Exploration and biological evaluation of 7-methoxy-3-methyl-1H-chromeno[4,3-c]pyrazol-4-one as an activating transcription factor 3 inducer for managing metabolic syndrome

Yi Han Chang, Heng Lin, Hsiao Fen Li, Hsi Hsien Chen, Hsin Yi Hung

研究成果: Article同行評審

2 引文 斯高帕斯(Scopus)

摘要

The induction of activating transcription factor 3 (ATF3) was identified as a promising therapeutic mechanism to overcome metabolic syndrome. Hence, a structure-activity relationship campaign on the chiral lead (1b) was conducted with a scaffold-hopping approach, whereby achiral 7-methoxy-3-methyl-1H-chromeno[4,3-c]pyrazol-4-one (16c) was recognized as a potential ATF3 inducer with a lipid-lowering feature in a pre-differentiated 3T3-L1 cell model. Also, in a high-fat diet scenario, mice subjected to 16c demonstrated robust weight loss with shrinkage of the white adipose mass and fewer hypertrophic adipocytes, accompanied by a preferable glycemic profile compared to 1b. Additionally, the biochemical analysis revealed that 16c further ameliorated the liver function and improved the plasma triglyceride profile that were absent from mice treated with 1b. Taken together, 16c shows promise as an ATF3 stimulant for further development to alleviate metabolic syndrome.

原文English
文章編號114951
期刊European Journal of Medicinal Chemistry
246
DOIs
出版狀態Published - 2023 1月 15

All Science Journal Classification (ASJC) codes

  • 藥理
  • 藥物發現
  • 有機化學

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