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Study of the inhibitory effects on TNF ‐α‐induced NF ‐κB activation of IMD 0354 analogs
Author(s) -
Li YiRong,
Lin ChiChen,
Huang ChihYuan,
Wong YungHao,
Hsieh ChengHung,
Wu HanWei,
Chen Jeremy J. W.,
Wu YuShan
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13032
Subject(s) - nf κb , chemistry , iκbα , western blot , iκb kinase , tumor necrosis factor alpha , nfkb1 , cytokine , mediator , phosphorylation , inflammation , pharmacology , transcription factor , proinflammatory cytokine , biochemistry , signal transduction , microbiology and biotechnology , biology , immunology , gene
Nuclear factor–κB ( NF –κB) is an important nuclear transcription factor which regulates pro‐inflammatory cytokines such as TNF ‐α, IL ‐6. Its role as immunoregulatory mediator makes it an attractive target in the development of treatments for inflammatory and autoimmune diseases. In this study, we synthesized derivatives of IMD 0354, a known inhibitor for NF ‐κB, in attempt to understand the effect of benzanilide substitutions on its activity. The inhibition of these analogs on NF ‐κB activation was analyzed by luciferase assay. The inhibition of IKK β phosphorylation and pro‐inflammatory cytokines was determined by Western blot and real‐time PCR . The structure activity relationships showed that the hydroxyl group on IMD 0354 is a critical moiety that resulting in the inhibition of NF ‐κB. Derivatives 1m , 2b, and 2c were shown to inhibit pro‐inflammatory cytokine production at low concentration. These newly synthesized compounds may be useful for the treatment of chronic inflammatory disorders or for cancer prevention.