Macakurzin C Derivatives as a Novel Pharmacophore for Pan-Peroxisome Proliferator-Activated Receptor Modulator
  • Ko, Hyejin
  • An, Seungchan
  • Jang, Hongjun
  • Ahn, Sungjin
  • Park, In Guk
  • ... Choi, Won Jun
  • 외 6명
Citations

WEB OF SCIENCE

5
Citations

SCOPUS

5

초록

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.

키워드

Macakurzin C derivativePeroxisome proliferator-activated receptorAdiponectinHuman bone marrow mesenchymal stem cellsPPARa/? dual modulatorPPAR-GAMMAINFLAMMATIONMETABOLISMAGONISTSLIGANDS
제목
Macakurzin C Derivatives as a Novel Pharmacophore for Pan-Peroxisome Proliferator-Activated Receptor Modulator
저자
Ko, HyejinAn, SeungchanJang, HongjunAhn, SungjinPark, In GukHwang, Seok YoungGong, JunpyoOh, SoyeonKwak, Soo YeonChoi, Won JunKim, HyoungsuNoh, Minsoo
DOI
10.4062/biomolther.2022.097
발행일
2023-05
유형
Article
저널명
Biomolecules & Therapeutics
31
3
페이지
312 ~ 318