Efficient synthesis and antitumor evaluation of 4-aminomethyl-N-arylpyrazoles: Discovery of potent and selective agents for ovarian cancer.
Bioorg Med Chem
; 29: 115835, 2021 01 01.
Article
en En
| MEDLINE
| ID: mdl-33214037
ABSTRACT
A new one-pot two-step sequential methodology for synthesis of novel 3-carboxyethyl 4-[(tert-butylamino)methyl]-N-arylpyrazole derivatives is reported. One-pot transformation of ß-enamino diketones and arylhydrazines generated 4-iminium-N-arylpyrazole salt intermediates in situ, which were easily transformed into 4-[(tert-butylamino)methyl]-N-arylpyrazole derivatives by NaBH3CN. The products could be isolated in the free or hydrochloride salt forms. Also, it was possible to obtain the products in the zwitterionic form by ester group hydrolysis. Furthermore, all synthesised compounds were evaluated in vitro against a panel of eight human tumor cell lines. The 4-[(tert-butylamino)methyl]-N-arylpyrazole derivatives were much more powerful than the hydrochloride and zwitterionic forms. Moreover, the results suggest that the N-aryl group at the pyrazole ring is vital for modulating antiproliferative activity. The 3-carboxyethyl 4-[(tert-butylamino)methyl]-N-phenylpyrazoles 3a-g exhibited higher inhibitory activities against OVCAR-3, with GI50 values of 0.013-8.78⯵M, and lower inhibitory activities against normal human cell lines. Molecular docking was performed to evaluate the probable binding mode of 3a into active site of CDK2.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
/
Pirazoles
/
Descubrimiento de Drogas
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Antineoplásicos
Límite:
Female
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Brasil