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

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number114951
JournalEuropean Journal of Medicinal Chemistry
Volume246
DOIs
Publication statusPublished - 2023 Jan 15

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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