10.1021/jm901183d
The research focuses on the discovery of a novel glitazone, (Z)-5-(4-methoxybenzylidene)thiazolidine-2,4-dione, as an orally active and readily available treatment for Concanavalin A-induced acute liver injury in BALB/c mice. The study involves the synthesis and screening of 53 small molecules from a small-molecule library, using a quick screening method to evaluate their potency in inhibiting chemotaxis of RAW264.7 cells stimulated by monocyte chemoattractant protein 1 (MCP-1). The most effective compounds were identified through in vitro inhibitory effects and further assessed in vivo for their hepatoprotective effects. The experiments utilized various reactants, including aromatic aldehydes, β-alanine, barbituric acid, thiobarbituric acid, and other chemical reagents, and employed techniques such as Knoevenagel reaction, Wittig reaction, and HPLC for compound synthesis and purity analysis. The biological activity was assessed through chemotaxis assays, serum aminotransferase level measurements, and histopathological evaluations. The study demonstrated that compound 4f significantly reduced serum levels of alanine aminotransaminase (ALT) and asparate aminotransaminase (AST) and showed hepatoprotective effects in the liver injury model, with minimal toxicity observed in histopathological assessments of major organs.