New chalcone derivative, preparation method and application thereof in autoimmune diseases

A chalcone derivative and autoimmune technology, which is applied in the field of medicine, can solve the problems of lack of in-depth evaluation of animal models of autoimmune diseases, limited immune regulation and anti-inflammatory activity, and lack of specificity of immune cells

Inactive Publication Date: 2016-10-12
云南省中医医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, in terms of immune regulation, single use of chalcones lacks specificity to immune cells. At present, chalcones lack in-depth evaluation on animal models of autoimmune diseases, and the strength of immune regulation and anti-inflammatory activities is limited.

Method used

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  • New chalcone derivative, preparation method and application thereof in autoimmune diseases
  • New chalcone derivative, preparation method and application thereof in autoimmune diseases
  • New chalcone derivative, preparation method and application thereof in autoimmune diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] Embodiment 1: preparation method

[0020] The synthetic method of 4-dimethylamino-4'-(1-piperazinyl)chalcone (the following formula II, referred to as compound 1) is as follows: weigh 4-fluoroacetophenone (2.76g, 20mmol) and p- - Dimethylaminobenzaldehyde (3.28g, 22mmol) In a 100mL round bottom flask, add 30mL ethanol and 20mL 20% KOH, and stir overnight at room temperature. Add 50mL of water, filter with suction, wash the solid twice with 50mL of water and 50mL of 30% ethanol-water successively, and obtain an orange-yellow solid after drying. The above solid and 5.48g (40mmol) potassium carbonate were placed in a 100mL round bottom flask, 5.8g (30mmol) piperazine hexahydrate and 60mL DMF were added, and reacted at 120°C overnight. After cooling, the reactant was poured into 150 mL of water and extracted with DCM (30 mL×3). The organic phase was dried over anhydrous sodium sulfate and concentrated, and the residue was subjected to column chromatography (with 2% CH 3 ...

Embodiment 2

[0044] Example 2: In vitro immune activity screening

[0045] 1. Build a screening model

[0046] Spleen lymphocytes of BALB / C mice undergo a series of changes in morphology and metabolism under the stimulation of mitogen ConA, transform into mother cells, and differentiate and proliferate. In this experiment, 5 μg / ml of ConA (ConA) was added to induce the proliferation of T lymphocytes. Cell proliferation was quantified by MTT assay. Mitochondrial dehydrogenase in living cells can reduce the yellow color of MTT to blue formazan, and the production of formazan is directly proportional to living cells. After dissolving in an organic solvent, the OD value can be detected with a microplate reader.

[0047] Result evaluation: for the proliferation of lymphocytes, the OD value of the tested sample minus the OD value of the control well is used, and the OD value of the control well is multiplied by %.

[0048] A negative sign before the percentage indicates that the sample has a...

Embodiment 3

[0059] Example 3: Anti-inflammatory activity screening in vitro

[0060] 1. Build a screening model

[0061] Raw 264.7 mouse macrophage cell line was purchased from American Cell Bank (ATCC), and cultured in RPMI-1640 medium containing 10% FBS. Raw264.7 cells (1×10 5 Each / well) was inoculated in a 24-well plate, and different concentrations of chalcone derivatives obtained in the present invention were added at the same time, and cultured for 24 hours under the stimulation of 1 μg / ml LPS, and a solvent control and no stimulant background control were set up separately. The culture supernatant was collected by centrifugation (5000rpm, 4°C, 5min), and the NO in the supernatant was detected by the Griess method. 2 - content.

[0062] Table 2. Screening results of anti-inflammatory activity of chalcone derivatives

[0063]

[0064] The results of anti-inflammatory activity screening are shown in Table 2. The six chalcone derivatives significantly inhibited LPS-induced macrop...

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Abstract

The invention discloses a new chalcone derivative with anti-inflammatory and immunosuppression effects, a preparation method and application thereof in preparation of drugs for autoimmune diseases. The study adopts an active substructure splicing method to form a fluorine-containing chalcone derivative, then the fluorine-containing chalcone derivative and a piperazine fragment are connected together to finally synthesize 6 new 4'-(1-piperazinyl)chalcone derivatives. Based on in-vitro immunoactivity screening and 2 autoimmune disease models (multiple sclerosis disease animal model and arthritis model) as the screening platform, the invention for the first time finds that the 6 compounds have significant immunosuppression effect, and show good drug development prospects in treatment of autoimmune diseases (e.g. multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and enteritis).

Description

technical field [0001] The invention relates to the field of medicine, in particular to a novel chalcone derivative with immunosuppressive effect, its preparation method and its application in the preparation of autoimmune disease medicine. technical background [0002] Autoimmune diseases are diseases caused by refractory immune disorders, especially rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus and other autoimmune diseases that mainly respond to T cells have been plagued by many patients. These diseases are long-lasting and intractable, and have always been a difficult problem in the field of medicine in the world today. Immunosuppressants can block the disease process by regulating all aspects of the immune response to achieve the purpose of treating autoimmune diseases. At present, my country's immunosuppressants mainly rely on imports, and most immunosuppressants lack specificity and selectivity to the body's immune system, and their toxic and...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D295/112A61K31/495A61P37/06A61P19/02A61P29/00
CPCC07D295/112
Inventor 万春平毛泽伟郑喜祁燕李小丝
Owner 云南省中医医院
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