The structure-activity relationship between oxycoumarin derivatives showing inhibitory effects on iNOS in mouse macrophage RAW264.7 cells

J Nat Med. 2009 Jan;63(1):15-20. doi: 10.1007/s11418-008-0268-6. Epub 2008 Jul 9.

Abstract

We have investigated the structure-activity relationship between 63 natural oxycoumarin derivatives and their effects on the expression of inducible-nitric oxide synthase (iNOS) induced by lipopolysaccharide. The protein expression of iNOS was screened by Western blot analysis, and four 5,7-dimethoxycoumarins were selected as potent inhibitors of iNOS expression. In terms of structural specificity, the methoxyl group on C-5 and C-7 and the short alkyl chain (1-5 carbons) on C-6 may be essential for the potent activities. These compounds also showed inhibitory effects on nitric oxide generation and mRNA expression of inflammatory mediators, namely, iNOS and COX-2. Interestingly, the inhibitory effect on mRNA expression was specific for iNOS and was not detected for neuronal NOS. It is expected that these compounds will show anti-inflammatory activities via inhibition of the expressions of iNOS and COX-2.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • Coumarins / chemistry
  • Coumarins / pharmacology*
  • Lipopolysaccharides / pharmacology
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / enzymology
  • Mice
  • Molecular Structure
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Structure-Activity Relationship

Substances

  • Coumarins
  • Lipopolysaccharides
  • Nitric Oxide
  • coumarin
  • Nitric Oxide Synthase Type II
  • 5,7-dimethoxycoumarin