本文選題：去甲基斑蝥酸根 + 苯并咪唑��； 參考：《浙江師范大學(xué)》2014年碩士論文

【摘要】：癌癥是嚴(yán)重危害人們安全的疾病。研發(fā)新型的治療腫瘤的金屬配合物類藥物是生物化學(xué)家探究的熱點(diǎn)�！藗儼l(fā)現(xiàn)過渡金屬類配合物越來越多地顯示出廣泛的生物活性。去甲斑蝥素是一種傳統(tǒng)抗癌藥物斑蝥素的衍生物。它不但具有很強(qiáng)的抗癌活性,并且對正常細(xì)胞的傷害較小。因此,我們以去甲斑蝥素為先導(dǎo)化合物,不僅設(shè)計合成了三種N-氮雜環(huán)去甲斑蝥素酰亞胺,而且合成了幾種新型的過渡金屬與去甲斑蝥素和苯并咪唑類化合物的配合物；研究了其與DNA和牛血清白蛋白(BSA)的作用,并測試了它們對人宮頸癌細(xì)胞(Hela)和人肝癌細(xì)胞(SMMC7721)的體外抗增殖活性。主要研究內(nèi)容如下： 1、合成了三種N-芳(雜)環(huán)去甲斑蝥素酰亞胺化合物：N-苯去甲斑蝥素酰亞胺(L1)、N-2-吡啶去甲斑蝥素酰亞胺(L2)和N-2-甲基苯并咪唑去甲斑蝥素酰亞胺(L3)�；衔锏慕M成通過元素分析、紅外光譜、核磁共振等方法確定。它們的組成為：C14H13NO3(L1), C13H12N2O3(L2), C16H15N3O3(L3)�；衔锱cDNA的相互作用通過紫外光譜法、熒光光譜法、粘度法研究。研究結(jié)果表明三種化合物以中等強(qiáng)度與DNA發(fā)生部分插入作用。另外通過熒光光譜法探究了化合物和BSA的相互作用�；衔锱cBSA通過靜態(tài)猝滅機(jī)制發(fā)生強(qiáng)烈的相互作用。同時測試了化合物對人宮頸癌細(xì)胞(Hela)的體外抗增殖活性,實(shí)驗(yàn)表明,化合物L(fēng)2和L3抗癌細(xì)胞的增殖活性較化合物L(fēng)1高。其中化合物L(fēng)3具有最強(qiáng)的抗增殖活性。 2、采用溶液法合成了兩種新穎的銅配合物：N-2-甲基苯并咪唑去甲斑蝥素酰亞胺合銅(Ⅱ)配合物(1)、苯并咪唑與去甲斑蝥酸根合銅(Ⅱ)混配配合物(2)。配合物的成和結(jié)構(gòu)通過元素分析、紅外光譜、X-射線單晶衍射等方法被確定下來。它們的組成為：[Cu(Ac)2(L3)2]·3H2O(1)(Ac=醋酸根,C2H3O2;L3=N-2-甲基苯并咪唑去甲斑蝥素酰亞胺,C16H15O3N3)、[Cu(bimz)2(DCA)](2)(bimz=苯并咪唑,C7H6N2; DCA=去甲斑蝥酸根,C8H805)。通過X-單晶衍射法確定了配合物1的配位中心空間結(jié)構(gòu)是配位數(shù)為四的平面四方型；配合物2的配位中心空間結(jié)構(gòu)是配位數(shù)為五的四方錐型。配合物與DNA的相互作用是通過紫外光譜法、熒光光譜法、粘度法和瓊脂糖凝膠電泳法進(jìn)行了研究。配合物和BSA的相互作用是運(yùn)用熒光光譜法進(jìn)行研究的。同時測試了配合物1和2對人肝癌細(xì)胞(SMMC-7221)的體外抗增殖活性。結(jié)果顯示配合物和DNA以中等強(qiáng)度發(fā)生部分插入作用,配合物1和2均以氧化還原機(jī)制切割超螺旋質(zhì)粒DNA。配合物與BSA通過靜態(tài)猝滅機(jī)制發(fā)生強(qiáng)烈的相互作用。同時在測試濃度范圍內(nèi),配合物1和2比化合物L(fēng)3和Na2(DCA)有很強(qiáng)的體外抗人肝癌細(xì)胞(SMMC-7221)的效果。其中,配合物1的體外抗增殖活性最強(qiáng)。 3、合成了四種2-氨基苯并咪唑與去甲斑蝥酸根(DCA)合過渡金屬(鈷、鎳、銅和鋅)的混配配合物。采用元素分析、紅外光譜和X-射線單晶衍射法確定了它們的組成和結(jié)構(gòu)。組成為：(Habiz)2[M(DCA)2]-4H2O(M=Co (Ⅱ)(3), Ni(Ⅱ)(4),Cu(Ⅱ)(5),Zn(Ⅱ)(6); Habiz=質(zhì)子化的2-氨基苯并咪唑)。確定了四種配合物的配位中心的空間結(jié)構(gòu)均為配位數(shù)為六的八面體型,配位的基團(tuán)呈現(xiàn)中心對稱結(jié)構(gòu)。通過紫外吸收光譜法、粘度法和瓊脂糖凝膠電泳法研究了配合物和DNA的作用,結(jié)果顯示配合物以較強(qiáng)的強(qiáng)度與DNA發(fā)生部分插入作用,配合物5的作用最強(qiáng)。通過熒光光譜法研究了配合物和BSA的作用,研究發(fā)現(xiàn)配合物均以靜態(tài)猝滅模式猝滅BSA的熒光,發(fā)生強(qiáng)烈的相互作用。配合物6對人肝癌細(xì)胞SMMC-7221具有很強(qiáng)的體外抗增殖活性。
[Abstract]:Cancer is a disease that seriously endangers people's safety. Developing a new type of metal complex to treat tumors is a hot spot for biochemists. 'people find that the transition metal complexes are increasingly showing extensive biological activity. Norcantharidin is a derivative of cantharidin, a traditional anticancer drug. It is not only very good. Strong anticancer activity and less harm to normal cells. Therefore, we use norcantharidin as the precursor compound, not only designed and synthesized three kinds of N- nitrogen heterocyclic norcantharidin, but also synthesized several new transition metals with norcantharidin and benzimidazole compound, and studied it with DNA and bovine blood. The effect of albumin (BSA) and their antiproliferative activity to human cervical cancer cells (Hela) and human hepatoma cells (SMMC7721) in vitro were tested. The main contents are as follows:
1, three kinds of N- aromatic (heterozygous) norcantharidin imide compounds are synthesized: N- benzocancantharidimide (L1), N-2- pyridine norcantharidimide imide (L2) and N-2- methyl benzimidazole norcantharidimide (L3). The composition of the compounds is determined by elemental analysis, red spectrum, nuclear magnetic resonance and so on. Their composition is C14H13NO 3 (L1), C13H12N2O3 (L2), C16H15N3O3 (L3). The interaction between compounds and DNA is studied by ultraviolet spectroscopy, fluorescence spectroscopy, viscosity method. The results show that the three compounds are partially inserted with DNA in medium strength. In addition, the interaction between compounds and BSA is explored by fluorescence spectroscopy. Compounds and BSA are static by static quenching. The antiproliferative activity of compounds on human cervical cancer cells (Hela) in vitro was also tested. The experimental results showed that the proliferation activity of compound L2 and L3 cancer cells was higher than that of compound L1. Compound L3 had the strongest antiproliferative activity.
2, two novel copper complexes were synthesized by solution method: N-2- methyl benzimidazole norcantharidimidimide copper (II) complex (1), benzimidazole and norcantharidis copper (II) mixed ligand complexes (2). The formation and structure of the complexes were determined by elemental analysis, infrared spectra, and single crystal diffraction of X- ray. The composition is: [Cu (Ac) 2 (L3) 2]. 3H2O (1) (Ac= acetate root, C2H3O2; L3=N-2- methyl benzimidazole norcantharidimide, C16H15O3N3), [Cu (bimz) 2 (DCA)] (2). The coordination center space structure of complex 1 is determined by the single crystal diffraction method of the planar Quartet of the coordination number of four. The coordination center space structure of the complex 2 is a four square cone type with a coordination number of five. The interaction between the complexes and DNA is studied by UV spectroscopy, fluorescence spectroscopy, viscosity and agarose gel electrophoresis. The interaction of the complexes and BSA is studied by fluorescence spectrometry. The complexes are also tested by 1 and 2. The anti proliferative activity of human hepatoma cells (SMMC-7221) in vitro. The results showed that the complexes and DNA were partially inserted at medium intensity, and the complexes 1 and 2 both cut the super helix plasmid DNA. complex with BSA by the mechanism of static quenching. Compounds L3 and Na2 (DCA) have strong anti human hepatoma cells (SMMC-7221) in vitro. Among them, complex 1 has the strongest antiproliferative activity in vitro.
3, four mixed complexes of 2- amino benzimidazole and norcantharidis (DCA) transition metals (cobalt, nickel, copper and zinc) were synthesized. Their composition and structure were determined by elemental analysis, IR and X- ray diffraction. The composition is: (Habiz) 2[M (DCA) 2]-4H2O (M=Co (II) (3), Ni (II) (4), Cu (5), Zn (6) (6); Habiz=); 2- amino benzimidazole is a protonated amino benzimidazole. The coordination center of the four complexes is determined that the coordination center of the complex is six of the coordination number and the coordination group presents a central symmetric structure. The complexes and DNA are studied by UV absorption spectrometry, viscosity method and agarose gel electrophoresis. The results show that the complexes are strong strong. The role of degree and DNA was partially inserted, the role of complex 5 was the strongest. The effects of complexes and BSA were studied by fluorescence spectroscopy. It was found that the complexes all quenched the fluorescence of BSA by static quenching mode and had strong interaction. Complex 6 had strong in vitro antiproliferative activity to human hepatoma cells in vitro.
【學(xué)位授予單位】：浙江師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R914

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