| Autor: |
Feng Y; Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai 264005, China., Wang Y; Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai 264005, China., Li X; School of Chemistry and Chemical Engineering, Yantai University, Yantai 264005, China., Sun Z; School of Chemistry and Chemical Engineering, Yantai University, Yantai 264005, China., Qiang S; School of Chemistry and Chemical Engineering, Yantai University, Yantai 264005, China., Wang H; Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai 264005, China., Liu Y; School of Chemistry and Chemical Engineering, Yantai University, Yantai 264005, China. |
| Abstrakt: |
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 IC 50 values lower than 2 μM. Notably, 13e showed the best anti-glioma activity, with an IC 50 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. |
