Swainsonine

• (1S, 2R, 8R, 8aR ) -1,2,8 - Trihydroxyindolizidin

• 72741-87-8
• 214462-68-7 ( Tridolgosirhydrochlorid )

A white crystalline solid

Fixed

140-142 ° C

Decomposition

Slightly soluble in water and ethanol

Attention

Template: Infobox chemical / molecular formula search available

Swainsonine is a naturally occurring indolizidine alkaloid with strong pharmacological effect. Sainsonin reversibly inhibits the enzymes α -mannosidase in the lysosome and the Golgi α -mannosidase II in the cells, resulting in an enrichment ( accumulation ) of the high-mannose oligosaccharides in the lysosome of the cell. When grazing animals that receive swainsonine on the food, this can lead to the so-called Locoismus, an induced mannosidosis.

Occurrence

Swainsonine is the toxin in Locoweed. These are several plant genera and species of fungi that occur primarily in western North America. The consumption of these plants results in grazing animals at the so-called Locoismus, a severe neurological disorder.

Biosynthesis

The biosynthesis of swainsonine has been extensively studied in the parasitic fungus Rhizoctonia leguminicola. From L- Lysine L - saccharopine is first formed. In the next stage is formed of L- 2- Aminoadipinsäuresemialdehyd which directly to Δ1 - piperidine - 6-carboxylic acid is cyclized. About the intermediates ( S)- pipecolic acid and 1- Ketooctahydroindolizin ultimately created the swainsonine.

Pharmacological potential

Swainsonine and some of its epimers in animal experiments show a strong pharmacological effect. Metastases and tumor growth can be suppressed. In addition, the formation of NK cells and the makrophagenmediierte killing of tumor cells is stimulated. Similarly, the proliferation of cells in the bone marrow is activated. As an inhibitor of α -mannosidase lysosmalen formation is inhibited by tumor-specific glycosylation patterns and inhibited the catabolic glycosidases. Both of which result in the animal experiment in a reduced tumor growth and a reduction in metastasis.

Swainsonine is currently in clinical trials. In a phase II study, however, no anti -tumor effect was shown in the treated patients with advanced or metastatisiertem renal cell carcinoma.

Swainsonine is an appetite suppressant.

The toxic effect of grazing animals based on the inhibition of the enzyme α -mannosidase. The symptoms of Locoismus therefore resemble those of α - mannosidosis, a genetic disease. Swainsonine reversibly inhibits the enzymes α -mannosidase in the lysosome and the Golgi α -mannosidase II in the cells, resulting in the accumulation of high-mannose oligosaccharides in the lysosome.

Discovery

Swainsonine was first isolated in 1973 from the fungus Rhizoctonia leguminicola and later from the eponymous legume Swainsona canescens and Astragalus lentiginosus.

Further Reading

• GG Habermehl include: Natural Products Chemistry: An Introduction. Springer Verlag, 2008, ISBN 3-540-73732-4, pp. 209-211.
• JB Astroga include: Maternal ingestion of locoweed: II The ability of intoxicated ewes to discriminate Their Own lamb. In: Small Ruminant Research 65, 2006, pp. 64-69.
• Y. Sichhart: genes, enzymes, and products of the Calystegia sepium in Calysteginbildung (L.) R. Br Dissertation, Martin -Luther- University Halle- Wittenberg, 2003.
• AG Armien: Comparative clinical and morphological studies on spontaneous and experimental poisoning by Ipomoea fistulosa ( Convolvulaceae ) in goats. PhD thesis, Justus -Liebig- University of Giessen, 2000.
• M. H. Ralphs and L. F. James: Locoweed grazing. In: J Nat Toxins 8, 1999, pp. 47-51, PMID 10,091,127th
• DR Tulsiani include: Swainsonine induces the production of hybrid glycoproteins and accumulation of oligosaccharides in male reproductive tissues of the rat. In: Biol Reprod 43, 1990, pp. 130-138, PMID 2,118,392th
• Skudlarek MD and MC Orgebin Crist: Effect of swainsonine on rat epididymal glycosidases. (PDF, 655 kB) In: J Reprod Fert " 84, 1988, pp. 611-617, PMID 3,143,832th
• DR Tulsiani include: Production of hybrid glycoproteins and accumulation of oligosaccharides in the brain of sheep and pigs administered swainsonine or locoweed. In: Arch Biochem Biophys 264, 1988, pp. 607-617, PMID 3,135,781th
• DR Tulsiani, among other things: The similar effects of swainsonine and locoweed on tissue glycosidases and oligosaccharides of the pig indicate indication did the alkaloid is the principle toxin responsible for the induction of locoism. In: Arch Biochem Biophys 232, 1984, pp. 76-85, PMID 6430242nd
• DR Tulsiani include: Swainsonine Inhibits the biosynthesis of complex glycoproteins by inhibition of Golgi mannosidase II In: J Biol Chem 257, 1982, p 7936-7939, PMID 6,806,288th