Synthesis, structure–activity relationship and biological evaluation of novel arylpiperzines as α1A/1D-AR subselective antagonists for BPH

Xu, Fang; Chen, Hong; Xu, Jingyi; Li, Xue; He, Xuelan; Shao, Binhao; Sun, Xianqiang; Li, Bing; Deng, Xiaoliang; Yuan, Ming

doi:10.1016/j.bmc.2015.11.020

Cited by 17 publications

(4 citation statements)

References 21 publications

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“…The antagonistic activity of these derivatives against AR was assessed using luciferase assays ( Xu et al, 2014 ; Xu et al, 2015 ; Zuo et al, 2017 ; Xu et al, 2018 ). As shown in Table 2 , the compounds 3–10 exhibited weak antagonistic potency against AR.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, biological evaluation, and molecular docking of novel hydroxyzine derivatives as potential AR antagonists

Xue²,

Chen³

et al. 2022

Front. Chem.

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Prostate cancer (PCa) is a malignant tumor with a higher mortality rate in the male reproductive system. In this study, the hydroxyazine derivatives were synthesized with different structure from traditional anti-prostate cancer drugs. In the evaluation of in vitro cytotoxicity and antagonistic activity of PC-3, LNCaP, DU145 and androgen receptor, it was found that the mono-substituted derivatives on the phenyl group (4, 6, 7, and 9) displayed strong cytotoxic activities, and compounds 11–16 showed relatively strong antagonistic potency against AR (Inhibition% >55). Docking analysis showed that compounds 11 and 12 mainly bind to AR receptor through hydrogen bonds and hydrophobic bonds, and the structure-activity relationship was discussed based on activity data. These results suggested that these compounds may have instructive implications for drug structural modification in prostate cancer.

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Section: Resultsmentioning

confidence: 99%

Synthesis, biological evaluation, and molecular docking of novel hydroxyzine derivatives as potential AR antagonists

Xue²,

Chen³

et al. 2022

Front. Chem.

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“…Naftopidil is a derivative of arylpiperazine ether and a specific antagonist targeted for the adrenergic receptor [6], which has alreadly been regarded as one of the most commonly utilized antagonists targeted for the adrenergic receptor to treat the benign prostatic hyperplasia (BPH) in Japan [7]. The title compound is a pivotal intermediate for some arylpiperazine derivatives [8,9]. The asymmetric unit contains only one molecule.…”

Section: Discussionmentioning

confidence: 99%

Crystal structure of 4-((1,3-dioxoisoindolin-2-yl)methyl)phenethyl 4-methylbenzenesulfonate, C₂₄H₂₁NO₅S

Cuicui

Shi

Liu

et al. 2018

Zeitschrift Für Kristallographie - New Crystal Structures

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“…The AR antagonist effect of tested compounds was evaluated using the luciferase reporter gene assay ( Xu et al, 2014 ; Xu et al, 2015 ; Zuo et al, 2017 ; Xu et al, 2018 ). Briefly, RLUs were used to indicate firefly and Renilla luciferase activity, and the activities were evaluated using dual luciferase assay kits (Promega) in accordance with the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

Synthesis, bioactivity, and molecular docking of novel arylpiperazine derivatives as potential AR antagonists

Chen²,

Chen³

et al. 2022

Front. Chem.

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Prostate cancer is one of the malignant tumors and the second most common malignant tumor in men. Clinically used androgen receptor (AR)–targeted drugs can antagonize androgen and inhibit tumor growth, but these drugs can cause serious resistance problems. To develop novel AR antagonists, 22 kinds of arylpiperazine derivatives were designed and synthesized, and the derivatives 5, 8, 12, 19, 21, 22, 25, and 26 not only showed strong antagonistic potency (>55% inhibition) and binding affinities (IC50 <3 μM) to AR, but also showed stronger inhibitory activity to LNCaP cells versus PC-3 cells. Among them, derivative 21 exhibited the highest binding affinity for AR (IC50 = 0.65 μM) and the highest antagonistic potency (76.2% inhibition). Docking studies suggested that the derivative 21 is primarily bound to the AR-LBP site by the hydrophobic interactions. Overall, those results provided experimental methods for developing novel arylpiperazine derivatives as potent AR antagonists.

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Synthesis, structure–activity relationship and biological evaluation of novel arylpiperzines as α1A/1D-AR subselective antagonists for BPH

Cited by 17 publications

References 21 publications

Synthesis, biological evaluation, and molecular docking of novel hydroxyzine derivatives as potential AR antagonists

Synthesis, biological evaluation, and molecular docking of novel hydroxyzine derivatives as potential AR antagonists

Crystal structure of 4-((1,3-dioxoisoindolin-2-yl)methyl)phenethyl 4-methylbenzenesulfonate, C₂₄H₂₁NO₅S

Synthesis, bioactivity, and molecular docking of novel arylpiperazine derivatives as potential AR antagonists

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Synthesis, structure–activity relationship and biological evaluation of novel arylpiperzines as α1A/1D-AR subselective antagonists for BPH

Cited by 17 publications

References 21 publications

Synthesis, biological evaluation, and molecular docking of novel hydroxyzine derivatives as potential AR antagonists

Synthesis, biological evaluation, and molecular docking of novel hydroxyzine derivatives as potential AR antagonists

Crystal structure of 4-((1,3-dioxoisoindolin-2-yl)methyl)phenethyl 4-methylbenzenesulfonate, C24H21NO5S

Synthesis, bioactivity, and molecular docking of novel arylpiperazine derivatives as potential AR antagonists

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Crystal structure of 4-((1,3-dioxoisoindolin-2-yl)methyl)phenethyl 4-methylbenzenesulfonate, C₂₄H₂₁NO₅S