Facile Synthesis and Nitric Oxide Inhibitory Activity of Aurones, Rugaurone A, Gramflavonoid A and Their Derivatives

Facile synthesis of natural aurones, rugaurone A (1a), gramflavonoid A (1b) and their novel derivatives (1c-1o) is accomplished in good to high yields with exceptional Z-selectivity (≥ 97%) from the commercially available starting materials. Herein, practically improved method was developed for the synthesis of common key intermediate, 5,6-dimethoxybenzofuran-3(2H)-one (5). Later, their nitric oxide (NO) production inhibition effects were estimated in lipopolysaccharide (LPS)-induced RAW-264.7 macrophages as an indicator of anti-inflammatory activity. All compounds exhibited weak to good strength against NO production in a concentration-dependent manner and none of the compound showed significant cytotoxicity against macrophages at the highest (10 μM) concentration. The IC50 values are showed in the range from 3.39 to 19.55 μM. Among the 15 aurones synthesized in this study, 3 compounds that is compound 1g (63.98%) followed by compound 1o (49.07%) and rugaurone A (1a) (41.72%) showed the maximum inhibitory activity with respective IC50 values of 4.50 μM, 4.98 μM and 3.39 μM compared to L-NMMA (IC50 = 5.19 μM), which was used as a standard NO inhibitor. This study suggests that compounds 1g, 1o and 1a may serve as favorable structures for further development of NO production-targeted anti-inflammatory agents.