title: Synthesis of Phthalimide Derivatives as Potential PPAR-γ Ligands.
abstract: 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.
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Korea. god5425um@naver.com.
authors.forename: So Hyeon
authors.initials: SH
authors.lastname: Eom
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Korea. ls691392008@sina.com.
authors.forename: Sen
authors.initials: S
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Korea. sumingzhi0310@gmail.com.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Su
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Korea. notea151@naver.com.
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Noh
authors.affiliation: College of Pharmacy, Kyung Hee University, Seoul 02447, Korea. jhong@khu.ac.kr.
authors.forename: Jongki
authors.initials: J
authors.lastname: Hong
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Korea. nadkim@pusan.ac.kr.
authors.forename: Nam Deuk
authors.initials: ND
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Korea. hyjung@pusan.ac.kr.
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Korea. jhjung@pusan.ac.kr.
authors.forename: Min Hye
authors.initials: MH
authors.lastname: Yang
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Korea. mhyang@pusan.ac.kr.
authors.forename: Jee H
authors.initials: JH
authors.lastname: Jung
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D056945:Hep G2 Cells; D006801:Humans; D008024:Ligands; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D010797:Phthalimides / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats
chemical_list: D001572:Benzofurans; D008024:Ligands; D047495:PPAR gamma; D010797:Phthalimides; C037431:phthalimide; C082022:phthalide
keywords: 3T3-L1; PPAR-γ agonist; adipogenesis; paecilocin A; phthalimide; type 2 diabetes