Fatty acid phenolic conjugates

Abstract

This invention relates to a biologically active formulation containing a conjugate of a fatty acid and a complex phenol. The fatty acid can be selected from a variety of fatty acids including acids have between 12 and 24 carbon atoms. The phenol can be a polynuclear phenol, a polyphenol or a polyfunctional phenol having a variety of substituents. The formulation can include pharmaceutically acceptable carrier, including diluent. The formulation can be provided in an active dosage form suitable to inhibit mammalian cell growth and/or metastasis of malignant cells. The formulation can be used to induce cytotoxicity in mammalian cells particularly tumor cells or to treat and prevent cellular injury or dysfunction.

What is claimed is:  
     
         1 . A composition comprising: a phenol ester of a fatty acid, formed of a phenol having greater than 11 carbons and a fatty acid having greater than 12 carbon atoms; and 
 a pharmaceutically acceptable carrier, said ester provided in a dosage form sufficient to induce cell cytotoxicity.    
     
     
         2 . The composition of  claim 1  wherein the fatty acid is a polyunsaturated fatty acid.  
     
     
         3 . The composition of  claim 2  wherein the fatty acid is an ω-3 long chain polyunsaturated fatty acid.  
     
     
         4 . The composition of  claim 1  wherein the fatty acid is selected from the group consisting of: lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, palmitoleic acid, oleic acid, linoleic acid, linolenic acid, and arachidonoic, docosahexanoic acid, and eicosopentenoic acid.  
     
     
         5 . The composition of  claim 1  wherein the phenol is a polyhydric phenol or a polynuclear phenol.  
     
     
         6 . The composition of  claim 1  wherein the phenol is selected from the group consisting of: resveratrol, quercetin, catechin, propofol, and genistein.  
     
     
         7 . The composition of  claim 1  wherein the phenol is selected from the group consisting of: resveratrol, quercetin, catechin, propofol, and genistein.  
     
     
         8 . A composition comprising: a phenol ester of a fatty acid, said phenol having greater than 11 carbons and said fatty acid having between 12 and 24 carbon atoms; and 
 a pharmaceutically acceptable carrier, said ester provided in a dosage form sufficient to induce cell cytotoxicity.    
     
     
         9 . The composition of  claim 8  wherein the fatty acid is an ω-3 long chain unsaturated or polyunsaturated fatty acid.  
     
     
         10 . The composition of  claim 8  wherein the phenol is a polyhydric phenol or a polynuclear phenol.  
     
     
         11 . The composition of  claim 8  wherein the phenol is selected from the group consisting of: resveratrol, quercetin, catechin, propofol, and genistein.  
     
     
         12 . The composition of  claim 8  wherein the phenol is selected from the group of phenols consisting of: resveratrol, catechins, flavonoids, and alpha-tocopherol.  
     
     
         13 . A method of treating mammalian cells, the method comprising administering to the cells a pharmaceutical formulation comprising a phenolic ester of a fatty acid in an amount effective to induce cytotoxicity in at least a portion of the cells.  
     
     
         14 . The method of  claim 13  wherein the mammalian cells are tumor cells.  
     
     
         15 . The method of  claim 13  wherein the fatty acid is ω-3 long chain unsaturated or polyunsaturated fatty acid  
     
     
         16 . The method of  claim 13  wherein the fatty acid is selected from the group of fatty acids consisting of: lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, palmitoleic acid, oleic acid, linoleic acid, linolenic acid, and arachidonoic, docosahexanoic acid, and eicosopentenoic acid.  
     
     
         17 . The method of  claim 13  wherein the phenol is a polyhydric phenol or a polynuclear phenol.  
     
     
         18 . The method of  claim 13  wherein the phenol is selected from the group consisting of: resveratrol, quercetin, catechin, propofol, and genistein.  
     
     
         19 . The method of  claim 13  wherein the phenol is selected from the group of phenols consisting of: resveratrol, catechins, flavonoids, and alpha-tocopherol.  
     
     
         20 . A method of treating mammalian cells, the method comprising: 
 administering to the cells a pharmaceutical formulation comprising a phenolic ester of a fatty acid in an amount effective to modulate cell injury or cell dysfunction or both.    
     
     
         21 . A method of inhibiting metastasis of malignant tumor cells or a malignant growth in a mammal, said method comprising administering to the mammal a pharmaceutical formulation comprising an effective amount of a phenolic ester of a fatty acid in a pharmaceutically acceptable carrier to inhibit the tumor cell or malignant growth from metastasizing to a secondary tissue site.  
     
     
         22 . The method of  claim 21  wherein the fatty acid is a polyunsaturated fatty acid.  
     
     
         23 . The method of  claim 21  wherein the fatty acid is an ω-3 long chain polyunsaturated fatty acid.  
     
     
         24 . The method of  claim 21  wherein the fatty acid is selected from the group consisting of: lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, palmitoleic acid, oleic acid, linoleic acid, linolenic acid, and arachidonoic, docosahexanoic acid, and eicosopentenoic acid.  
     
     
         25 . The method of  claim 21  wherein the phenol is a polyhydric phenol or a polynuclear phenol.  
     
     
         26 . The method of  claim 21  wherein the phenol is selected from the group consisting of: resveratrol, quercetin, catechin, propofol, and genistein.  
     
     
         27 . The method of  claim 21  wherein the phenol is selected from the group consisting of: resveratrol, quercetin, catechin, propofol, and genistein.  
     
     
         28 . The method of  claim 21  wherein the pharmaceutical formulation inhibits attachment of malignant cells to connective tissue at a site secondary to an initial site of invasion within the mammal.  
     
     
         29 . A composition comprising: 
 a histidyl conjugate of a fatty acid, said hystidyl having greater than 6 carbons and said fatty acid having between 12 and 24 carbon atoms; and    a pharmaceutically acceptable carrier, said ester provided in a dosage form sufficient to induce cell cytotoxicity.    
     
     
         30 . The composition of  claim 28  wherein the fatty acid is an ω-3 long chain polyunsaturated fatty acid.  
     
     
         31 . A method of treating mammalian cells, the method comprising administering to the cells a pharmaceutical formulation comprising a histidyl conjugate of a fatty acid in an amount effective to modulate cell injury or cell dysfunction or both.