Discovery of gemfibrozil analogues that activate PPARα and enhance the expression of gene CPT1A involved in fatty acids catabolism

• DOI: 10.1016/j.ejmech.2011.08.022
• Publication Date: 2011-08-25T04:31:54Z
• Authors: Barbara De Filippis; Antonella Giancri...; Alessandra Ammazz...; Alessandra D’Angelo; Marialuigia Fanta...; Letizia Giampietro; Cristina Maccallini; Michele Petruzzelli; Rosa Amoroso
• Keywords: 0303 health sciences; 03 medical and health sciences; Carnitine O-Palmitoyltransferase; Fatty Acids; Humans; PPAR alpha; Hep G2 Cells; Gemfibrozil; Up-Regulation

A new series of gemfibrozil analogues conjugated with α-asarone, trans-stilbene, chalcone, and their bioisosteric modifications were synthesized and evaluated to develop PPARα agonists. In this attempt, we have removed the methyls on the phenyl ring of gemfibrozil and introduced the above scaffolds in para position synthesizing two series of derivatives, keeping the dimethylpentanoic skeleton of gemfibrozil unaltered or demethylated. Four compounds exhibited good activation of the PPARα receptor and were also screened for their activity on PPARα-regulated gene CPT1A.