Galangin 3-benzyl-5-methylether derivatives function as an adiponectin synthesis-promoting peroxisome proliferator-activated receptor γ partial agonist.
Bioorg Med Chem
; 54: 116564, 2022 01 15.
Article
em En
| MEDLINE
| ID: mdl-34922307
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) ß. Novel galangin derivatives were synthesized to improve adiponectin synthesis-promoting compounds by increasing the PPARγ activity of galangin and reducing its ERß activity, because PPARγ functions can be inhibited by ERß. 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 ERß. 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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Flavonoides
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PPAR gama
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Adiponectina
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Hipoglicemiantes
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article