# US 8,772,331 B2 · Small molecule antagonists of bacterial quorum-sensing receptors

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 8,772,331 B2
- Document ID: US8772331B2
- Status: Granted
- Kind: B2
- Application number: 13/550,961
- Filed: 2012-07-17
- Published: 2014-01-23
- Granted: 2014-07-08
- Earliest claimed: 2012-07-17
- Assignees: The Trustees of Princeton University
- Applicants: Bonnie L. Bassler; Lee R. Swem; Scott M. Ulrich; Colleen T. O'Loughlin
- Inventors: Bonnie L. Bassler; Lee R. Swem; Scott M. Ulrich; Colleen T. O'Loughlin
- Web page: https://patentgrep.com/patent/US8772331B2

## CPC

- A61K 31/365: Lactones
- A01N 43/08: with oxygen as the ring hetero atom
- A01N 43/10: with sulfur as the ring hetero atom
- A01N 43/16: with oxygen as the ring hetero atom
- A01N 43/18: with sulfur as the ring hetero atom
- A61K 31/341: not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
- A61K 31/381: having five-membered rings
- A61P 31/04: Antibacterial agents
- C07D 307/33: in position 2, the oxygen atom being in its keto or unsubstituted enol form
- C07D 333/36: Nitrogen atoms
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

A novel small molecule antagonizes two types of acyl homoserine lactone receptors: membrane-bound and cytoplasmic. A focused library of analogs and derivatives of the original antagonist was synthesized. Analog and derivative molecules harbor a range of activities. The novel small molecule and most potent antagonist protects the eukaryote Caenorhabditis elegans from quorum-sensing-mediated killing by the bacterial pathogen Chromobacterium violaceum. The saving of C. elegans demonstrates the use of these molecules as small molecule antimicrobials.

## Claims

### Claim 1

A method of disrupting detection of acyl-homoserine lactone-type autoinducer in Gram-negative bacteria comprising contacting the bacteria with a small molecule represented by the formula:

### Claim 2

A method of inhibiting infection of a host by quorum sensing bacteria comprising contacting the bacteria with a small molecule represented by the formula:

### Claim 3 (depends on 2)

The method of claim 2 wherein a therapeutically effective amount of the small molecule is administered to the host.

### Claim 4

A method of controlling growth of quorum sensing Gram-negative bacteria that attach to a solid surface, comprising exposing the bacteria to a composition comprising one or more of the small molecules represented by the formula:
in an amount that affects biofilm formation.

### Claim 5 (depends on 4)

The method of claim 4 wherein the composition is applied to the surface.

### Claim 6 (depends on 4)

The method of claim 4 wherein the composition is administered to a host infected with the bacteria.

### Claim 7

A method of inhibiting quorum sensing-mediated activity in Gram-negative bacteria comprising contacting the bacteria with a small molecule represented by the formula:

### Claim 8 (depends on 7)

The method of claim 7 wherein the activity is bioluminescence, siderophore production, type III secretion, or metalloprotease production.

### Claim 9 (depends on 7)

The method of claim 7 wherein the activity is production of virulence factors.

### Claim 10 (depends on 9)

The method of claim 9 wherein the bacterial species is selected from the group consisting of V. harveyi, C. violaceum and P. aeroginosa.

### Claim 11 (depends on 9)

The method of claim 9 wherein the bacterial species is C. violaceum.

### Claim 12 (depends on 9)

The method of claim 9 wherein the bacteria are pathogenic to humans or animals.

### Claim 13 (depends on 9)

The method of claim 9 wherein the bacteria are pathogenic to plants.

### Claim 14 (depends on 9)

The method of claim 9 wherein the bacteria are pathogenic to marine life.

### Claim 15 (depends on 7)

The method of claim 7 wherein the small molecule is the chlorolactone.