Inhibition and dispersion of bacterial biofilms with imidazole-triazole derivatives
Disclosure is provided for imidazole-triazole derivative compounds such as those given in Formulas (I)-(VI) that prevent, remove and/or inhibit the formation of biofilms, compositions comprising these compounds, devices comprising these compounds, and methods of using the same.
1. A compound of Formula (II)(a):
wherein:
R 1a and R 1b are each H;
R 2 , R 3 and R 5 and are each independently H or alkyl;
each occurrence of R x , R y , R u and R v is present or absent (depending upon chain saturation), and are each independently H or alkyl;
R 6 is independently selected from the group consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acid sidechain, amino acid and peptide;
n=1 to 6; and
m=0 to 20;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein R 6 is aryl.
3. The compound of claim 1 , wherein R 6 is phenyl.
4. The compound of claim 1 , wherein said compound represented by Formula (II)(a) is a compound of Formula (II)(a)(5)(D):
or a pharmaceutically acceptable salt thereof.
5. A composition comprising the compound of claim 1 and a biocide.
6. A composition comprising the compound of claim 1 in a pharmaceutically acceptable carrier.
7. A composition comprising a compound of Formula (II)(a):
wherein:
R 1a and R 1b are each H;
R 2 , R 3 and R 5 and are each independently H or alkyl;
each occurrence of R x , R y , R u and R v is present or absent (depending upon chain saturation), and are each independently H or alkyl;
R 6 is independently selected from the group consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acid sidechain, amino acid and peptide;
n=0 to 10; and
m=0 to 20;
covalently coupled to a substrate.
8. A biofilm removing or inhibiting coating composition, comprising:
(a) a film-forming resin;
(b) a solvent that disperses said resin;
(c) an effective amount of a compound of Formula (II)(a):
wherein:
R 1a and R 1b are each H;
R 2 , R 3 and R 5 and are each independently H or alkyl;
each occurrence of R x , R y , R u and R v is present or absent (depending upon chain saturation), and are each independently H or alkyl;
R 6 is independently selected from the group consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acid sidechain, amino acid and peptide;
n=0 to 10; and
m=0 to 20;
wherein said effective amount of said compound prevents or inhibits the growth of a biofilm thereon; and
(d) optionally, at least one pigment.
9. The coating composition of claim 8 , wherein said compound is covalently coupled to said resin.
10. The coating composition of claim 8 , wherein said resin comprises a polymeric material.
11. A substrate coated with the coating composition of claim 8 .
12. The compound of claim 1 , wherein m=1 to 3.
13. The compound of claim 1 , wherein m=1 to 3 and R 6 is aryl.
14. The composition of claim 5 , wherein said biocide is an antibiotic.
15. The composition of claim 7 , wherein said substrate is a polymeric material.