2. Academic Validation
  3. Design, synthesis and biological evaluation of novel 2,4-bismorpholinothieno[3,2-d]pyrimidine and 2-morpholinothieno[3,2-d]pyrimidinone derivatives as potent antitumor agents

Design, synthesis and biological evaluation of novel 2,4-bismorpholinothieno[3,2-d]pyrimidine and 2-morpholinothieno[3,2-d]pyrimidinone derivatives as potent antitumor agents

  • Bioorg Chem. 2020 Jun;99:103796. doi: 10.1016/j.bioorg.2020.103796.
Tianyu Ye 1,  Yufei Han 1,  Ruxin Wang 1,  Pingzhen Yan 1,  Shaowei Chen 1,  Yunlei Hou 2,  Yanfang Zhao 3
Affiliations

Affiliations

  • 1 School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China.
  • 2 School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China. Electronic address: [email protected].
  • 3 School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China. Electronic address: [email protected].
PMID: 32283346 DOI: 10.1016/j.bioorg.2020.103796
Abstract

To develop novel therapeutic agents with Anticancer activities, two series of novel 2,4-bismorpholinyl-thieno[3,2-d]pyrimidine and 2-morpholinothieno[3,2-d]pyrimidinone derivatives were designed, synthesized and evaluated for their biological activities. Among them, compound A12 showed the most potent antitumor activities against HCT116, PC-3, MCF-7, A549 and MDA-MB-231 cell lines with IC50 values of 3.24 μM, 14.37 μM, 7.39 μM, 7.10 μM, and 16.85 μM, respectively. Further explorations in bioactivity were conducted to clarify the Anticancer mechanism of compound A12. The results showed that compound A12 obviously inhibited the proliferation of A549 cell lines and decreased mitochondrial membrane potential, which led to the Apoptosis of Cancer cells and suppressed the migration of tumor cells.

Keywords

Antiproliferative activities; PI3Kα; Synthesis; Thieno[3,2-d]pyrimidine.

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