Synthesis
Since the first artificial synthesis of SWAINSONINE in 1984, chemists worldwide have actively researched and developed its synthesis. Given that SWAINSONINE has a bicyclic heterocyclic structure with four chiral configurations, many chemists have designed synthetic routes using unsaturated indolizidine rings, bicyclic lactams, cycloenamines, and pyranones as key intermediates. Important reaction types such as olefin metathesis, dihydroxylation, asymmetric oxidation, and 1,3-dipolar cycloaddition are also employed in its synthesis. The synthetic route for SWAINSONINE is shown below:
Description
Swainsonine (72741-87-8) is a naturally occurring alkaloidal toxin found in locoweed. Inhibits the biosynthesis of complex glycoproteins by inhibition of Golgi mannosidase II (IC50 = 0.2 mM).1 Inhibits growth and potentiates the cytotoxic effect of taxol in hepatocellular carcinoma in vivo.2 Induces apoptosis in a variety of cell types including cerebral cortical neurons.3 Impairs adult neurogenesis and spatial learning and memory.4 Abrogation of complex glycosylation by swainsonine results in strain-and cell-specific inhibition of prion replication.5 Induces lysosomal storage disease in farm animals.6
Chemical Properties
White Crystalline Solid
Occurrence
Swainsonia canescens yields this simple alkaloid.
Uses
Swainsonine is an indolizidine alkaloid naturally found in certain plants including locoweed that inhibits N-linked glycoside hydrolases, preventing the processing of asparagine-linked glycoproteins. It reversibly inhibits lysosomal α-mannosidase and Golgi α-mannosidase II (IC50 = 0.2 μM). Swainsonine is used to study the role of N-linked glycosylation in cellular processes and has been shown to have antiproliferative and antimetastatic effects of cancer cells in culture and in mice. The inhibition of α-mannosidase activity in lysosomes produces an accumulation of partially-processed oligosaccharides and glycoproteins, giving rise to lysosomal storage disease. Swainsonine toxicity in herbivores results in a condition known as locoism, characterized by hyperactivity, aggression, stiff and clumsy gait, low head carriage, salivation, seizures, and apparent blindness, culminating in increased miscoordination, weakness and death.
Uses
Swainsonine is a plant alkaloid derived from Swainsona canescens (a leguminous plant). It is a reversible, active-site directed inhibitor of a-mannosidase at concentrations of 5-10mM. At acid pH, swainsonine resembles an intermediate in the hydrolysis of mannosidases.Swainsonine completely inhibits mammalian Golgi a-mannosidase II (a-3/6-mannosidase in the glycoprotein processing pathway) and mammalian lysosomal a-mannosidase (acid mannosidase). At higher concentrations, swainsonine also inhibits mammalian cytosolic a-mannosidase. It has been shown to inhibit growth of transformed fibroblasts in soft agar and to enhance the antiproliferative effects of INF on murine lymphoreticular tumor cells in vitro. It also blocks the expression of b1-6 branched complex-type oligosaccharides and shun
Definition
ChEBI: An indolizidine alkaloid isolated from the plant Swainsona canescens with three hydroxy substituents at positions 1, 2 and 8.
General Description
Swainsonine is produced by endophytes, plant and insect pathogens. It is synthesized from the pipecolic acid and mevalonic acid. Swainsonine is a water-soluble indole alkaloid.
Biological Activity
Inhibitor of α -mannosidase II which inhibits glycoprotein processing. Displays anticancer and immune modulatory properties.
Biochem/physiol Actions
Swainsonine is a potent α-mannosidase inhibitor. It also has antimetastatic, antiproliferative, and immunomodulatory activity . It also inhibits glycoprotein processing.
References
[1] D.R.P. TULSIANI O. T H P Broquist. Marked differences in the swainsonine inhibition of rat liver lysosomal α-d-mannosidase, rat liver golgi mannosidase II, and jack bean α-d-mannosidase[J]. Archives of biochemistry and biophysics, 1985, 236 1: Pages 427-434. DOI:
10.1016/0003-9861(85)90643-5[2] NAN YOU. Swainsonine inhibits growth and potentiates the cytotoxic effect of paclitaxel in hepatocellular carcinoma in vitro and in vivo.[J]. Oncology reports, 2012, 28 6: 2091-2100. DOI:
10.3892/or.2012.2035[3] HAO LU. Swainsonine-induced apoptosis pathway in cerebral cortical neurons[J]. Research in veterinary science, 2015, 102: Pages 34-37. DOI:
10.1016/j.rvsc.2015.07.005[4] JIUTAO WANG. Exposure to swainsonine impairs adult neurogenesis and spatial learning and memory[J]. Toxicology letters, 2015, 232 1: Pages 263-270. DOI:
10.1016/j.toxlet.2014.11.017[5] SHAWN BROWNING. Abrogation of complex glycosylation by swainsonine results in strain- and cell-specific inhibition of prion replication.[J]. The Journal of Biological Chemistry, 2011, 286 47: 40962-40973. DOI:
10.1074/jbc.m111.283978[6] A.F.M. DANTAS . Swainsonine-induced lysosomal storage disease in goats caused by the ingestion of Turbina cordata in Northeastern Brazil[J]. Toxicon, 2007, 49 1: Pages 111-116. DOI:
10.1016/j.toxicon.2006.08.012
