Discovery of Novel N-(Anthracen-9-ylmethyl) Benzamide Derivatives as ZNF207 Inhibitors Promising in Treating Glioma.
J Med Chem
; 67(5): 3909-3934, 2024 Mar 14.
Article
em En
| MEDLINE
| ID: mdl-38377560
ABSTRACT
Targeting tumor stemness is an innovative approach to cancer treatment. Zinc Finger Protein 207 (ZNF207) is a promising target for weakening the stemness of glioma cells. Here, a series of novel N-(anthracen-9-ylmethyl) benzamide derivatives against ZNF207 were rationally designed and synthesized. The inhibitory activity was evaluated, and their structure-activity relationships were summarized. Among them, C16 exhibited the most potent inhibitory activity, as evidenced by its IC50 values ranging from 0.5-2.5 µM for inhibiting sphere formation and 0.5-15 µM for cytotoxicity. Furthermore, we found that C16 could hinder tumorigenesis and migration and promote apoptosis in vitro. These effects were attributed to the downregulation of stem-related genes. The in vivo evaluation demonstrated that C16 exhibited efficient permeability across the blood-brain barrier and potent efficacy in both subcutaneous and orthotopic glioma tumor models. Hence, C16 may serve as a potential lead compound targeting ZNF207 and has promising therapeutic potential for glioma.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glioma
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
J Med Chem
/
J. med. chem
/
Journal of medicinal chemistry
Assunto da revista:
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article