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Application of curcumin analog S1 containing piperidone structure in preparation of anti-inflammation drugs

A technology of curcumin analogs and piperidone, which is applied in the field of Ming medicine and can solve the problems of weak stability of curcumin

Active Publication Date: 2014-07-16
WENZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Through a large number of documents and patents, we found that although it is generally believed that the active groups in the structure of curcumin are its phenolic hydroxyl group and β-diketone group, in the related research on curcumin analogues, it was also found that no Monocarbonyl curcumin analogues of β-diketones sometimes also exhibit strong biological activity, which also raises doubts that the β-diketone group is an essential group for the activity of curcumin
Moreover, the β-diketone skeleton is the main reason for the weaker stability of curcumin

Method used

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  • Application of curcumin analog S1 containing piperidone structure in preparation of anti-inflammation drugs
  • Application of curcumin analog S1 containing piperidone structure in preparation of anti-inflammation drugs
  • Application of curcumin analog S1 containing piperidone structure in preparation of anti-inflammation drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Synthesis of Compound S1

[0023] At room temperature, 10 mmol of vanillin was dissolved in 12 mL of ethanol, and then 5 mmol of piperidone was added thereto. After reacting at room temperature for half an hour, HCl gas was passed into it until TLC detected that the raw material point disappeared. Then the reaction mixture was poured into 25 mL of ice water, and a yellow precipitate was produced. After filtration, the residual solid was washed with water without further purification, and was directly carried out to the next reaction. Dissolve the residual solid in 10 mL of tetrahydrofuran, add 3 mL of triethylamine, stir for half an hour, then add corresponding 10 mmol of propionyl chloride to it, after the reaction is complete, concentrate, pass through a silica gel column to obtain the target compound S1 with a purity greater than 98%. compound.

[0024] [(1E,1′E)-(4-Oxo-1-propionylpiperidine-3,5-diylidene)bis(methylidene)]bis(2-methoxy-4,1-phenylene)dipropionate (S...

Embodiment 2

[0026] Compound S1 inhibits the release of inflammatory factors (TNF-α and IL-6) from macrophages stimulated by LPS

[0027] The method of inhibiting the release of inflammatory factors by LPS-stimulated macrophages using compounds, the detailed steps are as follows: 1.2×10 6 RAW264.7 macrophages were cultured with DMEM medium at 37°C. After 24 hours, the medium was renewed, and the test compound (the final concentration was 10 μM) was added for pretreatment for 2 hours, and then continued to be treated with 0.5 μg / mL LPS. After 22 hours, the culture fluid was collected, and the contents of TNF-α and IL-6 were detected by ELISA; The -6 content was calibrated to 100; each compound was tested three times, and the average value and error value were calculated. During the test, the positive drug curcumin (cur) was used as a control. The inhibitory activities of compound S1 on the release of IL-6 and TNF-α are shown in figure 1 .

[0028] At the same time, we further tested the...

Embodiment 3

[0030] Toxicity of compound S1 to normal human liver cells HL-7702 and the stability test of its compound

[0031] After being treated with 10 μM compound S1 for 24 hours, the cell survival rate of human normal hepatocyte cell HL-7702 was detected by MTT (thiazolium blue), which was used to characterize the activity of the compound on hepatocyte HL-7702 ( image 3 A); Compound S1 was dissolved in DMSO to prepare a 10 μM solution. The absorbance of the compound at 0, 5, 10, 15, 20, and 25 min was detected in the wavelength range of 250-600 nm. Because the intensity of absorbance is directly proportional to the content or concentration of the compound in the solution, this parameter is used to characterize the stability of the compound ( image 3 B).

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Abstract

The invention belongs to the field of the pharmaceutical chemistry and pharmacology, and concretely relates to an application of a compound of [(1E,1'E)-(4-Oxo-1-propionylpiperidine-3,5-diylidene)bis(methanylylidene)]bis(2-methoxy-4,1-phenylene)dipropionate (S1) in the preparation of anti-inflammation or / and anti-oxidation drugs. The above piperidone type curcumin analog S1 can dose-dependently inhibit the expression and release of inflammation factors comprising TNF-alpha, IL-6 and the like, and can also obviously improve the survival rate of mice death-induced by LPS. The compound has a good safety and stability, and can be exploited to inflammation or / and oxidation stress related disease treatment drugs.

Description

Technical field: [0001] The invention belongs to the field of medicinal chemistry and pharmacology, and specifically relates to compound S1, whose chemical name is [(1E, 1′E)-(4-Oxo-1-propionylpiperidine-3,5-diylidene)bis(methylidene)]bis( 2-methoxy-4, 1-phenylene)dipropionate is used in the treatment of diseases caused by inflammation or / and oxidative stress. This compound achieves good anti-inflammatory effects in vitro and in vivo by inhibiting the expression and release of various inflammatory factors At the same time, they also have good antioxidant activity, and have the prospect of being developed as therapeutic drugs related to inflammation and / or oxidative stress. Background technique: [0002] Current status of anti-inflammatory drugs: [0003] Inflammation is a pathological process shared by many important diseases, and some people even put forward the saying that "inflammation is the root of all diseases". Studies have confirmed that, in addition to various typ...

Claims

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Application Information

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IPC IPC(8): A61K31/4412A61P29/00A61P39/06A61P9/10A61P9/00A61P7/10A61P19/02A61P25/16
Inventor 刘志国冯建鹏吴建章姜鑫唐龙光俞鹏天胡杰梁广
Owner WENZHOU MEDICAL UNIV
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