title: Potential anti-inflammatory actions of the elmiric (lipoamino) acids.
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.
authors: Department of Biochemistry & Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, USA. sumner.burstein@umassmed.edu
authors: Sumner H
authors: SH
authors: Burstein
authors: Jeffrey K
authors: JK
authors: Adams
authors: Heather B
authors: HB
authors: Bradshaw
authors: Cristian
authors: C
authors: Fraioli
authors: Ronald G
authors: RG
authors: Rossetti
authors: Rebecca A
authors: RA
authors: Salmonsen
authors: John W
authors: JW
authors: Shaw
authors: J Michael
authors: JM
authors: Walker
authors: Robert E
authors: RE
authors: Zipkin
authors: Robert B
authors: RB
authors: Zurier
mesh_terms: D000409:Alanine / Q000737:chemistry; D000818:Animals; D000893:Anti-Inflammatory Agents; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002855:Chromatography, Thin Layer; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005227:Fatty Acids / Q000737:chemistry; D005998:Glycine / Q000737:chemistry; D007202:Indicators and Reagents; D008264:Macrophages / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D010703:Phorbol Esters; D011448:Prostaglandin Antagonists / Q000138:chemical synthesis / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D005227:Fatty Acids; D007202:Indicators and Reagents; D010703:Phorbol Esters; D011448:Prostaglandin Antagonists; D000409:Alanine; D005998:Glycine