Synthesis and anti-inflammatory evaluation of novel mono-carbonyl analogues of curcumin in LPS-stimulated RAW 264.7 macrophages

Eur J Med Chem. 2010 Dec;45(12):5773-80. doi: 10.1016/j.ejmech.2010.09.037. Epub 2010 Oct 8.

Abstract

Curcumin is a multifunctional natural product with regulatory effects on inflammation. However, a major limitation for the application of curcumin is its poor bioavailability. We previously demonstrated that the mono-carbonyl analogues of curcumin possessed improved pharmacokinetic profiles. In this study, 33 novel mono-carbonyl analogues of curcumin were synthesized and their inhibition against TNF-α and IL-6 release was evaluated in LPS-stimulated RAW 264.7 macrophages. Based on the screening data, quantitative structure-activity relationship was conducted, indicating that electron-withdrawing groups in benzene ring are favourable to anti-inflammatory activities of B-class compounds. Furthermore, compounds AN1 and B82 demonstrated anti-inflammatory abilities in a dose-dependent manner. These raise the possibility that these compounds might serve as potential agents for the treatment of inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Curcumin / chemical synthesis*
  • Curcumin / chemistry
  • Curcumin / pharmacology*
  • Dose-Response Relationship, Drug
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / pharmacology*
  • Macrophages / drug effects*
  • Mice
  • Molecular Structure
  • Quantitative Structure-Activity Relationship
  • Stereoisomerism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-6
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Curcumin