Note: This page contains sample records for the topic numerous norditerpenoid alkaloids from
While these samples are representative of the content of,
they are not comprehensive nor are they the most current set.
We encourage you to perform a real-time search of
to obtain the most current and comprehensive results.
Last update: November 12, 2013.

N-oxides of some norditerpenoid alkaloids.  


Eight new N-oxides [1-8] of the norditerpenoid alkaloids aconitine, ajacine, delphinine, delphisine, deltaline, heteratisine, lappaconitine, and N-deacetyllappaconitine have been prepared with m-chloroperbenzoic acid. The structures of these compounds were established on the basis of their spectroscopic data (1H, 13C, DEPT, COSY, HETCOR, and selective INEPT nmr experiments). The complete nmr chemical shift assignments for all eight N-oxides are reported. Table 2 shows the differences between the 13C-nmr shifts of the N-oxides compared with those of the parent alkaloids. PMID:7673939

Bai, Y; Desai, H K; Pelletier, S W



Norditerpenoid alkaloids and other components from the processed tubers of aconitum carmichaeli  

Microsoft Academic Search

A new norditerpenoid and a known alkaloid were isolated from the alkaloidal fraction of the processed tubers ofAconitum carmichaeli. The structure of the new norditerpenoid alkaloid was elucidated as lipoforesaconitine (1) on the basis of spectroscopic analysis. The known norditerpenoid alkaloid was characterized as lipoyunanaconitine (2). In addition, a new flavonoid, 6C;-O-acetylliquiritin (7), along with a known ceramide, (2S,3S,4R,8E)-2-[(2?R)-2?-hydroxylignoceroylamino]-8(E)-octadecene-1.3,4-triol (3),

Sang Hee Shim; So Young Lee; Ju Sun Kim; Kun Ho Son; Sam Sik Kang



Total synthesis, relay synthesis, and structural confirmation of the c18-norditerpenoid alkaloid neofinaconitine.  


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

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



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

Technology Transfer Automated Retrieval System (TEKTRAN)

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


Diterpenoid alkaloids of Aconitum vulparia Rchb.  


From the roots of Aconitum vulparia Rchb., collected in Prüm (Germany), a new norditerpenoid alkaloid, named alexhumboldtine, has been isolated along with the known norditerpenoid alkaloids lappaconitine, anthranoyllycoctonine, lycoctonine, puberaconitine, ajacine, and septentriodine. The structure of alexhumboldtine was established on the basis of 1H, 13C, DEPT, homonuclear 1H COSY, NOESY, HSQC, and HMBC NMR studies. From the aerial parts of the plant another norditerpenoid alkaloid, aconorine, has been isolated. PMID:22624325

Kurto?lu, Sezin; Sen, Burcu; Meliko?lu, Gülay; Becker, Hans; Zapp, Josef; Kiemer, Alexandra K; Meriçli, Filiz; Meriçli, Ali H


Influence of Light and Photosynthesis on Alkaloid Concentration in Larkspur  

Microsoft Academic Search

Concentrations of toxic norditerpenoid alkaloids vary greatly in tall larkspur (Delphinium barbeyi) and may be influenced by environmental stress. We evaluated the effect of shade, darkness, and inhibition of photosynthesis on toxic alkaloid concentration. In plants treated with metribuzin to inhibit photosynthesis, alkaloid concentration increased, but dry weight of the plants decreased as growth ceased, leaving absolute alkaloid content similar

M. H. Ralphs; G. D. Manners; D. R. Gardner



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

Technology Transfer Automated Retrieval System (TEKTRAN)

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


Cyclopeptide alkaloids  

Microsoft Academic Search

In this review, we discuss cyclopeptide alkaloids, their plant origin, and the way of separation, spectral analysis done for\\u000a structure elucidation, stereochemistry, and their biological activities. In addition, we discuss briefly the chemosystematic\\u000a significance of the cyclopeptide alkaloids based on their discovery in the family Olacaceae.

Hesham R. El-Seedi; Maram H. Zahra; Ulf Goransson; Robert Verpoorte



Ergot Alkaloids  

Microsoft Academic Search

\\u000a Ergot alkaloids are mycotoxins of agricultural and medical importance produced by at least two different lineages of fungi.\\u000a Fungi from different lineages share early steps of the biosynthetic pathway, and gene knockout studies and genomic analyses\\u000a indicate a common set of clustered genes encodes these early pathway steps. Different taxa follow different terminal branches\\u000a of the pathway to produce profiles

Daniel G. Panaccione


Alkaloids in Marine Algae  

PubMed Central

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.

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



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

Technology Transfer Automated Retrieval System (TEKTRAN)

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


BBB - Pyrrolizidine Alkaloids  

Center for Food Safety and Applied Nutrition (CFSAN)

... alkaloids. 3. Nature of Disease: Most cases of pyrrolizidine alkaloid toxicity result in moderate to severe liver damage. Gastrointestinal ... More results from


Alkaloids from Melochia chamaedrys.  


Investigation of the chemical constituents from the roots of Melochia chamaedrys (Sterculiaceae) resulted in the isolation of two quinolinone alkaloids: a new alkaloid, named chamaedrone (1), and a known alkaloid, antidesmone (2). Their structures and stereochemistry were elucidated on the basis of 2D NMR and X-ray crystallographic analysis. Furthermore, alkaloids 1 and 2, and the synthetic analogues 3-6 obtained from 2, were screened for antimicrobial activities. PMID:17354172

Dias, Gilvan O C; Porto, Carla; Stüker, Caroline Z; Graessler, Vanessa; Burrow, Robert A; Dalcol, Ionara I; da Silva, Ubiratan F; Morel, Ademir F



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


From leaves, root - and stem - barks of Annona muricata L., seven isoquinoline alkaloids have been isolated: reticuline (main alkaloid), coclaurine, coreximine, atherosperminine, stepharine. Anomurine and anomuricine, two minor alkaloids, are new tetrahydrobenzylisoquinolines, with 5, 6, 7 substituted ring A. The phytochemical significance of these alkaloids is discussed. PMID:17401878

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



Two Faces of Alkaloids  

NASA Astrophysics Data System (ADS)

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.

Dostál, Jirí



Alkaloids from Hippeastrum papilio.  


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 11?-hydroxygalanthamine, an epimer of the previously isolated alkaloid habranthine, which was identified using NMR techniques. It has been shown that 11?-hydroxygalanthamine has an important in vitro acetylcholinesterase inhibitory activity. Additionally, Hippeastrum papilio yielded substantial quantities of galanthamine. PMID:21852767

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



Alkaloids from Narcissus serotinus.  


Narcissus serotinus belongs to the Amaryllidaceae family, a group well known for an exclusive variety of alkaloids with interesting biological activities. This study was aimed at identifying the alkaloid constituents of N. serotinus collected in the Spanish region of Valencia, using a combination of chromatographic, spectroscopic, and spectrometric methods, including GC-MS and 2D NMR techniques. GC-MS analysis allowed for the direct identification of five known compounds. In addition, the isolation and structure elucidation of six new Amaryllidaceae alkaloids are described. PMID:22917000

Pigni, Natalia B; Ríos-Ruiz, Segundo; Martínez-Francés, Vanessa; Nair, Jerald J; Viladomat, Francesc; Codina, Carles; Bastida, Jaume



Alkaloids from Esenbeckia pilocarpoides.  


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. PMID:17340368

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



[Alkaloids from annonaceae.].  


From diverse parts of POLYALTHIA NITIDISSIMA, thirteen isoquinoline alkaloids have been isolated and identified. They belong to the structural types of benzylisoquinolines, aporphinoids, protoberberines and mainly bisbenzylisoquinolines. Four of these dimers, namely N,N'-dimethyllindoldhamine, isodaurisoline, 7-O-methyllindoldhamine and 7'-O-methyllindoldhamine, are new natural products. PMID:17405004

Jossang, A; Lebœuf, M; Cabalion, P; Cavé, A



Alkaloids from Cinnamomum philippinense.  


A new pyridine, 2-(4'-hydroxypyridin-3'-yl)-acetic acid (1), along with five known alkaloids, cinnaretamine (2), crykonisine (3), corydaldine (4), glaziovine (5) and zenkerine (6), were isolated from the roots of Cinnamomum philippinense (Lauraceae). Their structures were characterized and identified by spectral analysis. PMID:23413556

Li, Hsing-Tan; Li, Wei-Jen; Wu, Hui-Ming; Chen, Chung-Yi



New alkaloids from Pandanus amaryllifolius.  


Three new alkaloids, the two pyrrolidine type alkaloids (1 and 2) and 6E-pandanamine (3), together with five known alkaloids (4-8), were isolated from the leaves of Pandanus amaryllifolius collected in West Java, Indonesia. All the new alkaloids have two alpha-methyl alpha,beta-unsaturated gamma-lactone moieties, while compound 2 also has an additional seven-membered ring, which has not been encountered before in Pandanus alkaloids. Two different extraction methods, namely, a solvent partitioning extraction and acid-base treatment, were tested, giving secondary and tertiary amines, respectively. Spectroscopic and chemical studies showed that the tertiary amines isolated from the acid-base treatment were artifacts formed during the extraction process. This finding suggests that the use of conventional acid-base treatment in isolating Pandanus alkaloids should be reviewed since it can introduce artifacts. PMID:14738386

Salim, Angela A; Garson, Mary J; Craik, David J



Lycopodium alkaloids from Huperzia serrata.  


A new lycopodane-type Lycopodium alkaloid, 6?-hydroxy-5,15-oxide-lycopodane (1), and seven known alkaloids were isolated from the whole plants of Huperzia serrata. Their structures were elucidated by means of spectroscopic methods. 12-Deoxyhuperzine O (2) was reported as a naturally occurring alkaloid for the first time, and showed an antagonist effect on the N-methyl-d-aspartate receptor with an IC(50) value of 0.92 ?M. PMID:21061224

Yang, Yan-Fang; Qu, Shi-Jin; Xiao, Kai; Jiang, Shan-Hao; Tan, Jun-Jie; Tan, Chang-Heng; Zhu, Da-Yuan



Quaternary alkaloids of Argemone mexicana.  


Four quaternary isoquinoline alkaloids, dehydrocorydalmine, jatrorrhizine, columbamine, and oxyberberine, have been isolated from the whole plant of Argemone mexicana Linn. (Papaveraceae) and their structures established by spectral evidence. This is the first report of these alkaloids (dehydrocorydalmine, jatrorrhizine, columbamine, and oxyberberine) from Argemone mexicana and the Argemone genus. PMID:20645832

Singh, Sarita; Singh, Tryambak Deo; Singh, Virendra Pratap; Pandey, Vidya Bhushan



Antibacterial alkaloids from Zanthoxylum rhoifolium.  


Two new dihydrobenzophenanthridine-type alkaloids, 6-methoxy dioxolo[4',5':4,5]benzo[c] dioxolo[4,5- j]phenanthridine (1) and 2,3,13-trimethoxy-5,11a-dihydro dioxolo[4',5':4,5]benzo[c]phenanthridine (2) were isolated from the stem bark of Zanthoxylum rhoifolium, together with four other previously known benzophenanthridine alkaloids, 6-acetonyldihydronitidine (3) [= 8-acetonyldihydronitidine], 6-acetonyldihydroavicine (4) [= 8-acetonyldihydroavicine], 6-acetonyldihydrochelerythrine (5) and xanthoxyline (6). The structures were elucidated mainly by spectroscopic methods, including 1D and 2D NMR spectroscopy. For alkaloids 1 and 2 we propose the trivial names rhoifolines A and B. The crude plant extracts and the alkaloids 3, 4 and 6 showed activity against Gram (+/-) bacteria, while the new alkaloids 1 and 2 were inactive. PMID:12709908

de A Gonzaga, Wellington; Weber, Andréia D; Giacomelli, Sandro R; Dalcol, Ionara I; Hoelzel, Solange C S; Morel, Ademir F



Genotoxic effects of structurally related ?-carboline alkaloids  

Microsoft Academic Search

?-Carboline alkaloids, found in medicinal plants, tobacco smoke and well-cooked foods, have shown a variety of actions in biological systems related to their interaction with DNA. Therefore, these alkaloids can be considered potentially mutagenic. In this work, the genotoxic, mutagenic, and cytotoxic activities of three aromatic ?-carboline alkaloids (harman, harmine, and harmol) and two dihydro-?-carboline alkaloids (harmaline and harmalol) were

Jaqueline N Picada; Katia V. C. L da Silva; Bernardo Erdtmann; Amélia T Henriques; João A. P Henriques



Inhibition of seed germination by quinolizidine alkaloids  

Microsoft Academic Search

Germination of Lactuca sativa L. was inhibited by mixtures of quinolizidine alkaloids. The alkaloid esters resulted in the strongest inhibition: 6 mM 13-tigloyloxylupanine inhibited germination by 100%, whereas the other lupin alkaloids, such as lupanine and sparteine, gave a 45 and 20% inhibition, respectively. Seedlings of Lupinus albus L., which are not affected by quinolizidine alkaloids, excrete lupanine and 13-tigloyloxylupanine

Michael Wink



21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.  

Code of Federal Regulations, 2013 CFR

...false Dietary supplements containing ephedrine alkaloids. 119.1 Section 119...119.1 Dietary supplements containing ephedrine alkaloids. Dietary supplements containing ephedrine alkaloids present an...



21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.  

Code of Federal Regulations, 2010 CFR

...false Dietary supplements containing ephedrine alkaloids. 119.1 Section 119...119.1 Dietary supplements containing ephedrine alkaloids. Dietary supplements containing ephedrine alkaloids present an...



21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.  

Code of Federal Regulations, 2010 CFR

...false Dietary supplements containing ephedrine alkaloids. 119.1 Section 119...119.1 Dietary supplements containing ephedrine alkaloids. Dietary supplements containing ephedrine alkaloids present an...



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

Technology Transfer Automated Retrieval System (TEKTRAN)

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


Alkaloids from Toddalia aculeata.  


Two alkaloids N-methyl-4-hydroxy-7-methoxy-3-(2,3-epoxy-3-methylbutyl)-1H-quinolin-2-one (1) and 3-(2,3-dihydroxy-3-methylbutyl)-4,7-dimethoxy-1-methyl-1H-quinolin-2-one (2a) have been isolated from CH(2)Cl(2):methanol (1:1) and methanol extracts of leaves and stems of Toddalia aculeata. Their structures along with that of 15 other compounds, of which three are isolated for the first time from genus Toddalia, were established by their detailed spectral studies including 2D NMR viz. (1)H-(1)H COSY, (1)H-(13)C COSY, and HMBC. PMID:16647728

Jain, Subhash C; Pandey, Mukesh K; Upadhyay, Ravi K; Kumar, Rohtash; Hundal, Geeta; Hundal, Maninder S



Biosynthesis and Regulation of Alkaloids  

Microsoft Academic Search

\\u000a Alkaloids constitute a very chemically diverse group of plant natural products. These molecules, of which about 12,000 have\\u000a been identified, share the common presence of a nitrogen atom in a heterocyclic ring. Because of their toxicity, many alkaloids\\u000a are used for human health benefit. This review presents recent progresses in the elucidation of the biosynthetic pathways\\u000a of four major classes

G. Guirimand; V. Courdavault; B. St-Pierre; V. Burlat


Antibacterial activity of alkaloids from Sida acuta  

Microsoft Academic Search

Sida acuta is a shrub indigenous to pantropical regions. The plant is widely used for its various pharmacological properties. Among compounds of pharmacological interest occurring in the plant, are indoloquinoline alkaloids. The aim of the present study was to investigate the antimicrobial activity of alkaloids of S. acuta from Burkina Faso. The alkaloids had a good antimicrobial activity against the

Damintoti Karou; Aly Savadogo; Antonella Canini; Saydou Yameogo; Carla Montesano; Jacques Simpore; Vittorio Colizzi; Alfred S. Traore


A new benzylisoquinoline alkaloid from Argemone mexicana.  


A new benzylisoquinoline alkaloid, argemexirine, together with two known protoberberine alkaloids, dl-tetrahydrocoptisine and dihydrocoptisine, have been isolated from the methanolic extract of the whole plant of Argemone mexicana L. The compounds were identified by spectral and chemical evidence. This is the first report of these alkaloids in this plant species. PMID:20013474

Singh, Sarita; Singh, T D; Singh, V P; Pandey, V B



BIAdb: A curated database of benzylisoquinoline alkaloids  

Microsoft Academic Search

BACKGROUND: Benzylisoquinoline is the structural backbone of many alkaloids with a wide variety of structures including papaverine, noscapine, codeine, morphine, apomorphine, berberine, protopine and tubocurarine. Many benzylisoquinoline alkaloids have been reported to show therapeutic properties and to act as novel medicines. Thus it is important to collect and compile benzylisoquinoline alkaloids in order to explore their usage in medicine. DESCRIPTION:

Deepak Singla; Arun Sharma; Jasjit Kaur; Bharat Panwar; Gajendra PS Raghava



Quinolone alkaloids from Waltheria douradinha.  


A phytochemical investigation of the stems of Waltheria douradinha resulted in isolation of two 4-quinolone alkaloids, waltherione B and vanessine, along with three known alkaloids, waltherione A, antidesmone and O-methyltembamide. Their structures were elucidated on the basis of their 2D NMR spectroscopic analyses, and from X-ray crystallographic analysis of waltherione A and the O-methyl derivative of waltherione B. Additionally, waltherione B and vanessine, and the O- and N-methyl derivatives of waltherione A and waltherione B, were evaluated for their antimicrobial activities; only vanessine displayed any (weak) antimicrobial activity. PMID:18076957

Gressler, Vanessa; Stüker, Caroline Z; Dias, Gilvan de O C; Dalcol, Ionara I; Burrow, Robert A; Schmidt, Juergen; Wessjohann, Ludger; Morel, Ademir F



New alkaloids from Cephalotaxus fortunei.  


Four new cephalotaxus alkaloids, cephalotaxine alpha-N-oxide (1), cephalotaxine beta-N-oxide (2), 11-beta-hydroxycephalotaxine beta-N-oxide (3), and isocephalotaxine (4), were isolated, together with several known alkaloids from an EtOAc extract of the fruits of Cephalotaxus fortunei. The structures were determined by spectral analysis including mass spectrometry and 2D NMR. Compounds 1, 2, 3, and 4 displayed cytotoxicity against nasopharynx KB cells with IC50 values of 30, 14, 31, and 15 micro g/mL, respectively. PMID:12542368

Bocar, Mamadou; Jossang, Akino; Bodo, Bernard



Loline alkaloids: Currencies of mutualism  

Microsoft Academic Search

Several species of Lolium and other cool-season grasses (Poaceae subfamily Pooideae) tend to harbor symbiotic, seed-transmitted, fungi that enhance their fitness by various means. These fungal endophytes – species of Neotyphodium or Epichloë (Clavicipitaceae) – are known for production of antiherbivore metabolites such as the bioprotective loline alkaloids. Lolines are saturated pyrrolizidines with an exo-1-amine and an ether bridge between

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



Indole alkaloids from Antirhea lucida.  


A new indole alkaloid, N,N-methyl-3'-indolylmethyl-5-methoxytryptamine, as well as the known gramine, N,N-dimethyltryptamine and 6-methoxy-2-methyl-1,2,3,4-tetrahydro-beta-carboline were isolated from the roots of Antirhea lucida (Sw.) Hook (Rubiaceae). Their structures were established by spectroscopic methods. PMID:17238112

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



Indole Alkaloids from Kopsia deverrei  

Microsoft Academic Search

Three new monoterpene indole alkaloids, 16-hydroxymethyl-pleiocarpamine 2, 16-epi-deacetylakuammiline 4 and 14?-hydroxycondylocarpine 8, have been isolated from the stem bark of Kopsia deverrei (Apocynaceae). The proposed structures were assigned after detailed analysis of their H and C NMR spectra and by chemical correlation.

Christiane Kan; Jean-Robert Deverre; Thierry Sevenet; Jean-Charles Quirion; Henri-Philippe Husson



Alkaloids of Arundo donax L  

Microsoft Academic Search

The structure of a new dimeric indole alkaloid, arundarine, isolated from the roots of the plant Arundo donax L. (Poaceae) was determined. On the basis of spectroscopic data, arundarine was identified as 5-[3-(2-dimethylaminoethyl)indol-1-yl]-6-hydroxy-N2-methyl-1,2,3,4-tetrahydro-ß-carboline.

V. U. Khuzhaev; I. Zh. Zhalolov; M. G. Levkovich; S. F. Aripova; A. S. Shashkov



Alkaloid Changes in Tobacco Seeds during Germination.  


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

Weeks, W W; Bush, L P



Alkaloids from Narcissus angustifolius subsp. transcarpathicus (Amaryllidaceae)  

Microsoft Academic Search

Seven alkaloids have been isolated from fresh bulbs of Narcissus angustifolius subsp. transcarpathicus (Amaryllidaceae). Nangustine, reported here for the first time, is the first 5,11-methanomorphanthridine alkaloid with a C-3\\/C-4 substitution. The structure and stereochemistry of this new alkaloid, as well as those previously known, have been determined by physical and spectroscopic methods. Spectroscopic data of pancracine have been completed. The

Josep Labraña; Alex King'ori Machocho; Vladimir Kricsfalusy; Reto Brun; Carles Codina; Francesc Viladomat; Jaume Bastida



Microbial metabolites of harman alkaloids.  


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

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



Benzophenanthridine alkaloids from Corydalis flabellata.  


Four new alkaloids, characterized as 6-(2-hydroxyethyl)-5,6-dihydrosanguinarine (1), 6-acetonyl-5,6-dihydrosanguinarine (2), N-methyl-2,3,7,8-tetramethoxy-5,6-dihydrobenzophenanthridine-6-ethanoic acid (3), N-methyl-2,3,7,8-tetramethoxy-6-oxo-5,6-dihydrobenzophenanthridine (4), together with oxosanguinarine (5), spallidamine (6), 6-acetonyl-5,6-dihydrochelerythrine (7), 6-oxochelerythrine (8) and sanguidimerine (9) were isolated from the roots of Corydalis flabellata. PMID:11914966

Koul, Summon; Razdan, T K; Andotra, C S; Kalla, A K; Koul, S; Taneja, S C



Morphinane alkaloid dimers from Sinomenium acutum.  


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. PMID:18081254

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



BBB - Pyrrolizidine Alkaloid structures: Senecio longilobus ...  

Center for Food Safety and Applied Nutrition (CFSAN)

... BBB - Pyrrolizidine Alkaloid structures: Senecio longilobus Benth. ... by plants from the Boraginaceae, Compositae, and Leguminosae families. -. -. ... More results from


New Alkaloids from Pancratium maritimum.  


As a part of ongoing search efforts for the discovery of anticancer lead entities from natural sources, bulbs and flowers of the amaryllidaceous plant Pancratium maritimum have been investigated. Fractionation of the extracts of the fresh flowers and bulbs of P. maritimum led to the isolation of four new alkaloids, namely pancrimatines A (1) and B (2), norismine (3), and pancrimatine C (4), together with the previously reported N-methyl-8,9-methylenedioxy-6-phenanthridone (5), trispheridine (6), and N-methyl-8,9-methylenedioxyphenanthridine (7). The structures of these alkaloids were established on the basis of extensive 1D and 2D NMR and high-resolution mass spectral analyses as well as comparison with the literature. Compounds 2 and 7 showed antiproliferative and antimigratory activity against the highly metastatic human prostate cancer cell line PC-3 cells without cytotoxicity. The phenanthridine alkaloid class was identified as having potential for use to control prostate cancer proliferation and migration. PMID:23970422

Ibrahim, Sabrin R M; Mohamed, Gamal A; Shaala, Lamiaa A; Youssef, Diaa T A; El Sayed, Khalid A



[New bisbenzylisoquinoline alkaloids from Tiliacora triandra].  


Beside the known alkaloids magnoflorine ( 12), nortiliacorine A ( 4), and tiliacorinin-2'- N-oxide ( 8), two new bisbenzylisoquinoline alkaloids, noryanangine ( 1) and norisoyanangine ( 2) were isolated from the aerial parts of TILIACORA TRIANDRA Diels (Menispermaceae) and their structures elucidated by spectroscopic methods. PMID:17265307

Pachaly, P; Khosravian, H



Ergot alkaloids: toxicokinetics and vascular effects  

Technology Transfer Automated Retrieval System (TEKTRAN)

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


27 CFR 21.99 - Brucine alkaloid.  

Code of Federal Regulations, 2013 CFR

...solution. A reddish purple (violet) color is produced. (b) Melting point. 178 °±1 °C. Dry the alkaloid in an oven for one...temperature to 110° and dry to a constant weight before taking melting point. Note. Brucine alkaloid tetrahydrate melts at...



Strictosidine: from alkaloid to enzyme to gene.  


In this review, the elucidation of the structure of the first key alkaloidal intermediate in monoterpenoid indole alkaloid biosynthesis, 3 alpha(S)-strictosidine, is presented. The discovery of the enzyme which catalyses the stereospecific formation of this alkaloidal precursor from tryptamine and secologanin, strictosidine synthase, is also detailed. From the knowledge provided by the stereochemical structure of strictosidine and the biochemical characteristics of the biosynthetic enzyme, strictosidine synthase, a new approach to the study of monoterpenoid indole alkaloid biosynthesis was developed. Physiological studies of monoterpenoid indole alkaloid biosynthesis at the enzymic level in plants and plant cell cultures were performed followed by the analyses of these systems at the level of molecular genetics. PMID:7763429

Kutchan, T M



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


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

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



A novel alkaloid from Huperzia crispate.  


A novel alkaloid, hupcrispatine (1), has been isolated from the unique Chinese species Huperzia crispate Ching. The structure of hupcrispatine has been elucidated as 9-amino-6-methyl-3-quinolone on the basis of spectral evidence. PMID:19003610

Pei, Gang; He, Gui-Xia; Du, Fang-Lu; Jiang, Dao-Song


Modified alkaloid pattern in developing tobacco callus.  


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

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



Bioactive Heterocyclic Alkaloids of Marine Origin  

Microsoft Academic Search

Many kinds of alkaloids with extraordinary structures and significant biological activities\\u000a have been isolated from marine organisms. This work features the structures, biological activities,\\u000a and biogenesis of novel heterocyclic marine alkaloids, which control biologically and physiologically\\u000a intriguing phenomena. Pinnatoxins and pteriatoxins, potent shellfish poisons, were isolated from\\u000a the Okinawan bivalve Pinna sp. and Pteria\\u000a sp. Norzoanthamine hydrochloride, isolated from the

Masaki Kita; Daisuke Uemura


Selagoline, a new alkaloid from Huperzia selago.  


A new natural product, named selagoline, and two known alkaloids, huperzine A and serratidine, were isolated from Huperzia selago (Lycopodiaceae) collected in Iceland. Their structures were determined using 600 and 800MHz one- and two-dimensional NMR methods supported by Fourier-transform mass spectrometry. Possible role of selagoline as a precursor of 5,15-oxidolycopodane, a component of the classical alkaloids L28 and L31, is discussed. PMID:15143827

Staerk, Dan; Larsen, Jesper; Larsen, Line A; Olafsdottir, Elin S; Witt, Matthias; Jaroszewski, Jerzy W



Pharmacokinetics of Hoasca alkaloids in healthy humans  

Microsoft Academic Search

N,N-Dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine (THH) are the characteristic alkaloids found in Amazonian sacraments known as hoasca, ayahuasca, and yajè. Such beverages are characterized by the presence of these three harmala alkaloids, where harmine and harmaline reversibly inhibit monoamine oxidase A (MAO-A) while tetrahydroharmine weakly inhibits the uptake of serotonin. Together, both actions increase central and peripheral serotonergic activity

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



Antiplasmodial indole alkaloids from Leuconotis griffithii  

Microsoft Academic Search

A new indole alkaloid, leucoridine A N-oxide (1), consisting of two units of a strychnan type of skeleton, was isolated from the leaves of Leuconotis griffithii. Its structure was elucidated by various spectroscopic means such as NMR and MS, and also by chemical means. Antiplasmodial\\u000a activity against Plasmodium falciparum 3D7 of indole alkaloids isolated from L. griffithii was investigated.

Alfarius E. Nugroho; Yusuke Hirasawa; Wong Chin Piow; Toshio Kaneda; A. Hamid A. Hadi; Osamu Shirota; Wiwied Ekasari; Aty Widyawaruyanti; Hiroshi Morita


Flexible Synthetic Approaches to Monoterpene Indole Alkaloids  

Microsoft Academic Search

Preliminary model studies have demonstrated that our novel synthetic approaches to the Iboga- and seco-Yohimbine alkaloid families represent viable concepts for flexible strategies towards these alkaloid classes. The key step in the iboga case consists of an intramolecular nitrone-olefin 1,3-dipolar cycloaddition reaction of a monocyclic intermediate to yield a tricyclic isoxazolidine derivative that contains all of the stereochemical information of

Christine Frauenfelder; Gavin A. Schmid; Thomas Vogelsang; Hans-Jürg Borschberg


BIAdb: A curated database of benzylisoquinoline alkaloids  

PubMed Central

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



[Genetic aspects of the interrelation between alkaloids and chemical elements in Atropa belladonna L. and Glaucium flavum Grantz. plants].  


The variability of the contents of tropane and isoquinoline alkaloids, ashes, Na, K, Ca, Mg, Fe, Mn, Cu, Zn, Co, Mo, Cr, Al, Ba, V, Ni, Sr, Cd, Pb, J, and Ag was studied in individual plants of the industrial population of belladonna (Atropa belladonna L.) and yellow horned poppy (Glaucium flavum Crantz.). Numerous linear and nonlinear correlations of isoquinoline and tropane alkaloids with ashes and mineral elements were revealed by means of correlation and regression analyses. Alkaline earth elements (especially Sr and Ba) were shown to have a major role in the regulation of tropane alkaloid accumulation in belladonna leaves. K and Ni were of particular importance in the aerial part of yellow horned poppy. These elements at the suboptimal concentrations were most favorable for isoquinoline alkaloid accumulation in yellow horned poppy. Analytical mathematical models were derived for the regulation of alkaloid metabolism in test plants by some mineral elements (Ba, Mg, Al, Sr, Ni, Mn, and K). Our results indicate that the interrelation between alkaloids and elements in these plants is genetically determined. PMID:18924415

Lovkova, M Ia; Buzuk, G N; Sokolova, S M


Determining important parameters related to cyanobacterial alkaloid toxin exposure  

SciTech Connect

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.

Love, A H



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...


Rotational Investigation of Tropane Alkaloids  

NASA Astrophysics Data System (ADS)

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

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



Multicomponent Therapeutics of Berberine Alkaloids  

PubMed Central

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.

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



Acetylcholinesterase inhibitory activity of some Amaryllidaceae alkaloids and Narcissus extracts  

Microsoft Academic Search

Amaryllidaceous plants produce pharmacologically active alkaloids, galanthamine being the most interesting for its use in the treatment of Alzheimer's disease as a cholinesterase inhibitor. The aim of this work was to test 23 pure Amaryllidaceae alkaloids and 26 extracts from different species of the genus Narcissus for their acetylcholinesterase inhibitory activity using galanthamine as a reference. Only seven alkaloids, belonging

Susana López; Jaume Bastida; Francesc Viladomat; Carles Codina



Indole and monoterpene alkaloids from the leaves of Kopsia dasyrachis  

Microsoft Academic Search

A new monoterpene alkaloid, kinabalurine G, in addition to 11 indole alkaloids and the catechine–skytanthine compound, kopsirachine, was obtained from the leaf extract of Kopsia dasyrachis. The structure of the novel alkaloid, danuphylline, was confirmed by an X-ray analysis.

Toh-Seok Kam; Yeun-Mun Choo; Wei Chen; Jia-Xing Yao



Ephedrine-type alkaloid content of nutritional supplements containingephedra sinica (ma-huang) as determined by high performance liquid chromatography  

Microsoft Academic Search

Nutritional supplements containing Ephedra sinica (ma- huang), a botanical source of ephedrine-type alkaloids, have been linked to numerous episodes of ephedrine (EPH) toxicity. With passage of the 1994 Dietary Supplement Health and Education Act, nutritional supplements are no longer subject to the same FDA preapproval requirements as food additives, prescription, or nonpre- scription medications. As a consequence, EPH content is

B. J. Gurley; P. Wang; S. F. Gardner



Alkaloids from Cephalotaxus lanceolata and their cytotoxicities.  


A phytochemical investigation of the branches and leaves of Cephalotaxus lanceolata resulted in the isolation of three new cephalotaxus alkaloids, cephalancetines A, B, and D (1, 2, and 4, resp.), together with ten known alkaloids, 3 and 5-13. The structures of the alkaloids were elucidated on the basis of spectroscopic analyses, including 1D- and 2D-NMR, and HR-ESI-MS, and single-crystal X-ray diffraction. All isolated compounds were tested for their cytotoxicities against four human tumor cell lines, A549, HCT116, SK-BR-3, and HepG2. Compounds 12 and 13 showed remarkable activities against A549, HCT116, and HepG2 cell lines. PMID:23576344

He, Yi-Ren; Shen, Yun-Heng; Li, Bo; Li, Bo; Lu, Lu; Tian, Jun-Mian; Zhang, Wei-Dong



Alkaloids of anuran skin: antimicrobial function?  


A variety of alkaloids, most of which occur or are structurally related to alkaloids that occur in skin glands of dendrobatid poison frogs, were assayed for antimicrobial activity against the Gram-positive bacterium Bacillus subtilis, the Gram-negative bacterium Escherichia coli and the fungus Candida albicans. Certain pyrrolidines, piperidines and decahydroquinolines, perhydro-histrionicotoxin, and a synthetic pumiliotoxin were active against B. subtilis. Only 2-n-nonylpiperidine was active against E. coli. One pyrrolidine, two piperidines, two decahydroquinolines, and the synthetic pumiliotoxin were active against the fungus C. albicans. The results suggest that certain of the skin alkaloids of poison frogs, in addition to being noxious to predators, may also benefit the frog through protection against skin infections. PMID:16402556

Macfoy, Cyrus; Danosus, Douglas; Sandit, Raj; Jones, Tappey H; Garraffo, H Martin; Spande, Thomas F; Daly, John W


Two new alkaloids from Narcissus serotinus L.  


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. PMID:20948496

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




Microsoft Academic Search

Plants that contain pyrrolizidine alkaloids and pyrrolizidine alkaloid N-oxides are widely distributed in the world. These plants are probably the most common poisonous plants affecting livestock, wildlife, and humans. Although pyrrolizidine alkaloids have been shown to be genotoxic, including tumorigenic in experimental animals, the mechanisms of tumor formation have not been fully understood. Our recent studies on riddelliine, riddelline N-oxide,

P. P. Fu; M. W. Chou; Q. Xia; Y.-C. Yang; J. Yan; D. R. Doerge; P. C. Chan



Ephedra alkaloids inhibit platelet aggregation.  


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

Watson, Rex; Woodman, Ryan; Lockette, Warren



Capillary supercritical fluid chromatography of pyrrolizidine alkaloids.  


The application of capillary supercritical fluid chromatography (SFC) for the separation of pyrrolizidine alkaloids (PAs) is examined. Most of these compounds are powerful toxins. Because they are present in at least 3% of all flowering plants, they are responsible for serious losses of livestock and human disease. Capillary SFC, with its high separation efficiency, is shown to be an excellent method for the chromatographic analysis of complex PA mixtures. Complete separation of the PAs of the retronecine and otonecine family has been achieved by pressure-programmed capillary SFC. The operating conditions are mild enough to prevent thermal decomposition of the alkaloids during analysis. PMID:3117819

Holzer, G; Zalkow, L H; Asibal, C F



Pyrrolizidine alkaloids from Echium glomeratum (Boraginaceae).  


The methanolic extract of the whole plant of Echium glomeratum Poir. (Boraginaceae) has afforded five pyrrolizidine alkaloids, three that were (7S, 8R)-petranine (1), (7S, 8S)-petranine (2), and (7R, 8R)-petranine (3a) or (7R, 8S)-petranine (3b), comprising a tricyclic pyrrolizidine alkaloids subclass; and two that were known but to the species: 7-angeloylretronecine (4) and 9-angeloylretronecine (5). All compounds were tested against a human tumor panel for cytotoxicity; no activity was observed (EC50 values>20microg/ml). PMID:18691727

Alali, Feras Q; Tahboub, Yahya R; Ibrahim, Eyad S; Qandil, Amjad M; Tawaha, Khaled; Burgess, Jason P; Sy, Arlene; Nakanishi, Yuka; Kroll, David J; Oberlies, Nicholas H



Evaporative light scattering detection of pyrrolizidine alkaloids.  


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

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


Physiologisch - Chemische Grundlagen der Chinolizidin-Alkaloid - Biosynthese (Physiological - Chemical Bases of Quinolizidine Alkaloid - Biosynthesis).  

National Technical Information Service (NTIS)

Callus cultures were established from 14 alkaloid plants. Cultivation as a suspension culture was possible for 10 of these. Growth conditions were optimized for Lupinus polyphyllus, Sarothamnus scoparius, Baptisia australis, Conium maculatum and Symphytum...

M. Wink



Polyhydroxylated Pyrrolizidines - Total Synthesis of Casuarine Alkaloids  

Microsoft Academic Search

The important role played by glycosidases and glycosyltransferases in molecular biology is well recognised, and equally well known is the fact that any interference with the enzymatic activity of these biomolecules caused by inhibitors such as imino sugars (polyhydroxylated alkaloids) and related compounds can have profound effects on the processes, which they mediate. Imino sugars have shown potential as small

G. Horne; J. van Ameijde; A. E. Håkansson; R. J. Nash; G. W. J. Fleet



Analysis of Catharanthus roseus alkaloids by HPLC  

Microsoft Academic Search

Catharanthus roseus is a medicinal plant from which secondary metabolites used in chemotherapy to treat diverse cancers are extracted. The well\\u000a known high value metabolites vincristine and vinblastine are just 2 of 130 alkaloids that can be found in C. roseus. However, only few (?11) of this high number of chemical entities are frequently analyzed and even fewer (?8) are

Steve Hisiger; Mario Jolicoeur



New lycopodium alkaloids from Huperzia serrata.  


Three new lycopodium alkaloids, 11alpha-hydroxyphlegmariurine B (2), 7alpha-hydroxyphlegmariurine B (3) and 7alpha,11alpha-dihydroxyphlegmariurine B (4) along with a known compound, phlegmariurine B (1), were isolated from the herb Huperzia serrata. The structures of the above compounds were elucidated based on spectroscopic studies. PMID:11859480

Tan, Chang-Heng; Wang, Bao-De; Jiang, Shan-Hao; Zhu, Da-Yuan



Pharmacokinetics of Hoasca alkaloids in healthy humans.  


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

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



Histrionicotoxin Alkaloids Finally Detected in an Ant.  


Workers of the ant Carebarella bicolor collected in Panama were found to have two major poison-frog alkaloids, cis- and trans-fused decahydroquinolines (DHQs) of the 269AB type, four minor 269AB isomers, two minor 269B isomers, and three isomers of DHQ 271D. For the first time in an ant, however, the DHQs were accompanied by six histrionicotoxins (HTXs), viz., 283A, 285A, 285B, 285C, 287A, and 287D. This co-occurrence of the HTX and DHQ alkaloids is the usual pattern seen in dendrobatid frogs. This finding contrasts with our earlier study, where workers of a Brazilian ant, Solenopsis (Diplorhoptrum) sp., were found to have a very similar DHQ complex but failed to show HTXs. Several new DHQ alkaloids of MW 271 (named in the frog as 271G) are reported from the above ants that have both m/z 202 and 204 as major fragment ions, unlike the spectrum seen for the poison-frog alkaloid 271D, which has only an m/z 204 base peak. Found also for the first time in skin extracts from the comparison frog Oophaga granulifera of Costa Rica is a trace DHQ of MW 273. It is coded as 273F in the frog; a different isomer is found in the ant. PMID:23088730

Jones, Tappey H; Adams, Rachelle M M; Spande, Thomas F; Garraffo, H Martin; Kaneko, Tetsuo; Schultz, Ted R



Alkaloidal constituents of Mucuna pruriens seeds.  


The seeds of Mucuna pruriens (L.) DC. after chemical analysis afforded four tetrahydroisoquinoline alkaloids which have been isolated for the first time from M. pruriens. Out of them, two are new whose structures have been elucidated by spectroscopic methods. PMID:15451318

Misra, Laxminarain; Wagner, Hildebert



New spermidine alkaloids from Capparis spinosa roots  

Microsoft Academic Search

Three new spermidine alkaloids capparispine (1), capparispine 26-O-?-d-glucoside (2) and cadabicine 26-O-?-d-glucoside hydrochloride (3) were isolated from the roots of Capparis spinosa. Their structures were established on the basis of spectroscopic analysis, including 1D and 2D NMR experiments (1H–1H COSY, HSQC, HMBC).

Xiao Pu Fu; Tao Wu; Miriban Abdurahim; Zhen Su; Xue Ling Hou; Haji Akber Aisa; Hankui Wu



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


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

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



Discovery of skin alkaloids in a miniaturized eleutherodactylid frog from Cuba  

PubMed Central

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

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



Enzymology of indole alkaloid biosynthesis in Catharanthus roseus.  


Indole alkaloids in Catharanthus roseus have been in focus because of their medicinal value. These alkaloids consist of an indole moiety provided by tryptamine and a terpenoid portion provided by the secologanin. The most important catharanthus alkaloids are vinblastine (VLB), vincristine (VCR) and ajmalicine. VLB and VCR are clinically useful anticancer agents whereas ajmalicine is used for the treatment of circulatory diseases. VCR and VLB are the most expensive because of their low abundance in the plant, and are formed by the coupling of monomeric indole alkaloids vindoline and catharanthine, catalysed by peroxidases. The pathway that lead to monomeric indole alkaloids involves more than 20 enzymes of which 16 enzymes have been isolated and characterized biochemically, and only three at the molecular level. The present state of knowledge on enzymes and genes involved in indole alkaloid biosynthesis and various aspects of their regulation has been discussed. PMID:8936815

Misra, N; Luthra, R; Kumar, S



Quinolizidine alkaloid biosynthesis: recent advances and future prospects  

PubMed Central

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.

Bunsupa, Somnuk; Yamazaki, Mami; Saito, Kazuki



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


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

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



Analysis and modification of ergot alkaloid profiles in fungi.  


The ergot alkaloids are a family of secondary metabolites produced by a phylogenetically discontinuous group of fungi. Various members of the family are important in agriculture, where they accumulate in grain crops or forage grasses and adversely affect humans or animals who consume them. Other ergot alkaloids have been used clinically to treat a variety of diseases. Because of their significance in agriculture and medicine, the ability to detect and quantify these alkaloids from a variety of substrates is important. The primary analytical approach for these purposes has been high performance liquid chromatography. The ability to manipulate ergot alkaloid production in fungi, by transformation-mediated approaches, has been useful for studies on the biosynthesis of these alkaloids and may have practical application in agriculture and medicine. Such modifications have been informed by comparative genomic approaches, which have provided information on the gene clusters associated with ergot alkaloid biosynthesis. PMID:22999178

Panaccione, Daniel G; Ryan, Katy L; Schardl, Christopher L; Florea, Simona



Pyrrolizidine alkaloids in overwintering monarch butterflies ( Danaus plexippus ) from mexico  

Microsoft Academic Search

Summary North American populations of the monarch butterfly,Danaus plexippus, have been found to contain pyrrolizidine alkaloids and their N-oxides. Analytical methods (TLC, GC, and GC\\/MS) have been developed to isolate, quantitate, and structurally elucidate the alkaloids. Examples of at least two classes of pyrrolizidine alkaloids have been identified, the macrocyclic diesters, senecionine, integerrimine, and seneciphylline, and the monoesters, echinatine, intermedine,

R. B. Kelley; J. N. Seiber; A. D. Jones; H. J. Segall; L. P. Brower



Two new morphinane alkaloids from Sinomenium acutum.  


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 ?M. Compound 2 was tested for neuroprotective effect and showed significant activity against ?-amyloid(25-35)-induced oxidative injury (*P < 0.05) at 10 ?M in PC-12 cells. PMID:21623515

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



Cyclopeptide alkaloids from Scutia buxifolia Reiss.  


Scutianene E (1), 3,4,28-tris-epi-scutiaene E (2), 28-epi-scutianene E (3) and scutianene L (4), four neutral cyclopeptide alkaloids, were isolated from Scutia buxifolia Reiss, together with four known cyclopeptide alkaloids, scutianines B, C, D and E. Scutianenes 1-3 are diastereoisomeric compounds, with 3-hydroxyleucine as a ?-hydroxy amino acid unit, which is connected to the styryl fragment via an ether bridge, ?-phenylserine, as a common ring-bonded amino acid residue. Attached to the amino group of ?-hydroxyamino acid is a side chain [trans-CH=CH-Ph]. The structures of the peptides were elucidated by means of spectroscopic analysis, including extensive 2D NMR studies. The stereochemistry for the diastereomeric 3,4,28-tris-epi-scutiaene E and 28-epi-scutianene E was confirmed by X-ray diffraction analysis of their O-acetyl derivatives. PMID:21420695

Maldaner, Graciela; Marangon, Patricia; Ilha, Vinicius; Caro, Miguel S Balparda; Burrow, Robert A; Dalcol, Ionara Irion; Morel, Ademir F



Pregnane alkaloids from Sarcococca hookeriana var. digyna.  


Fourteen pregnane-type steroidal alkaloids were isolated from the ethanolic extracts of whole Sarcococca hookeriana var. digyna plants. Their structures were elucidated on the basis of spectral data. Three of them were identified as new steroidal alkaloids: (S)-20-(N,N-dimethylamino)-16?,17?-epoxy-3?-methoxy-pregn-5-ene (1), (20S)-20-(N,N-dimethylamino)-3?-tigloylamino-5?-pregn-11?-ol (2), and (20S)-2?,4?-bis(acetoxy)-20-(N,N-dimethylamino)-3?-tigloylamino-5?-pregnane (3). Some of the isolated compounds showed estrogen biosynthesis-promoting effects in human ovarian granulosa-like KGN cells. The EC50 values for the most effective compounds, vagnine B (6) and funtumafrine C (12), were 71 ?M and 67 ?M, respectively. PMID:23651560

Zhang, Pu-zhao; Wang, Fei; Yang, Li-juan; Zhang, Guo-lin



Adsorption of alkaloids on ordered mesoporous carbon.  


An ordered mesoporous carbon (OMC) adsorbent was synthesized, characterized, and evaluated for effective separation and purification of alkaloid compounds from aqueous solutions. The OMC adsorbent has a large BET specific surface area (1532.2m(2)/g), large pore volume (2.13cm(3)/g), and narrow pore diameter distribution with a median pore diameter of 4.21nm. Berberine hydrochloride, colchicine, and matrine were selected as the model compounds for evaluating the adsorption properties of the OMC adsorbent for alkaloid purification. Batch adsorption experiments of pure components in water were carried out to measure both adsorption equilibria and kinetics, and column breakthrough and desorption experiments were performed to validate the separation and regeneration efficacy of the OMC adsorbent. The adsorption equilibrium capacities of berberine hydrochloride, colchicine, and matrine on the OMC adsorbent at 0.100mg/L and 298K are 450, 600, and 480mg/g, respectively, which are more than double the adsorption capacities of these compounds on two commonly used commercial resins (HPD300 and HPD100B) at similar conditions. Adsorption equilibrium of all three alkaloids could be obtained within 120min at 298K. The dynamic adsorption capacities determined from the breakthrough experiments are within 12% of the estimated equilibrium capacities from the Langmuir isotherms; and 74.3-92.8% of the adsorbed amounts could be recovered by desorbing with a 70% alcohol solution. The adsorption isotherms are analyzed with both Langmuir and Freundlich models, the adsorption kinetic data with the pseudo-first-order and pseudo-second-order models, and the breakthrough curves with four breakthrough models. The large adsorption capacity, fast adsorption rate, and easy regeneration make the ordered mesoporous carbon a promising adsorbent for adsorption and purification of alkaloid compounds from the extracts of herbal plants. PMID:23953651

Li, Yin; Yuan, Bin; Fu, Jie; Deng, Shuguang; Lu, Xiuyang



Benhamycin, novel alkaloid from terrestrial Streptomyces sp  

Microsoft Academic Search

During our screening for bioactive natural compounds from microorganisms, a novel alkaloid has been isolated from a terrestrial Streptomyces sp. isolate NR12, and named as benhamycin (1). This was along with the known metabolites, uracil, thymine, p-hydroxybenzoic acid, 2?-deoxyuridin, tryptophol, indolyl-3-carboxylic acid, and indolyl-3-carbaldehyde. Chemical structure of the novel compound was determined by detailed analysis of its spectroscopic data (extensive

Mohamed Shaaban; Mohamed S. Abdel-Aziz



Synthesis studies on the Melodinus alkaloid meloscine.  


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

Feldman, Ken S; Antoline, Joshua F



A chromanone alkaloid from Derris ovalifolia stem.  


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

Shankar, Thangaraj; Muthusubramanian, Shanmugam; Gandhidasan, Rathinasamy



An unusual quinolinone alkaloid from Waltheria douradinha.  


The chemical investigation of the methanolic extract of the root bark of Waltheria douradinha (Sterculiaceae) afforded an unusual quinolinone alkaloid named waltherione-A (1). Its structure was determined mainly by NMR spectroscopic methods. The antibacterial activity of waltherione-A (1) and the corresponding O-methylated derivative (2) was tested against three gram-negative and three gram-positive bacteria, with only (2) having moderate activity. PMID:15924921

Hoelzel, Solange C S M; Vieira, Eleno R; Giacomelli, Sandro R; Dalcol, Ionara I; Zanatta, Nilo; Morel, Ademir F



Two new alkaloids from Capparis himalayensis.  


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. PMID:18239306

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



Cytotoxic dimeric indole alkaloids from Catharanthus roseus.  


Three new dimeric indole alkaloids (1-3), together with five known ones (4-8), were isolated from the whole plants of Catharanthus roseus. The structures and absolute configurations of new compounds were elucidated by means of NMR and CD analyses. All these compounds were evaluated for their in vitro cytotoxic activities against human breast cancer cell line MDA-MB-231. PMID:22445552

Wang, Chun-Hua; Wang, Guo-Cai; Wang, Ying; Zhang, Xiao-Qi; Huang, Xiao-Jun; Zhang, Dong-Mei; Chen, Min-Feng; Ye, Wen-Cai



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


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

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



Three new phlegmariurine B type lycopodium alkaloids from Huperzia serrata.  


Phlegmariurine B (1), a known alkaloid, along with three new analogous compounds, 2alpha-hydroxyphlegmariurine B (2), 2-oxoyphlegmariurine B (3) and 11-oxophlegmariurine B (4), were isolated from the CHCl3 fraction of total alkaloids of whole plant of the Chinese medicinal herb Huperzia serrata. Their structures were elucidated by spectral analysis. PMID:12118514

Tan, Chang-Heng; Chen, Guo-Fu; Ma, Xiao-Qiang; Jiang, Shan-Hao; Zhu, Da-Yuan



Two new N-oxide Lycopodium alkaloids from Huperzia serrata.  


Two new Lycopodium alkaloids, N-oxidehuperzine E (1) and N-oxidehuperzine F (2), along with two known alkaloids, huperzines E (3) and F (4), were isolated from Huperzia serrata (Thunb.) Trev. Their structures were elucidated by spectroscopic and chemical transformations. PMID:19809906

Wang, Heng-Bin; Tan, Chang-Heng; Tan, Jun-Jie; Qu, Shi-Jin; Chen, Yi-Lei; Li, Yi-Ming; Jiang, Shan-Hao; Zhu, Da-Yuan



Non-toxic pyrrolizidine alkaloids from Eupatorium semialatum.  


The leaves of Eupatorium semialatum were investigated for the occurrence of pyrrolizidine alkaloids. Although this type of alkaloids generally occurs in the Eupatorieae, only unusual non-toxic pyrrolizidines of the tussilagin type were identified. All compounds are methyl esters of the corresponding beta-amino acids. PMID:11106842

Lang; Passreiter; Medinilla; Castillo; Witte



Alkaloids and aromatics of Cyathobasis fruticulosa (Bunge) Aellen.  


A beta-carboline-, a tryptamine-, and two phenylethylamine-derived alkaloids and three known aromatic compounds were isolated from the aerial parts and roots of Cyathobasis fruticulosa (Bunge) Aellen, and their structures were elucidated by spectroscopic techniques. The one new alkaloid, N-methyl-N-formyl-4-hydroxy-beta-phenylethylamine (1), showed marginal antifungal activity. PMID:15974629

Bahçeevli, Arzu Küçükosmanogiu; Kurucu, Semra; Kolak, Ufuk; Topçu, Gülaçti; Adou, Eba; Kingston, David G I



A cage-monoterpene indole alkaloid from Alstonia scholaris.  


An unprecedented cage-like alkaloid, scholarisine A was isolated from the leaves of Alstonia scholaris and its structure determined on the basis of 1D and 2D NMR, FTIR, UV, and high-resolution mass spectroscopic data. This alkaloid might be derived from picrinine via oxygenation, rearrangement, and lactonization. PMID:18205369

Cai, Xiang-Hai; Tan, Qin-Gang; Liu, Ya-Ping; Feng, Tao; Du, Zhi-Zhi; Li, Wei-Qi; Luo, Xiao-Dong



Antitumor agents 248. Chemistry and antitumor activity of tylophorinerelated alkaloids  

Microsoft Academic Search

Tylophorine (1) and related phenanthroindolizidine alkaloids, also known as Tyophora alkaloids, have been isolated principally from plants of the family Asclepiadaceae, including members of the genus Tylophora. Because of their profound cytotoxicity, these compounds have been targets of synthetic modification. Evaluation of (+)-(S)-tylophorine and its analogs in the National Cancer Institute's antitumor screen showed a uniform and potent inhibitory effect

Linyi Wei; Arnold Brossi; Susan L. Morris-Natschke; Kenneth F. Bastow; Kuo-Hsiung Lee



Alkaloid production in Catharanthus roseus (L.) G. Don  

Microsoft Academic Search

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

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



Pandanus alkaloids in Stemonaceae: finding of a plausible biogenetic origin of Stemona alkaloids.  


The isolation of (Z,Z)-pandanamine (1) and its corresponding isomers (Z,E)-pandanamine (2) and (E,E)-pandanamine (3) from Stichoneuron calcicola of the family Stemonaceae is of outstanding chemosystematic importance. This alkaloid was previously only known from the family Pandanaceae, where it was accompanied by a series of pyrrolidines, collectively called Pandanus alkaloids. The pyrrolidines pandamarilactonines A (4), B (5), C (6), and D (7) were also detected in the present study, most likely representing artificial cyclization products of pandanamine (1-3) formed by acidic conditions during chromatographic separation on silica gel. Similar structures were found in various Stemona alkaloids, suggesting a close relationship between the two plant families. Structurally, pandanamine (1-3) can be regarded as a direct precursor of croomine (8), originally isolated from Croomia, a genus closely related to Stichoneuron, but later also found in various Stemona species. The co-occurrence of pandanamine (1-3), croomine (8), and stichoneurin (9) in the family Stemonaceae represents a sound argument for a new interpretation of the biogenetic origin of Stemona alkaloids and at the same time substantiates the removal of the family from the order Dioscoreales and its inclusion into Pandanales, as already suggested by DNA sequencing. PMID:19725518

Greger, Harald; Schinnerl, Johann; Vajrodaya, Srunya; Brecker, Lothar; Hofer, Otmar



Alkaloids from Arundo donax . XVII. Structure of the Dimeric Indole Alkaloid Arundaphine  

Microsoft Academic Search

The newdimeric alkaloid arundaphine, a tryptamine-tryptamine base, was isolated from roots and rhizomes of Arundo donax (Poaceae). Spectral data and an x-ray structure analysis established its structure as 1-[3-(2-dimethylaminoethyl)-5-hydroxy-1H-4-indolyl]-3-hydroxy-3-(2-methylaminoethyl)-2-indolinone.

V. U. Khuzhaev; I. Zhalolov; K. K. Turgunov; B. Tashkhodzhaev; M. G. Levkovich; S. F. Aripova; A. S. Shashkov



A systematic analysis of alkaloids by thin layer chromatography  

NASA Astrophysics Data System (ADS)

Fifty-four alkaloids previously divided into four groups on the basis of their behavior in solvents of different compositions using paper chromatography, were subdivided into two groups by thin paper chromatography. The behavior of the alkaloids in different support layers (silica gel, aluminum oxide alkaline, and diatomite G) was examined. It was found that the maximum amount of coating that can be developed without tailing came to a few milligrams on the silica gel plates, a few tenths of a milligram on aluminum oxide, and generally only 25 mg to 50 mg on inactive diatomite plates. The alkaloids could be adequately distinguished from one another by the spraying reagent ince not only color differences but also color changes could be seen during and after spraying. The coloring of the alkaloids by iodine plateate reagent was also determined by the concentration of the alkaloid used. The edge was often a different color from the center.

Waldi, D.



Do naïve ruminants degrade alkaloids in the rumen?  


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

Aguiar, Ramón; Wink, Michael



Biparental endowment of endogenous defensive alkaloids in Epilachna paenulata.  


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

Camarano, Soledad; González, Andrés; Rossini, Carmen



Increasing the content of leaf and root alkaloids of high alkaloid content mutants of periwinkle through nitrogen fertilization  

Microsoft Academic Search

In industrial plants such as medicinal plants, the content of the economically important metabolite is more important than the yield of the plant part containing the metabolite, as it determines the cost of extraction of the metabolite. Two high alkaloid content mutants of periwinkle (Catharanthus roseus, a medicinal plant yielding anti-cancer and anti-hypertension alkaloids) were developed through induced mutagenesis. Since

Y. Sreevalli; R. N. Kulkarni; K. Baskaran; R. S. Chandrashekara



Muscarine, imidaozle, oxazole and thiazole alkaloids.  


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

Jin, Zhong



Alkaloids; Strychnine, Codeine, Heroin, and Morphine  

NSDL National Science Digital Library

The featured molecules this month come from the article "The Conversion of Carboxylic Acids to Ketones: A Repeated Discovery" by John W. Nicholson and Alan D. Wilson. The authors describe the repeated discovery of this reaction and illustrate its central role in Woodward's total synthesis of strychnine. Strychnine is a member of a large class of nitrogen heterocycles known as alkaloids, a name derived from the fact that all produce basic solutions in water. Other well-known members of this class of compounds, all of which are pharmacologically active, are nicotine, atropine (deadly nightshade), quinine, lysergic acid, cocaine, and the three structurally similar compounds codeine, heroin, and morphine.


Total synthesis of the monoterpenoid alkaloid (±)-tangutorine.  


A novel approach to a formal total synthesis of the monoterpenoid indole alkaloid (±)-tangutorine has been developed starting from an ?,?-unsaturated cyclic dehydroamino ester. Synthesis of the rather unusual trans-substituted 2,3-indoloquinolizidine substructure was accomplished via Cu(II)-mediated conjugate addition and organozinc/copper coupling as the key steps, thereby setting the stage for ring-closing metathesis to produce the quinolone substructure. Finally, Bischler-Napieralski cyclization gave rise to the pentacyclic system of (±)-tangutorine thereby realizing a formal synthesis in an overall yield of 5.2% in eight consecutive steps. PMID:22130791

van den Broek, Sebastiaan A M W; Lemmers, Jaap G H; van Delft, Floris L; Rutjes, Floris P J T



Neurotoxic alkaloids: saxitoxin and its analogs.  


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

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



Pyrrolizidine alkaloids of Echium vulgare honey found in pure pollen.  


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

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



Canthin-6-one and ?-carboline alkaloids from Eurycoma harmandiana  

Microsoft Academic Search

Two alkaloids, canthin-6-one 9-O-?-glucopyranoside and 7-hydroxy-?-carboline 1-propionic acid, were isolated from the roots of Eurycoma harmandiana, together with the five known canthin-6-one alkaloids, 9-hydroxycanthin-6-one, 9-methoxycanthin-6-one, 9,10-dimethoxycanthin-6-one, canthin-6-one and canthin-6-one N-oxide, and the two known ?-carboline alkaloids, ?-carboline 1-propionic acid and 7-methoxy-?-carboline 1-propionic acid. Their structures were based on analyses of spectroscopic data.

Tripetch Kanchanapoom; Ryoji Kasai; Phannipha Chumsri; Yoshikazu Hiraga; Kazuo Yamasaki



Aporphine alkaloids from the roots of Stephania viridiflavens.  


Further investigation on the phytochemistry of the medicinal plant Stephania viridiflavens led to the isolation of a new naturally occurring aporphine alkaloid, (+)-6R, 6aS-isocorydine N(beta)-oxide (1), together with three known aporphine alkaloids: (+)-6R, 6aS-corydine N(beta)-oxide (2), (+)-N-methyl-laurotetanine (3) and (+)-stepharine (4). The structure and stereochemistry of 1 were determined on the basis of spectroscopic methods and confirmed by synthesis. Alkaloids 2-4 were isolated for the first time from this species. PMID:20645211

Zhang, Maosheng; Liang, Guangyi; Yu, Jianping; Pan, Weidong



Five new fawcettimine-related alkaloids from Lycopodium japonicum Thunb.  


Five new trace alkaloids with fawcettimine-related structures (1-5), i.e., 6-hydroxyl-6,7-dehydrolycoflexine (1), 6-hydroxyl-6,7-dehydro-8-deoxy-13-dehydroserratinine (2), together with three known ones (6-8), were isolated from the club moss Lycopodium japonicum Thunb. Their structures were elucidated by extensive NMR spectroscopic analysis, HRESIMS, CD and comparison with known ones. Compounds 1 and 2 are characterized by the enol moiety that is rarely reported in Lycopodium alkaloids, and Compound 5 is the second example of Lycopodium alkaloids with a C-16-C-4 linkage. A plausible biogenetic pathway for the isolates was proposed. PMID:23994627

Wang, Xiao-Jing; Li, Li; Yu, Shi-Shan; Ma, Shuang-Gang; Qu, Jing; Liu, Yun-Bao; Li, Yong; Wang, Yadan; Tang, Weibin



Daphmacromines A-J, alkaloids from Daphniphyllum macropodum.  


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

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



Cyclic peptide alkaloids from the bark of Discaria americana.  


The isolation and structure determination of cyclic peptide alkaloids, discarine-M and discarine-N, along with seven known cyclic peptide alkaloids, adouetine-Y', franganine, frangulanine, discarines-A, -B, -C, and -D from the root bark of Discaria americana are described. Structures were determined spectroscopically, especially using 2D NMR spectroscopic analysis. The crude methanol extract, the basic ether extract, and the alkaloids 6 and 7 also weakly inhibited growth of gram-negative and gram-positive bacteria. PMID:15081298

Giacomelli, Sandro R; Maldaner, Graciela; Gonzaga, Wellington A; Garcia, Claudia M; da Silva, Ubiratan F; Dalcol, Ionara I; Morel, Ademir F



Two new quaternary protoberberine alkaloids from Corydalis yanhusuo.  


Two new quaternary protoberberine alkaloids, namely corydayanine (1) and yanhusuine (2), were isolated from the tubers of Corydalis yanhusuo. On the basis of extensive chemical and spectroscopic evidences, especially 1D and 2D NMR and HRMS experiments, their structures were elucidated as 5,6-dihydro-3,9-dihydroxy-2,10-dimethoxy-13-methyl-dibenzo[a,g] quinolizinium alkaloid and 5,6-dihydro-12-hydroxy-2,3,9-trimethoxy-13-methyl-dibenzo[a,g] quinolizinium alkaloid, respectively. PMID:22530675

Zhou, Qiong; Deng, An-Jun; Qin, Hai-Lin



[Extraction and HPLC analysis of alkaloids in goldenseal].  


An ambient extraction of goldenseal root powder followed by HPLC analysis of the alkaloids on a Zorbax Rapid Resolution Eclipse XDB-C18 column provides an accurate method for the determination of key alkaloids in goldenseal, including berberine and hydrastine. The extraction and HPLC analysis can be applied to several other alkaloids, including canadine, hydrastinine, and palmatine, and may be applicable to other berberine-containing plant roots. The Rapid Resolution Eclipse XDB-C18 column is used for an isocratic separation with high resolution of all componentsin under 15 minutes. PMID:15969129

Weber, Holly A; Joseph, Maureen



Antibacterial carbazole alkaloids from Clausena harmandiana twigs.  


Three new carbazole alkaloids, harmandianamines A-C (1-3), together with fifteen known compounds (4-18) were isolated from the twigs of Clausena harmandiana. The structures were elucidated by spectroscopic methods, including UV, IR, NMR, and MS. The antibacterial activity against Escherichia coli TISTR 780, Salmonella typhimurium TISTR 292, Staphylococcus aureus TISTR 1466 and methicillin-resistant S. aureus (MRSA) SK1 of some isolated compounds was also evaluated. Compound 6 exhibited significant antibacterial activity against MRSA SK1 with an MIC value of 0.25 ?g/mL which higher than that of standard drug, vancomycin (MIC value=1 ?g/mL) whereas compounds 14 and 5 showed strong activity with MIC values of 4 and 8 ?g/mL, respectively. Only compound 14 showed strong antibacterial activity against S. aureus TISTR 1466 with an MIC value of 4 ?g/mL. PMID:22579839

Maneerat, Wisanu; Phakhodee, Wong; Ritthiwigrom, Thunwadee; Cheenpracha, Sarot; Promgool, Trinop; Yossathera, Kulsiri; Deachathai, Suwanna; Laphookhieo, Surat



Kukoamine B, a spermine alkaloid from Lycium chinense  

Microsoft Academic Search

A new spermine alkaloid, kukoamine B, was isolated from the root bark of Lycium chinense and its structure was characterized by a combination of spectroscopic analyses and chemical degradation. Kukoamine B consists of two dihydrocaffeoyl moieties and a spermine unit.

Shinji Funayama; Gui-Rong Zhang; Shigeo Nozoe



A New Alkaloid Ajmalimine from the Roots of Rauwolfia serpentina.  


A new indole alkaloid ajmalimine has been isolated from the roots of RAUWOLFIA SERPENTINA collected in Thailand. Its structure, 21-(trimethoxybenzoyl)-ajmaline, was established by spectroscopic and chemical means. PMID:17269023

Siddiqui, S; Ahmad, S S; Haider, S I



Determination of pyrrolizidine alkaloids in commercial comfrey products (Symphytum sp.).  


The presence of hepatotoxic pyrrolizidine alkaloids in comfrey (Symphytum sp.) and the widespread use of decoctions of this plant as a beverage (herbal tea) are of increasing concern. A method for the extraction and solid-phase concentration and capillary gas chromatographic determination of these alkaloids and their N-oxides in botanical materials has been developed and was applied to eleven comfrey-containing products purchased from retail health-food outlets in the Washington, DC, area during May-June 1989. Nine of the 11 products were found to contain measurable quantities of one or more of the alkaloids, in ranges from 0.1 to 400.0 ppm. Products containing comfrey leaf in combination with one or more other ingredients were found to contain the lowest alkaloid levels. Highest levels were found in bulk comfrey root, followed by bulk comfrey leaf. The species of the bulk material was verified by thin-layer chromatography and other means. PMID:8071814

Betz, J M; Eppley, R M; Taylor, W C; Andrzejewski, D



A bacterial platform for fermentative production of plant alkaloids  

PubMed Central

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

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



Pyrrolizidine alkaloids in pollen and pollen products.  


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

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



Inhibition of acetyl cholinesterase by solanaceous glycoalkaloids and alkaloids  

Microsoft Academic Search

Seven solanaceous glycoalkaloids (?-chaconine, ?2-chaconine, ?-solanine, dehydrocommersonine, commersonine, demissine and tomatine) and three alkaloids (solanidine, tomatidine\\u000a and demissidine) were tested for their ability to inhibit acetyl cholinesterase in anin vitro system. Glycoalkaloids at concentrations of 33–41 parts per million (ppm) gave cholinesterase inhibition ranging from 4.2\\u000a to 26.8%. All three alkaloids had lower anticholinesterase (4.2 to 15.4%) than the seven

Rodney J. Bushway; Sharon A. Savage; Bruce S. Ferguson



Effects of Psychotria colorata alkaloids in brain opioid system  

Microsoft Academic Search

An ethnopharmacological survey showed that home remedies prepared with flowers and fruits ofPsychotria colorata are used by Amazonian peasants as pain killers. Psychopharmacological in vivo evaluation of alkaloids obtained from leaves\\u000a and flowers of this species showed a marked dose-dependent naloxone-reversible analgesic activity, therefore suggesting an\\u000a opioid-like pharmacological profile. This paper reports an inhibitory effect ofP. colorata flower alkaloids on

Tânia Alves Amador; Elaine Elisabetsky; Diogo Onofre de Souza



Suppression of ochratoxin biosynthesis by naturally occurring alkaloids  

Microsoft Academic Search

The effects of four alkaloids on the biosynthesis of ochratoxin A (OTA), ochratoxin B (OTB) and citrinin were examined on four OTA-producing aspergilli: Aspergillus auricomus, A. sclerotiorum and two isolates of A. alliaceus. Piperine and piperlongumine, natural alkaloids of Piper longum, significantly inhibited OTA production at 0.001% (w\\/v) for all aspergilli examined. Piperine and piperlongumine affected the polyketide synthesis step

S. E. Lee; B. S. Park; P. Bayman; J. L. Baker; W. S. Choi; B. C. Campbell



Main stages in the development of domestic alkaloid chemistry  

Microsoft Academic Search

The following are considered: 1) the study of alkaloids in Russia before the Great October Socialist Revolution. 2) The development\\u000a of industry and of scientific investigations in the field of alkaloid chemistry at the end of the XIXth and the beginning\\u000a of the XXth centuries and the influence of social factors on the development of this part of knowledge. 3)

V. N. Ryzhikov; N. A. Figurovskii; T. A. Komarova; T. V. Bogatova



Detection and quantification of pyrrolizidine alkaloids in antibacterial medical honeys.  


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

Cramer, Luise; Beuerle, Till



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


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

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



Java Numerics  

NSDL National Science Digital Library

The JavaNumerics website "provides a focal point for information on numerical computing in Java." The project is headed by the Java Grande Forum Numerics Working Group, and sponsored by the Mathematical and Computational Sciences Division of the NIST Information Technology Laboratory. Reports, presentations and proposed APIs for numerical computing from the JavaNumerics working groups are posted here, along with links providing information on Java-related meetings, proposals, and benchmarks. Links to general numerics and linear algebra libraries, along with other tools and utilities, are also provided.


Bromo- and Iodo-Containing Alkaloids from Marine Microorganisms and Sponges  

Microsoft Academic Search

The taxonomic distribution, structure, and biological activity of halogenated alkaloids isolated from marine microorganisms and sponges are reviewed. The structures of nearly 140 natural bromo- and iodo-containing alkaloids are shown.

V. M. Dembitsky



New humantenine-type indole alkaloids with iridoid unit from Gelsemium species  

Microsoft Academic Search

Two new oxindole alkaloids, rankiniridine (1) and humanteniridine (2), having a nitrogen–carbon linkage between a humantenine-type monoterpenoid indole alkaloid and a monoterpene unit with an iridoid skeleton, were isolated from Gelsemium rankinii and Gelsemium elegans, respectively.

Noriyuki Kogure; Hiromi Kobayashi; Naoko Ishii; Mariko Kitajima; Sumphan Wongseripipatana; Hiromitsu Takayama



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

Technology Transfer Automated Retrieval System (TEKTRAN)

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


Dietary Supplements: Uncertainties in Analyses Underlying FDA's Proposed Rule on Ephedrine Alkaloids.  

National Technical Information Service (NTIS)

The dietary supplement industry estimates that as many as 2 billion doses of dietary supplements containing botanical ephedrine alkaloids are consumed each year in the United States. The principal source of botanical ephedrine alkaloids is the Chinese her...



Roman Numerals  

NSDL National Science Digital Library

This website provides an overview of the Principles of Roman numerals as well as a history of Roman numerals, which dates back to 1st millennium BC when they were used by Romans to record numbers in stone, art and coins. Some pictures in the gallery highlight the ways in which Roman Numerals are used today, such as on watch and clock faces. The authors point out that Roman numerals have a classic style and are less functional than the Arabic (decimal) numbers ( 0 to 9 ) which were introduced into Europe about 900 AD and adopted quickly because of their convenience and mathematical ease of use. They also provide lists (including one of Roman Numerals 1 to 2016), tables, and a converter that visitors can use to convert Roman numeral numbers to decimal numbers. Another section provides resources for teachers on lesson ides for teaching Roman Numerals.


Pyrrolizidine alkaloids in honey and bee pollen.  


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

Dübecke, A; Beckh, G; Lüllmann, C



Implementation of functional genomics for gene discovery in alkaloid producing plants  

Microsoft Academic Search

Two centuries after the discovery of the first alkaloids, many enzymes involved in plant alkaloid biosynthesis have been identified.\\u000a Nevertheless, the biosynthetic pathways for most of the plant alkaloids still remain incompletely characterised and understanding\\u000a the regulatory mechanisms controlling the onset and flux of alkaloid biosynthesis is virtually inexistent. This information\\u000a is however crucial to allow modelling of metabolic networks

Alain Goossens; Heiko Rischer



Numerical Errors: Reliable Numerical Simulations  

SciTech Connect

Understanding numerical errors in long calculations is a very subtle science and is critical to understanding the reliability of the final answer. We will carefully examine the accumulation of numerical errors over time and discuss how these can lead to reliability estimates. The primary focus will be on a newly uncovered understanding of mode resolution which is at the heart of all numerical computations.

Jameson, L



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

SciTech Connect

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.

Molyneux, R.J.; Benson, M. (Dept. of Agriculture, Albany, CA (United States)); Pan, Y.T.; Tropea, J.E.; Kaushal, G.P.; Elbein, A.D. (Univ. of Texas, San Antonio (United States))



Alkaloids from some amaryllidaceae species and their cholinesterase activity.  


Alkaloid extracts of four Amaryllidaceae species were studied with respect to their acetylcholinesterase and butyrylcholinesterase inhibitory activity and alkaloid patterns. Twenty-one alkaloids were determined by GC/MS, and seventeen of them identified from their mass spectra and retention times. The GC/MS analysis of the alkaloid extract of Nerine filamentosa is the first phytochemical investigation of this species. Promising erythrocytic acetylcholinesterase inhibitory activity was demonstrated by the alkaloid extracts of Narcissus poeticus var recurvus, Nerine filifolia and N. filamentosa (IC(50,HuAChE) = 6.0 +/- 0.1 microg/mL; IC(50,HuAChE) = 18.5 +/- 0.8 microg/mL, IC(50,HuAChE) = 21.6 +/- 1.1 microg/mL). The most potent inhibitory activity against serum butyrylcholinesterase was shown by extracts of Sternbergia lutea and Nerinefilamentosa (IC(50,HuBuChE) = 3.7 +/- 0.1 microg/mL; IC(50.HuBuChE) = 13.0 +/- 0.7 microg/mL). PMID:22799078

Cahlíková, Lucie; Benesová, Nina; Macáková, Katerina; Kucera, Radim; Hrstka, Václav; Klimes, Jirí; Jahodár, Ludek; Opletal, Lubomír



LC-MS determination of Taxus alkaloids in biological specimens.  


A semi-quantitative LC-MS method was developed for the detection of the pseudo alkaloids of Taxus baccata (yew) from human body fluids and tissue samples. This method was used to examine the cause of death of a 43-year-old man who died several hours after he drank a decoction of taxus leaves. Autopsy and histology demonstrated early signs of myocardial hypoxia. Since investigation of the stomach content did not yield evidence of taxus ingestion, the taxus alkaloids were determined in blood, stomach content and tissue samples of the deceased by LC-MS. The samples were prepared by solid phase extraction on RP-18 columns. Chromatographic separation was achieved by HPLC on a RP-8 column, coupled to an ion trap mass spectrometer (Finnigan LCQ). An atmospheric pressure electrospray ionisation was performed. Spectra of the alkaloids were recorded in the single MS mode and in the MS-MS mode and compared with reference spectra obtained from an extract of yew leaves. In the stomach content, the kidneys, the liver and a heart blood sample of the deceased, alkaloids of Taxus baccata, predominantly taxine B and iso-taxine B, were identified. The semi-quantitative evaluation of the heart blood revealed a taxine concentration of 11 micro g taxine/g. As far as we know this is the first case in which a semi-quantitative analysis of taxine alkaloids has been performed. PMID:14530985

Beike, J; Karger, B; Meiners, T; Brinkmann, B; Köhler, H



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


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

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



The alkaloidal responses of wild tobacco to real and simulated herbivory  

Microsoft Academic Search

I compared the induced alkaloidal response in undamaged leaves of plants subjected to herbivory by the larvae of Manduca sexta and to different simulations of this herbivory; all herbivory treatments removed similar amounts of leaf mass. Although larval feeding induced a significant increase (2.2x) in alkaloid concentrations compared to undamaged plants, the alkaloid responses to larval feeding were significantly lower

Ian T. Baldwin



The Alkaloids of Penicillium aurantiogriseum Dierckx (1901) var. aurantiogriseum VKM F-1298  

Microsoft Academic Search

The fungus Penicillium aurantiogriseum var. aurantiogriseum VKM F-1298 produces two benzodiazepine alkaloids (anacine and aurantine) and one diketopiperazine alkaloid (aurantiamine). When cultured in a submerged mode in Abe medium, the alkaloids are mostly secreted into the medium. The dynamics of aurantine and aurantiamine accumulation in the medium is characterized by the presence of a relatively sharp maximum in the idiophase,

N. G. Vinokurova; B. P. Baskunov; N. F. Zelenkova; M. U. Arinbasarov



Overexpression of tropinone reductases alters alkaloid composition in Atropa belladonna root cultures  

Microsoft Academic Search

The medicinally applied tropane alkaloids hyoscy- amine and scopolamine are produced in Atropa bella- donna L. and in a small number of other Solanaceae. Calystegines are nortropane alkaloids that derive from a branching point in the tropane alkaloid biosynthetic pathway. In A. belladonna root cultures, calystegine molar concentration is 2-fold higher than that of hyo- scyamine and scopolamine. In this

Ute Richter; Grit Rothe; Anne-Katrin Fabian; Bettina Rahfeld; Birgit Drager



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


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 ?mol/kg body weight test article in 0.5 mL of 10% DMSO in water. Twenty-four hours after the last dose, the rats were sacrificed, livers were removed, and liver DNA was isolated for DNA adduct analysis. DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4 adducts were formed in the liver of rats treated with the individual seven hepatocarcinogenic pyrrolizidine alkaloids and riddelliine N-oxide. These DNA adducts were not formed in the liver of rats administered retronecine, the nontumorigenic pyrrolizidine alkaloid, platyphylliine, or vehicle control. These results indicate that this set of DNA adducts, DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4, is a common biological biomarker of pyrrolizidine alkaloid-induced liver tumor formation. To date, this is the first finding that a set of exogenous DNA adducts are commonly formed from a series of tumorigenic xenobiotics. PMID:23937665

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



Cytotoxic and Anti-HIV Phenanthroindolizidine Alkaloids from Cryptocarya chinensis  

PubMed Central

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

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



Aza-tryptamine substrates in monoterpene indole alkaloid biosynthesis.  


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

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



Aza-tryptamine substrates in monoterpene indole alkaloid biosynthesis  

PubMed Central

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.

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



Phenanthroindolizidine alkaloids from the stems of Ficus septica.  


In addition to six known phenanthroindolizidine alkaloids, eight new alkaloids, namely, ficuseptines B-D (1-3), 10R,13aR-tylophorine N-oxide (4), 10R,13aR-tylocrebrine N-oxide (5), 10S,13aR-tylocrebrine N-oxide (6), 10S,13aR-isotylocrebrine N-oxide (7), and 10S,13aS-isotylocrebrine N-oxide (8), were isolated from a methanol extract of the stems of Ficus septica. The structures of the new compounds were elucidated by means of spectroscopic data interpretation. Cytotoxicity of some of these alkaloids was assessed in vitro using the HONE-1 and NUGC cell lines. PMID:16038551

Damu, Amooru G; Kuo, Ping-Chung; Shi, Li-Shian; Li, Chia-Ying; Kuoh, Chang-Sheng; Wu, Pei-Lin; Wu, Tian-Shung



Localization of enzymes and alkaloidal metabolites in Papaver latex.  


In continuing studies on the metabolic activity of Papaver somniferum, latex has been examined for its enzyme and alkaloidal metabolite content. After an initial centrifugation of latex at 1000g, the pellet which contained a heterogeneous population of dense organelles was further resolved on sucrose gradients. Of the enzymes monitored, acid phosphatase and L-3,4-dihydroxyphenylalanine decarboxylase were found to be in the latex 1000g supernatant, whereas catecholase (polyphenolase) was localized in two distinct organelles within the 1000g sediment. The lighter organelles, sedimenting at 30% sucrose, contained a soluble enzyme which was readily released on organelle plasmolysis, whereas the catecholase found within the heavier organelles, sedimenting at 55-60% sucrose, was membrane bound and showed significant activity only in the presence of Triton X-100. These latter organelles also contained the alkaloids, including morphine and thebaine, and were observed to readily accumulate [14CH3]morphine. The alkaloid precursor, dopamine, was localized in the same dense vesicle fraction as the alkaloids. The rate of uptake of [7-14C]dopamine into these fractions at room temperature, however, was markedly lower than that of morphine. Electron microscopic examination of the organelles of various densities revealed that they possessed different morphology. The results are consistent with the concept that both the 1000g and supernatant fractions of the latex are required for alkaloid biosynthesis and that a subpopulation of dense organelles found in the 1000g sediment have at least a function as a storage compartment for both alkaloids and their catecholamine precursor. PMID:6847205

Roberts, M F; McCarthy, D; Kutchan, T M; Coscia, C J



Anti-Alzheimer and antioxidant activities of Coptidis Rhizoma alkaloids.  


Coptidis Rhizoma and its isolated alkaloids are reported to possess a variety of activities, including neuroprotective and antioxidant effects. Thus, the anti-Alzheimer and antioxidant effects of six protoberberine alkaloids (berberine, palmatine, jateorrhizine, epiberberine, coptisine, and groenlandicine) and one aporphine alkaloid (magnoflorine) from Coptidis Rhizoma were evaluated via beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) assays, along with peroxynitrite (ONOO(-)) scavenging and total reactive oxygen species (ROS) inhibitory assays. Six protoberberine alkaloids exhibited predominant cholinesterases (ChEs) inhibitory effects with IC(50) values ranging between 0.44-1.07 microM for AChE and 3.32-6.84 microM for BChE; only epiberberine (K(i)=10.0) and groenlandicine (K(i)=21.2) exerted good, non-competitive BACE1 inhibitory activities with IC(50) values of 8.55 and 19.68 microM, respectively. In two antioxidant assays, jateorrhizine and groenlandicine exhibited significant ONOO(-) scavenging activities with IC(50) values of 0.78 and 0.84 microM, respectively; coptisine and groenlandicine exhibited moderate total ROS inhibitory activities with IC(50) values of 48.93 and 51.78 microM, respectively. These results indicate that Coptidis Rhizoma alkaloids have a strong potential of inhibition and prevention of Alzheimer's disease (AD) mainly through both ChEs and beta-amyloids pathways, and additionally through antioxidant capacities. In particular, groenlandicine may be a promising anti-AD agent due to its potent inhibitory activity of both ChEs and beta-amyloids formation, as well as marked ONOO(-) scavenging and good ROS inhibitory capacities. As a result, Coptidis Rhizoma and the alkaloids contained therein would clearly have beneficial uses in the development of therapeutic and preventive agents for AD and oxidative stress-related disease. PMID:19652386

Jung, Hyun Ah; Min, Byung-Sun; Yokozawa, Takako; Lee, Je-Hyun; Kim, Yeong Shik; Choi, Jae Sue



Alkaloid-fullerene systems through photocycloaddition reactions.  


The photocycloaddition of tertiary amines to ¿60fullerene (C(60)) is an interesting and useful reaction. We wished to extend the applications of this type of reaction through an investigation of the photoaddition of alkaloids to C(60) for the purpose of synthesizing novel and complex photoadducts that are difficult to obtain by usual methods. Irradiation of tazettine (2) or gramine (3) with C(60) in toluene leads to formation of one monoadduct (6 or 7), whereas scandine (1a) or 10-hydroxyscandine (1b) reacts with C(60) photochemically to give two products, the expected ¿6,6 monoadduct (5a, 5b) and a new type of monoadduct with a bis-¿6, 6 closed structure (4a, 4b). These new structures were characterized by UV-vis, FT-IR, (1)H NMR, (13)C NMR, (1)H-(1)H COSY, ROESY, HMQC (heteronuclear multiple-quantum coherence), and HMBC (heteronuclear multiple-bond connectivity) spectroscopy. The techniques of time-of-flight secondary ion MS (TOF-SIMS) and field desorption MS (FD-MS) were used for the mass determination. (3)He NMR analysis of the product mixture from photoaddition of 1a to C(60) containing a (3)He atom ((3)He@C(60)) led to two peaks at -9.091 and -11.090 ppm relative to gaseous (3)He, consistent with formation of a ¿6, 6-closed monoadduct and a bis-¿6,6 closed adduct. Presumably, the bis-¿6, 6 closed adducts are formed by an intramolecular ¿2 + 2 cycloaddition of the vinyl group to the adjacent 6,6-ring junction of C(60) after the initial photocycloaddition. PMID:10864768

Guo, L W; Gao, X; Zhang, D W; Wu, S H; Wu, H M; Li, Y J; Wilson, S R; Richardson, C F; Schuster, D I



Facile Access to Mono-Cinchona Alkaloid-Derived Ligands  

Microsoft Academic Search

Two facile accesses to mono-cinchona alkaloid-derived ligands, by conventional heating conditions and solvent-free microwave irradiation, are described. 1,4-Dichlorophthalazine (PHAL) or 3,6-dichloropyridazine (PYDZ) reacted with quinine (QN), cinchonine (CN), or cinchonidine (CND) by using CaH2 as acid-bonding reagent in DMF at 90–100°C to provide mono-cinchona alkaloid-derived ligands 2a–f (87–95%) in 1.5 h. However, the coupling reactions were performed under solvent-free microwave conditions

Hai-Bo Wang; Xiao-Li Sun; Ping-An Wang; Quan-Jun Wang; Peng-Juan Nan; Lin-Lin Jing



Recent Advances in the Synthesis of Morphine and Related Alkaloids  

NASA Astrophysics Data System (ADS)

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.

Chida, Noritaka


Alkaloid-derived molecules in low rank Argonne premium coals.  

SciTech Connect

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.

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



Cytotoxic quaternary alkaloids from the flowers of Narcissus tazetta.  


Intensive chromatographic separation of the polar fraction of an ethanolic extract of the fresh flowers of Narcissus tazetta L. (Amaryllidaceae) yielded two new quaternary alkaloids with a phenanthrene skeleton, N-methyl-8,9-methylenedioxy-phenantridinium methylsulfate (1) and N-methyl-8,9-methylenedioxy-phenantridinium malate (2). The structure determination of the alkaloids was based on one- and two-dimensional NMR studies including HMQC, and HMBC studies, and mass spectroscopic analysis. The existence, in 1, of the methylsulfate group was confirmed by X-ray diffraction analysis. Cytotoxic activities for 1 and 2 against a panel of cancer cell lines are also reported. PMID:11683132

Youssef, D T; Khalifa, A A



The advances of electromigration techniques applied for alkaloid analysis.  


Alkaloids are natural products of metabolism found mainly in plants. Their diversified pharmacological activities as medical agents and extensive occurrence in nutritional products demand the development of reliable and sensitive analytical tools. This review presents the developments in the field of electromigration techniques and specifically capillary and microchip electrophoresis. We include the main aspects of interest to researches over the past 12 years. The scope of this review covers detection, on- and off-line preconcentration techniques, chiral separation and developments in the field of microchip electrophoresis. Their applications in alkaloid determination, capillary electrochromatography and inter-molecular interactions are also examined. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23813479

Dziomba, Szymon; Belka, Mariusz; Kowalski, Piotr; Plenis, Alina; B?czek, Tomasz



Structural Analogs of Tylophora Alkaloids may not be Functional Analogs  

PubMed Central

Phenanthroindolizidine-based tylophora alkaloids have been reported to have potential antitumor, anti-immuno and anti-inflammatory activity. The structure-activity relationships of a series of tylophora alkaloids were studied to guide future drug design. Our results indicate that although these compounds are structural analogs, their potency of cytotoxicity, selectivity against NF-?B signaling pathway, and their inhibitory effects against protein and nucleic acid synthesis are different. Because they do not have an identical spectrum of targets, the studied compounds are structural, but may not be functional analogs.

Gao, Wenli; Chen, Annie Pei-Chun; Leung, Chung-Hang; Gullen, Elizabeth A.; Furstner, Alois; Shi, Qian; Wei, Linyi; Lee, Kuo-Hsiung; Cheng, Yung-Chi



Hindi Numerals.  

ERIC Educational Resources Information Center

In most languages encountered by linguists, the numerals, considered as a paradigmatic set, constitute a morpho-syntactic problem of only moderate complexity. The Indo-Aryan language family of North India, however, presents a curious contrast. The relatively regular numeral system of Sanskrit, as it has developed historically into the modern…

Bright, William


Identification of pavinane alkaloids in the genera Argemone and Eschscholzia by GC-MS.  


The genera Eschscholtzia and Argemone (Papaveraceae) represent a rich source of pavinane alkaloids, the identification of which in alkaloid extracts is generally problematic without standards. The alkaloid extracts of three Argemone and four Eschscholtzia species were analyzed using GC-MS. The alkaloids were identified based on comparison of their mass spectra with commercial libraries, with reported data in the literature and with spectra of reference compounds. A total of 23 alkaloids of six structural types (pavinane, protopine, benzylisoquinoline, benzophenanthridine, aporphine and protoberberine) were identified. The fragmentation pathway of pavinane alkaloids was used for their identification. O-Methylneocaryachine has been reported for the first time from a natural sources and the alkaloid pattern of Eschscholzia pulchella has been analyzed and described for the first time. PMID:23156990

Cahlíková, Lucie; Kucera, Radim; Host'álková, Anna; Klimes, Jirí; Opletal, Lubomír



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


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

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



Synthesis of the pentacyclic skeleton of the indole alkaloid arboflorine.  


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

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



Synthesis of the Pentacyclic Skeleton of the Indole Alkaloid Arboflorine  

PubMed Central

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

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



Amaryllidaceae Isocarbostyril Alkaloids and Their Derivatives as Promising Antitumor Agents  

Microsoft Academic Search

This review covers the isolation, total synthesis, biologic activity, and more particularly the in vitro and in vivo anti- tumor 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

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


Diversity-oriented approach to pyrrole-imidazole alkaloid frameworks.  


An exploration of imidazolylpropargyl amides as linchpin synthons for the construction of a diverse array of heterocyclic frameworks, many of which are related to those found in the oroidin derived alkaloids, is described. One such intermediate has been used in a formal total synthesis of cyclooroidin. PMID:21338082

Bhandari, Manojkumar R; Yousufuddin, Muhammed; Lovely, Carl J



Alkaloid profiling and anticholinesterase activity of South American Lycopodiaceae species.  


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

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



Anticholinesterase activity in an alkaloid extract of Huperzia saururus.  


Huperzia saururus (Lam.) Trevis. (Lycopodiaceae) is used widely in Argentinian traditional medicine as an aphrodisiac and for memory improvement. An aqueous extract from the aerial parts was obtained by decoction, revealing the presence of alkaloids, among other constituents. By partition with organic solvent in alkaline media, alkaloids were extracted and then purified by gel permeation. We studied the anticholinesterase activity in vitro of the alkaloid extract using erythrocyte membranes and human serum as sources of acetylcholinesterase and pseudocholinesterase, respectively. The results show a marked inhibition of true acetylcholinesterase with an IC50 value of 0.58 microg/ml. Low inhibition of pseudocholinesterase was observed (IC50 value = 191 microg/ml). This shows a selectivity of the extract for the true acetylcholinesterase. Furthermore, chemical study of the bioactive extract was performed by GC-MS, revealing the presence of seven Lycopodium alkaloids, including some not identified previously: sauroxine, 6-hydroxylycopodine, N-acetyllycodine, lycopodine, lycodine, N-methyllycodine, and clavolonine. Further investigations will be undertaken in order to discover which compound/s are responsible for the aqueous extract's acetylcholinesterase activity. PMID:15500266

Ortega, M G; Agnese, A M; Cabrera, J L



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...


Three lycopodium alkaloid N-oxides from Huperzia serrata.  


Three lycopodium alkaloid N-oxides, huperzine J (1), huperzine K (2) and huperzine L (3) were obtained from Huperzia serrata (Thunb.) Trev. Their structures were elucidated by spectroscopic methods and the relative configurations of 1 and 3 were established via NOESY NMR observations; optical rotation values and CD data are presented. PMID:11105578

Gao, W; Li, Y; Jiang, S; Zhu, D



3-Alkylpyridinium alkaloids from the Pacific sponge Haliclona sp.  


The analysis of the polar extracts of the Pacific sponge Haliclona sp. yielded new dimeric (1), trimeric (2), and polymeric 3-alkylpyridinium alkaloids. Their isolation and structural elucidation, based on NMR and MS data, are discussed in detail, along with their cytotoxic activity. PMID:19133758

Casapullo, Agostino; Pinto, Oscar Cobar; Marzocco, Stefania; Autore, Giuseppina; Riccio, Raffaele



New alkaloid from Streptomyces koyangensis residing in Odontotermes formosanus.  


A new alkaloid was isolated from the ethyl acetate extract of the culture of a termite-associated Streptomyces koyangensis BY-4. The structure of 1 was elucidated by using MS, NMR, electronic circular dichroism data, and computational approaches. Compound 1 showed weak antimicrobial activities against a panel of test microbes. PMID:23418739

Bi, Shu-Feng; Guo, Zhi-Kai; Jiang, Nan; Jiao, Rui-Hua; Ge, Hui-Ming; Tan, Ren-Xiang



Australine, a pyrrolizidine alkaloid that inhibits amyloglucosidase and glycoprotein processing  

SciTech Connect

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.

Tropea, J.E.; Molyneux, R.J.; Kaushal, G.P.; Pan, Y.T.; Mitchell, M.; Elbein, A.D. (Univ. of Texas Health Science Center, San Antonio (USA))




Technology Transfer Automated Retrieval System (TEKTRAN)

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


Alkaloid and predation patterns in colorado lupine populations  

Microsoft Academic Search

Colorado populations of herbaceous perennial lupines show three distinct patterns of amounts, kinds, and individual variability of inflorescence alkaloids. These patterns, interpreted as alternative chemical defense strategies, can be related to the susceptibility of populations to attack by larvae of a small flower-feeding lycaenid butterfly, Glaucopsyche lygdamus.

Peter M. Dolinger; Paul R. Ehrlich; William L. Fitch; Dennis E. Breedlove



Biosynthesis of the defensive alkaloid cicindeloine in Stenus solutus beetles  

NASA Astrophysics Data System (ADS)

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.

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




Technology Transfer Automated Retrieval System (TEKTRAN)

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


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...


Antiphagocytic and Antioxidant Properties of Plant Alkaloid Tetrandrine  

Microsoft Academic Search

The effects of tetrandrine, a benzylisoquinoline alkaloid useful in the treatment of silicosis, on a broad range of human neutrophil activities was examined in vitro. Random movement, chemotaxis and phagocytosis were significantly suppressed. There was minimal but significant inhibition of lysosomal enzyme secretion from specific (secondary) but not azurophil (primary) granules. The same concentration of tetrandrine (10 ?g\\/ml) caused marked

W. K. Seow; A. Ferrante; Li Si-ying; Y. H. Thong



The effects of Aconitum alkaloids on the central nervous system  

Microsoft Academic Search

Preparations of Aconitum roots are employed in Chinese and Japanese medicine for analgesic, antirheumatic and neurological indications. The recent surge in use of phytomedicine derived from traditional Chinese medicine as well as increasing concerns about possible toxic effects of these compounds have inspired a great deal of research into the mechanisms by which certain Aconitum alkaloids may act on the

Angela Ameri



A new and weakly antispasmodic protoberberine alkaloid from Rhizoma Coptidis.  


A new protoberberine alkaloid, 3-hydroxy-2-methoxy-9,10-methylenedioxy-8-oxo-protoberberine, along with three known compounds, was isolated from Rhizoma Coptidis. The new compound displayed weak antispasmodic activity against acetylcholine-induced contraction in isolated guinea-pig ileum with an IC50 of 83.7 microm. PMID:20564546

Zhao, Ming; Xian, Yan-Fang; Ip, Siu-Po; Fong, Harry Hs; Che, Chun-Tao



Synthetic Studies Related to Illudinine - A Sesquiterpene Alkaloid  

Microsoft Academic Search

Illudinine (1) has special significance because of its biogenetic relations to illudalic acid, a sesqui-terpenoid with protoilludane skeleton. All these compounds possess highly pronounced physiological properties. For entry into the synthesis of the alkaloid (1) incorporating the sesquiterpene skeleton, the successful synthesis of (12) having all the C15-carbon atoms of (1) is described, along with a model study to build

Chittaranjan Misra; Anuradha Ghosh



Selection of Ergot Alkaloid Producers by Induced Mutagenesis  

Microsoft Academic Search

Using the induced mutagenesis technique, a series of genetically modified Clavicepssp. VKM F-2609 strains that display high levels of agroclavine and elymoclavine synthesis were selected by induced mutagenesis. Compared to the parent strain, c106 displayed a 40-fold higher level of agroclavine synthesis, and c66 displayed an eightfold higher level of elymoclavine synthesis. The levels of synthesis of other alkaloids were

I. G. Vepritskaya; L. V. Boichenko; M. U. Arinbasarov; N. F. Zelenkova; N. V. Bobkova



Pyrrolizidine alkaloid toxicity in livestock: A paradigm for human poisoning  

Technology Transfer Automated Retrieval System (TEKTRAN)

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


Alkaloid profiling of crude and processed Veratrum nigrum L. through simultaneous determination of ten steroidal alkaloids by HPLC-ELSD.  


Veratrum nigrum L., a traditional Chinese herb, has been used for treatment of hypertension, blood-stroke, excessive phlegm, epilepsy, etc. Steroidal alkaloids were well-known as both bioactive and toxic constituents of Veratrum species, the toxicity of which the traditional processing procedure can reduce. To reveal the mechanism of processing V. nigrum L., a high performance liquid chromatography (HPLC) with evaporative light scattering detector (ELSD) method was developed for the simultaneous determination of ten steroidal alkaloids in crude and processed V. nigrum L., comparison with ultrasound extract of crude V. nigrum L. With a Venusil XBP-C(18) analytical column, the analytes were separated efficiently using the mobile phase consisted of (A) 0.03% aqueous triethylamine (TEA) and (B) acetonitrile in a gradient program. The parameters for ELSD were set: S.C. (Spray Chamber)=35 degrees C, D.T. (Drift Tube)=70 degrees C, GAS=50 psi. All calibration curves showed good linear regression (gamma>or=0.9990) within the tested range. Additionally, reproducibility for the quantification of ten alkaloids in V. nigrum L. with intra- and inter-day variations of less than 5.0% was observed. The obtained alkaloid profiles performed by this newly established method, provided valuable information for the differentiation of crude and processed V. nigrum L. and for the explanation of the different toxicity. PMID:18599245

Cong, Yue; Zhou, Yu-Bo; Chen, Jing; Zeng, Yi-Mei; Wang, Jin-Hui



Solid-phase extraction and LC-MS analysis of pyrrolizidine alkaloids in honeys.  


Strong-cation-exchange, solid-phase extraction of pyrrolizidine alkaloids and their N-oxides from honey samples was followed by reduction of the N-oxides and subsequent analysis of total pyrrolizidine alkaloids using high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry. A limited survey of 63 preprocessing samples of honey, purposefully biased toward honeys attributed to floral sources known to produce pyrrolizidine alkaloids, demonstrated levels of pyrrolizidine alkaloids up to approximately 2000 parts per billion (ppb) in a sample attributed to Echium plantagineum. Up to 800 ppb pyrrolizidine alkaloids was detected in some honeys not attributed by the collector to any pyrrolizidine alkaloid-producing floral source. No pyrrolizidine alkaloids were detected in approximately 30% of the samples in this limited study, while some honeys showed the copresence of pyrrolizidine alkaloids from multiple floral sources such as E. plantagineum and Heliotropium europaeum. In addition, retail samples of blended honeys (with no labeling to suggest that pyrrolizidine alkaloid-producing floral sources were used in the blends) have been shown to contain up to approximately 250 ppb pyrrolizidine alkaloids. PMID:15479038

Beales, Kerrie A; Betteridge, Keith; Colegate, Steven M; Edgar, John A



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


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. PMID:12918918

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



Differential allocation of seed-borne ergot alkaloids during early ontogeny of morning glories (convolvulaceae).  


Ergot alkaloids are mycotoxins that can increase host plant resistance to above- and below-ground herbivores. Some morning glories (Convolvulaceae) are infected by clavicipitaceous fungi (Periglandula spp.) that produce high concentrations of ergot alkaloids in seeds-up to 1000-fold greater than endophyte-infected grasses. Here, we evaluated the diversity and distribution of alkaloids in seeds and seedlings and variation in alkaloid distribution among species. We treated half the plants with fungicide to differentiate seed-borne alkaloids from alkaloids produced de novo post-germination and sampled seedling tissues at the cotyledon and first-leaf stages. Seed-borne alkaloids in Ipomoea amnicola, I. argillicola, and I. hildebrandtii remained primarily in the cotyledons, whereas I. tricolor allocated lysergic acid amides to the roots while retaining clavines in the cotyledons. In I. hildebrandtii, almost all festuclavine was found in the cotyledons. These observations suggest differential allocation of individual alkaloids. Intraspecific patterns of alkaloid distribution did not vary between fungicide-treated and control seedlings. Each species contained four to six unique ergot alkaloids and two species had the ergopeptine ergobalansine. De novo production of alkaloids did not begin immediately, as total alkaloids in fungicide-treated and control seedlings did not differ through the first-leaf stage, except in I. argillicola. In an extended time-course experiment with I. tricolor, de novo production was detected after the first-leaf stage. Our results demonstrate that allocation of seed-borne ergot alkaloids varies among species and tissues but is not altered by fungicide treatment. This variation may reflect a response to selection for defense against natural enemies. PMID:23835852

Beaulieu, Wesley T; Panaccione, Daniel G; Hazekamp, Corey S; mckee, Michelle C; Ryan, Katy L; Clay, Keith



Numerical Recipes  

NSDL National Science Digital Library

The Numerical Recipes books are developed by Numerical Recipes Software and published by Cambridge University Press. The website provides information on how to purchase the books, which are part of a series entitled "Numerical Recipes: The Art of Scientific Computing." "Numerical Recipes" is also a copyrighted computer software included in those books and sold separately. The books and software are available in a variety of computer languages, such as C++, C, and Fortran, and provide routines and recipes, along with explanations and "tricks and tips for scientific computing." Visitors can download the whole C (or Fortran) book for free, although the publisher hopes that after sampling a few sections people will buy the book. The website also provides news updates on the products as well as access to the Numerical Recipes Forum, where those interested in scientific computing can interact, ask and answer questions, and trade tips and tricks. Registration is free and a prize is offered to encourage people to join and offer valuable comments.


Numeration Systems  

NSDL National Science Digital Library

All About Circuits is a website that âÂÂprovides a series of online textbooks covering electricity and electronics.â Written by Tony R. Kuphaldt, the textbooks available here are wonderful resources for students, teachers, and anyone who is interested in learning more about electronics. This specific section, Numeration Systems, is the first chapter in Volume IV âÂÂDigital. A few of the topics covered in this chapter include: Numbers and symbols; Octal and hexadecimal numeration; and Conversion from decimal numeration. Diagrams and detailed descriptions of concepts are included throughout the chapter to provide users with a comprehensive lesson. Visitors to the site are also encouraged to discuss concepts and topics using the All About Circuits discussion forums (registration with the site is required to post materials).

Kuphaldt, Tony R.



Ma Huang and the Ephedra Alkaloids  

Microsoft Academic Search

Ephedra has been used as a natural medicine for thousands of years by numerous cultures with very little concern about toxicity.\\u000a Its most recent popularity is related to its purported “weight loss” or “performance enhancing” attributes. In spite of that\\u000a in 2004, concerns over safety resulted in the banning of all over-the-counter (OTC) sales of ephedra-containing dietary supplements\\u000a by the

Steven B. Karch


Numerical Integration  

ERIC Educational Resources Information Center

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

Sozio, Gerry



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

PubMed Central

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

Rehacek, Z.; Sajdl, P.; Kozova, J.; Malik, K. A.; Ricicova, A.



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

Microsoft Academic Search

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

Cordula Frölich; Thomas Hartmann; Dietrich Ober



Chrotacumines E and F, Two New Chromone-Alkaloid Analogs from Dysoxylum acutangulum (Meliaceae) Leaves.  


A chemical investigation of the alkaloidal fraction of Dysoxylum acutangulum leaves led to the isolation and characterization of two new chromone alkaloid analogs named chrotacumines E and F (1 and 2, resp.). Structure elucidation of 1 and 2 was achieved by spectroscopic analyses, including 2D-NMR. Both of these alkaloids exhibited modest activities as tyrosinase inhibitors with 29.2 and 25.8% inhibition at 100??g/ml, respectively. PMID:24078592

Izwan Mohd Lazim, Mohd; Safinar Ismail, Intan; Shaari, Khozirah; Abd Latip, Jalifah; Ali Al-Mekhlafi, Nabil; Morita, Hiroshi



Thirty-five years of synthetic studies directed towards the histrionicotoxin family of alkaloids.  


This article brings together for the first time reviews of all the synthetic attempts towards the spirocyclic histrionicotoxin alkaloids published since the discovery of the group in 1971. This covers 5 total syntheses of the fully unsaturated parent alkaloid HTX-283A, 7 total syntheses of perhydrohistrionicotoxin, 15 total syntheses of other members of this alkaloid family, 25 formal syntheses, and 19 partial syntheses involving the successful formation of the core azaspirocyclic structure but lacking advancement towards the target structure. PMID:17389999

Sinclair, Alex; Stockman, Robert A



Effect of quaternary benzo[ c]phenanthridine alkaloids sanguilutine and chelilutine on normal and cancer cells  

Microsoft Academic Search

Sanguilutine and chelilutine, quaternary benzo[c]phenanthridine alkaloids, were studied for their antiproliferative activities with regard to their ability to induce oxidative stress.We observed potent antiproliferative activities for both alkaloids against three tumour (HeLa; HL-60; A-2780) and two normal (V-79; LEP) cell lines. Both alkaloids were efficient inductors of apoptosis. Statistical analysis revealed higher toxicity for sanguilutine compared to chelilutine and unequal

Z. Slunská; E. Gelnarová; J. Hammerová; E. Táborská; I. Slaninová



The effects of methyllycaconitine on the response of TE-671 cells to acetylcholine and epibatidine  

Technology Transfer Automated Retrieval System (TEKTRAN)

Methyllycaconitine (MLA) is a norditerpenoid alkaloid found in Delphinium spp., and is a potent and selective antagonist of a7-nicotinic acetylcholine receptors. Plants with high concentrations of MLA are responsible for many livestock poisonings in the Intermountain West of the United States of Am...


Suppression of ochratoxin biosynthesis by naturally occurring alkaloids.  


The effects of four alkaloids on the biosynthesis of ochratoxin A (OTA), ochratoxin B (OTB) and citrinin were examined on four OTA-producing aspergilli: Aspergillus auricomus, A. sclerotiorum and two isolates of A. alliaceus. Piperine and piperlongumine, natural alkaloids of Piper longum, significantly inhibited OTA production at 0.001% (w/v) for all aspergilli examined. Piperine and piperlongumine affected the polyketide synthesis step of OTA production and inhibited production of citrinin. Curcumin, a constituent of tumeric, completely inhibited mycelial growth of A. alliaceus isolate 791 at 0.1% (w/v) and decreased OTA production by approximately 70% at 0.01% (w/v). Sesamin, a constituent of sesame oil, inhibited OTA and OTB production by 60 and 45%, respectively, at 0.1% (w/v), showing its effect was on chloroperoxidase and polyketide synthase activity. The potential advantage of these natural products to reduce ochratoxin contamination of agricultural commodities is discussed. PMID:17454112

Lee, S E; Park, B S; Bayman, P; Baker, J L; Choi, W S; Campbell, B C



Indoloquinazoline alkaloids from Euodia rutaecarpa and their cytotoxic activities.  


Nine indoloquinazoline alkaloids (1-9) were isolated from the dried and nearly ripe fruits of Euodia rutaecarpa (Juss.) Benth. (Euodiae Fructus), along with limonin and ?-sitosterol. Their structures were elucidated on the basis of their spectroscopic data. Among them, compounds 1 and 2 were new compounds and characterized as (7R,8S)-7-hydroxy-8-methoxy-rutaecarpine and (7R,8S)-7-hydroxy-8-ethoxy-rutaecarpine, respectively, and 1-hydroxy-rutaecarpine (3) and (7R,8S)-7,8-dihydroxy-rutaecarpine (4) were isolated from Euodiae Fructus for the first time. The nine indoloquinazoline alkaloids were evaluated for their cytotoxic activities against human promyelocytic leukemia HL-60 cells and human gastric carcinoma N-87 cells. PMID:21985129

Huang, Xin; Zhang, You-Bo; Yang, Xiu-Wei



Extractions of isoquinoline alkaloids with butanol and octanol.  


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. PMID:20117181

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



Piperidine and tetrahydropyridine alkaloids from Lobelia siphilitica and Hippobroma longiflora.  


The hyphenated technique HPLC-PDA-MS-SPE-NMR was used to assist targeted preparative-scale isolation of constituents of Lobelia siphilitica and Hippobroma longiflora (both Campanulaceae). This resulted in the isolation of two new alkaloids, (S)-2-[(2S,6R)-1-methyl-6-(2-oxo-2-phenylethyl)piperidin-2-yl]-1-phenylethyl acetate (3) and 6-[(E)-2-(3-methoxyphenyl)ethenyl]-2,3,4,5-tetrahydropyridine (4), the latter possessing a skeleton hitherto unseen among alkaloids of Lobelia and related genera. Lobeline (1), (1S,1'S)-2,2'-[(2R,6S)-1-methylpiperidine-2,6-diyl]bis(1-phenylethanol) (2), and lobetyolin (5) were also isolated. The structures of 1-5 were established using spectroscopic methods including homo- and heteronuclear two-dimensional NMR experiments and optical rotation data. PMID:19206509

Kesting, Julie R; Tolderlund, Inge-Lise; Pedersen, Anders F; Witt, Matthias; Jaroszewski, Jerzy W; Staerk, Dan



Interrupted Fischer indolization approach toward the communesin alkaloids and perophoramidine.  


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

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



A torquoselective 6? electrocyclization approach to reserpine alkaloids.  


A highly torquoselective thermal triene 6? electrocyclization controls the relative stereochemistry between the C3 and C18 stereocenters of the dodecahydroindolo[2,3-a]benzo[g]quinolizine skeleton of reserpine-type alkaloids. Employing a tandem cross-coupling/electrocyclization protocol allowed us to form the requisite triene and ensure its subsequent cyclization. A novel low-temperature dibromoketene acetal Claisen rearrangement established the requisite exocyclic dienylbromide precursor for the palladium-catalyzed cross-coupling reaction. PMID:23039026

Barcan, Gregg A; Patel, Ashay; Houk, K N; Kwon, Ohyun



Three new hydroxylated serratidine alkaloids from Huperzia serrata.  


A known compound, serratidine (1), along with three hydroxylated serratidine alkaloids, 6alpha-hydroxyserrati dine (2), 4alpha-hydroxyserratidine (3) and 4alpha,6alpha-dihydroxyserratidine (4) were isolated from the CHCl3 fraction of basic materials of whole plant of the Chinese medicinal herb Huperzia serrata. The relative configurations of the above compounds were determined based on 2D NMR studies. PMID:12049213

Tan, Chang-Heng; Ma, Xiao-Qiang; Jiang, Shan-Hao; Zhu, Da-Yuan



Two new types of bisindole alkaloid from Trigonostemon lutescens.  


Six unprecedented bisindole alkaloids, trigolutesins A and B (1-2) with a unique polycyclic skeleton and trigolutes A-D (3-6) with another polycyclic skeleton, were isolated from the twigs of Trigonostemon lutescens. Their structures and relative configurations were elucidated by spectroscopic data and single-crystal X-ray diffraction crystallography. Trigolutesin A (1) showed weak AChE inhibitory activity. PMID:23480691

Ma, Shan-Shan; Mei, Wen-Li; Guo, Zhi-Kai; Liu, Shou-Bai; Zhao, You-Xing; Yang, De-Lan; Zeng, Yan-Bo; Jiang, Bei; Dai, Hao-Fu



Update on analytical methods for toxic pyrrolizidine alkaloids  

Microsoft Academic Search

Methods for the determination of toxic pyrrolizidine alkaloids in plants and foods are described with emphasis on the important\\u000a aspects of sample extraction and clean-up and the now preferred determination by liquid chromatography–mass spectrometry.\\u000a The efficiencies of different extraction solvents and methods are described, as are the methods of reduction of N-oxides. Appropriate liquid chromatography–mass spectrometry conditions are tabulated. This

Colin Crews; Franz Berthiller; Rudi Krska



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

Microsoft Academic Search

Livestock poisoning, primarily liver damage, caused by consumption of plants containing 1,2-dehydropyrrolizidine ester alkaloids (dehydroPAs), and the corresponding N-oxides, is a relatively common occurrence worldwide. Because of the economic impact, extensive investigations of such episodes have been performed, particularly in Australia, South Africa the United States and, more recently, South America. Plant species most commonly involved are members of the

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



Putrescine N-methyltransferase – The start for alkaloids  

Microsoft Academic Search

Putrescine N-methyltransferase (PMT) catalyses S-adenosylmethionine (SAM) dependent methylation of the diamine putrescine. The product N-methylputrescine is the first specific metabolite on the route to nicotine, tropane, and nortropane alkaloids. PMT cDNA sequences were cloned from tobacco species and other Solanaceae, also from nortropane-forming Convolvulaceae and enzyme proteins were synthesised in Escherichia coli. PMT activity was measured by HPLC separation of

Stefan Biastoff; Wolfgang Brandt; Birgit Dräger



2-substituted quinoline alkaloids as potential antileishmanial drugs.  

PubMed Central

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

Fournet, A; Barrios, A A; Munoz, V; Hocquemiller, R; Cave, A; Bruneton, J



Sequestration of Camptothecin, an Anticancer Alkaloid, by Chrysomelid Beetles  

Microsoft Academic Search

Camptothecin (CPT), a monoterpene indole alkaloid, is a potent inhibitor of eukaryotic toposiomerase-I. Several derivatives\\u000a of CPT are in clinical use against ovarian and lung cancers. CPT has been reported from several plant species belonging to\\u000a the order Asterids, with the highest concentration in Nothapodytes nimmoniana (family Icacinaceae). In this paper, we report an intriguing observation of chrysomelid beetles (Kanarella

B. T. Ramesha; S. Zuehlke; R. C. Vijaya; V. Priti; G. Ravikanth; K. N. Ganeshaiah; M. Spiteller; R. Uma Shaanker



Psychollatine, a glucosidic monoterpene indole alkaloid from Psychotria umbellata.  


A monoterpene indole alkaloid, psychollatine ( 1), was isolated from Psychotria umbellata leaves. Its structure was characterized by interpretation of spectroscopic data and by comparison of its NMR data with those of croceaine A ( 2) from Palicourea crocea. The configuration of psychollatine ( 1) was established by NOE difference and circular dichroism (CD) techniques, while its conformation was evaluated through molecular modeling studies and NMR coupling constants. PMID:18288808

Kerber, V A; Passos, C S; Verli, H; Fett-Neto, A G; Quirion, J P; Henriques, A T



The iridoid pathway in Catharanthus roseus alkaloid biosynthesis  

Microsoft Academic Search

The Apocynaceae Catharanthus roseus accumulates a number of monoterpene indole alkaloids (MIAs) that originate from the coupling of the indole and the iridoid\\u000a pathways. The latter pathway is usually considered as limiting for MIA biosynthesis, but evidence is now strong that the precursors\\u000a tryptamine (from the indole pathway) and secologanin (from the iridoid pathway) have to be provided within the

Audrey Oudin; Martine Courtois; Marc Rideau; Marc Clastre



Amaryllidaceae Isocarbostyril Alkaloids and Their Derivatives as Promising Antitumor Agents  

PubMed Central

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.

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



Allelopathy due to purine alkaloids in tea seeds during germination  

Microsoft Academic Search

Summary  During imbibition of whole tea seeds (6 days) two purine alkaloids, caffeine and theobromine, did not decrease in the seed\\u000a coats and there was no increase in the seeds. In parallel with and after the breaking of seed coats there was a gradual release\\u000a of caffeine from coats of germinating seeds. By contrast, when the seed was freed from the

T. Suzuki; G. R. Waller



Pyrrolizidine alkaloids in honey: comparison of analytical methods  

Microsoft Academic Search

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).

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



Chemical defense: Bestowal of a nuptial alkaloidal garment by a male moth on its mate  

PubMed Central

Males of the moth Cosmosoma myrodora (Arctiidae) acquire pyrrolizidine alkaloid by feeding on the excrescent fluids of certain plants (for instance, Eupatorium capillifolium). They incorporate the alkaloid systemically and as a result are protected against spiders. The males have a pair of abdominal pouches, densely packed with fine cuticular filaments, which in alkaloid-fed males are alkaloid laden. The males discharge the filaments on the female in bursts during courtship, embellishing her with alkaloid as a result. The topical investiture protects the female against spiders. Alkaloid-free filaments, from alkaloid-deprived males, convey no such protection. The males also transmit alkaloid to the female by seminal infusion. The systemic alkaloid thus received, which itself may contribute to the female's defense against spiders, is bestowed in part by the female on the eggs. Although paternal contribution to egg defense had previously been demonstrated for several arctiid moths, protective nuptial festooning of a female by its mate, such as is practiced by C. myrodora, appears to be without parallel among insects.

Conner, William E.; Boada, Ruth; Schroeder, Frank C.; Gonzalez, Andres; Meinwald, Jerrold; Eisner, Thomas



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

NASA Astrophysics Data System (ADS)

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.

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



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

PubMed Central

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, however 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 versus artificial substrates and has the potential to suggest deterrent alkaloids as possible candidates for agricultural use.

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



Ancistrolikokine D, a 5,8'-coupled naphthylisoquinoline alkaloid, and related natural products from Ancistrocladus likoko.  


A new naphthylisoquinoline alkaloid, ancistrolikokine D, and the likewise 5,8'-coupled alkaloid ancistroealaine A, as well as two further, biosynthetically related, but nitrogen-free natural products, ancistronaphthoic acid B and cis-isoshinanolone, have been isolated from Ancistrocladus likoko J. LEACUTE;ONARD (Ancistrocladaceae). The 5,8'-coupling of the new alkaloids and of the alkaloids isolated earlier hints at a close phylogenetic relationship of A. likoko to other Central African Ancistrocladus species. The compounds show moderate activities against Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei rhodesiense. PMID:12560038

Bringmann, Gerhard; Saeb, Wael; Rückert, Markus; Mies, Jan; Michel, Manuela; Mudogo, Virima; Brun, Reto



Distribution of opiate alkaloids in brain tissue of experimental animals  

PubMed Central

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.

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



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


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

Leal, M B; Elisabetsky, E



Isoquinoline alkaloids from Tinospora cordifolia inhibit rat lens aldose reductase.  


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

Patel, Mayurkumar B; Mishra, Shrihari



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

PubMed Central

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.

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



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

PubMed Central

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

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



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


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

Kubwabo, C; Rollmann, B; Tilquin, B



Qualitative and Quantitative Determination of Pyrrolizidine Alkaloids of Wheat and Flour Contaminated with Senecio in Mazandaran Province Farms  

Microsoft Academic Search

The Pyrrolizidine Alkaloids (PAs) are a group of chemicals found in a variety of plant species throughout the world. These toxic alkaloids are distributed mainly in Senecio (Compositae), Crotalaria (Legominosae) and Heliotropium (Boraginaceae) species. Plants containing these alkaloids cause significant mammalian morbidity and mortality, especially in humans. Upon ingestion, metabolic activation in liver converts the potent compounds into highly reactive

Mohammad Azadbakht; Mana Talavaki


Warifteine and milonine, alkaloids isolated from Cissampelos sympodialis Eichl: cytotoxicity on rat hepatocyte culture and in V79 cells  

Microsoft Academic Search

Two alkaloids were isolated from the leaves of Cissampelos sympodialis; a bisbenzylisoquinoline compound named warifteine and a novel 8,14-dihydromorphinandienone alkaloid named milonine. The cytotoxic effects of these alkaloids were assayed in cultured hepatocytes and V79 fibroblasts. Three independent endpoint assays for cytotoxicity in vitro were used: the nucleic acid content (NAC), tetrazolium reduction (MTT) and neutral red uptake (NRU). Milonine

Patricia Silva Melo; Horacinna Maria de Medeiros Cavalcante; José Maria Barbosa-Filho; Margareth de Fátima Formiga Melo Diniz; Isac Almeida de Medeiros; Marcela Haun



The effect of nitrate and ammonium concentrations on growth and alkaloid accumulation of Atropa belladonna hairy roots  

Microsoft Academic Search

The growth, the alkaloid production, as well as the scopolamine\\/hyoscyamine ratio of two clones of belladonna hairy roots were studied. The effects of nitrate and ammonium concentrations on these cultures were investigated. A rise in ammonium concentration caused the decline of the hairy roots, while nitrate had a marked effect on the alkaloid content. The alkaloid production obtained with 15.8

Lamine Bensaddek; Françoise Gillet; José Edmundo Nava Saucedo; Marc-André Fliniaux



Naucleamides A-E, new monoterpene indole alkaloids from Nauclea latifolia.  


Five new monoterpene indole alkaloids, naucleamides A-E (1-5), were isolated from the bark and wood of Nauclea latifolia, and the structures and relative stereochemistry were elucidated from the spectroscopic data. Naucleamide E (5) is a unique monoterpene indole alkaloid possessing a pentacyclic ring system with an amino acetal bridge. PMID:12520129

Shigemori, Hideyuki; Kagata, Toshinori; Ishiyama, Haruaki; Morah, Frank; Ohsaki, Ayumi; Kobayashi, Jun'ichi



Synthesis of alkaloidal compounds using an electrochemical reaction as a key step  

Microsoft Academic Search

This review describes application of electroorganic reactions to synthesis of some key skeletons which are commonly found in natural alkaloids and some key intermediates which are useful materials for formation of the alkaloidal structures. The methods of synthesis are classified into three categories, namely, (1) Oxidative coupling, (2) Oxidative activation of the position to the nitrogen atom of amines and

Tatsuya Shono


Isolation, structure, and synthesis of novel 4-quinolinone alkaloids from Esenbeckia leiocarpa.  


Two new biocidal quinolinone alkaloids, 3-methoxy-1-methyl-2-propyl-4-quinolone [1] and 2(1'-ethylpropyl)-1-methyl-4-quinolone [2], were efficiently isolated using reversed-phase recycling hplc from the leaves of Esenbeckia leiocarpa. The structures were determined through spectroscopic data and confirmed by total synthesis. These alkaloids have antifeedant activities against the pink bollworm, Pectinophora gossypiella. PMID:1965201

Nakatsu, T; Johns, T; Kubo, I; Milton, K; Sakai, M; Chatani, K; Saito, K; Yamagiwa, Y; Kamikawa, T


Repeated Evolution of the Pyrrolizidine Alkaloid-Mediated Defense System in Separate Angiosperm Lineages  

Microsoft Academic Search

Species of several unrelated families within the angiosperms are able to constitutively produce pyrrolizidine alkaloids as a defense against herbivores. In pyrrolizidine alkaloid (PA) biosynthesis, homospermidine synthase (HSS) catalyzes the first specific step. HSS was recruited during angiosperm evolution from deoxyhypusine synthase (DHS), an enzyme involved in the posttranslational activation of eukaryotic initiation factor 5A. Phylogenetic analysis of 23 cDNA

Andreas Reimann; Niknik Nurhayati; Anita Backenkohler; Dietrich Ober



Pyrrolizidine alkaloid biosynthesis, evolution of a pathway in plant secondary metabolism  

Microsoft Academic Search

The system of pyrrolizidine alkaloids has proven to be a powerful system for studying the evolution of a biosynthetic pathway in plant secondary metabolism. Pyrrolizidine alkaloids are typical plant secondary products produced by the plant as a defense against herbivores. The first specific enzyme, homospermidine synthase, has been shown to have evolved by duplication of the gene encoding deoxyhypusine synthase,

Dietrich Ober; Elisabeth Kaltenegger



O-Demethylation as a Biosynthetic Pattern in the Formation of Opium Alkaloids  

Microsoft Academic Search

COMPARATIVE rates of incorporation of carbon dioxide labelled with carbon-14 led to the proposal1 that, in Papaver somniferum, thebaine is the first octahydrophenanthrene alkaloid formed, and is converted by successive O-demethylations to codeine and finally to morphine. Although this sequence seemed best to explain the labelling ratio among these three alkaloids, conclusive proof was lacking. The results described here, considered

Frank R. Stermitz; Henry Rapoport



Stereocontrolled preparation of bicyclic alkaloid analogues: an approach towards the kinabalurine skeleton  

Microsoft Academic Search

An approach towards the construction of bicyclic analogues of monoterpene alkaloids belonging to the kinabalurine, incarvilline and skytanthine families of natural products is reported. These syntheses rely on a stereoselective intramolecular Pauson–Khand cyclisation of a chiral pool-derived enyne in order to prepare the bicyclic core. Stereoselective further elaboration generates diastereomeric analogues of the naturally occurring alkaloids.

Yvonne Kavanagh; Matthew O'Brien; Paul Evans



Does decreased mowing frequency enhance alkaloid production in endophytic tall fescue and perennial ryegrass?  


Tall fescue, Festuca arundinacea, and perennial ryegrass, Lolium perenne. are widely infected with fungal endophytes (Neotyphodium spp.). The symbiosis between plant and fungus leads to synthesis of alkaloids that have been shown to be either toxic or act as feeding deterrents against insect pests. As cultural practices have the potential to regulate production of plant secondary metabolites, we evaluated the influence of mowing frequency on the levels of major alkaloids in tall fescue and perennial ryegrass in the greenhouse. Tall fescue and perennial ryegrass maintained in 15-cm-diam. pots were cut to 5-cm height weekly or biweekly. Samples were taken monthly and the alkaloids extracted and analyzed by reverse-phase LC-MS. In tall fescue, ergovaline, ergonovine, and ergocristine were identified, whereas only ergocristine was identified in perennial ryegrass samples. In tall fescue, we observed a trend showing higher levels in samples cut biweekly than in those cut weekly. A similar pattern was seen in some putative alkaloids that were not identified. In perennial ryegrass, ergocristine and two putative alkaloids followed a pattern similar to that of alkaloids in tall fescue. A survey of a few samples of perennial ryegrass using extractions specific to peramine and lolitrem B yielded evidence suggesting their presence as well as several other identified alkaloids. These data support the hypothesis that decreased mowing frequency enhances alkaloid production/accumulation in tall fescue and perennial ryegrass. PMID:12049232

Salminen, Seppo O; Grewal, Parwinder S



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


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. PMID:3713232

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



Toxicokinetics of Riddelliine, a Carcinogenic Pyrrolizidine Alkaloid, and Metabolites in Rats and Mice  

Microsoft Academic Search

Riddelliine is a representative pyrrolizidine alkaloid, a class of naturally occurring toxic phytochemicals present in plant species worldwide. Human exposure to pyrrolizidine alkaloids occurs through consumption of herbal dietary supplements, including comfrey, and through contaminated livestock products (e.g., milk). A recently completed 2-year bioassay of riddelliine carcinogenicity showed that male and female rats and male mice, but not female mice,

Lee Williams; Ming W. Chou; Jian Yan; John F. Young; Po C. Chan; Daniel R. Doerge



Separation of ergot alkaloids and their epimers and determination in sclerotia by capillary electrophoresis  

Microsoft Academic Search

Capillary electrophoresis has been shown to be a very useful analysis technique for secondary metabolites of plants. In the present study a method is described for the qualitative and quantitative determination of ergot alkaloids and their epimers. The extraction from the biological matrix yields recoveries of 50–97%, depending on the individual alkaloid. Using a mixture of 20 mM ?-cyclodextrin (CD),

K Frach; G Blaschke



Alkaloid biosynthesis in somatic hybrids of Duboisia leichhardtii F. Muell. and Nicotiana tabacum L  

Microsoft Academic Search

Somatic hybrids of Duboisia leichhardtii and Nicotiana tabacum were obtained by electrofusion followed by individual cloning. The hybrid nature of the cloned cells and regenerated shoots was confirmed by cytological investigation and ribosomal-DNA analysis, respectively. The hybrid plantlets predominantly produced nicotine, while Duboisia plantlets produced both tropane and nicotine alkaloids. Activities involved in tropane-alkaloid biosynthesis were examined in a series

Tsuyoshi Endo; Nobuko Hamaguchi; Tage Eriksson; Yasuyuki Yamada



Optimisation of conditions for extracting pesticidal alkaloids from Cynanchum komarovii (Maxim.)  

Microsoft Academic Search

The methodology of a new OA9 (3) matrix and an analysis of variance technique were developed during the optimisation of extracting pesticidal alkaloids from Cynanchum komarovii. Many factors were found to affect the amount of alkaloids extracted: which parts of the plant were used – roots gave the highest yield; particle size of the material – highest yield when the

Zhen Congai; Guo Yanyan; Zhang Xuechang; Miao Jing; Shi Wangpeng



Simple indole alkaloids and those with a non-rearranged monoterpenoid unit.  


Covering: 2010-2011. Previous review: Nat. Prod. Rep. 2010, 27, 1630-1680This review covers the literature on simple indole alkaloids and those with a non-rearranged monoterpenoid unit from the beginning of 2010 up to the end of 2011, which includes newly isolated alkaloids, structure determinations, total syntheses and biological activities. PMID:23467716

Ishikura, Minoru; Abe, Takumi; Choshi, Tominari; Hibino, Satoshi



Analysis of Amaryllidaceae alkaloids from Narcissus by GC–MS and capillary electrophoresis  

Microsoft Academic Search

Amaryllidaceae are known as ornamental plants, furthermore some species of this family contain galanthamine, an acetylcholinesterase inhibitor approved for the treatment of Alzheimer's disease, and other alkaloids with interesting pharmacological activity. In the present work, the quali- and quantitative analysis of Amaryllidaceae-type alkaloids in the bulbs of Narcissus species is presented using different analytical approaches. Extracts of Narcissus pseudonarcissus cv.

R. Gotti; J. Fiori; M. Bartolini; V. Cavrini



A vinc A AlkAloid effect on microtubulues of helA cells  

Microsoft Academic Search

A b s t r a c t The study evaluated the effect of selected vinca alkaloids on the microtubule net- work of heLa cells and the recovery of its disruption. Model experiments were used for demonstration of the quantification of microtubule network changes induced by vinca alkaloids using computer-assisted image analysis. Cells were treated with vincristine or vinblastine at


Three new monomeric indole alkaloids from the roots of Catharanthus roseus.  


Two new alkaloid glycosides (1 and 2) and a new monomeric indole alkaloid (3), together with 13 known ones (4-16), were isolated from the roots of Catharanthus roseus. The structures of new compounds were elucidated on the basis of the spectroscopic methods. The absolute configuration of compound 3 was established by the modified Mosher's method. PMID:22332772

Wang, Chun-Hua; Wang, Guo-Cai; Wang, Ying; Zhang, Xiao-Qi; Huang, Xiao-Jun; Ye, Wen-Cai



Transgenic periwinkle tissues overproducing cytokinins do not accumulate enhanced levels of indole alkaloids  

Microsoft Academic Search

Cytokinins play a critical role in several aspects of plant growth, metabolism and development. We previously reported that adding cytokinins to the culture medium of a suspension-cultured cell line of periwinkle increased the accumulation of indole alkaloids, and our aim was to compare the effect of exogenously-applied cytokinins with that of elevated levels of endogenous cytokinins on indole alkaloid production.

Frédérique Garnier; Philippe Label; Didier Hallard; Jean-Claude Chrnieux I; Marc Rideau I; Saïd Hamdi



Molecular Architecture of Strictosidine Glucosidase: The Gateway to the Biosynthesis of the Monoterpenoid Indole Alkaloid Family  

Microsoft Academic Search

Strictosidine b-D-glucosidase (SG) follows strictosidine synthase (STR1) in the production of the reactive intermediate required for the formation of the large family of monoterpenoid indole alkaloids in plants. This family is composed of ;2000 structurally diverse compounds. SG plays an important role in the plant cell by activating the glucoside strictosidine and allowing it to enter the multiple indole alkaloid

Leif Barleben; Santosh Panjikar; Martin Ruppert; Juergen Koepke; J. Stockigt



Taxines: a review of the mechanism and toxicity of yew ( Taxus spp.) alkaloids  

Microsoft Academic Search

This literature review summarizes relevant information and recent progress regarding the scientific investigations of taxine alkaloids. Taxines are the active, poisonous constituents in yew plants (Taxus spp.) and have been implicated in animal and human poisonings. Several taxine alkaloids have been isolated and characterized through the use of high performance liquid chromatography, mass spectroscopy, and nuclear magnetic resonance. Recently, as

Christina R. Wilson; John-Michael Sauer; Stephen B. Hooser



Effect of feeding fescue seed containing ergot alkaloid toxins on stallion spermatogenesis and sperm cells.  


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

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



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

PubMed Central

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

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



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

PubMed Central

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

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



Antimicrobial and cytotoxic activity of the alkaloids of Amlaki (Emblica officinalis).  


Alkaloids are important sources of drug that's why we have conducted our research to find out the biological activity of the alkaloids of a plant that is the Amlaki. Alkaloids were extracted from the methanolic extract of the fresh ripe fruits of Amlaki (Emblica officinalis) through solvent-solvent partitioning method with n-hexane and chloroform. The chloroform soluble fraction of the crude methanolic extract of the ripe fruits of Amlaki containing alkaloids was subjected to antimicrobial activity and brine shrimp lethality bioassay for observing cytotoxic activity. The chloroform soluble fraction of the methanolic extract exhibited significant antimicrobial activity against some Gram positive and Gram negative pathogenic bacteria and strong cytotoxicity having a LC50 of 10.257 +/- 0.770 microg mL(-1). It is concluded that the chloroform soluble fraction of the ripe fruits of Amlaki containing alkaloids are biologically active. PMID:19899327

Rahman, S; Akbor, M M; Howlader, A; Jabbar, A



Wild daffodils of the section Ganymedes from the Iberian Peninsula as a source of mesembrane alkaloids.  


The aim of this work was to perform a detailed study of the alkaloid content of Narcissus triandrus, as well as a complete analysis of the alkaloid profile of 18 wild populations, comprising all the taxa of the section Ganymedes. Through the application of a combination of spectroscopic and chromatographic methods, the isolation and structural elucidation of 3 compounds are reported for the first time from a natural source (2-oxomesembrenone, 7,7a-dehydromesembrenone and 2-oxoepimesembranol), together with the identification of 5 major common mesembrane alkaloids. Additionally, the GC-MS analysis of the alkaloid profile demonstrated the regular presence of mesembranes in all the studied plants, showing mesembrenone as the predominant compound without any typical Amaryllidaceae alkaloid being detected. PMID:23932506

Pigni, Natalia B; Ríos-Ruiz, Segundo; Luque, F Javier; Viladomat, Francesc; Codina, Carles; Bastida, Jaume



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


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. PMID:18476877

Facchini, Peter J; De Luca, Vincenzo



Ampullosine, a new isoquinoline alkaloid from Sepedonium ampullosporum (Ascomycetes).  


A new isoquinoline alkaloid, ampullosine (3-methyl-isoquinoline-6-carboxylic acid, 1), was isolated from Sepedonium ampullosporum and characterized by spectroscopic analysis and chemical reactions. This compound is responsible for the deep yellow color of the culture fluid of this species. Moreover, the known compounds sepedonin (2) and anhydrosepedonin (3) were detected. Twelve strains belonging to eight species of Sepedonium have been screened for these three metabolites by LC/ESI-SRM (selected reaction monitoring). Ampullosine (1) could be detected in almost all species in Sepedonium, but not in the phylogenetically more distant species S. brunneum and S. tulasneanum. Anhydrosepedonin (3) showed antifungal activity against the phytopathogenic fungus Cladosporium cucumerinum. PMID:20614812

Quang, Dang Ngoc; Schmidt, Jürgen; Porzel, Andrea; Wessjohann, Ludger; Haid, Mark; Arnold, Norbert



Progress in the studies on tryptanthrin, an alkaloid of history.  


Tryptanthrin, an indoloquinazoline alkaloid, was first obtained by sublimation of natural indigo and later isolated from the culture of fungus Candida lipolytica and a variety of other natural sources. Tryptanthrin showed a variety of intriguing biological properties such as antibacterial, antifungal, antiprotozoal, and antiparasitic activities, inhibitory activities against COX-2, 5-LOX, NO synthase and PGE(2) expression, as well as cytotoxic and antitumor activities. Present review covers recent studies on the natural sources, biological activities and mechanisms of their actions, synthesis, structure-activity relationship, and metabolism of tryptanthrin. PMID:23543631

Jahng, Yurngdong



NMR study of quinolizidine alkaloids: relative configurations, conformations.  


Extracts of fruits and leaves of Connarus paniculatus afford six quinolizidine alkaloids which were identified as piptanthine, 18-epipiptanthine, ormosanine, homoormosanine, podopetaline (monohydrochloride) and homopodopetaline on the basis of high-field NMR studies. 1D and 2D NMR experiments provide complete assignments of the (1)H and (13)C spectra. In conjunction with detection of nuclear Overhauser effects (NOESY), these results allow detailed structure characterization including determination of relative configurations for the chiral sites and conformational analysis. Exchange phenomena involving nitrogen inversion were detected. PMID:15706612

Le, Phuong Mai; Martin, Marie-Thérèse; Van Hung, Nguyen; Guénard, Daniel; Sévenet, Thierry; Platzer, Nicole



Cyclopeptide alkaloids from Scutia buxifolia Reiss and their antimicrobial activity.  


The present study reports a cyclopeptide alkaloid, scutianine M, isolated from the methanolic root bark extract of Scutia buxifolia Reiss (Rhamnaceae) along with six known compounds, scutianines-B, -C, -D, -E, -F, and scutianene D. Its structure was established on the basis of spectroscopic analyses, including application of 2D NMR spectroscopic techniques. As part of a study of the bioactive compounds of medicinal plants from southern Brazil, we also compared the antimicrobial activity of the isolated compounds towards Gram (+), Gram (-) bacteria, and yeasts. PMID:16226284

Morel, Ademir F; Maldaner, Graciela; Ilha, Vinicius; Missau, Fabiana; Silva, Ubiratan F; Dalcol, Ionara I



Synthesis of unnatural alkaloid scaffolds by exploiting plant polyketide synthase.  


HsPKS1 from Huperzia serrata is a type III polyketide synthase (PKS) with remarkable substrate tolerance and catalytic potential. Here we present the synthesis of unnatural unique polyketide-alkaloid hybrid molecules by exploiting the enzyme reaction using precursor-directed and structure-based approaches. HsPKS1 produced novel pyridoisoindole (or benzopyridoisoindole) with the 6.5.6-fused (or ring system by the condensation of 2-carbamoylbenzoyl-CoA (or 3-carbamoyl-2-naphthoyl-CoA), a synthetic nitrogen-containing nonphysiological starter substrate, with two molecules of malonyl-CoA. The structure-based S348G mutant not only extended the product chain length but also altered the cyclization mechanism to produce a biologically active, ring-expanded 6.7.6-fused dibenzoazepine, by the condensation of 2-carbamoylbenzoyl-CoA with three malonyl-CoAs. Thus, the basic nitrogen atom and the structure-based mutagenesis enabled additional C?C and C?N bond formation to generate the novel polyketide-alkaloid scaffold. PMID:21825160

Morita, Hiroyuki; Yamashita, Makoto; Shi, She-Po; Wakimoto, Toshiyuki; Kondo, Shin; Kato, Ryohei; Sugio, Shigetoshi; Kohno, Toshiyuki; Abe, Ikuro



Synthesis of unnatural alkaloid scaffolds by exploiting plant polyketide synthase  

PubMed Central

HsPKS1 from Huperzia serrata is a type III polyketide synthase (PKS) with remarkable substrate tolerance and catalytic potential. Here we present the synthesis of unnatural unique polyketide–alkaloid hybrid molecules by exploiting the enzyme reaction using precursor-directed and structure-based approaches. HsPKS1 produced novel pyridoisoindole (or benzopyridoisoindole) with the 6.5.6-fused (or ring system by the condensation of 2-carbamoylbenzoyl-CoA (or 3-carbamoyl-2-naphthoyl-CoA), a synthetic nitrogen-containing nonphysiological starter substrate, with two molecules of malonyl-CoA. The structure-based S348G mutant not only extended the product chain length but also altered the cyclization mechanism to produce a biologically active, ring-expanded 6.7.6-fused dibenzoazepine, by the condensation of 2-carbamoylbenzoyl-CoA with three malonyl-CoAs. Thus, the basic nitrogen atom and the structure-based mutagenesis enabled additional C?C and C?N bond formation to generate the novel polyketide-alkaloid scaffold.

Morita, Hiroyuki; Yamashita, Makoto; Shi, She-Po; Wakimoto, Toshiyuki; Kondo, Shin; Kato, Ryohei; Sugio, Shigetoshi; Kohno, Toshiyuki; Abe, Ikuro



Phenanthroindolizidines and Phenanthroquinolizidines: Promising Alkaloids for Anti-Cancer Therapy  

PubMed Central

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

Chemler, Sherry R.



Antiplasmodial alkaloids from the bark of Cryptocarya nigra (Lauraceae).  


A dichloromethane extract of the stem bark of Cryptocarya nigra showed strong in vitro inhibition of Plasmodium falciparum growth, with an IC50 value of 2.82 ?g/mL. The phytochemical study of this extract has led to the isolation and characterization of four known alkaloids: (+)-N-methylisococlaurine (1), atherosperminine (2), 2-hydroxyathersperminine (3), and noratherosperminine (4). Structural elucidation of all alkaloids was accomplished by means of high field 1D- and 2D-NMR, IR, UV and LCMS spectral data. The isolated extract constituents (+)-N-methylisococlaurine (1), atherosperminine (2) and 2-hydroxy-atherosperminine (3) showed strong antiplasmodial activity, with IC50 values of 5.40, 5.80 and 0.75 ?M, respectively. In addition, (+)-N-methylisocolaurine (1) and atherosperminine (2) showed high antioxidant activity in a DPPH assay with IC50 values of 29.56 ug/mL and 54.53 ug/mL respectively. Compounds 1 and 2 also both showed high antioxidant activity in the FRAP assay, with percentages of 78.54 and 70.66 respectively and in the metal chelating assay, with IC50 values of 50.08 ug/mL and 42.87 ug/mL, respectively. PMID:23884132

Nasrullah, Ayu Afiqah; Zahari, Azeana; Mohamad, Jamaludin; Awang, Khalijah



The effects of comfrey derived pyrrolizidine alkaloids on rat liver.  


Three groups of young adult rats were fed pyrrolizidine alkaloids derived from Russian comfrey to study the effects of the herb on the liver. Group I animals received a single dose of 200 mg/kg body wt, Group II 100 mg/kg three times a week for 3 weeks and Group III 50 mg/kg three times a week for 3 weeks. All rats showed light and electron-microscopic evidence of liver damage, the severity of which was dose dependent. There was swelling of hepatocytes and hemorrhagic necrosis of perivenular cells. There was a concomitant loss of sinusoidal lining cells with disruption of sinusoidal wall and the sinusoids were filled with cellular debris, hepatocyte organelles and red blood cells. Extravasation of red blood cells was evident. Terminal hepatic venules were narrowed by intimal proliferation, and in Group II and III, reiculin fibres radiated from these vessels. These appearances have been described in veno-occlusive disease due to pyrrolizidine alkaloids from other plant sources such as Senecio and Crotalaria. The safety of comfrey, a widely used herb, in relation to human consumption requires further investigation. PMID:2062566

Yeong, M L; Clark, S P; Waring, J M; Wilson, R D; Wakefield, S J



Aristolochic acids, aristolactam alkaloids and amides from Aristolochia kankauensis.  


Fourteen aristolochic acid derivatives: ariskanins A-E, 3-hydroxy-4-methoxy-10-nitrophenanthrene-1-carboxylic acid methyl ester, aristolochic acid-II methyl ester, aristolochic acid-IV methyl ester, aristolochic acid-C, -I, -II, -III, -IV, -IVa; nine aristolactam alkaloids: aristolactam, aristolactam-AII, -BIII, -AIII, -III, cepharanone-A, 9-methoxy-aristolactam-I, aristolactam-N-beta-D-glucoside and aristolactam-C-N-beta-D-glucoside; a 4,5-dioxoaporphine alkaloid: cepharadione-A, together with 12 other compounds: methyl-p-coumarate, N-trans-feruloyltyramine, N-cis-feruloyltyramine, methyl vanillate, methyl paraben, allantoin, an octadecyl- and eicosyl ferulate mixture, cis- and trans-p-coumaric acid, N-p-coumaroyltyramine, N-p-cis-coumaroyltyramine, methyl ferulate and isorhamnetin-3-O-rutinoside were isolated and characterized from the fresh root and stem of Aristolochia kankauensis. Their structures were elucidated by spectral and chemical methods. Among them, ariskanins-A-E and N-p-cis-coumaroyltyramine are reported for the first time from a natural source. The cytotoxicity and antiplatelet activity of the compounds isolated are also discussed. PMID:7765207

Wu, T S; Ou, L F; Teng, C M



Antimicrobial, antiparasitic and cytotoxic spermine alkaloids from Albizia schimperiana.  


Albizia schimperiana Oliv. (Leguminosae) is a tree distributed in the highland of Kenya, where it is used as a traditional medicine for the treatment of bacterial and parasitic infections, notably pneumonia and malaria, respectively. Bioassay guided isolation of the CH2Cl2-MeOH 1:1/ MeOH-H20 9:1 (mixed) extract of A. schimperiana afforded the new bioactive macrocyclic spermine alkaloid, namely 5,14-dimethylbudmunchiamine L1 (1) and three known budmunchiamine analogs 2-4. The structures of the compounds 1-4 were determined by 1D and 2D NMR data, including COSY, HMQC, and HMBC experiments, and ESI-HRMS. Compounds 1 and 3 exhibited significant in vitro antimicrobial activity against a panel of microorganisms, including C neoformans, methicillin-resistant S. aureus, E. coli, M. intracellulare, and A. fumigatus. In Saddition, they demonstrated strong in vitro antimalarial activities against chloroquine-susceptible (D6) and -resistant (W2) strains of Plasmodium falciparum with IC50s ranging from 120-270 ng/mL. Compounds 1-4 were also evaluated for cytotoxic activity against selected human cancer cell lines and mammalian kidney fibroblasts (VERO cells). It was observed that hydroxyl substitution of the side chain of the budmunchiamines dramatically reduced the cytotoxicity and antimicrobial activity of the alkaloids 2 and 4 without decreasing antimalarial activity. PMID:19634324

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



Efficient enantiomeric synthesis of pyrrolidine and piperidine alkaloids from tobacco.  


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

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



Basic helix-loop-helix transcription factors and regulation of alkaloid biosynthesis.  


Transcription factors of the basic Helix-Loop-Helix (bHLH) family play a central role in cell proliferation, determination, and differentiation. In plants, the regulatory functions of bHLHs in phenylpropanoid biosynthesis have been well established with regard to other interacting-proteins; i.e., MYB and WD40 repeat proteins. On the other hand, those in alkaloid biosynthesis are greatly limited due to the limited distribution of alkaloids in plant species. Recently, several groups have reported the regulatory functions of bHLH in alkaloid biosynthesis: novel CjbHLH1 in isoquinoline alkaloid biosynthesis in Coptis japonica, and Jasmonate-inducible MYC2-type bHLHs in nicotine-alkaloid biosynthesis in Nicotiana plants and indole alkaloid biosynthesis in Catharanthus roseus. We report here the JA-inducibility of CjbHLH1 and discuss the similarity and differences of non-MYC2-resemblant CjbHLH1 and MYC2-type bHLHs in nicotine and indole alkaloid biosynthesis. PMID:22067108

Yamada, Yasuyuki; Koyama, Tomotsugu; Sato, Fumihiko



Basic helix-loop-helix transcription factors and regulation of alkaloid biosynthesis  

PubMed Central

Transcription factors of the basic Helix-Loop-Helix (bHLH) family play a central role in cell proliferation, determination, and differentiation. In plants, the regulatory functions of bHLHs in phenylpropanoid biosynthesis have been well established with regard to other interacting-proteins; i.e., MYB and WD40 repeat proteins. On the other hand, those in alkaloid biosynthesis are greatly limited due to the limited distribution of alkaloids in plant species. Recently, several groups have reported the regulatory functions of bHLH in alkaloid biosynthesis: novel CjbHLH1 in isoquinoline alkaloid biosynthesis in Coptis japonica, and Jasmonate-inducible MYC2-type bHLHs in nicotine-alkaloid biosynthesis in Nicotiana plants and indole alkaloid biosynthesis in Catharanthus roseus. We report here the JA-inducibility of CjbHLH1 and discuss the similarity and differences of non-MYC2-resemblant CjbHLH1 and MYC2-type bHLHs in nicotine and indole alkaloid biosynthesis.

Yamada, Yasuyuki; Koyama, Tomotsugu; Sato, Fumihiko



Pteridine-, thymidine-, choline- and imidazole-derived alkaloids from the Australian ascidian, Leptoclinides durus.  


Four new acylated pteridine alkaloids, duramidines A-D, two new acylated thymidine alkaloids, leptoclinidines A and B, two new 1-acylglyceryl-3-(O-carboxyhydroxymethylcholine) alkaloids, durabetaines A and B, three new 1,3-dimethyl-5-methylsulfanylimidazole alkaloids, leptoclinidamines D-F, and the known alkaloids leptoclinidamines B and C and 6-bromo-1H-indolo-3-yl-oxoacetic acid methyl ester were isolated from the Australian ascidian Leptoclinides durus. The duramidines are the first pteridine alkaloids, possessing a three carbon side chain esterified at C-1' with a 4-hydroxy-2'-methoxycinnamic acid, and are either hydroxylated or sulfated at C-2'. The leptoclinidines are the first 3'-indole-3-carboxylic acid ester derivatives of thymidine to be reported in the literature. The durabetaines are the first glyceryl-3-(O-carboxyhydroxymethylcholine) alkaloids to be reported from an animal source and are also the only known derivatives from this class to be acylated with aromatic carboxylic acids. MS and NMR data analysis established the structures of the new compounds. All compounds were shown to be inactive when tested for cytotoxic activity against prostate (LNCaP) and breast (MDA-MB-231) cancer cell lines and antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus. PMID:23160826

Rudolph, Kathryn E; Liberio, Michelle S; Davis, Rohan A; Carroll, Anthony R



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


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

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



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

PubMed Central

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

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



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

SciTech Connect

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.

Settivari, Raja S. [Division of Animal Science, University of Missouri, Columbia, MO 65211 (United States); Evans, Tim J. [Veterinary Diagnostic Laboratory, University of Missouri, Columbia, MO 65211 (United States); Rucker, Ed [Department of Veterinary Physiology and Pharmacology, Texas A and M University, College Station, TX77843 (United States); Rottinghaus, George E. [Veterinary Diagnostic Laboratory, University of Missouri, Columbia, MO 65211 (United States); Spiers, Donald E. [Division of Animal Science, University of Missouri, Columbia, MO 65211 (United States)], E-mail:



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


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. PMID:23847067

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



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


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 (IC?? = 2.5 mM), similar to that of the reference compound galanthamine (IC?? = 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. PMID:21160449

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



Canthin-6-one and beta-carboline alkaloids from Eurycoma harmandiana.  


Two alkaloids, canthin-6-one 9-O-beta-glucopyranoside and 7-hydroxy-beta-carboline 1-propionic acid, were isolated from the roots of Eurcoma harmandiana together with the five known canthin-6-one alkaloids, 9-hydroxycanthin-6-one, 9-methoxycanthin-6-one, 9,10-dimethoxycanthin-6-one, canthin-6-one and canthin-6-one N-oxide, and the two known beta-carboline alkaloids, beta-carboline 1-propionic acid and 7-methoxy-beta-carboline 1-propionic acid. Their structures were based on analyses of spectroscopic data. PMID:11249106

Kanchanapoom, T; Kasai, R; Chumsri, P; Hiraga, Y; Yamasaki, K



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

PubMed Central

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.

Pan, Guojun; Williams, Robert M.



Antimycobacterial activity of bisbenzylisoquinoline alkaloids from Tiliacora triandra against multidrug-resistant isolates of Mycobacterium tuberculosis.  


Bisbenzylisoquinoline alkaloids, tiliacorinine (1), 2'-nortiliacorinine (2), and tiliacorine (3), isolated from the edible plant, Tiliacora triandra, as well as a synthetic derivative, 13'-bromo-tiliacorinine (4), were tested against 59 clinical isolates of multidrug-resistant Mycobacterium tuberculosis (MDR-MTB). The alkaloids 1-4 showed MIC values ranging from 0.7 to 6.2 ?g/ml, but they exhibited the MIC value at 3.1 ?g/ml against most MDR-MTB isolates. The present work suggests that bisbenzylisoquinoline alkaloids are potential new chemical scaffolds for antimycobacterial activity. PMID:22418278

Sureram, Sanya; Senadeera, Sarath P D; Hongmanee, Poonpilas; Mahidol, Chulabhorn; Ruchirawat, Somsak; Kittakoop, Prasat



Additional Cytotoxic Pyridoacridine Alkaloids from the Ascidian Cystodytes violatinctus and Biogenetic Considerations.  


The extraction and purification of the bioactive extract of Cystodytes violatinctus (Solomon Islands) led to the isolation and identification of six pyridoacridine alkaloids. The structures of four new members of this family, shermilamine F (1), dehydrokuanoniamine F (2), and arnoamines C (3) and D (4), were elucidated on the basis of NMR and MS data and by comparison with data of known compounds isolated from this genus. A general hypothetical biogenetic pathway is then proposed for pyridoacridine alkaloids that contain a fused pyrrole ring. Comparison of the biological properties of the isolated alkaloids is also discussed. PMID:23961991

Bontemps, Nataly; Gattacceca, Florence; Long, Christophe; Thomas, Olivier P; Banaigs, Bernard



Study of alkaloids from Adhatoda vasica Nees on their antiinflammatory activity.  


Adhatoda vasica Nees is a shrub widespread throughout the tropical regions of southeast Asia. It possesses a wide spectrum of medicinal properties including positive effects on inflammatory diseases. The antiinflammatory activity of the methanol extract, the non-alkaloid fraction, the saponins and the alkaloids was evaluated by the modified hen's egg chorioallantoic membrane test. The alkaloid fraction showed potent activity at a dose of 50 microg/pellet equivalent to that of hydrocortisone while the MeOH extract and the other fractions showed less activity. PMID:11536385

Chakraborty, A; Brantner, A H



5'-O-demethyldioncophylline A, a new antimalarial alkaloid from triphyophyllum peltatum.  


From the root bark of Triphyophyllum peltatum, the new naphthylisoquinoline alkaloid 5'-O-demethyldioncophylline A has been isolated. Its otherwise difficult separation from the largely dominating main alkaloid, dioncophylline A, was greatly facilitated by a bromination-benzylation procedure. From the resulting derivative, a crystal structure analysis with an anomalous X-ray diffraction was achieved, allowing confirmation of the full absolute stereostructure of the new alkaloid. The structure was further corroborated by a partial synthesis from dioncopeltine A. The natural product was shown to exhibit antimalarial activity against erythrocytic forms of Plasmodium falciparum. PMID:11711079

Bringmann, Gerhard; Saeb, Wael; God, Ralf; Schäffer, Manuela; François, Guido; Peters, Karl; Peters, Eva Maria; Proksch, Peter; Kurt Hostettmann; Assi, Laurent Aké



Antimalarial activity screening of some alkaloids and the plant extracts from Amaryllidaceae.  


Four groups of Amaryllidaceae alkaloids, namely lycorine-, crinine-, tazettine-, and galanthamine-type, as well as plant extracts of the Amaryllidaceae plants (Pancratium maritimum, Leucojum aestivum, and Narcissus tazetta ssp. tazetta) growing in Turkey were evaluated in vitro for their ability to inhibit Plasmodium falciparum growth by a high-throughput screening method with a 96-well microtiter plate. All four groups of alkaloids exhibited antimalarial activity at different potencies. 6-Hydroxyhaemanthamine, haemanthamine and lycorine were found to be the most potent alkaloids against P. falciparum (T9.96) and galanthamine and tazettine had the least potent activity against P. falciparum (K1). PMID:14669261

Sener, Bilge; Orhan, Ilkay; Satayavivad, Jutamad



Monoterpenoid indole alkaloids bearing an N4-Iridoid from Gelsemium elegans.  


Five new alkaloids, gelseganines A-D (1-4) and humantenine N(4)-oxide (5), were isolated from the stems and leaves of Gelsemium elegans. Compounds 1-4 represent a rare class of monoterpenoid indole alkaloids that bear an N(4)-iridoid unit. The structures of 1-5 were determined by spectroscopic analysis, single-crystal X-ray diffraction, and chemical correlation, and their absolute configurations were elucidated by CD analysis. A plausible biogenetic pathway for alkaloids 1-5 was also postulated. PMID:18604820

Yin, Sheng; He, Xiu-Feng; Wu, Yan; Yue, Jian-Min



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


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). PMID:23678802

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



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


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

Bubenyák, Máté



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


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

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



Design, synthesis and antifungal activities of novel pyrrole alkaloid analogs.  


A series of novel analogs of pyrrole alkaloid were designed and synthesized by a facile method and their structures were characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry (HRMS). The structure of compound 2a was identified by 2D NMR including heteronuclear multiple-quantum coherence (HMQC), heteronuclear multiple-bond correlation (HMBC) and H-H correlation spectrometry (H-H COSY) spectra. Their antifungal activities against five fungi were evaluated, and the results indicated that some of the title compounds showed moderate fungicidal activities in vitro against Alternaria solani, Cercospora arachidicola, Fusarium omysporum, Gibberella zeae and Physalospora piricola at the dosage of 50 ?g mL(-1). Compound 2a and 3a exhibited good activities against P. piricola at low dosage. PMID:21356570

Wang, Ming-Zhong; Xu, Han; Liu, Tuan-Wei; Feng, Qi; Yu, Shu-Jing; Wang, Su-Hua; Li, Zheng-Ming



Vitiquinolone - A quinolone alkaloid from Hibiscus vitifolius Linn.  


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. ?-Amyrin acetate (1), n-octacosanol (2), ?-Amyrin (3), stigmasterol (4), xanthyletin (6), alloxanthoxyletin (7), xanthoxyletin (8) and betulinic acid (9) were isolated from chloroform extract by column chromatography over silica gel. The structure of vitiquinolone was established on the basis of spectroscopic methods including UV, IR, 1D, 2D NMR and ESI-MS. The known compounds were identified on the basis of their physical and spectroscopic data as reported in the literature. PMID:24128571

Ramasamy, D; Saraswathy, A



Epimediphine, a novel alkaloid from Epimedium koreanum inhibits acetylcholinesterase.  


A novel aporphine alkaloid was isolated from the leaves of Epimedium koreanum Nakai during activity-guided fractionation in search of compounds with an anticholinesterase activity. The structure of the new compound was assigned as 1,10-methoxy-7-hydroxy-aporphine (1), which we have named epimediphine. Unambiguous (1)H-NMR and (13)C-NMR data for epimediphine are described. Epimediphine inhibited an acetylcholinesterase (AchE) activity in a dose-dependent manner with an IC50 value of 3.1 µM. Meanwhile, tacrine, dehydroevodiamine and physostigmine, which are therapeutic drugs or candidates for AD, exhibited an anti-AchE activity with IC50 values of 0.4, 37.9 and 0.12 µM, respectively. PMID:22823459

Zhang, Xiaodan; Oh, Mihyue; Kim, Seulgi; Kim, Jimin; Kim, Hyeyeon; Kim, Sungun; Houghton, Peter J; Whang, Wankyunn



Inhibition of mouse liver respiration by Chelidonium majus isoquinoline alkaloids.  


The alkaloids from Chelidonium majus L. which had a significant inhibitory effect in mitochondrial respiration were those which contain a positive charge due to a quaternary nitrogen atom, i.e., chelerythrine, sanguinarine, berberine and coptisine, both with malate+glutamate or with succinate as substrates. When malate+glutamate was used as substrate, chelerythrine and berberine, which contain methoxy groups, were particularly more active, since they had a strong effect even at low concentrations. In submitochondrial particles, berberine and coptisine had a marked inhibitory effect on NADH dehydrogenase activity but practically no effect on succinate dehydrogenase activity, whereas chelerythrine and sanguinarine inhibited more strongly succinate dehydrogenase than NADH dehydrogenase, which is in agreement with the results found for mitochondrial respiration. Protopine and allocryptopine, which did not inhibit mitochondrial respiration, strongly inhibited NADH dehydrogenase in submitochondrial particles, but had no effect on succinate dehydrogenase activity. PMID:14615066

Barreto, M Carmo; Pinto, Ruy E; Arrabaça, João D; Pavão, M Leonor



Geraniol 10-hydroxylase, a cytochrome P450 enzyme involved in terpenoid indole alkaloid biosynthesis.  


Geraniol 10-hydroxylase (G10H) is a cytochrome P450 monooxygenase involved in the biosynthesis of iridoid monoterpenoids and several classes of monoterpenoid alkaloids found in a diverse range of plant species. Catharanthus roseus (Madagascar periwinkle) contains monoterpenoid indole alkaloids, several of which are pharmaceutically important. Vinblastine and vincristine, for example, find widespread use as anti-cancer drugs. G10H is thought to play a key regulatory role in terpenoid indole alkaloid biosynthesis. We purified G10H from C. roseus cells. Using degenerate PCR primers based on amino acid sequence information we cloned the corresponding cDNA. The encoded CYP76B6 protein has G10H activity when expressed in C. roseus and yeast cells. The stress hormone methyljasmonate strongly induced G10h gene expression coordinately with other terpenoid indole alkaloid biosynthesis genes in a C. roseus cell culture. PMID:11718718

Collu, G; Unver, N; Peltenburg-Looman, A M; van der Heijden, R; Verpoorte, R; Memelink, J



Huperzine R, a novel 15-carbon Lycopodium alkaloid from Huperzia serrata.  


Huperzine R (2), a novel 15-carbon Lycopodium alkaloid, was isolated from the whole plant of Huperzia serrata, and the relative configuration was established using spectroscopic and X-ray crystallographic techniques. PMID:12141864

Tan, Chang-Heng; Chen, Guo-Fu; Ma, Xiao-Qiang; Jiang, Shan-Hao; Zhu, Da-Yuan



Effect of certain elicitors on production of pyrrolizidine alkaloids in hairy root cultures of Echium rauwolfii.  


Hairy root cultures of Echium rauwolfii were obtained by infection of sterile apical shoots with Agrobacterium rhizogenes. The linear increase in fresh weight was found to be parallel to the alkaloids production. The transformed cultures were exposed to different elicitors, such as methyl jasmonate (MJ), quercetin and salicylic acid in order to increase their productivity. Pyrrolizidine alkaloids were quantitatively determined by HPLC. Estimation of total alkaloids was achieved by peak area calculations. MJ at a concentration of 100 microM induced the accumulation of total alkaloids about 19-fold compared to the untreated control. The flavonoid quercetin (Q) at a concentration of 50 microM enhanced the pyrrolizidine accumulation approximately 6-fold. The induction effect of both MJ and Q can be suppressed by pre-incubation of hairy root cultures with salicylic acid. PMID:20383945

Abd El-Mawla, A M A



Brønsted acid assisted activation of imide carbonyl group: regioselective synthesis of isoindoloisoquinolinone alkaloid (±)-nuevamine.  


Activation of imide carbonyl group with trifluoromethanesulfonic acid facilitates the intramolecular cyclization of phenethylphthalimides to give a fused isoindoloisoquinolinone skeleton. The first one pot regioselective synthesis of isoindoloisoquinolinone alkaloid (±)-nuevamine has been successfully executed using this methodology. PMID:21938306

Selvakumar, Jayaraman; Ramanathan, Chinnasamy Ramaraj



Copper-catalyzed arylation of o-bromoanilides: highly flexible synthesis of hexahydropyrroloindole alkaloids.  


In the presence of catalytic amount of copper iodide, a remote amide-assisted intramolecular arylation followed by alkylation leads to a general and flexible synthetic method toward the synthesis of medicinally interesting hexahydropyrroloindole alkaloids. PMID:22667443

Zhou, Yongyun; Xi, Yongkai; Zhao, Jingfeng; Sheng, Xianfu; Zhang, Shuqin; Zhang, Hongbin



Berbanine: a new isoquinoline-isoquinolone alkaloid from Berberis vulgaris (Berberidaceae).  


A new isoquinoline-isoquinolone alkaloid was isolated from the root bark of Berberis vulgaris and named berbanine. The structure was established by spectroscopic methods (including 2D NMR, HR-EI-MS). PMID:23738447

Host'álková, Anna; Novák, Zdenek; Pour, Milan; Jirosová, Anna; Opletal, Lubomír; Kunes, Jirí; Cahliková, Lucie



A simple and efficient enantioselective synthesis of piperidine alkaloids dihydropinidine and isosolenopsins A, B and C  

Microsoft Academic Search

A diastereospecific intramolecular Mannich-type reaction, involving enantiopure amine 4 and achiral aldehydes, is employed as the key step of an efficient total enantioselective synthesis of five piperidine alkaloids.

Stéphane Ciblat; Pascale Besse; Vassiliki Papastergiou; Henri Veschambre; Jean-Louis Canet; Yves Troin



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...


Isolation of biologically active alkaloids from Korean mistletoe Viscum album, coloratum.  


Anticancer activity of certain highly cytotoxic alkaloids present in Korean mistletoe has been demonstrated in experimental animals. Unlike European mistletoe, no cytotoxic proteins were found in the Korean mistletoe. PMID:7379970

Khwaja, T A; Varven, J C; Pentecost, S; Pande, H



The Structure of Ipalbine, a New Hexahydroindolizine Alkaloid, Isolated from Ipomoea Alba L..  

National Technical Information Service (NTIS)

Recent phytochemical studies have shown that the seeds of several members of the Convolvulaceae family, in particular certain Rivea, Ipomoea, and Argyreia species contain significant amounts of ergoline alkaloids. The isolation and structural determinatio...

J. M. Gourley R. A. Heacock A. G. McInnes B. Nikolin D. G. Smith



Dietary Supplements: Uncertainties in Analyses Underlying FDA's Proposed Rule on Ephedrine Alkaloids.  

National Technical Information Service (NTIS)

The dietary supplement industry estimates that as many as 2 billion doses of dietary supplements containing botanical ephedrine alkaloids are consumed each year in the United States. In June 1997, the Food and Drug Administration (FDA) published a propose...



Interactions of antiparasitic alkaloids with Leishmania protein targets: a molecular docking analysis.  


Background: Leishmaniasis is a collection of chronic diseases caused by protozoa of the genus Leishmania. Current antileishmanial chemotherapeutics have demonstrated adverse side effects and therefore R&D into new safer alternative treatments are needed. Methods: A molecular docking analysis has been carried out to assess possible Leishmania biochemical targets of antiparasitic alkaloids. A total of 209 antiparasitic alkaloids were docked with 24 Leishmania protein targets. Results: The strongest docking alkaloid ligands were flinderoles A and B and juliflorine with Leishmania major methionyl-tRNA synthetase; juliflorine, juliprosine, prosopilosidine and prosopilosine with Leishmania mexicana glycerol-3-phosphate dehydrogenase; and ancistrogriffithine A with L. major N-myristoyl transferase. Conclusion: This molecular docking study has provided evidence for what classes and structural types of alkaloids may be targeting specific Leishmania protein targets. PMID:24144413

Ogungbe, Ifedayo Victor; Ng, Joseph D; Setzer, William N



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


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

Huang, Hsi-Ya; Hsieh, Shih-Huan



Degradation of quinolizidine alkaloids of lupin by Rhizopus oligosporus.  


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

Ortega-David, Eduar; Rodríguez-Stouvenel, Aida



Phase I pharmacologic study of a new Vinca alkaloid: navelbine.  


Navelbine (NVB) is a new semi-synthetic Vinca alkaloid selected on the basis of its affinity for tubulin. NVB inhibits the polymerisation of tubulin and it has significant antitumor activity on P388 and L1210 leukemias and some other experimental tumors. In the present study, 20 patients (9 carcinomas, 10 lymphomas and 1 blastic crisis of chronic myeloid leukemia) received a median of 4 weekly i.v. doses of NVB. Two patients at least received each dose level: 3.6 mg/m2 (1/10 of the LD10 dose/kg in BDF1 mice), 7.2, 12, 18, 32.4, 35 and 43 mg/m2 per week. A total of 89 doses were administered. All patients had been first heavily pretreated and 17 of them had received a Vinca alkaloid. Leukopenia (neutropenia) was the dose-limiting toxicity. There was no thrombocytopenia. Leukopenia was dose-related and first seen at 32.4 mg/m2 per week. The maximal tolerated dose appears to be about 43 mg/m2. At that dose, 2 out of 3 patients developed severe leukopenia and neutropenia. One localized allergic reaction, one case of transient hepatic dysfunction, and 2 reversible peripheral neuropathies were seen. Pharmacokinetics, studied with a radioimmunoassay (RIA) method, suggested an elimination half-life of 30 h and a plasma clearance of 75 l/h. Four patients with Hodgkin's disease and two patients with non-Hodgkin's lymphoma, all of them refractory to vincristine (VCR) and/or vinblastine (VBL), showed minor responses lasting 2-8 weeks. They had received between 4 and 12 doses of 30 and 43 mg/m2. We recommend for phase 11 trials the dose of 40 mg/m2 per week. PMID:4016723

Mathé, G; Reizenstein, P



Anticancer evaluation of structurally diverse Amaryllidaceae alkaloids and their synthetic derivatives  

Microsoft Academic Search

Plants of the Amaryllidaceae family have been under intense scrutiny for the presence of the specific metabolites responsible\\u000a for the medicinal properties associated with them. The study began in 1877 with the isolation of alkaloid lycorine from Narcissus pseudonarcissus and since then more than 100 alkaloids, exhibiting diverse biological activities, have been isolated from the Amaryllidaceae\\u000a plants. Based on the

Antonio Evidente; Alexander Kornienko



Chemical Composition and Pharmacological Activity of Alkaloids from the Common Periwinkle Cultured in Georgia  

Microsoft Academic Search

periwinkle to the field of the Experimental Center of Medicinal Plants (Shiraki, East Kakhetia) was successful, leading to an increase in the alkaloid content. The total alkaloid yield reached up to 1 and 0.8%, in which the vincamine content amounted to 0.06 and 0.04%, in the blooming and fruitage stages, respectively. The purpose of this study was to refine the

V. Yu. Vachnadze; É. Z. Dzhakeli; Z. V. Robakidze; G. V. Chkhikvadze; M. M. Mudzhiri; G. V. Abuladze; N. A. Chuchulashvili



Production of steroidal alkaloids by hairy roots of Solanum aviculare and the effect of gibberellic acid  

Microsoft Academic Search

Cultures of Solanum aviculare hairy roots were established after transformation with Agrobacterium rhizogenes A4. High levels of steroidal alkaloids measured as solasodine equivalents were produced in shake-flasks and bioreactor, even though relatively low concentrations are found in roots in vivo. In shake flasks the maximum alkaloid yield was 32 mg g-1 dry weight; in a 3-1 air-driven bioreactor the yield

M. Ahkam Subroto; Pauline M. Doran



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


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

Kawai, K; Nozawa, Y; Ogihara, Y



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


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

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



Biochemical studies on peptide alkaloids: Induction of ion selective mitochondrial swelling  

Microsoft Academic Search

Summary The effect of frangulanine, a cyclopeptide alkaloid isolated fromHovenia dulcis Thunb., on mitochondrial swelling was studied. Frangulanine induced mitochondrial swelling in 0.15 M KCl solution at the concentration of 6.5 ?M. The alkaloid showed ion selectivity on the induction of mitochondrial swelling. Upon addition of frangulanine, mitochondria underwent swelling in 0.15 M KCl or RbCl solution but in neither

K. Kawai; Y. Nozawa; Y. Ogihara



A new alkaloid and a new diterpene from Cleome paradoxa B.Br. (Cleomaceae).  


A new alkaloid, paradoxonine, and its enol tautomer, paradoxenoline, in addition to a new cembranoid diterpene, paradoxenoic acid, were isolated from the chloroformic fraction of the methanolic extract of Cleome paradoxa B.Br. The structures of the isolated compounds were established based on their spectral data, including MS, (1)HNMR, (13)CNMR, COSY, HMBC and HMQC. This is the first report on the isolation of alkaloids from the family Cleomaceae. PMID:21827334

Abdel-Monem, Azza R



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

NASA Astrophysics Data System (ADS)

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

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



Exploratory studies towards a total synthesis of the unusual bridged tetracyclic Lycopodium alkaloid lycopladine H  

PubMed Central

A strategy for a total synthesis of the structurally novel Lycopodium alkaloid lycopladine H has been investigated. Key steps that have been tested include: 1.a regioselective Diels-Alder cycloaddition of nitroethylene with an o-quinone ketal to produce the bicyclo[2.2.2]octane moiety of the alkaloid; 2. a stereoselective Henry reaction to generate the requisite functionality and configuration at C-5; 3. a stereoselective catalytic hydrogenation of a trisubstituted alkene to set the C-15 methyl configuration.

Sacher, Joshua R.; Weinreb, Steven M.



Fire Ant Venom Alkaloid, Isosolenopsin A, a Potent and Selective Inhibitor of Neuronal Nitric Oxide Synthase  

Microsoft Academic Search

Massive, multiple fire ant, Solenopsis invicta, stings are often treated aggressively, particularly in the elderly, despite limited evidence of systemic toxicity due to the venom. Over 95% of the S. invicta venom is composed of piperidine alkaloid components, whose toxicity, if any, is unknown. To assess a possible pharmacological basis for systemic toxicity, an alkaloid-rich, protein-free methanol extract of the

G. B. Yi; D. Mc Clendon; D. Desaiah; J. Goddard; A. Lister; J. Moffitt; R. K. Vander Meer; R. de Shazo; K. S. Lee; R. W. Rockhold



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


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

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



Alkaloids in plants and root cultures of Atropa belladonna overexpressing putrescine N-methyltransferase  

Microsoft Academic Search

Putrescine N-methyltransferase (PMT) is the first alkaloid-specific enzyme for nicotine and tropane alkaloid formation. The pmt gene from Nicotiana tabacum was fused to the CaMV 35S promoter and integrated into the Atropa belladonna genome. Transgenic plants and derived root cultures were analysed for gene expression and for levels of alkal- oids and their precursors. Scopolamine, hyoscya- mine, tropine, pseudotropine, tropinone,

Grit Rothe; Akira Hachiya; Yasuyuki Yamada; Takashi Hashimoto; Birgit Drager



Biophysical aspects and biological implications of the interaction of benzophenanthridine alkaloids with DNA  

Microsoft Academic Search

Benzophenanthridine alkaloids represent a very interesting and significant group of natural products that exhibit a broad\\u000a range of biological and pharmacological properties. Among this group of alkaloids, sanguinarine, nitidine, fagaronine, and\\u000a chelerythrine have the potential to form molecular complexes with DNA structures and have attracted recent attention for their\\u000a possible clinical and pharmacological utility. This review focuses on the interaction

Motilal Maiti; Gopinatha Suresh Kumar



Synthesis of Amphibian Alkaloids and Synthesis and Affinity of Novel Cannabinoid Receptor Ligands  

Microsoft Academic Search

Amphibian alkaloids are attractive targets for synthesis due to their biological activity. An important class of amphibian alkaloids is the 2,5-disubstituted pyrrolidine-based family of compounds. There are many synthetic approaches for the preparation of the trans-2,5- disubstituted pyrrolidines, but methods for the construction of the cis-2,5-pyrrolidines are limited. Therefore, it was desired to develop an enantioselective approach for the preparation

April R. Noble



Alkaloid Composition of Chelidonium majus L. Studied by Different Chromatographic Techniques  

Microsoft Academic Search

The greater celandine (Chelidonium majus L.) is a well known source of isoquinoline alkaloids with therapeutic value. The aim of our work was to develop a simple\\u000a and fast method to determine the alkaloid composition in Chelidonium plant organs. TLC-densitometry seemed to be the most convenient analytical technique for routine, fast investigations and\\u000a its precision was controlled by using HPLC.

Á. Sárközi; G. Janicsák; L. Kursinszki; Á. Kéry



Absolute configuration of myrobotinol, new fused-hexacyclic alkaloid skeleton from Myrioneuron nutans.  


Myrobotinol (1) was isolated from the leaves of Myrioneuron nutans (Rubiaceae) and its structure determined from spectral data, including mass spectrometry and 2D NMR. This compound presents a new hexacyclic alkaloid skeleton including a 1,3-oxazine and aminal functionality. The absolute configuration of myrobotinol was established by using Mosher's method. A plausible biosynthetic pathway starting from L-lysine via Delta-piperideine was proposed for this hexacyclic alkaloid. PMID:17999527

Pham, Van Cuong; Jossang, Akino; Sévenet, Thierry; Nguyen, Van Hung; Bodo, Bernard



A novel quinoline alkaloid possessing a 7-benzyl group from the centipede, Scolopendra subspinipes.  


The novel quinoline alkaloid scolopendrine was isolated from the centipede, Scolopendra subspinipes mutilans L. Koch. The structure was determined to be 2-hydroxy-7-[(4-hydroxy-3-methoxyphenyl)methyl]-3-methoxy-8-quinolyl sulfate on the basis of high-resolution electron-spray ionization mass spectroscopy and two-dimensional NMR spectral data. Unlike quinoline alkaloids so far reported, scolopendrine is unique in having a 7-benzyl moiety in the quinoline ring. PMID:11456108

Noda, N; Yashiki, Y; Nakatani, T; Miyahara, K; Du, X M



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

NASA Astrophysics Data System (ADS)

The antiphotooxidative properties of boldine and chloride berberine were studied by time-resolved thermal lensing technique. These compounds belong to isoquinoline alkaloids possessing interesting biological activity (e.g. antibacterial, antimalarial, antitumor). Antiphotooxidative properties of the alkaloids were studied by mechanism of energy transference between powerful oxidizing agents such as singlet oxygen. Singlet oxygen was produced by energy transfer from chlorophyll-sensitized photooxidation of oil by exposure of high light intensities like laser. The lifetimes of singlet oxygen in dimethylsulfoxide, methanol and water were determined to confirm the assignment of the singlet molecular oxygen O2 (1?g) in the experiments. In order to understand the effect of the alkaloids on active oxygen species, we carried out in detail an analysis of the thermal lensing signal. It was shown that the alkaloids can act as quenchers of singlet oxygen. To demonstrate the ability of the alkaloids to act efficient singlet oxygen acceptors, we have measured the fluorescence spectra of the studied alkaloids in the presence and in the absence of singlet oxygen. The antiphotooxidative activity of boldine and chloride berberine can be explained by the ability to quench singlet oxygen.

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



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


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

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



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


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

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



Piperideine alkaloids from the poison gland of the red imported fire ant (Hymenoptera: Formicidae).  


The major chemical components in the venom of red imported fire ants, Solenopsis invicta Buren, are 2-methyl-6-alkyl or alkenyl piperidines. After isolating the extracts of poison glands and whole worker bodies with column chromatography, we obtained fractions containing a mixture of six piperideine alkaloids. Reduction of those samples using NaBH(4) in ethanol generated piperidine alkaloids found in the fire ant poison gland, resulting in both the cis- and the trans-piperidine alkaloids. The mass spectra and gas chromatographic behavior of most piperidine alkaloids from fire ant venom have been well-characterized, which significantly facilitated the identification of these piperdeine compounds. On the basis of the mass spectra and profiles of NaBH(4) reduction products, we identified these alkaloids as 2-methyl-6-tridecenyl-6-piperideine, 2-methyl-6-tridecyl-6-piperideine, 2-methyl-6-pentadecenyl-6-piperideine, 2-methyl-6-pentadecyl-6-piperideine, 2-methyl-6-heptadecenyl-6-piperideine, and 2-methyl-6-heptadecyl-6-piperideine. To our knowledge, this is the first time that these piperideine alkaloids have been reported in red imported fire ant poison glands. PMID:19326861

Chen, Jian; Cantrell, Charles L; Shang, Han-wu; Rojas, Maria G



Efficient and sensitive method for quantitative analysis of alkaloids in hardinggrass (Phalaris aquatica L.).  


An efficient high-performance thin-layer chromatography (HPTLC) method for the analysis of alkaloids in hardinggrass (Phalaris aquatica L.) was developed. The method employed HPTLC glass plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of ethyl acetate/chloroform/7 N NH4OH in methanol (8:2:1, v/v/v). Using unidimensional double-development, bands were well separated for 10 alkaloid standards as well as alkaloids observed in hardinggrass plant extracts. Identities of compounds observed using HPTLC were validated by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Software was used to quantify individual alkaloids in plant samples based on HPTLC retention factors and intensities relative to standards of known concentration. Correlation coefficients of 0.99 were obtained between estimated and actual concentrations for four standards (methyltyramine, hordenine, gramine, and 5-methoxydimethyltryptamine), with linearity in the range of 120-3840 ng/spot. The HPTLC method is repeatable and specific for beta-carboline, tryptamine, gramine, and tyramine type alkaloids in mixed standard and plant extracts. Initial results indicate substantial variation in alkaloid composition among and within hardinggrass populations. PMID:17147408

Zhou, Lili; Hopkins, Andrew A; Huhman, David V; Sumner, Lloyd W



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

PubMed Central

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

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



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

PubMed Central

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

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



Application of 1H-NMR spectroscopy to validation of berberine alkaloid reagents and to chemical evaluation of Coptidis Rhizoma.  


Berberine, palmatine, and coptisine are major pharmacologically active protoberberine alkaloids in Coptidis Rhizoma, and have been used as indices for chemical evaluation of the crude drug. (1)H-NMR spectroscopy was applied to determination of purities of commercial reagents of protoberberine alkaloids. The purities of the alkaloids were calculated from the ratios of the intensities of the H-13 singlet signal at about ? 8.7 ppm of target protoberberine alkaloids to integration of a hexamethyldisilane (HMD) signal at 0 ppm. The concentration of HMD was corrected with SI traceability using potassium hydrogen phthalate of certified reference material (CRM) grade. The purity of the reagent estimated by the (1)H-NMR was, in general, lower than that claimed by the manufacturer, leading to over-estimation of the alkaloid contents of Coptidis Rhizoma when determined by HPLC. The present quantitative (1)H-NMR method was also applicable to direct determination of protoberberine alkaloid contents in Coptidis Rhizoma. PMID:21188644

Hasada, Keiko; Yoshida, Takamitsu; Yamazaki, Takeshi; Sugimoto, Naoki; Nishimura, Tetsuji; Nagatsu, Akito; Mizukami, Hajime



Manipulating indole alkaloid production by Catharanthus roseus cell cultures in bioreactors: from biochemical processing to metabolic engineering  

Microsoft Academic Search

Catharanthus roseus plants produce many pharmaceutically important indole alkaloids, of which the bisindole alkaloids vinblastine and vincristine\\u000a are antineoplastic medicines and the monoindole alkaloids ajmalicine and serpentine are antihypertension drugs. C. roseus cell cultures have been studied for producing these medicines or precursors catharanthine and vindoline for almost four decades\\u000a but so far without a commercially successful process due to

Jian Zhao; Robert Verpoorte



The effect of varying alkaloid concentrations on the feeding behavior of gypsy moth larvae, Lymantria dispar (L.) (Lepidoptera: Lymantriidae)  

Microsoft Academic Search

Nine alkaloids (acridine, aristolochic acid, atropine, berberine, caffeine, nicotine, scopolamine, sparteine, and strychnine)\\u000a were evaluated as feeding deterrents for gypsy moth larvae (Lymantria dispar (L.); Lepidoptera: Lymantriidae). Our aim was to determine and compare the taste threshold concentrations, as well as the\\u000a ED50 values, of the nine alkaloids to determine their potency as feeding deterrents. The alkaloids were applied to

Vonnie D. C. Shields; Kristen P. Smith; Nicole S. Arnold; Ineta M. Gordon; Taharah E. Shaw; Danielle Waranch



Alstiphyllanines E–H, picraline and ajmaline-type alkaloids from Alstonia macrophylla inhibiting sodium glucose cotransporter  

Microsoft Academic Search

Three new picraline-type alkaloids, alstiphyllanines E–G (1–3) and a new ajmaline-type alkaloid, alstiphyllanine H (4) were isolated from the leaves of Alstonia macrophylla together with 16 related alkaloids (5–20). Structures and stereochemistry of 1–4 were fully elucidated and characterized by 2D NMR analysis. Alstiphyllanines E and F (1 and 2) showed moderate Na+-glucose cotransporter (SGLT1 and SGLT2) inhibitory activity. A

Hiroko Arai; Yusuke Hirasawa; Abdul Rahman; Idha Kusumawati; Noor Cholies Zaini; Seizo Sato; Chihiro Aoyama; Jiro Takeo; Hiroshi Morita



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


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

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



Metabolic Fate of Depsides and Alkaloid Constituents in Aqueous Extracts from Mercurialis perennis L. during Fermentation.  


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

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



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

PubMed Central

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

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



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

NASA Astrophysics Data System (ADS)

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

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



Pyrrolizidine Alkaloid Biosynthesis in Phalaenopsis Orchids: Developmental Expression of Alkaloid-Specific Homospermidine Synthase in Root Tips and Young Flower Buds  

Microsoft Academic Search

Pyrrolizidine alkaloids (PAs) are typical compounds of plant secondary metabolism and are believed to be part of the plant's chemical defense. Within the monocotyledonous plants, PAs have been described in only a few genera, mainly orchids, including Phalaenopsis. Because phylogenetic analyses suggest an independent origin of PA biosynthesis within the monocot lineage, we have analyzed the developmentally regulated expression of

Sven Anke; Daniela Gonde ´; Elisabeth Kaltenegger; Robert Hänsch; Claudine Theuring; Dietrich Ober



Cytotoxic Epipolythiodioxopiperazine Alkaloids from Filamentous Fungi of the Bionectriaceae  

PubMed Central

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

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



Biotransformation and pharmacokinetics of the antiplasmodial naphthylisoquinoline alkaloid dioncophylline A.  


The biotransformation of the antiplasmodial naphthylisoquinoline alkaloid dioncophylline A by rat liver microsomes and its pharmacokinetics in male rats were studied. Incubation of dioncophylline A with rat liver microsomes resulted in the formation of the major metabolite 5'-O-demethyldioncophylline A, and a second minor metabolite, corresponding to the mass of an as yet unknown 4-hydroxydioncophylline A. Kinetic constants of the formation of 5'-O-demethyldioncophylline A were Km = 32 nmol and Vmax = 20 pmol min-1 mg-1). Administration of dioncophylline A at a dose of 6.67 mg kg-1 body weight to rats intravenously and orally (n = 4 per group) resulted in peak plasma levels of 0.84 and 0.11 microg ml-1, respectively. Levels of metabolites were below the limit of quantitation (LOQ). The following pharmacokinetic parameters of dioncophylline A were determined: oral bioavailability of 25%, plasma half-life of 2.5 h and partition volume of 8 l kg-1 body weight. Concentrations of dioncophylline A metabolites in all plasma and urine samples were below the limit of detection (LOD) and recovery of dioncophylline A in urine was very low, suggesting distribution into lipid rich tissues. PMID:16971341

Sieber, M; Dekant, W; Faber, J H; Bringmann, G



Liriodenine alkaloid in Annona diversifolia during early development.  


Plants of the Annonaceae family produce a series of alkaloids, including liriodenine oxoaporphine. Its distribution in these primitive angiosperms suggests that it plays an important role, but very little is known about which plant organs it accumulates in, or in which developmental stages it is synthesised. Accordingly, liriodenine production was studied during the early stages of germination and seedling development in Annona diversifolia Saff. Liriodenine samples were obtained from the roots and were characterised on the basis of spectroscopic data. Quantification was done by HPLC in the organs and tissues of newly collected seeds, seeds following 1-, 2-, 5- and 10-day imbibitions, upon emergence of the radicle and at the seedling stage. According to our results, liriodenine could not have originated from the parent plant, nor during embryogenesis because it appears for the first time in the endosperm approximately 5 days after the start of imbibition. Therefore, its synthesis does not depend directly on photosynthesis. During the seedling stage it is found in the root and the stem but it is absent from the cotyledonary leaves and the first true leaves. Liriodenine biosynthesis begins during the early stages of development in the endosperm and seed radicles. PMID:21790492

de la Cruz Chacón, I; González-Esquinca, A R



Putrescine N-methyltransferase--the start for alkaloids.  


Putrescine N-methyltransferase (PMT) catalyses S-adenosylmethionine (SAM) dependent methylation of the diamine putrescine. The product N-methylputrescine is the first specific metabolite on the route to nicotine, tropane, and nortropane alkaloids. PMT cDNA sequences were cloned from tobacco species and other Solanaceae, also from nortropane-forming Convolvulaceae and enzyme proteins were synthesised in Escherichia coli. PMT activity was measured by HPLC separation of polyamine derivatives and by an enzyme-coupled colorimetric assay using S-adenosylhomocysteine. PMT cDNA sequences resemble those of plant spermidine synthases (putrescine aminopropyltransferases) and display little similarity to other plant methyltransferases. PMT is likely to have evolved from the ubiquitous enzyme spermidine synthase. PMT and spermidine synthase proteins share the same overall protein structure; they bind the same substrate putrescine and similar co-substrates, SAM and decarboxylated S-adenosylmethionine. The active sites of both proteins, however, were shaped differentially in the course of evolution. Phylogenetic analysis of both enzyme groups from plants revealed a deep bifurcation and confirmed an early descent of PMT from spermidine synthase in the course of angiosperm development. PMID:19651420

Biastoff, Stefan; Brandt, Wolfgang; Dräger, Birgit



Structures of alkaloid biosynthetic glucosidases decode substrate specificity.  


Two similar enzymes with different biosynthetic function in one species have evolved to catalyze two distinct reactions. X-ray structures of both enzymes help reveal their most important differences. The Rauvolfia alkaloid biosynthetic network harbors two O-glucosidases: raucaffricine glucosidase (RG), which hydrolyses raucaffricine to an intermediate downstream in the ajmaline pathway, and strictosidine glucosidase (SG), which operates upstream. RG converts strictosidine, the substrate of SG, but SG does not accept raucaffricine. Now elucidation of crystal structures of RG, inactive RG-E186Q mutant, and its complexes with ligands dihydro-raucaffricine and secologanin reveals that it is the "wider gate" of RG that allows strictosidine to enter the catalytic site, whereas the "slot-like" entrance of SG prohibits access by raucaffricine. Trp392 in RG and Trp388 in SG control the gate shape and acceptance of substrates. Ser390 directs the conformation of Trp392. 3D structures, supported by site-directed mutations and kinetic data of RG and SG, provide a structural and catalytic explanation of substrate specificity and deeper insights into O-glucosidase chemistry. PMID:22004291

Xia, Liqun; Ruppert, Martin; Wang, Meitian; Panjikar, Santosh; Lin, Haili; Rajendran, Chitra; Barleben, Leif; Stöckigt, Joachim



Sequestration of camptothecin, an anticancer alkaloid, by chrysomelid beetles.  


Camptothecin (CPT), a monoterpene indole alkaloid, is a potent inhibitor of eukaryotic toposiomerase-I. Several derivatives of CPT are in clinical use against ovarian and lung cancers. CPT has been reported from several plant species belonging to the order Asterids, with the highest concentration in Nothapodytes nimmoniana (family Icacinaceae). In this paper, we report an intriguing observation of chrysomelid beetles (Kanarella unicolor Jacobby) feeding on the leaves of N. nimmoniana without any apparent adverse effect. LC-MS/MS analysis of the beetles indicated that 54.9% of the ingested CPT's was recovered from the wings, followed by lesser amounts in the head and abdomen. LC-HRMS analysis revealed that most of the CPT in the insect body was in the parental form available in the plants without any major metabolizable products, including sulfated and glucuronilated forms. The mechanism by which the beetles are able to tolerate substantially high levels of CPT in their body tissue is under investigation. PMID:21499721

Ramesha, B T; Zuehlke, S; Vijaya, R C; Priti, V; Ravikanth, G; Ganeshaiah, K N; Spiteller, M; Shaanker, R Uma



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


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

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



Managing murine food allergy with Cissampelos sympodialis Eichl (Menispermaceae) and its alkaloids.  


Food allergy is a severe human disease with imminent risk of life. Cissampelos sympodialis (Menispermaceae) is a native Brazilian plant used in Brazilian folk medicine for the treatment of respiratory allergies. In this study the experimental model of food allergy induced by ovalbumin (OVA) was used to determine whether the alcoholic extract of the plant (AFL) and its alkaloids match a therapeutic approach for this disease. Animal weight, diarrhea, OVA-specific IgE levels, inflammatory cell and cytokine profiles, mucus production and proportion of T cells on the mesenteric lymph node (MLN) were evaluated. Warifteine (W) or methyl-warifteine (MW) alkaloids slightly improve diarrhea score independently of AFL and all treatments decreased the OVA-specific IgE levels. Stimulated mesenteric lymph node (MLN) cells in the presence of the alkaloids diminished the IL-12p70 levels independently of IFN-? or IL-13 secretion. The alkaloids increased the number of Treg cells on MLN and reduced the number of eosinophils and mast cells as well as mucus production in the gut. Therefore, the alkaloids modulate the immune response in food allergy by increasing regulatory T cells in MLN independently of Th1 or Th2 profiles. PMID:23810408

Costa, Hermann Ferreira; Leite, Fagner Carvalho; Alves, Adriano Francisco; Barbosa-Filho, José Maria; dos Santos, Claudio Roberto Bezerra; Piuvezam, Marcia Regina



N-Methyldecahydroquinolines: An Unexpected Class of Alkaloids from Amazonian Poison Frogs (Dendrobatidae)  

PubMed Central

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

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



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


The Amaryllidaceae family is well known for its pharmacologically active alkaloids. An important approach to treat Alzheimer’s disease involves the inhibition of the enzyme acetylcholinesterase (AChE). Galanthamine, an Amaryllidaceae alkaloid, is an effective, selective, reversible, and competitive AchE inhibitor. This work was aimed at studying the alkaloid composition of four wild Argentinian Amarillydaceae species for the first time, as well as analyzing their inhibitory activity on acetylcholinesterase. Alkaloid content was characterized by means of GC-MS analysis. Chloroform basic extracts from Habranthus jamesonii, Phycella herbertiana, Rhodophiala mendocina and Zephyranthes filifolia collected in the Argentinian Andean region all contained galanthamine, and showed a strong AChE inhibitory activity (IC50 between 1.2 and 2 µg/mL). To our knowledge, no previous reports on alkaloid profiles and AChEIs activity of wild Argentinian Amarillydaceae species have been publisihed. The demand for renewable sources of industrial products like galanthamine and the need to protect plant biodiversity creates an opportunity for Argentinian farmers to produce such crops. PMID:23149565

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



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

NASA Astrophysics Data System (ADS)

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

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



Seasonal accumulation of major alkaloids in organs of pharmaceutical crop Narcissus Carlton.  


Narcissus pseudonarcissus (L.) cv. Carlton is being cultivated as a main source of galanthamine from the bulbs. After galanthamine, haemanthamine and narciclasine are the next most abundant alkaloids in this cultivar. Both these compounds are promising chemical scaffolds for potential anticancer drugs. For further research and drug development, a reliable supply of these compounds will be needed. In this study a field experiment was conducted to investigate the levels of galanthamine, haemanthamine and narciclasine in plants of N. pseudonarcissus cv. Carlton. In a field experiment alkaloids in the bulbs, leaves and roots were analyzed by quantitative (1)H NMR to monitor the variations during the growing season. Major primary and secondary metabolites were identified in the various plant parts. Multivariate data analysis was performed on the (1)H NMR spectra to investigate how metabolites changed in the plant organs over time. The results show that the leaves have relatively high concentrations of the alkaloids before flowering. The bulbs had lower concentrations of the compounds of interest but would have a higher total yield of alkaloids due to bigger biomass. Narcissus pseudonarcissus cv. Carlton represents a good source of galanthamine, and can potentially be a source of the other major alkaloids depending on choice of organ and harvest time. PMID:23318143

Lubbe, Andrea; Gude, Henk; Verpoorte, Robert; Choi, Young Hae



Medicinally important secondary metabolites in recombinant microorganisms or plants: progress in alkaloid biosynthesis.  


Plants produce a high diversity of natural products or secondary metabolites which are important for the communication of plants with other organisms. A prominent function is the protection against herbivores and/or microbial pathogens. Some natural products are also involved in defence against abiotic stress, e.g. UV-B exposure. Many of the secondary metabolites have interesting biological properties and quite a number are of medicinal importance. Because the production of the valuable natural products, such as the anticancer drugs paclitaxel, vinblastine or camptothecin in plants is a costly process, biotechnological alternatives to produce these alkaloids more economically become increasingly important. This review provides an overview of the state of art to produce alkaloids in recombinant microorganisms, such as bacteria or yeast. Some progress has been made in metabolic engineering usually employing a single recombinant alkaloid gene. More importantly, for benzylisoquinoline, monoterpene indole and diterpene alkaloids (taxanes) as well as some terpenoids and phenolics the proof of concept for production of complex alkaloids in recombinant Escherichia coli and yeast has already been achieved. In a long-term perspective, it will probably be possible to generate gene cassettes for complete pathways, which could then be used for production of valuable natural products in bioreactors or for metabolic engineering of crop plants. This will improve their resistance against herbivores and/or microbial pathogens. PMID:19946877

Schäfer, Holger; Wink, Michael



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


The hydroxyl radical (*OH) scavenging and ferrous ion chelating activities of four isoquinoline alkaloids isolated from Coptis chinensis Franch were studied for the identification of their structural characteristics to scavenge *OH. The *OH was generated via Fe(II)-catalazed Fenton reaction in this study and the reliable measurement of *OH scavenging activities of isoquinoline alkaloids were achieved using electron spin resonance (ESR) spectrometry method. At the 1 mM concentration, berberrubine (85%) showed the strongest *OH scavenging activity and the next were in the decreasing order of coptisine (79%), berberine (23%), and palmatine (22%). The ferrous ion chelating effects of the alkaloids showed similar pattern with their *OH scavenging effects. These results suggest that *OH scavenging effects of the alkaloids were closely related to their ferrous ion chelating activities. In addition, metal chelating functional groups such as hydroxy group at C-9 and methylenedioxy group at C-9 and C-10 were thought to contribute to the *OH scavenging activities of the isoquinoline alkaloids. PMID:19387576

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



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


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

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



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


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

Evans, Ronald L; Siitonen, Paul H



Dietary alkaloids and the development of androconial organs in Estigmene acrea  

PubMed Central

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

Davenport, Jason W.; Conner, William E.



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


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

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




Technology Transfer Automated Retrieval System (TEKTRAN)

Six cows with a history of lupine induced crooked calf disease and 6 cows with no history of lupine induced birth defects were challenged with lupine and plasma alkaloid pharmacokinetic parameters compared. Anagyrine, the alkaloid known to cause crooked calf disease, and two other alkaloids, 5, 6-d...


The effect of body condition on serum concentrations of two teratogenic alkaloids (anagyrine and ammodendrine) from lupines (Lupinus species) that cause crooked calf disease1  

Microsoft Academic Search

Several species of lupine (Lupinus spp.) are toxic to livestock, causing death losses in sheep and cattle but more commonly crooked calf disease in preg- nant range cows. The major toxic alkaloids in lupine are of the quinolizidine alkaloid group and include the teratogen anagyrine, which is primarily responsible for crooked calf disease. Lupines also contain teratogenic piperidine alkaloids including

S. T. Lee; K. E. Panter; J. A. Pfister; D. R. Gardner; K. D. Welch


Efficient incorporation of 10-hydroxygeraniol and 10-hydroxynerol into indole alkaloids by a cell suspension culture of Catharanthus roseus.  


A cell suspension culture of Catharanthus roseus was evaluated with regard to its potential usage in studies of early stage indole alkaloid biosynthesis. Employing this material, 1,1,7-trideutero-10-hydroxygeraniol and 1,1,7-trideutero-10-hydroxynerol were incorporated into the alkaloids ajmalicine and strictosidine lactam in approximate proportions of 50% and 80% respectively. PMID:17402127

Balsevich, J; Constabel, F; Kurz, W G



Integration of deep transcriptome and proteome analyses reveals the components of alkaloid metabolism in opium poppy cell cultures  

Microsoft Academic Search

BACKGROUND: Papaver somniferum (opium poppy) is the source for several pharmaceutical benzylisoquinoline alkaloids including morphine, the codeine and sanguinarine. In response to treatment with a fungal elicitor, the biosynthesis and accumulation of sanguinarine is induced along with other plant defense responses in opium poppy cell cultures. The transcriptional induction of alkaloid metabolism in cultured cells provides an opportunity to identify

Isabel Desgagné-Penix; Morgan F Khan; David C Schriemer; Dustin Cram; Jacek Nowak; Peter J Facchini



13C, 15N CPMAS NMR and GIAO DFT calculations of stereoisomeric oxindole alkaloids from Cat's Claw ( Uncaria tomentosa)  

Microsoft Academic Search

Oxindole alkaloids, isolated from the bark of Uncaria tomentosa [Willd. ex Schult.] Rubiaceae, are considered to be responsible for the biological activity of this herb. Five pentacyclic and two tetracyclic alkaloids were studied by solid-state NMR and theoretical GIAO DFT methods. The 13C and 15N CPMAS NMR spectra were recorded for mitraphylline, isomitraphylline, pteropodine (uncarine C), isopteropodine (uncarine E), speciophylline

Katarzyna Paradowska; Micha? Wolniak; Maciej Pisklak; Jan A. Gli?ski; Matthew H. Davey; Iwona Wawer



Antibacterial activity against resistant bacteria and cytotoxicity of four alkaloid toxins isolated from the marine sponge Arenosclera brasiliensis  

Microsoft Academic Search

Arenosclerins A–C and haliclonacyclamine E, new tetracyclic alkylpiperidine alkaloids isolated from the marine sponge Arenosclera brasiliensis, were subjected to antimicrobial and cytotoxic bioassays. Fourteen samples of microorganisms were used: Candida albicans, Staphylococcus aureus, Escherichia coli, and 12 antibiotic-resistant bacteria isolated from hospital environment. The minimum inhibitory concentration activity of each alkaloid was determined. The four compounds displayed antibacterial activity, but

Yohandra R Torres; Roberto G. S Berlinck; Gislene G. F Nascimento; Sérgio C Fortier; Claudia Pessoa; Manoel O de Moraes



Cyclohaliclonamines A-E: dimeric, trimeric, tetrameric, pentameric, and hexameric 3-alkyl pyridinium alkaloids from a marine sponge Haliclona sp.  


A mixture of cyclohaliclonamines A-E (1-5), novel dimeric, trimeric, tetrameric, pentameric, and hexameric 3-alkylpyridinium alkaloids, was obtained from an Okinawan sponge Haliclona sp. Cyclohaliclonamines C-E are the first tetrameric, pentameric, and hexameric 3-alkylpyridinium alkaloids from natural sources. The structure determination of cyclohaliclonamines is discussed in detail. PMID:16441085

Teruya, Toshiaki; Kobayashi, Keiko; Suenaga, Kiyotake; Kigoshi, Hideo



Four spiroquinazoline alkaloids from Eupenicillium sp. isolated as an endophytic fungus from leaves of Murraya paniculata (Rutaceae)  

Microsoft Academic Search

A Eupenicillium spp. was isolated from healthy leaves of Murraya paniculata (Rutaceae) after surface sterilization. This fungus was cultivated in sterilized white-corn, where the spiroquinazoline alkaloids alanditrypinone, alantryphenone, alantrypinene and alantryleunone were produced. The culture was extracted with methanol and the alkaloids were isolated by a combination of silica gel chromatography and HPLC. The structures were elucidated by extensive spectroscopic

Fábio A. Proença Barros; Edson Rodrigues-Filho



Difference in the signals of the NH proton in the NMR spectra of the indole, indoline, and hydroxyindole alkaloids  

Microsoft Academic Search

Conclusions  On the basis of the results of measurements of the chemical shifts of the signal of the NH proton in Vinca alkaloids, it has\\u000a been established that the CS of the NH group in the ?-methyleneindoline alkaloids and their 2, 16-dihydro derivatives differ\\u000a substantially.

M. R. Yagudaev; V. M. Malikov; S. Yu. Yunusov



Effects of the steroidal alkaloid tomatine in auxin bioassays and its interaction with indole-3-acetic acid  

Microsoft Academic Search

The steroidal alkaloid tomatine did not enhance elongation of oat coleoptile and first internode sections, or of wheat coleoptile sections. Higher concentrations of the alkaloid inhibited elongation and interacted antagonistically with IAA. Although 10-4 M tomatine alone did not influence elongation of oat coleoptile sections, it did reduce growth response to exogenous IAA. Tomatine concentrations less than 10-4 M did

J. G. Roddick



Antioxidant and antimutagenic properties of the monoterpene indole alkaloid psychollatine and the crude foliar extract of Psychotria umbellata Vell  

Microsoft Academic Search

Psychollatine is a monoterpene indole alkaloid produced and accumulated by Psychotria umbellata Vell. (Rubiaceae) leaves in relatively high amounts (approximately 3% of the dry weight). The alkaloid has been shown to display opioid-like analgesic, anxiolytic, antidepressive and antipsychotic activities in rodents. In vitro assays suggested a protective role for this molecule in plant oxidative stress responses. This work reports antioxidant

Variluska Fragoso; Naíla Cannes do Nascimento; Dinara Jaqueline Moura; Ana Catarina Romano e Silva; Marc François Richter; Jenifer Saffi; Arthur Germano Fett-Neto



Isolation and characterization of two new alkaloids, norpandamarilactonine-A and -B, from Pandanus amaryllifolius by spectroscopic and synthetic methods.  


Two new alkaloids, norpandamarilactonine-A (1) and -B (2), which have a pyrrolidinyl-alpha,beta-unsaturated gamma-lactone moiety as in the known pandamarilactonine alkaloids, were isolated from the leaves of Pandanus amaryllifolius. Their structures were determined by spectroscopic analysis and total synthesis. PMID:11575961

Takayama, H; Ichikawa, T; Kitajima, M; Nonato, M G; Aimi, N



Antisense RNA-Mediated Suppression of Benzophenanthridine Alkaloid Biosynthesis in Transgenic Cell Cultures of California Poppy1  

PubMed Central

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

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



The Actions of Piperidine Alkaloids at Fetal Muscle-Type and Autonomic-Type Nicotinic Acetylcholine Receptors  

Technology Transfer Automated Retrieval System (TEKTRAN)

Piperidine alkaloids are found in many species of plants including Conium maculatum, Nicotiana spp., and Lupinus spp. A pharmacodynamic comparison was made of the alkaloids ammodendrine, anabasine, anabaseine, and coniine in; SH-SY5Y cells which express autonomic-type nicotinic acetylcholine recept...


Two-phase culture for enhanced alkaloid synthesis and release in a new airlift reactor by Catharanthus roseus  

Microsoft Academic Search

A new airlift reactor was used to culture Catharanthus roseus cells, in which the draft tube was made up of polyurethane foam and acted as the immobilizing matrix. The reactor was connected in series to an adsorbent column with a neutral polymeric resin which absorbs these alkaloids. The synthesis of alkaloid was stimulated by adding the resin column and the

Qipeng Yuan; Hui Xu; Zongding Hu



Subcellular Localization of Enzymes Involved in Indole Alkaloid Biosynthesis in Catharanthus roseus.  


The subcellular localization of enzymes involved in indole alkaloid biosynthesis in leaves of Catharanthus roseus has been investigated. Tryptophan decarboxylase and strictosidine synthase which together produce strictosidine, the first indole alkaloid of this pathway, are both cytoplasmic enzymes. S-Adenosyl-l-methionine: 16-methoxy-2,3-dihydro-3-hydroxytabersonine-N-methyltransferase which catalyses the third to last step in vindoline biosynthesis could be localized in the chloroplasts of Catharanthus leaves and is specifically associated with thylakoids. Acetyl-coenzyme-A-deacetylvindoline-O-acetyltransferase which catalyses the last step in vindoline biosynthesis could also be localized in the cytoplasm. The participation of the chloroplast in this pathway suggests that indole alkaloid intermediates enter and exit this compartment during the biosynthesis of vindoline. PMID:16665811

De Luca, V; Cutler, A J



Role of Glycols and Tweens in the Production of Ergot Alkaloids by Claviceps paspali  

PubMed Central

Several glycols and Tweens markedly stimulated the production of ergot alkaloids in submerged cultures of Claviceps paspali. The role of these compounds was investigated in shake flasks and bench-scale fermentors. 2,3-Butanediol was not utilized by the fungus, and 1,2-propanediol-1-14C was not incorporated into the alkaloids. Glycols and Tweens lowered the surface tension of the basal medium and promoted the utilization of metabolites. In the presence of glycols and Tweens, an increased uptake of labeled sorbitol and succinic acid took place, whereas the specific radioactivity of the alkaloids was not affected. These results indicated that glycols and Tweens are not involved directly in the biosynthetic process; they apparently acted as surface-active agents, facilitating transport of metabolites into the cells.

Mizrahi, A.; Miller, G.



Total synthesis and absolute stereochemical assignment of (+)- and (-)-galbulimima alkaloid 13.  


We describe the total synthesis of (+)- and (-)-galbulimima alkaloid 13. The absolute stereochemistry of natural (-)-galbulimima alkaloid 13 is revised to 2S. Sequential use of catalytic cross-coupling and cross-metathesis reactions followed by an intramolecular Diels-Alder reaction provided the required trans-decalin AB-ring system and masked the C16 carbonyl as an N-vinyl carbamate for late-stage unveiling in the form of the necessary C16 enone. A vinyl radical cyclization secured the C-ring, while successful execution of our strategy for introduction of the CDE-ring system in complex galbulimima alkaloids provided the target pentacycle with complete diastereoselection. PMID:16787063

Movassaghi, Mohammad; Hunt, Diana K; Tjandra, Meiliana



The determinant step in ergot alkaloid biosynthesis by an endophyte of perennial ryegrass.  


Many cool-season grasses harbor fungal endophytes in the genus Neotyphodium, which enhance host fitness, but some also produce metabolites--such as ergovaline--believed to cause livestock toxicoses. In Claviceps species the first step in ergot alkaloid biosynthesis is thought to be dimethylallyltryptophan (DMAT) synthase, encoded by dmaW, previously cloned from Claviceps fusiformis. Here we report the cloning and characterization of dmaW from Neotyphodium sp. isolate Lp1, an endophyte of perennial ryegrass (Lolium perenne). The gene was then disrupted, and the mutant failed to produce any detectable ergovaline or simpler ergot and clavine alkaloids. The disruption was complemented with the C. fusiformis gene, which restored ergovaline production. Thus, the biosynthetic role of DMAT synthase was confirmed, and a mutant was generated for future studies of the ecological and agricultural importance of ergot alkaloids in endophytes of grasses. PMID:14732265

Wang, Jinghong; Machado, Caroline; Panaccione, Daniel G; Tsai, Huei-Fung; Schardl, Christopher L



Two new vinblastine-type N-oxide alkaloids from Catharanthus roseus.  


Two new vinblastine-type N-oxide alkaloids, 17-desacetoxyvinblastine [Formula: see text]-oxide (1) and 20'-deoxyvinblastine [Formula: see text]-oxide (2), were isolated from the leaves of Catharanthus roseus. The structures of 1 and 2 were established by the analysis of their nuclear magnetic resonance and HR-ESI-MS spectroscopic data. All alkaloids were evaluated for their cytotoxic activities against the human hepatocellular carcinoma (HepG2) cell line, human colorectal carcinoma (Lovo) cell line and human breast carcinoma (MCF-7) cell line by the MTT method in vitro, respectively. The results showed that cytotoxic activities of alkaloids 1 and 2 exhibited moderate inhibitory activity on the proliferation of three cancer cells. PMID:23621523

Zhang, Wei-Ku; Xu, Jie-Kun; Tian, Hai-Yan; Wang, Lei; Zhang, Xiao-Qi; Xiao, Xu-Zhi; Li, Ping; Ye, Wen-Cai



Alkaloids from Lycoris caldwellii and their particular cytotoxicities against the astrocytoma and glioma cell lines.  


Phytochemical investigation of the ethanol extract of the bulbs of Lycoris caldwellii afforded four new alkaloids, (+)-N-methoxylcarbonyl-nandigerine (1), (+)-N-methoxycarbonyl-lindcarpine (2), (+)-10-O-methylhernovine N-oxide (3), and (+)-3-hydroxy-anhydrolycorine N-oxide (4). Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D (¹H-¹H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. All the alkaloids were in vitro evaluated for their cytotoxic activities against eight tumor cell lines (BEN-MEN-1, CCF-STTG1, CHG-5, SHG-44, U251, BGC-823, HepG2, and SK-OV-3). Alkaloids 1 and 2 exhibited particular cytotoxic activities against astrocytoma and glioma cell lines with IC?? of 9.2-11.3 ?M and 10.4-12.2 ?M respectively. PMID:23526231

Cao, Peng; Pan, Dong-Sheng; Han, Song; Yu, Chun-Yong; Zhao, Qing-Jie; Song, Yan; Liang, Yong



Rapid identification of enzyme variants for reengineered alkaloid biosynthesis in periwinkle.  


Monoterpene indole alkaloids from Catharanthus roseus (Madagascar periwinkle), such as the anticancer agents vinblastine and vincristine, have important pharmacological activities. Metabolic engineering of alkaloid biosynthesis can provide an efficient and environmentally friendly route to analogs of these synthetically challenging and pharmaceutically valuable natural products. However, the narrow substrate scope of strictosidine synthase, the enzyme at the entry point of the pathway, limits a pathway engineering approach. We demonstrate that with a different expression system and screening method it is possible to rapidly identify strictosidine synthase variants that accept tryptamine analogs not turned over by the wild-type enzyme. The variants are used in stereoselective synthesis of beta-carboline analogs and are assessed for biosynthetic competence within the terpene indole alkaloid pathway. These results present an opportunity to explore metabolic engineering of "unnatural" product production in the plant periwinkle. PMID:17719488

Bernhardt, Peter; McCoy, Elizabeth; O'Connor, Sarah E



Subcellular Localization of Enzymes Involved in Indole Alkaloid Biosynthesis in Catharanthus roseus1  

PubMed Central

The subcellular localization of enzymes involved in indole alkaloid biosynthesis in leaves of Catharanthus roseus has been investigated. Tryptophan decarboxylase and strictosidine synthase which together produce strictosidine, the first indole alkaloid of this pathway, are both cytoplasmic enzymes. S-Adenosyl-l-methionine: 16-methoxy-2,3-dihydro-3-hydroxytabersonine-N-methyltransferase which catalyses the third to last step in vindoline biosynthesis could be localized in the chloroplasts of Catharanthus leaves and is specifically associated with thylakoids. Acetyl-coenzyme-A-deacetylvindoline-O-acetyltransferase which catalyses the last step in vindoline biosynthesis could also be localized in the cytoplasm. The participation of the chloroplast in this pathway suggests that indole alkaloid intermediates enter and exit this compartment during the biosynthesis of vindoline.

De Luca, Vincenzo; Cutler, Adrian J.



Berberine: a plant alkaloid with therapeutic potential for central nervous system disorders.  


Berberine, an isoquinoline alkaloid of the protoberberine type found in an array of plants, has been used in Indian and Chinese medicines as an antimicrobial, stomachic, bitter tonic and in the treatment of oriental sores. Although pharmacological investigations of berberine have been reported by many in the past, there is renewed interest in berberine because of its reported beneficial effect in various neurodegenerative and neuropsychiatric disorders. The alkaloid is reported to modulate neurotransmitters and their receptor systems in the brain. This review attempts to discuss the pharmacological basis of the use of berberine in various central nervous system and related disorders. Its protective effect in Alzheimer's, cerebral ischemia, mental depression, schizophrenia and anxiety are highlighted. However, more detailed clinical trials along with a safety assessment of berberine are warranted for positioning the alkaloid in the treatment of neurological disorders. PMID:19998323

Kulkarni, S K; Dhir, Ashish



Plant tropane alkaloid biosynthesis evolved independently in the Solanaceae and Erythroxylaceae.  


The pharmacologically important tropane alkaloids have a scattered distribution among angiosperm families, like many other groups of secondary metabolites. To determine whether tropane alkaloids have evolved repeatedly in different lineages or arise from an ancestral pathway that has been lost in most lines, we investigated the tropinone-reduction step of their biosynthesis. In species of the Solanaceae, which produce compounds such as atropine and scopolamine, this reaction is known to be catalyzed by enzymes of the short-chain dehydrogenase/reductase family. However, in Erythroxylum coca (Erythroxylaceae), which accumulates cocaine and other tropane alkaloids, no proteins of the short-chain dehydrogenase/reductase family were found that could catalyze this reaction. Instead, purification of E. coca tropinone-reduction activity and cloning of the corresponding gene revealed that a protein of the aldo-keto reductase family carries out this reaction in E. coca. This protein, designated methylecgonone reductase, converts methylecgonone to methylecgonine, the penultimate step in cocaine biosynthesis. The protein has highest sequence similarity to other aldo-keto reductases, such as chalcone reductase, an enzyme of flavonoid biosynthesis, and codeinone reductase, an enzyme of morphine alkaloid biosynthesis. Methylecgonone reductase reduces methylecgonone (2-carbomethoxy-3-tropinone) stereospecifically to 2-carbomethoxy-3?-tropine (methylecgonine), and has its highest activity, protein level, and gene transcript level in young, expanding leaves of E. coca. This enzyme is not found at all in root tissues, which are the site of tropane alkaloid biosynthesis in the Solanaceae. This evidence supports the theory that the ability to produce tropane alkaloids has arisen more than once during the evolution of the angiosperms. PMID:22665766

Jirschitzka, Jan; Schmidt, Gregor W; Reichelt, Michael; Schneider, Bernd; Gershenzon, Jonathan; D'Auria, John Charles



The New ?-D-Glucosidase in Terpenoid-Isoquinoline Alkaloid Biosynthesis in Psychotria ipecacuanha*S?  

PubMed Central

Ipecac alkaloids produced in the medicinal plant Psychotria ipecacuanha such as emetine and cephaeline possess a monoterpenoid-tetrahydroisoquinoline skeleton, which is formed by condensation of dopamine and secologanin. Deglucosylation of one of the condensed products N-deacetylisoipecoside (1?(S)-epimer) is considered to be a part of the reactions for emetine biosynthesis, whereas its 1?(R)-epimer N-deacetylipecoside is converted to ipecoside in P. ipecacuanha. Here, we isolated a cDNA clone Ipeglu1 encoding Ipecac alkaloid ?-d-glucosidase from P. ipecacuanha. The deduced protein showed 54 and 48% identities to raucaffricine ?-glucosidase and strictosidine ?-glucosidase, respectively. Recombinant IpeGlu1 enzyme preferentially hydrolyzed glucosidic Ipecac alkaloids except for their lactams, but showed poor or no activity toward other substrates, including terpenoid-indole alkaloid glucosides. Liquid chromatography-tandem mass spectrometry analysis of deglucosylated products of N-deacetylisoipecoside revealed spontaneous transitions of the highly reactive aglycons, one of which was supposed to be the intermediate for emetine biosynthesis. IpeGlu1 activity was extremely poor toward 7-O-methyl and 6,7-O,O-dimethyl derivatives. However, 6-O-methyl derivatives were hydrolyzed as efficiently as non-methylated substrates, suggesting the possibility of 6-O-methylation prior to deglucosylation by IpeGlu1. In contrast to the strictosidine ?-glucosidase that stereospecifically hydrolyzes 3?(S)-epimer in terpenoid-indole alkaloid biosynthesis, IpeGlu1 lacked stereospecificity for its substrates where 1?(R)-epimers were preferred to 1?(S)-epimers, although ipecoside (1?(R)) is a major alkaloidal glucoside in P. ipecacuanha, suggesting the compartmentalization of IpeGlu1 from ipecoside. These facts have significant implications for distinct physiological roles of 1?(S)- and 1?(R)-epimers and for the involvement of IpeGlu1 in the metabolic fate of both of them.

Nomura, Taiji; Quesada, Alfonso Lara; Kutchan, Toni M.



In vitro and in vivo hepatoprotective effects of the total alkaloid fraction of Hygrophila auriculata leaves  

PubMed Central

Objective: To investigate the total alkaloid fraction of the methanol extract of leaves of Hygrophila auriculata for its hepatoprotective activity against CCl4-induced toxicity in freshly isolated rat hepatocytes, HepG2 cells, and animal models. Materials and Methods: Mature leaves of H. auriculata were collected, authenticated, and subjected to methanolic extraction followed by isolation of total alkaloid fraction. Freshly isolated rat hepatocytes were exposed to CCl4 (1%) along with/without various concentrations of the total alkaloid fraction (80–40 µg/ml). Protection of human liver-derived HepG2 cells against CCl4-induced damage was determined by the MTT assay. Twenty-four healthy Wistar albino rats (150–200 g) of either sex were used for the in vivo investigations. Liver damage was induced by administration of 30% CCl4 suspended in olive oil (1 ml/kg body weight, i.p). Results: The antihepatotoxic effect of the total alkaloid fraction was observed in freshly isolated rat hepatocytes at very low concentrations (80–40 µg/ml). A dose-dependent increase in the percentage viability was observed when CCl4-exposed HepG2 cells were treated with different concentrations of the total alkaloid fraction. Its in vivo hepatoprotective effect at 80 mg/kg body weight was comparable with that of the standard Silymarin at 250 mg/kg body weight. Conclusion: The total alkaloid fraction was able to normalize the biochemical levels which were altered due to CCl4 intoxication.

Raj, Vasanth P.; Chandrasekhar, Raghu H.; P., Vijayan; S. A., Dhanaraj; Rao, Mallikarjuna C.; Rao, Venkata J.; Nitesh, K.



New semisynthetic vinca alkaloids: chemical, biochemical and cellular studies  

PubMed Central

A new semisynthetic anti-tumour bis-indol compound, KAR-2 [3?-(?-chloroethyl)-2?,4?-dioxo-3,5?-spiro-oxazolidino-4-deacetoxy-vinblastine] with lower toxicity than vinca alkaloids used in chemotherapy binds to calmodulin but, in contrast to vinblastine, does not exhibit anti-calmodulin activity. To investigate whether the modest chemical modification of bis-indol structure is responsible for the lack of anti-calmodulin potency and for the different pharmacological effects, new derivatives have been synthesized for comparative studies. The synthesis of the KAR derivatives are presented. The comparative studies showed that the spiro-oxazolidino ring and the substitution of a formyl group to a methyl one were responsible for the lack of anti-calmodulin activities. The new derivatives, similar to the mother compounds, inhibited the tubulin assembly in polymerization tests in vitro, however their inhibitory effect was highly dependent on the organization state of microtubules; bundled microtubules appeared to be resistant against the drugs. The maximal cytotoxic activities of KAR derivatives in in vivo mice hosting leukaemia P388 or Ehrlich ascites tumour cells appeared similar to that of vinblastine or vincristine, however significant prolongation of life span could be reached with KAR derivatives only after the administration of a single dose. These studies plus data obtained using a cultured human neuroblastoma cell line showed that KAR compounds displayed their cytotoxic activities at significantly higher concentrations than the mother compounds, although their antimicrotubular activities were similar in vitro. These data suggest that vinblastine/vincristine damage additional crucial cell functions, one of which could be related to calmodulin-mediated processes. © 1999 Cancer Research Campaign

Orosz, F; Comin, B; Rais, B; Puigjaner, J; Kovacs, J; Tarkanyi, G; Acs, T; Keve, T; Cascante, M; Ovadi, J



Fusion with fluorescent proteins for subcellular localization of enzymes involved in plant alkaloid biosynthesis.  


To establish the role in alkaloid metabolism of candidate genes identified in silico or by Omics approaches, it may be essential to determine the subcellular localization of the encoded proteins. The fusion with fluorescent proteins (FP) may now be used as a quite effective and reliable tool to investigate this question. The methodology involves the choice of the FP, the design and production of the appropriate FP fusions, and the use of a transient or stable transformation protocol applied to a homologous or heterologous plant system. This chapter describes the application of this methodology to an enzyme involved in indole alkaloid biosynthesis, with general considerations on the development of the approach. PMID:20552458

Duarte, Patrícia; Memelink, Johan; Sottomayor, Mariana



Production of Peptide Ergot Alkaloids in Submerged Culture by Three Isolates of Claviceps purpurea  

PubMed Central

Three strains of Claviceps purpurea (Fr.) Tul., isolated from sclerotia grown on rye, produce under submerged conditions ergocryptine and ergotamine, ergocornine and ergosine, and ergocristine, respectively. All of the strains either lacked the ability to produce conidia or formed them sparingly, but they accumulated large quantities of lipids and sterols. The fermentations are typically divided into two phases. The first is characterized by the rapid utilization and exhaustion of the phosphate contained in the medium, rapid uptake of ammonium nitrogen and of citric acid, rapid growth, and low alkaloid production; the second phase is characterized by slower growth and by a marked accumulation of lipids, sterols, and alkaloids.

Amici, A. M.; Minghetti, A.; ScottI, T.; Spalla, C.; Tognoli, L.



Exploratory studies towards a total synthesis of the unusual bridged tetracyclic Lycopodium alkaloid lycopladine H.  


A strategy for a total synthesis of the structurally novel Lycopodium alkaloid lycopladine H has been investigated. Key steps that have been tested include: 1.a regioselective Diels-Alder cycloaddition of nitroethylene with an o-quinone ketal to produce the bicyclo[2.2.2]octane moiety of the alkaloid; 2. a stereoselective Henry reaction to generate the requisite functionality and configuration at C-5; 3. a stereoselective catalytic hydrogenation of a trisubstituted alkene to set the C-15 methyl configuration. PMID:22125345

Sacher, Joshua R; Weinreb, Steven M



Alkaloids from Zephyranthes robusta BAKER and their acetylcholinesterase- and butyrylcholinesterase-inhibitory activity.  


The bulbs of Zephyranthes robusta (Amaryllidaceae) have been extensively analyzed for their chemical constituents, resulting in the isolation of 13 alkaloids. The chemical structures of the isolated compounds were elucidated by mass-spectrometric, and 1D- and 2D-NMR spectroscopic experiments. The complete NMR assignments were achieved for hippeastidine. All isolated alkaloids were evaluated for their erythrocytic acetylcholinesterase and serum butyrylcholinesterase inhibitory activities using the Ellman's method. Significant acetylcholinesterase inhibition activity was exhibited by 8-O-demethylmaritidine (IC?? (HuAChE) 28.0±0.9 ?M). PMID:23776027

Kulhánková, Andrea; Cahlíková, Lucie; Novák, Zden?k; Macáková, Kate?ina; Kuneš, Ji?í; Opletal, Lubomír



Natural aristolactams and aporphine alkaloids as inhibitors of CDK1/cyclin B and DYRK1A.  


In an effort to find potent inhibitors of the protein kinases DYRK1A and CDK1/Cyclin B, a systematic in vitro evaluation of 2,500 plant extracts from New Caledonia and French Guyana was performed. Some extracts were found to strongly inhibit the activity of these kinases. Four aristolactams and one lignan were purified from the ethyl acetate extracts of Oxandra asbeckii and Goniothalamus dumontetii, and eleven aporphine alkaloids were isolated from the alkaloid extracts of Siparuna pachyantha, S. decipiens, S. guianensis and S. poeppigii. Among these compounds, velutinam, aristolactam AIIIA and medioresinol showed submicromolar IC50 values on DYRK1A. PMID:23467012

Marti, Guillaume; Eparvier, Véronique; Morleo, Barbara; Le Ven, Jessica; Apel, Cécile; Bodo, Bernard; Amand, Séverine; Dumontet, Vincent; Lozach, Olivier; Meijer, Laurent; Guéritte, Françoise; Litaudon, Marc



Bisindole alkaloids and secoiridoids from Alstonia macrophylla Wall. ex G. Don.  


The ethanolic extract from stems of a Thai medicinal plant, Alstonia macrophylla Wall. ex G. Don (Apocynaceae) showed a significant inhibitory effect on acetylcholinesterase (AChE) determined by using Ellman assay. Four compounds i.e., a bisindole alkaloid, macralstonine (1), a new bisindole alkaloid, thungfaine (2), a secoiridoid glycoside, sweroside (3) and a new secoiridoid glycoside, naresuanoside (4) were isolated. Compound 4 showed moderate AChE and butyrylcholinesterase (BChE) inhibitory effects. Interestingly, compound 4 inhibited cell growth on human androgen-sensitive prostate cancer cell line (LNCaP) but no effect on viability of human foreskin fibroblast cells (HF). PMID:21601617

Changwichit, Kanokwan; Khorana, Nantaka; Suwanborirux, Khanit; Waranuch, Neti; Limpeanchob, Nanteetip; Wisuitiprot, Wutichai; Suphrom, Nungruthai; Ingkaninan, Kornkanok



New cytotoxic tetrahydroprotoberberine-aporphine dimeric and aporphine alkaloids from Corydalis turtschaninovii.  


Two new tetrahydroprotoberberine-aporphine dimeric alkaloids, corydaturtschines A (1) and B (2), and a new aporphine derivative, ethyl glausuccinate (3), together with 13 known protoberberine (4-16) and nine known aporphine alkaloids (17-25), were isolated from the tubers of Corydalis turtschaninovii. The structures of these new compounds were determined through spectral analyses, including extensive 2D-NMR data. The absolute configurations of the compounds were clarified by CD spectroscopic studies. The isolated compounds were tested for their cytotoxicity against four human cancer cell lines in vitro using a sulforhodamine B bioassay. PMID:20509105

Kim, Ki Hyun; Piao, Cheng Jie; Choi, Sang Un; Son, Mi Won; Lee, Kang Ro



Evaluation of micellar electrokinetic capillary chromatography for the analysis of selected tobacco alkaloids.  


Micellar electrokinetic capillary chromatography was evaluated for simultaneous determination of several tobacco alkaloids with similar molecular structure. Satisfactory separation of nicotine, nornicotine, myosmine, anatabine and anabasine extracted from tobacco was achieved by introducing an ionic surfactant, sodium dodecyl sulfate, into the buffer system at a concentration of 100 mM. Sample preparation involved a single extraction with water containing 1% triethanolamine. Separation was performed on a 72 cm long, uncoated fused-silica capillary. Experimental parameters such as applied voltage, pH value, buffer composition and surfactant concentration were optimized. Enhancement of UV absorption of alkaloids in the presence of micelles was also studied. PMID:8885385

Yang, S S; Smetena, I; Goldsmith, A I



Numerical Controlled Tool Systems.  

National Technical Information Service (NTIS)

Lists 75 references on numerical controlled tool systems added to the CFSTI collection through March 1965. Includes research on automatically programmed tools (APT); numerically controlled machine tools, milling machines, machining of forging dies, shipya...



Evolutionary recruitment of a flavin-dependent monooxygenase for the detoxification of host plant-acquired pyrrolizidine alkaloids in the alkaloid-defended arctiid moth Tyria jacobaeae  

PubMed Central

Larvae of Tyria jacobaeae feed solely upon the pyrrolizidine alkaloid-containing plant Senecio jacobaea. Ingested pyrrolizidine alkaloids (PAs), which are toxic to unspecialized insects and vertebrates, are efficiently N-oxidized in the hemolymph of T. jacobaeae by senecionine N-oxygenase (SNO), a flavin-dependent monooxygenase (FMO) with a high substrate specificity for PAs. Peptide microsequences obtained from purified T. jacobaeae SNO were used to clone the corresponding cDNA, which was expressed in active form in Escherichia coli. T. jacobaeae SNO possesses a signal peptide characteristic of extracellular proteins, and it belongs to a large family of mainly FMO-like sequences of mostly unknown function, including two predicted Drosophila melanogaster gene products. The data indicate that the gene for T. jacobaeae SNO, highly specific for toxic pyrrolizidine alkaloids, was recruited from a preexisting insect-specific FMO gene family of hitherto unknown function. The enzyme allows the larvae to feed on PA-containing plants and to accumulate predation-deterrent PAs in the hemolymph.

Naumann, Claudia; Hartmann, Thomas; Ober, Dietrich



Minor tobacco alkaloids as biomarkers for tobacco use: comparison of users of cigarettes, smokeless tobacco, cigars, and pipes.  

PubMed Central

OBJECTIVES: This study (1) determined levels of various tobacco alkaloids in commercial tobacco products. (2) determined urinary concentrations, urinary excretion, and half-lives of the alkaloids in humans; and (3) examined the possibility that urine concentrations of nicotine-related alkaloids can be used as biomarkers of tobacco use. METHODS: Nicotine intake from various tobacco products was determined through pharmacokinetic techniques. Correlations of nicotine intake with urinary excretion and concentrations of anabasine, anatabine, nornicotine, nicotine, and cotinine were examined. By using urinary excretion data, elimination half-lives of the alkaloids were calculated. RESULTS: Alkaloid levels in commercial tobacco products, in milligrams per gram, were as follows: nicotine, 6.5 to 17.5; nornicotine, 0.14 to 0.66; anabasine, 0.008 to 0.030; and anatabine, 0.065 to 0.27. Measurable concentrations of all alkaloids were excreted in the urine of most subjects smoking cigarettes, cigars, and pipes and using smokeless tobacco. Correlations between nicotine intake and alkaloid concentrations were good to excellent. CONCLUSIONS: Anabasine and anatabine, which are present in tobacco but not in nicotine medications, can be used to assess tobacco use in persons undergoing nicotine replacement therapy.

Jacob, P; Yu, L; Shulgin, A T; Benowitz, N L



Study on the aconitine-type alkaloids of Radix Aconiti Lateralis and its processed products using HPLC-ESI-MSn.  


The type and content change of alkaloids of Radix Aconiti Lateralis (Lateral root of Aconitum carmichaeli Debx, an important and popular medicinal herb in Traditional Chinese Medicine) in processing were studied using high performance liquid chromatography-electrospray ionization-multi-stage mass spectrometry (HPLC-ESI-MS(n)). Extract containing alkaloids, which were known to be the main bioactive components of the herb, was prepared by 1% (v/v) hydrochloric acid solution. An HPLC method which can simultaneously separate these alkaloids was established with gradient elution mode. Forty-eight compounds were structurally identified by employing LC-MS(n) techniques; the MS(n) spectra of most alkaloids displayed a characteristic behaviour of loss of CH(3)COOH (60 u), CH(3)OH (32 u), C(6)H(5)COOH (122 u), CO (28 u) and H(2)O (18 u). Among them, the fragmentation ion C6H5COOH (122 u) was reported for the first time. By comparison, 22 compounds were found both in the crude materials and the processed products; 17 alkaloids were only found in the processed products and 9 alkaloids,which existed in crude material, could not be detected after processing. In the process of identification, we found new kinds of alkaloids, with protonated molecules at m/z 452, 468, and 482. We called these compounds dehydra-hypaconine, dehydra-mesaconine, and dehydra-aconine, respectively. PMID:22447443

Liu, Yonggang; Tan, Peng; Li, Fei; Qiao, Yanjiang



Alkaloid analysis by high-performance liquid chromatography-solid phase extraction-nuclear magnetic resonance: new strategies going beyond the standard.  


The hyphenated technique HPLC-SPE-NMR is an important tool for rapid dereplication of complex mixtures of in particular small molecules and has been successfully employed in natural product research. However, positively charged alkaloids at low pH are often poorly trapped on the generally used SPE cartridge limiting the general application of the procedure. In this work, two new approaches for efficient SPE trapping of alkaloids and elution efficiencies were evaluated using 24 model alkaloids. Use of a 0.1 M NaOH solution as the post-column dilution greatly enhanced trapping of alkaloids on the commonly used cartridge containing divinylbenzene polymer (GP resin). This procedure, however, was unsuitable for trapping phenolic alkaloids. Severe line broadening and immiscibility with water made chloroform-d(1) unsuited as eluent. None of these problems occurred when methanol-d(4) was used as eluent. Previously, mixed mode cation exchange sorbents have not been used in HPLC-SPE-NMR analysis of natural products. In contrast to GP resin this material showed good retention and elution characteristics for retention and elution of alkaloids. As well the use of methanol-d(4) containing 1% aqueous NaOD (40%) as methanol-d(4) containing 5% aqueous NH(4)OH (30%) as eluents were successful, even though elution of alkaloids with pK(a) of the corresponding acid above 10 proved difficult. Alkaloid extracts of Huperzia selago containing complex aliphatic alkaloids and Triclisia patens containing bisbenzylisoquinoline alkaloids were used for validation of the protocols for analysis of a diverse collection of alkaloids. Mixed mode cation exchange sorbent was efficient for trapping and elution of both types of alkaloids as evidenced by acquisition of 2D NMR data for all trapped compounds. In contrast, GP resin proved only viable for all the H. selago alkaloids whereas trapping and elution of bisbenzylisoquinoline alkaloids were dubious. PMID:23195707

Johansen, Kenneth T; Ebild, Sarah J; Christensen, S Brøgger; Godejohann, Markus; Jaroszewski, Jerzy W



A vacuolar class III peroxidase and the metabolism of anticancer indole alkaloids in Catharanthus roseus  

PubMed Central

Plants possess a unique metabolic diversity commonly designated as secondary metabolism, of which the anticancer alkaloids from Catharanthus roseus are among the most studied. Recently, in a classical function-to-protein-to-gene approach, we have characterized the main class III peroxidase (Prx) expressed in C. roseus leaves, CrPrx1, implicated in a key biosynthetic step of the anticancer alkaloids. We have shown the vacuolar sorting determination of CrPrx1 using GFP fusions and we have obtained further evidence supporting the role of this enzyme in alkaloid biosynthesis, indicating the potential of CrPrx1 as a molecular tool for the manipulation of alkaloid metabolism. Here, we discuss how plant cells may regulate Prx reactions. In fact, Prxs form a large multigenic family whose members accept a broad range of substrates and, in their two subcellular localizations, the cell wall and the vacuole, Prxs co-locate with a large variety of secondary metabolites which can be accepted as substrates. How then, are Prx reactions regulated? Localization data obtained in our lab suggest that arabinogalactan proteins (AGPs) and Prxs may be associated in membrane microdomains, evocative of lipid rafts. Whether plasma membrane and/or tonoplast microcompartmentation involve AGPs and Prxs and whether this enables metabolic channeling determining Prx substrate selection are challenging questions ahead.

Duarte, Patricia; Figueiredo, Raquel; Ros Barcelo, Alfonso



Facile [7C+1C] Annulation as an Efficient Route to Tricyclic Indolizidine Alkaloids.  


A handle on annulation: The two alkenoyl moieties of the cyclic dithiolane are parallel to each other and enables the [7C+1C] annulation with ethyl isocyanoacetate to occur. As a result, tricyclic indolizidine alkaloids are constructed by a two-step, base-catalyzed [7C+1C] annulation/intramolecular cyclization with subsequent reduction/cyclization. PMID:23821349

Xu, Xianxiu; Zhang, Lingjuan; Liu, Xiqing; Pan, Ling; Liu, Qun



Dimerization of functional pyrroloindolizines for the synthesis of complex myrmicarin alkaloids  

PubMed Central

The union of functionalized pyrroloindolizines for the synthesis of heterodimeric products relevant to myrmicarin alkaloids is described. Design and synthesis of tricyclic substrates and new methods for their union enable the investigation of late-stage cyclopentannulation strategies. The rapid assembly of dimeric structures using unique modes of pyrroloindolizine reactivity presents a concise approach to the dimeric myrmicarins and relevant derivatives.

Ondrus, Alison E.; Kaniskan, H. Umit; Movassaghi, Mohammad



Gardovatine, a novel Strychnos-Strychnos bisindole alkaloid with cytotoxicity from Gardneria oveta.  


Gardovatine (1), the first Strychnos-Strychnos alkaloid with a C3/C7 cleaved backbone, was isolated from twigs and leaves of Gardneria ovate, together with an analogue divarine (2). The structure was established by extensive spectroscopic methods. Both compounds showed potential cytotoxicities against five human cancer cell lines. PMID:24012119

Feng, Tao; Li, Xiao-Ning; Zhang, Bao-Hong; Li, Yan; Cai, Xiang-Hai; Liu, Ya-Ping; Luo, Xiao-Dong



Antidepressant-like effect of total alkaloids extracted from Semen Zizyphi Sponosae  

Microsoft Academic Search

The present study was undertaken to investigate the antidepressant potential of total alkaloids isolated from Semen Zizyphi Sponosae (TAS) and its possible mechanisms Mouse models of depression including the forced swimming test (FST) and the tail suspension test (TST) were used to evaluate the effects of TAS. A possible mechanism was explored in the test of antagonism of reserpine-induced hypothermia

Wei Qiao; Lu Li; Jingshu Liu; Yi Yang; Liyan Ren



Alkaloid presence and brine shrimp (Artemia salina) bioassay of medicinal species of eastern Nicaragua.  


We used an alkaloid test and a brine shrimp bioassay to assess the bioactivity of the medicinal plants used by eastern Nicaraguan healers in traditional medicine. Ethnomedicinal uses were obtained from interviews of traditional healers. Aqueous extracts derived from 30 species of angiosperms were assayed for the presence of alkaloids and toxicity. Species tested are distributed in 30 genera and 21 families. Of the 30 species tested for alkaloids with Dragendorff's reagent, 29 contained alkaloids. Toxicological analysis was conducted using the brine shrimp lethal assay (BSLA). Biological activity using BSLA was recorded as the median lethal concentration (LC50) that kills 50% of the larvae within 24 h of contact with the aqueous plant extracts. The LC50 of the shrimp was less than 2500 microg/mL for 3 (10%) species, 2500-5000 microg/mL for 9 (30%), 5001-7500 microg/mL for 7 (23%), 7501-10000 microg/mL for 3 (10%), and greater than 10000 microg/mL for 8 (27%) of the species. The members of the orders Santales and Rubiales in general contained species with greater toxicity than any other group. Struthanthus cassythoides (Struthanthus cassythoides Millsp.(Loranthaceae)). (LC50 1574 microg/mL) and Alibertia edulis (Rich.) A. Rich. (Rubiaceae) (LC50 1741 microg/mL) were the most toxic. PMID:20645724

Coe, Felix G; Parikh, Dimpi M; Johnson, Caley A




Technology Transfer Automated Retrieval System (TEKTRAN)

Certain lupines (Lupinus spp.) contain alkaloids that cause contracture-type skeletal birth defects and cleft palate (“Crooked calf syndrome”) if the pregnant cow consumes them during the 40 – 70th day of gestation. The objective of this study was to determine when cattle graze velvet lupine (Lupi...


A virus-induced gene silencing approach to understanding alkaloid metabolism in Catharanthus roseus  

PubMed Central

The anticancer agents vinblastine and vincristine are bisindole alkaloids derived from coupling vindoline and catharanthine, monoterpenoid indole alkaloids produced exclusively by Madagascar periwinkle (Catharanthus roseus) plants. Industrial production of vinblastine and vincristine currently relies on isolation from C. roseus leaves, a process that affords these compounds in 0.0003–0.01% yields. Metabolic engineering efforts to improve alkaloid content or provide alternative sources of the bisindole alkaloids ultimately rely on the isolation and characterization of the genes involved. Several vindoline biosynthetic genes have been isolated, and the cellular and subcellular organization of the corresponding enzymes has been well studied. However, due to the leaf-specific localization of vindoline biosynthesis, and the lack of production of this precursor in cell suspension and hairy root cultures of C. roseus, further elucidation of this pathway demands the development of reverse genetics approaches to assay gene function in planta. The bipartite pTRV vector system is a Tobacco Rattle Virus-based virus-induced gene silencing (VIGS) platform that has provided efficient and effective means to assay gene function in diverse plant systems. We have developed a VIGS method to investigate gene function in C. roseus plants using the pTRV vector system. The utility of this approach in understanding gene function in C. roseus leaves is demonstrated by silencing known vindoline biosynthetic genes previously characterized in vitro.

Liscombe, David K.; O'Connor, Sarah E.




Microsoft Academic Search

An overview of the recent molecular spectroscopic work on the methylxanthine alkaloid, theobromine and its two closely related relatives, caffeine and theophylline is presented. The role of molecular spectroscopy in studies of the coordination chemistry of these methylxanthine compounds is also discussed briefly.

Brij B. Tewari; Guillaume Beaulieu-Houle; Aaron Larsen; Rosine Kengne-Momo; Karine Auclair; Ian S. Butler



Reagent?Controlled Asymmetric Iodolactonization Using Cinchona Alkaloids as Chiral Sources  

Microsoft Academic Search

A novel method for reagent?controlled asymmetric iodolactonization of 5?aryl?4?pentenoic acids is reported. This work uses carboxylate ion pairs combined with cinchona alkaloids as chiral sources of carboxylate anion for the first time leading to a mixture of two regio?isomeric iodolactones with moderate enantioselectivity (exo?18.5% ee, endo?35.0% ee) under mild reaction conditions.

Mang Wang; Lian Xun Gao; Wei Yue; Wen Peng Mai



Synergistic Hepatotoxicity from Coexposure to Bacterial Endotoxin and the Pyrrolizidine Alkaloid Monocrotaline  

Microsoft Academic Search

Individuals are commonly exposed to bacterial endotoxin (lipopolysaccharide [LPS]) through gram-negative bacterial infection and from its translocation from the gastrointestinal lumen into the circulation. Inasmuch as noninjurious doses of LPS augment the hepatotoxicity of certain xenobiotic agents, exposure to small amounts of LPS may be an important determinant of susceptibility to chemical intoxication. Monocrotaline (MCT) is a pyrrolizidine alkaloid phytotoxin

Steven B. Yee; Shawn Kinser; Dwayne A. Hill; C. Charles Barton; Jon A. Hotchkiss; Jack R. Harkema; Patricia E. Ganey; Robert A. Roth



Doppler ultrasonography for evaluating vascular responses to ergopeptine alkaloids in livestock  

Technology Transfer Automated Retrieval System (TEKTRAN)

Ergot alkaloids are produced by non-spore producing fungal endophytes that infect certain species of grasses, most notably tall fescue [Lolium arundinaceum (Schreb.) Darbysh.] and perennial ryegrass (Lolium perenne L.), and the spore producing Claviceps spp. that infect seed heads of certain grasses...


Novel and efficient synthetic path to proaporphine alkaloids: total synthesis of (+/-)-stepharine and (+/-)-pronuciferine.  


[reaction: see text] A novel synthetic path to proaporphine alkaloids was established by employing aromatic oxidation with a hypervalent iodine reagent, where an unprecedented carbon-carbon bond forming reaction between the para-position of a phenol group and an enamide-carbon took place smoothly to give the desired spiro-cyclohexadienone. PMID:16468735

Honda, Toshio; Shigehisa, Hiroki



Development of enantioselective synthetic routes to the hasubanan and acutumine alkaloids.  


We describe a general strategy to prepare the hasubanan and acutumine alkaloids, a large family of botanical natural products that display antitumor, antiviral, and memory-enhancing effects. The absolute stereochemistry of the targets is established by an enantioselective Diels-Alder reaction between 5-(trimethylsilyl)cyclopentadiene (36) and 5-(2-azidoethyl)-2,3-dimethoxybenzoquinone (24). The Diels-Alder adduct 38 is transformed to the tetracyclic imine 39 by a Staudinger reduction-aza-Wittig sequence. The latter serves as a universal precursor to the targets. Key carbon-carbon bond constructions include highly diastereoselective acetylide additions to the N-methyliminium ion derived from 39 and Friedel-Crafts and Hosomi-Sakurai cyclizations to construct the carbocyclic skeleton of the targets. Initially, this strategy was applied to the syntheses of (-)-acutumine (4), (-)-dechloroacutumine (5), and four hasubanan alkaloids (1, 2, 3, and 8). Herein, the synthetic route is adapted to the syntheses of six additional hasubanan alkaloids (12, 13, 14, 15, 18, and 19). The strategic advantage of 5-(trimethylsilyl)cyclopentadiene Diels-Alder adducts is demonstrated by site-selective functionalization of distal carbon-carbon ?-bonds in the presence of an otherwise reactive norbornene substructure. Evaluation of the antiproliferative properties of the synthetic metabolites revealed that four hasubanan alkaloids are submicromolar inhibitors of the N87 cell line. PMID:24032758

Calandra, Nicholas A; King, Sandra M; Herzon, Seth B



Saoussanabiloïde, a novel antifungal alkaloid from Echiochilon fruticosum Desf. growing in Tunisia  

Microsoft Academic Search

Bioactivity guided fractionation of Echiochilon fruticosum Desf. (Boraginaceae) butanolic extract biautography assay against fungi led to the isolation of a new bioactive alkaloid, named saoussanabiloïde (1). Its structure was established on the basis of spectroscopic measurements, IR, MS and 2D NMR using COSY, HMQC and HMBC experiments. The strongest inhibitory effect of the butanolic extract, from fractions derived from the

S. Hammami; N. Mighri; H. Ben Jannet; N. Boughalleb; A. Zardi-Bergaoui; A. Nefzi; P. Abreu; Z. Mighri



Studies on the alkaloidal components of the fruits of Lycium chinense  

Microsoft Academic Search

N9-Formylharman, 1-carbomethoxy-?-carboline and perlolyrine with an unidentified alkaloid (C10H13NO2, M+ 179.094) have been isolated from the fruits ofLycium chinense Miller (Solanaceae) and characterized on the basis of chemical and physical evidence.

Byung Hoon Han; Jeong Hill Park; Myung Hwan Park; Yong Nam Han



Cytotoxicity of the ?-carboline alkaloids harmine and harmaline in human cell assays in vitro  

Microsoft Academic Search

?-Carboline alkaloids are natural products widely distributed in plants and also found in alcoholic beverages, well-cooked foods and tobacco smoke. Various authors have reported genotoxic activities of several carboline in prokaryotic and eukaryotic cells that have been attributed to their abilities to intercalate into DNA. But studies on the genotoxic and on the cytotoxic potencies in human cells in vitro

Judith Jiménez; Leticia Riverón-Negrete; Fikrat Abdullaev; Javier Espinosa-Aguirre; Rosario Rodríguez-Arnaiz



Extraction, Identification, and Quantification of Harmala Alkaloids in Three Species of Passiflora  

Microsoft Academic Search

Harmala alkaloids are a common plant extract with a number of reported uses including as stimulants and monoamine oxidase (MAO) inhibitors. Their reported activity has led some researchers to identify them as the principal active constituent in passion flowers, an abundant plant which has been identified to have a number of pharmaceutical uses of its own. Harmalas are commonly extracted

Abigail Frye; Catherine Haustein


Pyrrolizidine alkaloid biosynthesis, evolution of a pathway in plant secondary metabolism.  


The system of pyrrolizidine alkaloids has proven to be a powerful system for studying the evolution of a biosynthetic pathway in plant secondary metabolism. Pyrrolizidine alkaloids are typical plant secondary products produced by the plant as a defense against herbivores. The first specific enzyme, homospermidine synthase, has been shown to have evolved by duplication of the gene encoding deoxyhypusine synthase, which is involved in primary metabolism. Despite the identical function of homospermidine synthase for pyrrolizidine alkaloid biosynthesis in the various plant lineages, this gene duplication has occurred several times independently during angiosperm evolution. After duplication, these gene copies diverged with respect to gene function and regulation. In the diverse plant lineages producing pyrrolizidine alkaloids, homospermidine synthase has been shown to be expressed in a variety of tissues, suggesting that the regulatory elements were recruited individually after the duplication of the structural gene. The molecular, kinetic, and expression data of this system are discussed with respect to current models of gene and pathway evolution. PMID:19545881

Ober, Dietrich; Kaltenegger, Elisabeth



The total synthesis of alkaloids (-)-histrionicotoxin 259A, 285C and 285E.  


The first total syntheses of three "unsymmetrical" (i.e. different terminal groups in the side chains) members of the histrionicotoxin family of alkaloids have been accomplished via stepwise introduction of the two side chain moieties onto a common tricyclic core. PMID:12109088

Smith, Catherine J; Holmes, Andrew B; Press, Neil J



Yuehchukene, a Novel Anti-implantation Indole Alkaloid from Murraya paniculata.  


Yuehchukene, 11beta-(3'-indolyl-7,9alpha,9beta-trimethyl-5beta,8,9,10beta-tetrahydroindano-[2,3- B]indole, a novel dimeric indole alkaloid from the roots of MURRAY A PANICULATA has potent anti-implantation activity in rats at 3 mg/kg P. O. dosing on pregnancy day 2. PMID:17340519

Kong, Y C; Ng, K H; Wat, K H; Wong, A; Saxena, I F; Cheng, K F; But, P P; Chang, H T



Determination of pyrrolizidine alkaloids in comfrey by liquid chromatography–electrospray ionization mass spectrometry  

Microsoft Academic Search

Symphytum officinale L. (comfrey) is a medicinal plant commonly used in decoctions and aliments. Besides therapeutic bioactive compounds present in the herb, it is found to contain hepatotoxic pyrrolizidine alkaloids (PAs), such as lycopsamine and others. In the present study, PAs such as lycopsamine, echimidine and lasiocarpine were determined using electrospray liquid chromatography–mass spectrometry (LC–MS) with the method precision (relative

Feng Liu; Sow Yin Wan; Zhangjian Jiang; Sam Fong Yau Li; Eng Shi Ong; Jhon Carlos Castaño Osorio



A potential role of alkaloid extracts from Salsola species (Chenopodiaceae) in the treatment of Alzheimer's disease.  


From the aerial parts of Salsola oppositofolia, S. soda and S. tragus an alkaloid extract was obtained and tested to evaluate antioxidant and anti-cholinesterase activities. The in vitro study of the antioxidant activity by the DPPH method revealed a significant activity of Salsola alkaloid extracts with IC(50) values ranging from 16.30 microg/mL for S. oppositifolia to 26.17 microg/mL for S. tragus. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were evaluated. S. tragus alkaloid extract exerted the highest inhibitory activity against AChE (IC(50) of 30.2 microg/mL) and BChE (IC(50) of 26.5 microg/mL). Interestingly, S. soda and S. oppositifolia exhibited a selective inhibitory activity against BChE with IC(50) values of 34.3 microg/mL and 32.7 microg/mL, respectively. Tetrahydroisoquinoline alkaloids were identified and quantified by GC/MS analysis. PMID:18720188

Tundis, Rosa; Menichini, Federica; Conforti, Filomena; Loizzo, Monica R; Bonesi, Marco; Statti, Giancarlo; Menichini, Francesco



Coordinated regulation of two indole alkaloid biosynthetic genes from Catharanthus roseus by auxin and elicitors  

Microsoft Academic Search

Catharanthus roseus (periwinkle) produces a wide range of terpenoid indole alkaloids, including several pharmaceutically important compounds, from the intermediate strictosidine. The complete mRNA sequence for the enzyme strictosidine synthase (SSS) was determined. Comparison of the primary structure of the encoded protein with the amino-terminal sequence of purified SSS indicated the presence of a signal peptide of 31 amino acids in

Giancarlo Pasquali; Oscar J. M. Goddijn; Anthony Waal; Robert Verpoorte; Rob A. Schilperoort; J. Harry C. Hoge; Johan Memelink



In Vitro Toxicity of Kava Alkaloid, Pipermethystine, in HepG2 Cells Compared to Kavalactones  

Microsoft Academic Search

Kava herbal supplements have been recently associated with acute hepatotoxicity, leading to the ban of kava products in ap- proximately a dozen countries around the world. It is suspected that some alkaloids from aerial kava may have contributed to the problem. Traditionally, Pacific Islanders use primarily the under- ground parts of the shrub to prepare the kava beverage. However, some

Pratibha V. Nerurkar; Klaus Dragull; Chung-Shih Tang



Suppression of Puerperal Lactation with an Ergot Alkaloid: A Double-blind Study  

PubMed Central

A double-blind trial was performed in 60 women to establish the effectiveness of an ergot alkaloid, 2-Br-alpha-ergocryptine (ergocryptine; CB 154), in suppressing puerperal lactation and to compare it with stilboestrol and a placebo. At the doses selected ergocryptine and stilboestrol were equally effective.

Varga, L.; Lutterbeck, P. M.; Pryor, J. S.; Wenner, R.; Erb, H.



Synthesis of Notoamide J: A Potentially Pivotal Intermediate in the Biosynthesis of Several Prenylated Indole Alkaloids  

PubMed Central

An efficient total synthesis of notoamide J, a new prenylated indole alkaloid and potential biosynthetic precursor, is described herein. Starting from L-proline and a substituted tryptophan derivative, this synthesis also employs an oxidation and pinacol rearrangment for the formation of the oxindole in the final step.

Finefield, Jennifer M.; Williams, Robert M.



Divergent and efficient syntheses of the lycopodium alkaloids (-)-lycojaponicumin?c, (-)-8-deoxyserratinine, (+)-fawcettimine, and (+)-fawcettidine.  


Four from one: The four title alkaloids (structures shown in blue box) have been synthesized by using a common versatile intermediate with a 6/5/5 tricyclic skeleton. This tricyclic intermediate could be easily assembled by using an intramolecular carbene addition/cyclization and a Dieckmann condensation/Tsuji-Trost allylation as key steps. PMID:24000162

Hou, Si-Hua; Tu, Yong-Qiang; Liu, Lin; Zhang, Fu-Min; Wang, Shao-Hua; Zhang, Xiao-Ming



An Overview of Molecular Spectroscopic Studies on Theobromine and Related Alkaloids  

Microsoft Academic Search

Abstract: An overview of the recent molecular spectroscopic work on the methylxanthine alkaloid theobromine and its two closely related relatives, caffeine and theophylline, is presented. The role of molecular spectroscopy in studies of the coordination chemistry of these methylxanthine compounds is also briefly discussed.

Brij B. Tewari; Guillaume Beaulieu-Houle; Aaron Larsen; Rosine Kengne-Momo; Karine Auclair; Ian S. Butler



The effect of dosage forms on the duration and continuity of action of belladonna alkaloids  

Microsoft Academic Search

A placebo-controlled, double-blind evaluation of encapsulated sustained release and nonsustained release forms of belladonna alkaloids was conducted to compare the effectiveness of these oral dosage forms. The evaluation was conducted according to a balanced, Latin Square design. A modified Mushin Salivary Suppression Test was used as the criteria for measuring results.

Davis R. Reese; Spencer M. Free; Joseph V. Swintosky; Morton I. Grossman



Tropane alkaloids — metabolic response to carbohydrate signal in root cultures of Atropa belladonna  

Microsoft Academic Search

Elevated sucrose enhanced the tropane alkaloid accumulation, in particular of calystegines, in root cultures of Atropabelladonna (A.belladonna). Sucrose, several hexoses and sugar analogues were applied to distinguish the effects of sugars as nutrients versus signals, and to investigate the role of sucrose, monosaccharides, sugar transport, sugar phosphorylation by hexokinase and Ca2+ as part of the sugar sensing and signal transfer

Grit Rothe; Birgit Dräger



Silencing of tryptamine biosynthesis for production of nonnatural alkaloids in plant culture  

PubMed Central

Natural products have long served as both a source and inspiration for pharmaceuticals. Modifying the structure of a natural product often improves the biological activity of the compound. Metabolic engineering strategies to ferment “unnatural” products have been enormously successful in microbial organisms. However, despite the importance of plant derived natural products, metabolic engineering strategies to yield unnatural products from complex, lengthy plant pathways have not been widely explored. Here, we show that RNA mediated suppression of tryptamine biosynthesis in Catharanthus roseus hairy root culture eliminates all production of monoterpene indole alkaloids, a class of natural products derived from two starting substrates, tryptamine and secologanin. To exploit this chemically silent background, we introduced an unnatural tryptamine analog to the production media and demonstrated that the silenced plant culture could produce a variety of novel products derived from this unnatural starting substrate. The novel alkaloids were not contaminated by the presence of the natural alkaloids normally present in C. roseus. Suppression of tryptamine biosynthesis therefore did not appear to adversely affect expression of downstream biosynthetic enzymes. Targeted suppression of substrate biosynthesis therefore appears to be a viable strategy for programming a plant alkaloid pathway to more effectively produce desirable unnatural products. Moreover, although tryptamine is widely found among plants, this silenced line demonstrates that tryptamine does not play an essential role in growth or development in C. roseus root culture. Silencing the biosynthesis of an early starting substrate enhances our ability to harness the rich diversity of plant based natural products.

Runguphan, Weerawat; Maresh, Justin J.; O'Connor, Sarah E.



Structure elucidation and NMR assignments of two unusual monoterpene indole alkaloids from Psychotria stachyoides.  


Two unusual monoterpene indole alkaloids, stachyoside (1) and nor-methyl-23-oxo-correantoside (2), have been isolated from the aerial parts of Psychotria stachyoides. The structural elucidation of both compounds was performed by the aid of HRESIMS, FT-IR, and 1D- and 2D-NMR techniques including COSY, HSQC, HMBC, and NOESY. PMID:20641135

Pimenta, Antonia Torres Avila; Braz-Filho, Raimundo; Delprete, Piero Giuseppe; de Souza, Elnatan Bezerra; Silveira, Edilberto Rocha; Lima, Mary Anne Sousa



Alasmontamine A, A first tetrakis monoterpene indole alkaloid from Tabernaemontana elegans.  


A novel tetrakis monoterpene indole alkaloid, alasmontamine A (1) consisting of bis-vobtusine-type skeletons, was isolated from the leaves of Tabernaemontana elegans. The structure including the relative stereochemistry was elucidated on the basis of spectroscopic data. Alasmontamine A (1) exhibited moderate cell growth inhibitory activity against HL-60 cells. PMID:19921789

Hirasawa, Yusuke; Miyama, Saori; Hosoya, Takahiro; Koyama, Koichiro; Rahman, Abdul; Kusumawati, Idha; Zaini, Noor Cholies; Morita, Hiroshi



Substrate specificity and diastereoselectivity of strictosidine glucosidase, a key enzyme in monoterpene indole alkaloid biosynthesis  

Microsoft Academic Search

Strictosidine glucosidase (SGD) from Catharanthus roseus catalyzes the deglycosylation of strictosidine, an intermediate from which thousands of monoterpene indole alkaloids are derived. The steady-state kinetics of SGD with a variety of strictosidine analogs revealed the substrate preferences of this enzyme at two key positions of the strictosidine substrate. Additionally, SGD from C. roseus turns over both strictosidine and its stereoisomer

Nancy Yerkes; Jia Xin Wu; Elizabeth McCoy; M. Carmen Galan; Shi Chen; Sarah E. O’Connor



Animal and Plant Members of a Gene Family with Similarity to Alkaloid-Synthesizing Enzymes  

Microsoft Academic Search

Here we describe novel members of a gene family which have similarity to strictosidine synthase (SS), one of the key enzymes in the production of monoterpene indole alkaloids. In addition to the first animal member of the family described previously (Drosophila hemomucin), a second Drosophila member has been identified, which appears to differ in subcellular distribution from hemomucin. In Arabidopsis,

Marco Fabbri; Gabriele Delp; Otto Schmidt; Ulrich Theopold



Silencing of tryptamine biosynthesis for production of nonnatural alkaloids in plant culture.  


Natural products have long served as both a source and inspiration for pharmaceuticals. Modifying the structure of a natural product often improves the biological activity of the compound. Metabolic engineering strategies to ferment "unnatural" products have been enormously successful in microbial organisms. However, despite the importance of plant derived natural products, metabolic engineering strategies to yield unnatural products from complex, lengthy plant pathways have not been widely explored. Here, we show that RNA mediated suppression of tryptamine biosynthesis in Catharanthus roseus hairy root culture eliminates all production of monoterpene indole alkaloids, a class of natural products derived from two starting substrates, tryptamine and secologanin. To exploit this chemically silent background, we introduced an unnatural tryptamine analog to the production media and demonstrated that the silenced plant culture could produce a variety of novel products derived from this unnatural starting substrate. The novel alkaloids were not contaminated by the presence of the natural alkaloids normally present in C. roseus. Suppression of tryptamine biosynthesis therefore did not appear to adversely affect expression of downstream biosynthetic enzymes. Targeted suppression of substrate biosynthesis therefore appears to be a viable strategy for programming a plant alkaloid pathway to more effectively produce desirable unnatural products. Moreover, although tryptamine is widely found among plants, this silenced line demonstrates that tryptamine does not play an essential role in growth or development in C. roseus root culture. Silencing the biosynthesis of an early starting substrate enhances our ability to harness the rich diversity of plant based natural products. PMID:19666570

Runguphan, Weerawat; Maresh, Justin J; O'Connor, Sarah E



Seasonal variation in pyrrolizidine alkaloid concentration and plant development in Senecio madagascariensis poir. (Asteraceae) in Brazil  

Technology Transfer Automated Retrieval System (TEKTRAN)

This chapter presents the results of studies conducted in the municipality of Eldorado do Sul, State of Rio Grande do Sul, Brazil, in July and October 2007 and January and May 2008 to measure the pyrrolizidine alkaloid (PA) concentrations of S. madagascariensis plant material (including leaves, flow...


Gene expression changes induced by the tumorigenic pyrrolizidine alkaloid riddelliine in liver of Big Blue rats  

Microsoft Academic Search

BACKGROUND: Pyrrolizidine alkaloids (PAs) are probably the most common plant constituents that poison livestock, wildlife, and humans worldwide. Riddelliine is isolated from plants grown in the western United States and is a prototype of genotoxic PAs. Riddelliine was used to investigate the genotoxic effects of PAs via analysis of gene expression in the target tissue of rats in this study.

Nan Mei; Lei Guo; Ruqing Liu; James C. Fuscoe; Tao Chen



New alkaloids from a marine-derived fungus Neosartorya sp.HN-M-3.  


Two new indole alkaloids, tryptoquivalines R and S, have been isolated from a marine-derived fungus Neosartorya sp.HN-M-3. Their structures were determined on the basis of spectroscopic methods including 1D and 2D NMR experiments. PMID:23768000

Xu, Nan; Cao, Yue; Wang, Li; Chen, Gang; Pei, Yue-Hu



Contact toxicities of Anuran Skin Alkaloids against the Red Imported Fire Ant (Solenopsis invicta)  

Technology Transfer Automated Retrieval System (TEKTRAN)

Nearly 500 alkaloids, representing over 20 structural classes, have been identified from the skin of poison frogs (Dendrobatidae). These cutaneous compounds, which are derived from leaf-litter arthropods eaten by the frogs, generally are believed to deter predators. We tested the red imported fire a...


Damage-induced alkaloids in tobacco: Pot-bound plants are not inducible  

Microsoft Academic Search

Field-grown wild tobacco plants (Nicotiana sylvestris) were subjected to a defoliation regime designed to mimic the rate and amount of leaf mass removed by one tobacco hornworm per plant. Undamaged leaves on these plants undergo a dramatic (457% for leaf position 5, 410% for leaf position 8) increase in total leaf alkaloids compared to same-age and positioned control leaves on

Ian T. Baldwin



Pharmacology of ephedra alkaloids and caffeine after single-dose dietary supplement use  

Microsoft Academic Search

Objective: Serious cardiovascular toxicity has been reported in people taking dietary supplements that contain ma huang (Ephedra) and guarana (caffeine). We assessed the pharmacokinetics and pharmacodynamics of a dietary supplement that contains these herbal stimulants.Methods: Eight healthy adults received a single oral dose of a thermogenic dietary supplement labeled to contain 20 mg ephedrine alkaloids and 200 mg caffeine after

Christine A. Haller; Peyton Jacob; Neal L. Benowitz



Evaluation of the Vasoconstrictive Capacity of Tall Fescue Alkaloids Using Fescue Naive Bovine Lateral Saphenous Veins  

Technology Transfer Automated Retrieval System (TEKTRAN)

Vasoconstriction is associated with consumption of toxic endophyte-infected tall fescue. Because it is not known if endophyte-produced alkaloids act alone or in concert, the objective of this study was to examine the vasoconstrictive potentials of D-lysergic acid (LSA) and ergovaline (ERV) individua...


On the elucidation of the mechanism of Vinca alkaloid fluorination in superacidic medium.  


Detailed investigations on one of the key steps of the superacidic fluorination of Vinca alkaloids that is the origin of C20' activation are reported. While two different pathways can be envisioned for the emergence of the transient secondary carbocationic intermediate, isotopic labeling experiments unambiguously revealed the involvement of a 1,2-hydride shift mechanism. PMID:21732596

Giovanelli, Emerson; Leroux, Sébastien; Moisan, Lionel; Carreyre, Hélène; Thuéry, Pierre; Buisson, David-Alexandre; Meddour, Abdelkrim; Coustard, Jean-Marie; Thibaudeau, Sébastien; Rousseau, Bernard; Nicolas, Marc; Hellier, Paul; Doris, Eric



High performance liquid chromatography of selected alkaloids in ion-exchange systems.  


A HPLC procedure on strong cation exchange column (SCX) has been developed for the analysis of selected alkaloids from different chemical groups. The retention, separation selectivity, symmetry of peaks and system efficiency were examined in different eluent systems containing different types or concentrations of buffers at various pH and the addition of organic modifiers: methanol (MeOH), acetonitrile (CH3CN), tetrahydrofuran (THF) or dioxane (Dx). The retention factors as the function of the concentration of buffers, the mobile phase pH and the percentage of modifier in the eluents were investigated. More symmetrical peaks and the highest theoretical plate number were obtained in eluents containing acetonitrile or tetrahydrofuran. In most cases, the increase of buffer concentration caused the decrease of alkaloids' retention, the improvement of peaks' symmetry and the increase of theoretical plate number. The improved peak symmetry and the efficiency of system for most investigated alkaloids were observed in the systems containing buffers at strongly acidic pH. The obtained results also reveal a large influence of salt cation used for buffer preparation. The results obtained on SCX column were compared with those obtained on a C18 column. The most efficient and selective systems were used for the separation of alkaloid standard mixture. PMID:24007682

Petruczynik, Anna; Waksmundzka-Hajnos, Monika



Gene clusters for insecticidal loline alkaloids in the grass-endophytic fungus Neotyphodium uncinatum.  


Loline alkaloids are produced by mutualistic fungi symbiotic with grasses, and they protect the host plants from insects. Here we identify in the fungal symbiont, Neotyphodium uncinatum, two homologous gene clusters (LOL-1 and LOL-2) associated with loline-alkaloid production. Nine genes were identified in a 25-kb region of LOL-1 and designated (in order) lolF-1, lolC-1, lolD-1, lolO-1, lolA-1, lolU-1, lolP-1, lolT-1, and lolE-1. LOL-2 contained the homologs lolC-2 through lolE-2 in the same order and orientation. Also identified was lolF-2, but its possible linkage with either cluster was undetermined. Most lol genes were regulated in N. uncinatum and N. coenophialum, and all were expressed concomitantly with loline-alkaloid biosynthesis. A lolC-2 RNA-interference (RNAi) construct was introduced into N. uncinatum, and in two independent transformants, RNAi significantly decreased lolC expression (P < 0.01) and loline-alkaloid accumulation in culture (P < 0.001) compared to vector-only controls, indicating involvement of lolC in biosynthesis of lolines. The predicted LolU protein has a DNA-binding site signature, and the relationships of other lol-gene products indicate that the pathway has evolved from various different primary and secondary biosynthesis pathways. PMID:15654104

Spiering, Martin J; Moon, Christina D; Wilkinson, Heather H; Schardl, Christopher L



Determination of tobacco alkaloids by gas chromatography with nitrogen-phosphorus detection.  


An improved method, gas chromatography (GC) with nitrogen-phosphorus detection (NPD), has been used for determination of alkaloids in green and cured tobacco. Tobacco alkaloids of interest included nicotine, nornicotine, myosmine, anabasine, and anatabine. Tobacco samples were treated with a small quantity of aqueous ammonia solution to "loosen" tobacco tissue and to adjust pH, then extracted with solvent. The composition of the extraction solvent solution affected recoveries of the alkaloids, particularly nornicotine, and also contributed to other phenomena such as carry-over in the injection liner and "quenching" of the nitrogen-phosphorus detector. Use of a packed injection liner (e.g. with Carbowax-KOH on Chromosorb) to reduce carry-over was studied. Quenching of the nitrogen-phosphorus detector was eliminated by reducing the injection volume (i.e. increasing the split ratio), by use of a packed injection liner, and by reducing the amount of pretreatment with aqueous ammonia. A narrow bore capillary column (i.e. 0.18 mm id) was used to improve sensitivity and resolution and to increase the speed of GC analysis. An internal standard, 2,4'-dipyridyl, was used for quantitative measurement of these tobacco alkaloids. PMID:12194047

Yang, S S; Smetena, I; Huang, C B



Visualizing a plant defense and insect counterploy: alkaloid distribution in Lobelia leaves trenched by a plusiine caterpillar.  


Insects that feed on plants protected by latex canals often sever leaf veins or cut trenches across leaves before feeding distal to the cuts. The insects thereby depressurize the canals and reduce latex exudation at their prospective feeding site. How the cuts affect the distribution and concentration of latex chemicals was not known. We modified a microwave-assisted extraction technique to analyze the spatial distribution of alkaloids in leaves of Lobelia cardinalis (Campanulaceae) that have been trenched by a plusiine caterpillar, Enigmogramma basigera (Lepidoptera: Noctuidae). We produced sharp two dimensional maps of alkaloid distribution by microwaving leaves to transfer alkaloids to TLC plates that were then sprayed with Dragendorff's reagent to visualize the alkaloids. The leaf prints were photographed and analyzed with image processing software for quantifying alkaloid levels. A comparison of control and trenched leaves documented that trenching reduces alkaloid levels by approximately 50% both distal and proximal to the trench. The trench becomes greatly enriched in alkaloids due to latex draining from surrounding areas. Measurements of exudation from trenched leaves demonstrate that latex pressures are rapidly restored proximal, but not distal to the trench. Thus, the trench serves not only to drain latex with alkaloids from the caterpillar's prospective feeding site, but also to isolate this section, thereby preventing an influx of latex from an extensive area that likely extends beyond the leaf. Microwave-assisted extraction of leaves has potential for diverse applications that include visualizing the impact of pathogens, leaf miners, sap-sucking insects, and other herbivores on the distribution and abundance of alkaloids and other important defensive compounds. PMID:19468794

Oppel, Craig B; Dussourd, David E; Garimella, Umadevi



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

PubMed Central

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 0.69–3.23, exclusive of the results from the high protein drink). On the basis of these results, the method is recommended for Official First Action for determination of EP and PS in dietary supplements exclusive of the high protein drinks.

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



Toward a total synthesis of the stemofoline alkaloids: Advancement of a 1,3-dipolar cycloaddition strategy  

PubMed Central

Novel, intramolecular 1,3-dipolar cycloadditions of azomethine ylides have been applied to the synthesis of functionalized core structures of the stemofoline alkaloids. In an effort to maximize the efficiency of this key transformation in the context of an eventual total synthesis of these complex natural products, a number of strategic modifications to the cycloaddition substrate were investigated. These collective efforts have provided useful insights into the operative, regiochemical control elements for 1,3-dipolar cycloadditions leading to stemofoline alkaloids. A potential intermediate in the synthesis of these alkaloids was prepared.

Shanahan, Charles S.; Fuller, Nathan O.; Ludolph, Bjoern; Martin, Stephen F.



Enzymatic and Chemo-Enzymatic Approaches Towards Natural and Non-Natural Alkaloids: Indoles, Isoquinolines, and Others  

NASA Astrophysics Data System (ADS)

The multi-step enzyme catalysed biosyntheses of monoterpenoid indole and isoquinoline alkaloids are described. Special emphasis is placed on those pathways leading to alkaloids of pharmacological and medicinal significance which have been fully elucidated at the enzyme level. The successful identification and cloning of cDNAs of single enzymes and their application provides great opportunities to develop novel strategies for both in vitro and in vivo alkaloid production in whole plants or tissue cultures, as well as in microbial systems such as Escherichia coli and yeast.

Stöckigt, Joachim; Chen, Zhong; Ruppert, Martin


Plant cell bioreactor for the production of protoberberine alkaloids from immobilized Thalictrum rugosum cultures.  


Cultured Thalictrum rugosum cells were immobilized using a glass fiber substratum previously shown to provide optimum immobilization efficiency based on spontaneous adhesion mechanisms. When cultivated in shake flasks, immobilized cells exhibited decreased growth and protoberberine alkaloid production rates in comparison to freely suspended cells. Since alkaloid production is growth associated in T. rugosum, the decreased specific production rate was a function of the slower growth rate. Cells immobilized on glass fiber mats appear to be amenable for extended culture periods. Maximum biomass and protoberberine alkaloid levels were maintained for at least 14 days in immobilized cultures. In contrast, fresh weight, dry weight, and total alkaloid content decreased in suspension cultures following the linear growth phase. Glass fiber mats were incorporated in to a 4.5-L plant cell bioreactor as horizontal disks supported on a central rod. Mixing in the reactor was provided by the combined actions of a magnetic impeller and a cylindrical sparging column. The magnetic impeller and a cylindrical sparging column. The entire inoculum biomass of T. rougosum, introduced as suspension, was spontaneously immobilized with in 8 h. During liner phase, the growth rate of bioreactor cultivated immobilized cells (mu = 0.06 day(-1)) was 50% that immobilized cell viability in both mmobilized cells cultivated in shake flasks (mu = 0.12 day(-1)). Percentage of cell viability in both systems was determined to be similar. The growing biomass in the bioreactor was completely retained by the glass fiber substratum during a 28-day culture period. The increase in specific production of protoberberine alkaloids was initially similar in bioreactor- and shake-flask-cultivated immobilized cells. However, the maximum specific production of bioreactor-grown cultures was lower. The scaleup potential of an immobilization strategy based on the spontaneous adhesion of cultured plant cells to glass fibers is demonstrated. PMID:18597386

Facchini, P J; Dicosmo, F



Indole alkaloids of Psychotria as multifunctional cholinesterases and monoamine oxidases inhibitors.  


Thirteen Psychotria alkaloids were evaluated regarding their interactions with acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and monoamine oxidases A and B (MAO-A and MAO-B), which are enzymatic targets related with neurodegenerative diseases. Two quaternary ?-carboline alkaloids, prunifoleine and 14-oxoprunifoleine, inhibited AChE, BChE and MAO-A with IC(50) values corresponding to 10 and 3.39 ?M for AChE, 100 and 11 ?M for BChE, and 7.41 and 6.92 ?M for MAO-A, respectively. Both compounds seem to behave as noncompetitive AChE inhibitors and time-dependent MAO-A inhibitors. In addition, the monoterpene indole alkaloids (MIAs) angustine, vallesiachotamine lactone, E-vallesiachotamine and Z-vallesiachotamine inhibited BChE and MAO-A with IC(50) values ranging from 3.47 to 14 ?M for BChE inhibition and from 0.85 to 2.14 ?M for MAO-A inhibition. Among the tested MIAs, angustine is able to inhibit MAO-A in a reversible and competitive way while the three vallesiachotamine-like alkaloids display a time-dependent inhibition on this target. Docking calculations were performed in order to understand the binding mode between the most active ligands and the selected targets. Taken together, our findings established molecular details of AChE, BChE and MAO-A inhibition by quaternary ?-carboline alkaloids and MIAs from Psychotria, suggesting these secondary metabolites are scaffolds for the development of multifunctional compounds against neurodegeneration. PMID:23261030

Passos, Carolina S; Simões-Pires, Claudia A; Nurisso, Alessandra; Soldi, Tatiane C; Kato, Lucilia; de Oliveira, Cecilia M A; de Faria, Emiret O; Marcourt, Laurence; Gottfried, Carmem; Carrupt, Pierre-Alain; Henriques, Amélia T



Establishment of a search library about benzylisoquinoline alkaloids based on selective separation on the binaphthyl column and standard analysis on C18 column.  


A search library about benzylisoquinoline alkaloids was established based on preparation of alkaloid fractions from Rhizoma coptidis, Cortex phellodendri, and Rhizoma corydalis. In this work, two alkaloid fractions from each herbal medicine were first prepared based on selective separation on the "click" binaphthyl column. And then these alkaloid fractions were analyzed on C18 column by liquid chromatography coupled with tandem mass spectrometry. Many structure-related compounds were included in these alkaloids fractions, which led to easy separation and good MS response in further work. Therefore, a search library of 52 benzylisoquinoline alkaloids was established, which included eight aporphine, 19 tetrahydroprotoberberine, two protopine, two benzyltetrahydroisoquinoline, and 21 protoberberine alkaloids. The information of the search library contained compound names, structures, retention times, accurate masses, fragmentation pathways of benzylisoquionline alkaloids, and their sources from three herbal medicines. Using such a library, the alkaloids, especially those trace and unknown components in some herbal medicine could be accurately and quickly identified. In addition, the distribution of benzylisoquinoline alkaloids in the herbal medicines could be also summarized by searching the source samples in the library. PMID:23109405

Liu, Qiaoxia; Zhou, Binbin; Wang, Xinliang; Ke, Yanxiong; Jin, Yu; Yin, Lihui; Liang, Xinmiao



Selective separation of structure-related alkaloids in Rhizoma coptidis with "click" binaphthyl stationary phase and their structural elucidation with liquid chromatography-mass spectrometry.  


It is a new task to separate structure-related compounds into a fraction according to their structural characteristics in a complex traditional Chinese medicine (TCM). This method makes separation of the components of the sample simple and structural elucidation easy. In this study, selective separation of alkaloids in Rhizoma coptidis was realized on a "click" binaphthyl column possessing a planar conjugate structure. Three kinds of alkaloids, aporphine, tetrahydroprotoberberine and protoberberine in Rhizoma coptidis showed better retention than other compounds by virtue of ?-? interactions with the stationary phase. Moreover, the "click" binaphthyl column could distinguish the aporphine and tetrahydroprotoberberine alkaloids possessing two benzene rings from the protoberberine alkaloids possessing three benzene rings. After separating on the "click" binaphthyl column, the fractions containing the alkaloids were collected and then analyzed with liquid chromatography-mass spectrometry (LC-MS). Totally, 23 alkaloids were identified, and among these alkaloids, three tetrahydroprotoberberine, two aporphine and seven protoberberine alkaloids were first found in Rhizoma coptidis. These newly found alkaloids are minor compounds, and they are always neglected without eliminating the interference of compounds in large amounts by pre-separation on the "click" binaphthyl column. The typical fragmentation pathways of each class of alkaloids were summarized to illustrate their structures. In the MS(2) spectrum, the loss of a molecule of dimethylamine ((CH(3))(2)NH) was observed as the characteristic loss of aporphine alkaloids. All the tetrahydroprotoberberine alkaloids would undergo the Retro-Diels-Alder (RDA) fragmentation reaction in the MS(2) fragmentation. For protoberberine alkaloids, different characteristic fragmentations were observed with different skeleton structures. PMID:21881639

Liu, Qiaoxia; Qiu, Shiyi; Yu, Hui; Ke, Yanxiong; Jin, Yu; Liang, Xinmiao



Pyrrolizidine alkaloids in honey: comparison of analytical methods.  


Pyrrolizidine alkaloids (PAs) are a structurally diverse group of toxicologically relevant secondary plant metabolites. Currently, two analytical methods are used to determine PA content in honey. To achieve reasonably high sensitivity and selectivity, mass spectrometry detection is demanded. One method is an HPLC-ESI-MS-MS approach, the other a sum parameter method utilising HRGC-EI-MS operated in the selected ion monitoring mode (SIM). To date, no fully validated or standardised method exists to measure the PA content in honey. To establish an LC-MS method, several hundred standard pollen analysis results of raw honey were analysed. Possible PA plants were identified and typical commercially available marker PA-N-oxides (PANOs). Three distinct honey sets were analysed with both methods. Set A consisted of pure Echium honey (61-80% Echium pollen). Echium is an attractive bee plant. It is quite common in all temperate zones worldwide and is one of the major reasons for PA contamination in honey. Although only echimidine/echimidine-N-oxide were available as reference for the LC-MS target approach, the results for both analytical techniques matched very well (n = 8; PA content ranging from 311 to 520 µg kg(-1)). The second batch (B) consisted of a set of randomly picked raw honeys, mostly originating from Eupatorium spp. (0-15%), another common PA plant, usually characterised by the occurrence of lycopsamine-type PA. Again, the results showed good consistency in terms of PA-positive samples and quantification results (n = 8; ranging from 0 to 625 µg kg(-1) retronecine equivalents). The last set (C) was obtained by consciously placing beehives in areas with a high abundance of Jacobaea vulgaris (ragwort) from the Veluwe region (the Netherlands). J. vulgaris increasingly invades countrysides in Central Europe, especially areas with reduced farming or sites with natural restorations. Honey from two seasons (2007 and 2008) was sampled. While only trace amounts of ragwort pollen were detected (0-6.3%), in some cases extremely high PA values were detected (n = 31; ranging from 0 to 13019 µg kg(-1), average = 1261 or 76 µg kg(-1) for GC-MS and LC-MS, respectively). Here the results showed significantly different quantification results. The GC-MS sum parameter showed in average higher values (on average differing by a factor 17). The main reason for the discrepancy is most likely the incomplete coverage of the J. vulgaris PA pattern. Major J. vulgaris PAs like jacobine-type PAs or erucifoline/acetylerucifoline were not available as reference compounds for the LC-MS target approach. Based on the direct comparison, both methods are considered from various perspectives and the respective individual strengths and weaknesses for each method are presented in detail. PMID:21082464

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



Seasonal variation of alkaloids of Adhatoda vasica and detection of glycosides and N-Oxides of vasicine and vasicinone.  


The distribution pattern of the alkaloids of A. Vasica has been studied with change of season. The study also resulted in the detection of glycosides and N-oxides of vasicine and vasicinone. PMID:17404955

Pandita, K; Bhatia, M S; Thappa, R K; Agarwal, S G; Dhar, K L; Atal, C K



Molluscicidal activity of Hammada scoparia (Pomel) Iljin leaf extracts and the principal alkaloids isolated from them against Galba truncatula.  


The molluscicidal activity of Hammada scoparia leaf extracts and the principal alkaloids isolated from them (carnegine and N-methylisosalsoline) were tested against the mollusc gastropod, Galba truncatula, the intermediate host of Fasciola hepatica in Tunisia. The results indicated that the molluscicidal activity was correlated with the presence of alkaloids. A significant molluscicidal value, according to the World Health Organization, was found with the methanol extract (LC50 = 28.93 ppm). Further fractionation of the methanolic extract led to the isolation of two principal alkaloids: carnegine and N-methylisosalsoline. These alkaloids are isoquinolines that have not previously been characterised for their molluscicidal activity. The N-methylisosalsoline possesses the highest molluscicidal activity (LC50 = 0.47 microM against G. truncatula). PMID:20027474

Mezghani-Jarraya, R; Hammami, H; Ayadi, A; Damak, M



Production of the alkaloid swainsonine by a fungal endosymbiont of the ascomycete order Chaetothyriales in the host Ipomoea carnea.  

Technology Transfer Automated Retrieval System (TEKTRAN)

Some plant species within the Convolvulaceae (morning glory family) from South America, Africa, and Australia cause a neurologic disease in grazing livestock caused by swainsonine. These convolvulaceous species including Ipomoea carnea contain the indolizidine alkaloid swainsonine, an inhibitor of ...


Studies on Anti-Tumor Drugs. Xx. Therapeutic Effect and Toxicity of Total Alkaloids from Narcissus Tazetta from Changchow.  

National Technical Information Service (NTIS)

The article introduces the total alkaloids (AC-445) isolated from Narcissus tazetta L. var. chinensis Roem collected from Changchow Muncipality China which has definite anti-tumor effects. Intraperitoneal injection against Jensen sarcoma in rats, and Croc...

T. Wu J. Chen T. Wang P. Hsu



What Is Numerical Control?  

ERIC Educational Resources Information Center

|Numerical control (a technique involving coded, numerical instructions for the automatic control and performance of a machine tool) does not replace fundamental machine tool training. It should be added to the training program to give the student an additional tool to accomplish production rates and accuracy that were not possible before. (HD)|

Goold, Vernell C.



Numerical Memory Experiment  

NSDL National Science Digital Library

This is the entry page for the Numerical Memory Experiment. This Numerical Memory experiment employs a similar format to Digit Span tasks found in assessment instruments, comparing the individual's short-term memory for digits presented in an auditory vs. visual format.


Validated Numerics for Pedestrians  

Microsoft Academic Search

The aim of this paper is to give a very brief introduction to the emerg- ing area of validated numerics. This is a rapidly growing field of research faced with the challenge of interfacing computer science and pure mathematics. Most validated numerics is based on interval analysis, which allows its users to account for both rounding and discretization errors in

Warwick Tucker



Hybridaphniphyllines A and B, Daphniphyllum alkaloid and iridoid hybrids suggestive of Diels-Alder cycloaddition in Daphniphyllum longeracemosum.  


Two Daphniphyllum alkaloid and iridoid hybrids with the hitherto unknown decacyclic fused skeletons, hybridaphniphyllines A and B, along with one diamino Daphniphyllum alkaloid, daphnicyclidin I, were isolated from dried stems and leaves of Daphniphyllum longeracemosum. Their structures were elucidated on the basis of extensive spectroscopic analysis, and the absolute configuration of daphnicyclidin I was deduced by the CD exciton chirality method. A biogenetic pathway for 1 and 2 involving natural Diels-Alder cycloaddition is proposed. PMID:23906551

Wang, Fei; Mao, Mei-Fen; Wei, Guo-Zhu; Gao, Yuan; Ren, Fu-Cai; Liu, Ji-Kai



An old yellow enzyme gene controls the branch point between Aspergillus fumigatus and Claviceps purpurea ergot alkaloid pathways.  


Ergot fungi in the genus Claviceps and several related fungal groups in the family Clavicipitaceae produce toxic ergot alkaloids. These fungi produce a variety of ergot alkaloids, including clavines as well as lysergic acid derivatives. Ergot alkaloids are also produced by the distantly related, opportunistic human pathogen Aspergillus fumigatus. However, this fungus produces festuclavine and fumigaclavines A, B, and C, which collectively differ from clavines of clavicipitaceous fungi in saturation of the last assembled of four rings in the ergoline ring structure. The two lineages are hypothesized to share early steps of the ergot alkaloid pathway before diverging at some point after the synthesis of the tricyclic intermediate chanoclavine-I. Disruption of easA, a gene predicted to encode a flavin-dependent oxidoreductase of the old yellow enzyme class, in A. fumigatus led to accumulation of chanoclavine-I and chanoclavine-I-aldehyde. Complementation of the A. fumigatus easA mutant with a wild-type allele from the same fungus restored the wild-type profile of ergot alkaloids. These data demonstrate that