Chen Hong, Wang Cai-Lu, Sun Tao, Zhou Zhan, Niu Jiang-Xiu, Tian Xiu-Mei, Yuan Mu
College of Food and Drug, Luoyang Normal University, Luoyang, Henan 471934, China.
School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, China.
Bioorg Med Chem Lett. 2018 May 15;28(9):1534-1539. doi: 10.1016/j.bmcl.2018.03.070. Epub 2018 Mar 26.
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 (IC < 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 a-ARs (α, α, and α) were further evaluated using dual-luciferase reporter assays, and the compounds 13 and 17 exhibited better a-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.
为了开发潜在的抗前列腺癌药物，已合成了24种新型萘哌地尔基芳基哌嗪衍生物，并通过光谱方法对其进行了表征。评估了它们对几种经典前列腺癌细胞系（包括PC-3、LNCaP和DU145）的抗肿瘤活性。在所有化合物中，9、13、17、21和27对DU145细胞表现出较强的细胞毒活性（IC＜1μM）。进一步测试证实，化合物17通过诱导细胞周期停滞在G0/G1期来抑制DU145细胞的生长。此外，使用双荧光素酶报告基因检测进一步评估了化合物（9、13、17、21和27）对α-ARs（α1A、α1B和α1D）的拮抗活性，化合物13和17表现出更好的α-ARs亚型选择性。对这些开发的芳基哌嗪衍生物的构效关系（SAR）进行了合理讨论。综上所述，这些结果表明进一步开发此类化合物可能具有重要意义。
