Autoinducer compounds

Abstract

Autoinducer compounds which enhance gene expression in a wide variety of microorganisms, therapeutic compositions and therapeutic methods wherein gene expression within microorganisms is regulated are disclosed.

1 . A compound of the following formula:  
       
         
           
           
               
               
           
         
       
       wherein R 1 -R 2 , are selected from the group consisting of H, C 1 -C 4  alkyl group, OH, NH 2 , SH and a halogen, wherein the halogen is selected from the group consisting of fluorine, chlorine, bromine, and iodine; 
 R 22  and R 23  are selected from H, S, O, and N—Y,  
 Y is selected from H, C 1 -C 4  alkyl group, OH, NH 2 , SH or a halogen, wherein the halogen is selected from the group consisting of fluorine, chlorine, bromine, and iodine,  
 R 24 -R 28  is H or a halogen, and  
 X 1  and X 2  are selected from O, S, NH, H 2 , H plus OH or NH 2 , or any combination of H plus one halogen or two halogens when one or more R groups is substituted, and at least one of R 1 -R 21  is halogen, or the alkylene chain of the molecule contains a sulfur in the chain.  
 
     
     
         2 . The compound of  claim 1 , wherein R 24  through R 28  are a H or halogen, and R 22 -R 23  are a H.  
     
     
         3 . The compound of  claim 2 , wherein one or more carbons forming the backbone of the molecule are substituted with S or S-substituted moieties.  
     
     
         4 . The compound of  claim 2 , wherein the carbonyl group at X 1  and/or X 2  is substituted with H 2 , H plus a halogen or two halogens.  
     
     
         5 . The compound of  claim 1 , wherein R 22  is selected from H, S, O and N—Y, and R 23  is independently selected from S, O, and N—Y, wherein Y is selected from H, C 1 -C 4  alkyl group, OH, NH 2 , SH or a halogen, wherein the halogen is selected from the group consisting of fluorine, chlorine, bromine, and iodine.  
     
     
         6 . The compound of  claim 1 , wherein the alkylene side chain contains one or more double bonds or triple bonds between carbon atoms within the alkylene side chain.  
     
     
         7 . The compound of  claim 1 , wherein X 1 -X 2  is selected from H 2 , H plus a halogen, two halogens, H plus OH or NH 2 , a double bonded O, NH, or S.  
     
     
         8 . The compound of  claim 1 , which is an optically active isomer.  
     
     
         9 . A compound of the following formula:  
       
         
           
           
               
               
           
         
       
       wherein R 1 -R 7  are selected from the group consisting of H, C 1 -C 4  alkyl group, OH, NH 2 , SH or a halogen, wherein the halogen is selected from the group consisting of fluorine, chlorine, bromine, and iodine; 
 R 22  and R 23  are selected from H, S, O, and N—Y,  
 Y is selected from H, C 1 -C 4  alkyl group, OH, NH 2 , SH or a halogen, wherein the halogen is selected from the group consisting of fluorine, chlorine, bromine, and iodine,  
 R 24 —R 29  is H or a halogen, and  
 X is selected from O, S, NH, H 2 , H plus OH or NH 2 , or any combination of H plus one halogen or two halogens when one or more R groups is substituted, and at least one of R 1 -R 7  is halogen, or the alkylene chain of the molecule contains a sulfur in the chain.  
 
     
     
         10 . The compound of  claim 9 , wherein R 22  is selected from H, S, O and N—Y, and R 23  is independently selected from S, O, and N—Y, wherein Y is selected from H, C 1 -C 4  alkyl group, OH, NH 2 , SH or a halogen, wherein the halogen is selected from the group consisting of fluorine, chlorine, bromine, and iodine.  
     
     
         11 . The compound of  claim 9 , wherein the alkylene side chain contains one or more double bonds or triple bonds between carbon atoms within the alkylene side chain.  
     
     
         12 . The compound of  claim 9 , wherein X is selected from H 2 , H plus a halogen, two halogens, H plus OH or NH 2 , a double bonded O, NH or S.  
     
     
         13 . The compound of  claim 9 , which is an optically active isomer.  
     
     
         14 . The compound of  claim 1 , which is selected from the group consisting of:  
       
         
           
           
               
               
           
         
       
     
     
         15 . The compound of  claim 1 , which is selected from the group consisting of:  
       
         
           
           
               
               
           
         
       
     
     
         16 . A pharmaceutical composition comprising at least one compound of the following formulae:  
       
         
           
           
               
               
           
         
       
       wherein R 1 -R 2 , are selected from the group consisting of H, C 1 -C 4  alkyl group, OH, NH 2 , SH or a halogen, wherein the halogen is selected from the group consisting of fluorine, chlorine, bromine, and iodine; 
 R 22  and R 23  are selected from H, S, O, and N—Y,  
 Y is selected from H, C 1 -C 4  alkyl group, OH, NH 2 , SH or a halogen, wherein the halogen is selected from the group consisting of fluorine, chlorine, bromine, and iodine,  
 R 24 -R 28  is H or a halogen, and  
 X, X 1  and X 2  are selected from O, S, NH, H 2 , H plus OH or NH 2 , or any combination of H plus one halogen or two halogens when one or more R groups is substituted, and at least one of R 1 -R 21  is halogen, or the alkylene chain of the molecule contains a sulfur in the chain, 
 and a pharmaceutically acceptable carrier.  
 
 
     
     
         17 . The composition of  claim 16 , wherein the compound is present in an amount effective to affect the ability of a microorganism to initially infect or further infect an organism.  
     
     
         18 . The composition of  claim 16 , further comprising an antimicrobial, antibacterial or antifungal agent.  
     
     
         19 . A growth medium for microorganisms comprising a compound of the formula as defined in  claim 1  or  9 , at a concentration effective to stimulate or promote the metabolism, growth and/or recovery of the microorganisms.  
     
     
         20 . A method for regulating gene expression with a microorganism, which method comprises inserting a gene into a microorganism chosen for enhancement of gene expression by a compound of the formula as defined in  claim 1  or  9 , capable of stimulating the activity of a selected protein and incubating the microorganism with the compound.  
     
     
         21 . A method for regulating gene expression comprising adding a compound of the formula as defined in  claim 1  or  9 , to a microorganism culture to cause expression of a selected gene that would not otherwise be expressed.  
     
     
         22 . A method of inhibiting the infectivity of a selected microorganism, comprising contacting the selected microorganism with a compound of the formula as defined in  claim 1  or  9 .  
     
     
         23 . A compound according to  claim 1  wherein R 1 -R 21  is CH 3 .  
     
     
         24 . A compound according to  claim 9  wherein R 1 -R 7  is CH 3 .  
     
     
         25 . A composition according to  claim 16  wherein R 1 -R 21  is CH 3 .  
     
     
         26 . A compound according to  claim 1  which is an optical isomer.  
     
     
         27 . A compound according to  claim 9  which is an optical isomer.  
     
     
         28 . A composition of  claim 16  wherein the compound is an optical isomer.