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Application of amino acid ester compounds in preparation of anti-CVB3 (anti-coxsackie B virus 3) drugs

A technology of amino acid esters and compounds, which is applied in the field of application of amino acid ester compounds in the preparation of anti-CVB3 virus drugs, and can solve the problems of unreported inhibitory activity

Active Publication Date: 2018-09-28
HUBEI UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the inhibitory activity of amino acid esters on CVB3 virus has not been reported so far.

Method used

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  • Application of amino acid ester compounds in preparation of anti-CVB3 (anti-coxsackie B virus 3) drugs
  • Application of amino acid ester compounds in preparation of anti-CVB3 (anti-coxsackie B virus 3) drugs
  • Application of amino acid ester compounds in preparation of anti-CVB3 (anti-coxsackie B virus 3) drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Embodiment 1 Amino acid ester compound anti-CVB3 activity analysis

[0021] Amino acid ester compounds tested include glycine ethyl ester (1), L-leucine methyl ester (2), L-alanine methyl ester (3), L-alanine tert-butyl ester (4), β-propanine Ethyl Alanate (5), D-Leucine Methyl Ester (6), Glycine tert-Butyl Ester (7), β-Alanine tert-Butyl Ester (8), L-Leucine tert-Butyl Ester (9) .

[0022] (1) Toxicity of compounds to host Hep-2 cells

[0023] Hep-2 cells were plated in 96-well plates at 37°C, 5% CO 2 After the incubator was cultured to cover the monolayer, the cell culture medium was discarded, and the cell maintenance medium containing different concentrations of the test compound (ribavirin as a positive control drug) was added to continue the culture. After 48 hours, the cytotoxicity was visually observed under a microscope and recorded respectively. Cell viability was determined by MTT method. The specific steps of the MTT method are as follows: add 30 μL of M...

Embodiment 2

[0040] Example 2 Compound 5 (beta-alanine ethyl ester) inhibits the production of CVB3 progeny virus

[0041] Hep-2 cells in the logarithmic growth phase were plated in 96-well plates, and 100TCID after the monolayer was overgrown 50 CVB3 infected cells, incubated at 37°C for 1.5h, removed the virus solution, washed three times with PBS, and added cell maintenance solution containing 50 μg / mL compound 5 (β-alanine ethyl ester). Cells and supernatant culture fluid were collected at 12h and 36h respectively, and after three freeze-thaw lysis at -20°C and 37°C, TCID 50 Methods To determine the titer of CVB3 virus.

[0042] The result is as image 3 As shown, after 12 hours of virus infection, obvious progeny virus titers can be detected, and after 36 hours of infection, the progeny virus titers showed a substantial increase. Compared with the virus control group, the Hep-2 cells treated with 50 μg / mL No. 5 compound showed a certain inhibitory effect at 12 hours, and showed a s...

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Abstract

The invention discloses application of amino acid ester compounds in the preparation of anti-CVB3 (anti-coxsackie B virus 3) drugs and belongs to the technical field of antiviral drugs. Verification by massive biological experiments shows that amino acid ester compounds (glycine ethyl ester, L-leucine methyl ester, L-alanine methyl ester, tert-butyl L-alaninate, beta-alanine ethyl ester, D-leucinemethyl ester, tert-butyl glycinate, beta-alanine tert-butyl ester, and L-leucine tert-butyl ester) can inhibit replication and proliferation of CVB3 in cells, can strongly inhibit cytopathic effect due to CVB3 and increase the survival rate of infected cells, and is applicable to the preparation of anti-CVB3 drugs or drugs to treat diseases due to CVB3 infections. Novel pharmaceutical applicationof amino acid ester compounds is discovered herein, and a new direction is provided for the development of anti-CVB3 drugs.

Description

technical field [0001] The invention relates to the technical field of antiviral drugs, in particular to the application of amino acid ester compounds in the preparation of anti-CVB3 virus drugs. Background technique [0002] Coxsackievirus (CV) is a member of Picornaviridae Enterovirus, its infection can cause a variety of diseases, such as hand, foot and mouth disease, aseptic meningitis, encephalitis, myocarditis, Epidemic myositis pain, herpetic angina, etc. There are 29 serotypes of CV reported, which can be divided into two groups, A and B, according to their pathogenic characteristics and cell sensitivity to suckling mice, namely CVA (CVA1-22, 24) and CVB ( CVB1-6). CVBs infection is the most common, among which CVB3 is the most pathogenic type among the six CVB serotypes, and is the main cause of viral myocarditis. According to the statistics of the US Centers for Disease Control and Prevention (CDC), CVB (type 1-6) can cause about 5 million people to suffer from ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/223A61K31/221A61P9/00A61P11/04A61P21/00A61P25/00A61P31/14
CPCA61K31/221A61K31/223A61P9/00A61P11/04A61P21/00A61P25/00A61P31/14A61K2300/00
Inventor 魏艳红李妮胡康洪吕诗韵杜仓浩
Owner HUBEI UNIV OF TECH
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