CN101591228A - New azulenoid and application thereof - Google Patents
New azulenoid and application thereof Download PDFInfo
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- CN101591228A CN101591228A CNA2009100123138A CN200910012313A CN101591228A CN 101591228 A CN101591228 A CN 101591228A CN A2009100123138 A CNA2009100123138 A CN A2009100123138A CN 200910012313 A CN200910012313 A CN 200910012313A CN 101591228 A CN101591228 A CN 101591228A
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Abstract
The invention belongs to medical technical field, relate to new azulenoid and application thereof, the chemical formula that is specifically related to treat disease of immune system and have anti-aging effects is the new azulenoid of I and II.Such compound structure is comparatively stable, and is fat-soluble stronger, is equipped with proper pharmaceutical excipients and can be made into the pharmaceutically various preparations of acceptable.The immunological experiment result shows that Compound I and II have the effect of stronger rise immunity function, and anti-oxidant experiment shows that the two has stronger removal free radical activity.Azulenoid of the present invention and preparation thereof are mainly used in the various diseases that hypoimmunity causes, also can be used for anti-ageing.
Description
Technical field
The invention belongs to medical technical field, relate to new azulenoid and application thereof, be specifically related to new azulenoid and the application in the medicine of the various diseases that the preparation immunologic hypofunction causes thereof.
Background technology
Modern pharmacology studies show that azulenoid has and removes free radical, anti-ageing, anti-inflammatory, healing wound, improves immunizing power and effect such as antibiotic.Be mainly used in now skin injury reparation and antiphlogiston or skin-protection health products etc. that wound such as burn and scald causes in the medical treatment.But be not applied to immunoregulatory precedent, because common azulenoid substituting group is less, kind is comparatively single and rare, defines its applied research greatly.
Summary of the invention
The objective of the invention is to find polysubstituted new azulenoid, and they are preparing the relevant medicine of immunomodulatory or are preparing anti-ageing, as to remove healthcare products such as free radical new function.
Structural formula of compound is as shown below among the present invention, and I has the new azulenoid that connects oxygen isopentene group and indandione ring, and II is that the polymkeric substance that Claisen resets back dimerization formation takes place isopentene group.
The preparation method of compound can be implemented by following technical solution among the present invention:
(1) with the mycelium volume fraction of fungi Nigrospora sphaerica be 80% acetone extraction, extract separates through silica gel column chromatography, is that moving phase is carried out wash-out with chloroform and methyl alcohol, gets 20: 1 parts.
(2) with LH-20 depigmentation on 20: 1 parts, with chloroform and methyl alcohol volume ratio be 1: 1 be moving phase, it is standby to get the more shallow interruption of color.
(3) will slightly break apart by chopping through mesolow through the part that above method makes, and reach the preparation liquid phase more by analysis and produce that (methyl alcohol: water=70%), elution time was respectively 40 minutes and 44 minutes, can obtain two compounds.
(4) nuclear magnetic data of Compound I and II is as shown in the table.
Table?1.
1H?and?
13C?NMR?Data?for?I
aData?recorded?in?DMSO-d
6.
b1H?was?recorded?at?600MHz?and?
13C?at?150MHzTable2.
1H?and?
13C?NMR?Data?for?II
aData?recorded?in?DMSO-d
6.
b1H?was?recorded?at?600MHz?and?
13C?at?150MH
Compound of the present invention can be made injection, oral and exterior-applied formulation, and the immunological experiment result shows that Compound I and II have the effect of stronger rise immunity function, and anti-oxidant experiment shows that the two has stronger removal free radical activity.
Description of drawings
Fig. 1 carries out the evaluation map of radical scavenging activity for adopting the DPPH method to compound.
Embodiment
The following examples can help those skilled in the art more fully to understand the present invention, but limit the present invention never in any form.
Embodiment 1:
Under room temperature, 300g (weight in wet base) mycelium is placed Erlenmeyer flask, with the acetone extraction of 800ml 80%, extract separates through silica gel column chromatography, with chloroform and methyl alcohol be moving phase carry out wash-out (100: 1,100: 3,100: 5,100: 8,100: 10,9: 1,7: 1,5: 1,3: 1), get 100: 5 parts.With sephadex lh-20 depigmentation on 100: 5 parts, with chloroform and methyl alcohol volume ratio be 1: 1 be moving phase, it is standby to get flavous interruption.The part that will make through above method is through the mesolow rough segmentation, getting 70% and 80% part merges, reach the preparation liquid phase more by analysis and produce (methyl alcohol: water=70%), elution time was respectively 40 minutes and 44 minutes, can obtain two compounds, Compound I (3.2mg), Compound I I (4.1mg), purity has all reached more than 98% by analysis.
Embodiment 2:
Under room temperature, 300g (weight in wet base) mycelium is placed Erlenmeyer flask, with the acetone extraction of 800ml 100%, extract separates through silica gel column chromatography, is that moving phase is carried out wash-out with chloroform and methyl alcohol, gets 20: 1 parts.With LH-20 depigmentation on 20: 1 parts, with chloroform and methyl alcohol volume ratio be 1: 1 be moving phase, it is standby to get the more shallow interruption of color.To slightly break apart by chopping through mesolow through the part that above method makes, reach the preparation liquid phase more by analysis and produce (methyl alcohol: water=70%), elution time was respectively 40 minutes and 44 minutes, can obtain two compounds, Compound I (2.2mg), Compound I I (3.3mg), purity has all reached more than 98% by analysis.
Embodiment 3:
Respectively accurately draw little sample solution with volume in the 5mL volumetric flask, all accurate 31.52 μ g/mL DPPH Ji liquid that adds 3mL is used methanol constant volume.Lucifuge leaves standstill behind the 1h and to measure light absorption value in the 516nm place under the room temperature.
The clearance rate calculation formula of DPPH: clearance rate (%)=[1 one (DPPH)
t,/(DPPH)
T=0] * 100%
In the formula (DPPH)
T=0Starting point concentration for DPPH free radical in the system; (DPPH)
tConcentration for DPPH free radical in the Ji liquid behind the 1h.With sample (μ g)/DPPH (μ g) the DPPH free radical scavenging activity is mapped.
Increase clearance rate with dosage and also strengthen gradually, up to reaching a comparatively horizontal fixed level, the variation tendency of clearance rate just thaws.
Embodiment 4:
Mtt assay detects decide compound and the influence of ConA inductive mice spleen T cell proliferation is provided with Control group, ConA group, ConA+I 5 μ g/ml group, ConA+II 5 μ g/ml group, ConA+I 20 μ g/ml group, ConA+II 20 μ g/ml group, ConA+I 60 μ g/ml group, ConA+II 60 μ g/ml group, ConA+I 100 μ g/ml group and ConA+II 100 μ g/ml respectively organizes.Cell inoculation is in 96 porocyte culture plates, and every hole adds the medicine (final concentration is respectively 5,20,60,100 μ g/ml) of 10 μ L different concns, and each concentration is established 3 multiple holes, and constant volume 200 μ L in every hole are in 37 ℃, 50mL/L CO
2Incubator preincubate 2h adds ConA (final concentration 5mg/L) then and continues to cultivate.Add 48h behind the ConA, every hole adds 20 μ L MTT working fluids, in 37 ℃, 50mL/LCO
2Incubator is hatched 4h, and centrifugal 5min sops up supernatant liquid, and every hole adds 100 μ L DMSO, vibration 10min, and immune microplate reader 490nm wavelength detects absorbancy (A value).
The OD value of table 3. compound 1
Attention: with blank group contrast * P＜0.05; * P＜0.01.
The OD value of table 4. compound 2
Attention: with blank group contrast * P＜0.05; * P＜0.01.
Claims (4)
1. new azulenoid is characterized in that: its structural formula is as (I) with (II):
2. new azulenoid according to claim 1 is characterized in that: I has the new azulenoid that connects oxygen isopentene group and indandione ring, and II is that the polymkeric substance that Claisen resets back dimerization formation takes place isopentene group.
3. new azulenoid according to claim 1 is characterized in that: described azulenoid can be prepared into the various preparations of acceptable clinically with pharmaceutically acceptable carrier or mixed with excipients.
The various diseases that causes at preparation treatment immunologic hypofunction of any one described new azulenoid of claim 1-3 and anti-ageing, remove the application in free radical medicine or the healthcare products.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN2009100123138A CN101591228B (en) | 2009-06-30 | 2009-06-30 | Novel azulene compounds and application thereof |
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| CN2009100123138A CN101591228B (en) | 2009-06-30 | 2009-06-30 | Novel azulene compounds and application thereof |
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| CN101591228A true CN101591228A (en) | 2009-12-02 |
| CN101591228B CN101591228B (en) | 2013-09-25 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102267929A (en) * | 2011-06-20 | 2011-12-07 | 四川国康药业有限公司 | Preparation of novel N-amino acid substituted azulene sulfamide medicine and anti-gastric ulcer actions thereof |
| CN103159702A (en) * | 2013-04-15 | 2013-06-19 | 四川国康药业有限公司 | Synthesis of 1-substituent-5-isopropyl-3, 8-dimethyl azulenyl sulfonyl piperazine and anti-gastric ulcer activity research |
-
2009
- 2009-06-30 CN CN2009100123138A patent/CN101591228B/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102267929A (en) * | 2011-06-20 | 2011-12-07 | 四川国康药业有限公司 | Preparation of novel N-amino acid substituted azulene sulfamide medicine and anti-gastric ulcer actions thereof |
| CN102267929B (en) * | 2011-06-20 | 2014-02-19 | 四川国康药业有限公司 | Preparation of novel N-amino acid substituted azulene sulfamide medicine and anti-gastric ulcer actions thereof |
| CN103159702A (en) * | 2013-04-15 | 2013-06-19 | 四川国康药业有限公司 | Synthesis of 1-substituent-5-isopropyl-3, 8-dimethyl azulenyl sulfonyl piperazine and anti-gastric ulcer activity research |
| CN103159702B (en) * | 2013-04-15 | 2014-10-01 | 四川国康药业有限公司 | Synthesis of 1-substituent-5-isopropyl-3, 8-dimethyl azulenyl sulfonyl piperazine and anti-gastric ulcer activity research |
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| Publication number | Publication date |
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| CN101591228B (en) | 2013-09-25 |
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