2. Academic Validation
  3. Synthesis and evaluation of new 2-chloro-4-aminopyrimidine and 2,6-dimethyl-4-aminopyrimidine derivatives as tubulin polymerization inhibitors

Synthesis and evaluation of new 2-chloro-4-aminopyrimidine and 2,6-dimethyl-4-aminopyrimidine derivatives as tubulin polymerization inhibitors

  • Bioorg Med Chem Lett. 2018 Jun 1;28(10):1769-1775. doi: 10.1016/j.bmcl.2018.04.026.
Shaoyu Xu 1,  Baijiao An 2,  Yuxin Li 3,  Xunbang Luo 1,  Xingshu Li 4,  Xian Jia 5
Affiliations

Affiliations

  • 1 School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • 2 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
  • 3 School of Life Sciences & Biopharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • 4 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: lixsh@mail.sysu.edu.cn.
  • 5 School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: jiaxian@syphu.edu.cn.
PMID: 29673981 DOI: 10.1016/j.bmcl.2018.04.026
Abstract

Eighteen new 2-chloro-4-aminopyrimidine and 2,6-dimethyl-4-aminopyrimidine derivatives were synthesized and evaluated as tubulin polymerization inhibitor for the treatment of Cancer. Among them, compounds 10, 17, 20 and 21 exhibited potent antiproliferative activities against five human Cancer cell lines. Microtubule dynamics assay showed that compound 17 could effectively inhibit tubulin polymerization. Molecular docking studies were also carried out to understand the binding pattern. Further mechanism studies revealed that 17 could induce G2/M phase arrest, disrupt the organization of the cellular microtubule network and induce cell Apoptosis and mitochondrial dysfunction.

Keywords

Antiproliferative activity; Design and synthesis; Mechanism; Tubulin polymerization inhibitors.

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