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Tetrahydroquinoline alkaloid Malaysiensin with immunosuppression activity and production method and application of tetrahydroquinoline alkaloid Malaysiensin with immunosuppression activity

An immunosuppressive and tetrahydroquinoline technology, applied in the field of biomedicine, can solve problems such as expensive, induced tumors, and hyperlipidemia

Active Publication Date: 2020-01-24
HAINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The immunosuppressive drugs clinically used to treat autoimmune diseases and transplant rejection mainly include cyclosporin A (CsA), tacrolimus (FK506), etc. With different degrees of liver and kidney toxicity or neurotoxicity, long-term use can cause hyperlipidemia, metabolic bone disease and even induce tumors; at the same time, these immunosuppressive drugs are also relatively expensive

Method used

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  • Tetrahydroquinoline alkaloid Malaysiensin with immunosuppression activity and production method and application of tetrahydroquinoline alkaloid Malaysiensin with immunosuppression activity
  • Tetrahydroquinoline alkaloid Malaysiensin with immunosuppression activity and production method and application of tetrahydroquinoline alkaloid Malaysiensin with immunosuppression activity
  • Tetrahydroquinoline alkaloid Malaysiensin with immunosuppression activity and production method and application of tetrahydroquinoline alkaloid Malaysiensin with immunosuppression activity

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] The preparation of embodiment 1-compound

[0045] A kind of tetrahydroquinoline alkaloid with immunosuppressive activity, its preparation method comprises the following steps:

[0046] S1. Streptomyces sp.DSM 4137 was fermented and cultured; Streptomyces sp.DSM 4137 was deposited in the China Center for Type Culture Collection, date of deposit: August 1, 2018, deposit number: CCTCCNo: M 2018512; Streptomyces For the fermentation and cultivation method of Streptomyces sp.DSM 4137, refer to the patent previously applied by the inventor, publication number CN 109467579A, title of invention: a PKS type I polyketide compound with immunosuppressive activity and its preparation method and application.

[0047] S2. After the fermentation culture is completed, fully soak in methanol, filter to obtain methanol extract, concentrate under reduced pressure, recover methanol, and obtain 6.2g of strain fermentation product;

[0048] S3. Gradient elution is performed on the fermentati...

Embodiment 2

[0050] Embodiment 2-confirmation of compound structure

[0051] Using a variety of spectra (IR, UV, CD), spectrum ( 1 H NMR, 13 C NMR, DEPT, H-HCOSY, HMQC, HMBC, NOESY) and MS (ESI-MS, HRMS) and other structural identification techniques to determine the chemical structure of the obtained active ingredients and discover new structural active ingredients. see results Figure 1-Figure 3 .

[0052] Malaysiensin (compound 1), white solid, specific rotation [α] 25 D =+10 (c 0.001, MeOH), UV absorption UV(MeOH) λmax 202, 332nm, cationic HRESI-MS gives [M+Na] at m / z 451.2193 + peak( figure 1 ), so the molecular formula of this compound is C 24 h 32 N 2 o 5 , with an unsaturation of 10. The hydrogen-carbon spectrum of compound 1 ( figure 2 , image 3 , Table 1) show that 7 unsaturations originate from one amide carbonyl, one keto carbonyl and five carbon-carbon double bonds. Therefore, the molecule is presumed to be a tricyclic structure. DEPT spectrum ( Figure 4 ) s...

Embodiment 3

[0057] Example 3-Con A induced T cell proliferation experiment

[0058] 1. Experimental materials

[0059] 1.1 Experimental animals

[0060] Healthy Balb / c mice, female, weighing 18-20g / mouse, aged 6-8 weeks, were purchased from Hainan Medical College and kept at about 25°C and 50-80% relative humidity.

[0061] 1.2 Drugs and reagents

[0062] Concanavalin A (Sigma), CCK-8 (Biosharp), RPMI-1640 culture medium (HyClone), fetal bovine serum (Sijiqing), red blood cell lysate (Biosharp), trypan blue (Sigma)), etc.

[0063] 1.3 Main instruments

[0064] CO 2 Cell incubator (Galaxy R, British RS Biotech company), ultra-clean bench (SW-CJ-2FD, Suzhou Purification Equipment Co., Ltd.), inverted microscope (BX51-32P01, Japan Olympus), autoclave (HVE-50 , Japan Co., Ltd.), centrifuge (DM0412S, American SCILOGEX), microplate reader (ST-360, Shanghai Kehua Experimental System Co., Ltd.), 96-well cell culture plate (3599, American Costar), constant temperature water bath (DK- S28, Sh...

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PUM

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Abstract

The invention provides a tetrahydroquinoline alkaloid Malaysiensin with immunosuppression activity and a production method and application of the tetrahydroquinoline alkaloid Malaysiensin with the immunosuppression activity. The compound is obtained by conducting SFM solid medium fermentation on Streptomyces sp.DSM 4137 and separating and purifying a fermentation product. The compound can significantly inhibit ConA-induced proliferation of T cells, an immunosuppression effect of the compound is equivalent to that of an immunosuppressor cyclosporin A which is clinically and widely used, and action mechanism studies show that Malaysiensin exerts the immunosuppression activity for a targeted NFAT signal path, is an efficient immunosuppressor, and can be used for producing immunosuppressive medicines for organ transplantation and autoimmune diseases.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a tetrahydroquinoline alkaloid Malaysiensin with immunosuppressive activity and its preparation method and application. Background technique [0002] Immunosuppressive drugs refer to drugs that have an inhibitory effect on the body's immune response. They are developed for autoimmune diseases. They can inhibit the proliferation and function of cells related to immune responses and reduce the body's immune response. There are five main types of immunosuppressants commonly used: (1) glucocorticoids, such as cortisone and prednisone; (2) microbial metabolites, such as cyclosporine and tacrolimus; (3) anti-metabolites (4) Polyclonal and monoclonal anti-lymphocyte antibodies, such as anti-lymphocyte globulin and OKT3; (5) Alkylating agents, such as cyclophosphamide. The immunosuppressive drugs clinically used to treat autoimmune diseases and transplant rejection mainly include cy...

Claims

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Application Information

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IPC IPC(8): C07D215/48A61K31/47A61P37/06
CPCA61P37/06C07D215/48
Inventor 徐静张雪侠
Owner HAINAN UNIVERSITY
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