Compounds for inhibiting bacterial growth via phosphatidylglycerol binding

Patent metadata

Field	Value
Publication number	US-10668048-B2
Application number	US-201816048009-A
Country	US
Kind code	B2
Filing date	Jul 27, 2018
Priority date	Jan 29, 2016
Publication date	Jun 2, 2020
Grant date	Jun 2, 2020

Abstract

Antibacterial small molecule compounds, termed liptins, bind to phosphatidylglycerol in bacterial plasma membranes. The small molecule compounds comprise a three-dimensional complementary binding pocket for phosphatidylglycerol, disrupting membrane function in a bacteriostatic or bactericidal manner. Methods of inhibiting bacterial growth and/or treating Gram-positive or Gram-negative bacterial infection using such compounds are also disclosed.

First claim

The invention claimed is:

1. An antibacterial small molecule compound that binds to phosphatidylglycerol in bacterial plasma membranes, said small molecule comprising a central scaffold and a plurality of functional groups cooperatively forming a three-dimensional complementary binding pocket for said phosphatidylglycerol, wherein said compound is selected from the group consisting of 1h, 1i, 1j, and 1k of the formula:

1h: m is 5, n is 3, and each R a is —(CH 2 ) 2 CONHC 6 H 13 ,
1i: m is 4, n is 3, and each R a is —(CH 2 ) 2 CONHC 6 H 13 ,
1j: m is 4, n is 4, and each R a is —(CH 2 ) 2 CONHC 6 H 13 ,
1k: m is 4, n is 4, each R a is —CH 2 CONHC 6 H 13 ,
where X − is any anionic counter ion.

2. The compound of claim 1 , wherein said compound is bacteriostatic.

3. The compound of claim 1 , wherein said compound is bactericidal.

4. An antibacterial composition comprising a bacteriostatic or bactericidal amount of an antibacterial small molecule compound according to claim 1 dispersed in a pharmaceutically-acceptable carrier.

5. The composition of claim 4 , wherein said carrier is selected from the group consisting of saline, buffered saline, sterile water, aqueous dextrose solutions, aqueous glycerol solutions, ethanol, allantoic fluid, oil-in-water emulsion, water-in-oil emulsions, dimethyl sulfoxide, petroleum jelly, cocoa butter, cottonseed oil, olive oil, sodium pyruvate, vitamin E, white petrolatum, white wax, stearyl alcohol, cholesterol, mineral oil, ceryl ester wax, sodium lauryl sulfate, propylene glycol, polyethylene glycol, and mixtures thereof.

6. The composition of claim 4 , said composition being substantially free of antibiotics and/or antimicrobial peptides.

7. The composition of claim 4 , said composition consisting essentially of said small molecule compound and said carrier.

8. The composition of claim 4 , said compound has a minimum inhibitory concentration (MIC) of from about 1 to about 4 μM.

Assignees

• Univ Wichita State

Inventors

• Burns Dennis H
• English Douglas S

Classifications

• A61K31/407 Primary

  condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine · CPC title

• C07D273/08

  having two nitrogen atoms and more than one oxygen atom · CPC title

• C07D321/00

  Heterocyclic compounds containing rings having two oxygen atoms as the only ring hetero atoms, not provided for by groups C07D317/00 - C07D319/00 · CPC title

• C07D487/22

  in which the condensed system contains four or more hetero rings · CPC title

• A61K31/395

  having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins · CPC title