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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 the prevention and / or treatment of bacterial diseases in view of the deficiency of relatively effective QS system inhibitor in the prior art

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
Effect test

Embodiment 1

[0037] Example 1 Screening of Quorum Sensing Inhibitors

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

[0039] figure 1 4-nitropyridine-N-oxide (4-nitropyridine-N-oxide, 4-NPO) marked in the positive control group, DMSO as the solvent control group, AHL...

Embodiment 2

[0041] Embodiment 2 tests the minimum inhibitory concentration (MIC) determination of methyl cinnamate compound to A.tumefaciens N5 (pBA7P)

[0042] In order to exclude the influence of the compound on the growth of A. tumefaciens N5(pBA7P), the MIC value of the screened compounds on A. tumefaciens N5(pBA7P) was determined. Add 1 / 1000th of A. tumefaciens N5 (pBA7P) that was shaken overnight into LB liquid medium, and mix well; add 196 μL of the above mixture to each well of the 96-well bacterial culture plate; The concentration gradient was 3.125, 6.25, 12.5, 25, 50, 100 and 200 μg / mL; the same volume of DMSO was used as the control, with three repetitions; the results were observed after standing at 28°C for 24 hours. Within the range visible to the naked eye, it can obviously inhibit the growth of microorganisms, and the minimum drug concentration that is still clear without turbidity in the bacterial solution is MIC.

[0043] Experimental results: The MIC of methyl cinnama...

Embodiment 3

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

[0046] To exclude methyl cinnamate as a β-lactamase inhibitor, the compound methyl cinnamate was tested for β-lactamase activity.

[0047] Take one-thousandth of the A. tumefaciens N5 (pBA7P) bacterial solution and put it into the liquid ABM medium (100mL), and shake it at 28°C; after about 16h, it reaches OD 600 =0.4 or so, dispense it into a 96-well bacterial culture plate with a row gun, 196 μL per well; add 10 μL of signal molecule 3OC6-HSL with a concentration of 5 μM to the 96-well plate, mix well on a microplate shaker, and shake at 28 °C Incubate for 2 hours; add 4 μL of 10,000 μg / mL of the compound to be tested to a final concentration of 200 μg / mL, shake at 28°C for 2 hours; dilute nitrothiophene to 250 μg / mL with pH=7.0 0.2M phosphate buffer, add 10 μL to 96 wells In the bacterial culture plate; observe the color change within 1 hour, and measure the OD value a...

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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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