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: sqy_2000@163.com.
5 Department of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China; Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China. Electronic address: wdzhangy@hotmail.com.

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.

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