Methyl cinnamate is used as quorum sensing inhibitor and application of methyl cinnamate in treatment of bacterial diseases

A technology of methyl cinnamate and quorum sensing system, which is applied in the treatment of bacterial diseases. As a quorum sensing inhibitor, methyl cinnamate can solve problems such as deficiency, reduce pathogenicity, have broad application prospects, and delay Effects of drug resistance

Active Publication Date: 2020-12-08
SOUTH CHINA AGRI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The object of the present invention is to provide the application of methyl cinnamate and pharmaceutically acceptable salt thereof in

Method used

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  • Methyl cinnamate is used as quorum sensing inhibitor and application of methyl cinnamate in treatment of bacterial diseases
  • Methyl cinnamate is used as quorum sensing inhibitor and application of methyl cinnamate in treatment of bacterial diseases
  • Methyl cinnamate is used as quorum sensing inhibitor and application of methyl cinnamate in treatment of bacterial diseases

Examples

Experimental program
Comparison scheme
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Example Embodiment

[0037] Example 1 Screening of Quorum Sensing Inhibitors

[0038] Method: Take one thousandth of the preserved A. tumefaciens N5 (pBA7P) bacterial solution into liquid ABM medium (100 mL), and cultivate at 28°C on a shaker; after about 16 hours, it reaches OD. 600 = about 0.4, dispense into a 96-well cell culture plate with a discharge gun, 196 μL per well; add 4 μL of 10 mg / mL of the test compound to a final concentration of 200 μg / mL, and mix on a microplate shaker at 28°C. Shaker for 2 hours; add 10 μL of 5 μM signal molecule 3OC6-HSL to the 96-well plate, mix well on a microplate shaker, and shake at 28°C for 2 hours; nitrothiophene is buffered with 0.2M phosphate at pH=7.0 The solution was diluted to 250 μg / mL, and 10 μL was added to a 96-well bacterial culture plate, and the color change was observed within 1 h, recorded and photographed. See figure 1 .

[0039] figure 1 The 4-nitropyridine-N-oxide (4-NPO) marked in the label is the positive control group, DMSO is use...

Example Embodiment

[0041] Example 2 Testing the minimum inhibitory concentration (MIC) determination of methyl cinnamate compounds against A. tumefaciens N5 (pBA7P)

[0042] In order to exclude the effect of the compounds on the growth of A. tumefaciens N5 (pBA7P), the compounds obtained from the screening were determined for the MIC value of A. tumefaciens N5 (pBA7P). Add 1 / 1,000 of A. tumefaciens N5 (pBA7P) cultured overnight to LB liquid medium and mix well; add 196 μL of the above mixture to each well of a 96-well bacterial culture plate with a row gun; The concentration gradients were 3.125, 6.25, 12.5, 25, 50, 100 and 200 μg / mL; the same volume of DMSO was used as a control, with three replicates; the results were observed after 24 hours of static culture at 28°C. In the range visible to the naked eye, the growth of microorganisms is obviously inhibited, and the lowest drug concentration that the bacterial liquid does not appear turbid and remains clear is MIC.

[0043] Experimental resul...

Example Embodiment

[0045] Example 3 Effect of compound methyl cinnamate on β-lactamase activity and rescreening

[0046] In order to rule out methyl cinnamate as a beta-lactamase inhibitor, the compound methyl cinnamate was tested for beta-lactamase activity.

[0047] Take one thousandth of A.tumefaciens N5 (pBA7P) bacterial solution into liquid ABM medium (100mL), and shake at 28°C; after about 16h, it will reach OD 600 = about 0.4, dispense 196 μL per well into a 96-well bacterial culture plate with a spray gun; add 10 μL of the signal molecule 3OC6-HSL at a concentration of 5 μM to the 96-well plate, mix well on a microplate shaker, and shake at 28°C Incubate for 2 h; add 4 μL of 10000 μg / mL of the test compound to a final concentration of 200 μg / mL, shake at 28 °C for 2 h; dilute nitrothiophene with 0.2 M phosphate buffer pH=7.0 to 250 μg / mL, and add 10 μL to 96 wells In the bacterial culture plate; observe the color change within 1 h, and measure the OD value at 490 nm with a microplate re...

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Abstract

The invention discloses application of methyl cinnamate or pharmaceutically acceptable salt thereof as a quorum sensing inhibitor in treatment of bacterial diseases. The methyl cinnamate has a stronginhibition effect on quorum sensing system related pathogenic phenotypes of pseudomonas aeruginosa PAO1 and pectobacterium carotovorum subsp. Carotovorum S1, and does not influence the normal growth of the two pathogenic bacteria at the same time, that is, the compound does not influence the growth of the pathogenic bacteria, but also does not influence the growth of the pathogenic bacteria. A pathogenic bacteria quorum sensing system can be strongly inhibited, the pathogenicity of pathogenic bacteria is remarkably reduced, and diseases caused by the pathogenic bacteria are prevented and/or treated; the compound can be used as a pathogenic bacteria quorum sensing system inhibitor or prepared into a related drug for preventing and/or treating bacterial diseases, also has the effects of reducing and delaying the generation of drug resistance of pathogenic bacteria to the compound, has a relatively long effective service life in the aspect of disease prevention and/or treatment, and has awide application prospect.

Description

technical field [0001] The invention relates to the technical field of bacterial disease prevention and control, and more specifically relates to methyl cinnamate as a quorum sensing inhibitor and its application in treating bacterial diseases. Background technique [0002] Pseudomonas aeruginosa (P.aeruginosa) is a Gram-negative bacterium that is ubiquitous in various environments, including water, air, soil, plants, and animals. It is also present in the skin, intestinal tract, and respiratory tract of normal people. exist. After Pseudomonas aeruginosa infects the host, it will release a variety of virulence factors, including extracellular enzymes, pyocyanin, elastase and hemolysin, which will cause complex pathological changes in the host. Pseudomonas aeruginosa coordinates some important functions related to pathogenesis through the QS system, including biofilm formation, regulation of immune response, swarm motility, exopolysaccharide and toxin production. Quorum sen...

Claims

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Application Information

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IPC IPC(8): A01N37/10A01P1/00
CPCA01N37/10
Inventor 崔紫宁邵将贺露露古景文高冬倪
Owner SOUTH CHINA AGRI UNIV
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