Synthesis of Phthalimide Derivatives as Potential PPAR-γ Ligands

被引：13

作者：

Eom, So Hyeon ^{[1
]}

Liu, Sen ^{[1
]}

Su, Mingzhi ^{[1
]}

Noh, Tae Hwan ^{[1
]}

Hong, Jongki ^{[2
]}

Kim, Nam Deuk ^{[1
]}

Chung, Hae Young ^{[1
]}

Yang, Min Hye ^{[1
]}

Jung, Jee H. ^{[1
]}

机构：

[1] Pusan Natl Univ, Coll Pharm, Busan 46241, South Korea

[2] Kyung Hee Univ, Coll Pharm, Seoul 02447, South Korea

来源：

MARINE DRUGS | 2016年 / 14卷 / 06期

基金：

新加坡国家研究基金会;

关键词：

PPAR-gamma agonist; paecilocin A; type; 2; diabetes; phthalimide; adipogenesis; 3T3-L1; STIMULATION;

D O I：

10.3390/md14060112

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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

引用

页数：10

共 18 条

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