Author/Authors :
Keiko Yamamoto، نويسنده , , Toshimasa Itoh، نويسنده , , Daijiro Abe، نويسنده , , Masato Shimizu، نويسنده , , Tomoatsu Kanda، نويسنده , , Takatoshi Koyama، نويسنده , , Masazumi Nishikawa، نويسنده , , Tadakazu Tamai، نويسنده , , Hiroshi Ooizumi، نويسنده , , Sachiko Yamada، نويسنده ,
Abstract :
We found that putative metabolites of docosahexaenoic acid (DHA) are strong PPARγ activators and potential antidiabetic agents. We designed DHA derivatives based on the crystal structure of PPARγ, synthesized them and evaluated their activities in vitro and in vivo. The efficacy of 5E-4-hydroxy-DHA 2a as a PPARγ 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.
