Cytochalasin compound with immunosuppressive activity as well as preparation method and application of cytochalasin compound

A cytochalasin and compound technology, applied in the field of biomedicine, can solve problems such as killing of resting splenocytes, and achieve the effect of obvious immunosuppressive activity and low cytotoxicity

Active Publication Date: 2021-11-05
HAINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In vitro immune activity test showed that compounds 1-6 cytochalasin compounds showed strong inhibitory activity, but at the same time had a killing effect on resting splenocytes at low concentrations

Method used

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  • Cytochalasin compound with immunosuppressive activity as well as preparation method and application of cytochalasin compound
  • Cytochalasin compound with immunosuppressive activity as well as preparation method and application of cytochalasin compound
  • Cytochalasin compound with immunosuppressive activity as well as preparation method and application of cytochalasin compound

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] The preparation of embodiment 1-compound

[0046] Phomopsis asparagi DHS-48 was inoculated into rice culture medium (100 g of rice, 3 g of coarse sea salt, 0.6 g of peptone, 100 mL of water, placed in a 500 mL Erlenmeyer flask), a total of 100 flasks were placed in 25 ° C for 28 days in the dark to obtain fermented product;

[0047] Pour the fermented product into an appropriate amount of ethyl acetate, ultrasonically extract for 30 minutes for the first time, and then soak and extract for 24 hours. The total fermentation product of the target bacterial strain was finally obtained, and the total fermentation product was dissolved and suspended with an appropriate amount of water, and the total fermentation product was dissolved and suspended with petroleum ether, dichloromethane, ethyl acetate, and n-butanol respectively. After extraction, petroleum ether extracts, dichloromethane extracts, ethyl acetate extracts and n-butanol extracts were obtained; the dichloromethan...

Embodiment 2

[0048] Example 2 Compound Structure Identification

[0049] The plane structure and three-dimensional structure of the new compound were determined by analyzing its NMR, MS and electron circular dichroism (ECD) calculation data.

[0050] Compound 1, colorless amorphous powder, specific rotation [α] 25 D = (c 0.001, MeOH), UV absorbance UV(MeOH) λmax nm, cationic HR-ESI-MS gives [M+H] at m / z 434.2644 + peak, so the molecular formula of this compound is C 28 h 35 NO 3 , with an unsaturation of 12. The proton spectral data of compound 1 and the coupling constant of the attached proton indicate that at δ H(1.74,3H,s,H 3 There is a tertiary methyl group at -23), at δ H (0.73,3H,d,J=6.1Hz,H 3 -11; 0.95,3H,d,J=6.7Hz,H 3 There are two secondary methyl groups at -22), at δ H (5.13 and 4.96,2H, both s,H 2 There is an exocyclic methylene at -12), at δ H There are three Oxymethine, at δ H There is an alkenyl methine at (5.28,1H,br s,H-19), at δ H (7.22-7.30,5H) has a typic...

Embodiment 3

[0055] Calmodulin phosphatase inhibitory activity of embodiment 3 compound 2

[0056] Experimental program:

[0057] Dilute CNA into a suitable enzyme solution for later use, take several 5ml test tubes and put them on ice, add 10 μL of drug and 10 μL of enzyme solution in turn and incubate on ice for 5 minutes, add 180 μL of assay solution and react in a water bath at 30°C for 20 minutes, add 1800 μL of stop solution Terminate the reaction, measure the OD on the 720 type spectrophotometer 410 value.

[0058] Blank control: 10μL Enzyme Diluent + 10μL Buffer

[0059] Enzyme: 10μL Enzyme + 10μL Buffer

[0060] Control group: 10 μL enzyme diluent + 10 μL medicine

[0061] Enzyme + drug: 10μL enzyme + 10μL drug

[0062] Note: Buffer is the solution used to dissolve the drug

[0063] Calculate the relative inhibition rate of drugs on CNA according to the following formula:

[0064] Relative inhibition rate (%)=[1-(OD 药+酶 -OD 药对照 ) / OD 酶 ]×100%

[0065] See the experimenta...

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Abstract

According to the present invention, a Phomopsis asparagi DHS-48 fermentation product is further separated and purified to obtain a compound having a novel structure, and the evaluation on the cytotoxicity and the immunosuppressive activity of the compound proves that the compound has low cytotoxicity and significant immunosuppressive activity on mouse splenocytes. The study on the mechanism of action shows that the compound is a potential immunosuppressor capable of inhibiting the dephosphorylation of the intracellular phosphorylated NFAT protein, and can be used for preparing immunosuppressive drugs aiming at organ transplantation and autoimmune diseases.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a cytochalasin compound with immunosuppressive activity and its preparation method and application. Background technique [0002] Cytochalasins, also known as phytoalexins, are a large class of fungal metabolites typically characterized by a highly alternative hydrogenated isoindole ring linked to a large ring. Due to structural differences, these compounds exhibit diverse biological activities, including immunomodulatory, cytotoxic, tumor-inhibitory, and nematicidal activities. Currently, at least 300 compounds have been isolated from this family, including common cytochalasins A to H, among which cytochalasins B and cytochalasins C are the two most widely studied. [0003] At present, there are few studies on the immunosuppressive effect of cytochalasin compounds. Xu Guobo et al. reported in "Isolation and Identification of Secondary Metabolites of Chaetomium ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/96C12P17/18C12N1/14A61P37/06C12R1/645
CPCC07D209/96C12P17/182C12N1/14A61P37/06C07B2200/07Y02A50/30
Inventor 徐静张雪侠冯昭韦成文
Owner HAINAN UNIVERSITY
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