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Potential multifunctional agents with anti-hepatoma and anti-inflammation properties by inhibiting NF-кB activation

Inhibition of NF-κB signalling has been demonstrated as a therapeutic option in treating inflammatory diseases and cancers. Herein, we synthesized novel dissymmetric 3,5-bis(arylidene)-4-piperidones (BAPs, 83–102) and characterized fully. MTT and ELISA assay were performed to screen the anti-hepatom...

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Autores principales: Su, Chang-Ming, Hou, Gui-Ge, Wang, Chun-Hua, Zhang, Hong-Qin, Yang, Cheng, Liu, Mei, Hou, Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691761/
https://www.ncbi.nlm.nih.gov/pubmed/31288582
http://dx.doi.org/10.1080/14756366.2019.1635124
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author Su, Chang-Ming
Hou, Gui-Ge
Wang, Chun-Hua
Zhang, Hong-Qin
Yang, Cheng
Liu, Mei
Hou, Yun
author_facet Su, Chang-Ming
Hou, Gui-Ge
Wang, Chun-Hua
Zhang, Hong-Qin
Yang, Cheng
Liu, Mei
Hou, Yun
author_sort Su, Chang-Ming
collection PubMed
description Inhibition of NF-κB signalling has been demonstrated as a therapeutic option in treating inflammatory diseases and cancers. Herein, we synthesized novel dissymmetric 3,5-bis(arylidene)-4-piperidones (BAPs, 83–102) and characterized fully. MTT and ELISA assay were performed to screen the anti-hepatoma and anti-inflammation properties. 96 showed the most potential bioactivity. 96 could promote HepG2 apoptosis through up-regulating the expression of C-Caspase-3 and Bax, down-regulating the expression of Bcl-2, while markedly inhibit LPS or TNF-α-induced activation of NF-κB through both inhibiting the phosphorylation of IκBα and p65, and preventing the p65 nuclear translocation to exhibit both anti-hepatoma and anti-inflammatory activities. Molecular docking verified that simulated 96 can effectively bond to the active site of Bcl-2 and NF-κB/p65 proteins. 96 inhibited xenografts growth by reducing the expression of TNF-α and Bcl-2 in the tumour tissue. This study suggested that 96 could be developed as a potential multifunctional agent for treatment of inflammatory diseases and cancers.
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spelling pubmed-66917612019-08-23 Potential multifunctional agents with anti-hepatoma and anti-inflammation properties by inhibiting NF-кB activation Su, Chang-Ming Hou, Gui-Ge Wang, Chun-Hua Zhang, Hong-Qin Yang, Cheng Liu, Mei Hou, Yun J Enzyme Inhib Med Chem Original Article Inhibition of NF-κB signalling has been demonstrated as a therapeutic option in treating inflammatory diseases and cancers. Herein, we synthesized novel dissymmetric 3,5-bis(arylidene)-4-piperidones (BAPs, 83–102) and characterized fully. MTT and ELISA assay were performed to screen the anti-hepatoma and anti-inflammation properties. 96 showed the most potential bioactivity. 96 could promote HepG2 apoptosis through up-regulating the expression of C-Caspase-3 and Bax, down-regulating the expression of Bcl-2, while markedly inhibit LPS or TNF-α-induced activation of NF-κB through both inhibiting the phosphorylation of IκBα and p65, and preventing the p65 nuclear translocation to exhibit both anti-hepatoma and anti-inflammatory activities. Molecular docking verified that simulated 96 can effectively bond to the active site of Bcl-2 and NF-κB/p65 proteins. 96 inhibited xenografts growth by reducing the expression of TNF-α and Bcl-2 in the tumour tissue. This study suggested that 96 could be developed as a potential multifunctional agent for treatment of inflammatory diseases and cancers. Taylor & Francis 2019-07-10 /pmc/articles/PMC6691761/ /pubmed/31288582 http://dx.doi.org/10.1080/14756366.2019.1635124 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Su, Chang-Ming
Hou, Gui-Ge
Wang, Chun-Hua
Zhang, Hong-Qin
Yang, Cheng
Liu, Mei
Hou, Yun
Potential multifunctional agents with anti-hepatoma and anti-inflammation properties by inhibiting NF-кB activation
title Potential multifunctional agents with anti-hepatoma and anti-inflammation properties by inhibiting NF-кB activation
title_full Potential multifunctional agents with anti-hepatoma and anti-inflammation properties by inhibiting NF-кB activation
title_fullStr Potential multifunctional agents with anti-hepatoma and anti-inflammation properties by inhibiting NF-кB activation
title_full_unstemmed Potential multifunctional agents with anti-hepatoma and anti-inflammation properties by inhibiting NF-кB activation
title_short Potential multifunctional agents with anti-hepatoma and anti-inflammation properties by inhibiting NF-кB activation
title_sort potential multifunctional agents with anti-hepatoma and anti-inflammation properties by inhibiting nf-кb activation
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691761/
https://www.ncbi.nlm.nih.gov/pubmed/31288582
http://dx.doi.org/10.1080/14756366.2019.1635124
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