【摘要】：脲酶廣泛存在于真菌、細菌以及植物中，被認為是許多病原微生物的毒力因子。脲酶是第一個被發(fā)現(xiàn)含有鎳離子的酶，在催化尿素水解的過程中，其活性中心的鎳離子發(fā)揮了重要的作用。不同脲酶的結(jié)構(gòu)雖然不同，但它們活性中心的蛋白序列卻是高度相似的，因此不同脲酶的催化機制本質(zhì)上來說也是相同的。幽門螺桿菌（H. pylori）是胃部疾病的主要致病菌，并被證明其與胃癌有著直接的關(guān)系。越來越多的證據(jù)表明脲酶在幽門螺桿菌感染胃部的過程中起到了關(guān)鍵作用，因此脲酶抑制劑的研究越來越受到人們關(guān)注。 肉桂酸是一種在香料、食品添加劑等方面具有廣泛應用的天然產(chǎn)物，隨著研究的深入，人們發(fā)現(xiàn)肉桂酸衍生物還具有一定的抗菌、抗氧化、抗癌等藥物活性。以順鉑、卡鉑等為代表的金屬配位化合物除了具有優(yōu)異的抗癌活性外，還具有殺菌、消炎、抗病毒等多種生物活性。據(jù)有關(guān)文獻報道，過渡金屬配合物也有著不錯的脲酶抑制活性。 本文以對硝基苯甲醛和丙二酸為原料合成了對硝基肉桂酸，以其為主配體輔以有機胺，采用常規(guī)的溶液結(jié)晶法，合成得到了5種新型的對硝基肉桂酸過渡金屬配合物，通過紅外和單晶X射線衍射方法確定了這5種配合物的具體結(jié)構(gòu)。分別為：配合物1是單核鎳配合物，鎳與對硝基肉桂酸、N,N’-二甲基乙二胺和配位水成六配位結(jié)構(gòu)。空間群為P-1，晶胞參數(shù)為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也是單核鎳配合物，但對硝基肉桂酸未參與配位，鎳與乙二胺和配位水成六配位結(jié)構(gòu)�？臻g群為C2/c，晶胞參數(shù)為a=31.0943(17), b=6.5008(4), c=14.6306(8),α=90°, β=105.478(2)°, γ=90°；配合物3是雙核銅配合物，對硝基肉桂酸未參與配位，兩個氧原子充當橋連原子，，每個銅原子與N,N’-二甲基乙二胺、橋連氧原子和配位水成五配位結(jié)構(gòu)�？臻g群為P-1，晶胞參數(shù)為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與配合物2結(jié)構(gòu)類似，是單核銅配合物，銅與乙二胺和配位水成六配位結(jié)構(gòu)�？臻g群為C2/c，晶胞參數(shù)為a=31.0826(13), b=6.0511(3), c=14.6480(7), α=90°, β=105.535(2)°, γ=90°；配合物5是單核鋅配合物，兩分子對硝基肉桂酸和一分子1,2-丙二胺與鋅成四配位結(jié)構(gòu)�？臻g群為Pnma，晶胞參數(shù)為a=6.0983(2), b=25.9204(9), c=13.9274(4), α=90°, β=90°, γ=90°。 采用pH增值法檢測了這5種配合物對刀豆（Jack bean）脲酶的抑制活性。試驗結(jié)果顯示，5種對硝基肉桂酸過渡金屬配合物均顯示出了相當或好于陽性對照（乙酰氧肟酸）的脲酶抑制活性，其中配合物3和配合物4具有明顯好于陽性對照的脲酶抑制活性，IC50值分別達到了1.23μM和1.17μM。本文關(guān)于對硝基肉桂酸過渡金屬配合物研究，拓展了肉桂酸衍生物的應用，并且脲酶抑制活性結(jié)果顯示對硝基肉桂酸過渡金屬配合物可作為潛在的脲酶抑制劑繼續(xù)進行研究。
[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) 擄, C = 82.061 (3) 擄, 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 擄, b = 105.478 (2) 擄,1 = 90 擄; 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) 擄, c = 76.433 (3) 擄, p = 79.479 (3) 擄, 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 擄,1 = 105.535 (2) 擄,1 = 90 擄, 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 擄, xt = 90 擄, 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.
【學位授予單位】：山東理工大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R914.5;R96

【共引文獻】

相關(guān)期刊論文 前2條

1 黃振龍;湯立軍;;一種基于聯(lián)二萘酚的縮氨基硫脲化合物的合成及其對鋅離子的熒光識別[J];渤海大學學報(自然科學版);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

本文編號：2486501