Discovery of new cinnamic derivatives as anti‐inflammatory agents for treating acute lung injury in mice

The blockade of the overexpression of pro‐inflammatory cytokines by anti‐inflammatory natural products has been proven therapeutically beneficial in the treatment of acute lung injury (ALI). Given the fact that cinnamic acid has been proven to have significant anti‐inflammatory activity, we selected it as a promising lead compound to develop more effective analogs in treating ALI. Learning from the symmetric structure of curcumin, 32 new symmetric cinnamic derivatives were designed, synthesized, and evaluated for their anti‐inflammatory activity. Among them, 6h not only displayed a remarkable inhibitory activity in vitro (85.9% and 65.7% for IL‐6 and TNF‐α, respectively) without cytotoxicity but also possessed chemical structure stability. Furthermore, an in vivo study in mice revealed that the administration of 6h significantly attenuated lipopolysaccharide‐induced ALI, providing new lead structures for the development of anti‐inflammatory drugs for the treatment of ALI. A series of 32 symmetric cinnamic analogs were designed, synthesized, and evaluated for their anti‐inflammatory activities. The most potent compound 6h showed marked in vitro inhibitory activities without cell cytotoxicity. Furthermore, 6h effectively attenuated LPS‐induced acute lung injury. Docking analysis demonstrated that 6h might be an MD2‐targeted compound.