羟基肉桂酸衍生物的合成及其与人血清白蛋白的相互作用  

Preparation of Hydroxy-Cinnamic Acid Derivatives and Their Interaction with Human Serum Albumin

作　　者：杜传荣[1] 陈丹丹[1] 樊希望[2] 林翠梧[1,3] 

机构地区：[1]广西大学化学化工学院,广西南宁530004 [2]南宁市化工研究设计院,广西南宁530022 [3]广西高校应用化学技术与资源开发重点实验室,广西南宁530004

出　　处：《精细化工》2015年第9期1014-1021,1026,共9页Fine Chemicals

基　　金：国家自然科学基金(21362001);广西研究生教育创新计划资助项目(YCBZ2013011);广西自然科学基金重点项目(2013GXNSFDA019005)~~

摘　　要：以咖啡酸、间羟基肉桂酸为母体,分别与止血芳酸反应,设计合成两种羟基肉桂酸衍生物(E)-4-{[1'-(3″,4″-二羟基苯基)丙烯酰氨基]甲基}苯甲酸(Ⅰ)、(E)-4-{[1'-(3″-羟基苯基)丙烯酰氨基]甲基}苯甲酸(Ⅱ),并用MS、IR、1HNMR、13CNMR进行结构表征。采用荧光光谱法、同步荧光光谱法、紫外可见光谱法结合分子对接技术研究其在体外生理条件下与人血清白蛋白(HSA)之间的相互作用机制。光谱实验结果表明,衍生物Ⅰ和Ⅱ都可以使HSA的内源荧光发生静态猝灭,相互作用力主要是氢键和范德华力,且对HSA的构象产生一定影响。分子对接结果表明,衍生物Ⅰ、Ⅱ与HSA结合在亚结构域ⅡA(即site I)中,作用力主要是氢键和范德华力,同时还存在着疏水作用,且衍生物距色氨酸残基(Trp214)很近,很好地解释了衍生物有效猝灭HSA内源荧光的实验现象。分子对接与实验获得了一致性的结果,二者相互佐证,提高了实验结果推断的准确度。Two hydroxy-cinnamic acid derivatives（ compound Ⅰ：（ E）-4-{ [1＇-（ 3″, 4″-dihydroxyphenyl） acrylamido ] methyl } benzoic acid and compound Ⅱ：（ E）-4-{ [1＇-（ 3″-hydroxyphenyl） acrylamido]methyl} benzoic acid） were synthesised by the reaction of caffeic acid and m-hydroxybenzoic acid with p-aminomethylbenzoic acid（ AMBA）,respectively. The chemical structures were confirmed by MS,IR,1HNMR and13 CNMR. The interactions between compounds and human serum albumin（ HSA） were investigated under imitated physiological condition by fluorescence spectroscopy,UV-visible absorption spectroscopy and molecular docking. The experimental results indicate that the quenching mechanism of HSA by the derivatives was static quenching mechanism at different temperatures. The derivatives-HSA interactions were mainly driven by hydrogen bonds and Van der Waals＇ s forces. Meanwhile,derivatives Ⅰ and Ⅱ affected the conformation of HSA. The molecular docking indicated that derivatives Ⅰ and Ⅱ existed in subdomain ⅡA（ site Ⅰ） of HSA.Furthermore,the derivatives were close to tryptophan residues（ Trp214）. The results reveal that the intrinsic fluorescence of HSA could be successfully decreased by derivatives interactions. The experimental results were in agreement with molecular docking.

关 键 词：羟基肉桂酸衍生物 人血清白蛋白(HSA) 荧光光谱法 分子对接 医药与日化原料 

分 类 号：O625.5[理学—有机化学]