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Sample records for labeled glucopyranosyl triazole

  1. C-Glucopyranosyl-1,2,4-triazol-5-ones: synthesis and inhibition of glycogen phosphorylase.

    PubMed

    Bokor, Éva; Széles, Zsolt; Docsa, Tibor; Gergely, Pál; Somsák, László

    2016-06-24

    Various C-glucopyranosyl-1,2,4-triazolones were designed as potential inhibitors of glycogen phosphorylase. Syntheses of these compounds were performed with O-perbenzoylated glucose derivatives as precursors. High temperature ring closure of N(1)-carbamoyl-C-β-D-glucopyranosyl formamidrazone gave 3-β-D-glucopyranosyl-1,2,4-triazol-5-one. Reaction of N(1)-tosyl-C-β-D-glucopyranosyl formamidrazone with ClCOOEt furnished 3-β-D-glucopyranosyl-1-tosyl-1,2,4-triazol-5-one. In situ prepared β-D-glucopyranosylcarbonyl isocyanate was transformed by PhNHNHBoc into 3-β-D-glucopyranosyl-1-phenyl-1,2,4-triazol-5-one, while the analogous 1-(2-naphthyl) derivative was obtained from the unsubstituted triazolone by naphthalene-2-boronic acid in a Cu(II) catalyzed N-arylation. Test compounds were prepared by Zemplén deacylation. The new glucose derivatives had weak or no inhibition of rabbit muscle glycogen phosphorylase b: the best inhibitor was 3-β-D-glucopyranosyl-1-(2-naphthyl)-1,2,4-triazol-5-one (Ki = 80 µM). PMID:26818133

  2. Synthesis and characterization of new 1,4 and 1,5-disubstituted glucopyranosyl 1,2,3-triazole by 1,3-dipolar cycloaddition

    NASA Astrophysics Data System (ADS)

    El Moncef, Abdelkarim; El Hadrami, El Mestafa; Ben-Tama, Abdeslem; de Arellano, Carmen Ramírez; Zaballos-Garcia, Elena; Stiriba, Salah-Eddine

    2009-07-01

    A series of 1,4 and 1,5-disubstituted 1-(β- D-glucopyranosyl)-1,2,3-triazoles has been prepared in an efficient manner with excellent yields using the intermolecular 1,3-dipolar cycloaddition of 1-azido-2,3,4,6-tetra- O-acetyl-β- D-glucopyranose 2 to a variety of substituted alkynes phenylacethylene 3, propargyl alcohol 4, 2-butyn-1,4-diol, 5, 3-propargylbenzimidazole 6 and propargylpyrazole 7 in toluene. The reaction takes place with the formation of both 4- and 5-regioisomers.

  3. Crystallographic and computational studies on 4-phenyl-N-(beta-D-glucopyranosyl)-1H-1,2,3-triazole-1-acetamide, an inhibitor of glycogen phosphorylase: comparison with alpha-D-glucose, N-acetyl-beta-D-glucopyranosylamine and N-benzoyl-N'-beta-D-glucopyranosyl urea binding.

    PubMed

    Alexacou, Kyra-Melinda; Hayes, Joseph M; Tiraidis, Costas; Zographos, Spyros E; Leonidas, Demetres D; Chrysina, Evangelia D; Archontis, Georgios; Oikonomakos, Nikos G; Paul, Jashuva V; Varghese, Babu; Loganathan, Duraikkannu

    2008-05-15

    4-Phenyl-N-(beta-D-glucopyranosyl)-1H-1,2,3-triazole-1-acetamide (glucosyltriazolylacetamide) has been studied in kinetic and crystallographic experiments with glycogen phosphorylase b (GPb), in an effort to utilize its potential as a lead for the design of potent antihyperglycaemic agents. Docking and molecular dynamics (MD) calculations have been used to monitor more closely the binding modes in operation and compare the results with experiment. Kinetic experiments in the direction of glycogen synthesis showed that glucosyltriazolylacetamide is a better inhibitor (K(i) = 0.18 mM) than the parent compound alpha-D-glucose (K(i) = 1.7 mM) or beta-D-glucose (K(i) = 7.4 mM) but less potent inhibitor than the lead compound N-acetyl-beta-D-glucopyranosylamine (K(i) = 32 microM). To elucidate the molecular basis underlying the inhibition of the newly identified compound, we determined the structure of GPb in complex with glucosyltriazolylacetamide at 100 K to 1.88 A resolution, and the structure of the compound in the free form. Glucosyltriazolylacetamide is accommodated in the catalytic site of the enzyme and the glucopyranose interacts in a manner similar to that observed in the GPb-alpha-D-glucose complex, while the substituent group in the beta-position of the C1 atom makes additional hydrogen bonding and van der Waals interactions to the protein. A bifurcated donor type hydrogen bonding involving O3H, N3, and N4 is seen as an important structural motif strengthening the binding of glucosyltriazolylacetamide with GP which necessitated change in the torsion about C8-N2 bond by about 62 degrees going from its free to the complex form with GPb. On binding to GP, glucosyltriazolylacetamide induces significant conformational changes in the vicinity of this site. Specifically, the 280s loop (residues 282-288) shifts 0.7 to 3.1 A (CA atoms) to accommodate glucosyltriazolylacetamide. These conformational changes do not lead to increased contacts between the inhibitor and the

  4. Photoluminescence and labelling for microcrack bone of N-salicylidene-3-amino-1,2,4-triazole.

    PubMed

    Li, Zhi-Xin; Ma, Chang-Yan; Chen, Wen-Bin; Ou-Yang, Zhi-Jian; Feng, Wei-Jin; Dong, Wen

    2015-02-01

    A new Schiff base of N-salicylidene-3-amino-1,2,4-triazole (SAT) was synthesized and its photoluminescent, photochromic and thermochromic properties were characterized and demonstrated. The fluorescence lifetime and quantum yield of SAT were measured and the microcrack bone imaging using SAT as a fluorescent label was observed by laser scanning confocal microscope (LSCM). The absorption spectrum of SAT was demonstrated using DFT/TD-DFT calculation. PMID:25468441

  5. Photoluminescence and labelling for microcrack bone of N-salicylidene-3-amino-1,2,4-triazole

    NASA Astrophysics Data System (ADS)

    Li, Zhi-Xin; Ma, Chang-Yan; Chen, Wen-Bin; Ou-Yang, Zhi-Jian; Feng, Wei-Jin; Dong, Wen

    2015-02-01

    A new Schiff base of N-salicylidene-3-amino-1,2,4-triazole (SAT) was synthesized and its photoluminescent, photochromic and thermochromic properties were characterized and demonstrated. The fluorescence lifetime and quantum yield of SAT were measured and the microcrack bone imaging using SAT as a fluorescent label was observed by laser scanning confocal microscope (LSCM). The absorption spectrum of SAT was demonstrated using DFT/TD-DFT calculation.

  6. Isolation, characterization and sensory evaluation of a Hexa beta-D-glucopyranosyl diterpene from Stevia rebaudiana.

    PubMed

    Prakash, Indra; Chaturvedula, Venkata Sai Prakash; Markosyan, Avetik

    2013-11-01

    From the extract of the leaves of Stevia rebaudiana Bertoni, a diterpene glycoside was isolated which was identified as 13-[(2-O-beta-D-glucopyranosyl-3-O-beta-D-glucopyranosyl-beta-D-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid-(2-O-beta-D-glucopyranosyl-3-O-beta-D-glucopyranosyl-D-glucopyranosyl) ester (1). The complete 1H and 13C NMR assignment of 1 is reported for the first time, from extensive NMR (1H and 13C, COSY, HSQC, and HMBC) and mass spectral data. Also, we report the sensory evaluation of 1 against sucrose for the sweetness property of this molecule. PMID:24427932

  7. N-Succinimidyl 3-((4-(4-[18F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate ([18F]SFBTMGMB): A Residualizing Label for 18F-labeling of internalizing biomolecules

    PubMed Central

    Vaidyanathan, Ganesan; McDougald, Darryl; Choi, Jaeyeon; Pruszynski, Marek; Koumarianou, Eftychia; Zhou, Zhengyuan; Zalutsky, Michael R.

    2015-01-01

    Residualizing labeling methods for internalizing peptides and proteins are designed to trap the radionuclide inside the cell after intracellular degradation of the biomolecule. The goal of this work was to develop a residualizing label for the 18F-labeling of internalizing biomolecules based on a template used successfully for radioiodination. N-succinimidyl 3-((4-(4-[18F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(bis-Boc-guanidinomethyl)benzoate (Boc2-[18F]SFBTMGMB) was synthesized by click reaction of an azide precursor and [18F]fluorohexyne in 8.5 ± 2.8% average decay-corrected radiochemical yield (n =15). An anti-HER2 nanobody 5F7 was labeled with 18F using [18F]SFBTMGMB ([18F]RL-I), obtained by the deprotection of Boc2-[18F]SFBTMGMB, in 31.2 ± 6.7% (n =5) conjugation efficiency. Thus labeled nanobody had a radiochemical purity of >95%, bound to the HER2-expressing BT474M1 breast cancer cells with an affinity of 4.7 ± 0.9 nM, and had an immunoreactive fraction of 62–80%. In summary, a novel residualizing prosthetic agent for labeling biomolecules with 18F has been developed. An anti-HER2 nanobody was labeled using this prosthetic group with retention of affinity and immunoreactivity to HER2. PMID:26645790

  8. Triazole antifungals: a review.

    PubMed

    Peyton, L R; Gallagher, S; Hashemzadeh, M

    2015-12-01

    Invasive fungal infections and systemic mycosis, whether from nosocomial infection or immunodeficiency, have been on an upward trend for numerous years. Despite advancements in antifungal medication, treatment in certain patients can still be difficult for reasons such as impaired organ function, limited administration routes or poor safety profiles of the available antifungal medications. The growing number of invasive fungal species becoming resistant to current antifungal medications is of appreciable concern. Triazole compounds containing one or more 1,2,4-triazole rings have been shown to contain some of the most potent antifungal properties. Itracon-azole and fluconazole were some of the first triazoles synthesized, but had limitations associated with their use. Second-generation triazoles such as voriconazole, posa-conazole, albaconazole, efinaconazole, ravuconazole and isavuconazole are all derivatives of either itraconazole or fluconazole, and designed to overcome the deficiencies of their parent drugs. The goal of this manuscript is to review antifungal agents derived from triazole. PMID:26798851

  9. Synthesis of a D-Glucopyranosyl Azide: Spectroscopic Evidence for Stereochemical Inversion in the S[subscript N]2 Reaction

    ERIC Educational Resources Information Center

    Adesoye, Olumuyiwa G.; Mills, Isaac N.; Temelkoff, David P.; Jackson, John A.; Norris, Peter

    2012-01-01

    Stereospecific S[subscript N]2 conversion of configurationally pure acetobromoglucose (2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide) to the corresponding beta-D-glucopyranosyl azide is a useful exercise in the advanced organic undergraduate teaching laboratory. The procedure is safe and suitable for small-scale implementation, and firm…

  10. Triazole: A Promising Antitubercular Agent.

    PubMed

    Keri, Rangappa S; Patil, Siddappa A; Budagumpi, Srinivasa; Nagaraja, Bhari Mallanna

    2015-10-01

    Tuberculosis is a contagious disease with comparatively high mortality worldwide. The statistics shows that around three million people throughout the world die annually from tuberculosis and there are around eight million new cases each year, of which developing countries showed major share. Therefore, the discovery and development of effective antituberculosis drugs with novel mechanism of action have become an insistent task for infectious diseases research programs. The literature reveals that, heterocyclic moieties have drawn attention of the chemists, pharmacologists, microbiologists, and other researchers owing to its indomitable biological potential as anti-infective agents. Among heterocyclic compounds, triazole (1,2,3-triazole/1,2,4-triazole) nucleus is one of the most important and well-known heterocycles, which is a common and integral feature of a variety of natural products and medicinal agents. Triazole core is considered as a privileged structure in medicinal chemistry and is widely used as 'parental' compounds to synthesize molecules with medical benefits, especially with infection-related activities. In the present review, we have collated published reports on this versatile core to provide an insight so that its complete therapeutic potential can be utilized for the treatment of tuberculosis. This review also explores triazole as a potential targeted core moiety against tuberculosis and various research ongoing worldwide. It is hoped that this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic triazole-based antituberculosis drugs. PMID:25643871

  11. 40 CFR 721.9820 - Substituted triazole.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted triazole. 721.9820 Section... Substances § 721.9820 Substituted triazole. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as a substituted triazole (PMN P-90-1731)...

  12. 40 CFR 721.9820 - Substituted triazole.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Substituted triazole. 721.9820 Section... Substances § 721.9820 Substituted triazole. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as a substituted triazole (PMN P-90-1731)...

  13. 40 CFR 721.9820 - Substituted triazole.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Substituted triazole. 721.9820 Section... Substances § 721.9820 Substituted triazole. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as a substituted triazole (PMN P-90-1731)...

  14. 40 CFR 721.9820 - Substituted triazole.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Substituted triazole. 721.9820 Section... Substances § 721.9820 Substituted triazole. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as a substituted triazole (PMN P-90-1731)...

  15. 40 CFR 721.9820 - Substituted triazole.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Substituted triazole. 721.9820 Section... Substances § 721.9820 Substituted triazole. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as a substituted triazole (PMN P-90-1731)...

  16. Synthesis of 5-aryl-4-(2-acetylaminobenzoyl)-1,2,3-triazoles with the /sup 15/N isotope at the terminal positions of the triazole rings and the tautomeric composition

    SciTech Connect

    Kurkovskaya, L.N.; Velezheva, V.S.; Sorokina, I.K.; Dmitrevskaya, L.I.; Zhil'nikov, V.G.

    1988-12-20

    A mixture of 4-(2-acetylaminobenzoyl)-5-phenyl(p-cumenyl)-1-/sup 15/N,2,3- and 4-(2-acetylaminobenzoyl)-5-phenyl(p-cumenyl)-1,2,3-/sup 15/N-triazoles was obtained from 1-acetyl-2-arylmethylene-3-indolinones and Na/sup 15/N/sub 3/ with the label at the terminal position. The tautomeric composition of the mixture, which corresponds to a state of equilibrium between the 2H and 3H forms of the triazole ring, was established by /sup 1/H (at low temperatures) and /sup 15/N NMR spectroscopy. The 4-(2-acetylaminobenzoyl)-5-aryl-1,2,3-triazoles are acylated at the sterically less hindered position 2 of the triazole ring.

  17. Isavuconazole: A New Broad-Spectrum Triazole Antifungal Agent.

    PubMed

    Miceli, Marisa H; Kauffman, Carol A

    2015-11-15

    Isavuconazole is a new extended-spectrum triazole with activity against yeasts, molds, and dimorphic fungi. It is approved for the treatment of invasive aspergillosis and mucormycosis. Advantages of this triazole include the availability of a water-soluble intravenous formulation, excellent bioavailability of the oral formulation, and predictable pharmacokinetics in adults. A randomized, double-blind comparison clinical trial for treatment of invasive aspergillosis found that the efficacy of isavuconazole was noninferior to that of voriconazole. An open-label trial that studied primary as well as salvage therapy of invasive mucormycosis showed efficacy with isavuconazole that was similar to that reported for amphotericin B and posaconazole. In patients in these studies, as well as in normal volunteers, isavuconazole was well tolerated, appeared to have few serious adverse effects, and had fewer drug-drug interactions than those noted with voriconazole. As clinical experience increases, the role of this new triazole in the treatment of invasive fungal infections will be better defined. PMID:26179012

  18. Synthesis and Antimicrobial Screening of Novel Thioglycosides and Acyclonucleoside Analogs Carrying 1,2,3-Triazole and 1,3,4-Oxadiazole Moieties.

    PubMed

    Aouad, M R

    2016-01-01

    The solvent-free 1,3-dipolar cycloaddition reaction of dimethylacetylene dicarboxylate (1) with 2-chlorophenyl azide (2) afforded 1,2,3-triazole diester 3 that upon hydrazinolysis, furnished the corresponding bis-acid hydrazide 4. The treatment of compound 4 with carbon disulfide in a refluxing potassium hydroxide solution furnished the desired bis-1,3,4-oxadiazole-2-thione 5 tethered to a 1,2,3-triazole moiety. The respective SOx-glycosides 9-11 were obtained by glycosylation of bis-oxadiazole 5 with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide (6), 2,3,4,6-tetra-O-acetyl-α-d-galactopyranosyl bromide (7), and 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-d-glucopyranosyl chloride (8) in dry acetone in the presence of Et3N, which acted as a base. However, alkylation of 5 with halogeno-alkanol 12 or 13, chloroglycerol 14, bromoethers 20 or 21, and epichlohydrin 22 in the presence of K2CO3 in DMF yielded the corresponding acyclonucleoside analogs 16-18 and 23-25. The isopropylidenes 19 and acetyl derivatives 26-28 of the products were also prepared. The newly synthesized compounds were characterized by (1)H NMR, (13)C NMR, 2D NMR, and mass spectra. The compounds were screened for their antibacterial and antifungal activities. A number of the tested compounds exhibited significant antimicrobial activity compared to the reference drugs. PMID:26810028

  19. Evidence of Splitting 1,2,3-Triazole into an Alkyne and Azide by Low Mechanical Force in the Presence of Other Covalent Bonds.

    PubMed

    Khanal, Ashok; Long, Fei; Cao, Bin; Shahbazian-Yassar, Reza; Fang, Shiyue

    2016-07-01

    The cycloaddition reaction of an alkyne and azide to form a 1,2,3-triazole is widely used in many areas. However, the stability of the triazole moiety under mechanical stress is unclear. To see if a triazole could be selectively split into an alkyne and azide in the presence of other typical covalent bonds, a mica surface functionalized with a molecule containing a triazole moiety in the middle and an activated ester at the end was prepared. An atomic force microscope (AFM) tip with amino groups on its surface was ramped over the mica surface at predefined locations, which could temporarily link the tip to the surface through amide bond formation. During retraction, the triazole or another bond in the linkage broke, and a force was recorded. The forces varied widely at different ramps from close to 0 pN to 860 pN due to nonspecific adhesions and to the inherent inconsistency of single bond rupture. If some of the forces were from triazole cycloreversion, there would be alkynes at the predefined ramping locations. The surface was reacted with an azide carboxylic acid followed by labeling with amino Au nanoparticles (AuNPs). AFM imaging revealed AuNPs at the predicted locations, which provided evidence that under certain conditions triazole could be split selectively in the presence of other bonds at forces below 860 pN. PMID:27246264

  20. Environmental fungicides and triazole resistance in Aspergillus.

    PubMed

    Bowyer, Paul; Denning, David W

    2014-02-01

    Fungal diseases are problematic in both human health and agriculture. Treatment options are limited and resistance may emerge. The relatively recent recognition of triazole resistance in Aspergillus fumigatus has prompted questioning of the origin of resistance. While multiple mechanisms are described in clinical isolates from triazole-treated patients, some de novo resistance is also recognised, especially attributable to TR34 /L98H. Such strains probably arose in the environment, and, indeed, multiple studies have now demonstrated TR(34) /L98H triazole resistance strains of A. fumigatus from soil. Docking and other in vitro studies are consistent with environmental resistance induction through exposure to certain triazole fungicides, notably difenoconazole, propiconazole, epoxiconazole, bromuconazole and tebuconazole. This article addresses the potential implications of this issue for both human health and food security. PMID:23616354

  1. Isavuconazole: a new extended spectrum triazole for invasive mold diseases.

    PubMed

    Ananda-Rajah, Michelle R; Kontoyiannis, Dimitrios

    2015-01-01

    Isavuconazole is the first broad spectrum prodrug triazole with efficacy against invasive fungal diseases including aspergillosis and mucormycosis. Characteristics include linear dose-proportional pharmacokinetics, intravenous and oral formulations allowing therapeutic streamlining, once daily dosing, absence of nephrotoxic solubilizing agents and excellent oral bioavailability independent of prandial status and gastric acidity. An open label noncomparator study demonstrated encouraging results for isavuconazole as primary or salvage therapy for a range of fungi including mucormycosis. Isavuconazole had fewer premature drug discontinuations and adverse events in the eye, hepatobiliary and psychiatry systems than the comparator agent, voriconazole in a randomized double-blind clinical trial. Cross-resistance of isavuconazole best correlates with voriconazole. In vitro resistance is not invariably predictive of clinical failure. Isavuconazole signals progress in pharmacokinetics, bioavailability and toxicity/tolerability supported by clinical efficacy from Phase III trials. PMID:26000646

  2. Crystal structure and IR spectrum of 1- O- α- D-glucopyranosyl- D-mannitol-ethanol (2/1)

    NASA Astrophysics Data System (ADS)

    Perkkalainen, P.; Pitkänen, I.; Huuskonen, J.

    1999-11-01

    1- O- α- D-Glucopyranosyl- D-mannitol-ethanol (2/1), (C 12H 24O 11) 2-C 2H 5OH, crystallizes in the monoclinic space group P2 1 with unit cell dimensions a=11.4230(8) Å, b=9.525(4) Å, c=15.854(2) Å, β=102.751(7)° and V=1682.4(7) Å 3, Z=2, Dx=1.45 Mg m -3, λ (Mo-K α)=0.71069 Å, μ=0.128 mm -1, F(000)=788 and T=293(2) K. The structure was solved by direct methods and refined by least-squares calculations on F2 to R1=0.0371[ I>2 σ( I)], and 0.0930 (all data, 3542 independent reflections, Rint=0.021). There are two molecules of glucopyranosylmannitol (GPM) and one ethanol molecule in the asymmetric unit, and the glucopyranosyl ring adopts a chair conformation in both GPM molecules. Bond lengths and angles accord well with the mean values of related structures. The conformation along the mannitol side chain for one of the GPM molecules was the same as for the known polymorphs of D-mannitol, while the conformation of the other molecule was different, indicating different conformational arrangements in the terminal carbon atoms of the mannitol side chains of the two GPM molecules. The structure in 1- O- α- D-glucopyranosyl- D-mannitol-ethanol (2/1) is held together by a very complex hydrogen bonding system, which consists of an infinte chain propagating along the b-axis and a discontinuous chain, which binds the ethanol molecule to the structure. The FTIR spectra for anhydrous GPM, GPM dihydrate and GPM-ethanol (2/1) were recorded. Both IR and X-ray results indicate the extensive hydrogen bonding in crystalline state.

  3. New alpha-selective thermal glycosylation of acetyl-protected 2-acetamido-2-deoxy-beta-D-glucopyranosyl diphenylphosphinate.

    PubMed

    Kadokawa, J; Nagaoka, T; Ebana, J; Tagaya, H; Chiba, K

    2000-07-24

    This paper describes new alpha-selective thermal glycosylation using acetyl-protected 2-acetamido-2-deoxy-beta-D-glucopyranosyl diphenylphosphinate (4) as a glycosyl donor. When the glycosylation of 4 with 1-hexanol was carried out under various conditions, the conditions using trimethylsilyl trifluoromethanesulfonate as a promoter in nitromethane at reflux temperature were most suitable for the formation of the alpha anomer. The glycosylation of 4 with the other common alcohols gave corresponding alpha-glycosides in relatively high yields under the conditions. When cholesterol, a very steric hindered alcohol, was used as a glycosyl acceptor, alpha-glycoside was also produced predominantly. PMID:10945682

  4. Binding of N-acetyl-N '-beta-D-glucopyranosyl urea and N-benzoyl-N '-beta-D-glucopyranosyl urea to glycogen phosphorylase b: kinetic and crystallographic studies.

    PubMed

    Oikonomakos, Nikos G; Kosmopoulou, Magda; Zographos, Spyros E; Leonidas, Demetres D; Chrysina, Evangelia D; Somsák, László; Nagy, Veronika; Praly, Jean-Pierre; Docsa, Tibor; Tóth, Béla; Gergely, Pál

    2002-03-01

    Two substituted ureas of beta-D-glucose, N-acetyl-N'-beta-D-glucopyranosyl urea (Acurea) and N-benzoyl-N'-beta-D-glucopyranosyl urea (Bzurea), have been identified as inhibitors of glycogen phosphorylase, a potential target for therapeutic intervention in type 2 diabetes. To elucidate the structural basis of inhibition, we determined the structure of muscle glycogen phosphorylase b (GPb) complexed with the two compounds at 2.0 A and 1.8 A resolution, respectively. The structure of the GPb-Acurea complex reveals that the inhibitor can be accommodated in the catalytic site of T-state GPb with very little change in the tertiary structure. The glucopyranose moiety makes the standard hydrogen bonds and van der Waals contacts as observed in the GPb-glucose complex, while the acetyl urea moiety is in a favourable electrostatic environment and makes additional polar contacts with the protein. The structure of the GPb-Bzurea complex shows that Bzurea binds tightly at the catalytic site and induces substantial conformational changes in the vicinity of the catalytic site. In particular, the loop of the polypeptide chain containing residues 282-287 shifts 1.3-3.7 A (Calpha atoms) to accommodate Bzurea. Bzurea can also occupy the new allosteric site, some 33 A from the catalytic site, which is currently the target for the design of antidiabetic drugs. PMID:11895439

  5. Determination of 22 triazole compounds including parent fungicides and metabolites in apples, peaches, flour, and water by liquid chromatography/tandem mass spectrometry.

    PubMed

    Schermerhorn, Patricia G; Golden, Paul E; Krynitsky, Alexander J; Leimkuehler, William M

    2005-01-01

    A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed for the determination of 14 parent triazole fungicides and 8 of their metabolites found in apples, peaches, flour, raw water, and tap water. The triazole fungicides chosen for this multiresidue method development project included propiconazole, fenbuconazole and its RH-9129 and RH-9130 metabolites, cyproconazole, difenoconazole, tebuconazole and its HWG 2061 metabolite, hexaconazole, bromuconazole (both stereoisomers), epoxiconazole, tetraconazole, triticonazole and its RPA-404886 and RPA-406341 metabolites, triadimefon, triadimenol, and myclobutanil. Of special concern to the U.S. Environmental Protection Agency were the metabolites common to all triazole fungicides: free triazole, 1,2,4-triazole (T), and its 2 conjugates: triazolylalanine (TA) and triazolylacetic acid (TAA). These metabolites were the primary focus of this project. All samples we cleaned up by a combination of C18 solid-phase extraction (SPE), mixed-mode cationic SPE, and mixed-mode anionic SPE columns. A triple-stage quadrupole mass spectrometer, equipped with electrospray ionization in the positive-ion mode, was used to determine the compounds of interest. T, TA, and TAA were quantitated using isotopically labeled internal standards (IS), in which the 1,2,4-triazole ring had been synthesized by using 13C and 15N (IS_T, IS_TA, and IS_TAA). These isotopically labeled internal standards were necessary to correct for matrix effects. The T, TA, and TAA metabolites were quantitated at the 25-50 parts-per-billion (ppb) level in food commodities and at 0.50 ppb in water. Recoveries were 70-101% from apples, 60-121% from peaches, 57-118% from flour, 75-99% from raw water, and 79-99% from tap water. PMID:16386000

  6. The binding of β-d-glucopyranosyl-thiosemicarbazone derivatives to glycogen phosphorylase: A new class of inhibitors.

    PubMed

    Alexacou, Kyra-Melinda; Tenchiu Deleanu, Alia-Cristina; Chrysina, Evangelia D; Charavgi, Maria-Despoina; Kostas, Ioannis D; Zographos, Spyros E; Oikonomakos, Nikos G; Leonidas, Demetres D

    2010-11-15

    Glycogen phosphorylase (GP) is a promising target for the treatment of type 2 diabetes. In the process of structure based drug design for GP, a group of 15 aromatic aldehyde 4-(β-d-glucopyranosyl)thiosemicarbazones have been synthesized and evaluated as inhibitors of rabbit muscle glycogen phosphorylase b (GPb) by kinetic studies. These compounds are competitive inhibitors of GPb with respect to α-d-glucose-1-phosphate with IC(50) values ranging from 5.7 to 524.3μM. In order to elucidate the structural basis of their inhibition, the crystal structures of these compounds in complex with GPb at 1.95-2.23Å resolution were determined. The complex structures reveal that the inhibitors are accommodated at the catalytic site with the glucopyranosyl moiety at approximately the same position as α-d-glucose and stabilize the T conformation of the 280s loop. The thiosemicarbazone part of the studied glucosyl thiosemicarbazones possess a moiety derived from substituted benzaldehydes with NO(2), F, Cl, Br, OH, OMe, CF(3), or Me at the ortho-, meta- or para-position of the aromatic ring as well as a moiety derived from 4-pyridinecarboxaldehyde. These fit tightly into the β-pocket, a side channel from the catalytic site with no access to the bulk solvent. The differences in their inhibitory potency can be interpreted in terms of variations in the interactions of the aldehyde-derived moiety with protein residues in the β-pocket. In addition, 14 out of the 15 studied inhibitors were found bound at the new allosteric site of the enzyme. PMID:20947361

  7. Halogen-substituted (C-β-D-glucopyranosyl)-hydroquinone regioisomers: synthesis, enzymatic evaluation and their binding to glycogen phosphorylase.

    PubMed

    Alexacou, Kyra-Melinda; Zhang, Yun Zhi; Praly, Jean-Pierre; Zographos, Spyros E; Chrysina, Evangelia D; Oikonomakos, Nikos G; Leonidas, Demetres D

    2011-09-01

    Electrophilic halogenation of C-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl) 1,4-dimethoxybenzene (1) afforded regioselectively products halogenated at the para position to the D-glucosyl moiety (8, 9) that were deacetylated to 3 (chloride) and 16 (bromide). For preparing meta regioisomers, 1 was efficiently oxidized with CAN to afford C-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl) 1,4-benzoquinone 2 which, in either MeOH or H(2)O-THF containing few equivalents of AcCl, added hydrochloric acid to produce predominantly meta (with respect to the sugar moiety) chlorinated hydroquinone derivatives 5 and 18, this latter being deacetylated to 4. The deacetylated meta (4, 5) or para (3, 16) halohydroquinones were evaluated as inhibitors of glycogen phosphorylase (GP, a molecular target for inhibition of hepatic glycogenolysis under high glucose concentrations) by kinetics and X-ray crystallography. These compounds are competitive inhibitors of GPb with respect to α-D-glucose-1-phosphate. The measured IC(50) values (μM) [169.9±10.0 (3), 95 (4), 39.8±0.3 (5) 136.4±4.9 (16)] showed that the meta halogenated inhibitors (4, 5) are more potent than their para analogs (3, 16). The crystal structures of GPb in complex with these compounds at high resolution (1.97-2.05 Å) revealed that the inhibitors are accommodated at the catalytic site and stabilize the T conformation of the enzyme. The differences in their inhibitory potency can be interpreted in terms of variations in the interactions with protein residues of the different substituents on the aromatic part of the inhibitors. PMID:21821421

  8. Stereo- and regio-selective one-pot synthesis of triazole-based unnatural amino acids and β- amino triazoles

    EPA Science Inventory

    Synthesis of triazole based unnatural amino acids and β-amino triazole has been described via stereo and regioselective one-pot multi-component reaction of sulfamidates, sodium azide, and alkynes under MW conditions. The developed method is applicable to a broad substrate scope a...

  9. New triazole and triazolothiadiazine derivatives as possible antimicrobial agents.

    PubMed

    Kaplancikli, Zafer Asim; Turan-Zitouni, Gülhan; Ozdemir, Ahmet; Revial, Gilbert

    2008-01-01

    Triazole and triazoles fused with six-membered ring systems are found to possess diverse applications in the fields of medicine, agriculture and industry. The new 1,2,4-triazole and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazine derivatives were synthesized as novel antimicrobial agents. The reaction of 1H-indol-3-acetic acid with thiocarbohydrazide gave the 4-amino-3-mercapto-5-[(1H-indol-3-yl)methyl]-4H-1,2,4-triazole. The reaction of triazole with arylaldehydes in ethanol gave the 4-arylideneamino-3-mercapto-5-[(1H-indol-3-yl)methyl]-4H-1,2,4-triazoles (I). The 3-[(1H-indol-3-yl)methyl]-6-aryl-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazines (II) were obtained by condensing triazole with phenacyl bromides in absolute ethanol . The chemical structures of the compounds were elucidated by IR, (1)H NMR and FAB(+)-MS spectral data. Their antimicrobial activities against Micrococcus luteus (NRLL B-4375), Bacillus cereus (NRRL B-3711), Proteus vulgaris (NRRL B-123), Salmonella typhimurium (NRRL B-4420), Staphylococcus aureus (NRRL B-767), Escherichia coli (NRRL B-3704), Candida albicans and Candida glabrata (isolates obtained from Osmangazi University, Faculty of Medicine) were investigated and significant activity was obtained. PMID:17499887

  10. Triazole Fungicides Can Induce Cross-Resistance to Medical Triazoles in Aspergillus fumigatus

    PubMed Central

    Karawajczyk, Anna; Schaftenaar, Gijs; Kema, Gert H. J.; van der Lee, Henrich A.; Klaassen, Corné H.; Melchers, Willem J. G.; Verweij, Paul E.

    2012-01-01

    Background Azoles play an important role in the management of Aspergillus diseases. Azole resistance is an emerging global problem in Aspergillus fumigatus, and may develop through patient therapy. In addition, an environmental route of resistance development has been suggested through exposure to 14α-demethylase inhibitors (DMIs). The main resistance mechanism associated with this putative fungicide-driven route is a combination of alterations in the Cyp51A-gene (TR34/L98H). We investigated if TR34/L98H could have developed through exposure to DMIs. Methods and Findings Thirty-one compounds that have been authorized for use as fungicides, herbicides, herbicide safeners and plant growth regulators in the Netherlands between 1970 and 2005, were investigated for cross-resistance to medical triazoles. Furthermore, CYP51-protein homology modeling and molecule alignment studies were performed to identify similarity in molecule structure and docking modes. Five triazole DMIs, propiconazole, bromuconazole, tebuconazole, epoxiconazole and difenoconazole, showed very similar molecule structures to the medical triazoles and adopted similar poses while docking the protein. These DMIs also showed the greatest cross-resistance and, importantly, were authorized for use between 1990 and 1996, directly preceding the recovery of the first clinical TR34/L98H isolate in 1998. Through microsatellite genotyping of TR34/L98H isolates we were able to calculate that the first isolate would have arisen in 1997, confirming the results of the abovementioned experiments. Finally, we performed induction experiments to investigate if TR34/L98H could be induced under laboratory conditions. One isolate evolved from two copies of the tandem repeat to three, indicating that fungicide pressure can indeed result in these genomic changes. Conclusions Our findings support a fungicide-driven route of TR34/L98H development in A. fumigatus. Similar molecule structure characteristics of five triazole DMIs

  11. The stimulatory effect of the TLR4-mediated adjuvant glucopyranosyl lipid A is well preserved in old age.

    PubMed

    Weinberger, Birgit; Joos, Clemens; Reed, Steven G; Coler, Rhea; Grubeck-Loebenstein, Beatrix

    2016-02-01

    Many subunit vaccines require adjuvants to improve their limited immunogenicity. Various adjuvant candidates targeting toll-like receptors (TLRs) are currently under development including the synthetic TLR4 agonist glucopyranosyl lipid A (GLA). GLA has been investigated in the context of influenza vaccine, which is of particular importance for the elderly population. This study investigates the effect of GLA on antigen-presenting cells from young (median age 29 years, range 26-33 years) and older (median age 72 years, range 61-78 years) adults. Treatment with GLA efficiently increases the expression of co-stimulatory molecules on human monocyte-derived dendritic cells (DC) as well as on ex vivo myeloid DC. Expression of co-stimulatory molecules is less pronounced on ex vivo monocytes. Production of pro-inflammatory cytokines (IL-6, TNF-α, IL-12) as well as of the anti-inflammatory cytokine IL-10 is induced in monocyte-derived DC. In PBMC cultures myeloid DC and to an even greater extent monocytes produce TNF-α and IL-6 after stimulation with GLA. Production of IL-12 can also be observed in these cultures. There are no age-related differences in the capacity of GLA to induce expression of co-stimulatory molecules or production of cytokines by human antigen-presenting cells. Therefore, TLR4 agonists like GLA are particularly promising candidates as adjuvants of vaccines designed for elderly individuals. PMID:25957253

  12. Postulated pathogenic pathway in triazole fungicide induced dysmorphogenic effects.

    PubMed

    Menegola, Elena; Broccia, Maria L; Di Renzo, Francesca; Giavini, Erminio

    2006-08-01

    Triazole fungicides are used in medicine as well as in agricultural treatment of mycoses. The pharmacological mechanism is related to the inhibition of CYP enzymes involved in the formation of the fungal walls. A similar inhibition of human CYP enzymes has been suggested as the cause of triazole side effects in humans. An important role of some CYP isoforms (CYP26 isoforms) expressed during mammalian development is the catabolism of retinoic acid, a known morphogen in vertebrates and invertebrates. The adverse effects on morphogenesis, observed after exposure of mammalian, amphibian and ascidiacea, are compared to the reported effects of triazole in humans. The possible pathogenic pathway in triazole-related teratogenesis is discussed on the basis of different experimental approaches. PMID:16781842

  13. TOXICOGENOMIC STUDY OF TRIAZOLE FUNGICIDES AND PERFLUOROALKYL ACIDS

    EPA Science Inventory

    Toxicogenomic analysis of five environmental contaminants was performed to investigate the ability of genomics to categorize chemicals and elucidate mechanisms of toxicity. Three triazole antifungals (myclobutanil, propiconazole and triadimefon) and two perfluorinated compounds (...

  14. Inhibition of Rat and Human Steroidogenesis by Triazole Antifungals

    EPA Science Inventory

    Environmental chemicals that alter steroid production could interfere with male reproductive development and function. Three agricultural antifungal triazoles (myclobutanil, propiconazole and triadimefon) that are known to modulate expression of cytochrome P450 (CYP) genes and e...

  15. The σ-hole phenomenon of halogen atoms forms the structural basis of the strong inhibitory potency of C5 halogen substituted glucopyranosyl nucleosides towards glycogen phosphorylase b.

    PubMed

    Kantsadi, Anastasia L; Hayes, Joseph M; Manta, Stella; Skamnaki, Vicky T; Kiritsis, Christos; Psarra, Anna-Maria G; Koutsogiannis, Zissis; Dimopoulou, Athina; Theofanous, Stavroula; Nikoleousakos, Nikolaos; Zoumpoulakis, Panagiotis; Kontou, Maria; Papadopoulos, George; Zographos, Spyros E; Komiotis, Dimitris; Leonidas, Demetres D

    2012-04-01

    C5 halogen substituted glucopyranosyl nucleosides (1-(β-D-glucopyranosyl)-5-X-uracil; X=Cl, Br, I) have been discovered as some of the most potent active site inhibitors of glycogen phosphorylase (GP), with respective K(i) values of 1.02, 3.27, and 1.94 μM. The ability of the halogen atom to form intermolecular electrostatic interactions through the σ-hole phenomenon rather than through steric effects alone forms the structural basis of their improved inhibitory potential relative to the unsubstituted 1-(β-D-glucopyranosyl)uracil (K(i) =12.39 μM), as revealed by X-ray crystallography and modeling calculations exploiting quantum mechanics methods. Good agreement was obtained between kinetics results and relative binding affinities calculated by QM/MM-PBSA methodology for various substitutions at C5. Ex vivo experiments demonstrated that the most potent derivative (X=Cl) toward purified GP has no cytotoxicity and moderate inhibitory potency at the cellular level. In accordance, ADMET property predictions were performed, and suggest decreased polar surface areas as a potential means of improving activity in the cell. PMID:22267166

  16. Drug-Drug Interaction Associated with Mold-Active Triazoles among Hospitalized Patients.

    PubMed

    Andes, David; Azie, Nkechi; Yang, Hongbo; Harrington, Rachel; Kelley, Caroline; Tan, Ruo-Ding; Wu, Eric Q; Franks, Billy; Kristy, Rita; Lee, Edward; Khandelwal, Nikhil; Spalding, James

    2016-06-01

    The majority of hospitalized patients receiving mold-active triazoles are at risk of drug-drug interactions (DDIs). Efforts are needed to increase awareness of DDIs that pose a serious risk of adverse events. Triazoles remain the most commonly utilized antifungals. Recent developments have included the mold-active triazoles (MATs) itraconazole, voriconazole, and posaconazole, which are first-line agents for the treatment of filamentous fungal infections but have the potential for DDIs. This objective of this study was to evaluate the prevalence of triazole DDIs. Hospitalized U.S. adults with MAT use were identified in the Cerner HealthFacts database, which contained data from over 150 hospitals (2005 to 2013). The severities of DDIs with MATs were categorized, using drug labels and the drug information from the Drugdex system (Thompson Micromedex), into four groups (contraindicated, major, moderate, and minor severity). DDIs of minor severity were not counted. A DDI event was considered to have occurred if the following two conditions were met: (i) the patient used at least one drug with a classification of at least a moderate interaction with the MAT during the hospitalization and (ii) there was a period of overlap between the administration of the MAT and that of the interacting drug of at least 1 day. A total of 6,962 hospitalizations with MAT use were identified. Among them, 88% of hospitalizations with voriconazole use, 86% of hospitalizations with itraconazole use, and 93% of hospitalizations with posaconazole use included the use of a concomitant interacting drug. A total of 68% of hospitalizations with posaconazole use, 34% of hospitalizations with itraconazole use, and 20% of hospitalizations with voriconazole use included the use of at least one drug with a DDI of contraindicated severity. A total of 83% of hospitalizations with posaconazole use, 61% of hospitalizations with itraconazole use, and 82% of hospitalizations with voriconazole use included the

  17. Biosynthesis of 2-O-D-glucopyranosyl-l-ascorbic acid from maltose by an engineered cyclodextrin glycosyltransferase from Paenibacillus macerans.

    PubMed

    Liu, Long; Han, Ruizhi; Shin, Hyun-Dong; Li, Jianghua; Du, Guocheng; Chen, Jian

    2013-12-15

    In this work, the specificity of cyclodextrin glycosyltransferase (CGTase) of Paenibacillus macerans towards maltose was improved by the site-saturation engineering of lysine 47, and the enzymatic synthesis of 2-O-d-glucopyranosyl-l-ascorbic acid (AA-2G) with l-ascorbic acid and maltose as substrates was optimized. Compared to the AA-2G yield of the wild-type CGTase, that of the mutants K47F (lysine→phenylalanine), K47P (lysine→proline), and K47Y (lysine→tyrosine) was increased by 17.1%, 32.9%, and 21.1%, respectively. Under the optimal transformation conditions (pH 6.5, temperature 36°C, the mass ratio of l-ascorbic acid to maltose 1:1), the highest AA-2G titer by the K47P reached 1.12g/L, which was 1.32-fold of that (0.85g/L) obtained by the wild-type CGTase. The reaction kinetics analysis confirmed the enhanced maltose specificity of the mutants K47F, K47P, and K47Y. It was also found that compared to the wild-type CGTase, the three mutants had relatively lower cyclization activities and higher disproportionation activities, which was favorable for AA-2G synthesis. As revealed by the interaction structure model of CGTase with substrate, the enhancement of maltose specificity may be due to the removal of hydrogen bonding interactions between the side chain of residue 47 and the sugar at -3 subsite. The obtained mutant CGTases, especially the K47P, has a great potential in the large-scale production of AA-2G with maltose as a cheap and soluble substrate. PMID:24239542

  18. Glucopyranosyl-1,4-dihydropyridine as a new fluorescent chemosensor for selective detection of 2,4,6-trinitrophenol.

    PubMed

    Pinrat, Oran; Boonkitpatarakul, Kanokthorn; Paisuwan, Waroton; Sukwattanasinitt, Mongkol; Ajavakom, Anawat

    2015-03-21

    Glucopyranosyl-1,4-dihydropyridine (Glc-DHP) was synthesized as a new fluorescent chemosensor via cyclotrimerization of the β-amino acrylate in the presence of TiCl4. This DHP derivative is soluble in aqueous medium and the solution gives a blue fluorescence signal with a quantum yield of 29%. The fluorescence signal of Glc-DHP was selectively quenched by 2,4,6-trinitrophenol (TNP) with a quenching coefficient (Ksv) of 4.47 × 10(4) and at one of the best reported detection limits of 0.94 μM. The quenching mechanism was confirmed to be of the static type at the low concentration region (less than 50 μM) with the significant quenching effect of competitive absorption starting from the concentration of 50 μM. Even in the real sample (seawater and industrial water), the quenching efficiencies of TNP on the fluorescence emission of Glc-DHP were proven to be at the same level with that of the test in pure water, demonstrating the practicability of the detection. Furthermore, a fluorescent paper sensor could be prepared by immersing the paper into the Glc-DHP solution. The fluorescence of the paper sensor disappeared either by writing with TNP solution or by exposure to TNP vapor. This detection could be observed by the naked eye under black light. The pH effect was proven to be a substantial factor in the quenching mechanism, providing an accurate determination of TNP, 2,4-dinitrophenol (DNP) and 4-nitrophenol (4NP) in real mixed-samples. PMID:25646174

  19. Triazole fungicide tebuconazole disrupts human placental trophoblast cell functions.

    PubMed

    Zhou, Jinghua; Zhang, Jianyun; Li, Feixue; Liu, Jing

    2016-05-01

    Triazole fungicides are one of the top ten classes of current-use pesticides. Although exposure to triazole fungicides is associated with reproductive toxicity in mammals, limited information is available regarding the effects of triazole fungicides on human placental trophoblast function. Tebuconazole (TEB) is a common triazole fungicide that has been extensively used for fungi control. In this work, we showed that TEB could reduce cell viability, disturb normal cell cycle distribution and induce apoptosis of human placental trophoblast cell line HTR-8/SVneo (HTR-8). Bcl-2 protein expression decreased and the level of Bax protein increased after TEB treatment in HTR-8 cells. The results demonstrated that this fungicide induced apoptosis of trophoblast cells via mitochondrial pathway. Importantly, we found that the invasive and migratory capacities of HTR-8 cells decreased significantly after TEB administration. TEB altered the expression of key regulatory genes involved in the modulation of trophoblast functions. Taken together, TEB suppressed human trophoblast invasion and migration through affecting the expression of protease, hormones, angiogenic factors, growth factors and cytokines. As the invasive and migratory abilities of trophoblast are essential for successful placentation and fetus development, our findings suggest a potential risk of triazole fungicides to human pregnancy. PMID:26852204

  20. Nucleosides of 4-methylthio-1,2,3-triazol-5-yl-carboxylic acid derivatives

    SciTech Connect

    Shingarova, I.D.; Yartseva, I.V.; Preobrazhenskaya, M.N.

    1987-08-01

    2-..beta..-D-Ribofuranosyl-4-methylthio-5-methoxycarbonyl-1,2,3-triazole was obtained by fusing 4-methylthio-5-methoxycarbonyl-1,2,3-triazole together with tetraacyl-D-ribofuranose, followed by deacylation, and its amide and hydrazide were prepared. The structures of the new nucleosides were established by converting them into known 2-nucleosides of 1,2,3-triazol-4-yl-carboxylic acid derivatives. By comparing PMR spectra with previously reported PMR spectra for the isomeric 1- and 2-nucleosides of 1,2,3-triazol-4-yl-carboxylic acid derivatives, the synthesized nucleosides could be assigned to 2-substituted triazoles.

  1. Sequential synthesis of amino-1,4-naphthoquinone-appended triazoles and triazole-chromene hybrids and their antimycobacterial evaluation.

    PubMed

    Devi Bala, Balasubramanian; Muthusaravanan, Sivasubramanian; Choon, Tan Soo; Ashraf Ali, Mohamed; Perumal, Subbu

    2014-10-01

    A general method for the synthesis of a library of hitherto unreported amino-1,4-naphthoquinone-appended triazoles was accomplished via a sequential three-component reaction of substituted N-propargylaminonaphthoquinones with variously substituted alkyl bromides/2-bromonaphthalene-1,4-dione and sodium azide in the presence of Et3N/CuI in water. Aminonaphthoquinone-appended iminochromene-triazole hybrid heterocycles were also synthesized from the amino-1,4-naphthoquinone-appended-1,2,3-triazolylacetonitriles. All the triazole hybrids were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB). Among the triazoles, 2-(((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)(4-(trifluoromethyl)phenyl)amino)naphthalene-1,4-dione (7d) emerged as the most active one with IC50 = 1.87 μM, being more potent than the anti-TB drugs, cycloserine (6 times), pyrimethamine (20 times) and equipotent as the drug ethambutol (IC50 < 1.56 μM). PMID:25129868

  2. Advances in synthetic approach to and antifungal activity of triazoles

    PubMed Central

    Kumar, Nitin; Drabu, Sushma; Sharma, Pramod Kumar

    2011-01-01

    Summary Several five membered ring systems, e.g., triazole, oxadiazole dithiazole and thiadiazole with three heteroatoms at symmetrical or asymmetrical positions have been studied because of their interesting pharmacological properties. In this article our emphasis is on synthetic development and pharmacological activity of the triazole moiety which exhibit a broad spectrum of pharmacological activity such as antifungal, antibacterial, anti-inflammatory and anticancer etc. Triazoles have increased our ability to treat many fungal infections, for example, candidiasis, cryptococcal meningitis, aspergillosis etc. However, mortality due to these infections even with antifungal therapy is still unacceptably high. Therefore, the development of new antifungal agents targeting specific fungal structures or functions is being actively pursued. Rapid developments in molecular mycology have led to a concentrated search for more target antifungals. Although we are entering a new era of antifungal therapy in which we will continue to be challenged by systemic fungal diseases, the options for treatment will have greatly expanded. PMID:21804864

  3. Metronidazole-triazole conjugates: Activity against Clostridium difficile and parasites

    PubMed Central

    Jarrad, Angie M.; Karoli, Tomislav; Debnath, Anjan; Tay, Chin Yen; Huang, Johnny X.; Kaeslin, Geraldine; Elliott, Alysha G.; Miyamoto, Yukiko; Ramu, Soumya; Kavanagh, Angela M.; Zuegg, Johannes; Eckmann, Lars; Blaskovich, Mark A.T.; Cooper, Matthew A.

    2015-01-01

    Metronidazole has been used clinically for over 50 years as an antiparasitic and broad-spectrum antibacterial agent effective against anaerobic bacteria. However resistance to metronidazole in parasites and bacteria has been reported, and improved second-generation metronidazole analogues are needed. The copper catalysed Huigsen azide-alkyne 1,3-dipolar cycloaddition offers a way to efficiently assemble new libraries of metronidazole analogues. Several new metronidazole-triazole conjugates (Mtz-triazoles) have been identified with excellent broad spectrum antimicrobial and antiparasitic activity targeting Clostridium difficile, Entamoeba histolytica and Giardia lamblia. Cross resistance to metronidazole was observed against stable metronidazole resistant C. difficile and G. lamblia strains. However for the most potent Mtz-triazoles, the activity remained in a therapeutically relevant window. PMID:26117821

  4. CuO-promoted construction of N-2-aryl-substituted-1,2,3-triazoles via azide-chalcone oxidative cycloaddition and post-triazole arylation.

    PubMed

    Zhang, Yuanqing; Li, Xiaolong; Li, Jihui; Chen, Jinying; Meng, Xu; Zhao, Mingming; Chen, Baohua

    2012-01-01

    An efficient one-pot three-component stepwise approach for the synthesis of N-2-aryl-substituted-1,2,3-triazoles has been developed. By using this azide-chalcone oxidative cycloaddition and post-triazole arylation, a series of N-2-aryl-substituted-1,2,3-triazoles are readily prepared under mild conditions in excellent yields and high regioselectivity. Both the catalyst and substrates are readily available. PMID:22133007

  5. Chlorine's effects on triazole inhibitor layers on copper

    SciTech Connect

    Holm, R.; Over, J.; Wittig, M.; Minnich, R.; Berg, D. ); Eickmans, J.; Holtkamp, D. ); Meyer, K.; Benninghoven, A. )

    1994-05-01

    The triazole film on copper (Cu) is the result of a dynamic equilibrium between the inhibitor film formation and the corrosion reaction of the underlying metal; therefore, it can be penetrated by water and chlorine molecules, as well as by protons, chloride, and metallic ions. This penetration results in Cu corrosion and is immediately detected through electrochemistry. Degradation of the inhibitor film, which takes some time, can best be observed by surface analysis. Once film degradation has started, penetration is enhanced, and both processes lead to excessive Cu corrosion rates. The effect of this two-step interaction between chlorine and two triazole inhibitors now primarily in use in the industry was investigated.

  6. N-(4-Substituted-benzoyl)-N'-(β-d-glucopyranosyl)ureas as inhibitors of glycogen phosphorylase: Synthesis and evaluation by kinetic, crystallographic, and molecular modelling methods.

    PubMed

    Nagy, Veronika; Felföldi, Nóra; Kónya, Bálint; Praly, Jean-Pierre; Docsa, Tibor; Gergely, Pál; Chrysina, Evangelia D; Tiraidis, Costas; Kosmopoulou, Magda N; Alexacou, Kyra-Melinda; Konstantakaki, Maria; Leonidas, Demetres D; Zographos, Spyros E; Oikonomakos, Nikos G; Kozmon, Stanislav; Tvaroška, Igor; Somsák, László

    2012-03-01

    N-(4-Substituted-benzoyl)-N'-(β-d-glucopyranosyl) ureas (substituents: Me, Ph, Cl, OH, OMe, NO(2), NH(2), COOH, and COOMe) were synthesised by ZnCl(2) catalysed acylation of O-peracetylated β-d-glucopyranosyl urea as well as in reactions of O-peracetylated or O-unprotected glucopyranosylamines and acyl-isocyanates. O-deprotections were carried out by base or acid catalysed transesterifications where necessary. Kinetic studies revealed that most of these compounds were low micromolar inhibitors of rabbit muscle glycogen phosphorylase b (RMGPb). The best inhibitor was the 4-methylbenzoyl compound (K(i)=2.3μM). Crystallographic analyses of complexes of several of the compounds with RMGPb showed that the analogues exploited, together with water molecules, the available space at the β-pocket subsite and induced a more extended shift of the 280s loop compared to RMGPb in complex with the unsubstituted benzoyl urea. The results suggest the key role of the water molecules in ligand binding and structure-based ligand design. Molecular docking study of selected inhibitors was done to show the ability of the binding affinity prediction. The binding affinity of the highest scored docked poses was calculated and correlated with experimentally measured K(i) values. Results show that correlation is high with the R-squared (R(2)) coefficient over 0.9. PMID:22325154

  7. Synthesis and antifungal activity of the novel triazole derivatives containing 1,2,3-triazole fragment.

    PubMed

    Yu, Shichong; Wang, Nan; Chai, Xiaoyun; Wang, Baogang; Cui, Hong; Zhao, Qingjie; Zou, Yan; Sun, Qingyan; Meng, Qingguo; Wu, Qiuye

    2013-10-01

    A series of fluconazole analogues containing 1,2,3-triazole fragment have been designed and synthesized on the basis of the active site of the cytochrome P450 14α-demethylase (CYP51). Their structures were characterized by (1)H NMR, (13)C NMR and LC-MS. The MIC80 values indicate that the target compounds 1a-r showed higher activities against nearly all the fungi tested to some extent except against Aspergillus fumigatus. Compounds 1c, e, f, l and p showed 128 times higher activity (with the MIC80 value of 0.0039 mg/mL) than that of fluconazole against Candida albicans and also showed higher activity than that of the other positive controls. PMID:23640383

  8. Mono- and diiodo-1,2,3-triazoles and their mono nitro derivatives.

    PubMed

    Chand, Deepak; He, Chunlin; Hooper, Joseph P; Mitchell, Lauren A; Parrish, Damon A; Shreeve, Jean'ne M

    2016-06-21

    4-Iodo-1H-1,2,3-triazole (2) and 4,5-diiodo-1H-1,2,3-triazole (3) were synthesized using an efficient and viable synthetic route. The N-alkylation of 3 resulted in the formation of two tautomers. The N-alkyl-diiodo-triazoles were nitrated with 100% nitric acid to form monoiodo-mononitro-triazoles. The structures of 2-methyl-4,5-diiodo-1,2,3-triazole (5), 1-ethyl-4,5-diiodo-1,2,3-triazole (6), 1-methyl-4-nitro-5-iodo-1,2,3-triazole (8) and 1-ethyl-4-nitro-5-iodo-1,2,3-triazole (10) were confirmed by X-ray crystal analysis. All of the new triazoles were fully characterized via NMR, and infrared spectra, and elemental analyses as well as by their thermal and sensitivity properties. Decomposition products calculated using Cheetah 7 software show that these iodo-nitro triazoles liberate iodine. PMID:27226283

  9. Sorption of triazoles to soil and iron minerals.

    PubMed

    Jia, Yu; Aagaard, Per; Breedveld, Gijs D

    2007-02-01

    Triazoles, additives in runway de-icers, are found in soil and groundwater at airport sites. To better understand the fate and transport of benzotriazole (BTA) and methylbenzotriazole (MeBTA) and to assess possible remediation options of contaminated groundwater, sorption to various soils and ferrous sorbents has been studied. In batch experiments, limited non-linear sorption of BTA to mineral subsoil from the Oslo International Airport, Gardermoen was observed. The sorption to soil could be described using a Freundlich isotherm. pH affected sorption of BTA to subsoil, although the effect was not strong. Increased sorption was observed to zerovalent iron (Fe(0)). MeBTA showed similar sorption behaviour as BTA although the sorption coefficient was generally higher. Sorption to Fe(0) seems to be controlled by multi-layer coverage. Our data suggest that sorption of triazoles to Fe(2)O(3) is negligible. However BTA sorption to 2-line and 6-line ferrihydrites showed strong sorption. The results demonstrate that triazoles are highly mobile in the subsurface environment, however zerovalent iron can be an effective medium for groundwater remediation. Without remediation, wide distribution of triazoles in the environment can be expected due to its extensive application and limited degradability. PMID:17123582

  10. Structural basis of the impact sensitivities of 1-picryl-1,2,3-triazole, 2-picryl-1,2,3-triazole, 4-nitro-1-picryl-1,2,3-triazole, and 4-nitro-2-picryl-1,2,3-triazole

    SciTech Connect

    Storm, C.B.; Ryan, R.R.; Ritchie, J.P.; Hall, J.H.; Bachrach, S.M. )

    1989-01-26

    The isomeric pairs 1-picryl-1,2,3-triazole, 2-picryl-1,2,3-triazole and 4-nitro-1-picryl-1,2,3-triazole, 4-nitro-1-picryl-1,2,3-triazole differ dramatically in their impact sensitivity. Since these pairs of compounds have identical oxygen balance this strongly suggests that there is a difference in the decomposition mechanism. The authors report here the x-ray crystal structure, molecular orbital calculations, and {sup 13}C and {sup 1}H NMR spectra of the four compounds. The picryl substituents are essentially identical in all four cases. The most significant structural difference in the X-ray structures and in the molecular orbital calculations is a decrease in the N2-N3 bond length, accompanied by a lengthening of the adjacent bonds, in the two 1-picryl isomers relative to the corresponding bond lengths in the 2-picryl isomers. Molecular orbital calculations show that this leads to a low activation energy for the elimination of N{sub 2} from the 1-picryl isomers. They suggest that this initial step then leads to a reactive intermediate and is responsible for the large difference in sensitivity.

  11. Di(hydroxyphenyl)- 1,2,4-triazole monomers

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Wolf, Peter (Inventor)

    1993-01-01

    The di(hydroxyphenyl)- 1,2,4-triazole monomers were first synthesized by reacting bis (4-hydroxyphenyl) hydrazide with aniline hydrochloride at 250 C in the melt and also by reacting 1,3 or 1,4-bis- (4-hydroxyphenyl)- phenylene- dihydrazide with 2 moles of aniline hydrochloride in the melt. Purification of the di(hydroxyphenyl)- 1,2,4-triazole monomers was accomplished by recrystallization. Poly (1,2,4-triazoles) (PT) were prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenyl)- 1,2,4-triazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The reactions were carried out in polar aprotic solvents such as sulfolane or diphenylsulfone using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. This synthetic route has provided high molecular weight PT of new chemical structure, is economically and synthetically more favorable than other routes, and allows for facile chemical structure variation due to the availability of a large variety of activated aromatic dihalides.

  12. Effect of halogenation on yellow metal corrosion: Inhibition by triazoles

    SciTech Connect

    Lu, F.; Rao, N.M.; Yang, B.; Hoots, J.E.; Budrys, R.S. )

    1994-06-01

    Tolyltriazole (TT) is fed continuously into recirculating cooling water systems to inhibit corrosion of copper (Cu)-alloy heat exchangers. The adsorption isotherm and the corrosion rate profile for TT and butylbenzotriazole (BBT) were presented as functions of immersion time in triazole solution. Formation of a triazole film on a yellow metal surface was shown to play a major role in corrosion inhibition. In the absence of triazole in bulk solution, halogenation was detrimental to TT and BBT surface films. The disruption mechanism was attributable to chemical decomposition of the adsorbed triazole by halogen. However, adding TT (> 0.2 mg/l) to the halogen-based biocide solution improved stability of the protective TT film significantly. The improvement in stability was evident from the nearly unchanged surface coverage and lower corrosion rate. Based on this result, an enhanced TT-intermittent-feed method was developed. The metal surface was passivated initially with TT. Addition of halogen-based biocide was accompanied by a concurrent addition of TT (0.5 mg/l to 2 mg/l). Results demonstrated that the enhanced TT-intermittent-feed method performed better than the initial slug feeding of TT and BBT in inhibiting yellow metal corrosion.

  13. Triazole induced drought tolerance in horse chestnut (Aesculus hippocastanum).

    PubMed

    Percival, Glynn C; Noviss, Kelly

    2008-11-01

    We determined the influence of the triazole derivatives paclobutrazol, penconazole, epixiconazole, propiconazole and myclobutanil on the drought tolerance and post drought recovery of container-grown horse chestnut (Aesculus hippocastanum L.) saplings. Myclobutanil neither conferred drought resistance, as assessed by its effects on a number of physiological and biochemical parameters, nor affected growth parameters measured after recovery from drought. Chlorophyll fluorescence (F(v)/F(m)), photosynthetic rates, total foliar chlorophyll and carotenoid concentrations, foliar proline concentration and superoxide dismutase and catalase activities were consistently higher and leaf necrosis and cellular electrolyte leakage was lower at the end of a 3-week drought in trees treated with paclobutrazol, penconazole, epixiconazole or propiconazole than in control trees. Twelve weeks after drought treatment, leaf area and shoot, root and total plant dry masses were greater in triazole-treated trees than in control trees with the exception of those treated with myclobutanil. In a separate study, trees were subjected to a 2-week drought and then sprayed with paclobutrazol, penconazole, epixiconazole, propiconazole or myclobutanil. Chlorophyll fluorescence, photosynthetic rate, foliar chlorophyll concentration and catalase activity over the following 12 weeks were 20 to 50% higher in triazole-treated trees than in control trees. At the end of the 12-week recovery period, leaf area and shoot, root and total plant dry masses were higher in triazole-treated trees than in control trees, with the exception of trees treated with myclobutanil. Application of triazole derivatives, with the exception of myclobutanil, enhanced tolerance to prolonged drought and, when applied after a 2-week drought, hastened recovery from drought. The magnitude of treatment effects was in the order epixiconazole approximately propiconazole > penconazole > paclobutrazol > myclobutanil. PMID:18765373

  14. Transition-Metal-Catalyzed Denitrogenative Transannulation: Converting Triazoles into Other Heterocyclic Systems

    PubMed Central

    Chattopadhyay, Buddhadeb

    2012-01-01

    Transition metal catalyzed denitrogenative transannulation of a triazole ring has recently received considerable attention as a new concept for the construction of diverse nitrogen-containing heterocyclic cores. This method allows a single-step synthesis of complex nitrogen heterocycles from easily available and cheap triazole precursors. In this Minireview, recent progress of the transition metal catalyzed denitrogenative transannulation of a triazole ring, which was discovered in 2007, is discussed. PMID:22121072

  15. Heparin trisaccharides with nonreducing 2-amino-2-deoxy-alpha-D-glucopyranosyl end-groups suitable as substrates for catabolic enzymes.

    PubMed

    Weissmann, B; Chao, H

    1986-10-15

    Heparin trisaccharides having the sequence O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-(1----4)-O-alpha-L- idopyranosyluronic acid-(1----4)-2,5-anhydro-D-[1-3H]mannitol have been prepared, as substrate models for studying sulfatases of heparan sulfate catabolism, by alpha-L-iduronidase cleavage of previously reported heparin tetrasaccharides, with additional chemical and enzymic modification as required. Three series are described, including isomeric sulfate esters of that trisaccharide with no N-substituent, with N-acetyl substitution, and with N-sulfate substitution. New features of the substrate specificity of the hydrolases used, including iduronate sulfatase, alpha-L-iduronidase, glucosamine 6-sulfate sulfatase, and heparin sulfamidase, were observed, and simple procedures for partial purification of these hydrolases are reported. The structures assigned to the trisaccharides are supported by the mode of preparation, reactions, regularities in electrophoretic behavior, and identities of the products of deamination. PMID:3791294

  16. Synthesis and cytotoxic evaluation of novel indenoisoquinoline-substituted triazole hybrids.

    PubMed

    Pham Thi, Tham; Le Nhat, Thuy Giang; Ngo Hanh, Thuong; Luc Quang, Tan; Pham The, Chinh; Dang Thi, Tuyet Anh; Nguyen, Ha Thanh; Nguyen, Thu Ha; Hoang Thi, Phuong; Van Nguyen, Tuyen

    2016-08-01

    The synthesis of various substituted triazole-indenoisoquinoline hybrids was performed based on a CuI-catalyzed 1,3-cycloaddition between propargyl-substituted derivatives and the azide-containing indenoisoquinoline. Besides, a variety of N-(alkyl)propargylindenoisoquinolines was used as substrates for the construction of triazole-indenoisoquinoline-AZT conjugated via a click chemistry-mediated coupling with 3'-azido-3'-deoxythymidine (AZT). Thus, twenty three new indenoisoquinoline-substituted triazole hybrids were successfully prepared and evaluated as cytotoxic agents, revealing an interesting anticancer activity of four triazole linker-indenoisoquinoline-AZT hybrids in KB and HepG2 cancer cell lines. PMID:27342752

  17. Thermotropic phase properties of 1,2-di-O-tetradecyl-3-O-(3-O-methyl- beta-D-glucopyranosyl)-sn-glycerol.

    PubMed Central

    Trouard, T P; Mannock, D A; Lindblom, G; Rilfors, L; Akiyama, M; McElhaney, R N

    1994-01-01

    The hydration properties and the phase structure of 1,2-di-O-tetradecyl-3-O(3-O-methyl-beta-D-glucopyranosyl)-sn-glycerol (3-O-Me-beta-D-GlcDAIG) in water have been studied via differential scanning calorimetry, 1H-NMR and 2H-NMR spectroscopy, and x-ray diffraction. Results indicate that this lipid forms a crystalline (Lc) phase up to temperatures of 60-70 degrees C, where a transition through a metastable reversed hexagonal (Hll) phase to a reversed micellar solution (L2) phase occurs. Experiments were carried out at water concentrations in a range from 0 to 35 wt%, which indicate that all phases are poorly hydrated, taking up < 5 mol water/mol lipid. The absence of a lamellar liquid crystalline (L alpha) phase and the low levels of hydration measured in the discernible phases suggest that the methylation of the saccharide moiety alters the hydrogen bonding properties of the headgroup in such a way that the 3-O-Me-beta-D-GlcDAIG headgroup cannot achieve the same level of hydration as the unmethylated form. Thus, in spite of the small increase in steric bulk resulting from methylation, there is an increase in the tendency of 3-O-Me-beta-D-GlcDAIG to form nonlamellar structures. A similar phase behavior has previously been observed for the Acholeplasma laidlawii A membrane lipid 1,2-diacyl-3-O-(6-O-acyl-alpha-D-glucopyranosyl)-sn-glycerol in water (Lindblom et al. 1993. J. Biol. Chem. 268:16198-16207). The phase behavior of the two lipids suggests that hydrophobic substitution of a hydroxyl group in the sugar ring of the glucopyranosylglycerols has a very strong effect on their physicochemical properties, i.e., headgroup hydration and the formation of different lipid aggregate structures. PMID:7811919

  18. Regioselective Amine-Borane Cyclization: Towards the Synthesis of 1,2-BN-3-Cyclohexene by Copper-Assisted Triazole/Gold Catalysis.

    PubMed

    Motika, Stephen E; Wang, Qiaoyi; Akhmedov, Novruz G; Wojtas, Lukasz; Shi, Xiaodong

    2016-09-12

    The combination of triazole/gold (TA-Au) and Cu(OTf)2 is identified as the optimal catalytic system for promoting intramolecular hydroboration for the synthesis of a six-membered cyclic amine-borane. Excellent yields (up to 95 %) and regioselectivities (5-exo vs. 6-endo) were achieved through catalyst control and sequential dilution. Good functional-group tolerance was attained, thus allowing the preparation of highly functionalized cyclic amine-borane substrates, which could not be achieved using other methods. Deuterium-labeling studies support the involvement of a hydride addition to a gold-activated alkyne with subsequent C-B bond formation. PMID:27532900

  19. Itraconazole, a new triazole that is orally active in aspergillosis.

    PubMed Central

    Van Cutsem, J; Van Gerven, F; Van de Ven, M A; Borgers, M; Janssen, P A

    1984-01-01

    Itraconazole is a new orally active triazole derivative with broad-spectrum antifungal activity. This drug is effective in experimental aspergillosis and possesses in vitro activity against various species and strains of Aspergillus. Morphological destruction of inoculated hyphae and complete inhibition of hyphal outgrowth in culture is obtained from 0.07 micrograms ml-1 (10(-7)M) onward. These properties make itraconazole a likely candidate for clinical evaluation in disseminated aspergillosis. Images PMID:6097167

  20. Cationic heteroleptic cyclometalated iridium(III) complexes containing phenyl-triazole and triazole-pyridine clicked ligands.

    PubMed

    Felici, Marco; Contreras-Carballada, Pablo; Smits, Jan M M; Nolte, Roeland J M; Williams, René M; De Cola, Luisa; Feiters, Martin C

    2010-03-01

    Novel heteroleptic iridium complexes containing the 1-substituted-4-phenyl-1H-1,2,3-triazole (phtl) cyclometalating ligand have been synthesized. The 3+2 Huisgen dipolar cycloaddition method ('click' chemistry) was utilized to prepare a class of bidentate ligands (phtl) bearing different substituents on the triazole moiety. By using various ligands (phtl-R1 and pytl-R2) (R1 = adamantane, methyl and R2 = adamantane, methyl, beta-cyclodextrin, ursodeoxycholic acid), we prepared a small library of new luminescent ionic iridium complexes [Ir(phtr-R1)2(pytl-R2)]Cl and report on their photophysical properties. The flexibility of the clicking approach allows a straightforward control on the chemical-physical properties of the complexes by varying the nature of the substituent on the ligand. PMID:20336031

  1. ENANTIOSELECTIVE IN VITRO METABOLISM OF THE TRIAZOLE FUNGICIDES BROMUCONAZOLE AND TRIADIMEFON USING RAT HEPATIC MICROSOMES

    EPA Science Inventory

    We report on the in vitro metabolism of the enantiomers of two triazole fungicides: triadimefon [two enantiomers; 1-(4-chlorophneoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one] and bromuconazole {two diastereomers, each having two enantiomers; 1-[(2RS,4RS:2RS,4SR)-4-brom...

  2. Synthesis of 1,4,5-trisubstituted 1,2,3-triazoles amicable for automation.

    PubMed

    Kavitha, Mitta; Mahipal, Bodugam; Mainkar, Prathama S; Chandrasekhar, Srivari

    2013-09-01

    A three-component 3+2 cycloaddition reaction followed by Suzuki coupling reaction was carried out to synthesize a library of compounds using automation (parallel synthesizer). Scaffolds that are unexplored in literature were used for the synthesis of library. The iodo-triazoles formed by 3+2 cycloaddition reaction were coupled with boronic acids to get tri-substituted triazoles. PMID:23597250

  3. Nutrition Labeling

    NASA Astrophysics Data System (ADS)

    Metzger, Lloyd E.

    Nutrition labeling regulations differ in countries around the world. The focus of this chapter is on nutrition labeling regulations in the USA, as specified by the Food and Drug Administration (FDA) and the Food Safety and Inspection Service (FSIS) of the United States Department of Agriculture (USDA). A major reason for analyzing the chemical components of foods in the USA is nutrition labeling regulations. Nutrition label information is not only legally required in many countries, but also is of increasing importance to consumers as they focus more on health and wellness.

  4. Carbohydrate-Binding Module–Cyclodextrin Glycosyltransferase Fusion Enables Efficient Synthesis of 2-O-d-Glucopyranosyl-l-Ascorbic Acid with Soluble Starch as the Glycosyl Donor

    PubMed Central

    Han, Ruizhi; Li, Jianghua; Shin, Hyun-Dong; Chen, Rachel R.; Du, Guocheng

    2013-01-01

    In this study, we achieved the efficient synthesis of 2-O-d-glucopyranosyl-l-ascorbic acid (AA-2G) from soluble starch by fusing a carbohydrate-binding module (CBM) from Alkalimonas amylolytica α-amylase (CBMAmy) to cyclodextrin glycosyltransferase (CGTase) from Paenibacillus macerans. One fusion enzyme, CGT-CBMAmy, was constructed by fusing the CBMAmy to the C-terminal region of CGTase, and the other fusion enzyme, CGTΔE-CBMAmy, was obtained by replacing the E domain of CGTase with CBMAmy. The two fusion enzymes were then used to synthesize AA-2G from soluble starch as a cheap and easily soluble glycosyl donor. Under the optimal conditions, the AA-2G yields produced using CGTΔE-CBMAmy and CGT-CBMAmy were 2.01 g/liter and 3.03 g/liter, respectively, which were 3.94- and 5.94-fold of the yield from the wild-type CGTase (0.51 g/liter). The reaction kinetics of the two fusion enzymes were analyzed and modeled to confirm the enhanced specificity toward soluble starch. It was also found that, compared to the wild-type CGTase, the two fusion enzymes had relatively high hydrolysis and disproportionation activities, factors that favor AA-2G synthesis. Finally, it was speculated that the enhancement of soluble starch specificity may be related to the changes of substrate binding ability and the substrate binding sites between the CBM and the starch granule. PMID:23503312

  5. 3-β-D-Glucopyranosyl-6-methoxy-2-benzoxazolinone (MBOA-N-Glc) is an insect detoxification product of maize 1,4-benzoxazin-3-ones.

    PubMed

    Maag, Daniel; Dalvit, Claudio; Thevenet, Damien; Köhler, Angela; Wouters, Felipe C; Vassão, Daniel G; Gershenzon, Jonathan; Wolfender, Jean-Luc; Turlings, Ted C J; Erb, Matthias; Glauser, Gaetan

    2014-06-01

    In order to defend themselves against arthropod herbivores, maize plants produce 1,4-benzoxazin-3-ones (BXs), which are stored as weakly active glucosides in the vacuole. Upon tissue disruption, BXs come into contact with β-glucosidases, resulting in the release of active aglycones and their breakdown products. While some aglycones can be reglucosylated by specialist herbivores, little is known about how they detoxify BX breakdown products. Here we report on the structure of an N-glucoside, 3-β-d-glucopyranosyl-6-methoxy-2-benzoxazolinone (MBOA-N-Glc), purified from Spodoptera frugiperda faeces. In vitro assays showed that MBOA-N-Glc is formed enzymatically in the insect gut using the BX breakdown product 6-methoxy-2-benzoxazolinone (MBOA) as precursor. While Spodoptera littoralis and S. frugiperda caterpillars readily glucosylated MBOA, larvae of the European corn borer Ostrinia nubilalis were hardly able to process the molecule. Accordingly, Spodoptera caterpillar growth was unaffected by the presence of MBOA, while O. nubilalis growth was reduced. We conclude that glucosylation of MBOA is an important detoxification mechanism that helps insects tolerate maize BXs. PMID:24713572

  6. Isolation of sophorose during sophorolipid production and studies of its stability in aqueous alkali: epimerisation of sophorose to 2-O-β-D-glucopyranosyl-D-mannose.

    PubMed

    Al-Jasim, Ammar; Davis, Mark; Cossar, Douglas; Miller, Timothy; Humphreys, Paul; Laws, Andrew P

    2016-02-01

    NMR and anion exchange chromatography analysis of the waste streams generated during the commercial production of sophorolipids by the yeast Candida bombicola identified the presence of small but significant quantities (1% w/v) of free sophorose. Sophorose, a valuable disaccharide, was isolated from the aqueous wastes using a simple extraction procedure and was purified by chromatography on a carbon celite column providing easy access to large quantities of the disaccharide. Experiments were undertaken to identify the origin of sophorose and it is likely that acetylated sophorose derivatives were produced by an enzyme catalysed hydrolysis of the glucosyl-lipid bond of sophorolipids; the acetylated sophorose derivatives then undergo hydrolysis to release the parent disaccharide. Treatment of sophorose with aqueous alkali at elevated temperatures (0.1M NaOH at 50 °C) resulted in C2-epimerisation of the terminal reducing sugar and its conversion to the corresponding 2-O-β-D-glucopyranosyl-D-mannose which was isolated and characterised. In aqueous alkaline solution β-(1,2)-linked glycosidic bonds do not undergo either hydrolysis or peeling reactions. PMID:26774878

  7. The ginsenoside 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol induces autophagy and apoptosis in human melanoma via AMPK/JNK phosphorylation.

    PubMed

    Kang, Soouk; Kim, Jong-Eun; Song, Nu Ry; Jung, Sung Keun; Lee, Mee Hyun; Park, Jun Seong; Yeom, Myeong-Hun; Bode, Ann M; Dong, Zigang; Lee, Ki Won

    2014-01-01

    Studies have shown that a major metabolite of the red ginseng ginsenoside Rb1, called 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol (GPD), exhibits anticancer properties. However, the chemotherapeutic effects and molecular mechanisms behind GPD action in human melanoma have not been previously investigated. Here we report the anticancer activity of GPD and its mechanism of action in melanoma cells. GPD, but not its parent compound Rb1, inhibited melanoma cell proliferation in a dose-dependent manner. Further investigation revealed that GPD treatment achieved this inhibition through the induction of autophagy and apoptosis, while Rb1 failed to show significant effect at the same concentrations. The inhibitory effect of GPD appears to be mediated through the induction of AMPK and the subsequent attenuation of mTOR phosphorylation. In addition, GPD activated c-Jun by inducing JNK phosphorylation. Our findings suggest that GPD suppresses melanoma growth by inducing autophagic cell death and apoptosis via AMPK/JNK pathway activation. GPD therefore has the potential to be developed as a chemotherapeutic agent for the treatment of human melanoma. PMID:25137374

  8. Protection of free radical-induced cytotoxicity by 2-O-α-D-glucopyranosyl-L-ascorbic acid in human dermal fibroblasts.

    PubMed

    Hanada, Yukako; Iomori, Atsuko; Ishii, Rie; Gohda, Eiichi; Tai, Akihiro

    2014-01-01

    The stable ascorbic acid (AA) derivative, 2-O-α-D-glucopyranosyl-L-ascorbic acid (AA-2G), exhibits vitamin C activity after enzymatic hydrolysis to AA. The biological activity of AA-2G per se has not been studied in detail, although AA-2G has been noted as a stable source for AA supply. The protective effect of AA-2G against the oxidative cell death of human dermal fibroblasts induced by incubating with 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) for 24 h was investigated in this study. AA-2G showed a significant protective effect against the oxidative stress in a concentration-dependent manner. AA-2G did not exert a protective effect during the initial 12 h of incubation, but had a significant protective effect in the later part of the incubation period. Experiments using a α-glucosidase inhibitor and comparative experiments using a stereoisomer of AA-2G confirmed that AA-2G had a protective effect against AAPH-induced cytotoxicity without being converted to AA. Our results provide an insight into the efficacy of AA-2G as a biologically interesting antioxidant and suggest the practical use of AA-2G even before being converted into AA as a beneficial antioxidant. PMID:25036685

  9. Mechanism of Action of Efinaconazole, a Novel Triazole Antifungal Agent

    PubMed Central

    Nagashima, Maria; Shibanushi, Toshiyuki; Iwata, Atsushi; Kangawa, Yumi; Inui, Fumie; Siu, William J. Jo; Pillai, Radhakrishnan; Nishiyama, Yayoi

    2013-01-01

    The mechanism of action of efinaconazole, a new triazole antifungal, was investigated with Trichophyton mentagrophytes and Candida albicans. Efinaconazole dose-dependently decreased ergosterol production and accumulated 4,4-dimethylsterols and 4α-methylsterols at concentrations below its MICs. Efinaconazole induced morphological and ultrastructural changes in T. mentagrophytes hyphae that became more prominent with increasing drug concentrations. In conclusion, the primary mechanism of action of efinaconazole is blockage of ergosterol biosynthesis, presumably through sterol 14α-demethylase inhibition, leading to secondary degenerative changes. PMID:23459486

  10. Towards alpha- or beta-D-C-glycosyl compounds by tin-catalyzed addition of glycosyl radicals to acrylonitrile and vinylphosphonate, and flexible reduction of tetra-O-acetyl-alpha-D-glucopyranosyl bromide with cyanoborohydride.

    PubMed

    Praly, Jean-Pierre; Ardakani, Azin Salek; Bruyère, Isabelle; Marie-Luce, Chrystelle; Bing Qin, Bing

    2002-10-01

    Photo-induced radical addition of acetylated alpha-D-glucopyranosyl bromide (1). to acrylonitrile or diethyl vinylphosphonate, in the presence of catalytic amounts of tri-n-butyltin chloride and sodium (or tetra-n-butylammonium) cyanoborohydride in excess, allowed efficient preparations of alpha-configurated nonononitrile and 2-(alpha-D-glucopyranosyl)-ethylphosphonate (79, 70% yields, respectively). These conditions led to 2-(alpha-D-manno-, and galactopyranosyl)-ethylphosphonates in 68 and 76% yields. Similarly, radical addition of acetylated 1-bromo-beta-D-glucopyranosyl chloride (2). to acrylonitrile or diethyl vinylphosphonate afforded mainly intermediate chlorides which, upon radical reduction with excess tri-n-butyltin hydride, afforded the corresponding beta anomers (40 and 38%, respectively) by sequential C-C and C-H bond formation. Stereocontrol relies on the alpha-stereoselective quenching of D-glycopyranos-1-yl radicals. We found also that UV light irradiation of 1 with excess NaBH(3)CN in tert-butanol afforded either 1,3,4,6-tetra-O-acetyl-2-deoxy-alpha-D-arabino-hexopyranose (65% after crystallization) or, when 10% mol thiophenol was added, 2,3,4,6-tetra-O-acetyl-1,5-anhydro-D-glucitol (79%). These are simple, tin-free, and easily controlled conditions, which compare well with known preparations of these reduced sugars. PMID:12423963

  11. S-Farnesyl-Thiopropionic Acid Triazoles as Potent Inhibitors of Isoprenylcysteine Carboxyl Methyltransferase

    PubMed Central

    2011-01-01

    We report the design and synthesis of novel FTPA-triazole compounds as potent inhibitors of isoprenylcysteine carboxyl methyltransferase (Icmt), through a focus on thioether and isoprenoid mimetics. These mimetics were coupled utilizing a copper-assisted cycloaddition to assemble the potential inhibitors. Using the resulting triazole from the coupling as an isoprenyl mimetic resulted in the biphenyl-substituted FTPA triazole 10n. This lipid-modified analogue is a potent inhibitor of Icmt (IC50 = 0.8 ± 0.1 μM; calculated Ki = 0.4 μM). PMID:22754607

  12. Therapeutic drug monitoring for triazoles: A needs assessment review and recommendations from a Canadian perspective

    PubMed Central

    Laverdiere, Michel; Bow, Eric J; Rotstein, Coleman; Autmizguine, Julie; Broady, Raewyn; Garber, Gary; Haider, Shariq; Hussaini, Trana; Husain, Shahid; Ovetchkine, Philippe; Seki, Jack T; Théorêt, Yves

    2014-01-01

    Invasive fungal infections cause significant morbidity and mortality in patients with concomitant underlying immunosuppressive diseases. The recent addition of new triazoles to the antifungal armamentarium has allowed for extended-spectrum activity and flexibility of administration. Over the years, clinical use has raised concerns about the degree of drug exposure following standard approved drug dosing, questioning the need for therapeutic drug monitoring (TDM). Accordingly, the present guidelines focus on TDM of triazole antifungal agents. A review of the rationale for triazole TDM, the targeted patient populations and available laboratory methods, as well as practical recommendations based on current evidence from an extended literature review are provided in the present document. PMID:25587296

  13. Synthesis and biochemical evaluation of triazole/tetrazole-containing sulfonamides against thrombin and related serine proteases

    PubMed Central

    Siles, Rogelio; Kawasaki, Yuko; Ross, Patrick; Freire, Ernesto

    2011-01-01

    A small library of 25 triazole/tetrazole-based sulfonamides have been synthesized and further evaluated for their inhibitory activity against thrombin, trypsin, tryptase and chymase. In general, the triazole-based sulfonamides inhibited thrombin more efficiently than the tetrazole counterparts. Particularly, compound 26 showed strong thrombin inhibition (Ki =880 nM) and significant selectivity against other human related serine proteases like trypsin (Ki =729 µM). Thrombin binding affinity of the same compound was determined by ITC and demonstrated that the binding of this new triazole-based scaffold is enthalpically driven, making it a good candidate for further development. PMID:21807511

  14. Synthesis of a simplified triazole analogue of pateamine A.

    PubMed

    Hemi Cumming, A; Brown, Sarah L; Tao, Xu; Cuyamendous, Claire; Field, Jessica J; Miller, John H; Harvey, Joanne E; Teesdale-Spittle, Paul H

    2016-06-14

    Pateamine A is a naturally occurring metabolite extracted from the marine sponge Mycale hentscheli. It exhibits potent cytotoxicity towards cancer cell lines and has been shown to target protein translation initiation via inhibition of the function of eukaryotic initiation factor 4A proteins. We have synthesised a simplified analogue of pateamine A, consisting of the skeletal core of the natural product but with the thiazole heterocycle replaced by a triazole. The convergent design of the synthesis features a base-induced opening of a δ-valerolactone to access the Z,E-dienoate moiety, Julia-Kocienski olefination and copper-catalysed azide-alkyne cycloaddition. Bioactivity testing of the simplified pateamine A analogue (3) indicated a significant reduction in cytotoxicity, compared to natural pateamine A. We propose that this reduced activity is due mainly to the substitution of the thiazole for the triazole heterocycle. This supports the hypothesis that the thiazole of pateamine A is important for binding to its biological target. PMID:27180995

  15. Cytotoxicity, Antioxidant and Apoptosis Studies of Quercetin-3-O Glucoside and 4-(β-D-Glucopyranosyl-1→4-α-L-Rhamnopyranosyloxy)-Benzyl Isothiocyanate from Moringa oleifera.

    PubMed

    Maiyo, Fiona C; Moodley, Roshila; Singh, Moganavelli

    2016-01-01

    Moringa oleifera, from the family Moringaceae, is used as a source of vegetable and herbal medicine and in the treatment of various cancers in many African countries, including Kenya. The present study involved the phytochemical analyses of the crude extracts of M.oleifera and biological activities (antioxidant, cytotoxicity and induction of apoptosis in-vitro) of selected isolated compounds. The compounds isolated from the leaves and seeds of the plant were quercetin-3-O-glucoside (1), 4-(β-D-glucopyranosyl-1→4-α-L-rhamnopyranosyloxy)-benzyl isothiocyanate (2), lutein (3), and sitosterol (4). Antioxidant activity of compound 1 was significant when compared to that of the control, while compound 2 showed moderate activity. The cytotoxicity of compounds 1 and 2 were tested in three cell lines, viz. liver hepatocellular carcinoma (HepG2), colon carcinoma (Caco-2) and a non-cancer cell line Human Embryonic Kidney (HEK293), using the MTT cell viability assay and compared against a standard anticancer drug, 5-fluorouracil. Apoptosis studies were carried out using the acridine orange/ethidium bromide dual staining method. The isolated compounds showed selective in vitro cytotoxic and apoptotic activity against human cancer and non-cancer cell lines, respectively. Compound 1 showed significant cytotoxicity against the Caco-2 cell line with an IC50 of 79 μg mL(-1) and moderate cytotoxicity against the HepG2 cell line with an IC50 of 150 μg mL(-1), while compound 2 showed significant cytotoxicity against the Caco- 2 and HepG2 cell lines with an IC50 of 45 μg mL(-1) and 60 μg mL(-1), respectively. Comparatively both compounds showed much lower cytotoxicity against the HEK293 cell line with IC50 values of 186 μg mL(-1) and 224 μg mL(-1), respectively. PMID:26428271

  16. Anti-inflammatory effect of 3-O-[(6'-O-palmitoyl)-β-D-glucopyranosyl sitosterol] from Agave angustifolia on ear edema in mice.

    PubMed

    Hernández-Valle, Elizabeth; Herrera-Ruiz, Maribel; Salgado, Gabriela Rosas; Zamilpa, Alejandro; Ocampo, Martha Lucia Arenas; Aparicio, Antonio Jiménez; Tortoriello, Jaime; Jiménez-Ferrer, Enrique

    2014-01-01

    In Mexico Agave angustifolia has traditionally been used to treat inflammation. The aim of this study was to measure the anti-inflammatory effect of the extract of A. angustifolia, the isolation and identification of active compounds. From the acetone extract two active fractions were obtained, (AsF13 and AaF16). For the characterization of pharmacological activity, the acute inflammatory model of mouse ear edema induced with TPA was used. The tissue exposed to TPA and treatments were subjected to two analysis, cytokine quantification (IL-1β, IL-6, IL-10 and TNF-α) and histopathological evaluation. The active fraction (AaF16) consisted principally of 3-O-[(6'-O-palmitoyl)-β-D-glucopyranpsyl] sitosterol. In AaF13 fraction was identified β-sitosteryl glucoside (2) and stigmasterol (3). The three treatments tested showed a concentration-dependent anti-inflammatory effect (AaAc Emax = 33.10%, EC50 = 0.126 mg/ear; AaF13 Emax = 54.22%, EC50 = 0.0524 mg/ear; AaF16 Emax = 61.01%, EC50 = 0.050 mg/ear). The application of TPA caused a significant increase on level of IL-1β, IL-6 and TNFα compared with basal condition, which was countered by any of the experimental treatments. Moreover, the experimental treatments induced a significant increase in the levels of IL-4 and IL-10, compared to the level observed when stimulated with TPA. Therefore, the anti-inflammatory effect of Agave angustifolia, is associated with the presence of 3-O-[(6'-O-palmitoyl)-β-D-glucopyranosyl] sitosterol. PMID:25268718

  17. Iterative Saturation Mutagenesis of −6 Subsite Residues in Cyclodextrin Glycosyltransferase from Paenibacillus macerans To Improve Maltodextrin Specificity for 2-O-d-Glucopyranosyl-l-Ascorbic Acid Synthesis

    PubMed Central

    Han, Ruizhi; Shin, Hyun-dong; Chen, Rachel R.; Li, Jianghua; Chen, Jian

    2013-01-01

    2-O-d-Glucopyranosyl-l-ascorbic acid (AA-2G), a stable l-ascorbic acid derivative, is usually synthesized by cyclodextrin glycosyltransferase (CGTase), which contains nine substrate-binding subsites (from +2 to −7). In this study, iterative saturation mutagenesis (ISM) was performed on the −6 subsite residues (Y167, G179, G180, and N193) in the CGTase from Paenibacillus macerans to improve its specificity for maltodextrin, which is a cheap and easily soluble glycosyl donor for AA-2G synthesis. Site saturation mutagenesis of four sites—Y167, G179, G180, and N193—was first performed and revealed that four mutants—Y167S, G179R, N193R, and G180R—produced AA-2G yields higher than those of other mutant and wild-type CGTases. ISM was then conducted with the best positive mutant as a template. Under optimal conditions, mutant Y167S/G179K/N193R/G180R produced the highest AA-2G titer of 2.12 g/liter, which was 84% higher than that (1.15 g/liter) produced by the wild-type CGTase. Kinetics analysis of AA-2G synthesis using mutant CGTases confirmed the enhanced maltodextrin specificity and showed that compared to the wild-type CGTase, the mutants had no cyclization activity but high hydrolysis and disproportionation activities. A possible mechanism for the enhanced substrate specificity was also analyzed through structure modeling of the mutant and wild-type CGTases. These results indicated that the −6 subsite played crucial roles in the substrate binding and catalytic reactions of CGTase and that the obtained CGTase mutants, especially Y167S/G179K/N193R/G180R, are promising starting points for further development through protein engineering. PMID:24077706

  18. Therapeutic effect of umbelliferon-α-D-glucopyranosyl-(2(I)→1(II))-α-D-glucopyranoside on adjuvant-induced arthritic rats.

    PubMed

    Kumar, Vikas; Anwar, Firoz; Verma, Amita; Mujeeb, Mohd

    2015-06-01

    The aim and objective of the present investigation was to evaluate the antiarthritic and antioxidant effect of umbelliferon-α-D-glucopyranosyl-(2I→1II)-α-D-glucopyranoside (UFD) in chemically induced arthritic rats. The different doses of the UFD were tested against the turpentine oil (TO), formaldehyde induced acute arthritis and complete fruend's adjuvant (CFA) induced chronic arthritis in Wistar rats. Arthritic assessment and body weight was measured at regular interval till 28 days. On day 28, all the groups animals were anaesthetized, blood were collected from the puncturing the ratro orbital and estimated the hematological parameters. The animals were sacrificed; synovial tissue was extracted and estimated the malonaldehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD). The different doses of the UFD showed the protective effect against turpentine oil, formaldehyde induced acute arthritis and CFA induced chronic arthritis at dose dependent manner. Acute model of arthritis such as TOand formaldehyde induced inflammation due to releasing of the inflammatory mediators; significantly inhibited by the UFD at dose dependent manner. CFA induced arthritic rats treated with the different doses of the UFD showed the inhibitory effect on the delayed increase in joint diameter as seen in arthritic control group rats. UFD significantly improved the arthritic index, body weight and confirmed the antiarthritic effect. UFD showed the effect on the hematological parameter such as improved the level of the RBC, Hb and decline the level of the EBC, ESR and confirmed the immune suppressive effect. UFD significantly improved the level of the endogenous antioxidant and confirmed the antioxidant effect. This present investigation suggests that the UFD has prominent antiarthritic impact which can be endorsed to its antiarthritic and antioxidant effects. PMID:26028721

  19. Computational studies on energetic properties of trinitro-substituted imidazole-triazole and pyrazole-triazole derivatives.

    PubMed

    Ghule, Vikas D

    2012-09-20

    Heats of formation (HOFs) for 24 designed compounds were obtained by using the density functional theory (DFT). Molecular structures were investigated at the B3PW91/6-31G(d,p) level, and isodesmic reactions were designed for calculating the gas phase heats of formation. The solid state heats of formation for designed compounds were calculated by the Politzer approach using heats of sublimation. All the designed compounds possess solid state heats of formation above 140 kJ/mol. The distance between nitro groups influences the steric and repulsive interactions. Detonation performances were evaluated by the Kamlet-Jacobs equations based on the predicted densities and solid state heats of formation, and susceptibility of decomposition was studied by the computations of bond dissociation energy (BDE). Further, the present study might provide useful information for the structure-property relationship, the laboratory synthesis of imidazole-triazole and pyrazole-triazole based nitro derivatives and the development of novel high energy materials (HEMs). PMID:22924573

  20. RAMAN SPECTROSCOPY-BASED METABOLOMICS FOR DIFFERENTIATING EXPOSURES TO TRIAZOLE FUNGICIDES USING RAT URINE

    EPA Science Inventory

    Normal Raman spectroscopy was evaluated as a metabolomic tool for assessing the impacts of exposure to environmental contaminants, using rat urine collected during the course of a toxicological study. Specifically, one of three triazole fungicides, myclobutanil, propiconazole or ...

  1. TRIADIMEFON, A TRIAZOLE FUNGICIDE, INDUCES STEREOTYPED BEHAVIOR AND ALTERS MONOAMINE METABOLISM IN RATS

    EPA Science Inventory

    Triadimefon, a triazole fungicide, has been observed to increase locomotion and induce stereotyped behavior in rodents. he present experiments characterized the stereotyped behavior induced by triadimefon using a computer-supported observational method, and tested the hypothesis ...

  2. 1,2,4-triazole derivatives as potential scaffold for anticonvulsant activity.

    PubMed

    Kamboj, Vipan K; Verma, Prabhakar K; Dhanda, Anu; Ranjan, Sudhir

    2015-01-01

    The search for new anticonvulsant agent with more selectivity and lower toxicity continues to be an area of rigorous investigation in medicinal chemistry. Epilepsy is a chronic disorder of brain whose treatment consists of controlling seizures with antiepileptic drugs that very often related with side-effects which in rare circumstances can be potentially life-threatening. Triazolam and Alprazolam are established drugs used in epilepsy which have triazole moiety. The potency and broad spectrum of the pharmacological response of triazole moiety as anticonvulsant agent have attracted the attention of medicinal chemists to explore this framework for its potential. The literature shows that different substitution on triazole ring exhibit potent antiepileptic activity with no or lesser neurotoxicity. The present review is a sincere attempt to compile the reported potent triazole derivatives with significant anticonvulsant action. PMID:25675400

  3. Toxicogenomic Effects Common to Triazole Antifungals and Conserved Between Rats and Humans

    EPA Science Inventory

    The triazole antifungals myclobutanil, propiconazole and triadimefon cause varying degrees of hepatic toxicity and disrupt steroid hormone homeostasis in rodent in vivo models. To identify biological pathways consistently modulated across multiple time-points and various study d...

  4. Mode of Action for Reproductive and Hepatic Toxicity Inferred from a Genomic Study of Triazole Antifungals

    EPA Science Inventory

    The mode of action for the reproductive toxicity of triazole antifungals have been previously characterized by an observed increased in serum testosterone, hepatotoxicity, and reduced insemination and fertility indices. In order to refine our mechanistic understanding of these m...

  5. USING PHARMACOKINETIC DATA TO INTERPRET METABOLOMIC CHANGES IN CD-1 MICE TREATED WITH TRIAZOLE FUNGICIDES

    EPA Science Inventory

    Triazoles are a class of fungicides widely used in both pharmaceutical and agricultural applications. These compounds elicit a variety of toxic effects including disruption of normal metabolic processes such as steroidogenesis. Metabolomics is used to measure dynamic changes in e...

  6. ENANTIOSELECTIVE FORMATION OF THE TRIAZOLE FUNGICIDE TRIADIMENOL FROM TRIADIMEFON IN MAMMAL AND FISH HEPATIC MICROSOMES

    EPA Science Inventory

    Triazole containing compounds are used extensively in both agriculture and medicine for the control of fungal infections. Recently, emphasis has been placed on the potential adverse effects of these compounds within mammalian systems. Triadimefon is a common agricultural fungici...

  7. Diesel lubricant composition containing 5-amino-triazole-succinic anhydride reaction product

    SciTech Connect

    Sung, R.L.; Zoleski, B.H.

    1981-03-17

    A diesel crankcase lubricant is described. It contains a lubricating oil base and the reaction product of a hydrocarbyl succinic anhydride. The hydrocarbyl radical has from 12 to 30 carbon atoms and 5-amino-triazole.

  8. Gene Expression Profiling in Liver and Testis of Rats to Characterize the Toxicity of Triazole Fungicides

    EPA Science Inventory

    Four triazole fungicides were studied using toxicogenomic techniques to identify potential mechanisms of action. Adult male Sprague-Dawley rats were dosed for 14 days by gavage with fluconazole, myclobutanil, propiconazole, or triadimefon. Following exposure, serum was collected ...

  9. GENE EXPRESSION PROFILING IN LIVER AND TESTIS OF RATS TO CHARACTERIZE THE TOXICITY OF TRIAZOLE FUNGICIDES.

    EPA Science Inventory

    Four triazole fungicides were studied using toxicogenomic techniques to identify potential mechanisms of action. Adult male Sprague-Dawley rats were dosed for 14 days by gavage with fluconazole, myclobutanil, propiconazole, or triadimefon. Following exposure, serum was collected ...

  10. Gene expression profiling in liver and testis of rats to characterize the toxicity of triazole fungicides

    SciTech Connect

    Tully, Douglas B.; Bao Wenjun; Goetz, Amber K.; Blystone, Chad R.; Ren, Hongzu; Schmid, Judith E.; Strader, Lillian F.; Wood, Carmen R.; Best, Deborah S.; Narotsky, Michael G.; Wolf, Douglas C.; Rockett, John C.; Dix, David J. . E-mail: dix.david@epa.gov

    2006-09-15

    Four triazole fungicides were studied using toxicogenomic techniques to identify potential mechanisms of action. Adult male Sprague-Dawley rats were dosed for 14 days by gavage with fluconazole, myclobutanil, propiconazole, or triadimefon. Following exposure, serum was collected for hormone measurements, and liver and testes were collected for histology, enzyme biochemistry, or gene expression profiling. Body and testis weights were unaffected, but liver weights were significantly increased by all four triazoles, and hepatocytes exhibited centrilobular hypertrophy. Myclobutanil exposure increased serum testosterone and decreased sperm motility, but no treatment-related testis histopathology was observed. We hypothesized that gene expression profiles would identify potential mechanisms of toxicity and used DNA microarrays and quantitative real-time PCR (qPCR) to generate profiles. Triazole fungicides are designed to inhibit fungal cytochrome P450 (CYP) 51 enzyme but can also modulate the expression and function of mammalian CYP genes and enzymes. Triazoles affected the expression of numerous CYP genes in rat liver and testis, including multiple Cyp2c and Cyp3a isoforms as well as other xenobiotic metabolizing enzyme (XME) and transporter genes. For some genes, such as Ces2 and Udpgtr2, all four triazoles had similar effects on expression, suggesting possible common mechanisms of action. Many of these CYP, XME and transporter genes are regulated by xeno-sensing nuclear receptors, and hierarchical clustering of CAR/PXR-regulated genes demonstrated the similarities of toxicogenomic responses in liver between all four triazoles and in testis between myclobutanil and triadimefon. Triazoles also affected expression of multiple genes involved in steroid hormone metabolism in the two tissues. Thus, gene expression profiles helped identify possible toxicological mechanisms of the triazole fungicides.

  11. 1,2,3-Triazoles from carbonyl azides and alkynes: filling the gap.

    PubMed

    Haldón, Estela; Álvarez, Eleuterio; Nicasio, M Carmen; Pérez, Pedro J

    2014-08-18

    Electron deficient azides are challenging substrates in CuAAC reactions. Particularly, when N-carbonyl azides are applied the formation of N-carbonyl triazoles has not yet been observed. We report herein the first example of this class of reaction, with a copper-based system that efficiently enables the synthesis of N-carbamoyl 1,2,3-triazoles by [3+2] cycloaddition of N-carbamoyl azides and alkynes. PMID:24980244

  12. Triazole bridges as versatile linkers in electron donor-acceptor conjugates

    PubMed Central

    de Miguel, Gustavo; Wielopolski, Mateusz; Schuster, David I.; Fazio, Michael A; Lee, Olivia P.; Haley, Christopher K.; Ortiz, Angy L.; Echegoyen, Luis; Clark, Timothy; Guldi, Dirk M.

    2011-01-01

    Aromatic triazoles have been frequently used as π-conjugated linkers in intramolecular electron transfer processes. To gain a deeper understanding of the electron mediating function of triazoles, we have synthesized a family of new triazole-based electron donor-acceptor conjugates. We have connected porphyrins and fullerenes through a central triazole moiety – (ZnP-Tri-C60) – each with a single change in their connection through the linker. An extensive photophysical and computational investigation reveals that the electron transfer dynamics – charge separation and charge recombination – in the different ZnP-Tri-C60 conjugates reflect a significant influence of the connectivity at the triazole linker. Except for m4m-ZnP-Tri-C60 17, the conjugates exhibit through-bond electron transfer with varying rate constants. Since the through-bond distance is nearly equal in the ZnP-Tri-C60 conjugates, the variation in charge separation and charge recombination dynamics is mainly associated with the electronic properties of the conjugates, including orbital energies, electron affinity, and the energies of the excited states. The changes of the electronic couplings are, in turn, a consequence of the different connectivity patterns at the triazole moieties. PMID:21702513

  13. Clinical safety and tolerability issues in use of triazole derivatives in management of fungal infections

    PubMed Central

    Neofytos, Dionissios; Avdic, Edina; Magiorakos, Anna-Pelagia

    2010-01-01

    There has been an increase in the number of patients susceptible to invasive fungal infections (IFIs) leading to a greater need for effective, well tolerated, and easily administered antifungal agents. The advent of triazoles has revolutionized the care of patients requiring treatment or prophylaxis for IFIs. However, triazoles have been associated with a number of adverse events and significant drug–drug interactions. While commonly used, physicians and patients should be aware of the distinct properties of these agents in order to ensure that patients are optimally treated with the least amount of toxicity possible. Clinicians should have a full understanding of the basic pharmacokinetics, absorption, and bioavailability of triazoles. Moreover, knowledge of the drug–drug interactions and potential toxicities of each agent is critical prior to administering a triazole. Careful history taking, thorough review of the patient’s medication list, and detailed discussion with the patients and their families about the efficacy, safety, and tolerability of these agents should be performed. Clinicians treating patients with triazoles should closely follow them, monitor pertinent laboratory tests, and consider measuring drug levels as needed. This article will review the basic pharmacokinetic properties and most frequently encountered adverse events and pitfalls associated with triazoles in clinical practice. PMID:21701616

  14. Cyclic four-coordinate boron compounds from 5-amino-1,2,4-triazole and aromatic nitriles

    SciTech Connect

    Dorokhov, V.A.; Amamchyan, A.R.; Bochkareva, M.N.; Teslya, I.A.; Starikova, Z.A.

    1987-07-20

    A new series of cyclic compounds of four coordinate boron- the dialkylboryl-((1,2,4-triazol-5-yl)amidinates) (IX)- has been synthesized from 5-amino-1,2,4-triazole, aromatic nitriles, and trialkylboranes. In the crystalline, dimeric dialkylboryl derivatives of 5-amino-1,2,4-triazole the Alk/sub 2/B groups are bonded to the ring N atoms. The crystalline and molecular structure of dipropylboryl((1,2,4-triazol-5-yl)benzamidinate) (IXa) have been determined by X-ray crystallography.

  15. Triazole Susceptibilities in Thermotolerant Fungal Isolates from Outdoor Air in the Seoul Capital Area in South Korea

    PubMed Central

    Lee, Seungeun; Xu, Siyu; Bivila, Chemmeri Padasseri; Lee, Hyeyoung; Park, Myung Soo; Lim, Young Woon; Yamamoto, Naomichi

    2015-01-01

    Emerging fungi resistant to triazoles are a concern because of the increased use of medical triazoles and exposure to agricultural triazoles. However, little is known about the levels of triazole susceptibility in outdoor airborne fungi making it difficult to assess the risks of inhalation exposure to airborne, antifungal-resistant fungi. This study examined triazole susceptibilities of the airborne thermotolerant fungi isolated from the ambient air of the Seoul Capital Area of South Korea. We used impactor air sampling with triazole-containing nutrient agar plates as the collection substrates to screen for airborne fungal isolates based on their triazole susceptibilities. This study estimated that 0.17% of all the culturable fungi belong to the pathogenic thermotolerant taxa, among which each isolate of Aspergillus niger and Aspergillus tubingensis showed a minimum inhibitory concentration (MIC) of 2 μg/mL or greater for itraconazole. Their concentration in air was 0.4 CFU/m3. Seven human pathogenic Paecilomyces variotii isolates had MICs of 32 μg/mL or greater and lower than 2 μg/mL for the agricultural fungicide tebuconazole and the medical triazole itraconazole, respectively. Though the concentration was low, our results confirm the presence of airborne fungi with high MICs for itraconazole in ambient air. Inhalation is an important exposure route because people inhale more than 10 m3 of air each day. Vigilance is preferred over monitoring for the emergence of triazole-resistant fungal pathogens in ambient outdoor air. PMID:26405807

  16. Design and synthesis of isosteviol triazole conjugates for cancer therapy.

    PubMed

    Khaybullin, Ravil N; Zhang, Mei; Fu, Junjie; Liang, Xiao; Li, Tammy; Katritzky, Alan R; Okunieff, Paul; Qi, Xin

    2014-01-01

    One of the keys for successfully developing drugs against the broad spectrum of cancer cell types is structural diversity. In the current study, we focused on a family of isosteviol derivatives as potential novel antitumor agents. Isosteviol is a tetracyclic diterpenoid obtained by acid hydrolysis of steviol glycoside extracts isolated from abundant Stevia rebaudiana plants. In this work, we have designed and synthesized a panel of isosteviol triazole conjugates using "click" chemistry methodology. Evaluation of these compounds against a series of cancer cell lines derived from primary and metastatic tumors demonstrated that these conjugates exhibit cytotoxic activities with IC50 in the low μM range. In addition, their anti-proliferative activities are cancer cell type specific. Taken together, our studies underscore the importance of structural diversity in achieving cancer cell type specific drug development. PMID:25405286

  17. Copper-triazole interaction and coolant inhibitor depletion

    SciTech Connect

    Bartley, L.S.; Fritz, P.O.; Pellet, R.J.; Taylor, S.A.; Van de Ven, P.

    1999-08-01

    To a large extent, the depletion of tolyltriazole (TTZ) observed in several field tests may be attributed to the formation of a protective copper-triazole layer. Laboratory aging studies, shown to correlate with field experience, reveal that copper-TTZ layer formation depletes coolant TTZ levels in a fashion analogous to changes observed in the field. XPS and TPD-MS characterization of the complex formed indicates a strong chemical bond between copper and the adsorbed TTZ which can be desorbed thermally only at elevated temperatures. Electrochemical polarization experiments indicate that the layer provides good copper protection even when TTZ is absent from the coolant phase. Examination of copper cooling system components obtained after extensive field use reveals the presence of a similar protective layer.

  18. Synthesis of [18F]-labelled Maltose Derivatives as PET Tracers for Imaging Bacterial Infection

    PubMed Central

    Namavari, Mohammad; Gowrishankar, Gayatri; Hoehne, Aileen; Jouannot, Erwan; Gambhir, Sanjiv S

    2015-01-01

    Purpose To develop novel positron emission tomography (PET) agents for visualization and therapy monitoring of bacterial infections. Procedures It is known that maltose and maltodextrins are energy sources for bacteria. Hence, 18F-labelled maltose derivatives could be a valuable tool for imaging bacterial infections. We have developed methods to synthesize 4-O-(α-D-glucopyranosyl)-6-deoxy-6-[18F]fluoro-D-glucopyranoside (6-[18F]fluoromaltose) and 4-O-(α-D-glucopyranosyl)-1-deoxy-1-[18F]fluoro-D-glucopyranoside (1-[18F]fluoromaltose) as bacterial infection PET imaging agents. 6-[18F]fluoromaltose was prepared from precursor 1,2,3-tri-O-acetyl-4-O-(2′,3′,-di-O-acetyl-4′,6′-benzylidene-α-D-glucopyranosyl)-6-deoxy-6-nosyl-D-glucopranoside (5). The synthesis involved the radio-fluorination of 5 followed by acidic and basic hydrolysis to give 6-[18F]fluoromaltose. In an analogous procedure, 1-[18F]fluoromaltose was synthesized from 2,3, 6-tri-O-acetyl-4-O-(2′,3′,4′,6-tetra-O-acetyl-α-D-glucopyranosyl)-1-deoxy-1-O-triflyl-D-glucopranoside (9). Stability of 6-[18F]fluoromaltose in phosphate-buffered saline (PBS) and human and mouse serum at 37 °C was determined. Escherichia coli uptake of 6-[18F]fluoromaltose was examined. Results A reliable synthesis of 1- and 6-[18F]fluoromaltose has been accomplished with 4–6 and 5–8 % radiochemical yields, respectively (decay-corrected with 95 % radiochemical purity). 6-[18F]fluoromaltose was sufficiently stable over the time span needed for PET studies (~96 % intact compound after 1-h and ~65 % after 2-h incubation in serum). Bacterial uptake experiments indicated that E. coli transports 6-[18F]fluoromaltose. Competition assays showed that the uptake of 6-[18F]fluoromaltose was completely blocked by co-incubation with 1 mM of the natural substrate maltose. Conclusion We have successfully synthesized 1- and 6-[18F]fluoromaltose via direct fluorination of appropriate protected maltose precursors. Bacterial uptake

  19. Preparation of 1,1'-dinitro-3,3'-azo-1,2,4-triazole. [1,1'-dinitro-3,3'-azo-1,2,4-triazole

    DOEpatents

    Lee, K.Y.

    1985-03-05

    A new high density composition of matter, 1,1'-dinitro-3,3'-azo-1,2,4-triazole, has been synthesized using inexpensive, commonly available compounds. This compound has been found to be an explosive, and its use as a propellant is anticipated. 1 fig., 1 tab.

  20. Four triazole-bridging coordination polymers containing (m-phenol)-1,2,4-triazole: Syntheses, structures and properties of fluorescence and magnetism

    SciTech Connect

    Liu Bing; Guo Guocong . E-mail: gcguo@ms.fjirsm.ac.cn; Huang Jinshun

    2006-10-15

    Four triazole-bridging coordination complexes, [Zn{sub 4}(ptr){sub 2}(SO{sub 4}){sub 3}({mu} {sub 3}-OH){sub 2}(H{sub 2}O){sub 4}] {sub n} (1), [Hg(CN){sub 2}(ptr)] {sub n} (2), [Hg(Cl){sub 2}(ptr)] {sub n} (3), and [Cu{sub 2}({mu} {sub 2}-ptr){sub 2}({mu} {sub 2}-F){sub 2}] {sub n} (SiF{sub 6}) {sub n} .2nH{sub 2}O (4), were synthesized with (m-phenol)-1,2,4-triazole (ptr). Compounds 1-4 with extended structures of 4-substituted 1,2,4-triazole are rarely reported. The layered structure of 1 can be regarded as constructed from the 2-D inorganic backbone of SO{sub 4} {sup 2-}(2) anions bridging [Zn{sub 4}({mu} {sub 3}-OH){sub 2}(H{sub 2}O){sub 2}]{sup 6-} subunits with the ptr ligands anchoring to both sides of backbone. Compounds 2 and 3 are the first mercury(II) complexes with 4-substituted 1,2,4-triazole, which feature the ptr ligand acting as a bidentate ligand bridging the Hg(II) atoms to form arciform -Hg-ptr-Hg-ptr chains. The structure of 4 is constructed from the F atoms bridging Cu atoms in symmetrical {mu} {sub 2}-coordination mode to form a zigzag cationic chain with each ptr ligand bridging a pair of Cu atom on the both sides, resulting in a nonplanar 5-membered [Cu{sub 2}N{sub 2}F] ring. Fluorescent properties of 1-4 were characterized and the magnetic property of 4 shows antiferromagnetic interaction between the copper(II) ions. - Four triazole-bridging coordination complexes, [Zn{sub 4}(ptr){sub 2}(SO{sub 4}){sub 3}({mu} {sub 3}-OH){sub 2}(H{sub 2}O){sub 4}] {sub n} (1), [Hg(CN){sub 2}(ptr)] {sub n} (2), [Hg(Cl){sub 2}(ptr)] {sub n} (3) and [Cu{sub 2}({mu} {sub 2}-ptr){sub 2}({mu} {sub 2}-F){sub 2}] {sub n} (SiF{sub 6}) {sub n} .2nH{sub 2}O (4), were synthesized with (m-phenol)-1,2,4-triazole (ptr). Compounds 1-4 with extended structures of 4-substituted 1,2,4-triazole are rarely reported.

  1. Pharmacokinetics, Pharmacodynamics, and Stereoselective Metabolism of the 1,2,4-Triazole Fungicide, Triadimefon, in Vertebrate Species

    EPA Science Inventory

    Questions Agricultural and pharmaceutical 1,2,4-triazole fungicides are potent cytochrome P450 modulators that can disrupt mammalian steroid biosynthesis. Triadimefon [(RS)-1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one] is unique with respect to tumorige...

  2. Visualization of Active Glucocerebrosidase in Rodent Brain with High Spatial Resolution following In Situ Labeling with Fluorescent Activity Based Probes

    PubMed Central

    Herrera Moro Chao, Daniela; Kallemeijn, Wouter W.; Marques, Andre R. A.; Orre, Marie; Ottenhoff, Roelof; van Roomen, Cindy; Foppen, Ewout; Renner, Maria C.; Moeton, Martina; van Eijk, Marco; Boot, Rolf G.; Kamphuis, Willem; Hol, Elly M.; Aten, Jan; Overkleeft, Hermen S.; Kalsbeek, Andries; Aerts, Johannes M. F. G.

    2015-01-01

    Gaucher disease is characterized by lysosomal accumulation of glucosylceramide due to deficient activity of lysosomal glucocerebrosidase (GBA). In cells, glucosylceramide is also degraded outside lysosomes by the enzyme glucosylceramidase 2 (GBA2) of which inherited deficiency is associated with ataxias. The interest in GBA and glucosylceramide metabolism in the brain has grown following the notion that mutations in the GBA gene impose a risk factor for motor disorders such as α-synucleinopathies. We earlier developed a β-glucopyranosyl-configured cyclophellitol-epoxide type activity based probe (ABP) allowing in vivo and in vitro visualization of active molecules of GBA with high spatial resolution. Labeling occurs through covalent linkage of the ABP to the catalytic nucleophile residue in the enzyme pocket. Here, we describe a method to visualize active GBA molecules in rat brain slices using in vivo labeling. Brain areas related to motor control, like the basal ganglia and motor related structures in the brainstem, show a high content of active GBA. We also developed a β-glucopyranosyl cyclophellitol-aziridine ABP allowing in situ labeling of GBA2. Labeled GBA2 in brain areas can be identified and quantified upon gel electrophoresis. The distribution of active GBA2 markedly differs from that of GBA, being highest in the cerebellar cortex. The histological findings with ABP labeling were confirmed by biochemical analysis of isolated brain areas. In conclusion, ABPs offer sensitive tools to visualize active GBA and to study the distribution of GBA2 in the brain and thus may find application to establish the role of these enzymes in neurodegenerative disease conditions such as α-synucleinopathies and cerebellar ataxia. PMID:26418157

  3. From antidiabetic to antifungal: discovery of highly potent triazole-thiazolidinedione hybrids as novel antifungal agents.

    PubMed

    Wu, Shanchao; Zhang, Yongqiang; He, Xiaomeng; Che, Xiaoying; Wang, Shengzheng; Liu, Yang; Jiang, Yan; Liu, Na; Dong, Guoqiang; Yao, Jianzhong; Miao, Zhenyuan; Wang, Yan; Zhang, Wannian; Sheng, Chunquan

    2014-12-01

    In an attempt to discover a new generation of triazole antifungal agents, a series of triazole-thiazolidinedione hybrids were designed and synthesized by molecular hybridization of the antifungal agent fluconazole and rosiglitazone (an antidiabetic). Most of the target compounds showed good to excellent inhibitory activity against a variety of clinically important fungal pathogens. In particular, compounds (Z)-5-(2,4-dichlorobenzylidene)-3-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)thiazolidine-2,4-dione) (15 c), (Z)-3-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-5-(furan-3-ylmethylene)thiazolidine-2,4-dione (15 j), and (Z)-3-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-5-(furan-3-ylmethylene)thiazolidine-2,4-dione (15 r) were highly active against Candida albicans, with MIC80 values in the range of 0.03-0.15 μM. Moreover, compounds 15 j and 15 r were found to be effective against four fluconazole-resistant clinical isolates; these two compounds are particularly promising antifungal leads for further optimization. Molecular docking studies revealed that the hydrogen bonding interactions between thiazolidinedione and CYP51 from C. albicans are important for antifungal activity. This study also demonstrates the effectiveness of molecular hybridization in antifungal drug discovery. PMID:25196996

  4. Impact of Pendant 1, 2, 3-Triazole on the Synthesis and Properties of Thiophene-Based Polymers

    SciTech Connect

    Nagarjuna, G.; Yurt, Serkan; Jadhav, Kedar G.; Venkataraman, D.

    2010-10-12

    π-Conjugated moieties are often attached to conjugated polymers to systematically alter their electronic properties. Herein, we report the synthesis and properties of a thiophene polymer bearing a triazole moiety in the third position. Through NMR-based quenching studies, we show that the placement of the triazole moiety alters reaction pathway of the Ni(0)-mediated Grignard metathesis polymerization possibly through chelation. When compared with a triazole on the main chain, the pendant triazole moiety acts as an electron donor and lowers the band gap of the polymer. The triazole moiety also does not hinder the packing of the conjugated backbone. We also show that the fluorescence of this polymer is quenched with PCBM, indicating its potential as a candidate for organic photovoltaic devices.

  5. Synthesis, structure and antimicrobial evaluation of a new gossypol triazole conjugates functionalized with aliphatic chains and benzyloxy groups.

    PubMed

    Pyta, Krystian; Blecha, Marietta; Janas, Anna; Klich, Katarzyna; Pecyna, Paulina; Gajecka, Marzena; Przybylski, Piotr

    2016-09-01

    Synthetic limitations in the copper-catalyzed azide alkyne cycloaddition (CuAAC) on gossypol's skeleton functionalized with alkyne (2) or azide (3) groups have been indicated. Modified approach to the synthesis of new gossypol-triazole conjugates yielded new compounds (24-31) being potential fungicides. Spectroscopic studies of triazole conjugates 24-31 have revealed their structures in solution, i.e., the presence of enamine-enamine tautomeric forms and π-π stacking intramolecular interactions between triazole arms. Biological evaluation of the new gossypol-triazole conjugates revealed the potency of 30 and 31 derivatives, having triazole-benzyloxy moieties, comparable with that of miconazole against Fusarium oxysporum. The results of HPLC evaluation of ergosterol content in different fungi strains upon treatment of gossypol and its derivatives enabled to propose a mechanism of antifungal activity of these compounds. PMID:27469129

  6. Functionalization of 2H-1,2,3-Triazole C-Nucleoside Template via N(2) Selective Arylation.

    PubMed

    Lopes, Alexandra Basilio; Wagner, Patrick; de Souza, Rodrigo Octavio Mendonça Alves; Germain, Nadège Lubin; Uziel, Jacques; Bourguignon, Jean-Jacques; Schmitt, Martine; Miranda, Leandro S M

    2016-06-01

    C-Nucleosides are an underexplored and important class of nucleosides with antiviral and anticancer activity. In addition, triazole heterocycles are well employed as a strategy to modify nucleobase in nucleoside analogues, although rare examples were described for triazoyl C-nucleosides. N(2)-Aryl-1,2,3-triazole C-nucleoside compounds that could be obtained by selective 1,2,3-triazole heterocycle N(2) arylation in 1-β-d-ribofuranosyl-2H-1,2,3-triazole substrate were designed in this study. The optimized condition used AdBrettPhos/[PdCl(allyl)]2 as the catalyst system. This transformation was accomplished by aryl halides bearing an electron donor and withdrawing groups, as well as by heterocyclic halides in good to excellent yields. The transformation developed in this study represents a significant contribution to the nucleoside field, once it allows for the synthesis of unexplored scaffolds through selective functionalization of triazole nucleosides. PMID:27166644

  7. Effect of the chirality of the glycerol backbone on the bilayer and nonbilayer phase transitions in the diastereomers of di-dodecyl-beta-D-glucopyranosyl glycerol.

    PubMed Central

    Mannock, D A; Lewis, R N; McElhaney, R N; Akiyama, M; Yamada, H; Turner, D C; Gruner, S M

    1992-01-01

    We have studied the physical properties of aqueous dispersions of 1,2-sn- and 2,3-sn-didodecyl-beta-D-glucopyranosyl glycerols, as well as their diastereomeric mixture, using differential scanning calorimetry and low angle x-ray diffraction. Upon heating, both the chiral lipids and the diastereomeric mixture exhibit characteristically energetic L beta/L alpha phase transitions at 31.7-32.8 degrees C and two or three weakly energetic thermal events between 49 degrees C and 89 degrees C. In the diastereomeric mixture and the 1,2-sn glycerol derivative, these higher temperature endotherms correspond to the formation of, and interconversions between, several nonlamellar structures and have been assigned to L alpha/QIIa, QIIa/QIIb, and QIIb/HII phase transitions, respectively. The cubic phases QIIa and QIIb, whose cell lattice parameters are strongly temperature dependent, can be identified as belonging to space groups Ia3d and Pn3m/Pn3, respectively. In the equivalent 2,3-sn glucolipid, the QIIa phase is not observed and only two transitions are seen at 49 degrees C and 77 degrees C, which are identified as L alpha/QIIb and QIIb/HII phase transitions, respectively. These phase transitions temperatures are some 10 degrees C lower than those of the corresponding phase transitions observed in the diastereomeric mixture and the 1,2-sn glycerol derivative. On cooling, all three lipids exhibit a minor higher temperature exothermic event, which can be assigned to a HII/QIIb phase transition. An exothermic L alpha/L beta phase transition is observed at 30-31 degrees C. A shoulder is sometimes discernible on the high temperature side of the L alpha/L beta event, which may originate from a QIIb/L alpha phase transition prior to the freezing of the hydrocarbon chains. None of the lipids show evidence of a QIIa phase on cooling. No additional exothermic transitions are observed on further cooling to -3 degrees C. However, after nucleation at 0 degrees C followed by a short period

  8. A convenient synthesis and screening of benzosuberone bearing 1,2,3-triazoles against Mycobacterium tuberculosis.

    PubMed

    Sajja, Yasodakrishna; Vanguru, Sowmya; Jilla, Lavanya; Vulupala, Hanmanth Reddy; Bantu, Rajashaker; Yogeswari, Perumal; Sriram, Dharmarajan; Nagarapu, Lingaiah

    2016-09-01

    A series of benzosuberone bearing 1,2,3-triazoles were rationally designed and alkyl/aryl groups appended on 1,2,3-triazole derivatives 5a-o were synthesized using click chemistry and evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC27294). Compounds 5h (MIC: 3.125μg/mL) and 5l, 5m, 5o (MIC: 6.25μg/mL) exhibited promising hits. This is the first Letter on the synthesis and in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv of benzosuberone alkyl/aryl groups appended on 1,2,3-triazole derivatives. PMID:27476139

  9. Discovery of novel diaryl urea derivatives bearing a triazole moiety as potential antitumor agents.

    PubMed

    Qin, Mingze; Yan, Shuang; Wang, Lei; Zhang, Haotian; Zhao, Yanfang; Wu, Shasha; Wu, Di; Gong, Ping

    2016-06-10

    Herein, we report a novel series of diaryl urea derivatives bearing a triazole moiety, from which potent antitumor agents have been identified. With a modified triazole, most compounds showed high level activity in both cellular and enzymatic assays, accompanied with a suitable ClogD7.4 value. The most active compound, 13i, effectively suppressed proliferation of HT-29, H460 and MDA-MB-231 cancer cells, with IC50 values of 0.90, 0.85 and 1.54 μM, respectively. Compound 13i also exhibited significant inhibition of tyrosine kinases including c-Kit, RET and FLT3. Furthermore, compound 13i could obviously induce apoptosis of HT-29 cells in a concentration-dependent manner. The study of structure-activity relationships also revealed that a hydrophilic tail at the 4-position of the triazole was crucial for high activity of the compound. PMID:26991938

  10. Polynuclear Silver(I) Triazole Complexes: Ion Conduction and Nanowire Formation in the Mesophase.

    PubMed

    Su, Padi Y S; Hsu, S J; Tseng, Jing C W; Hsu, Hsiu-Fu; Wang, Wen-Jwu; Lin, Ivan J B

    2016-01-01

    Examples of polynuclear metallomesogens are few. Herein,1,2,4-triazole ligands were used to prepare mono- and polynuclear silver(I) triazole metallomesogens. Besides showing an SmA phase in the mesophase, two interesting properties were observed. First, higher ion conductivity is always found for the polynuclear complexes than for the mononuclear complexes with the same anion, an observation contrary to the knowledge that migration of a monomeric cation should be faster than that of a polymeric cation. Second, thermolysis of the polynuclear silver(I) triazole complexes in the assembled mesophase yielded Ag nanowires, in an excellent demonstration of the assembled nature of the polynuclear silver(I) ions in the thermolysis process. PMID:26602494

  11. Fused triazoles via tandem reactions of activated Cinchona alkaloids with azide ion. Second Cinchona rearrangement exemplified.

    PubMed

    Röper, S; Franz, M H; Wartchow, R; Hoffmann, H M R

    2003-08-01

    [reaction: see text] Intramolecular 1,3-dipolar cycloadditions of cinchona azides to the C10-C11 alkyne and C10-C11 olefin unit of the alkaloid have been designed via tandem strategy. A variety of fused triazoles and triazolines with a bis-azahomotwistane skeleton have been prepared. In trifluoroethanol, O-mesylcinchonidine 7-OMs and NaN(3) furnish triazole 8 as well as cage-expanded 1,5-diazatricyclo[4.4.1.0(3,8)]undecane derivative 10. Both fused triazoles 8 and 10 are formed with retention of configuration at C9 and C3, respectively. 1-Azabicyclo[3.2.2]cage expansion is shown to be reversible. PMID:12889871

  12. Synthesis of sansalvamide A peptidomimetics: triazole, oxazole, thiazole, and pseudoproline containing compounds

    PubMed Central

    Davis, Melinda R.; Singh, Erinprit K.; Wahyudi, Hendra; Alexander, Leslie D.; Kunicki, Joseph B.; Nazarova, Lidia A.; Fairweather, Kelly A.; Giltrap, Andrew M.; Jolliffe, Katrina A.; McAlpine, Shelli R.

    2011-01-01

    Peptidomimetic-based macrocycles typically have improved pharmacokinetic properties over those observed with peptide analogs. Described are the syntheses of 13 peptidomimetic derivatives that are based on active Sansalvamide A structures, where these analogs incorporate heterocycles (triazoles, oxazoles, thiazoles, or pseudoprolines) along the macrocyclic backbone. The syntheses of these derivatives employ several approaches that can be applied to convert a macrocyclic peptide into its peptidomimetic counterpart. These approaches include peptide modifications to generate the alkyne and azide for click chemistry, a serine conversion into an oxazole, a Hantzsch reaction to generate the thiazole, and protected threonine to generate the pseudoproline derivatives. Furthermore, we show that two different peptidomimetic moieties, triazoles and thiazoles, can be incorporated into the macrocyclic backbone without reducing cytotoxicity: triazole and thiazole. PMID:22287031

  13. Borated triazole-substituted polyalkenyl succinimides as multifunctional lubricant and fuel additives

    SciTech Connect

    Blain, D.A.; Cardis, A.B.; Poole, R.J.

    1991-09-17

    This patent describes a lubricant composition. It comprises a major proportion of an oil of lubricating viscosity or grease prepared therefrom and a minor proportion of a reaction product obtained by reacting a polyalkenyl-substituted succinimide, a triazole, and an aldehyde and thereafter boronating the resultant intermediate product and wherein the polyalkenyl-substituted succinimide, aldehyde, triazole and boronating agent are reacted in a mole ratio of succinimide to aldehyde to triazole to boronating agent respectively of between about 1:0.1:0.1:0.1 and about 1:4:4:4 and wherein the reaction is conducted at a temperature of about 100{degrees} C to about 200{degrees} C at ambient pressure. This patent also describes a lubricant composition comprising a major proportion of an oil of lubricating viscosity or grease prepared therefrom and a minor proportion of a reaction product obtained by reacting a polyalkenyl-substituted succinimide.

  14. Uranyl triazolate formation via an in situ Huisgen 1,3-dipolar cycloaddition reaction

    SciTech Connect

    Knope, Karah E.; Cahill, Christopher L.

    2010-08-27

    A two dimensional UO22+ coordination polymer, (UO2)3(C10H5N3O4)2(OH)2(H2O)2, has been synthesized under solvothermal conditions. The triazolate ligand, 1-(4-carboxyphenyl)-1H-1,2,3-triazole-4-carboxylic acid (CPTAZ) has been generated via a 1,3-dipolar cycloaddition of 4-azidobenzoic acid and propiolic acid. Reactions of the UO22+ cation with both the in situ generated triazolate ligand and the presynthesized ligand have been explored. The structure, fluorescent and thermal behaviour of this material are presented, as is a discussion of the utility of in situ ligand formation versus direct assembly.

  15. Facile diverted synthesis of pyrrolidinyl triazoles using organotrifluoroborate: discovery of potential mPTP blockers.

    PubMed

    Jung, Sun hwa; Choi, Kihang; Pae, Ae Nim; Lee, Jae Kyun; Choo, Hyunah; Keum, Gyochang; Cho, Yong Seo; Min, Sun-Joon

    2014-12-21

    This article describes the rapid and diversified synthesis of pyrrolidinyl triazoles for the discovery of mitochondrial permeability transition pore (mPTP) blockers. The 1,3-dipolar cycloaddition of ethynyl trifluoroborate with azidopyrrolidine produced a key intermediate, triazolyl trifluoroborate 4, which subsequently underwent a Suzuki-Miyaura coupling reaction to afford a series of 1,4-disubstituted triazoles 2. Subsequent biological evaluation of these derivatives indicated 2ag and 2aj as the most potent mPTP blockers exhibiting excellent cytochrome P450 (CYP) stability when compared to the previously reported oxime analogue 1. The present work clearly demonstrates that a 1,2,3-triazole can be used as a stable oxime surrogate. Furthermore, it suggests that late-stage diversification through coupling reactions of organotrifluoroborates is suitable for the rapid discovery of biologically active molecules. PMID:25348904

  16. Novel triazole alcohol antifungals derived from fluconazole: design, synthesis, and biological activity.

    PubMed

    Hashemi, Seyedeh Mahdieh; Badali, Hamid; Faramarzi, Mohammad Ali; Samadi, Nasrin; Afsarian, Mohammad Hosein; Irannejad, Hamid; Emami, Saeed

    2015-02-01

    A series of new triazole alcohol antifungals were designed by replacing one of the triazolyl moiety from fluconazole with a distinct 4-amino-3-mercapto-1,2,4-triazole motif, which is found in some antimicrobial agents. The antimicrobial susceptibility testing of target compounds demonstrated that the direct analogs of fluconazole (difluorophenethyl-triazoles) were less active against fungi, while compound 10h containing dichloro substitutions on both phenyl rings of the molecule had potent activity against yeasts including Candida albicans (four strains) and Cryptococcus neoformans (MICs = 2-8 μg/mL). Also, compound 10h was active against Candida parapsilosis, Epidermophyton floccosum, and Trichophyton mentagrophytes, while it showed no activity against Gram-positive and Gram-negative bacteria. Finally, a molecular docking study suggested that compound 10h interacts suitably with lanosterol 14α-demethylase, which is the key enzyme in ergosterol biosynthesis. PMID:25182365

  17. 1,2,3-Triazole-Heme Interactions in Cytochrome P450: Functionally Competent Triazole-Water- Heme Complexes

    PubMed Central

    Conner, Kip P.; Vennam, Preethi; Woods, Caleb M.; Krzyaniak, Matthew D.; Bowman, Michael K.; Atkins, William M.

    2012-01-01

    In comparison to imidazole (IMZ) and 1,2,4-triazole (1,2,4-TRZ) the isosteric 1,2,3-triazole (1,2,3-TRZ) is unrepresented among CYP inhibitors. This is surprising because 1,2,3-TRZs are easily obtained via ‘click’ chemistry. To understand this underrepresentation of 1,2,3-TRZs among CYP inhibitors, thermodynamic and DFT computational studies were performed with unsusbstituted IMZ, 1,2,4-TRZ, and 1,2,3-TRZ. The results indicate that the lower affinity of 1,2,3-TRZ for the heme iron includes a large unfavorable entropy term likely originating in solvent – 1,2,3-TRZ interactions; the difference is not solely due to differences in the enthalpy of heme – ligand interactions. In addition, the 1,2,3-TRZ fragment was incorporated into a well-established CYP3A4 substrate and mechanism based inactivator, 17-α-ethynylestradiol (17EE), via click chemistry. This derivative, 17-click, yielded optical spectra consistent with low spin ferric heme iron (type II) in contrast to 17EE, which yields a high spin complex (type I). Furthermore, the rate of CYP3A4-mediated metabolism of 17-click was comparable to 17EE, and with different regioselectivity. Surprisingly, CW EPR and HYSCORE EPR spectroscopy indicate that the 17-click does not displace water from the 6th axial ligand position of CYP3A4 as expected for a type II ligand. We propose a binding model where 17-click pendant 1,2,3-TRZ hydrogen bonds with the 6th axial water ligand. The results demonstrate the potential for 1,2,3-TRZ to form metabolically labile water-bridged low spin heme complexes, consistent with recent evidence that nitrogenous type II ligands of CYPs can be efficiently metabolized. The specific case of [CYP3A4•17-click] highlights the risk of interpreting CYP-ligand complex structure on the basis of optical spectra. PMID:22809252

  18. Chiral Heteroditopic Baskets Designed from Triazolated Calixarenes and Short Peptides.

    PubMed

    Gorbunov, Alexander; Sokolova, Nadezhda; Kudryashova, Elena; Nenajdenko, Valentine; Kovalev, Vladimir; Vatsouro, Ivan

    2016-08-22

    Cone calix[4]arenes and calix[6]arenes bearing two, three, and four short peptide units each having two chiral carbon atoms were prepared. The syntheses were performed by using an efficient modular approach that includes the Ugi preparation of the azido-peptide followed by its reactions with the propargylated calixarenes under CuAAC (Cu(I) -catalyzed azide-alkyne cycloaddition) conditions. The three novel multitopic hosts were probed for their ability to bind metal ions by UV titration, and showed the highest complexation efficiency towards copper(II) and lead(II). These two cations possessed quite different complexation modes with copper(II) bound predominantly by multiple-triazole sites, in contrast to lead(II), which is stabilized mainly by multiple interactions with amide groups of the peptide units. Circular dichroism data for the free chiral hosts, their equimolar mixtures with copper(II) perchlorate and lead(II) perchlorate, and for tertiary mixtures of all three compounds showed the formation of mono- and binuclear complexes, or a switching behavior, depending on the structure of the host and the addition order of the cations. PMID:27444143

  19. Toxicogenomic effects common to triazole antifungals and conserved between rats and humans

    SciTech Connect

    Goetz, Amber K.; Dix, David J.

    2009-07-01

    The triazole antifungals myclobutanil, propiconazole and triadimefon cause varying degrees of hepatic toxicity and disrupt steroid hormone homeostasis in rodent in vivo models. To identify biological pathways consistently modulated across multiple timepoints and various study designs, gene expression profiling was conducted on rat livers from three separate studies with triazole treatment groups ranging from 6 h after a single oral gavage exposure, to prenatal to adult exposures via feed. To explore conservation of responses across species, gene expression from the rat liver studies were compared to in vitro data from rat and human primary hepatocytes exposed to the triazoles. Toxicogenomic data on triazoles from 33 different treatment groups and 135 samples (microarrays) identified thousands of probe sets and dozens of pathways differentially expressed across time, dose, and species - many of these were common to all three triazoles, or conserved between rodents and humans. Common and conserved pathways included androgen and estrogen metabolism, xenobiotic metabolism signaling through CAR and PXR, and CYP mediated metabolism. Differentially expressed genes included the Phase I xenobiotic, fatty acid, sterol and steroid metabolism genes Cyp2b2 and CYP2B6, Cyp3a1 and CYP3A4, and Cyp4a22 and CYP4A11; Phase II conjugation enzyme genes Ugt1a1 and UGT1A1; and Phase III ABC transporter genes Abcb1 and ABCB1. Gene expression changes caused by all three triazoles in liver and hepatocytes were concentrated in biological pathways regulating lipid, sterol and steroid homeostasis, identifying a potential common mode of action conserved between rodents and humans. Modulation of hepatic sterol and steroid metabolism is a plausible mode of action for changes in serum testosterone and adverse reproductive outcomes observed in rat studies, and may be relevant to human risk assessment.

  20. Toxicogenomic effects common to triazole antifungals and conserved between rats and humans.

    PubMed

    Goetz, Amber K; Dix, David J

    2009-07-01

    The triazole antifungals myclobutanil, propiconazole and triadimefon cause varying degrees of hepatic toxicity and disrupt steroid hormone homeostasis in rodent in vivo models. To identify biological pathways consistently modulated across multiple timepoints and various study designs, gene expression profiling was conducted on rat livers from three separate studies with triazole treatment groups ranging from 6 h after a single oral gavage exposure, to prenatal to adult exposures via feed. To explore conservation of responses across species, gene expression from the rat liver studies were compared to in vitro data from rat and human primary hepatocytes exposed to the triazoles. Toxicogenomic data on triazoles from 33 different treatment groups and 135 samples (microarrays) identified thousands of probe sets and dozens of pathways differentially expressed across time, dose, and species--many of these were common to all three triazoles, or conserved between rodents and humans. Common and conserved pathways included androgen and estrogen metabolism, xenobiotic metabolism signaling through CAR and PXR, and CYP mediated metabolism. Differentially expressed genes included the Phase I xenobiotic, fatty acid, sterol and steroid metabolism genes Cyp2b2 and CYP2B6, Cyp3a1 and CYP3A4, and Cyp4a22 and CYP4A11; Phase II conjugation enzyme genes Ugt1a1 and UGT1A1; and Phase III ABC transporter genes Abcb1 and ABCB1. Gene expression changes caused by all three triazoles in liver and hepatocytes were concentrated in biological pathways regulating lipid, sterol and steroid homeostasis, identifying a potential common mode of action conserved between rodents and humans. Modulation of hepatic sterol and steroid metabolism is a plausible mode of action for changes in serum testosterone and adverse reproductive outcomes observed in rat studies, and may be relevant to human risk assessment. PMID:19409404

  1. 1,4-Bis(4H-1,2,4-triazol-4-yl)benzene dihydrate

    PubMed Central

    Wang, Xiu-Guang; Li, Jian-Hui; Ding, Bin; Du, Gui-Xiang

    2012-01-01

    The asymmetric unit of the title compound, C10H8N6·2H2O, comprises half the organic species, the mol­ecule being completed by inversion symmetry, and one water mol­ecule. The dihedral angle between the 1,2,4-triazole ring and the central benzene ring is 32.2 (2)°. The water mol­ecules form O—H⋯N hydrogen bonds with N-atom acceptors of the triazole rings. C—H⋯N hydrogen bonds are also observed, giving a three-dimensional framework. PMID:22904851

  2. Preparation and reactions of sugar azides with alkynes: synthesis of sugar triazoles as antitubercular agents.

    PubMed

    Singh, Biswajit Kumar; Yadav, Amit Kumar; Kumar, Brijesh; Gaikwad, A; Sinha, Sudhir Kumar; Chaturvedi, Vinita; Tripathi, Rama Pati

    2008-05-19

    5-azido-5-deoxy-xylo-, ribo-, and arabinofuranoses were prepared by the reaction of the respective 5-O-(methanesulfonyl) or p-toluenesulfonyl derivatives with NaN3 in DMF. The intermediate 5-azido-5-deoxy glycofuranoses on 1,3-cycloaddition with different alkynes in the presence of CuSO4 and sodium ascorbate gave the corresponding sugar triazoles in very good yields. The synthesized sugar triazoles were evaluated for their antitubercular activity against Mycobacterium tuberculosis H37Rv, where one of the compounds displayed mild antitubercular activity in vitro with MIC 12.5 microg/mL. PMID:18346719

  3. Metal-Free Three-Component Domino Approach to Phosphonylated Triazolines and Triazoles.

    PubMed

    Ahamad, Shakir; Kant, Ruchir; Mohanan, Kishor

    2016-01-15

    An efficient, three-component domino reaction between aldehydes, amines, and the Bestmann-Ohira reagent is reported that enables a general, mild, and straightforward access to 1,4,5-trisubstituted 1,2,3-triazolines and triazoles. The reaction proceeds through a domino-condensation/1,3-dipolar cycloaddition sequence to afford the triazoline derivatives with excellent diastereoselectivity. Moreover, when both amine and aldehyde employed for this reaction are aromatic, a spontaneous oxidation afforded 1,4,5-trisubstituted triazoles in moderate yields. PMID:26727129

  4. Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions

    PubMed Central

    Okkel, Andreas; Schwach, Lukas; Wagner, Laura; Selig, Anja; Prokop, Aram

    2014-01-01

    Summary An operationally simple, convenient, and mild strategy for the synthesis of triazole-substituted titanocenes via strain-driven 1,3-dipolar cycloadditions between azide-functionalized titanocenes and cyclooctyne has been developed. It features the first synthesis of titanocenes containing azide groups. These compounds constitute ‘second-generation’ functionalized titanocene building blocks for further synthetic elaboration. Our synthesis is modular and large numbers of the complexes can in principle be prepared in short periods of time. Some of the triazole-substituted titanocenes display high cyctotoxic activity against BJAB cells. Comparison of the most active complexes allows the identification of structural features essential for biological activity. PMID:25161720

  5. 3-nitro-1,2,4-triazol-5-one, a less sensitive explosive

    DOEpatents

    Lee, Kien-Yin; Coburn, Michael D.

    1988-01-01

    A less sensitive explosive, 3-nitro-1,2,4-triazol-5-one. The compound 3-nitro-1,2,4-triazol-5-one (NTO) has a crystal density of 1.93 g/cm.sup.3 and calculated detonation velocity and pressure equivalent to those of RDX. It can be prepared in high yield from inexpensive starting materials in a safe synthesis. Results from initial small-scale sensitivity tests indicate that NTO is less sensitive than RDX and HMX in all respects. A 4.13 cm diameter, unconfined plate-dent test at 92% of crystal density gave the detonation pressure predicted for NTO by the BKW calculation.

  6. Dimensional modulation and magnetic properties of triazole- and bis(triazole)-based copper(II) coordination polymers tuned by aromatic polycarboxylates

    SciTech Connect

    Zhang, Ju-Wen; Zhao, Wei; Lu, Qi-Lin; Luan, Jian; Qu, Yun; Wang, Xiu-Li

    2014-04-01

    Five new metal–organic coordination polymers ([Cu{sub 3}(μ{sub 2}-OH){sub 2}(atrz){sub 2}(nph){sub 2}(H{sub 2}O){sub 2}]·2H{sub 2}O){sub n} (1), ([Cu{sub 2}(μ{sub 3}-OH)(atrz)(1,2,4-btc)]·2H{sub 2}O){sub n} (2), ([Cu{sub 2}(μ{sub 3}-OH)(atrz)(1,2,4-btc)(H{sub 2}O)]·H{sub 2}O){sub n} (3), [Cu(dth){sub 0.5}(nph)(H{sub 2}O)]{sub n} (4) and [Cu(dth)(Hnip){sub 2}]{sub n} (5) [atrz=4-amino-1,2,4-triazole, dth=N,N'-di(4H-1,2,4-triazole)hexanamide, H{sub 2}nph=3-nitrophthalic acid, 1,2,4-H{sub 3}btc=1,2,4-benzenetricarboxylic acid and H{sub 2}nip=5-nitroisophthalic acid] were hydrothermally synthesized and structurally characterized. Polymer 1 shows a one-dimensional (1D) chain. Polymers 2 and 3 exhibit similar tetranuclear Cu{sup II}{sub 4} cluster-based three-dimensional (3D) frameworks with the same components. Polymer 4 possesses a 3D framework with a 4{sup 12}·6{sup 3}-pcu topology. Polymer 5 displays a 3D framework with a 4{sup 4}·6{sup 10}·8-mab topology. The magnetic properties of 1–4 were investigated. - Graphical abstract: Five triazole-based copper(II) polymers modulated by polycarboxylates were synthesized. Bis-triazole-bis-amide ligand and polycarboxylates play important roles in tuning dimensionality of polymers. Magnetic properties of polymers were investigated. - Highlights: • Five triazole- and bis(triazole)-based copper(II) coordination polymers tuned by aromatic polycarboxylates were obtained. • The aromatic polycarboxylates have an important influence on the dimensionality of five polymers. • The magnetic properties of four polymers were investigated.

  7. Chemistry and properties of poly(arylene ether 1,3,4-oxadiazole)s and poly(arylene ether 1,2,4-triazole)s

    NASA Technical Reports Server (NTRS)

    Connell, J. W.; Hergenrother, P. M.; Wolf, P.

    1992-01-01

    Poly(arylene ether)s containing l,3,4-oxadiazole and 1,2,4-triazole units were prepared by the aromatic nucleophilic displacement reaction of bisphenol oxadiazole and bisphenol triazole compounds with activated aromatic dihalides. The polymers exhibited glass transition temperatures (Tg) ranging from 182 to 242 C, and several polymers exhibited melting transitions (Tm) ranging from 265 to 390 C. Inherent viscosities ranged from 1.02 to 3.40 dl/g, indicating relatively high molecular weights. Thin films exhibited tensile strengths, moduli, and elongations at 23 C of 90-110 MPa, 2.7-3.6 GPa, and 4-7 percent, respectively. Titanium-to-titanium tensile shear specimens of a poly(arylene ether 1,3,4-oxadiazole) exhibited tensile shear strengths at 23 and 150 C of 22.1 and 17.9 MPa, respectively.

  8. Last Generation Triazoles for Imported Eumycetoma in Eleven Consecutive Adults

    PubMed Central

    Crabol, Yoann; Poiree, Sylvain; Bougnoux, Marie-Elisabeth; Maunoury, Christophe; Barete, Stéphane; Zeller, Valérie; Arvieux, Cédric; Pineau, Samuel; Amazzough, Karima; Lecuit, Marc; Lanternier, Fanny; Lortholary, Olivier

    2014-01-01

    Background Optimal management of eumycetoma, a severely debilitating chronic progressive fungal infection of skin, disseminating to bone and viscera, remains challenging. Especially, optimal antifungal treatment and duration are ill defined. Methodology/Principal Findings We conducted a monocentric retrospective study of 11 imported cases of eumycetoma treated by voriconazole or posaconazole for at least 6 months. Response to treatment was assessed through evolution of clinical and magnetic resonance imaging (MRI). (1→3) ß-D-glucan (BG) and positron emission tomography using [18F] fluorodeoxyglucose (PET/CT) results were also assessed. Identified species were Fusarium solani complex (n = 3); Madurella mycetomatis, (n = 3), and Exophiala jeanselmei, (n = 1). Moreover, two coelomycetes and one phaeohyphomycetes strains without species identification were retrieved. Serum BG and PET/CT were abnormal in 7/8 and 6/6 patients tested, respectively. Patients received last generation azoles for a mean duration of 25.9±18 months. Complete response (major clinical and MRI improvement) was observed in 5/11 patients, partial response (minor MRI improvement or stable MRI findings) in 5 and failure (MRI evidence of disease progression) in one, with a 73±39 [6–132] months mean follow-up. Relapse occurred in 2 patients after treatment discontinuation. Optimal outcome was associated with fungal species, initiation of last generation triazole therapy (<65 months since first symptoms), negative serum BG and PET/CT normalization. Conclusions/Significance MRI, PET/CT and serum BG appear as promising tools to assess optimal time of antifungal treatment for eumycetoma. PMID:25299610

  9. Benzyl-1,2,4-triazoles as CB1 Cannabinoid Receptor Ligands: Preparation and In Vitro Pharmacological Evaluation

    PubMed Central

    Hernandez-Folgado, Laura; Decara, Juan; Rodríguez de Fonseca, Fernando; Goya, Pilar; Jagerovic, Nadine

    2016-01-01

    In a previous study, we have identified 3-alkyl-1,5-diaryl-1H-1,2,4-triazoles to be a novel class of cannabinoid type 1 receptor (CB1R) antagonists. In order to expand the number of cannabinoid ligands with a central 1,2,4-triazole scaffold, we have synthesized a novel series of 1-benzyl-1H-1,2,4-triazoles, and some of them were evaluated by CB1R radioligand binding assays. Compound 12a showed the most interesting pharmacological properties, possessing a CB1R affinity in the nanomolar range. PMID:27127651

  10. A new 3D Cd-triazolate framework obtained from in situ decarboxylication of 5-amino-3-carboxyl-1,2,4-triazole

    NASA Astrophysics Data System (ADS)

    Liu, Bing; Feng, Hui-Jun; Zhang, Zong-Hui; Xu, Ling; Jiao, Huan

    2015-10-01

    A new 3D Cd-triazolate MOF compound [Cd(Hatrz) (SO4)] (1) (Hatrz = 3-amino-1H-1,2,4-triazole) was obtained from in situ decarboxylication of 5-amino-3-carboxyl-1,2,4-triazole (H2atrc) under the hydrothermal reaction of CdSO4 with H2atrc. Compound 1 features itself a Hatrz-supporting 3D architecture based on the connection of inorganic [CdSO4] layers with Hatrz spacers. Cd(II) atom, SO4 2 - and Hatrz dummied as 6-, 4- and 2-connected nodes respectively, compound 1 can be simplified to a (2,4,6)-connected {44.62.88.12}{44.62}{8} topological network. The thermal stability of 1 is up to ca. 402 °C, and the fluorescence of 1 shows an emission at 366 nm, originating from SO4 2 - → Cd transfer. PXRD of compound 1 confirms the phase purity of the bulk sample. FT-IR spectrum of 1 is in accord with the structure analysis.

  11. Isavuconazole: Pharmacology, Pharmacodynamics, and Current Clinical Experience with a New Triazole Antifungal Agent.

    PubMed

    Rybak, Jeffrey M; Marx, Kayleigh R; Nishimoto, Andrew T; Rogers, P David

    2015-11-01

    Coinciding with the continually increasing population of immunocompromised patients worldwide, the incidence of invasive fungal infections has grown over the past 4 decades. Unfortunately, infections caused by both yeasts such as Candida and molds such as Aspergillus or Mucorales remain associated with unacceptably high morbidity and mortality. In addition, the available antifungals with proven efficacy in the treatment of these infections remain severely limited. Although previously available second-generation triazole antifungals have significantly expanded the spectrum of the triazole antifungal class, these agents are laden with shortcomings in their safety profiles as well as formulation and pharmacokinetic challenges. Isavuconazole, administered as the prodrug isavuconazonium, is the latest second-generation triazole antifungal to receive U.S. Food and Drug Administration approval. Approved for the treatment of both invasive aspergillosis and invasive mucormycosis, and currently under investigation for the treatment of candidemia and invasive candidiasis, isavuconazole may have therapeutic advantages over its predecessors. With clinically relevant antifungal potency against a broad range of yeasts, dimorphic fungi, and molds, isavuconazole has a spectrum of activity reminiscent of the polyene amphotericin B. Moreover, clinical experience thus far has revealed isavuconazole to be associated with fewer toxicities than voriconazole, even when administered without therapeutic drug monitoring. These characteristics, in an agent available in both a highly bioavailable oral and a β-cyclodextrin-free intravenous formulation, will likely make isavuconazole a welcome addition to the triazole class of antifungals. PMID:26598096

  12. METABOLOMIC EVALUATION OF RAT LIVER AND TESTIS TO CHARACTERIZE THE TOXICITY OF TRIAZOLE FUNGICIDES

    EPA Science Inventory

    The effects of two triazole fungicides, myclobutanil and triadimefon, on endogenous rat metabolite profiles in blood serum, liver, and testis was assessed using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Adult male Sprague-Dawley rats were dosed daily by gavage for...

  13. THE IN VITRO PHASE I METABOLISM OF THE TRIAZOLE FUNGICIDE BROMUCONAZOLE AND ITS FOUR ENANTIOMERS

    EPA Science Inventory

    The triazole fungicide bromuconazole contains two chiral centers and exists as two diastereomers, each with two enantiomers. It has been widely used as a mixture of its diastereomers on food products. Here we report on the in vitro metabolism of the individual and combined dias...

  14. Rate of Interfacial Electron Transfer through the 1,2,3-Triazole Linkage

    PubMed Central

    Devaraj, Neal K.; Decreau, Richard A.; Ebina, Wataru; Collman, James P.; Chidsey, Christopher E. D.

    2012-01-01

    The rate of electron transfer is measured to two ferrocene and one iron tetraphenylporphyrin redox species coupled through terminal acetylenes to azide-terminated thiol monolayers by the Cu(I)-catalyzed azide–alkyne cycloaddition (a Sharpless “click” reaction) to form the 1,2,3-triazole linkage. The high yield, chemoselectivity, convenience, and broad applicability of this triazole formation reaction make such a modular assembly strategy very attractive. Electron-transfer rate constants from greater than 60,000 to 1 s−1 are obtained by varying the length and conjugation of the electron-transfer bridge and by varying the surrounding diluent thiols in the monolayer. Triazole and the triazole carbonyl linkages provide similar electronic coupling for electron transfer as esters. The ability to vary the rate of electron transfer to many different redox species over many orders of magnitude by using modular coupling chemistry provides a convenient way to study and control the delivery of electrons to multielectron redox catalysts and similar interfacial systems that require controlled delivery of electrons. PMID:16898751

  15. Aryl-triazole foldamers incorporating a pyridinium motif for halide anion binding in aqueous media.

    PubMed

    Shang, Jie; Zhao, Wei; Li, Xichen; Wang, Ying; Jiang, Hua

    2016-03-15

    Aryl-triazole oligomers incorporating a pyridinium motif have been synthesized from their pyridine precursors. Anion binding studies show that methylation of the pyridine units can significantly enhance the halide anion affinities of the folded oligomers so that the foldamers are capable of binding halide anions in aqueous solutions. PMID:26933696

  16. BITERTANOL, A TRIAZOLE FUNGICIDE, INCREASES OPERANT RESPONDING BUT NOT MOTOR ACTIVITY

    EPA Science Inventory

    Several recent reports indicate that triadimefon, a triazole fungicide, has effects on behavior that are similar to those of psychomotor stimulants. or example, both d-amphetamine and triadimefon increase rates and disrupt patterns of responding maintained under FI schedules of r...

  17. Synthesis of 1,2,4-triazolines and triazoles utilizing oxazolones.

    PubMed

    Saleem, Rahman Shah Zaib; Tepe, Jetze J

    2010-06-18

    We describe herein a convenient method for the synthesis of 1,2,4-triazolines using oxazolones and azodicarboxylates. Subsequent treatment of these 1,2,4-triazolines with NaOH provides efficient access to the corresponding triazoles. PMID:20481587

  18. Luminescent Iridium(III) Cyclometalated Complexes with 1,2,3-Triazole "Click" Ligands.

    PubMed

    Connell, Timothy U; White, Jonathan M; Smith, Trevor A; Donnelly, Paul S

    2016-03-21

    A series of cyclometalated iridium(III) complexes with either 4-(2-pyridyl)-1,2,3-triazole or 1-(2-picolyl)-1,2,3-triazole ancillary ligands to give complexes with either 5- or 6-membered chelate rings were synthesized and characterized by a combination of X-ray crystallography, electron spin ionization-high-resolution mass spectroscopy (ESI-HRMS), and nuclear magnetic resonance (NMR) spectroscopy. The electronic properties of the complexes were probed using absorption and emission spectroscopy, as well as cyclic voltammetry. The relative stability of the complexes formed from each ligand class was measured, and their excited-state properties were compared. The emissive properties are, with the exception of complexes that contain a nitroaromatic substituent, insensitive to functionalization of the ancillary pyridyl-1,2,3-triazole ligand but tuning of the emission maxima was possible by modification of the cyclometalating ligands. It is possible to prepare a wide range of optimally substituted pyridyl-1,2,3-triazoles using copper Cu(I)-catalyzed azide alkyne cycloaddition, which is a commonly used "click" reaction, and this family of ligands represent an useful alternative to bipyridine ligands for the preparation of luminescent iridium(III) complexes. PMID:26938838

  19. Synthesis of divinyl derivatives of 5-substituted 1,2,4-triazole-3-thiones

    SciTech Connect

    Trzhtsinskaya, B.V.; Rudakova, E.V.; Afonin, A.V.; Pertsikov, B.Z.; Mansurov, Yu.A.; Aksenov, V.P.

    1987-01-20

    The authors have previously described the synthesis of two divinyl derivatives of unsubstituted triazolethione. In order to expand the range of such compounds, they studied the reaction of 5-methyl- (I), 5-phenyl- (II), and 5-..cap alpha..-furyl-1,2,4-triazole-3-thione (III) with acetylene. Triazoles (I) and (III) in the presence of alkali add one acetylene molecule. An increase in the reaction time yields the product of the addition of two acetylene molecules to (I) in yields up to 50%. The substitution of the alkaline catalyst by CuCl facilitates the formation of divinyl derivatives. However, the use of CuCl in this case led to a decrease in the yield of the desired product. N-Vinyl-3-vinylthio-5-methyl-1,2,4-triazoles were obtained in yields up to 64% in the presence of cadmium acetate. On the other hand, the use of CuCl as the catalyst facilitates the synthesis of N-vinyl-3-vinylthio-5-phenyl- and N-vinyl-3-vinylthio-5-..cap alpha..-furyl-1,2,4-triazoles.

  20. Synthesis of 1,1'-dinitro-3,3'-azo-1,2,4-triazole

    SciTech Connect

    Lee, K.Y.

    1985-04-01

    A novel compound has been prepared and is a candidate for high-energy propellant applications. The 1,1'-dinitro-3,3'-azo-1,2,4-triazole (N-DNAT) has a density of 1.77 g/cm/sup 3/ and can be prepared from inexpensive starting materials.

  1. Dose-response involvement of constitutive androstane receptor in mouse liver hypertrophy induced by triazole fungicides.

    PubMed

    Tamura, Kei; Inoue, Kaoru; Takahashi, Miwa; Matsuo, Saori; Irie, Kaoru; Kodama, Yukio; Ozawa, Shogo; Nishikawa, Akiyoshi; Yoshida, Midori

    2013-07-31

    To clarify the dose-response relationship between constitutive androstane receptor (CAR) activity and induction of cytochrome P450 2B (CYP2B) expression and hypertrophy by triazole fungicides in mouse liver, three dose levels of cyproconazole (Cypro), tebuconazole (Teb), fluconazole (Flu), and phenobarbital (PB), a typical CYP2B inducer, were administrated in diet to male wild-type (WT) and CAR-knockout (CARKO) mice for one week. In WT mice, all compounds dose-dependently induced liver weight increases and hepatocellular hypertrophy accompanied by CYP2B expression. In CARKO mice, these effects were not induced by PB, while Cypro or Flu induced these effects only at the highest dose. Dose-dependent liver hypertrophy was detected in CARKO mice treated with Teb, but at the lowest dose the intensity was weakened compared to WT mice. The present results indicate that Cypro and Flu mainly induced CAR-mediated liver hypertrophy, while Teb slightly involved CAR. The involvement of CAR in triazole-induced liver hypertrophy was dose-responsive. In addition, all three triazoles have non-CAR-mediated liver hypertrophy pathways, indicating that the hypertrophy induced by these triazoles differs from that of PB. PMID:23721867

  2. AN IN SILICO INVESTIGATION OF THE ENANTIOSELECTIVE METABOLISM RATES OF TRIAZOLE FUGICIDES

    EPA Science Inventory

    The objective of this work is to use in silico methods such as ab initio quantum and classical force-field methods to explore and develop an understanding for the enantioselective metabolism rates experimentally observed in the triazole fungicide bromuconazole. This directed stud...

  3. Searching for novel scaffold of triazole non-nucleoside inhibitors of HIV-1 reverse transcriptase.

    PubMed

    Frączek, Tomasz; Paneth, Agata; Kamiński, Rafał; Krakowiak, Agnieszka; Paneth, Piotr

    2016-06-01

    Azoles are a promising class of the new generation of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). From thousands of reported compounds, many possess the same basic structure of an aryl substituted azole ring linked by a thioglycolamide chain with another aromatic ring. In order to find novel extensions for this basic scaffold, we explored the 5-position substitution pattern of triazole NNRTIs using molecular docking followed by the synthesis of selected compounds. We found that heterocyclic substituents in the 5-position of the triazole ring are detrimental to the inhibitory activity of compounds with four-membered thioglycolamide linker and this substitution seems to be viable only for compounds with shorter two-membered linker. Promising compound, N-(4-carboxy-2-chlorophenyl)-2-((4-benzyl-5-methyl-4H-1,2,4-triazol-3-yl)sulfanyl)acetamide, with potent inhibitory activity and acceptable aqueous solubility has been identified in this study that could serve as lead scaffold for the development of novel water-soluble salts of triazole NNRTIs. PMID:25942362

  4. Preparation of 1,1'-dinitro-3,3'-azo-1,2,4-triazole

    DOEpatents

    Lee, Kien-Yin

    1986-01-01

    A new high density composition of matter, 1,1'-dinitro-3,3'-azo-1,2,4-triazole, has been synthesized using inexpensive, commonly available compounds. This compound has been found to be an explosive, and its use as a propellant is anticipated.

  5. Synthesis of Triazole Schiff’s Base Derivatives and Their Inhibitory Kinetics on Tyrosinase Activity

    PubMed Central

    Wang, Hui-Fang; Zheng, Jing; Cui, Yi; Fang, Xin-Yu; Zhang, Lin-Min; Chen, Qing-Xi

    2015-01-01

    In the present study, new Schiff’s base derivatives: (Z)-4-amino-5-(2-(3- fluorobenzylidene)hydrazinyl)-4H-1,2,4-triazole-3-thiol (Y1), (Z)-3-((2-(4-amino-5- mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y2), (Z)-2-((2-(4-amino-5- mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y3) and 3-((Z)-(2-(4- (((E)-3-hydroxybenzylidene)amino)-5-mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y4) were synthesized and their structures were characterized by LC-MS, IR and 1H NMR. The inhibitory effects of these compounds on tyrosinase activites were evaluated. Compounds Y1, Y2 and Y3 showed potent inhibitory effects with respective IC50 value of 12.5, 7.0 and 1.5 μM on the diphenolase activities. Moreover, the inhibition mechanisms were determined to be reversible and mixed types. Interactions of the compounds with tyrosinase were further analyzed by fluorescence quenching, copper interaction, and molecular simulation assays. The results together with the anti-tyrosinase activities data indicated that substitution on the second position of benzene ring showed superior ant-ityrosinase activities than that on third position, and that hydroxyl substitutes were better than fluorine substitutes. In addition, two benzene rings connecting to the triazole ring would produce larger steric hindrance, and affect the bonding between tyrosinase and inhibitors to decrease the inhibitory effects. The anti-tyrosinase effects of these compounds were in contrast to their antioxidant activities. In summary, this research will contribute to the development and design of antityrosinase agents. PMID:26422245

  6. Triazole pyrimidine nucleosides as inhibitors of Ribonuclease A. Synthesis, biochemical, and structural evaluation.

    PubMed

    Parmenopoulou, Vanessa; Chatzileontiadou, Demetra S M; Manta, Stella; Bougiatioti, Stamatina; Maragozidis, Panagiotis; Gkaragkouni, Dimitra-Niki; Kaffesaki, Eleni; Kantsadi, Anastassia L; Skamnaki, Vassiliki T; Zographos, Spyridon E; Zounpoulakis, Panagiotis; Balatsos, Nikolaos A A; Komiotis, Dimitris; Leonidas, Demetres D

    2012-12-15

    Five ribofuranosyl pyrimidine nucleosides and their corresponding 1,2,3-triazole derivatives have been synthesized and characterized. Their inhibitory action to Ribonuclease A has been studied by biochemical analysis and X-ray crystallography. These compounds are potent competitive inhibitors of RNase A with low μM inhibition constant (K(i)) values with the ones having a triazolo linker being more potent than the ones without. The most potent of these is 1-[(β-D-ribofuranosyl)-1,2,3-triazol-4-yl]uracil being with K(i) = 1.6 μM. The high resolution X-ray crystal structures of the RNase A in complex with three most potent inhibitors of these inhibitors have shown that they bind at the enzyme catalytic cleft with the pyrimidine nucleobase at the B(1) subsite while the triazole moiety binds at the main subsite P(1), where P-O5' bond cleavage occurs, and the ribose at the interface between subsites P(1) and P(0) exploiting interactions with residues from both subsites. The effect of a susbsituent group at the 5-pyrimidine position at the inhibitory potency has been also examined and results show that any addition at this position leads to a less efficient inhibitor. Comparative structural analysis of these RNase A complexes with other similar RNase A-ligand complexes reveals that the triazole moiety interactions with the protein form the structural basis of their increased potency. The insertion of a triazole linker between the pyrimidine base and the ribose forms the starting point for further improvement of these inhibitors in the quest for potent ribonucleolytic inhibitors with pharmaceutical potential. PMID:23122937

  7. TOXICOGENOMIC STUDY OF TRIAZOLE FUNGICIDES AND PERFLUOROALKYL ACIDS IN RAT LIVERS ACCURATELY CATEGORIZES CHEMICALS AND IDENTIFIES MECHANISMS OF TOXICITY

    EPA Science Inventory

    Toxicogenomic analysis of five environmental chemicals was performed to investigate the ability of genomics to predict toxicity, categorize chemicals, and elucidate mechanisms of toxicity. Three triazole antifungals (myclobutanil, propiconazole, and triadimefon) and two perfluori...

  8. GENE EXPRESSION PROFILING IN THE LIVER OF CD-1 MICE TO CHARACTERIZE THE HEPATOTOXICITY OF TRIAZOLE FUNGICIDES.

    EPA Science Inventory

    Four triazole fungicides used in agricultural or pharmaceutical applications were examined for hepatotoxic effects in mouse liver. Besides organ weight, histopathology, and cytochrome P450 (CYP) enzyme induction, DNA microarrays were used to generate gene expression profiles and ...

  9. A triazole based fluorescence "turn-on" sensor for Al(Ⅲ) and Zn(Ⅱ) ions

    NASA Astrophysics Data System (ADS)

    Bian, Gao-Feng; Guo, Yun; Lv, Xiao-Jing; Zhang, Cheng

    2016-05-01

    A triazole derivative containing trifluoromethyl and diphenol unit was synthesized as a fluorescent 'turn-on' chemosensor for Al3+ and Zn2+ ions with high sensitivity, a rapid response time and specific selectivity over other cations.

  10. GENE EXPRESSION PROFILING IN THE LIVER OF CD-1 MICE TO CHARACTERIZE THE HEPATOTOXICITY OF TRIAZOLE FUNGICIDES

    EPA Science Inventory

    Four triazole fungicides used in agricultural or pharmaceutical applications were examined for hepatotoxic effects in mouse liver. Besides organ weight, histopathology, and cytochrome P450 (CYP) enzyme induction, DNA microarrays were used to generate gene expression profiles and ...

  11. Comparison of inverse and regular 2-pyridyl-1,2,3-triazole "click" complexes: structures, stability, electrochemical, and photophysical properties.

    PubMed

    Lo, Warrick K C; Huff, Gregory S; Cubanski, John R; Kennedy, Aaron D W; McAdam, C John; McMorran, David A; Gordon, Keith C; Crowley, James D

    2015-02-16

    Two inverse 2-pyridyl-1,2,3-triazole "click" ligands, 2-(4-phenyl-1H-1,2,3-triazol-1-yl)pyridine and 2-(4-benzyl-1H-1,2,3-triazol-1-yl)pyridine, and their palladium(II), platinum(II), rhenium(I), and ruthenium(II) complexes have been synthesized in good to excellent yields. The properties of these inverse "click" complexes have been compared to the isomeric regular compounds using a variety of techniques. X-ray crystallographic analysis shows that the regular and inverse complexes are structurally very similar. However, the chemical and physical properties of the isomers are quite different. Ligand exchange studies and density functional theory (DFT) calculations indicate that metal complexes of the regular 2-(1-R-1H-1,2,3-triazol-4-yl)pyridine (R = phenyl, benzyl) ligands are more stable than those formed with the inverse 2-(4-R-1H-1,2,3-triazol-1-yl)pyridine (R = phenyl, benzyl) "click" chelators. Additionally, the bis-2,2'-bipyridine (bpy) ruthenium(II) complexes of the "click" chelators have been shown to have short excited state lifetimes, which in the inverse triazole case, resulted in ejection of the 2-pyridyl-1,2,3-triazole ligand from the complex. Under identical conditions, the isomeric regular 2-pyridyl-1,2,3-triazole ruthenium(II) bpy complexes are photochemically inert. The absorption spectra of the inverse rhenium(I) and platinum(II) complexes are red-shifted compared to the regular compounds. It is shown that conjugation between the substituent group R and triazolyl unit has a negligible effect on the photophysical properties of the complexes. The inverse rhenium(I) complexes have large Stokes shifts, long metal-to-ligand charge transfer (MLCT) excited state lifetimes, and respectable quantum yields which are relatively solvent insensitive. PMID:25615621

  12. Sequential decarboxylative azide–alkyne cycloaddition and dehydrogenative coupling reactions: one-pot synthesis of polycyclic fused triazoles

    PubMed Central

    Bharathimohan, Kuppusamy; Ponpandian, Thanasekaran; Bhuvanesh, Nattamai

    2014-01-01

    Summary Herein, we describe a one-pot protocol for the synthesis of a novel series of polycyclic triazole derivatives. Transition metal-catalyzed decarboxylative CuAAC and dehydrogenative cross coupling reactions are combined in a single flask and achieved good yields of the respective triazoles (up to 97% yield). This methodology is more convenient to produce the complex polycyclic molecules in a simple way. PMID:25670973

  13. Sequential decarboxylative azide-alkyne cycloaddition and dehydrogenative coupling reactions: one-pot synthesis of polycyclic fused triazoles.

    PubMed

    Bharathimohan, Kuppusamy; Ponpandian, Thanasekaran; Ahamed, A Jafar; Bhuvanesh, Nattamai

    2014-01-01

    Herein, we describe a one-pot protocol for the synthesis of a novel series of polycyclic triazole derivatives. Transition metal-catalyzed decarboxylative CuAAC and dehydrogenative cross coupling reactions are combined in a single flask and achieved good yields of the respective triazoles (up to 97% yield). This methodology is more convenient to produce the complex polycyclic molecules in a simple way. PMID:25670973

  14. Tuning the microstructures of decavanadate-based supramolecular hybrids via regularly changing the spacers of bis(triazole) ligands

    NASA Astrophysics Data System (ADS)

    Wang, Mo; Sun, Wenlong; Pang, Haijun; Ma, Huiyuan; Yu, Jia; Zhang, Zhuanfang; Niu, Ying; Yin, Mingming

    2016-03-01

    With tuning the ligands from bte, btp, btb to bth, four new decavanadate-based metal-organic hybrid compounds, [Zn(bte)(H2O)4][Zn2(bte)(H2O)10](V10O28)·8H2O, [Zn2(btp)4(H2O)6](H2V10O28)·4H2O, [Zn(H2O)6][Zn2(btb)2V10O28(H2O)6]·4H2O, and [Zn2(bth)(H2O)10](H2V10O28)·6H2O (bte=1,2-bis(1,2,4-triazol-1-yl)ethane, btp=1,3-bis(1,2,4-triazol-1-y1)propane, btb=1,4-bis(1,2,4-triazol-1-y1)butane, bth=1,6-bis(1,2,4-triazol-1-y1)hexane), have been synthesized under conventional conditions. The four compounds represent the first examples of decavanadate-based metal-organic hybrids constructed by Zn-bis(triazole) complexes. Their structural analyses show that the four compounds possess different Zn-bis(triazole) structural motifs and various finally structures, which verifies that regular changing the spacers of ligands is an effective strategy to tuning the structures of polyoxometalate-based hybrids. Also, the electrochemical studies show that the compounds have good electrocatalytic activities towards oxidation of nitrite molecules ascribed to V-centers.

  15. Tetrathiafulvalene mono- and bis-1,2,3-triazole precursors by click chemistry: structural diversity and reactivity.

    PubMed

    Biet, Thomas; Avarvari, Narcis

    2014-05-28

    The donor ortho-dimethyl-TTF-(N-n-Bu-1,2,3-triazole) 1,5-isomer has been synthesized by click chemistry following a ruthenium-catalyzed azide-alkyne cycloaddition procedure. The single crystal X-ray analysis showed a planar conformation between the TTF and triazole units and a set of intermolecular interactions at the supramolecular level in the solid state. The same procedure allowed the preparation of the corresponding ortho-dimethyl-TTF-bis(triazole) which was also structurally characterized. Because of the steric hindrance, the triazole units are no longer planar with the TTF backbone. The reactivity of the triazole ring has been investigated in protonation and alkylation reactions, monitored by UV-visible spectroscopy, which clearly showed the red shift of the intramolecular charge transfer band. A TTF-methyl-triazolium salt has been isolated and analyzed by single crystal X-ray analysis. All of the TTF-triazoles and triazolium salts are valuable precursors for radical cation salts due to their oxidation potentials and variety of possible intermolecular interactions. PMID:24682102

  16. Are 1,4- and 1,5-disubstituted 1,2,3-triazoles good pharmacophoric groups?

    PubMed

    Massarotti, Alberto; Aprile, Silvio; Mercalli, Valentina; Del Grosso, Erika; Grosa, Giorgio; Sorba, Giovanni; Tron, Gian Cesare

    2014-11-01

    Over the last decade, 1,2,3-triazoles have received increasing attention in medicinal chemistry thanks to the discovery of the highly useful and widely applicable 1,3-dipolar cycloaddition reaction between azides and alkynes (click chemistry) catalyzed by copper salts and ruthenium complexes. After a decade of medicinal chemistry research on 1,2,3-triazoles, we feel that the time is ripe to demonstrate the real ability of this heterocycle to participate in important and pivotal binding interactions with biological targets while maintaining a good pharmacokinetic profile. In this study, we retrieved and analyzed X-ray crystal structures of complexes between 1,2,3-triazoles and either proteins or DNA to understand the pharmacophoric role of the triazole. Furthermore, the metabolic stability, the capacity to inhibit cytochromes, and the contribution of 1,2,3-triazoles to the overall aqueous solubility of compounds containing them have been analyzed. This information should furnish fresh insight for medicinal chemists in the design of novel bioactive molecules that contain the triazole nucleus. PMID:25079879

  17. Triazole resistance mediated by mutations of a conserved active site tyrosine in fungal lanosterol 14α-demethylase.

    PubMed

    Sagatova, Alia A; Keniya, Mikhail V; Wilson, Rajni K; Sabherwal, Manya; Tyndall, Joel D A; Monk, Brian C

    2016-01-01

    Emergence of fungal strains showing resistance to triazole drugs can make treatment of fungal disease problematic. Triazole resistance can arise due to single mutations in the drug target lanosterol 14α-demethylase (Erg11p/CYP51). We have determined how commonly occurring single site mutations in pathogenic fungi affect triazole binding using Saccharomyces cerevisiae Erg11p (ScErg11p) as a target surrogate. The mutations Y140F/H were introduced into full-length hexahistidine-tagged ScErg11p. Phenotypes and high-resolution X-ray crystal structures were determined for the mutant enzymes complexed with short-tailed (fluconazole and voriconazole) or long-tailed (itraconazole and posaconazole) triazoles and wild type enzyme complexed with voriconazole. The mutations disrupted a water-mediated hydrogen bond network involved in binding of short-tailed triazoles, which contain a tertiary hydroxyl not present in long-tailed triazoles. This appears to be the mechanism by which resistance to these short chain azoles occurs. Understanding how these mutations affect drug affinity will aid the design of azoles that overcome resistance. PMID:27188873

  18. Triazole resistance mediated by mutations of a conserved active site tyrosine in fungal lanosterol 14α-demethylase

    PubMed Central

    Sagatova, Alia A.; Keniya, Mikhail V.; Wilson, Rajni K.; Sabherwal, Manya; Tyndall, Joel D. A.; Monk, Brian C.

    2016-01-01

    Emergence of fungal strains showing resistance to triazole drugs can make treatment of fungal disease problematic. Triazole resistance can arise due to single mutations in the drug target lanosterol 14α-demethylase (Erg11p/CYP51). We have determined how commonly occurring single site mutations in pathogenic fungi affect triazole binding using Saccharomyces cerevisiae Erg11p (ScErg11p) as a target surrogate. The mutations Y140F/H were introduced into full-length hexahistidine-tagged ScErg11p. Phenotypes and high-resolution X-ray crystal structures were determined for the mutant enzymes complexed with short-tailed (fluconazole and voriconazole) or long-tailed (itraconazole and posaconazole) triazoles and wild type enzyme complexed with voriconazole. The mutations disrupted a water-mediated hydrogen bond network involved in binding of short-tailed triazoles, which contain a tertiary hydroxyl not present in long-tailed triazoles. This appears to be the mechanism by which resistance to these short chain azoles occurs. Understanding how these mutations affect drug affinity will aid the design of azoles that overcome resistance. PMID:27188873

  19. Chromatographic and electrophoretic techniques used in the analysis of triazole antifungal agents-a review.

    PubMed

    Ekiert, R J; Krzek, J; Talik, P

    2010-09-15

    Systematic review of literature coupled with integrative research of published data for triazole antifungal agents was done. The investigated literature covered chromatographic and electrophoretic methods developed in the last 10 years (2000-2009). The aim of this review was to compare different methodologies, assess preferences in the selection of analytical methods and to find still existing analytical problems. Last decade is characterized by dynamic development of instrumental methods, that results in advance and diversity of applied analytical procedures. The main focus was given to high-performance liquid chromatography (HPLC), the technique of choice in the analysis of most of pharmaceuticals. The review includes literature on 8 triazole antifungal drugs: fluconazole, itraconazole and terconazole from the first generation and posaconazole, voriconazole, ravuconazole, isavuconazole and albaconazole classified in second generation. Investigations of pharmaceutical formulations and biological samples were considered. PMID:20801303

  20. Benzimidazole-1,2,3-triazole Hybrid Molecules: Synthesis and Evaluation for Antibacterial/Antifungal Activity

    PubMed Central

    Ouahrouch, Abdelaaziz; Ighachane, Hana; Taourirte, Moha; Engels, Joachim W; Sedra, My Hassan; Lazrek, Hassan B

    2014-01-01

    A novel series of hybrid molecules 4a–i and 5a–i were prepared by condensation of 4-(trimethylsilylethynyl)benzaldehyde 1 with substituted o-phenylenediamines. These in turn were reacted with 2-(azidomethoxy)ethyl acetate in a Cu alkyne–azide cycloaddition (CuAAC) to generate the 1,2,3-triazole pharmacophore under microwave assistance. The newly synthesized compounds were examined for their in vitro antimicrobial activities against Gram-positive and Gram-negative bacteria and the phytopathogenic fungi Verticillium dahliae and Fusarium oxysporum f. sp. albedinis. 2-((4-(4-(5-Trifluoromethyl benzimidazol-2-yl)phenyl)-1,2,3-triazol-1-yl)methoxy)ethanol 5e showed a moderate inhibition of 30% in the Foa sporulation test. PMID:25088180

  1. Reaction of 1,2,4-triazole-3-thiones with 1-chloro-2,3-epoxypropane

    SciTech Connect

    Trzhtsinskaya, B.V.; Kositsyna, E.I.; Pertsikov, B.Z.; Rudakova, E.V.; Voronov, V.K.; Skvortsova, G.G.

    1987-08-01

    Addition of 1-chloro-2,3-epoxypropane to 1,2,4-triazole-3-thiones depending on the ratio of the reactants leads to the formation of 3-(1-chloro-2-hydroxypropyl)-3-(1-chloro-2-hydroxypropylthio)-1,2,4-triazoles. 3-Hydroxy-1,2,4-triazolo(2,3-b) tetrahydro-1,3-triazines have been synthesized by intramolecular cyclization of the monoadducts. IR spectra were recorded on a Specord 75-IR instrument as a thin layer, in KBr pellets, an in chloroform solution; PMR spectra were recorded on a Tesla BS-497 instrument (100 MHz) at 20/sup 0/C in CD/sub 3/OD with TMS as internal standard.

  2. Preparation and properties of 3-amino-5-nitro-1,2,4-triazole

    SciTech Connect

    Lee, Kien-Yin; Storm, C.B.

    1990-10-01

    A novel method for the preparation of 3-amino-5-nitro-1,2,4-triazole (ANTA) has been invented. The yield of ANTA by selective reduction of the ammonium salt of 3,5-dinitro-1,2,4-triazole with hydrazine hydrate is 94% to 96% under mild reaction conditions. There is no volatile hydrazine present at the end of the reaction as it is isolated as hydrazine hydrochloride. ANTA, a potential insensitive explosive, has a crystal density of 1.82 g/cm{sup 3}, and a positive heat of formation ({Delta}H{sub f}) of 21.0 kcal/mol, and is thermally stable. The detonation velocity of ANTA, calculated at crystal density, is higher than that of triaminotrinitrobenzene. In addition to the preparation of ANTA, we have also synthesized a new hydrazinium salt of ANTA. 6 refs., 2 tabs.

  3. Hypervalent-Iodine(III)-Mediated Oxidative Methodology for the Synthesis of Fused Triazoles.

    PubMed

    Kamal, Raj; Kumar, Vipan; Kumar, Ravinder

    2016-07-20

    The organic chemistry of hypervalent organoiodine compounds has been an area of unprecedented development. This surge in interest in the use of hypervalent iodine compounds has mainly been owing to their highly selective oxidizing properties, environmentally benign character and commercial availability. Hypervalent iodine reagents have also been used as an alternative to toxic heavy metals, owing to their low toxicity and ease of handling. Hypervalent organoiodine(III) reagents are versatile oxidants that have been successfully employed to extend the scope of selective oxidative transformations of complex organic molecules in synthetic chemistry. This Focus Review concerns the tandem in situ generation and 1,5-electrocyclization of N-heteroaryl nitrilimines into fused triazoles. We describe the importance of recently developed hypervalent-organoiodine(III)-catalyzed oxidative cyclization reactions, building towards the conclusion that hypervalent iodine chemistry is a promising frontier for oxidative cyclization, in particular of hydrazones, for the synthesis of fused triazoles. PMID:27123538

  4. 3-nitro-1,2,4-triazol-5-one: A less sensitive explosive

    DOEpatents

    Lee, Kien-Yin; Coburn, M.D.

    1987-01-30

    A less sensitive explosive, 3-nitro-1,2,4-triazol-5-one. The compound 3-nitro--1,2,4-triazol-5-one (NTO) has a crystal density of 1.93 g/cm/sup 3/ and calculated detonation velocity and pressure equivalent to those of RDX. It can be prepared in high yield from inexpensive starting materials in a safe synthesis. Results from initial small-scale sensitivity tests indicate that NTO is less sensitive than RDX and HMX in all respects. A 4.13 cm diameter, unconfined plate-dent test at 92% of crystal density gave the detonation pressure predicted for NTO by the BKW calculation. 3 tabs.

  5. Synthesis, In Vitro Biological Evaluation, and Molecular Docking of New Triazoles as Potent Antifungal Agents.

    PubMed

    Li, Xiang; Liu, Chao; Tang, Sheng; Wu, Qiuye; Hu, Honggang; Zhao, Qingjie; Zou, Yan

    2016-01-01

    Based on the structure of the active site of CYP51 and the structure-activity relationships of azole antifungal compounds that we designed in a previous study, a series of 1-{1-[2-(substitutedbenzyloxy)ethyl]-1H-1,2,3-triazol-4-yl}-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ols (6a-n) were designed and synthesized utilizing copper-catalyzed azide-alkyne cycloaddition. Preliminary antifungal tests against eight human pathogenic fungi in vitro showed that all the title compounds exhibited excellent antifungal activities with a broad spectrum in vitro. Molecular docking results indicated that the interaction between the title compounds and CYP51 comprised π-π interactions, hydrophobic interactions, and the narrow hydrophobic cleft. PMID:26641629

  6. Synthesis and antifungal activity of 1,2,3-triazole phenylhydrazone derivatives.

    PubMed

    Dai, Zhi-Cheng; Chen, Yong-Fei; Zhang, Mao; Li, Sheng-Kun; Yang, Ting-Ting; Shen, Li; Wang, Jian-Xin; Qian, Shao-Song; Zhu, Hai-Liang; Ye, Yong-Hao

    2015-01-14

    A series of 1,2,3-triazole phenylhydrazone derivatives were designed and synthesized as antifungal agents. Their structures were determined based on (1)H-NMR spectroscopy, MS, elemental analysis and X-ray single-crystal diffraction. The antifungal activities were evaluated against four phytopathogenic fungi including Rhizoctonia solani, Sclerotinia sclerotiorum, Fusarium graminearum and Phytophthora capsici, by the mycelium growth inhibition method in vitro. Compound 5p exhibited significant anti-phytopathogenic activity, with the EC50 values of 0.18, 2.28, 1.01, and 1.85 μg mL(-1), respectively. In vivo testing demonstrated that 5p was effective in the control of rice sheath blight, rape sclerotinia rot and fusarium head blight. A 3D-QSAR model was built for a systematic SAR profile to explore more potent 1,2,3-triazole phenylhydrazone analogs as novel fungicides. PMID:25374053

  7. Competitive Halide Binding by Halogen Versus Hydrogen Bonding: Bis-triazole Pyridinium.

    PubMed

    Nepal, Binod; Scheiner, Steve

    2015-09-14

    The binding of F(-) , Cl(-) , Br(-) , and I(-) anions by bis-triazole-pyridine (BTP) was examined by quantum chemical calculations. There is one H atom on each of the two triazole rings that chelate the halide via H bonds. These H atoms were replaced by halogens Cl, Br, and I, thus substituting H bonds by halogen bonds. I substitution strongly enhances the binding; Br has a smaller effect, and Cl weakens the interaction. The strength of the interaction is sensitive to the overall charge on the BTP, rising as the binding agent becomes singly and then doubly positively charged. The strongest preference of a halide for halogenated as compared to unsubstituted BTP, as much as several orders of magnitude, is observed for I(-) . Both unsubstituted and I-substituted BTP could be used to selectively extract F(-) from a mixture of halides. PMID:26234647

  8. Triazole: a unique building block for the construction of functional materials.

    PubMed

    Juríček, Michal; Kouwer, Paul H J; Rowan, Alan E

    2011-08-21

    Over the past 50 years, numerous roads towards carbon-based materials have been explored, all of them being paved using mainly one functional group as the brick: acetylene. The acetylene group, or the carbon-carbon triple bond, is one of the oldest and simplest functional groups in chemistry, and although not present in any of the naturally occurring carbon allotropes, it is an essential tool to access their synthetic carbon-rich family. In general, two strategies towards the synthesis of π-conjugated carbon-rich structures can be employed: (a) either the acetylene group serves as a building block to access acetylene-derived structures or (b) it serves as a synthetic tool to provide other, usually benzenoid, structures. The recently discovered copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction, however, represents a new powerful alternative: it transforms the acetylene group into a five-membered heteroaromatic 1H-1,2,3-triazole (triazole) ring and this gives rise to new opportunities. Compared with all-carbon aromatic non-functional rings, the triazole ring possesses three nitrogen atoms and, thus, can serve as a ligand to coordinate metals, or as a hydrogen bond acceptor and donor. This Feature Article summarises examples of using the triazole ring to construct conjugation- and/or function-related heteroaromatic materials, such as tuneable multichromophoric covalent ensembles, macrocyclic receptors or responsive foldamers. These recent examples, which open a new sub-field within organic materials, started to appear only few years ago and represent "a few more bricks" on the road to carbon-rich functional materials. PMID:21556388

  9. Synthesis and antifungal activity of novel triazole compounds containing piperazine moiety.

    PubMed

    Wang, Yanwei; Xu, Kehan; Bai, Guojing; Huang, Lei; Wu, Qiuye; Pan, Weihua; Yu, Shichong

    2014-01-01

    Design and synthesis of triazole library antifungal agents having piperazine side chains, analogues to fluconazole were documented. The synthesis highlighted utilization of the click chemistry on the basis of the active site of the cytochrome P450 14α-demethylase (CYP51). Their structures were characterized by (1)H-NMR, (13)C-NMR, MS and IR. The influences of piperazine moiety on in vitro antifungal activities of all the target compounds were evaluated against eight human pathogenic fungi. PMID:25090121

  10. Bis(4H-1,2,4-triazol-3-yl)disulfane

    PubMed Central

    Liu, Dongsheng; Xu, Yaping; Li, Xinfa; Ying, Shaoming; Chen, Wentong

    2008-01-01

    The title compound, C4H4N6S2, was synthesized by the reaction of 3-mercapto-1H-1,2,4-triazole with sodium hydrox­ide in ethanol. The mol­ecule possesses a crystallographically imposed twofold axis. Inter­molecular N—H⋯N hydrogen bonds link the mol­ecules into chains along the c axis. PMID:21200812

  11. SERS enhancement of silver nanoparticles prepared by a template-directed triazole ligand strategy.

    PubMed

    Kashmery, Heba A; Thompson, David G; Dondi, Ruggero; Mabbott, Samuel; Graham, Duncan; Clark, Alasdair W; Burley, Glenn A

    2015-08-21

    Two advances in the development of a one-pot method to prepare silver nanoparticles (AgNPs) using the Tollens' reagent are described. First, a template-directed process of AgNP synthesis using resorcinol triazole ligands bearing two pendent galactose sugars is shown. Second, the conversion of these AgNPs into SERS nanotags is demonstrated using malachite green isothiocyanate as the Raman reporter molecule. PMID:26179948

  12. 3-Substituted pyrazoles and 4-substituted triazoles as inhibitors of human 15-lipoxygenase-1.

    PubMed

    Pelcman, Benjamin; Sanin, Andrei; Nilsson, Peter; No, Kiyo; Schaal, Wesley; Öhrman, Sara; Krog-Jensen, Christian; Forsell, Pontus; Hallberg, Anders; Larhed, Mats; Boesen, Thomas; Kromann, Hasse; Vogensen, Stine Byskov; Groth, Thomas; Claesson, Hans-Erik

    2015-08-01

    Investigation of 1N-substituted pyrazole-3-carboxanilides as 15-lipoxygenase-1 (15-LOX-1) inhibitors demonstrated that the 1N-substituent was not essential for activity or selectivity. Additional halogen substituents on the pyrazole ring, however, increased activity. Further development led to triazole-4-carboxanilides and 2-(3-pyrazolyl) benzoxazoles, which are potent and selective 15-LOX-1 inhibitors. PMID:26037322

  13. Gene expression profiling in the liver of CD-1 mice to characterize the hepatotoxicity of triazole fungicides

    SciTech Connect

    Goetz, Amber K.; Bao, Wenjun; Ren, Hongzu; Schmid, Judith E.; Tully, Douglas B.; Wood, Carmen; Rockett, John C.; Narotsky, Michael G.; Sun, Guobin; Lambert, Guy R.; Thai, S.-F.; Wolf, Douglas C.; Nesnow, Stephen; Dix, David J. . E-mail: dix.david@epa.gov

    2006-09-15

    Four triazole fungicides used in agricultural or pharmaceutical applications were examined for hepatotoxic effects in mouse liver. Besides organ weight, histopathology, and cytochrome P450 (CYP) enzyme induction, DNA microarrays were used to generate gene expression profiles and hypotheses on potential mechanisms of action for this class of chemicals. Adult male CD-1 mice were exposed daily for 14 days to fluconazole, myclobutanil, propiconazole, or triadimefon at three dose levels by oral gavage. Doses were based on previous studies that resulted in liver hypertrophy or hepatotoxicity. All four triazoles caused hepatocyte hypertrophy, and all except triadimefon increased relative liver/body weight ratios at the middle and high dose levels. CYP enzyme activities were also induced by all four triazoles at the middle and high doses as measured by the dealkylations of four alkoxyresorufins, although some differences in substrate specificity were observed. Consistent with this common histopathology and biochemistry, several CYP and xenobiotic metabolizing enzyme (XME) genes were differentially expressed in response to all four (Cyp2d26 and Cyp3a11), or three of the four (Cyp2c40, Cyp2c55, Ces2, Slco1a4) triazoles. Differential expression of numerous other CYP and XME genes discriminated between the various triazoles, consistent with differences in CYP enzyme activities, and indicative of possible differences in mechanisms of hepatotoxicity or dose response. Multiple isoforms of Cyp1a, 2b, 2c, 3a, and other CYP and XME genes regulated by the nuclear receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) were differentially expressed following triazole exposure. Based on these results, we expanded on our original hypothesis that triazole hepatotoxicity was mediated by CYP induction, to include additional XME genes, many of which are modulated by CAR and PXR.

  14. Semiotic labelled deductive systems

    SciTech Connect

    Nossum, R.T.

    1996-12-31

    We review the class of Semiotic Models put forward by Pospelov, as well as the Labelled Deductive Systems developed by Gabbay, and construct an embedding of Semiotic Models into Labelled Deductive Systems.

  15. Mental Labels and Tattoos

    ERIC Educational Resources Information Center

    Hyatt, I. Ralph

    1977-01-01

    Discusses the ease with which mental labels become imprinted in our system, six basic axioms for maintaining negative mental tattoos, and psychological processes for eliminating mental tattoos and labels. (RK)

  16. Click-generated triazole ureas as ultrapotent, in vivo-active serine hydrolase inhibitors

    PubMed Central

    Adibekian, Alexander; Martin, Brent R.; Wang, Chu; Hsu, Ku-Lung; Bachovchin, Daniel A.; Niessen, Sherry; Hoover, Heather; Cravatt, Benjamin F.

    2011-01-01

    Serine hydrolases (SHs) are a diverse enzyme class representing > 1% of all human proteins. The biological functions for most SHs remain poorly characterized due to a lack of selective inhibitors to probe their activity in living systems. Here, we show that a substantial number of SHs can be irreversibly inactivated by 1,2,3-triazole ureas, which exhibit negligible cross-reactivity with other protein classes. Rapid lead optimization by click chemistry-enabled synthesis and competitive activity-based profiling identified 1,2,3-triazole ureas that selectively inhibit enzymes from diverse branches of the SH superfamily, including peptidases (acyl-peptide hydrolase or APEH), lipases (platelet-activating factor acetylhyrolase-2 or PAFAH2), and uncharacterized hydrolases (α, β-hydrolase 11 or ABHD11), with exceptional potency in cells (sub-nM) and mice (< 1 mg/kg). We show that APEH inhibition leads to accumulation of N-acetylated proteins and promotes proliferation in T-cells. These data designate 1,2,3-triazole ureas as a pharmacologically privileged chemotype for SH inhibition that shows broad activity across the SH class coupled with tunable selectivity for individual enzymes. PMID:21572424

  17. Click-generated triazole ureas as ultrapotent in vivo-active serine hydrolase inhibitors.

    PubMed

    Adibekian, Alexander; Martin, Brent R; Wang, Chu; Hsu, Ku-Lung; Bachovchin, Daniel A; Niessen, Sherry; Hoover, Heather; Cravatt, Benjamin F

    2011-07-01

    Serine hydrolases are a diverse enzyme class representing ∼1% of all human proteins. The biological functions of most serine hydrolases remain poorly characterized owing to a lack of selective inhibitors to probe their activity in living systems. Here we show that a substantial number of serine hydrolases can be irreversibly inactivated by 1,2,3-triazole ureas, which show negligible cross-reactivity with other protein classes. Rapid lead optimization by click chemistry-enabled synthesis and competitive activity-based profiling identified 1,2,3-triazole ureas that selectively inhibit enzymes from diverse branches of the serine hydrolase class, including peptidases (acyl-peptide hydrolase, or APEH), lipases (platelet-activating factor acetylhydrolase-2, or PAFAH2) and uncharacterized hydrolases (α,β-hydrolase-11, or ABHD11), with exceptional potency in cells (sub-nanomolar) and mice (<1 mg kg(-1)). We show that APEH inhibition leads to accumulation of N-acetylated proteins and promotes proliferation in T cells. These data indicate 1,2,3-triazole ureas are a pharmacologically privileged chemotype for serine hydrolase inhibition, combining broad activity across the serine hydrolase class with tunable selectivity for individual enzymes. PMID:21572424

  18. Antivenom Effects of 1,2,3-Triazoles against Bothrops jararaca and Lachesis muta Snakes

    PubMed Central

    Domingos, Thaisa F. S.; Moura, Laura de A.; Carvalho, Carla; Campos, Vinícius R.; Jordão, Alessandro K.; Cunha, Anna C.; Ferreira, Vitor F.; de Souza, Maria Cecília B. V.; Sanchez, Eladio F.; Fuly, André L.

    2013-01-01

    Snake venoms are complex mixtures of proteins of both enzymes and nonenzymes, which are responsible for producing several biological effects. Human envenomation by snake bites particularly those of the viperid family induces a complex pathophysiological picture characterized by spectacular changes in hemostasis and frequently hemorrhage is also seen. The present work reports the ability of six of a series of 1,2,3-triazole derivatives to inhibit some pharmacological effects caused by the venoms of Bothrops jararaca and Lachesis muta. In vitro assays showed that these compounds were impaired in a concentration-dependent manner, the fibrinogen or plasma clotting, hemolysis, and proteolysis produced by both venoms. Moreover, these compounds inhibited biological effects in vivo as well. Mice treated with these compounds were fully protected from hemorrhagic lesions caused by such venoms. But, only the B. jararaca edema-inducing activity was neutralized by the triazoles. So the inhibitory effect of triazoles derivatives against some in vitro and in vivo biological assays of snake venoms points to promising aspects that may indicate them as molecular models to improve the production of effective antivenom or to complement antivenom neutralization, especially the local pathological effects, which are partially neutralized by antivenoms. PMID:23710441

  19. Synthesis and Antimycobacterial Activity of some Triazole Derivatives–New Route to Functionalized Triazolopyridazines

    PubMed Central

    Tehrani, Kamaleddin Haj Mohammad Ebrahim; Mashayekhi, Vida; Azerang, Parisa; Minaei, Somayeh; Sardari, Soroush; Kobarfard, Farzad

    2015-01-01

    A series of cyclic analogues of bioactive thiosemicarbazide derivatives have been synthesized as potential antimycobacterial agents. The 4-amino-1,2,4-triazole-5-thione analogues (Ia-f) were prepared by heating a mixture of thiocarbohydrzide and appropriate carboxylic acids. Reaction of thiocarbohydrazide with γ-ketoesters in the presence of sodium methoxide furnished triazolopyridazine derivatives IIa-b. Finally, condensation of 4-amino-1,2,4-triazole-5-thione with some aldehydes gave Schiff bases IIIa-e. After characterization by different spectroscopic and analytical methods, the derivatives were tested for their inhibitory activity against Mycobacterium bovis BCG. Among the derivatives, compound Ib proved to be the most potent derivatives with MIC value of 31.25 µg/mL. Given the fact that 4-amino-1,2,4-triazole-5-thiones Ia-f were the most active derivatives, it could be suggested that this group of derivatives have the potential to be considered as lead compounds for future optimization efforts. PMID:26185506

  20. Synthesis and Antimycobacterial Activity of some Triazole Derivatives-New Route to Functionalized Triazolopyridazines.

    PubMed

    Tehrani, Kamaleddin Haj Mohammad Ebrahim; Mashayekhi, Vida; Azerang, Parisa; Minaei, Somayeh; Sardari, Soroush; Kobarfard, Farzad

    2015-01-01

    A series of cyclic analogues of bioactive thiosemicarbazide derivatives have been synthesized as potential antimycobacterial agents. The 4-amino-1,2,4-triazole-5-thione analogues (Ia-f) were prepared by heating a mixture of thiocarbohydrzide and appropriate carboxylic acids. Reaction of thiocarbohydrazide with γ-ketoesters in the presence of sodium methoxide furnished triazolopyridazine derivatives IIa-b. Finally, condensation of 4-amino-1,2,4-triazole-5-thione with some aldehydes gave Schiff bases IIIa-e. After characterization by different spectroscopic and analytical methods, the derivatives were tested for their inhibitory activity against Mycobacterium bovis BCG. Among the derivatives, compound Ib proved to be the most potent derivatives with MIC value of 31.25 µg/mL. Given the fact that 4-amino-1,2,4-triazole-5-thiones Ia-f were the most active derivatives, it could be suggested that this group of derivatives have the potential to be considered as lead compounds for future optimization efforts. PMID:26185506

  1. Diversity and origins of Indian multi-triazole resistant strains of Aspergillus fumigatus.

    PubMed

    Chang, Howard; Ashu, Eta; Sharma, Cheshta; Kathuria, Shallu; Chowdhary, Anuradha; Xu, Jianping

    2016-07-01

    Aspergillus fumigatus is a widespread opportunistic fungal pathogen causing an alarmingly high mortality rate in immunocompromised patients. Nosocomial infections by drug-resistant A. fumigatus strains are of particular concern, and there is a pressing need to understand the origin, dispersal and long-term evolution of drug resistance in this organism. The objective of this study was to investigate the diversity and putative origins of triazole resistance of A. fumigatus from India. Eighty-nine isolates, including 51 multiple triazole resistant (MTR) isolates and 38 azole-susceptible isolates, were genotyped using multilocus sequence typing (MLST), mating typing and PCR fingerprinting. MLST resolved the 51 MTR isolates into three genotypes, two of which have susceptible counterparts, suggesting that MTR isolates originated multiple times in India. The multiple-origin hypothesis was further supported by the diversity of sequences at the triazole target gene CYP51A among the MTR isolates, and by PCR fingerprints. Interestingly, there is abundant evidence for mating and recombination in natural population of A. fumigatus in India, suggesting that sexual spread of TR34 /L98H, the dominant MTR allele, is possible. Our results call for greater attention to MTR in A. fumigatus and for better management of antifungal drug use. PMID:26931802

  2. Separation of silver from other metal cations using pyridone and triazole macrocycles in liquid membrane systems

    SciTech Connect

    Izatt, R.M.; LindH, G.C.; Bruening, R.L.; Huszthy, P.; McDaniel, C.W.; Bradshaw, J.S.; Christensen, J.J.

    1988-09-01

    Selective transport of Ag/sup +/ over other metal ions in competitive experiments in bulk and emulsion liquid membrane systems has been accomplished by using macrocycles of the proton-ionizable pyridone and triazole types. The transport of Ag/sup +/ by the pyridone macrocycles involves the cotransport of an anion, while transport by the triazole macrocycles can involve either co-anion transport or the counter transport of H/sup +/. In particular, the affinity of Ag/sup +/ for the triazole moiety, the excellent fit of Ag/sup +/ into an 18-crown-6 sized cavity, and the presence of only one proton-ionizable site per macrocycle molecule combine to produce highly selective transport of Ag/sup +/ over Pb/sup 2 +/ and Tl/sup +/ with triazolo-18-crown-6 derivatives in membrane systems containing acid receiving phases. Transport of alkali-, alkaline-earth-, and several transition-metal cations is minimal in similar membrane systems and, hence, selective transport of Ag/sup +/ over these cations is also expected.

  3. Synthesis and bioactivity of pyrazole and triazole derivatives as potential PDE4 inhibitors.

    PubMed

    Li, Ya-Sheng; Tian, Hao; Zhao, Dong-Sheng; Hu, De-Kun; Liu, Xing-Yu; Jin, Hong-Wei; Song, Gao-Peng; Cui, Zi-Ning

    2016-08-01

    A series of pyrazole and triazole derivatives containing 5-phenyl-2-furan functionality were designed and synthesized as phosphodiesterase type 4 (PDE4) inhibitors. The bioassay results showed that title compounds exhibited considerable inhibitory activity against PDE4B and blockade of LPS-induced TNFα release. Meanwhile, the activity of compounds containing 1,2,4-triazole (series II) was higher than that of pyrazole-attached derivatives (series I). The primary structure-activity relationship study and docking results showed that the 1,2,4-triazole moiety of compound IIk played a key role to form integral hydrogen bonds and π-π stacking interaction with PDE4B protein while the rest part of the molecule extended into the catalytic domain to block the access of cAMP and formed the foundation for inhibition of PDE4. Compound IIk would be great promise as a hit compound for further study based on the preliminary structure-activity relationship and molecular modeling studies. PMID:27289320

  4. Triazole-curcuminoids: A new class of derivatives for 'tuning' curcumin bioactivities?

    PubMed

    Caprioglio, Diego; Torretta, Simone; Ferrari, Maila; Travelli, Cristina; Grolla, Ambra A; Condorelli, Fabrizio; Genazzani, Armando A; Minassi, Alberto

    2016-01-15

    Curcumin is a unique blend of pharmacophores responsible for the pleiotropy of this natural pigment. In the present study we have replaced the 1,3-dicarbonyl moiety with a 1,2,3-triazole ring to furnish a new class of triazole-curcuminoids as a possible strategy to generate new compounds with different potency and selectivity compared to curcumin. We obtained a proof-of-principle library of 28 compounds tested for their cytotoxicity (SY-SY5Y and HeLa cells) and for their ability to inhibit NF-κB. Furthermore, we also generated 1,3-dicarbonyl curcuminoids of selected click compounds. Triazole-curcuminoids lost their ability to be Michael's acceptors, yet maintained some of the features of the parent compounds and disclosed new ones. In particular, we found that some compounds were able to inhibit NF-κB without showing cytotoxicity, while others, unlike curcumin, activated NF-κB signalling. This validates the hypothesis that click libraries can be used to investigate the biological activities of curcumin as well as generate analogs with selected features. PMID:26705144

  5. Triazole linkages and backbone branches in nucleic acids for biological and extra-biological applications

    NASA Astrophysics Data System (ADS)

    Paredes, Eduardo

    The recently increasing evidence of nucleic acids' alternative roles in biology and potential as useful nanomaterials and therapeutic agents has enabled the development of useful probes, elaborate nanostructures and therapeutic effectors based on nucleic acids. The study of alternative nucleic acid structure and function, particularly RNA, hinges on the ability to introduce site-specific modifications that either provide clues to the nucleic acid structure function relationship or alter the nucleic acid's function. Although the available chemistries allow for the conjugation of useful labels and molecules, their limitations lie in their tedious conjugation conditions or the lability of the installed probes. The development and optimization of click chemistry with RNA now provides the access to a robust and orthogonal conjugation methodology while providing stable conjugates. Our ability to introduce click reactive groups enzymatically, rather than only in the solid-phase, allows for the modification of larger, more cell relevant RNAs. Additionally, ligation of modified RNAs with larger RNA constructs through click chemistry represents an improvement over traditional ligation techniques. We determined that the triazole linkage generated through click chemistry is compatible in diverse nucleic acid based biological systems. Click chemistry has also been developed for extra-biological applications, particularly with DNA. We have expanded its use to generate useful polymer-DNA conjugates which can form controllable soft nanoparticles which take advantage of DNA's properties, i.e. DNA hybridization and computing. Additionally, we have generated protein-DNA conjugates and assembled protein-polymer hybrids mediated by DNA hybridization. The use of click chemistry in these reactions allows for the facile synthesis of these unnatural conjugates. We have also developed backbone branched DNA through click chemistry and showed that these branched DNAs are useful in generating

  6. Protein Labelling with Versatile Phosphorescent Metal Complexes for Live Cell Luminescence Imaging.

    PubMed

    Connell, Timothy U; James, Janine L; White, Anthony R; Donnelly, Paul S

    2015-09-28

    To take advantage of the luminescent properties of d(6) transition metal complexes to label proteins, versatile bifunctional ligands were prepared. Ligands that contain a 1,2,3-triazole heterocycle were synthesised using Cu(I) catalysed azide-alkyne cycloaddition "click" chemistry and were used to form phosphorescent Ir(III) and Ru(II) complexes. Their emission properties were readily tuned, by changing either the metal ion or the co-ligands. The complexes were tethered to the metalloprotein transferrin using several conjugation strategies. The Ir(III)/Ru(II)-protein conjugates could be visualised in cancer cells using live cell imaging for extended periods without significant photobleaching. These versatile phosphorescent protein-labelling agents could be widely applied to other proteins and biomolecules and are useful alternatives to conventional organic fluorophores for several applications. PMID:26264214

  7. Dimensional modulation and magnetic properties of triazole- and bis(triazole)-based copper(II) coordination polymers tuned by aromatic polycarboxylates

    NASA Astrophysics Data System (ADS)

    Zhang, Ju-Wen; Zhao, Wei; Lu, Qi-Lin; Luan, Jian; Qu, Yun; Wang, Xiu-Li

    2014-04-01

    Five new metal-organic coordination polymers {[Cu3(μ2-OH)2(atrz)2(nph)2(H2O)2]·2H2O}n (1), {[Cu2(μ3-OH)(atrz)(1,2,4-btc)]·2H2O}n (2), {[Cu2(μ3-OH)(atrz)(1,2,4-btc)(H2O)]·H2O}n (3), [Cu(dth)0.5(nph)(H2O)]n (4) and [Cu(dth)(Hnip)2]n (5) [atrz=4-amino-1,2,4-triazole, dth=N,N'-di(4H-1,2,4-triazole)hexanamide, H2nph=3-nitrophthalic acid, 1,2,4-H3btc=1,2,4-benzenetricarboxylic acid and H2nip=5-nitroisophthalic acid] were hydrothermally synthesized and structurally characterized. Polymer 1 shows a one-dimensional (1D) chain. Polymers 2 and 3 exhibit similar tetranuclear CuII4 cluster-based three-dimensional (3D) frameworks with the same components. Polymer 4 possesses a 3D framework with a 412·63-pcu topology. Polymer 5 displays a 3D framework with a 44·610·8-mab topology. The magnetic properties of 1-4 were investigated.

  8. Selenocysteine vs Cysteine: Tuning the Derivatization on Benzenesulfonyl Moiety of a Triazole Linked Dansyl Connected Glycoconjugate for Selective Recognition of Selenocysteine and the Applicability of the Conjugate in Buffer, in Serum, on Silica Gel, and in HepG2 Cells.

    PubMed

    Areti, Sivaiah; Verma, Surendra Kumar; Bellare, Jayesh; Rao, Chebrolu Pulla

    2016-07-19

    A dansyl derivatized triazole linked glucopyranosyl conjugate ((NO2)L) has been synthesized and characterized and was used in the present study. The conjugate (NO2)L releases a fluorescent product upon reaction by Cys-SeH in aqueous PBS buffer by exhibiting a ∼210-fold fluorescence enhancement even in the presence of 20 other amino acids with a minimum detection limit of (1.5 ± 0.2) × 10(-7) M. The selectivity of the Cys-SeH to (NO2)L was further proven by extending the fluorescence study to different other selenium compounds. The role of para-nitrobenzenesulfonyl (pNBS) center in (NO2)L in the selective recognition of Cys-SeH was confirmed when the fluorescence emission studies were carried out using five different derivatizations possessing two NO2, five fluoro, two fluoro, one fluoro, and no fluoro groups. The nucleophilic substitution reaction of Cys-SeH on (NO2)L has been clearly demonstrated on the basis of (1)H NMR, ESI-MS, and absorption spectroscopy, and the heat changes were monitored by isothermal titration calorimetry. The application potential of (NO2)L has been demonstrated by studying its selectivity toward Cys-SeH in aqueous PBS buffer, in bovine serum, and on the silica gel surface that lead to minimum detection limits of (25 ± 2), (80 ± 5), and (168 ± 16) ppb, respectively. The biological applicability of (NO2)L for Cys-SeH was further demonstrated in HepG2 cells by fluorescence microscopy. Thus, (NO2)L is aqueous soluble and a biologically acceptable probe for Cys-SeH. PMID:27310767

  9. Bioaccumulation and biotransformation of chiral triazole fungicides in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Konwick, Brad J; Garrison, Arthur W; Avants, Jimmy K; Fisk, Aaron T

    2006-12-30

    There are very little data on the bioaccumulation and biotransformation of current-use pesticides (CUPs) despite the fact that such data are critical in assessing their fate and potential toxic effects in aquatic organisms. To help address this issue, juvenile rainbow trout (Oncorhynchus mykiss) were exposed to dietary concentrations of a mixture of chiral triazole fungicides (bromuconazole, cyproconazole, metconazole, myclobutanil, penconazole, propiconazole, tebuconazole, tetraconazole, and triadimefon) and a chiral legacy pesticide [alpha-hexachlorocyclohexane (alpha-HCH)] to study the bioaccumulation and biotransformation of these CUPs. Fish accumulated all triazoles rapidly during the 8 day uptake phase, and was followed by rapid elimination, which was estimated by taking accelerated sampling times during the 16 day depuration period. Half-lives (t1/2s) and times to 95% elimination (t95s) ranged from 1.0 to 2.5 and 4.5 to 11.0 days, respectively. Chiral analysis suggested no significant selectivity in biotransformation for most of the compounds based on statistically unaltered enantiomer fractions (EFs) in the fish compared to food values; exceptions were a change in EF of myclobutanil and changes in diastereomer fractions (DFs) of propiconazole and cyproconazole. No biotransformation was observed for alpha-HCH based on consistent EFs in the fish throughout the experiment and a t1/2 (15.8 days) that fell within the 95% confidence interval of a log K(ow)-log t1/2 relationship developed for assessing biotransformation of organic contaminants. This relationship did show that biotransformation accounted for the majority (ranging from 59.9 to 90.4%) of the elimination for all triazoles, and that triazole compounds with oxygen and hydroxyl functional groups were more easily biotransformed. This research indicated that chiral analysis may potentially miss biotransformation of CUPs and other potential non-persistent organic contaminants and shows the utility of the

  10. A rapid and sensitive LC-MS/MS method for quantification of quercetin-3-O-β-d-glucopyranosyl-7-O-β-d-gentiobioside in plasma and its application to a pharmacokinetic study.

    PubMed

    He, Xin; Tao, Guizhou; Gao, Hang; Li, Keyan; Zhang, Yazhuo; Sun, Limin; Zhang, Yingjie

    2016-09-01

    A rapid and sensitive LC-MS/MS method with good accuracy and precision was developed and validated for the pharmacokinetic study of quercetin-3-O-β-d-glucopyranosyl-7-O-β-d-gentiobioside (QGG) in Sprague-Dawley rats. Plasma samples were simply precipitated by methanol and then analyzed by LC-MS/MS. A Venusil® ASB C18 column (2.1 × 50 mm, i.d. 5 μm) was used for separation, with methanol-water (50:50, v/v) as the mobile phase at a flow rate of 300 μL/min. The optimized mass transition ion-pairs (m/z) for quantitation were 787.3/301.3 for QGG, and 725.3/293.3 for internal standard. The linear range was 7.32-1830 ng/mL with an average correlation coefficient of 0.9992, and the limit of quantification was 7.32 ng/mL. The intra- and inter-day precision and accuracy were less than ±15%. At low, medium and high quality control concentrations, the recovery and matrix effect of the analyte and IS were in the range of 89.06-92.43 and 88.58-97.62%, respectively. The method was applied for the pharmacokinetic study of QGG in Sprague-Dawley rats. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26848536

  11. 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol, a metabolite of ginsenoside Rb1, enhances the production of hyaluronic acid through the activation of ERK and Akt mediated by Src tyrosin kinase in human keratinocytes.

    PubMed

    Lim, Tae-Gyu; Jeon, Ae Ji; Yoon, Ji Hye; Song, Dasom; Kim, Jong-Eun; Kwon, Jung Yeon; Kim, Jong Rhan; Kang, Nam Joo; Park, Jun-Seong; Yeom, Myeong Hun; Oh, Deok-Kun; Lim, Yoongho; Lee, Charles C; Lee, Chang Yong; Lee, Ki Won

    2015-05-01

    The aim of the present study was to determine the mechanisms through which 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol (20GPPD) promotes the production of hyaluronic acid (HA) in human keratinocytes. 20GPPD is the primary bioactive metabolite of Rb1, a major ginsenoside found in ginseng (Panax ginseng). We sought to elucidate the underlying mechanisms behind the 20GPPD-induced production of HA. We found that 20GPPD induced an increase in HA production by elevating hyaluronan synthase 2 (HAS2) expression in human keratinocytes. The phosphorylation of extracellular signal-regulated kinase (ERK) and Akt was also enhanced by 20GPPD in a dose-dependent manner. The pharmacological inhibition of ERK (using U0126) or Akt (using LY294002) suppressed the 20GPPD-induced expression of HAS2, whereas treatment with an epidermal growth factor receptor (EGFR) inhibitor (AG1478) or an intracellular Ca2+ chelator (BAPTA/AM) did not exert any observable effects. The increased Src phosphorylation was also confirmed following treatment with 20GPPD in the human keratinocytes. Following pre-treatment with the Src inhibitor, PP2, both HA production and HAS2 expression were attenuated. Furthermore, the 20GPPD-enhanced ERK and Akt signaling decreased following treatment with PP2. Taken together, our results suggest that Src kinase plays a critical role in the 20GPPD-induced production of HA by acting as an upstream modulator of ERK and Akt activity in human keratinocytes. PMID:25738334

  12. Planococcus maritimus VITP21 synthesizes (2-acetamido-2-deoxy-α-d-glucopyranosyl)-(1→2)-β-d-fructofuranose under osmotic stress: a novel protein stabilizing sugar osmolyte.

    PubMed

    Joghee, Nidhya Nadarajan; Gurunathan, Jayaraman

    2014-01-13

    A halotolerant bacterium, Planococcus maritimus VITP21 isolated from a saltern region in Kumta along the Arabian Sea Coast of India was found to have increased cellular levels of sugars (up to 2.3-fold) under osmotic stress when grown in minimal medium with glucose as the sole carbon and energy source supplemented with 10% w/v NaCl. The major sugar osmolyte which increased with the concentration of NaCl in the growth medium was purified and characterized using various nuclear magnetic resonance spectroscopy techniques. The sugar was found to be similar to sucrose but with the C-2 hydroxyl group of the glucose ring substituted with acetamido group, which is not previously reported for its natural synthesis by any other organism. This novel sugar, (2-acetamido-2-deoxy-α-d-glucopyranosyl)-(1→2)-β-d-fructofuranose, exhibited stabilizing effect on a model protein α-amylase by increasing the apparent midpoint transition, onset temperature of denaturation, and free energy of thermal unfolding. PMID:24333897

  13. Deprotometalation-iodolysis and computed CH acidity of 1,2,3- and 1,2,4-triazoles. Application to the synthesis of resveratrol analogues.

    PubMed

    Nagaradja, Elisabeth; Bentabed-Ababsa, Ghenia; Scalabrini, Mathieu; Chevallier, Floris; Philippot, Stéphanie; Fontanay, Stéphane; Duval, Raphaël E; Halauko, Yury S; Ivashkevich, Oleg A; Matulis, Vadim E; Roisnel, Thierry; Mongin, Florence

    2015-10-01

    1-Aryl- and 2-aryl-1,2,3-triazoles were synthesized by N-arylation of the corresponding azoles using aryl iodides. The deprotometalations of 1-phenyl-1,2,3-triazole and -1,2,4-triazole were performed using a 2,2,6,6-tetramethylpiperidino-based mixed lithium-zinc combination and occurred at the most acidic site, affording by iodolysis the 5-substituted derivatives. Dideprotonation was noted from 1-(2-thienyl)-1,2,4-triazole by increasing the amount of base. From 2-phenyl-1,2,3-triazoles, and in particular from 2-(4-trifluoromethoxy)phenyl-1,2,3-triazole, reactions at the 4 position of the triazolyl, but also ortho to the triazolyl on the phenyl group, were observed. The results were analyzed with the help of the CH acidities of the substrates, determined in THF solution using the DFT B3LYP method. 4-Iodo-2-phenyl-1,2,3-triazole and 4-iodo-2-(2-iodophenyl)-1,2,3-triazole were next involved in Suzuki coupling reactions to furnish the corresponding 4-arylated and 4,2'-diarylated derivatives. When evaluated for biological activities, the latter (which are resveratrol analogues) showed moderate antibacterial activity and promising antiproliferative effect against MDA-MB-231 cell line. PMID:26344592

  14. 40 CFR 180.450 - Beta-(4-Chlorophenoxy)-alpha-(1,1-dimethylethyl)-1H-1,2,4-triazole-1-ethanol; tolerances for...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-dimethylethyl)-1H-1,2,4-triazole-1-ethanol; tolerances for residues. 180.450 Section 180.450 Protection of...-dimethylethyl)-1H-1,2,4-triazole-1-ethanol; tolerances for residues. (a) General. Tolerances are established for...-ethanol (triadimenol) and its butanediol metabolite,...

  15. 40 CFR 180.450 - Beta-(4-Chlorophenoxy)-alpha-(1,1-dimethylethyl)-1H-1,2,4-triazole-1-ethanol; tolerances for...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-dimethylethyl)-1H-1,2,4-triazole-1-ethanol; tolerances for residues. 180.450 Section 180.450 Protection of...-dimethylethyl)-1H-1,2,4-triazole-1-ethanol; tolerances for residues. (a) General. Tolerances are established for...-ethanol (triadimenol) and its butanediol metabolite,...

  16. 40 CFR 180.450 - Beta-(4-Chlorophenoxy)-alpha-(1,1-dimethylethyl)-1H-1,2,4-triazole-1-ethanol; tolerances for...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-dimethylethyl)-1H-1,2,4-triazole-1-ethanol; tolerances for residues. 180.450 Section 180.450 Protection of...-dimethylethyl)-1H-1,2,4-triazole-1-ethanol; tolerances for residues. (a) General. Tolerances are established for...-ethanol (triadimenol) and its butanediol metabolite,...

  17. 40 CFR 180.450 - Beta-(4-Chlorophenoxy)-alpha-(1,1-dimethylethyl)-1H-1,2,4-triazole-1-ethanol; tolerances for...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-dimethylethyl)-1H-1,2,4-triazole-1-ethanol; tolerances for residues. 180.450 Section 180.450 Protection of...-dimethylethyl)-1H-1,2,4-triazole-1-ethanol; tolerances for residues. (a) General. Tolerances are established for...-ethanol (triadimenol) and its butanediol metabolite,...

  18. 40 CFR 180.450 - Beta-(4-Chlorophenoxy)-alpha-(1,1-dimethylethyl)-1H-1,2,4-triazole-1-ethanol; tolerances for...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-dimethylethyl)-1H-1,2,4-triazole-1-ethanol; tolerances for residues. 180.450 Section 180.450 Protection of...-dimethylethyl)-1H-1,2,4-triazole-1-ethanol; tolerances for residues. (a) General. Tolerances are established for...-ethanol (triadimenol) and its butanediol metabolite,...

  19. 1,1'-Azobis-1,2,3-triazole: a high-nitrogen compound with stable N8 structure and photochromism.

    PubMed

    Li, Yu-Chuan; Qi, Cai; Li, Sheng-Hua; Zhang, Hui-Juan; Sun, Cheng-Hui; Yu, Yong-Zhong; Pang, Si-Ping

    2010-09-01

    Treatment of 1-amino-1,2,3-triazole with sodium dichloroisocyanurate led to isolation of 1,1'-azobis-1,2,3-triazole, which was well characterized. Its structure was determined by X-ray crystallographic analysis, and its thermal stability and photochromic properties were investigated. PMID:20715773

  20. Crystal structures of five 1-alkyl-4-aryl-1,2,4-triazol-1-ium halide salts.

    PubMed

    Guino-O, Marites A; Talbot, Meghan O; Slitts, Michael M; Pham, Theresa N; Audi, Maya C; Janzen, Daron E

    2015-06-01

    The asymmetric units for the salts 4-(4-fluoro-phen-yl)-1-isopropyl-1,2,4-triazol-1-ium iodide, C11H13FN3 (+)·I(-), (1), 1-isopropyl-4-(4-methyl-phen-yl)-1,2,4-triazol-1-ium iodide, C12H16N3 (+)·I(-), (2), 1-isopropyl-4-phenyl-1,2,4-triazol-1-ium iodide, C11H14N3 (+)·I(-), (3), and 1-methyl-4-phenyl-1,2,4-triazol-1-ium iodide, C9H10N3 (+)·I(-), (4), contain one cation and one iodide ion, whereas in 1-benzyl-4-phenyl-1,2,4-triazol-1-ium bromide monohydrate, C15H14N3 (+)·Br(-)·H2O, (5), there is an additional single water mol-ecule. There is a predominant C-H⋯X(halide) inter-action for all salts, resulting in a two-dimensional extended sheet network between the triazolium cation and the halide ions. For salts with para-substitution on the aryl ring, there is an additional π-anion inter-action between a triazolium carbon and iodide displayed by the layers. For salts without the para-substitution on the aryl ring, the π-π inter-actions are between the triazolium and aryl rings. The melting points of these salts agree with the predicted substituent inductive effects. PMID:26090137

  1. Quantum chemical studies on three novel 1,2,4-triazole N-oxides as potential insensitive high explosives.

    PubMed

    Wu, Qiong; Zhu, Weihua; Xiao, Heming

    2014-09-01

    Three novel explosives were designed by introducing N-oxides into 1,2,4-triazole: 1-amino-3,5-dinitro-1,2,4-triazole-2 N-oxide (ADT2NO), 1-amino-2,5-dinitro-1,2,4-triazole-3 N-oxide (ADT3NO), and 1-amino-3,5-dinitro-1,2,4-triazole-4 N-oxide (ADT4NO). Their detonation performance and sensitivity were estimated by using density functional theory and compared with some famous explosives like 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX) and 1-methyl-2,4,6-trinitrobenzene (TNT). All three designed molecules are more powerful than HMX and less sensitive than TNT, indicating that ADT2NO, ADT3NO, and ADT4NO have high detonation performance as HMX and low sensitivity as TNT, making them being very valuable and may be considered as the potential candidates of insensitive high explosives. Properly introducing N-oxides into the energetic triazole derivatives can generate some superior energetic compounds with both high explosive performance and reduced sensitivity. PMID:25213112

  2. [18F]azadibenzocyclooctyne ([18F]ADIBO): a biocompatible radioactive labeling synthon for peptides using catalyst free [3+2] cycloaddition.

    PubMed

    Arumugam, Selvanathan; Chin, Joshua; Schirrmacher, Ralf; Popik, Vladimir V; Kostikov, Alexey P

    2011-12-01

    N-Terminally azido-modified peptides were labeled with the novel prosthetic labeling synthon [(18)F]azadibenzocyclooctyne ([(18)F]ADIBO) using copper-free azide-alkyne [3+2]-dipolar cycloaddition in high radiochemical yields (RCYs). (18)F-Labeled [(18)F]ADIBO was prepared by nucleophilic substitution of the corresponding tosylate in 21% overall RCY (EOB) in a fully automated synthesis unit within 55 min. [(18)F]ADIBO was incubated with azide-containing peptides at room temperature in the absence of toxic metal catalysts and the formation of the triazole conjugate was confirmed. Finally, the azide-alkyne [3+2]-dipolar cycloaddition was shown to proceed with 95% radiochemical yield in ethanol within 30 min, allowing for a development of a kit-like peptide labeling approach with [(18)F]ADIBO. PMID:22024032

  3. Multicomponent Synthesis and Evaluation of New 1,2,3-Triazole Derivatives of Dihydropyrimidinones as Acidic Corrosion Inhibitors for Steel.

    PubMed

    González-Olvera, Rodrigo; Román-Rodríguez, Viridiana; Negrón-Silva, Guillermo E; Espinoza-Vázquez, Araceli; Rodríguez-Gómez, Francisco Javier; Santillan, Rosa

    2016-01-01

    An efficient one-pot synthesis of 1,2,3-triazole derivatives of dihydropyrimidinones has been developed using two multicomponent reactions. The aldehyde-1,2,3-triazoles were obtained in good yields from in situ-generated organic azides and O-propargylbenzaldehyde. The target heterocycles were synthesized through the Biginelli reaction in which the aldehyde-1,2,3-triazoles reacted with ethyl acetoacetate and urea in the presence of Ce(OTf)₃ as the catalyst. The corrosion inhibition of steel grade API 5 L X52 in 1 M HCl by the synthesized compounds was investigated using the electrochemical impedance spectroscopy technique. The measurements revealed that these heterocycles are promising candidates to inhibit acidic corrosion of steel. PMID:26907242

  4. Detection of triazole deicing additives in soil samples from airports with low, mid, and large volume aircraft deicing activities.

    PubMed

    McNeill, K S; Cancilla, D A

    2009-03-01

    Soil samples from three USA airports representing low, mid, and large volume users of aircraft deicing fluids (ADAFs) were analyzed by LC/MS/MS for the presence of triazoles, a class of corrosion inhibitors historically used in ADAFs. Triazoles, specifically the 4-methyl-1H-benzotriazole and the 5-methyl-1H-benzotriazole, were detected in a majority of samples and ranged from 2.35 to 424.19 microg/kg. Previous studies have focused primarily on ground and surface water impacts of larger volume ADAF users. The detection of triazoles in soils at low volume ADAF use airports suggests that deicing activities may have a broader environmental impact than previously considered. PMID:19082516

  5. Synthesis and antiproliferative evaluation of 3,5-disubstituted 1,2,4-triazoles containing flurophenyl and trifluoromethanephenyl moieties.

    PubMed

    Wang, Li-Ya; Tseng, Wen-Che; Wu, Tian-Shung; Kaneko, Kimiyoshi; Takayama, Hiroyuki; Kimura, Masayuki; Yang, Wen-Chin; Wu, Jin Bin; Juang, Shin-Hun; Wong, Fung Fuh

    2011-09-15

    An efficient 1,3-dipolar cycloaddition method was performed for the synthesis of a series of monofluoro- and trifluoromethane-3,5-disubstituted 1,2,4-triazoles. This efficient cycloaddition method was to react hydrazonoyl hydrochlorides with a series of aldehydes in the presence of NEt(3) as catalytic basic agent to provide the corresponding product in 28-94%. Their growth inhibitory results against cancer cells indicated that some of the fluorine- and trifluoromethane-containing compounds could effectively inhibit the growth of NCI-H226 and T-cell leukemia (Jurkat) cells. Among the compounds, trifluoromethane-containing 1,2,4-triazoles possessed the five-membered ring groups on the C-5 position of the triazolic ring, including cyclopentyl, 3-furyl, 3-thienyl, and 2-pyrrolyl, possessed the significant inhibitory activity for NCI-H226 cancer cells. PMID:21802949

  6. 1,2,3-Triazole/MWCNT conjugates as filler for gelcoat nanocomposites: new active antibiofouling coatings for marine application

    NASA Astrophysics Data System (ADS)

    Iannazzo, Daniela; Pistone, Alessandro; Visco, Annamaria; Galtieri, Giovanna; Giofrè, Salvatore V.; Romeo, Roberto; Romeo, Giovanni; Cappello, Simone; Bonsignore, Martina; Denaro, Renata; Galvagno, Signorino

    2015-11-01

    A polyester-based gelcoat nanocomposite was synthesized by using as nanofiller multi-walled carbon nanotubes (MWCNTs) conjugated with a biocidal 1,2,3-triazole to be used as a new eco-friendly antibiofouling coating. 1,2,3-Triazole/MWCNT conjugates containing differently substituted 1,2,3-triazoles have been synthesized and characterized by physical, chemical, and morphological analyses. Ecotoxicological studies, performed on marine organisms belonging to different evolutive classes, provided information about the choice of the more interesting nanofiller. The synthesized gelcoat nanocomposite showed a significant improvement in the wet ability with respect to the Gelcoat alone. Preliminary biological tests performed on the nanocomposite revealed great biocidal properties, thus providing new opportunities to develop an effective antibiofouling coating.

  7. Corrosion Inhibition Performance of Triazole Derivatives on Copper-Nickel Alloy in 3.5 wt.% NaCl Solution

    NASA Astrophysics Data System (ADS)

    Jiang, B.; Jiang, S. L.; Liu, X.; Ma, A. L.; Zheng, Y. G.

    2015-12-01

    This study investigates the performance of three triazole derivatives with different molecular structures as corrosion inhibitors for the copper-nickel alloy CuNi 90/10 in 3.5 wt.% NaCl solution. Inhibition behavior was systematically determined through electrochemical measurements, scanning electron microscopy, energy-dispersive spectroscopy, and Fourier transform infrared spectroscopy. In addition, adsorption behavior and the inhibition mechanism were investigated via quantum chemical calculation and molecular dynamic simulation. Experimental results indicate that the three inhibitors with triazole rings and heteroatoms exhibited excellent corrosion inhibition capabilities on the copper-nickel alloy surface through physisorption and chemisorption. In particular, 3-amino-5-mercapto-1,2,4-triazole showed the best inhibition capability according to the concentration ranges considered in the experiments. The results of quantum chemical calculation agreed with the experimental findings.

  8. Synthesis of some benzimidazole derivatives endowed with 1,2,3-triazole as potential inhibitors of hepatitis C virus.

    PubMed

    Youssif, Bahaa G M; Mohamed, Yaseen A M; Salim, Mohammed T A; Inagaki, Fuyuhiko; Mukai, Chisato; Abdu-Allah, Hajjaj H M

    2016-06-01

    New derivatives of 2-thiobenzimidazole incorporating triazole moiety were synthesized, characterized and tested in vitro for antiviral activity against hepatitis C virus (HCV) and hepatitis B virus (HBV). Their cytotoxicity was determined by the reduction in the number of viable cell. All of the synthesized compounds are inactive against HBV and some showed activity against HCV. In particular, two compounds showed significant activity, 2-{4-[(1-benzoylbenzimidazol-2-ylthio)methyl]-1H-1,2,3-triazol-1-yl}-N-(p-nitro-phenyl)-acetamide (13) and 2-(4-{[1-(p-chlorobenzoyl)-benzimidazol-2-ylthio)methyl]-1H-1,2,3-triazol-1-yl}-N-(p-nitrophenyl)-acetamide (17). The results give an insight into the importance of the substituent at position 2 of benzimidazole for the inhibition of HCV. PMID:27279065

  9. New 1,2,4-triazole-based azo-azomethine dyes. Part I: Synthesis, characterization and spectroscopic studies

    NASA Astrophysics Data System (ADS)

    Khanmohammadi, Hamid; Erfantalab, Malihe

    2012-02-01

    Four new 1,2,4-triazole-based azo-azomethine dyes were synthesized via condensation of 3,5-diamino-1,2,4-triazole with azo-coupled o-vanillin precursors. The prepared dyes were characterized by IR, UV-vis and 1H NMR spectroscopic methods as well as elemental analyses. Thermal properties of the prepared dyes were examined by thermogravimetric analysis. Results indicated that the framework of the dyes was stable up to 225 °C. Also, the influence of various factors including time and mixed DMSO/EtOH solution on UV-vis spectra of the dyes were investigated.

  10. 4-Salicylideneamino-3-methyl-1,2,4-triazole-5-thione as a sensor for aniline recognition

    NASA Astrophysics Data System (ADS)

    Kumar, M. Saravana; Tamilarasan, R.; Sreekanth, A.

    2011-07-01

    Tridentate triazole based Schiff base 4-salicylideneamino-3-methyl-1,2,4-triazole-5-thione has been found to selectively detect toxic aromatic amines such as aniline and benzene-1,4-diamine by simple titration techniques like UV-visible, fluorescence spectral studies (PL) and 1H NMR titrations. The Schiff base receptor utilizes, thione sulfur, NH-thione and the phenolic hydroxyl group to form hydrogen bonded adduct of aniline and benzene-1,4-diamine with high binding affinity, followed by a slow removal of the corresponding hydrogens thus providing a promising candidate and an unique receptor for toxic aromatic amines.

  11. Production of the ammonium salt of 3,5-dinitro-1,2,4-triazole by solvent extraction

    SciTech Connect

    Lee, K.Y.; Ott, D.G.

    1980-11-25

    The ammonium salt of 3,5-dinitro-1,2,4-triazole has utility as a chemical explosive. In accordance with the present invention, it may readily be produced by solvent extraction using high molecular weight, water-insoluble amines followed by amination with anhydrous ammonia gas. The aqueous reaction mixture produced in the synthesis of the parent compound, 3,5-dinitro-1,2,4triazole, is quite suitable--and indeed is preferred--for use as the feed material in the process of the invention.

  12. Production of the ammonium salt of 3,5-dinitro-1,2,4-triazole by solvent extraction

    DOEpatents

    Lee, K.Y.; Ott, D.G.

    1979-11-07

    The ammonium salt of 3,5-dinitro-1,2,4-triazole has utility as a chemical explosive. In accordance with the present invention, it may readily be produced by solvent extraction using high-molecular weight, water-insoluble amines, followed by amination with anhydrous ammonia gas. The aqueous reaction mixture produced in the synthesis of the parent compound, 3,5-dinitro-1,2,4-triazole, is quite suitable - and indeed is preferred - for use as the feed material in the process of the invention.

  13. Production of the ammonium salt of 3,5-dinitro-1,2,4-triazole by solvent extraction

    DOEpatents

    Lee, Kien Y.; Ott, Donald G.

    1980-01-01

    The ammonium salt of 3,5-dinitro-1,2,4-triazole has utility as a chemical explosive. In accordance with the present invention, it may readily be produced by solvent extraction using high-molecular weight, water-insoluble amines followed by amination with anhydrous ammonia gas. The aqueous reaction mixture produced in the synthesis of the parent compound, 3,5-dinitro-1,2,4-triazole, is quite suitable--and indeed is preferred--for use as the feed material in the process of the invention.

  14. Silica-Supported Oligomeric Benzyl Phosphate (Si-OBP) and Triazole Phosphate (Si-OTP) Alkylating Reagents.

    PubMed

    Maity, Pradip K; Faisal, Saqib; Rolfe, Alan; Stoianova, Diana; Hanson, Paul R

    2015-10-16

    The syntheses of silica-supported oligomeric benzyl phosphates (Si-OBP(n)) and triazole phosphates (Si-OTP(n)) using ring-opening metathesis polymerization (ROMP) for use as efficient alkylating reagents is reported. Ease of synthesis and grafting onto the surface of norbornenyl-tagged (Nb-tagged) silica particles has been demonstrated for benzyl phosphate and triazole phosphate monomers. It is shown that these silica polymer hybrid reagents, Si-OBP(n) and Si-OTP(n), can be used to carry out alkylation reactions with an array of different nucleophiles to afford the corresponding benzylated and (triazolyl)methylated products in good yield and high purity. PMID:26430955

  15. Bar Code Labels

    NASA Technical Reports Server (NTRS)

    1988-01-01

    American Bar Codes, Inc. developed special bar code labels for inventory control of space shuttle parts and other space system components. ABC labels are made in a company-developed anodizing aluminum process and consecutively marketed with bar code symbology and human readable numbers. They offer extreme abrasion resistance and indefinite resistance to ultraviolet radiation, capable of withstanding 700 degree temperatures without deterioration and up to 1400 degrees with special designs. They offer high resistance to salt spray, cleaning fluids and mild acids. ABC is now producing these bar code labels commercially or industrial customers who also need labels to resist harsh environments.

  16. Steric and Dynamic Parameters Influencing In Situ Cycloadditions to Form Triazole Inhibitors with Crystalline Acetylcholinesterase.

    PubMed

    Bourne, Yves; Sharpless, K Barry; Taylor, Palmer; Marchot, Pascale

    2016-02-10

    Ligand binding sites on acetylcholinesterase (AChE) comprise an active center, at the base of a deep and narrow gorge lined by aromatic residues, and a peripheral site at the gorge entry. These features launched AChE as a reaction vessel for in situ click-chemistry synthesis of high-affinity TZ2PA6 and TZ2PA5 inhibitors, forming a syn-triazole upon cycloaddition within the gorge from alkyne and azide reactants bound at the two sites, respectively. Subsequent crystallographic analyses of AChE complexes with the TZ2PA6 regioisomers demonstrated that syn product association is accompanied by side chain reorganization within the gorge, freezing-in-frame a conformation distinct from an unbound state or anti complex. To correlate inhibitor dimensions with reactivity and explore whether in situ cycloaddition could be accelerated in a concentrated, crystalline template, we developed crystal-soaking procedures and solved structures of AChE complexes with the TZ2PA5 regioisomers and their TZ2/PA5 precursors (2.1-2.7 Å resolution). The structures reveal motions of residue His447 in the active site and, unprecedentedly, residue Tyr341 at the gorge mouth, associated with TZ2 binding and coordinated with other side chain motions in the gorge that may guide AChE toward a transient state favoring syn-triazole formation. Despite precursor binding to crystalline AChE, coupling of rapid electric field fluctuations in the gorge with proper alignments of the azide and alkyne reactants to form the triazole remains a likely limiting step. These observations point to a prime requirement for AChE to interconvert dynamically between sequential conformations to promote favorable electrostatic factors enabling a productive apposition of the reactants for reactivity. PMID:26731630

  17. Mechanism of multivalent nanoparticle encounter with HIV-1 for potency enhancement of peptide triazole virus inactivation.

    PubMed

    Rosemary Bastian, Arangassery; Nangarlia, Aakansha; Bailey, Lauren D; Holmes, Andrew; Kalyana Sundaram, R Venkat; Ang, Charles; Moreira, Diogo R M; Freedman, Kevin; Duffy, Caitlin; Contarino, Mark; Abrams, Cameron; Root, Michael; Chaiken, Irwin

    2015-01-01

    Entry of HIV-1 into host cells remains a compelling yet elusive target for developing agents to prevent infection. A peptide triazole (PT) class of entry inhibitor has previously been shown to bind to HIV-1 gp120, suppress interactions of the Env protein at host cell receptor binding sites, inhibit cell infection, and cause envelope spike protein breakdown, including gp120 shedding and, for some variants, virus membrane lysis. We found that gold nanoparticle-conjugated forms of peptide triazoles (AuNP-PT) exhibit substantially more potent antiviral effects against HIV-1 than corresponding peptide triazoles alone. Here, we sought to reveal the mechanism of potency enhancement underlying nanoparticle conjugate function. We found that altering the physical properties of the nanoparticle conjugate, by increasing the AuNP diameter and/or the density of PT conjugated on the AuNP surface, enhanced potency of infection inhibition to impressive picomolar levels. Further, compared with unconjugated PT, AuNP-PT was less susceptible to reduction of antiviral potency when the density of PT-competent Env spikes on the virus was reduced by incorporating a peptide-resistant mutant gp120. We conclude that potency enhancement of virolytic activity and corresponding irreversible HIV-1 inactivation of PTs upon AuNP conjugation derives from multivalent contact between the nanoconjugates and metastable Env spikes on the HIV-1 virus. The findings reveal that multispike engagement can exploit the metastability built into virus the envelope to irreversibly inactivate HIV-1 and provide a conceptual platform to design nanoparticle-based antiviral agents for HIV-1 specifically and putatively for metastable enveloped viruses generally. PMID:25371202

  18. Site-saturation engineering of lysine 47 in cyclodextrin glycosyltransferase from Paenibacillus macerans to enhance substrate specificity towards maltodextrin for enzymatic synthesis of 2-O-D-glucopyranosyl-L-ascorbic acid (AA-2G).

    PubMed

    Han, Ruizhi; Liu, Long; Shin, Hyun-dong; Chen, Rachel R; Du, Guocheng; Chen, Jian

    2013-07-01

    In this work, the site-saturation engineering of lysine 47 in cyclodextrin glycosyltransferase (CGTase) from Paenibacillus macerans was conducted to improve the specificity of CGTase towards maltodextrin, which can be used as a cheap and easily soluble glycosyl donor for the enzymatic synthesis of 2-O-D-glucopyranosyl-L-ascorbic acid (AA-2G) by CGTase. When using maltodextrin as glycosyl donor, four mutants K47F (lysine→ phenylalanine), K47L (lysine→ leucine), K47V (lysine→ valine) and K47W (lysine→ tryptophan) showed higher AA-2G yield as compared with that produced by the wild-type CGTase. The transformation conditions (temperature, pH and the mass ratio of L-ascorbic acid to maltodextrin) were optimized and the highest titer of AA-2G produced by the mutant K47L could reach 1.97 g/l, which was 64.2% higher than that (1.20 g/l) produced by the wild-type CGTase. The reaction kinetics analysis confirmed the enhanced maltodextrin specificity, and it was also found that compared with the wild-type CGTase, the four mutants had relatively lower cyclization activities and higher disproportionation activities, which was favorable for AA-2G synthesis. The mechanism responsible for the enhanced substrate specificity was further explored by structure modeling and it was indicated that the enhancement of maltodextrin specificity may be due to the short residue chain and the removal of hydrogen bonding interactions between the side chain of residue 47 and the sugar at -3 subsite. Here the obtained mutant CGTases, especially the K47L, has a great potential in the production of AA-2G with maltodextrin as a cheap and easily soluble substrate. PMID:23129181

  19. Synthesis, antimalarial properties and 2D-QSAR studies of novel triazole-quinine conjugates.

    PubMed

    Faidallah, Hassan M; Panda, Siva S; Serrano, Juan C; Girgis, Adel S; Khan, Khalid A; Alamry, Khalid A; Therathanakorn, Tanya; Meyers, Marvin J; Sverdrup, Francis M; Eickhoff, Christopher S; Getchell, Stephen G; Katritzky, Alan R

    2016-08-15

    Click chemistry technique led to novel 1,2,3-triazole-quinine conjugates 8a-g, 10a-o, 11a-h and 13 utilizing benzotriazole-mediated synthetic approach with excellent yields. Some of the synthesized analogs (11a, 11d-h) exhibited antimalarial properties against Plasmodium falciparum strain 3D7 with potency higher than that of quinine (standard reference used) through in vitro standard procedure bio-assay. Statistically significant BMLR-QSAR model describes the bio-properties, validates the observed biological observations and identifies the most important parameters governing bio-activity. PMID:27298002

  20. 1,2,4-Triazole derivatives as transient inactivators of kallikreins involved in skin diseases.

    PubMed

    Tan, Xiao; Furio, Laetitia; Reboud-Ravaux, Michèle; Villoutreix, Bruno O; Hovnanian, Alain; El Amri, Chahrazade

    2013-08-15

    We describe here 1,2,4-triazoles derivatives identified as transient inactivators acting at the nanomolar level on human kallikreins (hK5, hK7 and hK14) and matriptase. Both the nature of the targeted enzymes and structural variations of the inhibitors influence the life-times of acyl-enzymes. These nonpeptidic, transient and low-molecular-weight inhibitors were found to be noncytotoxic against healthy human keratinocytes. These molecules may be useful to counteract dysregulated proteolytic cascades observed in dermatological disorders such as Netherton syndrome. PMID:23849879

  1. Studies on green and efficient catalytic oxidation of a triazole compound

    NASA Astrophysics Data System (ADS)

    Luo, J.; Liu, Y. C.; Huang, K. H.; Chai, T.; Wang, J. H.; Yu, Y. W.; Yuan, J. M.; Chang, S. J.; Guo, J. H.; Zhang, J.

    2016-07-01

    1-Methyl-3,5-dinitro-1,2,4-triazole is an insensitive energetic compound that can be prepared by oxidizing the nitrate salt of 1-methylguanazole. The influence of the reaction time, reaction temperature, reactant ratio, feeding method and catalytic oxidation method on the yield were discussed. The results show that the optimum reaction conditions are as follows: mass ratio of sodium tungstate to nitrate salt to 1-methylguanazole, 4:4.4; time, 5.5h; and temperature, 65-75°C. The yield of this oxidation reaction reached 51.36%.

  2. Design, Synthesis and Antifungal Activity of Novel Benzofuran-Triazole Hybrids.

    PubMed

    Liang, Zhen; Xu, Hang; Tian, Ye; Guo, Mengbi; Su, Xin; Guo, Chun

    2016-01-01

    A series of novel benzofuran-triazole hybrids was designed and synthesized by click chemistry, and their structures were characterized by HRMS, FTIR and NMR. The in vitro antifungal activity of target compounds was evaluated using the microdilution broth method against five strains of pathogenic fungi. The result indicated that the target compounds exhibited moderate to satisfactory activity. Furthermore, molecular docking was performed to investigate the binding affinities and interaction modes between the target compound and N-myristoyltransferase. Based on the results, preliminary structure activity relationships (SARs) were summarized to serve as a foundation for further investigation. PMID:27338311

  3. Triazole-Based Compound as a Candidate To Develop Novel Medicines To Treat Toxoplasmosis

    PubMed Central

    Paneth, Agata; Plech, Tomasz; Pawełczyk, Jakub; Węglińska, Lidia; Paneth, Piotr

    2014-01-01

    This article reports anti-Toxoplasma gondii activity of 3-(thiophen-2-yl)-1,2,4-triazole-5-thione. The compound displayed significant and reproducible antiparasitic effects at nontoxic concentrations for the host cells, with an experimentally determined 50% inhibitory concentration (IC50) at least 30 times better than that of the known chemotherapeutic agent sulfadiazine. Purine nucleoside phosphorylase was defined as the probable target for anti-Toxoplasma activity of the tested compound. These results provide the foundation for future work to develop a new class of medicines to better treat toxoplasmosis. PMID:25288090

  4. Preliminary Pharmacological Screening of Some Thiosemicarbazide, s-triazole, and Thiadiazole Derivatives.

    PubMed

    Paneth, Agata; Wujec, Monika; Plech, Tomasz; Kuśmierz, Edyta; Hagel, Dominika; Kosiek, Szymon; Jagiello-Wójtowicz, Ewa; Piątkowska-Chmiel, Iwona; Herbet, Mariola; Izdebska, Magdalena; Kędzierska, Ewa; Orzelska-Górka, Jolanta

    2016-01-01

    Two thiosemicarbazide derivatives 1 and 2, three 2-amino-1,3,4-thiadiazole derivatives 3-5, and three N1- substituted-4-methyl-1,2,4-triazole-5-thione derivatives 6-8 were synthesized and evaluated for their central nervous system effects using rodent behavioral models. With the exception of 6, all compounds were devoid of neurotoxicity and they did not affect the body temperature of mice. New lead structures 1-4 with potential analgesic activity were identified. PMID:26996168

  5. Nano-interconnection for microelectronics and polymers with benzo-triazole

    NASA Technical Reports Server (NTRS)

    Park, Yeonjoon; Choi, Sang H.; Noh, Hyunpil; Kuk, Young

    2006-01-01

    Benzo-Triazole (BTA) is considered as an important bridging material that can connect an organic polymer to the metal electrode on silicon wafers as a part of the microelectronics fabrication technology. We report a detailed process of surface induced 3-D polymerization of BTA on the Cu electrode material which was measured with the Ultraviolet Photoemission Spectroscopy (UPS), X-ray Photoemission Spectroscopy (XPS), and Scanning Tunneling Microscope (STM). The electric utilization of shield and chain polymerization of BTA on Cu surface is contemplated in this study.

  6. New Iridium Complex Coordinated with Tetrathiafulvalene Substituted Triazole-pyridine Ligand: Synthesis, Photophysical and Electrochemical Properties.

    PubMed

    Niu, Zhi-Gang; Xie, Hui; He, Li-Rong; Li, Kai-Xiu; Xia, Qing; Wu, Dong-Min; Li, Gao-Nan

    2016-01-01

    A new iridium(III) complex based on the triazole-pyridine ligand with tetrathiafulvalene unit, [Ir(ppy)2(L)]PF6 (1), has been synthesized and structurally characterized. The absorption spectra, luminescent spectra and electrochemical behaviors of L and 1 have been investigated. Complex 1 is found to be emissive at room temperature with maxima at 481 and 510 nm. The broad and structured emission bands are suggested a mixing of 3LC (3π-π*) and 3CT (3MLCT) excited states. The influence of iridium ion coordination on the redox properties of the TTF has also been investigated by cyclic voltammetry. PMID:27333555

  7. Design, synthesis, and antifungal activities of novel triazole derivatives containing the benzyl group

    PubMed Central

    Xu, Kehan; Huang, Lei; Xu, Zheng; Wang, Yanwei; Bai, Guojing; Wu, Qiuye; Wang, Xiaoyan; Yu, Shichong; Jiang, Yuanying

    2015-01-01

    In previous studies undertaken by our group, a series of 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted-2-propanols (1a–r), which were analogs of fluconazole, was designed and synthesized by click chemistry. In the study reported here, the in vitro antifungal activities of all the target compounds were evaluated against eight human pathogenic fungi. Compounds 1a, 1q, and 1r showed the more antifungal activity than the others. PMID:25792806

  8. In vivo pharmacokinetics and pharmacodynamics of a new triazole, voriconazole, in a murine candidiasis model.

    PubMed

    Andes, D; Marchillo, K; Stamstad, T; Conklin, R

    2003-10-01

    In vivo studies have described the pharmacodynamic (PD) characteristics of several triazoles. These investigations have demonstrated that the 24-h area under the concentration-time curve (AUC)/MIC ratio is the critical pharmacokinetic (PK)-PD parameter associated with treatment efficacy. Further analyses from these in vivo studies have demonstrated that a triazole free drug 24-h AUC/MIC of 20 to 25 is predictive of treatment success. We used a neutropenic murine model of disseminated Candida albicans infection to similarly characterize the PK-PD of the new triazole voriconazole. PK and PD parameters (percentage of time that the concentration remains above the MIC [T > MIC], AUC/MIC ratio, and peak level in serum/MIC ratio) were correlated with in vivo efficacy, as measured by the organism number in kidney cultures after 24 h of therapy. Voriconazole kinetics and protein binding were studied in infected neutropenic mice. Peak level/dose and AUC/dose values ranged from 0.1 to 0.2 and 0.1 to 0.7, respectively. The serum elimination half-life ranged from 0.7 to 2.9 h. The level of protein binding in mouse serum was 78%. Treatment efficacy with the four dosing intervals studied was similar, supporting the AUC/MIC ratio as the PK-PD parameter predictive of efficacy. Nonlinear regression analysis also suggested that the AUC/MIC ratio was strongly predictive of treatment outcomes (R(2) for AUC/MIC ratio = 82%, R(2) for peak level/MIC ratio = 63%, R(2) for T > MIC = 75%). Similar studies were conducted with nine additional C. albicans isolates with various voriconazole susceptibilities (MICs, 0.007 to 0.25 micro g/ml) to determine if a similar 24-h AUC/MIC ratio was associated with efficacy. The voriconazole free drug AUC/MIC ratios were similar for all of the organisms studied (range, 11 to 58; mean +/- standard deviation, 24 +/- 17 [P = 0.45]). These AUC/MIC ratios observed for free drug are similar to those observed for other triazoles in this model. PMID:14506026

  9. In Vivo Pharmacokinetics and Pharmacodynamics of a New Triazole, Voriconazole, in a Murine Candidiasis Model

    PubMed Central

    Andes, D.; Marchillo, K.; Stamstad, T.; Conklin, R.

    2003-01-01

    In vivo studies have described the pharmacodynamic (PD) characteristics of several triazoles. These investigations have demonstrated that the 24-h area under the concentration-time curve (AUC)/MIC ratio is the critical pharmacokinetic (PK)-PD parameter associated with treatment efficacy. Further analyses from these in vivo studies have demonstrated that a triazole free drug 24-h AUC/MIC of 20 to 25 is predictive of treatment success. We used a neutropenic murine model of disseminated Candida albicans infection to similarly characterize the PK-PD of the new triazole voriconazole. PK and PD parameters (percentage of time that the concentration remains above the MIC [T > MIC], AUC/MIC ratio, and peak level in serum/MIC ratio) were correlated with in vivo efficacy, as measured by the organism number in kidney cultures after 24 h of therapy. Voriconazole kinetics and protein binding were studied in infected neutropenic mice. Peak level/dose and AUC/dose values ranged from 0.1 to 0.2 and 0.1 to 0.7, respectively. The serum elimination half-life ranged from 0.7 to 2.9 h. The level of protein binding in mouse serum was 78%. Treatment efficacy with the four dosing intervals studied was similar, supporting the AUC/MIC ratio as the PK-PD parameter predictive of efficacy. Nonlinear regression analysis also suggested that the AUC/MIC ratio was strongly predictive of treatment outcomes (R2 for AUC/MIC ratio = 82%, R2 for peak level/MIC ratio = 63%, R2 for T > MIC = 75%). Similar studies were conducted with nine additional C. albicans isolates with various voriconazole susceptibilities (MICs, 0.007 to 0.25 μg/ml) to determine if a similar 24-h AUC/MIC ratio was associated with efficacy. The voriconazole free drug AUC/MIC ratios were similar for all of the organisms studied (range, 11 to 58; mean ± standard deviation, 24 ± 17 [P = 0.45]). These AUC/MIC ratios observed for free drug are similar to those observed for other triazoles in this model. PMID:14506026

  10. Covalent Conjugation of a Peptide Triazole to HIV-1 gp120 Enables Intramolecular Binding Site Occupancy

    PubMed Central

    2015-01-01

    The HIV-1 gp120 glycoprotein is the main viral surface protein responsible for initiation of the entry process and, as such, can be targeted for the development of entry inhibitors. We previously identified a class of broadly active peptide triazole (PT) dual antagonists that inhibit gp120 interactions at both its target receptor and coreceptor binding sites, induce shedding of gp120 from virus particles prior to host–cell encounter, and consequently can prevent viral entry and infection. However, our understanding of the conformational alterations in gp120 by which PT elicits its dual receptor antagonism and virus inactivation functions is limited. Here, we used a recently developed computational model of the PT–gp120 complex as a blueprint to design a covalently conjugated PT–gp120 recombinant protein. Initially, a single-cysteine gp120 mutant, E275CYU-2, was expressed and characterized. This variant retains excellent binding affinity for peptide triazoles, for sCD4 and other CD4 binding site (CD4bs) ligands, and for a CD4-induced (CD4i) ligand that binds the coreceptor recognition site. In parallel, we synthesized a PEGylated and biotinylated peptide triazole variant that retained gp120 binding activity. An N-terminally maleimido variant of this PEGylated PT, denoted AE21, was conjugated to E275C gp120 to produce the AE21–E275C covalent conjugate. Surface plasmon resonance interaction analysis revealed that the PT–gp120 conjugate exhibited suppressed binding of sCD4 and 17b to gp120, signatures of a PT-bound state of envelope protein. Similar to the noncovalent PT–gp120 complex, the covalent conjugate was able to bind the conformationally dependent mAb 2G12. The results argue that the PT–gp120 conjugate is structurally organized, with an intramolecular interaction between the PT and gp120 domains, and that this structured state embodies a conformationally entrapped gp120 with an altered bridging sheet but intact 2G12 epitope. The similarities of

  11. Phenylethynyl Terminated Arylene Ether Oxadiazole and Triazole Oligomers and Their Cured Polymers

    NASA Technical Reports Server (NTRS)

    Thompson, C. M.; Hergenrother, P. M.

    2001-01-01

    Several novel phenylethynyl terminated arylene ether oligomers containing oxadiazole and triazole rings were prepared as part of an effort to develop high performance polymers with an attractive combination of properties (e.g. processability and mechanical performance) for future NASA applications. The oligomers displayed low melt viscosities and good solubilities. Thin films cast from solutions of the oligomers and cured for one hour at 350 C in air gave good tensile properties. Titanium to titanium (6Al-4V) tensile shear specimens were readily fabricated and provided moderate strengths. The chemistry and properties of these new materials are discussed.

  12. A toxicological study of 1,2,4-triazole-5-one

    SciTech Connect

    London, J.

    1988-12-01

    The acute oral LD/sub 50/ values for 1,2,4-triazole-5-one (TO) are greater than 5g/kg. According to classical guidelines, the material would be considered only slightly toxic or practically nontoxic in both rats and mice. The sensitization study in the guinea pig did not show TO to have potential sensitizing effects. Skin application studies on the rabbit demonstrated it was cutaneously nonirritating. This material was also nonirritating in the rabbit eye application studies. 4 refs., 1 tab.

  13. Design, synthesis, and antifungal activities of novel triazole derivatives containing the benzyl group.

    PubMed

    Xu, Kehan; Huang, Lei; Xu, Zheng; Wang, Yanwei; Bai, Guojing; Wu, Qiuye; Wang, Xiaoyan; Yu, Shichong; Jiang, Yuanying

    2015-01-01

    In previous studies undertaken by our group, a series of 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted-2-propanols (1a-r), which were analogs of fluconazole, was designed and synthesized by click chemistry. In the study reported here, the in vitro antifungal activities of all the target compounds were evaluated against eight human pathogenic fungi. Compounds 1a, 1q, and 1r showed the more antifungal activity than the others. PMID:25792806

  14. Labeling and Delinquency.

    ERIC Educational Resources Information Center

    Adams, Mike S.; Robertson, Craig T.; Gray-Ray, Phyllis; Ray, Melvin C.

    2003-01-01

    Index comprised of six contrasting descriptive adjectives was used to measure incarcerated youths' perceived negative labeling from the perspective of parents, teachers, and peers. Results provided partial support for hypothesis that juveniles who choose a greater number of negative labels will report more frequent delinquent involvement. Labeling…

  15. Label fusion strategy selection.

    PubMed

    Robitaille, Nicolas; Duchesne, Simon

    2012-01-01

    Label fusion is used in medical image segmentation to combine several different labels of the same entity into a single discrete label, potentially more accurate, with respect to the exact, sought segmentation, than the best input element. Using simulated data, we compared three existing label fusion techniques-STAPLE, Voting, and Shape-Based Averaging (SBA)-and observed that none could be considered superior depending on the dissimilarity between the input elements. We thus developed an empirical, hybrid technique called SVS, which selects the most appropriate technique to apply based on this dissimilarity. We evaluated the label fusion strategies on two- and three-dimensional simulated data and showed that SVS is superior to any of the three existing methods examined. On real data, we used SVS to perform fusions of 10 segmentations of the hippocampus and amygdala in 78 subjects from the ICBM dataset. SVS selected SBA in almost all cases, which was the most appropriate method overall. PMID:22518113

  16. OR Specimen Labeling.

    PubMed

    Zervakis Brent, Mary Ann

    2016-02-01

    Mislabeled surgical specimens jeopardize patient safety and quality care. The purpose of this project was to determine whether labeling surgical specimens with two patient identifiers would result in an 80% reduction in specimen labeling errors within six months and a 100% reduction in errors within 12 months. Our failure mode effects analysis found that the lack of two patient identifiers per label was the most unsafe step in our specimen handling process. We piloted and implemented a new process in the OR using the Plan-Do-Check-Act conceptual framework. The audit process included collecting data and making direct observations to determine the sustainability of the process change; however, the leadership team halted the direct observation audit after four months. The total number of surgical specimen labeling errors was reduced by only 60% within six months and 62% within 12 months; therefore, the goal of the project was not met. However, OR specimen labeling errors were reduced. PMID:26849982

  17. Nanovehicles based Bioassay Labels

    SciTech Connect

    Liu, Guodong; Wang, Jun; Wu, Hong; Lin, Ying-Ying; Lin, Yuehe

    2007-04-01

    In this article, we review recent advances of our group in nanoparticle labels based bioassay. Apoferritin and silica nanoparticles have been used as nanovehicles to load large amount of markers for highly sensitive bioassay. Markers loaded apoferritin, apoferritin-templated metallic phosphate nanoparticles, and poly [guanine] coated silica nanoparticles have been prepared, characterized and used as labels for highly sensitive bioassay of protein and DNA. Dissociation and reconstitution characteristics at different pH as well as the special cavity structure of apoferritin nanovehicle provides a simple and convenient route to prepare versatile nanoparticle labels and avoid the complicated and tedious synthesis process of conventional nanoparticle labels. The optical and electrochemical characteristics of the prepared nanoparticle labels are easily controlled by loading different optical or electrochemical markers. Additionally, the use of apoferritin nanovehicle as template for synthesis of metallic phosphate nanoparticle labels offers fast route to prepare uniform-size metallic nanoparticle labels for electrochemical bioassay and avoids the traditional harsh dissolution conditions to dissolve metallic nanoparticle tags (that is, the strong-acid dissolution of quantum dots and gold nanoparticles) during the stripping analysis step. Silica nanoparticle has also been used as nanovehicle to carry thousands of poly [guanine] tracers, which was used to enhance the oxidation current of Ru(bpy)32+, resulting in enhanced sensitivity of electrochemical immunoassay. The new nanovehicle-based labels have been used for highly sensitive electrochemical detection of DNA and protein biomarkers, such as tumor necrosis factor-alpha (TNF-a). The high sensitivity and selectivity make these labels a useful addition to the armory of nanoparticle-based bioassay. The new nanovehicles based labels hold great promise for multiplex protein and DNA detection and for enhancing the sensitivity

  18. Synthesis and in vitro anti-tubercular evaluation of 1,2,3-triazole tethered β-lactam-ferrocene and β-lactam-ferrocenylchalcone chimeric scaffolds.

    PubMed

    Kumar, Kewal; Singh, Pardeep; Kremer, Laurent; Guérardel, Yann; Biot, Christophe; Kumar, Vipan

    2012-05-21

    Twenty different triazoles were prepared to probe the anti-tubercular structure-activity relationships (SAR) within the β-lactam-ferrocene-triazole conjugate family. The compounds have been synthesized by copper-catalyzed "click chemistry". In vitro anti-tubercular activity was determined for each compound but the synthesized hybrids failed to inhibit Mycobacterium tuberculosis growth even at high doses. The manuscript assumes significance as this is the first report on the inclusion of ferrocene nucleus in the well established β-lactam family via triazole linkers with reputed physicochemical profiles. PMID:22473422

  19. Alkenes as azido precursors for the one-pot synthesis of 1,2,3-triazoles catalyzed by copper nanoparticles on activated carbon.

    PubMed

    Alonso, Francisco; Moglie, Yanina; Radivoy, Gabriel; Yus, Miguel

    2013-05-17

    A one-pot protocol for the synthesis of 1,2,3-triazoles has been developed starting from inactivated alkenes and based on two click reactions: the azidosulfenylation of the carbon-carbon double bond and the copper-catalyzed azide-alkyne cycloaddition (CuAAC). High yields of the β-methylsulfanyl triazoles have been attained using CuNPs/C as catalyst, with other commercial copper catalysts being completely inactive. The versatility of the methylsulfanyl group has been demonstrated through a series of synthetic transformations, including direct access to 1-vinyl and 4-monosubstituted triazoles. PMID:23617398

  20. From Mono to Tris-1,2,3-triazole-Stabilized Gold Nanoparticles and Their Compared Catalytic Efficiency in 4-Nitrophenol Reduction.

    PubMed

    Wang, Changlong; Salmon, Lionel; Li, Qian; Igartua, María Echeverría; Moya, Sergio; Ciganda, Roberto; Ruiz, Jaime; Astruc, Didier

    2016-07-01

    Mono-, bis-, and tris-1,2,3-triazole ligands are used for the stabilization of gold nanoparticles (AuNPs), and the catalytic activities of these AuNPs in 4-nitrophenol reduction by NaBH4 in water are compared as well as with polyethylene glycol 2000 (PEG)- and polyvinylpyrrolidone (PVP)-stabilized AuNPs. The excellent catalytic results specifically obtained with the tris-triazolate ligand terminated by a PEG tail are taken into account by the synergy between the weakness of the tris-triazole-AuNP bond combined with the stabilizing ligand bulk. PMID:27304517

  1. Design and synthesis of 1,2,3-triazole-fused chiral medium-ring benzo-heterocycles, scaffolds mimicking benzolactams.

    PubMed

    Das Adhikary, Nirmal; Chattopadhyay, Partha

    2012-06-15

    Based on "amide-triazole bioequivalence" principle, 1,2,3-triazole-fused chiral medium ring benzo-heterocycles capable of mimicking benzolactams were designed. Their syntheses were accomplished by cycloaddition of different sugar-derived azidoalkynes. While triazole-fused eight-membered benzo-heterocycles were formed by exclusive intramolecuclar [3 + 2] cycloaddition, attempted preparation of seven-membered analogues led to some intermolecular cycloaddition resulting in a dimeric macrocyclic product, in addition to intramolecular cycloaddition furnishing the expected heterocycle. PMID:22647142

  2. Synthesis and biological activity of substituted urea and thiourea derivatives containing 1,2,4-triazole moiety

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A series of novel thiourea and urea derivatives carrying 1,2,4-triazole moiety were synthesized and evaluated for their antifungal and larvicidal activity. Thiourea (1a-e) and urea derivatives (2a-e) were prepared by reacting 4-(aminophenyl)acetic acid with corresponding isothiocyanates and isocyana...

  3. Stereoselective Metabolism of 1,2,4-Triazole Fungicides in Hepatic Microsomes and Implications for Risk Assessment

    EPA Science Inventory

    The 1,2,4-triazole fungicides (i.e., conazoles) are potent cytochrome P450 (CYP) modulators and have been used extensively in agriculture and medicine. Recently, emphasis has been placed on the potential adverse effects of these compounds on mammalian steroid biosynthesis and en...

  4. Facile synthesis of 4-vinyl- and 4-fluorovinyl-1,2,3-triazoles via bifunctional “click-olefination” reagents

    PubMed Central

    Kumar, Rakesh; Pradhan, Padmanava; Zajc, Barbara

    2011-01-01

    Modular synthesis of vinyl and fluorovinyl triazoles can be achieved from bifunctional propargyl and fluoropropargyl sulfones by Cu-catalyzed azide-alkyne ligation and Julia-Kocienski olefination. Competitive click reactions of the protio and fluoropropargyl sulfones show higher reactivity of the latter, and a preliminary DFT analysis was performed. PMID:21336351

  5. 1,2,3-Triazole Bridge as Conformational Constrain in β-Hairpin Peptides: Analysis of Hydrogen-Bonded Positions.

    PubMed

    Celentano, V; Diana, D; Di Salvo, C; De Rosa, L; Romanelli, A; Fattorusso, R; D'Andrea, L D

    2016-04-11

    Conformational constrained β-hairpin peptides are useful tool to modulate protein-protein interactions. A triazole bridge in hydrogen-bonded positions between two antiparallel strands induces a conformational stabilization of the β-hairpin peptide. The entity of the stability of the β-hairpin peptide depends on the length of the bridge. PMID:26938670

  6. TRANSCRIPTIONAL RESPONSES IN THYROID TISSUES FROM RATS TREATED WITH A TUMORIGENIC AND A NON-TUMORIGENIC TRIAZOLE CONAZOLE FUNGICIDE

    EPA Science Inventory

    What is the study?
    Conazoles are triazole- or imidazole-containing fungicides that are used in agriculture and medicine. Conazoles can induce follicular cell adenomas of the thyroid in rats after chronic bioassay. The goal of this study was to identify pathways and network...

  7. Asymmetric azidation-cycloaddition with open-chain peptide-based catalysts. A sequential enantioselective route to triazoles.

    PubMed

    Guerin, David J; Miller, Scott J

    2002-03-13

    A family of beta-substituted histidine-containing peptides has been synthesized to probe the effect of noncovalent conformational rigidification on catalyst enantioselectivity. Unambiguous enhancement of enantioselectivity in the conjugate addition of azide to alpha,beta-unsaturated carboxylate derivatives has been achieved, enabling application to a sequential asymmetric azidation/cycloaddition for the synthesis of optically enriched triazoles and triazolines. PMID:11878965

  8. A facile and regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles using click chemistry

    EPA Science Inventory

    The reaction of α-tosyloxy ketones, sodium azide and terminal alkynes in presence of copper(I) in aqueous polyethylene glycol afforded regioselectively 1,4-disubstituted 1,2,3-triazoles in good yield at ambient temperature. The one-pot exclusive formation of 1,4-disubstituted 1,2...

  9. Reactions of 4-nitro-1,2,3-triazole with alkylating agents and compounds with activated multiple bonds

    SciTech Connect

    Vereshchagin, L.I.; Kuznetsova, N.I.; Kirillova, L.P.; Shcherbakov, V.V.; Sukhanov, G.T.; Gareev, G.A.

    1987-01-01

    When 4-nitro-1,2,3-triazole is alkylated, a mixture of N1- and N2-isomers is formed, with the latter usually predominating. The same behavior is also observed in addition reactions of 4-nitrotriazole to activated multiple bonds.

  10. INFLUENCE OF MATRIX FORMULATION ON DERMAL PERCUTANEOUS ABSORPTION OF TRIAZOLE FUNGICIDES USING QSAR AND PBPK / PD MODELS

    EPA Science Inventory

    The objective of this work is to use the Exposure Related Dose Estimating Model (ERDEM) and quantitative structure-activity relationship (QSAR) models to develop an assessment tool for human exposure assessment to triazole fungicides. A dermal exposure route is used for the physi...

  11. 40 CFR 721.10077 - 3H-1,2,4-Triazol-3-one, 1,2-dihydro-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 3H-1,2,4-Triazol-3-one, 1,2-dihydro-. 721.10077 Section 721.10077 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10077...

  12. Study on the stereoselective degradation of three triazole fungicides in sediment.

    PubMed

    Zhang, Qing; Zhou, Liangliang; Yang, Yu; Hua, Xiude; Shi, Haiyan; Wang, Minghua

    2015-07-01

    The stereoselective degradation behaviors of chiral triazole fungicides (hexaconazole, flutriafol and tebuconazole) in sediment were investigated under laboratory conditions. The enantiomers were completely separated by high-performance liquid chromatography on a cellulose tris(3-chloro-4-methylphenylcarbamate) (Lux Cellulose-2) column. The mean recoveries of hexaconazole, flutriafol and tebuconazole in sediment ranged from 86.7% to 105.9%. The methods were successfully applied for the enantioselective degradation analysis of fungicides in sediment. The results showed that the dissipation of hexaconazole, flutriafol and tebuconazole stereoisomers in sediment followed first-order kinetics (R(2)>0.95). The degradation rate of the enantiomers was different in sediment, and the (-)-enantiomer (t(1/2) was 86 days for hexaconazole, 139 for flutriafol and 136 for tebuconazole) degraded faster than the (+)-enantiomer (t(1/2) was 94 days for hexaconazole, 144 for flutriafol and 151 for tebuconazole) in native condition. The fungicides were degraded slowly, and no significant enantioselective degradation were observed under sterilized conditions. The results may hold promising implications for the environmental and ecological risk assessment of three important chiral triazole fungicides. PMID:25814463

  13. Synthesis of novel triazoles and a tetrazole of escitalopram as cholinesterase inhibitors.

    PubMed

    Mehr-un-Nisa; Munawar, Munawar A; Chattha, Fauzia A; Kousar, Samina; Munir, Jawaria; Ismail, Tayaba; Ashraf, Muhammad; Khan, Misbahul A

    2015-09-01

    A novel serie of escitalopram triazoles (60-88) and a tetrazole (89) have been synthesized and subjected to a study to establish the inhibitory potential of these compounds toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Some selectivity in inhibition has been observed. The 4-chlorophenyl- (75, IC50, 6.71 ± 0.25 μM) and 2-methylphenyl- (70, IC50, 9.52 ± 0.23 μM) escitalopram triazole derivatives depicted high AChE inhibition, while 2-fluorophenyl- (76, IC50 = 4.52 ± 0.17 μM) and 4-fluorophenyl- (78, IC50 = 5.31 ± 0.43 μM) have found to be excellent BChE inhibitors. It has also been observed that ortho, meta and para substituted electron donating groups increase the inhibition, while electron withdrawing groups reduce the inhibition. Docking analyses of inhibitors with AChE have depicted the binding energies for 70 and 75 as ΔG(bind) -6.42 and -6.93 kcal/mol, respectively, while ligands 76 and 78 have shown the binding affinity ΔG(bind) -9.04 and -8.51 kcal/mol, respectively, for BChE. PMID:26189031

  14. Structure cristalline de la 4-méthyl-1,2,4-triazole-thione

    NASA Astrophysics Data System (ADS)

    El Hajji, A.; El Ammari, L.; Mattern, G.; Benarafa, L.; Saidi Idrissi, M.

    1998-10-01

    The 4-methyl-1,2,4-triazole-thione crystalizes in the monoclinic system with the space group P21/n. The unit cell parameters are: a = 7.946 Å; b = 6.295 Å; c = 20.901 Å; β=100.47circ and Z = 8. The structure refinement lead to R = 0.047 and Rw = 0.035 factors. The molecules are planar and are joined together through hydrogen bonds N-H...N. Among the two possible tautomeric forms, only the thione form is present in the crystal structure. La 4-méthyl-1,2,4-triazole-thione cristallise dans un système monoclinique avec un groupe d'espace P21/n. Les paramètres cristallins sont : a = 7,946 Å ; b = 6,295 Å ; c = 20,901 Å ; β=100,47circ et Z = 8. L'affinement de la structure a conduit aux facteurs R = 0,047 et Rw = 0,035. Les molécules sont planes et sont liées entre elles par des liaisons hydrogène N- - -H....N. Parmi les deux formes tautomères possibles pour cette molécule, seule existe dans le cristal, la forme thione.

  15. The electrochemical and spectroelectrochemical properties of metal free and metallophthalocyanines containing triazole/piperazine units

    NASA Astrophysics Data System (ADS)

    Demirbaş, Ümit; Akyüz, Duygu; Mermer, Arif; Akçay, Hakkı Türker; Demirbaş, Neslihan; Koca, Atıf; Kantekin, Halit

    2016-01-01

    The synthesis and characterization of novel peripherally tetra [1,2,4]-triazole substituted metal-free phthalocyanine and its metal complexes (Zn(II), Ni(II), Pb(II), Cu(II) and Fe(II)) and the investigation of electrochemical and spectroelectrochemical properties of metal-free, Zn(II), Pb(II), Fe(II) phthalocyanines were performed for the first time in this study. Electrochemical characterizations of the complexes were performed with voltammetric and in situ spectroelectrochemical measurements. Voltammetric responses of the complexes supported the proposed structures, since complexes bearing redox inactive Pc ring metal centers just gave Pc based electron transfer reactions, while iron phthalocyanine went to metal based electron transfer reaction in addition to the Pc based ones. Electron withdrawing nature of [1,2,4]-triazole substituents shifted the redox processes toward the positive potentials. All complexes were electropolymerized during the oxidation reactions in dichloromethane (DCM) solvent. Types of the metal center of the complexes altered the electropolymerization reactions of the complexes. Spectra and colors of the electrogenerated redox species of the complexes were also determined with in situ spectroelectrochemical and in situ electrocolorimetric measurements.

  16. Involvement of constitutive androstane receptor in liver hypertrophy and liver tumor development induced by triazole fungicides.

    PubMed

    Tamura, Kei; Inoue, Kaoru; Takahashi, Miwa; Matsuo, Saori; Irie, Kaoru; Kodama, Yukio; Gamo, Toshie; Ozawa, Shogo; Yoshida, Midori

    2015-04-01

    We clarified the involvement of constitutive androstane receptor (CAR) in triazole-induced liver hypertrophy and tumorigenesis using CAR-knockout (CARKO) mice. Seven-week-old male CARKO and wild-type (WT) mice were treated with 200 ppm cyproconazole (Cypro), 1500 ppm tebuconazole (Teb), or 200 ppm fluconazole (Flu) in the diet for 27 weeks after initiation by diethylnitrosamine (DEN). At weeks 4 (without DEN) and 13 (with DEN), WT mice in all treatment groups and CARKO mice in Teb group revealed liver hypertrophy with mainly Cyp2b10 and following Cyp3a11 inductions in the liver. Teb also induced Cyp4a10 in both genotypes. Cypro induced slight and duration-dependent liver hypertrophy in CARKO mice. At week 27, Cypro and Teb significantly increased eosinophilic altered foci and/or adenomas in WT mice. These proliferating lesions were clearly reduced in CARKO mice administered both compounds. The eosinophilic adenomas caused by Flu decreased in CARKO mice. The present study indicates that CAR is the main mediator of liver hypertrophy induced by Cypro and Flu, but not Teb. In contrast, CAR played a crucial role in liver tumor development induced by all three triazoles. PMID:25656644

  17. Enantioselective bioactivity, acute toxicity and dissipation in vegetables of the chiral triazole fungicide flutriafol.

    PubMed

    Zhang, Qing; Hua, Xiu-de; Shi, Hai-yan; Liu, Ji-song; Tian, Ming-ming; Wang, Ming-hua

    2015-03-01

    The enantioselective bioactivity, acute toxicity and stereoselective degradation of the chiral triazole fungicide flutriafol in vegetables were investigated for the first time using the (R)-, (S)- and rac-flutriafol. The order of the bioactivity against five target pathogens (Rhizoctonia solani, Alternaria solani, Pyricularia grisea, Gibberella zeae, Botrytis cinerea) was found to be (R)-flutriafol>rac-flutriafol>(S)-flutriafol. The fungicidal activity of (R)-flutriafol was 1.49-6.23 times higher than that of (S)-flutriafol. The (R)-flutriafol also showed 2.17-3.52 times higher acute toxicity to Eisenia fetida and Scenedesmus obliquus than (S)-flutriafol. The stereoselective degradation of flutriafol in tomato showed that the active (R)-flutriafol degraded faster, resulting in an enrichment of inactive (S)-form, and the half-lives were 9.23 d and 10.18 d, respectively. Inversely, the (S)-flutriafol, with a half-life of 4.76 d, was preferentially degraded in cucumber. In conclusion, the systemic assessments of the triazole fungicide flutriafol stereoisomers on the enantioselective bioactivity, acute toxicity and environmental behavior may have implications for better environmental and ecological risk assessment. PMID:25463219

  18. Design, spectral characterization and biological studies of transition metal(II) complexes with triazole Schiff bases

    NASA Astrophysics Data System (ADS)

    Hanif, Muhammad; Chohan, Zahid H.

    2013-03-01

    A new series of three biologically active triazole derived Schiff base ligands L1-L3 have been synthesized in equimolar reaction of 3-amino-1H-1,2,4-triazole with pyrrol-2-carboxaldehyde, 4-bromo-thiophene-2-carboxaldehyde, and 5-iodo-2-hydroxy benzaldehyde. The prepared Schiff bases were used for further complex formation reaction with different metal elements like Co(II), Ni(II), Cu(II) and Zn(II) as chlorides by using a molar ratio of ligand:metal as 2:1. The structure and bonding nature of all the compounds were identified by their physical, spectral and analytical data. All the metal(II) complexes possessed an octahedral geometry except the Cu(II) complexes which showed a distorted octahedral geometry. All the synthesized compounds, were studied for their in vitro antibacterial, and antifungal activities, against four Gram-negative (Escherichia coli, Shigella sonnei, Pseudomonas aeruginosa and Salmonella typhi) and two Gram-positive (Bacillus subtilis and Staphylococcus aureus) bacterial strains and against six fungal strains (Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glabrata) by using agar-well diffusion method. It has been shown that all the synthesized compounds showed moderate to significant antibacterial activity against one or more bacterial strains. In vitro Brine Shrimp bioassay was also carried out to investigate the cytotoxic properties of these compounds. The data also revealed that the metal complexes showed better activity than the ligands due to chelation/coordination.

  19. Metal based new triazoles: Their synthesis, characterization and antibacterial/antifungal activities

    NASA Astrophysics Data System (ADS)

    Sumrra, Sajjad H.; Chohan, Zahid H.

    2012-12-01

    A series of new triazoles and their oxovanadium(IV) complexes have been synthesized, characterized and evaluated for antibacterial/antifungal properties. The new Schiff bases ligands (L1)-(L5) were prepared by the condensation reaction of 3,5-diamino-1,2,4-triazole with 2-hydroxy-1-naphthaldehyde, pyrrole-2-carboxaldehyde, pyridine-2-carboxaldehyde, 2-acetyl pyridine and 2-methoxy benzaldehyde. The structures of the ligands have been established on the basis of their physical, spectral (IR, 1H and 13C NMR and mass spectrometry) and elemental analytical data. The prepared ligands were used to synthesize their oxovanadium(IV) complexes (1)-(5) which were also characterized by their physical, spectral and analytical data and proposed to have a square pyramidal geometry. The ligands and their complexes were screened for in vitro antibacterial activity against six bacterial species such as, Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus aureus, and Bacillus subtilis and for in vitro antifungal activity against six fungal strains, Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani, and Candida glabrata. Cytotoxic nature of the compounds was also reported using brine shrimp bioassay method against Artemia salina.

  20. Phosphonylated Acyclic Guanosine Analogues with the 1,2,3-Triazole Linker.

    PubMed

    Głowacka, Iwona E; Andrei, Graciela; Schols, Dominique; Snoeck, Robert; Piotrowska, Dorota G

    2015-01-01

    A novel series of {4-[(2-amino-6-chloro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates and {4-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates as acyclic analogues of guanosine were synthesized and assessed for antiviral activity against a broad range of DNA and RNA viruses and for their cytostatic activity toward three cancerous cell lines (HeLa, L1210 and CEM). They were devoid of antiviral activity; however, several phosphonates were found slightly cytostatic against HeLa cells at an IC50 in the 80-210 µM range. Compounds (1R,2S)-17k and (1S,2S)-17k showed the highest inhibitory effects (IC50=15-30 µM) against the proliferation of murine leukemia (L1210) and human T-lymphocyte (CEM) cell lines. PMID:26501246

  1. Design, spectral characterization and biological studies of transition metal(II) complexes with triazole Schiff bases.

    PubMed

    Hanif, Muhammad; Chohan, Zahid H

    2013-03-01

    A new series of three biologically active triazole derived Schiff base ligands L(1)-L(3) have been synthesized in equimolar reaction of 3-amino-1H-1,2,4-triazole with pyrrol-2-carboxaldehyde, 4-bromo-thiophene-2-carboxaldehyde, and 5-iodo-2-hydroxy benzaldehyde. The prepared Schiff bases were used for further complex formation reaction with different metal elements like Co(II), Ni(II), Cu(II) and Zn(II) as chlorides by using a molar ratio of ligand:metal as 2:1. The structure and bonding nature of all the compounds were identified by their physical, spectral and analytical data. All the metal(II) complexes possessed an octahedral geometry except the Cu(II) complexes which showed a distorted octahedral geometry. All the synthesized compounds, were studied for their in vitro antibacterial, and antifungal activities, against four Gram-negative (Escherichia coli, Shigella sonnei, Pseudomonas aeruginosa and Salmonella typhi) and two Gram-positive (Bacillus subtilis and Staphylococcus aureus) bacterial strains and against six fungal strains (Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glabrata) by using agar-well diffusion method. It has been shown that all the synthesized compounds showed moderate to significant antibacterial activity against one or more bacterial strains. In vitro Brine Shrimp bioassay was also carried out to investigate the cytotoxic properties of these compounds. The data also revealed that the metal complexes showed better activity than the ligands due to chelation/coordination. PMID:23277183

  2. Metal based new triazoles: their synthesis, characterization and antibacterial/antifungal activities.

    PubMed

    Sumrra, Sajjad H; Chohan, Zahid H

    2012-12-01

    A series of new triazoles and their oxovanadium(IV) complexes have been synthesized, characterized and evaluated for antibacterial/antifungal properties. The new Schiff bases ligands (L(1))-(L(5)) were prepared by the condensation reaction of 3,5-diamino-1,2,4-triazole with 2-hydroxy-1-naphthaldehyde, pyrrole-2-carboxaldehyde, pyridine-2-carboxaldehyde, 2-acetyl pyridine and 2-methoxy benzaldehyde. The structures of the ligands have been established on the basis of their physical, spectral (IR, (1)H and (13)C NMR and mass spectrometry) and elemental analytical data. The prepared ligands were used to synthesize their oxovanadium(IV) complexes (1)-(5) which were also characterized by their physical, spectral and analytical data and proposed to have a square pyramidal geometry. The ligands and their complexes were screened for in vitro antibacterial activity against six bacterial species such as, Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus aureus, and Bacillus subtilis and for in vitro antifungal activity against six fungal strains, Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani, and Candida glabrata. Cytotoxic nature of the compounds was also reported using brine shrimp bioassay method against Artemia salina. PMID:22982389

  3. Synthesis, characterization, and antibacterial property of novel starch derivatives with 1,2,3-triazole.

    PubMed

    Tan, Wenqiang; Li, Qing; Wang, Huali; Liu, Yan; Zhang, Jingjing; Dong, Fang; Guo, Zhanyong

    2016-05-20

    Four novel starch-linked-1,2,3-triazole derivatives were synthesized including 6-hydroxymethyltriazole-6-deoxy starch (HMTST), 6-bromomethyltriazole-6-deoxy starch (BMTST), 6-chloromethyltriazole-6-deoxy starch (CMTST), and 6-carboxyltriazole-6-deoxy starch (CBTST). Their antibacterial properties against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were evaluated in vitro, respectively. The inhibitory property of the obtained amphiprotic starch derivatives exhibited a remarkable improvement over starch. And the antibacterial indices of most of the products were higher than 60% and 40% at 1.0 mg/mL when the culture time was 8 h and 16 h, respectively. Moreover, the inhibitory index of CBTST attained 97% above at 1.0 mg/mL. Generally, the inhibitory activity decreased in the order: CBTST>CMTST>BMTST>HMTST>starch. Furthermore, the order of their antibacterial activity was consistent with the electron-withdrawing property of different substituted groups of the 1,2,3-triazole groups. The substituted groups with stronger electron withdrawing ability relatively possessed greater antibacterial activity. PMID:26917366

  4. Probing the Backbone Function of Tumor Targeting Peptides by an Amide-to-Triazole Substitution Strategy.

    PubMed

    Valverde, Ibai E; Vomstein, Sandra; Fischer, Christiane A; Mascarin, Alba; Mindt, Thomas L

    2015-09-24

    Novel backbone-modified radiolabeled analogs based on the tumor targeting peptide bombesin were synthesized and fully evaluated in vitro and in vivo. We have recently introduced the use of 1,4-disubstituted 1,2,3-triazoles as metabolically stable trans-amide bond surrogates in radiolabeled peptides in order to improve their tumor targeting. As an extension of our approach, we now report several backbone-modified analogs of the studied bombesin peptide bearing multiple triazole substitutions. We investigated the effect of the modifications on several biological parameters including the internalization of the radiopeptidomimetics into tumor cells, their affinity toward the gastrin releasing peptide receptor (GRPr), metabolic stability in blood plasma, and biodistribution in mice bearing GRPr-expressing xenografts. The backbone-modified radiotracers exhibited a significantly increased resistance to proteolytic degradation. In addition, some of the radiopeptidomimetics retained a nanomolar affinity toward GRPr, resulting in an up to 2-fold increased tumor uptake in vivo in comparison to a (all amide bond) reference compound. PMID:26309061

  5. Fluorescent labelling of in situ hybridisation probes through the copper-catalysed azide-alkyne cycloaddition reaction.

    PubMed

    Hesse, Susann; Manetto, Antonio; Cassinelli, Valentina; Fuchs, Jörg; Ma, Lu; Raddaoui, Nada; Houben, Andreas

    2016-09-01

    In situ hybridisation is a powerful tool to investigate the genome and chromosome architecture. Nick translation (NT) is widely used to label DNA probes for fluorescence in situ hybridisation (FISH). However, NT is limited to the use of long double-stranded DNA and does not allow the labelling of single-stranded and short DNA, e.g. oligonucleotides. An alternative technique is the copper(I)-catalysed azide-alkyne cycloaddition (CuAAC), at which azide and alkyne functional groups react in a multistep process catalysed by copper(I) ions to give 1,4-distributed 1,2,3-triazoles at a high yield (also called 'click reaction'). We successfully applied this technique to label short single-stranded DNA probes as well as long PCR-derived double-stranded probes and tested them by FISH on plant chromosomes and nuclei. The hybridisation efficiency of differently labelled probes was compared to those obtained by conventional labelling techniques. We show that copper(I)-catalysed azide-alkyne cycloaddition-labelled probes are reliable tools to detect different types of repetitive sequences on chromosomes opening new promising routes for the detection of single copy gene. Moreover, a combination of FISH using such probes with other techniques, e.g. immunohistochemistry (IHC) and cell proliferation assays using 5-ethynyl-deoxyuridine, is herein shown to be easily feasible. PMID:27095480

  6. A model of the peptide triazole entry inhibitor binding to HIV-1 gp120 and mechanism of bridging sheet disruption

    PubMed Central

    Emileh, Ali; Tuzer, Ferit; Yeh, Herman; Umashankara, Muddegowda; Moreira, Diogo R. M.; LaLonde, Judith M.; Bewley, Carole A.; Abrams, Cameron F.; Chaiken, Irwin M.

    2013-01-01

    Peptide-triazole (PT) entry inhibitors prevent HIV-1 infection by blocking viral gp120 binding to both HIV-1 receptor and coreceptor on target cells. Here, we used all-atom explicit solvent molecular dynamics (MD) to propose a model for the encounter complex of the peptide-triazoles with gp120. Saturation Transfer Difference NMR (STD NMR) and single-site mutagenesis experiments were performed to test the simulation results. We found that docking of the peptide to a conserved patch of residues lining the “F43 pocket” of gp120 in a bridging sheet naïve gp120 conformation of the glycoprotein, led to a stable complex. This pose prevents formation of the bridging sheet minidomain, which is required for receptor/coreceptor binding, providing a mechanistic basis for dual-site antagonism of this class of inhibitors. Burial of the peptide triazole at gp120 inner/outer domain interface significantly contributed to complex stability and rationalizes the significant contribution of hydrophobic triazole groups to peptide potency. Both the simulation model and STD NMR experiments suggest that the I-X-W (where X=(2S, 4S)-4-(4-phenyl-1H-1, 2, 3-triazol-1-yl) pyrrolidine) tripartite hydrophobic motif in the peptide is the major contributor of contacts at the gp120/PT interface. Since the model predicts that the peptide Trp side chain hydrogen bonding with gp120 S375 contributes to stability of the PT/gp120 complex, we tested this prediction through analysis of peptide binding to gp120 mutant S375A. The results showed that a peptide triazole KR21 inhibits S375A with 20-fold less potency versus WT, consistent with predictions of the model. Overall, the PT/gp120 model provides a starting point for both rational design of higher affinity peptide triazoles and development of structure-minimized entry inhibitors that can trap gp120 into an inactive conformation and prevent infection. PMID:23470147

  7. How to Read Drug Labels

    MedlinePlus

    ... and alternative medicine Healthy Aging How to read drug labels Printer-friendly version How to Read Drug ... read drug labels How to read a prescription drug label View a text version of this picture. ...

  8. Nutrition Facts: Reading the Label

    MedlinePlus

    ... My Go4Life Get Free Stuff Be a Partner Nutrition Facts: Reading the Label Reading labels can help ... of information on their labels or packaging about nutrition and food safety. Product dates . You might see ...

  9. Noise labeling in Brazil

    NASA Astrophysics Data System (ADS)

    de Araujo, Marco A. N.; Massarani, Paulo M.; de Azevedo, Jose A. J.; Gerges, Samir N. Y.

    2002-11-01

    The Brazilian Silence Program, created in 1990 by the Brazilian Ministry of Environment, advocates the production and use of equipment with lower noise level. The subcommittee of Noise Labeling of the Brazilian Committee of Certification is composed of INMETRO acoustic specialists to organize and implement the Brazilian Labeling Program. This subcommittee elaborated the label form and test procedure. The noise-labeling program will first concentrate on the following household devices, both manufactured in Brazil or imported from abroad; mixers, blenders, hairdryers, refrigerators, and vacuum cleaners. The label should contain the sound-power level in dBA. INMETRO or other credited laboratories are responsible for the measurements. The ISO 4871, 3740 (1 to 5), ISO 8960, and IEC 704 (1 to 4) and also the equivalent Brazilian standards are used for the measurements, such as ABNT NBR 13910-1. The main objective of the label is to inform the consumer about the emitted noise level. The label offers the noise parameter to be used by the consumer when comparing devices, considering price, performance, and now also noise. No restriction for noise level was established.

  10. Direct formation of small Cu2O nanocubes, octahedra, and octapods for efficient synthesis of triazoles

    NASA Astrophysics Data System (ADS)

    Tsai, Ya-Huei; Chanda, Kaushik; Chu, Yi-Ting; Chiu, Chun-Ya; Huang, Michael H.

    2014-07-01

    In most studies describing the preparation of Cu2O crystals of various morphologies, the particle sizes are normally hundreds of nanometers to micrometers due to rapid particle growth, so they are not exactly nanocrystals. Here we report surfactant-free formation of sub-100 nm Cu2O nanocrystals with systematic shape evolution from cubic to octahedral structures by preparing an aqueous mixture of Cu(OAc)2, NaOH, and N2H4 solution. Adjustment of the hydrazine volume enables the particle shape control. Uniform nanocubes and octahedra were synthesized with edge lengths of 37 and 67 nm, respectively. Novel Cu2O octapods with an edge length of 135 nm were also produced by mixing CuCl2 solution, SDS surfactant, NaOH solution, and NH2OH.HCl reductant solution. All of them are nearly the smallest Cu2O nanocrystals of the same shapes ever reported. These small cubes, octahedra, and octapods were employed as catalysts in the direct synthesis of 1,2,3-triazoles from the reaction of alkynes, organic halides, and NaN3 at 55 °C. All of them displayed high product yields in short reaction times. The octahedra enclosed by the {111} facets are the best catalysts, and can catalyze this cycloaddition reaction with high yields in just 2 h when different alkynes were used to make diverse triazole products. Hence, the small Cu2O particles provide time-saving, energy-efficient, and high product yield benefits to organocatalysis.In most studies describing the preparation of Cu2O crystals of various morphologies, the particle sizes are normally hundreds of nanometers to micrometers due to rapid particle growth, so they are not exactly nanocrystals. Here we report surfactant-free formation of sub-100 nm Cu2O nanocrystals with systematic shape evolution from cubic to octahedral structures by preparing an aqueous mixture of Cu(OAc)2, NaOH, and N2H4 solution. Adjustment of the hydrazine volume enables the particle shape control. Uniform nanocubes and octahedra were synthesized with edge

  11. Capacitive label reader

    DOEpatents

    Arlowe, H.D.

    1983-07-15

    A capacitive label reader includes an outer ring transmitting portion, an inner ring transmitting portion, and a plurality of insulated receiving portions. A label is the mirror-image of the reader except that identifying portions corresponding to the receiving portions are insulated from only one of two coupling elements. Positive and negative pulses applied, respectively, to the two transmitting rings biased a CMOS shift register positively to either a 1 or 0 condition. The output of the CMOS may be read as an indication of the label.

  12. Capacitive label reader

    DOEpatents

    Arlowe, H. Duane

    1985-01-01

    A capacitive label reader includes an outer ring transmitting portion, an inner ring transmitting portion, and a plurality of insulated receiving portions. A label is the mirror-image of the reader except that identifying portions corresponding to the receiving portions are insulated from only one of two coupling elements. Positive and negative pulses applied, respectively, to the two transmitting rings biased a CMOS shift register positively to either a 1 or 0 condition. The output of the CMOS may be read as an indication of the label.

  13. Capacitive label reader

    DOEpatents

    Arlowe, H.D.

    1985-11-12

    A capacitive label reader includes an outer ring transmitting portion, an inner ring transmitting portion, and a plurality of insulated receiving portions. A label is the mirror-image of the reader except that identifying portions corresponding to the receiving portions are insulated from only one of two coupling elements. Positive and negative pulses applied, respectively, to the two transmitting rings biased a CMOS shift register positively to either a 1 or 0 condition. The output of the CMOS may be read as an indication of the label. 5 figs.

  14. Combining the Advantages of Tetrazoles and 1,2,3-Triazoles: 4,5-Bis(tetrazol-5-yl)-1,2,3-triazole, 4,5-Bis(1-hydroxytetrazol-5-yl)-1,2,3-triazole, and their Energetic Derivatives.

    PubMed

    Dippold, Alexander A; Izsák, Dániel; Klapötke, Thomas M; Pflüger, Carolin

    2016-01-26

    In the development of new energetic materials, the main challenge is the combination of high energy content with chemical and mechanical stability, two properties that are often contradictory. In this study, the syntheses and comprehensive characterizations of 4,5-bis(tetrazole-5-yl)-1,2,3-triazole and the novel 4,5-bis(1-hydroxytetrazole-5-yl)-1,2,3-triazole, as well as their energetic properties, are presented, combining the advantages of the more energetic tetrazole and the more stable 1,2,3-triazole rings. Nitrogen-rich salts of both compounds were synthesized to investigate their detonation performances and combustion behavior calculated by computer codes for potential application in erosion-reduced gun propellant mixtures due to their high nitrogen content. The structures of several of the compounds were studied by single-crystal X-ray diffraction and, especially in the case of 4,5-bis(tetrazol-5-yl)-1,2,3-triazole, revealed the site of deprotonation. PMID:26744139

  15. Crystal structures of five 1-alkyl-4-aryl-1,2,4-triazol-1-ium halide salts

    PubMed Central

    Guino-o, Marites A.; Talbot, Meghan O.; Slitts, Michael M.; Pham, Theresa N.; Audi, Maya C.; Janzen, Daron E.

    2015-01-01

    The asymmetric units for the salts 4-(4-fluoro­phen­yl)-1-isopropyl-1,2,4-triazol-1-ium iodide, C11H13FN3 +·I−, (1), 1-isopropyl-4-(4-methyl­phen­yl)-1,2,4-triazol-1-ium iodide, C12H16N3 +·I−, (2), 1-isopropyl-4-phenyl-1,2,4-triazol-1-ium iodide, C11H14N3 +·I−, (3), and 1-methyl-4-phenyl-1,2,4-triazol-1-ium iodide, C9H10N3 +·I−, (4), contain one cation and one iodide ion, whereas in 1-benzyl-4-phenyl-1,2,4-triazol-1-ium bromide monohydrate, C15H14N3 +·Br−·H2O, (5), there is an additional single water mol­ecule. There is a predominant C—H⋯X(halide) inter­action for all salts, resulting in a two-dimensional extended sheet network between the triazolium cation and the halide ions. For salts with para-substitution on the aryl ring, there is an additional π–anion inter­action between a triazolium carbon and iodide displayed by the layers. For salts without the para-substitution on the aryl ring, the π–π inter­actions are between the triazolium and aryl rings. The melting points of these salts agree with the predicted substituent inductive effects. PMID:26090137

  16. 1,2,3-Triazole pharmacophore-based benzofused nitrogen/sulfur heterocycles with potential anti-Moraxella catarrhalis activity.

    PubMed

    Maračić, Silvija; Kraljević, Tatjana Gazivoda; Paljetak, Hana Čipčić; Perić, Mihaela; Matijašić, Mario; Verbanac, Donatella; Cetina, Mario; Raić-Malić, Silvana

    2015-12-01

    Versatile 1,2,3-triazole pharmacophore-based benzofused heterocycles containing halogen-substituted aromatic (9-17 and 25-28), 7-substituted coumarin (18-23 and 29-30) or penciclovir-like subunit (31a,b-38a) were designed and synthesized to evaluate their antibacterial activities against selected Gram-positive and Gram-negative bacteria. Hybridization approach using environmentally friendly Cu(I)-catalyzed click reaction under microwave irradiation was adopted in the synthesis of regioselective 1,4-disubstituted 1,2,3-triazole tethered heterocycles (9-23 and 25-30), while post-N-alkylation of NH-1,2,3-triazoles afforded both 2,4- (31a-38a) and 1,4-disubstituted (31b-33b, 35b-37b) 1,2,3-triazole regioisomers. The compounds 18-23 and 25-30 revealed fluorescence in the violet region of the visible spectrum with a strong influence of phenyl spacer in 25-30 on both wavelength and emission intensity. Fusion of selected subunits led to new hybrid architecture, benzothiazole-1,2,3-triazole-coumarin 29 that demonstrated extremely narrow spectrum activity towards fastidious Gram-negative bacteria Moraxella catarrhalis. Selected hybrid showed the potency against Moraxella catarrhalis (MIC⩽0.25μg/mL) comparable to that of reference antibiotic azithromycin, which suggested that further investigations are necessary to optimize this potential hit compound as a new anti-Moraxella catarrhalis agent. PMID:26578325

  17. Boosting with Subtype C CN54rgp140 Protein Adjuvanted with Glucopyranosyl Lipid Adjuvant after Priming with HIV-DNA and HIV-MVA Is Safe and Enhances Immune Responses: A Phase I Trial

    PubMed Central

    Joseph, Sarah; Geldmacher, Christof; Munseri, Patricia J.; Aboud, Said; Missanga, Marco; Mann, Philipp; Wahren, Britta; Ferrari, Guido; Polonis, Victoria R.; Robb, Merlin L.; Weber, Jonathan; Tatoud, Roger; Maboko, Leonard; Hoelscher, Michael; Lyamuya, Eligius F.; Biberfeld, Gunnel; Sandström, Eric; Kroidl, Arne; Bakari, Muhammad; Nilsson, Charlotta; McCormack, Sheena

    2016-01-01

    Background A vaccine against HIV is widely considered the most effective and sustainable way of reducing new infections. We evaluated the safety and impact of boosting with subtype C CN54rgp140 envelope protein adjuvanted in glucopyranosyl lipid adjuvant (GLA-AF) in Tanzanian volunteers previously given three immunizations with HIV-DNA followed by two immunizations with recombinant modified vaccinia virus Ankara (HIV-MVA). Methods Forty volunteers (35 vaccinees and five placebo recipients) were given two CN54rgp140/GLA-AF immunizations 30–71 weeks after the last HIV-MVA vaccination. These immunizations were delivered intramuscularly four weeks apart. Results The vaccine was safe and well tolerated except for one episode of asymptomatic hypoglycaemia that was classified as severe adverse event. Two weeks after the second HIV-MVA vaccination 34 (97%) of the 35 previously vaccinated developed Env-specific binding antibodies, and 79% and 84% displayed IFN-γ ELISpot responses to Gag and Env, respectively. Binding antibodies to subtype C Env (included in HIV-DNA and protein boost), subtype B Env (included only in HIV-DNA) and CRF01_AE Env (included only in HIV-MVA) were significantly boosted by the CN54rgp140/GLA-AF immunizations. Functional antibodies detected using an infectious molecular clone virus/peripheral blood mononuclear cell neutralization assay, a pseudovirus/TZM-bl neutralization assay or by assays for antibody-dependent cellular cytotoxicity (ADCC) were not significantly boosted. In contrast, T-cell proliferative responses to subtype B MN antigen and IFN-γ ELISpot responses to Env peptides were significantly enhanced. Four volunteers not primed with HIV-DNA and HIV-MVA before the CN54rgp140/GLA-AF immunizations mounted an antibody response, while cell-mediated responses were rare. After the two Env subtype C protein immunizations, a trend towards higher median subtype C Env binding antibody titers was found in vaccinees who had received HIV-DNA and HIV

  18. Systems engineering of tyrosine 195, tyrosine 260, and glutamine 265 in cyclodextrin glycosyltransferase from Paenibacillus macerans to enhance maltodextrin specificity for 2-O-(D)-glucopyranosyl-(L)-ascorbic acid synthesis.

    PubMed

    Han, Ruizhi; Liu, Long; Shin, Hyun-Dong; Chen, Rachel R; Li, Jianghua; Du, Guocheng; Chen, Jian

    2013-01-01

    In this work, the site saturation mutagenesis of tyrosine 195, tyrosine 260 and glutamine 265 in the cyclodextrin glycosyltransferase (CGTase) from Paenibacillus macerans was conducted to improve the specificity of CGTase for maltodextrin, which can be used as a cheap and easily soluble glycosyl donor for the synthesis of 2-O-d-glucopyranosyl-l-ascorbic acid (AA-2G). Specifically, the site-saturation mutagenesis of three sites-tyrosine 195, tyrosine 260, and glutamine 265-was performed, and it was found that the resulting mutants (containing the mutations Y195S [tyrosine → serine], Y260R [tyrosine → arginine], and Q265K [glutamine → lysine]) produced higher AA-2G yields than the wild type and the other mutant CGTases when maltodextrin was used as the glycosyl donor. Furthermore, double and triple mutations were introduced, and four mutants (containing Y195S/Y260R, Y195S/Q265K, Y260R/Q265K, and Y260R/Q265K/Y195S) were obtained and evaluated for the capacity to produce AA-2G. The Y260R/Q265K/Y195S triple mutant produced the highest titer of AA-2G at 1.92 g/liter, which was 60% higher than that (1.20 g/liter) produced by the wild-type CGTase. The kinetics analysis of AA-2G synthesis by the mutant CGTases confirmed the enhanced maltodextrin specificity, and it was also found that compared with the wild-type CGTase, all seven mutants had lower cyclization activities and higher hydrolysis and disproportionation activities. Finally, the mechanism responsible for the enhanced substrate specificity was explored by structure modeling, which indicated that the enhancement of maltodextrin specificity may be related to the changes of hydrogen bonding interactions between the side chain of residue at the three positions (195, 260, and 265) and the substrate sugars. This work adds to our understanding of the synthesis of AA-2G and makes the Y260R/Q265K/Y195S mutant a good starting point for further development by protein engineering. PMID:23160123

  19. Like your labels?

    PubMed

    Field, Michele

    2010-01-01

    The descriptive “conventions” used on food labels are always evolving. Today, however, the changes are so complicated (partly driven by legislation requiring disclosures about environmental impacts, health issues, and geographical provenance) that these labels more often baffle buyers than enlighten them. In a light-handed manner, the article points to how sometimes reading label language can be like deciphering runes—and how if we are familiar with the technical terms, we can find a literal meaning, but still not see the implications. The article could be ten times longer because food labels vary according to cultures—but all food-exporting cultures now take advantage of our short attention-span when faced with these texts. The question is whether less is more—and if so, in this contest for our attention, what “contestant” is voted off. PMID:21539053

  20. IN VITRO METABOLISM OF THE CHIRAL TRIAZOLE FUNGICIDE BROMUCONAZOLE 47 USING SUBSTRATE DEPLETION AND PRODUCT FORMATION KINETICS IN RAT HEPATIC MICROSOMES

    EPA Science Inventory

    Kinetic analysis of xenobiotic metabolism using in vitro hepatic microsomes are needed for predictive in vivo physiological modeling. Recently, much emphasis has been placed on the adverse effects of triazole fungicides in mammalian steroid metabolism. In vitro metabolism of the ...

  1. Computational studies on the regioselectivity of metal-catalyzed synthesis of 1,2,3 triazoles via click reaction: a review.

    PubMed

    Hosseinnejad, Tayebeh; Fattahi, Bahareh; Heravi, Majid M

    2015-10-01

    Recently, the experimental and computational chemists have been attracted widely to the click synthesis of 1,2,3 triazoles and their derivatives, mainly due to the fact that they are interesting from structural and mechanistic points of view. Moreover, catalyzed click have been well established as a successful strategy showing high regioselectivity and high yield for the synthesis of 1,2,3-triazoles. In this review, we try to highlight the recently reported computational assessments on the origins and predection of regioselectivity in the catalyzed click synthesis of triazoles from the mechanistic and thermodynamical points of view. In this light, density functional theory (DFT) calculations on the free energy profiles of azide-alkyne cycloaddition reactions have been underscored. The stereoelectronic features for the role of copper, ruthenium, and iridium as catalyst on regioselectivity of click reactions have also be discussed. Graphical Abstract Computational origins for the regioselective behavior of 1,2,3 triazoles click synthesis. PMID:26385849

  2. Proton-ionizable crown compounds. 1. Synthesis, complexation properties, and structural studies of macrocyclic polyether-diester ligands containing a triazole subcyclic unit

    SciTech Connect

    Bradshaw, J.S.; Chamberlin, D.A.; Harrison, P.E.; Wilson, B.E.; Arena, G.; Dalley, N.K.; Lamb, J.D.; Izatt, R.M.; Morin, F.G.; Grant, D.M.

    1985-08-23

    A series of macrocyclic polyether-diester ligands containing a proton-ionizable triazole subcyclic unit has been prepared. The crystal structure of one ligand shows that it forms a hydrate with the water molecule located in the macrocyclic cavity. The water is coordinated by hydrogen bonding to two oxygen atoms of the macrocycle and to the NH group of the triazole moiety. These macrocycles also form complexes with amines. These amine complexes are kinetically more stable than complexes formed by the triazole ligands with the corresponding alkylammonium perchlorate salts. The crystal structure of one of these complexes shows that the triazole ring has donated a proton to the amine group. 41 references, 4 figures, 2 tables.

  3. Cu-catalyzed direct C-H bond functionalization: a regioselective protocol to 5-aryl thiazolo[3,2-b]-1,2,4-triazoles.

    PubMed

    Xie, Zengyang; Zhu, Xiaojun; Guan, Yangfan; Zhu, Dunru; Hu, Hongwen; Lin, Chen; Pan, Yi; Jiang, Juli; Wang, Leyong

    2013-02-28

    An efficient, regioselective C-5 arylation of thiazolo[3,2-b]-1,2,4-triazoles catalyzed by a simple copper catalyst was developed. This arylation proceeded smoothly and tolerated a variety of functional groups (44 examples). A wide range of functionalized thiazolo[3,2-b]-1,2,4-triazole derivatives were obtained in high yields (up to 99% yield). Possible catalytic cycles of the arylation were also discussed. PMID:23328869

  4. Automated Synthesis of a Library of Triazolated 1,2,5-Thiadiazepane 1,1-Dioxides via a Double aza-Michael Strategy

    PubMed Central

    Zang, Qin; Javed, Salim; Hill, David; Ullah, Farman; Bi, Danse; Porubsky, Patrick; Neuenswander, Benjamin; Lushington, Gerald H.; Santini, Conrad; Organ, Michael G.; Hanson, Paul R.

    2013-01-01

    The construction of a 96-member library of triazolated 1,2,5-thiadiazepane 1,1-dioxides was performed on a Chemspeed Accelerator (SLT-100) automated parallel synthesis platform, culminating in the successful preparation of 94 out of 96 possible products. The key step, a one-pot, sequential elimination, double-aza-Michael reaction, and [3+2] Huisgen cycloaddition pathway has been automated and utilized in the production of two sets of triazolated sultam products. PMID:22853708

  5. Selective, Tunable O2 Binding in Cobalt(II)–Triazolate/Pyrazolate Metal–Organic Frameworks

    PubMed Central

    2016-01-01

    The air-free reaction of CoCl2 with 1,3,5-tri(1H-1,2,3-triazol-5-yl)benzene (H3BTTri) in N,N-dimethylformamide (DMF) and methanol leads to the formation of Co-BTTri (Co3[(Co4Cl)3(BTTri)8]2·DMF), a sodalite-type metal–organic framework. Desolvation of this material generates coordinatively unsaturated low-spin cobalt(II) centers that exhibit a strong preference for binding O2 over N2, with isosteric heats of adsorption (Qst) of −34(1) and −12(1) kJ/mol, respectively. The low-spin (S = 1/2) electronic configuration of the metal centers in the desolvated framework is supported by structural, magnetic susceptibility, and computational studies. A single-crystal X-ray structure determination reveals that O2 binds end-on to each framework cobalt center in a 1:1 ratio with a Co–O2 bond distance of 1.973(6) Å. Replacement of one of the triazolate linkers with a more electron-donating pyrazolate group leads to the isostructural framework Co-BDTriP (Co3[(Co4Cl)3(BDTriP)8]2·DMF; H3BDTriP = 5,5′-(5-(1H-pyrazol-4-yl)-1,3-phenylene)bis(1H-1,2,3-triazole)), which demonstrates markedly higher yet still fully reversible O2 affinities (Qst = −47(1) kJ/mol at low loadings). Electronic structure calculations suggest that the O2 adducts in Co-BTTri are best described as cobalt(II)–dioxygen species with partial electron transfer, while the stronger binding sites in Co-BDTriP form cobalt(III)–superoxo moieties. The stability, selectivity, and high O2 adsorption capacity of these materials render them promising new adsorbents for air separation processes. PMID:27180991

  6. Hydrothermal Synthesis and Structural Characterization of Novel Zn-Triazole-Benzenedicarboxylate Frameworks

    SciTech Connect

    Park, Hyunsoo; Moureau, David M.; Parise, John B.

    2008-10-03

    Three new metal-organic coordination polymers were synthesized hydrothermally using Zn2+ ion, 1,2,4-triazole, and 1,4-benzenedicarboxylic acid (BDC): Zn5(H2O)2(C2H2N3)4(C8H4O4)3 {center_dot} 3.9H2O (1), Zn2(C2H2N3)2(C2H3N3)(C8H4O4) {center_dot} 2.5H2O (2), and Zn4(H2O)2(C2H2N3)4(C8H4O4)2 {center_dot} 14H2O (3). Their crystal structures were determined by single-crystal X-ray diffraction. Their thermal properties were examined by thermogravimetric analysis. Structure 1 crystallizes in the monoclinic P21/n space group with a = 10.192(2) {angstrom}, b = 17.764(4) {angstrom}, c = 24.437(5) {angstrom}, {beta} = 91.19(3){sup o}, and V = 4423.3(15) {angstrom}3. Structure 2 crystallizes in the triclinic P space group with a = 7.797(2) {angstrom}, b = 10.047(2) {angstrom}, c = 13.577(3) {angstrom}, {alpha} = 110.18(3){sup o}, {beta} = 105.46(3){sup o}, {gamma} = 93.90(3){sup o}, and V = 947.0(3) {angstrom}3. Structure 3 crystallizes in monoclinic P21/n space group with a = 13.475(3) {angstrom}, b = 26.949(5) {angstrom}, c = 13.509(3) {angstrom}, {beta} = 95.18(3){sup o}, and V = 4885.7(17) {angstrom}3. In structure 1, the units of the triazole-Zn polyhedra are linked by BDC in a zigzag fashion to create the stacking of phenyl groups along the a axis. In structure 2, both triazole and BDC bridge Zn polyhedra in the (011) plane, resulting in the eight-membered channels along the a axis. In the case of structure 3, the BDC links the Zn polyhedra along the b axis to form a pillared open framework. This structure is the most porous of the compounds presented in this work.

  7. High-temperature spin transition in coordination compounds of iron(II) with triazoles

    SciTech Connect

    Lavrenova, L.G.; Ikorskii, V.N.; Varnek, V.A.; Oglezneva, I.M.; Larionov, S.V.

    1986-12-01

    Methods for the synthesis of the complexes FeL/sub 3/(NO/sub 3/)/sub 2/, where L = 1,2,4-triazole (TR) (I) and 4-amino-1,2,4-triazole (ATR) (II), Fe(ATR)/sub 2.5/Cl/sub 2/ x H/sub 2/O (III), and Fe(TR)/sub 2/Cl/sub 2/ (IV) have been developed. A high-temperature (340-350/sup 0/K) reversible transition of Fe/sup II/ from the low-spin (LS) state to the high-spin (HS) state has been discovered during the study of the magnetic properties of complexes I-III. The plots of the dependence of ..mu../sub eff/ on T display hysteresis. Thus, the complexes of Fe/sup II/ with triazoles comprise a new group of compounds having this special feature. Complex III has different values of ..mu../sub eff/ at 300/sup 0/K, depending on the synthesis conditions. The plots of the dependence of ..mu../sub eff/ on T for complexes I and II and for III are different. Complex IV is basically a high-spin complex with a weakly expressed dependence of ..mu../sub eff/ on T. The Moessbauer spectra for complexes I and II and for a sample of III with ..mu../sub eff/ = 0.86 Bohr magneton at 300/sup 0/K display singlet lines with a value of delta typical of Fe/sup II/ in the LS state. In the spectra of samples of III with ..mu../sub eff/(T) = 2.05 Bohr magnetons at 300/sup 0/K there are peaks for the HS form along with the line of the LS form, the complex having two modifications in the HS form with different values of epsilon. The data form diffuse reflectance spectroscopy and the values of delta and ..mu../sub eff/ point out the octahedral coordination of Fe/sup II/, the presence of an FeN/sub 6/ chromophore in complexes I and II, and the presence of an FeN/sub 4/Cl/sub 2/ chromophore in III and IV. From an analysis of the IR spectra in the region of the torsional vibrations of the ring it follows that the ligands L are coordinated by the ring N(1) and N(2) atoms, indicating that the ligands L have bridging function.

  8. Selective, Tunable O2 Binding in Cobalt(II)-Triazolate/Pyrazolate Metal-Organic Frameworks.

    PubMed

    Xiao, Dianne J; Gonzalez, Miguel I; Darago, Lucy E; Vogiatzis, Konstantinos D; Haldoupis, Emmanuel; Gagliardi, Laura; Long, Jeffrey R

    2016-06-01

    The air-free reaction of CoCl2 with 1,3,5-tri(1H-1,2,3-triazol-5-yl)benzene (H3BTTri) in N,N-dimethylformamide (DMF) and methanol leads to the formation of Co-BTTri (Co3[(Co4Cl)3(BTTri)8]2·DMF), a sodalite-type metal-organic framework. Desolvation of this material generates coordinatively unsaturated low-spin cobalt(II) centers that exhibit a strong preference for binding O2 over N2, with isosteric heats of adsorption (Qst) of -34(1) and -12(1) kJ/mol, respectively. The low-spin (S = 1/2) electronic configuration of the metal centers in the desolvated framework is supported by structural, magnetic susceptibility, and computational studies. A single-crystal X-ray structure determination reveals that O2 binds end-on to each framework cobalt center in a 1:1 ratio with a Co-O2 bond distance of 1.973(6) Å. Replacement of one of the triazolate linkers with a more electron-donating pyrazolate group leads to the isostructural framework Co-BDTriP (Co3[(Co4Cl)3(BDTriP)8]2·DMF; H3BDTriP = 5,5'-(5-(1H-pyrazol-4-yl)-1,3-phenylene)bis(1H-1,2,3-triazole)), which demonstrates markedly higher yet still fully reversible O2 affinities (Qst = -47(1) kJ/mol at low loadings). Electronic structure calculations suggest that the O2 adducts in Co-BTTri are best described as cobalt(II)-dioxygen species with partial electron transfer, while the stronger binding sites in Co-BDTriP form cobalt(III)-superoxo moieties. The stability, selectivity, and high O2 adsorption capacity of these materials render them promising new adsorbents for air separation processes. PMID:27180991

  9. Synthesis of 1,2,4-Triazoles via Oxidative Heterocyclization: Selective C-N Bond Over C-S Bond Formation.

    PubMed

    Gogoi, Anupal; Guin, Srimanta; Rajamanickam, Suresh; Rout, Saroj Kumar; Patel, Bhisma K

    2015-09-18

    The higher propensity of C-N over C-S bond forming ability was demonstrated, through formal C-H functionalization during the construction of 4,5-disubstituted 1,2,4-triazole-3-thiones from arylidenearylthiosemicarbazides catalyzed by Cu(II). However, steric factors imparted by the o-disubstituted substrates tend to change the reaction path giving thiodiazole as the major or an exclusive product. Upon prolonging the reaction time, the in situ generated thiones are transformed to 4,5-disubstituted 1,2,4-triazoles via a desulfurization process. Two classes of heterocycles viz. 4,5-disubstituted 1,2,4-triazole-3-thiones and 4,5-disubstituted 1,2,4-triazoles can be synthesized from arylidenearylthiosemicarbazides by simply adjusting the reaction time. Desulfurization of 1,2,4-triazole-3-thiones is assisted by thiophilic Cu to provide 1,2,4-triazoles with concomitant formation of CuS and polynuclear sulfur anions as confirmed from scanning electron microscope and energy dispersive X-ray spectroscopy measurements. A one-pot synthesis of an antimicrobial compound has been successfully achieved following this strategy. PMID:26332253

  10. Off-Label Drug Use

    MedlinePlus

    ... Your Local Offices Close + - Text Size Off-label Drug Use What is off-label drug use? In the United States new drugs are ... unapproved use of a drug. Is off-label drug use legal? The off-label use of FDA- ...

  11. Design, synthesis and antifungal activities of novel 1,2,4-triazole derivatives.

    PubMed

    Xu, Jianming; Cao, Yongbing; Zhang, Jun; Yu, Shichong; Zou, Yan; Chai, Xiaoyun; Wu, Qiuye; Zhang, Dazhi; Jiang, Yuanying; Sun, Qingyan

    2011-07-01

    A series of novel 1,2,4-triazole derivatives with a 4-(4-substitutedphenyl) piperazine side chain were designed and synthesized based on the structure of lanosterol 14α-demethylase (CYP51). Their antifungal activities against eight human pathogenic fungi were evaluated in vitro by measuring the minimal inhibitory concentrations. Nearly all tested compounds were found to be more potent against Candida albicans than control drug fluconazole. Noticeably, the MIC(80) value of compounds 6,7,9,14 and 29 is 16 times lower than that of voriconazole against C. albicans. The activities of compounds 7 and 21 against Cryptococcus neoformans in vitro are comparable to that of voriconazole with a MIC(80) value of 0.0156 μg/mL. Moreover, the molecular model for the binding between compound 7 and the active site of CACYP51 was provided based on the computational docking results. PMID:21420761

  12. Design, synthesis and molecular docking studies of novel triazole as antifungal agent.

    PubMed

    Chai, Xiaoyun; Zhang, Jun; Cao, Yongbing; Zou, Yan; Wu, Qiuye; Zhang, Dazhi; Jiang, Yuanying; Sun, Qingyan

    2011-07-01

    In order to meet the urgent need for novel antifungal agents with improved activity and broader spectrum, a series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substituted trifluoromethyl phenyl)-piperazin-1-yl]-propan-2-ols were designed, synthesized and evaluated as antifungal agents. The MIC(80) values indicate that the compounds 7a-7q, 8a-8d showed higher antifungal activities against Candida albicans than 5a-5i, 6a-6j. Moreover, the molecular model for the binding between compound 5a, 7a and the active site of CACYP51 was provided based on the computational docking results, and the structure-activity relationship was analyzed. PMID:21531485

  13. Association between Virulence and Triazole Tolerance in the Phytopathogenic Fungus Mycosphaerella graminicola

    PubMed Central

    Yang, Lina; Gao, Fangluan; Shang, Liping; Zhan, Jiasui; McDonald, Bruce A.

    2013-01-01

    Host resistance and synthetic antimicrobials such as fungicides are two of the main approaches used to control plant diseases in conventional agriculture. Although pathogens often evolve to overcome host resistance and antimicrobials, the majority of reports have involved qualitative host – pathogen interactions or antimicrobials targeting a single pathogen protein or metabolic pathway. Studies that consider jointly the evolution of virulence, defined as the degree of damage caused to a host by parasite infection, and antimicrobial resistance are rare. Here we compared virulence and fungicide tolerance in the fungal pathogen Mycosphaerella graminicola sampled from wheat fields across three continents and found a positive correlation between virulence and tolerance to a triazole fungicide. We also found that quantitative host resistance selected for higher pathogen virulence. The possible mechanisms responsible for these observations and their consequences for sustainable disease management are discussed. PMID:23555044

  14. Excitonic Coupling and Femtosecond Relaxation of Zinc Porphyrin Oligomers Linked with Triazole Bridge: Dynamics and Modeling.

    PubMed

    Bukreev, Alexey; Mikhailov, Konstantin; Shelaev, Ivan; Gostev, Fedor; Polevaya, Yuliya; Tyurin, Vladimir; Beletskaya, Irina; Umansky, Stanislav; Nadtochenko, Victor

    2016-03-31

    The synthesis of new zinc porphyrin oligomers linked by a triazole bridge was carried out via "click" reaction. A split in the porphyrin oligomer B-band was observed. It was considered as evidence of exciton-excitonic coupling. The relaxation of excited states in Q-band porphyrin oligomers was studied by the femtosecond laser spectroscopy technique with a 20 fs pump pulse. The transient oscillations of two B-band excitonic peaks have a π-radian shift. For explanation of the coherent oscillation, a theoretical model was developed. The model considered the combination of the exciton-excitonic coupling between porphyrin rings in dimer and weak exciton-vibronic coupling in one porphyrin ring. By varying the values of the structural parameters of porphyrins (the strength values of this couplings and measure of symmetry breaking), we obtained correspondence between the experimental data (phase shift and amplitudes of the spectrum oscillations) and the predictions of the model developed here. PMID:26935579

  15. Organocatalytic triazole formation, followed by oxidative aromatization: regioselective metal-free synthesis of benzotriazoles.

    PubMed

    Ramachary, Dhevalapally B; Shashank, Adluri B

    2013-09-23

    Herein we report on our studies on the sequential one-pot combinations of amine-catalyzed multicomponent reactions (MCRs). We have developed the copper-free synthesis of functionalized bicyclic N-aryl-1,2,3-triazole and N-arylbenzotriazole products 4 and 5 from the simple unmodified starting materials through [3+2]-cycloaddition ([3+2]-CA) and oxidative aromatization reactions in one pot under amine catalysis. The sequential one-pot reaction proceeds in good yields with high selectivity by using pyrrolidine as the catalyst from the simple unmodified substrates of enones, aryl azides, and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Furthermore, we have demonstrated the medicinal applications of products 4 and 5 through simple organic reactions. PMID:24038664

  16. Synthesis, antimicrobial evaluation and spectroscopic characterization of novel imidazolone, triazole and triazinone derivatives

    NASA Astrophysics Data System (ADS)

    Abu-Melha, Sraa

    2012-10-01

    The reactions of 2-phenyl-4-arylmethylene-2-oxazolin-5-ones (1a, b) and 2-phenyl-4-arylazo-2-oxazolin-5-ones (8a, b) with p-aminoazobenzene derivatives (2a-c) gave the corresponding imidazolone derivatives (4a-f) and triazole derivatives (10a-f), respectively. Also, the reaction of 1a with o-aminophenol to give the imidazolone derivative 5 was studied. The reaction of 1a with 2,4-dinitrophenylhydrazine gave the corresponding 1,2,4-triazine derivatives 14a-c, respectively. The newly synthesized compounds were screened for their antibacterial activity against Gram-positive (Bacillus subtilis and Bacillus thuringiensis), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and in vitro antifungal potential against Fusarium oxysporum and Botrytis fabae fungal strains. The results revealed that the investigated compounds exhibited antibacterial and a significant antifungal activity.

  17. 1,2,3-Triazoles as inhibitors of indoleamine 2,3-dioxygenase 2 (IDO2).

    PubMed

    Röhrig, Ute F; Majjigapu, Somi Reddy; Caldelari, Daniela; Dilek, Nahzli; Reichenbach, Patrick; Ascencao, Kelly; Irving, Melita; Coukos, George; Vogel, Pierre; Zoete, Vincent; Michielin, Olivier

    2016-09-01

    Indoleamine 2,3-dioxygenase 2 (IDO2) is a potential therapeutic target for the treatment of diseases that involve immune escape such as cancer. In contrast to IDO1, only a very limited number of inhibitors have been described for IDO2 due to inherent difficulties in expressing and purifying a functionally active, soluble form of the enzyme. Starting from our previously discovered highly efficient 4-aryl-1,2,3-triazole IDO1 inhibitor scaffold, we used computational structure-based methods to design inhibitors of IDO2 which we then tested in cellular assays. Our approach yielded low molecular weight inhibitors of IDO2, the most active displaying an IC50 value of 51μM for mIDO2, and twofold selectivity over hIDO1. These compounds could be useful as molecular probes to investigate the biological role of IDO2, and could inspire the design of new IDO2 inhibitors. PMID:27469130

  18. EPR and polarography of nitroazoles. 6. 3-Nitro-1,2,4-triazoles

    SciTech Connect

    Vakul'skaya, T.I.; Rakhmatulina, T.N.; Pevzner, M.S.; Kofman, T.P.; Lopyrev, V.A.

    1987-09-01

    The electrochemical reduction of eight 3-nitro-1,2,4-triazole derivatives in acetonitrile was investigated by polarography and EPR spectroscopy. Two different signals were recorded in the EPR spectra in the electrochemical reduction of derivative I. The first signal shows up at the potentials of the second wave with a hyperfine structure corresponding to coupling of an unpaired electron with five nitrogen atoms and to a symmetrical distribution of the spin density as shown. Electrochemical generation of the ion radicals was realized in special electrochemical cells that had been previously deoxygenated by successive freezing and thawing of solutions in vacuo and were then filled with argon purified over potassium-sodium alloy.

  19. Synthesis and Biological Evaluation of 1,2,3-triazole tethered Pyrazoline and Chalcone Derivatives.

    PubMed

    Hussaini, Syed Mohammed Ali; Yedla, Poornachandra; Babu, Korrapati Suresh; Shaik, Thokhir B; Chityal, Ganesh Kumar; Kamal, Ahmed

    2016-07-01

    A series of pyrazoline derivatives and corresponding chalcone intermediates with substituents same as combretastatin-A4(CA-4) conjugated with triazole nucleus has been synthesized and evaluated for their anticancer potential. Sulphorhodamine B(SRB) assay indicated compound 12c to be the most active compound from the series with GI50 value of 6.7 μm against the human liver carcinoma cell line HepG2. Interestingly, the intermediate 11c exhibited more promising cytotoxicity demonstrating GI50 value of 1.3 μm against the prostate cancer cell line DU145. Compounds 11c and 12c caused accumulation of cells in G2/M phase and inhibited tubulin polymerization. Furthermore, these compounds reduce the mitochondrial membrane potential and activate caspases 3 and 9, thereby indicating their ability to trigger apoptosis. PMID:26854643

  20. Triazole-based Zn²⁺-specific molecular marker for fluorescence bioimaging.

    PubMed

    Sinha, Sougata; Mukherjee, Trinetra; Mathew, Jomon; Mukhopadhyay, Subhra K; Ghosh, Subrata

    2014-04-25

    Fluorescence bioimaging potential, both in vitro and in vivo, of a yellow emissive triazole-based molecular marker has been investigated and demonstrated. Three different kinds of cells, viz Bacillus thuringiensis, Candida albicans, and Techoma stans pollen grains were used to investigate the intracellular zinc imaging potential of 1 (in vitro studies). Fluorescence imaging of translocation of zinc through the stem of small herb, Peperomia pellucida, having transparent stem proved in vivo bioimaging capability of 1. This approach will enable in screening cell permeability and biostability of a newly developed probe. Similarly, the current method for detection and localization of zinc in Gram seed sprouts could be an easy and potential alternative of the existing analytical methods to investigate the efficiency of various strategies applied for increasing zinc-content in cereal crops. The probe-zinc ensemble has efficiently been applied for detecting phosphate-based biomolecules. PMID:24725748

  1. Investigation of biological effects of some Mannich Bases containing Bis-1,2,4- Triazole.

    PubMed

    Parlak, A E; Celik, S; Karatepe, M; Turkoglu, S; Alayunt, N O; Dastan, S D; Ulas, M; Sandal, S; Tekin, S; Koparir, M

    2016-01-01

    In this study, the effects of Mannich bases containing bis-1,2,4-triazole on the levels of in vivo malondialdehyde (MDA) and antioxidant vitamins (A, E, C) were examined in serum, livers and kidneys of rats. DA and vitamin (A, E, C) levels were determined by high performance liquid chromatography (HPLC). Antioxidant effect was investigated by determining the MDA levels in Saccharomyces cerevisiae cells as in vitro. Furthermore, the antitumor effects of compounds were investigated against MCF-7 human breast cancer cells. Interrelations of results among control and compound groups were evaluated using SPSS statistical software package. As a result, some of the compounds showed effective biological activity when compared to control conditions. The test compounds used in this study may be effective for utilization in the selection and design of model compounds for further studies. PMID:27453272

  2. Modelling physico-chemical properties of (benzo)triazoles, and screening for environmental partitioning.

    PubMed

    Bhhatarai, B; Gramatica, P

    2011-01-01

    (Benzo)triazoles are distributed throughout the environment, mainly in water compartments, because of their wide use in industry where they are employed in pharmaceutical, agricultural and deicing products. They are hazardous chemicals that adversely affect humans and other non-target species, and are on the list of substances of very high concern (SVHC) in the new European regulation of chemicals - REACH (Registration, Evaluation, Authorization and Restriction of Chemical substances). Thus there is a vital need for further investigations to understand the behavior of these compounds in biota and the environment. In such a scenario, physico-chemical properties like aqueous solubility, hydrophobicity, vapor pressure and melting point can be useful. However, the limited availability and the high cost of lab testing prevents the acquisition of necessary experimental data that industry must submit for the registration of these chemicals. In such cases a preliminary analysis can be made using Quantitative Structure-Property Relationships (QSPR) models. For such an analysis, we propose Multiple Linear Regression (MLR) models based on theoretical molecular descriptors selected by Genetic Algorithm (GA). Training and prediction sets were prepared a priori by splitting the available experimental data, which were then used to derive statistically robust and predictive (both internally and externally) models. These models, after verification of their structural applicability domain (AD), were used to predict the properties of a total of 351 compounds, including those in the REACH preregistration list. Finally, Principal Component Analysis was applied to the predictions to rank the environmental partitioning properties (relevant for leaching and volatility) of new and untested (benzo)triazoles within the AD of each model. Our study using this approach highlighted compounds dangerous for the aquatic compartment. Similar analyses using predictions obtained by the EPI Suite and

  3. High CO2-capture ability of a porous organic polymer bifunctionalized with carboxy and triazole groups.

    PubMed

    Xie, Lin-Hua; Suh, Myunghyun Paik

    2013-08-26

    A new porous organic polymer, SNU-C1, incorporating two different CO2 -attracting groups, namely, carboxy and triazole groups, has been synthesized. By activating SNU-C1 with two different methods, vacuum drying and supercritical-CO2 treatment, the guest-free phases, SNU-C1-va and SNU-C1-sca, respectively, were obtained. Brunauer-Emmett-Teller (BET) surface areas of SNU-C1-va and SNU-C1-sca are 595 and 830 m(2) g(-1), respectively, as estimated by the N2-adsorption isotherms at 77 K. At 298 K and 1 atm, SNU-C1-va and SNU-C1-sca show high CO2 uptakes, 2.31 mmol  g(-1) and 3.14 mmol  g(-1), respectively, the high level being due to the presence of abundant polar groups (carboxy and triazole) exposed on the pore surfaces. Five separation parameters for flue gas and landfill gas in vacuum-swing adsorption were calculated from single-component gas-sorption isotherms by using the ideal adsorbed solution theory (IAST). The data reveal excellent CO2-separation abilities of SNU-C1-va and SNU-C1-sca, namely high CO2-uptake capacity, high selectivity, and high regenerability. The gas-cycling experiments for the materials and the water-treated samples, experiments that involved treating the samples with a CO2-N2 gas mixture (15:85, v/v) followed by a pure N2 purge, further verified the high regenerability and water stability. The results suggest that these materials have great potential applications in CO2 separation. PMID:23881821

  4. Thermodynamic studies of thermochromic phase transition in coordination compound of iron with triazole

    NASA Astrophysics Data System (ADS)

    Bessergenev, V. G.; Berezovski, G. A.; Lavrenova, L. G.; Larionov, Stanislav V.

    1995-08-01

    The aim of this work was to investigate the thermodynamic properties of nitrate tris(4-amino- 1,2,4-triazole) iron(II) for which a thermochromic effect takes place at T equals 342 K on heating and at 310 K on cooling. For the measurement of the isobaric heat capacity in the 5 - 355 K range, a vacuum adiabatic calorimeter was used. Below 300 K, the Cp,m(T) curve has no anomalies; the average deviation of the experimental heat-capacity values from the smoothed Cp,m(T) curve was 0.1 percent. Above 300 K, the Cp,m(T) curve shows a complicated behavior. The abnormal part of the heat capacity first increases smoothly, then from 330 K a sharp rise begins. There is a peak on the Cp,m-curve at T equals 343.0 K. This fact is in a good agreement with the magnetic measurement data. The transition enthalpy was determined to be 22.8 kJ(DOT)mol-1 (M equals 432.10 g(DOT)mol-1). Further increase of the heat capacity suggests the existence of a new phase transition above 350 K. This suggestion was confirmed qualitatively by the measurements on a differential scanning calorimeter. It should be noted that on the low- temperature slope of the anomaly, at 320 < T < 330 K, there is a small anomaly with the maximum deviation of 5 - 10% from the regular part. To compare the phonon characteristics, the heat capacity of nitrate tris(4-amino-1,2,4-triazole) copper(II) was studied.

  5. Dsc orthologs are required for hypoxia adaptation, triazole drug responses, and fungal virulence in Aspergillus fumigatus.

    PubMed

    Willger, Sven D; Cornish, E Jean; Chung, Dawoon; Fleming, Brittany A; Lehmann, Margaret M; Puttikamonkul, Srisombat; Cramer, Robert A

    2012-12-01

    Hypoxia is an environmental stress encountered by Aspergillus fumigatus during invasive pulmonary aspergillosis (IPA). The ability of this mold to adapt to hypoxia is important for fungal virulence and genetically regulated in part by the sterol regulatory element binding protein (SREBP) SrbA. SrbA is required for fungal growth in the murine lung and to ultimately cause lethal disease in murine models of IPA. Here we identified and partially characterized four genes (dscA, dscB, dscC, and dscD, here referred to as dscA-D) with previously unknown functions in A. fumigatus that are orthologs of the Schizosaccharomyces pombe genes dsc1, dsc2, dsc3, and dsc4 (dsc1-4), which encode a Golgi E3 ligase complex critical for SREBP activation by proteolytic cleavage. A. fumigatus null dscA-D mutants displayed remarkable defects in hypoxic growth and increased susceptibility to triazole antifungal drugs. Consistent with the confirmed role of these genes in S. pombe, both ΔdscA and ΔdscC resulted in reduced cleavage of the SrbA precursor protein in A. fumigatus. Inoculation of corticosteroid immunosuppressed mice with ΔdscA and ΔdscC strains revealed that these genes are critical for A. fumigatus virulence. Reintroduction of SrbA amino acids 1 to 425, encompassing the N terminus DNA binding domain, into the ΔdscA strain was able to partially restore virulence, further supporting a mechanistic link between DscA and SrbA function. Thus, we have shown for the first time the importance of a previously uncharacterized group of genes in A. fumigatus that mediate hypoxia adaptation, fungal virulence, and triazole drug susceptibility and that are likely linked to regulation of SrbA function. PMID:23104569

  6. Atomistic simulation of solid-liquid coexistence for molecular systems: Application to triazole and benzene

    NASA Astrophysics Data System (ADS)

    Eike, David M.; Maginn, Edward J.

    2006-04-01

    A method recently developed to rigorously determine solid-liquid equilibrium using a free-energy-based analysis has been extended to analyze multiatom molecular systems. This method is based on using a pseudosupercritical transformation path to reversibly transform between solid and liquid phases. Integration along this path yields the free energy difference at a single state point, which can then be used to determine the free energy difference as a function of temperature and therefore locate the coexistence temperature at a fixed pressure. The primary extension reported here is the introduction of an external potential field capable of inducing center of mass order along with secondary orientational order for molecules. The method is used to calculate the melting point of 1-H-1,2,4-triazole and benzene. Despite the fact that the triazole model gives accurate bulk densities for the liquid and crystal phases, it is found to do a poor job of reproducing the experimental crystal structure and heat of fusion. Consequently, it yields a melting point that is 100K lower than the experimental value. On the other hand, the benzene model has been parametrized extensively to match a wide range of properties and yields a melting point that is only 20K lower than the experimental value. Previous work in which a simple "direct heating" method was used actually found that the melting point of the benzene model was 50K higher than the experimental value. This demonstrates the importance of using proper free energy methods to compute phase behavior. It also shows that the melting point is a very sensitive measure of force field quality that should be considered in parametrization efforts. The method described here provides a relatively simple approach for computing melting points of molecular systems.

  7. Selectivity optimization of substituted 1,2,3-triazoles as α7 nicotinic acetylcholine receptor agonists.

    PubMed

    Arunrungvichian, Kuntarat; Fokin, Valery V; Vajragupta, Opa; Taylor, Palmer

    2015-08-19

    Three series of substituted anti-1,2,3-triazoles (IND, PPRD, and QND), synthesized by cycloaddition from azide and alkyne building blocks, were designed to enhance selectivity and potency profiles of a lead α7 nicotinic acetylcholine receptor (α7-nAChR) agonist, TTIn-1. Designed compounds were synthesized and screened for affinity by a radioligand binding assay. Their functional characterization as agonists and antagonists was performed by fluorescence resonance energy transfer assay using cell lines expressing transfected cDNAs, α7-nAChRs, α4β2-nAChRs, and 5HT3A receptors, and a fluorescence cell reporter. In the IND series, a tropane ring of TTIn-1, substituted at N1, was replaced by mono- and bicyclic amines to vary length and conformational flexibility of a carbon linker between nitrogen atom and N1 of the triazole. Compounds with a two-carbon atom linker optimized binding with Kd's at the submicromolar level. Further modification at the hydrophobic indole of TTIn-1 was made in PPRD and QND series by fixing the amine center with the highest affinity building blocks in the IND series. Compounds from IND and PPRD series are selective as agonists for the α7-nAChRs over α4β2-nAChRs and 5HT3A receptors. Lead compounds in the three series have EC50's between 28 and 260 nM. Based on the EC50, affinity, and selectivity determined from the binding and cellular responses, two of the leads have been advanced to behavioral studies described in the companion article (DOI: 10.1021/acschemneuro.5b00059). PMID:25932897

  8. Multiple Species of Trichosporon Produce Biofilms Highly Resistant to Triazoles and Amphotericin B

    PubMed Central

    Iturrieta-González, Isabel Antonieta; Padovan, Ana Carolina Barbosa; Bizerra, Fernando César; Hahn, Rosane Christine; Colombo, Arnaldo Lopes

    2014-01-01

    Invasive infections caused by Trichosporon spp. have increased considerably in recent years, especially in neutropenic and critically ill patients using catheters and antibiotics. The genus presents limited sensitivity to different antifungal agents, but triazoles are the first choice for treatment. Here, we investigated the biofilm production and antifungal susceptibility to triazoles and amphotericin B of 54 Trichosporon spp. isolates obtained from blood samples (19), urine (20) and superficial mycosis (15). All isolates and 7 reference strains were identified by sequence analysis and phylogenetic inferences of the IGS1 region of the rDNA. Biofilms were grown on 96-well plates and quantitation was performed using crystal violet staining, complemented with Scanning Electron Microscopy (SEM). Susceptibility tests for fluconazole, itraconazole, voriconazole and amphotericin B were processed using the microdilution broth method (CLSI) for planktonic cells and XTT reduction assay for biofilm-forming cells. Our results showed that T. asahii was the most frequent species identified (66.7%), followed by T. faecale (11.1%), T. asteroides (9.3%), T. inkin (7.4%), T. dermatis (3.7%) and one T. coremiiforme (1.8%). We identified 4 genotypes within T. asahii isolates (G1, G3, G4 and G5) and 2 genotypes within T. faecale (G1 and G3). All species exhibited high adhesion and biofilm formation capabilities, mainly T. inkin, T. asteroides and T. faecale. Microscopy images of high biofilm-producing isolates showed that T. asahii presented mainly hyphae and arthroconidia, whereas T. asteroides exhibited mainly short arthroconidia and few filaments. Voriconazole exhibited the best in vitro activity against all species tested. Biofilm-forming cells of isolates and reference strains were highly resistant to all antifungals tested. We concluded that levels of biofilm formation by Trichosporon spp. were similar or even greater than those described for the Candida genus. Biofilm

  9. Thermodynamic studies of the thermochromic phase transition in coordination compound of iron with triazole

    SciTech Connect

    Bessergenev, V.G.; Berezovski, G.A.; Lavrenova, L.G.; Larionov, S.V.

    1995-12-31

    The aim of this work was to investigate the thermodynamic properties of nitrate tris(4-amino-1,2,4-triazole) iron(II) for which a thermochromic effect takes place at T=342 K on heating and at 310 K on cooling. For the measurement of the isobaric heat capacity in the 5--355 K range, a vacuum adiabatic calorimeter was used. Below 300 K, the C{sub p,m}(T) curve has no anomalies; the average deviation of the experimental heat-capacity values from the smoothed C{sub p,m}(T) curve was 0.1 percent. Above 300 K, the C{sub p,m}(T) curve shows a complicated behavior. The abnormal part of the heat capacity first increases smoothly, then from 330 K a sharp rise begins. There is a peak on the C{sub p,m}-curve at T=343.0 K. This fact is in a good agreement with the magnetic measurement data. The transition enthalpy was determined to be 22.8 kJ{center_dot}mol{sup {minus}1} (M=432.10 g{center_dot}-mol{sup {minus}1}). Further increase of the heat capacity suggests the existence of a new phase transition above 350 K. This suggestion was confirmed qualitatively by the measurements on a differential scanning calorimeter. It should be noted that on the low-temperature slope of the anomaly, at 320triazole) copper(II) was studied.

  10. Synthesis, characterization and photophysical studies of a novel schiff base bearing 1, 2, 4-Triazole scaffold

    NASA Astrophysics Data System (ADS)

    Alphonse, Roshmy; Varghese, Anitha; George, Louis

    2016-06-01

    A novel Schiff base derivative containing 1, 2, 4-triazole nucleus (TMPIMP) was synthesized from 4- [1,2,4] triazol-1-ylmethyl-phenylamine and salicylaldehyde in the presence of glacial acetic acid in an ethanolic medium. The synthesized compound was characterized by 1H-NMR, IR and UV spectral analysis. The excitation and emission spectra of triazolyl methyl phenyl imino methyl phenol (abbreviated as TMPIMP) were recorded in various solvents to investigate their solvatochromic behaviour. Dipole moments of the two electronic states of TMPIMP were calculated from solvatochromic spectral shifts. These were correlated with refractive index (η) and dielectric constant (ε) of various solvents. Theoretical calculations were performed to estimate the excited state dipole moment on the basis of different solvent correlation methods, like the Bilot-Kawski, Bakhshiev, Lippert-Mataga, Kawski-Chamma-Viallet and Reichardt methods. The dipole moment in the excited state was found to be higher than that in the ground state due to a substantial redistribution of electron densities and charges. Using a multiple regression analysis, the solvent-solute interactions were determined by means of Kamlet Taft parameters (α, β, π*). Computational studies were performed by Gaussian 09 W software using a time-dependent density functional theory (TD-DFT) in order to calculate the atomic charges and frontier molecular orbital energies in the solvent phase. The calculations indicated that the dipole moment of the molecule in an excited state is much higher than that in a ground state. The chemical stability of TMPIMP was determined by means of chemical hardness (η) using HOMO-LUMO energies. The reactive centers in the molecule were also identified by molecular electrostatic potential (MESP) 3D plots as a result of TD-DFT computational analysis.

  11. Triazole-containing monophosphate mRNA cap analogs as effective translation inhibitors

    PubMed Central

    Piecyk, Karolina; Lukaszewicz, Maciej; Darzynkiewicz, Edward

    2014-01-01

    Synthetic analogs of the 5′ end of mRNA (cap structure) are widely used in molecular studies on mechanisms of cellular processes such as translation, intracellular transport, splicing, and turnover. The best-characterized cap binding protein is translation initiation factor 4E (eIF4E). Recognition of the mRNA cap by eIF4E is a critical, rate-limiting step for efficient translation initiation and is considered a major target for anticancer therapy. Here, we report a facile methodology for the preparation of N2-triazole-containing monophosphate cap analogs and present their biological evaluation as inhibitors of protein synthesis. Five analogs possessing this unique hetero-cyclic ring spaced from the m7-guanine of the cap structure at a distance of one or three carbon atoms and/or additionally substituted by various groups containing the benzene ring were synthesized. All obtained compounds turned out to be effective translation inhibitors with IC50 similar to dinucleotide triphosphate m7GpppG. As these compounds possess a reduced number of phosphate groups and, thereby, a negative charge, which may support their cell penetration, this type of cap analog might be promising in terms of designing new potential therapeutic molecules. In addition, an exemplary dinucleotide from a corresponding mononucleotide containing benzyl substituted 1,2,3-triazole was prepared and examined. The superior inhibitory properties of this analog (10-fold vs. m7GpppG) suggest the usefulness of such compounds for the preparation of mRNA transcripts with high translational activity. PMID:25150228

  12. Spectral Label Fusion

    PubMed Central

    Wachinger, Christian; Golland, Polina

    2012-01-01

    We present a new segmentation approach that combines the strengths of label fusion and spectral clustering. The result is an atlas-based segmentation method guided by contour and texture cues in the test image. This offers advantages for datasets with high variability, making the segmentation less prone to registration errors. We achieve the integration by letting the weights of the graph Laplacian depend on image data, as well as atlas-based label priors. The extracted contours are converted to regions, arranged in a hierarchy depending on the strength of the separating boundary. Finally, we construct the segmentation by a region-wise, instead of voxel-wise, voting, increasing the robustness. Our experiments on cardiac MRI show a clear improvement over majority voting and intensity-weighted label fusion. PMID:23286157

  13. Spin labeling EPR.

    PubMed

    Klare, Johann P; Steinhoff, Heinz-Jürgen

    2009-01-01

    Site-directed spin labeling in combination with electron paramagnetic resonance spectroscopy has emerged as an efficient tool to elucidate the structure and conformational dynamics of biomolecules under native-like conditions. This article summarizes the basics as well as recent progress of site-directed spin labeling. Continuous wave EPR spectra analyses and pulse EPR techniques are reviewed with special emphasis on applications to the sensory rhodopsin-transducer complex mediating the photophobic response of the halophilic archaeum Natronomonas pharaonis and the photosynthetic reaction center from Rhodobacter sphaeroides R26. PMID:19728138

  14. Selective adsorption in two porous triazolate-oxalate-bridged antiferromagnetic metal-azolate frameworks obtained via in situ decarboxylation of 3-amino-1,2,4-triazole-5-carboxylic acid

    NASA Astrophysics Data System (ADS)

    Hou, Juan-Juan; Xu, Xia; Jiang, Ning; Wu, Ya-Qin; Zhang, Xian-Ming

    2015-03-01

    Solvothermal reactions of metal salts, 3-amino-1,2,4-triazole-5-carboxylic acid (H2atzc) and ammonium oxalate in different temperature produced two metal azolate frameworks, namely, [Cu3(atzc)2(atz)(ox)]·1.5H2O (1) and [Co5(atz)4(ox)3(HCOO)2]·DMF (2) (H2atzc=3-amino-1,2,4-triazole-5-carboxylic acid, Hatz=3-amino-1,2,4-triazole, and ox=oxalate), in which the atzc precusor was in situ decarboxylated. Structural determination reveals that 1 contains [Cu3(atzc)2(atz)]2- layers of mixed μ4-atzc and μ3-atz ligands, which are pillared by ox2- groups to form a 3D porous framework. Compound 2 contains 2D layers with basic spindle-shaped decanuclear units, which extended by ox2- and formates to form 3D porous framework. Gas adsorption investigation revealed that two kinds of frameworks exhibited selective CO2 over N2 sorption. Moreover, activated 2 shows H2 storage capacity. Additionally, magnetic properties of both the compounds have been investigated.

  15. A triazole Schiff base-based selective and sensitive fluorescent probe for Zn2 +: A combined experimental and theoretical study

    NASA Astrophysics Data System (ADS)

    Yuan, Caixia; Liu, Xinyu; Wu, Yanbo; Lu, Liping; Zhu, Miaoli

    2016-02-01

    A triazole-Schiff base, 4-(5-Chloro-2-hydroxybenzylideneamino)-1H-1,2,4-triazole-5(4H)-thione (HL), exhibits the high selectivity and sensitivity for Zn2 + in the fluorescence spectrometry over other common metal ions, especially Cd2 + in DMSO:H2O (1:9, v/v) solution. A 1:1 binding ratio of Zn2 +/L for the complex has been obtained by Uv-Vis titration experiments and Job's plot with the detection limit of 51 nmol/L. The coordination mode of the complex in solution was further confirmed by density functional theory (DFT) calculations. Time-dependent density functional theory (TD-DFT) calculations indicate that a chelation-enhanced fluorescence (CHEF) effect occurs in the process of detecting Zn ion.

  16. Metal-Free Route for the Synthesis of 4-Acyl-1,2,3-Triazoles from Readily Available Building Blocks.

    PubMed

    Thomas, Joice; Goyvaerts, Vince; Liekens, Sandra; Dehaen, Wim

    2016-07-11

    Functionalized 1,2,3-triazole heterocycles have been known for a long time and hold an extraordinary potential in diverse research areas ranging from medicinal chemistry to material science. However, the scope of therapeutically important 1-substituted 4-acyl-1H-1,2,3-triazoles is much less explored, probably due to the lack of synthetic methodologies of good scope and practicality. Here, we describe a practical and efficient one-pot multicomponent reaction for the synthesis of α-ketotriazoles from readily available building blocks such as methyl ketones, N,N-dimethylformamide dimethyl acetal, and organic azides with 100 % regioselectivity. This reaction is enabled by the in situ formation of an enaminone intermediate followed by its 1,3-dipolar cycloaddition reaction with an organic azide. We effectively utilized the developed strategy for the derivatization of various heterocycles and natural products, a protocol which is difficult or impossible to realize by other means. PMID:27172985

  17. Synthesis of water soluble chitosan derivatives with halogeno-1,2,3-triazole and their antifungal activity.

    PubMed

    Li, Qing; Tan, Wenqiang; Zhang, Caili; Gu, Guodong; Guo, Zhanyong

    2016-10-01

    Chitosan is an abundant and renewable polysaccharide, which exhibits attractive bioactivities and natural properties. Improvement such as chemical modification of chitosan is often performed prior to further utilization. Three novel water soluble chitosan derivatives containing 1,2,3- triazole with or without halogen was designed and synthesized. Their antifungal activity against three kinds of phytopathogens was estimated by hyphal measurement in vitro. The inhibitory property and water solubility of the synthesized chitosan derivatives exhibited a remarkable improvement over chitosan. It is hypothesized that thiazolyl groups enable the synthesized chitosan to possess obviously better antifungal activity. Moreover, CTCTS and BTCTS, which have halogens at the periphery of polymers, inhibited the growth of tested phytopathogens more effectively with inhibitory indices of 81-93% at 1.0mg/mL. The halogens could have a synergistic effect with triazole as they exhibited antifungal activity and electron-withdrawing capacity, which improve the antifungal activity of chitosan derivatives. PMID:27267573

  18. Design, Synthesis and Biological Evaluation of Sulfamide and Triazole Benzodiazepines as Novel p53-MDM2 Inhibitors

    PubMed Central

    Yu, Zhiliang; Zhuang, Chunlin; Wu, Yuelin; Guo, Zizhao; Li, Jin; Dong, Guoqiang; Yao, Jianzhong; Sheng, Chunquan; Miao, Zhenyuan; Zhang, Wannian

    2014-01-01

    A series of sulfamide and triazole benzodiazepines were obtained with the principle of bioisosterism. The p53-murine double minute 2 (MDM2) inhibitory activity and in vitro antitumor activity were evaluated. Most of the novel benzodiazepines exhibited moderate protein binding inhibitory activity. Particularly, triazole benzodiazepines showed good inhibitory activity and antitumor potency. Compound 16 had promising antitumor activity against the U-2 OS human osteosarcoma cell line with an IC50 value of 4.17 μM, which was much better than that of nutlin-3. The molecular docking model also successfully predicted that this class of compounds mimicked the three critical residues of p53 binding to MDM2. PMID:25198897

  19. Molecular properties prediction, docking studies, and antimicrobial screening of 1,3,4-thiadiazole and s-triazole derivatives.

    PubMed

    Siwek, Agata; Plech, Tomasz; Stefańska, Joanna; Stączek, Pawel; Strzelczyk, Aleksandra

    2014-03-01

    A series of 1,3,4-thiadiazoles and s-triazoles were subjected to Molinspiration, ALOGPS 2.1, and Osiris programs to predict their molecular properties that are important for drug candidates. Subsequently, all of them were docked into the active sites of enzymes namely glucosamine-6-phosphate synthase (GlcN-6-P), VIM-2 metallo-β- lactamase (VIM-2), chitinase A1 (ChiA1), and sterol 14 alpha-demethylase (CYP51) that were considered in antimicrobial studies of thiadiazole and s-triazole derivatives. Since all compounds fulfilled the criteria for good membrane permeability, oral bioavailability, low toxicity and the potential inhibitory activities towards VIM-2, ChiA1, and CYP51, most of them were synthesized and their antimicrobial activity has been tested. PMID:24138398

  20. [Cumulative risk assessment for consumers of agricultural crops polluted with one chemical class pesticide residues (case of triazole fungicides)].

    PubMed

    Koval'chuk, N M; Omel'chuk, S T

    2011-01-01

    Different indices of cumulative risk assessment of combination of residues of pesticides which may simultaneously be present in raw agricultural crops, based on toxic evaluation of such combination have been presented. Risk for population health due to consumption of raw agricultural crops with triazole residues is acceptable on hazard index, point of departure index and cumulative risk index, exceeds allowable level on criterion "total margin of exposure". PMID:22768736

  1. 2,6-Diphenylthiazolo[3,2-b][1,2,4]triazoles as telomeric G-quadruplex stabilizers.

    PubMed

    El Bakali, Jamal; Klupsch, Frédérique; Guédin, Aurore; Brassart, Bertrand; Fontaine, Gaëlle; Farce, Amaury; Roussel, Pascal; Houssin, Raymond; Bernier, Jean-Luc; Chavatte, Philippe; Mergny, Jean-Louis; Riou, Jean-François; Hénichart, Jean-Pierre

    2009-07-01

    The design and synthesis of 2,6-diphenylthiazolo[3,2-b][1,2,4]triazoles characterized by a large aromatic building block bearing cationic side chains are reported. These molecules are evaluated as telomeric G-quadruplex stabilizers and for their selectivity towards duplex DNA by competition experiments. Two compounds (14a, 19) were found active with high selectivity for telomeric G-quadruplex over duplex DNA. PMID:19473838

  2. Synthesis and biological activities of some new 4,5-dihydro-1H-1,2,4-triazol-5-ones.

    PubMed

    Demirbas, A; Johansson, C B; Duman, N; Ikizler, A A

    1996-01-01

    The reactions of 3-alkyl(aryl)-4-phenylamino-4,5-dihydro-1H-1,2,4-triazol-5-ones with appropriate alkyl halides via sodio derivatives were studied and the corresponding 1-alkyl-3-alkyl(aryl)-4-phenylamino-4,5-dihydro-1H-1,2,4-traizol-5 -ones were synthesized. Next, the new compounds were tested for their in vitro antimicrobial activities. PMID:8960286

  3. Copper(I)-catalyzed cycloaddition of bismuth(III) acetylides with organic azides: synthesis of stable triazole anion equivalents.

    PubMed

    Worrell, Brady T; Ellery, Shelby P; Fokin, Valery V

    2013-12-01

    Fully loaded: Readily accessible and shelf-stable 1-bismuth(III) acetylides react rapidly and regiospecifically with organic azides in the presence of a copper(I) catalyst. The reaction tolerates many functional groups and gives excellent yields of the previously unreported 5-bismuth triazolides. This uniquely reactive intermediate is functionalized under mild reaction conditions to give fully substituted 1,2,3-triazoles. PMID:24130150

  4. Labeling the Children.

    ERIC Educational Resources Information Center

    Krasner, William

    The report describes research on the effects of labeling children from minority groups as retarded and includes a review of a system of multiculturalistic pluralistic assessment (SOMPA), an instrument for evaluating the abilities and potentialities of children based on different aspects of performance. Listed among findings of the Riverside study,…

  5. A Deceiving Label?

    ERIC Educational Resources Information Center

    Lum, Lydia

    2009-01-01

    The author reports on the growing debate among educators on whether the umbrella Asian Pacific Islander label conceals disparities among Asian American students or provides political power in numbers. Nationally, experts say that support services aimed at not only Southeast Asians, but all Asian Pacific Islander students, remain scarce in higher…

  6. Synthesis, antiproliferative and antifungal activities of 1,2,3-triazole-substituted carnosic Acid and carnosol derivatives.

    PubMed

    Pertino, Mariano Walter; Theoduloz, Cristina; Butassi, Estefania; Zacchino, Susana; Schmeda-Hirschmann, Guillermo

    2015-01-01

    Abietane diterpenes exhibit an array of interesting biological activities, which have generated significant interest among the pharmacological community. Starting from the abietane diterpenes carnosic acid and carnosol, twenty four new triazole derivatives were synthesized using click chemistry. The compounds differ in the length of the linker and the substituent on the triazole moiety. The compounds were assessed as antiproliferative and antifungal agents. The antiproliferative activity was determined on normal lung fibroblasts (MRC-5), gastric epithelial adenocarcinoma (AGS), lung cancer (SK-MES-1) and bladder carcinoma (J82) cells while the antifungal activity was assessed against Candida albicans ATCC 10231 and Cryptococcus neoformans ATCC 32264. The carnosic acid γ-lactone derivatives 1-3 were the most active antiproliferative compounds of the series, with IC50 values in the range of 43.4-46.9 μM and 39.2-48.9 μM for MRC-5 and AGS cells, respectively. Regarding antifungal activity, C. neoformans was the most sensitive fungus, with nine compounds inhibiting more than 50% of its fungal growth at concentrations ≤250 µg∙mL-1. Compound 22, possessing a p-Br-benzyl substituent on the triazole ring, showed the best activity (91% growth inhibition) at 250 µg∙mL-1 In turn, six compounds inhibited 50% C. albicans growth at concentrations lower than 250 µg∙mL-1. PMID:26007173

  7. Three 3D hybrid networks based on octamolybdates and different Cu I/Cu II-bis(triazole) motifs

    NASA Astrophysics Data System (ADS)

    Zhang, Chun-Jing; Pang, Hai-Jun; Tang, Qun; Wang, Hui-Yuan; Chen, Ya-Guang

    2010-12-01

    Three 3D compounds based on octamolybdate clusters and various Cu I/Cu II-bis(triazole) motifs, [Cu I2btb][ β-Mo 8O 26] 0.5 ( 1), [Cu I2btpe][ β-Mo 8O 26] 0.5 ( 2), and [Cu II(btpe) 2][ β-Mo 8O 26] 0.5 ( 3) [btb=1,4-bis(1,2,4-triazol-1-yl)butane, btpe=1,5-bis(1,2,4-triazol-1-yl)pentane], were isolated via tuning flexible ligand spacer length and metal coordination preferences. In 1, the copper(I)-btb motif is a one-dimensional (1D) chain which is further linked by hexadentate β-[Mo 8O 26] 4- clusters via coordinating to Cu I cations giving a 3D structure. In 2, the copper(I)-btpe motif exhibits a "stairs"-like [Cu I2btpe] 2+ sheet, and the tetradentate β-[Mo 8O 26] 4- clusters interact with two neighboring [Cu I2btpe] 2+ sheets constructing a 3D framework. In 3, the copper(II)-btpe motif possesses a novel (2D→3D) interdigitated structure, which is further connected by the tetradentate β-[Mo 8O 26] 4- clusters forming a 3D framework. The thermal stability and luminescent properties of 1- 3 are investigated in the solid state.

  8. The effect of triazole induced photosynthetic pigments and biochemical constituents of Zea mays L. (Maize) under drought stress

    NASA Astrophysics Data System (ADS)

    Rajasekar, Mahalingam; Rabert, Gabriel Amalan; Manivannan, Paramasivam

    2015-07-01

    In this investigation, pot culture experiment was carried out to estimate the ameliorating effect of triazole compounds, namely Triadimefon (TDM), Tebuconazole (TBZ), and Propiconazole (PCZ) on drought stress, photosynthetic pigments, and biochemical constituents of Zea mays L. (Maize). From 30 days after sowing (DAS), the plants were subjected to 4 days interval drought (DID) stress and drought with TDM at 15 mg l-1, TBZ at 10 mg l-1, and PCZ at 15 mg l-1. Irrigation at 1-day interval was kept as control. Irrigation performed on alternative day. The plant samples were collected on 40, 50, and 60 DAS and separated into root, stem, and leaf for estimating the photosynthetic pigments and biochemical constituents. Drought and drought with triazole compounds treatment increased the biochemical glycine betaine content, whereas the protein and the pigments contents chlorophyll-a, chlorophyll-b, total chlorophyll, carotenoid, and anthocyanin decreased when compared to control. The triazole treatment mitigated the adverse effects of drought stress by increasing the biochemical potentials and paved the way to overcome drought stress in corn plant.

  9. Study of acoustic fingerprinting of nitromethane and some triazole derivatives using UV 266 nm pulsed photoacoustic pyrolysis technique

    NASA Astrophysics Data System (ADS)

    Rao, K. S.; Chaudhary, A. K.; Yehya, F.; Kumar, A. Sudheer

    2015-08-01

    We report a comparative study of acoustic fingerprints of nitromethane, nitrobenzene and some nitro rich triazole derivatives using pulsed photoacoustic technique. UV 266 nm wavelength i.e. Fourth harmonic of Q-switched Nd: YAG laser having pulse duration 7 ns and 10 Hz repetition rate is employed to record the time resolved PA spectrum. The PA fingerprint is produced due to absorption of incident UV light by molecule itself and photo dissociation of nitromethane and nitrobenzene at room temperature while in case of triazole it is attributed to the combination of thermal and photo-dissociation process. The entire dissociation process follows the root of cleavage of C-NO2 bond to produce free NO, NO2 and other by product gases due to π∗ ← n excitation. In addition, we have studied the thermal stability criteria of nitro rich triazoles based on the quality factor of acoustic resonance frequencies of the PA cavity. We have also studied the effect of data acquisition time to ascertain the decay behavior of HEMs samples.

  10. Novel triazole hybrids of myrrhanone C, a natural polypodane triterpene: Synthesis, cytotoxic activity and cell based studies.

    PubMed

    Chandrashekhar, Madasu; Nayak, Vadithe Lakshma; Ramakrishna, Sistla; Mallavadhani, Uppuluri Venkata

    2016-05-23

    The 3-keto functionality in ring A of myrrhanone C, a natural bicyclic triterpene has been chemically modified and synthesized 27 novel triazole hybrids belonging to two different series in very good to excellent yields (66-83%). The synthesized compounds were thoroughly characterized by their spectroscopic data (IR, (1)H&(13)C NMR, HRMS). All the synthesized compounds were evaluated for their cytotoxic potential against a panel of five human cancer cell lines by employing MTT assay using doxorubicin as the standard. In general the synthesized compounds showed anticancer activity against almost all the cell lines screened. Interestingly, the oxime based triazoles (4a-4n) showed higher activity than the benzylidene triazoles (6a-6m). Most significantly compound 4a showed potent activity against all the tested cell lines, especially against lung cancer (A-549) with an IC 50 of 6.16 μm. In view of their significant activity against lung cancer cell lines, compounds 4a and 4l were subjected to detailed biological studies, which revealed that they arrested cell cycle in G2/M phase and induced cell death by apoptosis that was further confirmed by Hoechst staining, measurement of mitochondrial membrane potential (ΔΨm) and Annexin V-FITC assay. These compounds will serve as lead molecules in the development of potent anticancer drug candidates especially for lung cancer. PMID:27015609

  11. The effect of triazole induced photosynthetic pigments and biochemical constituents of Zea mays L. (Maize) under drought stress

    NASA Astrophysics Data System (ADS)

    Rajasekar, Mahalingam; Rabert, Gabriel Amalan; Manivannan, Paramasivam

    2016-06-01

    In this investigation, pot culture experiment was carried out to estimate the ameliorating effect of triazole compounds, namely Triadimefon (TDM), Tebuconazole (TBZ), and Propiconazole (PCZ) on drought stress, photosynthetic pigments, and biochemical constituents of Zea mays L. (Maize). From 30 days after sowing (DAS), the plants were subjected to 4 days interval drought (DID) stress and drought with TDM at 15 mg l-1, TBZ at 10 mg l-1, and PCZ at 15 mg l-1. Irrigation at 1-day interval was kept as control. Irrigation performed on alternative day. The plant samples were collected on 40, 50, and 60 DAS and separated into root, stem, and leaf for estimating the photosynthetic pigments and biochemical constituents. Drought and drought with triazole compounds treatment increased the biochemical glycine betaine content, whereas the protein and the pigments contents chlorophyll-a, chlorophyll-b, total chlorophyll, carotenoid, and anthocyanin decreased when compared to control. The triazole treatment mitigated the adverse effects of drought stress by increasing the biochemical potentials and paved the way to overcome drought stress in corn plant.

  12. Labeling lake water with tritium

    USGS Publications Warehouse

    Frederick, B.J.

    1963-01-01

    A method of packaging tritiated water in a manner that facilitates safe handling in environmental labeling operations, and procedures followed in labeling a large body of water with a small volume of tritiated water are described. ?? 1963.

  13. 99m tc labeled liposomes

    SciTech Connect

    Phillips, W.T.; Klipper, R.W.; Timmons, J.H.; Rudolph, A.S.

    1992-10-27

    This patent describes a method of preparing stable gamma-emitting radionuclide-labeled alkyleneamine oxime, the incubating being for a period of time sufficient to form labeled liposome-encapsulated protein.

  14. Decode the Sodium Label Lingo

    MedlinePlus

    ... For Preschooler For Gradeschooler For Teen Decode the Sodium Label Lingo Published January 24, 2013 Print Email Reading food labels can help you slash sodium. Here's how to decipher them. "Sodium free" or " ...

  15. A study on the condensation reaction of aryl substituted 4-amine-1,2,4-triazole with benzaldehydes: Structures and spectroscopic properties of schiff bases and stable hemiaminals

    NASA Astrophysics Data System (ADS)

    Wajda-Hermanowicz, Katarzyna; Pieniążczak, Damian; Wróbel, Robert; Zatajska, Aleksandra; Ciunik, Zbigniew; Berski, Sławomir

    2016-06-01

    A series of stable hemiaminals and Schiff bases containing 3,5-disubstituted 1,2,4-triazole derivatives were synthesized. The structure of the prepared compounds was confirmed by means of 1H NMR, 13C NMR, IR, MS and elemental analysis. The steric and electronic effects of the triazole ring substituents on the hemiaminal formation was also discussed. Single crystal X-ray diffraction studies of hemiaminals obtained from 4-amino-3,5-dipyridyn-2-yl-1,2,4- triazole (4, 5) revealed the formation of centrosymmetric dimers linked by strong O-H … .N1Tr hydrogen bonds. The Schiff bases obtained from the unsymmetrical 3-methyl,5-phenyl-1,2,4-triazole was found to be a different E-conformer which was determined through solution NMR and crystallographic diffraction analysis (13). The molecular geometry of the unsymmetrical triazole derivatives: hemiaminal (12) and Schiff base (13) were also optimized using density functional theory (DFT/M062x) method with the 6-311++G (d,p) basis set in ground state and compared with the experimental data.

  16. Synthesis of 5-iodo-1,4-disubstituted-1,2,3-triazoles mediated by in situ generated copper(I) catalyst and electrophilic triiodide ion.

    PubMed

    Brotherton, Wendy S; Clark, Ronald J; Zhu, Lei

    2012-08-01

    Mixing copper(II) perchlorate and sodium iodide solutions results in copper(I) species and the electrophilic triiodide ions, which collectively mediate the cycloaddition reaction of organic azide and terminal alkyne to afford 5-iodo-1,4-disubstituted-1,2,3-triazoles. One molar equivalent of an amine additive is required for achieving a full conversion. Excessive addition of the amine compromises the selectivity for 5-iodo-1,2,3-triazole by promoting the formation of 5-proto-1,2,3-triazole. Based on preliminary kinetic and structural evidence, a mechanistic model is formulated in which a 5-iodo-1,2,3-triazole is formed via iodination of a copper(I) triazolide intermediate by the electrophilic triiodide ions (and possibly triethyliodoammonium ions). The experimental evidence explains the higher reactivity of the in situ generated copper(I) species and triiodide ion in the formation of 5-iodo-1,2,3-triazoles than that of the pure forms of copper(I) iodide and iodine. PMID:22780866

  17. Learning with imperfectly labeled patterns

    NASA Technical Reports Server (NTRS)

    Chittineni, C. B.

    1979-01-01

    The problem of learning in pattern recognition using imperfectly labeled patterns is considered. The performance of the Bayes and nearest neighbor classifiers with imperfect labels is discussed using a probabilistic model for the mislabeling of the training patterns. Schemes for training the classifier using both parametric and non parametric techniques are presented. Methods for the correction of imperfect labels were developed. To gain an understanding of the learning process, expressions are derived for success probability as a function of training time for a one dimensional increment error correction classifier with imperfect labels. Feature selection with imperfectly labeled patterns is described.

  18. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ....12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels must...) If installation instructions are included on the label or with the package, add this statement:...

  19. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ....12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels must...) If installation instructions are included on the label or with the package, add this statement:...

  20. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ....12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels must...) If installation instructions are included on the label or with the package, add this statement:...

  1. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ....12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels must...) If installation instructions are included on the label or with the package, add this statement:...

  2. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ....12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels must...) If installation instructions are included on the label or with the package, add this statement:...

  3. Application of the Huisgen cycloaddition and 'click' reaction toward various 1,2,3-triazoles as HIV non-nucleoside reverse transcriptase inhibitors.

    PubMed

    Pribut, Nicole; Veale, Clinton G L; Basson, Adriaan E; van Otterlo, Willem A L; Pelly, Stephen C

    2016-08-01

    The development of novel anti-HIV agents remains an important medicinal chemistry challenge given that no cure for the disease is imminent, and the continued use of current NNRTIs inevitably leads to problems associated with resistance. Inspired by the pyrazole-containing NNRTI lersivirine (LSV), we embarked upon a study to establish whether 1,2,3-triazole heterocycles could be used as a new scaffold for the creation of novel NNRTIs. An especially attractive feature of triazoles used for this purpose is the versatility in accessing variously functionalised systems using either the thermally regulated Huisgen cycloaddition, or the related 'click' reaction. Employing three alternative forms of these reactions, we were able to synthesise a range of triazole compounds and evaluate their efficacy in a phenotypic HIV assay. To our astonishment, even compounds closely mimicking LSV were only moderately effective against HIV. PMID:27287366

  4. Optimization of a Series of Triazole Containing Mammalian Target of Rapamycin (mTOR) Kinase Inhibitors and the Discovery of CC-115.

    PubMed

    Mortensen, Deborah S; Perrin-Ninkovic, Sophie M; Shevlin, Graziella; Elsner, Jan; Zhao, Jingjing; Whitefield, Brandon; Tehrani, Lida; Sapienza, John; Riggs, Jennifer R; Parnes, Jason S; Papa, Patrick; Packard, Garrick; Lee, Branden G S; Harris, Roy; Correa, Matthew; Bahmanyar, Sogole; Richardson, Samantha J; Peng, Sophie X; Leisten, Jim; Khambatta, Godrej; Hickman, Matt; Gamez, James C; Bisonette, René R; Apuy, Julius; Cathers, Brian E; Canan, Stacie S; Moghaddam, Mehran F; Raymon, Heather K; Worland, Peter; Narla, Rama Krishna; Fultz, Kimberly E; Sankar, Sabita

    2015-07-23

    We report here the synthesis and structure-activity relationship (SAR) of a novel series of triazole containing mammalian target of rapamycin (mTOR) kinase inhibitors. SAR studies examining the potency, selectivity, and PK parameters for a series of triazole containing 4,6- or 1,7-disubstituted-3,4-dihydropyrazino[2,3-b]pyrazine-2(1H)-ones resulted in the identification of triazole containing mTOR kinase inhibitors with improved PK properties. Potent compounds from this series were found to block both mTORC1(pS6) and mTORC2(pAktS473) signaling in PC-3 cancer cells, in vitro and in vivo. When assessed in efficacy models, analogs exhibited dose-dependent efficacy in tumor xenograft models. This work resulted in the selection of CC-115 for clinical development. PMID:26102506

  5. Synthesis and in vitro evaluation of potential anticancer activity of mono- and bis-1,2,3-triazole derivatives of bis-alkynes.

    PubMed

    Elamari, Hichem; Slimi, Riadh; Chabot, Guy G; Quentin, Lionel; Scherman, Daniel; Girard, Christian

    2013-02-01

    In order to find new molecules with cytotoxic activity against cancer cells, we prepared bis-akyne amides derived from propiolic acid. The bis-alkynes were then transformed in their mono-1,2,3-triazole analogs onto the amide side, due to its greater reactivity, using a catalyst-free Huisgen's reaction. The mono-triazoles were then subjected to the copper (I)-catalyzed version of the previous reaction (CuAAC), using a supported catalyst, to produce bis-triazoles. All products were obtained pure after simple trituration or filtration procedures. All synthetic compounds were tested in vitro for their cytotoxic activity using B16 melanoma cells. Four compounds (7, 23, 25 and 33) showed activities in the micromolar range (<21 μM) whereas three compounds (3, 22 and 38) presented activity at low micromolar concentrations (<10 μM), and two analogs (2 and 13) were active at nanomolar levels (<1 μM). PMID:23314049

  6. Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2-S100A10 protein interaction.

    PubMed

    Reddy, Tummala R K; Li, Chan; Guo, Xiaoxia; Fischer, Peter M; Dekker, Lodewijk V

    2014-10-01

    Recent target validation studies have shown that inhibition of the protein interaction between annexin A2 and the S100A10 protein may have potential therapeutic benefits in cancer. Virtual screening identified certain 3,4,5-trisubstituted 4H-1,2,4-triazoles as moderately potent inhibitors of this interaction. A series of analogues were synthesized based on the 1,2,4-triazole scaffold and were evaluated for inhibition of the annexin A2-S100A10 protein interaction in competitive binding assays. 2-[(5-{[(4,6-Dimethylpyrimidin-2-yl)sulfanyl]methyl}-4-(furan-2-ylmethyl)-4H-1,2,4-triazol-3-yl)sulfanyl]-N-[4-(propan-2-yl)phenyl]acetamide (36) showed improved potency and was shown to disrupt the native complex between annexin A2 and S100A10. PMID:25172147

  7. HPLC-MS/MS enantioseparation of triazole fungicides using polysaccharide-based stationary phases.

    PubMed

    Zhang, Hu; Qian, Mingrong; Wang, Xinquan; Wang, Xiangyun; Xu, Hao; Wang, Qiang; Wang, Minghua

    2012-04-01

    The enantiomeric separation of 21 triazole fungicides was carried out on four polysaccharide-derived chiral stationary phases in the reversed phase separation mode using high performance liquid chromatography coupled with tandem mass spectrometry. All fungicides were detected in electrospray ionization (ESI) positive mode with selected reaction monitoring (SRM). Complete enantioseparation was achieved for 21 fungicides except for difenoconazole based on cellulose tris (3,5-dimethylphenylcarbamate) and cellulose tris (3-chloro-4-methylphenyl carbamate) columns by optimizing experimental conditions including mobile phase and column temperature. Mobile phase was 0.1% formic acid aqueous solution mixed with methanol or acetonitrile in different proportions. Among all the fungicides, 15 with two enantiomers and three with four stereoisomers (bitertanol, bromuconazole, and cyproconazole) were successfully separated at 25°C. Enantioseparation for the other three fungicides (propiconazole, triadimenol, and difenoconazole) with four stereoisomers could be achieved by changing the column temperature from 10 to 40°C. Propiconazole and triadimenol were enantioseparated on baseline at 40 and at 35°C, respectively, and difenoconazole was enantioseparated partially with the R(s) > 1.1 at 25°C. Moreover, linearities and limits of detection (LODs) of 21 fungicides except for difenoconazole were studied, showing coefficients of determination (R(2)) higher than 0.99 and LODs lower than 2.5 μg/L. PMID:22532344

  8. Spectroscopic studies on the interaction of fluorine containing triazole with bovine serum albumin.

    PubMed

    Liu, Yang; Mei, Ping; Zhang, Ye-Zhong; Sun, Xiao-Hong; Liu, Yi

    2010-12-01

    The binding of one fluorine including triazole (C(10)H(9)FN(4)S, FTZ) to bovine serum albumin (BSA) was studied by spectroscopic techniques including fluorescence spectroscopy, UV-Vis absorption, and circular dichroism (CD) spectroscopy under simulative physiological conditions. Fluorescence data revealed that the fluorescence quenching of BSA by FTZ was the result of forming a complex of BSA-FTZ, and the binding constants (K (a)) at three different temperatures (298, 304, and 310 K) were 1.516 × 10(4), 1.627 × 10(4), and 1.711 × 10(4) mol L(-1), respectively, according to the modified Stern-Volmer equation. The thermodynamic parameters ΔH and ΔS were estimated to be 7.752 kJ mol(-1) and 125.217 J mol(-1) K(-1), respectively, indicating that hydrophobic interaction played a major role in stabilizing the BSA-FTZ complex. It was observed that site I was the main binding site for FTZ to BSA from the competitive experiments. The distance r between donor (BSA) and acceptor (FTZ) was calculated to be 7.42 nm based on the Förster theory of non-radioactive energy transfer. Furthermore, the analysis of fluorescence data and CD data revealed that the conformation of BSA changed upon the interaction with FTZ. PMID:20195922

  9. Antioxidant, tautomerism and antibacterial studies of Fe(III)-1,2,4-triazole based complexes

    NASA Astrophysics Data System (ADS)

    Kharadi, G. J.

    2013-06-01

    New Fe(III) complexes have been synthesized by the reactions of ferric nitrate with Schiff base derived from 3-substituted phenyl-4-amino-5-hydrazino-1,2,4-triazole and indoline-2,3-dione. All these complexes are soluble in DMF and DMSO; low molar conductance values indicate that they are non-electrolytes. Elemental analyses suggest that the complexes have 1:1 stoichiometry of the type [FeLn(H2O)(OH)]·xH2O. Structural and spectroscopic properties have been studied on the basis of elemental analyses, infrared spectra, 1H and 13H NMR spectra, electronic spectra, magnetic measurements and FAB mass spectra. FT-IR, 1H and 13H NMR studies reveal that the ligand (Ln) exists in the tautomeric enol form in both the states with intramolecular hydrogen bonding. Magnetic moment and reflectance spectral studies reveal that an octahedral geometry has been assigned to all the prepared complexes. FRAP values indicate that all the compounds have a ferric reducing antioxidant power. The compounds 2 and 3 showed relatively high antioxidant activity while compound 1 and 4 shows poor antioxidant power. Also good antimicrobial activities of the complexes against Staphylococcus aureus, Bacillus subtilis, Serratia marcescens, Pseudomonas aeruginosa and Escherichia coli have been found compared to its free ligands.

  10. Alkyl triazole glycosides (ATGs)--a new class of bio-related surfactants.

    PubMed

    Sani, Faramarz Aliasghari; Heidelberg, Thorsten; Hashim, Rauzah; Farhanullah

    2012-09-01

    A series of glucose based surfactants varying in chain length and anomeric configuration were synthesized and investigated on their surfactant properties. The synthesis applied glycosylation of propargyl alcohol followed by cycloaddition with alkyl azides in CLICK chemistry fashion. This approach enables a homogeneous coupling of hydrophilic unprotected sugars and hydrophobic paraffin components in low molecular weight alcohols without solvent side reactions, as commonly found for APGs. The combination of alcohols as inert medium with practically quantitative coupling of the surfactant domains avoids particularly hydrophobic contaminations of the surfactant, thus providing access to pure surfactants. ATGs with chain lengths up to 12 carbons exhibit Krafft points below room temperature and no cloud points were detected. The values for the CMC of ATGs with 12 carbon alkyl chains and above were in good agreement with those of corresponding alkyl glucosides. However, lower homologues exhibited significantly smaller CMCs, and the trend of the CMC upon the chain length did not match common surfactant behavior. This deviation may be related to the triazole that links the two surfactant domains. PMID:22609603

  11. Scrutinizing the DNA damaging and antimicrobial abilities of triazole appended metal complexes.

    PubMed

    Utthra, Ponnukalai Ponya; Pravin, Narayanaperumal; Raman, Natarajan

    2016-05-01

    New mononuclear transition metal complexes 1-12 bearing the bioactive triazole analogues were synthesized and characterized by elemental analysis and spectroscopic techniques. The interaction of calf thymus DNA (CT-DNA) with the synthesized compounds was studied at physiological pH by spectrophotometric, spectrofluorometric, cyclic voltammetry, and viscometric techniques. The entire DNA binding results suggested the intercalative mode of binding for the synthesized compounds. Interestingly, the binding strength of the complexes is found to be greater than that of the free ligands. Among the complexes explored, complex 5 reveals strong hypochromism and a slight red shift as compared to the other complexes highlighting its higher DNA binding propensity. The intrinsic binding constant values of the complexes compared to cisplatin reveal that all the complexes are greater in magnitude than that of cisplatin. Fluorescence titrations show that the Cu(II) complexes have the ability to displace DNA-bound ethidium bromide. Also, these compounds induce cleavage in pBR322 plasmid DNA as indicated in gel electrophoresis and exhibit excellent nuclease activity in the presence of H2O2. Moreover, the complexes were screened for in vitro antimicrobial activity along with free ligands and solvent control. The outcome is that the complexes possess good activity than the free ligands. These complexes may have further scope in developing them into antimicrobial drugs and DNA probes. PMID:26971279

  12. Synthesis, Pharmacological Evaluation and Molecular Modeling Studies of Triazole Containing Dopamine D3 Receptor Ligands

    PubMed Central

    Peng, Xin; Wang, Qi; Mishra, Yogesh; Xu, Jinbin; Reichert, David E.; Malik, Maninder; Taylor, Michelle; Luedtke, Robert R.; Mach, Robert H.

    2015-01-01

    A series of 2-methoxyphenyl piperazine analogues containing a triazole ring were synthesized and their in vitro binding affinities at human dopamine D2 and D3 receptors were evaluated. Compounds 5b, 5c, 5d, and 4g, demonstrate high affinity for dopamine D3 receptors and moderate selectivity for the dopamine D3 versus D2 receptor subtypes. To further examine their potential as therapeutic agents, their intrinsic efficacy at both D2 and D3 receptors was determined using a forskolin-dependent adenylyl cyclase inhibition assay. Affinity at dopamine D4 and serotonin 5-HT1A receptors was also determined. In addition, information from previous molecular modeling studies of the binding of a panel of 163 structurally-related benzamide analogues at dopamine D2 and D3 receptors was applied to this series of compounds. The results of the modeling studies were consistent with our previous experimental data. More importantly, the modeling study results explained why the replacement of the amide linkage with the hetero-aromatic ring leads to a reduction in the affinity of these compounds at D3 receptors. PMID:25556097

  13. Synthesis of novel 1,2,4-triazoles, triazolothiadiazines and triazolothiadiazoles as potential anticancer agents.

    PubMed

    Kamel, Mona M; Megally Abdo, Nadia Y

    2014-10-30

    A series of new N-substituted-3-mercapto-1,2,4-triazoles (3a,b and 7a-d), triazolo[1,3,4]thiadiazines (5a,b) and triazolo[1,3,4]thiadiazoles (4a-d, 6 and 8a-d) have been synthesized starting from isonicotinic acid hydrazide. The structure of the newly synthesized compounds was confirmed on the basis of their spectral data and elemental analyses. All the compounds were screened for their in vitro anticancer activity against 6 human cancer cell lines and normal fibroblasts. Seven of the tested compounds (3a,b, 4c, 5a and 8b-d) exhibited significant cytotoxicity against most cell lines. Among these derivatives compound 4c exhibited equivalent cytotoxic effect to the standard CHS 828 against gastric cancer cell line (IC50 = 25 nM). Normal fibroblast cells (WI38) were affected to a much lesser extent (IC50 > 10,000 nM). PMID:25147148

  14. Treatment trial of clinically ill corroboree frogs with chytridiomycosis with two triazole antifungals and electrolyte therapy.

    PubMed

    Brannelly, Laura A; Skerratt, Lee F; Berger, Lee

    2015-09-01

    Chytridiomycosis caused by the pathogen Batrachochytrium dendrobatidis is an important cause of amphibian declines globally, and is the worst pathogen on record for causing biodiversity loss. The critically endangered southern corroboree frog, Pseudophryne corroboree, is functionally extinct in the wild and is surviving in captive assurance colonies. These captive colonies must remain disease free, and there is no known treatment for corroboree frogs with terminal chytridiomycosis. In this study we tested two triazole antifungals (itraconazole and voriconazole) coupled with aggressive electrolyte therapy on moribund corroboree frogs with severe chytridiomycosis. Six moribund frogs were given 20 mL baths of 0.5 μg/mL itraconazole for 5 min/day for 5 days coupled with electrolyte injections every 8 h for 3 days followed by every 12 h for 3 days. Six other moribund frogs were given 1 mL drops of 1.25 μg/mL voriconazole daily for 7 days coupled with the aggressive electrolyte therapy. While only one animal survived this treatment regime, time until death was extended for all animals by at least 3 days and infection load decreased by an average of 89.3%. Our results suggest there is potential for recovery of terminally ill P. corroboree, and we suggest further trials include antibiotics as well as exploring variations on the above treatment regime with other antifungals. PMID:26246159

  15. Nav1.1 Modulation by a Novel Triazole Compound Attenuates Epileptic Seizures in Rodents

    PubMed Central

    2015-01-01

    Here, we report the discovery of a novel anticonvulsant drug with a molecular organization based on the unique scaffold of rufinamide, an anti-epileptic compound used in a clinical setting to treat severe epilepsy disorders such as Lennox-Gastaut syndrome. Although accumulating evidence supports a working mechanism through voltage-gated sodium (Nav) channels, we found that a clinically relevant rufinamide concentration inhibits human (h)Nav1.1 activation, a distinct working mechanism among anticonvulsants and a feature worth exploring for treating a growing number of debilitating disorders involving hNav1.1. Subsequent structure–activity relationship experiments with related N-benzyl triazole compounds on four brain hNav channel isoforms revealed a novel drug variant that (1) shifts hNav1.1 opening to more depolarized voltages without further alterations in the gating properties of hNav1.1, hNav1.2, hNav1.3, and hNav1.6; (2) increases the threshold to action potential initiation in hippocampal neurons; and (3) greatly reduces the frequency of seizures in three animal models. Altogether, our results provide novel molecular insights into the rational development of Nav channel-targeting molecules based on the unique rufinamide scaffold, an outcome that may be exploited to design drugs for treating disorders involving particular Nav channel isoforms while limiting adverse effects. PMID:24635129

  16. Triazole-containing copolymer for use as an electron transport material in multilayer LEDs

    NASA Astrophysics Data System (ADS)

    Grice, Alan W.; Tajbakhsh, Ali R.; Burn, Paul L.; Bradley, Donal D. C.

    1997-12-01

    We report investigations into a poly(1,20-distyrylbenzene- co-1,2-[4-(p-ethylphenyl)]triazole) (TRIDSB) electron transport material and its incorporation into single and multilayer LEDs. Multilayer devices have been investigated with poly(p-phenylenevinylene) (PPV) and poly(2-methoxy-5- (2'-ethylhexyloxy)-1,4-phenylenevinylene) as hole transport layers (HTLs). The incorporation of the polymer into an ITO/PPV/TRIDSB/Al LED facilitates electron injection into the hole transporting emissive layer and results in a ten fold increase in the external quantum efficiency for electroluminescence (EL) of the PPV layer from 0.008 percent to 0.08-0.1 percent. In an ITO/I-MEHPPV/TRIDSB/Al device the corresponding increase in the quantum efficiency for EL from the 1-MEHPPV is fifty fold, from 0.002 percent to between 0.06-0.11 percent. The polymer has been shown to be thermally stable with no glass transition temperature or melting point detected within the range 25-250 degrees C.

  17. Design, synthesis and antitrypanosomal activity of some nitrofurazone 1,2,4-triazolic bioisosteric analogues.

    PubMed

    Silva, Fredson T; Franco, Caio H; Favaro, Denize C; Freitas-Junior, Lucio H; Moraes, Carolina B; Ferreira, Elizabeth I

    2016-10-01

    Chagas disease, caused by Trypanosoma cruzi, is a parasitosis that predominates in Latin America. It is estimated that 25 million people are under the risk of infection and, in 2008, more than 10 thousand deaths were registered. The only two drugs available in the therapeutics, nifurtimox and benznidazole, showed to be more effective in the acute phase of the disease. However, there is no standard treatment protocol effective for the chronic phase. Nitrofurazone (NF), an antimicrobial drug, has activity against T. cruzi, although being toxic. Considering the need for new antichagasic drugs, the existence of promising new therapeutic targets, as 14α-sterol demethylase and cruzain, and employing the bioisosterism and molecular hybridization approaches, four novel compounds were synthesized, characterized by melting point range, elemental analysis, IR and NMR spectroscopy. The compounds were tested against T. cruzi amastigotes in infected U2OS cells. All compounds showed selectivity towards T. cruzi and showed trypanomicidal activity in low micromolar range. The compound 3 showed potency similar to benznidazole, but lower efficacy. These results highlight the importance of the 1,2,4-triazole, thiosemicarbazonic and nitro group moieties for designing new efficient compounds, potentially for the chronic phase of Chagas disease. PMID:27318979

  18. Synthesis and antifungal evaluation of (1,2,3-triazol-4-yl)methyl nicotinate chitosan.

    PubMed

    Qin, Yukun; Liu, Song; Xing, Ronge; Li, Kecheng; Yu, Huahua; Li, Pengcheng

    2013-10-01

    With an aim to discover novel chitosan derivatives with significant activities against crop-threatening fungi, (1,2,3-triazol-4-yl)methyl nicotinate chitosan (TAMNCS) was prepared via azide-alkyne click reaction. Its structure was characterized by FT-IR, (1)H NMR, elemental analysis, DSC, and SEM. In vitro antifungal properties of TAMNCS against Rhizoctonia solani Kühn (R. solani), Stemphylium solani weber (S. solani), and Alternaria porri (A. porri) were studied at the concentrations ranged from 0.25 mg/mL to 1.0 mg/mL. Experiments conducted displayed the derivative had obviously enhanced antifungal activity after chemical modification compared with original chitosan. Moreover, it was shown that TAMNCS can 94.2% inhibit growth of A. porri at 1.0 mg/mL, while dose at which the fungicide triadimefon had lower inhibitory index (62.2%). The primary antifungal results described here indicate this derivative may be a promising candidate as an antifungal agent. PMID:23732332

  19. Triazole-dithiocarbamate based, selective LSD1 inactivators inhibit gastric cancer cell growth, invasion and migration

    PubMed Central

    Ma, Jin-Lian; Xu, Rui-Min; Zi, Xiaolin; Lv, Wen-Lei; Wang, Meng-Meng; Ye, Xian-Wei; Zhu, Shun; Mobley, David; Zhu, Yan-Yan; Wang, Jun-Wei; Li, Jin-Feng; Wang, Zhi-Ru; Zhao, Wen; Liu, Hong-Min

    2013-01-01

    Lysine specific demethylase 1 (LSD1), the first identified histone demethylase, plays an important role in epigenetic regulation of gene activation and repression. The up-regulated LSD1's expression has been reported in several malignant tumors. In the current study, we designed and synthesized five series of 1, 2, 3-triazole-dithiocarbamate hybrids and screened their inhibitory activity toward LSD1. We found that some of these compounds, especially compound 26, exhibited the most specific and robust inhibition of LSD1. Interestingly, compound 26 also showed potent and selective cytotoxicity against LSD1 overexpressing gastric cancer cell lines MGC-803 and HGC-27, as well as marked inhibition of cell migration and invasion, compared to 2-PCPA. Furthermore, compound 26 effectively reduced the tumor growth bared by human gastric cancer cells in vivo with no signs of adverse side effects. These findings suggested that compound 26 deserves further investigation as a lead compound in the treatment of LSD1 overexpressing gastric cancer. PMID:24131029

  20. Triazole-based highly selective supramolecular sensor for the detection of diclofenac in real samples.

    PubMed

    Ahmed, Farid; Shah, Kiramat; Awan, Iqra Zubair; Shah, Muhammad Raza

    2016-07-01

    A triazole-based supramolecular chemosensor 6 for the selective spectrophotometric detection of diclofenac in human plasma and tap water was developed. The 6 was synthesized through click approach and characterized via UV-vis spectroscopy, FT-IR, Mass and NMR spectroscopy. The supramolecular interaction of compound 6 with commonly used drugs has been investigated with the help of UV-vis spectral titrations, FT-IR and (1)H, (13)C NMR spectroscopy. The UV-visible spectral changes upon addition of various commonly used drugs showed that compound 6 is highly selective for diclofenac over other drugs. The supramolecule 6 exhibited a selective enhancement in the absorbance intensity after mixing with diclofenac in human plasma and water samples in the presence of other drugs at pH 6-7, with a linear range of 0.938 (R(2)=0.938) and a limit of detection 10µM. The relative standard deviation (RSD) for 100µM diclofenac was found to be 0.462. The Job's plot analysis revealed that diclofenac bind to compound 6 in 1:1 stoichiometry. PMID:27003618

  1. Efficient Hole-Transporting Materials with Triazole Core for High-Efficiency Perovskite Solar Cells.

    PubMed

    Choi, Hyeju; Jo, Hyeonjun; Paek, Sanghyun; Koh, Kyungkuk; Ko, Haye Min; Lee, Jae Kwan; Ko, Jaejung

    2016-02-18

    Efficient hole-transporting materials (HTMs), TAZ-[MeOTPA]2 and TAZ-[MeOTPATh]2 incorporating two electron-rich diphenylamino side arms, through direct linkage or thiophen bridges, respectively, on the C3- and C5-positions of a 4-phenyl-1,2,4-triazole core were synthesized. These synthetic HTMs with donor-acceptor type molecular structures exhibited effective intramolecular charge transfer for improving the hole-transporting properties. The structural modification of HTMs by thiophene bridging might increase intermolecular π-π stacking in the solid state and afford a better spectral response because of their increased π-conjugation length. Perovskite-based cells using TAZ-[MeOTPA]2 and TAZ-[MeOTPATh]2 as HTMs afforded high power conversion efficiencies of 10.9 % and 14.4 %, respectively, showing a photovoltaic performance comparable to that obtained using spiro-OMeTAD. These synthetically simple and inexpensive HTMs hold promise for replacing the more expensive spiro-OMeTAD in high-efficiency perovskite solar cells. PMID:26573775

  2. Tuning zinc coordination architectures by benzenedicarboxylate position isomers and bis(triazole)

    NASA Astrophysics Data System (ADS)

    Peng, Yan-fen; Li, Ke; Zhao, Shan; Han, Shan-shan; Li, Bao-long; Li, Hai-Yan

    2015-08-01

    Three position isomers 1,2-, 1,3-, 1,4-benzenedicarboxylate and 1,4-bis(1,2,4-triazol-4-yl)benzene were used to assembly zinc(II) coordination polymers {[Zn2(btx)0.5(1,2-bdc)2(H2O)]·H2O}n (1), {[Zn(btx)(1,3-bdc)]·2H2O·(DMF)}n (2) and {[Zn(btx)(1,4-bdc)]·3H2O}n (3). 1 is a (3,4,4,4)-connected two-dimensional network with point symbol (42·6)(44·62)(43·62·8)(42·6·103). 2 shows a two-dimensional (4,4) network. 3 exhibits a 5-fold interpenetrated three-dimensional diamondoid network. The structural versatility shows that the structures of coordination polymers can be tuned by the position isomers ligands. The luminescence and thermal stability were investigated.

  3. Efficient Synthesis of Conformationally Restricted Apoptosis Inhibitors Bearing a Triazole Moiety.

    PubMed

    Corredor, Miriam; Garrido, Maria; Bujons, Jordi; Orzáez, Mar; Pérez-Payá, Enrique; Alfonso, Ignacio; Messeguer, Angel

    2015-09-28

    Apoptosis is a biological process relevant to different human diseases that is regulated through protein-protein interactions and complex formation. Peptidomimetic compounds based on linear peptoids and cyclic analogues with different ring sizes have been previously reported as potent apoptotic inhibitors. Among them, the presence of cis/trans conformers of an exocyclic tertiary amide bond in slow exchange has been characterized. This information encouraged us to perform an isosteric replacement of the amide bond by a 1,2,3-triazole moiety, in which different substitution patterns would mimic different amide rotamers. The syntheses of these restricted analogues have been carried out through an Ugi multicomponent reaction followed by an intramolecular cyclization. The unexpected formation of a β-lactam scaffold prompted us to study the course of the intramolecular cyclization of the Ugi adducts. In order to modulate this cyclization, a small library of compounds bearing both heterocyclic scaffolds has been synthesized and their activities as apoptosis inhibitors have been evaluated. PMID:26270744

  4. Enzymatic Macrocyclization of 1,2,3‐Triazole Peptide Mimetics

    PubMed Central

    Oueis, Emilia; Jaspars, Marcel; Westwood, Nicholas J.

    2016-01-01

    Abstract The macrocyclization of linear peptides is very often accompanied by significant improvements in their stability and biological activity. Many strategies are available for their chemical macrocyclization, however, enzyme‐mediated methods remain of great interest in terms of synthetic utility. To date, known macrocyclization enzymes have been shown to be active on both peptide and protein substrates. Here we show that the macrocyclization enzyme of the cyanobactin family, PatGmac, is capable of macrocyclizing substrates with one, two, or three 1,4‐substituted 1,2,3‐triazole moieties. The introduction of non‐peptidic scaffolds into macrocycles is highly desirable in tuning the activity and physical properties of peptidic macrocycles. We have isolated and fully characterized nine non‐natural triazole‐containing cyclic peptides, a further ten molecules are also synthesized. PatGmac has now been shown to be an effective and versatile tool for the ring closure by peptide bond formation. PMID:27059105

  5. Triazole antifungals used for prophylaxis and treatment of invasive fungal disease in adult haematology patients: Trough serum concentrations in relation to outcome.

    PubMed

    Ceesay, M Mansour; Couchman, Lewis; Smith, Melvyn; Wade, Jim; Flanagan, Robert J; Pagliuca, Antonio

    2016-10-01

    Triazole antifungal drugs are widely used for the prophylaxis and treatment of invasive fungal disease (IFD). Efficacy may depend on attaining minimum effective plasma concentrations. The aim of this study was to ascertain the proportion of samples in which the recommended concentrations were achieved in patients given these drugs in relation to outcome. In-patients prescribed standard doses of fluconazole, itraconazole solution, posaconazole suspension, or oral voriconazole for at least one week were studied. Pre-dose serum triazole concentrations were measured using validated methods. There were 359 samples from 90 patients. The median (range) number of samples per patient was 3 (1-13), and the median (range) fluconazole, itraconazole, posaconazole (prophylaxis), posaconazole (treatment), and voriconazole serum concentrations were 5.64 (0.11-18), 0.57 (0-5.3), 0.31 (0.02-2.5), 0.65 (0.02-2.5), and 0.95 (0.10-5.4) mg/l, respectively. The number of samples in which the recommended pre-dose concentrations were achieved was 98 (54%), 9 (20%), 2 (18%), and 29 (49%) for itraconazole, posaconazole (>0.7 mg/l prophylaxis), posaconazole (treatment), and voriconazole, respectively. No significant differences were detected in the median triazole trough concentrations between patients with proven/probable IFD compared to those with no evidence of IFD. However, itraconazole was not detected in 10 samples (7 patients). The small number of patients who achieved the recommended trough posaconazole concentrations may explain the high rate of break-through IFD observed in patients prescribed this drug. Except for fluconazole, the number of patients prescribed standard doses of triazoles who achieved recommended trough triazole concentrations was low. The prospective use of serum triazole measurements assay may have improved outcomes with itraconazole, posaconazole, and with voriconazole. PMID:27161786

  6. 1,2,3-Triazole-Functionalized Polysulfone Synthesis through Microwave-Assisted Copper-Catalyzed Click Chemistry: A Highly Proton Conducting High Temperature Membrane.

    PubMed

    Sood, Rakhi; Donnadio, Anna; Giancola, Stefano; Kreisz, Aurélien; Jones, Deborah J; Cavaliere, Sara

    2016-07-01

    Microwave heating holds all the aces regarding development of effective and environmentally friendly methods to perform chemical transformations. Coupling the benefits of microwave-enhanced chemistry with highly reliable copper-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry paves the way for a rapid and efficient synthesis procedure to afford high performance thermoplastic materials. We describe herein fast and high yielding synthesis of 1,2,3-triazole-functionalized polysulfone through microwave-assisted CuAAC as well as explore their potential as phosphoric acid doped polymer electrolyte membranes (PEM) for high temperature PEM fuel cells. Polymers with various degrees of substitution of the side-chain functionality of 1,4-substituted 1,2,3-triazole with alkyl and aryl pendant structures are prepared by sequential chloromethylation, azidation, and microwave-assisted CuAAC using a range of alkynes (1-pentyne, 1-nonyne, and phenylacetylene). The completeness of reaction at each step and the purity of the clicked polymers were confirmed by (1)H-(13)C NMR, DOSY-NMR and FTIR-ATR spectroscopies. The thermal and thermochemical properties of the modified polymers were characterized by differential scanning calorimetry and thermogravimetric analysis coupled with mass spectroscopy (TG-MS), respectively. TG-MS analysis demonstrated that the commencement of the thermal degradation takes place with the decomposition of the triazole ring while its substituents have critical influence on the initiation temperature. Polysulfone functionalized with 4-phenyl-1,2,3-triazole demonstrates significantly higher Tg, Td, and elastic modulus than the ones bearing 4-propyl-1,2,3-triazole and 4-heptyl-1,2,3-triazole groups. After doping with phosphoric acid, the functionalized polymers with acid doping level of 5 show promising performance with high proton conductivity in anhydrous conditions (in the range of 27-35 mS/cm) and satisfactorily high elastic modulus (in the range

  7. 9 CFR 412.1 - Label approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    .... Jan. 6, 2014) § 412.1 Label approval. (a) No final label may be used on any product unless the label... for a corporation may submit only one label application for a product produced in other establishments...) The proposed label would not misrepresent the product; (ii) The use of the label would not present...

  8. Supplementing National Menu Labeling

    PubMed Central

    White, Lexi C.

    2012-01-01

    The US Food and Drug Administration’s forthcoming national menu labeling regulations are designed to help curb the national obesity epidemic by requiring calorie counts on restaurants’ menus. However, posted calories can be easily ignored or misunderstood by consumers and fail to accurately describe the healthiness of foods. We propose supplemental models that include nutritional information (e.g., fat, salt, sugar) or specific guidance (e.g., “heart-healthy” graphics). The goal is to empower restaurant patrons with better data to make healthier choices, and ultimately to reduce obesity prevalence. PMID:23078494

  9. Supplementing national menu labeling.

    PubMed

    Hodge, James G; White, Lexi C

    2012-12-01

    The US Food and Drug Administration's forthcoming national menu labeling regulations are designed to help curb the national obesity epidemic by requiring calorie counts on restaurants' menus. However, posted calories can be easily ignored or misunderstood by consumers and fail to accurately describe the healthiness of foods. We propose supplemental models that include nutritional information (e.g., fat, salt, sugar) or specific guidance (e.g., "heart-healthy" graphics). The goal is to empower restaurant patrons with better data to make healthier choices, and ultimately to reduce obesity prevalence. PMID:23078494

  10. Rhodium-catalyzed denitrogenative thioacetalization of N-sulfonyl-1,2,3-triazoles with disulfides: an entry to diverse transformation of terminal alkynes.

    PubMed

    Zhang, Hao; Wang, Hui; Yang, Haijun; Fu, Hua

    2015-06-14

    An efficient and useful rhodium-catalyzed denitrogenative thioacetalization of N-sulfonyl-1,2,3-triazoles has been developed for the first time. The protocol uses readily available N-sulfonyl-1,2,3-triazoles and diaryl disulfides as the starting materials. The corresponding hydrolytic and reductive products with thioacetals were obtained in good to excellent yields, and the reactions were carried out easily under mild conditions with tolerance of some functional groups. Furthermore, the generated thioacetals could be transformed into some useful compounds. Therefore, the present method provides a novel and valuable strategy for the diverse transformation of alkynes. PMID:25927418

  11. Synthesis of triazoles from nonactivated terminal alkynes via the three-component coupling reaction using a Pd(0)-Cu(I) bimetallic catalyst.

    PubMed

    Kamijo, Shin; Jin, Tienan; Huo, Zhibao; Yamamoto, Yoshinori

    2003-07-01

    The synthesis of triazoles via the three-component coupling reaction of unactivated terminal alkynes, allyl carbonate, and trimethylsiyl azide under the Pd(0)-Cu(I) bimetallic catalyst is developed. The reaction most probably proceeds through the formation of a pi-allylpalladium azide complex and a copper-acetylide followed by a successive [3 + 2] cycloaddition. The deallylation of the resulting allyltriazoles proceeds very easily by the Ru-catalyzed isomerization followed by the ozonolysis of the resulting propenyltriazoles to give the triazoles in high yields. PMID:12822981

  12. Mössbauer spectroscopy monitoring the spin transition of a FeII 1D chain with a fluorinated 4-R-1,2,4-triazole

    NASA Astrophysics Data System (ADS)

    Railliet, Antoine P.; Naik, Anil D.; Rotaru, Aurelian; Garcia, Yann

    2014-04-01

    The spin transition properties of [Fe(fletrz)3](BF4)2•2H2O are described. Fletrz (4-(2'-fluoroethyl)-4H-1,2,4-triazole) is a novel fluorine substituted 1,2,4-triazole ligand which forms 1D chain upon self-assembly with FeII ions. This coordination polymer exhibits reversible abrupt thermochromic spin transition that has been probed by SQUID magnetometry, variable temperature 57Fe Mossbauer spectroscopy (77-300 K) and differential scanning calorimetry (100-300 K).

  13. Silver-Free Palladium-Catalyzed sp(3) and sp(2) C-H Alkynylation Promoted by a 1,2,3-Triazole Amine Directing Group.

    PubMed

    Ye, Xiaohan; Xu, Chang; Wojtas, Lukasz; Akhmedov, Novruz G; Chen, Hao; Shi, Xiaodong

    2016-06-17

    Triazole amine was identified as an effective directing group in promoting C-H alkynylation under silver-free conditions. No other external oxidant was required, and the alkynylation products were received in good to excellent yields. X-ray crystallographic analysis confirmed a direct C-H activation intermediate. Other typical directing groups, including pyridine amine (PIP) and 8-aminoquinoline (QA), gave almost no reaction under identical conditions, which highlighted the unique reactivity of the triazole directing group in direct C-H functionalization. PMID:27267908

  14. Triazolines. 14. 1,2,3-Triazolines and triazoles, a new class of anticonvulsants. Drug design and structure-activity relationships.

    PubMed

    Kadaba, P K

    1988-01-01

    Pioneering studies in our laboratories have led to the emergence of the delta 2-1,2,3-triazolines (4,5-dihydro-1H-1,2,3-triazoles) and the closely related 1H-1,2,3-triazoles as a unique family of anticonvulsant agents hitherto unknown. Unlike the traditional anticonvulsants, the dicarboximide moiety is absent from the traiazoline ring system. This paper examines the results of evaluation of several groups of 1-aryl-5-pyridyl-substituted triazolines and triazoles with particular reference to structure-activity relationships in each compound group as well as between compounds in the different groups and the 1,5-diaryl compounds. The Topliss manual approach for application fo the Hansch method is employed for the rational design of triazoline/triazole anticonvulsants. Anticonvulsant activity was determined, after intraperitoneal administration, in two standard seizure models in the mouse, the MES and scMet tests. Central nervous system toxicity was evaluated in the rotorod ataxia test. Analysis of structure-activity relationships using the Topliss scheme indicated a clear pi + sigma dependency in the 1-aryl-5-(4-pyridyl)triazolines while an adverse steric effect (Es) from 4-substitution appeared to be present in the 1-aryl-5-(3-pyridyl) compounds. A similar but strong steric effect dominated the structure-activity pattern of the 1-aryl-5-(4-pyridyl)triazoles, although a sigma dependency was more evident in the 1-aryl-5-(3-pyridyl)- and the 1,5-diaryltriazole series. No significant activity was observed among the 1-aryl-5-(2-pyridyl)triazolines, and although the respective triazoles were active, the parameter dependency was not clearly defined. Similarly, the 1,5-diaryltriazolines, as a group, showed no pronounced anticonvulsant activity. However, replacement of the 5-aryl with a pyridyl group, particularly a 4-pyridyl, led to highly enhanced anticonvulsant activity. In addition, oxidation of triazolines with no anticonvulsant activity yielded, as a rule, triazoles

  15. A New Multicomponent Multicatalyst Reaction (MC)(2)R: Chemoselective Cycloaddition and Latent Catalyst Activation for the Synthesis of Fully Substituted 1,2,3-Triazoles.

    PubMed

    Yamamoto, Kosuke; Bruun, Theodora; Kim, Jung Yun; Zhang, Lei; Lautens, Mark

    2016-06-01

    A multicomponent multicatalyst reaction (MC)(2)R for constructing fully substituted 1,2,3-triazoles is reported. An application of chemoselectivity and latent catalysis in a sequence of multicatalytic reactions confers control over a number of undesired processes, where all of the reagents coexist in the same reaction vessel. The sequence of a chemoselective copper-catalyzed azide alkyne cycloaddition followed by a palladium/copper-catalyzed Sonogashira cross-coupling afforded 1,2,3-triazoles regioselectively with good to high yields and a broad scope. PMID:27213631

  16. Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

    PubMed Central

    Wang, Ding; Xu, Zheng

    2015-01-01

    Summary The Cu(I)-catalyzed azide-alkyne cycloaddition reaction, also known as click chemistry, has become a useful tool for the facile formation of 1,2,3-triazoles. Specifically, the utility of this reaction has been demonstrated by the synthesis of structurally diverse bi- and bis-1,2,3-triazoles. The present review focuses on the synthesis of such bi- and bistriazoles and the importance of using copper-promoted click chemistry (CuAAC) for such transformations. In addition, the application of bitriazoles and the related CuAAAC reaction in different fields, including medicinal chemistry, coordination chemistry, biochemistry, and supramolecular chemistry, have been highlighted. PMID:26734102

  17. One-pot synthesis of 3,4,5-trisubstituted 1,2,4-triazoles via the addition of hydrazides to activated secondary amides.

    PubMed

    Bechara, William S; Khazhieva, Inna S; Rodriguez, Elsa; Charette, André B

    2015-03-01

    A general approach has been developed for the one-pot synthesis of 3,4,5-trisubstituted 1,2,4-triazoles from secondary amides and hydrazides via triflic anhydride activation followed by microwave-induced cyclodehydration. In addition, the 1,2,4-triazole moiety is shown to be a useful directing group for Ru-catalyzed C-H arylation. Access to 1,2,4-triazolophenanthridine can be achieved from the reaction products using a Pd-catalyzed intramolecular C-H functionalization reaction. PMID:25700199

  18. Label and Label-Free Detection Techniques for Protein Microarrays

    PubMed Central

    Syahir, Amir; Usui, Kenji; Tomizaki, Kin-ya; Kajikawa, Kotaro; Mihara, Hisakazu

    2015-01-01

    Protein microarray technology has gone through numerous innovative developments in recent decades. In this review, we focus on the development of protein detection methods embedded in the technology. Early microarrays utilized useful chromophores and versatile biochemical techniques dominated by high-throughput illumination. Recently, the realization of label-free techniques has been greatly advanced by the combination of knowledge in material sciences, computational design and nanofabrication. These rapidly advancing techniques aim to provide data without the intervention of label molecules. Here, we present a brief overview of this remarkable innovation from the perspectives of label and label-free techniques in transducing nano-biological events.

  19. Label scrambling during CID of covalently labeled peptide ions.

    PubMed

    Borotto, Nicholas B; Degraan-Weber, Nicholas; Zhou, Yuping; Vachet, Richard W

    2014-10-01

    Covalent labeling along with mass spectrometry is finding more use as a means of studying the higher order structure of proteins and protein complexes. Diethylpyrocarbonate (DEPC) is an increasingly used reagent for these labeling experiments because it is capable of modifying multiple residues at the same time. Pinpointing DEPC-labeled sites on proteins is typically needed to obtain more resolved structural information, and tandem mass spectrometry after protein proteolysis is often used for this purpose. In this work, we demonstrate that in certain instances, scrambling of the DEPC label from one residue to another can occur during collision-induced dissociation (CID) of labeled peptide ions, resulting in ambiguity in label site identity. From a preliminary study of over 30 labeled peptides, we find that scrambling occurs in about 25% of the peptides and most commonly occurs when histidine residues are labeled. Moreover, this scrambling appears to occur more readily under non-mobile proton conditions, meaning that low charge-state peptide ions are more prone to this reaction. For all peptides, we find that scrambling does not occur during electron transfer dissociation, which suggests that this dissociation technique is a safe alternative to CID for correct label site identification. PMID:25056863

  20. In vivo click reaction between Tc-99m-labeled azadibenzocyclooctyne-MAMA and 2-nitroimidazole-azide for tumor hypoxia targeting.

    PubMed

    Sun, Wenjing; Chu, Taiwei

    2015-10-15

    The bioactivity of nitroimidazole in Tc-99m-labeled 2-nitroimidazole, a traditional solid tumor hypoxia-imaging agent for single photon emission computed tomography (SPECT), is reduced by the presence of large ligand and metallic radionuclide, exhibiting lower tumor-to-nontumor ratios. In an effort to solve this general problem, a pretargeting strategy based on click chemistry (strain-promoted cyclooctyne-azide cycloaddition) was applied. The functional click synthons were synthesized as pretargeting components: an azide group linked to 2-nitroimidazole (2NIM-Az) serves for tumor hypoxia-targeting and azadibenzocyclooctyne conjugated with monoamine monoamide dithiol ligand (AM) functions as radiolabeling and binding group to azides in vivo. 2NIM-triazole-MAMA was obtained from in vitro click reaction with a reaction rate constant of 0.98M(-1)s(-1). AM and 2NIM-triazole-MAMA were radiolabeled with Tc-99m. The hypoxia-pretargeting biodistribution was studied in Kunming mice bearing S180 tumor; (99m)Tc-AM and (99m)Tc-triazole-2NIM were used as blank control and conventional control. Compared to the control groups, the pretargeting experiment exhibits the best radio-uptake and retention in tumor, with higher tumor-to-muscle and tumor-to-blood ratios (up to 8.55 and 1.44 at 8h post-(99m)Tc-complex-injection, respectively). To some extent, the pretargeting strategy protects the bioactivity of nitroimidazole and therefore provides an innovative approach for the development of tumor hypoxia-SPECT imaging agents. PMID:26358160

  1. Cognitive improvements in a mouse model with substituted 1,2,3-triazole agonists for nicotinic acetylcholine receptors.

    PubMed

    Arunrungvichian, Kuntarat; Boonyarat, Chantana; Fokin, Valery V; Taylor, Palmer; Vajragupta, Opa

    2015-08-19

    The α7 nicotinic acetylcholine receptor (nAChR) is a recognized drug target for dementias of aging and certain developmental disorders. Two selective and potent α7-nAChR agonists, winnowed from a list of 43 compounds characterized in a companion article (DOI: 10.1021/acschemneuro.5b00058), 5-((quinuclid-3-yl)-1H-1,2,3-triazol-4-yl)-1H-indole (IND8) and 3-(4-hydroxyphenyl-1,2,3-triazol-1-yl) quinuclidine (QND8), were evaluated for cognitive improvement in both short- and long-term memory. Tacrine, a centrally active acetylcholinesterase inhibitor, and PNU-282987, a congeneric α7 nAChR agonist, were employed as reference standards. Three behavioral tests, modified Y-maze, object recognition test (ORT), and water maze, were performed in scopolamine-induced amnesic mice. Intraperitoneal injection of these two compounds significantly improved the cognitive impairment in a modified Y-maze test (5 μmol/kg for IND8 and 10 μmol/kg for QND8), ORT (10 μmol/kg), and water maze test (25 μmol/kg). For delay induced memory deficit or natural memory loss in mice, IND8 and QND8 at 10 μmol/kg were able to enhance memory comparable to PNU-282987 when evaluated using ORT time delay model. Cognitive enhancement of IND8 and QND8 was mediated through α7-nAChRs as evidenced by its complete abolition after pretreatment with a selective α7-nAChR antagonist, methyllycaconitine. These data demonstrate that IND8 and QND8 and their congeners are potential candidates for treatment of cognitive disorders, and the substituted triazole series formed by cycloaddition of alkynes and azides warrant further preclinical optimization. PMID:25978789

  2. Electrochemical and photophysical properties of new triazole-bridged heterobimetallic ruthenium-rhodium and ruthenium-iridium complexes

    SciTech Connect

    Diemen, J.H. van; Hage, R.; Haasnoot, J.G.; Lempers, H.E.B.; Reedijk, J. ); Vos, J.G. ); Cola, L. de; Barigelletti, F.; Balzani, V. )

    1992-08-19

    The synthesis, characterization, and the electrochemical and photophysical properties of ((bpy){sub 2}Ru{sup II}(bpt)Rh{sup III}(ppy){sub 2}){sup 2+}, ((bpy){sub 2}Ru{sup II}(bpt)Ir{sup III}(ppy){sub 2}){sup 2+}, ((Rh{sup III}(ppy){sub 2}){sub 2}(bpt)){sup +}, and ((Ir{sup III}(ppy){sub 2}){sub 2}(bpt)){sup +} are reported (Hppy = 2-phenylpyridine; bpy = 2,2{prime}-bipyridine, Hbpt = 3,5-bis(pyridin-2-yl)-1,2,4-triazole). The Ru(bpy){sub 2} moiety is bound via N1 of the triazole ring, while the M(ppy){sub 2} center (M = Rh or Ir) is coordinated via the N4 of the triazole ring. The electrochemical measurements show that in the mixed-metal complexes the first oxidized metal is Ru and the first reduced ligand is bpy. The homobimetallic Ir and Rh complexes exhibit a bpt{sup {minus}}-based reduction. The absorption spectra of the mixed-metal complexes exhibit both Ru {yields} bpy and M {yields} ppy{sup {minus}} transitions. The energies of these transitions are different from those of their homobimetallic analogs. The emission observed for ((Rh(ppy){sub 2}){sub 2}-(bpt)){sup +} at 77 K corresponds to a ligand-centered excited state, while for the analogous iridium complex a charge-transfer emission, which involves the bpt{sup {minus}} ligand, is observed. In the mixed-metal complexes efficient energy transfer occurs from higher energy excited states centered on the M(ppy){sub 2} component to the lowest energy excited state, which is a metal-to-ligand charge transfer level localized on the Ru(bpy){sub 2} component.

  3. Cd(II) complexes with different nuclearity and dimensionality based on 3-hydrazino-4-amino-1,2,4-triazole

    SciTech Connect

    Xu, Cai-Xia; Zhang, Jian-Guo Yin, Xin; Jin, Xin; Li, Tong; Zhang, Tong-Lai; Zhou, Zun-Ning

    2015-03-15

    A series of zero- to two-dimensional Cd(II) coordination compounds have been synthesized by the reaction of Cd(II) salts and 3-hydrazino-4-amino-1,2,4-triazole di-hydrochloride (HATr·2HCl). [CdCl{sub 2}(HATr){sub 2}] (1) and [Cd{sub 2}Cl{sub 4}(HATr){sub 2}(H{sub 2}O){sub 2}] (2) have discrete mononuclear and binuclear structures, respectively. [Cd(HATr){sub 2}(ClO{sub 4}){sub 2}]{sub n} (3) presents polymeric 1-D chain and [Cd{sub 2}(NO{sub 3}){sub 2}Cl{sub 2}(HATr){sub 2}]{sub n} (4) shows 2-D frameworks. All Cd(II) ions exhibit distorted octahedral configurations in 1–3, whilst both hexa and heptacoordinated Cd(II) are formed in 4. The HATr ligands adopt chelating coordinated mode in 1, while tri-dentate bridging–chelating mode in 2–4. The chloride ion is a mono-coordinated ligand in 1 and 2, but it bridges two adjacent metal ions in 4. Furthermore, thermal behaviors have been investigated and the results reveal that all complexes have good thermal stability. The impact sensitivity test indicates that complex 3 is sensitive to impact stimuli. - Graphical abstract: Four Cd(II) complexes based on 3-hydrazino-4-amino-1,2,4-triazole ligands exhibit diverse structures from mononuclear to 2D networks. - Highlights: • Cd(II) complexes containing 3-hydrazino-4-amino-1,2,4-triazole ligands. • Mononuclear, binuclear, 1-D and 2-D structures. • Good thermal stability. • Thermal decomposition kinetics.

  4. High prevalence of clinical and environmental triazole-resistant Aspergillus fumigatus in Iran: is it a challenging issue?

    PubMed

    Nabili, Mojtaba; Shokohi, Tahereh; Moazeni, Maryam; Khodavaisy, Sadegh; Aliyali, Masoud; Badiee, Parisa; Zarrinfar, Hossein; Hagen, Ferry; Badali, Hamid

    2016-06-01

    Triazole antifungal agents are the mainstay of aspergillosis treatment. As highlighted in numerous studies, the global increase in the prevalence of triazole resistance could hamper the management of aspergillosis. In the present three-year study, 513 samples (213 clinical and 300 environmental samples) from 10 provinces of Iran were processed and screened in terms of azole resistance (4 and 1 mg l-1 of itraconazole and voriconazole, respectively), using selective plates. Overall, 150 A. fumigatus isolates (71 clinical and 79 environmental isolates) were detected. The isolates were confirmed by partial sequencing of the β-tubulin gene. Afterwards, in vitro antifungal susceptibility tests against triazole agents were performed, based on the Clinical and Laboratory Standards Institute (CLSI) M38-A2 document. The CYP51A gene was sequenced in order to detect mutations. The MIC of itraconazole against 10 (6.6 %) strains, including clinical (n=3, 4.2 %) and environmental (n=7, 8.8 %) strains, was higher than the breakpoint and epidemiological cut-off value. Based on the findings, the prevalence of azole-resistant A. fumigatus in Iran has increased remarkablyfrom 3.3 % to 6.6 % in comparison with earlier epidemiological research. Among resistant isolates, TR34/L98H mutations in the CYP51A gene were the most prevalent (n=8, 80 %), whereas other point mutations (F46Y, G54W, Y121F, G138C, M172V, F219C, M220I, D255E, T289F, G432C and G448S mutations) were not detected. Although the number of patients affected by azole-resistant A. fumigatus isolates was limited, strict supervision of clinical azole-resistant A. fumigatus isolates and persistent environmental screening of azole resistance are vital to the development of approaches for the management of azole resistance in human pathogenic fungi. PMID:27008655

  5. Synthesis and spectral characterization of bis(4-amino-5-mercapto-1,2,4-triazol-3-yl)propane

    NASA Astrophysics Data System (ADS)

    Subashchandrabose, S.; Thanikachalam, V.; Manikandan, G.; Saleem, H.; Erdogdu, Y.

    2016-03-01

    Bis(4-amino-5-mercapto-1,2,4-triazol-3-yl)propane (BAMTP) was synthesized and characterized by FT-IR and FT-Raman spectra. Gas phase structure of BAMTP was examined under density functional theory B3LYP/6-311 ++G(d, p) level of basis set, wherein the molecule was subjected to conformational analysis. Thus the identified stable structure utilized for the calculations such as geometry optimization, vibrational behavior, hyperpolarizability analysis, natural bond orbital analysis, band gap, chemical hard/softness and stability. Geometry of BAMTP has been discussed elaborately with related crystal data. The results found from experimental and theoretical methods were reported herewith.

  6. Synthesis of L-rhamnose derived chiral bicyclic triazoles as novel sodium-glucose transporter (SGLT) inhibitors.

    PubMed

    Putapatri, Siddamal Reddy; Kanwal, Abhinav; Sridhar, Balasubramanian; Banerjee, Sanjay K; Kantevari, Srinivas

    2014-11-14

    Herein we describe the synthesis of a series of novel fused bicyclic 1,2,3-triazoles from commercially available, natural deoxy sugar, L-rhamnose. The key reactions involved are (i) Zn(OTf)2 catalyzed enantioselective alkynylation of L-rhamnose derived azidoaldehyde and (ii) deprotection of the acid sensitive 1,2-isopropylidene group followed by in situ intramolecular click-cycloaddition of azidoalkynols. Some compounds exhibit excellent sodium-glucose transporter (SGLT1 and SGLT2) inhibition activity. PMID:25175761

  7. A single-step acid catalyzed reaction for rapid assembly of NH-1,2,3-triazoles.

    PubMed

    Thomas, Joice; Jana, Sampad; Liekens, Sandra; Dehaen, Wim

    2016-07-28

    NH-1,2,3-Triazole moieties are a part of the design of various biologically active compounds, pharmaceutical agents and functional materials. Unfortunately, the applications of this heterocycle are still underexplored due to the lack of a general synthetic protocol. Here we outline a novel, general and facile metal-free pathway that enables the direct synthesis of these heterocycles by combining readily accessible and abundant precursors such as enolizable ketones and NH4OAc with high levels of regioselectivity via an organocascade process. The developed chemistry has been successfully applied to the synthesis of several structurally diverse products, pharmaceutical agents and supramolecular receptors. PMID:27353974

  8. Synthesis and Some Reactions of 1-aryl-4-acetyl-5-methyl-1,2,3-triazole Derivatives with Anticonvulsant Activity.

    PubMed

    Nassar, Ekhlass M; Abdelrazek, Fathy M; Ayyad, Rezk R; El-Farargy, Ahmed F

    2016-01-01

    The triazoles 3a-d underwent condensation reactions with 4-(piperidin-1-yl)-benzaldehyde to afford the chalcones 5a-d. Chalcone derivatives 5a-d were reacted with 2,3-diaminomaleonitrile, thiourea and hydrazine hydrate to afford the novel diazepine-dicarbonitrile derivatives 7a-d, the pyrimidine-2-thiol derivatives 9a-d and hydrazino-pyrimidines 10a-d respectively. Structures of the prepared compounds were elucidated by physical and spectral data like FT-IR, (1)H NMR, (13)C NMR, and mass spectroscopy. Some of the synthesized compounds were screened for their anticonvulsant activity and SAR. PMID:26776225

  9. 2-[4-(1H-1,2,4-Triazol-1-yl)phen­yl]-1H-benzimidazole

    PubMed Central

    Cheng, Long-Huai; Zheng, Zheng; Han, Zhi-Li; Wu, Zhi-Chao; Zhou, Hong-Ping

    2012-01-01

    In the title compound, C15H11N5, the benzimidazole ring system is nearly planar [maximum deviation = 0.039 (2) Å], and is oriented at a dihedral angle of 28.85 (10)° with respect to the benzene ring; the dihedral angle between the triazole and benzene rings is 17.30 (15)°. In the crystal N—H⋯N hydrogen bonds link the mol­ecules into chains. Weak C—H⋯N inter­actions are also present. PMID:23125686

  10. Co-Labeling for Multi-View Weakly Labeled Learning.

    PubMed

    Xu, Xinxing; Li, Wen; Xu, Dong; Tsang, Ivor W

    2016-06-01

    It is often expensive and time consuming to collect labeled training samples in many real-world applications. To reduce human effort on annotating training samples, many machine learning techniques (e.g., semi-supervised learning (SSL), multi-instance learning (MIL), etc.) have been studied to exploit weakly labeled training samples. Meanwhile, when the training data is represented with multiple types of features, many multi-view learning methods have shown that classifiers trained on different views can help each other to better utilize the unlabeled training samples for the SSL task. In this paper, we study a new learning problem called multi-view weakly labeled learning, in which we aim to develop a unified approach to learn robust classifiers by effectively utilizing different types of weakly labeled multi-view data from a broad range of tasks including SSL, MIL and relative outlier detection (ROD). We propose an effective approach called co-labeling to solve the multi-view weakly labeled learning problem. Specifically, we model the learning problem on each view as a weakly labeled learning problem, which aims to learn an optimal classifier from a set of pseudo-label vectors generated by using the classifiers trained from other views. Unlike traditional co-training approaches using a single pseudo-label vector for training each classifier, our co-labeling approach explores different strategies to utilize the predictions from different views, biases and iterations for generating the pseudo-label vectors, making our approach more robust for real-world applications. Moreover, to further improve the weakly labeled learning on each view, we also exploit the inherent group structure in the pseudo-label vectors generated from different strategies, which leads to a new multi-layer multiple kernel learning problem. Promising results for text-based image retrieval on the NUS-WIDE dataset as well as news classification and text categorization on several real-world multi

  11. [(18)F]Fluoroethyl Triazole Substituted PSMA Inhibitor Exhibiting Rapid Normal Organ Clearance.

    PubMed

    Chen, Ying; Lisok, Ala; Chatterjee, Samit; Wharram, Bryan; Pullambhatla, Mrudula; Wang, Yuchuan; Sgouros, George; Mease, Ronnie C; Pomper, Martin G

    2016-07-20

    Prostate-specific membrane antigen (PSMA) is overexpressed in the epithelium of prostate cancer and nonprostate solid tumor neovasculature. PSMA is increasingly utilized as a target for cancer imaging and therapy. Here, we report the synthesis and in vivo biodistribution of a low-molecular-weight PSMA-based imaging agent, 2-[3-(1-carboxy-5-{3-[1-(2-[(18)F]fluoroethyl)-1H-1,2,3-triazol-yl]propanamido}pentyl)ureido]pentanedioic acid ([(18)F]YC-88), containing an [(18)F]fluoroethyl triazole moiety. [(18)F]YC-88 was synthesized from 2-[(18)F]fluoroethyl azide and the corresponding alkyne precursor in two steps using either a one- or two-pot procedure. Biodistribution and positron emission tomography (PET) imaging were performed in immunocompromised mice using isogenic PSMA(+) PC3 PIP and PSMA(-) PC3 flu xenografts. YC-88 exhibited high affinity for PSMA as evidenced by a Ki value of 12.9 nM. The non-decay corrected radiochemical yields of [(18)F]YC-88 averaged 14 ± 1% (n = 5). Specific radioactivities ranged from 320 to 2,460 Ci/mmol (12-91 GBq/μmol) with an average of 940 Ci/mmol (35 GBq/μmol, n = 5). In an immunocompromised mouse model, [(18)F]YC-88 clearly delineated PSMA(+) PC3 PIP prostate tumor xenografts on imaging with PET. At 1 h postinjection, 47.58 ± 5.19% injected dose per gram of tissue (% ID/g) was evident within the PSMA(+) PC3 PIP tumor, with a ratio of 170:1 of uptake within PSMA(+) PC3 PIP to PSMA(-) PC3 flu tumor placed in the opposite flank. The tumor-to-kidney ratio at 2 h postinjection was 4:1. At or after 30 min postinjection, minimal nontarget tissue uptake of [(18)F]YC-88 was observed. Compared to [(18)F]DCFPyL, which is currently in clinical trials, the uptake of [(18)F]YC-88 within the kidney, liver, and spleen was significantly lower at all time-points studied. At 30 min and 1 h postinjection, salivary gland uptake of [(18)F]YC-88 was significantly less than that of [(18)F]DCFPyL. [(18)F]YC-88 is a new PSMA-targeted PET agent synthesized

  12. 76 FR 75809 - Prior Label Approval System: Generic Label Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-05

    ... limited types of labels (e.g., labels for raw, single ingredient meat and poultry products) (48 FR 11410... poultry products will take effect January 1, 2012 (75 FR 82148, Dec. 29, 2010). These mandatory features... Agency. On March 25, 1992, FSIS published an Advance Notice of Proposed Rulemaking (ANPRM) (57 FR...

  13. Laser labeling, a safe technology to label produce

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Laser labeling of fruits and vegetables is an alternative means to label produce. Low energy CO2 laser beams etch the surface showing the contrasting underlying layer. These etched surfaces can promote water loss and potentially allow for entry of decay organisms. The long-term effects of laser labe...

  14. Laser labeling, a safe technology to label produce

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Labeling of the produce has gained marked attention in recent years. Laser labeling technology involves the etching of required information on the surface using a low energy CO2 laser beam. The etching forms alphanumerical characters by pinhole dot matrix depressions. These openings can lead to wat...

  15. 78 FR 66826 - Prior Label Approval System: Generic Label Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... the Agency (76 FR 75809). FSIS also proposed to combine the regulations that provide for the approval... preamble (76 FR 75814), FSIS wrote: . . . statements on labels that are defined in FSIS's regulations or... ``Product Labeling: Definition of the Term ``Natural'' and related materials (71 FR 70503, Dec. 5, 2006)...

  16. Labeled Cocaine Analogs

    DOEpatents

    Goodman, Mark M.; Shi, Bing Zhi; Keil, Robert N.

    1999-03-30

    Novel methods for positron emission tomography or single photon emission spectroscopy using tracer compounds having the structure: ##STR1## where X in .beta. configuration is phenyl, naphthyl; 2,3 or 4-iodophenyl; 2,3 or 4-(trimethylsilyl)phenyl; 3,4,5 or 6-iodonaphthyl; 3,4,5 or 6-(trimethylsilyl)naphthyl; 2,3 or 4-(trialkylstannyl)phenyl; or 3,4,5 or 6-(trialkylstannyl)napthyl Y in .beta. configuration is 2-fluoroethoxy, 3-fluoropropoxy, 4-fluorobutoxy, 2-fluorocyclopropoxy, 2 or 3-fluorocyclobutoxy, R,S 1'-fluoroisopropoxy, R 1'-fluoroisopropoxy, S 1'-fluoroisopropoxy, 1',3'-difluoroisopropoxy, R,S 1'-fluoroisobutoxy, R 1'-fluoroisobutoxy, S 1'-fluoroisobutoxy, R,S 4'-fluoroisobutoxy, R 4'-fluoroisobutoxy, S 4'-fluoroisobutoxy, or 1',1'-di(fluoromethyl)isobutoxy, The compounds bind dopamine transporter protein and can be labeled with .sup.18 F or .sup.123 I for imaging.

  17. The electronic states of 1,2,4-triazoles: A study of 1H- and 1-methyl-1,2,4-triazole by vacuum ultraviolet photoabsorption and ultraviolet photoelectron spectroscopy and a comparison with ab initio configuration interaction computations

    NASA Astrophysics Data System (ADS)

    Palmer, Michael H.; Camp, Philip J.; Hoffmann, Søren Vrønning; Jones, Nykola C.; Head, Ashley R.; Lichtenberger, Dennis L.

    2012-03-01

    The first vacuum ultraviolet absorption spectrum of a 1,2,4-triazole has been obtained and analyzed in detail, with assistance from both an enhanced UV photoelectron spectroscopic study and ab initio multi-reference multi-root configuration interaction procedures. For both 1H- and 1-methyl-1,2,4-triazoles, the first ionization energy bands show complex vibrational structure on the low-energy edges of otherwise unstructured bands. Detailed analysis of these bands confirms the presence of three ionized states. The 6-7 eV VUV spectral region shows an unusual absorption plateau, which is interpreted in terms of the near degeneracy of the first two ionization energies, leading to a pseudo Jahn-Teller effect. The "fingerprint" of the ionization spectrum yields band origins for several Rydberg states. The configuration interaction study shows that although the equilibrium structure for the first cation is effectively planar, the second cation shows significant twisting of the ring system. Some calculated singlet electronic states also show skeletal twisting in which the ring C-H is substantially out of plane.

  18. Synthesis of thin film containing 4-amino-1,2,4-triazole iron(II) complexes

    NASA Astrophysics Data System (ADS)

    Onggo, Djulia

    2014-03-01

    The Iron(II) complex with 4-amino-1,2,4 triazole (NH2-trz) ligand has potential applications as smart material since the compounds show a distinct color change from lilac at low temperature to colorless at high temperature. The lilac color of the complex represent the diamagnetic low spin state while the colorless correspond to the paramagnetic high spin state of iron(II). The transition between the two states could be tuned by changing the anionic group. Generally, the complex was synthesized directly from aqueous solution of iron(II) salt with considerable amounts of NH2-trz solution produced solid powder compound. For application as an electronic molecular device, the complex should be obtained as a thin film. The transparent [Fe(NH2trz)3]-Nafion film has been successfully obtained, however, no anion variation can be produced since the nafion is an anionic resin. In this work, the [Fe(NH2trz)3]-complexes with several anions have been synthesized inside nata de coco membrane that commonly used as a medium for deposition metal nano-particles. After drying the membrane containing the complex became a thin film. At room temperature, the film containing iron(II) complexes of sulphate and nitrate salts show lilac color, similar to that of the original complexes in the powder form. On heating, the color of the complex film changed to colorless and this color change was observed reversibly. In contrast, the films containing perchlorate and tetrafluoroborate iron(II) complexes are colorless at room temperature and changed to lilac on cooling. The significant color changing of the iron(II)complexes in the nata de coco film can be used for demonstration thermo chromic effect of smart materials with relatively small amount of the compounds.

  19. Synthesis and biological evaluation of novel tamoxifen-1,2,4-triazole conjugates.

    PubMed

    Murty, M S R; Katiki, Mohana Rao; Nanubolu, Jagadeesh Babu; Garimella, Srujana; Polepalli, Sowjanya; Jain, Nishant; Buddana, Sudheer Kumar; Prakasham, R S

    2016-08-01

    A new class of compounds, structurally related to the breast cancer drug tamoxifen, was designed and synthesized. The McMurry coupling reaction was used as the key synthetic step in the preparation of these analogs, and the structural assignments were made on the basis of [Formula: see text] NMR, [Formula: see text] NMR, and HRMS studies. The absolute stereochemistry of E and Z isomers was unambiguously confirmed by a single-crystal X-ray diffraction analysis. Water was found to be an inexpensive nontoxic and effective medium for the C-N bond formation. Utilizing this protocol, various tamoxifen derivatives were synthesized in good yields. Environmental acceptability, low cost, and high yields are the important features of this protocol. These compounds were evaluated for their antiproliferative activity on five human tumor cell lines. Compound 4p ([Formula: see text]) showed improved antiproliferative activity against breast cancer cell line (MDA-MB-231) compared to tamoxifen ([Formula: see text]), while the compound 4o ([Formula: see text]) exhibited similar activity against SiHa compared to the reference drug, tamoxifen ([Formula: see text]). In addition, these analogs were investigated for their antibacterial activity against six bacterial strains. Preliminary results indicate that some of the newly synthesized title compounds exhibited promising antibacterial activity compared with the standard drug, vancomycin. A new class of compounds were designed rationally by the replacement of a ethyl group in tamoxifen with a methylene (1H-1,2,4-triazole) group. The absolute stereochemistry of E and Z isomers were unambiguously confirmed by a single-crystal X-ray diffraction analysis. The title compounds were evaluated for their antiproliferative and antibacterial activities. PMID:27278444

  20. Disulfide Sensitivity in the Env Protein Underlies Lytic Inactivation of HIV-1 by Peptide Triazole Thiols.

    PubMed

    Bailey, Lauren D; Kalyana Sundaram, Ramalingam Venkat; Li, Huiyuan; Duffy, Caitlin; Aneja, Rachna; Rosemary Bastian, Arangassery; Holmes, Andrew P; Kamanna, Kantharaju; Rashad, Adel A; Chaiken, Irwin

    2015-12-18

    We investigated the mode of action underlying lytic inactivation of HIV-1 virions by peptide triazole thiol (PTT), in particular the relationship between gp120 disulfides and the C-terminal cysteine-SH required for virolysis. Obligate PTT dimer obtained by PTT SH cross-linking and PTTs with serially truncated linkers between pharmacophore isoleucine-ferrocenyltriazole-proline-tryptophan and cysteine-SH were synthesized. PTT variants showed loss of lytic activity but not binding and infection inhibition upon SH blockade. A disproportionate loss of lysis activity vs binding and infection inhibition was observed upon linker truncation. Molecular docking of PTT onto gp120 argued that, with sufficient linker length, the peptide SH could approach and disrupt several alternative gp120 disulfides. Inhibition of lysis by gp120 mAb 2G12, which binds at the base of the V3 loop, as well as disulfide mutational effects, argued that PTT-induced disruption of the gp120 disulfide cluster at the base of the V3 loop is an important step in lytic inactivation of HIV-1. Further, PTT-induced lysis was enhanced after treating virus with reducing agents dithiothreitol and tris (2-carboxyethyl)phosphine. Overall, the results are consistent with the view that the binding of PTT positions the peptide SH group to interfere with conserved disulfides clustered proximal to the CD4 binding site in gp120, leading to disulfide exchange in gp120 and possibly gp41, rearrangement of the Env spike, and ultimately disruption of the viral membrane. The dependence of lysis activity on thiol-disulfide interaction may be related to intrinsic disulfide exchange susceptibility in gp120 that has been reported previously to play a role in HIV-1 cell infection. PMID:26458166

  1. Design, synthesis and biological evaluation of chalconyl blended triazole allied organosilatranes as giardicidal and trichomonacidal agents.

    PubMed

    Singh, Gurjaspreet; Arora, Aanchal; Mangat, Satinderpal Singh; Rani, Sunita; Kaur, Hargobinder; Goyal, Kapil; Sehgal, Rakesh; Maurya, Indresh Kumar; Tewari, Rupinder; Choquesillo-Lazarte, Duane; Sahoo, Subash; Kaur, Navneet

    2016-01-27

    A series of chalconyl blended triazole allied silatranes (7a-g/8a-g/9a-g) were synthesized in good yields using a simple, economical and biocompatible synthetic route. The blend of three different pharmacologically active moieties into a single scaffold resulted into synergistic effect in their bio-activity. Various substitutions were tried to study the structure activity relationship (SAR) of the synthesized compounds on the basis of biological results. All the newly synthesized compounds were well characterized by IR, (1)H and (13)C NMR, low resolution mass spectroscopy and elemental analysis. The structures of 7a and 7c were authenticated by single crystal X-ray crystallography. These compounds were screened by using Molinspiration software for their physicochemical properties and all the compounds showed good oral bioavailability. The antiparasitic activity of the newly synthesized compounds was evaluated against unicellular parasites (Giardia lamblia and Trichomonas vaginalis) in comparison to standard drug (metronidazole) by 3-(4,5-dimethylthiazol-yl)-diphenyl tetrazolium bromide (MTT) assay. All the compounds displayed significant activity against G. lamblia and T. vaginalis with IC50 values ranging from 19.58-131.2 μM to 18.24-101.26 μM respectively. The entire library of compounds was found to be more active than metronidazole except 9a, 9f and 9g. Notably, 9e and 7e were found to be most significant against G. lamblia and T. vaginalis respectively. PMID:26695730

  2. Synthesis of thin film containing 4-amino-1,2,4-triazole iron(II) complexes

    SciTech Connect

    Onggo, Djulia

    2014-03-24

    The Iron(II) complex with 4-amino-1,2,4 triazole (NH{sub 2}-trz) ligand has potential applications as smart material since the compounds show a distinct color change from lilac at low temperature to colorless at high temperature. The lilac color of the complex represent the diamagnetic low spin state while the colorless correspond to the paramagnetic high spin state of iron(II). The transition between the two states could be tuned by changing the anionic group. Generally, the complex was synthesized directly from aqueous solution of iron(II) salt with considerable amounts of NH{sub 2}-trz solution produced solid powder compound. For application as an electronic molecular device, the complex should be obtained as a thin film. The transparent [Fe(NH{sub 2}trz){sub 3}]-Nafion film has been successfully obtained, however, no anion variation can be produced since the nafion is an anionic resin. In this work, the [Fe(NH{sub 2}trz){sub 3}]-complexes with several anions have been synthesized inside nata de coco membrane that commonly used as a medium for deposition metal nano-particles. After drying the membrane containing the complex became a thin film. At room temperature, the film containing iron(II) complexes of sulphate and nitrate salts show lilac color, similar to that of the original complexes in the powder form. On heating, the color of the complex film changed to colorless and this color change was observed reversibly. In contrast, the films containing perchlorate and tetrafluoroborate iron(II) complexes are colorless at room temperature and changed to lilac on cooling. The significant color changing of the iron(II)complexes in the nata de coco film can be used for demonstration thermo chromic effect of smart materials with relatively small amount of the compounds.

  3. Determination of D-serine in human serum by LC-MS/MS using a triazole-bonded column after pre-column derivatization with (S)-4-(3-isothiocyanatopyrrolidin-1-yl)-7- (N, N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole.

    PubMed

    Sakamoto, Tatsuya; Kuwabara, Ryousuke; Takahashi, Shuhei; Onozato, Mayu; Ichiba, Hideaki; Iizuka, Hideaki; Fukushima, Takeshi

    2016-01-01

    An LC-MS/MS-based method for determining D-serine (Ser), an endogenous co-agonist of the N-methyl-D-aspartate receptor, in human serum, was developed and validated using a triazole-bonded silica-packed column after pre-column fluorescence derivatization with a chiral labeling reagent, (S)-4-(3-isothiocyanatopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole. Enantiomeric separation of the D- and L-Ser derivatives occurred in the triazole-bonded column (R s: 1.85) with CH3CN/100 mM HCO2NH4 in H2O (95.5:4.5) as the mobile phase with isocratic elution. The ln(capacity factor of D-Ser) in the van't Hoff plot gradually decreased with the inverse of temperature, suggesting enhanced hydrophilic interactions with the triazole-bonded stationary phase with increasing column temperature, owing to decrease in the partition coefficient to the mobile phase. Multiple reaction monitoring (m/z 457.10 > 409.00) by triple quadrupole mass spectrometry was used for quantifying D-Ser in human serum. The presence of D-Ser in the serum was confirmed by treatment with commercial D-amino acid oxidase. A linear calibration curve was constructed in the D-Ser concentration range of 0.5-5.0 μM (r (2) = 0.999, n = 3) using D-homoserine as the internal standard. The precision and recovery values were adequate for quantification. The detection limit for D-Ser was 1.1 fmol/injection (signal-to-noise ratio = 3), owing to the high CH3CN content in the mobile phase. The proposed LC-MS/MS method showed few fluctuations in the retention times of D- and L-Ser, and R s was stable until the 40th injection of serum without column washing, and thus can be useful for D-Ser determination in human serum in clinical research. PMID:26542833

  4. Structure-Based Design of 3-(4-Aryl-1H-1,2,3-triazol-1-yl)-Biphenyl Derivatives as P2Y14 Receptor Antagonists.

    PubMed

    Junker, Anna; Balasubramanian, Ramachandran; Ciancetta, Antonella; Uliassi, Elisa; Kiselev, Evgeny; Martiriggiano, Chiara; Trujillo, Kevin; Mtchedlidze, Giorgi; Birdwell, Leah; Brown, Kyle A; Harden, T Kendall; Jacobson, Kenneth A

    2016-07-14

    UDP and UDP-glucose activate the P2Y14 receptor (P2Y14R) to modulate processes related to inflammation, diabetes, and asthma. A computational pipeline suggested alternatives to naphthalene of a previously reported P2Y14R antagonist (3, PPTN) using docking and molecular dynamics simulations on a hP2Y14R homology model based on P2Y12R structures. By reevaluating the binding of 3 to P2Y14R computationally, two alternatives, i.e., alkynyl and triazolyl derivatives, were identified. Improved synthesis of fluorescent antagonist 4 enabled affinity quantification (IC50s, nM) using flow cytometry of P2Y14R-expressing CHO cells. p-F3C-phenyl-triazole 65 (32) was more potent than a corresponding alkyne 11. Thus, additional triazolyl derivatives were prepared, as guided by docking simulations, with nonpolar aryl substituents favored. Although triazoles were less potent than 3 (6), simpler synthesis facilitated further structural optimization. Additionally, relative P2Y14R affinities agreed with predicted binding of alkynyl and triazole analogues. These triazoles, designed through a structure-based approach, can be assessed in disease models. PMID:27331270

  5. Synthesis and in vitro pharmacological evaluation of N-[(1-benzyl-1,2,3-triazol-4-yl)methyl]-carboxamides on d-secoestrone scaffolds.

    PubMed

    Szabó, Johanna; Bacsa, Ildikó; Wölfling, János; Schneider, Gyula; Zupkó, István; Varga, Mónika; Herman, Bianka E; Kalmár, László; Szécsi, Mihály; Mernyák, Erzsébet

    2016-08-01

    An efficient synthesis of several N-[(1-benzyl-1,2,3-triazol-4-yl)methyl]carboxamides in the 13β- and 13α-d-secoestrone series is reported. Novel triazoles were synthesized via the Cu(I)-catalyzed azide-alkyne cycloaddition of steroidal alkynyl carboxamides and p-substituted benzyl azides. Each of the products was evaluated in vitro by means of MTT assays for antiproliferative activity against a panel of human adherent cancer cell lines (HeLa, MCF-7, A431 and A2780). Some of them exhibited activities similar to those of the reference agent cisplatin. On change of the substitution pattern of the benzyl group of the azide, great differences in the cell growth-inhibitory properties were observed. The p-alkylbenzyl-substituted triazoles selectively exerted high cytostatic action against A2780 cells, with IC50 values of 1 µM. We investigated the potential inhibitory action exerted on the human 17β-HSD1 activity of the new secosteroids. Three triazoles effectively suppressed the estrone to 17β-estradiol conversion with IC50 values in low micromolar range. PMID:26360618

  6. Structure-Based Design of 3-(4-Aryl-1H-1,2,3-triazol-1-yl)-Biphenyl Derivatives as P2Y14 Receptor Antagonists

    PubMed Central

    2016-01-01

    UDP and UDP-glucose activate the P2Y14 receptor (P2Y14R) to modulate processes related to inflammation, diabetes, and asthma. A computational pipeline suggested alternatives to naphthalene of a previously reported P2Y14R antagonist (3, PPTN) using docking and molecular dynamics simulations on a hP2Y14R homology model based on P2Y12R structures. By reevaluating the binding of 3 to P2Y14R computationally, two alternatives, i.e., alkynyl and triazolyl derivatives, were identified. Improved synthesis of fluorescent antagonist 4 enabled affinity quantification (IC50s, nM) using flow cytometry of P2Y14R-expressing CHO cells. p-F3C-phenyl-triazole 65 (32) was more potent than a corresponding alkyne 11. Thus, additional triazolyl derivatives were prepared, as guided by docking simulations, with nonpolar aryl substituents favored. Although triazoles were less potent than 3 (6), simpler synthesis facilitated further structural optimization. Additionally, relative P2Y14R affinities agreed with predicted binding of alkynyl and triazole analogues. These triazoles, designed through a structure-based approach, can be assessed in disease models. PMID:27331270

  7. Rational design and synthesis of novel dibenzo[b,d]furan-1,2,3-triazole conjugates as potent inhibitors of Mycobacterium tuberculosis.

    PubMed

    Yempala, Thirumal; Sridevi, Jonnalagadda Padma; Yogeeswari, Perumal; Sriram, Dharmarajan; Kantevari, Srinivas

    2014-01-01

    A series of novel dibenzo[b,d]furan-1,2,3-triazole conjugates, rationally designed by reorientation of dibenzo[b,d]furan pharmacophore and alkyl/aryl groups appended on 1,2,3-triazole core, were synthesized using click chemistry. The required key intermediate, 2-ethynyl dibenzo[b,d]furan 3 was prepared from dibenzofuran-2-carboxaldehyde using Corey-Fuchs reaction. Further reaction of 3 with various alkyl/aryl azides in the presence of copper catalyst produced 1,2,3-triazole conjugates in excellent yields. Evaluation of all the new compounds for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC27294), resulted 5a (MIC: 1.56 μg/mL), 5d (MIC: 0.78 μg/mL) and 5f (MIC: 0.78 μg/mL) as promising lead analogues. Among these three compounds, 1-(4-bromobenzyl)-4-(dibenzo[b,d]furan-2-yl)-1H-1,2,3-triazole (5f) emerged as the most promising antitubercular agent with lowest cytotoxicity (selectivity index: ≫25) against the HEK-293T cell line. PMID:24292337

  8. MS/MS Digital Readout: Analysis of Binary Information Encoded in the Monomer Sequences of Poly(triazole amide)s.

    PubMed

    Amalian, Jean-Arthur; Trinh, Thanh Tam; Lutz, Jean-François; Charles, Laurence

    2016-04-01

    Tandem mass spectrometry was evaluated as a reliable sequencing methodology to read codes encrypted in monodisperse sequence-coded oligo(triazole amide)s. The studied oligomers were composed of monomers containing a triazole ring, a short ethylene oxide segment, and an amide group as well as a short alkyl chain (propyl or isobutyl) which defined the 0/1 molecular binary code. Using electrospray ionization, oligo(triazole amide)s were best ionized as protonated molecules and were observed to adopt a single charge state, suggesting that adducted protons were located on every other monomer unit. Upon collisional activation, cleavages of the amide bond and of one ether bond were observed to proceed in each monomer, yielding two sets of complementary product ions. Distribution of protons over the precursor structure was found to remain unchanged upon activation, allowing charge state to be anticipated for product ions in the four series and hence facilitating their assignment for a straightforward characterization of any encoded oligo(triazole amide)s. PMID:26950162

  9. SOT 2008- TRANSCRIPTIONAL RESPONSES IN THYROID TISSUES FROM RATS TREATED WITH A TUMORIGENIC AND A NON-TUMORIGENIC TRIAZOLE CONAZOLE FUNGICIDE

    EPA Science Inventory

    Conazoles are triazole- or imidazole-containing fungicides that are used in agriculture and medicine. Conazoles can induce follicular cell adenomas of the thyroid in rats after chronic bioassay. The goal of this study was to identify pathways and networks of genes that were assoc...

  10. A syn-Selective Aza-Aldol Reaction of Boron Aza-Enolates Generated from N-Sulfonyl-1,2,3-Triazoles and 9-BBN-H.

    PubMed

    Miura, Tomoya; Nakamuro, Takayuki; Miyakawa, Sho; Murakami, Masahiro

    2016-07-18

    A syn-selective aza-aldol reaction of boron aza-enolates, generated from N-sulfonyl-1,2,3-triazoles and 9-BBN-H, is reported. It provides a sequential one-pot procedure for the stereoselective construction of 1,3-amino alcohols, having contiguous stereocenters, starting from terminal alkynes. PMID:27258810

  11. Discovery of a new class of cinnamyl-triazole as potent and selective inhibitors of aromatase (cytochrome P450 19A1).

    PubMed

    McNulty, James; Keskar, Kunal; Crankshaw, Denis J; Holloway, Alison C

    2014-09-15

    Synthesis of a novel class of natural product inspired cinnamyl-containing 1,4,5-triazole and the potent inhibition of human aromatase (CYP 450 19A1) by select members is described. Structure-activity data generated provides insights into the requirements for potency particularly the inclusion of an aryl bromide or chloride residue as a keto-bioisostere. PMID:25155384

  12. Just Click It: Undergraduate Procedures for the Copper(I)-Catalyzed Formation of 1,2,3-Triazoles from Azides and Terminal Acetylenes

    ERIC Educational Resources Information Center

    Sharpless, William D.; Peng Wu; Hansen, Trond Vidar; Lindberg, James G.

    2005-01-01

    The click chemistry uses only the most reliable reactions to build complex molecules from olefins, electrophiles and heteroatom linkers. A variation on Huisgen's azide-alkyne 1,2,3-triazole synthesis, the addition of the copper (I), the premium example of the click reaction, catalyst strongly activates terminal acetylenes towards the 1,3-dipole in…

  13. Nutrition Marketing on Food Labels

    ERIC Educational Resources Information Center

    Colby, Sarah E.; Johnson, LuAnn; Scheett, Angela; Hoverson, Bonita

    2010-01-01

    Objective: This research sought to determine how often nutrition marketing is used on labels of foods that are high in saturated fat, sodium, and/or sugar. Design and Setting: All items packaged with food labels (N = 56,900) in all 6 grocery stores in Grand Forks, ND were surveyed. Main Outcome Measure(s): Marketing strategy, nutrient label…

  14. Meat and Poultry Labeling Terms

    MedlinePlus

    ... Food Standards and Labels: The Facts Labeling and Marketing Information [ Top of Page ] OVEN PREPARED: Product is fully cooked and ready to eat. [ Top of Page ] YOUNG TURKEY: Turkeys of either sex that are less than 8 months of age according to present regulations. [ Top of Page ] Last ...

  15. Synthesis, Surface Properties and Biocompatibility of 1,2,3-Triazole-containing Alkyl β-D-xylopyranoside Surfactants

    PubMed Central

    Oldham, E. Davis; Seelam, Srivenu; Lema, Carolina; Aguilera, Renato J.; Fiegel, Jennifer; Rankin, Stephen E.; Knutson, Barbara L.; Lehmler, Hans-Joachim

    2013-01-01

    We are interested in the development of surfactants derived from hemicellulosic biomass, as they are potential components in pharmaceuticals, personal care products and other detergents. Such surfactants should exhibit low toxicity in mammalian cells. In this study we synthesized a series of alkyl or fluoroalkyl β-xylopyranosides from azides and an alkyne using the copper-catalyzed azide-alkyne (CuAAC) “Click” reaction in 4 steps from xylose. The purified products were evaluated for both their surfactant properties, and for their biocompatibility. Unlike other carbohydrate-based surfactants, liquid-crystalline behavior was not observed by differential scanning calorimetry. The triazole-containing β-xylopyranosides with short (6 carbons) and long (>12 carbons) chains exhibited no toxicity at concentrations ranging from 1 to 1000 μM. Triazole-containing β-xylopyranosides with 8, 10 or 12 carbons caused toxicity via apoptosis, with CC50 values ranging from 26-890 μM. The two longest chain compounds did form stable monolayers at the air-water interface over a range of temperatures, although a brief transition to an unstable monolayer was observed. PMID:23872788

  16. Daphnia and fish toxicity of (benzo)triazoles: validated QSAR models, and interspecies quantitative activity-activity modelling.

    PubMed

    Cassani, Stefano; Kovarich, Simona; Papa, Ester; Roy, Partha Pratim; van der Wal, Leon; Gramatica, Paola

    2013-08-15

    Due to their chemical properties synthetic triazoles and benzo-triazoles ((B)TAZs) are mainly distributed to the water compartments in the environment, and because of their wide use the potential effects on aquatic organisms are cause of concern. Non testing approaches like those based on quantitative structure-activity relationships (QSARs) are valuable tools to maximize the information contained in existing experimental data and predict missing information while minimizing animal testing. In the present study, externally validated QSAR models for the prediction of acute (B)TAZs toxicity in Daphnia magna and Oncorhynchus mykiss have been developed according to the principles for the validation of QSARs and their acceptability for regulatory purposes, proposed by the Organization for Economic Co-operation and Development (OECD). These models are based on theoretical molecular descriptors, and are statistically robust, externally predictive and characterized by a verifiable structural applicability domain. They have been applied to predict acute toxicity for over 300 (B)TAZs without experimental data, many of which are in the pre-registration list of the REACH regulation. Additionally, a model based on quantitative activity-activity relationships (QAAR) has been developed, which allows for interspecies extrapolation from daphnids to fish. The importance of QSAR/QAAR, especially when dealing with specific chemical classes like (B)TAZs, for screening and prioritization of pollutants under REACH, has been highlighted. PMID:23702385

  17. Synthesis of some new 1,2,4-triazoles starting from isonicotinic acid hydrazide and evaluation of their antimicrobial activities.

    PubMed

    Bayrak, Hacer; Demirbas, Ahmet; Demirbas, Neslihan; Karaoglu, Sengül Alpay

    2009-11-01

    5-Pyridin-4-yl-1,3,4-oxadiazole-2-thiol (2) was obtained from the reaction of isonicotinic acid hydrazide with carbon disulfide in basic media and converted into 4-amino-5-pyridin-4-yl-4H-1,2,4-triazole-3-thiol (5) by the treatment with hydrazine hydrate. The synthesis of 3 and 6 was performed from the reaction of 2 and 5 with ethyl bromide. The treatment of 5 with 4-fluorobenzaldehyde or indol-3-carbaldehyde resulted in the formation of 4-[(arylmethylene)amino]-5-pyridin-4-yl-4H-1,2,4-triazole-3-thiols (7a and 7b). The reactions of 2, 5 and 7a with some primary and secondary amines in the presence of formaldehyde afforded the corresponding Mannich bases, 4a, 4b, 9a-9c and 8. All newly synthesized compounds were screened for their antimicrobial activity. The antimicrobial activity study revealed that all the compounds screened showed good or moderate activity except compounds 2, 7a, 7b, 8 and 9b. PMID:19647352

  18. [Determination of nine triazole pesticides in environmental waters using solid phase extraction and gas chromatography-mass spectrometry].

    PubMed

    You, Minghua; Sun, Guangda; Chen, Meng; Yuan, Dongxing

    2008-11-01

    A method was developed for the simultaneous determination of 9 triazole pesticides in environmental water using C18 cartridge for the extraction and enrichment, NH2 cartridge for the clean-up and gas chromatography-mass spectrometry for the detection. The linear range of calibration curves for the 9 target pesticides was between 0.025 mg/L and 0.500 mg/L. The detection limits were in the range of 0.002 - 0.009 microg/L. The 9 target pesticides were measured in river water and sea water at 0.025 microg/L and 0.100 microg/L spiking levels, recoveries and relative standard deviations (RSD, n = 3) were 68.4% - 113.9% and 1.6% - 6.9% for river water and 70.3% - 115.2% and 0.8% - 8.2% for sea water, respectively. The method is simple, sensitive, selective and suitable for the qualification of pesticide multiresidue analysis. It has been successfully applied to the survey of 9 triazole pesticide residues in Jiulong River Estuary, Fujian. PMID:19253548

  19. Enhanced Dissipation of Triazole and Multiclass Pesticide Residues on Grapes after Foliar Application of Grapevine-Associated Bacillus Species.

    PubMed

    Salunkhe, Varsha P; Sawant, Indu S; Banerjee, Kaushik; Wadkar, Pallavi N; Sawant, Sanjay D

    2015-12-23

    Disease management in vineyards with fungicides sometimes results in undesirable residue accumulations in grapes at harvest. Bioaugmentation of the grape fructosphere can be a useful approach for enhancing the degradation rate and reducing the residues to safe levels. This paper reports the in vitro and in vivo biodegradation of three triazole fungicides commonly used in Indian vineyards, by Bacillus strains, namely, DR-39, CS-126, TL-171, and TS-204, which were earlier found to enhance the dissipation rate of profenophos and carbendazim. The strains utilized the triazoles as carbon source and enhanced their in vitro rate of degradation. Myclobutanil, tetraconazole, and flusilazole were applied in separate vineyard plots at field doses of 0.40 g L(-1), 0.75 mL L(-1), and 0.125 mL L(-1), respectively. Residue analysis of field samples from the treated fields reflected 87.38 and >99% degradations of myclobutanil and tetraconazole, respectively, by the strain DR-39, and 90.82% degradation of flusilazole by the strain CS-126 after 15-20 days of treatment. In the respective controls, the corresponding percent degradations were 72.07, 58.88, and 54.28, respectively. These Bacillus strains could also simultaneously degrade the residues of profenofos, carbendazim, and tetraconazole on the grape berries and can be useful in multiclass pesticide residue biodegradation. PMID:26492206

  20. Biodegradation mechanism of 1H-1,2,4-triazole by a newly isolated strain Shinella sp. NJUST26

    PubMed Central

    Wu, Haobo; Shen, Jinyou; Wu, Ruiqin; Sun, Xiuyun; Li, Jiansheng; Han, Weiqing; Wang, Lianjun

    2016-01-01

    The highly recalcitrant 1H-1,2,4-triazole (TZ) is widely used in the synthesis of agricultural pesticide and considered to be an environmental pollutant. In this study, a novel strain NJUST26 capable of utilizing TZ as the sole carbon and nitrogen source, was isolated from TZ-contaminated soil, and identified as Shinella sp. The biodegradation assays suggested that optimal temperature and pH for TZ degradation by NJUST26 were 30 °C and 6–7, respectively. With the increase of initial TZ concentration from 100 to 320 mg L−1, the maximum volumetric degradation rate increased from 29.06 to 82.96 mg L−1 d−1, indicating high tolerance of NJUST26 towards TZ. TZ biodegradation could be accelerated through the addition of glucose, sucrose and yeast extract at relatively low dosage. The main metabolites, including 1,2-dihydro-3H-1,2,4-triazol-3-one (DHTO), semicarbazide and urea were identified. Based on these results, biodegradation pathway of TZ by NJUST26 was proposed, i.e., TZ was firstly oxidized to DHTO, and then the cleavage of DHTO ring occurred to generate N-hydrazonomethyl-formamide, which could be further degraded to biodegradable semicarbazide and urea. PMID:27436634

  1. Retention-property relationships of 1,2,4-triazoles by micellar and reversed-phase liquid chromatography.

    PubMed

    Janicka, Małgorzata; Pachuta-Stec, Anna

    2014-06-01

    The properties of 21 1,2,4-triazoles, relevant to their pharmacokinetics, were investigated using experimental methods and in silico calculations. The lipophilicities of the compounds were determined experimentally using reversed-phase chromatography and liquid chromatography with micellar mobile phases, or they were calculated in silico from their molecular structures. In the reversed-phase technique, an octadecylsilyl, immobilized artificial membrane and immobilized cholesterol were used as the stationary phases. Biological descriptors of compounds, i.e. log BB, log KHSA, Caco-2, and fu,brain, were determined in silico by using ACD/Percepta software. Principal component analysis was used to indicate similarities between chromatographic, partitioning, and biological variables. Highly significant relationships were determined to exist between the chromatographic parameters and the biological descriptors, especially for log BB and log KHSA. The chromatographic parameters measured on the cholesterol column were recommended for use in predicting the lipophilic and biological properties of the 1,2,4-triazoles that were tested. PMID:24723541

  2. Synthesis of 1H-1,2,3-triazole linked aryl(arylamidomethyl) - dihydrofurocoumarin hybrids and analysis of their cytotoxicity.

    PubMed

    Lipeeva, Alla V; Pokrovsky, Mikhail A; Baev, Dmitry S; Shakirov, Makhmut M; Bagryanskaya, Irina Y; Tolstikova, Tatijana G; Pokrovsky, Andrey G; Shults, Elvira E

    2015-07-15

    A series of 2-(4-R-triazolyl)substituted 3-oxo-2,3-dihydrofurocoumarins have been synthesized by a regioselective cycloaddition of 2-azidooreoselone 1 or 2-azido-9-[(4-methylpiperazin-1-yl)methyl]oreoselone 2 with various alkynes in the presence of Cu(II)/ascorbate in water/methylene chloride reaction medium. The structure of 2-azidooreoselone was established by X-ray structure analysis. The cytotoxicity of 2-substituted dihydrofurocoumarins was determined against three cancer cell lines (CEM-13, MT-4, U-937) using the conventional MTT assays. Among the tested molecules, most of the analogs displayed better cytotoxic activity then the parent natural furocoumarin peucedanin 3. The activity and selectivity to the cell line increased even further in the series of 2-(4-{2,3-dihydrobenzo[b][1,4]dioxine}triazolyl)-3-oxo-2,3-dihydrofurocoumarins and 2-(4-aryltriazolyl)-3-oxo-2,3-dihydrofurocoumarins having the (4-methylpiperazin-1-ylmethyl) substituent in the 9-th position. The most active compound 20 contain the 4-hydroxy-3-methoxybenzamidomethyl substituent in the 4-th position at the triazole ring of 2-(triazol-1-yl)dihydrofurocoumarins. The obtained 2-triazolyl substituted dihydrofurocoumarins were studied as inhibitors of phosphodiesterase (PDE-4B) using docking experiments. As a result of virtual screening 3 compounds are selected based on minimum binding energy. The interactions of the most active compound and amino acid residues in the binding site were studied. PMID:26079088

  3. Antibiofilm effect enhanced by modification of 1,2,3-triazole and palladium nanoparticles on polysulfone membranes

    PubMed Central

    Cheng, Hong; Xie, Yihui; Villalobos, Luis Francisco; Song, Liyan; Peinemann, Klaus-Viktor; Nunes, Suzana; Hong, Pei-Ying

    2016-01-01

    Biofouling impedes the performance of membrane bioreactors. In this study, we investigated the antifouling effects of polysulfone membranes that were modified by 1,2,3-triazole and palladium (Pd) nanoparticles. The modified membranes were evaluated for antibacterial and antifouling efficacy in a monoculture species biofilm (i.e., drip flow biofilm reactor, DFR) and mixed species biofilm experiment (i.e., aerobic membrane reactor, AeMBR). 1,2,3-triazole and Pd nanoparticles inhibited growth of Pseudomonas aeruginosa in both aerobic and anaerobic conditions. The decrease in bacterial growth was observed along with a decrease in the amount of total polysaccharide within the monoculture species biofilm matrix. When the modified membranes were connected to AeMBR, the increase in transmembrane pressure was lower than that of the non-modified membranes. This was accompanied by a decrease in protein and polysaccharide concentrations within the mixed species biofilm matrix. Biomass amount in the biofilm layer was also lower in the presence of modified membranes, and there was no detrimental effect on the performance of the reactor as evaluated from the nutrient removal rates. 16S rRNA analysis further attributed the delay in membrane fouling to the decrease in relative abundance of selected bacterial groups. These observations collectively point to a lower fouling occurrence achieved by the modified membranes. PMID:27068576

  4. 2-Triazole-Substituted Adenosines: A New Class of Selective A3 Adenosine Receptor Agonists, Partial Agonists, and Antagonists

    PubMed Central

    Cosyn, Liesbet; Palaniappan, Krishnan K.; Kim, Soo-Kyung; Duong, Heng T.; Gao, Zhan-Guo; Jacobson, Kenneth A.; Van Calenbergh, Serge

    2016-01-01

    “Click chemistry” was explored to synthesize two series of 2-(1,2,3-triazolyl)adenosine derivatives (1–14). Binding affinity at the human A1, A2A, and A3ARs (adenosine receptors) and relative efficacy at the A3AR were determined. Some triazol-1-yl analogues showed A3AR affinity in the low nanomolar range, a high ratio of A3/A2A selectivity, and a moderate-to-high A3/A1 ratio. The 1,2,3-triazol-4-yl regiomers typically showed decreased A3AR affinity. Sterically demanding groups at the adenine C2 position tended to reduce relative A3AR efficacy. Thus, several 5′-OH derivatives appeared to be selective A3AR antagonists, i.e., 10, with 260-fold binding selectivity in comparison to the A1AR and displaying a characteristic docking mode in an A3AR model. The corresponding 5′-ethyluronamide analogues generally showed increased A3AR affinity and behaved as full agonists, i.e., 17, with 910-fold A3/A1 selectivity. Thus, N6-substituted 2-(1,2,3-triazolyl)-adenosine analogues constitute a novel class of highly potent and selective nucleoside-based A3AR antagonists, partial agonists, and agonists. PMID:17149867

  5. Synthesis and cytotoxicity evaluation of aryl triazolic derivatives and their hydroxymethine homologues against B16 melanoma cell line.

    PubMed

    Kalhor-Monfared, Shiva; Beauvineau, Claire; Scherman, Daniel; Girard, Christian

    2016-10-21

    In this manuscript we describe synthesis and cytotoxicity evaluation of some triazolic derivatives against B16 melanoma cell line. For this purpose, we transformed a set of aromatic aldehydes into terminal alkynes, using Besthmann-Ohira reagent, and we made the corresponding hydroxymethyl homologated alkynes by an acetylene Grignard reagent. These generated two sets of alkynes were then subjected to a copper(I)-catalyzed alkyne-azide cycloaddition reaction (CuAAC) using a solid-supported catalyst (Amberlyst A-21 CuI), with a third set composed of organic azides. Synthesized triazoles were then tested in vitro against B16 melanoma cell line. Amongst them, compounds a1b1 (R(1) = p-nitrophenyl, R(2) = benzyl), a4b1 (R(1) = naphthyl, R(2) = benzyl) and a4b5 (R(1) = naphthyl, R(2) = (R/S)- dioxolane) showed the best activity against B16 melanoma cells, with IC50 of 5.12, 3.89 and 6.60 μM respectively. PMID:27404558

  6. New routes to Cu(I)/Cu nanocatalysts for the multicomponent click synthesis of 1,2,3-triazoles.

    PubMed

    Abdulkin, Pavel; Moglie, Yanina; Knappett, Benjamin R; Jefferson, David A; Yus, Miguel; Alonso, Francisco; Wheatley, Andrew E H

    2013-01-01

    An array of copper and copper-zinc based nanoparticles (NPs) have been fabricated employing a variety of polymeric capping agents. Analysis by TEM, XRPD and XPS suggests that by manipulating reagent, reductant and solvent conditions it is possible to achieve materials that are mono-/narrow disperse with mean particle sizes in the ≤10 nm regime. Oxidative stability in air is achieved for monometallic NPs using poly(methyl methacrylate) (PMMA) anti-agglomerant in conjunction with a variety of reducing conditions. In contrast, those encapsulated by either poly(1-vinylpyrrolidin-2-one) (PVP) or poly(4-vinylpyridine) (PVPy) rapidly show Cu(2)O formation, with all data suggesting progressive oxidation from Cu to Cu@Cu(2)O core-shell structure and finally Cu(2)O. Bimetallic copper-zinc systems, reveal metal segregation and the formation of Cu(2)O and ZnO. Catalysts have been screened in the synthesis of 1,2,3-triazoles through multicomponent azide-alkyne 1,3-dipolar cycloaddition. Whereas PMMA- and PVPy-coating results in reduced catalytic activity, those protected by PVP are highly active, with quantitative triazole syntheses achieved at room temperature and with catalyst loadings of 0.03 mol% metal for Cu and CuZn systems prepared using NaH(2)PO(2), N(2)H(4) or NaBH(4) reductants. PMID:23166008

  7. New CD1d agonists: Synthesis and biological activity of 6″-triazole-substituted α-galactosyl ceramides

    PubMed Central

    Jervis, Peter J.; Graham, Lisa M.; Foster, Erin L.; Cox, Liam R.; Porcelli, Steven A.; Besra, Gurdyal S.

    2012-01-01

    Huisgen [3+2] dipolar cycloaddition of 6″-azido-6″-deoxy-α-galactosyl ceramide 11 with a range of alkynes (or a benzyne precursor) yielded a series of triazole-containing α-galactosyl ceramide (α-GalCer) analogues in high yield. These α-GalCer analogues and the precursor azide 11 were tested for their ability to activate iNKT cells and stimulate IL-2 cytokine secretion in vitro, and IFN-γ and IL-4 cytokine secretion in vivo. Some of these analogues, specifically 11, 12b, 12f and 13, were more potent IL-2 stimulators than the prototypical CD1d agonist, α-GalCer 1. In terms of any cytokine bias, most of the triazole-containing analogues exhibited a small Th2 cytokine-biasing response relative to that shown by α-GalCer 1. In contrast, the cycloaddition precursor, namely azide 11, provided a small Th1 cytokine-biasing response. PMID:22652050

  8. Synthesis and antioxidant property of novel 1,2,3-triazole-linked starch derivatives via 'click chemistry'.

    PubMed

    Tan, Wenqiang; Li, Qing; Li, Wancong; Dong, Fang; Guo, Zhanyong

    2016-01-01

    Based on the copper (I) catalyzed Huisgen azide-alkyne cycloaddition (click chemistry), the novel synthesis of a variety of 1,2,3-triazole-linked starch derivatives was developed, including 6-hydroxymethyltriazole-6-deoxy starch (HMTST), 6-hydroxyethyltriazole-6-deoxy starch (HETST), 6-hydroxypropyltriazole-6-deoxy starch (HPTST), and 6-hydroxybutyltriazole-6-deoxy starch (HBTST). Their antioxidant properties against hydroxyl-radical, DPPH-radical, and superoxide-radical were evaluated in vitro, respectively. The antioxidant activity of the obtained novel amphiprotic starch derivatives via 'click reaction' exhibited remarkable improvement over starch. And the scavenging effect indices of most of the products were higher than 60% at 1.6 mg/mL against hydroxyl-radical and DPPH-radical. Moreover, the scavenging effect of the products against superoxide-radical attained 90% above at 0.1mg/mL. Generally, the antioxidant activity decreased in the order: HBTST>HPTST>HETST>HMTST>starch. Furthermore, the order of their antioxidant activity was consistent with the electron-donating ability of different substituted groups of the 1,2,3-triazoles. The substituted groups with stronger electron supplying capacity provided more electrons to the various radicals, which relatively enhanced the capacity for scavenging free radicals. PMID:26449530

  9. Antileishmanial Activity and Structure-Activity Relationship of Triazolic Compounds Derived from the Neolignans Grandisin, Veraguensin, and Machilin G.

    PubMed

    Costa, Eduarda C; Cassamale, Tatiana B; Carvalho, Diego B; Bosquiroli, Lauriane S S; Ojeda, Mariáh; Ximenes, Thalita V; Matos, Maria F C; Kadri, Mônica C T; Baroni, Adriano C M; Arruda, Carla C P

    2016-01-01

    Sixteen 1,4-diaryl-1,2,3-triazole compounds 4-19 derived from the tetrahydrofuran neolignans veraguensin 1, grandisin 2, and machilin G 3 were tested against Leishmania (Leishmania) amazonensis intracellular amastigotes. Triazole compounds 4-19 were synthetized via Click Chemistry strategy by 1,3-dipolar cycloaddition between terminal acetylenes and aryl azides containing methoxy and methylenedioxy groups as substituents. Our results suggest that most derivatives were active against intracellular amastigotes, with IC50 values ranging from 4.4 to 32.7 µM. The index of molecular hydrophobicity (ClogP) ranged from 2.8 to 3.4, reflecting a lipophilicity/hydrosolubility rate suitable for transport across membranes, which may have resulted in the potent antileishmanial activity observed. Regarding structure-activity relationship (SAR), compounds 14 and 19, containing a trimethoxy group, were the most active (IC50 values of 5.6 and 4.4 µM, respectively), with low cytotoxicity on mammalian cells (SI = 14.1 and 10.6). These compounds induced nitric oxide production by the host macrophage cells, which could be suggested as the mechanism involved in the intracellular killing of parasites. These results would be useful for the planning of new derivatives with higher antileishmanial activities. PMID:27331807

  10. Biodegradation mechanism of 1H-1,2,4-triazole by a newly isolated strain Shinella sp. NJUST26.

    PubMed

    Wu, Haobo; Shen, Jinyou; Wu, Ruiqin; Sun, Xiuyun; Li, Jiansheng; Han, Weiqing; Wang, Lianjun

    2016-01-01

    The highly recalcitrant 1H-1,2,4-triazole (TZ) is widely used in the synthesis of agricultural pesticide and considered to be an environmental pollutant. In this study, a novel strain NJUST26 capable of utilizing TZ as the sole carbon and nitrogen source, was isolated from TZ-contaminated soil, and identified as Shinella sp. The biodegradation assays suggested that optimal temperature and pH for TZ degradation by NJUST26 were 30 °C and 6-7, respectively. With the increase of initial TZ concentration from 100 to 320 mg L(-1), the maximum volumetric degradation rate increased from 29.06 to 82.96 mg L(-1) d(-1), indicating high tolerance of NJUST26 towards TZ. TZ biodegradation could be accelerated through the addition of glucose, sucrose and yeast extract at relatively low dosage. The main metabolites, including 1,2-dihydro-3H-1,2,4-triazol-3-one (DHTO), semicarbazide and urea were identified. Based on these results, biodegradation pathway of TZ by NJUST26 was proposed, i.e., TZ was firstly oxidized to DHTO, and then the cleavage of DHTO ring occurred to generate N-hydrazonomethyl-formamide, which could be further degraded to biodegradable semicarbazide and urea. PMID:27436634

  11. Synthesis and thermoreversible gelation properties of main-chain poly(pyridine-2,6-dicarboxamide-triazole)s.

    PubMed

    Yim, Sui-Lung; Chow, Hak-Fun; Chan, Man-Chor; Che, Chi-Ming; Low, Kam-Hung

    2013-02-11

    A series of main-chain poly(amide-triazole)s were prepared by copper(I)-catalyzed alkyne-azide AABB-type copolymerizatons between five structurally similar diacetylenes 1-5 with the same diazide 6. The acetylene units in monomers 1-5 possessed different degrees of conformational flexibility due to the different number of intramolecular hydrogen bonds built inside the monomer architecture. Our study showed that the conformational freedom of the monomer had a profound effect on the polymerization efficiency and the thermoreversible gelation properties of the resulting copolymers. Among all five diacetylene monomers, only the one, that is, 1-Py(NH)(2) which possesses the pyridine-2,6-dicarboxamide unit with two built-in intramolecular H bonds could produce the corresponding poly(amide-triazole) Poly-(PyNH)(2) with a significantly higher degree of polymerization (DP) than other monomers with a lesser number of intramolecular H bonds. In addition, it was found that only this polymer exhibited excellent thermoreversible gelation ability in aromatic solvents. A self-assembling model of the organogelating polymer Poly-(PyNH)(2) was proposed based on FTIR spectroscopy, XRD, and SEM analyses, in which H bonding, π-π aromatic stacking, hydrophobic interactions, and the structural rigidity of the polymer backbone were identified as the main driving forces for the polymer self-assembly process. PMID:23297251

  12. Antibiofilm effect enhanced by modification of 1,2,3-triazole and palladium nanoparticles on polysulfone membranes.

    PubMed

    Cheng, Hong; Xie, Yihui; Villalobos, Luis Francisco; Song, Liyan; Peinemann, Klaus-Viktor; Nunes, Suzana; Hong, Pei-Ying

    2016-01-01

    Biofouling impedes the performance of membrane bioreactors. In this study, we investigated the antifouling effects of polysulfone membranes that were modified by 1,2,3-triazole and palladium (Pd) nanoparticles. The modified membranes were evaluated for antibacterial and antifouling efficacy in a monoculture species biofilm (i.e., drip flow biofilm reactor, DFR) and mixed species biofilm experiment (i.e., aerobic membrane reactor, AeMBR). 1,2,3-triazole and Pd nanoparticles inhibited growth of Pseudomonas aeruginosa in both aerobic and anaerobic conditions. The decrease in bacterial growth was observed along with a decrease in the amount of total polysaccharide within the monoculture species biofilm matrix. When the modified membranes were connected to AeMBR, the increase in transmembrane pressure was lower than that of the non-modified membranes. This was accompanied by a decrease in protein and polysaccharide concentrations within the mixed species biofilm matrix. Biomass amount in the biofilm layer was also lower in the presence of modified membranes, and there was no detrimental effect on the performance of the reactor as evaluated from the nutrient removal rates. 16S rRNA analysis further attributed the delay in membrane fouling to the decrease in relative abundance of selected bacterial groups. These observations collectively point to a lower fouling occurrence achieved by the modified membranes. PMID:27068576

  13. Mechanochemical click reaction as a tool for making carbohydrate-based triazole-linked self-assembling materials (CTSAMs).

    PubMed

    Tyagi, Mohit; Taxak, Nikhil; Bharatam, Prasad V; Nandanwar, Hemraj; Kartha, K P Ravindranathan

    2015-04-30

    Various glycosides in which glycosylated triazole residues are anchored on to a central phenyl ring have been prepared under green reaction conditions by a solvent-free mechanochemical method. Some of the glycosides exhibited the ability to form gels when in contact with long chain hydrocarbons, e.g. hexane, heptane and octane, and this property was phase-selective. Thus, from a mixture of hexane-water, the compounds preferably absorbed the alkane to form a gel. The gelation ability was found to increase with an increasing number of substituents on the phenyl ring but only up to tetra-substitution. The hexa-substituted phenyl derivative did not swell in the hydrocarbon solvents investigated. The spontaneous self-assembling properties of these compounds in hexane have been investigated by transmission electron microscopy (TEM). Molecular modelling was used to optimize the structural geometry of these carbohydrate-based triazole-linked self-assembling materials (CTSAMs) and to rationalize their behaviour. PMID:25771296

  14. Synthesis, structural elucidation and bioevaluation of 4-amino-1,2,4-triazole-3-thione's Schiff base derivatives.

    PubMed

    Rafiq, Muhammad; Saleem, Muhammad; Hanif, Muhammad; Kang, Sung Kwon; Seo, Sung-Yum; Lee, Ki Hwan

    2016-02-01

    In this study, a series of ten triazole Schiff base derivatives 6a-j were synthesized through microwave assisted imine formation by reacting substituted amino triazole 5 with different substituted aldehydes. All the synthesized compounds were evaluated for their inhibitory activity against mushroom tyrosinase. Two of the compounds 6a and 6b among the series 6a-j were found to be highly potent tyrosinase inhibitors with IC50 values of 10.09 ± 1.03 and 6.23 ± 0.85 µM, respectively, which were even higher than that of the reference inhibitor kojic acid (IC50 = 16.6 ± 2.8 µM). Compounds 6e and 6f with IC50 values of 20.27 ± 2.78 and 26.02 ± 4.14 µM, respectively, were comparable to the reference inhibitor, and the remaining compounds had a moderate inhibitory activity against mushroom tyrosinase. The most potent compounds (6a, 6b) were used in the kinetic and optical analyses. The inhibition kinetics analyzed with Lineweaver-Burk plots revealed that both compounds 6a and 6b were non-competitive inhibitors of tyrosinase with inhibition constant values of 0.023 and 0.022 mM, respectively. PMID:26608953

  15. Three inorganic-organic hybrids of bismuth(III) iodide complexes containing substituted 1,2,4-triazole organic components with charaterizations of diffuse reflectance spectra

    SciTech Connect

    Liu Bing . E-mail: bliu_1203@yahoo.com.cn; Xu Ling; Guo Guocong; Huang Jinshun

    2006-06-15

    The reactions of two kinds of substituted 1,2,4-triazoles with BiI{sub 3} yielded three inorganic-organic hybrids: [HL1]{sub 4}[Bi{sub 6}I{sub 22}].[L1]{sub 4}.4H{sub 2}O (1) (L1=3-(1,2,4-triazole-4-yl)-1H-1,2,4-triazole); [HL2]{sub 4}[Bi{sub 6}I{sub 22}].6H{sub 2}O (2); [HL2]{sub 2}[Bi{sub 2}I{sub 8}].[L2]{sub 2} (3) (L2=(m-phenol)-1,2,4-triazole). Both 1 and 2 have polynuclear anions of [Bi{sub 6}I{sub 22}]{sup 4-} to build up the inorganic layers and substituted 1,2,4-triazoles as the organic layers. Hybrid 3 consists of two BiI{sub 5} square pyramids as inorganic layers. There exist hydrogen bondings and I...;I interactions in the structures of 1, 2 and 3. Optical absorption spectra of 1, 2 and 3 reveal the presence of sharp optical gaps of 1.77, 1.77 and 2.07 eV, respectively, suggesting that these materials behave as semiconductors. - Graphical abstract: The reactions of two kinds of the substituted 1,2,4-triazoles with BiI{sub 3} yielded three layered inorganic-organic hybrids [HL1]{sub 4}[Bi{sub 6}I{sub 22}].[L1]{sub 4}.4H{sub 2}O (1), [HL2]{sub 4}[Bi{sub 6}I{sub 22}].6H{sub 2}O (2), [HL2]{sub 2}[Bi{sub 2}I{sub 8}].[L2]{sub 2} (3) with optical gaps of 1.77, 1.77 and 2.07 eV, respectively. The structures of 1-3 are constructed from inorganic layers of polynuclear anions of bismuth iodine and organic layers of the substituted 1,2,4-triazoles.

  16. 21 CFR 201.71 - Magnesium labeling.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Magnesium labeling. 201.71 Section 201.71 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.71 Magnesium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the magnesium...

  17. 21 CFR 201.70 - Calcium labeling.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Calcium labeling. 201.70 Section 201.70 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.70 Calcium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the calcium content...

  18. 21 CFR 201.72 - Potassium labeling.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Potassium labeling. 201.72 Section 201.72 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.72 Potassium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the potassium...

  19. 21 CFR 201.72 - Potassium labeling.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Potassium labeling. 201.72 Section 201.72 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.72 Potassium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the potassium...

  20. 21 CFR 201.72 - Potassium labeling.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Potassium labeling. 201.72 Section 201.72 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.72 Potassium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the potassium...

  1. 21 CFR 201.72 - Potassium labeling.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Potassium labeling. 201.72 Section 201.72 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.72 Potassium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the potassium...

  2. 21 CFR 201.72 - Potassium labeling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Potassium labeling. 201.72 Section 201.72 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.72 Potassium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the potassium...

  3. 21 CFR 201.64 - Sodium labeling.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... contains sodium bicarbonate, sodium phosphate, or sodium biphosphate as an active ingredient for oral... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Sodium labeling. 201.64 Section 201.64 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.64 Sodium labeling. (a) The labeling...

  4. 21 CFR 201.64 - Sodium labeling.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... contains sodium bicarbonate, sodium phosphate, or sodium biphosphate as an active ingredient for oral... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Sodium labeling. 201.64 Section 201.64 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.64 Sodium labeling. (a) The labeling...

  5. 21 CFR 201.64 - Sodium labeling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... contains sodium bicarbonate, sodium phosphate, or sodium biphosphate as an active ingredient for oral... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Sodium labeling. 201.64 Section 201.64 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.64 Sodium labeling. (a) The labeling...

  6. 21 CFR 201.64 - Sodium labeling.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... contains sodium bicarbonate, sodium phosphate, or sodium biphosphate as an active ingredient for oral... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Sodium labeling. 201.64 Section 201.64 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.64 Sodium labeling. (a) The labeling...

  7. New routes to Cu(i)/Cu nanocatalysts for the multicomponent click synthesis of 1,2,3-triazoles

    NASA Astrophysics Data System (ADS)

    Abdulkin, Pavel; Moglie, Yanina; Knappett, Benjamin R.; Jefferson, David A.; Yus, Miguel; Alonso, Francisco; Wheatley, Andrew E. H.

    2012-12-01

    An array of copper and copper-zinc based nanoparticles (NPs) have been fabricated employing a variety of polymeric capping agents. Analysis by TEM, XRPD and XPS suggests that by manipulating reagent, reductant and solvent conditions it is possible to achieve materials that are mono-/narrow disperse with mean particle sizes in the <=10 nm regime. Oxidative stability in air is achieved for monometallic NPs using poly(methyl methacrylate) (PMMA) anti-agglomerant in conjunction with a variety of reducing conditions. In contrast, those encapsulated by either poly(1-vinylpyrrolidin-2-one) (PVP) or poly(4-vinylpyridine) (PVPy) rapidly show Cu2O formation, with all data suggesting progressive oxidation from Cu to Cu@Cu2O core-shell structure and finally Cu2O. Bimetallic copper-zinc systems, reveal metal segregation and the formation of Cu2O and ZnO. Catalysts have been screened in the synthesis of 1,2,3-triazoles through multicomponent azide-alkyne 1,3-dipolar cycloaddition. Whereas PMMA- and PVPy-coating results in reduced catalytic activity, those protected by PVP are highly active, with quantitative triazole syntheses achieved at room temperature and with catalyst loadings of 0.03 mol% metal for Cu and CuZn systems prepared using NaH2PO2, N2H4 or NaBH4 reductants.An array of copper and copper-zinc based nanoparticles (NPs) have been fabricated employing a variety of polymeric capping agents. Analysis by TEM, XRPD and XPS suggests that by manipulating reagent, reductant and solvent conditions it is possible to achieve materials that are mono-/narrow disperse with mean particle sizes in the <=10 nm regime. Oxidative stability in air is achieved for monometallic NPs using poly(methyl methacrylate) (PMMA) anti-agglomerant in conjunction with a variety of reducing conditions. In contrast, those encapsulated by either poly(1-vinylpyrrolidin-2-one) (PVP) or poly(4-vinylpyridine) (PVPy) rapidly show Cu2O formation, with all data suggesting progressive oxidation from Cu to Cu

  8. Synthesis and anti-cancer screening of novel heterocyclic-(2H)-1,2,3-triazoles as potential anti-cancer agents

    PubMed Central

    Penthala, Narsimha Reddy; Madhukuri, Leena; Thakkar, Shraddha; Madadi, Nikhil Reddy; Lamture, Gauri; Eoff, Robert L.; Crooks, Peter A.

    2015-01-01

    trans-Cyanocombretastatin A-4 (trans-CA-4) analogues have been structurally modified to afford their more stable CA-4-(2H)-1,2,3-triazole analogues. Fifteen novel, stable 4-heteroaryl-5-aryl-(2H)-1,2,3-triazole CA-4 analogues (8a–i, 9 and 11a–e) were evaluated for anti-cancer activity against a panel of 60 human cancer cell lines. These analogues displayed potent cytotoxic activity against both hematological and solid tumor cell lines with GI50 values in the low nanomolar range. The most potent compound, 8a, was a benzothiophen-2-yl analogue that incorporated a 3,4,5-trimethoxyphenyl moiety connected to the (2H)-1,2,3-triazole ring system. Compound 8a exhibited GI50 values of <10 nM against 80% of the cancer cell lines in the panel. Three triazole analogues, 8a, 8b and 8g, showed particularly potent growth inhibition against the triple negative Hs578T breast cancer cell line with GI50 values of 10.3 nM, 66.5 nM and 20.3 nM, respectively. Molecular docking studies suggest that these compounds bind to the same hydrophobic pocket at the interface of α- and β-tubulin that is occupied by colchicine and cis-CA-4, and are stabilized by Van der Waals’ interactions with surrounding amino acid residues. Compound 8a was found to inhibit tubulin polymerization in vitro with an IC50 value of 1.7 µM. The potent cytotoxicity of these novel compounds and their inhibition of tubulin dynamics make these triazole analogues promising candidates for development as anti-cancer drugs. PMID:27066215

  9. Synthesis Of Labeled Metabolites

    DOEpatents

    Martinez, Rodolfo A.; Silks, III, Louis A.; Unkefer, Clifford J.; Atcher, Robert

    2004-03-23

    The present invention is directed to labeled compounds, for example, isotopically enriched mustard gas metabolites including: [1,1',2,2'-.sup.13 C.sub.4 ]ethane, 1,1'-sulfonylbis[2-(methylthio); [1,1',2,2'-.sup.13 C.sub.4 ]ethane, 1-[[2-(methylsulfinyl)ethyl]sulfonyl]-2-(methylthio); [1,1',2,2'-.sup.13 C.sub.4 ]ethane, 1,1'-sulfonylbis[2-(methylsulfinyl)]; and, 2,2'-sulfinylbis([1,2-.sup.13 C.sub.2 ]ethanol of the general formula ##STR1## where Q.sup.1 is selected from the group consisting of sulfide (--S--), sulfone (--S(O)--), sulfoxide (--S(O.sub.2)--) and oxide (--O--), at least one C* is .sup.13 C, X is selected from the group consisting of hydrogen and deuterium, and Z is selected from the group consisting of hydroxide (--OH), and --Q.sup.2 --R where Q.sup.2 is selected from the group consisting of sulfide (--S--), sulfone(--S(O)--), sulfoxide (--S(O.sub.2)--) and oxide (--O--), and R is selected from the group consisting of hydrogen, a C.sub.1 to C.sub.4 lower alkyl, and amino acid moieties, with the proviso that when Z is a hydroxide and Q.sup.1 is a sulfide, then at least one X is deuterium.

  10. Labeled Cocaine Analogs

    DOEpatents

    Goodman, Mark M.; Shi, Bing Zhi; Keil, Robert N.

    1999-01-26

    Novel compounds having the structure: ##STR1## where X in .beta. configuration is phenyl, naphthyl; 2,3 or 4-iodophenyl; 2,3 or 4-(trimethylsilyl)phenyl; 3,4,5 or 6-iodonaphthyl; 3,4,5 or 6-(trimethylsilyl)naphthyl; 2,3 or 4-(trialkylstannyl)phenyl; or 3,4,5 or 6-(trialkylstannyl)naphthyl Y in .beta. configuration is Y.sub.1 or Y.sub.2, where Y.sub.1 is 2-fluoroethoxy, 3-fluoropropoxy, 4-fluorobutoxy, 2-fluorocyclopropoxy, 2 or 3-fluorocyclobutoxy, R,S 1'-fluoroisopropoxy, R 1'-fluoroisopropoxy, S 1'-fluoroisopropoxy, 1',3'-difluoroisopropoxy, R,S 1'-fluoroisobutoxy, R 1'-fluoroisobutoxy, S 1'-fluoroisobutoxy, R,S 4'-fluoroisobutoxy, R 4'-fluoroisobutoxy, S 4'-fluoroisobutoxy, or 1',1'-di(fluoromethyl)isobutoxy, and Y.sub.2 is 2-methanesulfonyloxy ethoxy, 3-methanesulfonyloxy propoxy, 4-methanesulfonyloxy butoxy, 2-methanesulfonyloxy cyclopropoxy, 2 or 3-methanesulfonyloxy cyclobutoxy, 1'methanesulfonyloxy isopropoxy, 1'-fluoro, 3'-methanesulfonyloxy isopropoxy, 1'-methanesulfonyloxy, 3'-fluoro isopropoxy, 1'-methanesulfonyloxy isobutoxy, or 4'-methanesulfonyloxy isobutoxy bind dopamine transporter protein and can be labeled with .sup.18 F or .sup.123 I for imaging.

  11. A survey of the lone pair effect on the ring geometry of 1,2,4-triazoles and analogous 1,2,3-triazoles and imidazoles. The structures of 1-methyl-5-amino-3-methylthio-1,2,4-triazole, 1-phenyl-5-amino-3-methylthio-1,2,4-triazole and 1-(4-methylbenzyl)-3-amino-5-methylthio-1,2,4-triazole

    NASA Astrophysics Data System (ADS)

    Kálmán, A.; Argay, Gy.

    1983-11-01

    The structures of the title compounds have been established by X-ray crystallography from diffractometer data. Crystals of the first ( I), C 4H 8N 4S, are monoclinic, space group P2 1/ c, with a = 8.166(2), b = 10.481(1), c = 8.585(1) Å, β = 109.33(2)°, Z = 4, D c = 1.381 g cm -3. Crystals of the second ( II), C 9H 10N 4S, are monoclinic, space group P2 1/ c, with a = 11.850(4), b = 7.898(1), c = 23.981 (6) Å, β = 117.23(2)°, Z = 8, D c = 1.373 g cm -3. Crystals of the third ( III), C 11H 14N 4S 1 are also monoclinic, space group P2 1/ c with a = 12.829(3), b = 8.348(1), c = 11.088(4) Å, β = 94.40(4)°, Z = 4, Dc = 1.314 g cm -3. The structures, determined by direct methods ( I, III) and Patterson synthesis ( II) were refined to R = 0.039 for 1070 reflections of I, R = 0.040 for 2792 reflections of II and R = 0.041 for 1900 reflections of III. The characteristic features of the planar five-membered rings are studied in comparison with the analogous 1,2,3-triazoles and imidazoles. It is shown that these planar rings exhibit only two patterns of the endocyclic bond angles induced dominantly by the number and relative position of the N-lone pairs. A similar effect of the double bonds (attached to C atoms) is also discussed.

  12. 27 CFR 19.517 - Statements required on labels under an exemption from label approval.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... labels under an exemption from label approval. 19.517 Section 19.517 Alcohol, Tobacco Products and... PLANTS Liquor Bottle, Label, and Closure Requirements Labeling Requirements § 19.517 Statements required on labels under an exemption from label approval. If a proprietor bottles spirits for domestic...

  13. 27 CFR 19.517 - Statements required on labels under an exemption from label approval.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... labels under an exemption from label approval. 19.517 Section 19.517 Alcohol, Tobacco Products and... PLANTS Liquor Bottle, Label, and Closure Requirements Labeling Requirements § 19.517 Statements required on labels under an exemption from label approval. If a proprietor bottles spirits for domestic...

  14. 27 CFR 19.517 - Statements required on labels under an exemption from label approval.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... labels under an exemption from label approval. 19.517 Section 19.517 Alcohol, Tobacco Products and... PLANTS Liquor Bottle, Label, and Closure Requirements Labeling Requirements § 19.517 Statements required on labels under an exemption from label approval. If a proprietor bottles spirits for domestic...

  15. 27 CFR 19.517 - Statements required on labels under an exemption from label approval.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... labels under an exemption from label approval. 19.517 Section 19.517 Alcohol, Tobacco Products and... PLANTS Liquor Bottle, Label, and Closure Requirements Labeling Requirements § 19.517 Statements required on labels under an exemption from label approval. If a proprietor bottles spirits for domestic...

  16. The use of stable isotope labeling and liquid chromatography/tandem mass spectrometry techniques to study the pharmacokinetics and bioavailability of the antimigraine drug, MK-0462 (rizatriptan) in dogs.

    PubMed

    Barrish, A; Olah, T V; Gatto, G J; Michel, K B; Dobrinska, M R; Gilbert, J D

    1996-01-01

    MK-0462 (rizatriptan) is a 5HT1D agonist being developed for the treatment of migraine. The assay for this substance in plasma and urine is based on HPLC with tandem mass spectrometry (MS/MS) detection. The procedure has been modified to include the simultaneous determination of the [triazole-13C2, 15N3-] stable-isotope-labelled analogue for which the lower quantifiable limit was 0.1 ng mL-1. The assay has been applied to study the pharmacokinetics of MK-0462 after simultaneous oral and intravenous administration of the drug and its stable-isotope-labelled analogue to dogs. The experiment afforded an estimate of plasma clearance concomitant with a precise measurement of the drug's oral bioavailability. The increasing use of LC-MS/MS in quantitative experiments may renew interest in stable isotopes as tools for pharmaceutical research. PMID:8755236

  17. Selective chemical labeling of proteins.

    PubMed

    Chen, Xi; Wu, Yao-Wen

    2016-06-28

    Over the years, there have been remarkable efforts in the development of selective protein labeling strategies. In this review, we deliver a comprehensive overview of the currently available bioorthogonal and chemoselective reactions. The ability to introduce bioorthogonal handles to proteins is essential to carry out bioorthogonal reactions for protein labeling in living systems. We therefore summarize the techniques that allow for site-specific "installation" of bioorthogonal handles into proteins. We also highlight the biological applications that have been achieved by selective chemical labeling of proteins. PMID:26940577

  18. Utilization of Stearic acid Extracted from Olive Pomace for Production of Triazoles, Thiadiazoles and Thiadiazines Derivatives of Potential Biological Activities.

    PubMed

    Soliman, Hanaa Mohamad; Basuny, Amany M; Arafat, Shaker M

    2015-01-01

    Olive Pomace was firstly dried, then pomace olive oil was extracted, and the obtained oil was hydrolyzed to produce glycerol and mixture of fatty acids. Fatty acids mixture was separated, this mixture was then cooled, where the all saturated fatty acids were solidified, and then they were filtered off. These saturated fatty acids were identified by GC mass after esterification, and were identified as stearic, palmitic and myristic acids. Stearic acid was extracted using supercritical CO2 extractor. The stearic acid was confirmed by means of GC mass after its esterification, and it was used as starting material for preparation of a variety of heterocyclic compounds, which were then tested for their antimicrobial activities. Thus the long-chain fatty acid hydrazide (2) was prepared from the corresponding long-chain fatty ester with hydrazine hydrate. Reacting 2 with phenyl isothiocyanate afforded the corresponding thiosemicarbazide 4. The later 4 underwent intramolecular cyclization in basic medium, and gave the s-triazole derivative 5, which was methylated and afforded 3-heptadecanyl-5-(methylthio)-4-phenyl-4H-1,3,4-triazole (7), which was then treated with hydrazine hydrate and afforded the corresponding 1-(5-heptadecanyl-4-phenyl-4H-1,2,4-triazol-3-yl) hydrazine (8).On the other hand, thiosemicarbazide 4 underwent intramolecular cyclization in acid medium and afforded the corresponding thiadiazole derivative 6.Treatment of thiosemicarbazide 4 with ethyl chloro(arylhydrazono) acetate derivatives 9a-b, furnished a single product 13 (Scheme 6). Similarly, when the thiosemicarbazide 4 was treated with the phenylcarbamoylarylhydrazonyl chloride 10a-c, it afforded (3-Aryl-N-5-(phenylcarbamoyl)-1,3,4-thiadiazol-2(3H)-ylidene)octadecanehydrazide 15a-c (Scheme 7). Also the reaction of thiosemicarbazide 4 with 2-oxo-N-arylpropanehydrazonoyl chlorides 11a-c and N-phenylbenzohydrazonoyl chloride 11d gave the corresponding thiadiazole derivatives 16a-d as shown in Scheme 8. A

  19. How to read food labels

    MedlinePlus

    ... 1 serving. You should also pay attention to trans fats on any food label. These fats raise "bad" ... foods and desserts. Many fast food restaurants use trans fats for frying. If a food has these fats, ...

  20. Dietary Supplement Label Database (DSLD)

    MedlinePlus

    ... Print Report Error T he Dietary Supplement Label Database (DSLD) is a joint project of the National ... participants in the latest survey in the DSLD database (NHANES): The search options: Quick Search, Browse Dietary ...

  1. Food Labels Tell the Story!

    MedlinePlus

    ... Environment Kids Health Topics Environment & Health Healthy Living Pollution Reduce, Reuse, Recycle Science – How It Works The ... Pay close attention to serving sizes. Products labeled "light" or "lite" must have 1/3 fewer calories ...

  2. Metabolic profile of FYX-051 (4-(5-pyridin-4-yl-1h-[1,2,4]triazol-3-yl)pyridine-2-carbonitrile) in the rat, dog, monkey, and human: identification of N-glucuronides and N-glucosides.

    PubMed

    Nakazawa, Takashi; Miyata, Kengo; Omura, Koichi; Iwanaga, Takashi; Nagata, Osamu

    2006-11-01

    FYX-051, 4-(5-pyridin-4-yl-1H-[1,2,4]triazol-3-yl)pyridine-2-carbonitrile, is a novel xanthine oxidoreductase inhibitor that can be used for the treatment of gout and hyperuricemia. We examined the metabolism of FYX-051 in rats, dogs, monkeys, and human volunteers after the p.o. administration of this inhibitor. The main metabolites in urine were pyridine N-oxide in rats, triazole N-glucoside in dogs, and triazole N-glucuronide in monkeys and humans, respectively. Furthermore, N-glucuronidation and N-glucosidation were characterized by two types of conjugation: triazole N(1)- and N(2)-glucuronidation and N(1)- and N(2)-glucosidation, respectively. N(1)- and N(2)-glucuronidation was observed in each species, whereas N(1)- and N(2)-glucosidation was mainly observed in dogs. With regard to the position of conjugation, N(1)-conjugation was predominant; this resulted in a considerably higher amount of N(1)-conjugate in each species than N(2)-conjugate. The present results indicate that the conjugation reaction observed in FYX-051 metabolism is unique, i.e., N-glucuronidation and N-glucosidation occur at the same position of the triazole ring, resulting in the generation of four different conjugates in mammals. In addition, a urinary profile of FYX-051 metabolites in monkeys and humans was relatively similar; triazole N-glucuronides were mainly excreted in urine. PMID:16914512

  3. General role of the amino and methylsulfamoyl groups in selective cyclooxygenase(COX)-1 inhibition by 1,4-diaryl-1,2,3-triazoles and validation of a predictive pharmacometric PLS model.

    PubMed

    Perrone, Maria Grazia; Vitale, Paola; Panella, Andrea; Fortuna, Cosimo G; Scilimati, Antonio

    2015-04-13

    A novel set of 1,4-diaryl-1,2,3-triazoles were projected as a tool to study the effect of both the heteroaromatic triazole as a core ring and a variety of chemical groups with different electronic features, size and shape on the catalytic activity of the two COX isoenzymes. The new triazoles were synthesized in fair to good yields and then evaluated for their inhibitory activity towards COXs arachidonic acid conversion catalysis. Their COXs selectivity was also measured. A predictive pharmacometric Volsurf plus model, experimentally confirmed by the percentage (%) of COXs inhibition at the concentration of 50 μM and IC50 values of the tested compounds, was built by using a number of isoxazoles of known COXs inhibitory activity as a training set. It was found that two compounds {4-(5-methyl-4-phenyl-1H-1,2,3-triazol-1-yl)benzenamine (18) and 4-[1-(4-methoxyphenyl)-5-methyl-1H-1,2,3-triazole-4-yl]benzenamine (19)} bearing an amino group (NH2) are potent and selective COX-1 inhibitors (IC50 = 15 and 3 μM, respectively) and that the presence of a methylsulfamoyl group (SO2CH3) is not a rule to have a Coxib. In fact, 4-(4-methoxyphenyl)-5-methyl-1-[4-(methylsulfonyl)phenyl]-1H-1,2,3-triazole (23) has COX-1 IC50 = 23 μM and was found inactive towards COX-2. PMID:25768707

  4. Enhanced Absorption Study of Ginsenoside Compound K (20-O-β-(D-Glucopyranosyl)-20(S)-protopanaxadiol) after Oral Administration of Fermented Red Ginseng Extract (HYFRG™) in Healthy Korean Volunteers and Rats

    PubMed Central

    Choi, Il-Dong; Ryu, Ju-Hee; Lee, Dong-Eun; Lee, Myoung-Hee; Shim, Jae-Joong; Ahn, Young-Tae; Sim, Jae-Hun; Huh, Chul-Sung; Shim, Wang-Seob; Yim, Sung-Vin; Chung, Eun-Kyoung

    2016-01-01

    To evaluate the pharmacokinetics of compound K after oral administration of HYFRG and RG in humans, an open-label, randomized, single-dose, fasting, and one-period pharmacokinetic study was conducted. After oral administration of a single 3 g dose of HYFRG and RG to 24 healthy Korean males, the mean (±SD) of AUC0–t and Cmax of compound K from HYFRG were 1466.83 ± 295.89 ng·h/mL and 254.45 ± 51.20 ng/mL, being 115.2- and 80-fold higher than those for RG (12.73 ± 7.83 ng·h/mL and 3.18 ± 1.70 ng/mL), respectively; in case of Sprague Dawley rats the mean (±SD) of AUC0–t and Cmax of compound K from HYFRG was 58.03 ± 32.53 ng·h/mL and 15.19 ± 10.69 ng/mL, being 6.3- and 6.0-fold higher than those from RG (9.21 ± 7.52 ng·h/mL and 2.55 ± 0.99 ng/mL), respectively. Tmax of compound K in humans and rats was 2.54 ± 0.92 and 3.33 ± 0.50 h for HYFRG and 9.11 ± 1.45 and 6.75 ± 3.97 hours for RG, respectively. In conclusion, the administration of HYFRG resulted in a higher and faster absorption of compound K in both humans and rats compared to RG. PMID:27516803

  5. LabeledIn: cataloging labeled indications for human drugs.

    PubMed

    Khare, Ritu; Li, Jiao; Lu, Zhiyong

    2014-12-01

    Drug-disease treatment relationships, i.e., which drug(s) are indicated to treat which disease(s), are among the most frequently sought information in PubMed®. Such information is useful for feeding the Google Knowledge Graph, designing computational methods to predict novel drug indications, and validating clinical information in EMRs. Given the importance and utility of this information, there have been several efforts to create repositories of drugs and their indications. However, existing resources are incomplete. Furthermore, they neither label indications in a structured way nor differentiate them by drug-specific properties such as dosage form, and thus do not support computer processing or semantic interoperability. More recently, several studies have proposed automatic methods to extract structured indications from drug descriptions; however, their performance is limited by natural language challenges in disease named entity recognition and indication selection. In response, we report LabeledIn: a human-reviewed, machine-readable and source-linked catalog of labeled indications for human drugs. More specifically, we describe our semi-automatic approach to derive LabeledIn from drug descriptions through human annotations with aids from automatic methods. As the data source, we use the drug labels (or package inserts) submitted to the FDA by drug manufacturers and made available in DailyMed. Our machine-assisted human annotation workflow comprises: (i) a grouping method to remove redundancy and identify representative drug labels to be used for human annotation, (ii) an automatic method to recognize and normalize mentions of diseases in drug labels as candidate indications, and (iii) a two-round annotation workflow for human experts to judge the pre-computed candidates and deliver the final gold standard. In this study, we focused on 250 highly accessed drugs in PubMed Health, a newly developed public web resource for consumers and clinicians on prevention

  6. Multi-focus cluster labeling.

    PubMed

    Eikvil, Line; Jenssen, Tor-Kristian; Holden, Marit

    2015-06-01

    Document collections resulting from searches in the biomedical literature, for instance, in PubMed, are often so large that some organization of the returned information is necessary. Clustering is an efficient tool for organizing search results. To help the user to decide how to continue the search for relevant documents, the content of each cluster can be characterized by a set of representative keywords or cluster labels. As different users may have different interests, it can be desirable with solutions that make it possible to produce labels from a selection of different topical categories. We therefore introduce the concept of multi-focus cluster labeling to give users the possibility to get an overview of the contents through labels from multiple viewpoints. The concept for multi-focus cluster labeling has been established and has been demonstrated on three different document collections. We illustrate that multi-focus visualizations can give an overview of clusters along axes that general labels are not able to convey. The approach is generic and should be applicable to any biomedical (or other) domain with any selection of foci where appropriate focus vocabularies can be established. A user evaluation also indicates that such a multi-focus concept is useful. PMID:25869415

  7. Discovery of 7-Methyl-10-Hydroxyhomocamptothecins with 1,2,3-Triazole Moiety as Potent Topoisomerase I Inhibitors.

    PubMed

    Xu, Xiguo; Wu, Yuelin; Liu, Wenfeng; Sheng, Chuanquan; Yao, Jianzhong; Dong, Guoqiang; Fang, Kun; Li, Jin; Yu, Zhiliang; Min, Xiao; Zhang, Huojun; Miao, Zhenyuan; Zhang, Wannian

    2016-09-01

    Homocamptothecin is emerging as an important topoisomerase I inhibitor originating in natural product camptothecin. We report the modifications and SAR of homocamptothecin on position C10 to develop potent topoisomerase I inhibitors for anticancer drug discovery. Based on click chemistry, twenty-one 1,2,3-triazole-substituted homocamptothecin derivatives were readily synthesized in two steps. For A549, cycloalkyl- and alkyl-substituted compounds 6j, 6l, and 6o revealed highly antiproliferative inhibitory activities with IC50 value of 30, 30, and 50 nm, respectively. In addition, cyclopropyl 6j exhibited greater Topo I inhibitory activity than 20(S)-Camptothecin, which indicated suitability for further drug development. PMID:27062430

  8. Design, synthesis and evaluation of semi-synthetic triazole-containing caffeic acid analogues as 5-lipoxygenase inhibitors.

    PubMed

    De Lucia, Daniela; Lucio, Oscar Méndez; Musio, Biagia; Bender, Andreas; Listing, Monika; Dennhardt, Sophie; Koeberle, Andreas; Garscha, Ulrike; Rizzo, Roberta; Manfredini, Stefano; Werz, Oliver; Ley, Steven V

    2015-08-28

    In this work the synthesis, structure-activity relationship (SAR) and biological evaluation of a novel series of triazole-containing 5-lipoxygenase (5-LO) inhibitors are described. The use of structure-guided drug design techniques provided compounds that demonstrated excellent 5-LO inhibition with IC50 of 0.2 and 3.2 μm in cell-based and cell-free assays, respectively. Optimization of binding and functional potencies resulted in the identification of compound 13d, which showed an enhanced activity compared to the parent bioactive compound caffeic acid 5 and the clinically approved zileuton 3. Compounds 15 and 16 were identified as lead compounds in inhibiting 5-LO products formation in neutrophils. Their interference with other targets on the arachidonic acid pathway was also assessed. Cytotoxicity tests were performed to exclude a relationship between cytotoxicity and the increased activity observed after structure optimization. PMID:26197161

  9. Water soluble poly(1-vinyl-1,2,4-triazole) as novel dielectric layer for organic field effect transistors

    PubMed Central

    Abbas, Mamatimin; Cakmak, Gulbeden; Tekin, Nalan; Kara, Ali; Guney, Hasan Yuksel; Arici, Elif; Sariciftci, Niyazi Serdar

    2011-01-01

    Water soluble poly(1-vinyl-1,2,4-triazole) (PVT) as a novel dielectric layer for organic field effect transistor is studied. Dielectric spectroscopy characterization reveals it has low leakage current and rather high breakdown voltage. Both n-channel and p-channel organic field effect transistors are fabricated using pentacene and fullerene as active layers. Both devices show device performances with lack of hysteresis, very low threshold voltages and high on/off ratios. Excellent film formation property is utilized to make AlOx and thin PVT bilayer in order to decrease the operating voltage of the devices. All solution processed ambipolar device is fabricated with simple spin coating steps using poly(2-methoxy-5-(2-ethyl-hexyloxy)-1,4-phenylenevinylene) (MEH–PPV) end capped with polyhedral oligomeric silsesquioxanes (POSS) as active layer. Our investigations show that PVT can be a very promising dielectric for organic field effect transistors. PMID:23794963

  10. A new three-dimensional Zn2 + coordination polymer constructed from oxalate and 1,2,4-triazolate

    NASA Astrophysics Data System (ADS)

    Wang, Yan-Ning; Zhu, Wan-Chun; Huo, Qi-Sheng; Yu, Jie-Hui; Xu, Ji-Qing

    2016-05-01

    A new 3-D Zn2 + coordination polymer (CP) [(CH3)2NH2]3[Zn6(ox)4.5(trz)6]ṡ 4H2O (ox = oxalate; trz = 1,2,4-triazolate) 1 was obtained by a simple solvothermal self-assembly. The crystal structural analysis demonstrates that the trz molecules link the Zn2 + ions into a two-dimensional (2-D) layer network, which is based on the trinuclear Zn3(trz)6 clusters. The ox molecules serve as the linkers to propagate the 2-D layers into a three-dimensional (3-D) network of 1. The thermogravimetry (TG) behavior, photoluminescence property, and the sensing ability of 1 are investigated. The sensing experiment on nitrobenzene (NB) reveals that 1 can serve as a fluorescence probe to detect NB at the ppm concentration.

  11. Some biologically active oxovanadium(IV) complexes of triazole derived Schiff bases: their synthesis, characterization and biological properties.

    PubMed

    Chohan, Zahid H; Sumrra, Sajjad H

    2010-10-01

    A series of biologically active oxovanadium(IV) complexes of triazole derived Schiff bases L(1)-L(5) have been synthesized and characterized by their physical, analytical, and spectral data. The synthesized ligands potentially act as bidentate, in which the oxygen of furfural and nitrogen of azomethine coordinate with the oxovanadium atom to give a stoichiometry of vanadyl complexes 1:2 (M:L) in a square-pyramidal geometry. In vitro antibacterial and antifungal activities on different species of pathogenic bacteria (E. coli, S. flexneri, P. aeruginosa, S. typhi, S. aureus, and B. subtilis) and fungi (T. longifusus, C. albicans, A. flavus, M. canis, F. solani, and C. glabrata) have been studied. All compounds showed moderate to significant antibacterial activity against one or more bacterial strains and good antifungal activity against most of the fungal strains. The brine shrimp bioassay was also carried out to check the cytotoxicity of coordinated and uncoordinated synthesized compounds. PMID:20429776

  12. Toxicokinetic Model Development for the Insensitive Munitions Component 3-Nitro-1,2,4-Triazol-5-One.

    PubMed

    Sweeney, Lisa M; Phillips, Elizabeth A; Goodwin, Michelle R; Bannon, Desmond I

    2015-01-01

    3-Nitro-1,2,4-triazol-5-one (NTO) is a component of insensitive munitions that are potential replacements for conventional explosives. Toxicokinetic data can aid in the interpretation of toxicity studies and interspecies extrapolation, but only limited data on the toxicokinetics and metabolism of NTO are available. To supplement these limited data, further in vivo studies of NTO in rats were conducted and blood concentrations were measured, tissue distribution of NTO was estimated using an in silico method, and physiologically based pharmacokinetic models of the disposition of NTO in rats and macaques were developed and extrapolated to humans. The model predictions can be used to extrapolate from designated points of departure identified from rat toxicology studies to provide a scientific basis for estimates of acceptable human exposure levels for NTO. PMID:26060267

  13. 5-(Adamantan-1-yl)-3-(benzyl­sulfan­yl)-4-methyl-4H-1,2,4-triazole

    PubMed Central

    Al-Abdullah, Ebtehal S.; El-Emam, Ali A.; Ghabbour, Hazem A.; Chantrapromma, Suchada; Fun, Hoong-Kun

    2012-01-01

    In the asymmetric unit of the title adamantyl derivative, C20H25N3S, there are two crystallographic independent mol­ecules with slightly different conformations. In one mol­ecule, the whole benzyl group is disordered over two orientations with the refined site-occupancy ratio of 0.63 (2):0.37 (2). The dihedral angles between the 1,2,4-triazole and phenyl rings are 24.3 (8) (major component) and 25.8 (13)° (minor component) in the disordered mol­ecule, whereas the corresponding angle is 51.53 (16)° in the other mol­ecule. In the crystal, mol­ecules are linked into a chain along the a axis by a weak C—H⋯N inter­action. Weak C—H⋯π inter­actions are also observed. PMID:22904878

  14. Synthesis and Anti-Inflammatory Activity of New Alkyl-Substituted Phthalimide 1H-1,2,3-Triazole Derivatives

    PubMed Central

    Assis, Shalom Pôrto de Oliveira; da Silva, Moara Targino; de Oliveira, Ronaldo Nascimento; Lima, Vera Lúcia de Menezes

    2012-01-01

    Four new 1,2,3-triazole phthalimide derivatives with a potent anti-inflammatory activity have been synthesized in the good yields by the 1,3-dipolar cycloaddition reaction from N-(azido-alkyl)phthalimides and terminal alkynes. The anti-inflammatory activity was determined by injecting carrageenan through the plantar tissue of the right hind paw of Swiss white mice to produce inflammation. All the compounds 3a–c and 5a–c exhibited an important anti-inflammatory activity; the best activity was found for the compounds 3b and 5c, which showed to be able to decrease by 69% and 56.2% carrageenan-induced edema in mice. These compounds may also offer a future promise as a new anti-inflammatory agent. PMID:23304092

  15. Multicomponent click synthesis of 1,2,3-triazoles from epoxides in water catalyzed by copper nanoparticles on activated carbon.

    PubMed

    Alonso, Francisco; Moglie, Yanina; Radivoy, Gabriel; Yus, Miguel

    2011-10-21

    Copper nanoparticles on activated carbon have been found to effectively catalyze the multicomponent synthesis of β-hydroxy-1,2,3-triazoles from a variety of epoxides and alkynes in water. The catalyst is easy to prepare, reusable at a low copper loading (0.5 mol %), and exhibits higher catalytic activity than some commercially available copper sources. The regio- and stereochemistry of the reaction has been revised and unequivocally established on the basis of X-ray crystallographic analyses. An NMR experiment has been implemented for the rapid and unmistakable determination of the regiochemistry of the process. Some mechanistic aspects of the reaction have been also undertaken which unveil the participation of copper(I) acetylides. PMID:21894972

  16. A new three-dimensional Zn(2+) coordination polymer constructed from oxalate and 1,2,4-triazolate.

    PubMed

    Wang, Yan-Ning; Zhu, Wan-Chun; Huo, Qi-Sheng; Yu, Jie-Hui; Xu, Ji-Qing

    2016-05-15

    A new 3-D Zn(2+) coordination polymer (CP) [(CH3)2NH2]3[Zn6(ox)4.5(trz)6]⋅4H2O (ox=oxalate; trz=1,2,4-triazolate) 1 was obtained by a simple solvothermal self-assembly. The crystal structural analysis demonstrates that the trz molecules link the Zn(2+) ions into a two-dimensional (2-D) layer network, which is based on the trinuclear Zn3(trz)6 clusters. The ox molecules serve as the linkers to propagate the 2-D layers into a three-dimensional (3-D) network of 1. The thermogravimetry (TG) behavior, photoluminescence property, and the sensing ability of 1 are investigated. The sensing experiment on nitrobenzene (NB) reveals that 1 can serve as a fluorescence probe to detect NB at the ppm concentration. PMID:26971022

  17. Synthesis, characterization and biological properties of thienyl derived triazole Schiff bases and their oxovanadium(IV) complexes.

    PubMed

    Chohan, Zahid H; Sumrra, Sajjad H

    2012-04-01

    A new series of biologically active thienyl derived triazole Schiff bases and their oxovanadium(IV) complexes have been synthesized and characterized on the basis of physical (m.p., magnetic susceptibility and conductivity), spectral (IR, ¹H and ¹³C NMR, electronic and mass spectrometry) and microanalytical data. All the Schiff base ligands and their oxovanadium(IV) complexes have been subjected to in vitro antibacterial activity against four Gram-negative (Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa, Salmonella enterica serover typhi) and two Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacterial strains and, for in vitro antifungal activity against Trichophyton longifucus, Candida albican, Aspergillus flavus, Microscopum canis, Fusarium solani and Candida glabrata. Brine shrimp bioassay was also carried out to check the cytotoxic nature of these compounds. PMID:21635212

  18. Energetic derivatives of 5-(5-amino-2H-1,2,3-triazol-4-yl)-1H-tetrazole.

    PubMed

    Izsák, Dániel; Klapötke, Thomas M; Pflüger, Carolin

    2015-10-21

    This study presents the preparation of the novel nitrogen-rich compound 5-(5-amino-2H-1,2,3-triazol-4-yl)-1H-tetrazole (5) from commercially available chemicals in a five step synthesis. The more energetic derivatives with azido (6) and nitro (7) groups, as well as a diazene bridge (8) were also successfully prepared. The energetic compounds were comprehensively characterized by various means, including vibrational (IR, Raman) and multinuclear ((1)H, (13)C, (14)N, (15)N) NMR spectroscopy, mass spectrometry and differential thermal analysis. The sensitivities towards important outer stimuli (impact, friction, electrostatic discharge) were determined according to BAM standards. The enthalpies of formation were calculated on the CBS-4M level of theory, revealing highly endothermic values, and were utilized to calculate the detonation parameters using EPXLO5 (6.02). PMID:26361356

  19. Halogen bonding in the antibacterial 1,2,4-triazole-3-thione derivative - Spectroscopic properties, crystal structure and conformational analysis

    NASA Astrophysics Data System (ADS)

    Miroslaw, Barbara; Plech, Tomasz; Wujec, Monika

    2015-03-01

    The molecular structure of 4-(4-bromophenyl)-5-(3-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (TP-4) has been determined by the X-ray diffraction experiment and compared to the geometry calculated in the ground state by using HF and DFT methods. The compound crystallizes in the triclinic P-1 space group. To explain the observed rotational disorder of meta-chloro-substituted aromatic ring the conformational analysis was performed for TP-4 and the molecular energy profile has been obtained. The vibrational frequencies in the solid state were recorded and compared to the calculated in the ground state. The molecular electrostatic potential isosurfaces (MEPS) were calculated to confirm the role of halogen bonds in stabilizing the crystal structure.

  20. Effect of a glucose-triazole-hydrogenated cardanol conjugate on lipid bilayer membrane organization and thermotropic phase transition

    NASA Astrophysics Data System (ADS)

    Swain, Jitendriya; Kamalraj, M.; Surya Prakash Rao, H.; Mishra, Ashok K.

    2015-02-01

    This work focuses on the membrane perturbation, solubilisation and thermotropic phase transition process of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) MLVs induced by a glucose-triazole-hydrogenated cardanol conjugate (GTHCC). GTHCC is a recently introduced non toxic sugar derivative. Differential scanning calorimetry (DSC) and fluorescence molecular probe based techniques have been used to understand the concentration dependent membrane perturbation, solubilisation and thermotropic phase transition process of DPPC MLVs. The phase transition temperature of DPPC MLVs decreases with increase in mol% of GTHCC. At higher concentration above 10 mol%, GTHCC was significantly perturbed the membrane organization. The intrinsic fluorescence of GTHCC is also found to be sensitive towards phase behaviour and changes in membrane organization of DPPC MLVs.

  1. Synthesis and evaluation of novel 1,2,3-triazole-based acetylcholinesterase inhibitors with neuroprotective activity.

    PubMed

    Li, Jia-Cheng; Zhang, Juan; Rodrigues, Mosar Corrêa; Ding, De-Jun; Longo, João Paulo Figueiró; Azevedo, Ricardo Bentes; Muehlmann, Luis Alexandre; Jiang, Cheng-Shi

    2016-08-15

    A series of new 1,2,3-triazole derivatives were synthesized and evaluated for anticholinesterase and neuroprotective activities. Some synthetic derivatives, especially compound 32, exhibited improved acetylcholinesterase (AChE) inhibitory activity by comparison with the hit 1, high selectivity toward AChE over butyrylcholinesterase (BuChE), and suitable in vitro neuroprotective effect against amyloid-β25-35 (Aβ25-35)-induced neurotoxicity in SH-SY5Y cells. Furthermore, these molecules have desired physicochemical properties in the range of CNS drugs and showed no cytotoxicity against two normal cells, including human keratinocytes HaCaT and murine fibroblasts NIH-3T3. The preliminary bioassay results and docking study indicated that compound 32 might be a promising lead compound with dual action for the treatment of Alzheimer's disease. PMID:27426301

  2. Trinitromethyl-substituted 5-nitro- or 3-azo-1,2,4-triazoles: synthesis, characterization, and energetic properties.

    PubMed

    Thottempudi, Venugopal; Gao, Haixiang; Shreeve, Jean'ne M

    2011-04-27

    Various new polynitro-1,2,4-triazoles containing a trinitromethyl group were synthesized by straightforward routes. These high nitrogen and oxygen-rich compounds were fully characterized using IR and multinuclear NMR spectroscopy, elemental analysis, natural bonding orbital (NBO) analysis, and differential scanning calorimetry (DSC) and, in the case of 12, with single crystal X-ray structuring. The heats of formation for all compounds were calculated with Gaussian 03 (revision D.01) and then combined with experimentally determined densities to determine detonation pressures (P) and velocities (D) of the energetic materials (Cheetah 5.0). They exhibit high density, good thermal stability, acceptable oxygen balance, positive heat of formation, and excellent detonation properties, which, in some cases, are superior to those of TNT, RDX, and HMX. PMID:21449560

  3. Anti-methicillin resistant Staphylococcus aureus activity, synergism with oxacillin and molecular docking studies of metronidazole-triazole hybrids.

    PubMed

    Negi, Beena; Kumar, Deepak; Kumbukgolla, Widuranga; Jayaweera, Sampath; Ponnan, Prija; Singh, Ramandeep; Agarwal, Sakshi; Rawat, Diwan S

    2016-06-10

    MRSA causes 60-70% of Staphylococcus aureus infection in hospitals and it has developed resistance against the currently available drugs. Interestingly, a series of 35 metronidazole-triazole hybrids on screening against MRSA were found to be active. Compound 22 was found to be effective at 4 μg/mL concentration against nine strains of MRSA. The inhibitory activity was further enhanced upto 1 μg/mL when this compound was used in combination with oxacillin in 1:1 ratio. All the compounds were found to be non-toxic in THP-1 cell line upto a concentration of 50 μM. The time-kill kinetics studies suggested bacteriostatic nature of the compounds. In silico studies show that these compounds interact with Thr600, Ser598, Asn464, His583 and Tyr446 in the active site of PBP2a crystal structure from MRSA. PMID:27046397

  4. Syntheses and biological evaluation of 1,2,3-triazole and 1,3,4-oxadiazole derivatives of imatinib.

    PubMed

    Li, Yong-Tao; Wang, Jing-Han; Pan, Cheng-Wen; Meng, Fan-Fei; Chu, Xiao-Qian; Ding, Ya-hui; Qu, Wen-Zheng; Li, Hui-ying; Yang, Cheng; Zhang, Quan; Bai, Cui-Gai; Chen, Yue

    2016-03-01

    Three novel series of 1,2,3-triazole and 1,3,4-oxadiazole derivatives of imatinib were prepared and evaluated in vitro for their cytostatic effects against a human chronic myeloid leukemia (K562), acute myeloid leukemia (HL60), and human leukemia stem-like cell line (KG1a). The structure-activity relationship was analyzed by determining the inhibitory rate of each imatinib analog. Benzene and piperazine rings were necessary groups in these compounds for maintaining inhibitory activities against the K562 and HL60 cell lines. Introducing a trifluoromethyl group significantly enhanced the potency of the compounds against these two cell lines. Surprisingly, some compounds showed significant inhibitory activities against KG1a cells without inhibiting common leukemia cell lines (K562 and HL60). These findings suggest that these compounds are able to inhibit leukemia stem-like cells. PMID:26850004

  5. Quercetin-3-O-β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranoside suppresses melanin synthesis by augmenting p38 MAPK and CREB signaling pathways and subsequent cAMP down-regulation in murine melanoma cells

    PubMed Central

    Jung, Hyun Gug; Kim, Han Hyuk; Paul, Souren; Jang, Jae Yoon; Cho, Yong Hun; Kim, Hyeon Jeong; Yu, Jae Myo; Lee, Eun Su; An, Bong Jeun; Kang, Sun Chul; Bang, Byung Ho

    2015-01-01

    In this study, the effect of purified quercetin-3-O-β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranosid (QCGG) on melanogenesis was investigated. QCGG was isolated from the calyx of a traditional Korean medicinal herb, Persimmon (Diospyros kaki). The hypopigmentation effects of QCGG were determined by examination of cellular melanin contents, tyrosinase activity assay, cAMP assay, and Western blotting of α-MSH-stimulated B16F10 mouse melanoma cells. Our results showed that QCGG inhibited both melanin synthesis and tyrosinase activity in a concentration-dependent manner as well as significantly reduced the expression of melanogenic proteins such as microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1, tyrosinase-related protein-2, and tyrosinase. Moreover, QCGG inhibited intracellular cAMP levels, cAMP response element-binding protein (CREB), and p38 MAPK expression in α-MSH-stimulated B16F10 cells. Taken together, the suppressive effects of QCGG on melanogenesis may involve down-regulation of MITF and its downstream signaling pathway via phosphorylation of p38 MAPK and CREB along with reduced cAMP levels. These results indicate that QCGG reduced melanin synthesis by reducing expression of tyrosine and tyrosine-related proteins via extracellular signal-related protein kinase (ERK) activation, followed by down-regulation of CREB, p38, and MITF. PMID:26586997

  6. Quercetin-3-O-β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranoside suppresses melanin synthesis by augmenting p38 MAPK and CREB signaling pathways and subsequent cAMP down-regulation in murine melanoma cells.

    PubMed

    Jung, Hyun Gug; Kim, Han Hyuk; Paul, Souren; Jang, Jae Yoon; Cho, Yong Hun; Kim, Hyeon Jeong; Yu, Jae Myo; Lee, Eun Su; An, Bong Jeun; Kang, Sun Chul; Bang, Byung Ho

    2015-11-01

    In this study, the effect of purified quercetin-3-O-β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranosid (QCGG) on melanogenesis was investigated. QCGG was isolated from the calyx of a traditional Korean medicinal herb, Persimmon (Diospyros kaki). The hypopigmentation effects of QCGG were determined by examination of cellular melanin contents, tyrosinase activity assay, cAMP assay, and Western blotting of α-MSH-stimulated B16F10 mouse melanoma cells. Our results showed that QCGG inhibited both melanin synthesis and tyrosinase activity in a concentration-dependent manner as well as significantly reduced the expression of melanogenic proteins such as microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1, tyrosinase-related protein-2, and tyrosinase. Moreover, QCGG inhibited intracellular cAMP levels, cAMP response element-binding protein (CREB), and p38 MAPK expression in α-MSH-stimulated B16F10 cells. Taken together, the suppressive effects of QCGG on melanogenesis may involve down-regulation of MITF and its downstream signaling pathway via phosphorylation of p38 MAPK and CREB along with reduced cAMP levels. These results indicate that QCGG reduced melanin synthesis by reducing expression of tyrosine and tyrosine-related proteins via extracellular signal-related protein kinase (ERK) activation, followed by down-regulation of CREB, p38, and MITF. PMID:26586997

  7. Synthesis and biological activity of two pregnane derivatives with a triazole or imidazole ring at C-21.

    PubMed

    Silva-Ortiz, Aylin Viviana; Bratoeff, Eugene; Ramírez-Apan, María Teresa; García-Becerra, Rocío; Ordaz-Rosado, David; Noyola-Martínez, Nancy; Castillo-Bocanegra, Rafael; Barrera, David

    2016-05-01

    Pregnane derivatives are studied as agents for the treatment of different hormone-dependent diseases. The biological importance of these steroids is based on their potential use against cancer. In this study, we report the synthesis, characterization and biological activity of two pregnane derivatives with a triazole (3β-hydroxy-21-(1H-1,2,4-triazol-1-yl)pregna-5,16-dien-20-one; T-OH) or imidazole (3β-hydroxy-21-(1H-imidazol-1-yl)pregna-5,16-dien-20-one; I-OH) moieties at C-21. These derivatives were synthesized from 16-dehydropregnenolone acetate. The activity on cell proliferation of the compounds was measured on three human cancer cells lines: prostate cancer (PC-3), breast cancer (MCF7) and lung cancer (SK-LU-1). The cytotoxic and antiproliferative effects of T-OH and I-OH were assessed by using SBR and XTT methods, respectively. The gene expressions were evaluated by real time PCR. In addition, results were complemented by docking studies and transactivation assays using an expression vector to progesterone and androgen receptor. Results show that the two compounds inhibited the three cell lines proliferation in a dose-dependent manner. Compound I-OH downregulated the gene expression of the cyclins D1 and E1 in PC-3 and MFC7 cells; however, effect upon Ki-67, EAG1, BIM or survivin genes was not observed. Docking studies show poor interaction with the steroid receptors. Nevertheless, the transactivation assays show a weak antagonist effect of I-OH on progesterone receptor but not androgenic or antiandrogenic actions. In conclusion, the synthesized compounds inhibited cell proliferation as well as genes key to cell cycle of PC-3 and MCF7 cell lines. Therefore, these compounds could be considered a good starting point for the development of novel therapeutic alternatives to treat cancer. PMID:26924581

  8. Synthesis, Structure Determination, and Hydrogen Sorption Studies of New Metal-Organic Frameworks Using Triazole and Naphthalenedicarboxylic Acid

    SciTech Connect

    Park,H.; Britten, J.; Mueller, U.; Lee, J.; Li, J.; Parise, J.

    2007-01-01

    Two new metal-organic framework compounds were synthesized under solvothermal conditions using Zn{sup 2+} ion, 1,2,4-triazole (TRZ), and 1,4- and 2,6-naphthalenedicarboxylic acids (NDC): Zn{sub 4}(TRZ){sub 4}(1,4-NDC){sub 2}-2DMF-2H{sub 2}O (1) and Zn{sub 4}(TRZ){sub 4}(2,6-NDC){sub 2}-2DMF-4H{sub 2}O (2). Their crystal structures were characterized by single-crystal X-ray diffraction. Structure 1 crystallizes in the P2{sub 1}/n space group with a = 13.609(2) {angstrom}, b = 27.181(5){angstrom}, c = 13.617(3) {angstrom}, {beta} = 92.46(1){sup o}, V = 5032.4(16) {angstrom}{sup 3}, and Z = 4. Structure 2 crystallizes in orthorhombic Pna2{sub 2} space group with a = 30.978(6) {angstrom}, b = 12.620(3) {angstrom}, c = 13.339(3) {angstrom}, V = 5215(2) {angstrom}{sup 3}, and Z = 4. Both structures are analogues of the previously reported Zn{sub 4}(TRZ){sub 4}(1,4-BDC){sub 2}-16H{sub 2}O where the layers of Zn-triazole moieties are pillared by aromatic dicarboxylates to create 3-D open frameworks. Nitrogen sorption studies revealed that these structures have Brunaer-Emmett-Teller (BET) surface areas of 362.1-584.1 m{sup 2}/g. Hydrogen sorption experiments showed they can store 0.84-1.09 wt % H{sub 2} at 77 K and 1 atm. Although they do not contain large pores or surface areas, they possess the hydrogen sorption capacities comparable to those of highly porous metal-organic frameworks.

  9. Calorimetric investigation of triazole-bridged Fe(II) spin-crossover one-dimensional materials: measuring the cooperativity.

    PubMed

    Roubeau, Olivier; Castro, Miguel; Burriel, Ramón; Haasnoot, Jaap G; Reedijk, Jan

    2011-03-31

    The relevance of abrupt magnetic and optical transitions exhibiting bistability in spin-crossover solids has been pointed out for their potential applications in optical or memory devices. In this respect, triazole-based one-dimensional coordination polymers are widely recognized as one of the most interesting systems. The measure of the interaction among spin-crossover centers at the origin of such cooperative behavior is of paramount importance and has so far been realized through modeling of spin-crossover curves derived mostly from magnetic measurements. Here, a new series of triazole-based one-dimensional coordination polymers of formula [Fe(Rtrz)(3)](A)(2)·xH(2)O with R = methoxyethyl and A = monovalent anion has been prepared that show complete and abrupt spin-crossover phenomenon as shown by magnetic measurements. The spin-crossover transition in these and related compounds is studied by differential scanning calorimetry, and the thermodynamic excess enthalpies and entropies associated with the phenomenon are derived systematically. Then the cooperative character of the spin-crossover in these materials is quantified by use of two widely used models, so-called Slichter and Drickamer and domain models. The same procedure is applied to spin-crossover curves of similar compounds available in the literature and for which calorimetric studies have been reported. The experimental thermodynamic figures, in particular the excess enthalpies, are shown to be clearly correlated to the output parameters of both models, thus providing a direct, experimental, quantitative measure of the cooperative character of the spin-crossover phenomenon. PMID:21381636

  10. Synthesis of Rapamycin Derivatives Containing the Triazole Moiety Used as Potential mTOR-Targeted Anticancer Agents.

    PubMed

    Xie, Lijun; Huang, Jie; Chen, Xiaoming; Yu, Hui; Li, Kualiang; Yang, Dan; Chen, Xiaqin; Ying, Jiayin; Pan, Fusheng; Lv, Youbing; Cheng, Yuanrong

    2016-06-01

    Rapamycin, a potent antifungal antibiotic, was approved as immunosuppressant, and lately its derivatives have been developed into mTOR targeting anticancer drugs. Structure modification was performed at the C-42 position of rapamycin, and a novel series of rapamycin triazole hybrids (4a-d, 5a-e, 8a-e, and 9a-e) was facilely synthesized via Huisgen's reaction. The anticancer activity of these compounds was evaluated against the Caski, H1299, MGC-803, and H460 human cancer cell lines. Some of the derivatives (8a-e, 9a-e) appeared to have stronger activity than that of rapamycin; however, 4a-d and 5a-e failed to show potential anticancer activity. Compound 9e with a (2,4-dichlorophenylamino)methyl moiety on the triazole ring was the most active anticancer compound, which showed IC50 values of 6.05 (Caski), 7.89 (H1299), 25.88 (MGC-803), and 8.60 μM (H460). In addition, research on the mechanism showed that 9e was able to cause cell morphological changes and to induce apoptosis in the Caski cell line. Most importantly, 9e can decrease the phosphorylation of mTOR and of its downstream key proteins, S6 and P70S6K1, indicating that 9e can effectively inhibit the mTOR signaling pathway. Thus, it may have the potential to become a new mTOR inhibitor against various cancers. PMID:27150260

  11. 49 CFR 172.426 - OXIDIZER label.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SECURITY PLANS Labeling § 172.426 OXIDIZER label. (a) Except for size and color, the OXIDIZER label must be as follows: EC02MR91.027 (b) In addition to complying with § 172.407, the background color on the OXIDIZER label must be yellow....

  12. 49 CFR 172.426 - OXIDIZER label.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... SECURITY PLANS Labeling § 172.426 OXIDIZER label. (a) Except for size and color, the OXIDIZER label must be as follows: EC02MR91.027 (b) In addition to complying with § 172.407, the background color on the OXIDIZER label must be yellow....

  13. 49 CFR 172.426 - OXIDIZER label.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... SECURITY PLANS Labeling § 172.426 OXIDIZER label. (a) Except for size and color, the OXIDIZER label must be as follows: EC02MR91.027 (b) In addition to complying with § 172.407, the background color on the OXIDIZER label must be yellow....

  14. 49 CFR 172.426 - OXIDIZER label.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... SECURITY PLANS Labeling § 172.426 OXIDIZER label. (a) Except for size and color, the OXIDIZER label must be as follows: EC02MR91.027 (b) In addition to complying with § 172.407, the background color on the OXIDIZER label must be yellow....

  15. 21 CFR 610.61 - Package label.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... GENERAL BIOLOGICAL PRODUCTS STANDARDS Labeling Standards § 610.61 Package label. The following items shall appear on the label affixed to each package containing a product: (a) The proper name of the product; (b... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Package label. 610.61 Section 610.61 Food...

  16. 40 CFR 211.108 - Sample label.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Sample label. 211.108 Section 211.108 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS PRODUCT NOISE LABELING General Provisions § 211.108 Sample label. Examples of labels conforming to the requirements...

  17. 40 CFR 211.108 - Sample label.

    Code of Federal Regulations, 2010 CFR

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    Code of Federal Regulations, 2014 CFR

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    Code of Federal Regulations, 2013 CFR

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    Code of Federal Regulations, 2011 CFR

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