Novel phospholipid analogues of pan-PPAR activator tetradecylthioacetic acid are more PPAR alpha selective.

Abstract

Tetradecylthioacetic acid (TTA) is a modified fatty acid that appears to improve insulin sensitivity, lower blood lipid levels, enhance fatty acid oxidation and promote anti-inflammatory action in vivo, through mechanisms partly dependent upon peroxisome proliferator-activated receptors (PPARs). In order to improve the biological efficacy of TTA as a PPAR agonist, two novel phospholipid analogue lyso tetradecylthioacetyl-L-alpha-phosphatidylcholine and di-tetradecylthioacetyl-L-alpha-phosphatidylglycerol have been developed. Here we report on the syntheses of these novel phospholipids and their relative potential to act as PPAR agonists in vitro, in comparison to TTA and other positive controls.

• Authors: Yushma Bhurruth-Alcor, Therese H Rost, Michael R Jorgensen, Rajender, Melanie Müller, Jon Skorve, Rolf K Berge, Andrew D Miller
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 20 Issue 3 Pg. 1252-5 (Feb 01 2010) ISSN: 1464-3405 [Electronic] England
• PMID: 20036122 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Chemical References

• PPAR alpha
• Peroxisome Proliferator-Activated Receptors
• Phospholipids
• Sulfides
• 1-(carboxymethylthio)tetradecane

Topics

• Animals
• Cell Line
• Humans
• PPAR alpha (metabolism)
• Peroxisome Proliferator-Activated Receptors (agonists, metabolism)
• Phospholipids (chemical synthesis, metabolism, pharmacology)
• Rats
• Rats, Wistar
• Sulfides (chemistry, pharmacology)