Synthesis of pyranochalcone derivatives and their inhibitory effect on NF-κB activation

Bioorg Med Chem Lett. 2021 Jun 15:42:128042. doi: 10.1016/j.bmcl.2021.128042. Epub 2021 Apr 13.

Abstract

In an effort to identify novel inhibitors of nuclear factor kappa B (NF-κB), twenty five pyranochalcone derivatives were synthesized and evaluated for their in vitro activities against TNF-α induced NF-κB inhibition in HEK293T cells. Among all of these derivatives, several displaying the same acrylate moiety on the B ring exhibited potent inhibition, with IC50 values ranging from 0.29 to 10.46 μM. A functional study of the most potent of these compounds, designated 6b, revealed that it significantly suppressed the transcriptional expression of inflammatory factor IL-1β in lipopolysaccharide-induced RAW 264.7 macrophages, and also mildly inhibited CCL2, IL6 and TNF-α. In addition, compound 6b was found to inhibit IL-1β released in LPS-induced BMDM cells. This study demonstrates that the inhibitory effect of 6b on LPS-stimulated inflammatory mediator production in the mouse macrophage cell line RAW 264.7 correlates with the suppression of the NF-κB and MAPK signaling pathways.

Keywords: Anti-inflammatory; Inflammatory factor; NF-κB inhibitor; Pyranochalcone derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chalcones / chemical synthesis
  • Chalcones / chemistry
  • Chalcones / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Pyrans / chemical synthesis
  • Pyrans / chemistry
  • Pyrans / pharmacology*
  • Structure-Activity Relationship

Substances

  • Chalcones
  • NF-kappa B
  • Pyrans