Rational design and eco-friendly one-pot multicomponent synthesis of novel ethylidenehydrazineylthiazol-4(5H)-ones as potential apoptotic inducers targeting wild and mutant EGFR-TK in triple negative breast cancer.
Bioorg Chem
; 142: 106936, 2024 01.
Article
em En
| MEDLINE
| ID: mdl-37890211
ABSTRACT
A novel series of ethylidenehydrazineylthiazol-4(5H)-ones were synthesized using various eco-friendly one-pot multicomponent synthetic techniques. The anticancer activity of compounds (4a-m) was tested against 11 cancer cell lines. While the IC50 of all compounds was evaluated against the most sensitive cell lines (MDA-MB-468 and FaDu). Our SAR study pinpointed that compound 4a, having a phenyl substituent, exhibited a significant growth inhibition % against all cancer cell lines. The frontier anticancer candidates against the MDA-MB-468 were also examined against the wild EGFR (EGFR-WT) and mutant EGFR (EGFR-T790M) receptors. Most of the synthesized compounds exhibited a higher inhibitory potential against EGFR-T790M than the wild type of EGFR. Remarkably, compound 4k exhibited the highest inhibitory activity against both EGFR-WT and EGFR-T790M with IC50 values (0.051 and 0.021 µM), respectively. The pro-apoptotic protein markers (p53, BAX, caspase 3, caspase 6, caspase 8, and caspase 9) and the anti-apoptotic key marker (BCL-2) were also measured to propose a mechanism of action for the compound 4k as an apoptotic inducer for MDA-MB-468. Investigation of the cell cycle arrest potential of compound 4k was also conducted on MDA-MB-468 cancer cells. We also evaluated the inhibitory activities of compounds (4a-m) against both EGFR-WT and EGFR-T790M using two different molecular docking processes.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias de Mama Triplo Negativas
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Neoplasias Pulmonares
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Egito