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.
Eur J Med Chem
; 246: 114951, 2023 Jan 15.
Article
en En
| MEDLINE
| ID: mdl-36455354
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Síndrome Metabólico
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Eur J Med Chem
Año:
2023
Tipo del documento:
Article