Deacetylnemorone Abietane Diterpenoids for Use in Cancer Treatment

Abstract

or a tautomer there of in which R1, R2, and R3 are independently selected from —H, C1-10 alkyl, C1-10 alkoxy, C1-10 alkenyl, C1-10 alkenoxy, —OH, —OAc, —CHO, -Ph, —OC6H5, —OC6H4OH, —COC6H5, —OCONH2, —OCONHCH3, —OCOC6H4NH2, —NH2, or ═O. The deacetylnemorone shows efficacy in treatment and prevention of a wide range of cancer types, as well as other neoplastic diseases as a chemo-preventative, a primary or secondary cytotoxic agent, a sensitizer for other therapies, or one component of a combinatorial treatment.

What is claimed is: 
     
         1 . A method for inhibiting angiogenesis, the method comprising delivering a deacetylnemorone abietane diterpenoid to an area comprising endothelial cells. 
     
     
         2 . The method of  claim 1 , wherein the deacetylnemorone abietane diterpenoid has a structure as follows: 
       
         
           
           
               
               
           
         
         or a tautomer there of in which R 1 , R 2 , and R 3  are independently selected from —H, C 1-10  alkyl, C 1-10  alkoxy, C 1-10  alkenyl, C 1-10  alkenoxy, —OH, —OAc, —CHO, -Ph, —OC 6 H 5 , —OC 6 H 4 OH, —COC 6 H 5 , —OCONH 2 , —OCONHCH 3 , —OCOC 6 H 4 NH 2 , —NH 2 , or ═O. 
       
     
     
         3 . The method of  claim 1 , wherein the deacetylnemorone abietane diterpenoid has a structure as follows: 
       
         
           
           
               
               
           
         
       
     
     
         4 . The method of  claim 1 , wherein the deacetylnemorone abietane diterpenoid contacts the epithelial cells at a concentration of from about 0.1 μg/mL to about 10 μg/mL. 
     
     
         5 . The method of  claim 1 , the area further comprising cancer cells. 
     
     
         6 . The method of  claim 1 , the method comprising delivering the deacetylnemorone abietane diterpenoid to the area in conjunction with a second bioactive agent. 
     
     
         7 . The method of  claim 6 , the method comprising delivering the deacetylnemorone abietane diterpenoid and the second bioactive agent together in a single composition. 
     
     
         8 . The method of  claim 6 , the method comprising delivering the deacetylnemorone abietane diterpenoid separately from the delivery of the second bioactive agent to the area. 
     
     
         9 . The method of  claim 6 , wherein the second bioactive agent comprises a chemotherapy agent. 
     
     
         10 . The method of  claim 1 , wherein the deacetylnemorone abietane diterpenoid is delivered to the area in multiple doses. 
     
     
         11 . A composition comprising a deacetylnemorone abietane diterpenoid and a pharmaceutically compatible carrier, the deacetylnemorone abietane diterpenoid having the following structure: 
       
         
           
           
               
               
           
         
         or a tautomer there of in which R 1 , R 2 , and R 3  are independently selected from —H, C 1-10  alkyl, C 1-10  alkoxy, C 1-10  alkenyl, C 1-10  alkenoxy, —OH, —OAc, —CHO, -Ph, —OC 6 H 5 , —OC 6 H 4 OH, —COC 6 H 5 , —OCONH 2 , —OCONHCH 3 , —OCOC 6 H 4 NH 2 , —NH 2 , or ═O. 
       
     
     
         12 . The composition of  claim 11 , wherein the deacetylnemorone abietane diterpenoid has a structure as follows: 
       
         
           
           
               
               
           
         
       
     
     
         13 . The composition of  claim 11 , further comprising a second bioactive agent. 
     
     
         14 . The composition of  claim 13 , wherein the second bioactive agent comprises a chemotherapy agent. 
     
     
         15 . The composition of  claim 14 , wherein the chemotherapy agent comprises 5-fluoro-2′-deoxyuridine. 
     
     
         16 . The composition of  claim 14 , wherein the chemotherapy agent exhibits activity against breast cancer cells, bladder cancer cells, Kaposi's sarcoma cells, lymphoma cells, or leukemia cells. 
     
     
         17 . The composition of  claim 11 , wherein the composition is configured for in vivo delivery. 
     
     
         18 . The composition of  claim 11 , wherein the composition comprises a liquid or an edible carrier. 
     
     
         19 . The composition of  claim 11 , wherein the composition is an aerosol. 
     
     
         20 . The composition of  claim 11 , wherein the composition is a sustained release composition.