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Ergot Alkaloids (ergot + alkaloid)
Selected AbstractsOrigins and significance of ergot alkaloid diversity in fungiFEMS MICROBIOLOGY LETTERS, Issue 1 2005Daniel G. Panaccione Abstract Ergot alkaloids are a diverse family of indole-derived mycotoxins that collectively have activities against a variety of organisms including bacteria, nematodes, insects, and mammals. Different fungi accumulate different, often characteristic, profiles of ergot alkaloids rather than a single pathway end product. These ergot alkaloid profiles result from inefficiency in the pathway leading to accumulation of certain intermediates or diversion of intermediates into shunts along the pathway. The inefficiency generating these ergot alkaloid profiles may have been selected for as a means of accumulating a diversity of ergot alkaloids, potentially contributing in different ways to benefit the producing fungus. [source] Total Synthesis without Protection: Three-Step Synthesis of Optically Active Clavicipitic Acids by a Biomimetic RouteEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 6 2004Yuusaku Yokoyama Abstract A three-step synthesis of a mixture of optically active cis - and trans -clavicipitic acids 6, which are ergot alkaloids, was achieved, starting from 4-bromoindole (7) and dl -serine (dl - 2). This short synthesis was made possible by omitting the protection and deprotection steps from the synthetic route. The key step was the spontaneous cyclization of 4-vinyltryptophan (10) formed from the Heck reaction of 4-bromotryptophan (8) with 2-methyl-3-buten-2-ol (9) in aqueous media. During this investigation, we also found that the palladium-catalyzed reaction of 8 with 9 showed an interesting pH dependence; under strongly basic conditions, the Heck reaction occurred to give a C4 -vinylated product 10, whereas an N -allylated product 19b was formed under neutral or weakly basic conditions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Origins and significance of ergot alkaloid diversity in fungiFEMS MICROBIOLOGY LETTERS, Issue 1 2005Daniel G. Panaccione Abstract Ergot alkaloids are a diverse family of indole-derived mycotoxins that collectively have activities against a variety of organisms including bacteria, nematodes, insects, and mammals. Different fungi accumulate different, often characteristic, profiles of ergot alkaloids rather than a single pathway end product. These ergot alkaloid profiles result from inefficiency in the pathway leading to accumulation of certain intermediates or diversion of intermediates into shunts along the pathway. The inefficiency generating these ergot alkaloid profiles may have been selected for as a means of accumulating a diversity of ergot alkaloids, potentially contributing in different ways to benefit the producing fungus. [source] The therapeutic profile of zolmitriptan in clinical practiceINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 8 2004H.C. Diener Summary The efficacy and tolerability of the 5-HT1B/1D -receptor agonist zolmitriptan was evaluated in an open post-marketing surveillance study in 12,919 patients, treating 36,510 migraine attacks. Mean visual analogue scale scores for pain decreased (6.9,2.2; 68% improvement) and scores for impairment of normal activities decreased (6.6,2.2; 67% improvement) at 2 h after dose. Non-headache symptoms of migraine resolved in 73,86% of attacks. Improvement was achieved within 2 h in >80% of attacks and within 1 h in 37% of attacks. This high level of efficacy was achieved with a single 2.5 mg dose in 95% of attacks. Compared with previous migraine treatments, 85% of patients preferred zolmitriptan for efficacy and 56% for better tolerability. Corresponding preference rates were 87 and 63% when compared with ergot alkaloids. Adverse events occurred in 2% of patients and were either typical class effects or known symptoms and complications of migraine. These results provide evidence for the high efficacy and good tolerability of the 2.5 mg dose of zolmitriptan in clinical practice in migraine. Zolmitriptan was very well tolerated, with patients expressing a distinct preference for zolmitriptan over previous treatments. [source] Development and validation of a liquid chromatography/tandem mass spectrometric method for the determination of 39 mycotoxins in wheat and maizeRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 18 2006Michael Sulyok This paper describes the first validated method for the determination of 39 mycotoxins in wheat and maize using a single extraction step followed by liquid chromatography with electrospray ionization triple quadrupole mass spectrometry (LC/ESI-MS/MS) without the need for any clean-up. The 39 analytes included A- and B-trichothecenes (including deoxynivalenol-3-glucoside), zearalenone and related derivatives, fumonisins, enniatins, ergot alkaloids, ochratoxins, aflatoxins and moniliformin. The large number and the chemical diversity of the analytes required the application of the positive as well as the negative ion ESI mode in two consecutive chromatographic runs of 21,min each. The solvent mixture acetonitrile/water/acetic acid 79,+,20,+,1 (v/v/v) has been determined as the best compromise for the extraction of the analytes from wheat and maize. Raw extracts were diluted 1,+,1 and were injected without any clean-up. Ion-suppression effects due to co-eluting matrix components were negligible in the case of wheat, whereas significant signal suppression for 12 analytes was observed in maize, causing purely proportional systematic errors. Method performance characteristics were determined after spiking blank samples on multiple levels in triplicate. Coefficients of variation of the overall process of <5.1% and <3.0% were obtained for wheat and maize, respectively, from linear calibration data. Limits of detection ranged from 0.03 to 220,µg/kg. Apparent recoveries (including both the recoveries of the extraction step and matrix effects) were within the range of 100,±,10% for approximately half of the analytes. In extreme cases the apparent recoveries dropped to about 20%, but this could be compensated for to a large extent by the application of matrix-matched standards to correct for matrix-induced signal suppression, as only a few analytes such as nivalenol and the fumonisins exhibited incomplete extraction. For deoxynivalenol and zearalenone, the trueness of the method was confirmed through the analysis of certified reference materials. Copyright © 2006 John Wiley & Sons, Ltd. [source] Identification and human pharmacokinetics of dihydroergotoxine metabolites in man: preliminary resultsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2008Beatriz Bicalho Abstract Dihydroergotoxine is a mixture of semi-synthetic ergot alkaloids mainly used for age-related cognitive impairment. In this study, dihydroergotoxine (30,µM) was added to incubates of rat and bovine liver microsomes, and the resulting major metabolites were identified as hydroxy-dihydroergocornine, hydroxy-dihydroergocryptine and hydroxy-dihydroergocristine on the basis of molecular mass measurements, determined with a time-of-flight mass spectrometer. The relevance of these to humans was then investigated by simultaneously monitoring dihydroergotoxine and its hydroxy-metabolites in human plasma by LC-MS/MS after oral dosing of dihydroergotoxine mesylate (27,mg) to a healthy volunteer (male, age 45, height 1.93,m, weight 103,kg). In this preliminary approach, the peaks (Cmax) of dihydroergocornine, dihydroergocryptine and dihydroergocristine were about 0.04,µg/l. The peaks (Cmax) of their hydroxy-metabolites were 0.98, 0.53 and 0.30,µg/l, respectively. In conclusion, in this preliminary approach it was found that hydroxy-dihydroergocornine, hydroxy-dihydroergocryptine and hydroxy-dihydroergocristine were one order of magnitude higher in concentration than their parents in human plasma. Copyright © 2007 John Wiley & Sons, Ltd. [source] | |||||||||||||