Biomolecules & Therapeutics
Macakurzin C Derivatives as a Novel Pharmacophore for Pan-Peroxisome Proliferator-Activated Receptor Modulator
Hyejin Ko1,†, Seungchan An1,†, Hongjun Jang2, Sungjin Ahn1, In Guk Park1, Seok Young Hwang1, Junpyo Gong1, Soyeon Oh1, Soo Yeon Kwak2, Won Jun Choi3, Hyoungsu Kim2,* and Minsoo Noh1,*
1College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826,
2Research Institute of Pharmaceutical Science and Technology, College of Pharmacy, Ajou University, Suwon 16499,
3College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of Korea
*E-mail: (Noh M), (Kim H)
Tel: +82-2-880-2481 (Noh M), +82-31-219-3448 (Kim H)
The first two authors contributed equally to this work.
Received: July 19, 2022; Revised: September 2, 2022; Accepted: September 5, 2022; Published online: November 16, 2022.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords: Macakurzin C derivative, Peroxisome proliferator-activated receptor, Adiponectin, Human bone marrow mesenchymal stem cells, PPARα/γ dual modulator

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