Synthesis and Antitumor Activity of Novel Arylpiperazine Derivatives Containing the Saccharin Moiety

Chen, Hong; Xu, Bingbing; Sun, Tao; Zhan, Zhuang‐Ping; Ya, Huiyuan; Yuan, Ming

doi:10.3390/molecules22111857

Cited by 14 publications

(13 citation statements)

References 32 publications

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“…But, methoxylsubstituted derivatives exhibited weak or no cytotoxic activity LNCaP cells except the derivative 11 (Chen et al, 2017;Chen et al, 2018). Moreover, the m-substituted phenyl group derivative ( 14) and p-substituted phenyl group derivative (15) also exhibited toxicity against PC-3 cells (Iwasa et al, 2007;Dreaden et al, 2012;George et al, 2018;Saito et al, 2018), and methoxyl-substituted derivatives also exhibited toxicity against PC-3 cells except the derivative 12 (Chen et al, 2017;Chen et al, 2018). ( 5) Compared with 16, strong cytotoxic activity was displayed by 17 and 18 against PC-3 cells.…”

Section: Sar Analysis For Antiproliferative and Ar Antagonist Assaymentioning

confidence: 95%

“…(4) Methoxyl-substituted derivatives 12 (2-OCH 3 ), 14 (3-OCH 3 ), and 15 (4-OCH 3 ) had strong cytotoxic activities against LNCaP cells and relatively strong antagonistic potency against AR. But, methoxylsubstituted derivatives exhibited weak or no cytotoxic activity LNCaP cells except the derivative 11 (Chen et al, 2017;Chen et al, 2018). Moreover, the m-substituted phenyl group derivative ( 14) and p-substituted phenyl group derivative (15) also exhibited toxicity against PC-3 cells (Iwasa et al, 2007;Dreaden et al, 2012;George et al, 2018;Saito et al, 2018), and methoxyl-substituted derivatives also exhibited toxicity against PC-3 cells except the derivative 12 (Chen et al, 2017;Chen et al, 2018).…”

Section: Sar Analysis For Antiproliferative and Ar Antagonist Assaymentioning

confidence: 99%

“…Meanwhile, estrone piperazine derivatives (2-CH 3; IC 50 = 0.83 μM) displayed strong cytotoxic activity against LNCaP cells (Chen et al, 2018). However, other derivatives with a methyl substituent on the phenyl group exhibited weak cytotoxic activity against the tested cells (Chen et al, 2017;Chen et al, 2018). The activity profiles indicated that the o-substituted phenyl group derivative (2-CH 3 ) was beneficial for cytotoxic activity and antagonistic activity.…”

Section: Sar Analysis For Antiproliferative and Ar Antagonist Assaymentioning

confidence: 99%

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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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Section: Sar Analysis For Antiproliferative and Ar Antagonist Assaymentioning

confidence: 95%

Section: Sar Analysis For Antiproliferative and Ar Antagonist Assaymentioning

confidence: 99%

Section: Sar Analysis For Antiproliferative and Ar Antagonist Assaymentioning

confidence: 99%

See 1 more Smart Citation

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

Chen²,

Chen³

et al. 2022

Front. Chem.

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“…For example, an 1-(2-aryl-2-adamantyl)piperazine derivate reduced viability of cervical, breast, pancreatic and lung cancer cells in a dose-dependent manner without exerting any toxicity on normal cell lines [ 79 ] while others seem to have HDAC (Histone deacetylase) inhibitor properties [ 80 ]. Moreover, several aryl-piperazine derivatives containing the saccharin moiety were shown to reduce cell viability of cancer prostate models in a dose-dependent manner [ 81 ]. These structure-activity relationships open the perspective of their use as anti-cancer drugs as illustrated by the anti-cancer effects of naftopidil in vitro and in vivo but also led to synthesis of naftopidil derivatives as HUHS1015 and compound 12 to improve its efficacy as it is discussed thereafter.…”

Section: Molecular Mechanisms Involved In the Anti-cancerous Propementioning

confidence: 99%

Drug Repositioning of the α1-Adrenergic Receptor Antagonist Naftopidil: A Potential New Anti-Cancer Drug?

Florent

Poulain

N’Diaye

2020

IJMS

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Failure of conventional treatments is often observed in cancer management and this requires the development of alternative therapeutic strategies. However, new drug development is known to be a high-failure process because of the possibility of a lower efficacy than expected for the drug or appearance of non-manageable side effects. Another way to find alternative therapeutic drugs consists in identifying new applications for drugs already approved for a particular disease: a concept named “drug repurposing”. In this context, several studies demonstrated the potential anti-tumour activity exerted by α1-adrenergic receptor antagonists and notably renewed interest for naftopidil as an anti-cancer drug. Naftopidil is used for benign prostatic hyperplasia management in Japan and a retrospective study brought out a reduced incidence of prostate cancer in patients that had been prescribed this drug. Further studies showed that naftopidil exerted anti-proliferative and cytotoxic effects on prostate cancer as well as several other cancer types in vitro, as well as ex vivo and in vivo. Moreover, naftopidil was demonstrated to modulate the expression of Bcl-2 family pro-apoptotic members which could be used to sensitise cancer cells to targeting therapies and to overcome resistance of cancer cells to apoptosis. For most of these anti-cancer effects, the molecular pathway is either not fully deciphered or shown to involve α1-adrenergic receptor-independent pathway, suggesting off target transduction signals. In order to improve its efficacy, naftopidil analogues were designed and shown to be effective in several studies. Thereby, naftopidil appears to display anti-cancer properties on different cancer types and could be considered as a candidate for drug repurposing although its anti-cancerous activities need to be studied more deeply in prospective randomized clinical trials.

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“…with a combination of a heterocyclic compound such as benzothiazole, benzoxazole, benzimiazole, and indole, etc. [17][18][19] Bacterial infections are among the important infectious diseases [20][21][22] .…”

mentioning

confidence: 99%

Untitled

2020

IJPSR

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In this planed research work, aryl piperazine derivatives will be synthesized because aryl piperazine currently the most important constructive block in drug discovery with positive pharmacological evaluation. A series N-(4-(benzo[d]thiazol-2-yl) phenyl)-2-[4-(arylsubstituted) piperazines-1-yl]acetamide, N-(4-(benzo[d]oxazol-2-yl)phenyl)-2-[4-(arylsubstituted)piperazines-1-yl]acetamide and Synthesis of N-(4-(benzo[d]imidazol-2-yl) phenyl)-2-(4-(arylsubstituted)piperazin-1-yl) acetamide will be synthesized with their characterization such as melting point determination, Thin-layer chromatography (TLC) and spectral analysis. After that, pharmacological evaluation, such as antibacterial activity, will be performed for synthesized compounds. All the synthesized compounds were reported for determination of zone of inhibition (mm), minimum inhibitory concentrations (MIC) were also calculated for effective derivatives, with an objective to offer some potent antimicrobial agents to human beings. Antimicrobial activity is determined based on their in-vitro activity in pure cultures. In-vitro susceptibility testing is done by two methods i.e., Turbidimetric/photometric/tube dilution method and agar diffusion/cupplate/cylinder plate method. INTRODUCTION: According to present scenario the appearance of multidrug microbial resistance and worldwide warming are among the main challenges that modern scientists have so far been facing in the recent decades 1-6. From this information that many pathogenic microorganisms accountable for several human being and animal diseases have developed resistance mechanisms to the classical therapies has stimulated intensive investigations in the fields of natural and synthetic chemistry, with the aim of discovering new drug classes having much better therapeutic profiles 7-12 .

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Synthesis and Antitumor Activity of Novel Arylpiperazine Derivatives Containing the Saccharin Moiety

Cited by 14 publications

References 32 publications

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

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

Drug Repositioning of the α1-Adrenergic Receptor Antagonist Naftopidil: A Potential New Anti-Cancer Drug?

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