A facile and efficient method for the preparation of 2-non-substituted quinoline-4-carboxylic acids is described via the Pfitzinger reaction of isatins with sodium pyruvate following consequent decarboxylation under m...A facile and efficient method for the preparation of 2-non-substituted quinoline-4-carboxylic acids is described via the Pfitzinger reaction of isatins with sodium pyruvate following consequent decarboxylation under microwave irradiation.展开更多
In order to understand the chemical-biological interactions governing their activities toward neuraminidase (NA), QSAR models of 28 thiazolidine-4-carboxylic acid derivatives with inhibitory influenza A virus were d...In order to understand the chemical-biological interactions governing their activities toward neuraminidase (NA), QSAR models of 28 thiazolidine-4-carboxylic acid derivatives with inhibitory influenza A virus were developed. The obtained HQSAR (hologram quantitative structure activity relationship), Topomer CoMFA and CoMSIA (comparative molecular similarity indices analysis) models were robust and had good exterior predictive capabilities. Moreover, QSAR modeling results elucidated that hydrogen bonds highly contributed to the inhibitory activity, then electrostatic and hydrophobic factors. Squared multiple correlation coefficients (R2) of HQSAR, Topomer CoMFA and CoMSIA models were 0.994, 0.978 and 0.996, respectively. Squared cross-validated correlation coefficients (Q2) of HQSAR, Topomer CoMFA and CoMSIA models were in turn 0.951, 919 and 0.820. Furthermore, squared multiple correlation coefficients for the test set (R2test) of HQSAR, CoMFA and CoMSIA models were 0.879, 0.912 and 0.953, respectively. Squared cross-validated correlation coefficients for the test set (Q2ext) of HQSAR, Topomer CoMFA and CoMSIA models were 0.867, 0.884 and 0.899, correspondingly.展开更多
AIM: To demonstrate the potential of using 2-aminothiazoline-4-carboxylic acid(ATCA) as a novel biomarker/forensic biomarker for cyanide poisoning. METHODS: A sensitive method was developed and employed for the identi...AIM: To demonstrate the potential of using 2-aminothiazoline-4-carboxylic acid(ATCA) as a novel biomarker/forensic biomarker for cyanide poisoning. METHODS: A sensitive method was developed and employed for the identification and quantification of ATCA in biological samples, where the sample extraction and clean up were achieved by solid phase extraction(SPE). After optimization of SPE procedures, ATCA was analyzed by high performance liquid chromatographytandem mass spectrometry. ATCA levels following the administration of different doses of potassium cyanide(KCN) to mice were measured and compared to endogenous ATCA levels in order to study the significance of using ATCA as a biomarker for cyanide poisoning.RESULTS: A custom made analytical method was established for a new(mice) model when animals were exposed to increasing KCN doses. The application of this method provided important new information on ATCA as a potential cyanide biomarker. ATCA concentration in mice plasma samples were increased from 189 ± 28 ng/mL(n = 3) to 413 ± 66 ng/mL(n = 3) following a 10 mg/kg body weight dose of KCN introduced subcutaneously. The sensitivity of this analytical method proved to be a tool for measuring endogenous level of ATCA in mice organs as follows: 1.2 ± 0.1 μg/g for kidney samples, 1.6 ± 0.1 μg/g for brain samples, 1.8 ± 0.2 μg/g for lung samples, 2.9 ± 0.1 μg/g for heart samples, and 3.6 ± 0.9 μg/g for liver samples. CONCLUSION: This finding suggests that ATCA has the potential to serve as a plasma biomarker / forensic biomarker for cyanide poisoning.展开更多
Highly efficient syntheses of novel fluorine bearing quinoline-4-carboxylic acids and the related compounds had been achieved from cyclocondensation of 2-amino-5-fluorophenyl glyoxylic acid 1 with benzoyle asetanilide...Highly efficient syntheses of novel fluorine bearing quinoline-4-carboxylic acids and the related compounds had been achieved from cyclocondensation of 2-amino-5-fluorophenyl glyoxylic acid 1 with benzoyle asetanilides 2 in boiling DMF, to give the target 3. Decarboxylation of 3 produced 6-fluoro-2-phenyl-3-(substituted amino)-keto-quinolines 4, while that reaction underwent refluxing, afforded 7-fluoro-1-(aryl)-3-phenyl-pyrrolo[3,4-c] quinoline-2,9-diones 5. Structure of the products has been established from their elemental and spectral analysis. All targets exhibited a high to moderate activity against some Aspergillus fungi as amylolytic agents.展开更多
Proceeding from natural amino acid L-asparagine and commercially available aldehydes a stereoselective synthesis was developed of (2S,4S)-2-alkyl(aryl)-3-(3-sulfanylpropanoyl)-6-oxohexahy- dropyrimidine-4-carboxylic a...Proceeding from natural amino acid L-asparagine and commercially available aldehydes a stereoselective synthesis was developed of (2S,4S)-2-alkyl(aryl)-3-(3-sulfanylpropanoyl)-6-oxohexahy- dropyrimidine-4-carboxylic acids, potential antihypertensive drugs, inhibitors of the angiotensin converting enzyme.展开更多
A series of esters of R-tetrahydrothiazo-2-thione-4-carboxylic acid [ R-TTCA ] was synthesized by direct esterifica- tion of R-TTCA with alcohols(CH3OH, C2H5OH, n-C3HTOH, i-C3HTOH, n-C4H9OH, sec-C4H9OH) in the prese...A series of esters of R-tetrahydrothiazo-2-thione-4-carboxylic acid [ R-TTCA ] was synthesized by direct esterifica- tion of R-TTCA with alcohols(CH3OH, C2H5OH, n-C3HTOH, i-C3HTOH, n-C4H9OH, sec-C4H9OH) in the presence of TiCl4 as the catalyst at room temperature without using any other solvent or dehydrant in high yields, 91.6%-99.1% for primary alcohols and 55%- 80% for secondary alcohols. The catalyst has a strong chemoselec-tive activity for the esterification of primary alcohols with R-TTCA in the presence of secondary alcohols. Owing to high yield, high chemoselectivity, and mild conditions used, this is an efficient method for the esterification of prima-ry alcohols with R-TTCA.展开更多
A 3D coordination polymer [Zn2(hqc)2(H2O)]n has been obtained from the reaction of 4-hydroxyquinoline-2-carboxylic acid (H2hqc) with zinc(II) salt under hydrothermal condition, and characterized by elemental a...A 3D coordination polymer [Zn2(hqc)2(H2O)]n has been obtained from the reaction of 4-hydroxyquinoline-2-carboxylic acid (H2hqc) with zinc(II) salt under hydrothermal condition, and characterized by elemental analysis, IR, TGA, PXRD and X-ray single-crystal diffraction. The complex crystallizes in the monoclinic system, space group P21/c with a = 14.305(2), b = 9.132(2), c = 15.356(2), β = 103.586(7)o, V = 1949.9(4)3, Z = 4, Dc = 1.782 g/cm3, μ = 2.508 mm-1, Mr = 523.06, F(000) = 1048, T = 293(2) K, λ(MoKα) = 0.71073, S = 1.008, the final R = 0.0329 and wR = 0.0745 for 3849 observed reflections (I 〉 2σ(I)). The title complex features a 3D framework via Zn(2) linking the 1D {Zn1(hqc)2}n chains. Thermogravimetric analysis shows that its framework is highly thermally stable up to 556 ℃ in the solid state.展开更多
A new 3D Ag(I) coordination polymer, [Ag8(btc)2(bpp)2]n(1, H4btc = biphenyl- 2,2ˊ,4,4ˊ-tetracarboxylic acid, bpp = 1,2-bis(4-pyridyl)propane), has been hydrothermally synthesi- zed and characterized by sin...A new 3D Ag(I) coordination polymer, [Ag8(btc)2(bpp)2]n(1, H4btc = biphenyl- 2,2ˊ,4,4ˊ-tetracarboxylic acid, bpp = 1,2-bis(4-pyridyl)propane), has been hydrothermally synthesi- zed and characterized by single-crystal X-ray diffraction analysis, elemental analysis and IR spectroscopy. Complex 1 crystallizes in the triclinic system, space group P1 with a = 13.4899(8), b = 13.4928(8), c = 16.4575(10) , α = 102.7640(10), β = 108.8100(10), γ = 101.4940(10)°, V = 2644.1(3) 3, Z = 2, Dc = 2.401 Mg·m-3, μ = 2.978 mm-1, F(000) = 1840, the final R = 0.0481 and wR = 0.0955 for 6794 observed reflections with I 〉 2σ(I). Complex 1 features a 3D framework formed by Ag(I)-carboxylate chains containing [Ag16(COO)16] secondary building block. Furthermore, thermal stability and electrochemical property of 1 are also investigated in detail.展开更多
Based on the structure of natural product 2-aryl-4,5-dihydrothiazole-4-carboxylic acid, a series of novel (R)-2-aryl-4,5-dihydrothiazole-4-carboxylic acid derivatives were designed and synthesized. Their structures ...Based on the structure of natural product 2-aryl-4,5-dihydrothiazole-4-carboxylic acid, a series of novel (R)-2-aryl-4,5-dihydrothiazole-4-carboxylic acid derivatives were designed and synthesized. Their structures were characterized by ^1H NMR, ^13C NMR and HRMS. The single crystal structure of compound 9b was determined by X-ray diffraction analysis. The antifungal activities were evaluated for the first time. The bioassay results indicated that most compounds exhibited moderate to good antifungal activities. The antifungal activities of compound 13a (against Cercospora arachidicola Hori), 13d (against Alternaria solani), and 16e (against Cercospora arachidieola Hori) were 61.9%, 67.3% and 61.9%, respectively, which are higher than those of the commercial fungicides chlorothalonil and carbendazim. Moreover, compound 13d exhibited excellent antifungal activities against 7 kinds of the fungi tested (66.7%, 77.3%, 63.0%, 87.9%, 70.0%, 70.0% and 80.0% at 50 μg/mL). Therefore, 13d can be used as a new lead structure for the development of antifungal agents.展开更多
L-Thiazolidine-4-carboxylic acid monolayer was prepared on gold electrodes through the self-assembly approach.Such novel thioether-based monolayer could efficiently preconcentrate Cu2+,which provided a simple,stable a...L-Thiazolidine-4-carboxylic acid monolayer was prepared on gold electrodes through the self-assembly approach.Such novel thioether-based monolayer could efficiently preconcentrate Cu2+,which provided a simple,stable and reproducible method for the determination of Cu2+.The modified electrodes were stable enough to be continuously used for one week(more than 30 times regeneration) with lower than 10% decrease in the response.They retained their initial activity for more than one month if used once a day.The calibration curve was linear for Cu2+ from 0.6 to 158.8 μg L?1 with a detection limit of 0.38 μg L?1.The relative standard deviation was 3.2% for a series of six successive measurements.The proposed method was applied in the determination of Cu2+ in mineral water and human hair samples.展开更多
In order to understand the chemical-biological interactions governing their activities toward neuraminidase(NA),QSAR models of 28 thiazolidine-4-carboxylic acid derivatives with inhibitory influenza A virus were devel...In order to understand the chemical-biological interactions governing their activities toward neuraminidase(NA),QSAR models of 28 thiazolidine-4-carboxylic acid derivatives with inhibitory influenza A virus were developed.Here a quantitative structure activity relationship(QSAR)model was built by three-dimensional holographic atomic vector field(3D-HoVAIF)and multiple linear regression(MLR).The estimation stability and prediction ability of the model were strictly analyzed by both internal and external validations.The correlation coefficient(R2)of established MLR model was 0.984,and the cross-validated correlation coefficient(Q2)of MLR model was 0.947.Furthermore,the cross-validated correlation coefficient for the test set(Qext 2)was 0.967.The binding mode pattern of the compounds to the binding site of integrase enzyme was confirmed by docking studies.The results of present study indicated that this model can aid in designing more potent neuraminidase inhibitors.展开更多
Racemic R.S-α-arylethylamine was resolved by R (-) thiazolidine-2-thione-4-carboxylic acid, a new resolving agent abbreviated as [R (-) TTCA], by which R (-) TTCA.S(-) arylethylamine salts2a-2e, [α] D 20 =-47.24...Racemic R.S-α-arylethylamine was resolved by R (-) thiazolidine-2-thione-4-carboxylic acid, a new resolving agent abbreviated as [R (-) TTCA], by which R (-) TTCA.S(-) arylethylamine salts2a-2e, [α] D 20 =-47.24° — 64.40° and optically active R(+)-a-arylethylamines3a – 3e, 74. 54%-94. 45% e, e., were obtained. Optically active S (-) -α-arylethylamines4a-4e, 72.84%-90.36% e.e., were obtained by the decomposition of2a-2e in basic solutions. The influence of substitutive group of the benzene ring on the basicity of the amino group was studied by semiempirical PM3 method. The structures of the R (-) TTCA.S (-) -α-phenylethylamine salt (2a(R-S) configuration) and R (-) TTCA-R(+)-a-phenylethylamine salt (2a(R-R) configuration) have been established by means of X-ray diffraction. They crystallize in a monoclinic system. Space group isP21. The cell constants of2a(R-S) configuration were obtained as follows: α = 1.387 8(2), b = 0.664 05(101,c = 1.580 O(2) nm; β = 90.844(10)° Z = 4; those obtained for2a(R-R) configuration were α = 1.080 6(2),b = 0.584 80(12),c = 1.2188(2) nm, β= 110.38(3)dg, V = 0.7220nm3,Z = 2. There are intermolecular hydrogen bonds in the crystals of the two kinds of configurations of the amine salt. The hydrogen bond number in the unit cell of R (-) TTCA.S (-)-α-phenylethylamine salt is twice as much as that of R (-) TTCA.R(+)-a-phenylethylamine salt.展开更多
By choosing neuroimmunophilin FKBP12 as a therapeutical target, we have attempted to discover a new structural drug for treating neurodegenerative disease. This drug should possess neurotrophic activity and not affect...By choosing neuroimmunophilin FKBP12 as a therapeutical target, we have attempted to discover a new structural drug for treating neurodegenerative disease. This drug should possess neurotrophic activity and not affect the immune system. Based on the crystal structure of FKBP12, FK506 and Calcineurin complex, a series of small organic molecules were designed. These molecules were to have the ability of binding to FKBP12 in a virtual screening. By using a solution parallel synthetic method, these compounds were synthesized. The neuroprotective and neuroregenerative activities of these compounds were evaluated by binding assays, PC12 cells survival and neurite outgrowth model, chick dorsal root ganglion cultures (DRG) and 6-OHDA lesioned mice sympathetic nerve endings model. The evaluation results of these compounds showed that compound N308 has great promise as a candidate for a neuroprotective and neuroregenerative agent.展开更多
Hydrothermal reactions of three aromatic polycarboxylic acids and the transitional metal cations in the presence of phen and 1,4-bib afford three new coordination polymers: [Cd2(bpp)1.5(Hbpp)(phen)2]n (1), [...Hydrothermal reactions of three aromatic polycarboxylic acids and the transitional metal cations in the presence of phen and 1,4-bib afford three new coordination polymers: [Cd2(bpp)1.5(Hbpp)(phen)2]n (1), [Mn3(Htptc)2(phen)2(H2O)2]n (2), and {[Cu(btc)0.5(1,4- bib)]·2H2O}n(3) (H2bpp = 2,6-bis(4'-carboxyphenyl)-4-phenylpyridine, H4tptc = terphenyl-2,5,2',5'-tetracar- boxylic acid, H4btc =biphenyl-2,2',4,4'-tetracarboxylic acid, phen =1,10-phenanthroline, and 1,4-bib = 1,4-bis(1H-imidazol-1-yl)benzene). Their structures have been determined by single- crystal X-ray diffraction analyses, elemental analyses, IR spectra, and powder X-ray diffraction (PXRD) analyses. In compound 1, the CdII cations are linked by bpp2- to form one ladder structure, based on which a 3D network is constructed with the help of non-covalent interactions. The topology of 2 is a 3D (3,4,5)-connected framework with the Point Schl?fli symbol of (42.6)2(43.62.8)(45.64.8)2. Compound 3 shows an unprecedented 3D (4,4)-connected framework with the Point Schl?fli symbol of (64.82)2(65.8). Moreover, the luminescent property of 1 has been investigated.展开更多
A concise and efficient method for the synthesis of novel 9,10-imethoxybenzo[6,7]oxepino[3,4-b]quinolin13(6H)-one and its derivatives 7a-p has been developed via the intramolecular Friedel-Crafts acylation reactions o...A concise and efficient method for the synthesis of novel 9,10-imethoxybenzo[6,7]oxepino[3,4-b]quinolin13(6H)-one and its derivatives 7a-p has been developed via the intramolecular Friedel-Crafts acylation reactions of 6,7-dimethoxy-2-(phenoxymethyl)quinoline-3-carboxylic acids 6a-p with polyphosphoric acid (PPA) as catalyst and solvent under mild conditions. The key intermediates 6a-p were prepared through the in situ formation of ethyl 6,7-dimethoxy-2-(phenoxymethyl)quinoline-3-carboxylates 5a-p followed by hydrolysis with aqueous ethanolic sodium hydroxide solution. The novel synthetic method has the advantages of good yields, easy work-up, and environmentally friendly character, which may provide a novel highly efficient process for making quinoline and related azaheterocycle libraries.展开更多
Two new indole alkaloids, named ibogamine-18-carboxylic acid, 3, 4-didehydro-7, 8-dioxo-methyl ester 1, ibogamine-18-carboxylic acid, 16, 17-didehydro-9, 17-dihydro-9-hydroxy (2-oxopropyl)-methyl ester 2, were isola...Two new indole alkaloids, named ibogamine-18-carboxylic acid, 3, 4-didehydro-7, 8-dioxo-methyl ester 1, ibogamine-18-carboxylic acid, 16, 17-didehydro-9, 17-dihydro-9-hydroxy (2-oxopropyl)-methyl ester 2, were isolated from Ervatamia hainanensis. Their structures were elucidated on the basis of spectroscopic methods.展开更多
One novel copper(II)-organic compound,namely Cu[Cu2(PP)2](CBPC)2]·2(H2O)(1,H2CBPC = 1-[(2'-carboxybiphenyl-4-yl)methyl]-2-propylimidazole-4-carboxylic acid,HPP = 3-(2-pyridyl)pyrazole),was designed...One novel copper(II)-organic compound,namely Cu[Cu2(PP)2](CBPC)2]·2(H2O)(1,H2CBPC = 1-[(2'-carboxybiphenyl-4-yl)methyl]-2-propylimidazole-4-carboxylic acid,HPP = 3-(2-pyridyl)pyrazole),was designed and synthesized under hydrothermal conditions.X-ray diffraction analysis reveals that two Cu(II)ions in the quasi-planar dimmer of [Cu2(PP)2] are linked by the carboxylate oxygen atoms on the phenyl ring and the imidazole ring,respectively,yielding one snake-shaped structure.Magnetic measurements reveal that compound 1 shows the strongly antiferromagnetic property.Crystal data of 1:C58H52Cu3N10O10,Mr = 1239.72,monoclinic,P21/c,a = 14.900(7),b = 15.029(7),c = 12.308(6),β = 102.519(9)o,V = 2691(2)3,Z = 2,Dc = 1.530 g/cm3,F(000)= 1274,μ = 1.246 mm-1,R = 0.0416,wR = 0.0780(I 2σ(I))and S = 0.999.展开更多
One novel 1-D copper(Ⅱ)-organic compound,namely {[Cu2(PP)2(CBPC)]2·7H2O}n(1,H2CBPC=1-[(2'-carboxybiphenyl-4-yl)methyl]-2-propylimidazole-4-carboxylic acid,HPP=3-(2-pyridyl)pyrazole),was synthesized ...One novel 1-D copper(Ⅱ)-organic compound,namely {[Cu2(PP)2(CBPC)]2·7H2O}n(1,H2CBPC=1-[(2'-carboxybiphenyl-4-yl)methyl]-2-propylimidazole-4-carboxylic acid,HPP=3-(2-pyridyl)pyrazole),was synthesized under hydrothermal conditions.X-ray diffraction analyses reveal that the two Cu(Ⅱ) ions in the distorted dimer [Cu2(PP)2] of 1 are linked by the carboxylate oxygen atoms on the phenyl and imidazole rings,respectively,forming one interesting snake-like chain.Single-crystal X-ray analyses reveal that it crystallizes in monoclinic,space group C2/c with a=30.656(8),b=12.715(3),c=22.405(5),β=122.758(3)°,V=7344(3)3,Z=4,Mr=1681.65,Dc=1.521 g/cm3,F(000)=3464,μ=1.221 mm-1,the final R=0.0453 and wR=0.1023 for 4617 observed reflections with Ⅰ 〉2σ(Ⅰ).展开更多
Two new 2-substituted thiazolidine-4(R)-carboxylic acids (TCAs), 2-glusosaminal-TCA (GIcNH2Cys) and 2-N-acetyl-glueosanlinal-TCA (GlcNAeCys), were synthesized. Their protective effects against liver toxicity i...Two new 2-substituted thiazolidine-4(R)-carboxylic acids (TCAs), 2-glusosaminal-TCA (GIcNH2Cys) and 2-N-acetyl-glueosanlinal-TCA (GlcNAeCys), were synthesized. Their protective effects against liver toxicity induced by acetaminophen (APAP) were investigated in a mice model. The resuits demonstrate that administration of TCAs ( i. p. , 800 mg/kg) 30 min after APAP challenge efficiently decrease ALF, AST, and LDH levels in liver. GlcNAcCys shows the best proteetive eftects, decreasing ALT, AST and LDH levels to 63%, 18.4% and 37% of the APAP group respectively. Comparison with the control showed that APAP greatly decreases total sulfhydlyl (T-SH) levels (43%), non-protein hound sulfhydryl (NP-SH) levels (50%) and total antioxidative capabilities (57%) in the liver 24 hr after challenge. TCAs treatments 30min after APAP challenge significantly elevate sulfhydryl levels and total antioxidative capabilities. APAP administration also markedly (P 〈 0.05) increases liver lipid peroxidation to 1.65 and 1.17 times that of the control 4 hr and 24 hr after APAP administration respectively. TCAs treatments can inhibit lipid peroxidation as measured by decreased malondialdehyde (MDA) contents in liver. The histopathological results also further confirm the hepatoprotective effects of TCAs. In conclusion, our data show that TCAs, GleNAcCys particularly, have hepatoprotective anti antioxidant etfects.展开更多
N-acetyl-glucosamine, the monomer of chitin, was cyclo-condensed with L-cysteine to prepare thiazolidine derivative: 2-N-acetyl-glucosamine-thiazolidine-4(R)-carboxylic acid (GlcNAcCys). The stability of GlcNAcCy...N-acetyl-glucosamine, the monomer of chitin, was cyclo-condensed with L-cysteine to prepare thiazolidine derivative: 2-N-acetyl-glucosamine-thiazolidine-4(R)-carboxylic acid (GlcNAcCys). The stability of GlcNAcCys was evaluated by high performance liquid chromatography (HPLC) measurement. The results showed that GlcNAcCys was more stable than other TCA derivatives, especially in alkaline condition. The direct in vitro antioxidative properties of GlcNAcCys were investigated by using UV radiation-induced lipid peroxidation (LPO) in mitochondria and nuclei and . OH-induced LPO in red blood cell (RBC) ghosts models. UV radiation caused dose-dependent LPO in both mitochondria and nuclei. This effect was catalyzed by addition of Fe^2 + while prevented by co-incubation with GlcNAcCys. When nuclei and mitochondria was treated with 100μl, 300μl, 500μl of GlcNAcCys and co-incubated at 37℃ for 30min, LPO was decreased to 96%, 72%, 68% in nuclei and 95%, 72%, 68% in mitochondria when compared to the UV radiation group respectively. Hydroxyl radicals (. OH) generated by Fenton reaction induced LPO in RBC ghosts. Pretreatment of RBC ghosts with GlcNAcCys could induce antioxidant RBC ghosts and inhibit concentration-dependent malondialdehyde (MDA) formation in antioxidant RBC ghosts. Its inhibition percent was 14%, 35%, 36%, 42% at 10, 20, 30, 40mg/ml respectively. In a conclusion, the data suggest that GlcNAcCys has antioxidant ability and can significantly inhibit lipid peroxidation in biological samples tested in vitro.展开更多
基金the National Basic Research Program(No.2003CB515400),administered by the Ministry of Science and Technology of China.
文摘A facile and efficient method for the preparation of 2-non-substituted quinoline-4-carboxylic acids is described via the Pfitzinger reaction of isatins with sodium pyruvate following consequent decarboxylation under microwave irradiation.
基金supported by the National Natural Science Foundation of China (No. 21202110)
文摘In order to understand the chemical-biological interactions governing their activities toward neuraminidase (NA), QSAR models of 28 thiazolidine-4-carboxylic acid derivatives with inhibitory influenza A virus were developed. The obtained HQSAR (hologram quantitative structure activity relationship), Topomer CoMFA and CoMSIA (comparative molecular similarity indices analysis) models were robust and had good exterior predictive capabilities. Moreover, QSAR modeling results elucidated that hydrogen bonds highly contributed to the inhibitory activity, then electrostatic and hydrophobic factors. Squared multiple correlation coefficients (R2) of HQSAR, Topomer CoMFA and CoMSIA models were 0.994, 0.978 and 0.996, respectively. Squared cross-validated correlation coefficients (Q2) of HQSAR, Topomer CoMFA and CoMSIA models were in turn 0.951, 919 and 0.820. Furthermore, squared multiple correlation coefficients for the test set (R2test) of HQSAR, CoMFA and CoMSIA models were 0.879, 0.912 and 0.953, respectively. Squared cross-validated correlation coefficients for the test set (Q2ext) of HQSAR, Topomer CoMFA and CoMSIA models were 0.867, 0.884 and 0.899, correspondingly.
基金Supported by NIH:NIAID/USAMRICD Interagency Agreements(W911NF-07-D-0001)the USAMRICD under the auspices of the US Army Research Office Scientific Services Program administered by Battelle(Delivery order 0557,Contract No TCN 08284)the Robert A.Welch Foundation at Sam Houston State University,Huntsville,TX,United States
文摘AIM: To demonstrate the potential of using 2-aminothiazoline-4-carboxylic acid(ATCA) as a novel biomarker/forensic biomarker for cyanide poisoning. METHODS: A sensitive method was developed and employed for the identification and quantification of ATCA in biological samples, where the sample extraction and clean up were achieved by solid phase extraction(SPE). After optimization of SPE procedures, ATCA was analyzed by high performance liquid chromatographytandem mass spectrometry. ATCA levels following the administration of different doses of potassium cyanide(KCN) to mice were measured and compared to endogenous ATCA levels in order to study the significance of using ATCA as a biomarker for cyanide poisoning.RESULTS: A custom made analytical method was established for a new(mice) model when animals were exposed to increasing KCN doses. The application of this method provided important new information on ATCA as a potential cyanide biomarker. ATCA concentration in mice plasma samples were increased from 189 ± 28 ng/mL(n = 3) to 413 ± 66 ng/mL(n = 3) following a 10 mg/kg body weight dose of KCN introduced subcutaneously. The sensitivity of this analytical method proved to be a tool for measuring endogenous level of ATCA in mice organs as follows: 1.2 ± 0.1 μg/g for kidney samples, 1.6 ± 0.1 μg/g for brain samples, 1.8 ± 0.2 μg/g for lung samples, 2.9 ± 0.1 μg/g for heart samples, and 3.6 ± 0.9 μg/g for liver samples. CONCLUSION: This finding suggests that ATCA has the potential to serve as a plasma biomarker / forensic biomarker for cyanide poisoning.
文摘Highly efficient syntheses of novel fluorine bearing quinoline-4-carboxylic acids and the related compounds had been achieved from cyclocondensation of 2-amino-5-fluorophenyl glyoxylic acid 1 with benzoyle asetanilides 2 in boiling DMF, to give the target 3. Decarboxylation of 3 produced 6-fluoro-2-phenyl-3-(substituted amino)-keto-quinolines 4, while that reaction underwent refluxing, afforded 7-fluoro-1-(aryl)-3-phenyl-pyrrolo[3,4-c] quinoline-2,9-diones 5. Structure of the products has been established from their elemental and spectral analysis. All targets exhibited a high to moderate activity against some Aspergillus fungi as amylolytic agents.
文摘Proceeding from natural amino acid L-asparagine and commercially available aldehydes a stereoselective synthesis was developed of (2S,4S)-2-alkyl(aryl)-3-(3-sulfanylpropanoyl)-6-oxohexahy- dropyrimidine-4-carboxylic acids, potential antihypertensive drugs, inhibitors of the angiotensin converting enzyme.
文摘A series of esters of R-tetrahydrothiazo-2-thione-4-carboxylic acid [ R-TTCA ] was synthesized by direct esterifica- tion of R-TTCA with alcohols(CH3OH, C2H5OH, n-C3HTOH, i-C3HTOH, n-C4H9OH, sec-C4H9OH) in the presence of TiCl4 as the catalyst at room temperature without using any other solvent or dehydrant in high yields, 91.6%-99.1% for primary alcohols and 55%- 80% for secondary alcohols. The catalyst has a strong chemoselec-tive activity for the esterification of primary alcohols with R-TTCA in the presence of secondary alcohols. Owing to high yield, high chemoselectivity, and mild conditions used, this is an efficient method for the esterification of prima-ry alcohols with R-TTCA.
基金supported by 973 (2011CB932504)NNSFC (20971121)NSF of Fujian Province
文摘A 3D coordination polymer [Zn2(hqc)2(H2O)]n has been obtained from the reaction of 4-hydroxyquinoline-2-carboxylic acid (H2hqc) with zinc(II) salt under hydrothermal condition, and characterized by elemental analysis, IR, TGA, PXRD and X-ray single-crystal diffraction. The complex crystallizes in the monoclinic system, space group P21/c with a = 14.305(2), b = 9.132(2), c = 15.356(2), β = 103.586(7)o, V = 1949.9(4)3, Z = 4, Dc = 1.782 g/cm3, μ = 2.508 mm-1, Mr = 523.06, F(000) = 1048, T = 293(2) K, λ(MoKα) = 0.71073, S = 1.008, the final R = 0.0329 and wR = 0.0745 for 3849 observed reflections (I 〉 2σ(I)). The title complex features a 3D framework via Zn(2) linking the 1D {Zn1(hqc)2}n chains. Thermogravimetric analysis shows that its framework is highly thermally stable up to 556 ℃ in the solid state.
基金supported by the National Natural Science Foundation of China(No.21373178)the Natural Scientific Research Foundation of Shaanxi Provincial Education Office of China(No.13JS124)
文摘A new 3D Ag(I) coordination polymer, [Ag8(btc)2(bpp)2]n(1, H4btc = biphenyl- 2,2ˊ,4,4ˊ-tetracarboxylic acid, bpp = 1,2-bis(4-pyridyl)propane), has been hydrothermally synthesi- zed and characterized by single-crystal X-ray diffraction analysis, elemental analysis and IR spectroscopy. Complex 1 crystallizes in the triclinic system, space group P1 with a = 13.4899(8), b = 13.4928(8), c = 16.4575(10) , α = 102.7640(10), β = 108.8100(10), γ = 101.4940(10)°, V = 2644.1(3) 3, Z = 2, Dc = 2.401 Mg·m-3, μ = 2.978 mm-1, F(000) = 1840, the final R = 0.0481 and wR = 0.0955 for 6794 observed reflections with I 〉 2σ(I). Complex 1 features a 3D framework formed by Ag(I)-carboxylate chains containing [Ag16(COO)16] secondary building block. Furthermore, thermal stability and electrochemical property of 1 are also investigated in detail.
基金We gratefully acknowledge the financial support of this work by the "111" Project of Ministry of Education of China (No. B06005) and the Natural Science Foundation of China (No. 31370039).
文摘Based on the structure of natural product 2-aryl-4,5-dihydrothiazole-4-carboxylic acid, a series of novel (R)-2-aryl-4,5-dihydrothiazole-4-carboxylic acid derivatives were designed and synthesized. Their structures were characterized by ^1H NMR, ^13C NMR and HRMS. The single crystal structure of compound 9b was determined by X-ray diffraction analysis. The antifungal activities were evaluated for the first time. The bioassay results indicated that most compounds exhibited moderate to good antifungal activities. The antifungal activities of compound 13a (against Cercospora arachidicola Hori), 13d (against Alternaria solani), and 16e (against Cercospora arachidieola Hori) were 61.9%, 67.3% and 61.9%, respectively, which are higher than those of the commercial fungicides chlorothalonil and carbendazim. Moreover, compound 13d exhibited excellent antifungal activities against 7 kinds of the fungi tested (66.7%, 77.3%, 63.0%, 87.9%, 70.0%, 70.0% and 80.0% at 50 μg/mL). Therefore, 13d can be used as a new lead structure for the development of antifungal agents.
基金support from the National Natural Science Foundation of China (Grant Nos. 20732003 & 20972128)
文摘L-Thiazolidine-4-carboxylic acid monolayer was prepared on gold electrodes through the self-assembly approach.Such novel thioether-based monolayer could efficiently preconcentrate Cu2+,which provided a simple,stable and reproducible method for the determination of Cu2+.The modified electrodes were stable enough to be continuously used for one week(more than 30 times regeneration) with lower than 10% decrease in the response.They retained their initial activity for more than one month if used once a day.The calibration curve was linear for Cu2+ from 0.6 to 158.8 μg L?1 with a detection limit of 0.38 μg L?1.The relative standard deviation was 3.2% for a series of six successive measurements.The proposed method was applied in the determination of Cu2+ in mineral water and human hair samples.
基金supported by the National Natural Science Funds of China(21475081)the Natural Science Foundation of Shaanxi Province(2019JM-237)the Graduate Innovation Fund of Shaanxi University of Science and Technology。
文摘In order to understand the chemical-biological interactions governing their activities toward neuraminidase(NA),QSAR models of 28 thiazolidine-4-carboxylic acid derivatives with inhibitory influenza A virus were developed.Here a quantitative structure activity relationship(QSAR)model was built by three-dimensional holographic atomic vector field(3D-HoVAIF)and multiple linear regression(MLR).The estimation stability and prediction ability of the model were strictly analyzed by both internal and external validations.The correlation coefficient(R2)of established MLR model was 0.984,and the cross-validated correlation coefficient(Q2)of MLR model was 0.947.Furthermore,the cross-validated correlation coefficient for the test set(Qext 2)was 0.967.The binding mode pattern of the compounds to the binding site of integrase enzyme was confirmed by docking studies.The results of present study indicated that this model can aid in designing more potent neuraminidase inhibitors.
文摘Racemic R.S-α-arylethylamine was resolved by R (-) thiazolidine-2-thione-4-carboxylic acid, a new resolving agent abbreviated as [R (-) TTCA], by which R (-) TTCA.S(-) arylethylamine salts2a-2e, [α] D 20 =-47.24° — 64.40° and optically active R(+)-a-arylethylamines3a – 3e, 74. 54%-94. 45% e, e., were obtained. Optically active S (-) -α-arylethylamines4a-4e, 72.84%-90.36% e.e., were obtained by the decomposition of2a-2e in basic solutions. The influence of substitutive group of the benzene ring on the basicity of the amino group was studied by semiempirical PM3 method. The structures of the R (-) TTCA.S (-) -α-phenylethylamine salt (2a(R-S) configuration) and R (-) TTCA-R(+)-a-phenylethylamine salt (2a(R-R) configuration) have been established by means of X-ray diffraction. They crystallize in a monoclinic system. Space group isP21. The cell constants of2a(R-S) configuration were obtained as follows: α = 1.387 8(2), b = 0.664 05(101,c = 1.580 O(2) nm; β = 90.844(10)° Z = 4; those obtained for2a(R-R) configuration were α = 1.080 6(2),b = 0.584 80(12),c = 1.2188(2) nm, β= 110.38(3)dg, V = 0.7220nm3,Z = 2. There are intermolecular hydrogen bonds in the crystals of the two kinds of configurations of the amine salt. The hydrogen bond number in the unit cell of R (-) TTCA.S (-)-α-phenylethylamine salt is twice as much as that of R (-) TTCA.R(+)-a-phenylethylamine salt.
基金Supported by the National Basic Research Program of China (Grant No. G1998051107)Hi-tech Research and Development Program of China (Grant No. 2002AA233051)
文摘By choosing neuroimmunophilin FKBP12 as a therapeutical target, we have attempted to discover a new structural drug for treating neurodegenerative disease. This drug should possess neurotrophic activity and not affect the immune system. Based on the crystal structure of FKBP12, FK506 and Calcineurin complex, a series of small organic molecules were designed. These molecules were to have the ability of binding to FKBP12 in a virtual screening. By using a solution parallel synthetic method, these compounds were synthesized. The neuroprotective and neuroregenerative activities of these compounds were evaluated by binding assays, PC12 cells survival and neurite outgrowth model, chick dorsal root ganglion cultures (DRG) and 6-OHDA lesioned mice sympathetic nerve endings model. The evaluation results of these compounds showed that compound N308 has great promise as a candidate for a neuroprotective and neuroregenerative agent.
基金supported by the National Natural Science Foundation of China(20873150)the Natural Science Foundation of Shandong Province(ZR2010BL012,ZR2010BQ023)
文摘Hydrothermal reactions of three aromatic polycarboxylic acids and the transitional metal cations in the presence of phen and 1,4-bib afford three new coordination polymers: [Cd2(bpp)1.5(Hbpp)(phen)2]n (1), [Mn3(Htptc)2(phen)2(H2O)2]n (2), and {[Cu(btc)0.5(1,4- bib)]·2H2O}n(3) (H2bpp = 2,6-bis(4'-carboxyphenyl)-4-phenylpyridine, H4tptc = terphenyl-2,5,2',5'-tetracar- boxylic acid, H4btc =biphenyl-2,2',4,4'-tetracarboxylic acid, phen =1,10-phenanthroline, and 1,4-bib = 1,4-bis(1H-imidazol-1-yl)benzene). Their structures have been determined by single- crystal X-ray diffraction analyses, elemental analyses, IR spectra, and powder X-ray diffraction (PXRD) analyses. In compound 1, the CdII cations are linked by bpp2- to form one ladder structure, based on which a 3D network is constructed with the help of non-covalent interactions. The topology of 2 is a 3D (3,4,5)-connected framework with the Point Schl?fli symbol of (42.6)2(43.62.8)(45.64.8)2. Compound 3 shows an unprecedented 3D (4,4)-connected framework with the Point Schl?fli symbol of (64.82)2(65.8). Moreover, the luminescent property of 1 has been investigated.
文摘A concise and efficient method for the synthesis of novel 9,10-imethoxybenzo[6,7]oxepino[3,4-b]quinolin13(6H)-one and its derivatives 7a-p has been developed via the intramolecular Friedel-Crafts acylation reactions of 6,7-dimethoxy-2-(phenoxymethyl)quinoline-3-carboxylic acids 6a-p with polyphosphoric acid (PPA) as catalyst and solvent under mild conditions. The key intermediates 6a-p were prepared through the in situ formation of ethyl 6,7-dimethoxy-2-(phenoxymethyl)quinoline-3-carboxylates 5a-p followed by hydrolysis with aqueous ethanolic sodium hydroxide solution. The novel synthetic method has the advantages of good yields, easy work-up, and environmentally friendly character, which may provide a novel highly efficient process for making quinoline and related azaheterocycle libraries.
文摘Two new indole alkaloids, named ibogamine-18-carboxylic acid, 3, 4-didehydro-7, 8-dioxo-methyl ester 1, ibogamine-18-carboxylic acid, 16, 17-didehydro-9, 17-dihydro-9-hydroxy (2-oxopropyl)-methyl ester 2, were isolated from Ervatamia hainanensis. Their structures were elucidated on the basis of spectroscopic methods.
基金supported by Financial support from the Natural Science Foundation of Shandong (BR2010BQ023) and Qilu Normal University
文摘One novel copper(II)-organic compound,namely Cu[Cu2(PP)2](CBPC)2]·2(H2O)(1,H2CBPC = 1-[(2'-carboxybiphenyl-4-yl)methyl]-2-propylimidazole-4-carboxylic acid,HPP = 3-(2-pyridyl)pyrazole),was designed and synthesized under hydrothermal conditions.X-ray diffraction analysis reveals that two Cu(II)ions in the quasi-planar dimmer of [Cu2(PP)2] are linked by the carboxylate oxygen atoms on the phenyl ring and the imidazole ring,respectively,yielding one snake-shaped structure.Magnetic measurements reveal that compound 1 shows the strongly antiferromagnetic property.Crystal data of 1:C58H52Cu3N10O10,Mr = 1239.72,monoclinic,P21/c,a = 14.900(7),b = 15.029(7),c = 12.308(6),β = 102.519(9)o,V = 2691(2)3,Z = 2,Dc = 1.530 g/cm3,F(000)= 1274,μ = 1.246 mm-1,R = 0.0416,wR = 0.0780(I 2σ(I))and S = 0.999.
基金supported by the Chinese Academy of Sciences (KJCX2-YW-M05,KJCX2-YW-319)the Natural Science Foundation of Fujian Province (2007HZ0001-1,2009HZ0004-1)
文摘One novel 1-D copper(Ⅱ)-organic compound,namely {[Cu2(PP)2(CBPC)]2·7H2O}n(1,H2CBPC=1-[(2'-carboxybiphenyl-4-yl)methyl]-2-propylimidazole-4-carboxylic acid,HPP=3-(2-pyridyl)pyrazole),was synthesized under hydrothermal conditions.X-ray diffraction analyses reveal that the two Cu(Ⅱ) ions in the distorted dimer [Cu2(PP)2] of 1 are linked by the carboxylate oxygen atoms on the phenyl and imidazole rings,respectively,forming one interesting snake-like chain.Single-crystal X-ray analyses reveal that it crystallizes in monoclinic,space group C2/c with a=30.656(8),b=12.715(3),c=22.405(5),β=122.758(3)°,V=7344(3)3,Z=4,Mr=1681.65,Dc=1.521 g/cm3,F(000)=3464,μ=1.221 mm-1,the final R=0.0453 and wR=0.1023 for 4617 observed reflections with Ⅰ 〉2σ(Ⅰ).
文摘Two new 2-substituted thiazolidine-4(R)-carboxylic acids (TCAs), 2-glusosaminal-TCA (GIcNH2Cys) and 2-N-acetyl-glueosanlinal-TCA (GlcNAeCys), were synthesized. Their protective effects against liver toxicity induced by acetaminophen (APAP) were investigated in a mice model. The resuits demonstrate that administration of TCAs ( i. p. , 800 mg/kg) 30 min after APAP challenge efficiently decrease ALF, AST, and LDH levels in liver. GlcNAcCys shows the best proteetive eftects, decreasing ALT, AST and LDH levels to 63%, 18.4% and 37% of the APAP group respectively. Comparison with the control showed that APAP greatly decreases total sulfhydlyl (T-SH) levels (43%), non-protein hound sulfhydryl (NP-SH) levels (50%) and total antioxidative capabilities (57%) in the liver 24 hr after challenge. TCAs treatments 30min after APAP challenge significantly elevate sulfhydryl levels and total antioxidative capabilities. APAP administration also markedly (P 〈 0.05) increases liver lipid peroxidation to 1.65 and 1.17 times that of the control 4 hr and 24 hr after APAP administration respectively. TCAs treatments can inhibit lipid peroxidation as measured by decreased malondialdehyde (MDA) contents in liver. The histopathological results also further confirm the hepatoprotective effects of TCAs. In conclusion, our data show that TCAs, GleNAcCys particularly, have hepatoprotective anti antioxidant etfects.
文摘N-acetyl-glucosamine, the monomer of chitin, was cyclo-condensed with L-cysteine to prepare thiazolidine derivative: 2-N-acetyl-glucosamine-thiazolidine-4(R)-carboxylic acid (GlcNAcCys). The stability of GlcNAcCys was evaluated by high performance liquid chromatography (HPLC) measurement. The results showed that GlcNAcCys was more stable than other TCA derivatives, especially in alkaline condition. The direct in vitro antioxidative properties of GlcNAcCys were investigated by using UV radiation-induced lipid peroxidation (LPO) in mitochondria and nuclei and . OH-induced LPO in red blood cell (RBC) ghosts models. UV radiation caused dose-dependent LPO in both mitochondria and nuclei. This effect was catalyzed by addition of Fe^2 + while prevented by co-incubation with GlcNAcCys. When nuclei and mitochondria was treated with 100μl, 300μl, 500μl of GlcNAcCys and co-incubated at 37℃ for 30min, LPO was decreased to 96%, 72%, 68% in nuclei and 95%, 72%, 68% in mitochondria when compared to the UV radiation group respectively. Hydroxyl radicals (. OH) generated by Fenton reaction induced LPO in RBC ghosts. Pretreatment of RBC ghosts with GlcNAcCys could induce antioxidant RBC ghosts and inhibit concentration-dependent malondialdehyde (MDA) formation in antioxidant RBC ghosts. Its inhibition percent was 14%, 35%, 36%, 42% at 10, 20, 30, 40mg/ml respectively. In a conclusion, the data suggest that GlcNAcCys has antioxidant ability and can significantly inhibit lipid peroxidation in biological samples tested in vitro.