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

Qi, Yueheng; Chen, Hong; Chen, Shijin; Shen, Jianliang; Li, Jingguo

doi:10.3389/fchem.2022.947065

Cited by 3 publications

(5 citation statements)

References 50 publications

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“…The crystal structure file of the complex was downloaded from the protein crystal structure database (Protein Data Bank, http://www.rcsb.org/pdb/ ) as the basis for molecular docking. Molecular docking was performed using the Surflex-Dock module in SYBYL-X 2.0 ( Chen et al, 2022 ; Qi et al, 2022a , b ). During pretreatment, the ligands and water molecules in the complex 2OZ7 were deleted, and only the structural part of the protein was retained.…”

Section: Methodsmentioning

confidence: 99%

Inactivation of Pseudomonas aeruginosa biofilms by thymoquinone in combination with nisin

Chen

Ji²,

Qi³

et al. 2023

Front. Microbiol.

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Pseudomonas aeruginosa is one of the most important foodborne pathogens that can persist in leafy green vegetables and subsequently produce biofilms. In this study, the synergistic effect of thymoquinone and nisin in reducing biofilm formation of P. aeruginosa on lettuce was evaluated, and their anti-virulence and anti-biofilm mechanisms were also investigated. At concentrations ranging from 0.5 to 2 mg/ml, thymoquinone inhibited the production of autoinducers and virulence factors, and enhanced the susceptibility of P. aeruginosa biofilms to nisin as evidenced by the scanning electron microscopy and confocal laser scanning microscopy. Integrated transcriptomics, metabolomics, and docking analyses indicated that thymoquinone treatment disrupted the quorum sensing (QS) system, altered cell membrane component, and down-regulated the expressions of genes related to virulence, efflux pump, and antioxidation. The changed membrane component and repressed efflux pump system enhanced membrane permeability and facilitated the entrance of nisin into cells, thus improving the susceptibility of biofilms to nisin. The dysfunctional QS and repressed antioxidant enzymes lead to the enhancement of oxidative stress. The enhanced oxidative stress disrupted energy metabolism and protein metabolism and ultimately attenuated the virulence and pathogenicity of P. aeruginosa PAO1. Our study indicated that thymoquinone has the potential to function as a QS-based agent to defend against foodborne pathogens in combination with nisin.

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Section: Methodsmentioning

confidence: 99%

Inactivation of Pseudomonas aeruginosa biofilms by thymoquinone in combination with nisin

Chen

Ji²,

Qi³

et al. 2023

Front. Microbiol.

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“…DU145 cells were cultured in MEM (PM150410) supplemented with 10% FBS (164210–50) and 1% P/S (PB180120). The cells were incubated at 37°C with 5% CO 2 ( Qi et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

“…RLUs were determined using the GloMax ® 96-Microplate Luminometer. IC 50 was calculated using the GraphPad Prism 5.0 ( He et al, 2022b ; Qi et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

“…Frontiers in Chemistry frontiersin.org IC 50 was calculated using the GraphPad Prism 5.0 (He et al, 2022b;Qi et al, 2022).…”

Section: Ar Reporter Gene Assaymentioning

confidence: 99%

“…However, there have been few studies on hydroxyzine derivatives. Based on the results of our group’s previous anti-prostate cancer study ( Chen et al, 2016 ; Chen et al, 2017 ; Chen et al, 2018a ; Chen et al, 2019a ; Chen et al, 2019b ; Qi et al, 2022 ), we tried to design and synthesize a series of novel hydroxyzine derivatives ( Scheme 1 ) with 2-p-tolylethanol group instead of 2-ethoxyethanol group in hydroxyzine. Unexpectedly, some derivatives exhibited strong anti-cancer activities and antagonistic activities.…”

Section: Introductionmentioning

confidence: 99%

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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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Arylpiperazine Derivatives and Cancer: A New Challenge in Medicinal Chemistry

Andreozzi,

Corvino,

Severino

et al. 2024

Pharmaceuticals

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Background: In recent decades, there has been a startling rise in the number of cancer patients worldwide, which has led to an amazing upsurge in the development of novel anticancer treatment candidates. On a positive note, arylpiperazines have garnered attention in cancer research due to their potential as scaffolds for developing anticancer agents. These compounds exhibit a diverse array of biological activities, including cytotoxic effects against cancer cells. Indeed, one of the key advantages of arylpiperazines lies in their ability to interact with various molecular targets implicated in cancer pathogenesis. Aim: Here, we focus on the chemical structures of several arylpiperazine derivatives, highlighting their anti-proliferative activity in different tumor cell lines. The modular structure, diverse biological activities, and potential for combination therapies of arylpiperazine compounds make them valuable candidates for further preclinical and clinical investigations in the fight against cancer. Conclusion: This review, providing a careful analysis of different arylpiperazines and their biological applications, allows researchers to refine the chemical structures to improve potency, selectivity, and pharmacokinetic properties, thus advancing their therapeutic potential in oncology.

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

Cited by 3 publications

References 50 publications

Inactivation of Pseudomonas aeruginosa biofilms by thymoquinone in combination with nisin

Inactivation of Pseudomonas aeruginosa biofilms by thymoquinone in combination with nisin

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

Arylpiperazine Derivatives and Cancer: A New Challenge in Medicinal Chemistry

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