Use of pyridoheterocyclic ester compounds in manufacture of anti coxsackievirus B3 drugs

A technology of coxsackie virus and heterocyclic ester, which is applied in the directions of active ingredients of heterocyclic compounds, antiviral agents, organic chemistry, etc., can solve the problems of biological activity evaluation and other problems, and achieves low price, simple synthesis process, and easy purchase. the effect

Active Publication Date: 2017-04-26
HUBEI UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Its biological activity has not been evaluated

Method used

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  • Use of pyridoheterocyclic ester compounds in manufacture of anti coxsackievirus B3 drugs
  • Use of pyridoheterocyclic ester compounds in manufacture of anti coxsackievirus B3 drugs
  • Use of pyridoheterocyclic ester compounds in manufacture of anti coxsackievirus B3 drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] [Example 1] Evaluate the anti-CVB3 activity of novel pyridine heterocyclic ester compounds

[0021] 1. Test method:

[0022] 1.1 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 monolayer was grown in the incubator, the cell culture solution was discarded, and the cell maintenance solution containing different concentrations of the test compound was added to continue the culture. After 48 hours, the cytotoxicity was visually observed under the microscope and recorded respectively, and the cell survival rate was determined by the MTT method. SPSS 11.5 software calculates the median toxic concentration (Median cyctoxic concentration, CC50) of the drug on the cells. Cell viability=(average OD of drug group 492 Value / average OD of cell control group 492 value) × 100%.

[0024] 1.2 Inhibitory activity of compounds against CVB3

[0025] Hep-2 cells were plated in 96-well plates at 37°C, 5% CO 2 Afte...

Embodiment 2

[0034] [Example 2] The inhibitory effect of WY94 and WY97 on the production of CVB3 progeny virus

[0035] 1. Test method

[0036] Hep-2 cells in the logarithmic growth phase were plated in 24-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 40 μg / mL WY94 and WY97. After 48 hours, the cells and supernatant were collected and lysed by freezing and thawing three times at -20°C and 37°C. TCID 50 Methods To determine the titer of CVB3 virus.

[0037] 2. Test results

[0038] like image 3 As shown, compared with the virus control group, the Hep-2 cells treated with 40 μg / mL WY94 and WY97 had a significantly decreased virus titer, showing a decrease of about 3.5 log. This shows that the compound has a strong inhibitory effect on the production of CVB3 progeny virus.

Embodiment 3

[0039] [Example 3] Inhibitory effect of WY94 and WY97 on Hep-2 cell apoptosis caused by CVB3

[0040] 1. Test method

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Abstract

The invention belongs to the technical field of antiviral drugs, and relates to use of novel pyridoheterocyclic ester compounds in manufacture of anti coxsackievirus B3 (CVB3) drugs. The pyridoheterocyclic ester compounds are as shown in formulas WY89, WY94, W95, WY96 and WY97. Through anti CVB3 activity study experiments, the WY89, the WY94, the W95, the WY96 and the WY97 can inhibit cytopathic effect (CPE) produced by CVB3 in host cell Hep-2, can enhance cell viability, reduces progeny virus production, and inhibits of host cell apoptosis caused by CVB3 infection. The anti CVB3 activity study experiments show that the novel pyridoheterocyclic ester compounds have potential in preparation of anti CVB3 infection specific therapeutic drugs, and the novel pyridoheterocyclic ester compounds are simple, rapid and economic in synthesis process and easy in mass production, and have prospects of clinical application.

Description

technical field [0001] The invention belongs to the field of antiviral drugs, and in particular relates to the application of pyridine heterocyclic ester compounds in the preparation of anti-Coxsackie virus type B3 drugs. Background technique [0002] Coxsackievirus (Coxsaekievirus) is a member of the genus Enterovirus of the family Picornaviridae, and 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...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/44A61K31/4402A61P31/14C07D213/30
CPCA61K31/44A61K31/4402C07D213/30
Inventor 魏艳红尧晨光奚彩丽张谦胡康洪李栋杨楠
Owner HUBEI UNIV OF TECH
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