title: Synthesis and structure-activity relationships of guaiane-type sesquiterpene lactone derivatives with respect to inhibiting NO production in lipopolysaccharide-induced RAW 264.7 macrophages.
abstract: 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.
authors: School of Pharmacy, Soochow University, Suzhou 215123, China; School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors: Hao
authors: H
authors: Chen
authors: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors: Bing-Yang
authors: BY
authors: Chen
authors: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors: Chun-Ting
authors: CT
authors: Liu
authors: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors: Zeng
authors: Z
authors: Zhao
authors: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors: Wen-Hao
authors: WH
authors: Shao
authors: School of Pharmacy, Second Military Medical University, Shanghai 200433, China; School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
authors: Hu
authors: H
authors: Yuan
authors: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors: Kai-Jian
authors: KJ
authors: Bi
authors: School of Pharmacy, Soochow University, Suzhou 215123, China. Electronic address: liujiangyun@suda.edu.cn.
authors: Jiang-Yun
authors: JY
authors: Liu
authors: School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: sqy_2000@163.com.
authors: Qing-Yan
authors: QY
authors: Sun
authors: School of Pharmacy, Soochow University, Suzhou 215123, China; School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: wdzhangy@hotmail.com.
authors: Wei-Dong
authors: WD
authors: Zhang
mesh_terms: D000818:Animals; D002460:Cell Line; D060326:Chemistry Techniques, Synthetic; D007783:Lactones / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D045789:Sesquiterpenes, Guaiane / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D007783:Lactones; D008070:Lipopolysaccharides; D045789:Sesquiterpenes, Guaiane; C421026:guaiane; D009569:Nitric Oxide
keywords: Guaiane-type derivatives; Inhibitory effect; Nitric oxide production; Structure–activity relationship