72741-87-8 Usage
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
Different sources of media describe the Uses of 72741-87-8 differently. You can refer to the following data:
1. 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
2. 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 shunts the pathway towards hybrid-type oligosaccharides. Swainsonine does not appear to inhibit secretion or expression of glycoproteins at the cell surface.
Swainsonine is stable for at least 24 h at 37oC in culture media at physiological pH. Working concentration range is 17-1700 ng/ml (0.1-10mM). Swainsonine (at 1 mg/ml) is not cytotoxic and does not inhibit the growth of a variety of mammalian cell lines. Concentrations required to inhibit Golgi a-mannosidase II in vivo may be somewhat higher, as swainsonine tends to concentrate in the acid environment of cell lysosomes, where it exists as a charged cation and does not permeate through membranes readily.
Swainsonine blocks the processing of high-mannose oligosaccharides to complex oligosaccharides. Glycoproteins synthesized in the presence of swainsonine tend to carry mostly high-mannose and hybrid oligosaccharide chains. With short treatments (<24 h) with the inhibitor, cells may retain some complex glycoproteins due to asynchronous cell growth and glycoprotein synthesis.
3. 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.
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) Tulsiani et al. (1985), Marked differences in the swainsonine inhibition of rat liver lysomal alpha-D-mannosidase, rat liver Golgi mannosidase II, and jack bean alpha-D-mannosidase; Arch. Biochem. Biophys., 236 427
2) You et al. (2012), Swainsonine inhibits growth and potentiates the cytotoxic effect of paclitaxel in hepatocellular carcinoma in vitro and in vivo; Oncol. Rep., 28 2091
3) Lu et al. (2015), Swainsonine-induced apoptosis pathway in cerebral cortical neurons; Res. Vet. Sci., 102 34
4) Wang et al. (2015), Exposure to swainsonine impairs adult neurogenesis and spatial learning and memory; Toxicol. Lett., 232 263
5) Browning et al. (2011), Abrogation of complex glycosylation by swainsonine results in strain- and cell-specific inhibition of prion replication; J. Biol. Chem., 286 40962
6) Dantas et al. (2007), Swainsonine-induced lysosomal storage disease in goats caused by the ingestion of Turbina cordata in Northeastern Brazil; Toxicon, 49 111
Check Digit Verification of cas no
The CAS Registry Mumber 72741-87-8 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 7,2,7,4 and 1 respectively; the second part has 2 digits, 8 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 72741-87:
(7*7)+(6*2)+(5*7)+(4*4)+(3*1)+(2*8)+(1*7)=138
138 % 10 = 8
So 72741-87-8 is a valid CAS Registry Number.
InChI:InChI=1/C8H15NO3/c10-5-2-1-3-9-4-6(11)8(12)7(5)9/h5-8,10-12H,1-4H2/t5-,6?,7-,8?/m1/s1
72741-87-8Relevant articles and documents
Nitrenium ion-mediated alkene bis-cyclofunctionalization: Total synthesis of (-)-swainsonine
Wardrop, Duncan J.,Bowen, Edward G.
, p. 2376 - 2379 (2011)
Chemical equations presented. The total synthesis of (-)-swainsonine from 2,3-O-isopropylidene-d-erythrose in 12 steps and an overall yield of 28% is reported. The pivotal transformation in our route to this indolizidine alkaloid is the formation of the pyrrolidine ring and C-8a/8 stereodiad through the diastereoselective, bis-cyclofunctionalization of an γ,ss-unsaturated O-alkyl hydroxamate. This transformation is believed to proceed via the intramolecular capture of an N-acyl-N-alkoxyaziridinium ion generated by the diastereoselective addition of a singlet acylnitrenium ion to the pendant alkene.
Concise and divergent total synthesis of swainsonine, 7-alkyl swainsonines, and 2,8a-diepilentiginosine via a chiral heterocyclic enaminoester intermediate
Shi, Gao-Feng,Li, Jia-Qi,Jiang, Xiao-Ping,Cheng, Ying
, p. 5005 - 5012 (2008)
The concise and divergent total syntheses of (-)-swainsonine, (-)-7-alkyl swainsonines, and (-)-2,8a-diepilentiginosine from a common chiral heterocyclic enaminoester intermediate in five-step sequences are presented. The highly efficient annulation reaction of the chiral heterocyclic enaminoester with various α,β-unsaturated carboxylates, and a straightforward carboxy inversion constituted the key features of the synthetic pathway. This work provides an example for divergent synthesis of different natural and unnatural polyhydroxylated indolizidines from a readily available platform.
Diisopropyl tartrate-modified (E)-γ-[(menthofuryl)dimethylsilyl]-allyl boronate, an improved chiral reagent for the anti α-hydroxyallylation of aldehydes. Application to the enantioselective synthesis of (-)-swainsonine
Hunt,Roush
, p. 501 - 504 (1995)
An enantioselective synthesis of anti 1,2-diols via the reactions of aldehydes and the tartrate ester-modified (E)-γ-(menthofurylsilyl)allylboronate 5 has been developed. This methodology is applied to a brief, enantioselective synthesis of (-)-swainsonine.
Epimerization of C5 of an: N -hydroxypyrrolidine in the synthesis of swainsonine related iminosugars
Qian, Bao-Chen,Kamori, Akiko,Kinami, Kyoko,Kato, Atsushi,Li, Yi-Xian,Fleet, George W. J.,Yu, Chu-Yi
, p. 4488 - 4498 (2016/06/06)
Epimerization of C5 of an N-hydroxypyrrolidine ring by regioselective oxidation to a nitrone followed by diastereoselective reduction provides a new approach to the synthesis of swainsonine and related compounds. The only protection in the synthesis of the potent mannosidase inhibitor DIM (1,4-dideoxy-1,4-imino-d-mannitol) was the acetonation of d-mannose.
Synthesis of pyrrolidine iminosugars, (-)-lentiginosine, (-)-swainsonine and their 8a-epimers from d-glycals
Ansari, Alafia A.,Vankar
, p. 12555 - 12567 (2014/03/21)
Synthesis of pyrrolidine iminosugars has been described from d-glycals via dihydroxylation, oxidative cleavage and double nucleophilic displacement as the key steps. The pyrrolidines obtained have been utilized for the synthesis of important bicyclic iminosugars, viz. (-)-lentiginosine and (-)-swainsonine and their 8a-epimers, which are known to be glycosidase inhibitors.
