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

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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.

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Acknowledgments

The authors are grateful to Ms. Hiromi Kajigaya and Ms. Ayumi Futoh for technical assistance.

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Correspondence to Tomonori Nakamura.

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Nakamura, T., Kodama, N., Oda, M. et al. The structure–activity relationship between oxycoumarin derivatives showing inhibitory effects on iNOS in mouse macrophage RAW264.7 cells. J Nat Med 63, 15–20 (2009). https://doi.org/10.1007/s11418-008-0268-6

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  • DOI: https://doi.org/10.1007/s11418-008-0268-6

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