Use Of 5,6-Dimethylxanthenone-4-Acetic Acid as an Antimicrobial Agent

Abstract

The invention relates to the areas of therapeutics, pharmaceuticals, drug discovery, and immunotherapy. More specifically, the present invention relates to methods of stimulating the immune system through the administration of flavone acetic acid [FAA] analogues, and in particular, the flavone acetic acid analogue, 5,6-dimethylxanthenone-4-acetic acid (DMXAA) so as to comprise an antimicrobial therapeutic agent for the treatment of viral, fungal, bacterial or parasitic infections in humans and non-human animals. The invention is especially suitable for use in a process of treating and preventing infection by viruses (for example, rhinoviruses, enteroviruses, and influenza viruses, etc.) and bacteria (especially intracellular bacterial pathogens such as Francisella tularensis ).

1 . A method of treating or preventing an infection in a mammal comprising administering to a mammal in need of such treatment a pharmacologically acceptable, therapeutically effective amount of a compound of formula (I): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or ester thereof with a pharmaceutically acceptable acid; 
       wherein:
 X and Y are O or N, and R 1 , R 2 , and R 3  are each independently chosen from H, C 1 -C 6  alkyl, halogen, CF 3 , CN, NO 2 , NH 2 , OH, OR, NHCOR, NHSO 2 R, SR, SO 2 R, CH 2 COOH, or NHR, wherein each R is independently C 1 -C 6  alkyl optionally substituted with one or more substituents selected from hydroxy, amino, ethoxy, and methoxy, and 
 each of R 1 , R 2 , and R 3  may be present at any one of the available carbon positions 1 to 8; and 
 in each of the carbocyclic aromatic rings in formula (I), up to two of the methine (—CH═) groups may be replaced by an aza (—N═) group; and 
 any two of R 1 , R 2 , and R 3  may additionally together represent the group —CH═CH—CH═CH—, such that this group, together with the carbon or nitrogen atoms to which it is attached, forms a fused six membered aromatic ring. 
 
     
     
         2 . The method of  claim 1 , wherein said FAA analogue is DMXAA (5,6-dimethylxanthenone-4-acetic acid). 
     
     
         3 . The method of  claim 1 , wherein said infection is caused by a bacterial pathogen. 
     
     
         4 . The method of  claim 3 , wherein said bacterial pathogen is an intracellular pathogen. 
     
     
         5 . The method of  claim 1 , wherein said infection is caused by a viral pathogen. 
     
     
         6 . The method of  claim 5 , wherein said viral pathogen is a DNA virus. 
     
     
         7 . The method of  claim 5 , wherein said viral pathogen is a RNA virus. 
     
     
         9 . The method of  claim 1 , wherein said treatment is prophylactic. 
     
     
         10 . The method of  claim 1 , wherein said treatment is therapeutic. 
     
     
         11 . The method of  claim 1 , wherein said compound is administered in conjunction with a second therapeutic agent. 
     
     
         12 . A pharmaceutical composition comprising an amount of a compound of formula (I): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or ester thereof with a pharmaceutically acceptable acid; 
       wherein:
 X and Y are O or N, and R 1 , R 2 , and R 3  are each independently chosen from H, C 1 -C 6  alkyl, halogen, CF 3 , CN, NO 2 , NH 2 , OH, OR, NHCOR, NHSO 2 R, SR, SO 2 R, CH 2 COOH, or NHR, wherein each R is independently C 1 -C 6  alkyl optionally substituted with one or more substituents selected from hydroxy, amino, ethoxy, and methoxy, and 
 each of R 1 , R 2 , and R 3  may be present at any one of the available carbon positions 1 to 8; and 
 in each of the carbocyclic aromatic rings in formula (I), up to two of the methine (—CH═) groups may be replaced by an aza (—N═) group; and 
 any two of R 1 , R 2 , and R 3  may additionally together represent the group —CH═CH—CH═CH—, such that this group, together with the carbon or nitrogen atoms to which it is attached, forms a fused six membered aromatic ring; 
 
       and one or more pharmaceutically acceptable carriers, diluents or excipients. 
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein said FAA analogue is DMXAA (5,6-dimethylxanthenone-4-acetic acid). 
     
     
         14 . The pharmaceutical composition of  claim 12 , wherein said infection is caused by a bacterial pathogen. 
     
     
         15 . The pharmaceutical composition of  claim 12 , wherein said infection is caused by a viral pathogen. 
     
     
         16 . The pharmaceutical composition of  claim 15 , wherein said viral pathogen is a DNA virus. 
     
     
         17 . The pharmaceutical composition of  claim 15 , wherein said viral pathogen is a RNA virus. 
     
     
         18 . The pharmaceutical composition of  claim 12 , wherein said composition is administered prophylactically to prevent an anticipated infection. 
     
     
         19 . The pharmaceutical composition of  claim 12 , wherein said composition is administered therapeutically to treat an existing infection. 
     
     
         20 . The pharmaceutical composition of  claim 12 , wherein said compound is administered in conjunction with a second therapeutic agent.