Macrocyclic compounds and uses thereof

Abstract

The present invention relates to a macrocyclic cavity-containing compound and its use in inhibiting or reducing the amount of a microbial signaling molecule in a subject. The present invention also relates to a method of inhibiting or reducing the amount of a microbial signaling molecule in a subject by contacting a macrocyclic cavity-containing compound with the subject.

Description

TECHNICAL FIELD

[0001] The present invention relates to a macrocyclic cavity-containing compound and its use in inhibiting or reducing the amount of a microbial signal molecule in a subject. The present invention also relates to a method of inhibiting or reducing the amount of a microbial signal molecule in a subject by contacting a macrocyclic cavity-containing compound with the subject. BACKGROUND

[0002] Antibiotic resistance is a rapidly growing problem, where the prescription of common antibiotics against a variety of diseases only amplifies the rate of resistance. Multi-drug resistance is so important that the World Health Organization (WHO) has published a list of priority pathogens for a global response to antibiotic resistance (WHO, 2017).

[0003] Microorganisms monitor their population density and coordinate the activity of individual cells at the population level by using intercellular communication mechanisms of microbial signal molecules. One of these intercellular communication mechanisms is quorum sensing. Quorum sensing is used by both Gram-negative and Gram-positive bacteria. Of particular interest are Gram-negative bacteria that are pathogenic to humans and in which quorum sensing often plays a central role in their virulence, such as Vibrio cholera, Yersinia pestis, Acinetobacter baumannii and Pseudomonas aeruginosa.

[0004] WO2017025951 discloses cationic pillar[n]arenes capable of inhibiting or preventing biofilm formation.

[0005] The publications and other materials used herein to elucidate the background of the invention, and in particular, to provide additional details with respect to the practice, are hereby incorporated by reference. SUMMARY

[0006] The present invention relates to a macrocyclic cavity-containing compound for use in inhibiting a microbial signal molecule in a subject. The present invention also relates to a macrocyclic cavity-containing compound for use in reducing the amount of a microbial signal molecule in a subject.

[0007] The present invention relates to a macrocyclic cavity-containing compound for use in inhibiting a microbial signal molecule in a subject. The present invention also relates to a macrocyclic cavity-containing compound for use in reducing the amount of a microbial signal molecule in a subject.

[0008] The present invention relates to a method for inhibiting a microbial signaling molecule in a subject, wherein the method comprises contacting a macrocyclic cavity-containing compound with the subject. The present invention also relates to a method for reducing the amount of a microbial signaling molecule in a subject, wherein the method comprises contacting a macrocyclic cavity-containing compound with the subject.

[0009] The present invention relates to a macrocyclic cavity-containing compound for use in the prevention or treatment of a microbial signaling molecule-dependent and / or mediated microbial infection in a subject.

[0010] The present invention also relates to the use of a macrocyclic cavity-containing compound for the prevention or treatment of a microbial signaling molecule-dependent and / or mediated infection in a subject.

[0011] The present invention relates to a method for the prevention or treatment of a microbial signaling molecule-dependent and / or mediated infection in a subject, wherein the method comprises contacting a macrocyclic cavity-containing compound with the subject.

[0012] The objects of the present invention are achieved by the compounds, uses and methods characterized in the independent claims. Preferred embodiments of the present invention are disclosed in the dependent claims. BRIEF DESCRIPTION OF DRAWINGS

[0013] Figure 1 Structures of resorcin[4]arene, pillar[5]arene and a-cyclodextrin are shown.

[0014] Figure 2 Structures of homoserine lactones (HSLs) with carbon chains of different lengths are shown.

[0015] Figure 3 Ability of pillar[5]arene to bind HSLs with carbon chains of different lengths is shown.

[0016] Figure 4 Ability of resorcin[4]arene to bind HSLs with carbon chains of different lengths is shown.

[0017] Figure 5 Ability of a-cyclodextrin to bind HSLs with carbon chains of different lengths is shown.

[0018] Figure 6 Ability of g-cyclodextrin to bind HSLs with carbon chains of different lengths is shown.

[0019] Figure 7 Ability of 18-crown-6 to bind HSLs with carbon chains of different lengths is shown.

[0020] Figure 8 Ability of 15-crown-5 to bind HSLs with carbon chains of different lengths is shown.

[0021] Figure 9 The ability of cucurbit[6]uril hydrate to bind HSLs with carbon chains of different lengths is shown.

[0022] Figure 10 The ability of 4-sulfonic acid calix[4]arene to bind HSLs with carbon chains of different lengths is shown.

[0023] Figure 11 The host-guest interaction of pillar[5]arene with HSLs with carbon chains of different lengths (C6, C12, C14) is shown.

[0024] Figure 12 The results of the pyocyanin assay of Example 1 are shown.

[0025] Figure 13 The concentration dependence between pyocyanin in P. aeruginosa and GFP fluorescence in E. coli is shown.

[0026] Figure 14 The results of Example 3 are shown.

[0027] Figure 15 The effect of pillar[5]arene on P. aeruginosa cell death in human lung cell (A549) cultures is shown. DETAILED DESCRIPTION

[0028] The terms used in the specification and claims, unless otherwise indicated, have meanings known to those of ordinary skill in the art.

[0029] In the present specification, the term "macrocyclic cavity-containing compound" refers to an organic ring compound that forms a cylindrical structure that provides a cavity for host-guest interactions. Examples of such compounds are cyclodextrins, cucurbiturils, pillar arenes, calixarenes, and crown ethers.

[0030] As many microorganisms, especially Gram-negative pathogens, only show virulence and express toxic effects when reaching cell population densities, targeting the population signal molecule forms an interesting strategy, called "quorum sensing quenching", to prevent pathogenicity. Quorum quenching includes all means designed to prevent the binding of the signal molecule to its intracellular receptor. As quorum sensing is not essential for the growth of the microorganism and quorum quenching usually does not provide stress for the survival of the microorganism, no development of resistance to the treatment is seen.

[0031] The present invention is based on the discovery that macrocyclic cavity-containing compounds can act as hosts for microbial signaling molecules, such as quorum sensing signaling molecules. Specifically, the present invention is based on the discovery that macrocyclic cavity-containing compounds, such as resorcin[4]arene, pillar[5]arene, a-cyclodextrin, γ-cyclodextrin, 18-crown-6, 15-crown-5, cucurbit[6]uril, and 4-sulfonic acid calix[4]arene, are able to non-covalently bind the microbial signaling molecule homoserine lactone HSL produced by Gram-negative bacteria. The binding of these compounds to HSL was shown to be an effective quorum sensing quenching technique that can be used to eliminate or reduce the virulence of HSL-expressing microorganisms.

[0032] In the present invention, macrocyclic cavity-containing compounds inhibit or reduce the amount of microbial signaling molecules by non-covalently binding the microbial signaling molecules through host-guest interactions. In the present invention, macrocyclic cavity-containing compounds prevent or treat microbial signaling molecule-dependent and / or mediated microbial infections by non-covalently binding the microbial signaling molecules through host-guest interactions.

[0033] The binding of macrocyclic cavity-containing compounds to microbial signaling molecules is selective. It was discovered that macrocyclic cavity-containing compounds, such as pillar[5]arene, resorcin[4]arene, a-cyclodextrin, γ-cyclodextrin, 18-crown-6, 15-crown-5, cucurbit[6]uril, and 4-sulfonic acid calix[4]arene, bind to N-acyl-homoserine lactones (AHLs). For example, it was discovered that pillar[5]arene selectively binds long-chain N-acyl-homoserine lactones (AHLs). This enables macrocyclic cavity-containing compounds to precisely target endophytic microorganisms that produce only such AHLs. The binding of macrocyclic cavity-containing compounds to microbial signaling molecules is strong, and the compounds can absorb microbial signaling molecule concentrations even much higher than normally produced by the native bacteria. Unlike antibiotic agents that also have toxic effects on human and / or animal cells, macrocyclic cavity-containing compounds as hosts have no damaging effects on human and / or animal cells. Macrocyclic cavity-containing compounds have no negative growth effects on microorganisms. Thus, microbial cells do not experience survival stress and are less likely to acquire and / or develop resistance. The host-guest binding of macrocyclic cavity-containing compounds and microbial signaling molecules is an extracellular process. Macrocyclic cavity-containing compounds are too large to enter microbial cells, which further reduces the chance of developing resistance in microorganisms. Macrocyclic cavity-containing compounds, such as pillar[5]arene, have good stability and are easily soluble, and even stable in water. Thus, these compounds can be applied in a wide variety of environments.

[0034] The present invention relates to a macrocyclic cavity-containing compound for use in inhibiting a microbial signaling molecule in a subject. The present invention also relates to a macrocyclic cavity-containing compound for use in reducing the amount of a microbial signaling molecule in a subject.

[0035] In an embodiment, at least one macrocyclic cavity-containing compound is used. In an embodiment, a combination of at least two macrocyclic cavity-containing compounds is used. In an embodiment, at least one macrocyclic cavity-containing compound is used with an antibiotic. In an embodiment, the macrocyclic cavity-containing compound is selected from a cyclodextrin, cucurbituril, pillararene, calixarene, crown ether, and / or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is selected from a cyclodextrin or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is selected from a-cyclodextrin, γ-cyclodextrin, or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is a-cyclodextrin or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is γ-cyclodextrin or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is selected from a calixarene or a salt thereof. In an embodiment, the calixarene is 4-sulfonic acid calix[4]arene. In an embodiment, the macrocyclic cavity-containing compound is selected from a resorcinarene and / or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is resorcin[4]arene or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is selected from a pillararene and / or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is selected from a pillar[5]arene or a salt thereof. In an embodiment, the pillar[5]arene is 4,9,14,19,24,26,28,30,32,34-deca[2-(trimethylamino)ethoxy]hexacyclo[21.2.2.2 3,6 .2 8,11 .2 13,16 .2 18,21 ]triaconta-1(25),3,5,8,10,13,15,18,20,23,26,28,30,32,34-pentadecaene·10 bromide. In an embodiment, the macrocyclic cavity-containing compound is selected from a crown ether. In an embodiment, the crown ether is 18-crown-6 (1,4,7,10,13,16-hexaoxacyclooctadecane). In an embodiment, the crown ether is 15-crown-5 (1,4,7,10,13-pentaoxacyclopentadecane). In an embodiment, the macrocyclic cavity-containing compound is selected from a cucurbituril. In an embodiment, the cucurbituril is cucurbit[6]uril.

[0036] In an embodiment, the microbial signal molecule is produced by a bacterium. In an embodiment, the microbial signal molecule is produced by a Gram-positive bacterium. In an embodiment, the microbial signal molecule is produced by a Gram-negative bacterium. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Pseudomonas, Acinetobacter, Vibrio, Yersinia, Rhizobium, Klebsiella or other virulent bacterial genera of the family Enterobacteriaceae. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Pseudomonas. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Acinetobacter. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Vibrio. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Yersinia. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Rhizobium. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Klebsiella. In an embodiment, the microbial signal molecule is produced by Pseudomonas aeruginosa, Acinetobacter baumannii, Vibrio cholera, Vibrio fischeri, Yersinia pestis, Rhizobium leguminosarum or Klebsiella pneumonia. In an embodiment, the microbial signal molecule is produced by Pseudomonas aeruginosa. In an embodiment, the microbial signal molecule is produced by Acinetobacter baumannii. In an embodiment, the microbial signal molecule is produced by Vibrio cholera. In an embodiment, the microbial signal molecule is produced by Vibrio fischeri. In an embodiment, the microbial signal molecule is produced by Yersinia pestis. In an embodiment, the microbial signal molecule is produced by Rhizobium leguminosarum. In an embodiment, the microbial signal molecule is produced by Klebsiella pneumonia.

[0037] In an embodiment, the microbial signal molecule is a microbial quorum sensing signal molecule. In an embodiment, the microbial signal molecule or microbial quorum sensing signal molecule is selected from the group consisting of homoserine lactones (HSLs) and / or N-acyl-homoserine lactones (AHLs). In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone has a length of 4 to 18 carbon atoms. In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) has a length of 6 to 14 carbon atoms. In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) is linear. In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) is branched.

[0038] In an embodiment, the subject is a human. In an embodiment, the subject is a mammal.

[0039] The present application also relates to the use of a macrocyclic cavity-containing compound for inhibiting a microbial signal molecule in a subject. Furthermore, the present application relates to the use of a macrocyclic cavity-containing compound for reducing the amount of a microbial signal molecule in a subject.

[0040] In one embodiment, at least one macrocyclic cavity-containing compound is used. In one embodiment, a combination of at least two macrocyclic cavity-containing compounds is used. In one embodiment, at least one macrocyclic cavity-containing compound is used together with an antibiotic. In one embodiment, the macrocyclic cavity-containing compound is selected from the group consisting of a cyclodextrin, a cucurbituril, a pillararene, a calixarene, a crown ether and / or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is selected from a cyclodextrin or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is selected from a-cyclodextrin, y-cyclodextrin or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is a-cyclodextrin or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is y-cyclodextrin or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is selected from a calixarene or a salt thereof. In one embodiment, the calixarene is 4-sulfonic acid calix[4]arene. In one embodiment, the macrocyclic cavity-containing compound is selected from a resorcinarene and / or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is resorcin[4]arene or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is selected from a pillararene or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is pillar[5]arene or a salt thereof. In one embodiment, the pillar[5]arene is 4,9,14,19,24,26,28,30,32,34-deca[2-(trimethylamino)ethoxy]hexacyclo[21.2.2.2 3,6 .2 8,11 .2 13,16 .2 18,21 ]triaconta-1(25),3,5,8,10,13,15,18,20,23,26,28,30,32,34-pentadecaene-10-bromo. In one embodiment, the macrocyclic cavity-containing compound is selected from a crown ether. In one embodiment, the crown ether is 18-crown-6 (1,4,7,10,13,16-hexaoxaoctadecane). In one embodiment, the crown ether is 15-crown-5 (1,4,7,10,13-pentaoxamethyldecane). In one embodiment, the macrocyclic cavity-containing compound is selected from a cucurbituril. In one embodiment, the cucurbituril is cucurbit[6]uril.

[0041] In an embodiment, the microbial signal molecule is produced by a bacterium. In an embodiment, the microbial signal molecule is produced by a Gram-positive bacterium. In an embodiment, the microbial signal molecule is produced by a Gram-negative bacterium. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Pseudomonas, Acinetobacter, Vibrio, Yersinia, Rhizobium, Klebsiella or other virulent bacterial genera of the family Enterobacteriaceae. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Pseudomonas. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Acinetobacter. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Vibrio. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Yersinia. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Rhizobium. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Klebsiella. In an embodiment, the microbial signal molecule is produced by Pseudomonas aeruginosa, Acinetobacter baumannii, Vibrio cholerae, Vibrio fischeri, Yersinia pestis, Rhizobium leguminosarum or Klebsiella pneumoniae. In an embodiment, the microbial signal molecule is produced by Pseudomonas aeruginosa. In an embodiment, the microbial signal molecule is produced by Acinetobacter baumannii. In an embodiment, the microbial signal molecule is produced by Vibrio cholerae. In an embodiment, the microbial signal molecule is produced by Vibrio fischeri. In an embodiment, the microbial signal molecule is produced by Yersinia pestis. In an embodiment, the microbial signal molecule is produced by Rhizobium leguminosarum. In an embodiment, the microbial signal molecule is produced by Klebsiella pneumoniae.

[0042] In an embodiment, the microbial signal molecule is a microbial quorum sensing signal molecule. In an embodiment, the microbial signal molecule or quorum sensing signal molecule is selected from the group consisting of homoserine lactones (HSLs) and / or N-acyl-homoserine lactones (AHLs). In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) has a length of 4 to 18 carbon atoms. In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) has a length of 6 to 14 carbon atoms. In an embodiment, the carbon chain is linear. In an embodiment, the carbon chain is branched.

[0043] In an embodiment, the subject is a human or an animal. In an embodiment, the subject is a plant. In an embodiment, the subject is a cell culture. In an embodiment, the subject is a non-living object. The non-living object can be a medical device or an implant. In an embodiment, the non-living object is an aqueous medium.

[0044] The present invention relates to a method for inhibiting a microbial signaling molecule in a subject, wherein the method comprises contacting a macrocyclic cavity-containing compound with the subject. The present invention also relates to a method for reducing the amount of a microbial signaling molecule in a subject, wherein the method comprises contacting a macrocyclic cavity-containing compound with the subject.

[0045] In an embodiment, at least one macrocyclic cavity-containing compound is used. In an embodiment, a combination of at least two macrocyclic cavity-containing compounds is used. In an embodiment, at least one macrocyclic cavity-containing compound is used together with an antibiotic. In an embodiment, the macrocyclic cavity-containing compound is selected from the group consisting of a cyclodextrin, a cucurbituril, a pillararene, a calixarene, a crown ether, and / or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is selected from a cyclodextrin or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is selected from a-cyclodextrin, γ-cyclodextrin, or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is a-cyclodextrin or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is γ-cyclodextrin or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is selected from a calixarene or a salt thereof. In an embodiment, the calixarene is 4-sulfonic acid calix[4]arene. In an embodiment, the macrocyclic cavity-containing compound is selected from a resorcinarene and / or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is resorcin[4]arene or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is selected from a pillararene or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is pillar[5]arene or a salt thereof. In an embodiment, the pillar[5]arene is 4,9,14,19,24,26,28,30,32,34-deca[2-(trimethylamino)ethoxy]hexacyclo[21.2.2.2 3,6 .2 8,11 .2 13,16 .2 18,21 ]pentacosa-1(25),3,5,8,10,13,15,18,20,23,26,28,30,32,34-pentadeca-10-bromo. In an embodiment, the macrocyclic cavity-containing compound is selected from a crown ether. In an embodiment, the crown ether is 18-crown-6 (1,4,7,10,13,16-hexaoxaoctadecane). In an embodiment, the crown ether is 15-crown-5 (1,4,7,10,13-pentaoxabicyclodecane). In an embodiment, the macrocyclic cavity-containing compound is selected from a cucurbituril. In an embodiment, the cucurbituril is cucurbit[6]uril.

[0046] In an embodiment, the microbial signal molecule is produced by a bacterium. In an embodiment, the microbial signal molecule is produced by a Gram-positive bacterium. In an embodiment, the microbial signal molecule is produced by a Gram-negative bacterium. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Pseudomonas, Acinetobacter, Vibrio, Yersinia, Rhizobium, Klebsiella or other virulent bacterial genera of the family Enterobacteriaceae. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Pseudomonas. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Acinetobacter. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Vibrio. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Yersinia. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Rhizobium. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Klebsiella. In an embodiment, the microbial signal molecule is produced by Pseudomonas aeruginosa, Acinetobacter baumannii, Vibrio cholerae, Vibrio fischeri, Yersinia pestis, Rhizobium leguminosarum or Klebsiella pneumoniae. In an embodiment, the microbial signal molecule is produced by Pseudomonas aeruginosa. In an embodiment, the microbial signal molecule is produced by Acinetobacter baumannii. In an embodiment, the microbial signal molecule is produced by Vibrio cholerae. In an embodiment, the microbial signal molecule is produced by Vibrio fischeri. In an embodiment, the microbial signal molecule is produced by Yersinia pestis. In an embodiment, the microbial signal molecule is produced by Rhizobium leguminosarum. In an embodiment, the microbial signal molecule is produced by Klebsiella pneumoniae.

[0047] In an embodiment, the microbial signal molecule is a microbial quorum sensing signal molecule. In an embodiment, the microbial signal molecule or microbial quorum sensing signal molecule is selected from the group consisting of homoserine lactones (HSLs) and / or N-acyl-homoserine lactones (AHLs). In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) has a length of 4 to 18 carbon atoms. In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) has a length of 6 to 14 carbon atoms. In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) is linear. In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) is branched.

[0048] In an embodiment, the subject is a human or an animal. In an embodiment, the subject is a plant. In an embodiment, the subject is a cell culture. In an embodiment, the subject is a non-living object. The non-living object can be a medical device or an implant. In an embodiment, the non-living object is an aqueous medium.

[0049] Further, the present application relates to a macrocyclic cavity-containing compound for use in the prevention or treatment of a microbial signal molecule-dependent and / or -mediated infection in a subject.

[0050] In an embodiment, at least one macrocyclic cavity-containing compound is used. In an embodiment, a combination of at least two macrocyclic cavity-containing compounds is used. In an embodiment, at least one macrocyclic cavity-containing compound is used in combination with an antibiotic. In an embodiment, the macrocyclic cavity-containing compound is selected from the group consisting of a cyclodextrin, a cucurbituril, a pillararene, a calixarene, a crown ether and / or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is selected from a cyclodextrin or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is selected from a-cyclodextrin, y-cyclodextrin or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is a-cyclodextrin or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is y-cyclodextrin or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is selected from a calixarene or a salt thereof. In an embodiment, the calixarene is 4-sulfonic acid calix[4]arene. In an embodiment, the macrocyclic cavity-containing compound is selected from a resorcinarene and / or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is resorcin[4]arene or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is selected from a pillararene or a salt thereof. In an embodiment, the macrocyclic cavity-containing compound is pillar[5]arene or a salt thereof. In an embodiment, the pillar[5]arene is 4,9,14,19,24,26,28,30,32,34-deca[2-(trimethylamino)ethoxy]hexacyclo[21.2.2.2 3,6 .2 8,11 .2 13,16 .2 18,21 ]triaconta-1(25),3,5,8,10,13,15,18,20,23,26,28,30,32,34-pentadecaene·10 bromide. In an embodiment, the macrocyclic cavity-containing compound is selected from a crown ether. In an embodiment, the crown ether is 18-crown-6 (1,4,7,10,13,16-hexaoxaoctadecane). In an embodiment, the crown ether is 15-crown-5 (1,4,7,10,13-pentaoxabicyclodecane). In an embodiment, the macrocyclic cavity-containing compound is selected from a cucurbituril. In an embodiment, the cucurbituril is cucurbit[6]uril.

[0051] In an embodiment, the microbial signal molecule is produced by a bacterium. In an embodiment, the microbial signal molecule is produced by a Gram-positive bacterium. In an embodiment, the microbial signal molecule is produced by a Gram-negative bacterium. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Pseudomonas, Acinetobacter, Vibrio, Yersinia, Rhizobium, Klebsiella or other virulent bacterial genera of the family Enterobacteriaceae. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Pseudomonas. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Acinetobacter. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Vibrio. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Yersinia. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Rhizobium. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Klebsiella. In an embodiment, the microbial signal molecule is produced by Pseudomonas aeruginosa, Acinetobacter baumannii, Vibrio cholerae, Vibrio fischeri, Yersinia pestis, Rhizobium leguminosarum or Klebsiella pneumoniae. In an embodiment, the microbial signal molecule is produced by Pseudomonas aeruginosa. In an embodiment, the microbial signal molecule is produced by Acinetobacter baumannii. In an embodiment, the microbial signal molecule is produced by Vibrio cholerae. In an embodiment, the microbial signal molecule is produced by Vibrio fischeri. In an embodiment, the microbial signal molecule is produced by Yersinia pestis. In an embodiment, the microbial signal molecule is produced by Rhizobium leguminosarum. In an embodiment, the microbial signal molecule is produced by Klebsiella pneumoniae.

[0052] In an embodiment, the microbial signal molecule is a microbial quorum sensing signal molecule. In an embodiment, the microbial signal molecule or microbial quorum sensing signal molecule is selected from the group consisting of homoserine lactones (HSLs) and / or N-acyl-homoserine lactones (AHLs). In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) has a length of 4 to 18 carbon atoms. In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) has a length of 6 to 14 carbon atoms. In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) is linear. In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) is branched.

[0053] In an embodiment, the microbial signal molecule-dependent or mediated infection is a chronic infection. In an embodiment, the infection is an acute infection or the infection is caused by planktonic microorganisms.

[0054] In one embodiment, the microbial signal molecule-dependent or mediated infection is a lung infection.

[0055] In one embodiment, the subject is a human. In one embodiment, the subject is a mammal.

[0056] The present application also relates to the use of a macrocyclic cavity-containing compound for preventing or treating a microbial signal molecule-dependent and / or mediated infection in a subject.

[0057] In one embodiment, at least one macrocyclic cavity-containing compound is used. In one embodiment, a combination of at least two macrocyclic cavity-containing compounds is used. In one embodiment, at least one macrocyclic cavity-containing compound is used in combination with an antibiotic. In one embodiment, the macrocyclic cavity-containing compound is selected from the group consisting of a cyclodextrin, a cucurbituril, a pillararene, a calixarene, a crown ether and / or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is selected from a cyclodextrin or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is selected from a-cyclodextrin, γ-cyclodextrin or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is a-cyclodextrin or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is γ-cyclodextrin or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is selected from a calixarene or a salt thereof. In one embodiment, the calixarene is 4-sulfonic acid calix[4]arene. In one embodiment, the macrocyclic cavity-containing compound is selected from a resorcinarene and / or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is resorcin[4]arene or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is selected from a pillararene or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is pillar[5]arene or a salt thereof. In one embodiment, the pillar[5]arene is 4,9,14,19,24,26,28,30,32,34-deca[2-(trimethylamino)ethoxy]hexa- cyclo[21.2.2.2 3,6 .2 8,11 .2 13,16 .2 18,21 ]triaconta-1(25),3,5,8,10,13,15,18,20,23,26,28,30,32,34-pentadecaene-10-bromo. In one embodiment, the macrocyclic cavity-containing compound is selected from a crown ether. In one embodiment, the crown ether is 18-crown-6 (1,4,7,10,13,16-hexaoxacyclooctadecane). In one embodiment, the crown ether is 15-crown-5 (1,4,7,10,13-pentaoxacyclopentadecane). In one embodiment, the macrocyclic cavity-containing compound is selected from a cucurbituril. In one embodiment, the cucurbituril is cucurbit[6]uril.

[0058] In an embodiment, the microbial signal molecule is produced by a bacterium. In an embodiment, the microbial signal molecule is produced by a Gram-positive bacterium. In an embodiment, the microbial signal molecule is produced by a Gram-negative bacterium. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Pseudomonas, Acinetobacter, Vibrio, Yersinia, Rhizobium, Klebsiella or other virulent bacterial genera of the family Enterobacteriaceae. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Pseudomonas. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Acinetobacter. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Vibrio. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Yersinia. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Rhizobium. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Klebsiella. In an embodiment, the microbial signal molecule is produced by Pseudomonas aeruginosa, Acinetobacter baumannii, Vibrio cholerae, Vibrio fischeri, Yersinia pestis, Rhizobium leguminosarum or Klebsiella pneumoniae. In an embodiment, the microbial signal molecule is produced by Pseudomonas aeruginosa. In an embodiment, the microbial signal molecule is produced by Acinetobacter baumannii. In an embodiment, the microbial signal molecule is produced by Vibrio cholerae. In an embodiment, the microbial signal molecule is produced by Vibrio fischeri. In an embodiment, the microbial signal molecule is produced by Yersinia pestis. In an embodiment, the microbial signal molecule is produced by Rhizobium leguminosarum. In an embodiment, the microbial signal molecule is produced by Klebsiella pneumoniae.

[0059] In an embodiment, the microbial signal molecule is a microbial quorum sensing signal molecule. In an embodiment, the microbial signal molecule or microbial quorum sensing signal molecule is selected from the group consisting of homoserine lactones (HSLs) and / or N-acyl-homoserine lactones (AHLs). In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) has a length of 4 to 18 carbon atoms. In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) has a length of 6 to 14 carbon atoms. In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) is linear. In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) is branched.

[0060] In an embodiment, the microbial signal molecule-dependent or mediated infection is a chronic infection. In an embodiment, the infection is an acute infection or the infection is caused by planktonic microorganisms.

[0061] In one embodiment, the subject is a human or an animal. In one embodiment, the microbial signal molecule-dependent or -mediated infection is a pulmonary infection.

[0062] In one embodiment, the subject is a plant.

[0063] The present application also relates to a method for preventing or treating a microbial signal molecule-dependent and / or -mediated infection in a subject or medium, wherein the method comprises contacting a macrocyclic cavity-containing compound with the subject or medium.

[0064] In one embodiment, the macrocyclic cavity-containing compound is selected from the group consisting of a cyclodextrin, a cucurbituril, a pillararene, a calixarene, a crown ether and / or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is selected from the group consisting of a cyclodextrin or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is selected from the group consisting of a-cyclodextrin, γ-cyclodextrin or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is a-cyclodextrin or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is γ-cyclodextrin or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is selected from the group consisting of a calixarene or a salt thereof. In one embodiment, the calixarene is 4-sulfonic acid calix[4]arene. In one embodiment, the macrocyclic cavity-containing compound is selected from the group consisting of a resorcinarene and / or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is resorcin[4]arene or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is selected from the group consisting of a pillararene or a salt thereof. In one embodiment, the macrocyclic cavity-containing compound is pillar[5]arene or a salt thereof. In one embodiment, the pillar[5]arene is 4,9,14,19,24,26,28,30,32,34-deca[2-(trimethylamino)ethoxy]hexa- cyclo[21.2.2.2 3,6 .2 8,11 .2 13,16 .2 18,21 ]triaconta-1(25),3,5,8,10,13,15,18,20,23,26,28,30,32,34-pentadecaene-10-bromo. In one embodiment, the macrocyclic cavity-containing compound is selected from the group consisting of a crown ether. In one embodiment, the crown ether is 18-crown-6 (1,4,7,10,13,16-hexaoxacyclooctadecane). In one embodiment, the crown ether is 15-crown-5 (1,4,7,10,13-pentaoxacyclopentadecane). In one embodiment, the macrocyclic cavity-containing compound is selected from the group consisting of a cucurbituril. In one embodiment, the cucurbituril is cucurbit[6]uril.

[0065] In an embodiment, the microbial signal molecule is produced by a bacterium. In an embodiment, the microbial signal molecule is produced by a Gram-positive bacterium. In an embodiment, the microbial signal molecule is produced by a Gram-negative bacterium. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Pseudomonas, Acinetobacter, Vibrio, Yersinia, Rhizobium, Klebsiella or other virulent bacterial genera of the family Enterobacteriaceae. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Pseudomonas. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Acinetobacter. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Vibrio. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Yersinia. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Rhizobium. In an embodiment, the microbial signal molecule is produced by a bacterium belonging to the genus Klebsiella. In an embodiment, the microbial signal molecule is produced by Pseudomonas aeruginosa, Acinetobacter baumannii, Vibrio cholerae, Vibrio fischeri, Yersinia pestis, Rhizobium leguminosarum or Klebsiella pneumoniae. In an embodiment, the microbial signal molecule is produced by Pseudomonas aeruginosa. In an embodiment, the microbial signal molecule is produced by Acinetobacter baumannii. In an embodiment, the microbial signal molecule is produced by Vibrio cholerae. In an embodiment, the microbial signal molecule is produced by Vibrio fischeri. In an embodiment, the microbial signal molecule is produced by Yersinia pestis. In an embodiment, the microbial signal molecule is produced by Rhizobium leguminosarum. In an embodiment, the microbial signal molecule is produced by Klebsiella pneumoniae. In an embodiment, the microbial signal molecule is a microbial quorum sensing signal molecule. In an embodiment, the microbial signal molecule or microbial quorum sensing signal molecule is selected from the group consisting of homoserine lactones (HSLs) and / or N-acyl-homoserine lactones (AHLs). In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) has a length of 4 to 18 carbon atoms. In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) has a length of 6 to 14 carbon atoms. In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) is linear. In an embodiment, the carbon chain of the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) is branched.

[0066] In an embodiment, the microbial signal molecule-dependent or mediated infection is a chronic infection. In an embodiment, the infection is an acute infection, or the infection is caused by a planktonic microorganism.

[0067] In one embodiment, the subject is a human or an animal. In one embodiment, the microbial signal molecule-dependent or -mediated infection is a lung infection.

[0068] In one embodiment, the subject is a plant.

[0069] In one embodiment, the present application relates to a method for preventing or treating a microbial signal molecule-dependent and / or -mediated infection in a human or an animal, wherein the method comprises administering to said human or said animal at least one macrocyclic cavity- containing compound.

[0070] In one embodiment, the present application relates to a composition comprising a macrocyclic cavity-containing compound and a suitable carrier. In one embodiment, the present application relates to a composition comprising a macrocyclic cavity-containing compound and a suitable carrier for use in inhibiting or reducing the amount of a microbial signal molecule in a subject or a medium or for use in preventing or treating a microbial signal molecule-dependent and / or -mediated infection in a subject. The compositions of the present application can be prepared by techniques known in the art. Thus, for example, the compositions of the present application can be in liquid or solid form, and they can comprise other additives and / or ingredients, such as fillers, diluents and / or adjuvants.

[0071] In one embodiment, the present application relates to a pharmaceutical composition comprising at least one macrocyclic cavity-containing compound and a pharmaceutically acceptable carrier. In one embodiment, the present application relates to a pharmaceutical composition comprising a macrocyclic cavity-containing compound and a pharmaceutically acceptable carrier for use in inhibiting or reducing the amount of a microbial signal molecule in a subject or for use in preventing or treating a microbial signal molecule-dependent and / or -mediated infection in a subject. The pharmaceutical compositions of the present application can be prepared by techniques known in the art. The pharmaceutical compositions of the present application can be administered, for example, orally, parenterally, topically or by inhalation. Thus, the pharmaceutical compositions can be, for example, in liquid, solid or powder form. In one embodiment, the pharmaceutical composition is in the form of microparticles. In one embodiment, the microparticles are in the range of 1-5 μm. Depending on its route of administration, the composition comprises the necessary pharmaceutically acceptable additives and / or ingredients, such as fillers, diluents and / or adjuvants.

[0072] The following examples are given to further illustrate the present application, but without limiting the present application.

[0073] Example

[0074] Example 1 - Pyocyanin Assay

[0075] In testing the functionality of P[5]a as an actual quorum sensing inhibitor, the pathogenic Gram-negative bacterium Pseudomonas aeruginosa was used, which contains a Lasl synthase producing 3-oxo-C12 HSL.

[0076] P. aeruginosa utilizes multiple quorum sensing systems (Las, Rhl and Pqs). The Las system is at the top of a cascade that leads to the activation of other quorum sensing systems and is directly responsible for the production of the green toxin pyocyanin. Pyocyanin is a toxin produced by P. aeruginosa and its production is directly activated by 3-oxo-C12 HSL. During cystic fibrosis, pyocyanin is responsible for the death of lung cells. Therefore, the production of this toxin is directly related to the C12 Las AHL signal in the quorum response.

[0077] Bacterial cells were grown in LB medium with 1% glucose for 24 hours. Then, the culture was separated from the cells and measured at OD695 (this measures the amount of green).

[0078] In the pyocyanin assay, the effect of different concentrations of P[5]a5 (4,9,14,19,24,26,28,30,32,34-deca[2-(trimethylamino)ethoxy]hexacyclo[21.2.2.2 3,6 .2 8,11 .2 13,16 .2 18,21 ]pentatriaconta-1(25),3,5,8,10,13,15,18,20,23,26,28,30,32,34-pentadecene.10 bromide, CAS number: 1351445-28-7) on the production of pyocyanin after 24 hours of growth was studied and the results are shown in Figure 12 In the absence or low concentrations of P[5]a, no significant differences were detected in the production of pyocyanin, as shown by the green color of the cultures. However, at higher concentrations, a shift to bright yellow (normal cell culture) was observed, indicating a complete inhibition of the production of pyocyanin by P[5]a.

[0079] It is shown that the host compound P[5]a completely inhibits the production of the toxin only by strong binding of the AHL. Cell growth is completely unaffected, only the toxin production (toxicity) is affected.

[0080] Example 2

[0081] To ensure that P[5]a does not react directly with the pyocyanin metabolites, but inhibits the production of the cell, a 24-hour culture with high levels of pyocyanin was taken and the cells were removed. A new concentration of the host was added and incubated for another 24 hours. No decrease in the levels of pyocyanin was detected, indicating that P[5]a inhibits the production of pyocyanin, not the breakdown of pyocyanin.

[0082] Example 3 - P[5]a microparticles

[0083] Pillar[5]arene (P[5]a) (4,9,14,19,24,26,28,30,32,34- decacyclo[21.2.2.2 3,6 .2 8,11 .2 13,16 .2 18,21 ]triacontane 1 (25), 3, 5, 8, 10, 13, 15, 18, 20, 23, 26, 28, 30, 32, 34-pentacosa-10-bromo) was formulated into microparticles by an aerosol flow reactor method. The particle size was in the range of 1-5 μm, which allowed the particles to reach the deep lung for high bioavailability of the active compound. The microparticles were made from a precursor solution of P[5]a, trehalose, sodium citrate and leucine for protection of the unstable peptide.

[0084] The effect of P[5]a microparticles at different concentrations was measured as described in Example 1. The results are shown in Figure 14 From the results it can be seen that the effect of P[5]a formulated into microparticles is in line with the results obtained in Example 1.

[0085] Example 4 - Lung cell experiments

[0086] To assess the possible toxicity of P[5]a on lung cells, two independent viability tests were performed. First, the viability of A549 cells grown in the presence of different concentrations of P[5]a was determined using trypan blue staining. The assay showed no significant difference between the viability of cells grown with or without pillar[5]arene. Subsequently, A549 cells grown with and without P[5]a were subjected to a CellTox Green cytotoxicity assay (Promega) in the presence or absence of PAOl Pseudomonas aeruginosa strain. The results showed that A549 cells infected with P. aeruginosa showed a rapid (3 h incubation) increase in fluorescence intensity, which is an indicator of cell death. This was not observed for cells grown with the addition of P[5]a in the growth medium. Interestingly, the addition of P[5]a in the growth medium during infection with the PAOl strain resulted in a dose-dependent decrease in cell death.

[0087] To further investigate the effects of P[5]a on eukaryotic cells, total RNA was isolated from A549 cells infected with P. aeruginosa in the presence or absence of 100 nM or 2.5 mM P[5]a. The expression of 46 genes was strongly affected, met our stringent criteria, and were considered to be differentially expressed during infection of PAOl. Analysis with GO biological processes and it showed that many of the differentially expressed genes were involved in the promotion of inflammatory responses, responses to bacterial-derived molecules, chemotaxis, and the regulation of cell proliferation. Chemokine ligands (CCL20, CXCL1, CXCL2, and CXCL3) along with intercellular adhesion molecule 1 (ICAM1) were among the most upregulated genes during infection. Importantly, the addition of P[5]a to the growth medium during infection reduced the overexpression of many of the differentially expressed genes. When infection of PAOl was performed in the presence of P[5]a, the expression of CXCL1, CXCL8, CCL20, and ICAM1 was significantly reduced in a dose-dependent manner. A similar pattern was observed for the gene encoding interferon regulatory factor 1 (IRF1), which is a transcriptional regulator that functions as an activator of genes involved in both innate and adaptive immune responses. In contrast, the addition of P[5]a to the infection culture of A549 resulted in further overexpression of adrenomedullin (ADM) and colony-stimulating factor 2 (CSF2), both of which are involved in the response to bacterial infection.

[0088] Example 5

[0089] The ability of pillar[5]arene, resorcin[4]arene, a-cyclodextrin, g-cyclodextrin, 18-crown-6, 15-crown-5, cucurbit[6]uril hydrate and 4-sulfonic acid calix[4]arene to bind HSL with different length of carbon chain (shown in Figure 2 ) was tested. The results are shown in Figures 3-10 .

[0090] The macrocyclic cavity-containing compounds tested were:

[0091] pillar[5]arene; 4,9,14,19,24,26,28,30,32,34-deca[2-(trimethylamine)ethoxy]hexa- cyclo[21.2.2.2 3,6 .2 8,11 .2 13,16 .2 18,21 ]tritriacontane-1(25),3,5,8,10,13,15,18,20,23,26,28,30,32,34-pentadecene. 10 bromo

[0092] resorcin[4]arene

[0093] a-cyclodextrin (molecular weight 973 g / mol),

[0094] gamma-cyclodextrin (molecular weight 1297 g / mol),

[0095] 18-crown-6; 1,4,7,10,13,16-hexaoxacyclooctadecane (molecular weight 264 g / mol),

[0096] 15-crown-5; 1,4,7,10,13-pentaoxacyclopentadecane (molecular weight 220 g / mol),

[0097] calix[6]urea hydrate (molecular weight 996 g / mol),

[0098] 4-sulfonic acid calix[4]arene; 25,26,27,28-tetrahydroxy calix[4]arene-5,1 1,17,23- tetrasulfonic acid; calix[4]arene-4-sulfonic acid (molecular weight 744 g / mol).

[0099] It will be obvious to a person skilled in the art that, as the technology advances, the basic idea of the application can be implemented in various ways. The application and its embodiments are not limited to the examples described above but can vary within the scope of the claims.

Claims

1. Use of a macrocyclic cavity-containing compound in the preparation of a medicament for inhibiting a microbial population signaling molecule or reducing the amount of a microbial population signaling molecule in a subject by non-covalent host-guest binding between the macrocyclic cavity-containing compound and a microbial population signaling molecule, wherein the macrocyclic cavity-containing compound is selected from pillar[5]arenes, wherein the microbial population signaling molecule is produced by Gram-negative bacteria, wherein the microbial population signaling molecule is selected from homoserine lactones (HSLs) or N-acyl-homoserine lactones (AHLs), and wherein the pillar[5]arenes are 4,9,14,19,24,26,28,30,32,34-decane[2-(trimethylamino)ethoxy]hexacyclo[21.2.2.2 3,6 .2 8,11 .2 13,16 .2 18,21 ] Pentatriacontane 1(25),3,5,8,10,13,15,18,20,23,26,28,30,32,34-pentadene·10-bromide, the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) having a carbon chain length of 4 to 14 carbon atoms.

2. Use of a macrocyclic cavity-containing compound in the preparation of a medicament for preventing or treating a microbial quorum signaling molecule-dependent and / or mediated microbial infection in a subject by non-covalent host-guest binding between the macrocyclic cavity-containing compound and a microbial quorum signaling molecule, wherein the microbial quorum signaling molecule-dependent and / or mediated infection is caused by Gram-negative bacteria, wherein the microbial quorum signaling molecule is selected from homoserine lactones (HSLs) or N-acyl-homoserine lactones (AHLs), and wherein the pillar[5]arene is 4,9,14,19,24,26,28,30,32,34-decane[2-(trimethylamino)ethoxy]hexacyclo[21.2.2.2] 3 ,6 .2 8,11 .2 13,16 .2 18,21 ] Pentatriacontane 1(25),3,5,8,10,13,15,18,20,23,26,28,30,32,34-pentadene·10-bromide, the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) having a carbon chain length of 4 to 14 carbon atoms.

3. The use according to claim 2, wherein The microbial infection is an acute infection.

4. Use of a macrocyclic cavity-containing compound in the preparation of an agent for reducing or eliminating virulence in Gram-negative bacteria by non-covalent host-guest binding between the macrocyclic cavity-containing compound and a microbial quorum signaling molecule produced by Gram-negative bacteria, wherein the macrocyclic cavity-containing compound is selected from pillar[5]arenes, wherein the microbial quorum signaling molecule is selected from homoserine lactones (HSLs) or N-acyl-homoserine lactones (AHLs), and wherein the pillar[5]arenes are 4,9,14,19,24,26,28,30,32,34-decane[2-(trimethylamino)ethoxy]hexacyclo[21.2.2.2] 3,6 .2 8, 11 .2 13,16 .2 18,21 ] Pentatriacontane 1(25),3,5,8,10,13,15,18,20,23,26,28,30,32,34-pentadene·10-bromide, the homoserine lactone (HSL) or N-acyl-homoserine lactone (AHL) having a carbon chain length of 4 to 14 carbon atoms.

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