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Inhibition of Nitric Oxide Production from lipopolysaccharide-Treated RAW 264.7 Cells by Synthetic Flavones：Structure-Activity Relationship and Action Mechanism  

Kim, Soo-Jin (College of Pharmacy, Kangwon National University)
Park, Hae-Il (College of Pharmacy, Kangwon National University)
Kim, Hyun-Pyo (College of Pharmacy, Kangwon National University)
Publication Information
Archives of Pharmacal Research / v.27, no.9, 2004 , pp. 937-943 More about this Journal
Abstract
Recent investigations have shown that certain flavonoids, especially flavone derivatives, inhibit nitric oxide (NO) production by inducible NO synthase (iNOS) in macrophages, which contrib-ute their anti-inflammatory action. For the purpose of finding the optimized chemical structures of flavonoids that inhibit NO production, various A- and B-ring substituted flavones were syn-thesized and evaluated for their inhibitory activity using lipopolysaccharide-treated RAW 264.7 cells. It was found that the optimal chemical structures were A-ring 5,7-dihydroxyflavones hav-ing the B-ring 2＇,3＇-dihydroxy or 3＇,4＇-dihydroxy or 3＇,4＇-hydroxy/methoxy (methoxy/hydroxy) groups. These structurally optimized compounds were revealed to be down-regulators of iNOS induction, but not direct iNOS inhibitors. Of these derivatives that were evaluated, 2＇,3＇,5,7-tet-rahydroxyflavone and 3＇,4＇,5,7-tetrahydroxyflavone (Iuteolin) showed the strongest inhibition. The $IC_{50}$/ values for these compounds were 19.7 and 17.1 11M, respectively. Therefore, these compounds may have a potential as new anti-inflammatory agents.
Keywords
Flavonoid, Nitric oxide; Inducible nitric oxide synthase; Anti-inflammation; Structure-activity relationship;
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