Methods and compositions for treating infection

Abstract

Provided herein are compositions and methods for treating or preventing infection.

1 . A method of treating or preventing an infection in a subject with or at risk of developing an infection, the method comprising administering to the subject a
 a compound of Formula I   
       
         
           
           
               
               
           
         
         wherein R represents hydrogen or hydroxyl and R 1  represents hydrogen, or R and R 1  taken together form a second bond between the carbon atoms bearing R and R 1 ; R 2  represents hydrogen or phenyl; n is zero or a positive whole integer of from 1 to 4; X represents CH 2 , CHOH, NH, C═O, CHNR 3 R 4 , where R 3  and R 4  independently are hydrogen or lower alkyl; and Z represents thienyl, pyridinyl, substituted pyridinyl, phenyl or substituted phenyl wherein the substituents on the substituted pyridinyl or substituted phenyl are selected from phenyl, pyridinyl, nitro, a halogen atom, such as chlorine, fluorine, bromine, or iodine, a straight or branched lower alkyl chain of from 1 to 4 carbon atoms, a lower alkoxy group of from 1 to 4 carbon atoms, amino, a mono or di(lower)alkylamino group, a saturated monocyclic heterocyclic group such as pyrrolidino, piperidino, morpholino, or N-(lower)alkylpiperazino, or a group having the structure —COOR 5 , —CR 6 R 7 COOR 5 , —CF 3 , CHF 2 , CH 2 F, or 
       
       
         
           
           
               
               
           
         
         where R 5  is hydrogen or lower alkyl, and R 6  and R 7  independently are hydrogen or methyl or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 - 4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the infection is a bacterial infection, a viral infection, a parasitic infection or a fungal infection. 
     
     
         6 . The method of  claim 1 , wherein the infection is a respiratory infection. 
     
     
         7 . The method of  claim 1 , wherein the infection is a gastrointestinal infection. 
     
     
         8 . The method of  claim 1 , wherein the infection is a skin infection. 
     
     
         9 . The method of  claim 5  wherein the bacterial infection is selected from the group consisting of  Enterobacterium faecium, Staphylococcus aureus, Klebsiella pneumonia, Acinebacter baumannii, Pseudomonas aeruginosa  and  Enterobacter  sp. 
     
     
         10 . The method of  claim 5 , wherein the bacterial infection is a small colony variant bacterial infection. 
     
     
         11 . A method of treating or preventing a bacterial infection in a subject with or at risk of developing a bacterial infection, the method comprising administering terfenadine to the subject. 
     
     
         12 . (canceled) 
     
     
         13 . A method of removing or preventing biofilm formation on a surface, the method comprising administering to a biofilm containing surface or a surface susceptible to biofilm formation an effective amount of a compound of Formula I 
       
         
           
           
               
               
           
         
         wherein R represents hydrogen or hydroxyl and R 1  represents hydrogen, or R and R 1  taken together form a second bond between the carbon atoms bearing R and R 1 ; R 2  represents hydrogen or phenyl; n is zero or a positive whole integer of from 1 to 4; X represents CH 2 , CHOH, NH, C═O, CHNR 3 R 4 , where R 3  and R 4  independently are hydrogen or lower alkyl; and Z represents thienyl, pyridinyl, substituted pyridinyl, phenyl or substituted phenyl wherein the substituents on the substituted pyridinyl or substituted phenyl are selected from phenyl, pyridinyl, nitro, a halogen atom, such as chlorine, fluorine, bromine, or iodine, a straight or branched lower alkyl chain of from 1 to 4 carbon atoms, a lower alkoxy group of from 1 to 4 carbon atoms, amino, a mono or di(lower)alkylamino group, a saturated monocyclic heterocyclic group such as pyrrolidino, piperidino, morpholino, or N-(lower)alkylpiperazino, or a group having the structure —COOR 5 , —CR 6 R 7 COOR 5 , —CF 3 , CHF 2 , CH 2 F, or 
       
       
         
           
           
               
               
           
         
         where R 5  is hydrogen or lower alkyl, and R 6  and R 7  independently are hydrogen or methyl or a pharmaceutically acceptable salt thereof. 
       
     
     
         14 . The method of  claim 13 , wherein the biofilm comprises one or more of  Staphylococcus aureus, Pseudomonas aeuroginosa, Staphylococcus epidermidis, Escherichia coli  or  Acinetobacter baummanii.   
     
     
         15 . A method of identifying an antimicrobial agent comprising:
 a) contacting a bacterial culture with a test agent;   b) and measuring adenylate kinase release in the supernatant of the bacterial culture, wherein an increase in adenylate kinase release as compared to a control indicates that the test compound is an antimicrobial agent.   
     
     
         16 . The method of  claim 15 , wherein the bacterial culture is selected from the group consisting of  Staphylococcus aureus, Pseudomonas aeuroginosa, Staphylococcus epidermidis, Escherichia coli  or  Acinetobacter baummanii.   
     
     
         17 . The method of  claim 5 , wherein the parasitic infection is not malaria.