Polycationic amphiphiles as antimicrobial agents and methods using same

Patent metadata

Field	Value
Publication number	US-12459898-B2
Application number	US-202117468349-A
Country	US
Kind code	B2
Filing date	Sep 7, 2021
Priority date	Oct 26, 2016
Publication date	Nov 4, 2025
Grant date	Nov 4, 2025

Abstract

The present invention includes novel polycationic amphiphilic compounds useful as antimicrobial agents. The present invention further includes methods useful for removing microorganisms and/or biofilm-embedded microorganisms from a surface. The present invention further includes compositions and methods useful for preventing or reducing the growth or proliferation of microorganisms and/or biofilm-embedded microorganisms on a surface.

First claim

The invention claimed is:

1 . A composition comprising
(i) at least one compound selected from the group consisting of formula I-IV:

wherein in formula I-III:
R 1 , R 2 , and R 3 are each independently selected from the group consisting of H and C 1 -C 25 alkyl, wherein the alkyl group may be optionally substituted with —OR′, —NR′ 2 , —NR′—C(O)R′, —C(O)NR′ 2 , —NR′—C(O)CR′═CR′, —SR′, —O—C(O)R′, —C(O)OR′, —C(O)R′, —CF 3 , —OCF 3 , halogen, benzyl, o-vinylbenzyl, m-vinylbenzyl, p-vinylbenzyl, phenyl, allyl, and substituted allyl, further wherein the alkyl group may optionally be interrupted with a —O—C(O)— group or a —C(O)O— group;
each occurrence of R a , R b , R c , R d , and R e is independently selected from the group consisting of H, C 1 -C 6 alkyl, —OR′, —CN, —NO 2 , —NR′ 2 , —N—C(O)R′, —C(O)NR′ 2 , —N—C(O)CR′═CR′, —SR′, —O—C(O)R′, —C(O)OR′, —C(O)R′, —CF 3 , —OCF 3 , and halogen;
each occurrence of R′ is independently selected from the group consisting of H and C 1-4 alkyl;
Y is N or CR″;
R″ is H or C 1 -C 6 alkyl, wherein the alkyl group may be optionally substituted and may combine with any of R a , R b , and R c to form a ring;
each occurrence of Z is independently a counterion;
m is an integer from 0 to 4;
n is an integer from 0 to 4; and
p is an integer from 0 to 4; and
wherein in formula IV: R 1 and R 2 are each independently selected from the group consisting of H and C 10 -C 13 alkyl, wherein the alkyl group may be optionally substituted with —OR′, —NR′ 2 , —NR′—C(O)R′, —C(O)NR′ 2 , —NR′—C(O)CR′═CR′, —SR′, —O—C(O)R′, —C(O)OR′, —C(O)R′, —CF 3 , —OCF 3 , halogen, benzyl, o-vinylbenzyl, m-vinylbenzyl, p-vinylbenzyl, allyl, and substituted allyl, further wherein the alkyl group may optionally be interrupted with a-O—C(O)-group or a-C(O)O— group;
each occurrence of R a , R b , R c , R d , and R e is independently selected from the group consisting of H, C 1 -C 6 alkyl, —OR′, —CN, —NO 2 , —NR′ 2 , —N—C(O)R′, —C(O)NR′ 2 , —N—C(O)CR′═CR′, —SR′, —O—C(O)R′, —C(O)OR′, —C(O)R′, —CF 3 , —OCF 3 , and halogen;
each occurrence of R′ is independently selected from the group consisting of H and C 1-4 alkyl;
Y is N or CR″;
R″ is H or C 1 -C 6 alkyl, wherein the alkyl group may be optionally substituted and may combine with any of R a , R b , and R c to form a ring;
each occurrence of Z is independently a counterion;
m is an integer from 0 to 4;
n is an integer from 0 to 4; and
p is an integer from 0 to 4; and
(ii) at least one selected from the group consisting of a pharmaceutically acceptable carrier, base material, antimicrobial agent, a second compound or a moiety, and any combination thereof.

2 . The composition of claim 1 , wherein in formula I-III: at least one of R 1 , R 2 , and R 3 is C 8 alkyl.

3 . The composition of claim 1 , wherein at least one of R 1 , R 2 , and R 3 is C 10 alkyl.

4 . The composition of claim 1 , wherein at least one of R 1 , R 2 , and R 3 is C 11 alkyl.

5 . The composition of claim 1 , wherein at least one of R 1 , R 2 , and R 3 is C 12 alkyl.

6 . The composition of claim 1 , wherein at least one of R 1 , R 2 , and R 3 is C 13 alkyl.

7 . The composition of claim 1 , wherein in formula I-III: at least one of R 1 , R 2 , and R 3 is C 16 alkyl.

8 . The composition of claim 1 , wherein in formula I-III: at least one of R 1 , R 2 , and R 3 is C 18 alkyl.

9 . The composition of claim 1 , wherein the C 1 -C 25 alkyl group is selected from the group consisting of —R 4 —O—C(O)—R 5 and —R 4 —(O)C—O—R 5 , wherein R 4 and R 5 are each independently an optionally substituted alkyl chain, provided that the total number of carbon atoms in the alkyl chains of R 4 and R 5 is 4 to 25 carbon atoms.

10 . The composition of claim 1 , wherein Z is Br − .

11 . The composition of claim 1 , wherein in formula I-III, R 1 , R 2 , and R 3 are each C 8 -C 18 alkyl; and in formula IV, R 1 and R 2 are each C 10 -C 13 alkyl.

12 . The composition of claim 1 , wherein the compound is selected from the group consisting of:

and
wherein each occurrence of Z is independently selected from the group consisting of I − and Br − .

13 . The composition of claim 1 , wherein the compound of formula IV is 2Pyr-11,11:

14 . The composition of claim 1 , wherein the at least one compound is attached to the second compound or moiety.

15 . The composition of claim 14 , wherein the second compound or moiety is selected from the group consisting of a QAC, an antimicrobial peptide, a sugar, an iron siderophore, a solid surface, a poly (alkyl ether), and a nucleophilic residue.

16 . The composition of claim 1 , wherein the composition is an antimicrobial composition.

17 . A method for preventing or reducing the growth or proliferation of microorganisms or biofilm-embedded microorganisms on at least one surface, comprising the steps of:
providing at least one surface; providing the composition of claim 1 ; and contacting the at least one surface with the composition in an amount sufficient to prevent or reduce the growth or proliferation of microorganisms or biofilm-embedded microorganisms on the at least one surface.

18 . The method of claim 17 , wherein the composition further comprises a base material.

19 . The method of claim 17 , wherein the composition further comprises at least one additional antimicrobial agent.

20 . The method of claim 19 , wherein the composition of claim 1 and the at least one additional antimicrobial agent act synergistically to prevent or reduce the growth or proliferation of microorganisms or biofilm-embedded microorganisms on the at least one surface.

21 . The method of claim 17 , wherein the composition is contacted with the at least one surface for a period of time sufficient to form a coating of the composition on the at least one surface.

22 . The method of claim 17 , wherein the surface is a subject's body.

23 . The method of claim 17 , wherein the surface is a solid surface.

24 . A method for removing at least a portion of or reducing the number of microorganisms or biofilm-embedded microorganisms attached to at least one surface, the method comprising the steps of:
providing at least one surface, wherein the microorganisms or biofilm-embedded microorganisms are attached to the at least one surface; providing the composition of claim 1 ; and contacting the composition with the at least one surface in an amount sufficient to remove at least a portion of or reduce the number of microorganisms or biofilm-embedded microorganisms attached to the at least one surface.

25 . The method of claim 24 , wherein the composition further comprises a base material.

26 . The method of claim 24 , wherein the composition further comprises at least one additional antimicrobial agent.

27 . The method of claim 26 , wherein the composition of claim 1 and the at least one additional antimicr

Assignees

• Univ Temple
• Univ Villanova

Inventors

• Wuest William M
• Minbiole Kevin P C

Classifications

• C07D401/14

  containing three or more hetero rings · CPC title

• C07D401/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07C211/63

  having quaternised nitrogen atoms bound to acyclic carbon atoms · CPC title

• A01N43/40 Primary

  six-membered rings · CPC title

• A01N33/12

  Quaternary ammonium compounds · CPC title