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

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Abstract

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 a1-adrenergic receptors (a1-ARs; α1a, α1b, and α1d-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 a1-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.

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (No. 31800833), Zhejiang Provincial Natural Science of Foundation of China (Nos. LZ19H180001 and LQ19C100001), the Wenzhou Medical University and Wenzhou Institute of Biomaterials and Engineering (WIBEZD2017001-03), the Science and Technology Planning Projects of Guangdong Province (No. 2016A020215175), the Natural Science Foundation of Guangdong Province (No. 2016A030313583), the Medical Scientific Research Foundation of Guangdong Province (No. A2016555), the Outstanding Youths Development Scheme of Nanfang Hospital, Southern Medical University (No. 2015J005) and the Science and Technology Planning Project of Guangzhou (No. 201704020070).

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  1. Hong Chen and Yuna Qian have contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China

    Hong Chen, Yuzhong Yu, Haibo Zhang & Shanchao Zhao

  2. Luoyang Key Laboratory of Organic Functional Molecules, College of Food and Drug, Luoyang Normal University, Luoyang, 471934, China

    Hong Chen & Huixia Jia

  3. State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325035, China

    Yuna Qian & Jianliang Shen

  4. Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Science, Wenzhou, 325001, China

    Yuna Qian & Jianliang Shen

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  1. Hong Chen
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Chen, H., Qian, Y., Jia, H. et al. Synthesis and pharmacological evaluation of naftopidil-based arylpiperazine derivatives containing the bromophenol moiety. Pharmacol. Rep 72, 1058–1068 (2020). https://doi.org/10.1007/s43440-019-00041-w

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  • DOI: https://doi.org/10.1007/s43440-019-00041-w

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