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Applications of Gramine and derivatives thereof to preparation of medicaments for resisting adenovirus Type 7

A technology of anophylline and its derivatives, applied in the direction of antiviral agents, drug combinations, antineoplastic drugs, etc., to achieve the effects of reducing the risk of later development and application, simple synthesis process, and easy purchase

Inactive Publication Date: 2017-05-17
HUBEI UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there are no effective preventive vaccines and therapeutic drugs for the infection caused by the virus clinically, and symptomatic treatment is mainly adopted

Method used

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  • Applications of Gramine and derivatives thereof to preparation of medicaments for resisting adenovirus Type 7
  • Applications of Gramine and derivatives thereof to preparation of medicaments for resisting adenovirus Type 7
  • Applications of Gramine and derivatives thereof to preparation of medicaments for resisting adenovirus Type 7

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] [Example 1] Assessing the anti-ADV7 activity of Gramine and its derivatives

[0027] 1. Test method:

[0028] 1.1 Toxicity of Gramine and its derivatives to host Hela and Hep-2 cells

[0029] Plate Hela and Hep-2 cells 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%.

[0030] 1.2 Inhibitory activity of Gramine and its derivatives on ADV7

[0031] Plate Hela and Hep-2 cells in 96-wel...

Embodiment 2

[0041] [Example 2] Carrying out pharmacological research on anti-ADV7 activity of Gramine derivatives

[0042] 1. Test method

[0043] 1.1 Analysis of the direct killing effect of derivatives on ADV7

[0044]The high-titer ADV7 suspension was incubated with Gramine and its derivatives (choose the concentration that can inhibit the cell CPE to the maximum extent) in a refrigerator at 4°C for 24 hours, and the virus suspension was diluted by a certain factor, making it far less than the effective concentration of the compound for virus inhibition. Titrate in Hela cells that have been prepared in advance and have adhered to the monolayer, and calculate the TCID of the virus suspension by the Reed and Muench method 50 value.

[0045] 1.2 Analysis of the mode of action of derivatives on ADV7

[0046] The effects of the compounds on ADV7 were determined by three different dosing methods (before ADV7 infection, between infections, and after infection with the test compound).

[0...

Embodiment 3

[0060] [Example 3] The inhibitory effect of Gramine derivative G19 on the production of ADV7 progeny virus

[0061] 1. Test method

[0062] Hep-2 and Hela cells in the logarithmic growth phase were plated in 24-well plates, and 100TCID after the monolayer was overgrown 50 ADV7 infected cells, incubated at 37°C for 1.5h, removed the virus solution, washed three times with PBS, and added cell maintenance solution containing G19. Cells and supernatant culture fluid were collected at 4, 8, 24 or 36 hours (pi), respectively, and after freeze-thawing and lysing three times at -20°C and 37°C, the ADV7 virus titer was determined by the TCID50 method.

[0063] 2. Test results

[0064] Such as Figure 4 As shown, in the virus control cells, the virus titer showed a substantial increase from 4h to 36h, indicating the replication status of the virus in the cells. However, in the Hep-2 cells treated with 40 μg / mL G19 until 36h, the virus titer did not increase significantly ( Figure ...

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Abstract

The invention belongs to the field of antiviral drugs. The invention provides applications of Gramine and derivatives thereof to preparation of medicaments for resisting adenovirus Type 7. Gramine derivatives are compounds shown in G1,G2,G3,G4,G5,G10,G17,G18,G19,G20, and G21. Experiments for researching activity of Gramine derivatives for resisting ADV7, pharmacology research of Gramine derivatives for resisting ADV7, and tests of inhibition effects of G19 for ADV7 duplication show that Gramine derivatives can inhibit cytopathic effects (CPE) generated by ADV7 on host cell Hela, enhance cell survival rate, inhibit yield of progeny virus, and mainly inhibit the duplication phase of ADV7 virus in host cells. The Gramine and derivatives thereof have potential for preparing anti-ADV1 virus medicaments, and the compounds have the advantages of simple synthesis process, and economy and fastness; the compounds are easy for large-scale production, and have clinic application prospects.

Description

technical field [0001] The invention belongs to the field of antiviral drugs, and in particular relates to the application of gramine and its derivatives in the preparation of anti-type 7 adenovirus drugs. Background technique [0002] Adenoviruses (adenoviruses, ADVs) are a group of widely distributed DNA viruses. There are 52 known species of human adenoviruses, named advl~adv52, divided into two genera, with a total of more than 100 serotypes. About one-third of the known serotypes of human adenoviruses are associated with human disease. Adenoviruses can invade various tissues and organs such as the respiratory tract, conjunctiva, gastrointestinal tract, and urinary tract. The main infection is the respiratory tract. In severe cases, it can cause pneumonia in children and accumulate in various systems of the body. Adenoviral pneumonia caused by adenovirus infection is one of the most serious types of pneumonia in children. The adenovirus types associated with respirato...

Claims

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Application Information

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IPC IPC(8): A61K31/4045A61K31/4439A61K31/4155A61K31/4196A61K31/428A61P31/20A61P35/00
CPCA61K31/4045A61K31/4155A61K31/4196A61K31/428A61K31/4439
Inventor 魏艳红柯少勇杨自文石丽桥
Owner HUBEI UNIV OF TECH
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