Design, synthesis and anti-inflammatory evaluation of novel 5-benzylidene-3,4-dihalo-furan-2-one derivatives

• A series of novel 5-benzylidene-3,4-dihalo-furan-2-one derivatives were designed and synthesized.
• Two compounds (6i and 6k) with excellent anti-inflammatory activity were identified.
• Anti-inflammatory mechanism of 6i and 6k was interaction with PPARγ.

Rosiglitazone has shown promising anti-inflammation effect. To develop preferable anti-inflammatory agents, twenty-two rosiglitazone analogs were synthesized and their anti-inflammatory activity was evaluated. Among these compounds, 6i and 6k displayed excellent inhibitory activities on the production of inflammatory mediators, including nitric oxide (NO), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Furthermore, 6i and 6k showed suppression effects on the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, and this suppression effects could be partially reversed by GW9662, which is a peroxisome proliferator-activated receptor γ (PPARγ) antagonist. Additionally, our docking results exhibited the well combination of 6i and 6k to PPARγ. So the anti-inflammation activity of 6i and 6k was due at least in part, to their interaction with PPARγ.

A series of novel 5-benzylidene-3,4-dihalo-furan-2-one derivatives were synthesized, characterized and their anti-inflammatory activities were evaluated. Among these compounds, 6i and 6k exhibited excellent anti-inflammatory potential.Figure optionsDownload as PowerPoint slide