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. Epub 2015 Feb 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Carbamates / chemical synthesis
  • Carbamates / chemistry*
  • Carbamates / pharmacology*
  • Chemistry Techniques, Synthetic
  • Lactones / chemistry*
  • Lipopolysaccharides / adverse effects*
  • Macrophages / drug effects*
  • Mice
  • Nitric Oxide / biosynthesis*
  • RAW 264.7 Cells

Substances

  • Anti-Inflammatory Agents
  • Carbamates
  • Lactones
  • Lipopolysaccharides
  • methylene-lactone
  • Nitric Oxide