Synthesis and cytotoxic activity of chalcone analogues containing a thieno[2,3-d]pyrimidin-2-yl group as the A-ring or B-ring.
Bioorg Chem
; 94: 103346, 2020 01.
Article
en En
| MEDLINE
| ID: mdl-31645277
Many natural or synthetic chalcones have potential anti-tumor activity. Here, we synthesized two series of chalcone analogues containing a thieno[2,3-d]pyrimidin-2-yl group and evaluated for their cytotoxic activity towards cultured human lung cancer A549 and colorectal HCT-116 cells. Among them, compound 8d was the most cytotoxic against HCT-116 cells, with an IC50 value of 2.65⯵M. Analyses of the phenotypic changes induced by this compound found a dose-dependent accumulation of HCT-116 cells in sub-G1 phase, indicating that compound 8d might induce apoptosis. Furthermore, we found that 8d triggered mitochondrial membrane potential depolarization, promoted reactive oxygen species formation in HCT-116 cells, and increased the percentage of early and late apoptotic cells. Finally, immunoblotting indicated that 8d increased PARP-1 and caspases 3, 7 and 9 cleavage. These data suggest that compound 8d induces apoptosis via the mitochondrial death pathway.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirimidinas
/
Chalconas
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Año:
2020
Tipo del documento:
Article