Design, Synthesis and Biological Activities Evaluation of Novel Pterostilbene‐Urea Derivatives as Potential Anti‐Inflammatory Agents

1. The toxicity of derivatives was removed by the reasonable modification of bioactive skeleton. 2. As potential COX-2 inhibitor with IC₅₀ values ranging from 39.42 to 179.84 nM/L, compounds (Q4-Q10, Q20) exhibited superior anti-inflammatory activity at low micromolar concentrations. 3. Q7 (IC_{50 (COX-2)}= 61.05 nM/L), Q10 (IC_{50 (COX-2)}= 54.68 nM/L) and Q20 (IC_{50 (COX-2)}= 39.42 nM/L) showed stronger COX-2 inhibitory abilities than Celecoxib (IC_{50 (COX-2)}= 67.89 nM/L). 4. The strongest anti-inflammatory agent, Q20 (IC_{50 NO}= 9.96 μM/L, IC_{50 (COX-2)}= 39.42 nM/L) effectively inhibited the secretion of IL-1β and TNF-α, exhibited the IC₅₀ values of 12.30 and 9.07 μM/L respectively. 5. Q20 exerted as anti-inflammatory actives via targeting COX-2, down-regulating iNOS and TLR4 protein, and inhibiting the activation of NLRP3 inflammasome and NF-κB signal pathway.