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

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.

Graphical abstractNovel bifendate derivatives containing thiazolidine-2,4-dione exhibited greater anti-inflammatory and hepatoprotective activity than bifendate as revealed by in vitro screening and in vivo testing.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Designed and synthesized a series of bifendate derivatives containing thiazolidine-2,4-dione. ► The biological activity of these compounds was evaluated in vitro and in vivo. ► 7k exhibited greater anti-inflammatory and hepatoprotective activity than bifendate.