2. Academic Validation
  3. Synthesis and identification of 2,4-bisanilinopyrimidines bearing 2,2,6,6-tetramethylpiperidine-N-oxyl as potential Aurora A inhibitors

Synthesis and identification of 2,4-bisanilinopyrimidines bearing 2,2,6,6-tetramethylpiperidine-N-oxyl as potential Aurora A inhibitors

  • Bioorg Med Chem. 2019 Jan 1;27(1):65-78. doi: 10.1016/j.bmc.2018.11.006.
Chun-Yan Sang 1,  Wen-Wen Qin 1,  Xiu-Juan Zhang 1,  Yu Xu 1,  You-Zhen Ma 1,  Xing-Rong Wang 1,  Ling Hui 2,  Shi-Wu Chen 3
Affiliations

Affiliations

  • 1 School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
  • 2 Experimental Center of Medicine, General Hospital of Lanzhou Military Command, Lanzhou 730050, China.
  • 3 School of Pharmacy, Lanzhou University, Lanzhou 730000, China. Electronic address: chenshw@lzu.edu.cn.
PMID: 30502115 DOI: 10.1016/j.bmc.2018.11.006
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.

Keywords

Anticancer agents; Aurora kinases; Pyrimidine; Stable nitroxides.

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