类丹皮酚的结构修饰与在模拟体液中的稳定性考察和抗炎活性研究
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摘要
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,再与酮洛芬合成系列目标化合物。用HPLC考察目标化合物在不同pH缓冲液中的降解情况,用二甲苯致小鼠耳肿胀模型对其进行抗炎活性筛选。合成了5个目标化合物,经MS和~1H-NMR确证其结构。HPLC证明其在体内稳定。小鼠实验表明,目标化合物具有较强的抗炎作用。目标化合物在胃肠道pH值中稳定,抗炎活性较强,值得进一步研究。
Paeonol,2-hydroxy-5-methoxyacetophenone,2-hydroxy-5-methoxyacetophenone,2-hydroxyacetophenone,3-hydroxyacetophenone,2,4-dihydroxyacetophenone were condensated with 1,4-dibromobutane,then reacted with ketoprofen to yield series of target products.The HPLC method was established for determination of 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.Five new compounds were synthesized and confirmed by MS and ~1H-NMR.Degradation kinetic experiments showed that these compounds were stable in buffers of different pHs.All the compounds showed anti-inflammatory activities.All the compounds were stable and exhibited potent anti-inflammatory activities.
Paeonol,2-hydroxy-5-methoxyacetophenone,2-hydroxy-5-methoxyacetophenone,2-hydroxyacetophenone,3-hydroxyacetophenone,2,4-dihydroxyacetophenone were condensated with 1,4-dibromobutane,then reacted with ketoprofen to yield series of target products.The HPLC method was established for determination of 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.Five new compounds were synthesized and confirmed by MS and ~1H-NMR.Degradation kinetic experiments showed that these compounds were stable in buffers of different pHs.All the compounds showed anti-inflammatory activities.All the compounds were stable and exhibited potent anti-inflammatory activities.
引文
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[3]张竞之,陈小忆,金伟孝,等.丹皮酚对高血压病血瘀证患者血清损伤的HUVEC-C形态学、活性的影响[J].辽宁中医药大学学报,2012(6):29-31.
[4]CHEN B D,NING M L,YANG G S.Effect of paeonol on antioxidant and immune regulatory activity in hepatocellular carcinoma rats[J].Molecules,2012,17:4 672-4 683.
[5]CHEN B Y,YUE R C,LIU F,et al.Acetophenones and antioxidant activity in cynanchum auriculatum royle ex Wight[J].J Pharm Sci,2013,31(5):351-354.
[6]Laine L,Smith R,Min K,et al.Systematic review:the lower gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs[J].Aliment Pharmacol Ther,2011,3(43):751-767.
[7]陈莉敏,姜玉才,彭永练.丹皮酚的孪药合成及降解动力学和抗炎活性研究[J].中国药学杂志,2016,51(1):61-64.
[8]孟策,沈雁.奥硝唑在水溶液中的降解动力学研究[J].药学与临床研究,2013,21(2):150-152.
[9]孙海林,朱培芳.云厚朴醇提物中厚朴酚与和厚朴酚降解动力学研究[J].环球中医药,2014,7(10):761-765.
[10]黄晓龙,雷继峰.溶出度在药品评价中的作用探讨[J].中国新药杂志,2015,24(14):1 584-1 589
[11]周勇,张洪健,尹秀梅.7-取代-[1,2,4]三唑[1,5-a]嘧啶-5(4H)-酮衍生物的合成及抗炎活性的研究[J].化学研究与应用,2018,30(2):196-200.
[12]徐桂清,杨军英,张鹏,等.2-[(2,6-二氯苯基)氨基]苯乙酸稀土配合物的合成及抗炎镇痛活性研究[J].化学研究与应用,2011,23(2):194-198.
[13]彭永练,胡丁旺,姜玉才,等.酯类双缩合化合物的合成及抗炎活性研究[J].中国医院药学杂志,2016,36(8):625-629.