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

Journal of Enzyme Inhibition and Medicinal Chemistry

Mei Liu¹  Cheng Yang²  Yun Hou²  Hong-Qin Zhang²  Gui-Ge Hou³  Chun-Hua Wang³  Chang-Ming Su³ 

[1] Pharmacy Department, The Second People’s Hospital of Dongying, Dongying, PR Chin;School of Basic Medical Sciences, Binzhou Medical University, Yantai, PR China;School of Pharmacy, The Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China, Binzhou Medical University, Yantai, PR China;

关键词: 3,5-Bis(arylidene)-4-piperidones;    anti-cancer;    anti-inflammation;    NF-κB inhibitor;    molecular docking;   

DOI  :  10.1080/14756366.2019.1635124

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY