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

Tomonori Nakamura, Naoko Kodama, Manabu Oda, Shizuko Tsuchiya, Yu Arai, Takuya Kumamoto, Tsutomu Ishikawa, Koichi Ueno, Shingo Yano

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28 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)15-20
Number of pages6
JournalJournal of Natural Medicines
Issue number1
Publication statusPublished - 2009 Jan 1
Externally publishedYes



  • Inducible nitric oxide synthase
  • Macrophage
  • Oxycoumarin
  • RAW264.7
  • Structure-activity relationship

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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