Novel inhibitors of arachidonic acid formation

Abstract

The invention relates to a novel class of inhibitors of arachidonic acid formation that can be useful for treating inflammatory conditions. Specifically, the invention relates to derivatives of sesamol that confer lower toxicity and increased circulatory lifetimes than pure sesamol.

1 . A method for reducing the level of arachidonic acid produced by Δ-5-desaturase (D5D) in a mammal, the method comprising administering to a mammal a composition comprising a non-toxic derivative of sesamol, wherein the non-toxic derivative of sesamol is an acylated sesamol. 
     
     
         2 . The method of  claim 1 , wherein the acylated sesamol is obtained by reacting a sesamol compound with an activated carboxylic acid. 
     
     
         3 . The method of  claim 2 , wherein the activated carboxylic acid is an acid chloride, an acid anhydride, or obtained by reacting a carboxylic acid with 1,1 carbonyl diimidazole. 
     
     
         4 . The method of  claim 3 , wherein the activated carboxylic acid is an activated fatty acid. 
     
     
         5 . The method of  claim 4 , wherein the activated fatty acid comprises 2 to 22 carbon atoms. 
     
     
         6 . The method of  claim 4 , wherein the degree of unsaturation of the activated fatty acid ranges from 0 to 6. 
     
     
         7 . The method of  claim 4 , wherein the activated fatty acid is an activated derivative of palmitic acid, oleic acid, linoleic acid, alpha-linolenic acid, arachidic acid, gadoleic acid, 5,8,11,14,17-eicosapentaenoic acid, or 4,7,10,13,16,19-docosahexaenoic acid. 
     
     
         8 . The method of  claim 1 , wherein the non-toxic derivative of sesamol is sesamol oleate. 
     
     
         9 . The method of  claim 1 , wherein the activated carboxylic acid is an acid chloride or an acid anhydride of CH 3 O(CH 2 CH 2 O) n CH 2 C(O)OH, or obtained by reacting CH 3 O(CH 2 CH 2 O) n CH 2 C(O)OH with 1,1 carbonyl diimidazole, wherein n ranges from 2 to 400. 
     
     
         10 . The method of  claim 1 , wherein the administering step is carried out enternally or parenternally. 
     
     
         11 . The method of  claim 1 , wherein the composition is prepared as a nutritional supplement in a form selected from the group consisting of a capsule, a bar, a tablet, a powder, and a beverage package. 
     
     
         12 . The method of  claim 1 , wherein the non-toxic derivative of sesamol is administered to the mammal in an amount that is effective to reduce the level of arachidonic acid in the mammal. 
     
     
         13 . The method of  claim 1 , wherein the composition further comprises a fish oil. 
     
     
         14 . The method of  claim 1 , wherein the composition further comprises one or more proteins and one or more carbohydrates, wherein the proteins and the carbohydrates are present at a ratio of between about 0.5 and about 1.0.