Synthesis and in vitro cytotoxicity of benzoxazole-based PPARα/γ antagonists in colorectal cancer cell lines.
Arch Pharm (Weinheim)
; 357(9): e2400086, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-38807029
ABSTRACT
A series of benzoxazole-based amides and sulfonamides were synthesized and evaluated for their human peroxisome proliferator-activated receptor (PPAR)α and PPARγ activity. All tested compounds showed a dual antagonist profile on both PPAR subtypes; based on transactivation results, seven compounds were selected to test their in vitro antiproliferative activity in a panel of eight cancer cell lines with different expression rates of PPARα and PPARγ. 3f was identified as the most cytotoxic compound, with higher potency in the colorectal cancer cell lines HT-29 and HCT116. Compound 3f induced a concentration-dependent activation of caspases and cell-cycle arrest in both colorectal cancer models. Docking experiments were also performed to shed light on the putative binding mode of this novel class of dual PPARα/γ antagonists.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Benzoxazoles
/
Neoplasias Colorrectales
/
PPAR alfa
/
PPAR gamma
/
Proliferación Celular
/
Simulación del Acoplamiento Molecular
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Arch Pharm (Weinheim)
Año:
2024
Tipo del documento:
Article
País de afiliación:
España
Pais de publicación:
Alemania