Potential anti-inflammatory actions of the elmiric (lipoamino) acids.
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.
Burstein
Sumner H
SH
Department of Biochemistry & Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, USA. sumner.burstein@umassmed.edu
Adams
Jeffrey K
JK
Bradshaw
Heather B
HB
Fraioli
Cristian
C
Rossetti
Ronald G
RG
Salmonsen
Rebecca A
RA
Shaw
John W
JW
Walker
J Michael
JM
Zipkin
Robert E
RE
Zurier
Robert B
RB
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
D000893:Anti-Inflammatory Agents; D005227:Fatty Acids; D007202:Indicators and Reagents; D010703:Phorbol Esters; D011448:Prostaglandin Antagonists; D000409:Alanine; D005998:Glycine