Nitric oxide production inhibition and mechanism of phenanthrene analogs in lipopolysaccharide-stimulated RAW264.7 macrophages

Natural phenanthrene derivatives are considered to be important resource for the anti-inflammatory therapeutics, but their structure-activity relationship and mechanisms are still unknown. In this study we evaluated 20 synthesized phenanthrene analogs in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Compounds 10, 11 and 17 were found to inhibit the production of nitric oxide (NO) with IC50 values of 37.26 mu M, 5.05 mu M and 20.31 mu M, respectively. Compound 11 decreased LPS-induced expression of inducible NO synthase (iNOS), inhibited phosphorylation of p38 mitogen-activated protein kinase (MAPK) and serine/threonine kinase Akt. It also suppressed the phosphorylation and degradation of inhibitory kappa B-alpha (I kappa B alpha). Data obtained suggest that compound 11 exerts anti-inflammatory effects by inhibiting p38 MAPK and nuclear factor kappa B (NF-kappa B) pathways, which warrants further investigation as a new anti-inflammatory pharmaceutical tool. (C) 2016 Elsevier Ltd. All rights reserved.