2. Academic Validation
  3. Design, synthesis and antitumor activity evaluation of trifluoromethyl-substituted pyrimidine derivatives

Design, synthesis and antitumor activity evaluation of trifluoromethyl-substituted pyrimidine derivatives

  • Bioorg Med Chem Lett. 2021 Nov 1:51:128268. doi: 10.1016/j.bmcl.2021.128268.
Limin Liu 1,  Zhengjie Wang 1,  Chao Gao 1,  Honglin Dai 1,  Xiaojie Si 1,  Yang Zhang 1,  Yaqi Meng 1,  Jiaxin Zheng 2,  Yu Ke 3,  Hongmin Liu 4,  Qiurong Zhang 5
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001, China.
  • 2 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou 450001, China.
  • 3 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou 450001, China. Electronic address: ky@zzu.edu.cn.
  • 4 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou 450001, China. Electronic address: liuhm@zzu.edu.cn.
  • 5 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou 450001, China. Electronic address: zqr409@yeah.net.
PMID: 34302974 DOI: 10.1016/j.bmcl.2021.128268
Abstract

In order to find efficient new antitumor drugs, a series of novel trifluoromethyl-substituted pyrimidine derivatives were designed and synthesized, and the bioactivity against four human tumor cells (PC-3, MGC-803, MCF-7 and H1975) was evaluated by MTT assay. Compound 17v displayed potent anti-proliferative activity on H1975 (IC50 = 2.27 μΜ), which was better than the positive control 5-FU (IC50 = 9.37 μΜ). Further biological evaluation studies showed that compound 17v induced Apoptosis of H1975 cells and arrested the cell cycle at G2/M phase. Furthermore, compound 17v induced H1975 cells Apoptosis through increasing the expression of pro-apoptotic proteins Bax and p53 and down-regulating the anti-apoptotic protein Bcl-2. In addition, compound 17v was able to be tightly embedded in the active pocket of EGFR. In summary, these results demonstrated that compound 17v has a potential as a lead compound for further investigation.

Keywords

Antitumor activity; Pyrimidine derivatives; Synthesis; Trifluoromethyl moiety.

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