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

Prostate cancer (PCa) is the most common malignancy in men and in the absence of any effective treatments available. 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 a1-adrenergic receptors (a1-ARs; α1a, α1b, and α1d-ARs). The structure–activity relationship of these designed arylpiperazine derivatives was rationally explored and discussed. 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 a1-AR subtype selectivity than others did (selectivity ratio > 10). This work provided a potential lead compound for the further development of anticancer agents for PCa therapy.