新型大黄酸丹皮酚偶联物的合成及抗炎活性

Synthesis and Anti-inflammatory Activity of Novel Rhein-paeonol Conjugates

为寻找安全有效的抗骨关节炎药物,利用拼合原理,以不同碳数的烷烃链为连接臂,将均具有抗炎作用的大黄酸和丹皮酚偶联,得到相应的新型大黄酸丹皮酚偶联物(3a~3e),其结构经^(1)H NMR、^(13)C NMR和HR-MS(ESI)表征。采用脂多糖(LPS)刺激巨噬细胞(RAW264.7)构建细胞炎症模型,RT-qPCR检测炎性因子TNF-α,IL-1β和IL-6的mRNA表达。结果显示:目标化合物能够抑制LPS诱导的炎症因子的表达,具有一定的抗炎活性。

To search for newer anti-arthritic agents that are both effective and safe,novel Rhein-Paeonol conjugates(3a~3e)were synthesized by reaction of rhein and paeonol with dibromoalkanes bearing two to six carbons to form compounds.Five new target compounds were synthesized and their structures were confirmed by ^(1)H NMR,^(13)C NMR and HR-ESI(MS)spectroscopy.To investigate the anti-inflammatory effects of 3a~3e in LPS-stimulated macrophages,the mRNA levels of TNF-α,IL-1β,and IL-6 were measured by RT-qPCR.The result showed that all of the synthesized compounds can decrease the expression of these cytokines and has anti-inflammatory effect.