Compounds, compositions, and methods for inhibiting bacterial growth

Patent metadata

Field	Value
Publication number	US-11717508-B2
Application number	US-201716339896-A
Country	US
Kind code	B2
Filing date	Oct 5, 2017
Priority date	Oct 5, 2016
Publication date	Aug 8, 2023
Grant date	Aug 8, 2023

Abstract

The present disclosure provides, among other things, compounds, compositions, and methods useful in inhibiting bacteria, such as Mycobacterium tuberculosis . These compositions and methods find many uses in medicine and research, e.g., treating subjects afflicted with active or latent bacterial infections.

First claim

What is claimed is:

1. A method for inhibiting growth of one or more mycobacterial cells in which an at least two-component regulatory system is conserved, said two-component regulatory system comprises one or more sensor histidine kinase and a cognate response regulator, the method comprising contacting the one or more mycobacterial cells with an effective amount of a compound that inhibits the at least two component regulatory system to thereby inhibit the growth of the one or more mycobacterial cells;
wherein the compound that inhibits the at least two-component regulatory system is an anti-virulence compound or analogs or derivatives thereof selected from the group consisting of HC101C, HC102A, HC103A, HC103B, HC104A, HC105A, and HC106A, or combinations thereof.

2. A method for treating a subject who is infected with mycobacterial cells in which an at least two-component regulatory system is conserved, said two-component regulatory system comprises one or more sensor histidine kinase and a cognate response regulator, the method comprising administering to the subject an effective amount of a compound that inhibits the at least two-component regulatory system to thereby treat the infection;
wherein the compound that inhibits the at least two-component regulatory system is an anti-virulence compound or analogs or derivatives thereof selected from the group consisting of HC101C, HC102A, HC103A, HC103B, HC104A, HC105A, and HC106A, or combinations thereof.

3. The method according to claim 1 , wherein the at least two-component regulatory system is a DosRST two-component regulatory system.

4. The method according to claim 1 , wherein the at least two-component regulatory system regulon is a DosRST regulon.

5. The method according to claim 2 , further comprising identifying the subject as having an infection with mycobacterial cells in which the two component regulatory system is conserved.

6. The method according to claim 1 , wherein the mycobacteria or mycobacterial cells are Mycobacterium tuberculosis , or nontuberculosis mycobacterium (NTM).

7. The method according to claim 6 , wherein the Mycobacterium tuberculosis is multi-drug resistant Mycobacterium tuberculosis.

8. A method for treating tuberculosis in a subject, the method comprising administering to the subject a compound that inhibits a DosRST two-component regulatory system and/or DosRST regulon in mycobacterial cells in an amount effective to treat tuberculosis;
wherein the compound is an anti-virulence compound or analogs or derivatives thereof selected from the group consisting of HC101C, HC102A, HC103A, HC103B, HC104A, HC105A, and HC106A, or combinations thereof.

Assignees

• Univ Michigan State

Inventors

• Abramovitch Robert
• Zheng Huiqing
• Colvin Christopher J
• Johnson Benjamin K

Classifications

• A61K31/357 Primary

  having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel · CPC title

• A61K31/167

  having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol · CPC title

• A61K31/381

  having five-membered rings · CPC title

• A61K31/4184

  condensed with carbocyclic rings, e.g. benzimidazoles · CPC title

• A61K31/42

  Oxazoles · CPC title