阿司匹林结构衍生物的合成及其体外活性研究
发布时间：2018-09-01 13:17
【摘要】：阿司匹林(简称Aspirin)是一种常用的解热、抗炎药物,其结构简单,疗效良好。越来越多的研究发现Aspirin具有治疗癌症和心脑血管疾病的作用,但其副作用也是不容忽略的。为了克服这些副作用,Aspirin的作用机理及药物改性方面的研究成为热点。本文从抑制环氧合酶、核转录因子、激活蛋白激酶等方面综述了Aspirin的作用机理,对Aspirin结构衍生物的研究进行了论述,进一步对Aspirin的结构进行修饰,并对其活性进行研究,期望提高其在解热、抗炎、抗肿瘤和抗心血管等方面疗效的同时降低副作用。论文共合成了六种Aspirin结构衍生物,并研究了Aspirin及其结构衍生物消除自由基的能力及与人血清白蛋白(简称HSA)之间的作用。利用紫外可见分光光度法研究了Aspirin衍生物对DPPH、O2及OH·的清除效果,利用荧光分光光度法研究了其与HSA之间之间的相互作用。实验结果表明,糖环的引入可增强Aspirin清除DPPH自由基的能力,而氨基酸结构的引入反而降低了Aspirin对DPPH的清除效果；两类结构衍生物对OH-的清除效果均低于Aspirin;糖环的引入可提高对02-·的清除率,而氨基酸Aspirin结构衍生物对O2-·的清除效果低于Aspirin; Aspirin及其衍生物可不同程度的降低HSA的荧光强度；Aspirin与HSA之间的作用主要是疏水作用,P1、P6与HSA之间的作用力主要是静电作用,P2、P3、P4、P5与HSA之间的作用力主要是氢键和范德华力；同步荧光光谱结果表明,Aspirin及其衍生物均能改变色氨酸残基的化学环境,使HSA腔内疏水环境中的极性增大,肽链的伸展程度有所增加,进而使蛋白质的构象发生了改变；等高线图和三维立体图结果表明,两类衍生物都能使HSA荧光强度猝灭,糖类衍生物较氨基酸类衍生物作用效果明显,而且并未使较弱的荧光区完全消失,说明在研究浓度范围内没有导致HSA结构破坏,保证了HSA的结构安全。
[Abstract]:Aspirin (Aspirin) is a common antipyretic and anti-inflammatory drug. More and more studies have found that Aspirin can treat cancer and cardiovascular and cerebrovascular diseases, but its side effects should not be ignored. In order to overcome these side effects, the mechanism of Aspirin and drug modification have become a hot topic. In this paper, the mechanism of Aspirin was reviewed from the aspects of inhibition of cyclooxygenase, nuclear transcription factor and activated protein kinase. The structure of Aspirin was studied, and the structure of Aspirin was modified and its activity was studied. It is expected to improve its antipyretic, anti-inflammatory, anti-tumor and anti-cardiovascular effects while reducing side effects. In this paper, six derivatives of Aspirin structure were synthesized, and the ability of Aspirin and its derivatives to eliminate free radicals and their interaction with human serum albumin (HSA) were studied. The scavenging effect of Aspirin derivatives on DPPH,O2 and OH was studied by UV-Vis spectrophotometry, and the interaction between HSA and DPPH,O2 was studied by fluorescence spectrophotometry. The experimental results show that the introduction of sugar ring can enhance the ability of Aspirin to scavenge DPPH free radical, while the introduction of amino acid structure reduces the scavenging effect of Aspirin on DPPH. The scavenging effect of two kinds of structure derivatives to OH- was lower than that of the introduction of Aspirin; sugar ring, while that of amino acid Aspirin derivatives to O 2-was lower than that of Aspirin; Aspirin and its derivatives, and the fluorescence intensity of HSA could be decreased to some extent. The interaction between Aspirin and HSA is mainly hydrophobic interaction between P1P6 and HSA is mainly electrostatic interaction between P2P3P4P4P5 and HSA is mainly hydrogen bond and van der Waals force. The results of synchronous fluorescence spectra showed that Aspirin and its derivatives could change the chemical environment of tryptophan residues, increase the polarity in the hydrophobic environment of HSA, increase the extension of peptide chain, and change the conformation of protein. The results of contour diagram and 3D stereogram show that both of them can quench the fluorescence intensity of HSA, the effect of carbohydrate derivatives is more obvious than that of amino acid derivatives, and the weak fluorescence region is not completely disappeared. It shows that the structure of HSA is not destroyed in the range of concentration, and the structural safety of HSA is ensured.
【学位授予单位】：太原理工大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914.5
本文编号：2217317
[Abstract]:Aspirin (Aspirin) is a common antipyretic and anti-inflammatory drug. More and more studies have found that Aspirin can treat cancer and cardiovascular and cerebrovascular diseases, but its side effects should not be ignored. In order to overcome these side effects, the mechanism of Aspirin and drug modification have become a hot topic. In this paper, the mechanism of Aspirin was reviewed from the aspects of inhibition of cyclooxygenase, nuclear transcription factor and activated protein kinase. The structure of Aspirin was studied, and the structure of Aspirin was modified and its activity was studied. It is expected to improve its antipyretic, anti-inflammatory, anti-tumor and anti-cardiovascular effects while reducing side effects. In this paper, six derivatives of Aspirin structure were synthesized, and the ability of Aspirin and its derivatives to eliminate free radicals and their interaction with human serum albumin (HSA) were studied. The scavenging effect of Aspirin derivatives on DPPH,O2 and OH was studied by UV-Vis spectrophotometry, and the interaction between HSA and DPPH,O2 was studied by fluorescence spectrophotometry. The experimental results show that the introduction of sugar ring can enhance the ability of Aspirin to scavenge DPPH free radical, while the introduction of amino acid structure reduces the scavenging effect of Aspirin on DPPH. The scavenging effect of two kinds of structure derivatives to OH- was lower than that of the introduction of Aspirin; sugar ring, while that of amino acid Aspirin derivatives to O 2-was lower than that of Aspirin; Aspirin and its derivatives, and the fluorescence intensity of HSA could be decreased to some extent. The interaction between Aspirin and HSA is mainly hydrophobic interaction between P1P6 and HSA is mainly electrostatic interaction between P2P3P4P4P5 and HSA is mainly hydrogen bond and van der Waals force. The results of synchronous fluorescence spectra showed that Aspirin and its derivatives could change the chemical environment of tryptophan residues, increase the polarity in the hydrophobic environment of HSA, increase the extension of peptide chain, and change the conformation of protein. The results of contour diagram and 3D stereogram show that both of them can quench the fluorescence intensity of HSA, the effect of carbohydrate derivatives is more obvious than that of amino acid derivatives, and the weak fluorescence region is not completely disappeared. It shows that the structure of HSA is not destroyed in the range of concentration, and the structural safety of HSA is ensured.
【学位授予单位】：太原理工大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914.5
【参考文献】
相关硕士学位论文 前1条
1 朱前进;T614衍生物的合成和阿司匹林及其衍生物的糖基化结构修饰研究[D];南京理工大学;2004年
，本文编号：2217317
本文链接：https://www.wllwen.com/yixuelunwen/yiyaoxuelunwen/2217317.html
最近更新
教材专著
