荞麦提取物对·OH诱导pBR322DNA损伤的影响

在研究Fe2+和二甲基亚砜(DMSO)浓度对羟基自由基诱导pBR322 DNA损伤结果分析基础上,建立评价羟基自由基致pBR322 DNA损伤体系。通过在损伤体系中加入不同浓度荞麦乙醇提取物2号和5号,考察对pBR322 DNA损伤的影响,结果显示:在实验浓度范围内两种荞麦乙醇提取物对羟基自由基致pBR322 DNA损伤都具有明显抑制作用,且均随浓度的增加抑制作用增强。     

三齿多吡啶钴(Ⅱ)配合物与DNA的相互作用研究

合成了2种三齿多吡啶钴(Ⅱ)配合物,用元素分析、IR等对它们进行了表征,用循环伏安法、电子吸收光谱、荧光光谱等方法研究了配合物与CT DNA的相互作用以及配合物对pBR322DNA的断裂作用.结果表明,配合物[Co(PhTPY)2]2+与DNA的作用属中等强度的部分插入,配合物[Co(H2 Bzimpy)2]2+与DNA的作用属静电作用.凝胶电泳实验表明,用310 nm光辐射15 min,配合物[Co(PhTPY)2]2+可选择性地断裂pBR322DNA为开环缺口性和线型DNA,配合物[Co(H2 Bzimpy)2]2+对DNA的断裂没有选择性.     

荞麦提取物对·OH诱导pBR322 DNA损伤的影响

在研究Fe2+和二甲基亚砜(DMSO)浓度对羟基自由基诱导pBR322 DNA损伤结果分析基础上,建立评价羟基自由基致pBR322 DNA损伤体系.通过在损伤体系中加入不同浓度荞麦乙醇提取物2号和5号,考察对pBR322 DNA损伤的影响,结果显示:在实验浓度范围内两种荞麦乙醇提取物对羟基自由基致pBR322 DNA损伤都具有明显抑制作用,且均随浓度的增加抑制作用增强.     

二氢杨梅素及其氧钒配合物与DNA的相互作用研究

二氢杨梅素是藤茶中重要的药效物质.合成了一种二氢杨梅素的氧钒配合物,其结构经元素分析、IR、ESI-MS、1HNMR和13CNMR表征.采用紫外分光光度法、荧光淬灭和流体力学等方法分别测定二氢杨梅素及其氧钒配合物与DNA的键合能力.结果显示,这两种化合物都能以插入方式与CT-DNA结合,DNA断裂实验证实该新型配合物可较好地断裂pBR322 DNA.     

化学核酸酶的合成、表征及与pBR322DNA的作用

合成了三角架配体L,用红外光谱、核磁共振氢谱、X单晶衍射等手段对配体进行了鉴定。在此基础上,用高氯酸镁与其合成镁的金属络合物,通过核磁共振氢谱、红外光谱等手段对配合物的结构进行了表征。最后,通过电泳技术研究了此配合物与pBR322DNA的作用,并对机理进行了初步探讨。电泳结果表明：配合物在生理条件下(pH=7．0,37℃)与pBR322DNA反应2h,能够断裂DNA,有的甚至断裂成线性。本工作的意义在于：配合物在生理条件下,能迅速水解DNA,甚至出现了线性断裂产物。     

L-赖氨酸多吡啶铜(Ⅱ)三元配合物的合成、表征及与DNA的相互作用

合成了3种L-赖氨酸多吡啶铜(Ⅱ)三元混配配合物[Cu(L-lysine)(Phen)(Cl O4)](Cl O4)(Ⅰ,Phen=1,10-菲咯啉)、[Cu(L-lysine)(IP)(Cl O4)](Cl O4)(Ⅱ,IP=咪唑并[4,5-f]1,10-菲咯啉)和[Cu(L-lysine)(PIP)(Cl O4)](Cl O4)(Ⅲ,PIP=2-苯基-咪唑并[4,5-f]1,10-菲咯啉),并用紫外光谱和红外光谱对配合物进行了表征。采用电子吸收光谱和荧光光谱等研究了配合物与小牛胸腺DNA的相互作用,用凝胶电泳法研究了配合物对pBR322 DNA的氧化切割活性。结果表明,随着多吡啶配体平面的增大,配合物与DNA的结合能力大小依次为配合物Ⅲ配合物Ⅱ配合物Ⅰ,配合物可能通过部分插入方式与DNA相互作用。     

多吡啶铜(Ⅱ)配合物的合成、表征与DNA作用及抗肿瘤活性

合成了一种多吡啶铜(Ⅱ)配合物,用红外光谱、元素分析、X-射线单晶衍射法对配合物的组成和结构进行了表征。该配合物的晶体属单斜晶系,P2(1)/c空间群。用荧光光谱、紫外光谱研究了配合物与小牛胸腺DNA的键合作用。结果表明,配合物与DNA的键合作用属部分插入,结合常数K_b=8.0×104L/mol。用凝胶电泳法研究了配合物对p BR322DNA的切割作用。实验表明,配合物用310 nm光辐射15 min,可将p BR322 DNA断裂为开口缺刻型和线型DNA。采用MTT法研究了配合物对人乳腺癌细胞和肺癌细胞的体外抗肿瘤活性。结果发现,所合成配合物能有效抑制这两种细胞增殖。     

β-萘并冠醚卟啉的合成及光敏活性

以2,3-二羟基萘基四苯基卟啉及其Cu（Ⅱ）配合物为原料制备了一类新型9-冠-3-四苯基卟啉,通过紫外可见吸收光谱、红外光谱、质谱、核磁共振氢谱等测试手段对冠醚卟啉进行结构表征,研究了冠醚卟啉产生单线态氧的能力、与DNA的相互作用及其对pBR322质粒DNA的切割。结果表明,冠醚卟啉具有明显的产生单线态氧的能力;与DNA的相互作用模式为外部自堆积;对DNA有较明显的切割效果。     

水溶性阳离子卟啉化合物i-TMPipEOPP的DNA光切割作用研究

利用琼脂糖凝胶电泳法研究了水溶性阳离子卟啉化合物i-TMPipEOPP对超螺旋pBR322质粒DNA的光切割作用。结果表明:i-TMPipEOPP对DNA具有较好的光切割作用。在黑暗条件下,i-TMPipEOPP的存在不会对DNA造成损伤;但在光照条件下,较低浓度(0.6μmol·L-1)i-TMPipEOPP表现出显著的光切割活性,将超螺旋pBR322DNA(FormⅠ)完全转化为缺口型DNA(FormⅡ),且反应符合伪一级动力学模型。机理研究表明,i-TMPipEOPP对DNA的光切割作用可能归因于在反应过程中生成的单线态氧和超氧阴离子。而i-TMPipEOPP在偏酸性条件下对DNA显示出更高的光切割活性,i-TMPipEOPP有望成为一种对肿瘤细胞具有更高选择性的潜在的光动力学治疗试剂。     

化合物[Cd·L·DMF·O2]n的合成、结构及其与DNA作用研究

选用2-氨基对苯二甲酸为配体与CdCl2反应,通过水热法合成了化合物[Cd·L·DMF·O2]n,利用元素分析和单晶X射线衍射对配合物结构进行了表征.通过荧光光谱法测定了化合物与鱼精DNA的结合作用.通过凝胶电泳技术分析了化合物切割pBR322质粒DNA的能力.这给了我们关于抗癌抗病毒药研究的建设性意见.     

Cytotoxicity of poly(phenolic)sulfonates and their sodium salts in l1210 lymphoid leukemia cells

Poly(phenolic)-sulfonates demonstrated very good cytotoxicity against the growth of tumor cell lines (L1210, Tmolt-(3), HeLa-S(3)) and are comparable in potency with typical clinically used anticancer drugs. Four of the most active compounds, i.e. GL-2021, GL-2029, GL-2041 and GL-2063, were selected for a mode of action study in L1210 lymphoid leukemia cells at concentration of 25muM to 100muM for 60 min. The agents did not alkylate bases of ct-DNA, cause intercalation between base pairs, produce cross linking of ct-DNA strands or generate free radicals although L1210 DNA fragmentation was observed after 24 hr incubation. L1210 DNA synthesis was preferentially inhibited which was achieved by (1) suppressing DNA polymerase alpha activity which reduced the synthesis of new strands of DNA, (2) reducing of de novo purine synthesis at the regulatory enzyme PRPP amido transferase which reduced d(GMP) levels, and (3) inhibiting of nucleoside kinase activities which further reduced DNA synthesis. DNA template activity was altered by the poly(phenolic)sulfonates since they reduced DNA polymerase alpha and m-RNA and t-RNA polymerase activities. The kinetic studies at 50 muM over 2 hr demonstrated that the agents' effect on PRPP-amido transferase activity is probably a major target of the compounds.     

Interaction of DNA with Simple and Mixed Ligand Copper(II) Complexes of 1,10-Phenanthrolines as Studied by DNA-Fiber EPR Spectroscopy

The interaction of simple and ternary Cu(II) complexes of 1,10-phenanthrolines with DNA has been studied extensively because of their various interesting and important functions such as DNA cleavage activity, cytotoxicity towards cancer cells, and DNA based asymmetric catalysis. Such functions are closely related to the DNA binding modes of the complexes such as intercalation, groove binding, and electrostatic surface binding. A variety of spectroscopic methods have been used to study the DNA binding mode of the Cu(II) complexes. Of all these methods, DNA-fiber electron paramagnetic resonance (EPR) spectroscopy affords unique information on the DNA binding structures of the complexes. In this review we summarize the results of our DNA-fiber EPR studies on the DNA binding structure of the complexes and discuss them together with the data accumulated by using other measurements.     

PLFX-Co(phen)_3~(2+)复合物与CT-DNA的结合性质及切割活性

利用荧光光谱及流体动力学等方法,研究了普利沙星(PLFX)-Co(phen)32+与CT-DNA间的作用机理。荧光光谱测量结果表明:普利沙星和Co(phen)32+发生了结合作用形成了复合物,配比为2∶1;向PLFX-Co(phen)32+体系中,加入CT-DNA后,复合物进一步与DNA相结合,结合常数为2.18×105L/mol。通过粘度法、熔点测定及凝胶电泳实验研究了复合物与CT-DNA的相互作用。结果表明体系与CT-DNA间主要是沟槽作用;PLFX-Co(phen)32+能够有效切割质粒DNA。     

诺氟沙星-邻菲罗啉-铜（Ⅱ）配合物的合成及生物活性的研究

合成了诺氟沙星-邻菲罗啉-铜（Ⅱ）配合物,并利用红外、电位滴定、电喷雾质谱等表征方法推测了其可能结构。采用紫外光谱,荧光光谱等方法研究了配合物与小牛胸腺DNA的作用方式;配合物与DNA作用时紫外光谱吸收谱带发生了红移和减色效应,荧光发生猝灭,结果都一致表明了该配合物与DNA的作用方式为嵌入作用。利用纸片法测定了药物配体和配合物对大肠杆菌及枯草杆菌的体外抑制活性。实验表明两个化合物具有不同的抗菌活性。     

Acridine/Acridone–Carborane Conjugates as Strong DNA-Binding Agents with Anticancer Potential

Synthesis of acridine derivatives that act as DNA-targeting anticancer agents is an evolving field and has resulted in the introduction of several drugs into clinical trials. Carboranes can be of importance in designing biologically active compounds due to their specific properties. Therefore, a series of novel acridine analogs modified with carborane clusters were synthesized. The DNA-binding ability of these analogs was evaluated on calf thymus DNA (ct-DNA). Results of these analyses showed that 9-[(1,7-dicarba-closo-dodecaborane-1-yl)propylamino]acridine ( 30 ) interacted strongly with ct-DNA, indicating its ability to intercalate into DNA, whereas 9-[(1,7-dicarba-closo-dodecaborane-1-yl)propanamido]acridine ( 29 ) changed the B-form of ct-DNA to the Z form. Compound 30 demonstrated cytotoxicity, was able to inhibit cell proliferation, arrest the cell cycle in the S phase in the HeLa cancer cell line, and induced the production of reactive oxygen species (ROS). In addition, it was specifically localized in lysosomes and was a weak inhibitor of Topo IIα.     

8-Hydroxyquinoline-Amino Acid Hybrids and Their Half-Sandwich Rh and Ru Complexes: Synthesis,Anticancer Activities,Solution Chemistry and Interaction with Biomolecules

Solution chemical properties of two novel 8-hydroxyquinoline-D-proline and homo-proline hybrids were investigated along with their complex formation with [Rh(η⁵-C₅Me₅)(H₂O)₃]²⁺ and [Ru(η⁶-p-cymene)(H₂O)₃]²⁺ ions by pH-potentiometry, UV-visible spectrophotometry and ¹H NMR spectroscopy. Due to the zwitterionic structure of the ligands, they possess excellent water solubility as well as their complexes. The complexes exhibit high solution stability in a wide pH range; no significant dissociation occurs at physiological pH. The hybrids and their Rh(η⁵-C₅Me₅) complexes displayed enhanced cytotoxicity in human colon adenocarcinoma cell lines and exhibited multidrug resistance selectivity. In addition, the Rh(η⁵-C₅Me₅) complexes showed increased selectivity to the chemosensitive cancer cells over the normal cells; meanwhile, the Ru(η⁶-p-cymene) complexes were inactive, most likely due to arene loss. Interaction of the complexes with human serum albumin (HSA) and calf-thymus DNA (ct-DNA) was investigated by capillary electrophoresis, fluorometry and circular dichroism. The complexes are able to bind strongly to HSA and ct-DNA, but DNA cleavage was not observed. Changing the five-membered proline ring to the six-membered homoproline resulted in increased lipophilicity and cytotoxicity of the Rh(η⁵-C₅Me₅) complexes while changing the configuration (L vs. D) rather has an impact on HSA or ct-DNA binding.     

阿魏酸双苄酯的合成及生物活性研究

摘要：以DMSO为溶剂,以阿魏酸与氯化苄在碱性条件下反应,合成了阿魏酸双苄酯,产率为94．32％、纯度为98．5％。通过紫外光谱、红外光谱、核磁共振氢谱、质谱及X-单晶衍射对产物结构进行了表征。用微量量热法证明了阿魏酸双苄酯对大肠杆菌具有一定的抑制作用,其最小抑茵浓度（MIC）为29．81btg·mL-1。通过紫外光谱、荧光光谱和粘度测定研究了阿魏酸双苄酯与ct-DNA的相互作用,证明其作用方式为经典插入方式,对ct-DNA的猝灭是由于形成复合物所引起的静态猝灭,与ct-DNA的结合常数为1．58×10。L·mol-1。     

Enantioseparation of chiral ofloxacin using biomacromolecules

Natural biomacromolecules including bovine serum albumin (BSA), calf thymus DNA (ct-DNA) and fish sperm DNA (fs-DNA) were studied as the free chiral selectors to separate R- and S-ofloxacin enantiomers from racemic ofloxacin, combined with ultrafiltration and subsequent crystallization. First, the interactions between chiral ofloxacin and biomacromolecules including BSA, ct-DNA, and fs-DNA were investigated using circular dichroism and fluorescence spectroscopy. BSA exhibited stereoselective adsorption towards R-ofloxacin at pH 9.0 with an enantioselectivity of 1.23, while ct-DNA showed enantiospecific interaction with S-enantiomer with the selectivity of 1.70 at pH 5.0. One single-stage adsorption by BSA provides an enantiomeric excess in the permeate (e.e. _p ) of 14% in S-enantiomer, and five-stage operations enhance the chiral resolution to reach the e.e.p value of 44%. R-enantiomer with an e.e. _p of ?26% can be obtained through one single-stage adsorption by using ct-DNA, and ?85% can be reached by five-stage operations. Enantiomeric mixtures with the intial e.e. of 44% (S-) can be upgraded to 95% (S-) through subsequent crystallization. This programmable process of adsorption and desorption using BSA or ct-DNA as chiral selectors can be successfully applied to produce the enantiomers with highly optical purity.     

Synthesis,Cytotoxicity, DNA Binding and Apoptosis of Rhein-Phosphonate Derivatives as Antitumor Agents

Several rhein-phosphonate derivatives (5a–c) were synthesized and evaluated for in vitro cytotoxicity against HepG-2, CNE, Spca-2, Hela and Hct-116 cell lines. Some compounds showed relatively high cytotoxicity. Especially compounds 5b exhibited the strongest cytotoxicity against HepG-2 and Spca-2 cells (IC₅₀ was 8.82 and 9.01 μM), respectively. All the synthesized compounds exhibited low cytotoxicity against HUVEC cells. Further experiments proved that 5b could disturb the cell cycle in HepG-2 cells and induce apoptosis. In addition, the binding properties of a model conjugate 5b to DNA were investigated by methods (UV-Vis, fluorescence, CD spectroscopy). Results indicated that 5b showed moderate ability to interact ct-DNA.