Sesamol Derivatives as Novel Inhibitors of Arachidonic Acid Formation

a technology of arachidonic acid and derivatives, which is applied in the direction of drug compositions, metabolic disorders, cardiovascular disorders, etc., can solve the problems of difficult synthesizing, potential toxicity of sesamol, and toxicity of sesame lignans, so as to reduce or completely eliminate the toxicity of sesamol

Inactive Publication Date: 2009-01-08
SEARS BARRY D
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0004]It has been discovered that the toxicity of sesamol can be reduced or completely eliminated by preparing a carboxylic derivative of sesamol without compromising its inhibitory effect on Δ-5-desaturase (D5D).
[0006]In some embodiments, the carboxylic derivative may comprise at least one fatty acid. In other embodiments, the carboxylic derivative may comprise a carboxylic acid derivative of polyethylene oxide, i.e., a polyethylene oxide with at least one carboxylic acid terminal group. Both types of derivatives allow sesamol to be released slowly in its active form, thus reducing any potential toxicity of the composition. Such controlled release of sesamol also helps to modulate the activity of D5D in a more consistent fashion.

Problems solved by technology

Unfortunately, sesamol is believed to be potentially toxic.
Additionally, although natural compounds such as sesame lignans and curcumin have been demonstrated to exhibit inhibitory activity on D5D, their complex structures make them difficult to synthesize.
Furthermore, sesame lignans also have potential toxicity.

Method used

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  • Sesamol Derivatives as Novel Inhibitors of Arachidonic Acid Formation
  • Sesamol Derivatives as Novel Inhibitors of Arachidonic Acid Formation
  • Sesamol Derivatives as Novel Inhibitors of Arachidonic Acid Formation

Examples

Experimental program
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Effect test

example 1

Acylated Sesamol Derivatives

[0019]Fatty acid is activated using a 1:1 molar amount of 1,1 carbonyl diimidazole in a dry benzene solution. The solution is taken to dryness at the completion of the activation. To the dried compound is added an equimolar amount of sesamol. The combined reactants are heated under vacuum at a low temperature for 1-2 hours. The completeness of the reaction is determined by thin layer chromatography. The acylated sesamol is then isolated by column chromatography to yield the isolated invention. The physical state of the invention depends on the chain length of the fatty acid and its degree of unsaturation.

example 2

Preparation of Sesamol Oleate

[0020]17.7 mmoles of oleic acid was dissolved in 40 ml of dry benzene. To the mixture was added 17.7 mmoles of 1,1 carbonyldiimidazole. The reaction to activate the oleic acid was continued at room temperature until vigorous evolution of carbon monoxide has ceased. The reaction was then driven to completion by driving off the excess benzene under vacuum at 60° C. To the neat activated oleic acid was added 21 mmoles of sesamol. The mixture was heated at 60° C. for 2 hours under vacuum with constant rotation. The crude reaction mixture was purified using 50 grams of silica gel 60 in 2×44 cm column eluting with hexane and increasing percentages of acetone. The fractions containing the active compound were collected and evaporated to dryness giving 10 mmoles of the sesamol oleate for a 56% yield. HPLC chromatography using a 98:2 cyclohexanone / isopropyl eluting solvent give a single component with greater than 90% purity.

example 3

Polyethylene Oxide Sesamol Derivatives

[0021]Methoxy polyethylene oxide molecules of various chain lengths are oxidized by KMnO4 to yield a carboxylic acid derivative. The carboxylic acid derivative of methoxy polyethylene oxide is activated using a 1:1 molar amount of 1,1 carbonyl diimidazole in a dry benzene solution. The solution is taken to dryness at the completion of the activation. To the dried compound is added an equimolar amount of sesamol. The combined reactants are heated under vacuum at a low temperature for 1-2 hours. The completeness of the reaction is determined by thin layer chromatography. The acylated sesamol is then isolated by column chromatography to yield the isolated invention. The physical state of the invention depends on the chain length of the methoxy polyethylene oxide molecule.

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Abstract

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

Description

FIELD OF INVENTION[0001]The invention relates to compositions and methods for treating, moderating, and preventing inflammation. Specifically, the invention relates to compositions useful for inhibiting the formation of arachidonic acids, which are precursors of pro-inflammatory eicosanoids. The invention also relates to methods of preparing and administering such compositions.BACKGROUND OF THE INVENTION[0002]It is becoming increasingly recognized that increased inflammation is strongly associated with, if not the underlying cause of, many disease conditions including obesity, type 2 diabetes, cancer, heart disease, and neurological conditions such as multiple sclerosis and Alzheimer's disease.[0003]It has been shown that the regulation of certain eicosanoids, a class of biologically active metabolites, can help control inflammation. While many anti-inflammatory drugs directly target the production of pro-inflammatory eicosanoids, e.g., by inhibiting the enzyme required in their pro...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/36A61P29/00
CPCA61K31/36A61K31/75A61K45/06A61K31/357A61K31/77A23L33/10A61P25/00A61P25/28A61P29/00A61P3/04A61P35/00A61P43/00A61P9/00A61P3/10A23L2/52A23V2002/00
Inventor SEARS, BARRY D.
Owner SEARS BARRY D
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