title: Synthesis and evaluation of 2,3-dinorprostaglandins: Dinor-PGD1 and 13-epi-dinor-PGD1 are peroxisome proliferator-activated receptor α/γ dual agonists.
abstract: 2,3-Dinorprostaglandins (dinor-PGs) have been regarded as β-oxidation products of arachidonic-acid-derived prostaglandins, but their biological activities in mammalian cells remain unclear. On the other hand, C18 polyunsaturated fatty acids (PUFAs), such as γ-linolenic acid (GLA), have various biological activities, and dinor-PGs are speculated to be biosynthesized from GLA. Here, we synthesized dinor-PGs that may possibly be derived from GLA and examined their activities towards peroxisome proliferator-activated receptors (PPARs). Dinor-PGD1 (1) and its epimer 13-epi-dinor-PGD1 (epi-1) were found to be dual agonists for PPARα/γ, whereas PGD2 derived from arachidonic acid is selective for PPARγ. Thus, GLA-derived dinor-PGs may have unique biological roles.
authors.affiliation: Sodeoka Live Cell Chemistry Project, ERATO, JST, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Ayato
authors.initials: A
authors.lastname: Sato
authors.forename: Kosuke
authors.initials: K
authors.lastname: Dodo
authors.forename: Makoto
authors.initials: M
authors.lastname: Makishima
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Mikiko
authors.initials: M
authors.lastname: Sodeoka
mesh_terms: D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D011453:Prostaglandins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D047493:PPAR alpha; D047495:PPAR gamma; D011453:Prostaglandins