β-环糊精与阿霉素表面包络作用的电化学研究

研究了阿霉素（ADM）在β-环糊精（β-CD）修饰金电极上（β-CD/Au）的电化学行为.结果表明,ADM在β-CD/Au电极上发生表面包络反应.25℃,pH=7.0时,该电极表面包络常数为9.54×104 L·mol^-1,并随温度呈规律性变化,最适宜反应温度为30℃.该电极ADM包络呈准可逆的电化学反应,速率常数为...     

Studies on drug–DNA complexes,adriamycin–d‐(TGATCA)2 and 4′‐epiadriamycin–d‐(CGATCG)2, by phosphorus‐31 nuclear magnetic resonance spectroscopy

The complexes of adriamycin–d‐(TGATCA)₂ and 4′‐epiadriamycin–d‐(CGATCG)₂ are studied by one‐ and two‐dimensional ³¹P nuclear magnetic resonance spectroscopy (NMR) at 500 MHz in the temperature range 275–328 K and as a function of drug to DNA ratio (0.0–2.0). The binding of drug to DNA is clearly evident in ³¹P? ³¹P exchange NOESY spectra that shows two sets of resonances in slow chemical exchange. The phosphate resonances at the intercalating steps, T1pG2/C1pG2 and C5pA6/C5pG6, shift downfield up to 1.7 ppm and that at the adjacent step shift downfield up to 0.7 ppm, whereas the central phosphate A3pT4 is relatively unaffected. The variations of chemical shift with drug to DNA ratio and temperature as well as linewidths are different in each of the two complexes. These observations reflect change in population of B_I/B_II conformation, stretching of backbone torsional angle ζ, and distortions in O? P? O bond angles that occur on binding of drug to DNA. To the best of our knowledge, there are no solution studies on 4′‐epiadriamycin, a better tolerated drug, and binding of daunomycin or its analogue to d‐(TGATCA)₂ hexamer sequence. The studies report the use of ³¹P NMR as a tool to differentiate various complexes. The specific differences may well be the reasons that are responsible for different antitumor action of these drugs due to different binding ability and distortions in DNA. Copyright © 2009 John Wiley & Sons, Ltd.     

载姜黄素/阿霉素叶酸偶联壳聚糖纳米粒的制备

姜黄素(CUR)是一种天然植物多酚,具有逆转肿瘤多药耐药的功效,与抗癌药物阿霉素(DOX)联合用药可以提高阿霉素对肿瘤细胞的敏感性,从而逆转肿瘤多药耐药性。以壳聚糖为载体,叶酸为靶向受体,三聚磷酸钠(TPP)为聚阴离子,姜黄素与阿霉素为药物模型,利用阴阳离子间的静电相互作用,制备了叶酸偶联壳聚糖载双药纳米粒,以达到纳米粒同时具有肿瘤靶向性和抗多药耐药的双重目的。目标产物通过红外光谱、SEM、Zeta电位仪表征了结构和形态,同时考察了不同反应条件对生成纳米粒的影响。结果显示在适宜反应条件(偶联叶酸的壳聚糖浓度和TPP的浓度分别为2.5 mg/m L和1 mg/m L,反应温度25℃,搅拌速度500 r/min,反应体系p H为5.0~6.0)下,得到载药纳米粒粒径约190 nm,Zeta电位为30.72 m V,阿霉素和姜黄素的包封率分别可达85.7%和93.9%,相比目前其他的一些双载药纳米粒,包封率具有明显的提高。     

Electrochemical behavior of adriamycin at a cobalt ion implantation modified electrode

With Co/GCE in 0.005 mol Tris/L/0.05 mol/L NaCl solution (pH 7.1), a sensitive reductive peak of adriamgcin (ADM) was obtained by the linear scan voltammetry. The peak potential is ?0.62 V (vs. SCE). The peak current is proportional to the concentration of ADM. The electrochemical behavior of the system was studied by the linear-sweep and cyclic voltammetry. The experiments showed that the reduction at Co/GCE is a quasi-reversible process with adsorption. According to Laviron’s theory, the electrode reaction rate constant k₀ and the electron transfer coefficient a are determined to be 2.15 s^-1 and 0.62, respectively. The composition of the surface, valence state of elements and depth distribution of elements on the surfaces of Co/GCE were determined by the X-ray photoelectron spectroscopy and Auger electron spectroscopy. The experiments showed that Co was surely implanted into the surface of GCE. The implanted Co element in the form of Co-C catalyzed the reduction of ADM.     

利用光学生物传感器研究阿霉素与人血清白蛋白的相互作用

用IAsys光生物传感器研究了阿霉素以及阿霉素铁配合物与人血清白蛋白的相互作用．求出了五个不同温度下．结合和解离的动力学平衡常数,并且对阿霉素与人血清白蛋白相互作用的热力学进行了研究,结果表明：随温度的升高,阿霉素与人血清白蛋白的结合作用逐渐增强,说明温度升高有利于结合反应的进行;相同温度下,阿霉素铁配合物与人血清白蛋白结合的平衡常数是阿霉素与该蛋白结合常数的7倍．阿霉素与人血清白蛋白的结合过程是一个吸热的熵驱动的过程,水分子重组在结合过程中起了重要作用,它们之间的作用力主要为疏水作用力．     

碳纳米管修饰金电极检测特定序列DNA

利用化学偶联法将末端修饰氨基的寡聚核苷酸固定在表面修饰有羧基化碳纳米管(CNTs-COOH)的金电极表面, 制备新型核酸探针, 可以特异性结合目标单链寡聚核苷酸. 以阿霉素作为嵌合指示剂, 利用示差脉冲法测定杂交的结果. 经过实验条件的优化, 测定DNA浓度在1.0×10^－6～1.0×10^－9 mol/L呈良好的线性关系. 检测限为: 2.54×10^－10 mol/L. 碳纳米管特有的纳米结构对检测结果的放大作用, 提高了该传感器的检测限和灵敏度.     

姜黄素联合阿霉素对膀胱癌 T24生长抑制的协同作用

目的探讨姜黄素联合阿霉素对人膀胱癌T24细胞的生长抑制及其诱导肿瘤凋亡的协同作用.方法用不同浓度的姜黄素和阿霉素分别及联合作用T24细胞,用MTT法检测细胞增殖抑制率,流式细胞仪检测细胞凋亡和细胞周期分布.结果阿霉素和姜黄素联用时,能较大幅度增强姜黄素的抑制效果(P<0.05);流式细胞仪检测结果显示:姜黄素与阿霉素联合将细胞周期阻滞于S期.结论姜黄素联合阿霉素对膀胱癌细胞T24的生长有协同抑制效应,能提高阿霉素对人膀胱癌T24细胞的敏感性.     

阿霉素及其铁配合物介导自由基产生的ESR研究

以 5 ,5 二甲基吡咯 N 氧化物 (DMPO)为自旋捕捉剂 ,运用ESR波谱法对比研究了阿霉素 (ADM )及ADM·Fe(Ⅲ )介导自由基产生的能力 .结果表明 :在DTT存在下ADM·Fe(Ⅲ )配合物介导生成·OH的能力要远强于ADM ,H2 O2 和DTT的存在能对ADM·Fe(Ⅲ )配合物介导产生·OH起促进作用 ,并说明了ADM·Fe(Ⅲ )配合物中铁离子的存在是其介导自由基产生的关键因素     

汉防己甲素有效地逆转肿瘤细胞抗药性

肿瘤细胞对多种结构不同、作用靶位不同的抗肿瘤药物的抗药性,往往使肿瘤患者的化疗彻底失败.为逆转肿瘤细胞抗药性,国外做了大量研究来寻找、合成逆转抗药性的药物.最近,我们应用从中草药中提取的生物碱汉防己甲素(Tet)和抗肿瘤药物阿霉素(ADM)合用,成功地逆转多药抗性株(CHO/ADM)对 ADM 的抗性(该抗性株由本室     

Studies directed towards the total synthesis of anthracycline antibiotics

At present anthracycline antibiotics have proven to be the most exciting agents in cancer chemotherapy. Both adriamycin and daunomycin are proven to be effective against a variety of human tumour cells, despite their cardiotoxicity. However, some synthetic analogues, such as 4-demethoxydaunomycin, are shown to be better therapeutic ratios compared to adriamycin or daunomycin. Various approaches have been successfully made for the total synthesis of (±) 4-demethoxydaunomycinone, the aglycone of (±) 4=demethoxydaunomycin, starting from benzoquinone, napthalene or anthraquinone precursors. Finally an elegant approach for the stereoconvergent synthesis of (+) 4-demethoxydaunomycinone has been worked out. New methods involving both Diels-Alder and Friedal-Crafts acylation, have been developed for the total synthesis of daunomycinone and 11-deoxydaunomycinone. The synthesis of L-daunosamine, the amino sugar unit present in the antitumor anthracyclines has been successfully elaborated starting either from D-glucose or D-glucosamine.