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A norditerpene compound, its separation method and application of anti-neuraminidase activity

A neuraminidase and compound technology, applied in the fields of medicinal chemistry and microbial medicine, can solve the problems of rapid mutation of influenza virus, easy drug resistance, and urgent need for anti-influenza drugs, and achieve low product cost, strong controllability, and easy implementation The effect of industrialization

Active Publication Date: 2022-03-08
INST OF OCEANOLOGY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, influenza virus mutates rapidly and is prone to drug resistance, so it is urgent to develop new anti-influenza drugs

Method used

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  • A norditerpene compound, its separation method and application of anti-neuraminidase activity
  • A norditerpene compound, its separation method and application of anti-neuraminidase activity
  • A norditerpene compound, its separation method and application of anti-neuraminidase activity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1. Fermentative production and separation and purification of compounds 1, 2, 3 and 4:

[0027] The marine fungus Aspergillus wentii used in the present invention is cultivated on PDB liquid medium after purification, and the formula of PDB liquid medium is: 200 grams of potato flour, 20 grams of glucose, 5 grams of peptone, and yeast extract powder in every liter of liquid medium 3 grams, 35 grams of sea salt.

[0028] The marine fungus Aspergillus wentii (size 2.5 cm × 2.5 cm) was inoculated in 300 mL PDB liquid medium and fermented on a shaker (200 rpm) at 28° C. for 7 days to obtain The bacterial liquid was introduced into 30L PDB liquid medium, and fermented in a 50L fermenter for 1 day, and then used as a seed liquid in a 300L PDB liquid medium and fermented in a 500L fermenter for 7 days. The fermentation product was repeatedly soaked and extracted with ethyl acetate, combined and extracted The liquid is concentrated to obtain a fermented crude extract; ...

Embodiment 2

[0044] Example 2. Neuraminidase inhibitor activity.

[0045] Neuraminidase inhibitor screening kit (including neuraminidase detection buffer, neuraminidase, neuraminidase fluorescent substrate, Milli-Q water) was used to test neuraminidase inhibitory activity. Neuraminidase is a special glycoprotein on the surface of influenza virus and an important target of influenza drugs, so the screening of its inhibitors has become a common method for screening potential anti-influenza drugs.

[0046] The operation steps are as follows: Accurately weigh the sample of the pure product compound shown in formula I prepared in the above example, and prepare solutions of the required concentration with dimethyl sulfoxide (DMSO), respectively, and the concentrations of the positive control Tamiflu and the sample are both 200 μM .

[0047] Preparation of sample detection: Add 70 μl neuraminidase detection buffer, 10 μl neuraminidase, the neuraminidase inhibitor sample or the positive control T...

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Abstract

The invention relates to the technical fields of medicinal chemistry and microbial medicine, in particular to a method for obtaining a norditerpene compound from a fermentation product of the marine fungus Aspergillus wentii and its separation and purification method, and for inhibiting neuraminidase activity. application. The shown norditerpene compound is a compound shown in formula I or formula II, wherein the compound shown in formula I is molecular formula C 19 h 26 o 3 Compound 1 or compound 2; the compound shown in formula II is molecular formula C 19 h 26 o 2 The compound 3 or compound 4; Activity test shows that this kind of compound has significant inhibitory activity to neuraminidase, and its half maximal inhibitory concentration (IC 50 ) are 18.2, 10.9, 14.2, and 16.7 μM, respectively, and are expected to become new anti-influenza virus potential drugs. The norditerpene compound prepared by the invention is fermented and produced by microorganisms, and has the characteristics of simple operation process, short production cycle and low product cost.

Description

technical field [0001] The invention relates to the technical fields of medicinal chemistry and microbial medicine, in particular to a method for obtaining a norditerpene compound from a fermentation product of the marine fungus Aspergillus wentii and its separation and purification method, and for inhibiting neuraminidase activity. application. Background technique [0002] Every autumn and winter is the period of high incidence of global influenza. Influenza can cause high fever, pain, fatigue and respiratory symptoms. In severe cases, it can cause death. It has become an important public health problem in the world today. Influenza viruses spread faster and are the culprit of influenza pandemics. Neuraminidase is a glycoprotein associated with pathogenicity on the surface of influenza virus, and it is also an important target of anti-influenza drugs. Neuraminidase inhibitors such as oseltamivir and zanamivir have become mainstream drugs for the treatment of influenza. ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C39/23A61P31/16C12P7/22
CPCA61P31/16C12P7/22C07C39/23C07C2603/26
Inventor 王斌贵李鑫李晓栋李晓明
Owner INST OF OCEANOLOGY - CHINESE ACAD OF SCI
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