类丹皮酚的结构修饰与其在模拟体液中的稳定性考察和抗炎活性研究

Structural modifications of paeonol and its analogs,and their stability in the simulated body fluids and anti-inflammatory activity

目的:丹皮酚及其类似物通过1,4-二溴丁烷连接,与萘普生反应合成一系列目标产物,研究其抗炎活性。方法:丹皮酚、2-羟基-5-甲氧基-苯乙酮、3-羟基苯乙酮、2-羟基苯乙酮和2,4-二羟基苯乙酮先与1,4-二溴丁烷合成缩合物,再与萘普生合成系列目标化合物。建立了HPLC的含量测定的方法在温度为37℃,p H分别为1.2,5.0和7.4的3种不同缓冲溶液条件下的降解情况,用二甲苯致小鼠耳肿胀模型对其进行抗炎活性筛选。结果:合成了5个目标化合物,经MS和1H-NMR确证其结构。降解试验说明这些化合物在不同p H的缓冲溶液体系中保持稳定。小鼠实验表明,目标化合物具有较强的抗炎作用。结论:目标化合物在胃肠道p H值中稳定,抗炎活性较强,值得进一步研究。

Objective： To connect paeonol and its analogs with 1,4-dibromobutane, then to afford a series of target products by reacting with naproxen, and investigate the anti-inflammatory activities of the products. Methods ： Paeonol, 2-hydroxy-5-methoxyacetophenone, 3-hydroxyacetophenone, 2-hydroxyacetophenone, and 2, 4-dihydroxyacetophenone were condensated with 1, 4-dibromobutane, then reacted with naproxen to yield series of target products. An HPLC method was established for determining the content of the target products. Their degradation dynamics was assessed under pH 1.2, 5.0 and 7.4 buffer conditions at 37℃. The anti-inflammatory activities of the compounds were evaluated in xylene-induced mouse ear swelling model. Results： Five new compounds were synthesized and confirmed by MS and 1^H-NMR. Degradation kinetic experiments showed that these compounds were stable in buffers of different pHs. All the compounds showed anti-inflammatory activities. Conclusion： All the compounds are stable and exhibit potent anti-inflammatory activities.