Inhibition and dispersion of biofilms in plants with imidazole-triazole derivatives

Abstract

Disclosure is provided for methods of preventing, removing or inhibiting microbial biofilm formation or microbial infection in a plant or plant part thereof, including applying thereto a treatment effective amount of an active compound as described herein, or an agriculturally acceptable salt thereof. Methods of enhancing a microbicide (e.g., including a copper, antibiotic, bacteriophage, etc.) and/or plant defense activator are also provided, including applying an active compound as described herein. Compositions comprising an active compound as described herein in an agriculturally acceptable carrier are also provided, and in some embodiments the compositions further include a microbicide (e.g., including copper, antibiotic, bacteriophage, etc.) and/or plant defense activator.

1 . A method of preventing, removing or inhibiting microbial biofilm formation or microbial infection in a plant or plant part thereof, comprising applying to said plant or plant part a treatment effective amount of a compound of Formula (II)(a): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1a  and R 1b  are each H; 
 R 2 , R 3 , 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, 
 wherein R 6  is optionally substituted with one, two, three or four substituents independently selected from: halo, 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; 
 or an agriculturally acceptable salt thereof; 
 or a compound of Formula (IV)(a): 
 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1a  and R 1b  are each H; 
 R 2 , R 3 , R 5  and are each independently H or alkyl; 
 each occurrence of R x , R y , R u , R v , R z  and R w  is present or absent (depending upon chain saturation), and is each independently H or alkyl; 
 n=0 to 10; 
 m=0 to 20; and 
 p=0 to 20 
 or an agriculturally acceptable salt thereof. 
 
     
     
         2 . The method of  claim 1 , wherein said plant is a fruit crop plant or a vegetable crop plant. 
     
     
         3 - 20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein said microbial biofilm formation or microbial infection is caused by a fungi. 
     
     
         22 . The method of  claim 1 , wherein said compound is applied to said plant in an amount effective to treat or control a fungal disease selected from the group consisting of rots, leaf molds, blights, wilts, damping-off, spot, root rot, stem rot, mildew, brown spot, gummosis, melanose, post-bloom fruit drop, scab, alternaria, canker, flyspeck, fruit blotch, dieback, downy mildews, ear rots, anthracnose bunts, smut, rust, eyespot and pecky rice. 
     
     
         23 - 34 . (canceled) 
     
     
         35 . An agricultural composition comprising:
 (a) an agriculturally acceptable carrier; and   (b) an antimicrobial or biofilm preventing, removing or inhibiting a compound of Formula (II)(a):   
       
         
           
           
               
               
           
         
       
       wherein:
 R 1a  and R 1b  are each H; 
 R 2 , R 3 , 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, 
 wherein R 6  is optionally substituted with one, two, three or four substituents independently selected from: halo, 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; 
 or an agriculturally acceptable salt thereof; 
 or a compound of Formula (IV)(a): 
 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1a  and R 1b  are each H; 
 R 2 , R 3 , R 5  and are each independently H or alkyl; 
 each occurrence of R x , R y , R u , R v , R z  and R w  is present or absent (depending upon chain saturation), and is each independently H or alkyl; 
 n=0 to 10; 
 m=0 to 20; and 
 p=0 to 20 
 or an agriculturally acceptable salt thereof. 
 
     
     
         36 . The composition of  claim 35 , further comprising a microbicide. 
     
     
         37 . The composition of  claim 36 , wherein said microbicide comprises copper. 
     
     
         38 . (canceled) 
     
     
         39 . The composition of  claim 35 , further comprising an antibiotic. 
     
     
         40 . The composition of  claim 35 , further comprising a bacteriophage. 
     
     
         41 . The composition of  claim 35 , further comprising a plant defense activator. 
     
     
         42 . The composition of  claim 35 , wherein said carrier is an aqueous carrier or a solid particulate carrier. 
     
     
         43 . (canceled) 
     
     
         44 . The method of  claim 1 , wherein said compound is a compound of Formula (II)(a)(5)(D): 
       
         
           
           
               
               
           
         
       
       or an agriculturally acceptable salt thereof. 
     
     
         45 . The composition of  claim 35 , wherein said compound is a compound of Formula (II)(a)(5)(D): 
       
         
           
           
               
               
           
         
       
       or an agriculturally acceptable salt thereof. 
     
     
         46 . A method of enhancing the effects of a microbicide comprising applying a compound of Formula (II)(a): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1a  and R 1b  are each H; 
 R 2 , R 3 , 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, 
 wherein R 6  is optionally substituted with one, two, three or four substituents independently selected from: halo, 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; 
 or an agriculturally acceptable salt thereof; 
 or a compound of Formula (IV)(a): 
 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1a  and R 1b  are each H; 
 R 2 , R 3 , R 5  and are each independently H or alkyl; 
 each occurrence of R x , R y , R u , R v , R z  and R w  is present or absent (depending upon chain saturation), and is each independently H or alkyl; 
 n=0 to 10; 
 m=0 to 20; and 
 p=0 to 20 
 or an agriculturally acceptable salt thereof; 
 in combination with said microbicide. 
 
     
     
         47 . The method of  claim 46 , wherein said microbicide comprises copper. 
     
     
         48 . (canceled) 
     
     
         49 . The method of  claim 46 , wherein said microbicide is an antibiotic or a bacteriophage. 
     
     
         50 - 51 . (canceled) 
     
     
         52 . The method of  claim 46 , wherein said active compound is a compound of Formula (II)(a)(5)(D): 
       
         
           
           
               
               
           
         
       
       or an agriculturally acceptable salt thereof. 
     
     
         53 . A method of enhancing the effects of a plant defense activator comprising applying a compound of Formula (II)(a): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1a  and R 1b  are each H; 
 R 2 , R 3 , 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, 
 wherein R 6  is optionally substituted with one, two, three or four substituents independently selected from: halo, 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; 
 or an agriculturally acceptable salt thereof; 
 or a compound of Formula (IV)(a): 
 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1a  and R 1b  are each H; 
 R 2 , R 3 , R 5  and are each independently H or alkyl; 
 each occurrence of R x , R y , R u , R v , R z  and R w  is present or absent (depending upon chain saturation), and is each independently H or alkyl; 
 n=0 to 10; 
 m=0 to 20; and 
 p=0 to 20 
 or an agriculturally acceptable salt thereof; 
 in combination with said plant defense activator. 
 
     
     
         54 - 55 . (canceled) 
     
     
         56 . The method of  claim 53 , wherein said active compound is a compound of Formula (II)(a)(5)(D): 
       
         
           
           
               
               
           
         
       
       or an agriculturally acceptable salt thereof.