新型钯抗癌配合物初步筛选与作用机制的荧光法研究

提出一种抗癌配合物体外初步筛选及作用机制研究的荧光新方法。对本室所合成的十余种平面型新钯配合物作为非顺铂抗癌药物进行了体外筛选及其与ＤＮＡ结合作用的研究。发现荧光新筛选法结果与其它方法如四唑蓝染色法等基本一致。其中［Ｐｄ（Ⅱ）／ｂｐｙ／ｌｙｓ］Ｃｌ·３Ｈ２Ｏ（ｄ），［Ｐｄ（Ⅱ）／ｔｃｄ／ｌｙｓ］Ｃｌ·３Ｈ２Ｏ（ｅ），［Ｐｄ（Ⅱ）／ｓｔｎ／ｌｙｓ］Ｃｌ·３Ｈ２Ｏ（ｆ）和［Ｐｄ（Ⅱ）／ｔｃｄ／（ＮＯ３     

14种钯抗癌络合物初步筛选的荧光法研究

本文提出抗癌络合物初步筛选的荧光新方法,对所合成的14种钯(Ⅱ)/邻菲咯啉/氨基酸/氯离子(Pd(Ⅱ)/phen/aa/Cl)络合物作为非顺铂抗癌药物进行了体外筛选及结合作用研究,发现荧光筛选法结果与其它如甲烯蓝试管法、苔盼蓝染料排斥法基本一致,其中络合物[Pd(phen)(lys)]Cl,[Pd(phen)(arg)]Cl,[Pd(phen)(pro)]Cl对小鼠S-180瘤株抑瘤率分别为56％,50％,48％,这同它们与DNA结合常数7.96×10~6,4.52×10~6,1.0×10~6顺序相一致,表明荧光筛选法具有一定可靠性,并且荧光法具有操作简便、耗费低廉、周期较短等优点,适于抗癌络合物的初步筛选。     

丙氨酸铂配合物的合成与表征

顺铂、卡铂等铂配合物目前已经应用于卵巢癌、睾丸癌等肿瘤疾患的治疗,然而这类药物在低剂量下也存在严重的毒副作用,同时还存在溶解性差、不稳定等缺点[1,2,3].寻找高效、低毒的新一代铂类抗癌药物是医药领域的迫切任务.     

Schiff碱非铂抗癌络合物初步筛选的荧光法研究

依据药物与DNA发生相互作用能抑制DNA的复制、合成和增殖且这种作用在体内与在体外的一致性,用荧光探剂溴化乙锭(EB,EthBr)示踪药物/DNA作用而提出了荧光筛选新方法。该法具有可靠性强、灵敏度高、操作简便、耗费很小、周期较短等特点,适合于抗癌药物的初步筛选。以所合成的Schiff碱非铂抗癌络合物为例,考察了方法的可行性,并进一步确定了Schiff碱络合物与DNA的结合常数K_M,发现其大小与抗癌活性顺序相一致。这一结果为解释络合物抗癌作用的生化基础提供了初步依据,同时还说明络合有利于抗癌并以载体或整体起作用。     

荧光法用于新型抗癌配合物pd（tcd）（NO3）2初步筛选及作用机制研究

荧光法用于新型抗癌配合物Ｐｄ（ｔｃｄ）（ＮＯ３）２初步筛选及作用机制研究李志良ａｂ毕琼斯ａ李俊忠ａｂ熊劲芳ａ林辉祥ａｂ俞汝勤ａ（ａ湖南大学化学化工系长沙４１００８２；ｂ湖南大学化学生物医药研究所长沙４１００８２）化学药物治疗是治疗癌症的重要手段之一，...     

一种多吡啶双核单功能铂配合物的合成、晶体结构及抗癌活性

合成了一种含有多吡啶基配体2,6-双((双(吡啶-2-基甲基)氨基)甲基)吡啶(BPA-TPA)的双核单功能铂(Ⅱ)配合物[Pt₂(BPA-TPA)Cl₂]Cl₂(Pt₂-BPA-TPA),以核磁共振波谱和高分辨质谱进行表征,并通过X射线单晶衍射确定了Pt₂-BPA-TPA的结构。琼脂凝胶电泳实验表明 Pt₂-BPA-TPA 在 10 μmol·L-1的低浓度下可有效切割 pBR322 DNA。通过 CCK-8(cell counting kit-8)实验检测了Pt₂-BPA-TPA 对人肺癌细胞系A549的细胞毒性,结果显示Pt₂-BPA-TPA 表现出比顺铂更好的抗癌活性,其主要通过触发DNA损伤和上调下游凋亡相关细胞信号通路蛋白(p21蛋白和cleaved-caspase-3)诱导细胞凋亡。     

一种多吡啶双核单功能铂配合物的合成、晶体结构及抗癌活性

合成了一种含有多吡啶基配体2,6-双((双(吡啶-2-基甲基)氨基)甲基)吡啶(BPA-TPA)的双核单功能铂(Ⅱ)配合物[Pt₂(BPA-TPA)Cl₂]Cl₂(Pt₂-BPA-TPA),以核磁共振波谱和高分辨质谱进行表征,并通过X射线单晶衍射确定了Pt₂-BPA-TPA的结构。琼脂凝胶电泳实验表明Pt₂-BPA-TPA在10μmol·L^-1的低浓度下可有效切割pBR322 DNA。通过CCK-8(cell counting kit-8)实验检测了Pt₂-BPA-TPA对人肺癌细胞系A549的细胞毒性,结果显示Pt₂-BPA-TPA表现出比顺铂更好的抗癌活性,其主要通过触发DNA损伤和上调下游凋亡相关细胞信号通路蛋白(p21蛋白和cleaved-caspase-3)诱导细胞凋亡。     

一些含TMCPDA抗癌铂配合物的研究

本文根据大量的抗癌铂配合物的构效关系研究结果,合成及表征了八种含TMCPDA的新铂配合物(TMCPDA=1,2,2’—三甲基—1,3—环戊二胺),测定了八种配合物对小鼠淋巴白血病L—1210及S—180肉瘤的抑制作用,并研究了配合物的电子结构。结果指出,该系列的配合物有较高的抗癌活性,特别是[Pt(TMCPDA)(Ac—Cl)_2]配合物对L—1210及S—180的抑制作用在此系列配合物中尤为突出。经进一步的临床前的药理研究表明,该配合物的活性较高、毒性较低。配合物的电子结构与抗癌活性的关系的研究结果与以前所得到的抗癌铂配合物的构效关系较一致,表明配合物的电子结构确实与其抗癌活性密切相关。     

四氯合铂（Ⅳ）类配合物的合成表征及其抗癌作用

顺铂作为第一代无机抗癌药物已被广泛使用,但副作用较大。碳铂是第二代无机抗癌药物,虽肾毒性和肠胃道反应比顺铂低,但在某些肿瘤治疗方面,活性低于顺铂。最近,Aderson等发现tetraplatin(tetrachloro(d,1-trans)1,2-dimino cyclohexane platinum     

Preliminary Screening of Non-platinum Complexes of Schiff Bases as Antitumour Agents Using Fluorimetry

Based on the consistency of the in vivo and in vitro interactions of drugs with DNA, a fluorimetric method has been developed as a new in vitro method for preliminary screening of antitumour agents. This method was tested using Schiff bases synthesized from salicylaldehyde with 1-alanine, 1-asparagine and 1-histidine, and complexes of these Schiff bases with Cu(Ⅱ), Zn(Ⅱ), Ni(Ⅱ) and Sn(Ⅳ) as potential antitumour agents.The study of the interaction of the complexes with DNA by a fluorescence probe ethidium bromide (EthBr)-DNA system indicated the parallelism between the binding constants and antineoplastic ratios. The relationship between structure and antitumonr activity was investigated.     

Preliminary Fluorimetric Screening of Fourteen Palladium Complexes as Potential Antitumor Agents

Making use of the fact that the combination of a drug substance with DNA may inhibit the duplication, synthesis and proliferation of DNA and the consistency of the in vivo and in vitro interactions, the authors worked out a preliminary screening method for testing complex agents as potential antitumor drugs using ethidium bromide as a fluorescence probe. In this report, the method was applied for in vitro testing fourteen synthesized palladium(Ⅱ)/phenanthroline/amino acid/chloride complexes as potential non-platinum antitumor agents. The fluorimetric screening method was compared with methylene blue tube test and trypan blue dye exclusion assay. All three methods gave agreeable results. Among the complexes tested, [Pd(phen)(lys)]Cl, [Pd(phen)(arg)]Cl and [Pd(phen)(pro)]Cl showed antineoplastic ratios for animal tumor S-180 56%, 50% and 48%, respectively, in accordance with the order of their binding constants with DNA, 7.96×10~6, 4.52×10~6 and 1.0×10~6, respectively. The test results show that fluor     

A 13C-NMR. Study of Some Arsenic Complexes of Platinum(II) and Palladium(II)

The ¹³C-NMR. spectra of a series of tri-n-alkyl arsenic complexes of platinum and palladium have been measured. In these complexes it is suggested that the carbon chemical shift of the atom bound directly to the arsenic is a useful structural probe. The chemical shift of the second carbon atom in the chain is interpreted in terms of interactions within the chains of anyone ligand. The values ²J(Pt, C) and ³J(Pt, C) are presented.     

Oxidation of Hydrogen by Metal Complexes of Platinum and Palladium Immobilized on Silica

The thermal stability of metal complexes immobilized on the surface of silica and its connection with the catalytic activity in the oxidation of hydrogen were investigated. High catalytic activity was exhibited by heterogenized platinum and palladium acetylacetonate near room temperatures in the initial state and by γ-aminopropylsilicas treated with platinum and palladium complexes. The catalytic activity of the metal complexes correlates with their thermal stability and with the ability to undergo oxidation to a metal state with high valence. This revised version was published online in August 2006 with corrections to the Cover Date.