1. Synthesis and identification of 2,4-bisanilinopyrimidines bearing 2,2,6,6-tetramethylpiperidine-N-oxyl as potential Aurora A inhibitors.
- Author
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Sang, Chun-Yan, Qin, Wen-Wen, Zhang, Xiu-Juan, Xu, Yu, Ma, You-Zhen, Wang, Xing-Rong, Hui, Ling, and Chen, Shi-Wu
- Subjects
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AURORA kinases , *CELL lines , *MOLECULAR docking , *APOPTOSIS , *CELL cycle - Abstract
Graphical abstract A series of stable nitroxyl radicals labeled 2,4-diaminopyrimidines exert their anti-proliferations in human tumor cell lines through targeting inhibition of Aurora A kinases. Highlights • 2,4-Bisanilinopyrimidines bearing nitroxides display potent anti-proliferations. • Compound 10a shows selectivity inhibitions for Aurora A over Aurora B. • Compound 10a disrupt the spindle formation. • Compound 10a blocks G2/M cell cycle arrest in HeLa cells. • Compound 10a induces apoptosis in HeLa cells. Abstract The Aurora kinases are a family of serine/threonine kinases that interact with components of the mitotic apparatus and serve as potential therapeutic targets in oncology. Herein, we reported a series of 2,4-bisanilinopyrimidines bearing 2,2,6,6-tetramethylpiperidine- N -oxyl with selective inhibition of Aurora A in either enzymatic assays or cellular phenotypic assays, and displaying more potent anti-proliferation compared with that of VX-680. The most potent compound 10a forms better interaction with Aurora A than Aurora B in molecular docking. Mechanistic studies revealed that 10a disrupt the spindle formation, block the cell cycle progression in the G2/M phase and induce apoptosis in HeLa cell. These results suggested that the produced series of compounds are potential anticancer agents for further development as selective Aurora A inhibitors. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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