Суэйнсонин

Description

Swainsonine is an indolizidine alkaloid isolated from the plant Swainsona canescens; the molecule is an octahydroindolysine with three hydroxyl groups at positions 1, 2 and 8. The compound is known to play two roles simultaneously. On the one hand, it is a powerful alpha-mannosidase inhibitor with antimetastatic, antiproliferative and immunomodulatory activity. On the other hand, it is a natural toxin: it is found in locospecies plants of the legume genera Oxytropis, Astragalus and Swainsona, and is also produced by the fungi Metarhizium anisopliae and Rhizoctonia leguminicola (Slafractonia leguminicola).

Basic Attributes

• CAS No: 72741-87-8
• Chemical formula: C8H15NO3
• Molecular weight: 173.21
• Exact weight according to card: 173.21
• EU number: 615-797-6
• UNII: RSY4RK37KQ
• NSC Number: 614553
• DSSTox ID: DTXSID5046356
• RTECS number: NM2408666
• HS code: 29339900
• PSA specifications: 63.9
• XLogP3: −0.79

Physico-chemical properties

• Appearance: White to pale yellow lyophilized powder
• Density: 1.38 ± 0.1 g/cm³
• Melting point: 138–142 °C
• Boiling point: 353.3 ± 21.0 °C at 760 mm Hg. Art.
• Flash point: 209.7 ± 20.7 °C
• Refractive index: 1.609
• Solubility in water: freely soluble, 170 g/l at 25 °C

The solubility of 170 g/L and the negative distribution coefficient XLogP3 of −0.79 are consistent with each other: three hydroxyl groups on the compact bicyclic framework make the molecule distinctly hydrophilic, so working solutions are prepared directly in water or buffer. The exact mass of 173.21 coincides with the rounded molecular weight and does not correspond to the monoisotopic mass of the formula C8H15NO3 - it must be recalculated for mass spectrometry.

Mechanism of action

Swainsonine competitively inhibits alpha-mannosidase II (αMII), a Golgi enzyme that processes the N-linked carbohydrate chains of newly synthesized glycoproteins en route to the cell surface. In parallel, lysosomal alpha-mannosidase is inhibited. The result is a violation of the degradation of oligosaccharides and incomplete processing of glycoproteins.

The practical significance of this mechanism is revealed in oncology. During normal operation of αMII, highly branched carbohydrate structures are formed on the cell surface, which bind to the lectin phytohemagglutinin L-PHA. Such structures are expressed in different tumor types and correlate with a metastatic phenotype and increased aggressiveness. Inhibition of αMII reduces the amount of carbohydrates that bind L-PHA, and along with this, the aggressiveness and metastatic potential of tumor cells.

According to the MeSH classification, the compound is classified into three groups: immunological adjuvants - substances that enhance, stimulate or modulate the immune response at the cellular or humoral level; antitumor agents of plant origin; enzyme inhibitors.

Toxic effect on farm animals

Swainsonine is the active principle of locovid poisoning. Livestock that eat these plants develop locoism, a potentially fatal disease of the central nervous system that is a significant cause of economic loss in the livestock industry. The mechanism is the same: suppression of lysosomal alpha-mannosidase and mannosidase II impairs the degradation of oligosaccharides and the processing of glycoproteins. Endophytic fungi that produce swainsonine have been isolated from various locospecies; There is a close relationship between the fungus and the plant - the endophyte promotes plant growth and increases the production of swainsonine. Together with slaframin, a second biologically active compound of Rhizoctonia leguminicola, the substance may be involved in the development of drooling syndrome in livestock when eating contaminated feed.

Scope of application

• biochemical reagent: selective alpha-mannosidase II inhibitor for protein glycosylation studies
• a tool for studying the processing of N-linked glycans in the Golgi apparatus
• object of research on antitumor, antimetastatic and immunomodulatory activity
• analytical standard for monitoring feed and plant materials for swainsonine content

Safety Information

• Transport codes: NONH for all modes of transport
• WGK Germany: 3
• Hazard class code: 20/21/22
• Safety instructions: 36
• Tags: Xn
• Hazard Statements: H302 - Harmful if swallowed; H312 - harmful in contact with skin; H332 - harmful if inhaled
• Precautionary statements: P280
• GHS classification: signal word "Warning", H302 (100%) - harmful if swallowed, with prescriptions P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P312, P304+P340, P312, P322, P330, P363 and P501. Aggregated GHS data provided by 39 companies for 2 notifications to the ECHA C and L register

Storage and handling

Storage conditions: 2–8 °C. Lyophilized powder is hygroscopic and easily dissolves in water - keep the container tightly closed and protected from moisture. The substance is harmful through all three routes of entry, therefore gloves, safety glasses and respiratory protection are required when hanging (P280, P261, P271). Work should be carried out under a hood, without dust; Do not eat or drink when working, wash your hands after work. Class WGK Germany 3 excludes discharge into sewerage. There are no transport restrictions - NONH status. As a biologically active alkaloid, the product requires limited access and separate accounting.