三硝基均苯三酚金属(Li,Na, K,Mg)化合物的快速热分解

利用温度快速跃升傅立叶变换红外(T-jump/FTIR)原位分析技术对三硝基均苯三酚(TNPG, 2,4,6-三硝基-1,3,5-苯三酚)的锂、钠、钾、镁金属盐的快速热分解反应过程进行了系统研究. 确定了三硝基均苯三酚系列化合物快速热分解过程产生的可挥发金属化合物的类型, 得到了快速热分解过程主要红外活性气体产物的种类、分布及浓度随时间的变化关系曲线, 提出了其快速热分解方程式. 利用计算机模拟方法, 采用REAL程序对三硝基均苯三酚系列化合物的燃烧性能(燃烧产物和燃烧温度等参数)进行了计算, 与T-jump/FTIR分析技术得到的实验结果进行比较分析和讨论.     

Determination of bithionol, bromophen, nitroxynil, oxyclozanide, and tribromsalan in milk with liquid chromatography coupled with tandem mass spectrometry

LC/MS/MS was developed to determine the residues of bithionol (BTN), bromofen (BMF), nitroxynil (NTX), oxyclozanide (OCZ), and tribromsalan (TBS) in milk. Samples were extracted with ethyl acetate and cleaned up by liquid-liquid separation with acetonitrile and n-hexane. The compounds were determined by RP-LC using a C18 column with 0.1% formic acid-methanol. Mass spectral acquisition was performed in the negative mode by applying selected-reaction monitoring. The method was validated in milk spiked with these compounds at 5-600 microg/kg; average recoveries were in the range 83.8-97.1%, with RSD values of 1.4-8.0%. The interassay RSDs were less than 11%. The LODs of these compounds in milk were 0.1 microg/kg. The method was applied to 24 raw milk samples. The concentration of these compounds in all samples was lower than the Japanese maximum residue limits. The method is rapid, sensitive, and specific for monitoring residues of BTN, BMF, NTX, OCZ, and TBS in milk.     

Synthesis,characterization, DNA binding,antibacterial, and antioxidant activity of new bis-phthalimides

New bis-phthalimides were synthesized by 2: 1 condensation of phthalic anhydride and tetrachlorophthalic anhydride with 1,2,4-triazole-3,5-diamine, pyridine-2,6-diamine, and 4-hydroxypyrimidine- 2,6-diamine. The synthesized compounds were characterized by elemental analyses and IR, ¹H NMR, and mass spectra. Their interaction with calf thymus DNA (ct-DNA) was studied by UV-Vis spectrophotometry, cyclic voltammetry, and viscosity measurements, which revealed intercalative mode of binding to ct-DNA. Antibacterial activity of the synthesized compounds against Escherichia coli and Streptococcus mutans was assessed in vitro by the agar well diffusion method. The antioxidant activity of these compounds was estimated by DPPH assay.     

2,4,5-三氧-1,3,2,4-二氮二磷杂环戊烷衍生物的合成和结构

本文报道了七个新的2,4,5-三氧-1,3,2,4-二氮二磷杂环戊烷衍生物的制备, 产物的结构经IR, ^1H和^31P NMR, MS以及元素分析证实, 并利用^31P NMR和GC-MS区分了化合物的顺式和反式异构体。     

Acidity trends in alpha,beta-unsaturated sulfur, selenium, and tellurium derivatives: comparison with C-, Si-, Ge-, Sn-, N-, P-, As-, and Sb-containing analogues

The gas-phase acidity of CH3-CH2XH (X=S, Se, Te), CH2=CHXH (X=S, Se, Te) and PhXH (X=S, Se) compounds was measured by means of Fourier transform ion cyclotron resonance mass spectrometry. To analyze the role that unsaturation plays on the intrinsic acidity of these systems, a parallel theoretical study, in the framework of the G2 and the G2(MP2) theories, was carried out for all ethyl, ethenyl (vinyl), ethynyl, and phenyl O-, S-, Se-, and Te-containing derivatives. Unsaturated compounds are stronger acids than their saturated analogues, because of the strong pi-electron donor ability of the heteroatoms that contributes to a large stabilization of the unsaturated anions. Ethynyl derivatives are stronger acids than vinyl compounds, while phenyl derivatives have an intrinsic acidity intermediate between that of the corresponding vinyl and ethynyl analogues. The CH2=CHXH vinyl compounds (enol-like) behave systematically as slightly stronger acids than their CH3-C(H)X (keto-like) tautomers. Vinyl derivatives are stronger acids than ethyl compounds, because the anion stabilization attributable to unsaturation is greater than that undergone in the neutral compounds. Conversely, the enhanced acidity of the ethynyl derivatives with respect to the vinyl compounds is due to two concomitant effects, the stabilization of the anion and the destabilization of the neutral compound. The acidities of ethyl, vinyl, and ethynyl derivatives containing heteroatoms of Groups 14, 15, and 16 of the periodic table are closely related, and reflect the differences in electronegativity of the CH3CH2-, CH2=CH-, and CH[triple chemical bond]C- groups.     

Design,synthesis, biological evaluation,and docking study of new acridine-9-carboxamide linked to 1,2,3-triazole derivatives as antidiabetic agents targeting α-glucosidase

A new series of acridine-9-carboxamide-1,2,3-triazole derivatives 7a-m were designed, synthesized, and evaluated as novel α-glucosidase inhibitors. Acridine-9-carboxamide-1,2,3-triazole scaffold has been designed by combination of effective moieties from potent α-glucosidase inhibitors. Most of the synthesized compounds were more potent than standard inhibitor acarbose. Among the title compounds, the most potent compounds were compounds 7j , 7k , and 7a with IC₅₀ values of 120.2 ± 1.0, 151.1 ± 1.4, and 157.6 ± 1.6 μM, respectively (IC₅₀ value of acarbose = 750.0 ± 10.0 μM). Docking study of the most potent compounds demonstrated that these compounds formed stable complexes with α-glucosidase active site. Anti-α-amylase assay of compounds 7j , 7k , and 7a was performed and no activity was observed. in vitro cytotoxicity assay of the latter compounds revealed that these compounds were not cytotoxic toward human normal (HDF) and cancer (MCF-7) cell lines. ADME and toxicity prediction of compounds 7j , 7k , and 7a were also performed.     

Design,synthesis, evaluation,and molecular dynamic simulation of triclosan mimic diphenyl ether derivatives as antitubercular and antibacterial agents

In the present work, we have explored triclosan mimic diphenyl ether derivatives as inhibitors of Mycobacterium tuberculosis enoyl acyl carrier protein reductase (InhA) using a structure-based drug design approach. The virtual library of diphenyl ethers was designed and compounds with acceptable absorption, distribution, metabolism, excretion, and toxicity properties were docked. The compounds with higher dock score (5a-g) than triclosan were synthesized, characterized, and evaluated for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. Among the synthesized compounds, compounds 5f and 5c appeared to be the most promising with minimum inhibitory concentration of 18 μM and 36 μM respectively. The molecular dynamics simulation study of the most active compound 5f and triclosan was performed, which correlates with its activity in comparison with triclosan. All the compounds were further evaluated for cytotoxicity studies against Vero, and HepG2 were found to be safe. Furthermore, compound 5f was evaluated for in vitro cytotoxicity against mouse macrophage cell lines (RAW 264.7), and the study indicated its safety in eukaryotes at 50-μM concentration. In addition, compounds 5a-g were also screened for their in vitro antibacterial activity against two gram-positive and two gram-negative bacteria by resazurin-based microtiter dilution assay method. Among the synthesized compounds, 5f and 5b appeared to be promising, against various gram-positive and gram-negative microorganisms, indicating its broad-spectrum potential.

     

奥拉西坦衍生物的设计、合成及抗血小板聚集活性研究

本文采用拼合策略,设计、合成了7个新型奥拉西坦衍生物。其中,化合物4a～4f由奥拉西坦与苯丙烯酸片段拼合得到; 4g则由奥拉西坦、吲哚布芬拼合得到。采用Bron比浊法测定目标化合物对花生四烯酸及二磷酸腺苷诱导的血小板聚集的抑制活性。结果表明,该系列化合物具有一定的抗血小板聚集活性,其中化合物4f的抗血小板聚集活性与阳性对照吲哚布芬相当。     

硝基苯并咪唑衍生物的合成、表征及抑菌活性的测定

以苯并咪唑为原料,经硝化、二茂铁磺酰化等步骤,合成了8种未见文献报道的硝基苯并咪唑衍生物,其结构经MS,¹H NMR和元素分析确证.由于硝基苯并咪唑的互变异构,二茂铁磺酰化后,产生两个异构体,用X射线衍射仪测定了化合物2a的晶体结构.初步的抑菌实验结果表明,该系列化合物具有良好的抑菌作用,其抑菌活性均优于对照药剂50%多菌灵可湿性粉剂.     

反相薄层色谱法测定1-1,2,4-三唑类杀菌剂的疏水性

1-1 ,2 ,4-三唑类农药是本世纪 60年代初期发展起来的新型杀菌剂 ,具有广谱、高效和内吸等优点 ,一直是农药研究的热门课题 [1] .多年的研究表明 ,其疏水性与活性有很好的相关性 ,因此快速准确地测定其疏水性显得十分重要 .与传统的振荡方法测定化合物的疏水性相比 ,反相高效液相色谱法( RP-HPLC) [2～ 4 ] 和反相薄层色谱法 ( RP-TL C) [5,6 ] 简单、快速、经济 ,所需样品量很少 ,对样品纯度要求也不高 .尤其是薄层色谱法所需仪器简单 ,耗时更短 .本文以甲醇 -水混合物为展开剂测定了我们合成的 2 3种新型三唑类化合物在 C2高效薄层板…     

Hydrazyl,Nitronyl-, and imino-nitroxides: Synthesis,properties and reaction with nitric oxide and nitrogen dioxide

Ten novel and stable free radicals of nitronyl-, imino-nitroxide and hydrazyl type compounds were synthesized and their physico-chemical properties investigated. UV-Vis and ESR spectroscopic data, as well as the lipophilicities and specific hydrophobic areas of the compounds are compiled. The reaction of these radical compounds with nitric oxide and nitrogen dioxide was also investigated. The radicals synthesized, show selectivity in their reaction with these nitric oxides, depending on their structure (nitronyl-nitroxide radicals react with NO, while hydrazyl radicals react with NO₂). The processes are easily monitored by UV-Vis or ESR spectroscopy.     

Synthesis,structural characterization,biological activity,and theoretical studies of some novel thioether-bridged 2,6-disubstituted imidazothiadiazole analogues

In this study, thioether-bridged imidazo[2,1-b][1,3,4]thiadiazole derivatives that contained both imidazole and 1,3,4-thiadiazole (compounds 7a-7i and 8a-8i ) were synthesized from the reactions of 2-amino-1,3,4-thiadiazole with phenacyl bromide ( 6a - 6i ) (at yields of 59% to 74%). The structure of the synthesized compounds was characterized using ¹H NMR, ¹³C NMR, Fourier-transform infrared spectroscopy, elemental analysis, mass spectroscopy, and X-ray diffraction analysis. Mycelial growth, mycelial growth inhibition, minimum inhibitory concentration, minimum fungicidal concentration, and lethal dose values against various plant pathogenic fungi were determined for all of the target compounds synthesized in the study. The test results showed that most of the compounds had moderate to good antifungal activity. In addition, the absorption, distribution, metabolism, excretion (ADME) parameters of the compounds were calculated, and it was observed that all of the compounds met the drug-likeness rules in general. Finally, using docking simulations, it was found that compounds 7h , 7i , 8h , and 8i showed high affinity to PDB ID:5TZ1, which is an CYP51 antifungal target structure.     

Synthesis of Anticancer Compounds, I, “Dual Function” Antitumor Agents Based on Bioreduction and DNA-Alkylation

We report the synthesis of novel anticancer compounds based on bioreductive and DNA-alkylating properties. The strategy was to combine a benzoquinone annelated pyrrole with bioreductive properties with a set of DNA-alkylating functionalities, thus resulting in bifunctional anticancer compounds. The biological activity of all compounds was evaluated against a number of cancer cell lines. One of the compounds should be emphasized.     

Synthesis and antitumor activity evaluation of some 1, 2, 4-triazine and fused triazine derivatives

Reactions of 3-hyrazino-5,6-diphenyl-1,2,4-triazine with various carbonyl compounds such as ethyl acetoacetate, acetylacetone, benzoin, isatin, phthalic anhydride, phenyl isocyanate and acetic anhydride were discussed. Its reactions with α, β unsaturated compounds such as arylidinemalononitrile, diethyl acetylenedicarboxylate, dibenzylidine hydrazine were studied. These reactions led to the formation of various triazine and fused-triazine derivatives. The antitumor activity of the synthesized compounds was tested against HePG2 and MCF-7 cell lines. Some of the tested compounds were most active, whereas other compounds exhibited little or no activity.     

Anti-malarial, anti-algal, anti-tubercular, anti-bacterial, anti-photosynthetic, and anti-fouling activity of diterpene and diterpene isonitriles from the tropical marine sponge Cymbastela hooperi

In an investigation into their potential ecological role(s), a group of mainly diterpene isonitriles, nine in total, isolated from the tropical marine sponge Cymbastela hooperi, and the sesquiterpene axisonitrile-3, isolated from the tropical marine sponge Acanthella kletra, were evaluated in a series of bioassays including anti-fouling, anti-algal, anti-photosynthetic, anti-bacterial (Gram +ve and -ve), anti-fungal, and anti-tubercular. The results of these assays showed that all of the tested compounds, with the exception of diterpene 9, were active in at least two of the applied test systems, with axisonitrile-3 (10) and diterpene isonitrile 1 being the two most active compounds overall, closely followed by diterpene isonitrile 3. Based on the results of the photosynthetic study a molecular modelling investigation was undertaken with all of the compounds used in that study. The results showed a positive correlation between reduction in photosynthetic activity and the interaction of the modelled compounds with a potential enzyme active site.     

Synthesis and molecular docking of some new 3,5-bis-(diazipine,pyrazolopyrimidine, pyrimidine,and pyrazole) pyridine derivatives and their in vitro and in vivo biological evaluation as potential antitumor agents

Bis enaminone derivative 6 was reactive enaminone to synthesize new heterocyclic compounds containing diazipine, pyrazolopyrimidine, triazolopyrimidine, and pyrazole moieties by reaction with different bifunctional reagents. Structures of new compounds were confirmed by analytical and spectral data. Moreover, the new compounds were screened in-vitro as antitumor agents for Ehrlich ascites at different concentration. The results showed the compounds 18 , 19, and 20a have a good activity. In addition to, the molecular docking of these mentioned compounds was studied using vascular endothelial growth factor receptor.     

Synthesis of new pyrazoles,oxadiazoles, triazoles,pyrrolotriazines, and pyrrolotriazepines as potential cytotoxic agents

4-Oxo-4-phenylbutanehydrazide (1) reacted with many active methylene reagents such as acetylacetone, diethylmalonate, ethylacetoacetate, ethylcyanoacetate, benzoyl-acetonitrile, and malononitrile under neat conditions to afford the corresponding pyrazoles (2–7) , also, treatment of butanehydrazide (1) with electrophilic reagents as triethylorthoformate, dimethylformamide-dimethylacetal, acetic anhydride, and carbon disulfide to give 1,3,4-oxadiazoles (8,10,11) and N′-acetyl-butanehydrazide (9) . Reacted of butanehydrazide (1) with potassium thiocyanate gave 1,2,4-triazoles (12) . Similarly, treatment of (1) with chloroacetamide gave 1,2,4-triazinones (13) . The pyrrolotriazinones (14) was obtained by cyclization of (13) . Also, butanehydrazide ( 1 ) was utilized as a starting material for the synthesized of new Schiff bases as N′-(4-sub-benzylidene)-phenylbutane-hydrazide (15a-c) , which are used as an initiative to prepare new compounds such as 1,2,4-triazepinones (16a-c) , pyrrolotriazepinones (17a-c) , 1,2,4-triazines (18a-c) , and pyrrolotriazines (19a-c) by reacted of (15a-c) with each chloroacetamide or formamide. The chemical structure of the newly prepared compounds was determined through the spectrum data, including IR, NMR, and MS. The prepared compounds were tested for their in vitro antitumor activities. The compounds 17a-c , 16a-c , and 19a-c displayed activity against several types of cancer cell lines.     

2- and 2,7-Substituted para-N-Methylpyridinium Pyrenes: Syntheses,Molecular and Electronic Structures,Photophysical, Electrochemical,and Spectroelectrochemical Properties and Binding to Double-Stranded (ds) DNA

Two N-methylpyridinium compounds and analogous N-protonated salts of 2- and 2,7-substituted 4-pyridyl-pyrene compounds were synthesised and their crystal structures, photophysical properties both in solution and in the solid state, electrochemical and spectroelectrochemical properties were studied. Upon methylation or protonation, the emission maxima are significantly bathochromically shifted compared to the neutral compounds, although the absorption maxima remain almost unchanged. As a result, the cationic compounds show very large apparent Stokes shifts of up to 7200 cm⁻¹. The N-methylpyridinium compounds have a single reduction at ca. −1.5 V vs. Fc/Fc⁺ in MeCN. While the reduction process was reversible for the 2,7-disubstituted compound, it was irreversible for the mono-substituted one. Experimental findings are complemented by DFT and TD-DFT calculations. Furthermore, the N-methylpyridinium compounds show strong interactions with calf thymus (ct)-DNA, presumably by intercalation, which paves the way for further applications of these multi-functional compounds as potential DNA-bioactive agents.     

The simultaneous microdetermination of carbon,hydrogen, arsenic,or selenium in organic compounds

Simple modifications have been described for the simultaneous microdetermination of carbon, hydrogen, and arsenic or selenium in organic compounds using the rapid straight empty tube combustion technique. A silica insertion tube placed in the combustion tube at the open end of the ignition capsule and cooled via external exposure of the combustion tube around it to a stream of air, was found to be suitable for the quantitative retention of arsenic trioxide produced during the combustion of organo-arsenic compounds. The same modification was proved to be suitable for complete trapping of selenium dioxide produced in the combustion of organo-selenium compounds. In the latter case, the insertion tube was packed at one end with a short silica wool plug and cooling it with air is unnecessary.Using these simple modifications, accurate and reproducible carbon, hydrogen, and arsenic or selenium results were obtained in the analysis of a wide range of organic compounds containing arsenic or selenium. The conventional gravimetric finish was employed for the evaluation of three elements.