Beta-Cyclodextrin Derivatives as Antibacterial Agents

Abstract

The invention provides a new class of antibiotics to which pathogenic bacteria have not been exposed, and thus should not have developed resistance. This new class of antibiotics are derivatives of β-cyclodextrin (β-CD), which is a cyclic molecule comprising seven D-glucose units.

1 . A compound having the formula 
       
         
           
           
               
               
           
         
       
       wherein
 R 2  is H, OH, OAc, O-lower alkyl, OMe, or O(CH 2 CH 2 O) n ; 
 R 3  is H, OH, OAc, O-lower alkyl, OMe, OSO 3 Na, or NH 2 ; and 
 R 6  is N which is mono, di or tri-substituted with alkyl, aralkyl, aryl, heterocyclic ring or heterocyclic alkyl, and any of which substituents can be further substituted with N, O or S which can be further substituted with H, alkyl, aralkyl or aryl. 
 
     
     
         2 . The compound according to  claim 1 , wherein  n  is from about 1 to about 10. 
     
     
         3 . The compound according to  claim 1 , wherein for each of R 2 , R 3  and R 6  any one or more of the carbon atoms may be optionally replaced by S, N or O. 
     
     
         4 . A pharmaceutical composition comprising a compound according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         5 . A method for inhibiting the growth of a bacterium, comprising contacting the bacterium with a compound having the formula 
       
         
           
           
               
               
           
         
       
       wherein
 R 2  is H, OH, OAc, OMe, O-lower alkyl, or O(CH 2 CH 2 O) n ; 
 R 3  is H, OH, OAc, OMe, O-lower alkyl, OSO 3 Na, or NH 2 ; and 
 R 6  is H, NH 2 , S(CH 2 ) m NH 2 , I, N 3 , SH, lower alkyl, S-alkylguanidyl, O-alkylguanidyl, S-aminoalkyl, O-aminoalkyl, aminoalkyl, O-lower alkyl, aralkyl, aryl, heterocyclic ring(s), OSO 3 Na or N which is mono, di or tri-substituted with alkyl, aralkyl, aryl, heterocyclic ring or heterocyclic alkyl, and any of which substituents can be further substituted with N, O or S which can be further substituted with H, alkyl, aralkyl or aryl. 
 
     
     
         6 . The method according to  claim 5 , wherein  n  is from about 1 to about 10, and wherein  m  is from about 1 to about 10. 
     
     
         7 . The method according to  claim 5 , wherein for each of R 2 , R 3  and R 6  any one or more of the carbon atoms may be optionally replaced by S, N or O. 
     
     
         8 . The method according to  claim 5 , wherein the bacterium is in a mammal. 
     
     
         9 . The method according to  claim 7 , wherein the mammal is a human. 
     
     
         10 . A method for treating a bacterial infection, comprising administering to a mammal with a bacterial infection a compound having the formula 
       
         
           
           
               
               
           
         
       
       wherein
 R 2  is H, OH, OAc, OMe, O-lower alkyl, or O(CH 2 CH 2 O) n ; 
 R 3  is H, OH, OAc, OMe, O-lower alkyl, OSO 3 Na, or NH 2 ; and 
 R 6  is H, NH 2 , S(CH 2 ) m NH 2 , I, N 3 , SH, lower alkyl, S-alkylguanidyl, O-alkylguanidyl, S-aminoalkyl, O-aminoalkyl, aminoalkyl, O-lower alkyl, aralkyl, aryl, heterocyclic ring(s), OSO 3 Na or N which is mono, di or tri-substituted with alkyl, aralkyl, aryl, heterocyclic ring or heterocyclic alkyl, and any of which substituents can be further substituted with N, O or S which can be further substituted with H, alkyl, aralkyl or aryl. 
 
     
     
         11 . The method according to  claim 10 , wherein  n  is from about 1 to about 10, and wherein  m  is from about 1 to about 10. 
     
     
         12 . The method according to  claim 10 , wherein for each of R 2 , R 3  and R 6  any one or more of the carbon atoms may be optionally replaced by S, N or O. 
     
     
         13 . The method according to  claim 10 , wherein the mammal is a human. 
     
     
         14 . A method for preventing a bacterial infection, comprising administering to a mammal susceptible to a bacterial infection a compound having the formula 
       
         
           
           
               
               
           
         
       
       wherein
 R 2  is H, OH, OAc, OMe, O-lower alkyl, or O(CH 2 CH 2 O) n ; 
 R 3  is H, OH, OAc, OMe, O-lower alkyl, OSO 3 Na, or NH 2 ; and 
 R 6  is H, NH 2 , S(CH 2 ) m NH 2 , I, N 3 , SH, lower alkyl, S-alkylguanidyl, O-alkylguanidyl, S-aminoalkyl, O-aminoalkyl, aminoalkyl, O-lower alkyl, aralkyl, aryl, heterocyclic ring(s), OSO 3 Na or N which is mono, di or tri-substituted with alkyl, aralkyl, aryl, heterocyclic ring or heterocyclic alkyl, and any of which substituents can be further substituted with N, O or S which can be further substituted with H, alkyl, aralkyl or aryl. 
 
     
     
         15 . The method according to  claim 14 , wherein  n  is from about 1 to about 10, and wherein  m  is from about 1 to about 10. 
     
     
         16 . The method according to  claim 14 , wherein for each of R 2 , R 3  and R 6  any one or more of the carbon atoms may be optionally replaced by S, N or O. 
     
     
         17 . The method according to  claim 14 , wherein the mammal is a human. 
     
     
         18 .- 22 . (canceled)