【摘要】：阿司匹林(簡稱Aspirin)是一種常用的解熱、抗炎藥物,其結(jié)構(gòu)簡單,療效良好。越來越多的研究發(fā)現(xiàn)Aspirin具有治療癌癥和心腦血管疾病的作用,但其副作用也是不容忽略的。為了克服這些副作用,Aspirin的作用機理及藥物改性方面的研究成為熱點。本文從抑制環(huán)氧合酶、核轉(zhuǎn)錄因子、激活蛋白激酶等方面綜述了Aspirin的作用機理,對Aspirin結(jié)構(gòu)衍生物的研究進行了論述,進一步對Aspirin的結(jié)構(gòu)進行修飾,并對其活性進行研究,期望提高其在解熱、抗炎、抗腫瘤和抗心血管等方面療效的同時降低副作用。論文共合成了六種Aspirin結(jié)構(gòu)衍生物,并研究了Aspirin及其結(jié)構(gòu)衍生物消除自由基的能力及與人血清白蛋白(簡稱HSA)之間的作用。利用紫外可見分光光度法研究了Aspirin衍生物對DPPH、O2及OH·的清除效果,利用熒光分光光度法研究了其與HSA之間之間的相互作用。實驗結(jié)果表明,糖環(huán)的引入可增強Aspirin清除DPPH自由基的能力,而氨基酸結(jié)構(gòu)的引入反而降低了Aspirin對DPPH的清除效果；兩類結(jié)構(gòu)衍生物對OH-的清除效果均低于Aspirin;糖環(huán)的引入可提高對02-·的清除率,而氨基酸Aspirin結(jié)構(gòu)衍生物對O2-·的清除效果低于Aspirin; Aspirin及其衍生物可不同程度的降低HSA的熒光強度；Aspirin與HSA之間的作用主要是疏水作用,P1、P6與HSA之間的作用力主要是靜電作用,P2、P3、P4、P5與HSA之間的作用力主要是氫鍵和范德華力；同步熒光光譜結(jié)果表明,Aspirin及其衍生物均能改變色氨酸殘基的化學(xué)環(huán)境,使HSA腔內(nèi)疏水環(huán)境中的極性增大,肽鏈的伸展程度有所增加,進而使蛋白質(zhì)的構(gòu)象發(fā)生了改變；等高線圖和三維立體圖結(jié)果表明,兩類衍生物都能使HSA熒光強度猝滅,糖類衍生物較氨基酸類衍生物作用效果明顯,而且并未使較弱的熒光區(qū)完全消失,說明在研究濃度范圍內(nèi)沒有導(dǎo)致HSA結(jié)構(gòu)破壞,保證了HSA的結(jié)構(gòu)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.
【學(xué)位授予單位】：太原理工大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R914.5

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相關(guān)碩士學(xué)位論文 前1條

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本文編號：2217317