Synthesis and anti-inflammatory effects of a series of novel 7-hydroxycoumarin derivatives

A number of 7-hydroxycoumarins have been synthesised by Pechmann cyclisation using differently substituted resorcinols employing perchloric acid as the condensing agent. All the compounds have been characterised by analytical and spectroscopic methods. The anti-inflammatory properties were tested with LPS-induced inflammation in J774 macrophages. Expression of iNOS and COX-2 was determined by Western blot, NO by nitrite assay and IL-6 by ELISA analyses. Fifteen of the tested 7-hydroxycoumarins also inhibited IL-6 production but none of them had any major inhibitory effect on COX-2 expression.

Graphical abstractA number of 7-hydroxycoumarins have been synthesised and their effects on LPS-induced inflammation in J774 macrophages have been studied. The most active compound was 7-hydroxy-3,4,5-trimethylcoumarin at 100 μmol (iNOS inhibition: 95%, NO: 92%, IL-6: 92%).Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Carrying von Pechmann reaction at RT has a positive effect on the purity. ► 7-Hydroxycoumarins inhibit iNOS expression in in a dose-dependent manner. ► 7-Hydroxycoumarins act by suppressing the activation of transcription factor NF-κB.