Synthesis and pharmacological evaluation of naftopidil-based arylpiperazine derivatives containing the bromophenol moiety

• Published in: Pharmacological reports 2020-08, Vol.72 (4), p.1058-1068
• Main Authors: Chen, Hong, Qian, Yuna, Jia, Huixia, Yu, Yuzhong, Zhang, Haibo, Shen, Jianliang, Zhao, Shanchao
• Format: Article
• Language: English
• Subjects: Drug Safety and Pharmacovigilance; Medicine; Pharmacotherapy; Pharmacy
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1007/s43440-019-00041-w

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 1 -adrenergic receptors (a 1 -ARs; α 1a , α 1b , and α 1d -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 1 -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. Graphic abstract