基于萘哌地尔的含溴苯酚部分的芳基哌嗪衍生物的合成及药理学评价。
Synthesis and pharmacological evaluation of naftopidil-based arylpiperazine derivatives containing the bromophenol moiety.
机构信息
Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Luoyang Key Laboratory of Organic Functional Molecules, College of Food and Drug, Luoyang Normal University, Luoyang, 471934, China.
出版信息
Pharmacol Rep. 2020 Aug;72(4):1058-1068. doi: 10.1007/s43440-019-00041-w. Epub 2020 Jan 23.
BACKGROUND
Prostate cancer (PCa) is the most common malignancy in men and in the absence of any effective treatments available.
METHODS
For the development of potential anticancer agents, 24 kinds of naftopidil-based arylpiperazine derivatives containing the bromophenol moiety were synthesized and characterized by using spectroscopic methods. Their pharmacological activities were evaluated against human PCa cell lines (PC-3 and LNCaP) and a-adrenergic receptors (a-ARs; α, α, and α-ARs). The structure-activity relationship of these designed arylpiperazine derivatives was rationally explored and discussed.
RESULTS
Among these derivatives, 3c, 3d, 3h, 3k, 3o, and 3s exhibited the most potent activity against the tested cancer cells, and some derivatives with potent anticancer activities exhibited better a-AR subtype selectivity than others did (selectivity ratio > 10).
CONCLUSION
This work provided a potential lead compound for the further development of anticancer agents for PCa therapy.
背景
前列腺癌（PCa）是男性最常见的恶性肿瘤，目前尚无有效的治疗方法。
方法
为了开发潜在的抗癌药物，我们合成了 24 种含有溴苯酚部分的萘夫替丁基芳基哌嗪衍生物，并通过光谱方法进行了表征。我们评估了它们对人前列腺癌细胞系（PC-3 和 LNCaP）和α-肾上腺素能受体（α、α1 和 α1D-ARs）的药理学活性。合理地探讨和讨论了这些设计的芳基哌嗪衍生物的构效关系。
结果
在这些衍生物中，3c、3d、3h、3k、3o 和 3s 对测试的癌细胞表现出最强的活性，一些具有强大抗癌活性的衍生物对 α-AR 亚型的选择性优于其他衍生物（选择性比>10）。
结论
这项工作为进一步开发用于前列腺癌治疗的抗癌药物提供了潜在的先导化合物。
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