N-phenylsulfonyl-3,5-bis(arylidene)-4-piperidone derivatives as activation NF-κB inhibitors in hepatic carcinoma cell lines.

Autor: Li N; 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, 264003, PR China., Xin WY; 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, 264003, PR China., Yao BR; 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, 264003, PR China., Cong W; 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, 264003, PR China., Wang CH; 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, 264003, PR China. Electronic address: chunhuawang508@126.com., Hou GG; 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, 264003, PR China. Electronic address: guigehou@163.com.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2018 Jul 15; Vol. 155, pp. 531-544. Date of Electronic Publication: 2018 Jun 12.
DOI: 10.1016/j.ejmech.2018.06.027
Abstrakt: Ten novel symmetric 3,5-bis(arylidene)-4-piperidone derivatives (BAPs, 1-10) and fourteen dissymmetric BAPs (11-24) were synthesized and evaluated the cytotoxicity. All of the compounds have been screened for their anti-inflammatory activity characterized by evaluating their inhibitory effects on LPS-induced IL-6, TNF-α secretion. Among them, BAP 23 exhibits both the highest anti-inflammatory and anti-cancer properties. Western blot analysis showed that BAP 23 markedly reduced the levels of Bcl-2 but increased the levels of cleaved caspase-3and Bax. Moreover, BAP 23 prominently inhibited LPS-induced activation of NF-κB in RAW264.7 cells as well as TNF-α-induced activation of NF-κB in HepG2 cells by blocking phosphorylation of inhibitor IκBα and p65. Consistent with these results, we found that BAP 23 prevented the nuclear translocation of NF-κB induced by LPS or TNF-α. BAP 23 could reasonably bind to the active site of Bcl-2 protein and p65 which is proved by molecular docking modes. These data indicate that BAP 23 is a more potent inhibitor of NF-κB activity which exhibites both anti-inflammatory and anticancer activities.
(Copyright © 2018 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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