castanospermine

Castanospermine^[1]^[2]
Names
	IUPAC name (1S,6S,7R,8R,8aR)-1,2,3,5,6,7,8,8a-octahydroindolizine-1,6,7,8-tetrol
Identifiers
CAS Registry Number	79831-76-8
ChEBI	CHEBI:27860
ChEMBL	ChEMBL311226
ChemSpider	49177
	InChI InChI=1S/C8H15NO4/c10-4-1-2-9-3-5(11)7(12)8(13)6(4)9/h4-8,10-13H,1-3H2/t4-,5-,6+,7+,8+/m0/s1 ; Key: JDVVGAQPNNXQDW-TVNFTVLESA-N ; InChI=1/C8H15NO4/c10-4-1-2-9-3-5(11)7(12)8(13)6(4)9/h4-8,10-13H,1-3H2/t4-,5-,6+,7+,8+/m0/s1; Key: JDVVGAQPNNXQDW-TVNFTVLEBE ;
Jmol-3D images	Image
PubChem	54445
	SMILES O[C@H]1CCN2[C@H]1[C@@H](O)[C@H](O)[C@@H](O)C2 ;
Properties
Chemical formula	C8H15NO4
Molar mass	189.209 g/mol
Appearance	White to off-white solid
Melting point	212 to 215 °C (414 to 419 °F; 485 to 488 K)
Solubility in water	Soluble
Hazards
R-phrases	R20/21/22
S-phrases	S26 S36
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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	Infobox references

カスタノスペルミン

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/08 13:30:24」(JST)

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Castanospermine is an indolizine alkaloid first isolated from the seeds of Castanospermum australe.^[3] It is a potent inhibitor of some glucosidase enzymes^[4] and has antiviral activity.^[5]

References

^ Merck Index, 11th Edition, 1902.
^ Castanospermine at Fermentek
^ Hohenschutz, Liza D.; Bell, E. Arthur; Jewess, Phillip J.; Leworthy, David P.; Pryce, Robert J.; Arnold, Edward; Clardy, Jon (1981). "Castanospermine, a 1,6,7,8-tetrahydroxyoctahydroindolizine alkaloid, from seeds of Castanospermum australe". Phytochemistry 20 (4): 811–14. doi:10.1016/0031-9422(81)85181-3.
^ R Saul, J J Ghidoni, R J Molyneux, and A D Elbein (1985). "Castanospermine inhibits alpha-glucosidase activities and alters glycogen distribution in animals". PNAS 82 (1): 93–97. doi:10.1073/pnas.82.1.93. PMC 396977. PMID 3881759.
^ Whitby K, Pierson TC, Geiss B, Lane K, Engle M, Zhou Y, Doms RW, Diamond MS (2005). "Castanospermine, a potent inhibitor of dengue virus infection in vitro and in vivo". J Virol 79 (14): 8698–706. doi:10.1128/JVI.79.14.8698-8706.2005. PMC 1168722. PMID 15994763.

English Journal

Tunicamycin inhibits Toll-like receptor-activated inflammation in RAW264.7 cells by suppression of NF-κB and c-Jun activity via a mechanism that is independent of ER-stress and N-glycosylation.

Kim SY, Hwang JS, Han IO.Author information Department of Physiology and Biophysics, College of Medicine, Inha University, 253, Shinheung-Dong, Jung-Ku, Incheon, Republic of Korea.AbstractIn this study, we investigated the effect of tunicamycin on the production of pro-inflammatory molecules in RAW264.7 macrophage cells in response to lipopolysaccharide (LPS) and Toll-like receptor (TLR) agonists. Tunicamycin caused a reduction in LPS-induced nitric oxide (NO) production and expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α). In contrast, other ER stress-inducing chemicals, such as A23187 and thapsigargin (TG), increased LPS-induced COX-2 expression and had no effect on LPS-induced iNOS, TNF-α or IL-1β expression. Furthermore, the inhibitory effect of tunicamycin on LPS-induced inflammation was not influenced by salubrinal, an ER stress inhibitor, suggesting that the anti-inflammatory effect of tunicamycin is independent of ER stress. Tunicamycin also inhibited the expression of inflammatory molecule mRNAs induced by stimulation of TLR2 (with lipoteichoic acid) or TLR3 (with polyinosinic:polycytidylic acid), which do not require myeloid differentiation protein-2 (MD2) for their activation. Moreover, inhibition of LPS-induced iNOS expression was not inhibited by castanospermine, another N-glycosylation inhibitor, suggesting that the inhibitory effect of tunicamycin on LPS-induced iNOS induction is likely independent of MD2 N-glycosylation. Tunicamycin inhibited nuclear factor-kappaB (NF-κB) activity by suppressing LPS-induced nuclear translocation of p50 and subsequent DNA binding of p50 and p65 to the NF-κB site of the iNOS promoter. Tunicamycin also inhibited the transcriptional activity of a cAMP-response element (CRE) reporter, possibly by inhibiting c-Jun activation. Therefore, we conclude that tunicamycin represses TLR-induced inflammation through suppression of NF-κB and CRE activity via a mechanism that is independent of ER-stress and N-glycosylation.
European journal of pharmacology.Eur J Pharmacol.2013 Dec 5;721(1-3):294-300. doi: 10.1016/j.ejphar.2013.09.022. Epub 2013 Sep 18.
In this study, we investigated the effect of tunicamycin on the production of pro-inflammatory molecules in RAW264.7 macrophage cells in response to lipopolysaccharide (LPS) and Toll-like receptor (TLR) agonists. Tunicamycin caused a reduction in LPS-induced nitric oxide (NO) production and expressi
PMID 24056124

New castanospermine glycoside analogues inhibit breast cancer cell proliferation and induce apoptosis without affecting normal cells.

Allan G, Ouadid-Ahidouch H, Sanchez-Fernandez EM, Risquez-Cuadro R, Fernandez JM, Ortiz-Mellet C, Ahidouch A.Author information Laboratory of Cellular and Molecular Physiology (EA 4667), SFR CAP-SANTE (FED 4132), UFR of Sciences, UPJV, Amiens, France.Abstractsp²-Iminosugar-type castanospermine analogues have been shown to exhibit anti-tumor activity. However, their effects on cell proliferation and apoptosis and the molecular mechanism at play are not fully understood. Here, we investigated the effect of two representatives, namely the pseudo-S- and C-octyl glycoside 2-oxa-3-oxocastanospermine derivatives SO-OCS and CO-OCS, on MCF-7 and MDA-MB-231 breast cancer and MCF-10A mammary normal cell lines. We found that SO-OCS and CO-OCS inhibited breast cancer cell viability in a concentration- and time-dependent manner. This effect is specific to breast cancer cells as both molecules had no impact on normal MCF-10A cell proliferation. Both drugs induced a cell cycle arrest. CO-OCS arrested cell cycle at G1 and G2/M in MCF-7 and MDA-MB-231 cells respectively. In MCF-7 cells, the G1 arrest is associated with a reduction of CDK4 (cyclin-dependent kinase 4), cyclin D1 and cyclin E expression, pRb phosphorylation, and an overexpression of p21(Waf1/Cip1). In MDA-MB-231 cells, CO-OCS reduced CDK1 but not cyclin B1 expression. SO-OCS accumulated cells in G2/M in both cell lines and this blockade was accompanied by a decrease of CDK1, but not cyclin B1 expression. Furthermore, both drugs induced apoptosis as demonstrated by the increased percentage of annexin V positive cells and Bax/Bcl-2 ratio. Interestingly, in normal MCF-10A cells the two drugs failed to modify cell proliferation, cell cycle progression, cyclins, or CDKs expression. These results demonstrate that the effect of CO-OCS and SO-OCS is triggered by both cell cycle arrest and apoptosis, suggesting that these castanospermine analogues may constitute potential anti-cancer agents against breast cancer.
PloS one.PLoS One.2013 Oct 4;8(10):e76411. doi: 10.1371/journal.pone.0076411.
sp²-Iminosugar-type castanospermine analogues have been shown to exhibit anti-tumor activity. However, their effects on cell proliferation and apoptosis and the molecular mechanism at play are not fully understood. Here, we investigated the effect of two representatives, namely the pseudo-S- and C-
PMID 24124558

Antiviral therapies targeting host ER alpha-glucosidases: current status and future directions.

Chang J, Block TM, Guo JT.Author information Department of Microbiology and Immunology, Drexel University College of Medicine, 3805 Old Easton Road, Doylestown, PA 18902, USA. Electronic address: jinhong.chang@drexelmed.edu.AbstractEndoplasmic reticulum (ER)-resident α-glucosidases I and II sequentially trim the three terminal glucose moieties on N-linked glycans attached to nascent glycoproteins. These reactions are the first steps of N-linked glycan processing and are essential for proper folding and function of many glycoproteins. Because most viral envelope glycoproteins contain N-linked glycans, inhibition of ER α-glucosidases with derivatives of 1-deoxynojirimycin (DNJ) or castanospermine (CAST), two well-studied pharmacophores of α-glucosidase inhibitors, efficiently disrupts the morphogenesis of a broad spectrum of enveloped viruses. Moreover, both DNJ and CAST derivatives have been demonstrated to prevent the death of mice infected with several distinct flaviviruses and filoviruses and suppress the multiplication of several other species of viruses in infected animals. N-Butyl derivative of DNJ (NB-DNJ) and 6 O-bytanoyl prodrug of CAST (Bu-CAST) have been evaluated in human clinical trials for their antiviral activities against human immunodeficiency virus and hepatitis C virus, and there is an ongoing trial of treating dengue patients with Bu-CAST. This article summarizes the current status of ER α-glucosidase-targeted antiviral therapy and proposes strategies for development of more efficacious and specific ER α-glucosidase inhibitors as broad-spectrum, drug resistance-refractory antiviral therapeutics. These host function-targeted, broad-spectrum antiviral agents do not rely on time-consuming etiologic diagnosis, and should therefore be particularly promising in the management of viral hemorrhagic fever and respiratory tract viral infections, medical conditions that can be caused by many different enveloped RNA viruses, with a short window for medical intervention.
Antiviral research.Antiviral Res.2013 Sep;99(3):251-60. doi: 10.1016/j.antiviral.2013.06.011. Epub 2013 Jun 29.
Endoplasmic reticulum (ER)-resident α-glucosidases I and II sequentially trim the three terminal glucose moieties on N-linked glycans attached to nascent glycoproteins. These reactions are the first steps of N-linked glycan processing and are essential for proper folding and function of many glycop
PMID 23816430

Japanese Journal

88.Oxytropis glabraに含まれるインドリジンアルカロイドのLC-MS/MSによる分析(口頭発表)

石原亨,中島廣光,島田章則
植物化学調節学会研究発表記録集 (45), 105, 2010-10-01
… In the present study, we developed a new method for the analysis of indolizine alkaloids including swainsonine, lentiginosine, and castanospermine by using LC-MS/MS, and investigated their accumulation in O. … Castanospermine was not detectable in the extract. …
NAID 110007767188

Promotion of IL-4- and IL-5-dependent differentiation of anti-μ-primed B cells by ascorbic acid 2-glucoside

Ichiyama Kenji,Mitsuzumi Hitoshi,Zhong Ming,Tai Akihiro,Tsuchioka Akihiro,Kawai Saeko,Yamamoto Itaru,Gohda Eiichi
Immunology Letters 122(2), 219-226, 2009-02-21
… AA-2G-induced IgM production in the presence of IL-4 and IL-5 was inhibited by the alpha-glucosidase inhibitor castanospermine. …
NAID 120003911639

Glucose Trimming of N-Glycan in Endoplasmic Reticulum Is Indispensable for the Growth of Raphanus sativus Seedling (kaiware radish)

Mega Tomohiro
Bioscience, biotechnology, and biochemistry 69(7), 1353-1364, 2005-07-23
… Recently I found that glycosidase inhibitors such as castanospermine, deoxynojirimycin, swainsonine, 2-acetamindo 2,3-dideoxynojirimycin, and deoxymannojirimycin change the <I>N</I>-glycan structure of root glycoproteins, and that the glucosidase inhibitors castanospermine and deoxynojirimycin suppress the growth of <I>Raphanus sativus</I> …
NAID 130000030279

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