Submitted to: Bioorganic and Medicinal Chemistry
Publication Type: Peer reviewed journal
Publication Acceptance Date: 1/25/2008
Publication Date: 1/31/2008
Citation: Mizuno, C.S., Ma, G., Khan, S., Patny, A., Avery, M.A., Rimando, A.M. 2008. Design, Synthesis, Biological Evaluation and Docking Studies of Pterostilbene Analogs Inside PPARa. Bioorganic and Medicinal Chemistry. 16:3800-3808. Interpretive Summary: Pterostilbene, a naturally occurring phenolic compound, was previously shown to decrease cholesterol levels of in animals and to activate the receptor PPARa. The chemical structure of pterostilbene was modified, with the objective of enhancing its activity. Among the compounds synthesized (E)-4-(3,5-dimethoxystyryl)phenyl dihydrogen phosphate showed activity higher than pterostilbene and ciprofibrate, a known lipid-lowering drug used as control in this study. Experiments to demonstrate fit in the active site of PPARa showed that the compounds synthesized had hydrogen bond interactions important for PPARa activation.
Technical Abstract: Pterostilbene, a naturally occurring analog of resveratrol, has previously shown PPARa activation in H4IIEC3 cells and was found to decrease cholesterol levels in animals. In this study, analogs of pterostilbene were synthesized and their ability to activate PPARa was investigated. Among the analogs (E)-4-(3,5-dimethoxystyryl)phenyl dihydrogen phosphate showed activity higher than those of pterostilbene and control drug ciprofibrate. Docking of the stilbenes inside PPARa showed the presence of important hydrogen bond interactions for PPARa activation.