Application of terpenoids in preparation of anti-influenza virus drugs

A terpenoid, anti-influenza virus technology, applied in the direction of antiviral agents, hydroxyl compound active ingredients, anhydride/acid/halide active ingredients, etc., can solve problems such as unpredictable inhibition, and achieve excellent anti-influenza virus activity. Effect

Active Publication Date: 2021-06-04
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

That is to say, those skilled in the art, on the basis that the compounds disclosed in the above-mentioned documents have anti-hepatitis B virus effects, cannot predict that these compounds also have inhibitory effects on other viruses, let alone predict which compounds will have an inhibitory effect on other viruses. virus has a significant inhibitory effect on

Method used

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  • Application of terpenoids in preparation of anti-influenza virus drugs
  • Application of terpenoids in preparation of anti-influenza virus drugs
  • Application of terpenoids in preparation of anti-influenza virus drugs

Examples

Experimental program
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Effect test

experiment example 1

[0037] Experimental example 1 in vitro anti-influenza virus activity test

[0038] Cytotoxicity test: 6×10 4 / mL MDCK cells were spread in a 96-well plate, placed in an incubator at 37°C overnight, then added a doubly diluted compound to be tested, and continued to cultivate for 48 hours, discarded the old medium, and added fresh medium containing 10% to continue to cultivate for 0.5 ~2 hours, then measure the OD value, and calculate the half lethal concentration (CC) of the compound with Graphpad Prime 6.0 software 50 ).

[0039] Plaque subtraction method: MDCK cells covered with a monolayer in a six-well plate were infected with virus (~50pfu / well), incubated in a 37°C incubator for 1 hour, and shaken every 15 minutes. The cells were washed twice with PBS, agarose containing different concentrations of compounds was added, and cultured for 48-72 hours. After the cells were fixed with paraformaldehyde for 15 minutes, they were stained with crystal violet, and then the spots...

Embodiment 2

[0056] Example 2 In vivo anti-influenza virus activity test

[0057] Male mice aged 4-6 weeks were randomly divided into 8 groups, 10 mice per group. Each mouse was intranasally infected with 50 μL of 2LD50 A / PR8 / 34 H1N1, and two hours later, the drugs were administered in the following groups; continuous administration for 5 days; used to test cyperenoic acid and oseltamivir phosphate (Oseltamivir) in vivo activity. After the administration, the body weight and death of the mice were recorded every day, and the records were observed for 14 days. See the experimental results figure 1 and Table 2.

[0058] Administration method and dose of CA (cyperenoic acid) test group:

[0059] (1) Oral administration, 2 times / day: high-dose group (80mg / kg / day), middle-dose group (40mg / kg / day), low-dose group (20mg / kg / day); cyperenoic acid intragastric administration The high, medium and low dose groups are abbreviated as: CA (o.p.80mg / kg / day), CA (o.p.40mg / kg / day), CA (o.p.20mg / kg / day...

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Abstract

The invention relates to the field of medicinal chemistry, and particularly discloses application of terpenoids in preparation of anti-influenza virus drugs. The terpenoid has a structure as shown in a general formula I. The inventor carries out activity screening on the terpenoids with the structure as shown in the general formula I, and finds that the terpenoids with the structure as shown in the general formula I have excellent anti-influenza virus activity for the first time; and in the compounds, the compounds such as the cycloenoic acid and the like have a very remarkable inhibition effect on influenza viruses. The in-vitro and in-vivo anti-influenza virus experiment screening shows that the inhibition effect of the cycloenoic acid on the influenza A H1N1 virus is equivalent to that of a positive control drug oseltamivir phosphate, and even is stronger than that of oseltamivir phosphate.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to the application of terpenoids in the preparation of anti-influenza virus drugs. Background technique [0002] Influenza viruses are a major threat to human health. The respiratory disease caused by influenza virus is called influenza (flu), which has the characteristics of wide prevalence, strong infectivity and high incidence rate. As a viral infectious disease, influenza not only seriously threatens the health of the people, but also brings a heavy burden to the country and society. How to effectively prevent and treat influenza, especially highly pathogenic influenza, has become a task that is placed in the world It is an important issue that needs to be studied and solved urgently in front of medical workers. Due to the variation of influenza virus antigens, conventional vaccines are still unable to effectively prevent influenza outbreaks and epidemics. Therefore, researc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/045A61K31/047A61K31/075A61K31/11A61K31/19A61K31/215A61K31/22A61K31/16A61K31/704A61P31/16
CPCA61K31/045A61K31/047A61K31/075A61K31/11A61K31/19A61K31/215A61K31/22A61K31/16A61K31/704A61P31/16Y02A50/30
Inventor 李药兰张晓丽王国才张玉波夏依萍
Owner JINAN UNIVERSITY
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