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

Hong Chen; Yuna Qian; Huixia Jia; Yuzhong Yu; Haibo Zhang; Jianliang Shen; Shanchao Zhao

doi:10.1007/s43440-019-00041-w

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

Pharmacol Rep. 2020 Aug;72(4):1058-1068. doi: 10.1007/s43440-019-00041-w. Epub 2020 Jan 23.

Authors

Hong Chen^{1

2}, Yuna Qian^{3

4}, Huixia Jia², Yuzhong Yu¹, Haibo Zhang¹, Jianliang Shen^{5

6}, Shanchao Zhao⁷

Affiliations

¹ Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
² Luoyang Key Laboratory of Organic Functional Molecules, College of Food and Drug, Luoyang Normal University, Luoyang, 471934, China.
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.
⁴ Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Science, Wenzhou, 325001, China.
⁵ State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325035, China. shenjl@wibe.ac.cn.
⁶ Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Science, Wenzhou, 325001, China. shenjl@wibe.ac.cn.
⁷ Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. zhaoshanchao@263.net.

PMID: 32048266
DOI: 10.1007/s43440-019-00041-w

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; 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 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.

Keywords: Antagonistic activity; Anticancer activity; Arylpiperazine derivatives; Prostate cancer; Synthesis.

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacology
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Proliferation / physiology
Drug Evaluation, Preclinical / methods
Drug Screening Assays, Antitumor / methods
Humans
Male
Naphthalenes / chemical synthesis*
Naphthalenes / pharmacology
Phenols / chemical synthesis*
Phenols / pharmacology
Piperazines / chemical synthesis*
Piperazines / pharmacology
Prostatic Neoplasms / drug therapy
Prostatic Neoplasms / pathology
Structure-Activity Relationship

Substances

Antineoplastic Agents
Naphthalenes
Phenols
Piperazines
naftopidil