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 composition;   
       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 composition 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. 
       
     
     
         28 . The method of  claim 14  wherein the composition is a platelet concentrate or a red blood cell concentrate. 
     
     
         29 . The method of  claim 28  wherein the pathogenic bacterial or viral contamination being reduced is from any one or more of hepatitis A virus, hepatitis B virus, human T-cell lymphotropic viruses, parvovirus B19 and hepatitis C virus.