Macakurzin C Derivatives as a Novel Pharmacophore for Pan-Peroxisome Proliferator-Activated Receptor Modulator

被引：4
作者：
Ko, Hyejin [1 ]
An, Seungchan [1 ]
Jang, Hongjun [2 ]
Ahn, Sungjin [1 ]
Park, In Guk [1 ]
Hwang, Seok Young [1 ]
Gong, Junpyo [1 ]
Oh, Soyeon [1 ]
Kwak, Soo Yeon [2 ]
Choi, Won Jun [3 ]
Kim, Hyoungsu [2 ]
Noh, Minsoo [1 ]
机构：
[1] Seoul Natl Univ, Nat Prod Res Inst, Coll Pharm, Seoul 08826, South Korea
[2] Ajou Univ, Res Inst Pharmaceut Sci & Technol, Coll Pharm, Suwon 16499, South Korea
[3] Dongguk Univ Seoul, Coll Pharm, Goyang 10326, South Korea
来源：
BIOMOLECULES & THERAPEUTICS | 2023年 / 31卷 / 03期
基金：
新加坡国家研究基金会;
关键词：
Macakurzin C derivative; Peroxisome proliferator-activated receptor; Adiponectin; Human bone marrow mesenchymal stem cells; PPARa/? dual modulator; PPAR-GAMMA; INFLAMMATION; METABOLISM; AGONISTS; LIGANDS;
D O I：
10.4062/biomolther.2022.097
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The natural flavonoid macakurzin C (1) exhibited adiponectin biosynthesis-inducing activity during adipogenesis in human bone marrow mesenchymal stem cells and its molecular mechanism was directly associated with a pan-peroxisome proliferator-activat-ed receptor (PPAR) modulator affecting all three PPAR subtypes a, ?, and 6. In this study, increases in adiponectin biosynthesis -inducing activity by macakurzin C derivatives (2-7) were studied. The most potent adiponectin biosynthesis-inducing compound 6, macakurzin C 3,5-dimethylether, was elucidated as a dual PPARa/? modulator. Compound 6 may exhibit the most potent activity because of the antagonistic relationship between PPAR6 and PPAR?. Docking studies revealed that the O-methylation of macakurzin C to generate compound 6 significantly disrupted PPAR6 binding. Compound 6 has therapeutic potential in hypoadi-ponectinemia-related metabolic diseases.
引用
收藏
页码：312 / 318
页数：7
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