2. Academic Validation
  3. 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.
PMID: 34922307 DOI: 10.1016/j.bmc.2021.116564
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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