Methods for screening antimicrobial and antiviral compounds and uses thereof

Abstract

The invention features compounds that have antibacterial activity, their use for the treatment of bacterial infections, screening methods that use whole animals or plant seedlings to identify compounds that inhibit a pathogen in the animal or plant, and screening methods to identify compounds that increase the lifespan of an organism.

What is claimed is: 
     
         1 - 4 . (canceled) 
     
     
         5 . A pharmaceutical composition comprising a compound of formula II: 
       
         
           
           
               
               
           
         
         or a salt thereof, and a pharmaceutically acceptable excipient, wherein 
         each of R 2A , R 2B , R 2C , R 2D , R 2E , and R 2F  is, independently, selected from H, halide, nitro, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, OR 2G , OC(O)R 2H , NR 2I R 2J , NHC(O)R 2K , NHC(S)R 2L , NHC(O)OR 2M , NHC(S)OR 2N , NHC(O)NHR 2O , NHC(S)NHR 2P , NHC(O)SR 2Q , NHC(S)SR 2R , NHS(O) 2 R 2S , C(O)OR 2T , and C(O)NHR 2U ; X 2  is independently selected from OR 2G , OC(O)R 2H , NR 2I R 2J , NHC(O)R 2K , NHC(S)R 2L , NHC(O)OR 2M , NHC(S)OR 2N , NHC(O)NHR 2O , NHC(S)NHR 2P , NHC(O)SR 2Q , NHC(S)SR 2R , and NHS(O) 2 R 2S ; and 
         each of R 2G , R 2H , R 2I , R 2J , R 2K , R 2L , R 2M , R 2N , R 2O , R 2P , R 2Q , R 2R , R 2S , R 2T , and R 2U  is, independently, selected from H, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 2-6  heterocyclyl, C 6-12  aryl, C 7-14  alkaryl, C 3-10  alkheterocyclyl, and C 1-4  heteroalkyl. 
       
     
     
         6 . A kit comprising: (i) a pharmaceutical composition of  claim 5  and (ii) instructions for administering the composition to a subject for the treatment of a microbial or viral infection. 
     
     
         7 . A method of treating a microbial or viral infection in a subject, said method comprising administering to said subject a pharmaceutical composition of  claim 5  in an amount effective to treat said infection. 
     
     
         8 . The method of  claim 7 , wherein said infection is a bacterial infection selected from community-acquired pneumonia, upper and lower respiratory tract infection, skin and soft tissue infection, bone and joint infection, hospital-acquired lung infection, acute bacterial otitis media, bacterial pneumonia, complicated infection, noncomplicated infection, pyelonephritis, intra-abdominal infection, deep-seated abcess, bacterial sepsis, central nervous system infection, bacteremia, wound infection, peritonitis, meningitis, infections after burn, urogenital tract infection, gastro-intestinal tract infection, pelvic inflammatory disease, endocarditis, and intravascular infection. 
     
     
         9 - 12 . (canceled) 
     
     
         13 . A pharmaceutical composition comprising a compound of formula IV: 
       
         
           
           
               
               
           
         
         or a salt thereof, and a pharmaceutically acceptable excipient, wherein 
         each of R 4A , R 4B , R 4C , R 4D , R 4E , and R 4F  is, independently, selected from H, halide, nitro, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, OR 4G , OC(O)R 4H , NR 4I R 4J , NHC(O)R 4K , NHC(S)R 4L , NHC(O)OR 4M , NHC(S)OR 4N , NHC(O)NHR 4O , NHC(S)NHR 4P , NHC(O)SR 4O , NHC(S)SR 4R , NHS(O) 2 R 4 , C(O)OR 4T , and C(O)NHR 4U ; X 4  is —S(O)— or —S(O) 2 —; and 
         each of R 4G , R 4H , R 4I , R 4J , R 4K , R 4L , R 4M , R 4N , R 4O , R 4P , R 4Q , R 4R , R 4S , R 4T , and R 4U  is, independently, selected from H, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 2-6  heterocyclyl, C 6-12  aryl, C 7-14  alkaryl, C 3-10  alkheterocyclyl, and C 1-4  heteroalkyl. 
       
     
     
         14 . A kit comprising: (i) a pharmaceutical composition of  claim 13  and (ii) instructions for administering the composition to a subject for the treatment of a microbial or viral infection. 
     
     
         15 . A method of treating a microbial or viral infection in a subject, said method comprising administering to said subject a pharmaceutical composition of  claim 13  in an amount effective to treat said infection. 
     
     
         16 . The method of  claim 15 , wherein said infection is a bacterial infection selected from community-acquired pneumonia, upper and lower respiratory tract infection, skin and soft tissue infection, bone and joint infection, hospital-acquired lung infection, acute bacterial otitis media, bacterial pneumonia, complicated infection, noncomplicated infection, pyelonephritis, intra-abdominal infection, deep-seated abcess, bacterial sepsis, central nervous system infection, bacteremia, wound infection, peritonitis, meningitis, infections after burn, urogenital tract infection, gastro-intestinal tract infection, pelvic inflammatory disease, endocarditis, and intravascular infection. 
     
     
         17 - 20 . (canceled) 
     
     
         21 . A pharmaceutical composition comprising a compound of formula VI: 
       
         
           
           
               
               
           
         
         or a salt thereof, and a pharmaceutically acceptable excipient, wherein 
         each of R 6A , R 6B , R 6C , R 6D , R 6E , and R 6F  is, independently, selected from H, halide, nitro, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, OR 6G , OC(O)R 6H , NR 6I R 6J , NHC(O)R 6K , NHC(S)R 6L , NHC(O)OR 6M , NHC(S)OR 6N , NHC(O)NHR 6O , NHC(S)NHR 6P , NHC(O)SR 6Q , NHC(S)SR 6R , NHS(O) 2 R 6S , C(O)OR 6T , and C(O)NHR 6U ; 
         each of X 6A  and X 6B  is, independently, selected from O and S; and 
         each of R 6G , R 6H , R 6I , R 6J , R 6K , R 6L , R 6M , R 6N , R 6O , R 6P , R 6Q , R 6R , R 6S , R 6T , and R 6U  is, independently, selected from H, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 2-6  heterocyclyl, C 6-12  aryl, C 7-14  alkaryl, C 3-10  alkheterocyclyl, and C 1-4  heteroalkyl. 
       
     
     
         22 . A kit comprising: (i) a pharmaceutical composition of  claim 21  and (ii) instructions for administering the composition to a subject for the treatment of a microbial or viral infection. 
     
     
         23 . A method of treating a microbial or viral infection in a subject, said method comprising administering to said subject a pharmaceutical composition of  claim 21  in an amount effective to treat said infection. 
     
     
         24 . The method of  claim 23 , wherein said infection is a bacterial infection selected from community-acquired pneumonia, upper and lower respiratory tract infection, skin and soft tissue infection, bone and joint infection, hospital-acquired lung infection, acute bacterial otitis media, bacterial pneumonia, complicated infection, noncomplicated infection, pyelonephritis, intra-abdominal infection, deep-seated abcess, bacterial sepsis, central nervous system infection, bacteremia, wound infection, peritonitis, meningitis, infections after burn, urogenital tract infection, gastro-intestinal tract infection, pelvic inflammatory disease, endocarditis, and intravascular infection. 
     
     
         25 - 48 . (canceled) 
     
     
         49 . A pharmaceutical composition comprising a compound of formula XIII: 
       
         
           
           
               
               
           
         
         or a salt thereof, and a pharmaceutically acceptable excipient, wherein 
         each of R 13A , R 13B , and R 13C  is, independently, selected from H, halide, nitro, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, OR 13G , OC(O)R 13H , NR 13I , R 13J , NHC(O)R 13K , NHC(S)R 13L , NHC(O)OR 13M , NHC(S)OR 13N , NHC(O)NHR 13O , NHC(S)NHR 13P , NHC(O)SR 13Q , NHC(S)SR 13R , NHS(O) 2 R 13S , C(O)OR 13T , and C(O)NHR 13U ; and each of R 13G , R 13H , R 13I , R 13J , R 13K , R 13L , R 13M , R 13N , R 13O , R 13P , R 13Q , R 13R , R 13S , R 13T , and R 13U  is, independently, selected from H, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 2-6  heterocyclyl, C 6-12  aryl, C 7-14  alkaryl, C 3-10  alkheterocyclyl, and C 1-4  heteroalkyl. 
       
     
     
         50 . A kit comprising: (i) a pharmaceutical composition of  claim 49  and (ii) instructions for administering the composition to a subject for the treatment of a microbial or viral infection. 
     
     
         51 . A method of treating a microbial or viral infection in a subject, said method comprising administering to said subject a pharmaceutical composition of  claim 49  in an amount effective to treat said infection. 
     
     
         52 . The method of  claim 51 , wherein said infection is a bacterial infection selected from community-acquired pneumonia, upper and lower respiratory tract infection, skin and soft tissue infection, bone and joint infection, hospital-acquired lung infection, acute bacterial otitis media, bacterial pneumonia, complicated infection, noncomplicated infection, pyelonephritis, intra-abdominal infection, deep-seated abcess, bacterial sepsis, central nervous system infection, bacteremia, wound infection, peritonitis, meningitis, infections after burn, urogenital tract infection, gastro-intestinal tract infection, pelvic inflammatory disease, endocarditis, and intravascular infection. 
     
     
         53 - 207 . (canceled)