Methods and Compositions for Treating Melanoma and Non-Melanoma Skin Cancers

Abstract

Compositions comprising select aryl alkanones and the use thereof in the treatment of melanoma and non-melanoma skin cancer.

We claim: 
     
         1 . A composition comprising (a) at least one compound according to Structure 1 
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , R 3 , R 4  and R 5 , which may be the same or different, are each independently H, OH, alkyl or alkoxy, provided that at least one of R 1 , R 2 , R 3 , R 4  and R 5  is not H, and wherein the alkyl or alkoxy groups, if present, are linear or branched and have from 1 to 8 carbon atoms and (b) a pharmaceutically acceptable carrier wherein pharmaceutically acceptable carrier is suitable for the oral, intravenous, intraperitoneal, and/or subcutaneous administration of a pharmaceutical active agent. 
     
     
         2 . The composition of  claim 1  wherein the pharmaceutically acceptable carrier is not one used for application of topical pharmaceuticals. 
     
     
         3 . The composition of  claim 1  wherein R 1  and R 2  are H and R 3 , R 4  and R 5 , which may be the same or different, are each independently H, OH, or C 1  to C 4  alkoxy, provided that at least one of R 3 , R 4  and R 5  is not H. 
     
     
         4 . The composition of  claim 1  wherein R 1  and R 2  are H and R 3 , R 4  and R 5 , which may be the same or different, are each independently H, OH, or OCH 3 ; provided at least one or two of R 3 , R 4  and R 5  is OH or OCH 3  or one of R 3 , R 4  and R 5  is OH and at least one of the remaining moieties is OH or OCH 3 . 
     
     
         5 . The composition of  claim 1  wherein the at least one compound according to Structure 1 is selected from the group consisting of:
 Compound 1 wherein R 1 ═R 2 =R 5 ═H; R 3 ═OH; and R 4 ═OCH 3 ; 
 Compound 2 wherein R 1 ═R 2 =R 4 ═R 5 ═H; and R 3 ═OCH 3 ; 
 Compound 3 wherein R 1 ═R 2 =R 4 ═R 5 ═H; and R 3 ═OH; 
 Compound 4 wherein R 1 ═R 2 =R 3 ═R 5 ═H; and R 4 ═OH; 
 Compound 5 wherein R 1 ═R 2 =R 3 ═R 5 ═H; and R 4 ═OCH 3 ; 
 Compound 6 wherein R 1 ═R 2 =R 3 ═R 4 ═H; and R 5 ═OH; 
 Compound 7 wherein R 1 ═R 2 =R 3 ═R 4 ═H; and R 5 ═OCH 3 ; and 
 Compound 8 wherein R 1 ═R 3 =R 5 ═H; and R 2 ═R 4 ═OH. 
 
     
     
         6 . The composition of  claim 1  wherein the compound according to Structure 1 is present in an effective amount for treating melanoma and/or non-melanoma skin cancer. 
     
     
         7 . A composition comprising (a) at least one compound according to Structure 1 
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , R 3 , R 4  and R 5 , which may be the same or different, are each independently H, OH, alkyl or alkoxy, provided that at least one of R 1 , R 2 , R 3 , R 4  and R 5  is not H, and wherein the alkyl or alkoxy groups, if present, are linear or branched and have from 1 to 8 carbon atoms and (b) at least one anti-cancer therapeutic active agent. 
     
     
         8 . The composition of  claim 7  wherein R 1  and R 2  are H and R 3 , R 4  and R 5 , which may be the same or different, are each independently H, OH, or C 1  to C 4  alkoxy, provided that at least one of R 3 , R 4  and R 5  is not H. 
     
     
         9 . The composition of  claim 7  wherein R 1  and R 2  are H and R 3 , R 4  and R 5 , which may be the same or different, are each independently H, OH, or OCH 3 ; provided at least one or two of R 3 , R 4  and R 5  is OH or OCH 3  or one of R 3 , R 4  and R 5  is OH and at least one of the remaining moieties is OH or OCH 3 . 
     
     
         10 . The composition of  claim 7  wherein the at least one compound according to Structure 1 is selected from the group consisting of:
 Compound 1 wherein R 1 ═R 2 =R 5 ═H; R 3 ═OH; and R 4 ═OCH 3 ; 
 Compound 2 wherein R 1 ═R 2 =R 4 ═R 5 ═H; and R 3 ═OCH 3 ; 
 Compound 3 wherein R 1 ═R 2 =R 4 ═R 5 ═H; and R 3 ═OH; 
 Compound 4 wherein R 1 ═R 2 =R 3 ═R 5 ═H; and R 4 ═OH; 
 Compound 5 wherein R 1 ═R 2 =R 3 ═R 5 ═H; and R 4 ═OCH 3 ; 
 Compound 6 wherein R 1 ═R 2 =R 3 ═R 4 ═H; and R 5 ═OH; 
 Compound 7 wherein R 1 ═R 2 =R 3 ═R 4 ═H; and R 5 ═OCH 3 ; and 
 Compound 8 wherein R 1 ═R 3 =R 5 ═H; and R 2 ═R 4 ═OH. 
 
     
     
         11 . The composition of  claim 7  wherein the compound according to Structure 1 is present in an effective amount for treating melanoma and/or non-melanoma skin cancer. 
     
     
         12 . The composition of  claim 7  wherein the at least one anti-cancer therapeutic active agent is a compound or composition know or believed to be effective in treating melanoma and/or non-melanoma skin cancer. 
     
     
         13 . The composition of  claim 12  wherein the at least one anti-cancer therapeutic active agent is selected from the group consisting of dacarbazine, an AMPK activator; an immune checkpoint inhibitor (ICI); a BRAF and/or MEK inhibitors, dabrafenib (Tafinlar), trametinib (Mekinist), vemurafenib (Zelboraf), cobimetinib (Cotellic), encorafenib (Braftovi), binimetinib (Mektovi), a PD-1 inhibitor, pembrolizumab (Keytruda), nivolumab (Opdivo), a CTLA-4 inhibitor, ipilimumab (Yervoy), and combinations of any two or more of the foregoing. 
     
     
         14 . The composition of  claim 7  further comprising a pharmaceutically acceptable carrier.