Synthesis and biological evaluation of novel dimethyl[1,1'-biphenyl]-2,2'-dicarboxylate derivatives containing thiazolidine-2,4-dione for the treatment of concanavalin A-induced acute liver injury of BALB/c mice

Eur J Med Chem. 2011 Dec;46(12):5941-8. doi: 10.1016/j.ejmech.2011.10.005. Epub 2011 Oct 8.

Abstract

In this paper, we reported the synthesis of bifendate derivatives and evaluation of anti-inflammatory activity by detecting the production of the Nitric Oxide (NO) in the lipopolysaccharide(LPS)-stimulated RAW 264.7 cell lines. Among the newly derivatives, compound 7k was the most potent one and two other compounds (7e and 7f) also exhibited greater anti-inflammatory activity than bifendate. Further in vivo studies confirmed that 7k significantly and dose-dependently inhibited carrageenan-induced paw edema and decreased the serum levels of alanine aminotransaminase, and aspartate aminotransaminase in concanavalin A-induced hepatitis model. Histopathological evaluation demonstrated that 7k has better hepatoprotective effect on acute liver injury induced by concanavalin A than bifendate, suggesting that 7k is a potential drug candidate for the treatment of hepatic injuries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Biphenyl Compounds / chemical synthesis
  • Biphenyl Compounds / chemistry*
  • Biphenyl Compounds / pharmacology
  • Biphenyl Compounds / therapeutic use*
  • Cell Line
  • Concanavalin A
  • Edema / chemically induced
  • Edema / drug therapy
  • Edema / pathology
  • Female
  • Hepatitis, Animal / chemically induced
  • Hepatitis, Animal / drug therapy*
  • Hepatitis, Animal / pathology
  • Lipopolysaccharides / immunology
  • Liver / drug effects*
  • Liver / pathology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide / immunology
  • Rats

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Biphenyl Compounds
  • Lipopolysaccharides
  • bifendate
  • Concanavalin A
  • Nitric Oxide