| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Platelet aggregation
|
|---|---|
| ln Vitro |
Six diterpene alkaloids with an atisine-type C20-skeleton isolated from the Chinese herbal medicines Spiraea japonica var. acuta and S. japonica var. ovalifolia, as well as eight derivatives of spiramine C and spiradine F were evaluated for the ability to inhibit aggregation of rabbit platelets induced by arachidonic acid, ADP, and platelet-activating factor (PAF) in vitro. The results showed that 12 of the 14 atisine-type diterpene alkaloids significantly inhibited PAF-induced platelet aggregation in a concentration-dependent manner, but had no effect on ADP- or arachidonic acid-induced aggregation, exhibiting a selective inhibition. It is the first report that C20-diterpene alkaloids inhibit PAF-induced platelet aggregation. However, spiramine C1 concentration-dependently inhibited platelet aggregation induced by PAF, ADP and arachidonic acid with IC50 values of 30.5±2.7, 56.8±8.4 and 29.9±9.9 μM, respectively, suggesting a non-selective antiplatelet aggregation action. The inhibitory effect of spiramine C1 on arachidonic acid was as potent as that of aspirin. Primary studies of the structure–activity relationships for inhibition of PAF-induced aggregation showed that the oxygen substitution at the C-15 position and the presence of an oxazolidine ring in spiramine alkaloids were essential to their antiplatelet aggregation effects. These results suggest that the atisine-type alkaloids isolated from S. japonica are a class of novel antiplatelet aggregation agents. [2]
|
| Enzyme Assay |
Effects of atisine-type alkaloids on platelet aggregation induced by PAF [2]
In vitro, all test compounds significantly inhibited 4.5 nM PAF-induced rabbit platelet aggregation in a concentration-dependent manner (Fig. 4). Among the natural alkaloids, spiramine A was the most potent with an IC50 value of 6.7±0.7 μM. The strongest semi-synthetic derivative was spiramine C1 with an IC50 value of 30.5±2.7 μM. Deacetylspiramine F and spiradine F2 had modest activity with an inhibitory rate of 41.0±3.0% and 37.7±3.8% at a final concentration of 240 μM. The rank order of the |
| References | |
| Additional Infomation |
Spiradine F has been reported in Spiraea japonica with data available.
Since 1987, a number of new atisine-type diterpenoid alkaloids with a C20 skeleton have been obtained from the roots of Spiraea japonica (Rosaceae) Hao et al., 1987, Hao et al., 1995, Hao and Nie, 1998, Wang et al., 2000a, He et al., 2001, a Chinese herbal medicine widespread in Yunnan Province which has long been used for anti-inflammation and analgesia in folk and ethnic traditions (Zhang and Wang, 1993). Previously, we found that the ethanol extract of this plant and the crude alkaloids inhibited rabbit platelet aggregation induced by platelet-activating factor (PAF) in vitro (data not shown). Recently, we reported that spiramine Q (Fig. 1, the structure of spiramine Q has been corrected to the present form, Wang et al., 2000b), a novel atisine-type diterpene alkaloid isolated from S. japonica var. incisa, was found to selectively inhibit rabbit platelet aggregation induced by arachidonic acid in vitro and ex vivo and that the inhibition was much stronger than that of aspirin (Shen et al., 2000). In the present study, the antiplatelet aggregation activities of some natural atisine-type alkaloids isolated from S. japonica var. acuta and S. japonica var. ovalifolia (Fig. 2), and the semi-synthetic derivatives of spiramine C and spiradine F (Fig. 3) were investigated. Their structure–activity relationships are discussed as well. [1] |
| Molecular Formula |
C24H33NO4
|
|---|---|
| Molecular Weight |
399.52
|
| Exact Mass |
399.24
|
| CAS # |
21040-64-2
|
| PubChem CID |
91895271
|
| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
510.5±50.0 °C at 760 mmHg
|
| Flash Point |
262.5±30.1 °C
|
| Vapour Pressure |
0.0±1.3 mmHg at 25°C
|
| Index of Refraction |
1.603
|
| LogP |
4.24
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
29
|
| Complexity |
813
|
| Defined Atom Stereocenter Count |
9
|
| SMILES |
CC(O[C@@H]1[C@@H]2OC3N4CCO[C@H]4[C@@]4(CCC[C@@]3([C@@H]3C[C@@H]5CC[C@@]32CC5=C)C14)C)=O
|
| InChi Key |
HSZMQRORNAEJTB-YBUCERMMSA-N
|
| InChi Code |
InChI=1S/C24H33NO4/c1-13-12-23-8-5-15(13)11-16(23)24-7-4-6-22(3)18(24)17(28-14(2)26)19(23)29-21(24)25-9-10-27-20(22)25/h15-21H,1,4-12H2,2-3H3/t15-,16+,17-,18+,19+,20-,21?,22+,23+,24+/m0/s1
|
| Chemical Name |
[(1S,2R,5S,7R,8R,12R,13S,20S,21R)-12-methyl-4-methylidene-14,19-dioxa-17-azaheptacyclo[10.7.2.22,5.02,7.08,18.08,21.013,17]tricosan-20-yl] acetate
|
| Synonyms |
Spiradine F; 21040-64-2; [(1S,2R,5S,7R,8R,12R,13S,20S,21R)-12-methyl-4-methylidene-14,19-dioxa-17-azaheptacyclo[10.7.2.22,5.02,7.08,18.08,21.013,17]tricosan-20-yl] acetate; O-Acetylspiradine G; Spiradin F; Spiradine G acetate;
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5030 mL | 12.5150 mL | 25.0300 mL | |
| 5 mM | 0.5006 mL | 2.5030 mL | 5.0060 mL | |
| 10 mM | 0.2503 mL | 1.2515 mL | 2.5030 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
