Modulatory Effects of Eschscholzia californica Alkaloids on Recombinant GABAA Receptors.

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

ER-27319, an acridone-related compound, inhibits release of antigen-induced allergic mediators from mast cells by selective inhibition of Fcɛ receptor I-mediated activation of Syk

Engagement of the mast cell high-affinity receptor for immunoglobulin E (IgE), FcɛRI, induces tyrosine phosphorylation of Syk, a non-receptor tyrosine kinase, that has been demonstrated as critical for degranulation. Herein we describe a synthetic compound, ER-27319, as a potent and selective inhibitor of antigen or anti-IgE-mediated degranulation of rodent and human mast cells. ER-27319 affected neither Lyn kinase activity nor the antigen-induced phosphorylation of the FcɛRI but did effectively inhibit the tyrosine phosphorylation of Syk and thus its activity. As a consequence, tyrosine phosphorylation of phospholipase C-γ1, generation of inositol phosphates, release of arachidonic acid, and secretion of histamine and tumor necrosis factor α were also inhibited. ER-27319 did not inhibit the anti-CD3-induced tyrosine phosphorylation of phospholipase C-γ1 in Jurkat T cells, demonstrating a specificity for Syk-induced signals. In contrast the tyrosine phosphorylation and activation of Syk, induced by in vitro incubation with the phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) of FcɛRI γ subunit or by antigen activation of RBL-2H3 cells, was specifically inhibited by ER-27319. However, when ER-27319 was added to immunoprecipitated Syk, derived from activated cells, no effect was seen on Syk activity. ER-27319 did not inhibit the tyrosine phosphorylation of Syk induced by activation in the presence of Igβ ITAM or the anti-IgM-induced phosphorylation of Syk in human peripheral B cells. Therefore, ER-27319 selectively interferes with the FcɛRI γ phospho-ITAM activation of Syk in vitro and in intact cells. These results confirm the importance of Syk in FcɛRI-mediated responses in mast cells and demonstrate the mast cell selectivity and therapeutic potential of ER-27319 in the treatment of allergic disease.

Batrachotoxin alkaloids from passerine birds: A second toxic bird genus (Ifrita kowaldi) from New Guinea

Batrachotoxins, including many congeners not previously described, were detected, and relative amounts were measured by using HPLC-mass spectrometry, in five species of New Guinean birds of the genus Pitohui as well as a species of a second toxic bird genus, Ifrita kowaldi. The alkaloids, identified in feathers and skin, were batrachotoxinin-A cis-crotonate (1), an allylically rearranged 16-acetate (2), which can form from 1 by sigmatropic rearrangement under basic conditions, batrachotoxinin-A and an isomer (3 and 3a, respectively), batrachotoxin (4), batrachotoxinin-A 3′-hydroxypentanoate (5), homobatrachotoxin (6), and mono- and dihydroxylated derivatives of homobatrachotoxin. The highest levels of batrachotoxins were generally present in the contour feathers of belly, breast, or legs in Pitohui dichrous, Pitohui kirhocephalus, and Ifrita kowaldi. Lesser amounts are found in head, back, tail, and wing feathers. Batrachotoxin (4) and homobatrachotoxin (6) were found only in feathers and not in skin. The levels of batrachotoxins varied widely for different populations of Pitohui and Ifrita, a result compatible with the hypothesis that these birds are sequestering toxins from a dietary source.

A general assay for antibody catalysis using acridone as a fluorescent tag.

A simple and highly sensitive catalysis assay is demonstrated based on analyzing reactions with acridonetagged compounds by thin-layer chromatography. As little as 1 pmol of product is readily visualized by its blue fluorescence under UV illumination and identified by its retention factor (Rf). Each assay requires only 10 microliters of solution. The method is reliable, inexpensive, versatile, and immediately applicable in repetitive format for screening catalytic antibody libraries. Three examples are presented: (i) the epoxidation of acridone labeled (S)-citronellol. The pair of stereoisomeric epoxides formed is resolved on the plate, which provides a direct selection method for enantioselective epoxidation catalysts. (ii) Oxidation of acridone-labeled 1-hexanol to 1-hexanal. The activity of horse liver alcohol dehydrogenase is detected. (iii) Indirect product labeling of released aldehyde groups by hydrazone formation with an acridone-labeled hydrazide. Activity of catalytic antibodies for hydrolysis of enol ethers is detected.

Tobacco alkaloids.

A reprint from Vegetable alkaloids ... by Amé Pictet, rendered into English, by H.C. Biddle.

Alkaloid-bearing plants and their contained alkaloids

Mode of access: Internet.

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.

New Indole Alkaloids from the bark of Alstonia scholaris

A new indole alkaloid, akuammiginone (1), and a new glycosidic indole alkaloid, echitamidine-N-oxide 19-O-beta-D-glucopyranoside (2), together with the five known alkaloids, echitaminic acid (3), echitamidine N-oxide (4), N-b-demethylalstogustine N-oxide (5), akuammicine N-oxide (6), and N-b-demethylalstogustine (7), were isolated from the trunk bark of Alstonia scholaris collected in Timor, Indonesia. The structures of all compounds were elucidated by spectroscopic methods. This is the first report of compounds 3-5 and 7 in A. scholaris. Some NMR assignments of the known compounds were revised.

New indole alkaloids from the roots of Ochrosia acuminata

Two new indole alkaloids, polyneuridine-N-oxide (1) and 17-hydroxy-10-methoxy-yohimbane (2), together with seven known alkaloids were isolated from the roots of Ochrosia acuminata collected in Savu, Indonesia. 9-Methoxyellipticine (3) and ellipticine (4) were responsible for the antitumor activities of the extract. The structures of all compounds were elucidated using MS and NMR methods.

Investigating direct routes to an advanced intermediate for the synthesis of C-20 diterpene alkaloids

Rapid access to the ABCE ring system of the C-20 diterpene alkaloids was achieved by silver (I) promoted intramolecular Friedel-Crafts arylation of a functional group specific 5-bromo-3-azabicyclo[3.3.1]nonane derivative. (c) 2005 Elsevier Ltd. All rights reserved.

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

The alkaloid content of Senecio madagascariensis collected from Australia and Hawaii was examined. Alkaloids were identified from the above ground whole plant (stems, leaves and flowers) by GUMS analysis and included: senecivernine, senecionine, integerrimine, senkirkine, mucronatinine, retrosine, usaramine, otosenine, acetylsenkirkine, desacetyldoronine, florosenine and doronine. Plant material collected from the Hawaiian Islands was found to be identical in pyrrolizidine alkaloid content to that from a single composite collection made from northern New South Wales, Australia. Overall, no appreciable differences in alkaloid content were found between locations, whereas variation among individual plants was evident. The average total pyrrolizidine alkaloid content varied from a low of 217 mu g/g to a high of 1990 mu g/g (dry weight basis) among the locations. Based on comparable alkaloid content and documented pyrrolizidine alkaloidosis cases from Australia, S. madagascariensis may pose a significant risk to livestock grazing heavily infested ranges on the Hawaiian Islands. (c) 2006 Elsevier Ltd. All rights reserved.