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Application of substituted indolindione compounds in the preparation of drugs for preventing and/or treating bacterial infections

A technology of indolindione and bacterial infection, which is applied in the field of biomedicine and can solve problems such as unreported activity

Active Publication Date: 2019-03-08
INST OF MICROBIOLOGY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But so far, the activity of benzyl and halogen-substituted indolindione compounds in the field of anti-infection has not been reported

Method used

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  • Application of substituted indolindione compounds in the preparation of drugs for preventing and/or treating bacterial infections
  • Application of substituted indolindione compounds in the preparation of drugs for preventing and/or treating bacterial infections
  • Application of substituted indolindione compounds in the preparation of drugs for preventing and/or treating bacterial infections

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1. The compound represented by formula I improves the survival rate of Caenorhabditis elegans infected by Enterococcus faecalis

[0036] 1. 54 hours before the nematode infection, the -80°C frozen Enterococcus faecalis (E.faecalis) was taken out of the refrigerator, streaked on the solid BHI medium, and cultivated at 37°C for 16 hours to obtain a single colony of Enterococcus faecalis.

[0037] 2. Inoculate the single colony of Enterococcus faecalis in step 1 into 5ml of BHI liquid medium, and culture on a shaker at 220rpm at 37°C for 14 hours.

[0038] 3. Take 100 μl of the Enterococcus faecalis cultured in step 2 and add it dropwise to the BHI solid plate medium and spread it evenly. After culturing at 25°C for 16 hours, transfer to 15°C for 8 hours to obtain the Enterococcus faecalis BHI plate.

[0039] 4. 48 hours before nematode infection, place the L1-stage larvae of Caenorhabditis elegans of the same generation thermosensitive sterile type (glp-4:sek-1) o...

Embodiment 2

[0049] Embodiment 2, the compound shown in formula I inhibits bacterial virulence gene expression

[0050] 1. Take the Enterococcus faecalis (E.faecalis) and Staphylococcus aureus (S.aureus) frozen at -80°C out of the refrigerator, streak them on solid BHI and TSB medium respectively, and culture them at 37°C for 16 hours Single colonies of E. faecalis and S. aureus were obtained.

[0051] 2. Inoculate the single clones of Enterococcus faecalis and Staphylococcus aureus in step 1 into 5ml of BHI and TSB liquid medium respectively, and cultivate them on a shaker at 37°C at 220rpm for 14 hours.

[0052]3. Take 100 μl of Enterococcus faecalis and Staphylococcus aureus cultured in step 2 and add it to 10ml of BHI and TSB liquid medium, culture on a shaker at 220rpm at 37°C for 5-6 hours, then add 200μl of the compound shown in formula Ⅰ at 10mg / ml Solution, continue to culture for 2 hours and then centrifuge the cells to extract the total RNA of Enterococcus faecalis and Staphylo...

Embodiment 3

[0057] Example 3. The compound represented by formula I regulates the expression of innate immune genes in Caenorhabditis elegans infected by Enterococcus faecalis

[0058] 1. 54 hours before the nematode infection, the -80°C frozen Enterococcus faecalis (E.faecalis) was taken out of the refrigerator, streaked on the solid BHI medium, and cultivated at 37°C for 16 hours to obtain a single colony of Enterococcus faecalis.

[0059] 2. Inoculate the single colony of Enterococcus faecalis in step 1 into 5ml of BHI liquid medium, and culture on a shaker at 220rpm at 37°C for 14 hours.

[0060] 3. Take 100 μl of the Enterococcus faecalis cultured in step 2 and add it dropwise to the BHI solid plate medium containing 20 μg / ml of the compound shown in formula Ⅰ and spread it evenly. After 16 hours of incubation at 25°C, turn to 15°C for 8 hours. Obtain E. faecalis BHI plates.

[0061] 4. 48 hours before the nematode infection, place the L1-stage larvae of the same-generation thermose...

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Abstract

The invention relates to application of a substitutive 2,3-didetonindoline compound in preparing bacterial infection preventing and / or treating medicines. Bacteria can be gram-positive bacteria, specifically, enterococcus faecalis and / or staphylococcus aureus. Pharmacodynamic tests show that the substitutive 2,3-didetonindoline compound has an obvious inhibiting function on virulence factors of the gram-positive bacteria, also has a regulating function on innate immune systems of caenorhabditis elegans, and can become a quite excellent candidate medicine for preventing and / or treating bacterial infection.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to the application of substituted indolindione compounds in the preparation of drugs for preventing and / or treating bacterial infections. Background technique [0002] In recent years, due to the widespread use of broad-spectrum antibiotics, the problem of drug resistance of pathogenic bacteria has become more and more serious, and the problem of bacterial multidrug resistance (Multidrug-resistant, MDR) has become increasingly common. On the other hand, the number of new antibiotics on the market is decreasing day by day, and the traditional antibiotic drug research and development strategy can no longer meet the needs of human beings to combat the threat of drug resistance of pathogenic bacteria. Therefore, it is of great significance to develop new antibiotics for the interaction between pathogens and hosts. [0003] The occurrence of infectious diseases is the process of i...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D209/38A61K31/404A61P31/04
CPCC07D209/38
Inventor 张立新代焕琴崔金辉赵宇王建国宋福行纪增春
Owner INST OF MICROBIOLOGY - CHINESE ACAD OF SCI
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