Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes targeting HSP90-HER2 axis in breast cancer cells.
Bioorg Med Chem
; 53: 116521, 2022 01 01.
Article
em En
| MEDLINE
| ID: mdl-34844036
ABSTRACT
Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes were designed as potential HSP90 inhibitors. A series of the compounds was synthesized by oximation of (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-ones followed by O-acylation with acylamidobenzoic acids. The obtained compounds showed an antiproliferative effect on three breast cancer cell lines (MCF7, MDA-MB-231 and HCC1954). Compound 16s exhibited high antiproliferative potency against HCC1954 breast cancer cells with the IC50 value of 6 µM was selected for in-depth evaluation. Compound 16s did not inhibit the growth of normal epithelial cells. We have demonstrated that the compound 16s can induce apoptosis in cancer cells via inhibition of HSP90 "client" proteins including a key oncogenic receptor, HER2/neu. Described here compounds can be considered for further basic and preclinical investigation as a part of HSP90/HER2-targeted therapies.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oxazóis
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Oximas
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Neoplasias da Mama
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Proteínas de Choque Térmico HSP90
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Antineoplásicos
Limite:
Female
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Humans
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Belarus