title: Synthesis and evaluation of fatty acid amides on the N-oleoylethanolamide-like activation of peroxisome proliferator activated receptor α.
abstract: A series of fatty acid amides were synthesized and their peroxisome proliferator-activated receptor α (PPAR-α) agonistic activities were evaluated in a normal rat liver cell line, clone 9. The mRNAs of the PPAR-α downstream genes, carnitine-palmitoyltransferase-1 and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase, were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) as PPAR-α agonistic activities. We prepared nine oleic acid amides. Their PPAR-α agonistic activities were, in decreasing order, N-oleoylhistamine (OLHA), N-oleoylglycine, Oleamide, N-oleoyltyramine, N-oleoylsertonin, and Olvanil. The highest activity was found with OLHA. We prepared and evaluated nine N-acylhistamines (N-acyl-HAs). Of these, OLHA, C16:0-HA, and C18:1Δ(9)-trans-HA showed similar activity. Activity due to the different chain length of the saturated fatty acid peaked at C16:0-HA. The PPAR-α antagonist, GW6471, inhibited the induction of the PPAR-α downstream genes by OLHA and N-oleoylethanolamide (OEA). These data suggest that N-acyl-HAs could be considered new PPAR-α agonists.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takao
authors.forename: Kaori
authors.initials: K
authors.lastname: Noguchi
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Akira
authors.initials: A
authors.lastname: Shirahata
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Sugita
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D005227:Fatty Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D047493:PPAR alpha / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000577:Amides; D005227:Fatty Acids; D047493:PPAR alpha; D012333:RNA, Messenger