Novel Pyrazole-Chalcone Hybrids: Synthesis and Computational Insights Against Breast Cancer.
Chem Biodivers
; 21(7): e202400015, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38705852
ABSTRACT
More women die of breast cancer than of any other malignancy. The resistance and toxicity of traditional hormone therapy created an urgent need for potential molecules for treating breast cancer effectively. Novel biphenyl-substituted pyrazole chalcones linked to a pyrrolidine ring were designed by using a hybridization approach. The hybrids were assessed against MCF-7 and MDA-MB-231 cells by NRU assay. Among them, 8 k, 8 d, 8 m, 8 h, and 8 f showed significantly potent IC50 values 0.17, 5.48, 8.13, 20.51, and 23.61â
µM) respectively, on MCF-7 cells compared to the positive control Raloxifene and Tamoxifen. Furthermore, most active compound 8 k [3-(3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)-1-(2-(2-(pyrrolidin-1-yl)-ethoxy)-phenyl)-chalcone] showed cell death induced through apoptosis, cell cycle arrest at the G2/M phase, and demonstrated decrease of ER-α protein in western blotting study. Docking studies of 8 k and 8 d established adequate interactions with estrogen receptor-α as required for SERM binding. The active hybrids exhibited good pharmacokinetic properties for oral bioavailability and drug-likeness. Whereas, RMSD, RMSF, and Rg values from Molecular dynamics studies stipulated stability of the complex formed between compound 8 k and receptor. All of these findings strongly indicate the antiproliferative potential of pyrazole-chalcone hybrids for the treatment of breast cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pirazoles
/
Neoplasias de la Mama
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Ensayos de Selección de Medicamentos Antitumorales
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Apoptosis
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Proliferación Celular
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Antineoplásicos
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Chem Biodivers
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
India