Novel 9-Methylanthracene Derivatives as p53 Activators for the Treatment of Glioblastoma Multiforme.
Molecules
; 29(10)2024 May 19.
Article
em En
| MEDLINE
| ID: mdl-38792257
ABSTRACT
Glioblastoma multiforme, a highly aggressive and lethal brain tumor, is a substantial clinical challenge and a focus of increasing concern globally. Hematological toxicity and drug resistance of first-line drugs underscore the necessity for new anti-glioma drug development. Here, 43 anthracenyl skeleton compounds as p53 activator XI-011 analogs were designed, synthesized, and evaluated for their cytotoxic effects. Five compounds (13d, 13e, 14a, 14b, and 14n) exhibited good anti-glioma activity against U87 cells, with IC50 values lower than 2 µM. Notably, 13e showed the best anti-glioma activity, with an IC50 value up to 0.53 µM, providing a promising lead compound for new anti-glioma drug development. Mechanistic analyses showed that 13e suppressed the MDM4 protein expression, upregulated the p53 protein level, and induced cell cycle arrest at G2/M phase and apoptosis based on Western blot and flow cytometry assays.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
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Proteína Supressora de Tumor p53
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Glioblastoma
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Antracenos
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Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article