Flavin N-oxides: new anti-cancer agents and pathogen eradication agents

Abstract

Compounds comprising flavin N-oxides for treatments of solid tumors, non-solid tumor masses, leukemias, and non-small cell lung cancers and for eradicating contaminants in blood products. Methods of treating patients having solid type cancers comprising administering a therapeutically effective amount of a flavin N-oxide to a subject in need of treatment and exposing the flavin N-oxide to an activator such that activation of the flavin N-oxide results in damage to the DNA in the cancer cells without substantial damage to the DNA of normal cells are also provided. Methods of using a flavin N-oxide as part of a combination therapy with chemotherapy, radiation therapy, or both are also provided. Methods of reducing pathogenic bacterial or viral contamination in a composition comprising a) mixing the composition with an efficacious amount of a flavin N-oxide and b) exposing the mixture of the composition and the flavin N-oxide to an activator for a period of time sufficient to activate the flavin N-oxide such that the flavin N-oxide reduces the contamination in the composition are also provided. Preferably, the composition is a blood product selected from plasma, platelets, and red blood cells and the activator is an enzyme.

1 - 13 . (canceled)  
   
   
       14 . A method for reducing pathogenic bacterial or viral contamination in a composition comprising the steps of: 
 a. mixing the composition with an efficacious amount of a flavin N-oxide; and    b. exposing the mixture of the composition and the flavin N-oxide to an activator for a period of time sufficient to activate the flavin N-oxide such that the activation of the flavin N-oxide reduces the contamination in the composition.    
   
   
       15 . The method of  claim 14  wherein the flavin N-oxide is of formula I:  
     
       
         
         
             
             
         
       
       wherein  
       X 1  is selected from H, monosaccharides, substitited monosaccharides, mono, di, and tri-ethylene glycol, alcohol, and alkyl ammonium ion; and  
       X 2 , X 3 , and X 4  can be the same or different and are selected from H, monosaccharides, substitited monosaccharides, glycol, alcohol, lower alkyl, and alkylene groups;  
       wherein X 2 , X 3 , and X 4  can be substituted with monosaccharides, substitited monosaccharides, mono, di, and tri- ethylene glycol, alcohol, alkyl ammonium ion, and combinations thereof.  
     
   
   
       16 . The method of  claim 15  wherein the flavin N-oxide is riboflavin N-oxide.  
   
   
       17 . The method of  claim 14  wherein the composition is a composition is a blood product used in transfusion medicine, selected from the group consisting of plasma, platelets, and red blood cells.  
   
   
       18 . The method of  claim 14  wherein the activator is electromagnetic radiation of sufficient wavelength and intensity to activate the flavin N-oxide.  
   
   
       19 . The method of  claim 18  wherein the electromagnetic radiation is in the visible region.  
   
   
       20 . The method of  claim 19  wherein the electromagnetic radiation is in the range from 400 to 500 nm.  
   
   
       21 . The method of  claim 14  wherein the activator comprises a reducing enzyme.  
   
   
       22 . The method of  claim 21  wherein the reducing enzyme is an enzyme present in the pathogenic bacterial or viral contaminants in the composition.  
   
   
       23 . The method of  claim 22  wherein the pathogenic contamination comprises hepatitis A virus, hepatitis B virus, human T-cell lymphotropic viruses, parvovirus B19, hepatitis C virus, and combinations thereof.  
   
   
       24 . A method of eradicating pathogenic contamination in platelet concentrates and red blood cell concentrates, the method comprising the steps of: 
 a. mixing the composition with an efficacious amount of a flavin N-oxide; and    b. exposing the mixture of the composition and the flavin N-oxide to an activator for a period of time sufficient to activate the flavin N-oxide such that activation of the flavin N-oxide reduce the contamination in the composisition;    wherein the contamination is from any one or more of hepatitis A virus, hepatitis B virus, human T-cell lymphotropic viruses, parvovirus B19, hepatitis C virus.    
   
   
       25 . The method of  claim 24  wherein the flavin N-oxide is of formula I:  
     
       
         
         
             
             
         
       
       wherein  
       X 1  is selected from H, monosaccharides, substitited monosaccharides, mono, di, and tri-ethylene glycol, alcohol, and alkyl ammonium ion; and  
       X 2 , X 3 , and X 4  can be the same or different and are selected from H, monosaccharides, substitited monosaccharides, glycol, alcohol, lower alkyl, and alkylene groups;  
       wherein X 2 , X 3 , and X 4  can be substituted with monosaccharides, substitited monosaccharides, mono, di, and tri- ethylene glycol, alcohol, alkyl ammonium ion, and combinations thereof.  
     
   
   
       26 . The method of  claim 25  wherein the flavin N-oxide is riboflavin N-oxide.  
   
   
       27 . A compound formula I:  
     
       
         
         
             
             
         
       
       wherein  
       X 1  is selected from H, monosaccharides, substitited monosaccharides, mono, di, and tri-ethylene glycol, alcohol, and alkyl ammonium ion; and  
       X 2 , X 3 , and X 4  can be the same or different and are selected from H, monosaccharides, substitited monosaccharides, glycol, alcohol, lower alkyl, and alkylene groups;  
       wherein X 2 , X 3 , and X 4  can be substituted with monosaccharides, substitited monosaccharides, mono, di, and tri- ethylene glycol, alcohol, alkyl ammonium ion, and combinations thereof, and  
       provided that the compound is not riboflavin N-oxide.