Study on Antibacterial Activity of 2-Methyl-3-(methylthio)Pyrazine Against Three Strains of Spoilage Bacteria

Previous studies have shown that glycine and proline are pharmacophores that display antibacterial activity.In the present study,glycine and proline were derivated to diketopiperazine compounds by chemical synthesis method,and their antibacterial activities were evaluated by three strains of spoilage bacteria,Escherichia coli,Pseudomonas aeruginosa and Shewanella putrefaciens,and the relationship of their antibacterial activities and structures was also investigated.Uv-vis spectrophotometry was used to determine the growth curves of three kinds of active indicator bacteria.Minimum inhibitory concentration(MIC)was determined by micro broth dilution method.The results showed that 2-methyl-3-(methylthio)pyrazine had significant antibacterial activity against three strains of the bacteria,and its MIC was 1.25%.It indicates 2-methyl-3-(methylthio)pyrazine has the potential to be developed as a kind of preservative in future.

Indirect Electroanalysis of 3-Methyl-4-Nitrophenol in Water Using Carbon Fiber Microelectrode Modified with Nickel Tetrasulfonated Phthalocyanine Complex

Electrochemical detection of 3-methyl-4-nitrophenol (MNP) in direct phenol oxidation occurs at high potentials and generally leads to progressive passivation of the electrochemical sensor. This study describes the use of a carbon fiber microelectrode modified with a tetrasulfonated nickel phthalocyanine complex for the detection of MNP at a lower potential than that of direct phenol oxidation. The MNP voltammogram showed the presence of an anodic peak at -0.11 V vs SCE, corresponding to the oxidation of the hydroxylamine group generated after the reduction of the nitro group. The effect of buffer pH on the peak current and SWV parameters such as frequency, scan increment, and pulse amplitude were studied and optimized to have better electrochemical response of the proposed sensor. With these optimal parameters, the calibration curve shows that the peak current varied linearly as a function of MNP concentration, leading to a limit of detection (LoD) of 1.1 μg/L. These results show an appreciable sensitivity of the sensor for detecting the MNP at relatively low potentials, making it possible to avoid passivation phenomena.

Synthesis, Structural Characterization and Antimicrobial Activity of a Novel Cobalt(II) Complex Based on 3-Methyl-1-Phenyl-4-(2-Thienoyl)-Pyrazol-5-One

New cobalt(II) complex, [Co(O2C15H11N2S)2(OH2)2]∙2H2O (1∙2H2O), has been synthesized upon reaction of cobalt chloride hexahydrate (Co(Cl)2∙6H2O) with 3-methyl-1-Phenyl-4-(2-thienoyl)-pyrazol-5-one (referred as HL) in ethanol at room temperature. Single crystal X-ray diffraction (XRD), spectroscopic methods, and microelemental analyses were used to characterize 1∙2H2O. Compound 1∙2H2O crystallizes in the orthorhombic crystal system with a Pbca space group and with the cobalt atom being pseudo-octahedral coordinated. The broth microdilution technique was used to screen the free ligand (HL) and the complex (1∙2H2O) for antimicrobial activities. HL has a low activity (MIC > 100 μg/mL) on all microorganisms, whereas compound 1∙2H2O displayed moderate activity (10 ∙2H2O exhibited bactericidal and fungicidal activity respectively on all the bacteria and yeasts tested. These findings reveal that the antimicrobial activity of HL was enhanced upon coordination to Co(II) ion against all microorganisms (bacteria and fungus).

Synthesis, Structural Characterization and Antimicrobial Activity of a Novel Cobalt(II) Complex Based on 3-Methyl-1-Phenyl-4-(2-Thienoyl)-Pyrazol-5-One

New cobalt(II) complex, [Co(O2C15H11N2S)2(OH2)2]∙2H2O (1∙2H2O), has been synthesized upon reaction of cobalt chloride hexahydrate (Co(Cl)2∙6H2O) with 3-methyl-1-Phenyl-4-(2-thienoyl)-pyrazol-5-one (referred as HL) in ethanol at room temperature. Single crystal X-ray diffraction (XRD), spectroscopic methods, and microelemental analyses were used to characterize 1∙2H2O. Compound 1∙2H2O crystallizes in the orthorhombic crystal system with a Pbca space group and with the cobalt atom being pseudo-octahedral coordinated. The broth microdilution technique was used to screen the free ligand (HL) and the complex (1∙2H2O) for antimicrobial activities. HL has a low activity (MIC > 100 μg/mL) on all microorganisms, whereas compound 1∙2H2O displayed moderate activity (10 ∙2H2O exhibited bactericidal and fungicidal activity respectively on all the bacteria and yeasts tested. These findings reveal that the antimicrobial activity of HL was enhanced upon coordination to Co(II) ion against all microorganisms (bacteria and fungus).

First Synthesis of (±)-3-(5-Hyd roxy-4-Methyl-7-Isopropyl-3E,7-Octadienyl)- △~2-Butenolide

An efficIent total synthesis of (±)-3-(5-hydroxy-4-methyl-7 △-butenolide, a new fi1n1esane-b;.Fed homosesquiterPeIle lactone. starting from geraniol through eightsteps are described.

Treatment of 2-phenylamino-3-methyl-6-di-n-butylaminofluoran production effluent by combination of biological treatments and Fenton's oxidation

High strength refractory organic stream is produced during the production of 2-phenylamino-3-methyl-6-di-n-butylaminofluoran （One Dye Black 2, abbr. ODB 2）, a novel heat-sensitive material with a promising market. In this study, a combination of acidificationprecipitation, primary biological treatment, Fenton＇s oxidation and another biological treatment was successfully used for the removal of COD from 18000-25000 mg/L to below 200 mg/L from the ODB 2 production wastewater in a pilot experiment. A COD removal of 70%-80% was achieved by acidification-precipitation under a pH of 2.5-3.0. The first step biodegradafion permitted an average COD removal of 70% under an hydraulic residence time （HRT） of 30 h. By batch tests, the optimum conditions of Fenton＇s oxidation were acquired as： Fe^2＋ dose 6.0 mmol/L; H2O2 dose 3000 mg/L; and reaction time 6 h. The second step biological treatment could ensure an effluent COD below 200 mg/L under an HRT of 10 h following the Fenton＇s treatment.

Theoretical Investigation on QSAR of(2-Methyl-3-biphenylyl)methanol Analogs as PD-L1 Inhibitor

Cancer is one of the most serious issues in human life.Blocking programmed cell death protein 1 and programmed death ligand-1(PD-L1)pathway is one of the great innovations in the last few years,a few numbers of inhibitors can be able to block it.(2-Methyl-3-biphenylyl)methanol derivative is one of them.Here,the quantitative structure-activity relationship(QSAR)established twenty(2-methyl-3-biphenylyl)methanol derivatives as the programmed death ligand-1 inhibitors.Density functional theory at the B3LPY/6-31+G(d,p)level was employed to study the chemical structure and properties of the chosen compounds.Highest occupied molecular orbital energy EHOMO,lowest unoccupied molecular orbital energy ELUMO,total energy ET,dipole moment DM,absolute hardnessη,absolute electronegativityχ,softness S,electrophilicityω,energy gap?E,etc.,were observed and determined.Principal component analysis(PCA),multiple linear regression(MLR)and multiple nonlinear regression(MNLR)analysis were carried out to establish the QSAR.The proposed quantitative models and interpreted outcomes of the compounds were based on statistical analysis.Statistical results of MLR and MNLR exhibited the coefficient R^2 was 0.661 and 0.758,respectively.Leave-one-out cross-validation,r_m^2 metric,r_m^2 test,and"Golbraikh&Tropsha’s criteria"analyses were applied for the validation of MLR and MNLR,which indicate two models are statistically significant and well stable with data variation in the external validation towards PD-L1.The obtained results showed that the MNLR model predicts the bioactivity more accurately than MLR,and it may be helpful and supporting for evaluation of the biological activity of PD-L1 inhibitors.

Synthesis, Crystal Structure and Antitumor Activity of 2-(3-Methyl-5-(methylthio)-4H-1,2,4-triazol-4-yl)isoindoline-1,3-dione

The title compound 2-（3-methyl-5-（methylthio）-4H-1,2,4-triazol-4-yl）isoindoline- 1,3-dione （C12H10NaO2S, Mr= 274.30） has been synthesized by a three-step procedure including the cyclization, hydrazinolysis and substitution reactions, and its crystal structure was determined by X-ray single-crystal diffraction. The crystal belongs to the monoclinic system, space group P2/c with a = 12.264（3）, b = 14.646（3）, c = 14.349（4） A,β = 91.69（3）°,μ = 0.255 mm1, Mr = 274.30, V = 2576.2（10） A3, Z =8, Dc = 1.414 g/cm3, F（000） = 1136, R = 0.0487 and wR = 0.1329 for 4048 observed reflections with I 〉 2σ（I）. In addition, the preliminary bioassay suggested that the title compound 6 exhibits relatively good antitumor activity against HT-29 and MCF-7.

Extraction Behavior of Rare Earths with 1-phenyl-3-methyl-4-benzoyl-pyrazolone-5 Using Solid-liquid Extraction Technique

The extraction behavior of rare earths was studied by using paraffin with ceresin as a diluent containing 1-phenyl-3-methyl-4-benzoyl-pyrazolone-5.In solid phase,the composition of complexes is REP_3.The equilib- rium extraction constants and pH_(1/2) values of solid-liquid extraction are higher than those of normal liquid-liquid extraction.The extraction efficiency tends to maximum when the ratio of phases is 1:1.When the extraction temperature is higher than the melting point of paraffin and the extraction time is over 10 min,the extraction efficiency keeps constant.Moreover,the relationship among separation factor,equilibrium extrac- tion constant,pH_(1/2) value and atomic number was obtained.The mechanism of solid-liquid extraction is analogous to that of liquid-liquid extraction.

Dissolution Properties of 2-(Dinitromethylene)-5-methyl-1,3-diazacyclopentane in Dimethyl Sulfoxide and N-Methyl Pyrrolidone

The molar enthalpies of dissolution for 2-（dinitromethylene）-5-methyl-1,3-diazacyclopentane（DNMDZ） in dimethyl sulfoxide（DMSO） and N-methyl pyrrolidone（NMP） were measured using an RD496-2000 Calvet microcalorimeter at 298.15 K under atmospheric pressure.Empirical formulae for the calculation of the molar enthalpies of dissolution（Δ diss H） were obtained from the experimental data of the dissolution processes of DNMDZ in DMSO or NMP.The relationships between the rate constant（k） and the molality（b） and between the reaction order（n） and the molality（b） were determined.The corresponding kinetic equations describing the two dissolution processes were dα/dt=10^-2.16（1-α） ^1.01 for the dissolution of DNMDZ in DMSO,and dα/dt=10^-2.02（1-α）^ 0.85 for the dissolution of DNMDZ in NMP,respectively.

Investigation of liquid–liquid equilibrium of the ternary system(water +1,6-diaminohexane + 2-methyl-1-propanol or 3-methyl-1-butanol) at different temperatures

In this study, the LLE data of ternary system(water + 1,6-diaminohexane + 2-methyl-1-propanol) and(water +1,6-diaminohexane + 3-methyl-1-butanol) were measured at 293.15, 303.15 and 313.15 K under atmospheric pressure. Reliability of the experimental tie-line data was checked by empirical Hand, Othmer-Tobias and Bachman equations. Distribution coefficient(D) and selectivity(S) were calculated in order to investigate capability of the studied organic solvents for 1,6-diaminohexane extraction. The high values of separation factors demonstrated that 2-methyl-1-propanol and 3-methyl-1-butanol were applicable for this purpose. The experimental data were correlated by nonrandom two-liquid(NRTL) and universal quasi-chemical(UNIQUAC) models.The percent-root-mean-square deviation(RMSD) values for NRTL and UNIQUAC models were less than 0.15,which indicated that the experimental data have been sufficiently correlated.

Differential protein expression in substantia nigra induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine in a mouse model of chronic Parkinson’s disease

BACKGROUND： To date, a complete protein expression profile of the midbrain substantia nigra in a mouse model of chronic Parkinson＇s disease, induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine （MPTP）, does not exist. In addition, there are no reports of analysis of differential protein expression. OBJECTIVE： To separate and evaluate MPTP-induced differential protein expression through the use of proteomics in the substantia nigra of a mouse model of chronic Parkinson＇s disease. DESIGN： Randomized controlled animal study. SETTING： Department of Neurology, the First Affiliated Hospital, Chongqing Medical University. MATERIALS： Sixteen 8-10-week old, healthy, male, C57BL mice, weighing 20-25 g, and of clean grade, were provided by the Experimental Animal Center of Chongqing Medical University. The experimental animals were disposed according to ethical criteria. MPTP was provided by Sigma Company, USA; Pdquest 2D image analysis software and gelatum/irradiance image analysis system （ChemiDoc XRS） by Bio-Rad, USA; and Voyager DE-PROMALD1-TOF-MS mass spectroscopy analyzer by AB1 Company, USA. METHODS： This study was performed in Chongqing Neurological Laboratory between November 2006 and July 2007. Mice were randomly divided into model and control groups, with 8 mice in each group. Mice in the model group were received a subcutaneous injection of MPTP （25 mg＆g）, twice a week, for five successive weeks, to establish a chronic Parkinson＇s disease model. Mice in the control group received the same volume of a subcutaneous saline injection at the same time points. Mice were sacrificed by anesthesia to rapidly obtain the midbrain for protein separation of the substantia nigra. MAIN OUTCOME MEASURES： （1） 2-ED handbook （Bio-Rad Company） was referenced for two-dimensional electrophoresis, （2） PDQUEST8,0 analytical electrophoresis pattern was adopted to evaluate differential protein expression. （3） Peptide mass finger print map and data were retrieved on http：//www.prospector.ucsf.edu to compare differential substantia nigral protein expression in the two groups. RESULTS： Two-dimensional gel electrophoresis of substantia nigra tissue indicated that there were 33 differential protein expressions between the two groups. Three new proteins were evaluated, including α -enolase, which exhibited regulated expression, tumor necrosis factor ligand superfamily member 4, and cyclin-dependent kinase inhibitor 1B. CONCLUSION： There are three proteins that exhibit differential expression in the substantia nigra- α -enolase, tumor necrosis factor ligand superfamily member 4, and cyclin-dependent kinase inhibitor 1B.

Synthesis and Crystal Structure of Trans-4-[(5-(2,4-Dichlorophenoxy)-3-methyl-1-phenyl-1H-pyrazol-4-yl)methyleneamino]-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one

The title compound trans-4-[（5-（2,4-dichlorophenoxy）-3-methyl- 1-phenyl-1H-pyrazol-4-yl）methyleneamino]- 1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 3 （C28H23Cl2N5O2, Mr = 532.41） has been synthesized and its crystal structure was determined by single-crystal X-ray diffraction analysis. It crystallizes in triclinic, space group P1- with a = 8.9438（4）, b = 11.6065（5）, c = 14.2215（6）A, α = 112.566（1）, β = 92.324（2）, γ = 102.91（1）°, V= 1315.65（10） A^3, Z = 2, Dc = 1.344 g/cm^3,μ（MoKa） = 0.282 mm^-1, λ = 0.71073 A, F（000） = 552, the final R = 0.0587 and wR = 0.1578 for 5071 observed reflections （I 〉 2σ（I））. X-ray analysis reveals that the product is a thermodynamically stable trans isomer. Intra- and intermolecular C（ 12）-H（12）…O（1） and C（28）-H（28）...O（1）# 1 hydrogen bonds were observed in the title compound.

Synthesis of fused pyran and arylbis(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)methane in ionic liquid

Promoted and mediated by an ionic liquid-[bmim][BF4], fused pyrans or arylbis（4-hydroxy-6-methyl-2-oxo-2H-pyran-3- yl）methanes were efficiently and selectively prepared from the reaction of aldehyde and 4-hydroxy-6-methyl-2-oxo-pyran with or without acetic anhydride. By using these novel procedures, pyrimidine nucleoside-fused pyran and arylbis（pyranon-3-yl）methane hybrids with potential biological activities were constructed.

Organic Synthesis in Ionic Liquids: Condensation of 3-Methyl-1-phenyl-5-pyrazolone with Carbonyl Compounds Catalyzed by Ethylenediammonium Diacetate (EDDA)

An efficient and environmental benign method is reported for the condensation of 3-methyl-1-phenyl-5-pyrazolone with carbonyl compounds in ionic liquids [Bmim]BF4 and [Bmim]PF6 catalyzed by ethylenediammonium diacetate.

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist inhibits apoptosis of retinal ganglion cells in a rabbit model of optic nerve injury

A rabbit model of traumatic optic nerve injury, established by occlusion of the optic nerve using a vascular clamp, was used to investigate the effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist GYKI 52466 on apoptosis of retinal ganglion cells following nerve injury. Hematoxylin-eosin staining and a terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that retinal ganglion cells gradually decreased with increasing time of optic nerve injury, while GYKI 52466 could inhibit this process. The results demonstrate that following acute optic nerve injury, apoptosis of retinal ganglion cells is a programmed process, which can be inhibited by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist.

1-methyl-4-phenylpyridinium ion induces endoplasmic reticulum stress through glycogen synthase kinase-3 beta activation in PC12 cells

1-methyl-4-phenylpyridinium ion （MPP^＋） induces endoplasmic reticulum stress and activates caspase-12 in PC12 cells, leading to neuronal apoptosis. However, the underlying molecular mechanism remains unknown. The present study investigated the regulatory effects of nerve growth factor （Akt activator） and lithium chloride （glycogen synthase kinase-3β inhibitor） on the endoplasmic reticulum stress signaling pathway. The results revealed that MPP＋ induced expression of Bip and C/EBP homologous protein. The upregulation of Bip and C/EBP homologous protein, as well as the decreased pro-caspase-12 level induced by MPP^＋ were inhibited by pretreatment of the nerve growth factor or lithium chloride. These results suggest that the phosphatidylinositol 3 kinase-Aktglycogen synthase kinase-3β pathway is involved in MPP-induced endoplasmic reticulum stress.

Synthesis of 1,2,3,4-Tetrahydro-1-Indolizinones and 3-Methyl-1,2-dihydro-1-Pyrrolizinones

4-(1-Pyrrolyl)butanenitrile(4), the key intermediate for the synthesis of 1,2,3,4-tetrahydro-1-indolizinone, was prepared with Clauson-Kass reation. When pyrrole reacted with 4-bromobutanenitrile in PEG-400 dimethyl ether catalyzed by NaOH, 3-(1-pyrrolyl)butanenitrile was obtained. The nitriles were converted into the corresponding ketones by Hoesch reaction. Some of the ketone derivatives were prepared.

Synthesis and Crystal Structure of Ethyl 3-(4-Chlorophenyl)-3,4-dihydro-6-methyl-4-oxo-2-(pyrrolidin-1-yl)furo[2,3-d]pyrimidine-5-carboxylate

The crystal structure of the title compound ethyl 3-（4-chlorophenyl）-3,4-dihydro-6- methyl-4-oxo-2-（pyrrolidin-1-yl）furo[2,3-d]pyrimidine-5-carboxylate （C20H20ClN3O4, Mr= 401.84） has been prepared and determined by single-crystal X-ray diffraction. The crystal is of monoclinic, space group P21/n with a = 20.6215（9）, b = 8.5311（4）, c = 21.6886（9） A^°, β = 91.607（1）°, V = 3814.0（3）A^°^3, Z = 8, Dc = 1.400 g/cm^3, F（000） = 1680, μ = 0.233 mm^-1, R = 0.0718 and wR = 0.1545 for 6717 observed reflections with I 〉 2σ（I）. X-ray diffraction analysis reveals two crystallographically independent molecules in the asymmetric unit.

Synthesis and Crystal Structure of (Z)-Methyl-3-methoxy-2-{2-[(4-(E-3-p-tolylacryloyl)phenoxy)methyl]phenyl}acrylate

The title compound,(Z)-methyl-3-methoxy-2-{2-[(4-(E-3-p-tolylacryloyl)phenoxy)-methyl]phenyl}acrylate,was synthesized and determined by X-ray single-crystal diffraction.The crystal belongs to the triclinic system,space group P1 with a=8.0157(8),b=12.5748(13),c=13.3768(14)Å,α=64.770(2),β=75.720(2),γ=89.784(2)°,μ=0.085 mm^(-1),Mr=442.49,V=1174.1(2)Å3,Z=2,Dc=1.252 g/cm^(3),F(000)=468,T=294(2)K,R=0.0603 and wR=0.1498 for 2644 observed reflections with I〉2σ(I).X-ray diffraction analysis reveals that the single crystal contains strong non-classical hydrogen bonds.The preliminary bioassay showed that the title compound exhibits inhibitory activity against the Pseudoperoniospora cubensis and Rhizoctonia solani at the test concentration of 200 mg/L.