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-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.