2. Academic Validation
  3. Synthesis and biological evaluation of 2,4-diaminopyrimidines as selective Aurora A kinase inhibitors

Synthesis and biological evaluation of 2,4-diaminopyrimidines as selective Aurora A kinase inhibitors

  • Eur J Med Chem. 2015 May 5:95:174-84. doi: 10.1016/j.ejmech.2015.03.044.
Wen-Wen Qin 1,  Chun-Yan Sang 1,  Lin-Lin Zhang 1,  Wei Wei 1,  Heng-Zhi Tian 1,  Huan-Xiang Liu 1,  Shi-Wu Chen 2,  Ling Hui 3
Affiliations

Affiliations

  • 1 School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
  • 2 School of Pharmacy, Lanzhou University, Lanzhou 730000, China. Electronic address: chenshw@lzu.edu.cn.
  • 3 Experimental Center of Medicine, General Hospital of Lanzhou Military Command, Lanzhou 730050, China; Key Laboratory of Stem Cells and Gene Drug of Gansu Province, General Hospital of Lanzhou Military Command, Lanzhou 730050, China.
PMID: 25812967 DOI: 10.1016/j.ejmech.2015.03.044
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. Here we synthesized 15 2,4-diaminopyrimidines and evaluated their biological activities, including antiproliferation, inhibition against Aurora kinases and cell cycle effects. These compounds generally exhibited more potent cytotoxicity against tumor cell lines compared with the VX-680 control, especially compound 11c, which showed the highest cytotoxicities, with IC50 values of 0.5-4.0 μM. Compound 11c had more than 35-fold more selectivity for Aurora A over Aurora B, and molecular docking analysis indicated that compound 11c form better interaction with Aurora A both from the perspective of structure and energy. Furthermore, compound 11c induced G2/M cell cycle arrest in HeLa cells. This series of compounds has the potential for further development as selective Aurora A inhibitors for Anticancer activity.

Keywords

Aurora kinase; Cell cycle; Kinase inhibitors; Pyrimidine.

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