Isolation, Purification, and Structure Elucidation of the Antiproliferative Compound Coibamide A

Abstract

Novel antiproliferative compounds, compositions comprising the same, and methods of use thereof are disclosed.

1 . A compound of formula I or a pharmaceutically acceptable salt thereof, wherein: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1 =Me, H 
         R 2 =Me, H 
         R 3 =L/D N,N-dimethylvaline, L/D valine, L/D leucine, L/D isoleucine, L/D allo-isoleucine 
         R 4 =O, NH, S, NMe R 5 =L/D 2-hydroxyisovaleric acid, L/D valine, L/D leucine, L/D isoleucine, L/D allo-isoleucine 
         R 6 =H, Me 
         R 7 =L/D serine, L/D O-methylserine 
         R 6 =H, Me 
         R 9 =L/D leucine, L/D valine, L/D isoleucine, L/D allo-isoleucine 
         R 10 =Me, H 
         R 11 =H, Me, CH 3 CH 2 —, CH 3 CH 2 CH 2 — 
         R 12 =O, N, S 
         R 13 =L/D alanine 
         R 14 =H, Me 
         R 15 =L/D tyrosine, L/D O-methyl tyrosine, L/D phenylalanine 
         R 16 =H, Me 
         R 17 =L/D leucine, L/D valine, L/D isoleucine, L/D allo-isoleucine 
         R 18 =H, Me 
         R 19 =L/D alanine 
         R 20 =H, Me 
         R 21 =L/D isoleucine, L/D allo-isoleucine, L/D leucine, L/D valine 
         R 22 =H, Me 
         R 23 =L/D serine, L/D O-methyl-serine 
         R 24 =H, Me, 
         wherein R 3 , R 5 , R 7 , R 9 , R 13 , R 15 , R 17 , R 19 , R 21 , R 23  are the amino acid side chains of the listed amino acids. 
       
     
     
         2 . The compound of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         3 . The compound of  claim 1 , wherein at least one of the amino acids of formula I are substituted with another amino acid. 
     
     
         4 . The compound of  claim 3 , wherein 1, 2, 3, 4, 5, 6, or 7 amino acids of formula I are substituted with another amino acid. 
     
     
         5 . A composition comprising at least one compound of  claim 1  and at least one pharmaceutically acceptable carrier. 
     
     
         6 . The composition of  claim 5 , further comprising at least one chemotherapeutic agent. 
     
     
         7 . A method for the treatment of cancer in a patient in need of such treatment comprising administering the composition of  claim 5 . 
     
     
         8 . The method of  claim 7 , further comprising the administration of at least one chemotherapeutic agent. 
     
     
         9 . The method of  claim 7 , wherein said cancer is selected from the group consisting of melanoma, lung cancer, leukemia, CNS cancer, colon cancer, renal cancer, prostate cancer, ovarian cancer, and breast cancer.