对硝基肉桂酸配合物的合成、结构分析及脲酶抑制活性研究
发布时间：2019-05-27 22:28
【摘要】：脲酶广泛存在于真菌、细菌以及植物中，被认为是许多病原微生物的毒力因子。脲酶是第一个被发现含有镍离子的酶，在催化尿素水解的过程中，其活性中心的镍离子发挥了重要的作用。不同脲酶的结构虽然不同，但它们活性中心的蛋白序列却是高度相似的，因此不同脲酶的催化机制本质上来说也是相同的。幽门螺杆菌（H. pylori）是胃部疾病的主要致病菌，并被证明其与胃癌有着直接的关系。越来越多的证据表明脲酶在幽门螺杆菌感染胃部的过程中起到了关键作用，因此脲酶抑制剂的研究越来越受到人们关注。 肉桂酸是一种在香料、食品添加剂等方面具有广泛应用的天然产物，随着研究的深入，人们发现肉桂酸衍生物还具有一定的抗菌、抗氧化、抗癌等药物活性。以顺铂、卡铂等为代表的金属配位化合物除了具有优异的抗癌活性外，还具有杀菌、消炎、抗病毒等多种生物活性。据有关文献报道，过渡金属配合物也有着不错的脲酶抑制活性。 本文以对硝基苯甲醛和丙二酸为原料合成了对硝基肉桂酸，以其为主配体辅以有机胺，采用常规的溶液结晶法，合成得到了5种新型的对硝基肉桂酸过渡金属配合物，通过红外和单晶X射线衍射方法确定了这5种配合物的具体结构。分别为：配合物1是单核镍配合物，镍与对硝基肉桂酸、N,N’-二甲基乙二胺和配位水成六配位结构。空间群为P-1，晶胞参数为a=6.2331(5), b=14.2263(11), c=15.0427(12), α=77.244(3)°, β=82.061(3)°, γ=81.259(3)°；配合物2也是单核镍配合物，但对硝基肉桂酸未参与配位，镍与乙二胺和配位水成六配位结构。空间群为C2/c，晶胞参数为a=31.0943(17), b=6.5008(4), c=14.6306(8),α=90°, β=105.478(2)°, γ=90°；配合物3是双核铜配合物，对硝基肉桂酸未参与配位，两个氧原子充当桥连原子，，每个铜原子与N,N’-二甲基乙二胺、桥连氧原子和配位水成五配位结构。空间群为P-1，晶胞参数为a=7.5763(7),b=8.0475(7), c=15.7825(14), α=77.404(3)°, β=76.433(3)°, γ=79.479(3)°；配合物4与配合物2结构类似，是单核铜配合物，铜与乙二胺和配位水成六配位结构。空间群为C2/c，晶胞参数为a=31.0826(13), b=6.0511(3), c=14.6480(7), α=90°, β=105.535(2)°, γ=90°；配合物5是单核锌配合物，两分子对硝基肉桂酸和一分子1,2-丙二胺与锌成四配位结构。空间群为Pnma，晶胞参数为a=6.0983(2), b=25.9204(9), c=13.9274(4), α=90°, β=90°, γ=90°。 采用pH增值法检测了这5种配合物对刀豆（Jack bean）脲酶的抑制活性。试验结果显示，5种对硝基肉桂酸过渡金属配合物均显示出了相当或好于阳性对照（乙酰氧肟酸）的脲酶抑制活性，其中配合物3和配合物4具有明显好于阳性对照的脲酶抑制活性，IC50值分别达到了1.23μM和1.17μM。本文关于对硝基肉桂酸过渡金属配合物研究，拓展了肉桂酸衍生物的应用，并且脲酶抑制活性结果显示对硝基肉桂酸过渡金属配合物可作为潜在的脲酶抑制剂继续进行研究。
[Abstract]:The enzymes are widely present in fungi, bacteria and plants, and are considered to be the virulence factors of many pathogenic microorganisms. The enzyme is the first enzyme to be found to contain nickel ions, and the nickel ion of its active center plays an important role in the process of catalytic urea hydrolysis. The structure of the different transposase is different, but the protein sequence of the active centers is highly similar, so the catalytic mechanism of the different transposase is also the same. Helicobacter pylori (H. pylori) is the main pathogenic bacteria of the stomach disease and is proved to have a direct relationship with the gastric cancer. There is a growing number of evidence that the enzyme plays a key role in the process of the infection of the stomach by Helicobacter pylori, so the study of the enzyme inhibitor is becoming more and more concerned. The cinnamic acid is a natural product which is widely used in the fields of spices, food additives and the like, and as the research goes deep, it is found that the cinnamic acid derivative has certain antibacterial, anti-oxidation, anti-cancer and other drug activity. The metal coordination compound represented by cisplatin, carboplatin and the like has the advantages of excellent anti-cancer activity, sterilization, anti-inflammatory, antiviral and the like The transition metal complex also has a good inhibitory activity against the enzyme, according to the literature. In this paper, p-nitrocinnamic acid is synthesized by using p-nitrobenzaldehyde and malonic acid as raw materials, and the main ligand is used as the main ligand and the organic amine is used, and the conventional solution crystallization method is adopted to synthesize five novel p-nitrocinnamic acid transition metals. The complexes are determined by means of an infrared and single crystal X-ray diffraction method. The space group is P-1, the cell parameters are a = 6.2331 (5), b = 14.2263 (11), c = 15.0427 (12), b = 77.244 (3) 掳, C = 82.061 (3) 掳, and P = 81.259 ( 3). The complex 2 is also a mononuclear nickel complex, but it is not involved in the coordination of the nitrocinnamic acid, and the nickel and the ethylenediamine and the coordination water are six coordination structures. The space group is C2/ c, the cell parameters are a = 31.0943 (17), b = 6.5008 (4), c = 14.6306 (8), b = 90 掳, b = 105.478 (2) 掳,1 = 90 掳; the complex 3 is a dual-core copper The complex, p-nitrocinnamic acid is not involved in coordination, two oxygen atoms act as bridging atoms, each copper atom is in a five-way with N, N '-dimethyl ethylenediamine, bridging oxygen atoms and coordination water The space group is P-1, and the cell parameters are a = 7.5763 (7), b = 8.0475 (7), c = 15.7825 (14), b = 77.404 (3) 掳, c = 76.433 (3) 掳, p = 79.479 (3) 掳, the complex 4 is similar to the structure of the complex 2, it is a mononuclear copper complex, and the copper and the ethylenediamine and the coordination water are 6. Bit structure. The space group is C2/ c, the cell parameters are a = 31.0826 (13), b = 6.0511 (3), c = 14.6480 (7), b = 90 掳,1 = 105.535 (2) 掳,1 = 90 掳, the complex 5 is a mononuclear zinc complex, the two molecules p-nitrocinnamic acid and a molecule of 1,2-propane diamine and zinc are four-matched. bit structure. The space group is sigma, the cell parameters are a = 6.0983 (2), b = 25.9204 (9), c = 13.9274 (4), b = 90 掳, xt = 90 掳, xt = The 5 kinds of complexes were detected by the pH value-added method. The results of the test show that 5 kinds of p-nitrocinnamic acid transition metal complexes show comparable or better positive control (ethmoximic acid), in which the complex 3 and the complex 4 have a better effect than that of the positive control. The enzyme-inhibitory activity and the IC50 value were 1.23. m u.M and 1.17. m u.M, respectively. The study on the transition metal complex of the nitrocinnamic acid extended the application of the cinnamic acid derivative, and the results showed that the transition metal complex of the nitrocinnamic acid can be used as a potential enzyme inhibitor.
【学位授予单位】：山东理工大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914.5;R96
本文编号：2486501
[Abstract]:The enzymes are widely present in fungi, bacteria and plants, and are considered to be the virulence factors of many pathogenic microorganisms. The enzyme is the first enzyme to be found to contain nickel ions, and the nickel ion of its active center plays an important role in the process of catalytic urea hydrolysis. The structure of the different transposase is different, but the protein sequence of the active centers is highly similar, so the catalytic mechanism of the different transposase is also the same. Helicobacter pylori (H. pylori) is the main pathogenic bacteria of the stomach disease and is proved to have a direct relationship with the gastric cancer. There is a growing number of evidence that the enzyme plays a key role in the process of the infection of the stomach by Helicobacter pylori, so the study of the enzyme inhibitor is becoming more and more concerned. The cinnamic acid is a natural product which is widely used in the fields of spices, food additives and the like, and as the research goes deep, it is found that the cinnamic acid derivative has certain antibacterial, anti-oxidation, anti-cancer and other drug activity. The metal coordination compound represented by cisplatin, carboplatin and the like has the advantages of excellent anti-cancer activity, sterilization, anti-inflammatory, antiviral and the like The transition metal complex also has a good inhibitory activity against the enzyme, according to the literature. In this paper, p-nitrocinnamic acid is synthesized by using p-nitrobenzaldehyde and malonic acid as raw materials, and the main ligand is used as the main ligand and the organic amine is used, and the conventional solution crystallization method is adopted to synthesize five novel p-nitrocinnamic acid transition metals. The complexes are determined by means of an infrared and single crystal X-ray diffraction method. The space group is P-1, the cell parameters are a = 6.2331 (5), b = 14.2263 (11), c = 15.0427 (12), b = 77.244 (3) 掳, C = 82.061 (3) 掳, and P = 81.259 ( 3). The complex 2 is also a mononuclear nickel complex, but it is not involved in the coordination of the nitrocinnamic acid, and the nickel and the ethylenediamine and the coordination water are six coordination structures. The space group is C2/ c, the cell parameters are a = 31.0943 (17), b = 6.5008 (4), c = 14.6306 (8), b = 90 掳, b = 105.478 (2) 掳,1 = 90 掳; the complex 3 is a dual-core copper The complex, p-nitrocinnamic acid is not involved in coordination, two oxygen atoms act as bridging atoms, each copper atom is in a five-way with N, N '-dimethyl ethylenediamine, bridging oxygen atoms and coordination water The space group is P-1, and the cell parameters are a = 7.5763 (7), b = 8.0475 (7), c = 15.7825 (14), b = 77.404 (3) 掳, c = 76.433 (3) 掳, p = 79.479 (3) 掳, the complex 4 is similar to the structure of the complex 2, it is a mononuclear copper complex, and the copper and the ethylenediamine and the coordination water are 6. Bit structure. The space group is C2/ c, the cell parameters are a = 31.0826 (13), b = 6.0511 (3), c = 14.6480 (7), b = 90 掳,1 = 105.535 (2) 掳,1 = 90 掳, the complex 5 is a mononuclear zinc complex, the two molecules p-nitrocinnamic acid and a molecule of 1,2-propane diamine and zinc are four-matched. bit structure. The space group is sigma, the cell parameters are a = 6.0983 (2), b = 25.9204 (9), c = 13.9274 (4), b = 90 掳, xt = 90 掳, xt = The 5 kinds of complexes were detected by the pH value-added method. The results of the test show that 5 kinds of p-nitrocinnamic acid transition metal complexes show comparable or better positive control (ethmoximic acid), in which the complex 3 and the complex 4 have a better effect than that of the positive control. The enzyme-inhibitory activity and the IC50 value were 1.23. m u.M and 1.17. m u.M, respectively. The study on the transition metal complex of the nitrocinnamic acid extended the application of the cinnamic acid derivative, and the results showed that the transition metal complex of the nitrocinnamic acid can be used as a potential enzyme inhibitor.
【学位授予单位】：山东理工大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914.5;R96
【共引文献】
相关期刊论文 前2条
1 黄振龙;汤立军;;一种基于联二萘酚的缩氨基硫脲化合物的合成及其对锌离子的荧光识别[J];渤海大学学报(自然科学版);2014年02期
2 Rui-Guang Ge;Dong-Xian Wang;Ming-Cong Hao;Xue-Song Sun;;Nickel trafficking system responsible for urease maturation inHelicobacter pylori[J];World Journal of Gastroenterology;2013年45期
本文编号：2486501
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