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Keywords = anthracenyl skeleton

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16 pages, 10592 KiB  
Article
Novel 9-Methylanthracene Derivatives as p53 Activators for the Treatment of Glioblastoma Multiforme
by Yuxin Feng, Yingjie Wang, Xiaoxue Li, Ziqiang Sun, Sihan Qiang, Hongbo Wang and Yi Liu
Molecules 2024, 29(10), 2396; https://doi.org/10.3390/molecules29102396 - 19 May 2024
Viewed by 1736
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Anticancer Drug Discovery and Development II)
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