2. Academic Validation
  3. Identification of putative metabolites of docosahexaenoic acid as potent PPARgamma agonists and antidiabetic agents

Identification of putative metabolites of docosahexaenoic acid as potent PPARgamma agonists and antidiabetic agents

  • Bioorg Med Chem Lett. 2005 Feb 1;15(3):517-22. doi: 10.1016/j.bmcl.2004.11.053.
Keiko Yamamoto 1,  Toshimasa Itoh,  Daijiro Abe,  Masato Shimizu,  Tomoatsu Kanda,  Takatoshi Koyama,  Masazumi Nishikawa,  Tadakazu Tamai,  Hiroshi Ooizumi,  Sachiko Yamada
Affiliations

Affiliation

  • 1 Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan. [email protected]
PMID: 15664804 DOI: 10.1016/j.bmcl.2004.11.053
Abstract

We found that putative metabolites of docosahexaenoic acid (DHA) are strong PPARgamma activators and potential antidiabetic agents. We designed DHA derivatives based on the crystal structure of PPARgamma, synthesized them and evaluated their activities in vitro and in vivo. The efficacy of 5E-4-hydroxy-DHA 2a as a PPARgamma activator was about fourfold stronger than that of pioglitazone. Furthermore, the 4-keto derivative (10b) showed antidiabetic activity in animal models without producing undesirable effects such as obesity and hepatotoxicity.

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