Design and synthesis of marine fungal phthalide derivatives as PPAR-γ agonists

On the basis of a marine fungal phthalide (paecilocin A) skeleton, we synthesized 20 analogs and evaluated them for peroxisome proliferator-activated receptor gamma (PPAR-γ) binding and activation. Among these analogs, 6 and 7 had significant PPAR-γ binding activity, and 7 showed further PPAR-γ activation in rat liver Ac2F cells. In docking simulation, 7 formed H bonds with key amino acid residues of the PPAR-γ binding domain, and the overall positioning was similar to rosiglitazone. This new phthalide derivative is considered an interesting new molecular class of PPAR-γ ligands.

On the basis of a marine fungal phthalide (paecilocin A) skeleton, we synthesized 20 analogs and evaluated them for peroxisome proliferator-activated receptor gamma (PPAR-γ) binding and activation. Among these analogs, 6 and 7 had significant PPAR-γ binding activity, and 7 showed further PPAR-γ activation in rat liver Ac2F cells. In docking simulation, 7 formed H bonds with key PPAR-γ-binding domain amino acid residues, and the overall positioning was similar to rosiglitazone. This new phthalide derivative is considered an interesting new molecular class of PPAR-γ ligands.Figure optionsDownload as PowerPoint slide