Title

Potential anti-inflammatory actions of the elmiric (lipoamino) acids

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Department of Medicine, Division of Rheumatology

Publication Date

3-27-2007

Document Type

Article

Subjects

Alanine; Animals; *Anti-Inflammatory Agents; Cell Line; Cell Proliferation; Chromatography, Thin Layer; Drug Evaluation, Preclinical; Edema; Fatty Acids; Glycine; Indicators and Reagents; Macrophages; Magnetic Resonance Spectroscopy; Male; Mice; Phorbol Esters; Prostaglandin Antagonists; Spectrophotometry, Ultraviolet; Structure-Activity Relationship

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

A library of amino acid-fatty acid conjugates (elmiric acids) was synthesized and evaluated for activity as potential anti-inflammatory agents. The compounds were tested in vitro for their effects on cell proliferation and prostaglandin production, and compared with their effects on in vivo models of inflammation. LPS stimulated RAW 267.4 mouse macrophage cells were the in vitro model and phorbol ester-induced mouse ear edema served as the principal in vivo model. The prostaglandin responses were found to be strongly dependent on the nature of the fatty acid part of the molecule. Polyunsaturated acid conjugates produced a marked increase in media levels of i15-deoxy-PGJ(2) with minimal effects on PGE production. It is reported in the literature that prostaglandin ratios in which the J series predominates over the E series promote the resolution of inflammatory conditions. Several of the elmiric acids tested here produced such favorable ratios suggesting that their potential anti-inflammatory activity occurs via a novel mechanism of action. The ear edema assay results were generally in agreement with the prostaglandin assay findings indicating a connection between them.

Rights and Permissions

Citation: Bioorg Med Chem. 2007 May 15;15(10):3345-55. Epub 2007 Mar 13. Link to article on publisher's site

DOI of Published Version

10.1016/j.bmc.2007.03.026

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Bioorganic and medicinal chemistry

PubMed ID

17383881