Synthesis and structure–activity relationships of guaiane-type sesquiterpene lactone derivatives with respect to inhibiting NO production in lipopolysaccharide-induced RAW 264.7 macrophages

• DOI: 10.1016/j.ejmech.2014.06.043
• Publication Date: 2014-06-21T11:45:43Z
• Authors: Hao Chen; Bing-Yang Chen; Chun-Ting Liu; Zeng Zhao; Wen-Hao Shao; Hu Yuan; Kai-Jian Bi; Jiang-Yun Liu; Qing-Yan Sun; Wei-Dong Zhang
• Keywords: Lipopolysaccharides; 0301 basic medicine; Lactones; Mice; Sesquiterpenes, Guaiane; Structure-Activity Relationship; 03 medical and health sciences; Macrophages; Animals; Chemistry Techniques, Synthetic; Nitric Oxide; Cell Line

A guaiane framework was scaffolded by photochemical rearrangement reactions using α-santonin 1 as a starting material. Then, using a series of reactions, we synthesized the guaiane-type sesquiterpene lactone 5 in high yield. The inhibitory activities of compound 5 and of a series of derivatives on nitric oxide (NO) release were evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Compounds 6g, 7h, 7i, 7k and 8g, exhibited significant inhibitory effects on NO production, with IC50 values of 14.8, 22.3, 18.3, 17.4 and 7.0 μM, respectively. Their cytotoxicities were also estimated using an MTT assay. The structure-activity relationships of these compounds were also discussed.