7-(2-Oxoalkoxy)coumarins: Synthesis and Anti-Inflammatory Activity of a Series of Substituted Coumarins

A series of 7-(2-oxoalkoxy)coumarins have been synthesized by conjugating substituted 7-hydroxycoumarins with different chloroketones. The anti-inflammatory properties of 7-(2-oxoalkoxy)coumarins were studied in LPS-induced inflammatory response in J774 macrophages. Western blot was used to determine the expression of iNOS and COX-2, NO was determined by measuring its metabolite nitrite by Griess reaction and IL-6 was measured by ELISA. Seventeen of the studied compounds inhibited NO and IL-6 production over 50% at 100 μM concentrations. IC50 values of the best inhibitors were 21 μM/24 μM (NO/IL-6) for compound 12 and 30 μM/10 μM (NO/IL-6) for compound 20. The main result was that the substitution with 7-(2-oxoalkoxy) group improved the anti-inflammatory properties of most of the investigated 7-hydroxycoumarins.