Fatty acid phenolic conjugates

• US 8,008,458 B2
• Filed: 03/27/2007
• Issued: 08/30/2011
• Est. Priority Date: 12/19/2002
• Status: Expired due to Fees

• Current Assignee: Indiana University Health Incorporated
• Original Assignee: Indiana University Health Incorporated
• Inventors: Stillwell, William, Siddiqui, Rafat, Zaloga, Gary P.
• Primary Examiner(s): Anderson; James
• Assistant Examiner(s): Vakili; Zohreh
• Application Number:
  US11/691,816
• Publication Number:
  US 20080004342A1
• Time in Patent Office: 1,617 Days
• Field of Search: 536/8, 549/403, 554/229
• US Class Current: 536/8
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07C 69/587 Monocarboxylic acid esters having at least two carbon-to-carbon double bonds
• CPC Class Codes: C07H 17/06 Benzopyran radicals

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.

Claims

1. 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.

2. The method of claim 1 wherein the mammalian cells are tumor cells.

3. The method of claim 1 wherein the fatty acid is ω

-3 long chain unsaturated or polyunsaturated fatty acid.

4. The method of claim 1 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.

5. The method of claim 1 wherein the phenol is a polyhydric phenol or a polynuclear phenol.

6. The method of claim 1 wherein the phenol is selected from the group consisting of:

resveratrol, quercetin, catechin, propofol, and genistein.

7. The method of claim 1 wherein the phenol is selected from the group of phenols consisting of resveratrol, catechins, flavonoids, and alpha-tocopherol.

8. 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.

9. 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.

10. The method of claim 9 wherein the fatty acid is a polyunsaturated fatty acid.

11. The method of claim 9 wherein the fatty acid is an ω

-3 long chain polyunsaturated fatty acid.

12. The method of claim 9 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.

13. The method of claim 9 wherein the phenol is a polyhydric phenol or a polynuclear phenol.

14. The method of claim 9 wherein the phenol is selected from the group consisting of:

resveratrol, quercetin, catechin, propofol, and genistein.

15. The method of claim 9 wherein the phenol is selected from the group consisting of:

resveratrol, quercetin, catechin, propofol, and genistein.

16. The method of claim 9 wherein the pharmaceutical formulation inhibits the tumor cell or malignant growth from metastasizing to a secondary tissue site, said secondary site involving connective tissue within the mammal.

17. 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.