Application of pyrimidine derivative in preparing medicine for inhibiting bacterial quorum sensing system

A technology of quorum sensing system and pyrimidine derivatives, which is applied in antibacterial drugs, pharmaceutical formulations, medical preparations containing active ingredients, etc., can solve the problems of reducing the antibacterial efficiency of antibiotics and increasing drug-resistant strains, and achieve the purpose of inhibiting bacterial populations effect, the effect of inhibiting pathogenicity

Inactive Publication Date: 2017-08-08
NORTH CHINA UNIVERSITY OF SCIENCE AND TECHNOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] The use of antibiotics has effectively controlled many serious bacterial infectious diseases in humans, but the widespread use of antibiotics has also led to the increase of drug-resistant strains, reducing the antibacterial efficiency of existing antibiotics

Method used

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  • Application of pyrimidine derivative in preparing medicine for inhibiting bacterial quorum sensing system
  • Application of pyrimidine derivative in preparing medicine for inhibiting bacterial quorum sensing system
  • Application of pyrimidine derivative in preparing medicine for inhibiting bacterial quorum sensing system

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Experimental program
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Effect test

Embodiment 1

[0027] The application of a pyrimidine derivative in the preparation of a drug for inhibiting the quorum sensing system of bacteria.

[0028] Application of pyrimidine derivatives in preparing medicines for inhibiting bacterial quorum sensing signal molecules.

[0029] Application of pyrimidine derivatives in the preparation of drugs for reducing bacterial colony motility.

[0030] 1.1 Materials

[0031] Computer, biological database (NCBI, PDB, etc. software): open babel; Mgltools AutoDock Vina software; Discovery Studio Viewer 3.5, etc.; LasR protein data from protein crystal database http: / / www.pdb.org / pdb / home / home.do (PDB ID: 2UVO); the database for virtual screening is the ZINC database ( https: / / zinc.docking.org / )

[0032] Strains: PA quality control strain (ATCC27853) (preserved in the Microbiology Laboratory of Kailuan General Hospital); PA clinical isolates (use bacterial identification and drug sensitivity tester to re-identify the clinical isolates. A patient ...

Embodiment 2

[0053] Application of pyrimidine derivatives in preparing medicines for reducing bacterial biofilm formation.

[0054] 2.1 Pseudomonas aeruginosa biofilm activity detection

[0055] Pick quality control strains and clinical isolates of Pseudomonas aeruginosa respectively in fresh LB liquid medium, 37 ° C, 150rpm shaker for overnight culture; use fresh LB liquid medium to culture the bacterial solution to the logarithmic phase at 1 : 100 proportional dilution, cultured for 1h. Each bacterial solution was divided into 5 groups, and each group had three parallels; 300 μM pyrimidine derivatives were added to them at a final concentration of 0 and 300 μM. Dispense into a 96-well plate, 150 μL per well, and incubate at 37°C for 20 hours; use a pipette to gently aspirate the bacterial solution, be careful not to touch the bottom and wall of the well with the tip of the pipette, and use PBS buffer to gently remove the bacteria. Wash the 96-well plate twice and air-dry; add 150 μL of...

Embodiment 3

[0059] Application of pyrimidine derivatives in the preparation of medicines for reducing the pathogenicity of bacterial virulence factors; the bacterial virulence factors are elastic

[0060] protease, hemolysin or exotoxin A.

[0061] 3 Effect detection of pyrimidine derivatives on virulence factors of Pseudomonas aeruginosa

[0062] 3.1 Detection of Pseudomonas aeruginosa elastase activity

[0063] Pick quality control strains and clinical isolates of Pseudomonas aeruginosa respectively in fresh LB liquid medium, 37 ° C, 150rpm shaker for overnight culture; use fresh LB liquid medium to culture the bacterial solution to the logarithmic phase at 1 : After 100 proportional dilution, each bacterial solution was divided into 5 groups, and each group was 3 parallel, and pyrimidine derivatives with a final concentration of 0 and 400 μM were added to it, and cultured on a shaking table at 37°C and 150 rpm for 12 hours; 1ml of bacterial cells were drawn, Centrifuge at 4°C and 120...

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Abstract

The invention discloses application of pyrimidine derivative in preparing medicine for inhibiting a bacterial quorum sensing system. According to the application disclosed by the invention, LasR protein is utilized as target protein to perform virtual screening to obtain the pyrimidine derivative with a higher score, and the pyrimidine derivative is utilized to perform biological activity evaluation on pseudomonas aeruginosa. Experiments prove that the pyrimidine derivative shows down-regulation on three kinds of genes of LasR, LasB and LasI related to the LasR in culture. Effects of the pyrimidine derivative with the higher score in screening results and the target protein are shown to have an inhibition effect on expression of downstream related genes. Namely, the pyrimidine derivative can inhibit quorum sensing signal molecules to finally reduce bacterial biofilm formation and effectively inhibit pathogenicity of virulence factors and quorum sensing of bacteria. Computer virtual screening is a compound screening method with high efficiency and low cost, so that feasibility for application of the technology in studying quorum sensing medicine is achieved.

Description

technical field [0001] The invention relates to the technical field of medicines, in particular to the application of a pyrimidine derivative in the preparation of medicines for inhibiting bacterial quorum sensing systems. Background technique [0002] The use of antibiotics has effectively controlled many serious bacterial infectious diseases in humans, but the widespread use of antibiotics has also led to the increase of drug-resistant strains, reducing the antibacterial efficiency of existing antibiotics. Therefore, it is extremely necessary to develop new antibiotics and establish new treatment models. At present, it is believed that the most promising treatment strategy should not kill the pathogenic bacteria cells but only weaken the pathogenicity of the pathogenic bacteria. This strategy does not threaten the survival of the pathogenic bacteria itself and will not cause drug resistance problems. Recent studies have found that the pathogenicity of pathogenic bacteria ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/519A61P31/04
CPCA61K31/519
Inventor 熊亚南刘颖
Owner NORTH CHINA UNIVERSITY OF SCIENCE AND TECHNOLOGY
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