CASTANOSPERMINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C8H15NO4
Molecular Weight	189.209
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12[C@@H](O)CCN1C[C@H](O)[C@@H](O)[C@@H]2O

InChI

InChIKey=JDVVGAQPNNXQDW-TVNFTVLESA-N

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

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27509020 | https://www.ncbi.nlm.nih.gov/pubmed/19649930 | https://www.ncbi.nlm.nih.gov/pubmed/26794905https://www.ncbi.nlm.nih.gov/pubmed/3881759
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27986123 | https://www.ncbi.nlm.nih.gov/pubmed/15994763 | https://www.ncbi.nlm.nih.gov/pubmed/3300654

Castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizine) is an indolizine alkaloid first isolated from the seeds of Australian tree Castanospermum austral. Castanospermine is a potent inhibitor of some glucosidase enzymes and has antiviral, immunosuppressant and anti-inflammatory activity in vitro and in animal models. Castanospermine has been shown to be a potent inhibitor of almond emulsion β-glucosidase, and also to inhibit fungal β-xylosidase. Additionally, castanospermine may have the potential ability to inhibit syncytium formation between HIV-infected and CD4-expressing cells and may also interfere with infectivity. It has also been demonstrated that this agent inhibits inflammation at the level of leukocyte extravasation in rat models of experimental adjuvant-induced arthritis and autoimmune encephalomyelitis. Celgosivir, Castanospermine’s oral prodrug, is currently tested in clinical trials.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Beta-glucosidase 3 Target ID: CHEMBL3761 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23363020	Inhibitor 8297		19.0 µM [IC50]
Alpha-glucosidase I 3 Target ID: Alpha-glucosidase I Sources: https://www.ncbi.nlm.nih.gov/pubmed/7986008	Inhibitor 8297		127.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Dengue virus infection 12 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15994763	Curative		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Glycosylation and the cystic fibrosis transmembrane conductance regulator.	2001	11686896
Synthesis of polyhydroxyindolizidines from 5,6-dihydro-2H-pyran-2-one.	2001 Dec 7	11728400
Interferon-gamma increases the expression of glycosylated CD95 in B-leukemic cells: an inducible model to study the role of glycosylation in CD95-signalling and trafficking.	2002 Apr 21	12096925
Biosynthesis and processing of Spodoptera frugiperda alpha-mannosidase III.	2002 Jun	12107079
Inhibition of bacterial alpha-glucosidases by castanospermine in pure cultures and activated sludge.	2002 Jun	12073134
Selection of a high-energy bioactive conformation of a sulfonium-ion glycosidase inhibitor by the enzyme glucoamylase G2.	2003 May 14	12733904
The cargo receptor ERGIC-53 is a target of the unfolded protein response.	2003 May 16	12727195
Indolizidine and quinolizidine alkaloids.	2004 Oct	15459758
Synthesis of 1-deoxy-1-hydroxymethyl- and 1-deoxy-1-epi-hydroxymethyl castanospermine as new potential immunomodulating agents.	2007 Nov 1	17918922
Vinylogous Mukaiyama aldol reactions with 4-oxy-2-trimethylsilyloxypyrroles: relevance to castanospermine synthesis.	2007 Nov 3	17980041
A divergent asymmetric approach to aza-spiropyran derivative and (1S,8aR)-1-hydroxyindolizidine.	2007 Nov 8	17996045
Role of receptor polymorphism and glycosylation in syncytium induction and host range variation of ecotropic mouse gammaretroviruses.	2008 Jan 10	18186934
The comparative pathology of the glycosidase inhibitors swainsonine, castanospermine, and calystegines A3, B2, and C1 in mice.	2008 Jul	18497426
Divergence of catalytic mechanism within a glycosidase family provides insight into evolution of carbohydrate metabolism by human gut flora.	2008 Oct 20	18848471
Tetrapisispora phaffii killer toxin is a highly specific beta-glucanase that disrupts the integrity of the yeast cell wall.	2009 Oct 27	19860881
Single chain variable fragment against nicastrin inhibits the gamma-secretase activity.	2009 Oct 9	19684016
A new synthetic access to bicyclic polyhydroxylated alkaloid analogues from pyranosides.	2010 Jun 7	20376396

Patents

Sample Use Guides

In Vivo Use Guide

400 mg loading dose and 200 mg bid

Route of Administration: Oral

In Vitro Use Guide

LoVo/Dx, W1PR, W1TR and A2780T1 cell lines were used for activity evaluation. The cells were seeded at 4x10^3 cells/well (200 μl) in 96-well culture plates and pre-incubated for 48 h. To examine the effect of BFA, CAS or chemotherapeutic drugs on cell survival, the cells were treated with increasing concentrations of BFA, CAS (Castanospermine, 10 μg/ml for LoVo/Dx, 50 μg/ml for W1PR and W1TR and 60 μg/ml for A2780T1 cells.) for 72 h. Subsequently, 10 μl of MTT labeling reagent was added to the medium (the final concentration of MTT was 0.5 mg/ml) for 4 h and 100 μl of the solubilized solution was then added to each well. After an overnight incubation, the absorbance was measured in a microplate reader at 570 nm with a reference wavelength of 720 nm.

Name

Type

Language

CASTANOSPERMINE

Common Name

English

(1S,6S,7R,8R,8AR)-OCTAHYDRO-1,6,7,8-INDOLIZINETETROL

Common Name

English

CASTANOSPERMINE [MI]

Common Name

English

NSC-625381

Code

English

Code System Code Type Description

NSC

625381