• Media type: E-Article
  • Title: Synthesis of Phthalimide Derivatives as Potential PPAR-γ Ligands
  • Contributor: Eom, So; Liu, Sen; Su, Mingzhi; Noh, Tae; Hong, Jongki; Kim, Nam; Chung, Hae; Yang, Min; Jung, Jee
  • Published: MDPI AG, 2016
  • Published in: Marine Drugs, 14 (2016) 6, Seite 112
  • Language: English
  • DOI: 10.3390/md14060112
  • ISSN: 1660-3397
  • Origination:
  • Footnote:
  • Description: Paecilocin A, a phthalide derivative isolated from the jellyfish-derived fungus Paecilomyces variotii, activates PPAR-γ (Peroxisome proliferator-activated receptor gamma) in rat liver Ac2F cells. Based on a SAR (Structure-activity relationships) study and in silico analysis of paecilocin A-mimetic derivatives, additional N-substituted phthalimide derivatives were synthesized and evaluated for PPAR-γ agonistic activity in both murine liver Ac2F cells and in human liver HepG2 cells by luciferase assay, and for adipogenic activity in 3T3-L1 cells. Docking simulation indicated PD6 was likely to bind most strongly to the ligand binding domain of PPAR-γ by establishing crucial H-bonds with key amino acid residues. However, in in vitro assays, PD1 and PD2 consistently displayed significant PPAR-γ activation in Ac2F and HepG2 cells, and adipogenic activity in 3T3-L1 preadipocytes.
  • Access State: Open Access