天然活性分子isatin经p53介导的线粒体途径诱导乳腺癌细胞MCF-7凋亡

目的探讨吲哚醌(isatin)对乳腺癌细胞MCF-7的抗肿瘤作用及其具体的调控机制。方法不同浓度isatin(0、50、100、200μmol·L^(-1))作用于乳腺癌细胞48 h后,利用细胞荧光染色、RT-PCR、Western blot及流式细胞术等方法检测isatin的促凋亡作用。结果不同浓度isatin处理MCF-7细胞48 h,荧光显微镜观察到细胞出现核染色质聚集、细胞体积缩小及DNA断裂等典型的凋亡形态学改变。RT-PCR和Western blot结果证实,随着isatin浓度的不断增加,p53、Bax mRNA和蛋白表达量也逐渐增加,而Bcl-2 mRNA及蛋白表达下降;流式细胞仪结果提示不同药物浓度作用的细胞膜电位出现不同程度的下降,caspase-9被激活。Western blot结果显示isatin处理组细胞胞质细胞色素C含量明显增加,相反线粒体中细胞色素C含量相应降低。结论 isatin具有明显诱导乳腺癌细胞MCF-7凋亡的作用,其可能的作用机制是经p53的线粒体凋亡通路被激活。

Synthesis and in vitro Antimycobacterial Activity of Moxifloxacin Methylene and Ethylene Isatin Derivatives

A series of novel moxifloxacin methylene and ethylene isatin derivatives with remarkable improvement in lipophilicity, compared to the parent moxifloxacin, was designed, synthesized and characterized by 1H NMR, MS and HRMS. These derivatives were initially evaluated for their in vitro antimycobacterial activity against M. smegmatis CMCC 93202. Compounds 3a―3f, 5a, 5f and 5j were chosen for the further evaluation of their in vitro activity against Mycobacterium tuberculosis（MTB） H37Rv ATCC 27294 and MDR-MTB 09710. All the target com pounds[minimum inhibitory concentration（MIC）： 0.39―〉16 μg/mL] were far more active than rifampin（MIC： 2.0―〉256 μg/mL）, but less active than moxifloxacin（MIC： 0.1―1.0 μg/mL） against the three tested strains. The most active compounds 3a and 3c were found to be 2―64 fold more potent than isoniazid and rifampin against M. smegmatis CMCC 93202, 2 fold more potent than rifampin against MTB H37Rv ATCC 27294, and 16―〉64 fold more potent than ethambutol, isoniazid and rifampin against MDR-MTB 09710.

Isatin decreases Bax protein expression in the substantia nigra of a mouse model of Parkinson's disease

The present study observed the action of 1H-indole-2, 3-dione （isatin） on Bax protein expression in the substantia nigra of a Parkinson＇s disease animal model. Parkinson＇s disease-like behaviors were induced in C57BL/6J mice treated with 1-methyl-4-phenyl-1,2, 3, 6-tetrahydropyridine （MPTP） Bax protein expression was significantly reduced in isatin （100, 200 mg/kg）-pretreated mice. Results demonstrate that isatin plays a neuroprotective role in mice treated with MPTP by down-regulating Bax protein expression.

Acylhydrazide and Isatin Schiff Bases as Alternate UV-Laser Desorption Ionization (LDI) Matrices for Low Molecular Weight (LMW) Peptides Analysis

Matrix-assisted laser desorption/ionization (MALDI) is a preferred and widely used mass spectrometric technique for the analysis of macromolecules. Limited UV-LDI matrices are available for the analysis of biomolecules due to the restricted structural features to serve in the laser desorption/ionization mechanism with a problem of background signals appearing in the low mass region. This paper describes the application of Schiff base derivatives of acylhydrazide and isatin as alternate UV-LDI matrices for the analysis of peptides with significantly low background signals. Thirty one compounds have been successfully employed as matrices for the analysis of low molecular weight (LMW) peptides (α-Cyano-4-hydroxycinnamic acid (HCCA), a preferred choice for peptide analysis.

Isatin抑制神经母细胞瘤机制的基因芯片技术研究

目的采用基因芯片技术研究2,3-吲哚醌(Isatin)抑制神经母细胞瘤的作用机制,并筛选与侵袭转移相关的可能效应靶点。方法体外培养神经母细胞瘤SH-SY5Y细胞,采用CCK8方法检测不同浓度Isatin处理组的细胞活力,用Affymetrix表达谱芯片检测Isatin对SH-SY5Y细胞基因表达谱的影响,然后用GeneGo软件进行GO分类分析,使用BIOCARTA和KEGG数据库筛选与侵袭转移相关的靶点。结果 Isatin对SH-SY5Y细胞的半抑制浓度为279.7μmol/L。与空白对照组相比,Isatin作用后,有284个基因上调,145个基因下调。GO分析显示,Isatin可以抑制细胞增殖、细胞循环,并对细胞内翻译、生物合成及代谢等过程有作用。哺乳动物雷帕霉素靶蛋白(mTOR)信号通路可能是侵袭转移相关的效应靶点,DDIT4、RHEB、EIF4EBP1、RPS6 KB1为mTOR信号通路的相关基因。结论 Isatin可能通过抑制mTOR信号通路,抑制SH-SY5Y细胞的侵袭转移。

New Approach to Synthesis of 6,7-Dimethoxyisatin

A new approach to synthesis of 6,7-dimethoxyisatin is reported. 2-nitro-3, 4- dimethoxy mandelonitrile in glacial acetic acid was treated with the solution of stannous chloride in hydrochloric acid to give 6, 7-dimethoxyisatin in a high yield.

Syntheses,Crystal Structures and Bioactivities of Two Isatin Derivatives

The title compounds（Z）-3-（2-（3-chloropyridin-2-yl）hydrazono）indolin-2-one（A） and 7-bromo-（Z）-3-（（4-pyridinyl）carboxlichydrazono）-2-indolinone（B） have been synthesized and structurally determined by elemental analysis and single-crystal X-ray diffraction studies.Compound A（C13H8ClN4O） belongs to the orthorhombic crystal system,space group Pca21 with a = 20.799（4）,b = 4.9312（10）,c = 11.764（2）,V = 1206.6（4）3,Mr = 271.68,Dc = 1.496 g/cm3,μ = 0.313 mm-1,F（000） = 556,Z = 4,the final R = 0.0346 and wR = 0.0831 for 2683 observed reflections with I 2σ（I）.Compound B（C14H9BrN4O2） belongs to the triclinic crystal system,space group P1 with a = 6.6834（13）,b = 7.0727（14）,c = 14.285（3）,α = 95.56（3）,β = 99.00（3）,γ = 102.95（3）°,V = 643.8（2）3,Mr = 345.16,Dc = 1.780 g/cm3,μ = 3.203 mm-1,F（000） = 344,Z = 2,the final R = 0.0487 and wR = 0.1167 for 2334 observed reflections with I 2σ（I）.The preliminary herbicidal bioassay reveals that compounds A and B have some inhibition both in vivo and in vitro against AHAS.

Syntheses,Crystal Structures and Bioactivities of Two Novel Isatin Derivatives

Two novel compounds 1-（4-fluorobenzyl）-4-chloro-（Z）-3-benzoylhydrazono-2-indolinone（1） and 1-（4-methoxybenzyl）-（Z）-3-benzoylhydrazono-2-indolinone（2） were synthesized and their crystal structures were determined by single-crystal X-ray diffraction.Compound 1（C22H15ClFN3O2） crystallized in the triclinic system,space group P1·with a=0.94198（19） nm,b=1.4339（3） nm,c=1.5018（3） nm,α=101.58（3）°,β=102.96（3）°,γ=102.73°,V=1.8602（6） nm3,Mr=407.82,Dc=1.456 g/cm3,μ=0.240 mm-1,F（000）=840,Z=4,R1=0.0442 and wR2=0.1064.Compound 2（C23H19N3O3） crystallized in the triclinic system,space group P1·with a=1.0022（2） nm,b=1.0192（2） nm,c=1.0461（2） nm,α=99.86（3）°,β=117.30（3）°,γ=94.13（3）°,V=0.9215（3） nm3,Mr=385.41,Dc=1.389 g/cm3,μ=0.094 mm-1,F（000）=404,Z=2,R1=0.0403 and wR2=0.1142.The preliminary herbicidal activities of the two compounds were also evaluated.

Antipyretic Action of Isatin and Its Analogues in Mice and Rats

The effects of isatin (2,3-dioxo-indole) and isatin analogues (5-methylisatin, 6-hydroxyisatin, 7-ethylisatin, N-acety- lisatin) were tested on prostaglandin E2 (PGE2)-induced fever in mice and rats. Two modes of administration were tested. Isatin or an analogue was injected simultaneously with PGE2 and the development of fever was tested, or the test compound was given 30 min following PGE2 administration and the effects on the already existing fever were measured, in mice and in rats. Isatin in a dose of 3.12 mg/kg ip was found to block the development of PGE2-induced fever in mice, while in a dose of 12.5 mg/kg ip it attenuated the existing fever. In rats isatin in a dose of 12.5 mg/kg ip blocked fever initiation, and at 25.0 mg/kg ip attenuated existing PGE2-induced fever. In mice, 5-methylisatin in a dose of 0.21 mg/kg ip blocked the initiation of fever, and at 6.72 mg/kg ip attenuated the existing fever. In rats in a dose of 3.36 mg/kg ip it blocked the development of fever, and at 13.44 mg/kg ip attenuated existing PGE2-induced fever. In mice 5,6-dimetylisatin in a dose of 0.02 mg/kg ip both blocked fever initiation and attenuated the existing fever in mice, in rats in a dose of 0.42 mg/kg ip it blocked the initiation of fever, and at 0.21 mg/kg ip attenuated the existing PGE2-induced fever. In mice 6-hydroxyisatin in a dose of 5.2 mg/kg blocked the development of fever, and at 10.4 mg/kg attenuated the existing fever. In rats in a dose of 10.40 mg/kg ip it blocked fever development and also attenuated the existing fever. In mice, 7-ethylisatin in a dose of 0.02 mg/kg ip both blocked fever initiation and also attenuated the existing fever. In rats, a dose of 0.11 mg/kg both blocked fever initiation and also attenuated the existing fever. In mice, N-acethylisatin in the dose of 0.005 mg/kg blocked fever initiation, while at 1.024 mg/kg it attenuated existing fever, in rats, in a dose of 0.096 mg/kg it blocked fever initiation, and at 0.384 mg/kg attenuated the existing fever. The results demonstrate that 7-ethyl- and N-acetylisatin are the most effective of these compounds both in blocking the development of PGE2-induced fever and also in attenuating existing the PGE 2-induced fever.

Synthesis, spectral, 3D molecular modeling and antibacterial studies of dibutyltin (IV) Schiff base complexes derived from substituted isatin and amino acids

New dibutyltin(IV) complexes of Schiff base derived from 5-chloroindoline-2,3-dione, indoline- 2,3-dione with amino acids (tryptophan, alanine and valine) were synthesized and characterized by elemental analysis, IR, electronic spectra, conductance measurements, and biological activity. The analytical data showed that the Schiff base ligand acts as bidentate towards metal ions via the azomethine nitrogen and carboxylate oxygen by a stoichiometric reaction of M:L (1:2) to form metal complexes. NMR (1H, 13C and 119Sn) spectral data of the ligands and metal complex agree with proposed structures. The conductivity values between 14 - 27 ohm-1cm2mol-1 in DMF imply the presence of non-electrolyte species. 3D molecular modeling and analysis of bond lengths and bond angles have also been conducted for a representative compound, [Bu2Sn(L2)2], to substantiate the proposed structures. Antibacterial results indicate that the metal complexes are more active than the free ligands.

Synthesis and Biological Activity Study of New Schiff and Mannich Base Ligands Derived from Isatin and 3-Amino-1,2,4-triazole and Their Metal Complexes

Two new Mannich and Schiff base ligands namely： （1-（3＇-amino-methyl-1＇（H）-1＇,2＇,4＇-triazole）-3-（1＇（H）-l＇,2＇,4＇- triazole-3＇-yl） iminoisatin （Lt） and l-morpholinomethyl-3-（1＇（H）-1＇,2＇,4＇-triazolyl）iminoisatin （LII） were prepared from condensation reaction of the new Schiff base 3-（l＇（H）-l＇,2＇,4＇-triazole-3＇-yl）iminoisatin （SBH） （0.01 mol） with formaldehyde and 3-amino-l,2,4-triazole （3-At） or with formaldehyde and morpholine （0.01 mole each） respectively. Structures were characterized by tH NMR, CHN analyses, mass spectra and IR spectra. Metal complexes were synthesized by heating each ligand （0.02 mo with metal salts （0.01 moo in ethanol or ethanol： acetone mixture respectively. The formula of metal complexes were suggested depending on CHN and thermal analyses, metal and chloride contents, IR and UV-visible spectra, magnetic moments （laefr） and conductivity measurements. All complexes were of octahedral geometry except palladium （II） complexes which were square planar. The two ligands and some selected metal complexes showed various antibacterial and cytotoxic effects.

Novel Isatin-Schiff Base Cu (II) and Ni(II) Complexes. X-ray Crystal Structure of Bis[3-(4-hexylphenylimino)-1H-indol-2(3H)-one]-dichlorocopper(II) Complex

Schiff base ligand （HL） derived from 4-hexylaniline with isatin （1H-indole-2,3-dione） and its complexes with Cu（Ⅱ）, Ni（Ⅱ） were prepared and characterized by analytical, spectroscopic （IR, UV-Vis, Mass） techniques, electrical conductivity, magnetic and thermal measurements. The crystal and molecular structure of [Cu（HL）2Cl2] was determined by a single-crystal X-ray diffraction study. The molecular structure of the title compound has an inversion center on the Cu atom.

ISA炉冷浇口智能清理设备设计

随着艾萨炼熔炼技术的不断的应用和发展,整体技术水平在不断的提高。然而对冷浇口的清理,目前仍采用人工方式定期用气锤冲击进行清理。整个清理过程劳动强度很大,作业环境很恶劣,具有一定的危险性。对于冷浇口的清理,本文提出一种新的清理思路及具体实现方法的设计;通过将冷浇口的转移替换来实现自动清理,改善了现有的工作条件,实现了艾萨炉冷浇口黏结物料的全自动清理,保障下料通道顺畅。对整个艾萨炉熔炼技术的发展起到了推动作用。

ISA总线与双口RAM芯片IDT7025的接口设计及应用

结合静电支承控制系统的任务要求，分析了主机与DSP系统间的多种通信方式。对采用16位ISA总线与双口RAM芯片IDT7025的接口电路设计进行了重点讨论，最后给出一个在WIN98下采用中断方式对IDT7025进行数据块读写的示例。

应用ISA总线实现高速数据采集

针对实际应用的需要 ,设计了一种基于工业控制机 ISA总线的数据传输系统。文中着重介绍了工业控制机 ISA总线及其与高速数据采集卡的接口技术。提出了一种解决慢速外设和高速系统机之间存在的时序问题的办法 ,无须插入等待周期。该系统应用于某高速数据采集系统 ,可靠性高 。

基于ISA总线的纳秒级同步器的研制

基于 ISA 总线的纳秒级同步器采用可编程硬件延时设计,其电路采用 10 片 MC100E195 级联,17 位地址选择线通过并行接口 8255 控制门电路。晶振脉冲分频后经 8254 计数并产生基准信号,送可编程门阵列 MC100E195,得到 20ns 级的延迟范围。采用 VC++ 对同步器硬件端口操作,通过参数设置,得到多路延时同步信号。

基于ISAS88标准的批量控制策略的研究与实现

简要介绍了批量过程控制标准ISAS88,该标准定义了适用于批量过程控制的专业术语和模型 ;详细说明了应用顺序功能图(SFC)来描述和实现批量过程控制策略的方法。应用SFC实现批量控制具有诸多优点。

一种基于ISA总线的步进电机多轴联动控制卡

介绍了一种基于PC的步进电机控制卡。借助于PC机丰富的软、硬件资源 ,实现了多轴联动控制。该卡采用开放式结构 ,使用简单、功能灵活、可靠性高 。

基于FPGA的PCI到ISA总线转换芯片的设计与实现

论文对PCI和ISA总线的原理以及接口转换的关键技术进行了阐述,提出了通过FPGA来实现PCI到ISA总线转换设计的方法。重点介绍了在PCI总线和PCI到ISA时序转换的逻辑电路中状态机的设计方法。最后分析了PCI到ISA总线转换的核心仿真时序图。