Use of resazurin, or analogs thereof, for antibacterial therapy

Patent metadata

Field	Value
Publication number	US-9642858-B2
Application number	US-201314439651-A
Country	US
Kind code	B2
Filing date	Oct 29, 2013
Priority date	Oct 30, 2012
Publication date	May 9, 2017
Grant date	May 9, 2017

Abstract

A method for treating infection by bacteria in a subject, comprising administering to the subject a therapeutically effective amount of resazurin or a resazurin analog, or a pharmaceutically acceptable salt or ester thereof, wherein the bacteria is selected from at least one of Francisella sp. or Neisseria sp.

First claim

We claim:

1. A method for treating infection by bacteria in a subject, comprising administering to the subject a therapeutically effective amount of a compound selected from resazurin, resorufin, a compound of formula II, or a compound of formula IV, or a pharmaceutically acceptable salt or ester thereof, and wherein the bacteria is selected from at least one of Francisella sp. or Neisseria sp., and the compound of formula II has a structure of:

or a pharmaceutically acceptable salt or ester thereof;
where R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are each independently hydrogen;
A is OR 8 ;
Z is O;
X is oxygen; and
R 8 is alkyl, aralkyl, alkylaryl, or hydrogen; and
the compound of formula IV has a structure of:

or a pharmaceutically acceptable salt or ester thereof;
where R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are each independently hydrogen;
A is OR 8 ;
Z is O;
X is oxygen; and
R 8 is alkyl, aralkyl, alkylaryl, or hydrogen.

2. The method of claim 1 , wherein the compound is resazurin or a pharmaceutically acceptable salt or ester thereof.

3. The method of claim 1 , wherein R 8 is selected from C 1 -C 6 alkyl, aralkyl or alkylaryl.

4. The method of claim 1 , wherein the bacteria is selected from F. tularensis, F. novicida, N. polysaccharea, N. sicca, N. gonorrhoeae, N. meningitides, N. bacilliformis, N. cinerea, N. elongate, N. flavescens, N. lactamica, N. macacae, N. mucosa , or N. subflava.

5. The method of claim 1 , wherein R 8 is alkyl.

6. The method of claim 1 , wherein the bacteria is selected from F. tularensis or N. gonorrhoeae.

7. The method of claim 6 , wherein R 8 is alkyl.

8. The method of claim 1 , wherein R 8 is C 1 -C 6 alkyl.

9. The method of claim 6 , wherein R 8 is C 1 -C 6 alkyl.

10. A method for inhibiting bacteria growth, comprising contacting an effective amount of a compound selected from resazurin, resorufin, or a compound of formula II, or a compound of formula IV, or a pharmaceutically acceptable salt or ester thereof, with at least one of Francisella sp. or Neisseria sp., wherein the compound of formula II has a structure of:

or a pharmaceutically acceptable salt or ester thereof;
where R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are each independently hydrogen;
A is OR 8 ;
Z is O;
X is oxygen; and
R 8 is alkyl, aralkyl, alkylaryl, or hydrogen; and
the compound of formula IV has a structure of:

or a pharmaceutically acceptable salt or ester thereof;
where R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are each independently hydrogen;
A is OR 8 ;
Z is O;
X is oxygen; and
R 8 is alkyl, aralkyl, alkylaryl, or hydrogen.

11. The method of claim 10 , wherein the compound is resorufin, or a pharmaceutically acceptable salt or ester thereof.

12. The method of claim 10 , wherein the compound has a formula
III:

or a pharmaceutically acceptable salt or ester thereof.

13. The method of claim 10 , wherein the compound is resazurin or a pharmaceutically acceptable salt or ester thereof.

14. A method for inhibiting the growth of at least one of Francisella sp. or Neisseria sp. on a substrate, comprising contacting the substrate with a compound selected from resazurin, resorufin, or a compound of formula II, or a compound of formula IV, or a pharmaceutically acceptable salt or ester thereof, wherein the compound of formula II has a structure of:

or a pharmaceutically acceptable salt or ester thereof;
where R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are each independently hydrogen;
A is OR 8 ;
Z is O;
X is oxygen; and
R 8 is alkyl, aralkyl, alkylaryl, or hydrogen; and
the compound of formula IV has a structure of:

or a pharmaceutically acceptable salt or ester thereof;
where R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are each independently hydrogen;
A is OR 8 ;
Z is O;
X is oxygen; and
R 8 is alkyl, aralkyl, alkylaryl, or hydrogen.

15. The method of claim 14 , wherein the compound is resorufin, or a pharmaceutically acceptable salt or ester thereof.

16. The method of claim 14 , wherein the compound is resazurin or a pharmaceutically acceptable salt or ester thereof.

17. The method of claim 14 , wherein R 8 is alkyl.

Assignees

• Horzempa Joseph Andrew
• Henson Dawn Marie
• Nau Gerard Joseph
• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Horzempa Joseph Andrew
• Henson Dawn Marie
• Nau Gerard Joseph

Classifications

• A61P31/04

  Antibacterial agents · CPC title

• A61K31/5415 Primary

  ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam · CPC title

• A61K31/538

  ortho- or peri-condensed with carbocyclic ring systems · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title