3 years ago

Study of the inhibitory effects on TNF-α-induced NF-κB activation of IMD0354 analogs

Study of the inhibitory effects on TNF-α-induced NF-κB activation of IMD0354 analogs
Chih-Yuan Huang, Jeremy J. W. Chen, Han-Wei Wu, Yi-Rong Li, Yu-Shan Wu, Cheng-Hung Hsieh, Yung-Hao Wong, Chi-Chen Lin
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 IMD0354, 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 IKKβ phosphorylation and pro-inflammatory cytokines was determined by Western blot and real-time PCR. The structure activity relationships showed that the hydroxyl group on IMD0354 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. Derivatives of IMD035 were synthesized and few of them were found to inhibit NF-κB activation and reduced the pro-inflammatory cytokine TNF-α and IL-6 expressions at low concentration. The structure activity relationships showed that the ortho hydroxyl group is an important moiety resulting in the inhibition. These compounds may be further developed into agents for the treatment of chronic inflammatory disorders or for cancer prevention.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/cbdd.13032

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.