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- Title
Novel 9-Methylanthracene Derivatives as p53 Activators for the Treatment of Glioblastoma Multiforme.
- Authors
Feng, Yuxin; Wang, Yingjie; Li, Xiaoxue; Sun, Ziqiang; Qiang, Sihan; Wang, Hongbo; Liu, Yi
- 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.
- Subjects
GLIOBLASTOMA multiforme; DRUG development; P53 protein; BRAIN tumors; DRUG resistance
- Publication
Molecules, 2024, Vol 29, Issue 10, p2396
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules29102396