B-cyclodextrin derivatives and their use against anthrax lethal toxin

Abstract

The invention provides low molecular weight compounds that block the pore formed by protective antigen and inhibit anthrax toxin action. Structures of the compounds are derivatives of β-cyclodextrin. Per-substituted alkylamino derivatives displayed inhibitory activity, and they were protective against anthrax lethal toxin action at low micromolar concentrations. Also, the addition of one of the alkylamino derivatives to the bilayer lipid membrane with multiple PA channels caused a significant decrease in membrane conductance. Thus, the invention also provides methods for protection against anthrax toxicity.

1 . A method for inhibiting the growth of a bacterium or virus, comprising contacting the bacterium or virus with a compound having the formula 
       
         
           
           
               
               
           
         
       
       wherein R 2  is H, OH, OAc, OMe, or O(CH 2 CH 2 O) n ; R 3  is H, OH, OAc, OMe, OSO 3 Na, or NH 2 ; and R 6  is H, NH 2 , SCH 2 CH 2 NH 2 , SCH 2 CH 2 CH 2 NH 2 , SCH 2 CH 2 CH 2 CH 2 NH 2 , I, N 3 , SH, lower alkyl, S-alkylguanidyl, O-alkylguanidyl, S-aminoalkyl, O-aminoalkyl, aminoalkyl aralkyl, aryl, heterocyclic ring(s), or OSO 3 Na. 
     
     
         2 . The method according to  claim 1 , wherein R 6  is NH 2 , SCH 2 CH 2 NH 2 , SCH 2 CH 2 CH 2 NH 2 , or SCH 2 CH 2 CH 2 CH 2 NH 2 . 
     
     
         3 . A method for inhibiting the growth of a bacterium or virus, comprising contacting the bacterium or virus with a compound shown in  FIG. 1 . 
     
     
         4 . A method for treating a bacterial or viral infection, comprising administering to a mammal with a bacterial infection a compound having the formula 
       
         
           
           
               
               
           
         
       
       wherein R 2  is H, OH, OAc, OMe, or O(CH 2 CH 2 O) n ; R 3  is H, OH, OAc, OMe, OSO 3 Na, or NH 2 ; and R 6  is H, NH 2 , SCH 2 CH 2 NH 2 , SCH 2 CH 2 CH 2 NH 2 , SCH 2 CH 2 CH 2 CH 2 NH 2 , I, N 3 , SH, lower alkyl, S-alkylguanidyl, O-alkylguanidyl, S-aminoalkyl, O-aminoalkyl, aminoalkyl, aralkyl, aryl, heterocyclic ring(s), or OSO 3 Na. 
     
     
         5 . The method according to  claim 4 , wherein R 6  is NH 2 , SCH 2 CH 2 NH 2 , SCH 2 CH 2 CH 2 NH 2 , or SCH 2 CH 2 CH 2 CH 2 NH 2 . 
     
     
         6 . A method for treating a bacterial or viral infection, comprising administering to a mammal with a bacterial infection a compound shown in  FIG. 1 . 
     
     
         7 . A method for preventing a bacterial or viral infection, comprising administering to a mammal susceptible to a bacterial infection a compound having the formula 
       
         
           
           
               
               
           
         
       
       wherein R 2  is H, OH, OAc, OMe, or O(CH 2 CH 2 O) n ; R 3  is H, OH, OAc, OMe, OSO 3 Na, or NH 2 ; and R 6  is H, NH 2 , SCH 2 CH 2 NH 2 , SCH 2 CH 2 CH 2 NH 2 , SCH 2 CH 2 CH 2 CH 2 NH 2 , I, N 3 , SH, lower alkyl, S-alkylguanidyl, O-alkylguanidyl, S-aminoalkyl, O-aminoalkyl, aminoalkyl, aralkyl, aryl, heterocyclic ring(s), or OSO 3 Na. 
     
     
         8 . The method according to  claim 7 , wherein R 6  is NH 2 , SCH 2 CH 2 NH 2 , SCH 2 CH 2 CH 2 NH 2 , or SCH 2 CH 2 CH 2 CH 2 NH 2 . 
     
     
         9 . A method for preventing a bacterial or viral infection, comprising administering to a mammal susceptible to a bacterial infection a compound shown in  FIG. 1 .