Synthesis and identification of 2,4-bisanilinopyrimidines bearing 2,2,6,6-tetramethylpiperidine-N-oxyl as potential Aurora A inhibitors |
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Authors: | Chun-Yan Sang Wen-Wen Qin Xiu-Juan Zhang Yu Xu You-Zhen Ma Xing-Rong Wang Ling Hui Shi-Wu Chen |
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Institution: | 1. School of Pharmacy, Lanzhou University, Lanzhou 730000, China;2. Experimental Center of Medicine, General Hospital of Lanzhou Military Command, Lanzhou 730050, China |
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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. |
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Keywords: | Aurora kinases Stable nitroxides Pyrimidine Anticancer agents |
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