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Synthesis of Phthalimide Derivatives as Potential PPAR-? Ligands.

ABSTRACT: Paecilocin A, a phthalide derivative isolated from the jellyfish-derived fungus Paecilomyces variotii, activates PPAR-? (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-? 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-? by establishing crucial H-bonds with key amino acid residues. However, in in vitro assays, PD1 and PD2 consistently displayed significant PPAR-? activation in Ac2F and HepG2 cells, and adipogenic activity in 3T3-L1 preadipocytes.

SUBMITTER: Eom SH

PROVIDER: S-EPMC4926071 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Synthesis of Phthalimide Derivatives as Potential PPAR-γ Ligands.

Eom So Hyeon SH Liu Sen S Su Mingzhi M Noh Tae Hwan TH Hong Jongki J Kim Nam Deuk ND Chung Hae Young HY Yang Min Hye MH Jung Jee H JH

Marine drugs 20160608 6

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 a ...[more]

PMID: 27338418

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