2. Academic Validation
  3. Synthesis, biological evaluation and SAR of naftopidil-based arylpiperazine derivatives

Synthesis, biological evaluation and SAR of naftopidil-based arylpiperazine derivatives

  • Bioorg Med Chem Lett. 2018 May 15;28(9):1534-1539. doi: 10.1016/j.bmcl.2018.03.070.
Hong Chen 1,  Cai-Lu Wang 1,  Tao Sun 1,  Zhan Zhou 1,  Jiang-Xiu Niu 1,  Xiu-Mei Tian 2,  Mu Yuan 3
Affiliations

Affiliations

  • 1 College of Food and Drug, Luoyang Normal University, Luoyang, Henan 471934, China.
  • 2 School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, China. Electronic address: chenwexpo@163.com.
  • 3 Pharmaceutical Research Center, Guangzhou Medical University, Guangzhou, Guangdong 511436, China. Electronic address: mryuanmu838@sina.com.
PMID: 29615343 DOI: 10.1016/j.bmcl.2018.03.070
Abstract

For the development of potential anti-prostate Cancer agents, 24 kinds of novel naftopidil-based arylpiperazine derivatives have been synthesized and characterized by spectroscopic methods. Their antitumor activities were evaluated against several classical prostate Cancer cell lines including PC-3, LNCaP, and DU145. Among all the compounds, 9, 13, 17, 21 and 27 showed strong cytotoxic activities against DU145 cells (IC50 < 1 μM). Further testing confirmed that compound 17 inhibited the growth of DU145 cells by inducing cell cycle arrest at G0/G1 phase. Besides, antagonistic activities of compounds (9, 13, 17, 21 and 27) towards a1-ARs (α1A, α1B, and α1D) were further evaluated using dual-luciferase reporter assays, and the compounds 13 and 17 exhibited better a1-ARs subtype selectivity. The structure-activity relationship (SAR) of these developed arylpiperazine derivatives was rationally discussed. Taken together, these results suggested that further development of such compounds may be of great interest.

Keywords

CCK-8; Derivatives; Prostate cancer; Structure-activity relationship; Synthesis.

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