Anticancer activity of N-heteroaryl acetic acid salts against breast cancer; in silico and in vitro investigation.
Mol Biol Rep
; 49(1): 363-372, 2022 Jan.
Article
em En
| MEDLINE
| ID: mdl-34714485
ABSTRACT
BACKGROUND:
The present research was performed to assess N-heteroaryl acetic acid salts' anticancer activity against the breast cancer cell in order to introduce new inhibitory agents for histone deacetylase. METHODS ANDRESULTS:
A molecular docking simulation was performed to design the rational novel compounds. Afterward, the best compounds were selected for synthesis. The cytotoxic effects and mechanism of action have been studied via (Methyl Thiazol-Tetrazolium) MTT assay. Flow cytometry and gene expression analyses were performed to introduce an effective acetic acid derivative as an anticancer agent. Molecular docking simulations demonstrated that all compounds have the best interaction with histone deacetylase. The fold changes of Bcl-2, Bak, Bim, Caspase-3, and Caspase-8 gene expressions were investigated and compared with reference gene using real-time PCR. The cytotoxic studies showed the best anticancer activity of 4-benzyl-1-(carboxymethyl) pyridinium bromide (compound 2) with a low IC50 value (32 µM, p < 0.05). Also, the best anti HDAC activity was obtained for compound 2 with IC50 value of 1.1 µM. Furthermore, this compound showed a high percentage of apoptosis among all tested compounds after 72 h incubation which was associated with the significant increase in mRNA level of Bim, Bax, Bak, Caspase-3, and Caspase-8 and the considerable decrease in Bcl2 gene expression.CONCLUSION:
These results suggest that compound 2 with the benzyl ring could be an effective anticancer compound for further investigation in breast cancer treatment.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos de Piridínio
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Neoplasias da Mama
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Inibidores de Histona Desacetilases
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Histona Desacetilases
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Antineoplásicos
Limite:
Female
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Humans
Idioma:
En
Revista:
Mol Biol Rep
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Irã