Therapeutic agents containing cannabis flavonoid derivatives targeting kinases, sirtuins and oncogenic agents for the treatment of cancers

Abstract

A cannabis -based flavonoid pharmaceutical composition including any one or more selected from among the group of Cannflavin A, Cannflavin B. Cannflavin C, Chrysoeriol, Cosmosiin, Flavocannabiside and their derivatives selected from among the group of Geraldol, Rhamnetin, Isorhamnetin, Rhamnazin, or their synthases, for the prevention and treatment of certain cancers that can be treated by therapeutically targeting oncogenic factors including kinases, sirtuins, bromodomains, matrix metalloproteinases and histone acetylases. Some of the cancers that can be treated by use of cannabis flavonoids based on the inhibition of these therapeutic targets include but are not limited to brain, breast, colon, renal liver, lung, pancreatic, pigmented villonodular synovitis, prostate, leukemia, melanomam, tenosynovial giant cell tumor, as well as any other cancers that overexpress the oncogenic factors inhibited, by the cannabis flavonoids or their derivatives herein identified.

1 . A  cannabis -based flavonoid pharmaceutical composition for the prevention and treatment of cancer having a flavone backbone (2-phenyl-1,4-benzopyrone) chemical structure as shown below, or any pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein R1, R3, R5, R6, R7 and R10 may be none, any one or more substituents selected from the group consisting of a hydrogen molecule (H), a hydroxide molecule (OH), a methyl group comprising one carbon atom bonded to three hydrogen atoms (CH3), an alkoxy group (O—CH3), a carboxyl group (COOH), chlorine (Cl), Bromine (Br), Fluorine (F), Glutamic acid (Glu), amine (NH2), amide (CONH2), imidazole (C3H4N2 and any salts or derivatives of the foregoing, R2, R4, R8 and R9 may be any one or more substituents selected from said group, and the carbon-to-carbon A and B bond is double flavone bond. 
       
     
     
         2 . The  cannabis -based flavonoid pharmaceutical composition according to  claim 1 , having a specific chemical structure as shown below, or any pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         3 . The  cannabis -based flavonoid pharmaceutical composition according to  claim 1 , having a specific chemical structure as shown below, or any pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         4 . The  cannabis -based flavonoid pharmaceutical composition according to  claim 1 , having a specific chemical structure as shown below, or any pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         5 . The  cannabis -based flavonoid pharmaceutical composition according to  claim 1 , having a specific chemical structure as shown below, or any pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The  cannabis -based flavonoid pharmaceutical composition according to  claim 1 , having a specific chemical structure as shown below, or any pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         7 . The  cannabis -based flavonoid pharmaceutical composition according to  claim 1 , having a specific chemical structure as shown below, or any pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         8 . The  cannabis -based flavonoid pharmaceutical composition according to  claim 1 , having a specific chemical structure as shown below, or any pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         9 . The  cannabis -based flavonoid pharmaceutical composition according to  claim 1 , having a specific chemical structure as shown below, or any pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         10 . The  cannabis -based flavonoid pharmaceutical composition according to  claim 1 , having a specific chemical structure as shown below, or any pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         11 . The  cannabis -based flavonoid pharmaceutical composition according to  claim 1 , having a specific chemical structure as shown below, or any pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         12 . The  cannabis -based flavonoid pharmaceutical composition according to  claim 1 , having a specific chemical structure as shown below, or any pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         13 . A  cannabis -based flavonoid pharmaceutical composition for the prevention and treatment of cancer and other diseases having a general flavone backbone (2-phenyl-1,4-benzopyrone) chemical structure as shown below, or any pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         R2 may be one or more substituents selected from the group consisting of a hydrogen molecule (H), a hydroxide molecule (OH), or an oxygen molecule (O); 
         R3 may be none, or one or more hydrogen molecules (H), 
         R4 may be none, or any one or more substituents selected from the group consisting of a hydroxide molecule (OH) or a nitrogen dioxide molecule (NO2); 
         R5 and R8 may be none, or a hydroxide molecule (OH); 
         R7 may be none, or the amine NH2; 
         R9 may be none, or any one or more substituents selected from the group consisting of a hydroxide molecule (OH) or an oxygen molecule (O); 
         and A and B are linked by a single bond. 
       
     
     
         14 . The  cannabis -based flavonoid pharmaceutical composition according to  claim 13 , having a specific chemical structure as shown below, or any pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         15 . The  cannabis -based flavonoid pharmaceutical composition according to  claim 13 , having a specific chemical structure as shown below, or any pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         16 . The  cannabis -based flavonoid pharmaceutical composition according to  claim 13 , having a specific chemical structure as shown below, or any pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         17 . The  cannabis -based flavonoid pharmaceutical composition according to  claim 13 , having a specific chemical structure as shown below, or any pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         18 . A method of treating cancer, the method comprising administering the general composition of  claim 1 . 
     
     
         19 . A method of treating cancer, the method comprising administering the specific composition of  claim 13 . 
     
     
         20 . A method of synthesizing the compound of  claim 1 , the method comprising:
 combining 4-coumaroyl-CoA with malonyl-CoA to yield a flavonoid backbone containing two phenyl rings; and   promoting conjugate ring-closure of chalcones.