Anti‐Inflammatory Activities of Melatonin Derivatives in Lipopolysaccharide‐Stimulated RAW 264.7 Cells and Antinociceptive Effects in Mice

Preclinical ResearchThis study describes the anti‐inflammatory activities of two semisynthesized melatonin ( MT ) derivatives, benzoyl‐melatonin ( BMT ) and acetyl‐melatonin ( AMT ), on the production of pro‐inflammatory mediators in lipopolysaccharide ( LPS )‐stimulated macrophage cells ( RAW 264.7) and their antinociceptive effects in mice. The MT derivatives inhibited production of nitric oxide NO and prostaglandin E 2 in LPS ‐stimulated RAW 264.7 cells in a dose‐dependent manner with IC 50 values lower than those of MT . BMT produced increased tail flick latency time, decreased number of writhes, and reduced nociceptive response in mice when compared with AMT and MT . BMT and AMT had enhanced anti‐inflammatory effects in LPS ‐stimulated RAW 264.7 compared with MT . However, in mouse studies BMT exhibited the highest potency as an anti‐inflammatory agent and was longer‐acting as an antinociceptive compound compared with AMT or MT , suggesting that BMT has potential as an anti‐inflammatory and analgesic compound.