Novel phospholipid analogues of pan-PPAR activator tetradecylthioacetic acid are more PPAR alpha selective.
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.
Bhurruth-Alcor
Yushma
Y
Department of Chemistry, Imperial College Genetic Therapies Centre, Imperial College London, London SW7 2AZ, UK.
Rost
Therese H
TH
Jorgensen
Michael R
MR
Rajender
Müller
Melanie
M
Skorve
Jon
J
Berge
Rolf K
RK
Miller
Andrew D
AD
D000818:Animals; D002460:Cell Line; D006801:Humans; D047493:PPAR alpha / Q000378:metabolism*; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists* / Q000378:metabolism; D010743:Phospholipids / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000737:chemistry* / Q000494:pharmacology*
D047493:PPAR alpha; D047492:Peroxisome Proliferator-Activated Receptors; D010743:Phospholipids; D013440:Sulfides; C062078:1-(carboxymethylthio)tetradecane