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

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

  • Eur J Med Chem. 2014 Aug 18:83:307-16. doi: 10.1016/j.ejmech.2014.06.043.
Hao Chen 1,  Bing-Yang Chen 2,  Chun-Ting Liu 2,  Zeng Zhao 2,  Wen-Hao Shao 2,  Hu Yuan 3,  Kai-Jian Bi 2,  Jiang-Yun Liu 4,  Qing-Yan Sun 5,  Wei-Dong Zhang 6
Affiliations

Affiliations

  • 1 School of Pharmacy, Soochow University, Suzhou 215123, China; School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
  • 2 School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
  • 3 School of Pharmacy, Second Military Medical University, Shanghai 200433, China; School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
  • 4 School of Pharmacy, Soochow University, Suzhou 215123, China. Electronic address: liujiangyun@suda.edu.cn.
  • 5 School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: sqy_2000@163.com.
  • 6 School of Pharmacy, Soochow University, Suzhou 215123, China; School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: wdzhangy@hotmail.com.
PMID: 24974350 DOI: 10.1016/j.ejmech.2014.06.043
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.

Keywords

Guaiane-type derivatives; Inhibitory effect; Nitric oxide production; Structure–activity relationship.

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