Method of treating microbial infections

Abstract

The disclosure provides for novel antimicrobial agents, methods of making, and methods of use thereof.

What is claimed is: 
     
         1 . A method for inhibiting the growth of a bacterium or fungus comprising contacting the bacterium or fungus with an inhibiting effective amount of a pharmaceutical composition comprising a compound that has the structure of Formula II: 
       
         
           
           
               
               
           
         
       
       wherein:
 X 11 -X 19  are each independently either a C, N or O; 
 R 19 -R 34  are each independently selected from the group comprising H, D, optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 1 -C 6 )alkenyl, optionally substituted (C 1 -C 6 )alkynyl, optionally substituted hetero-(C 1 -C 6 )alkyl, hetero-(C 1 -C 6 )alkenyl, optionally substituted hetero-(C 1 -C 6 )alkynyl, halogen, hydroxyl, ketone, aldehyde, acyl halide, carbonate, carboxylic acid, ester, hydroperoxide, peroxide, ether, hemiacetal, hemiketal, acetal, orthoester, orthocarbonate ester, amide, amine, imine, imide, azide, diimide, cyanate, nitrate, nitrile, nitro, nitroso, thiol, sulfide, disulfide, sulfoxide, sulfone, sulfinic acid, sulfonic acid, thicyanate, thione, thial, phosphine, phosphonic acid, phosphate, phosphodiester, boronic acid, boronic ester, and no atom if bound to X that has reached its maximum valence; and 
 derivatives or analogs of Formula II thereof, including pharmaceutical salts and prodrugs; 
 wherein the pharmaceutical composition inhibits the growth of the bacterium or fungus. 
 
     
     
         2 . The method of  claim 1 , wherein the pharmaceutical composition comprises a compound that has at least 5 carbon atoms, at least 5 nitrogen atoms, at least 5 hydrogen atoms, and at least one oxygen atom and has a structure of Formula II: 
       
         
           
           
               
               
           
         
       
       wherein:
 X 11 -X 19  are each independently either a C, N or O; 
 R 19 -R 34  are each independently selected from the group comprising H, D, optionally substituted (C 1 -C 2 )alkyl, optionally substituted (C 1 -C 2 )alkenyl, optionally substituted (C 1 -C 2 )alkynyl, optionally substituted hetero-(C 1 -C 2 )alkyl, hetero-(C 1 -C 2 )alkenyl, optionally substituted hetero-(C 1 -C 2 )alkynyl, hydroxyl, ketone, aldehyde, ester, ether, amide, amine, imine, imide, nitrate, nitrile, nitro, nitroso, and no atom if bound to X that has reached its maximum valence. 
 
     
     
         3 . The method of  claim 2 , wherein the pharmaceutical composition comprises a compound that has at least 5 carbon atoms, at least 5 nitrogen atoms, at least 5 hydrogen atoms, and at least one oxygen atom and has a structure of Formula II(a): 
       
         
           
           
               
               
           
         
       
       wherein:
 X 11 -X 19  are each independently either a C, N or O; 
 R 19 , R 23 , R 25 , R 27 , R 29 , R 31 , and R 33  are each independently selected from the group comprising H, D, optionally substituted (C 1 -C 2 )alkyl, optionally substituted (C 1 -C 2 )alkenyl, optionally substituted (C 1 -C 2 )alkynyl, optionally substituted hetero-(C 1 -C 2 )alkyl, hetero-(C 1 -C 2 )alkenyl, optionally substituted hetero-(C 1 -C 2 )alkynyl, hydroxyl, ketone, aldehyde, carbonate, amine, imine, nitrile, nitroso, and no atom if bound to X that has reached its maximum valence. 
 
     
     
         4 . The method of  claim 3 , wherein the pharmaceutical composition comprises a compound that has the molecular formula of C 5 H 5 N 5 O and comprises Formula II(a): 
       
         
           
           
               
               
           
         
       
       wherein:
 X 11 -X 19  are each independently either a C, N or O; 
 R 19 , R 23 , R 25 , R 27 , R 29 , R 31 , and R 33  are each independently selected from the group comprising H, D, optionally substituted (C 1 -C 2 )alkyl, optionally substituted (C 1 -C 2 )alkenyl, optionally substituted (C 1 -C 2 )alkynyl, optionally substituted hetero-(C 1 -C 2 )alkyl, hetero-(C 1 -C 2 )alkenyl, optionally substituted hetero-(C 1 -C 2 )alkynyl, hydroxyl, ketone, aldehyde, carbonate, amine, imine, nitrile, nitroso, and no atom if bound to X that has reached its maximum valence. 
 
     
     
         5 . The method of  claim 4 , wherein the composition comprises a compound that has the molecular formula of C 5 H 5 N 5 O and comprises Formula II(a): 
       
         
           
           
               
               
           
         
       
       wherein:
 X 11 , X 13 , X 14 , X 16 , X 18  are C; 
 X 12 , X 15 , X 17 , X 19  are N; 
 R 27 , R 29 , R 31 , and R 33  are H; 
 R 23  is either an imine or a nitroso group. 
 
     
     
         6 . The method of  claim 5 , wherein pharmaceutical composition comprises a compound that has the structure of: 
       
         
           
           
               
               
           
         
       
     
     
         7 . The method of  claim 5 , wherein pharmaceutical composition comprises a compound that has the structure of: 
       
         
           
           
               
               
           
         
       
     
     
         8 . The method of  claim 1 , further comprising contacting the bacterium or fungus with at least one additional antimicrobial agent. 
     
     
         9 . The method of  claim 1 , wherein the contacting is through topical administration. 
     
     
         10 . A method of treating an infection or a dermatological disorder comprising administering an effective amount of a pharmaceutical composition to a subject, the pharmaceutical composition comprising a compound of Formula II(a): 
       
         
           
           
               
               
           
         
       
       wherein:
 X 11 , X 13 , X 14 , X 16 , X 18  are C; 
 X 12 , X 15 , X 17 , X 19  are N; 
 R 27 , R 29 , R 31 , and R 33  are H; 
 
       R 23  is either an oximine or a nitroso group. 
     
     
         11 . The method of  claim 10 , wherein the infection comprises a bacterial, fungal, parasitic or viral infection. 
     
     
         12 . The method of  claim 10 , wherein the dermatological disorders comprise wounds, diabetic ulcers, acne, rosacea, atopic dermatitis, pyodermas, and burn wounds. 
     
     
         13 . The method of  claim 10 , wherein the composition is formulated for topical administration. 
     
     
         14 . The method of  claim 11 , wherein the bacterial infection is MRSA.