Castanospermine, a novel indolizidine alkaloid first isolated from the seeds of Castanospermum australe, is a potent inhibitor of some glucosidase enzymes and has antiviral activity in vitro and in mouse models. Castanospermine was a lead to celgosivir. Castanospermine inhibits all forms of α- and β-glucosidases, especially glucosidase l (required for glucoprotein processing by transfer of mannose and glucose from asparagine-linked lipids).
Physicochemical Properties
| Molecular Formula | C8H15NO4 |
| Molecular Weight | 189.209 |
| Exact Mass | 189.1 |
| CAS # | 79831-76-8 |
| Related CAS # | 141117-12-6 (HCl);79831-76-8; |
| PubChem CID | 54445 |
| Appearance | White to off-white solid powder |
| Density | 1.5±0.1 g/cm3 |
| Boiling Point | 421.9±45.0 °C at 760 mmHg |
| Melting Point | 213-217 °C(lit.) |
| Flash Point | 267.6±27.4 °C |
| Vapour Pressure | 0.0±2.3 mmHg at 25°C |
| Index of Refraction | 1.647 |
| LogP | -1.61 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 0 |
| Heavy Atom Count | 13 |
| Complexity | 201 |
| Defined Atom Stereocenter Count | 5 |
| SMILES | C1CN2C[C@@H]([C@H]([C@@H]([C@H]2[C@H]1O)O)O)O |
| InChi Key | JDVVGAQPNNXQDW-TVNFTVLESA-N |
| InChi Code | 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 |
| Chemical Name | (1S,6S,7R,8R,8aR)-1,2,3,5,6,7,8,8a-octahydroindolizine-1,6,7,8-tetrol |
| Synonyms | Castanospermine |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | In BGK-21 cells, castanospermine (0.01-1000 μM, 48 hours) suppresses the formation of DEN infectious virus in a dose-dependent manner and decreases the glycosylated structural protein DEN prM's electrophoretic mobility [1]. |
| ln Vivo | Mice can become more susceptible to DEN-2 virus infection when given castanospermine (10, 50, or 250 mg/kg) intraperitoneally once every ten days [1]. Mice's susceptibility to DEN-2 virus infection can be boosted by intraperitoneal injection of castanospermine (10–500 mg/kg) [1]. |
| Cell Assay |
RT-PCR[1] Cell Types: BHK-21 Tested Concentrations: 100, 500 μM Incubation Duration: 48 hrs (hours) Experimental Results: A modest reduction of up to 20 to 40% in marker gene expression or proliferation of WNV or DEN replicons, respectively. The effect on secretion of infectious WNV or WNV RNA-containing viral particles was minor, but the amount of DEN viral RNA and infectious virus was diminished. |
| Animal Protocol |
Animal/Disease Models: A/J mouse model [1] Doses: 10, 50, 250 mg/kg Route of Administration: intraperitoneal (ip) injection Experimental Results: The secretion and virus infectivity of DEN-infected mice were diminished, and the survival rate of the virus was increased. Animal/Disease Models: Acute pancreatitis (AP) rat model [2] Doses: 10, 50, 100, 200, 500 mg/kg Route of Administration: intraperitoneal (ip) injection Experimental Results: The extent and severity of pancreatic damage were Dramatically diminished. Reduces serum interleukin production and NF-kB activation. Increased levels of TNF-a, ICAM-1 and VCAM-1. |
| References |
[1]. Castanospermine, a potent inhibitor of dengue virus infection in vitro and in vivo. J Virol. 2005 Jul;79(14):8698-706. [2]. Effects of Castanospermine on Inflammatory Response in a Rat Model of Experimental Severe Acute Pancreatitis. Arch Med Res. 2016 Aug;47(6):436-445. [3]. Elbein AD. Glycosidase inhibitors: inhibitors of N-linked oligosaccharide processing. FASEB J. 1991 Dec;5(15):3055-63. [4]. Combined donor leucocyte administration and immunosuppressive drug treatment for survival of rat heart allografts. Transpl Immunol. 2004 Nov;13(3):177-84. |
| Additional Infomation |
Castanospermine is a tetrahydroxyindolizidine alkaloid that consists of octahydroindolizine having four hydroxy substituents located at positions 1, 6, 7 and 8 (the 1S,6S,7R,8R,8aR-diastereomer). It has a role as a metabolite, an anti-HIV-1 agent, an anti-inflammatory agent and an EC 3.2.1.* (glycosidase) inhibitor. Castanospermine has been reported in Alexa canaracunensis, Alexa grandiflora, and other organisms with data available. |
Solubility Data
| Solubility (In Vitro) |
H2O : ~100 mg/mL (~528.51 mM) DMSO : ~100 mg/mL (~528.51 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (13.21 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (13.21 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (13.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 120 mg/mL (634.22 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.2851 mL | 26.4257 mL | 52.8513 mL | |
| 5 mM | 1.0570 mL | 5.2851 mL | 10.5703 mL | |
| 10 mM | 0.5285 mL | 2.6426 mL | 5.2851 mL |