Urokinase-type plasminogen activator (uPA) plays a crucial role in the regulation of plasminogen activation, tumor cell adhesion and migration. The inhibition of uPA activity is a promising mechanism for anti-cancer...Urokinase-type plasminogen activator (uPA) plays a crucial role in the regulation of plasminogen activation, tumor cell adhesion and migration. The inhibition of uPA activity is a promising mechanism for anti-cancer therapy. Most current uPA inhibitors employ a highly basic group (either amidine or guanidine group) to target the S1 pocket of uPA active site, which leads to poor oral bioavailability. Here we study the possibility of using less basic 2-aminobenzothiazole (ABT) as S1 pocket binding group. We report the crystal structures of uPA complexes with ABT or 2-amino-benzothiazole-6-carboxylic acid ethyl ester (ABTCE). The inhibitory constants of these two inhibitors were measured by a chromogenic competitive assay, and it was found that ABTCE is a better inhibitor for uPA (Ki = 656 μM) than ABT (Ki = 5.03 mM). This work shows that 2-amniobenzothiazole can be used as P1 group which may have better oral bioavailability than the commonly used amidine or guanidine group. We also found the ethyl ester group occupies the characteristic oxyanion hole and contacts to uPA 37- and 60-loops. Such work provides structural information for further improvements of potency and selectivity of this new class of uPA inhibitor.展开更多
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...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.展开更多
The quantitative structure-activity relationship (QSAR) of 16 pyrazole compounds was studied by ab initio method at the HF/3-21G level using Guassian03 soft. The optimized structures together with some characteristi...The quantitative structure-activity relationship (QSAR) of 16 pyrazole compounds was studied by ab initio method at the HF/3-21G level using Guassian03 soft. The optimized structures together with some characteristic and electric parameters of the title compounds were obtained; some stereo-parameters were calculated by HyperChem software. Stepwise multiple regression method was adopted to establish bi- and tri-parametric models between biological activity and some parameters. The lager △E and logP, the higher biological activity; and the biological activity would be promoted with the smaller μ, QN and QPYRA. It provided a theory direction to synthesize some compounds with high activity.展开更多
The impurities in ethyl-2-[[2′-cyanobiphenyl-4-yl] methyl] amino]-3-nitrobenzoate,an intermediate for synthesis of candesartan cilexiti,were detected by LC-MSn. The structural assignment of these impurities was carri...The impurities in ethyl-2-[[2′-cyanobiphenyl-4-yl] methyl] amino]-3-nitrobenzoate,an intermediate for synthesis of candesartan cilexiti,were detected by LC-MSn. The structural assignment of these impurities was carried out by LC-MSn using electrospray ionization source and an ion trap mass analyzer. The formation of the impurities was discussed. Also the fragmentation pathways of these compounds were studied.展开更多
The oxidative polycondensation reaction conditions of 4-[(4-hydroxybenzylidene) amino] phenol (4-HBAP) were studied with H2O2, air oxygen and NaOCl in an aqueous alkaline medium between 50 and 90℃. The structures...The oxidative polycondensation reaction conditions of 4-[(4-hydroxybenzylidene) amino] phenol (4-HBAP) were studied with H2O2, air oxygen and NaOCl in an aqueous alkaline medium between 50 and 90℃. The structures of the obtained monomer and polymer were confirmed by FT-IR, UV-Vis, 1H- and 13C-NMR and elemental analysis. The characterization was made by TG-DTA, size exclusion chromatography (SEC) and solubility tests. At the optimum reaction conditions, the yield of poly[4-(4-hydroxybenzylidene amino) phenol] (P-4-HBAP) was found to be 48.3% (for H2O2 oxidant), 80.5% (for air O2 oxidant) and 86.4% (for NaOCl oxidant). According to the SEC analysis, the number-average molecular weight (Mn), weight-average molecular weight (Mw) and polydispersity index (PDI) values of P-4-HBAP was found to be 8950, 10970 g tool^-1 and 1.225, respectively, using H202; and l l610, 15190 g tool^-1 and 1.308 respectively, using air 02 and 7900, 9610 g mol^-1 and 1.216, respectively, using NaOC1. According to TG-DTA analyses, P-4-HBAP was more stable than 4-HBAP against thermal decomposition. The weight loss of P-4-HBAP was found to be 49.27% at 1000℃. The highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) values calculated from electrochemical measurement. Electrochemical energy gaps (Eg') of 4-HBAP and P-4-HBAP were found to be -5.46, -5.28; -2.26, -2.67; 3.20 and 2.61 eV, respectively. According to UV-Vis measurements, optical band gap (Eg) of 4-HBAP and P-4-HBAP were found to be 3.34 and 3.01 eV, respectively. Also, antimicrobial activities of 4-HBAP and P-4-HBAP were examined against selected some bacteria. The electrical conductivity of the polymer was measured after doping with iodine.展开更多
This paper demonstrates an all-optical switching model system comprising a single pulsed pump beam at 355 nm and a CW He-Ne signal beam at 632.8 nm with 2-(2'-hydroxyphenyl)benzothiazole (HBT) in ethanol solution...This paper demonstrates an all-optical switching model system comprising a single pulsed pump beam at 355 nm and a CW He-Ne signal beam at 632.8 nm with 2-(2'-hydroxyphenyl)benzothiazole (HBT) in ethanol solution. The origins of the optical switching effect were discussed. By the study of nonlinear optical properties for HBT in ethanol solvent, this paper verified that the excited-state intramolecular proton transfer (ESIPT) effect of HBT and the thermal effect of solvent worked on quite different time scales and together induced the change of the refractive index of HBT solution, leading to the signal beam deflection. The results indicated that the HBT molecule could be an excellent candidate for high-speed and high-sensitive optical switching devices.展开更多
Zn(Ⅱ), Ni(Ⅱ) and Co(Ⅱ) compounds(1~3) based on 2-(2-pyridyl)benzothiazole(bpt) and terephthalic acid(PTA) were synthesized. The crystal structures of [Zn(bpt)(PTA)2](1), [Ni(bpt)(PTA)2](2), and [Co(bpt)(PTA)2](3) ...Zn(Ⅱ), Ni(Ⅱ) and Co(Ⅱ) compounds(1~3) based on 2-(2-pyridyl)benzothiazole(bpt) and terephthalic acid(PTA) were synthesized. The crystal structures of [Zn(bpt)(PTA)2](1), [Ni(bpt)(PTA)2](2), and [Co(bpt)(PTA)2](3) have been determined by single-crystal X-ray diffraction analysis, which shows that all the three complexes belong to monoclinic system with space group P21/c. Time-dependent density functional theory(TD-DFT) calculation is performed on a reference structure of compound 3. The excited electrons mainly localized at the π* of ligand 2-(2-pyridyl)benzothiazole, which will be convenient for them to bind with the DNA reacting sites. Fluorescence spectroscopy, ultraviolet(UV) spectroscopy and viscosity were used to characterize the interaction of the compounds with Calf thymus DNA(CT-DNA). The results indicate that compounds 1~3 bind to CT-DNA and have a strong interaction with DNA. The compounds can probably bind to CT-DNA via a non-intercalative mode as concluded by studying the viscosity of a DNA solution in the presence of the compounds. This combination can effectively break DNA, which speculates that these three compounds may interact with the cancer cell DNA in this binding mode, thereby damaging the cancer cells.展开更多
A new ternary complex [Cu(PBT)(Gly)(H2O)]ClO4 (PBT=2-(2'-pyridyl)benzothiazole, and Gly=glycinate) has been synthesized and characterized by elemental analysis, molar conductivity, and IR methods. The compl...A new ternary complex [Cu(PBT)(Gly)(H2O)]ClO4 (PBT=2-(2'-pyridyl)benzothiazole, and Gly=glycinate) has been synthesized and characterized by elemental analysis, molar conductivity, and IR methods. The complex, structurally characterized by single-crystal X-ray crystallography, shows a slightly distorted square-pyramidal coordination geometry in which two nitrogen atoms of PBT and the carboxylate oxygen atom O and the amino nitrogen atom N of Gly bind at the basal plane, a water molecule is coordinated at the apical position. The complex, Cu(ClO4)2 and flee PBT were each tested for their ability to inhibit the growth of two Gram(--) (Escherichia coil, Salmonella) and two Gram(+) (Bacillus subtilis, Staphylococcus aureus) microorganisms. The complex showed good antibacterial activities against the microorganisms compared with free PBT and Cu(C104)2. The interaction between the complex and calf thymus DNA in aqueous solution was investigated using electronic spectroscopy, fluorescence spectroscopy, circular dichroic spectroscopy, and viscosity measurements. Results suggest that the complex could bind to DNA by an intercalative mode. In addition, the result of agarose gel electrophoresis showed that the complex can cleave the plasmid DNA by hydroxyl radicals and singlet oxygen-like species under the condition of physiological pH and room temperature.展开更多
Objective:To explore the effect of the protease inhibitor from Agaricus bisporus(J.E.Lange)Imbach(AbPI)on glucose uptake and oxidative stress in 3 T3-L1 adipocytes.Methods:Adipocytes were differentiated and stained wi...Objective:To explore the effect of the protease inhibitor from Agaricus bisporus(J.E.Lange)Imbach(AbPI)on glucose uptake and oxidative stress in 3 T3-L1 adipocytes.Methods:Adipocytes were differentiated and stained with OilRed-O staining to confirm adipogenesis.The toxic/protective effect of AbPI on the adipocytes was determined by MTT assay,intracellular reactive oxygen species generation through flow cytometry,and morphologically through confocal microscopy using propidium iodide,4,6-diamino-2-phenylindol dihydrochloride,and 2’,7’-dichlorofluorescein diacetate dyes.The uptake of fluorescent glucose analog,2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose by adipocytes was also studied through confocal microscopy.Results:MTT assay showed that the cell survival rate was(28.00±3.00)%,(92.33±2.60)%,and(71.34±2.10)%in the presence of 2 mM H2O2,AbPI alone,and AbPI and H2O2 both,respectively,in comparison to the control.Oil-Red-O staining indicated that Ab PI enhanced adipogenesis.AbPI stimulated the glucose uptake by adipocytes similar to the drug rosiglitazone,and showed insulinsensitizing effect in the presence of insulin,but failed to stimulate the uptake in the absence of insulin.Intracellular reactive oxygen species generation was reduced in differentiating adipocytes upon Ab PI treatment.Confocal microscopy showed that the damaged cell population rose to 3.50%,117.84%,and 261.50%in the presence of Ab PI alone,AbPI with H2O2,and H2O2 alone,respectively.Conclusions:The protease inhibitor enhances glucose uptake by adipocytes and exhibits a cytoprotective effect on them.展开更多
Using methanol-water mixtures as the mobile phase, the chromatographic retention parameters k' and Rf were determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and reversed-phase high-perf...Using methanol-water mixtures as the mobile phase, the chromatographic retention parameters k' and Rf were determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and reversed-phase high-performance thin-layer chromatography (RP-HPTLC) for N-(benzothiazol-2-yl)-α-amino alkyl phosphoric diesters and the correlation with lipophilicity parameter (Clog P) was established. Log Kw values obtained from RP-HPLC and Rm values obtained from RP-HPTLC can be used to evaluate the lipophilicity of this kind of compounds. Chromatographic method is a good alternative for lipophilicity measurement.展开更多
基金Supported by FJIRSM (SZD08003)National Natural Science Foundation of China (30811130467, 30625011)+1 种基金Ministry of Science of Technology (2006AA02A313, 2007CB914304)Chinese Academy of Sciences (KSCX2-YW-R-082)
文摘Urokinase-type plasminogen activator (uPA) plays a crucial role in the regulation of plasminogen activation, tumor cell adhesion and migration. The inhibition of uPA activity is a promising mechanism for anti-cancer therapy. Most current uPA inhibitors employ a highly basic group (either amidine or guanidine group) to target the S1 pocket of uPA active site, which leads to poor oral bioavailability. Here we study the possibility of using less basic 2-aminobenzothiazole (ABT) as S1 pocket binding group. We report the crystal structures of uPA complexes with ABT or 2-amino-benzothiazole-6-carboxylic acid ethyl ester (ABTCE). The inhibitory constants of these two inhibitors were measured by a chromogenic competitive assay, and it was found that ABTCE is a better inhibitor for uPA (Ki = 656 μM) than ABT (Ki = 5.03 mM). This work shows that 2-amniobenzothiazole can be used as P1 group which may have better oral bioavailability than the commonly used amidine or guanidine group. We also found the ethyl ester group occupies the characteristic oxyanion hole and contacts to uPA 37- and 60-loops. Such work provides structural information for further improvements of potency and selectivity of this new class of uPA inhibitor.
基金the Science Research Foundation of Henan Institute of Science and Technology (No. 06036)
文摘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.
基金talents in University (NCET-04-0649)the Natural Science Foundation of Shandong Province (Y2006B07, Z2006B01)
文摘The quantitative structure-activity relationship (QSAR) of 16 pyrazole compounds was studied by ab initio method at the HF/3-21G level using Guassian03 soft. The optimized structures together with some characteristic and electric parameters of the title compounds were obtained; some stereo-parameters were calculated by HyperChem software. Stepwise multiple regression method was adopted to establish bi- and tri-parametric models between biological activity and some parameters. The lager △E and logP, the higher biological activity; and the biological activity would be promoted with the smaller μ, QN and QPYRA. It provided a theory direction to synthesize some compounds with high activity.
文摘The impurities in ethyl-2-[[2′-cyanobiphenyl-4-yl] methyl] amino]-3-nitrobenzoate,an intermediate for synthesis of candesartan cilexiti,were detected by LC-MSn. The structural assignment of these impurities was carried out by LC-MSn using electrospray ionization source and an ion trap mass analyzer. The formation of the impurities was discussed. Also the fragmentation pathways of these compounds were studied.
基金This work was financially supported by the TUBITAK Grants Commission for a research grant(No.TBAG-2451(104T062)).
文摘The oxidative polycondensation reaction conditions of 4-[(4-hydroxybenzylidene) amino] phenol (4-HBAP) were studied with H2O2, air oxygen and NaOCl in an aqueous alkaline medium between 50 and 90℃. The structures of the obtained monomer and polymer were confirmed by FT-IR, UV-Vis, 1H- and 13C-NMR and elemental analysis. The characterization was made by TG-DTA, size exclusion chromatography (SEC) and solubility tests. At the optimum reaction conditions, the yield of poly[4-(4-hydroxybenzylidene amino) phenol] (P-4-HBAP) was found to be 48.3% (for H2O2 oxidant), 80.5% (for air O2 oxidant) and 86.4% (for NaOCl oxidant). According to the SEC analysis, the number-average molecular weight (Mn), weight-average molecular weight (Mw) and polydispersity index (PDI) values of P-4-HBAP was found to be 8950, 10970 g tool^-1 and 1.225, respectively, using H202; and l l610, 15190 g tool^-1 and 1.308 respectively, using air 02 and 7900, 9610 g mol^-1 and 1.216, respectively, using NaOC1. According to TG-DTA analyses, P-4-HBAP was more stable than 4-HBAP against thermal decomposition. The weight loss of P-4-HBAP was found to be 49.27% at 1000℃. The highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) values calculated from electrochemical measurement. Electrochemical energy gaps (Eg') of 4-HBAP and P-4-HBAP were found to be -5.46, -5.28; -2.26, -2.67; 3.20 and 2.61 eV, respectively. According to UV-Vis measurements, optical band gap (Eg) of 4-HBAP and P-4-HBAP were found to be 3.34 and 3.01 eV, respectively. Also, antimicrobial activities of 4-HBAP and P-4-HBAP were examined against selected some bacteria. The electrical conductivity of the polymer was measured after doping with iodine.
基金Project supported by the National Natural Science Foundation of China (Grant No 60178025) and the Key Laboratory of 0ptoelectronics Information Technical Science of Ministry of Education, Institute of Modern 0ptics, Nankai University, China.
文摘This paper demonstrates an all-optical switching model system comprising a single pulsed pump beam at 355 nm and a CW He-Ne signal beam at 632.8 nm with 2-(2'-hydroxyphenyl)benzothiazole (HBT) in ethanol solution. The origins of the optical switching effect were discussed. By the study of nonlinear optical properties for HBT in ethanol solvent, this paper verified that the excited-state intramolecular proton transfer (ESIPT) effect of HBT and the thermal effect of solvent worked on quite different time scales and together induced the change of the refractive index of HBT solution, leading to the signal beam deflection. The results indicated that the HBT molecule could be an excellent candidate for high-speed and high-sensitive optical switching devices.
基金Supported by the Foundation for Jilin of China of 2014 Human Resources Developmentthe Natural Science Project Foundation of Education Department of Jilin Province(No.2015358)the Natural Science Foundation of Changchun Normal University(No.201203)
文摘Zn(Ⅱ), Ni(Ⅱ) and Co(Ⅱ) compounds(1~3) based on 2-(2-pyridyl)benzothiazole(bpt) and terephthalic acid(PTA) were synthesized. The crystal structures of [Zn(bpt)(PTA)2](1), [Ni(bpt)(PTA)2](2), and [Co(bpt)(PTA)2](3) have been determined by single-crystal X-ray diffraction analysis, which shows that all the three complexes belong to monoclinic system with space group P21/c. Time-dependent density functional theory(TD-DFT) calculation is performed on a reference structure of compound 3. The excited electrons mainly localized at the π* of ligand 2-(2-pyridyl)benzothiazole, which will be convenient for them to bind with the DNA reacting sites. Fluorescence spectroscopy, ultraviolet(UV) spectroscopy and viscosity were used to characterize the interaction of the compounds with Calf thymus DNA(CT-DNA). The results indicate that compounds 1~3 bind to CT-DNA and have a strong interaction with DNA. The compounds can probably bind to CT-DNA via a non-intercalative mode as concluded by studying the viscosity of a DNA solution in the presence of the compounds. This combination can effectively break DNA, which speculates that these three compounds may interact with the cancer cell DNA in this binding mode, thereby damaging the cancer cells.
基金We are thankful for the Natural Science Foundation of Guangdong Province (No. 10151064201000016) and the 211 Project Program Foundation of South China Agricultural University (No. 2009B010100001).
文摘A new ternary complex [Cu(PBT)(Gly)(H2O)]ClO4 (PBT=2-(2'-pyridyl)benzothiazole, and Gly=glycinate) has been synthesized and characterized by elemental analysis, molar conductivity, and IR methods. The complex, structurally characterized by single-crystal X-ray crystallography, shows a slightly distorted square-pyramidal coordination geometry in which two nitrogen atoms of PBT and the carboxylate oxygen atom O and the amino nitrogen atom N of Gly bind at the basal plane, a water molecule is coordinated at the apical position. The complex, Cu(ClO4)2 and flee PBT were each tested for their ability to inhibit the growth of two Gram(--) (Escherichia coil, Salmonella) and two Gram(+) (Bacillus subtilis, Staphylococcus aureus) microorganisms. The complex showed good antibacterial activities against the microorganisms compared with free PBT and Cu(C104)2. The interaction between the complex and calf thymus DNA in aqueous solution was investigated using electronic spectroscopy, fluorescence spectroscopy, circular dichroic spectroscopy, and viscosity measurements. Results suggest that the complex could bind to DNA by an intercalative mode. In addition, the result of agarose gel electrophoresis showed that the complex can cleave the plasmid DNA by hydroxyl radicals and singlet oxygen-like species under the condition of physiological pH and room temperature.
文摘Objective:To explore the effect of the protease inhibitor from Agaricus bisporus(J.E.Lange)Imbach(AbPI)on glucose uptake and oxidative stress in 3 T3-L1 adipocytes.Methods:Adipocytes were differentiated and stained with OilRed-O staining to confirm adipogenesis.The toxic/protective effect of AbPI on the adipocytes was determined by MTT assay,intracellular reactive oxygen species generation through flow cytometry,and morphologically through confocal microscopy using propidium iodide,4,6-diamino-2-phenylindol dihydrochloride,and 2’,7’-dichlorofluorescein diacetate dyes.The uptake of fluorescent glucose analog,2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose by adipocytes was also studied through confocal microscopy.Results:MTT assay showed that the cell survival rate was(28.00±3.00)%,(92.33±2.60)%,and(71.34±2.10)%in the presence of 2 mM H2O2,AbPI alone,and AbPI and H2O2 both,respectively,in comparison to the control.Oil-Red-O staining indicated that Ab PI enhanced adipogenesis.AbPI stimulated the glucose uptake by adipocytes similar to the drug rosiglitazone,and showed insulinsensitizing effect in the presence of insulin,but failed to stimulate the uptake in the absence of insulin.Intracellular reactive oxygen species generation was reduced in differentiating adipocytes upon Ab PI treatment.Confocal microscopy showed that the damaged cell population rose to 3.50%,117.84%,and 261.50%in the presence of Ab PI alone,AbPI with H2O2,and H2O2 alone,respectively.Conclusions:The protease inhibitor enhances glucose uptake by adipocytes and exhibits a cytoprotective effect on them.
基金Project supported by the Fund of State Key Laboratory of Elemento-Organic Chemistry, Nankai University
文摘Using methanol-water mixtures as the mobile phase, the chromatographic retention parameters k' and Rf were determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and reversed-phase high-performance thin-layer chromatography (RP-HPTLC) for N-(benzothiazol-2-yl)-α-amino alkyl phosphoric diesters and the correlation with lipophilicity parameter (Clog P) was established. Log Kw values obtained from RP-HPLC and Rm values obtained from RP-HPTLC can be used to evaluate the lipophilicity of this kind of compounds. Chromatographic method is a good alternative for lipophilicity measurement.