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Novel marine fungus-derived skeleton meroterpenoid derivative and application thereof in preparation of anti-inflammatory drug

A technology of marine fungi and derivatives, applied in the field of medicine, can solve the problems of side effects, adverse reactions and tolerance of patients, and achieve the effects of improved anti-inflammatory activity, large safety factor, and strong anti-NO activity

Active Publication Date: 2020-05-12
GUANGZHOU UNIVERSITY OF CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The technical problem to be solved by the present invention is to overcome the defects and deficiencies of existing anti-inflammatory drugs that have side effects, adverse reactions and tolerance to patients, and provide a novel skeleton heteroterpene derivative derived from a marine fungus and its role in the preparation of anti-inflammatory drugs. application in

Method used

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  • Novel marine fungus-derived skeleton meroterpenoid derivative and application thereof in preparation of anti-inflammatory drug
  • Novel marine fungus-derived skeleton meroterpenoid derivative and application thereof in preparation of anti-inflammatory drug
  • Novel marine fungus-derived skeleton meroterpenoid derivative and application thereof in preparation of anti-inflammatory drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] The acquisition of embodiment 1 marine fungus Aspergillus terreus GZU-311

[0041] 1. Experimental method

[0042] The inventor's team isolated a marine fungus from the torso of Sulphur spp. on the coast of Xuwen County, Zhanjiang City, Guangdong Province. References (Nature protocols, 2010, 5, 480-490; Journal of Natural Products, 2006, 69, 11, 1622- 1625): Using the DNeasy Plant Mini Kit, the DNA of the marine fungus was extracted according to the steps in the manual, the ITS region was amplified using the DNA as a template, and the ITS-rRNA gene sequence of the marine fungus was obtained by sequencing, and identified through the sequence results.

[0043] 2. Experimental results

[0044] The ITS-rRNA gene sequence of the marine fungus is shown as SEQ ID NO.1, which was searched through the BLAST database for similarity. After comparison, the sequence has a similarity of more than 99% with the fungal sequence of Aspergillus terreus; therefore, it is identified that t...

Embodiment 2

[0045] The separation and identification of embodiment 2 heteroterpene derivatives

[0046] In this example, the marine fungus Aspergillus terreus GZU-311 was used to ferment and produce heteroterpene derivatives. The specific experimental methods and results are as follows:

[0047] 1. Separation of derivatives

[0048] The preparation method of derivative comprises the following steps:

[0049]S1. The marine fungus Aspergillus terreus GZU-311 screened in Example 1 was inoculated into a flat medium, then inoculated into a liquid medium, and cultivated at 30° C. for 6 days to obtain a seed solution;

[0050] S2. Inoculate the seed solution in step S1 into a solid rice medium, and let it stand at 35° C. for 60 days to obtain a fermentation culture product;

[0051] S3. extracting the fermentation culture product of step S2 with methanol for 3 times, concentrating the extract, and extracting the obtained concentrated extract with ethyl acetate to obtain a crude ethyl acetate e...

Embodiment 3

[0066] Example 3 Research on anti-inflammatory cell screening model and cytotoxicity screening of heteroterpene derivatives

[0067] When the exogenous antigen lipopolysaccharide LPS stimulates macrophages, a series of immune responses will be produced, and the inflammatory factor NO will be released at the same time. 2 - , NO 2 - The level of the level can indirectly reflect the degree of inflammation. Griess reagent is a kind of NO 2 - The interaction produces a pigmented azo dye compound, and the NO can be judged by detecting the absorbance of the dye with a microplate reader 2 - Therefore, this model is used to screen small molecule inhibitors with anti-inflammatory activity. Therefore, this example adopts the following experiments to study and prove the anti-inflammatory effect of heteroterpene derivatives. The specific experimental methods and experimental results are as follows:

[0068] 1. Anti-inflammatory cell screening model

[0069] 1) Experimental method...

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Abstract

The invention discloses a novel marine fungus-derived skeleton meroterpenoid derivative and an application thereof in preparation of an anti-inflammatory drug. According to the invention, the marine fungus, namely Aspergillus terreus GZU-311 is obtained through separation and screening; and the strain is preserved in the Guangdong Microbial Culture Collection Center on December 17th, 2019, and hasa preservation number of GDMCC No: 60789. Moreover, a meroterpenoid derivative is separated and identified from a fermentation culture product of the fungus; the meroterpenoid derivative has high NOproduction resisting activity; the anti-inflammatory activity of the meroterpenoid derivative is remarkably improved by about 2 times compared with the anti-inflammatory activity of a positive controlindomethacin; meanwhile, the meroterpenoid derivative has a high safety coefficient; thus, the meroterpenoid derivative provided by the invention has good clinical application prospect in preparationof anti-inflammatory drugs, specifically in preparation of drugs for inhibiting LPS-induced NO production.

Description

technical field [0001] The invention belongs to the technical field of medicine. More specifically, it relates to a novel framework heteroterpene derivative derived from a marine fungus and its application in the preparation of anti-inflammatory drugs. Background technique [0002] Inflammation is a defensive response when the body is stimulated by foreign antigens. Macrophages are an important type of immune cells in the body, which have the functions of regulating inflammatory factors, anti-infection, anti-tumor, and immune regulation. It is currently believed that macrophages and the inflammatory mediators they release are involved in the occurrence and development of various inflammatory diseases, such as atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, sepsis, gouty arthritis, etc. [0003] At present, there are two main types of anti-inflammatory drugs commonly used clinically: non-steroidal anti-inflammatory drugs and steroidal anti-inflammatory dr...

Claims

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Application Information

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IPC IPC(8): C12N1/14C12P17/18C12P33/20C07J73/00C07D493/10A61P29/00C12R1/66
CPCA61P29/00C07D493/10C07J73/003C12P17/181C12P33/20C12N1/145C12R2001/66
Inventor 崔辉唐渝茜张琪赵钟祥阮清锋赵敏
Owner GUANGZHOU UNIVERSITY OF CHINESE MEDICINE
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