Macakurzin C Derivatives as a Novel Pharmacophore for Pan-Peroxisome Proliferator-Activated Receptor Modulator
10.4062/biomolther.2022.097
- Author:
Hyejin KO
1
;
Seungchan AN
;
Hongjun JANG
;
Sungjin AHN
;
In Guk PARK
;
Seok Young HWANG
;
Junpyo GONG
;
Soyeon OH
;
Soo Yeon KWAK
;
Won Jun CHOI
;
Hyoungsu KIM
;
Minsoo NOH
Author Information
1. College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, Republic of Korea
- Publication Type:Original Article
- From:Biomolecules & Therapeutics
2023;31(3):312-318
- CountryRepublic of Korea
- Language:English
-
Abstract:
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-activated receptor (PPAR) modulator affecting all three PPAR subtypes α, γ, and δ. In this study, increases in adiponectin biosynthesisinducing 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 PPARα/γ modulator. Compound 6 may exhibit the most potent activity because of the antagonistic relationship between PPARδ and PPARγ. Docking studies revealed that the O-methylation of macakurzin C to generate compound 6 significantly disrupted PPARδ binding. Compound 6 has therapeutic potential in hypoadiponectinemia-related metabolic diseases.
