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Marine fungus-derived meroterpenoid compound and application in preparation of anti-hepatic fibrosis drugs

A technology of marine fungi and compounds, applied in the field of pharmaceutical compounds, can solve problems such as adverse reactions, lack of better drugs for treating liver fibrosis, etc., and achieve a promising effect.

Active Publication Date: 2021-07-27
GUANGZHOU UNIVERSITY OF CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, there is no better drug for the treatment of liver fibrosis in the first-line clinic. The commonly used drugs are: antiviral and anti-hepatic fibrosis, and long-term large-scale use will produce a series of adverse reactions and tolerance

Method used

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  • Marine fungus-derived meroterpenoid compound and application in preparation of anti-hepatic fibrosis drugs
  • Marine fungus-derived meroterpenoid compound and application in preparation of anti-hepatic fibrosis drugs
  • Marine fungus-derived meroterpenoid compound and application in preparation of anti-hepatic fibrosis drugs

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] The acquisition of embodiment 1 marine fungus Aspergillus terreus GZU-31-1

[0048] The inventor's team isolated and purified a marine fungus Aspergillus terreus GZU-31-1 from the trunk of the sulphurous sulphate on the back of the sea in Xuwen, Zhanjiang City, Guangdong Province. The fungus was identified by DNA amplification and sequencing of the ITS region of the fungus. For specific steps, refer to the literature (Nature protocols, 2010, 5, 480-490; Journal of Natural Products, 2006, 69, 11, 1622-1625): using DNeasy Plant Mini The Kit kit, according to the steps in the manual, extracts DNA, uses ITS as primers for PCR amplification, and the amplified products are sequenced. The sequence obtained by sequencing was searched through the BLAST database for similarity. After comparison, the similarity between the sequence and the Aspergillus terreus fungus sequence was 100%, and the fungus was determined to be the marine fungus Aspergillus terreus GZU-31-1. The strain w...

Embodiment 2

[0049] The separation of embodiment 2 compound

[0050] A novel heteroterpene derivative was isolated from the fermentation broth of the marine fungus Aspergillus terreus GZU-31-1. The specific method is as follows:

[0051] (1) Seed liquid culture of the fungus Aspergillus terreus GZU-31-1: pick the strain and inoculate it on a slant, cultivate it at 30°C for 6 days, then insert it into a potato dextrose water medium, and cultivate it at 30°C for 3 days to obtain a seed liquid. The composition of the slant medium is calculated by weight ratio: 0.3% of glucose, 0.1% of yeast extract, 0.5% of peptone, 2.5% of agar, 3% of sodium chloride, and 98% of water. The composition of the potato glucose water culture medium is calculated by weight: 20% of potatoes, 0.3% of glucose, 3% of sodium chloride, and 100% of water.

[0052] (2) Fermentation culture of the fungus Aspergillus terreus GZU-31-1: transfer the bacterial strain in the seed solution into the fermentation medium, and let ...

Embodiment 3

[0055] The structural analysis of embodiment 3 compound

[0056] Structural analysis of the new compound 1 was carried out, and the following experimental data were obtained:

[0057] New Compound 1: C 26 h 30 o 9 , HRESI-MS: 485.1805 [M-H] - (cald for C 26 h 29 o 9 485.1806).

[0058] See Table 1 for NMR data.

[0059] The structural formula of compound 1 is as follows:

[0060]

[0061] The NMR data (CDCl 3 , 400MHz / 101MHz,ppm)

[0062]

[0063]

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Abstract

The invention discloses a marine fungus-derived meroterpenoid compound and application in preparation of anti-hepatic fibrosis drugs. According to the present invention, the meroterpenoid derivative is separated from a fermentation product of a strain of marine fungi Aspergillus terreus GZU-31-1, and the novel compound can significantly down-regulate expression of alpha-SMA induced by TGF-beta1, shows relatively strong activity of inhibiting activation of hepatic stellate cells, has clinical application potential in anti-hepatic fibrosis treatment, can be used for preparing anti-hepatic fibrosis drugs, and has a good application prospect.

Description

technical field [0001] The invention belongs to the technical field of medical compounds, and in particular relates to a heteroterpene compound derived from marine fungi and its application in the preparation of anti-hepatic fibrosis drugs. Background technique [0002] Hepatic fibrosis (hepatic fibrosis, HF) is a common pathological process of various chronic liver diseases. A variety of cytokines secreted by long-term or repeatedly injured liver cells can stimulate hepatic stellate cells to transform into myofibroblasts and myogenic cells. Fibroblasts repair damaged liver cells by synthesizing extracellular matrix. However, when the synthesis and degradation of extracellular matrix are out of balance and a large amount of extracellular matrix is ​​deposited, it will lead to liver fibrosis. If there is no timely and effective intervention, it will evolve into hepatic fibrosis. Cirrhosis, liver cancer and other liver diseases. Because liver fibrosis is reversible, effective...

Claims

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Application Information

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IPC IPC(8): C07J73/00A61P1/16C12N1/14C12P33/20C12R1/66
CPCC07J73/003A61P1/16C12N1/14C12P33/20
Inventor 崔辉苏桃唐渝茜杨春芳赵钟祥
Owner GUANGZHOU UNIVERSITY OF CHINESE MEDICINE
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