Antimicrobial and radioprotective compounds

Abstract

The present invention relates to a method of treatment and/or prophylaxis of a microbial infection, comprising the step of administering an effective amount of a compound of formula (I), in which X and Y are either the same or different and selected from a heteroatom; is a double or single bond depending on the heteroatoms X and Y; R 1 to R 5 are either the same or different and selected from hydrogen or a non-deleterious substituent; and R 6 and R 7 are either the same or different and selected from hydrogen and a non-deleterious substituent or one of R 6 and R 7 are absent when there is a double bond present, pharmaceutically acceptable salts or derivatives, pro-drugs, tautomers and/or isomers thereof. The present invention also relates to a method for protecting a subject from radiation damage, a method of cancer radiotherapy and use as an antimicrobial or radioprotective agent of the compound of formula (I) defined above. Some of the compounds of formula (I) are novel and are also described in the present invention, together with pharmaceutical or veterinary compositions containing them.

1 . A method for the treatment of a bacterial infection, wherein the infection is caused by an organism selected from the group consisting of Methicillin-resistant  Staphylococcus aureus, Mycobacterium tuberculosis, Streptococcus pneumoniae  and  Haemophilus influenza,  comprising: administering to an animal in need thereof an effective amount of a compound of general formula I: 
       
         
           
           
               
               
           
         
         in which X and Y are either the same or different, and are each a heteroatom selected from the group consisting of O, N, and S; 
           is a double or single bond depending on the heteroatoms X and Y; 
         R 1  to R 5  are either the same or different and selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, halo, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, hydroxy, alkoxy, alkenyloxy, aryloxy, benzyloxy, haloalkoxy, haloalkenyloxy, haloaryloxy, nitro, nitroalkyl, nitroalkenyl, nitroalkynyl, nitroaryl, nitroheterocyclyl, amino, alkylamino, dialkylamino, alkenylamino, alkynylamino, arylamino, diarylamino, benzylamino, dibenzylamino, acyl, alkenylacyl, alkynylacyl, arylacyl, acylamino, diacylamino, acyloxy, alkylsulphonyloxy, arylsulphenyloxy, heterocyclyl, heterocycloxy, heterocyclamino, haloheterocyclyl, alkylsulphenyl, arylsulphenyl, carboalkoxy, carboaryloxy, mercapto, alkylthio, arylthio, acylthio, and a phosphorus-containing group; and 
         R 6  and R 7  are either the same or different, and selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, halo, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, hydroxy, alkoxy, alkenyloxy, aryloxy, benzyloxy, haloalkoxy, haloalkenyloxy, haloaryloxy, nitro, nitroalkyl, nitroalkenyl, nitroalkynyl, nitroaryl, nitroheterocyclyl, amino, alkylamino, dialkylamino, alkenylamino, alkynylamino, arylamino, diarylamino, benzylamino, dibenzylamino, acyl, alkenylacyl, alkynylacyl, arylacyl, acylamino, diacylamino, aryloxy, alkylsulphonyloxy, arylsulphenyloxy, heterocyclyl, heterocycloxy, heterocyclamino, haloheterocyclyl, alkylsulphenyl, arylsulphenyl, carboalkoxy, carboaryloxy, mercapto, alkylthio, arylthio, acylthio, and a phosphorus-containing group, or one of R 6  and R 7  are absent when there is a double-bond present, or a pharmaceutically-acceptable salt thereof. 
       
     
     
         2 . The method of  claim 1 , wherein the bacterial infection is a respiratory tract infection. 
     
     
         3 . The method of  claim 1 , wherein X and Y are both O. 
     
     
         4 . The method of  claim 1 , wherein R 1  and R 2  are either the same or different and selected from the group consisting of hydrogen, hydroxy, halogen, and optionally substituted C 1-6  alkyl. 
     
     
         5 . The method of  claim 1 , wherein R 3  to R 5  are either the same or different and selected from the group consisting of hydrogen, hydroxy, halogen, nitro, C 1-6  alkoxy, and optionally substituted C 1-6  alkyl. 
     
     
         6 . The method of  claim 1 , wherein X, Y,  , R 6  and R 7  are as defined in  claim 1 ; R 1  and R 2  are either the same or different and selected from hydrogen, hydroxy, Cl, Br, and C 1-4  alkyl; and R 3  to R 5  are either the same or different and selected from the group consisting of hydrogen, hydroxy, Cl, Br, nitro, C 1-4  alkoxy, and C 1-4  alkyl. 
     
     
         7 . The method of  claim 1 , wherein the compound is 3,4-methylenedioxy-β-methyl-β-nitrostyrene. 
     
     
         8 . The method of  claim 1 , wherein the compound is 3,4-methylenedioxy-β-nitrostyrene. 
     
     
         9 . The method of  claim 1 , wherein the organism is methicillin-resistant  Staphylococcus aureus.    
     
     
         10 . The method of  claim 1 , wherein the organism is  Mycobacterium tuberculosis.    
     
     
         11 . The method of  claim 1 , wherein the organism is  Streptococcus pneumoniae.    
     
     
         12 . The method of  claim 1 , wherein the organism is  Haemophilus influenzae.    
     
     
         13 . The method of  claim 1 , wherein the animal is human. 
     
     
         14 . A method for the treatment of a fungal infection, wherein the infection is caused by an organism selected from the group consisting of  Candida albicans, Candida glabrata, Trichophyton rubrum, Epidermophyton floccosum, Microsporum gypseum, Rhodotorula rubra, Fusarium graminearum, Rhizopus stolonifer, Aspergillus fumigatus, Penicillium chrysogenum,  and  Cryptococcus neoformans,  comprising: administering to an animal in need thereof an effective amount of a compound of general formula I: 
       
         
           
           
               
               
           
         
         in which X and Y are either the same or different, and are each a heteroatom selected from the group consisting of O, N, and S; 
           is a double or single bond depending on the heteroatoms X and Y; 
         R l  to R 5  are either the same or different and selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, halo, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, hydroxy, alkoxy, alkenyloxy, aryloxy, benzyloxy, haloalkoxy, haloalkenyloxy, haloaryloxy, nitro, nitroalkyl, nitroalkenyl, nitroalkynyl, nitroaryl, nitroheterocyclyl, amino, alkylamino, dialkylamino, alkenylamino, alkynylamino, arylamino, diarylamino, benzylamino, dibenzylamino, acyl, alkenylacyl, alkynylacyl, arylacyl, acylamino, diacylamino, aryloxy, alkylsulphonyloxy, arylsulphenyloxy, heterocyclyl, heterocycloxy, heterocyclamino, haloheterocyclyl, alkylsulphenyl, arylsulphenyl, carboalkoxy, carboaryloxy, mercapto, alkylthio, arylthio, acylthio, and a phosphorus-containing group; and 
         R 6  and R 7  are either the same or different, and selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, halo, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, hydroxy, alkoxy, alkenyloxy, aryloxy, benzyloxy, haloalkoxy, haloalkenyloxy, haloaryloxy, nitro, nitroalkyl, nitroalkenyl, nitroalkynyl, nitroaryl, nitroheterocyclyl, amino, alkylamino, dialkylamino, alkenylamino, alkynylamino, arylamino, diarylamino, benzylamino, dibenzylamino, acyl, alkenylacyl, alkynylacyl, arylacyl, acylamino, diacylamino, acyloxy, alkylsulphonyloxy, arylsulphenyloxy, heterocyclyl, heterocycloxy, heterocyclamino, haloheterocyclyl, alkylsulphenyl, arylsulphenyl, carboalkoxy, carboaryloxy, mercapto, alkylthio, arylthio, acylthio, and a phosphorus-containing group, or one of R 6  and R 7  are absent when there is a double bond present, or a pharmaceutically-acceptable salt thereof. 
       
     
     
         15 . The method of  claim 14 , wherein the animal is immunocompromised. 
     
     
         16 . The method of  claim 14 , wherein X and Y are both O. 
     
     
         17 . The method of  claim 14 , wherein R 1  and R 2  are either the same or different and are selected from the group consisting of hydrogen, hydroxy, halogen, and optionally substituted C 1-6  alkyl. 
     
     
         18 . The method of  claim 14 , wherein R 3  to R 5  are either the same or different and selected from the group consisting of hydrogen, hydroxy, halogen, nitro, C 1-6  alkoxy, and optionally substituted C 1-6  alkyl. 
     
     
         19 . The method of  claim 14 , wherein X, Y,  , R 6  and R 7  are as defined in  claim 1 ; R 1  and R 2  are either the same or different and selected from the group consisting of hydrogen, hydroxy, Cl, Br, and C 1-4  alkyl; and R 3  to R 5  are either the same or different and selected from the group consisting of hydrogen, hydroxy, Cl, Br, nitro, C 1-4  alkoxy, and C 1-4  alkyl. 
     
     
         20 . The method of  claim 14 , wherein the compound is 3,4-methylenedioxy-β-methyl-β-nitrostyrene. 
     
     
         21 . The method of  claim 14 , wherein the compound is 3,4-methylenedioxy-β-nitrostyrene. 
     
     
         22 . The method of  claim 14 , wherein the animal is human.