Design, synthesis, and biological evaluation of chalcone acetamide derivatives against triple negative breast cancer.
Bioorg Med Chem Lett
; 107: 129795, 2024 Jul 15.
Article
en En
| MEDLINE
| ID: mdl-38750906
ABSTRACT
Chalcones are chemical scaffolds found in natural products, particularly in plants, and are considered for structural diversity in medicinal chemistry for drug development. Herein, we designed and synthesised novel acetamide derivatives of chalcone, characterizing them using 1H NMR, 13C NMR, HRMS, and IR spectroscopic methods. These derivatives were then screened against human cancer cells for cytotoxicity using the SRB assay. Among the tested derivatives, 7g, with a pyrrolidine group, exhibited better cell growth inhibition activity against triple-negative breast cancer (TNBC) cells. Further assays, including SRB, colony formation, and fluorescent dye-based microscopic analysis, confirmed that 7g significantly inhibited MDA-MB-231 cell proliferation. Furthermore, 7g promoted apoptosis by upregulating cellular reactive oxygen species (ROS) levels and disrupting mitochondrial membrane potential (MMP). Elevated expression of pro-apoptotic proteins (Bax and caspase-3) and a higher Bax/Bcl-2 ratio with downregulation of anti-apoptotic (Bcl-2) protein levels were observed in TNBC cells. The above results suggest that 7g can promote cellular death through apoptotic mechanisms in TNBC cells.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Ensayos de Selección de Medicamentos Antitumorales
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Diseño de Fármacos
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Apoptosis
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Proliferación Celular
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Neoplasias de la Mama Triple Negativas
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Acetamidas
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Antineoplásicos
Límite:
Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article