Synthesis and evaluation of new α-methylene-γ-lactone carbamates with NO production inhibitory effects in lipopolysaccharide-induced RAW 264.7 macrophages

  • Eur J Med Chem. 2015 Mar 26:93:274-80. doi: 10.1016/j.ejmech.2015.02.016.
Wen-Hao Shao  1 ,  Bing-Yang Chen  1 ,  Xiang-Rong Cheng  2 ,  Hu Yuan  3 ,  Hao Chen  1 ,  Wan-Lin Chang  1 ,  Ji Ye  1 ,  Shan Lin  1 ,  Qing-Yan Sun  4 ,  Wei-Dong Zhang  5
Affiliations
  • 1. Department of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
  • 2. School of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
  • 3. Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China.
  • 4. Department of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China; Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China. Electronic address: [email protected].
  • 5. Department of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China; Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China. Electronic address: [email protected].
PMID: 25703295 DOI: 10.1016/j.ejmech.2015.02.016
Abstract

A series of new α-methylene-γ-lactone carbamates were synthesized by an asymmetric synthetic route. The activities on inhibiting nitric oxide (NO) release of these compounds were evaluated in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. The results indicated that most of the compounds except one exhibited potent NO inhibitory effect with IC50 value more than 2 μΜ. The cytotoxicities of these compounds were estimated via MTT assays. The results suggested that six compounds were accompanied by low cytotoxicity. The structure-activity relationships were also discussed. The S configuration of C3 on lactones ring would be more helpful to NO inhibitory effect.

Keywords
Carbamate; Cytotoxicity; NO inhibitory effect; α-Methylene-γ-lactone.