa, K; Moriyasu, M; Yamori, T; Turuo, T; Lee, D U; Wiegrebe, W

    2001-07-01

    In vitro cytotoxic activities of 24 quaternary protoberberine alkaloids related to berberine have been evaluated using a human cancer cell line panel coupled with a drug sensitivity database. Extending the alkyl chain at position 8 or 13 strongly influenced the cytotoxic activity, that is, relative lipophilicity as well as the size of the substituent affects cytotoxicity. The highest level of activity was observed in 8- or 13-hexyl-substituted derivatives of berberine. Structure-activity relationships are described.

  6. Alkaloid spectrum in diploid and tetraploid hairy root cultures of Datura stramonium.

    PubMed

    Berkov, Strahil; Pavlov, Atanas; Kovatcheva, Petia; Stanimirova, Pepa; Philipov, Stefan

    2003-01-01

    Hairy root cultures were obtained from diploid and induced tetraploid plants of Datura stramonium and analyzed by gas chromatography/mass spectrometry. Twenty alkaloids (19 for diploid and 9 for tetraploid hairy root cultures) were identified. A new tropane ester 3-tigloyloxy-6-propionyloxy-7-hydroxytropane was identified on the basis of mass spectral data. Hyoscyamine was the main alkaloid in both diploid and tetraploid cultures. In contrast to diploid hairy roots, the percentage contributions of the alkaloids, with exceptions for hyoscyamine and apoatropine, were higher in the total alkaloid mixture of tetraploid hairy roots.

  7. Directed biosynthesis of alkaloid analogs in the medicinal plant Catharanthus roseus.

    PubMed

    McCoy, Elizabeth; O'Connor, Sarah E

    2006-11-08

    Terpene indole alkaloids are plant natural products with diverse structures and biological activities. A highly branched biosynthetic pathway is responsible for the production of approximately 130 different alkaloids in Madagascar periwinkle (C. roseus) from a common biosynthetic intermediate derived from tryptamine. Although numerous biosynthetic pathways can incorporate unnatural starting materials to yield novel natural products, it was not clear how efficiently the complex, eukaryotic TIA pathway could utilize unnatural substrates to make new alkaloids. This work demonstrates that the TIA biosynthetic machinery can be used to produce novel alkaloid structures and also highlights the potential of this pathway for future metabolic engineering efforts.

  8. New cytotoxic alkaloids from the wood of Vepris punctata from the Madagascar rainforest.

    PubMed

    Prakash Chaturvedula, V S; Schilling, Jennifer K; Miller, James S; Andriantsiferana, Rabodo; Rasamison, Vincent E; Kingston, David G I

    2003-04-01

    Bioassay-guided fractionation of a CH(2)Cl(2)/MeOH extract of the wood of Vepris punctata resulted in the isolation of three new furoquinoline alkaloids, 5-methoxymaculine (1), 5,8-dimethoxymaculine (2), and 4,5,6,7,8-pentamethoxyfuroquinoline (3), in addition to the four known alkaloids flindersiamine (4), kokusaginine (5), maculine (6), and skimmianine (7). The structures of the new alkaloids 1-3 were established on the basis of extensive 1D and 2D NMR spectroscopic data interpretation. All the isolated compounds were tested against the A2780 human ovarian cancer cell line, and all seven alkaloids showed weak cytotoxic activity.

  9. New Alkaloids and α-Glucosidase Inhibitory Flavonoids from Ficus hispida.

    PubMed

    Shi, Zheng-Feng; Lei, Chun; Yu, Bang-Wei; Wang, He-Yao; Hou, Ai-Jun

    2016-04-01

    Two new pyrrolidine alkaloids, ficushispimines A (1) and B (2), a new ω-(dimethylamino)caprophenone alkaloid, ficushispimine C (3), and a new indolizidine alkaloid, ficushispidine (4), together with the known alkaloid 5 and 11 known isoprenylated flavonoids 6 - 16, were isolated from the twigs of Ficus hispida. Their structures were elucidated by spectroscopic methods. Isoderrone (8), 3'-(3-methylbut-2-en-1-yl)biochanin A (11), myrsininone A (12), ficusin A (13), and 4',5,7-trihydroxy-6-[(1R*,6R*)-3-methyl-6-(1-methylethenyl)cyclohex-2-en-1-yl]isoflavone (14) showed inhibitory effects on α-glucosidase in vitro.

  10. 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.

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

    PubMed

    Trost, Barry M; Osipov, Maksim

    2015-11-09

    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.

  13. Zephgrabetaine: a new betaine-type amaryllidaceae alkaloid from Zephyranthes grandiflora.

    PubMed

    Katoch, Deepali; Kumar, Dharmesh; Sharma, Upendra; Kumar, Neeraj; Padwad, Yogendra S; Lal, Brij; Singh, Bikram

    2013-02-01

    Zephgrabetaine (1), a new betaine type Amaryllidaceae alkaloid, along with seven known alkaloids, lycorine, galanthine, lycoramine, hamayne, haemanthamine, tortuosine, and ungeremine were isolated from the bulbs of Zephyranthes grandiflora and their structures elucidated by spectroscopic data analysis. The isolated alkaloids were tested for in vitro cytotoxic activities against two cell lines, C-6 (rat glioma cells) and CHO-K1 (Chinese hamster ovary cells). A dose dependent cytotoxic effect was exhibited by all the alkaloids on these two cancer cell lines with prominent activity of lycorine and haemanthamine.

  14. Analysis of Amaryllidaceae alkaloids from Chlidanthus fragrans by GC-MS and their cholinesterase activity.

    PubMed

    Cahlíková, Lucie; Macáková, Katerina; Zavadil, Stanislav; Jiros, Pavel; Opletal, Lubomír; Urbanová, Klára; Jahodár, Ludek

    2011-05-01

    The underivatized alkaloid mixture extracted from the bulbs of Chlidanthus fragrans Herb. was investigated by capillary GC/MS for the first time. Fifteen known Amaryllidaceae alkaloids of five structure types were identified. The main alkaloids were tazzetine (9, tazettine-type), chlidanthine (2, galanthamine-type), belladine (8, belladine-type) and lycorine (12, lycorine-type). The alkaloid extract from the bulbs showed promising human blood acetylcholinesterase (IC50 = 20.1 +/- 2.9 microg/mL) and human plasma butyrylcholinesterase (IC50 = 136.8 +/- 6.9 microg/mL) inhibitory activity.

  15. In vitro production of adaline and coccinelline, two defensive alkaloids from ladybird beetles (Coleoptera: Coccinellidae).

    PubMed

    Laurent, Pascal; Braekman, Jean-Claude; Daloze, Désiré; Pasteels, Jacques M

    2002-09-01

    In vitro experiments using [1-(14)C] and [2-(14)C]acetate were devised to study the biosynthesis of the defensive coccinellid alkaloids adaline and coccinelline in Adalia 2-punctata and Coccinella 7-punctata, respectively. The labelled alkaloids obtained in these experiments had a specific activity about ten times higher than that of the samples obtained in feeding experiments. This in vitro assay has enabled us to demonstrate that these two alkaloids are most likely biosynthesised through a fatty acid rather than a polyketide pathway, that glutamine is the preferred source of the nitrogen atom and that alkaloid biosynthesis takes place in the insect fat body.

  16. A hormonal role for endogenous opiate alkaloids: vascular tissues.

    PubMed

    Stefano, George B; Zhu, Wei; Cadet, Patrick; Mantione, Kirk; Bilfinger, Thomas V; Bianchi, Enrica; Guarna, Massimo

    2002-02-01

    The distribution of morphine-containing cells in the central nervous system, adrenal gland, and its presence in blood may serve to demonstrate that this signal molecule can act as a hormone besides its role in cell-to-cell signaling within the brain. This speculative review is the result of a literature evaluation with an emphasis on studies from our laboratory. Opioid peptides and opiate alkaloids have been found to influence cardiac and vascular function. They have also been reported to promote ischemic preconditioning protection in the heart. Given the presence of morphine and the novel mu(3) opiate receptor on vascular endothelial cells, including cardiac and vascular endothelial cells in the median eminence, it would appear that endogenous opiate alkaloids are involved in modulating cardiac function, possible at the hormonal level. This peripheral target tissue, via nitric oxide coupling to mu opiate receptors, may serve to down regulate the excitability of this tissue given the heart's high performance state as compared to that of the saphenous vein, a passive resistance conduit. With this in mind, morphine and other endogenous opiate alkaloids may function as a hormone.

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

    PubMed

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

    2012-12-01

    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.

  18. 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.

  19. 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

  20. Structurally Diverse Alkaloids from the Seeds of Peganum harmala.

    PubMed

    Wang, Kai-Bo; Li, Da-Hong; Bao, Yu; Cao, Fei; Wang, Wen-Jing; Lin, Clement; Bin, Wen; Bai, Jiao; Pei, Yue-Hu; Jing, Yong-Kui; Yang, Danzhou; Li, Zhan-Lin; Hua, Hui-Ming

    2017-02-24

    Investigation of the alkaloids from Peganum harmala seeds yielded two pairs of unique racemic pyrroloindole alkaloids, (±)-peganines A-B (1-2); two rare thiazole derivatives, peganumals A-B (3-4); six new β-carboline alkaloids, pegaharmines F-K (5-10); and 12 known analogues. Their structures, including stereochemistry, were elucidated through spectroscopic analyses, quantum chemistry calculations, and single-crystal X-ray diffraction. Notably, the incorporation of pyrrole and indole moieties in peganines A-B, thiazole fragments in peganumals A-B, and a C-1 α,β-unsaturated ester motif in pegaharmine F (5) are all rare, and their presence in the genus Peganum were demonstrated for the first time. All isolates were tested for antiproliferative activities against the HL-60, PC-3, and SGC-7901 cancer cell lines, and compounds 9, 11, 12, and 13 exhibited moderate cytotoxicity against HL-60 cancer cell lines with IC50 values in the range of 4.36-9.25 μM.

  1. In vitro metabolism studies of erythraline, the major spiroalkaloid from Erythrina verna

    PubMed Central

    2014-01-01

    Background Erythrina verna, popularly known as “mulungu”, is a Brazilian medicinal plant used to treat anxiety. Erythrina alkaloids have been described in several species of Erythrina, which have biological and therapeutic properties well known that include anxiolytic and sedative effects. Methods In this work, in vitro metabolism of erythraline (1), the major spirocyclic alkaloid of Erythrina verna, was studied in the pig cecum model and by biomimetic phase I reactions. The biomimetic reactions were performed with Jacobsen catalyst to produce oxidative metabolites and one metabolite was isolated and evaluated against cancer cells, as HL-60 (promyelocytic leukemia), SF-295 (Glioblastoma) and OVCAR-8 (ovarian carcinoma). Results Erythraline exhibited no metabolization by the pig microbiota and a main putative metabolite was formed in a biomimetic model using Jacobsen catalyst. This metabolite was isolated and identified as 8-oxo-erythraline (2). Finally, erythraline and the putative metabolite were tested in MTT model and both compounds showed no important cytotoxic activity against tumor cells. Conclusions The alkaloid erythraline was not metabolized by intestinal microbiota, but it was possible to identify its oxidative metabolite from biomimetic reactions. So these data are interesting and stimulate other studies involving this alkaloid, since it is present in phytomedicine products and there are not reported data about the metabolism of erythrina alkaloids. PMID:24548728

  2. Determination of N,N-dimethyltryptamine and beta-carboline alkaloids in human plasma following oral administration of Ayahuasca.

    PubMed

    Yritia, Mercedes; Riba, Jordi; Ortuño, Jordi; Ramirez, Ariel; Castillo, Araceli; Alfaro, Yolanda; de la Torre, Rafael; Barbanoj, Manel J

    2002-11-05

    Ayahuasca is a South American psychotropic beverage prepared from plants native to the Amazon River Basin. It combines the hallucinogenic agent and 5-HT(2A/2C) agonist N,N-dimethyltryptamine (DMT) with beta-carboline alkaloids showing monoamine oxidase-inhibiting properties. In the present paper, an analytical methodology for the plasma quantification of the four main alkaloids present in ayahuasca plus two major metabolites is described. DMT was extracted by liquid-liquid extraction with n-pentane and quantified by gas chromatography with nitrogen-phosphorus detection. Recovery was 74%, and precision and accuracy were better than 9.9%. The limit of quantification (LOQ) was 1.6 ng/ml. Harmine, harmaline, and tetrahydroharmine (THH), the three main beta-carbolines present in ayahuasca, and harmol and harmalol (O-demethylation metabolites of harmine and harmaline, respectively) were measured in plasma by means of high-performance liquid chromatography (HPLC) with fluorescence detection. Sample preparation was accomplished by solid-phase extraction, which facilitated the automation of the process. All five beta-carbolines were measured using a single detector by switching wavelengths. Separation of harmol and harmalol required only slight changes in the chromatographic conditions. Method validation demonstrated good recoveries, above 87%, and accuracy and precision better than 13.4%. The LOQ was 0.5 ng/ml for harmine, 0.3 ng/ml for harmaline, 1.0 ng/ml for THH, and 0.3 ng/ml for harmol and harmalol. Good linearity was observed in the concentration ranges evaluated for DMT (2.5-50 ng/ml) and the beta-carbolines (0.3-100 ng/ml). The gas chromatography and HPLC methods described allowed adequate characterization of the pharmacokinetics of the four main alkaloids present in ayahuasca, and also of two major beta-carboline metabolites not previously described in the literature.

  3. Syrtis Major

    NASA Technical Reports Server (NTRS)

    2002-01-01

    (Released 1 May 2002) The Science This image is from the region of Syrtis Major, which is dominated by a low-relief shield volcano. This area is believed to be an area of vigorous aeolian activity with strong winds in the east-west direction. The effects of these winds are observed as relatively bright streaks across the image, extending from topographic features such as craters. The brighter surface material probably indicates a smaller relative particle size in these areas, as finer particles have a higher albedo. The bright streaks seen off of craters are believed to have formed during dust storms. A raised crater rim can cause a reduction in the wind velocity directly behind it, which results in finer particles being preferentially deposited in this location. In the top half of the image, there is a large bright streak that crosses the entire image. There is no obvious topographic obstacle, therefore it is unclear whether it was formed in the same manner as described above. This image is located northwest of Nili Patera, a large caldera in Syrtis Major. Different flows from the caldera eruptions can be recognized as raised ridges, representing the edge of a flow lobe. The Story In the 17th century, Holland was in its Golden Age, a time of cultural greatness and immense political and economic influence in the world. In that time, lived a inquisitive person named Christian Huygens. As a boy, he loved to draw and to figure out problems in mathematics. As a man, he used these talents to make the first detailed drawings of the Martian surface - - only 50 years or so after Galileo first turned his telescope on Mars. Mars suddenly became something other than a small red dot in the sky. One of the drawings Huygens made was of a dark marking on the red planet's surface named Syrtis Major. Almost 350 years later, here we are with an orbiter that can show us this place in detail. Exploration lives! It's great we can study this area up close. In earlier periods of history

  4. Syrtis Major

    NASA Technical Reports Server (NTRS)

    2002-01-01

    (Released 6 June 2002) The Science This image, located near the equator and 288W (72E), is near the southern edge of a low, broad volcanic feature called Syrtis Major. A close look at this image reveals a wrinkly texture that indicates a very rough surface that is associated with the lava flows that cover this region. On a larger scale, there are numerous bright streaks that trail topographic features such as craters. These bright streaks are in the wind shadows of the craters where dust that settles onto the surface is not as easily scoured away. It is important to note that these streaks are only bright in a relative sense to the surrounding image. Syrtis Major is one of the darkest regions on Mars and it is as dark as fresh basalt flows or dunes are on Earth. The Story Cool! It almost looks as if nature has 'painted' comets on the surface of Mars, using craters as comet cores and dust as streaky tails. Of course, that's just an illusion. As in many areas of Mars, the wind is behind the creation of such fantastic landforms. The natural phenomenon seen here gives this particular surface of Mars a very dynamic, fast-moving, almost luminous 'cosmic personality.' The bright, powdery-looking streaks of dust are in the 'wind shadows' of craters, where dust that settles onto the surface is not as easily scoured away. That's because the wind moves across the land in a particular direction, and a raised surface like the rim of a crater 'protects' dust from being completely blown away on the other side. The raised landforms basically act as a buffer. From the streaks seen above, you can tell the wind was blowing in a northeast to southwest direction. Why are the streaks so bright? Because they contrast with the really dark underlying terrain in this volcanic area of Mars. Syrtis Major is one of the darkest regions on Mars because it is made of basalt. Basalt is typically dark gray or black, and forms when a certain type of molten lava cools. The meaning of the word basalt

  5. Identification of diterpene alkaloids from Aconitum napellus subsp. firmum and GIRK channel activities of some Aconitum alkaloids.

    PubMed

    Kiss, Tivadar; Orvos, Péter; Bánsághi, Száva; Forgo, Peter; Jedlinszki, Nikoletta; Tálosi, László; Hohmann, Judit; Csupor, Dezső

    2013-10-01

    Diterpene alkaloids neoline (1), napelline (2), isotalatizidine (3), karakoline (4), senbusine A (5), senbusine C (6), aconitine (7) and taurenine (8) were identified from Aconitum napellus L. subsp. firmum, four (2-4, 6) of which are reported for the first time from this plant. The structures were determined by means of LC-MS, 1D and 2D NMR spectroscopy, including (1)H-(1)H COSY, NOESY, HSQC and HMBC experiments. Electrophysiological effects of the isolated compounds, together with nine diterpene alkaloids previously obtained from Aconitum toxicum and Consolida orientalis were investigated on stable transfected HEK-hERG (Kv11.1) and HEK-GIRK1/4 (Kir3.1 and Kir3.4) cell lines using automated patch clamp equipment. Significant blocking activity on GIRK channel was exerted by aconitine (7) (45% at 10 μM), but no blocking activities of the other investigated compounds were detected. The tested compounds were inactive on hERG channel in the tested concentration. The comparison of the previously reported metabolites of A. napellus subsp. firmum and compounds identified in our experiment reveals substantial variability of the alkaloid profile of this taxon.

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-03-01

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

  8. Pyrrolizidine alkaloids in honey: comparison of analytical methods.

    PubMed

    Kempf, M; Wittig, M; Reinhard, A; von der Ohe, K; Blacquière, T; Raezke, K-P; Michel, R; Schreier, P; Beuerle, T

    2011-03-01

    Pyrrolizidine alkaloids (PAs) are a structurally diverse group of toxicologically relevant secondary plant metabolites. Currently, two analytical methods are used to determine PA content in honey. To achieve reasonably high sensitivity and selectivity, mass spectrometry detection is demanded. One method is an HPLC-ESI-MS-MS approach, the other a sum parameter method utilising HRGC-EI-MS operated in the selected ion monitoring mode (SIM). To date, no fully validated or standardised method exists to measure the PA content in honey. To establish an LC-MS method, several hundred standard pollen analysis results of raw honey were analysed. Possible PA plants were identified and typical commercially available marker PA-N-oxides (PANOs). Three distinct honey sets were analysed with both methods. Set A consisted of pure Echium honey (61-80% Echium pollen). Echium is an attractive bee plant. It is quite common in all temperate zones worldwide and is one of the major reasons for PA contamination in honey. Although only echimidine/echimidine-N-oxide were available as reference for the LC-MS target approach, the results for both analytical techniques matched very well (n = 8; PA content ranging from 311 to 520 µg kg(-1)). The second batch (B) consisted of a set of randomly picked raw honeys, mostly originating from Eupatorium spp. (0-15%), another common PA plant, usually characterised by the occurrence of lycopsamine-type PA. Again, the results showed good consistency in terms of PA-positive samples and quantification results (n = 8; ranging from 0 to 625 µg kg(-1) retronecine equivalents). The last set (C) was obtained by consciously placing beehives in areas with a high abundance of Jacobaea vulgaris (ragwort) from the Veluwe region (the Netherlands). J. vulgaris increasingly invades countrysides in Central Europe, especially areas with reduced farming or sites with natural restorations. Honey from two seasons (2007 and 2008) was sampled. While only trace amounts of

  9. 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.

  10. [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.

  11. 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 ...

  12. Anti-angiogenic effects of pterogynidine alkaloid isolated from Alchornea glandulosa

    PubMed Central

    Lopes, Flávia CM; Rocha, Ana; Pirraco, Ana; Regasini, Luis O; Silva, Dulce HS; Bolzani, Vanderlan S; Azevedo, Isabel; Carlos, Iracilda Z; Soares, Raquel

    2009-01-01

    Background Angiogenesis, a complex multistep process that comprehends proliferation, migration and anastomosis of endothelial cells (EC), has a major role in the development of pathologic conditions such as inflammatory diseases, tumor growth and metastasis. Brazilian flora, the most diverse in the world, is an interesting spot to prospect for new chemical leads, being an important source of new anticancer drugs. Plant-derived alkaloids have traditionally been of interest due to their pronounced physiological activities. We investigated the anti-angiogenic potential of the naturally occurring guanidine alkaloid pterogynidine (Pt) isolated from the Brazilian plant Alchornea glandulosa. The purpose of this study was to examine which features of the angiogenic process could be disturbed by Pt. Methods Human umbilical vein endothelial cells (HUVEC) were incubated with 8 μM Pt and cell viability, proliferation, apoptosis, invasion and capillary-like structures formation were addressed. Nuclear factor κB (NFκB), a transcription factor implicated in these processes, was also evaluated in HUVEC incubated with Pt. Quantifications were expressed as mean ± SD of five independent experiments and one-way analysis of variance (ANOVA) followed by the Dunnet test was used. Results A significant decrease in proliferation and invasion capacity and an effective increase in apoptosis as assessed by bromodeoxyuridine (BrdU), double-chamber and terminal transferase dUTP nick end labeling (TUNEL) assay, respectively, have been found. Pt also led to a drastic reduction in the number of capillary-like structures formation when HUVEC were cultured on growth factor reduced-Matrigel (GFR-Matrigel) coated plates. In addition, incubation of HUVEC with Pt resulted in reduced NFκB activity. Conclusion These findings emphasize the potential use of Pt against pathological situations where angiogenesis is stimulated as tumor development. PMID:19463163

  13. Docking of the alkaloid geissospermine into acetylcholinesterase: a natural scaffold targeting the treatment of Alzheimer's disease.

    PubMed

    Araújo, Jocley Queiroz; Lima, Josélia Alencar; Pinto, Angelo da Cunha; de Alencastro, Ricardo Bicca; Albuquerque, Magaly Girão

    2011-06-01

    Pharmacological studies from our group [Lima et al. Pharmacol Biochem Behav 92:508, (2009)] revealed that geissospermine (GSP), the major alkaloid of the bark extract of Brazilian Geissospermum vellosii, inhibits acetylcholinesterases (AChEs) in the brains of rats and electric eels (Electrophorus electricus). However, the binding mode (i.e., conformation and orientation) of this indole-indoline alkaloid into the AChE active site is unknown. Therefore, in order to propose a plausible binding mode between GSP and AChE, which might explain the observed experimental inhibitory activity, we performed comparative automatic molecular docking simulations using the AutoDock and Molegro Virtual Docker (MVD) programs. A sample of ten crystal structures of the Pacific electric ray (Torpedo californica) TcAChE, in complex with ten diverse active site ligands, was selected as a robust re-docking validation test, and also for GSP docking. The MVD results indicate a preferential binding mode between GSP and AChE, in which GSP functional groups may perform specific interactions with residues in the enzyme active site, according to the ligand-protein contacts detected by the LPC/CSU server. Four hydrogen bonds were detected between GSP and Tyr121, Ser122, Ser200, and His440, in which the last two residues belong to the catalytic triad (Ser200···His440···Glu327). Hydrophobic and π-π stacking interactions were also detected between GSP and Phe330 and Trp84, respectively; these are involved in substrate stabilization at the active site. This study provides the basis to propose structural changes to the GSP structure, such as molecular simplification and isosteric replacement, in order to aid the design of new potential AChE inhibitors that are relevant to the treatment of Alzheimer's disease.

  14. New method for the study of Amaryllidaceae alkaloid biosynthesis using biotransformation of deuterium-labeled precursor in tissue cultures.

    PubMed

    El Tahchy, Anna; Boisbrun, Michel; Ptak, Agata; Dupire, François; Chrétien, Françoise; Henry, Max; Chapleur, Yves; Laurain-Mattar, Dominique

    2010-01-01

    Biotransformation of deuterated-4'-O-methylnorbelladine into alkaloids galanthamine and lycorine in tissue cultures of Leucojum aestivum was demonstrated using HPLC coupled to mass spectrometry. GC-MS screening was also carried to investigate other native and deuterated alkaloids. A total of six labeled alkaloids were identified indicating that 4'-O-methyl-d(3)-norbelladine is incorporated into three different groups of Amaryllidaceae alkaloids that are biosynthesized by three modes of intramolecular oxidative phenol coupling.

  15. Alkaloid and flavonoid rich fractions of fenugreek seeds (Trigonella foenum-graecum L.) with antinociceptive and anti-inflammatory effects.

    PubMed

    Mandegary, Ali; Pournamdari, Mostafa; Sharififar, Fariba; Pournourmohammadi, Shirin; Fardiar, Reza; Shooli, Sedigheh

    2012-07-01

    The seeds of fenugreek (Trigonella foenum-graecum L.) have medicinal uses as hypoglycemic, antinociceptive and anti-inflammatory agents. We aimed to evaluate the antinociceptive and anti-inflammatory effects of the major fractions of fenugreek seeds. The methanolic extract of the plant seeds was partitioned using a liquid-liquid extraction procedure to give six major fractions. Following phytochemical screening of isolated fractions, the total extract and each fraction were evaluated for their antinociception and anti-inflammatory effects using formalin and carrageenan-induced paw edema tests respectively. The methanolic extract exhibited both antinociceptive and anti-inflammatory effects at a dose of 100mg/kg. Among the tested fractions, alkaline chloroform fraction (AKC), which was alkaloid positive in screening tests, showed the most anti-nociceptive effect in a dose-dependent manner. AKC fraction was as effective as morphine (5mg/kg) in this regard. Both aqueous and acidified chloroform fractions (ACC) could significantly inhibit paw edema at a different dose. The latter fraction dose-dependently inhibited carrageenan-induced paw edema. The results of phytochemical screening tests confirmed the presence of flavonoids in both ACC and aqueous fractions. It can be concluded that the alkaloid and flavonoid content of fenugreek seeds can be responsible for antinociception and anti-inflammatory effects of the plant respectively.

  16. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  18. Evaluation of analgesic activity and toxicity of alkaloids in Myristica fragrans seeds in mice

    PubMed Central

    Hayfaa, A Al-Shammary; Sahar, AA Malik Al-Saadi; Awatif, M Al-Saeidy

    2013-01-01

    Aim To examine the analgesic effect of alkaloids in Myristica fragrans seed in a mouse model of acetic acid-induced visceral pain. Methods Alkaloids were extracted from ground nutmeg seed kernels with 10% acetic acid in 95% ethyl alcohol. Visceral pain was induced in male and female BALB/c mice by intraperitoneal injection of 0.6% acetic acid. Analgesic effect of alkaloids (0.5 gram or 1 gram per kilogram [g/kg], by mouth) was assessed by evaluating writhing response. Acute toxicity was tested in response to 2, 3, 4, 5, or 6 g/kg of alkaloid extract; the median lethal dose (LD50) was determined by probit analysis. Results Alkaloid extract at a dose of 1 g/kg significantly reduced the number of writhing responses in female, but not male mice; 0.5 g/kg of alkaloid extract had no effect in either sex. The LD50 was 5.1 g/kg. Signs of abnormal behavior, including hypoactivity, unstable gait, and dizziness were seen in animals given a dose of 4 g/kg or higher; abnormal behavior lasted for several hours after administration of the alkaloids. Conclusion According to the classification of Loomis and Hayes, M. fragrans seed alkaloids have analgesic activity and are slightly toxic. PMID:23946667

  19. 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...

  20. Partial Reconstruction of the Ergot Alkaloid Pathway by Heterologous Gene Expression in Aspergillus nidulans

    PubMed Central

    Ryan, Katy L.; Moore, Christopher T.; Panaccione, Daniel G.

    2013-01-01

    Ergot alkaloids are pharmaceutically and agriculturally important secondary metabolites produced by several species of fungi. Ergot alkaloid pathways vary among different fungal lineages, but the pathway intermediate chanoclavine-I is evolutionarily conserved among ergot alkaloid producers. At least four genes, dmaW, easF, easE, and easC, are necessary for pathway steps prior to chanoclavine-I; however, the sufficiency of these genes for chanoclavine-I synthesis has not been established. A fragment of genomic DNA containing dmaW, easF, easE, and easC was amplified from the human-pathogenic, ergot alkaloid-producing fungus Aspergillus fumigatus and transformed into Aspergillus nidulans, a model fungus that does not contain any of the ergot alkaloid synthesis genes. HPLC and LC-MS analyses demonstrated that transformed A. nidulans strains produced chanoclavine-I and an earlier pathway intermediate. Aspergillus nidulans transformants containing dmaW, easF, and either easE or easC did not produce chanoclavine-I but did produce an early pathway intermediate and, in the case of the easC transformant, an additional ergot alkaloid-like compound. We conclude that dmaW, easF, easE, and easC are sufficient for the synthesis of chanoclavine-I in A. nidulans and expressing ergot alkaloid pathway genes in A. nidulans provides a novel approach to understanding the early steps in ergot alkaloid synthesis. PMID:23435153

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ergot alkaloids are hypothesized to cause vasoconstriction in the midgut, and prior exposure may affect 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...

  2. 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 ...

  3. 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...

  4. 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.

  5. Sources of the anti-implantation alkaloid yuehchukene in the genus Murraya.

    PubMed

    Kong, Y C; Ng, K H; But, P P; Li, Q; Yu, S X; Zhang, H T; Cheng, K F; Soejarto, D D; Kan, W S; Waterman, P G

    1986-02-01

    The genus Murraya has been widely used in traditional medicine in east Asia. In view of the recent isolation of the anti-implantation alkaloid yuehchukene from M. paniculata a search has now been made for other natural sources of this alkaloid within the genus. In this paper we report findings for nine taxa of Murraya.

  6. 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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  8. 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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2012-01-01

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

  11. Cytotoxic effects of β-carboline alkaloids on human gastric cancer SGC-7901 cells

    PubMed Central

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

    2015-01-01

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

  12. 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...

  13. 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

  14. New quinoline alkaloid from Ruta graveolens aerial parts and evaluation of the antifertility activity.

    PubMed

    Salib, Josline Y; El-Toumy, Sayed A; Hassan, Emad M; Shafik, Nabila H; Abdel-Latif, Sally M; Brouard, Ignacio

    2014-01-01

    Bioassay-guided isolation of methanol extract of Ruta graveolens L. leaves yielded a new quinoline alkaloid, (4S) 1,4-dihydro-4-methoxy-1,4-dimethyl-3-(3-methylbut-2-enyl)quinoline 2,7-diol, and nine phenolic compounds including rutin as a major compound. Structures of the isolated compounds were determined by using chromatography, UV, HR-ESI-MS and 1D/2D (1)H/(13)C NMR spectroscopy. The uterotonic activity of methanol extract fractions (ethyl acetate, n-butanol and aqueous fraction) as well as the isolated major compounds was tested in the isolated mouse uterus in vitro. The n-butanol-soluble fraction was found to demonstrate the most potent uterotonic activity in a dose-dependent manner, also the major isolated compound rutin revealed the occurrence of an uterotonic response, which was maximum at a concentration level of 0.25 mg/mL, accounting for 68.7% of that exhibited by the chosen concentration of oxytocin.

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

    PubMed

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

    2004-07-01

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

  16. 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.

  17. 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.

  18. Furoquinoline alkaloids isolated from Balfourodendron riedelianum as photosynthetic inhibitors in spinach chloroplasts.

    PubMed

    Veiga, Thiago André Moura; King-Díaz, Beatriz; Marques, Anna Sylvia Ferrari; Sampaio, Olivia Moreira; Vieira, Paulo Cezar; da Silva, Maria Fátima das Graças Fernandes; Lotina-Hennsen, Blas

    2013-03-05

    In the search for natural inhibitors of plant growth, we investigate the mechanism of action of the natural furoquinoline alkaloids isolated from Balfourodendron riedelianum (Rutaceae): evolitrine (1), kokusaginine (2), γ-fagarine (3), skimmianine (4) and maculosidine (5) on the photosynthesis light reactions. Their effect on the electron transport chain on thylakoids was analyzed. Alkaloids 1, 2, 4 and 5 inhibited ATP synthesis, basal, phosphorylating and uncoupled electron transport acting as Hill reaction inhibitors on spinach chloroplasts. Alkaloid 3 was not active. The inhibition and interaction site of alkaloids 1, 2, 4 and 5 on the non-cyclic electron transport chain was studied by polarography and fluorescence of the chlorophyll a (Chl a). The results indicate that the target for 1 was localized on the donor and acceptor side of PS II. In addition alkaloids 2 and 5 affect the PS I electron acceptors on leaf discs.

  19. 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

  20. Cytotoxic indole alkaloids against human leukemia cell lines from the toxic plant Peganum harmala.

    PubMed

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

    2015-11-03

    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.

  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. 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.

  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. 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.

  6. Gastroprotective mechanisms of indole alkaloids from Himatanthus lancifolius.

    PubMed

    Baggio, Cristiane Hatsuko; De Martini Otofuji, Glaucia; de Souza, Wesley Mauricio; de Moraes Santos, Cid Aimbiré; Torres, Luce Maria Brandao; Rieck, Lia; de Andrade Marques, Maria Consuelo; Mesia-Vela, Sonia

    2005-08-01

    The indole alkaloids mixture (AlkF) obtained from the barks of Himatanthus lancifolius (Muell. Arg.) Woodson was evaluated for gastroprotective properties in rodents. The AlkF potently protected rats from experimentally induced gastric lesions by ethanol (ED (50) = 30 mg/kg, p. o.) and reduced gastric acid hypersecretion induced by pylorus ligature (ED (50) = 82 mg/kg, i. d.). Protective effects of the AlkF in the ethanol and hypersecretion models included increase of GSH levels of gastric mucosa indicating activation of GSH-dependent cytoprotective mechanisms. Also, an increase of the antioxidant capacity as measured through glutathione S-transferase activity was observed in the hypersecretory but not in the ulcerative model. Furthermore, the amount of nitric oxide derivatives (NO (3) + NO (2)) in the forestomach was increased while the amount released into the gastric juice during pylorus ligature was decreased by the AlkF suggesting an alteration of NO-related mechanisms. Reduction of gastric acid hypersecretion induced by pylorus ligature seems to correlate with the blockade of H (+),K (+)-ATPase activity as determined in vitro by the capacity of the AlkF mix to decrease the hydrolysis of ATP by the ATPase isolated from dog gastric mucosa (EC (50) = 212 microg/mL). Cholinergic mechanisms can be excluded since intestinal transit was not modified with doses up to 100 mg/kg ( p. o.). GC-MS investigation of components of the AlkF resulted in the identification of 3 main indole alkaloids, uleine (53 %), its isomer (13 %), demethoxyaspidormine (23.8 %) and traces of at least other five alkaloids. Collectively, the results show the novel gastroprotective properties of the indole AlkF of H. lancifolius through a variety of mechanisms.

  7. Growth and production optimization of tropane alkaloids in Datura stramonium cell suspension culture.

    PubMed

    Iranbakhsh, A R; Oshagi, M A; Ebadi, M

    2007-04-15

    Abstract: A number of physicochemical conditions such different concentration of glucose, sucrose, potassium nitrate, ammonium nitrate, calcium chloride and temperatures were tested to optimize growth and production of tropane alkaloids from Datura stramonium (Solanaceae) plants. Cell suspension from semi-clear calli of leave explants developed in MS medium containing kinetin (0.5 mg L(-1)) and NAA (2 mg L(-1)) hormones was used to measure biomass and total alkaloids and comparison of treatments. The results showed that 30 and 40 g L(-1) glucose led to the highest level of alkaloids and biomass productions, respectively. 20 and 40 g L(-1) sucrose concentrations resulted in order the most rates of alkaloids and biomass productions. The results showed that increasing of nitrate concentration led to the reduction of the alkaloids. The best concentration of potassium nitrate for the production of tropane alkaloids and biomass were in order 9.4 and 3.76 mM. Also it was evinced that the optimized concentration of ammonium nitrate for alkaloids production was 10.3 mM and for the biomass was 41.22 mM. The best concentration of calcium chloride for growth and production of the alkaloids was 7.92 mM. Testing different temperature specified that the best condition for production of the alkaloids was 20 degrees C whereas it was 25 degrees C for biomass production. The results of this study could be recommended to farmers involved in production of D. stramonium for tropain alkaloids at industrial and semi-industrial scales.

  8. Opium poppy and Madagascar periwinkle: model non-model systems to investigate alkaloid biosynthesis in plants.

    PubMed

    Facchini, Peter J; De Luca, Vincenzo

    2008-05-01

    Alkaloids represent a large and diverse group of compounds that are related by the occurrence of a nitrogen atom within a heterocyclic backbone. Unlike other types of secondary metabolites, the various structural categories of alkaloids are unrelated in terms of biosynthesis and evolution. Although the biology of each group is unique, common patterns have become apparent. Opium poppy (Papaver somniferum), which produces several benzylisoquinoline alkaloids, and Madagascar periwinkle (Catharanthus roseus), which accumulates an array of monoterpenoid indole alkaloids, have emerged as the premier organisms used to study plant alkaloid metabolism. The status of these species as model systems results from decades of research on the chemistry, enzymology and molecular biology responsible for the biosynthesis of valuable pharmaceutical alkaloids. Opium poppy remains the only commercial source for morphine, codeine and semi-synthetic analgesics, such as oxycodone, derived from thebaine. Catharanthus roseus is the only source for the anti-cancer drugs vinblastine and vincristine. Impressive collections of cDNAs encoding biosynthetic enzymes and regulatory proteins involved in the formation of benzylisoquinoline and monoterpenoid indole alkaloids are now available, and the rate of gene discovery has accelerated with the application of genomics. Such tools have allowed the establishment of models that describe the complex cell biology of alkaloid metabolism in these important medicinal plants. A suite of biotechnological resources, including genetic transformation protocols, has allowed the application of metabolic engineering to modify the alkaloid content of these and related species. An overview of recent progress on benzylisoquinoline and monoterpenoid indole alkaloid biosynthesis in opium poppy and C. roseus is presented.

  9. 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.

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

    PubMed

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

    2002-08-01

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

  11. 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.

  12. New alkaloids and cytotoxic principles from Sinomenium acutum.

    PubMed

    Cheng, Jing-Jy; Tsai, Tung-Hu; Lin, Lie-Chwen

    2012-11-01

    Two new alkaloids, 2-demethyl-oxypalmatine (1) and 5-ethoxycarbonylsinoracutine (2), were isolated from the rhizomes of Sinomenium acutum, along with thirty-four known compounds. Cytotoxicity of the isolated compounds was examined for the MCF-7, H460, HT-29, and CEM human cancer cell lines. Dauriporphine (16), 6-O-demethylmenisporphine (17), bianfugecine (18), menisporphine (19), and 6-O-demethyldauriporphine (20) showed differential effects in their cytotoxic activity on the target cancer cell lines. Significant angiogenesis inhibitions of 16 and 19 were also observed.

  13. Phenolic dimers and an indole alkaloid from Campylospermum flavum (Ochnaceae).

    PubMed

    Ndongo, Joseph Thierry; Shaaban, Mohamed; Mbing, Joséphine Ngo; Bikobo, Dominique Ngono; Atchadé, Alex de Théodore; Pegnyemb, Dieudonné Emmanuel; Laatsch, Hartmut

    2010-11-01

    From the leaves and stem bark of Campylospermum flavum (Ochnaceae), three compounds, namely 4‴-O-methylagathisflavone, flavumchalcone, and flavumindole have been isolated together with 10 known compounds, including three flavonoids, two biflavonoids, two alkaloids, two nitrile glucosides, and glucopyranosyl-β-sistosterol. The structures of these compounds and their relative configurations were established by 1D and 2D NMR experiments. The methanolic crude extracts of leaves and stem bark of C. flavum and compounds displayed a significant cytotoxicity towards Artemia salina larvae.

  14. Aedes aegypti Larvicidal Sesquiterpene Alkaloids from Maytenus oblongata.

    PubMed

    Touré, Seindé; Nirma, Charlotte; Falkowski, Michael; Dusfour, Isabelle; Boulogne, Isabelle; Jahn-Oyac, Arnaud; Coke, Maïra; Azam, Didier; Girod, Romain; Moriou, Céline; Odonne, Guillaume; Stien, Didier; Houël, Emeline; Eparvier, Véronique

    2017-02-24

    Four new sesquiterpene alkaloids (1-4) with a β-dihydroagrofuran skeleton and a new triterpenoid (5) were isolated from an ethyl acetate extract of Maytenus oblongata stems. Their structures were elucidated using 1D and 2D NMR spectroscopy as well as MS and ECD experiments. The M. oblongata stem EtOAc extract and the pure compounds isolated were tested for larvicidal activity against Aedes aegypti under laboratory conditions, and compounds 2 and 3 were found to be active.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Göthel, Qun; Sirirak, Thanchanok

    2015-01-01

    Summary Three new bromotyrosine-derived alkaloids 14-debromo-11-deoxyfistularin-3 (1), aplysinin A (2), and aplysinin B (3), together with 15 known compounds (4–18) were isolated from the sponge Aplysina lacunosa collected from Stirrup Cay, Bahamas. The structures of the isolated compounds were identified on the basis of MS and NMR data analysis. The 13C NMR assignment of spirocyclohexadienylisoxazoline moieties of 1 and 2 were confirmed by an 1,1-ADEQUATE experiment. Compounds 1 and 2 showed a mild to moderate cytotoxic activities against KB-31 and FS4-LTM cell lines. Only aplysinin A (2) exhibited cytotoxicity against MCF-7 cells. PMID:26734082

  17. Asymmetric total synthesis of Apocynaceae hydrocarbazole alkaloids (+)-deethylibophyllidine and (+)-limaspermidine.

    PubMed

    Du, Ji-Yuan; Zeng, Chao; Han, Xiao-Jie; Qu, Hu; Zhao, Xian-He; An, Xian-Tao; Fan, Chun-An

    2015-04-01

    An unprecedented asymmetric catalytic tandem aminolysis/aza-Michael addition reaction of spirocyclic para-dienoneimides has been designed and developed through organocatalytic enantioselective desymmetrization. A unified strategy based on this key tandem methodology has been divergently explored for the asymmetric total synthesis of two natural Apocynaceae alkaloids, (+)-deethylibophyllidine and (+)-limaspermidine. The present studies not only enrich the tandem reaction design concerning the asymmetric catalytic assembly of a chiral all-carbon quaternary stereocenter contained in the densely functionalized hydrocarbazole synthons but also manifest the potential for the application of the asymmetric catalysis based on the para-dienone chemistry in asymmetric synthesis of natural products.

  18. Four New Amaryllidaceae Alkaloids from Lycoris radiata and Their Cytotoxicity.

    PubMed

    Ang, Song; Liu, Xia-Mei; Huang, Xiao-Jun; Zhang, Dong-Mei; Zhang, Wei; Wang, Lei; Ye, Wen-Cai

    2015-12-01

    Four new Amaryllidaceae alkaloids, named lycoranines C-F (1-4), together with seven known ones (5-11) were isolated from the bulbs of Lycoris radiata. Their structures with absolute configurations were elucidated by nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, circular dichroism spectra, modified Mosher's method, and molecular modeling calculation. Compounds 6, 7, 10, and 11 exhibited a potent inhibitory effect on A549 and LoVo cells with IC50 values ranging from 3.97 ± 0.36 to 17.37 ± 1.57 µM.

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

    PubMed

    Klotz, J L

    2015-12-01

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

  20. 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

  1. Mechanism of resistance to anthracyclines and vinca alkaloids.

    PubMed

    Danø, K; Skovsgaard, T; Nissen, N I; Friche, E; Di Marco, A

    1983-01-01

    Occurrence of cross-resistance between anthracyclines and vinca alkaloids is the rule in experimental tumors with acquired resistance to these drugs. So far, there is no indication that this phenomenon is due to an intracellular mechanism of action common to the two groups of drugs. In nearly all reported studies, acquired experimental resistance and cross-resistance are related to a decreased cellular accumulation of both types of drugs, although other factors also are involved. In Ehrlich ascites tumors, a number of findings at steady-state conditions indicate that the decreased accumulation is dependent on a cellular mechanism for active outward drug transport, which is common to anthracyclines and vinca alkaloids, but changes in inward transport and intracellular binding capacity also contribute. Similar findings have been reported for resistance and cross-resistance in P388 leukemia. Recent results with counteraction of acquired experimental resistance in animal tumors by inhibition of outward drug transport and studies on the effect of different anthracycline derivatives on accumulation of daunomycin in resistant cells are discussed.

  2. New cytotoxic quinolone alkaloids from fruits of Evodia rutaecarpa.

    PubMed

    Huang, Xin; Li, Wei; Yang, Xiu-Wei

    2012-06-01

    Three new quinolone alkaloids, 1-methyl-2-[7-hydroxy-(E)-9-tridecenyl]-4(1H)-quinolone (1), 1-methyl-2-[(Z)-4-nonenyl]-4(1H)-quinolone (2), 1-methyl-2-[(1E,5Z)-1,5-undecadienyl]-4(1H)-quinolone (3) and one new natural product, 1-methyl-2-[(E)-1-undecenyl]-4(1H)-quinolone (4), were isolated from the dried and nearly ripe fruits of Evodia rutaecarpa (Juss.) Benth., along with thirteen known compounds (5-17). In addition, one new artificial product, 1-methyl-2-[7-carbonyl-(E)-9-tridecenyl]-4(1H)-quinolone (1A) was also obtained. The structures of these compounds were determined by spectroscopic analyses. The cytotoxic activities of all of the compounds against the human cancer cell lines HL-60, N-87, H-460, and Hep G(2) cells were evaluated by MTT assay. The results showed that these alkaloids inhibited cell proliferation with IC(50) values between 14μM and 22μM.

  3. 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.

  4. Acridone alkaloids as potent inhibitors of cathepsin V.

    PubMed

    Severino, Richele P; Guido, Rafael V C; Marques, Emerson F; Brömme, Dieter; da Silva, M Fátima das G F; Fernandes, João B; Andricopulo, Adriano D; Vieira, Paulo C

    2011-02-15

    Cathepsin V is a lysosomal cysteine peptidase highly expressed in thymus, testis and corneal epithelium. Eleven acridone alkaloids were isolated from Swinglea glutinosa (Bl.) Merr. (Rutaceae), with eight of them being identified as potent and reversible inhibitors of cathepsin V (IC(50) values ranging from 1.2 to 3.9 μM). Detailed mechanistic characterization of the effects of these compounds on the cathepsin V-catalyzed reaction showed clear competitive inhibition with respect to substrate, with dissociation constants (K(i)) in the low micromolar range (2, K(i)=1.2 μM; 6, K(i)=1.0 μM; 7, K(i)=0.2 μM; and 11, K(i)=1.7 μM). Molecular modeling studies provided important insight into the structural basis for binding affinity and enzyme inhibition. Experimental and computational approaches, including biological evaluation, mode of action assessment and modeling studies were successfully employed in the discovery of a small series of acridone alkaloid derivatives as competitive inhibitors of catV. The most potent inhibitor (7) has a K(i) value of 200 nM.

  5. 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

    2016-07-08

    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.

  6. History of ergot alkaloids from ergotism to ergometrine.

    PubMed

    van Dongen, P W; de Groot, A N

    1995-06-01

    Epidemics of ergotism occurred frequently in the Middle Ages. They were a source of inspiration for artists and were popularly known as 'St. Anthony's Fire', resulting in gangrene, neurological diseases and death. It was caused by eating rye bread contaminated with the fungus claviceps purpurea. In 1582 it was described that a delivery could be hastened by administering a few spurs of the secale cornutum. The dosage was, however, very inaccurate resulting in frequent uterine ruptures. The nickname of the preparation of 'pulvis ad partum' was changed to 'pulvis ad mortem'. Therefore, after 1828 the ergot alkaloids were no longer used during delivery but only as a measure to prevent postpartum haemorrhage. From 1875 onwards many derivatives of ergot alkaloids were found. Dudley and Moir isolated ergometrine in 1932. It proved to have a very specific uterotonic action. However, because of severe and unpredictable side effects and the instability of the drug, ergometrine is not the drug of choice for either the prevention or the treatment of postpartum haemorrhage.

  7. 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

  8. Sarniensine, a mesembrine-type alkaloid isolated from Nerine sarniensis, an indigenous South African Amaryllidaceae, with larvicidal and adulticidal activities against Aedes aegypti.

    PubMed

    Masi, Marco; van der Westhuyzen, Alet E; Tabanca, Nurhayat; Evidente, Marco; Cimmino, Alessio; Green, Ivan R; Bernier, Ulrich R; Becnel, James J; Bloomquist, Jeffrey R; van Otterlo, Willem A L; Evidente, Antonio

    2017-01-01

    A new mesembrine-type alkaloid, named sarniensine, was isolated together with tazettine, lycorine, the main alkaloid, and 3-epimacronine from Nerine sarniensis, with the last two produced for the first time by this plant. This Amaryllidaceae, which is indigenous of South Africa, was investigated for its alkaloid content, because the organic extract of its bulbs showed strong larvicidal activity with an LC50 value of 0.008μgμL(-1) against first instar Aedes aegypti larvae and with an LD50 value 4.6μg/mosquito against adult female Ae. aegypti, which is the major vector for dengue, yellow fever and the Zika virus. The extract did not show repellency at MED value of 0.375mgcm(2) against adult Ae. aegypti. Sarniensine was characterized using spectroscopic and chiroptical methods as (3aR,4Z,6S,7aS)-6-methoxy-3a-(2'-methoxymethyl-benzo [1,3]dioxol-1'-yl)-1-methyl-2,3,3a,6,7,7a-hexahydro-1H-indole. It was less effective against larva at the lowest concentration of 0.1μgμL(-1), however it showed strong adulticidal activity with an LD50 value of 1.38±0.056μgmosquito(-1).

  9. Quantitative determination of alkaloids from roots of Hydrastis canadensis L. and dietary supplements using ultra-performance liquid chromatography with UV detection.

    PubMed

    Avula, Bharathi; Wang, Yan-Hong; Khan, Ikhlas A

    2012-01-01

    Ultra-performance liquid chromatography (UPLC) with UV detection was used for the quantification of alkaloids from roots of Hydrastis canadensis L. (goldenseal) and dietary supplements claiming to contain goldenseal. The analysis was performed on a Waters Acquity UPLC system with an Acquity UPLC BEH Shield RP18 column using gradient elution with ammonium formate and acetonitrile containing formic acid. The chromatographic run time was less than 6 min. The detection wavelength used for beta-hydrastine and canadine was 290 nm; for hydrastinine, coptisine, jatrorrhizine, palmatine, and berberine, it was 344 nm. A total of five different extraction solvents, including 100% methanol, 90% methanol, 90% methanol + 1% acetic acid, 90% acetonitrile + 0.1% phosphoric acid, and 100% acetonitrile, were tested for recovery of the major compounds. The samples extracted with the 90% methanol + 1% acetic acid displayed the best recovery (>97%). The analytical method was validated for linearity, repeatability, LOD, and LOQ. The RSDs for intraday and interday experiments were less than 3.5%, and the recovery was 98-103%. UPLC/MS with a quadrupole mass analyzer and electrospray ionization source was used to confirm the identity of seven alkaloids. The analytical method was successfully applied to confirm the identification of seven alkaloids from the roots of H. canadensis, dietary supplements that claimed to contain goldenseal, and possible adulterant species.

  10. In Silico Study of Alkaloids as α-Glucosidase Inhibitors: Hope for the Discovery of Effective Lead Compounds

    PubMed Central

    Zafar, Muhammad; Khan, Haroon; Rauf, Abdur; Khan, Ajmal; Lodhi, Muhammad Arif

    2016-01-01

    α-Glucosidase (extinction coefficient 3.2.1.20) is a primary carbohydrate metabolizing enzyme that acts on the 1–4 associated α-glucose residues. The inhibition of α-glucosidase slows down the process of carbohydrate digestion and avoids postprandial hyperglycemia, which is a major cause of chronic diabetes-associated complication. This study was designed to evaluate the binding capacity of isolated alkaloids with targeted receptor. For this purpose, the three-dimensional tertiary structure of the α-glucosidase was generated by using the Molecular Operating Environment (MOE). The generated model was then validated by using the RAMPAGE and ERRAT server. The molecular docking of 37 alkaloids along with standard acarbose and miglitol reported as a α-glucosidase inhibitor was performed via MOE-Dock implemented in MOE software to find the binding modes of these inhibitors. The results showed that compound 17 (oriciacridone F) and 24 (O-methylmahanine) demonstrated marked interaction with active residues and were comparable to standard inhibitors. In short, this study provided computational background to the reported α-glucosidase inhibitors and thus further detail studies could lead to novel effective compounds. PMID:28066324

  11. Analysis of yohimbine alkaloid from Pausinystalia yohimbe by non-aqueous capillary electrophoresis and gas chromatography-mass spectrometry.

    PubMed

    Chen, Qinhua; Li, Peng; Zhang, Zhuo; Li, Kaijun; Liu, Jia; Li, Qiang

    2008-07-01

    In the present work, the qualitative and quantitative analysis of Pausinystalia yohimbe-type alkaloids in the barks of Rubiaceae species is presented using different analytical approaches. Extracts of P. yohimbe were first examined by GC-MS and the major alkaloids were identified. The quantitation of yohimbine was then accomplished by non-aqueous CE (NACE) with diode array detection. This approach was selected in order to use a running buffer fully compatible with samples in organic solvent. In particular, a mixture of methanol containing ammonium acetate (20 mM) and glacial acetic acid was used as a BGE. The same analytical sample was subjected to GC-MS and NACE analysis; the different selectivity displayed by these techniques allowed different separation profiles that can be useful in phytochemical characterization of the extracts. The linear calibration ranges were all 10-1000 microg/mL for yohimbine by GC-MS and NACE analysis. The recovery of yohimbine was 91.2-94.0% with RSD 1.4-4.3%. The LOD for yohimbine were 0.6 microg/mL by GC-MS and 1.0 microg/mL by NACE, respectively. The GC-MS and NACE methods were successfully validated and applied to the quantitation of yohimbine.

  12. In Silico Study of Alkaloids as α-Glucosidase Inhibitors: Hope for the Discovery of Effective Lead Compounds.

    PubMed

    Zafar, Muhammad; Khan, Haroon; Rauf, Abdur; Khan, Ajmal; Lodhi, Muhammad Arif

    2016-01-01

    α-Glucosidase (extinction coefficient 3.2.1.20) is a primary carbohydrate metabolizing enzyme that acts on the 1-4 associated α-glucose residues. The inhibition of α-glucosidase slows down the process of carbohydrate digestion and avoids postprandial hyperglycemia, which is a major cause of chronic diabetes-associated complication. This study was designed to evaluate the binding capacity of isolated alkaloids with targeted receptor. For this purpose, the three-dimensional tertiary structure of the α-glucosidase was generated by using the Molecular Operating Environment (MOE). The generated model was then validated by using the RAMPAGE and ERRAT server. The molecular docking of 37 alkaloids along with standard acarbose and miglitol reported as a α-glucosidase inhibitor was performed via MOE-Dock implemented in MOE software to find the binding modes of these inhibitors. The results showed that compound 17 (oriciacridone F) and 24 (O-methylmahanine) demonstrated marked interaction with active residues and were comparable to standard inhibitors. In short, this study provided computational background to the reported α-glucosidase inhibitors and thus further detail studies could lead to novel effective compounds.

  13. Binding of plant alkaloids berberine and palmatine to serum albumins: a thermodynamic investigation.

    PubMed

    Khan, Asma Yasmeen; Hossain, Maidul; Kumar, Gopinatha Suresh

    2013-01-01

    The thermodynamics of the interaction of two pharmaceutically important isoquinoline alkaloids berberine and palmatine with bovine and human serum albumin was investigated using calorimetric techniques, and the data was supplemented with fluorescence and circular dichroism studies. Thermodynamic results revealed that there was only one class of binding sites for both alkaloids on BSA and HSA. The equilibrium constant was of the order of 10(4) M(-1) for both the alkaloids to serum albumins but the magnitude was slightly higher with HSA. Berberine showed higher affinity over palmatine to both proteins. The binding was enthalpy dominated and entropy favoured for both the alkaloids to BSA and HSA. Salt dependent studies suggested that electrostatic interaction had a significant role in the binding process, the binding affinity reduced as the salt concentration increased. Temperature dependent calorimetric data yielded heat capacity values that suggested the involvement of different molecular forces in the complexation of the two alkaloids with BSA and HSA. 3D fluorescence, synchronous fluorescence and circular dichroism data suggested that the binding of the alkaloids changed the conformation of proteins by reducing their helicity. Destabilization of the protein conformation was also revealed from differential scanning calorimetry studies. Overall, the alkaloids bound strongly to serum albumins, but berberine was a better binder to both serum proteins compared to palmatine.

  14. Automated multiple development thin-layer chromatography for separation of opiate alkaloids and derivatives.

    PubMed

    Pothier, Jacques; Galand, Nicole

    2005-07-08

    There are three types of opiate alkaloids. First, the poppy alkaloids: morphine, codeine, thebaine, noscapine and papaverine; then, the semi-synthetic and synthetic derivatives used in therapy as antitussives and analgesics, such as pholcodine, ethylmorphine and dextromethorphan; at last narcotic compounds, diacetylmorphine (heroin) and opiates employed as substitutes in treatment of addiction: buprenorphine and methadone. For classical thin-layer chromatography (TLC) of opium alkaloids, it is necessary to use complex eluents with strong alkaline substances to obtain a clean separation between morphinan and isoquinoline compounds. This study purposes the planar chromatographic analysis of these substances by the automated multiple development (AMD) compared with results obtained by classical TLC method. The aim of this work was to achieve the best separation of these opiate alkaloids and derivatives by this modern technique of planar chromatography. The AMD system provided a clean separation for each of three opiates groups studied and the best results have been obtained with universal gradient: methanol 100, methanol-dichloromethane 50/50, dichloromethane 100, dichloromethane 100, hexane 100 for opium alkaloids and with gradient A: 5% of 28% ammonia in methanol 100, acetone 100, acetone 100, ethyl acetate-dichloromethane 50/50, dichloromethane 100 for antitussives and substitutes. Two reagents were used for the detection of alkaloids by spraying: Dragendorff and iodoplatinate reagents. The detection limits with these two reagents were 1 microg for ethylmorphine, thebaine, papaverine, codeine, and 2 microg for morphine and noscapine and other alkaloids.

  15. Selective inhibition of in vitro synthesis of cancer DNA by alkaloids of beta-carboline class.

    PubMed

    Beljanski, M; Beljanski, M S

    1982-01-01

    The high template in vitro activity of native DNA from cancerous mammalian and plant tissues, compared to DNA from healthy tissues, enabled us to select substances which selectively inhibit cancer DNA synthesis. Among them, alstonine, serpentine, sempervirine and flavopereirine, all alkaloids which belong to the Beta-carboline class, distinguish cancer DNA from healthy tissue DNA inhibit DNA in vitro synthesis when native DNA from different cancerous tissues or cells is used as template. They have practically no effect on DNA from healthy tissues. The inhibitory effect of alkaloids is due to their capacity to form an 'alkaloid-cancer DNA' complex which has been characterized by use of the Sephadex column. Evidence is presented showing that these alkaloids inhibit the initiation of DNA synthesis but not chain elongation. The stimulating action caused by carcinogens during cancer DNA in vitro synthesis may be prevented and reversed by alkaloids. Furthermore, the stimulating action of steroids during in vitro synthesis of hormone target tissue DNA might be neutralized by alkaloids. However, at relatively high doses, steroids reversibly compete with alkaloids for binding sites on breast cancer DNA. This is not observed with DNA from nonhormone target tissues.

  16. Biogeographical patterns and phenological changes in Lapiedra martinezii LAG. related to its alkaloid diversity.

    PubMed

    Ríos, Segundo; Berkov, Strahil; Martínez-Francés, Vanessa; Bastida, Jaume

    2013-07-01

    The aim of this work was to investigate the alkaloid patterns of Lapiedra martinezii and their relation to biogeography and phenology focused in a phylogenetic comparison. Plants from 14 populations of L. martinezii, covering almost its entire distribution area, were subjected to morphological, ecological, and phytochemical analysis. Experiments for different alkaloid-type content are proposed as a new tool for analysis of plant distribution. Several plants were transplanted for weekly observation of their phenological changes, and alkaloids from different plant organs were extracted, listed, and compared. The alkaloid pattern of L. martinezii comprises 49 compounds of homolycorine, lycorine, tazettine, haemantamine, and narciclasine types. The populations located in the north and south margins of the distribution area displayed alkaloid patterns different from those of the central area. Changes in these patterns during their phenological cycle may be related to a better defence for plant reproduction. L. martinezii is an old relict plant, and it has maintained some of the more primitive morphological features and alkaloid profiles of the Mediterranean Amaryllidaceae. The variations in alkaloid content observed could be interpreted in a phylogenetic sense, and those found in their phenological changes, in an adaptive one.

  17. 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.

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2012-03-15

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

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

    PubMed Central

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

    2014-01-01

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

  1. 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

  2. [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.

  3. Enhanced anti-tumour effects of Vinca alkaloids given separately from cytostatic therapies

    PubMed Central

    Ehrhardt, H; Pannert, L; Pfeiffer, S; Wachter, F; Amtmann, E; Jeremias, I

    2013-01-01

    Background and Purpose In polychemotherapy protocols, that is for treatment of neuroblastoma and Ewing sarcoma, Vinca alkaloids and cell cycle-arresting drugs are usually administered on the same day. Here we studied whether this combination enables the optimal antitumour effects of Vinca alkaloids to be manifested. Experimental Approach Vinca alkaloids were tested in a preclinical mouse model in vivo and in vitro in combination with cell cycle-arresting drugs. Signalling pathways were characterized using RNA interference. Key Results In vitro, knockdown of cyclins significantly inhibited vincristine-induced cell death indicating, in accordance with previous findings, Vinca alkaloids require active cell cycling and M-phase transition for induction of cell death. In contrast, anthracyclines, irradiation and dexamethasone arrested the cell cycle and acted like cytostatic drugs. The combination of Vinca alkaloids with cytostatic therapeutics resulted in diminished cell death in 31 of 36 (86%) tumour cell lines. In a preclinical tumour model, anthracyclines significantly inhibited the antitumour effect of Vinca alkaloids in vivo. Antitumour effects of Vinca alkaloids in the presence of cytostatic drugs were restored by caffeine, which maintained active cell cycling, or by knockdown of p53, which prevented drug-induced cell cycle arrest. Therapeutically most important, optimal antitumour effects were obtained in vivo upon separating the application of Vinca alkaloids from cytostatic therapeutics. Conclusion and Implications Clinical trials are required to prove whether Vinca alkaloids act more efficiently in cancer patients if they are applied uncoupled from cytostatic therapies. On a conceptual level, our data suggest the implementation of polychemotherapy protocols based on molecular mechanisms of drug–drug interactions. Linked Article This article is commented on by Solary, pp 1555–1557 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph

  4. Jusbetonin, the first indolo[3,2-b]quinoline alkaloid glycoside, from Justicia betonica.

    PubMed

    Subbaraju, Gottumukkala V; Kavitha, Jakka; Rajasekhar, Dodda; Jimenez, Jorge I

    2004-03-01

    A new indolo[3,2-b]quinoline alkaloid glycoside, jusbetonin (1), and three known alkaloids, namely, 10H-quindoline (2), 6H-quinindoline (3), and 5H,6H-quinindolin-11-one (4), have been isolated from the leaves of Justicia betonica. The structure of 1 was established on the basis of 1D and 2D NMR ((1)H-(1)H COSY, HMQC, and HMBC) and HRFABMS data. Compound 1 is the first example of a glycosylated indolo[3,2-b]quinoline alkaloid, while compound 4 was isolated for the first time from a natural source.

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

    PubMed

    Baker, D; Keeler, R; Gaffield, W

    1987-01-01

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

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

    PubMed

    Peeples, A; Dalvi, R R

    1982-12-01

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

  7. 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.

  8. Alkaloids from stems of Esenbeckia leiocarpa Engl. (Rutaceae) as potential treatment for Alzheimer disease.

    PubMed

    Cardoso-Lopes, Elaine Monteiro; Maier, James Andreas; da Silva, Marcelo Rogério; Regasini, Luis Octávio; Simote, Simone Yasue; Lopes, Norberto Peporine; Pirani, José Rubens; Bolzani, Vanderlan da Silva; Young, Maria Cláudia Marx

    2010-12-13

    Esenbeckia leiocarpa Engl. (Rutaceae), popularly known as guarantã, goiabeira, is a native tree from Brazil. Bioactivity-guided fractionation of the ethanol stems extract afforded the isolation of six alkaloids: leiokinine A, leptomerine, kokusaginine, skimmianine, maculine and flindersiamine. All isolated compounds were tested for acetyl cholinesterase inhibition, in vitro and displayed anticholinesterasic activity. The alkaloid leptomerine showed the highest activity (IC₅₀ = 2.5 mM), similar to that of the reference compound galanthamine (IC₅₀ = 1.7 mM). The results showed for the first time the presence of alkaloids leptomerine and skimmianine in E. leiocarpa (Engl.) with potent anticholinesterasic activity.

  9. 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.

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

    PubMed Central

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

    2010-01-01

    A new tetracyclic bis-piperidine alkaloid, neopetrosiamine A (1), has been extracted from the marine sponge Neopetrosia proxima 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 1H and 13C NMR data with those of a well-known 3-alkylbispiperidine 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. PMID:20727745

  11. 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

  12. 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.

  13. [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.

  14. 3-O-Acetyl-narcissidine, a bioactive alkaloid from Hippeastrum puniceum Lam. (Amaryllidaceae).

    PubMed

    Santana, Omar; Reinab, Matías; Anaya, Ana Luisa; Hernández, Fidel; Izquierdo, M Elena; González-Coloma, Azucena

    2008-01-01

    In the context of the study on plant defensive compounds we have isolated the main alkaloid from Hippeastrum puniceum (Amaryllidaceae), 3-O-acetyl-narcissidine (1), and its biological activities tested against two divergent insect species and several plant species. 1 was isolated from the bioactive alkaloidal fraction of H. puniceum. Its chemical structure was established by spectroscopic analysis. The biological activity tests showed that 1 is an antifeedant against the polyphagous insect Spodoptera littoralis but not against the olyphage Leptinotarsa decemlineata. Furthermore, the root growth of Amaranthus hypochondriacus, Rottboellia cochinchinensis, Panicum maximum and Solanum lycopersicum was significantly affected by 1. These results suggest a plant protective role for H. puniceum alkaloids.

  15. The two facies of pyrrolizidine alkaloids: the role of the tertiary amine and its N-oxide in chemical defense of insects with acquired plant alkaloids.

    PubMed

    Lindigkeit, R; Biller, A; Buch, M; Schiebel, H M; Boppré, M; Hartmann, T

    1997-05-01

    Larvae of Creatonotos transiens (Lepidoptera, Arctiidae) and Zonocerus variegatus (Orthoptera, Pyrgomorphidae) ingest 14C-labeled senecionine and its N-oxide with the same efficiency but sequester the two tracers exclusively as N-oxide. Larvae of the non-sequestering Spodoptera littoralis eliminate efficiently the ingested alkaloids. During feeding on the two alkaloidal forms transient levels of senecionine (but not of the N-oxide) are built up in the haemolymph of S. littoralis larvae. Based on these results, senecionine [18O]N-oxide was fed to C. transiens larvae and Z. variegatus adults. The senecionine N-oxide recovered from the haemolymph of the two insects shows an almost complete loss of 18O label, indicating reduction of the orally fed N-oxide in the guts, uptake of the tertiary alkaloid and its re-N-oxidation in the haemolymph. The enzyme responsible for N-oxidation is a soluble mixed function monooxygenase. It was isolated from the haemolymph of the sequestering arctiid Tyria jacobaeae and purified to electrophoretic homogeneity. The enzyme is a flavoprotein with a native Mr of 200000 and a subunit Mr of 51000. It shows a pH optimum at 7.0, has its maximal activity at a temperature of 40-45 degrees C and an isoelectric point at pH 4.9. The reaction is strictly NADPH-dependent (Km 1.3 microM). From 20 pyrrolizidine alkaloids so far tested as substrates, the enyzme N-oxidizes only alkaloids with structural elements which are essential for hepatotoxic and genotoxic pyrrolizidine alkaloids (i.e. 1,2-double bond, esterification of the allylic hydroxyl group, presence of a second free or esterified hydroxyl group at carbon 7). A great variety of related alkaloids and xenobiotics were tested as substrate, none was accepted. The Km values of senecionine, monocrotaline and heliotrine, representing the three main types of pyrrolizidine alkaloids, are 1.3 microM, 12.5 microM and 290 microM, respectively. The novel enzyme was named senecionine N-oxygenase (SNO). The

  16. Biosynthesis and accumulation of ergoline alkaloids in a mutualistic association between Ipomoea asarifolia (Convolvulaceae) and a clavicipitalean fungus.

    PubMed

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

    2008-05-01

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

  17. Temporal and spatial variation in alkaloid levels in Achnatherum robustum, a native grass infected with the endophyte Neotyphodium.

    PubMed

    Faeth, Stanley H; Gardner, Dale R; Hayes, Cinnamon J; Jani, Andrea; Wittlinger, Sally K; Jones, Thomas A

    2006-02-01

    The native North American perennial grass Achnatherum robustum (Vasey) Barkworth [= Stipa robusta (Vasey) Scribn.] or sleepygrass is toxic and narcotic to livestock. The causative agents are alkaloidal mycotoxins produced from infections by a systemic and asexual Neotyphodium endophyte. Recent studies suggest that toxicity is limited across the range of sleepygrass in the Southwest USA. We sampled 17 populations of sleepygrass with varying distance from one focal population known for its high toxicity levels near Cloudcroft, NM, USA. For some, we sampled individual plants twice within the same growing season and over successive years (2001-2004). We also determined infection levels in each population. In general, all populations were highly infected, but infection levels were more variable near the focal population. Only infected plants within populations near the Cloudcroft area produced alkaloids. The ergot alkaloid, ergonovine, comprised the bulk of the alkaloids, with lesser amounts of lysergic and isolysergic acid amides and ergonovinine alkaloids. Levels of all alkaloids were positively correlated among individual plants within and between growing seasons. Infected plants that produced no alkaloids in 1 yr did not produce any alkaloids within the same growing season or in other years. Levels of alkaloids in sleepygrass populations declined with distance from the Cloudcroft population, although infection levels increased. Infected plants in populations in northern New Mexico and southern Colorado produced no alkaloids at all despite 100% infectivity. Our results suggest that only specific Neotyphodium haplotypes or specific Neotyphodium-grass combinations produce ergot alkaloids in sleepygrass. The Neotyphodium haplotype or host-endophyte combination that produces toxic levels of alkaloids appears restricted to one locality across the range of sleepygrass. Because of the wide variation in alkaloid levels among populations, interactions between the endophyte

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

    PubMed

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

    2012-01-01

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

  19. [Alkaloids and lignans from stems of Piper betle].

    PubMed

    Huang, Xiangzhong; Yin, Yan; Huang, Wenquan; Sun, Kuizong; Cheng, Chunmei; Bai, Lian; Dai, Yun

    2010-09-01

    Alkaloids and lignans from the stems of Piper betle were studied. Compounds were isolated and purified by repeated silica gel, reverse phase silica gel, Sephadex LH-20 column chromatography and preparative thin layer chromatography. The structures were elucidated on the basis of spectral analysis. From the ethyl acetate soluble fractions of the 70% acetone extract, ten compounds were isolated and identified as piperine (1), pellitorine (2), N-isobutyl-2E,4E-dodecadienamide (3), dehydropipernonaline (4), piperdardine (5), piperolein-B (6), guineensine (7), (2E,4E)-N-isobutyl-7-(3',4'-methylenedioxyphenyl)-2,4-heptadienamide (8), syringaresinol-O-beta-D-glucopyranoside (9),pinoresinol (10). All Compounds were isolated from the plant for the first time, and compounds 9 and 10 were isolated firstly from the genus.

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

    PubMed

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

    2012-03-01

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

  1. New quinolinone alkaloids from chestnut (Castanea crenata Sieb) honey.

    PubMed

    Cho, Jeong-Yong; Bae, Sun-Hee; Kim, Hye-Kyung; Lee, Myeong-Lyeol; Choi, Yong-Soo; Jin, Byung-Rae; Lee, Hyoung Jae; Jeong, Hang Yeon; Lee, Yu Geon; Moon, Jae-Hak

    2015-04-08

    Two new quinolinone alkaloids and 13 known compounds were isolated from chestnut (Castanea crenata Sieb) honey. Two new compounds were determined to be 3-dihydro-spiro[2(1H),3'(1'H)-diquinoline]-3',4,4'-trione (spirodiquinolinone) and 3-(2'-piperidine)-kynurenic acid. In addition, 2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-one was identified for the first time from nature. In addition, 2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-one was newly identified from chestnut honey, although this compound has been synthesized before. The structures were determined by the NMR and electrospray ionization-mass spectroscopy (ESI-MS). Three compounds were qualified and quantitated in chestnut honey by selective multiple reaction monitoring (MRM) detection of LC-ESI-MS using the isolated compounds as external standards.

  2. Supramolecular tilt chirality in crystals of steroids and alkaloids.

    PubMed

    Hisaki, Ichiro; Tohnai, Norimitsu; Miyata, Mikiji

    2008-03-01

    The concept of supramolecular chirality has assumed increasing importance in association with the development of supramolecular chemistry over the last two decades. In chiral crystals, 2 1 helical molecular assemblies are frequently observed as key motifs. Helical handedness of the 2 1 assemblies, however, has not been determined from the mathematical or crystallographical viewpoints. In this context, we have proposed two new concepts, three-axial chirality and tilt chirality. On the basis of the concepts, we describe supramolecular chirality and determine the handedness of 2 1 assemblies that are composed of relatively complicated molecules with multiple stereogenic centers such as brucine, bile acids, and cinchona alkaloids as well as those of simple molecules.

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

    PubMed

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

    2005-05-15

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

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

    PubMed

    Ramasamy, D; Saraswathy, A

    2014-02-15

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

  5. 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.

  6. 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.

  7. Pyrrolizidine alkaloids in medicinal plants from North America.

    PubMed

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

    2015-06-01

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

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

    PubMed

    Li, Yanran; Smolke, Christina D

    2016-07-05

    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.

  9. 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

  10. 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.

  11. Molecular properties of Cinchona alkaloids: a theoretical approach.

    PubMed

    Oleksyn, B J; Suszko-Purzycka, A; Dive, G; Lamotte-Brasseur, J

    1992-02-01

    In the present work, the conformation analysis, electrostatic potential calculations, and proton affinity evaluation are carried out for Cinchona alkaloids using theoretical molecular mechanics and quantum mechanical methods. The most probable conformation of the active erythro isomers at the receptor site seems to be that which enables the molecule to form intermolecular hydrogen bonds. In epiquinidine, the mutual orientation of O(12) and N(1) atoms favors intra- rather than intermolecular bonding, and this might be responsible for its inactivity. Comparison of the shape and size of the negative electrostatic potential areas provides a tentative explanation for the interaction of different erythro diastereoisomers with the same putative receptor, as well as for lack of such interaction in epiquinidine. The protonation energies calculated for cinchonidine and cinchonine confirm the higher basicity of the aliphatic N(1) as compared with that of the aromatic N(13) atom.

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

    PubMed Central

    Cai, Ru; Su, Huidan; Li, Yunlong

    2014-01-01

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

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

    PubMed

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

    2014-03-01

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

  14. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  16. 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 ...

  17. Total synthesis of a marine alkaloid from the tunicate Dendrodoa grossularia.

    PubMed

    Hupp, Christopher D; Tepe, Jetze J

    2008-09-04

    A short synthesis of an indole marine alkaloid (1) from the tunicate Dendrodoa grossularia is described. The key step in the synthesis involves a novel twist on an underutilized oxazole rearrangement, which produces the quaternary stereocenter in the molecule.

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    1999-02-01

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

  20. 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...