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

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.