铂类抗癌药物展望

在过去的10年里,铂类抗癌药物取得了重要的进展,又有4种新药,奈达铂、奥沙利铂、舒铂和洛铂相继于1995～2001年成功上市,同时也有多个候选药物因疗效低、毒性大,与顺铂、卡铂比较无优势而在临床试验中被淘汰。目前还有另外9种铂化合物仍在进行临床研究,这些化合物为顺铂和卡铂的类似物、亲脂性配合物、口服铂(Ⅳ)配合物、多核铂配合物以及具有空间位阻的铂配合物。新的铂类抗癌药将在今后10～20年内从那些在临床研究中显示出低毒性、抗癌谱广、与现有药物无交叉耐药性的化合物中产生。     

[Pt(en)(5-Fu)2]Cl2配合物的合成及抗肿瘤活性

为寻求高效低毒的新型顺铂类抗肿瘤药物,用K2PtCl4、乙二胺(en)、氟尿嘧啶(5-Fu)为原料,设计合成了顺铂类似物[Pt(en))(5-Fu)2]Cl2配合物,由元素分析、红外光谱和质谱分析初步证实了其化学结构,用改良MTT、SRB法,选用K562、A549、Bel-7402、BIU-87、Bcap-37细胞株对其进行体外抗肿瘤活性测定。结果表明,所合成的配合物除在浓度为0．01、0．1／μg／mL时对K562细胞株抗肿瘤活性大于顺铂和氟尿嘧啶外,其它情况下的抗肿瘤活性均小于顺铂和氟尿嘧啶。该配合物仍有进一步研究的价值。     

新型铂族金属抗肿瘤药物赛特铂的研究现状

铂族金属抗肿瘤药物顺铂和卡铂已广泛应用于临床，它们对治疗睾丸肿瘤、卵巢癌和肺癌等十几种肿瘤有显著的疗效。近年来又有奈达铂、 到铂和乐铂等获批准进入临床应用。但目前这些临床应用的铂族金属抗肿瘤药口服活性低，都是静脉途径给药。本文介绍了已进入Ⅲ期临床试验的第一个口服活性铂抗肿瘤药物赛特铂及其合成、化学特点、临床前和临床研究情况。     

阴离子交换色谱法分析铂抗癌药物

1.引言顺铂和碳铂是有效的抗癌药物.高效液相色谱法分析顺铂有使用乙酸-乙酸钠缓冲液流动相的强阴离子交换,反相离子对色谱法等.作者考虑顺铂和碳铂是中性配合物,在强阴离子交换色谱中不用缓冲液流动相,研究了四烷基铵键合硅胶柱-中性盐水流动相时,顺铂、碳铂和反铂的保留行为和外标法定量顺铂和碳铂的准确性.     

甲基丙二酸-(反式-1,2-二甲胺基环丁烷)合铂(II)的合成、结构及抗肿瘤活性

通过水解法合成了甲基丙二酸-(反式-1,2-二甲胺基环丁烷)合铂(Ⅱ)。采用元素分析、质谱(ESI-MS)、红外光谱(IR)和核磁共振氢谱(¹H NMR)确证了该配合物的组成和化学结构。采用MTS法评价其抗肿瘤活性,发现该配合物对常见5种癌细胞的生长有明显的抑制活性。     

奥沙利铂、顺铂和卡铂抗膀胱癌作用体外对比性研究

目的: 比较奥沙利铂、顺铂和卡铂对膀胱癌细胞株的杀伤效果。方法: 选取4种膀胱移行癌细胞5637、J82、T24和253J,分别用奥沙利铂、顺铂和卡铂 37 ℃ 培养12、48、72 h 后,应用噻唑兰比色法(MTT)检测每种药物IC₅₀值及细胞活力,并采用流式细胞仪对细胞参数进行检测,比较细胞凋亡率。结果: 在5637、J82和T24细胞系中,顺铂治疗后IC₅₀剂量和细胞活力均低于奥沙利铂,但差异无统计学意义（P>0.05）。在253J细胞系中,奥沙利铂IC₅₀剂量和细胞活力均明显高于顺铂和卡铂（P<0.05）;而卡铂处理后细胞凋亡率显著低于顺铂和奥沙利铂（P<0.05）,但顺铂和奥沙利铂之间细胞调亡率没有显著差异（P>0.05）。结论: 奥沙利铂能有效抑制膀胱癌细胞活力,促进细胞凋亡,效果优于顺铂和卡铂。     

铂类抗癌配合物构效关系的理论探讨

基于铂抗癌配合物在体内的历程和化学反应探讨了它们的结构和活性之间的关系，获得决定抗癌活性大小的主要因素，包括配合物分子的脂溶性和空间体积、构型、离去基团的反应性以及载体基团的特性。提出了铂配合物具有较高抗癌活性的结构要求①非离子型②小的空间体积③顺式构型④含脂溶性的氨（胺）载体和以Ｃｌ￣（－）或二元羧酸作离去基团。     

金属类抗癌药物研究新进展

<正>金属配合物的药用性引起了人们的广泛关注,开辟了金属配合物抗癌药物研究的新领域。随着人们对金属配合物的药理作用认识的进一步深入,新的高效、低毒、具有抗癌活性的金属化合物不断被合成出来。其中,包括某些有机铂类化合物、有机锡配合物、有     

顺式-甲基丙二酸-二氨合铂(II)的合成、表征及抗癌活性

为合成新的铂配合物顺式-甲基丙二酸-二氨合铂(II),以顺式二碘-二氨合铂(II)为起始原料,先后与硝酸银和甲基丙二酸反应合成目标化合物。采用元素分析、质谱、核磁共振氢谱和红外光谱分析其组成和结构,采用MTT法对配合物进行了初步的体外活性评价。结果显示合成的化合物结构与理论一致,具有一定的体外肿瘤生长抑制活性。     

含稳定氮氧自由基结构的铂配合物的合成和结构及体外抗癌活性的初步研究

合成并表征了一种新的未见文献报道的铂配合物。用元素分析、红外光谱、紫外光谱、质谱、差热分析等手段表征了该配合物。体外抑癌实验表明该配合物具有抗癌活性。     

培美曲塞联合卡铂与吉西他滨联合卡铂一线治疗晚期非鳞非小细胞肺癌的临床观察

目的: 观察培美曲塞联合卡铂与吉西他滨联合卡铂治疗晚期非鳞非小细胞肺癌(NSCLC)的近期疗效及毒副反应。方法: 57例ⅢB-Ⅳ期经病理组织学和(或)细胞学检查确诊的晚期非鳞NSCLC患者,其中培美曲塞组(PC组)26例,吉西他滨组(GC组)31例,分别给予培美曲塞联合卡铂和吉西他滨联合卡铂方案治疗至少2周期以上,评价其近期疗效及毒副反应。结果: PC组和GC组的客观缓解率(42.3% vs 41.9%),疾病控制率(88.5% vs 80.6%),中位无进展生存期(5.9 个月vs 4.7 个月)差异均无统计学意义(P＞0.05)。两组的主要毒副反应均为骨髓抑制和胃肠道反应,PC组Ⅲ-Ⅳ度血小板减少的发生率明显低于GC组(P=0.042)。结论: 培美曲塞联合卡铂和吉西他滨联合卡铂一线治疗晚期非鳞NSCLC疗效相近,培美曲塞组不良反应轻,安全性更好。     

Synthesis,characterization,and biological activities of Pt(Ⅱ) and Pd(Ⅱ)complexes with 2'',3'',4'',5,7-pentahydroxy flavone

Pt(Ⅱ) and Pd(Ⅱ) complexes with 2',3',4',5,7-pentahydroxy-flavone were synthesized and characterized by elemental analysis, molar conductance, IR, 1HNMR, TG-DTA, UV-Vis spectroscopic techniques, and fluorescence analysis.The scavenging effect on the superoxide radical ( O-2 ) and the inhibitory effect on lipid peroxides were also investigated.Both the ligand and the complexes exhibit scavenging effect on superoxide radicals, and the effect of the complexes is greater than that of the ligand. The Pt(Ⅱ) complex exhibits the strongest scavenging efficiency. Both Pt(Ⅱ) and Pd(Ⅱ) complexes have the inhibitory effect on lipid peroxides, and the effect of the complexes is greater than that of the ligand, but the Pt(Ⅱ) complex has a high effect of promoting lipid peroxides.     

溶液配位化学研究:IX.Pt(Ⅱ)-Phen-PCA体系

用pH电位滴定法测定了含 1 ,1 0 -邻菲咯啉 (Phen )和羧酸 (CA )配体的三元混配配合物Pt(Phen) (CA ) +体系的稳定常数 ,比较和讨论了各种三元混配配合物之间的稳定性差异。实验结果表明 :在三元混配配合物Pt(Phen) (PCA) +中 (PCA为苯基羧酸 )存在分子内芳环堆积作用 ,堆积程度依赖于苯基和配位的羧酸根之间的亚甲基数目 ,其中以 2 -苯乙酸和 3-苯丙酸与邻菲咯啉为最佳堆积。     

抗肿瘤纳米制剂药代动力学评价的研究进展

抗肿瘤药物水溶性差、药代动力学行为不理想等特征在临床应用中严重影响疗效。抗肿瘤纳米制剂的开发可以实现药物増溶的目的 ,能够改善抗肿瘤药物的药代动力学行为,具有良好的应用前景。本文综述了抗肿瘤纳米制剂的研究现状,分别从整体和细胞水平介绍其药代动力学行为特征,探讨抗肿瘤纳米制剂发挥优势可能的作用机制。     

Fe/Pt磁性薄膜的研究进展

Fe/Pt合金薄膜是重要的磁性材料。介绍了Fe／Pt合金的晶体结构以及磁控溅射法、真空电弧离子法、机械冷变形法和化学合成法4种主要制备Fe/Pt合金薄膜的方法，并对影响Fe／Pt合金薄膜磁性能的重要因素进行了评述，包括改变热处理工艺参数和添加掺杂元素。最后指出，Fe/Pt纳米结构材料具有良好的化学稳定性和较高的磁晶各向异性，因而在超高密度信息存储领域有着巨大的应用潜力。     

3-氯-1, 1-环丁烷二羧酸根·二氨合铂(Ⅱ)的合成及抗肿瘤活性研究

根据目前临床使用的铂类抗癌药物的缺点和不足,作者报道了一种结构新颖的铂类配合物的合成方法,通过元素分析、质谱、红外和核磁共振氢谱等对合成物进行了结构表征,确认合成物为目标化合物.采用SRB比色法,测定该化合物对A549细胞及KB细胞的半数抑制浓度(IC50)分别为4.8mg/L和18.0mg/L.     

Platinum-induced oxidation of chromium in O2 at 800 °C

The effects of porous Pt on the oxidation of Cr at 800 °C have been studied with the ¹⁸O-SIMS technique, gas phase analysis and XPS. In oxide areas with Pt a pronounced inward oxygen transport takes place and a substantial oxide growth near the Cr substrate is observed. In oxide grown on areas without Pt the counts of CrO ions in SIMS and the binding energy of O (1s) in XPS depend on the distance from the area with Pt. The experimental observations are believed to be a consequence of a high dissociation efficiency of O₂ on areas with Pt in combination with a high diffusivity of O in external and internal oxide surfaces on areas both with and without Pt.     

Selective synthesis and characterization of metallic cobalt, cobalt/platinum, and platinum microspheres

Metallic cobalt microspheres have been successfully synthesized via a facile hydrothermal method in the presence of poly (N-vinyl-2-pyrrolidone) (PVP), and the diameters of these spheres are in the range of 1-2 μm. Bimetallic Co/Pt microspheres and hollow noble metal Pt microspheres have also been selectively synthesized by adjusting the amount of reactants of replacement reaction in which corresponding noble metal compound and metallic cobalt microspheres are used as starting materials. The study on catalytic activities of the as-prepared metallic microspheres on hydrolysis of ammonia-borane for hydrogen generation reveals that Co/Pt (molar ratio 5:1) bimetallic microspheres are far more active than the hollow noble metal Pt microspheres.     

Novel processing in inert atmosphere and in air to manufacture high‐activity slurry aluminide coatings modified by Pt and Pt/Ir

Slurry‐derived coatings are an interesting alternative method to pack aluminization of nickel‐base superalloys, which provide similar properties and protection at high temperatures. For highest performance, these aluminide coatings are modified by the addition of Pt or, as recent research suggests, with Pt/Ir. While the combination of Pt and Pt/Ir with an out‐of‐pack process is state of the art, slurry coatings are of special interest as a repair method for turbine blades. In this study, the microstructural evolution of slurry‐derived coatings manufactured on CM 247 in inert atmosphere as well as in air was investigated. Layers of Ni, Pt, and Pt/Ir mixtures were electrodeposited. After annealing, a diffusion heat‐treatment with a slurry containing aluminum or aluminum–silicon powder was applied on the samples. The addition of silicon is well known to be beneficial for hot corrosion environments. The reaction and interdiffusion behavior of aluminum/aluminum–silicon determines the microstructural evolution of the coatings. Depending on the initial electroplated layer on the surface, different microstructures can be obtained, such as the Pt/Ir‐modified beta phase (Ni,Pt)Al or two‐phase layers of PtAl₂ and NiAl. Additionally, the reactivity between the elements at the surface and those from the slurry was shown to determine homogeneity and surface roughness of the diffusion coating, also depending on the atmosphere used during slurry aluminization. Finally, it was demonstrated that iridium has a high influence on the diffusion behavior and especially the distribution of platinum in the coatings. Such new coatings have the potential to overcome some disadvantages of conventionally manufactured high‐activity aluminide coatings, as the combination of Pt/Ir‐electroplating with the slurry process results in less detrimental substrate elements like molybdenum or tungsten close to the surface.