1. Academic Validation
  2. Galangin 3-benzyl-5-methylether derivatives function as an adiponectin synthesis-promoting peroxisome proliferator-activated receptor γ partial agonist

Galangin 3-benzyl-5-methylether derivatives function as an adiponectin synthesis-promoting peroxisome proliferator-activated receptor γ partial agonist

  • Bioorg Med Chem. 2022 Jan 15;54:116564. doi: 10.1016/j.bmc.2021.116564.
Hyejin Ko 1 Hongjun Jang 2 Seungchan An 1 In Guk Park 1 Sungjin Ahn 1 Junpyo Gong 1 Seok Young Hwang 1 Soyeon Oh 1 Soo Yeon Kwak 2 Won Jun Choi 3 Hyoungsu Kim 4 Minsoo Noh 5
Affiliations

Affiliations

  • 1 Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
  • 2 Research Institute of Pharmaceutical Science and Technology, College of Pharmacy, Ajou University, 206 World cup-ro, Yeongtong-gu, Suwon, Gyeonggi-do 16499, Republic of Korea.
  • 3 College of Pharmacy, Dongguk University-Seoul, 32 Dongguk-ro, Goyang, Gyeonggi-do 10326, Republic of Korea.
  • 4 Research Institute of Pharmaceutical Science and Technology, College of Pharmacy, Ajou University, 206 World cup-ro, Yeongtong-gu, Suwon, Gyeonggi-do 16499, Republic of Korea. Electronic address: hkimajou@ajou.ac.kr.
  • 5 Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea. Electronic address: minsoonoh@snu.ac.kr.
Abstract

The upregulation of Adiponectin production has been suggested as a novel strategy for the treatment of metabolic diseases. Galangin, a natural flavonoid, exhibited Adiponectin synthesis-promoting activity during adipogenesis in human bone marrow mesenchymal stem cells. In target identification, galangin bound both Peroxisome Proliferator-activated Receptor (PPAR) γ and Estrogen Receptor (ER) β. Novel galangin derivatives were synthesized to improve Adiponectin synthesis-promoting compounds by increasing the PPARγ activity of galangin and reducing its ERβ activity, because PPARγ functions can be inhibited by ERβ. Three galangin 3-benzyl-5-methylether derivatives significantly promoted Adiponectin production by 2.88-, 4.47-, and 2.76-fold, respectively, compared to the effect of galangin. The most potent compound, galangin 3-benzyl-5,7-dimethylether, selectively bound to PPARγ (Ki, 1.7 μM), whereas it did not bind to ERβ. Galangin 3-benzyl-5,7-dimethylether was identified as a PPARγ partial agonist in docking and pharmacological competition studies, suggesting that it may have diverse therapeutic potential in a variety of metabolic diseases.

Keywords

Adiponectin; Estrogen receptor beta; Galangin derivatives; Human bone marrow mesenchymal stem cells; Peroxisome proliferator-activated receptor gamma.

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