Synthesis of phenylisothiourea derivatives as inhibitors of NO production in LPS activated macrophages

A series of phenylisothioureas were synthesized as inhibitors of NO production in lipopolysaccharide-activated macrophages. We investigated the effect of lipophilic moiety and N- or S-substituents of the phenylisothioureas on the activity. Inhibitory activities of carbazole-linked phenylisothioureas were superior to the corresponding simple phenylisothiourea derivatives. Among these compounds, 12b having N-ethyl and S-isopropyl groups on phenylisothiourea moiety was the most potent in the inhibition of NO production. They inhibited NO production through the suppression of the LPS-induced translocation of p65 subunit of NF-κB and the followed suppression of the iNOS protein and mRNA expression.

Graphical abstractSynthesis of series of phenylisothioureas and their inhibitory activities on the NO production in lipopolysaccharide activated macrophages are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide