Science.gov

Sample records for labeled glucopyranosyl triazole

  1. Synthesis of alpha- and beta-D-glucopyranosyl triazoles by CuAAC 'click chemistry': reactant tolerance, reaction rate, product structure and glucosidase inhibitory properties.

    PubMed

    Dedola, Simone; Hughes, David L; Nepogodiev, Sergey A; Rejzek, Martin; Field, Robert A

    2010-06-16

    Cu(I)-catalysed azide alkyne 1,3-dipolar cycloaddition (CuAAC) 'click chemistry' was used to assemble a library of 21 alpha-D- and beta-D-glucopyranosyl triazoles, which were assessed as potential glycosidase inhibitors. In the course of this work, different reactivities of isomeric alpha- and beta-glucopyranosyl azides under CuAAC conditions were noted. This difference was further investigated using competition reactions and rationalised on the basis of X-ray crystallographic data, which revealed significant differences in bond lengths within the azido groups of the alpha- and beta-anomers. Structural studies also revealed a preference for perpendicular orientation of the sugar and triazole rings in both the alpha- and beta-glucosyl triazoles in the solid state. The triazole library was assayed for inhibition of sweet almond beta-glucosidase (GH1) and yeast alpha-glucosidase (GH13), which led to the identification of a set of glucosidase inhibitors effective in the 100 microM range. The preference for inhibition of one enzyme over the other proved to be dependent on the anomeric configuration of the inhibitor, as expected.

  2. A (18)F-labeled glucose analog: synthesis using a click labeling method and in vitro evaluation.

    PubMed

    Kim, Dong Hyun; Choe, Yearn Seong; Jung, Kyung-Ho; Lee, Kyung-Han; Choi, Joon Young; Choi, Yong; Kim, Byung-Tae

    2008-05-01

    A (18)F-labeled glucose analog, 4-[(2-[(18)F]fluoroethyl)-1-(beta-D: -glucopyranosyl)]-1H-1,2,3-triazole ([(18)F]1), was synthesized using a click labeling method and evaluated in vitro for its cellular transportation via glucose transporter (Glut-1) and its potential as a hexokinase substrate. The click labeling method was superior to conventional labeling method, due to a higher decay-corrected radiochemical yield (30% vs. 21%), higher specific activity (59.9 GBq/mumol vs. 23.5 GBq/mumol), and shorter synthesis time (75-80 min vs. 95-100 min). In vitro evaluation demonstrated that [(18)F]1 does not act as a hexokinase substrate and has low and non-specific uptake by SNU-C5 cells. These results suggest that click chemistry offers a rapid and efficient radiolabeling method which does not require the protection of functional groups, although a triazole moiety at C1 of [(18)F]1 is incompatible for hexokinase phosphorylation and facilitative diffusion via Glut-1. PMID:18481013

  3. 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.

  4. 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

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

    PubMed

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

    2016-01-28

    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 (18)F-labeling of internalizing biomolecules based on a template used successfully for radioiodination. N-Succinimidyl 3-((4-(4-[(18)F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(bis-Boc-guanidinomethyl)benzoate ([(18)F]SFBTMGMB-Boc2) was synthesized by a click reaction of an azide precursor and [(18)F]fluorohexyne in 8.5 ± 2.8% average decay-corrected radiochemical yield (n = 15). An anti-HER2 nanobody 5F7 was labeled with (18)F using [(18)F]SFBTMGMB ([(18)F]RL-I), obtained by the deprotection of [(18)F]SFBTMGMB-Boc2, in 31.2 ± 6.7% (n = 5) conjugation efficiency. The labeled nanobody had a radiochemical purity of >95%, bound to 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 (18)F has been developed. An anti-HER2 nanobody was labeled using this prosthetic group with retention of affinity and immunoreactivity to HER2.

  6. 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…

  7. 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.

  8. 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.

  9. Synthesis and characterisation of methyl 2-O-(beta-D- glucopyranosyl)-6-O-(alpha-L-rhamnopyranosyl)-alpha-D-glucopyranoside.

    PubMed

    Hansmann, C F

    1990-09-01

    The branched trisaccharide, 2-O-(beta-D-glucopyranosyl)-6-O-(alpha-L-rhamnopyranosyl)-D-glucopyranos e (2), is regarded as the sugar moiety of an anthocyanin pigment isolated from the fruits and flowers of certain Begonia, Clivia, Rubus, Prunus, and Ribis species. The cyanidin-3-glycoside of 1 has been identified as one of the major pigments of Montmorency cherries (Prunus cerasus). It has also been isolated as quercetin and kaempherol glycosides from the flowers of potato (Solanum tuberosum). Synthesis of the methyl glycoside of 1, methyl 2-O-(beta-D-glucopyranosyl)-6-O-(alpha-L-rhamnopyranosyl)-alpha-D-glucop yranoside (2) is reported. PMID:2279247

  10. 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.

  11. An azido-BODIPY probe for glycosylation: initiation of strong fluorescence upon triazole formation.

    PubMed

    Shie, Jiun-Jie; Liu, Ying-Chih; Lee, Yu-Ming; Lim, Carmay; Fang, Jim-Min; Wong, Chi-Huey

    2014-07-16

    We have designed a low fluorescent azido-BODIPY-based probe AzBOCEt (Az10) that undergoes copper(I)-catalyzed 1,3-dipolar cycloadditions with alkynes to yield strongly fluorescent triazole derivatives. The fluorescent quantum yield of a triazole product T10 is enhanced by 52-fold as compared to AzBOCEt upon excitation at a wavelength above 500 nm. Quantum mechanical calculations indicate that the increase in fluorescence upon triazole formation is due to the lowering of the HOMO energy level of the aryl moiety to reduce the process of acceptor photoinduced electron transfer. AzBOCEt is shown to label alkyne-functionalized proteins in vitro and glycoproteins in cells with excellent selectivity, and enables cell imaging and visualization of glycoconjugates in alkynyl-saccharide-treated cells at extremely low concentration (0.1 μM). Furthermore, the alkyne-tagged glycoproteins from cell lysates can be directly detected with AzBOCEt in gel electrophoresis. PMID:24955871

  12. Relative activity of N-(beta-D-glucopyranosyl)nicotinic acid to nicotinic acid as a niacin nutrient in rats and in Lactobacillus plantarum ATCC 8014.

    PubMed

    Nishitani, H; Taguchi, H; Yonezima, M; Shibata, K

    1996-02-01

    We investigated the relative activity of N-(beta-D-glucopyranosyl)-nicotinic acid as a niacin nutrient in rats and in Lactobacillus plantarum ATCC 8014. N-(beta-D-Glucopyranosyl)-nicotinic acid is a detoxified product or storage form of nicotinic acid that is found in plants. The relative activity of N-(beta-D-glucopyranosyl)nicotinic acid to nicotinic acid in rats was 1/2.3, 1/2.2, 1/1.0, and 1/1.7 as indices of the body weight gain, food intake, blood NAD content, and the increased urinary excretion of niacin and its metabolites, respectively. N-(beta-D-Glucopyranosyl)nicotinic acid had no niacin activity in Lactobacillus plantarum ATCC 8014.

  13. Synthetic, enzyme kinetic, and protein crystallographic studies of C-β-d-glucopyranosyl pyrroles and imidazoles reveal and explain low nanomolar inhibition of human liver glycogen phosphorylase.

    PubMed

    Kantsadi, Anastassia L; Bokor, Éva; Kun, Sándor; Stravodimos, George A; Chatzileontiadou, Demetra S M; Leonidas, Demetres D; Juhász-Tóth, Éva; Szakács, Andrea; Batta, Gyula; Docsa, Tibor; Gergely, Pál; Somsák, László

    2016-11-10

    C-β-d-Glucopyranosyl pyrrole derivatives were prepared in the reactions of pyrrole, 2-, and 3-aryl-pyrroles with O-peracetylated β-d-glucopyranosyl trichloroacetimidate, while 2-(β-d-glucopyranosyl) indole was obtained by a cross coupling of O-perbenzylated β-d-glucopyranosyl acetylene with N-tosyl-2-iodoaniline followed by spontaneous ring closure. An improved synthesis of O-perbenzoylated 2-(β-d-glucopyranosyl) imidazoles was achieved by reacting C-glucopyranosyl formimidates with α-aminoketones. The deprotected compounds were assayed with isoforms of glycogen phosphorylase (GP) to show no activity of the pyrroles against rabbit muscle GPb. The imidazoles proved to be the best known glucose derived inhibitors of not only the muscle enzymes (both a and b) but also of the pharmacologically relevant human liver GPa (Ki = 156 and 26 nM for the 4(5)-phenyl and -(2-naphthyl) derivatives, respectively). An X-ray crystallographic study of the rmGPb-imidazole complexes revealed structural features of the strong binding, and also allowed to explain the absence of inhibition for the pyrrole derivatives. PMID:27522507

  14. Novel transdermal drug penetration enhancer: synthesis and enhancing effect of alkyldisiloxane compounds containing glucopyranosyl group.

    PubMed

    Akimoto, Tomoko; Nagase, Yu

    2003-03-01

    The syntheses of alkyldisiloxanes containing sugar moiety with various alkyl chain length were investigated, in order to develop a silicone-based transdermal penetration enhancer which was expected to show a low irritation to the skin. 1-Alkyl-3-beta-D-glucopyranosyl-1,1,3,3-tetramethyldisiloxanes (Glc-SiCs) were prepared by two-step hydrosilylations of 1-alkene and 1-allyl-beta-D-glucose tetraacetate with 1,1,3,3-tetramethyldisiloxane in the presence of bis(benzonitrile)platinum dichloride as the catalyst, followed by hydrolysis of the acetyl groups with sodium methoxide. The enhancing effect of Glc-SiCs on the percutaneous drug penetration was evaluated by in vitro experiments using a two-chamber diffusion cell. Antipyrine (ANP) and indomethacin (IND) were used as hydrophilic and hydrophobic model drugs, respectively, and the amount of drug permeating through the rat abdominal skin with or without Glc-SiCs was estimated by HPLC. As a result, Glc-SiCs exhibited a enhancing effect on the permeation of both drugs through the skin, which was influenced by the alkyl chain length of Glc-SiCs. In addition, it was suggested that a suitable balance of polarity would be necessary to appear the high enhancing effect, where Glc-SiCs with octyl and decyl groups exhibited the highest enhancing effect. From the determination of kinetic parameters in the drug permeation, it was also found that this enhancing effect was due to the increase of both partition and diffusion coefficients of drug permeation through the skin. By experiments to determine the amount of cholesterol extracted from the skin, the defatting effect would be one of the functions of Glc-SiCs which resulted in the high enhancing activity. Furthermore, according to the Draize test, it was confirmed that Glc-SiCs showed a low irritation to the skin.

  15. Triazole fungicides and the selection of resistance to medical triazoles in the opportunistic mould Aspergillus fumigatus.

    PubMed

    Verweij, Paul E; Kema, Gert H J; Zwaan, Bas; Melchers, Willem J G

    2013-02-01

    Azole resistance is an emerging problem in the opportunistic mould Aspergillus fumigatus. The triazoles are the most important agents for the management of Aspergillus diseases in humans. Selection for acquired resistance may occur in the hospital setting through exposure to high doses of azoles during azole therapy, but evidence is accumulating that A. fumigatus may become resistant to medical triazoles through environmental exposure to fungicides. The recovery of A. fumigatus isolates resistant to the medical triazoles from azole-naive patients as well as from the environment strongly indicates an environmental route of resistance selection. Molecule alignment studies have identified five fungicides that share a very similar molecule structure with the medical triazoles, and thus may have selected for mechanisms that confer resistance to both groups of compounds. It is important to explore further the presumed fungicide-driven route of resistance selection in order to implement effective preventive measures as the prevalence of azole resistance in A. fumigatus continues to increase and causes major challenges in the management of azole-resistant Aspergillus diseases.

  16. 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...

  17. Primary structures of one elicitor-active and seven elicitor-inactive hexa(. beta. -D-glucopyranosyl)-D-glucitols isolated from the mycelial walls of Phytophthora megasperma f. sp. glycinea

    SciTech Connect

    Sharp, J.K.; McNeil, M.; Albersheim, P.

    1984-09-25

    The primary structures of eight hexa(..beta..-D-glucopyranosyl)-D-glucitols purified from partially hydrolyzed Phytophthora megasperma f. sp. glycinea mycelial walls were determined by microscale glycosyl-sequence analysis. The similarity in structure of six of the elicitor-inactive hexa(..beta..-D-glucopyranosyl)-D-glucitols to the elicitor-active hexa(..beta..-D-glucopyranosyl)-D-glucitol established that a highly defined structure is required for elicitor activity. The elicitor-active hexa(..beta..-D-glucopyranosyl)-D-glucitol is the first example of a complex carbohydrate acting as a regulatory molecule in plants. 49 references, 10 figures, 6 tables.

  18. 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

  19. 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 (...

  20. Triazole-substituted nitroarene derivatives: synthesis, characterization, and energetic studies.

    PubMed

    Kommu, Nagarjuna; Ghule, Vikas D; Kumar, A Sudheer; Sahoo, Akhila K

    2014-01-01

    A series of dense and energetic polynitroaryl-1,2,4-triazoles were synthesized through the nitration of aryl-1,2,4-triazoles. The Cu-catalyzed/base-mediated coupling reactions of haloarenes with 1,2,4-triazoles delivered N-aryl-1,2,4-triazoles. These new nitro-rich-aryltriazoles were characterized by analytical and spectroscopic methods. The solid-state structures of most of these compounds were established by X-ray diffraction analysis. Their thermal properties were determined by differential scanning calorimetry-thermogravimetric analysis. Their heats of formation (HOFs) and crystal densities were also calculated. The densities of the synthesized compounds ranged from 1.40 to 1.85 g cm(-3). Some of these newly synthesized compounds exhibited high positive HOFs, good thermal stabilities, high densities, and reasonable detonation velocities and pressures.

  1. 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...

  2. 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.

  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. 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

  5. Antibacterial and antifungal metal based triazole Schiff bases.

    PubMed

    Chohan, Zahid H; Hanif, Muhammad

    2013-10-01

    A new series of four biologically active triazole derived Schiff base ligands (L(1)-L(4)) and their cobalt(II), nickel(II), copper(II) and zinc(II) complexes (1-16) have been synthesized and characterized. The ligands were prepared by the condensation reaction of 3-amino-5-methylthio-1H-1,2,4-triazole with chloro-, bromo- and nitro-substituted 2-hydroxybenzaldehyde in an equimolar ratio. The antibacterial and antifungal bioactivity data showed the metal(II) complexes to be more potent antibacterial and antifungal than the parent Schiff bases against one or more bacterial and fungal species.

  6. Multi-triazole-resistant Aspergillus fumigatus infections in Australia.

    PubMed

    Kidd, Sarah E; Goeman, Emma; Meis, Jacques F; Slavin, Monica A; Verweij, Paul E

    2015-06-01

    The emergence of triazole resistance, including multi-triazole-resistant Aspergillus fumigatus is being reported around the world, but there has been little evidence of this problem to date in Australia. Here we describe a retrospective search of antifungal susceptibility results of all Australian clinical A. fumigatus isolates referred to the National Mycology Reference Centre, Adelaide, Australia between 2000 and 2013, yielding 13 isolates with elevated minimum inhibitory concentrations to itraconazole, posaconazole and/or voriconazole. Four isolates were found to be Aspergillus lentulus, a closely related, morphologically similar species known to have reduced susceptibility to triazoles. Analysis of the cyp51A gene of nine confirmed A. fumigatus isolates revealed two carrying the TR34 /L98H mutation, one apparently locally acquired in 2004, and the other probably acquired abroad in 2012. Four isolates possessed the G54R, F46Y, Y431S and G448S mutations, respectively, whereas three isolates did not possess known cyp51A resistance mutations, raising the possibility of other, undetected resistance mechanisms. Routine antifungal susceptibility testing is definitively recommended in patients on long term and sub-therapeutic triazole therapy with breakthrough Aspergillus infection and recommended for all clinically relevant A. fumigatus isolates. PMID:25885568

  7. 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.

  8. Inhibition of rat and human steroidogenesis by triazole antifungals.

    PubMed

    Goetz, Amber K; Rockett, John C; Ren, Hongzu; Thillainadarajah, Inthirany; Dix, David J

    2009-12-01

    Environmental chemicals that alter steroid production could interfere with male reproductive development and function. Three agricultural antifungal triazoles that are known to modulate expression of cytochrome P450 (CYP) genes and enzymatic activities were tested for effects on steroidogenesis using rat in vivo (triadimefon), rat in vitro (myclobutanil and triadimefon), and human in vitro (myclobutanil, propiconazole, and triadimefon) model systems. Hormone production was measured in testis organ cultures from untreated adult and neonatal rats, following in vitro exposure to 1, 10, or 100 muM of myclobutanil or triadimefon. Myclobutanil and triadimefon reduced media levels of testosterone by 40-68% in the adult and neonatal testis culture, and altered steroid production in a manner that indicated CYP17-hydroxylase/17,20 lyase (CYP17A1) inhibition at the highest concentration tested. Rat to human comparison was explored using the H295R (human adrenal adenocarcinoma) cell line. Following 48 h exposure to myclobutanil, propiconazole, or triadimefon at 1, 3, 10, 30, or 100 muM, there was an overall decrease in estradiol, progesterone, and testosterone by all three triazoles. These data indicate that myclobutanil, propiconazole, and triadimefon are weak inhibitors of testosterone production in vitro. However, in vivo exposure of rats to triazoles resulted in increased serum and intra-testicular testosterone levels. This discordance could be due to higher concentrations of triazoles tested in vitro, and differences within an in vitro model system lacking hepatic metabolism and neuroendocrine control.

  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.

  10. 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

  11. 1-Benzyl-4-(naphthalen-1-yl)-1H-1,2,3-triazole

    PubMed Central

    Sarmiento-Sánchez, Juan I.; Aguirre, Gerardo; Rivero, Ignacio A.

    2011-01-01

    In the title compound, C19H15N3, the benzyl group is almost perpendicular to the triazole ring [dihedral angle = 80.64 (8)°], while the napthyl group makes an angle of 30.27 (12)° with the plane of the triazole ring. This conformation is different from the 1-benzyl-4-phenyl-1H-1,2,3-triazole analogue, which has the benzyl ring system at an angle of 87.94° and the phenyl group at an angle of 3.35° to the plane of the triazole ring. PMID:21837221

  12. Glycogen phosphorylase as a target for type 2 diabetes: synthetic, biochemical, structural and computational evaluation of novel N-acyl-N´-(β-D-glucopyranosyl) urea inhibitors.

    PubMed

    Kantsadi, Anastassia L; Parmenopoulou, Vanessa; Bakalov, Dimitar N; Snelgrove, Laura; Stravodimos, George A; Chatzileontiadou, Demetra S M; Manta, Stella; Panagiotopoulou, Angeliki; Hayes, Joseph M; Komiotis, Dimitri; Leonidas, Demetres D

    2015-01-01

    Glycogen phosphorylase (GP), a validated target for the development of anti-hyperglycaemic agents, has been targeted for the design of novel glycopyranosylamine inhibitors. Exploiting the two most potent inhibitors from our previous study of N-acyl-β-D-glucopyranosylamines (Parmenopoulou et al., Bioorg. Med. Chem. 2014, 22, 4810), we have extended the linking group to -NHCONHCO- between the glucose moiety and the aliphatic/aromatic substituent in the GP catalytic site β-cavity. The N-acyl-N´-(β-D-glucopyranosyl) urea inhibitors were synthesized and their efficiency assessed by biochemical methods, revealing inhibition constant values of 4.95 µM and 2.53 µM. Crystal structures of GP in complex with these inhibitors were determined and analyzed, providing data for further structure based design efforts. A novel Linear Response - Molecular Mechanics Coulomb Surface Area (LR-MM-CBSA) method has been developed which relates predicted and experimental binding free energies for a training set of N-acyl-N´-(β-D-glucopyranosyl) urea ligands with a correlation coefficient R(2) of 0.89 and leave-one-out cross-validation (LOO-cv) Q(2) statistic of 0.79. The method has significant applications to direct future lead optimization studies, where ligand entropy loss on binding is revealed as a key factor to be considered. ADMET property predictions revealed that apart from potential permeability issues, the synthesized N-acyl-N´-(β-D-glucopyranosyl) urea inhibitors have drug-like potential without any toxicity warnings.

  13. Nitroxy/azido-functionalized triazoles as potential energetic plasticizers.

    PubMed

    Tang, Yongxing; Shreeve, Jean'ne M

    2015-05-01

    The synthesis of a series of nitroxy- and azido-functionalized compounds, based on 4-amino-3,5-di(hydroxymethyl)-1,2,4-triazole, for possible use as an energetic plasticizers is described. All compounds were fully characterized. Two of them were further confirmed by X-ray single crystal diffraction. Energetic performance was calculated by using EXPLO5 v6.01 based on calculated heats of formation (Gaussian 03) and experimentally determined densities at 25 °C. The results show that the nitration product 1-nitro-3,5-di(nitroxymethyl)-1,2,4-triazole, containing a nitro group and two nitroxy groups, exhibits good detonation properties (D=8574 m s(-1) , P=32.7 GPa). In addition, its low melting point makes it very attractive as an energetic plasticizer in solid propellants.

  14. 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

  15. 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

  16. Palladium-Catalyzed C–H Arylation of 1,2,3-Triazoles

    PubMed Central

    Zhang, Chengwei; You, Lin; Chen, Chuo

    2016-01-01

    Palladium(II) acetate, in combination with triphenylphosphine, catalyzes direct arylation of 1,4-disubstituted 1,2,3-triazoles effectively. This C–H arylation reaction provides facile access to fully substituted triazoles with well-defined regiochemistry. PMID:27669198

  17. Palladium-Catalyzed C-H Arylation of 1,2,3-Triazoles.

    PubMed

    Zhang, Chengwei; You, Lin; Chen, Chuo

    2016-01-01

    Palladium(II) acetate, in combination with triphenylphosphine, catalyzes direct arylation of 1,4-disubstituted 1,2,3-triazoles effectively. This C-H arylation reaction provides facile access to fully substituted triazoles with well-defined regiochemistry. PMID:27669198

  18. Synthesis and biological evaluation of fluconazole analogs with triazole-modified scaffold as potent antifungal agents.

    PubMed

    Hashemi, Seyedeh Mahdieh; Badali, Hamid; Irannejad, Hamid; Shokrzadeh, Mohammad; Emami, Saeed

    2015-04-01

    In order to find new azole antifungals, we have recently designed a series of triazole alcohols in which one of the 1,2,4-triazol-1-yl group in fluconazole structure has been replaced with 4-amino-5-aryl-3-mercapto-1,2,4-triazole motif. In this paper, we focused on the structural refinement of the primary lead, by removing the amino group from the structure to achieve 5-aryl-3-mercapto-1,2,4-triazole derivatives 10a-i and 11a-i. The in vitro antifungal susceptibility testing of title compounds demonstrated that most compounds had potent inhibitory activity against Candida species. Among them, 5-(2,4-dichlorophenyl)triazole analogs 10h and 11h with MIC values of <0.01 to 0.5μg/mL were 4-256 times more potent than fluconazole against Candida species.

  19. 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.

  20. 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

  1. A comparative monomolecular film study of 1,2-di-O-palmitoyl-3-O-(alpha- and beta-D-glucopyranosyl)-sn-glycerols.

    PubMed

    Asgharian, B; Cadenhead, D A; Mannock, D A; Lewis, R N; McElhaney, R N

    1989-08-22

    The polar headgroup contribution to monolayer behavior of dipalmitoylglucosylglycerol has been examined through studies of 1,2-di-O-palmitoyl-3-O-(alpha-D-glucopyranosyl)-sn-glycerol (di-16:0-alpha GlcDG) and 1,2-di-O-palmitoyl-3-O-(beta-D-glucopyranosyl)-sn-glycerol (di-16:0-beta GlcDG) in which the sugar headgroup is linked via an alpha or beta linkage to the diacylglycerol moiety. The results indicate that the limiting areas per molecule of the resultant condensed states are smaller than those of the corresponding phosphatidylcholine (DPPC) but larger than those of dipalmitoylphosphatidylethanolmine (DPPE). In the expanded state, while the areas per molecule are similar to those of DPPC at low pressures, both glycolipids occupy smaller areas at higher pressures. The expanded-state areas of the glucolipids are also slightly greater than those of DPPE. The initial compressional phase transition pressure of the glucolipid liquid-expanded/liquid-condensed transition (pi t) is, however, less sensitive to temperature than are the pi t values of phospholipids. Both of these effects must relate to strong headgroup/water interactions, which, in turn, result in a stabilization of the liquid-expanded states. In the expanded states the alpha anomers are slightly less tightly packed than the beta anomers, as is indicated by the somewhat higher areas per molecule of the expanded states and the lower transition temperatures. These differences in chain-melting temperatures are slightly smaller than those observed in bilayers. While the areas per molecule of the dipalmitoyl glucolipids are greater than those of dipalmitoylphosphatidylethanolamine, they nevertheless exhibit a greater tendency to form nonbilayer structures. Such observations indicate that other factors besides geometric shape play a role in bilayer/nonbilayer transitions.

  2. Preliminary investigations into triazole derived androgen receptor antagonists.

    PubMed

    Altimari, Jarrad M; Niranjan, Birunthi; Risbridger, Gail P; Schweiker, Stephanie S; Lohning, Anna E; Henderson, Luke C

    2014-05-01

    A range of 1,4-substituted-1,2,3-N-phenyltriazoles were synthesized and evaluated as non-steroidal androgen receptor (AR) antagonists. The motivation for this study was to replace the N-phenyl amide portion of small molecule antiandrogens with a 1,2,3-triazole and determine effects, if any, on biological activity. The synthetic methodology presented herein is robust, high yielding and extremely rapid. Using this methodology a series of 17 N-aryl triazoles were synthesized from commercially available starting materials in less than 3h. After preliminary biological screening at 20 and 40 μM, the most promising three compounds were found to display IC50 values of 40-50 μM against androgen dependent (LNCaP) cells and serve as a starting point for further structure-activity investigations. All compounds in this work were the focus of an in silico study to dock the compounds into the human androgen receptor ligand binding domain (hARLBD) and compare their predicted binding affinity with known antiandrogens. A comparison of receptor-ligand interactions for the wild type and T877A mutant AR revealed two novel polar interactions. One with Q738 of the wild type site and the second with the mutated A877 residue.

  3. 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

  4. 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).

  5. 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...

  6. 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...

  7. 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 ...

  8. 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...

  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

    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 ...

  11. 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...

  12. 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.

  13. 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

  14. A triazole-bearing picket fence type nickel porphyrin as a cyanide selective allosteric host.

    PubMed

    Hong, Kyeong-Im; Yoon, Hongsik; Jang, Woo-Dong

    2015-05-01

    A triazole-bearing picket fence type nickel porphyrin (1) has been synthesized as a host compound for anion binding. Among the various anionic species examined, cyanide was the only one that affected a spectral change of 1. Moreover, 1 exhibited strong homotropic positive allosterism against cyanide binding due to an electronic effect as well as multiple hydrogen bonds formed between cyanide and the triazole groups.

  15. 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.

  16. 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

  17. Development of monoclonal immunoassays for the determination of triazole fungicides in fruit juices.

    PubMed

    Manclús, Juan J; Moreno, María J; Plana, Emma; Montoya, Angel

    2008-10-01

    Enzyme-linked immunosorbent assays (ELISAs) based on monoclonal antibodies for the detection of triazole fungicides have been developed. With this aim, hapten-protein conjugates, containing the common triazole and chlorinated aromatic moieties, were prepared. From mice immunized with these conjugates, several monoclonal antibodies (MAbs) with the ability to sensitively bind several triazoles with different specificity were obtained. Both analyte- and class-specific ELISAs were developed. The hexaconazole-specific immunoassay can determine this fungicide with a limit of detection of 0.3 mug/L in standard buffer. The so-called triazole-specific immunoassay allowed for the detection of tetraconazole, penconazole, cyproconazole, and myclobutanil, with limits of detection in the 0.1-0.7 mug/L range. These immunoassays were applied to the determination of triazoles in spiked fruit juices. Samples were adequately diluted to minimize the matrix effects. Coefficients of variation were below 30%, and recoveries ranged from 62 to 135%. Therefore, the developed immunoassays can determine triazole fungicides in fruit juices down to the maximum residue limits currently legislated, without any sample treatment other than dilution.

  18. 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.

  19. 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.

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

    PubMed

    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.

  1. 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

  2. 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

  3. A water soluble glucopyranosyl conjugate as a selective and reactive probe for cysteine in a buffer and its application to living cells.

    PubMed

    Areti, Sivaiah; Teotia, Rohit; Rao, Chebrolu Pulla

    2015-11-01

    A water soluble and biocompatible glucopyranosyl conjugate (L) has been synthesized and characterized by various techniques. The L has been employed to recognize Cys selectively among the naturally occurring amino acids in HEPES buffer at physiological pH. A minimum detection limit of 2.5 × 10(-7) M was shown by L for Cys in the buffer at pH = 7.4. The reactivity of L towards biological thiols as demonstrated by emission and absorption is supported by the observed increase in the fluorescence intensity; however, Cys shows a maximum increase owing to its better nucleophilicity. The reactivity of Cys on L is demonstrated by (1)H NMR, ESI MS, emission and absorption spectroscopy, and the formation of the binary complex was supported by ESI MS. The control molecular study revealed the necessity of the glyco-moiety to bring water solubility and biological adaptability. The cellular studies support that the conjugate L is biologically adaptable and shows effective intracellular fluorescence emission upon reacting with intracellular thiols.

  4. 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.

  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. Glucopyranosyl Lipid Adjuvant (GLA), a Synthetic TLR4 Agonist, Promotes Potent Systemic and Mucosal Responses to Intranasal Immunization with HIVgp140

    PubMed Central

    Arias, Mauricio A.; Van Roey, Griet A.; Tregoning, John S.; Moutaftsi, Magdalini; Coler, Rhea N.; Windish, Hillarie P.; Reed, Steven G.; Carter, Darrick; Shattock, Robin J.

    2012-01-01

    Successful vaccine development against HIV will likely require the induction of strong, long-lasting humoral and cellular immune responses in both the systemic and mucosal compartments. Based on the known immunological linkage between the upper-respiratory and urogenital tracts, we explored the potential of nasal adjuvants to boost immunization for the induction of vaginal and systemic immune responses to gp140. Mice were immunized intranasally with HIV gp140 together with micellar and emulsion formulations of a synthetic TLR4 agonist, Glucopyranosyl Lipid Adjuvant (GLA) and responses were compared to R848, a TLR7/8 agonist, or chitosan, a non TLR adjuvant. GLA and chitosan but not R848 greatly enhanced serum immunoglobulin levels when compared to antigen alone. Both GLA and chitosan induced high IgG and IgA titers in nasal and vaginal lavage and feces. The high IgA and IgG titers in vaginal lavage were associated with high numbers of gp140-specific antibody secreting cells in the genital tract. Whilst both GLA and chitosan induced T cell responses to immunization, GLA induced a stronger Th17 response and chitosan induced a more Th2 skewed response. Our results show that GLA is a highly potent intranasal adjuvant greatly enhancing humoral and cellular immune responses, both systemically and mucosally. PMID:22829921

  7. Differently N-protected 3,4,6-tri-O-acetyl-2-amino-2-deoxy-D-glucopyranosyl chlorides and their application in the synthesis of diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside.

    PubMed

    Bednarczyk, Dorota; Walczewska, Agata; Grzywacz, Daria; Sikorski, Artur; Liberek, Beata; Myszka, Henryk

    2013-02-15

    Four differently N-protected 3,4,6-tri-O-acetyl-2-amino-2-deoxy-d-glucopyranosyl chlorides were synthesized and used as glycosyl donors in reactions with diosgenin. The following amine group protections were tested: trifluoroacetyl (TFA), 2,2,2-trichloroethoxycarbonyl (Troc), phthaloyl (Phth), and tetrachlorophthaloyl (TCP). Products of glycosylation were deprotected to yield diosgenyl 2-amino-2-deoxy-β-d-glucopyranoside. The efficiency of the procedures is discussed. Additionally, a single-crystal X-ray diffraction analysis for 3,4,6-tri-O-acetyl-2-deoxy-2-tetrachlorophthalimido-β-d-glucopyranosyl chloride is reported. Orientations of the pyranose substituents as well as the planarity of the acetoxy and phthalimide groups in the crystal lattice are discussed. Structural evidence is presented for a mesomeric effect in both groups. The preference of the cis over trans orientation of the acetoxy group is confirmed in the crystal lattice.

  8. Synthetic mucin fragments. Benzyl O-beta-D-galactopyranosyl-(1----3)-O-(2-acetamido-2-deoxy-beta-D- glucopyranosyl)-(1----6)-2-acetamido-2-deoxy-alpha-D-galactopyranoside and O-alpha-L-fucopyranosyl-(1----3)-O-(2-acetamido-2-deoxy-beta-D- glucopyranosyl)-(1----6)-2-acetamido-2-deoxy-D-galactopyranose.

    PubMed

    Thomas, R L; Rutan, J F; Abbas, S A; Matta, K L

    1989-06-15

    Benzyl 2-acetamido-6-O-(2-acetamido-2-deoxy-4,6-O-isopropylidene-beta-D- glucopyranosyl)-2-deoxy-3,4-O-isopropylidene-alpha-D-galactopyranoside (2) was obtained by acetalation of its parent disaccharide with 2,2-dimethoxypropane in hot N,N-dimethylformamide and in the presence of 4-toluenesulfonic acid. Glycosylation of 2 with 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide (catalyzed by mercuric cyanide), followed by removal of the protecting groups afforded the title trisaccharide 7. A second product was also isolated, which was identified as a derivative of 7 having a 2-cyanopropyl group. Glycosylation of diacetal 2 with 2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl bromide (under catalysis by bromide ion), followed by systematic removal of the protecting groups furnished the title trisaccharide 13. The structures of both 7 and 13 were established by 13C-n.m.r. spectroscopy.

  9. 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.

  10. 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...

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

    2014-09-29

    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.

  18. 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

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

    2013-12-01

    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.

  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. 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.

  1. 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.

  2. 10 years of click chemistry: synthesis and applications of ferrocene-derived triazoles.

    PubMed

    Ganesh, Venkataraman; Sudhir, V Sai; Kundu, Taraknath; Chandrasekaran, Srinivasan

    2011-10-01

    Click chemistry has played a significant role as a rapid and versatile strategy for conjugating two molecular fragments under very mild reaction conditions. Introduction of ferrocene-derived triazole systems using click chemistry has attracted enormous interest in various fields due to its potential applications in electrochemical techniques for detection and sensing. The present discussion focuses on the synthesis of ferrocene-triazole and the importance of using a CuAAC reaction for such conjugation. Applications of ferrocene-based click reactions in conjugate chemistry, asymmetric catalysis, medicinal chemistry, host-guest interactions, and materials chemistry have been highlighted.

  3. 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

  4. Bis(nitroamino-1,2,4-triazolates): N-bridging strategy toward insensitive energetic materials.

    PubMed

    Yin, Ping; Parrish, Damon A; Shreeve, Jean'ne M

    2014-11-17

    Modern energetic motifs for military and civilian applications are most often evaluated using various criteria, for example, energetic properties, production costs, and safety issues. Given this background, the design of energetic materials requires a deep understanding of both detonation performance and molecular stability. Here a new family of energetic bis(nitroamino-1,2,4-triazolates), which exhibit good thermal stabilities, excellent detonation properties, and low sensitivities, has been designed. Furthermore, two hydroxylammonium bis(azolates) with pyrazole and tetrazole backbones were synthesized, and they exhibit energetic properties analogous to the triazoles. This work highlights the application potential of N-bridged bis(azolates) as promising energetic materials.

  5. Synthesis and structural characterization of 3,5-dinitro-1,2,4-triazolates.

    PubMed

    Haiges, R; Bélanger-Chabot, G; Kaplan, S M; Christe, K O

    2015-02-21

    Salts of 3,5-dinitro-1H-1,2,4-triazole, a building block for energetic materials, have been prepared and fully characterized. Most of the studied salts exhibit high thermal stability and very low shock and friction sensitivities. 3,5-Dinitro-1,2,4-triazolates with the nitrogen-rich ammonium, guanidinium, aminoguanidinium, and aminotetrazolium cations are energetic and have potential for energetic material applications. Salts containing alkali, alkali earth metal, and silver cations exhibit coloured emissions upon combustion while salts with large organic cations such as PPh4(+) and (Ph3P)2N(+) are highly insensitive and can be easily crystallized.

  6. Isolation of a Moderately Stable but Sensitive Zwitterionic Diazonium Tetrazolyl-1,2,3-triazolate.

    PubMed

    Klapötke, Thomas M; Krumm, Burkhard; Pflüger, Carolin

    2016-07-15

    An unexpected formation of a diazonium compound was observed by nitration of an amino substituted triazolyl tetrazole with mixed acid. The crystal structure determination revealed a zwitterionic diazonium tetrazolyl-1,2,3-triazolate, whose constitution was supported by NMR and vibrational spectroscopic analysis. The thermal stability and sensitivity toward impact and friction were determined. In contrast, diazotriazoles are rather unstable and are mainly handled in solution and/or low temperatures, which is not the case for this diazonium tetrazolyl-1,2,3-triazolate, being stable at ambient temperature. PMID:27352144

  7. 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

  8. 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

  9. 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.

  10. 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

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

    PubMed

    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.

  12. 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

  13. Antimicrobial and cytotoxic activities of 1,2,3-triazole-sucrose derivatives.

    PubMed

    Petrova, Krasimira T; Potewar, Taterao M; Correia-da-Silva, Paula; Barros, M Teresa; Calhelha, Ricardo C; Ćiric, Ana; Soković, Marina; Ferreira, Isabel C F R

    2015-11-19

    A library of 1-(1',2,3,3',4,4',6-hepta-O-acetyl-6'-deoxy-sucros-6'-yl)-1,2,3-triazoles have been investigated for their antibacterial, antifungal and cytotoxic activities. Most of the target compounds showed good inhibitory activity against a variety of clinically and food contaminant important microbial pathogens. In particular, 1-(1',2,3,3',4,4',6-hepta-O-acetyl-6'-deoxy-sucros-6'-yl)-4-(4-pentylphenyl)-1,2,3-triazole (5) was highly active against all the tested bacteria with minimal inhibitory concentrations (MICs) ranging between 1.1 and 4.4 µM and bactericidal concentrations (MBCs) from 2.2 and 8.4 µM. The compound 1-(1',2,3,3',4,4',6-hepta-O-acetyl-6'-deoxy-sucros-6'-yl)-4-(4-bromophenyl)-1,2,3-triazole (3) showed antifungal activity with MICs from 0.6 to 4.8 µM and minimal fungicidal concentrations (MFCs) ranging between 1.2 and 8.9 µM. Furthermore, some of the compounds possessed moderate cytotoxicity against human breast, lung, cervical and hepatocellular carcinoma cell lines, without showing toxicity for non-tumor liver cells. The above mentioned derivatives represent promising leads for the development of new generation of sugar-triazole antifungal agents.

  14. 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.

  15. Synthesis, antifungal and antibacterial activity of novel 1,2,4-triazole derivatives

    PubMed Central

    Gupta, Deepa; Jain, D. K.

    2015-01-01

    A large number of 1,2,4-triazole-containing ring system have been incorporated into a wide variety of therapeutically interesting drug candidates including anti-inflammatory, central nervous system stimulants, antianxiety, and antimicrobial agents. To overcome the rapid development of drug resistance, new agents should preferably have chemical characteristics that clearly differ from those of existing agents. Thus led to the design and synthesize the new antimicrobial agents. A novel series of Schiff bases based on of 4-(benzylideneamino)-5-phenyl-4H-1,2,4-triazole-3-thiol scaffold was prepared by heating thiocarbohydrazide and substituted benzoic acid and subsequently, treating with substituted benzaldehydes. Seventeen derivatives were synthesized and were biologically screened for antifungal and antibacterial activity. The newly synthesized derivatives of triazole showed antifungal activity against fungal species, Microsporum gypseum; and antibacterial activity against bacterial species, Staphylococcus aureus. It was observed that none of the compounds tested showed positive results for fungi Candida albicans fungi Aspergillus niger, nor against bacterial strain Escherichia coli. Strong antifungal effects were obtained for the synthesized compounds against M. gypseum and were superior or comparable to standard drug ketoconazole. Similarly, all of the synthesized compounds exhibit strong antibacterial activity against S. aureus and were superior or comparable to standard drug streptomycin. It was found that among the triazole derivatives so synthesized, six of them, showed antifungal activity superior to ketoconazole while one of them, showed antibacterial activity superior to streptomycin. Thus, these can be the potential new molecule as an antimicrobial agent. PMID:26317080

  16. 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...

  17. 1,2,3-Triazole Stabilized Neurotensin-Based Radiopeptidomimetics for Improved Tumor Targeting.

    PubMed

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

    2015-10-21

    Neurotensin (NT) is a regulatory peptide with nanomolar affinity toward NT receptors, which are overexpressed by different clinically relevant tumors. Its binding sequence, NT(8-13), represents a promising vector for the development of peptidic radiotracers for tumor imaging and therapy. The main drawback of the peptide is its short biological half-life due to rapid proteolysis in vivo. Herein, we present an innovative strategy for the stabilization of peptides using nonhydrolizable 1,4-disubstituted, 1,2,3-triazoles as amide bond surrogates. A "triazole scan" of the peptide sequence yielded novel NT(8-13) analogues with enhanced stability, retained receptor affinity, and improved tumor targeting properties in vivo. The synthesis of libraries of triazole-based peptidomimetics was achieved efficiently on solid support by a combination of Fmoc-peptide chemistry, diazo transfer reactions, and the Cu(I)-catalyzed alkyne azide cycloaddition (CuAAC) employing methods that are fully compatible with standard solid phase peptide synthesis (SPPS) chemistry. Thus, the amide-to-triazole substitution strategy may represent a general methodology for the metabolic stabilization of biologically active peptides. PMID:26347939

  18. 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.

  19. 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...

  20. Synthesis and diversification of 1,2,3-triazole-fused 1,4-benzodiazepine scaffolds.

    PubMed

    Donald, James R; Martin, Stephen F

    2011-03-01

    A substituted heterocyclic scaffold comprising a 1,4-benzodiazepine fused with a 1,2,3-triazole ring has been synthesized and diversified via a variety of refunctionalizations. The strategy features the rapid assembly of the scaffold by combining 3-4 reactants in an efficient multicomponent assembly process, followed by an intramolecular Huisgen cycloaddition.

  1. 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...

  2. 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

  3. Synthesis of Triazole Schiff's Base Derivatives and Their Inhibitory Kinetics on Tyrosinase Activity.

    PubMed

    Yu, Feng; Jia, Yu-Long; 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

  4. Synthesis of novel sulfanilamide-derived 1,2,3-triazoles and their evaluation for antibacterial and antifungal activities.

    PubMed

    Wang, Xian-Long; Wan, Kun; Zhou, Cheng-He

    2010-10-01

    A series of novel sulfanilamide-derived 1,2,3-triazole compounds were synthesized in excellent yields via 1,3-dipolar cycloaddition and confirmed by MS, IR and NMR spectra as well as elemental analyses. All the compounds were screened in vitro for their antibacterial and antifungal activities. Preliminary results indicated that some target compounds exhibited promising antibacterial potency. Especially, 4-amino-N-((1-dodecyl-1H-1,2,3-triazol-4-yl)methyl) benzenesulfonamide, N-((1-(2,4-dichlorobenzyl)- 1H-1,2,3-triazol-4-yl)methyl)-4-aminobenzenesulfonamide and 4-amino-N-((1-(2,4-difluorobenzyl)- 1H-1,2,3-triazol-4-yl)methyl) benzenesulfonamide were found to be the most potent compounds against all the tested strains except for Candida albicans (ATCC76615) and Candida mycoderma. PMID:20708826

  5. Search for factors affecting antibacterial activity and toxicity of 1,2,4-triazole-ciprofloxacin hybrids.

    PubMed

    Plech, Tomasz; Kaproń, Barbara; Paneth, Agata; Kosikowska, Urszula; Malm, Anna; Strzelczyk, Aleksandra; Stączek, Paweł; Świątek, Łukasz; Rajtar, Barbara; Polz-Dacewicz, Małgorzata

    2015-06-01

    A series of 1,2,4-triazole-based compounds was designed as potential antibacterial agents using molecular hybridization approach. The target compounds (23-44) were synthesized by Mannich reaction of 1,2,4-triazole-3-thione derivatives with ciprofloxacin (CPX) and formaldehyde. Their potent antibacterial effect on Gram-positive bacteria was accompanied by similarly strong activity against Gram-negative strains. The toxicity of the CPX-triazole hybrids for bacterial cells was even up to 18930 times higher than the toxicity for human cells. The results of enzymatic studies showed that the antibacterial activity of the CPX-triazole hybrids is not dependent solely on the degree of their affinity to DNA gyrase and topoisomerase IV. PMID:25951434

  6. 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 ...

  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. 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.

  10. Tris(triazole) tripodal receptors as selective probes for citrate anion recognition and multichannel transition and heavy metal cation sensing.

    PubMed

    González, María del Carmen; Otón, Francisco; Espinosa, Arturo; Tárraga, Alberto; Molina, Pedro

    2015-02-01

    The three-armed pyrenyl-triazole receptor 1 behaves as a highly selective fluorescent molecular sensor for citrate anions over similar carboxylates such as malate or tartrate. In addition, this receptor senses Cu(2+) cations through absorption and emission channels even in the presence of Hg(2+) metal cations. The related three-armed ferrocenyl-triazole receptor 2 behaves as a highly selective dual (redox and chromogenic) chemosensor molecule for Pb(2+) metal cations.

  11. 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

  12. 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

  13. Permeation and metabolism of a series of novel lipophilic ascorbic acid derivatives, 6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acids with a branched-acyl chain, in a human living skin equivalent model.

    PubMed

    Tai, Akihiro; Goto, Satomi; Ishiguro, Yutaka; Suzuki, Kazuko; Nitoda, Teruhiko; Yamamoto, Itaru

    2004-02-01

    A series of novel lipophilic vitamin C derivatives, 6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acids possessing a branched-acyl chain of varying length from C(8) to C(16) (6-bAcyl-AA-2G), were evaluated as topical prodrugs of ascorbic acid (AA) with transdermal activity in a human living skin equivalent model. The permeability of 6-bAcyl-AA-2G was compared with those of the derivatives having a straight-acyl chain (6-sAcyl-AA-2G). Out of 10 derivatives of 6-sAcyl-AA-2G and 6-bAcyl-AA-2G, 6-sDode-AA-2G and 6-bDode-AA-2G exhibited most excellent permeability in this model. Measurement of the metabolites permeated from the skin model suggested that 6-bDode-AA-2G was mainly hydrolyzed via 6-O-acyl AA to AA by tissue enzymes, while 6-sDode-AA-2G was hydrolyzed via 2-O-alpha-D-glucopyranosyl-L-ascorbic acid to AA. The former metabolic pathway seems to be advantageous for a readily available source of AA, because 6-O-acyl AA, as well as AA, is able to show vitamin C activity.

  14. 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

  15. 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.

  16. 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.

  17. Synthesis of thermally stable energetic 1,2,3-triazole derivatives.

    PubMed

    Kumar, A Sudheer; Ghule, Vikas D; Subrahmanyam, S; Sahoo, Akhila K

    2013-01-01

    Various thermally stable energetic polynitro-aryl-1,2,3-triazoles have been synthesized through Cu-catalyzed [3+2] cycloaddition reactions between their corresponding azides and alkynes, followed by nitration. These compounds were characterized by analytical and spectroscopic methods and the solid-state structures of most of these compounds have been determined by using X-ray diffraction techniques. Most of the polynitro-bearing triazole derivatives decomposed within the range 142-319 °C and their heats of formation and crystal densities were determined from computational studies. By using the Kamlet-Jacobs empirical relation, their detonation velocities and pressures were calculated from their heats of formation and crystal densities. Most of these newly synthesized compounds exhibited high positive heats of formation, good thermal stabilities, reasonable densities, and acceptable detonation properties that were comparable to those of TNT.

  18. 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

  19. 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

  20. Computational Studies on Nitro Derivatives of 1-Hydroxy-1,2,4-triazole

    NASA Astrophysics Data System (ADS)

    Singh, Hariji; Mukherjee, Uttama; Shankar Saini, Ravi

    2012-07-01

    Thermodynamic properties and energetics of the nitro derivatives of 1-hydroxy-1,2,4-triazole, viz. 1-hydroxy-3-nitro-1,2,4-triazole (A), 1-hydroxy-5-nitro-1,2,4-triazole (B), and 1-hydroxy-3,5-dinitro-1,2,4-triazole (C), are considered for a detailed computational study during the present investigation using a density functional theory B3LYP/6-311G(d,p) method as implemented in the Gaussian 03 suite of programs. Heats of formation and other thermodynamic properties for all of the compounds considered were determined. Studies revealed that these compounds possess the requisite properties for use as high-density energetic materials. Detonation velocity (D) and detonation pressure (P) of the title compounds were evaluated using the Kamlet-Jacobs method based on the crystal densities calculated at the DFT(B3LYP)/6-311G(d,p) level incorporating the electrostatic interaction. Calculation showed that these compounds yielded a detonation pressure and detonation velocity in the range of 27-35 GPa and ∼8 km/s, respectively, at loading densities of 1.60-1.90 g/cm3. The calculated values are comparable to the values determined for powerful commercial explosives such as Research Department Explosive (RDX) (34.10 GPa, 8.75 km/s, 1.80 g/cm3), High Melting Explosive (HMX) (39.00 GPa, 9.11 km/s, 1.89 g/cm3), and Trinitrotoluene (TNT) (21.00 GPa, 6.93 km/s, 1.64 g/cm3).

  1. 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.

  2. 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

  3. Determination of acid dissociation constants of triazole fungicides by pressure assisted capillary electrophoresis.

    PubMed

    Konášová, Renáta; Dytrtová, Jana Jaklová; Kašička, Václav

    2015-08-21

    Pressure assisted capillary electrophoresis was applied to determination of acid dissociation constants (pKa) of six widely used triazole fungicides (cyproconazole, epoxiconazole, flusilazole, tebuconazole, penconazole and propiconazole) in aqueous medium. The pKa values were determined from the dependence of effective electrophoretic mobility of the triazole fungicides on p[H(+)] of the background electrolyte (BGE) using non-linear regression analysis. The p[H(+)] was used instead of pH to reflect the increased ionic strength of the strongly acidic BGEs (pH<1.75) as compared to the BGEs at pH equal to or greater than 1.75. Prior to the pKa calculation, the measured effective electrophoretic mobilities were corrected to the reference temperature (25°C) and constant ionic strength (25mM). The regression function was modified to allow the determination of pKa in the BGEs of varying ionic strength. The electrophoretic measurements showed that the above triazole fungicides are very weak bases - their pKa values were found to be in the range 1.05-1.97 and were in a good agreement with the values calculated by SPARC online pKa calculator.

  4. Synthesis, Antibacterial, and Anticancer Evaluation of Novel Spiramycin-Like Conjugates Containing C(5) Triazole Arm.

    PubMed

    Klich, Katarzyna; Pyta, Krystian; Kubicka, Marcelina M; Ruszkowski, Piotr; Celewicz, Lech; Gajecka, Marzena; Przybylski, Piotr

    2016-09-01

    Huisgen cycloaddition allowed obtaining of novel triazole-bridged antibiotics (6-16) with the reconstructed C(5) arm of spiramycin. (1)H-(1)H NOESY couplings indicated the structure of novel derivatives in solution and demonstrated that the rebuilt C(5) arm is slightly differently oriented relative to the aglycone part if compared to that of spiramycin (1). Combined analysis of biological data together with experimentally determined lipophilicity (clogP) and solubility show the importance of the chemical nature of the newly introduced triazole C(5) arm in the presence of attractive antibacterial and anticancer potency. The most cytotoxic active triazole conjugates having a hydrophobic and bulky C(5) arm showed higher selectivity toward cancer cell lines (HeLa, KB, MCF-7, Hep-G2, and U87) relative to HDF normal cells than that of the parent spiramycin. Our studies have demonstrated that the aldehyde group is not crucial for the presence of interesting antibacterial [MIC(S. pneumoniae) ∼ 1.2 μM] and anticancer [IC50(HepG2) ∼ 6 μM] properties of 16-membered lactone macrolides based on spiramycin's aglycone. PMID:27501415

  5. 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

  6. 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.

  7. 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

  8. Synthesis and evaluation of in vivo antioxidant, in vitro antibacterial, MRSA and antifungal activity of novel substituted isatin N-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)thiosemicarbazones.

    PubMed

    Thanh, Nguyen Dinh; Giang, Nguyen Thi Kim; Quyen, Tran Ha; Huong, Doan Thi; Toan, Vu Ngoc

    2016-11-10

    Some new isatin N-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)thiosemicarbazones 4a-t with different substituents at 1-, 5- and 7-positions of isatin ring have been synthesized by reaction of N-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)thiosemicarbazide 2 with corresponding isatins 3a-t. Compounds 4a-t were evaluated in vivo for antioxidant activity and in vitro for anti-microorganism activities. The MIC values were found for Gram positive bacteria (MIC = 1.56-6.25 μM), for Gram negative bacteria (MIC = 12.5 μM), and for fungi Aspergillus niger (MIC = 3.12-12.5 μM), Fusarium oxysporum (MIC = 6.25-12.5 μM) and Saccharomyces cerevisiae (MIC = 6.25-12.5 μM). Regarding the antioxidant activity, the SOD, GHS-Px and catalase activities of 4c-i and 4m-r were MIC = 10.57-10.85, 0.27-0.93 and 345.45-399.75 unit/mg protein, respectively. Compounds 4e-h had MIC values of 0.78, 1.56, and 3.12 μM for three clinical MRSA isolates. Compound 4e showed the selective cytotoxic effects against some cancer (LU-1, HepG2, MCF7, P338, SW480, KB) cell lines and normal fibroblast cell line NIH/3T3. PMID:27517802

  9. 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.

  10. 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.

  11. 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

  12. 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 the combined residues of the fungicide...

  13. 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 the combined residues of the fungicide...

  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, 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 the combined residues of the fungicide...

  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, 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 the combined residues of the fungicide...

  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, 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 the combined residues of the fungicide...

  17. 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.

  18. 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)

  19. Novel sesquiterpenes from Schisandra grandiflora: isolation, cytotoxic activity and synthesis of their triazole derivatives using "click" reaction.

    PubMed

    Poornima, B; Siva, Bandi; Shankaraiah, G; Venkanna, A; Nayak, V Lakshma; Ramakrishna, Sistla; Venkat Rao, C; Babu, K Suresh

    2015-03-01

    Phytochemical investigation of hexane extract from the fruits of Schisandra grandiflora afforded three novel sesquiterpenes (1-3) along with the three known compounds (4-6). The structures of these isolates were determined by extensive analysis of spectroscopic data (1D, 2D NMR). Further, a series of triazole analogues of 3 and 4 were prepared using "Click" reaction protocol. The reaction scheme involving one-carbon homologation of 3 and 4 using the Bestmann-Ohira reagent followed by regioselective Huisgen 1,3-dipolar cycloaddition reaction of various azides leading to the formation of triazole analogues (20a-20k &21a-21c) which is being reported for the first time. All the triazole products were characterized using spectral data analysis. The anti-proliferative activity of the isolates and the synthetic analogues were studied against Hela (Cervical cancer), A549 (Lung cancer), DU-145 (Prostate cancer), MCF-7 (Breast cancer) and B-16 (Mouse melanoma) cancer cell lines.

  20. 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

  1. 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

    2016-02-22

    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.

  2. A 1,4-diphenyl-1,2,3-triazole-based β-turn mimic constructed by click chemistry.

    PubMed

    Wu, Chun-Fang; Zhao, Xin; Lan, Wen-Xian; Cao, Chunyang; Liu, Jin-Tao; Jiang, Xi-Kui; Li, Zhan-Ting

    2012-05-01

    A series of 1,4-diphenyl-1,2,3-triazole-incorporated amide derivatives have been designed and prepared. X-ray crystallographic and (1D and 2D) (1)H NMR studies reveal that these compounds fold into stable U-shaped conformations driven by three-center intramolecular C-H···O hydrogen-bonding formed between the triazole C-5 H atom and the two ether O atoms. Such folded structures make this 1,4-diphenyl-1,2,3-triazole skeleton a good candidate to be used as β-turn mimic. To prove this, the formation of a β-hairpin structure induced by this β-turn motif has been further demonstrated.

  3. C-glycoside clustering on calix[4]arene, adamantane, and benzene scaffolds through 1,2,3-triazole linkers.

    PubMed

    Dondoni, Alessandro; Marra, Alberto

    2006-09-29

    A route has been paved toward the preparation of triazole glycocluster libraries via the copper(I)-catalyzed modern version of the classical Huisgen 1,3-dipolar cycloaddition of azides to alkynes. Up to four 1,4-disubstituted 1,2,3-triazole rings bearing carbon-linked glycosyl fragments were constructed on various scaffolds via multiple cycloadditions of suitably polyfunctionalized calix[4]arene, adamantane, and benzene derivatives with ethynyl and azidomethyl C-glycosides. Each cycloaddition occurred with high regioselectivity to give exclusively the 1,4-disubstituted triazole ring in very high yield up to an average value of 98%. The high degree of efficiency of this approach and its wide scope constitute a simple and practical means for the attachment of various sugar units to polyfunctionalized substrates.

  4. 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

  5. Disruption of testosterone homeostasis as a mode of action for the reproductive toxicity of triazole fungicides in the male rat.

    PubMed

    Goetz, Amber K; Ren, Hongzu; Schmid, Judith E; Blystone, Chad R; Thillainadarajah, Inthirany; Best, Deborah S; Nichols, Harriette P; Strader, Lillian F; Wolf, Douglas C; Narotsky, Michael G; Rockett, John C; Dix, David J

    2007-01-01

    Triazole fungicides associated with a range of reported male reproductive effects in experimental animals were selected to assess potential toxic modes of action. Wistar Han rats were fed myclobutanil (M: 100, 500, or 2000 ppm), propiconazole (P: 100, 500, or 2500 ppm), or triadimefon (T: 100, 500, or 1800 ppm) from gestation day 6 to postnatal day (PND) 120. One male per litter was necropsied on PND1, 22, 50, or 92. Measurements included anogenital distance (AGD) at PND0, body and organ weights, serum hormone levels, age at preputial separation (PPS), sperm morphology and motility, and fertility and fecundity. AGD was increased by the high dose of all three triazoles, indicating hypervirilization. Triadimefon delayed PPS, consistent with delayed puberty, at 1800 ppm. Relative liver weights were increased at PND1, 50, and 92 by all three triazoles. Hepatocellular hypertrophy was present at PND50 from propiconazole and triadimefon and at PND92 from all three high-dose triazole treatments. Relative pituitary weights were decreased at PND92 by middle- and high-dose myclobutanil treatment. Absolute testis weights were increased at PND1 by myclobutanil, at PND22 by myclobutanil and triadimefon, and at PND50 by propiconazole and triadimefon treatment. Relative ventral prostate weights were increased at PND92 by myclobutanil and triadimefon treatment. Serum testosterone was increased at PND50 by triadimefon and at PND92/99 by all three triazole treatments. Insemination and fertility were impaired by myclobutanil and triadimefon treatment. In addition to the reproductive system effects, total serum thyroxine levels were decreased at PND92 by high-dose triadimefon. These reproductive effects are consistent with the disruption of testosterone homeostasis as a key event in the mode of action for triazole-induced reproductive toxicity.

  6. 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.

  7. Design, synthesis and biological evaluation of sulfamide and triazole benzodiazepines as novel p53-MDM2 inhibitors.

    PubMed

    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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. Mechanism of Multivalent Nanoparticle Encounter with HIV-1 for Potency Enhancement of Peptide Triazole Virus Inactivation*

    PubMed Central

    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

  13. [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

  14. Determination of the primary molecular target of 1,2,4-triazole-ciprofloxacin hybrids.

    PubMed

    Plech, Tomasz; Kaproń, Barbara; Paneth, Agata; Kosikowska, Urszula; Malm, Anna; Strzelczyk, Aleksandra; Stączek, Paweł; Świątek, Łukasz; Rajtar, Barbara; Polz-Dacewicz, Małgorzata

    2015-01-01

    We have synthesized and examined the antibacterial activity, toxicity and affinity towards bacterial type II topoisomerases of a series of 1,2,4-triazole-ciprofloxacin hybrids. A number of these compounds displayed enhanced activity against Gram-positive and Gram-negative bacteria when compared to ciprofloxacin. The toxic concentrations of the obtained derivatives, evaluated on HEK-293 cells using MTT assay, were much higher than concentrations required to produce antibacterial effect. Finally, the results of enzymatic studies showed that the analyzed compounds demonstrated other preferences as regards primary and secondary molecular targets than ciprofloxacin. PMID:25859782

  15. 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

  16. Synthesis of Isomeric and Potent Impurities of the Triazole-Based Antifungal Drug Voriconazole.

    PubMed

    Sundaram, Dhanraj T S S; Mitra, Jayati; Islam, Aminul; Prabahar, Koilpillai Joseph; Venkateswara Rao, Battula; Paul Douglas, Sanasi

    2015-01-01

    We describe the synthesis of two positional isomers and a desfluoro impurity of Voriconazole starting with Friedel-Crafts acylation of mono- and difluorobenzene. These isomers are the crucial components in determining the quality of Voriconazole during its manufacturing from the key raw material, 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethan-1-one. All the prepared impurities were characterized by IR, (1)H-NMR, (13)C-NMR, and mass spectral data. PMID:26839829

  17. 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

  18. 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

  19. 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.

  20. Triazole-based monophosphine ligands for palladium-catalyzed cross-coupling reactions of aryl chlorides.

    PubMed

    Dai, Qian; Gao, Wenzhong; Liu, Duan; Kapes, Lea M; Zhang, Xumu

    2006-05-12

    A variety of triazole-based monophosphines (ClickPhos) have been prepared via efficient 1,3-dipolar cycloaddition of readily available azides and acetylenes. Their palladium complexes provided excellent yields in the amination reactions and Suzuki-Miyaura coupling reactions of unactivated aryl chlorides. Ligand 7i, which has a 2,6-dimethoxybenzene moiety, provided good results in Suzuki-Miyaura reaction to form hindered biaryls. A CAChe model for the Pd/7i complex shows that the likelihood of a Pd-arene interaction might be a rationale for its high catalytic reactivity.

  1. 4-Aryl-3,5-bis(arylethynyl)aryl-4H-1,2,4-triazoles: multitasking skeleton as a self-assembling unit.

    PubMed

    Pastor, M Jesús; Torres, Iván; Cebrián, Cristina; Carrillo, José Ramón; Díaz-Ortiz, Ángel; Matesanz, Emilio; Buendía, Julia; García, Fátima; Barberá, Joaquín; Prieto, Pilar; Sánchez, Luis

    2015-01-19

    The synthesis of a series of 4-aryl-3,5-bis(arylethynyl)aryl-4H-1,2,4-triazoles derivatives is reported and the influence exerted by peripheral substitution on the morphology of the aggregates generated from these 1,2,4-triazoles is investigated by SEM imaging. The presence of paraffinic side chains results in long fibrillar supramolecular structures, but unsubstituted triazoles self-assemble into thinner ribbons and needle-like aggregates. The crystals obtained from methoxy-substituted triazoles have been utilised to elaborate a model that helps to justify aggregation of the investigated 1,2,4-triazoles, in which the operation of arrays of C-H⋅⋅⋅π non-covalent interactions plays a significant role. The results presented herein demonstrate the ability of simple molecules to behave as multitasking scaffolds with different properties, depending on peripheral substitution. Thus, although 1,2,4-triazoles without long paraffinic side chains exhibit optical waveguiding behaviour, triazoles endowed with peripheral paraffinic side chains exhibit hexagonal columnar mesomorphism. PMID:25413614

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. A zeolite-like zinc triazolate framework with high gas adsorption and separation performance.

    PubMed

    Lin, Rui-Biao; Chen, Da; Lin, Yan-Yong; Zhang, Jie-Peng; Chen, Xiao-Ming

    2012-09-17

    The reaction of commercially available 3-amino-1,2,4-triazole (Hatz) and Zn(OH)(2) at room temperature produced a porous zeolite-like metal azolate framework, [Zn(atz)(2)] (MAF-66). Single-crystal X-ray diffraction studies of MAF-66 showed that atz(-) served as an imidazolate-type ligand, linking tetrahedral Zn(II) ions to form a noninterpenetrated dia framework, which contains a narrow, three-dimensional intersecting channel system (void = 49.8%) functionalized by amino groups and uncoordinated triazolate N atoms on the pore surface. Gas-sorption measurements of MAF-66 revealed high CO(2) uptakes (27.6/19.4 wt % at 273/298 K and 1 atm) and high Henry's law CO(2)/N(2) selectivity (403/225 at 273/298 K). The host-guest interactions between CO(2) and the pore surface were also studied by in situ IR absorption spectroscopy and powder X-ray diffraction measurements.

  9. 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.

  10. 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

  11. Novel Triazole-Quinoline Derivatives as Selective Dual Binding Site Acetylcholinesterase Inhibitors.

    PubMed

    Mantoani, Susimaire P; Chierrito, Talita P C; Vilela, Adriana F L; Cardoso, Carmen L; Martínez, Ana; Carvalho, Ivone

    2016-02-05

    Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide. Currently, the only strategy for palliative treatment of AD is to inhibit acetylcholinesterase (AChE) in order to increase the concentration of acetylcholine in the synaptic cleft. Evidence indicates that AChE also interacts with the β-amyloid (Aβ) protein, acting as a chaperone and increasing the number and neurotoxicity of Aβ fibrils. It is known that AChE has two binding sites: the peripheral site, responsible for the interactions with Aβ, and the catalytic site, related with acetylcholine hydrolysis. In this work, we reported the synthesis and biological evaluation of a library of new tacrine-donepezil hybrids, as a potential dual binding site AChE inhibitor, containing a triazole-quinoline system. The synthesis of hybrids was performed in four steps using the click chemistry strategy. These compounds were evaluated as hAChE and hBChE inhibitors, and some derivatives showed IC50 values in the micro-molar range and were remarkably selective towards hAChE. Kinetic assays and molecular modeling studies confirm that these compounds block both catalytic and peripheral AChE sites. These results are quite interesting since the triazole-quinoline system is a new structural scaffold for AChE inhibitors. Furthermore, the synthetic approach is very efficient for the preparation of target compounds, allowing a further fruitful new chemical library optimization.

  12. 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

  13. 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

  14. Synthesis and curing of hyperbranched poly(triazole)s with click polymerization for improved adhesion strength.

    PubMed

    Tang, Youhong; Jim, Cathy K W; Liu, Yang; Ye, Lin; Qin, Anjun; Lam, Jacky W Y; Zhao, Chengbi; Tang, Ben Zhong

    2010-02-01

    We successfully synthesized hyperbranched poly(triazole)s by in situ click polymerization of diazides 1 and triyne 2 monomers on different metal surfaces (copper, iron, and aluminum) and characterized their adhesive properties. Optimizations were performed to obtain high adhesive strength at different temperatures by analyzing the effects of curing kinetics, annealing temperature and time, catalyst, monomer ratio, surface conditions, alkyl chain length of diazides 1, etc. The adhesive bonding strength with metal substrate is 2 orders of magnitude higher than similar hyperbranched poly(triazole)s made by click polymerization and clearly higher than some commercial adhesives at elevated temperatures. With the same conditions, adhesives prepared on aluminum and iron substrates have higher adhesive strength than those prepared on copper substrate, and an excess of triyne 2 monomer in synthesis has greater adhesive strength than an excess of diazide 1 monomer. Tof-SIMS experiment was employed to understand these phenomena, and the existence of an interphase between the polymer and metal surface was found to be critical for adhesive bonding with thicker interphase (excess of triyne 2 monomer) and the higher binding energy between polymer atoms and substrate atoms (e.g., aluminum substrate) generating the higher bonding strength. In addition, the light-emitting property of synthesized polymers under UV irradiation can be used to check the failure mode of adhesive bonding. PMID:20356206

  15. 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.

  16. 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

  17. Synthesis, antibacterial, antielastase, antiurease and antioxidant activities of new 1,4-butylene bridged bis-1,2,4-triazole derivatives.

    PubMed

    Gumrukcuoglu, Nurhan; Sokmen, Bahar Bilgin; Ugras, Serpil; Ugras, Halil Ibrahim; Yanardag, Refiye

    2013-02-01

    A new bis schiffbases, 3 a-b were synthesized compound 2 with various bis aldehydes. Compounds 3 a-b have been reduced with NaBH(4) to afford the corresponding bis amino triazole compounds 4 a-b. The obtained products 3 a-b and 4 a-b were identified by FTIR, (1)H-NMR, (13)C-NMR. A series of triazol derivatives were evaluated for their antibacterial, antioxidant, antiurease and antielastase activities. The results showed that the synthesized new bis-1,2,4-triazole derivatives had effective antioxidant, antiurease and antielastase activities.

  18. 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...

  19. 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...

  20. Synthesis of pentafluorosulfanylpyrazole and pentafluorosulfanyl-1,2,3-triazole and their derivatives as energetic materials by click chemistry.

    PubMed

    Ye, Chengfeng; Gard, Gary L; Winter, Rolf W; Syvret, Robert G; Twamley, Brendan; Shreeve, Jean'ne M

    2007-09-13

    1-Pentafluorosulfanyl acetylene and its derivatives react with azide or diazomethane giving rise to an SF5-substituted 1,2,3-triazole or pyrazole. The SF5 group increases density remarkably and as a result enhances the detonation performance of the energetic materials relative to the CF3 group.

  1. 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...

  2. 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...

  3. Solvent-Induced Single Crystal-Single Crystal Transformation of an Interpenetrated Three-Dimensional Copper Triazole Catalytic Framework.

    PubMed

    Wang, Ying; Meng, Shan-Shan; Lin, Peng-Xiang; Xiao, Yi-Wei; Ma, Qing-Qing; Xie, Qiong; Chen, Yuan-Yuan; Zhao, Xiao-Jun; Chen, Jun

    2016-05-01

    The 2-fold interpenetrated 3D framework 1 can be solvent-induced to noninterpenetrated framework 1' in a reversible single crystal-single crystal transformation fashion. In addition, 1' represents the first catalyst based on triazole to catalyze the aerobic homocoupling of various substituted arylboronic acids.

  4. Using click chemistry toward novel 1,2,3-triazole-linked dopamine D3 receptor ligands

    PubMed Central

    Keck, Thomas M.; Banala, Ashwini K.; Slack, Rachel D.; Burzynski, Caitlin; Bonifazi, Alessandro; Okunola-Bakare, Oluyomi M.; Moore, Martin; Deschamps, Jeffrey R.; Rais, Rana; Slusher, Barbara S.; Newman, Amy Hauck

    2015-01-01

    The dopamine D3 receptor (D3R) is a target of pharmacotherapeutic interest in a variety of neurological disorders including schizophrenia, Parkinson's disease, restless leg syndrome, and drug addiction. A common molecular template used in the development of D3R-selective antagonists and partial agonists incorporates a butylamide linker between two pharmacophores, a phenylpiperazine moiety and an extended aryl ring system. The series of compounds described herein incorporates a change to that chemical template, replacing the amide functional group in the linker chain with a 1,2,3-triazole group. Although the amide linker in the 4-phenylpiperazine class of D3R ligands has been previously deemed critical for high D3R affinity and selectivity, the 1,2,3-triazole moiety serves as a suitable bioisosteric replacement and maintains desired D3R-binding functionality of the compounds. Additionally, using mouse liver microsomes to evaluate CYP450-mediated phase I metabolism, we determined that novel 1,2,3-triazole-containing compounds modestly improves metabolic stability compared to amide-containing analogues. The 1,2,3-triazole moiety allows for the modular attachment of chemical subunit libraries using copper-catalyzed azide-alkyne cycloaddition click chemistry, increasing the range of chemical entities that can be designed, synthesized, and developed toward D3R-selective therapeutic agents. PMID:25650314

  5. 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

  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. 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

  8. 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.

  9. 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

  10. Combination effects of (tri)azole fungicides on hormone production and xenobiotic metabolism in a human placental cell line.

    PubMed

    Rieke, Svenja; Koehn, Sophie; Hirsch-Ernst, Karen; Pfeil, Rudolf; Kneuer, Carsten; Marx-Stoelting, Philip

    2014-09-01

    Consumers are exposed to multiple residues of different pesticides via the diet. Therefore, EU legislation for pesticides requires the evaluation of single active substances as well as the consideration of combination effects. Hence the analysis of combined effects of substances in a broad dose range represents a key challenge to current experimental and regulatory toxicology. Here we report evidence for additive effects for (tri)azole fungicides, a widely used group of antifungal agents, in the human placental cell line Jeg-3. In addition to the triazoles cyproconazole, epoxiconazole, flusilazole and tebuconazole and the azole fungicide prochloraz also pesticides from other chemical classes assumed to act via different modes of action (i.e., the organophosphate chlorpyrifos and the triazinylsulfonylurea herbicide triflusulfuron-methyl) were investigated. Endpoints analysed include synthesis of steroid hormone production (progesterone and estradiol) and gene expression of steroidogenic and non-steroidogenic cytochrome-P-450 (CYP) enzymes. For the triazoles and prochloraz, a dose dependent inhibition of progesterone production was observed and additive effects could be confirmed for several combinations of these substances in vitro. The non-triazoles chlorpyrifos and triflusulfuron-methyl did not affect this endpoint and, in line with this finding, no additivity was observed when these substances were applied in mixtures with prochloraz. While prochloraz slightly increased aromatase expression and estradiol production and triflusulfuron-methyl decreased estradiol production, none of the other substances had effects on the expression levels of steroidogenic CYP-enzymes in Jeg-3 cells. For some triazoles, prochloraz and chlorpyrifos a significant induction of CYP1A1 mRNA expression and potential combination effects for this endpoint were observed. Inhibition of CYP1A1 mRNA induction by the AhR inhibitor CH223191 indicated AhR receptor dependence this effect. PMID

  11. 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

  12. Spanish labeling guide.

    PubMed

    Juliá, A M; García, S V; Breckinridge, M F

    1983-01-01

    A systematic reference of English-Spanish prescription label translations is presented. The purpose of the reference list (which is the most comprehensive published to date) is to enable a pharmacist to write precise, accurate label directions in Spanish for any patient who cannot read English.

  13. Neurite outgrowth of PC12 cells by 4'-O-β-D-glucopyranosyl-3',4-dimethoxychalcone from Brassica rapa L. 'hidabeni' was enhanced by pretreatment with p38MAPK inhibitor.

    PubMed

    Nishina, Atsuyoshi; Kimura, Hirokazu; Tsukagoshi, Hiroyuki; Kozawa, Kunihisa; Koketsu, Mamoru; Ninomiya, Masayuki; Sato, Daisuke; Obara, Yutaro; Furukawa, Shoei

    2013-11-01

    The cellular effects of eleven compounds including chalcone glycosides isolated from Brassica rapa L. 'hidabeni' and their synthetic derivatives were studied in rat pheochromocytoma PC12 cells. Of the compounds tested, 4'-O-β-D-glucopyranosyl-3',4-dimethoxychalcone (A2) significantly increased the levels of the phosphorylated forms of extracellular signal-regulated kinases 1/2 (ERK 1/2), p38 mitogen-activated protein kinase (p38MAPK), and stress-activated protein kinases/Jun amino-terminal kinases (JNK/SAPK), but it did not affect Akt. Nerve growth factor (NGF), a well-known neurotrophic factor, increased the levels of phosphorylated ERK1/2, JNK/SAPK, and Akt but not p38MAPK, which may mediate marked neurite outgrowth. Signals evoked by A2 shared common characteristics with those induced by NGF; therefore, we evaluated the neuritogenic activity of A2 and found it induced only weak neurite outgrowth. However, this effect was enhanced by pre-treatment with a p38MAPK inhibitor, suggesting that the phosphorylation of p38MAPK down-regulated neurite outgrowth. From the results of this study, it was found that A2 in combination with a p38MAPK inhibitor can induce NGF-like effects. Hence, a combination of chalcone glycosides containing A2 and a p38MAPK inhibitor increases the likelihood that chalcone glycosides could be put to practical use in the form of drugs or alternative medicines to maintain neural health.

  14. Enantiomeric purity test of bevantolol by reversed-phase high performance liquid chromatography after derivatization with 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate.

    PubMed

    Kim, K H; Heo, S Y; Hong, S P; Lee, B C

    2000-12-01

    A reversed-phase high-performance liquid chromatographic method was developed to determine the optical purity of bevantolol enantiomers. (S)-(-)-Menthyl chloroformate((-)-MCF), (S)-(-)-alpha-methylbenzyl isocyanate((-)-MBIC) and 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate(GITC), which can react with the secondary amine group of bevantolol were investigated as chiral derivatization reagents. Among them indirect chiral HPLC method using GITC gave the best result. The derivatization proceeded quantitatively within 20 min at room temperature. Separation of the enantiomers as diastereomers was achieved by reversed-phase HPLC within 20min using ODS column. Different ratios of (S)-(-)-bevantolol and (R)-(+)-bevantolol were prepared. Enantiomeric separation of these mixtures took place on a chiralcel OD column or, after derivatization with GITC, on a ODS column. No racemization was found during the experiment. This method allowed determination of 0.05% of either enantiomer in the presence of its stereoisomer and method validation showed adequete linearity over the required range.

  15. 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

  16. Improving maltodextrin specificity for enzymatic synthesis of 2-O-d-glucopyranosyl-l-ascorbic acid by site-saturation engineering of subsite-3 in cyclodextrin glycosyltransferase from Paenibacillus macerans.

    PubMed

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

    2013-07-20

    In this work, the subsite-3 of cyclodextrin glycosyltransferase (CGTase) from Paenibacillus macerans was engineered to improve maltodextrin specificity for 2-O-d-glucopyranosyl-l-ascorbic acid (AA-2G) synthesis. Specifically, the site-saturation mutagenesis of tyrosine 89, asparagine 94, aspartic acid 196, and aspartic acid 372 in subsite-3 was separately performed, and three mutants Y89F (tyrosine→phenylalanine), N94P (asparagine→proline), and D196Y (aspartic acid→tyrosine) produced higher AA-2G titer than the wild-type and the other mutants. Previously, we found the mutant K47L (lysine→leucine) also had a higher maltodextrin specificity. Therefore, the four mutants K47L, Y89F, N94P, and D196Y were further used to construct the double, triple, and quadruple mutations. Among the 11 combinational mutants, the quadruple mutant K47L/Y89F/N94P/D196Y produced the highest AA-2G titer of 2.23g/L, which was increased by 85.8% compared to that produced by the wild-type CGTase. The reaction kinetics of all the mutants were modeled, and the pH and thermal stabilities of all the mutants were analyzed. The structure modeling indicated that the enhanced maltodextrin specificity may be related with the changes of hydrogen bonding interactions between the side chain of residue at the four positions (47, 89, 94, and 196) and the substrate sugars.

  17. 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

  18. Spin-labeled polyribonucleotides.

    PubMed Central

    Petrov, A I; Sukhorukov, B I

    1980-01-01

    Poly (U), poly (C) and poly (A) were spin labeled with N-(2,2,5,5-tetramethyl-3-carbonylpyrroline-1-oxyl)-imidazole. This spin label interacts selectively with 2' OH ribose groups of polynucleotides and does not modify the nucleic acid bases. The extent of spin labeling is not dependent upon the nature of the base and is entirely determined by rigidity of the secondary structure of the polynucleotide. The extent of modification for poly (U), poly (C) and poly (A) was 4.2, 1.7 and 1.5 per cent, respectively, the secondary structure of the polynucleotides being practically unchanged. Some physico-chemical properties of the spin-labeled polynucleotides were investigated by ESR spectroscopy. Rotational correlation times of the spin label and activation energy of its motion were calculated. PMID:6253911

  19. 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

  20. Surface enhanced Raman scattering investigation of the halide anion effect on the adsorption of 1,2,3-triazole on silver and gold colloidal nanoparticles.

    PubMed

    Pergolese, Barbara; Muniz-Miranda, Maurizio; Bigotto, Adriano

    2005-05-19

    The halide anion effect on the adsorption of 1,2,3-triazole on Ag and Au colloidal nanoparticles has been investigated by means of surface enhanced Raman scattering (SERS), UV-visible absorption spectroscopy, and scanning electron microscopy. To interpret the SERS spectra, the vibrational spectra of 1,2,3-triazole were assigned with the help of density functional theoretical (DFT) calculations of the two tautomers of 1,2,3-triazole, both free and bound to Ag and Au adatoms. Upon addition of halide anions, both tautomers interact with the Ag surface through one nitrogen atom. Analogous behavior is observed in the case of basified Au colloids, whereas at the usual pH of these hydrosols (approximately 6) the adsorption of 1,2,3-triazole is the same of that observed in halide-free colloids.

  1. Molecular complexes of alprazolam with carboxylic acids, boric acid, boronic acids, and phenols. Evaluation of supramolecular heterosynthons mediated by a triazole ring.

    PubMed

    Varughese, Sunil; Azim, Yasser; Desiraju, Gautam R

    2010-09-01

    A series of molecular complexes, both co-crystals and salts, of a triazole drug-alprazolam-with carboxylic acids, boric acid, boronic acids, and phenols have been analyzed with respect to heterosynthons present in the crystal structures. In all cases, the triazole ring behaves as an efficient hydrogen bond acceptor with the acidic coformers. The hydrogen bond patterns exhibited with aromatic carboxylic acids were found to depend on the nature and position of the substituents. Being a strong acid, 2,6-dihydroxybenzoic acid forms a salt with alprazolam. With aliphatic dicarboxylic acids alprazolam forms hydrates and the water molecules play a central role in synthon formation and crystal packing. The triazole ring makes two distinct heterosynthons in the molecular complex with boric acid. Boronic acids and phenols form consistent hydrogen bond patterns, and these are seemingly independent of the substitutional effects. Boronic acids form noncentrosymmetric cyclic synthons, while phenols form O--H...N hydrogen bonds with the triazole ring.

  2. 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

  3. 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

  4. Cadmium(II)-Triazole Framework as a Luminescent Probe for Ca(2+) and Cyano Complexes.

    PubMed

    Wang, Ying; Xu, Ping; Xie, Qiong; Ma, Qing-Qing; Meng, Yan-Hui; Wang, Zi-Wen; Zhang, Shaowei; Zhao, Xiao-Jun; Chen, Jun; Wang, Zhong-Liang

    2016-07-18

    A bidentate ligand, 1-{4-[4-(1H-1,2,4-triazol-1-yl)phenoxy]phenyl}-1H-1,2,4-triazole (TPPT), has been designed and synthesized. By using TPPT as a building block for self-assembly with Cd(NO3 )2 ⋅4 H2 O and CdCl2 ⋅10.5 H2 O, novel 1D double-chain {[Cd(TPPT)(NO3 )2 ]⋅3 H2 O}n (1) and 2D (4,4) layer [Cd(TPPT)Cl2 (H2 O)]n (2) have been constructed. When 1 was employed as a precursor and exposed to DMF or N,N'-dimethylacetamide (DMAC), the crystals of 1 dissolved and reassembled into two types of brown block-shaped crystals of 1D double chains: {[Cd(TPPT)2 (NO3 )2 ]⋅DMF}n (1 a) and {[Cd(TPPT)2 (NO3 )2 ]⋅DMAC}n (1 b). The anion-exchange reactions of complex 2 have also been investigated. After gently stirring crystals of 2 in CHCl3 /C2 H5 OH/H2 O containing NaBr, NaI⋅2 H2 O, or NaOAc⋅3 H2 O, the crystals retained their crystalline appearances. A remarkable single crystal to single crystal transformation was observed and 1D double chains of {[Cd(TPPT)Br2 ]⋅C2 H5 OH}n (2 a) and {[Cd(TPPT)2 I2 ]⋅CHCl3 }n (2 b), and 1D single chains of [Cd(TPPT)(H2 O)2 (CH3 COO)2 ]n (2 c), can be obtained. Luminescent properties indicate that 1 shows excellent selectivity for Ca(2+) and cyano complexes. To the best of our knowledge, this is the first example of a luminescent probe for Ca(2+) based on triazole derivatives. PMID:27319279

  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. 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. ...

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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

  13. Triazole-containing N-acyl homoserine lactones targeting the quorum sensing system in Pseudomonas aeruginosa.

    PubMed

    Hansen, Mette R; Jakobsen, Tim H; Bang, Claus G; Cohrt, Anders Emil; Hansen, Casper L; Clausen, Janie W; Le Quement, Sebastian T; Tolker-Nielsen, Tim; Givskov, Michael; Nielsen, Thomas E

    2015-04-01

    In an attempt to devise new antimicrobial treatments for biofilm infections, the bacterial cell-cell communication system termed quorum sensing has emerged as an attractive target. It has proven possible to intercept the communication system by synthetic non-native ligands and thereby lower the pathogenesis and antibiotic tolerance of a bacterial biofilm. To identify the structural elements important for antagonistic or agonistic activity against the Pseudomonas aeruginosa LasR protein, we report the synthesis and screening of new triazole-containing mimics of natural N-acyl homoserine lactones. A series of azide- and alkyne-containing homoserine lactone building blocks was used to prepare an expanded set of 123 homoserine lactone analogues through a combination of solution- and solid-phase synthesis methods. The resulting compounds were subjected to cell-based quorum sensing screening assays, thereby revealing several bioactive compounds, including 13 compounds with antagonistic activity and 9 compounds with agonistic activity.

  14. Synthesis and in Vitro Antifungal Activities of Novel Benzamide Derivatives Containing a Triazole Moiety.

    PubMed

    Zhang, Wen; Sui, Guoqing; Li, Yulin; Fang, Mei; Yang, Xinjuan; Ma, Xihan; Zhou, Wenming

    2016-01-01

    The study reported the synthesis and antifungal activities in vitro against six phytopathogenic fungi of 17 novel N-[2-hydroxy-3,3-dimethyl-2-[(1H-1,2,4-triazol-1-yl)methyl]butyl]benzamide derivatives. All the target compounds were synthesized and elucidated by means of MS, high resolution (HR)-MS, IR, (1)H- and (13)C-NMR analysis. The results showed that almost all the derivatives exhibited good activities against each of the tested fungi at the concentration of 50 µg/mL. Among them, 6h displayed excellent activity against Alternaria alternata with the median effective concentration value (EC50) of 1.77 µg/mL, superior to myclobutanil (EC50=6.23 µg/mL), a commercial fungicide with broad-spectrum bioactivities for plant protection and high-efficiency. Compound 6k showed the broadest antifungal spectrum, demonstrating positive activities against the corresponding fungi with EC50 values ranging from 0.98 to 6.71 µg/mL. Furthermore, 6e to 6i revealed good activities against Alternaria solani with EC50 values of 1.90, 4.51, 7.07, 2.00 and 5.44 µg/mL, respectively. The preliminary analysis of structure-activity relationship (SAR) demonstrated that the presence of F or Cl on the benzene ring remarkably improved the activity, while the introduction of 4-OMe or CF3 group decreased the activity in varying degrees. Thus, the present results strongly suggest that N-[2-hydroxy-3,3-dimethyl-2-[(1H-1,2,4-triazol-1-yl)methyl]butyl]benzamide derivatives should be promising candidates for the development of novel antifungal agents in the effective control of phytopathogenic fungi. PMID:27250796

  15. 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

  16. 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

  17. Synthesis, QSAR and anticandidal evaluation of 1,2,3-triazoles derived from naturally bioactive scaffolds.

    PubMed

    Irfan, Mohammad; Aneja, Babita; Yadava, Umesh; Khan, Shabana I; Manzoor, Nikhat; Daniliuc, Constantin G; Abid, Mohammad

    2015-03-26

    In the present study, we used eight natural precursors (1a-h) with most of them having promising antimicrobial activities and synthesised their novel 1,2,3-triazole derivatives (3a-h). In the reaction sequences, the precursor compounds (1a-h) were converted to their respective alkyne (2a-h) followed by addition of benzyl azide freshly prepared by the reaction of benzyl bromide with sodium azide using [3 + 2] azide-alkyne cycloaddition strategy. Structural elucidation of all the triazole derivatives was done using FT-IR, (1)H, (13)C NMR, mass and elemental analysis techniques. The single crystal X-ray diffraction for 3d was also recorded. The result of in vitro anticandidal activity performed against three different strains of Candida showed that compound 3e was found superior/comparable to fluconazole (FLC) with IC50 values of 0.044 μg/mL against Candida albicans (ATCC 90028), 12.022 μg/mL against Candida glabrata (ATCC 90030), and 3.60 μg/mL against Candida tropicalis (ATCC 750). Moreover, at their IC50 values, compounds 3e and 3h showed <5% hemolysis which indicates the non-toxic behaviour of these inhibitors. Cytotoxicity assay was also performed on VERO cell line and all the derivatives were found non-toxic up to the concentration of 10.0 μg/mL. The in silico technique of 3D-QSAR was applied to establish structure activity relationship of the synthesized compounds. The results reveal the molecular fragments that play an essential role in improving the anticandidal activity.

  18. A predictive data-driven framework for endocrine prioritization: a triazole fungicide case study

    PubMed Central

    Paul Friedman, Katie; Papineni, Sabitha; Marty, M. Sue; Yi, Kun Don; Goetz, Amber K.; Rasoulpour, Reza J.; Kwiatkowski, Pat; Wolf, Douglas C.; Blacker, Ann M.; Peffer, Richard C.

    2016-01-01

    Abstract The US Environmental Protection Agency Endocrine Disruptor Screening Program (EDSP) is a tiered screening approach to determine the potential for a chemical to interact with estrogen, androgen, or thyroid hormone systems and/or perturb steroidogenesis. Use of high-throughput screening (HTS) to predict hazard and exposure is shifting the EDSP approach to (1) prioritization of chemicals for further screening; and (2) targeted use of EDSP Tier 1 assays to inform specific data needs. In this work, toxicology data for three triazole fungicides (triadimefon, propiconazole, and myclobutanil) were evaluated, including HTS results, EDSP Tier 1 screening (and other scientifically relevant information), and EPA guideline mammalian toxicology study data. The endocrine-related bioactivity predictions from HTS and information that satisfied the EDSP Tier 1 requirements were qualitatively concordant. Current limitations in the available HTS battery for thyroid and steroidogenesis pathways were mitigated by inclusion of guideline toxicology studies in this analysis. Similar margins (3–5 orders of magnitude) were observed between HTS-predicted human bioactivity and exposure values and between in vivo mammalian bioactivity and EPA chronic human exposure estimates for these products’ registered uses. Combined HTS hazard and human exposure predictions suggest low priority for higher-tiered endocrine testing of these triazoles. Comparison with the mammalian toxicology database indicated that this HTS-based prioritization would have been protective for any potential in vivo effects that form the basis of current risk assessment for these chemicals. This example demonstrates an effective, human health protective roadmap for EDSP evaluation of pesticide active ingredients via prioritization using HTS and guideline toxicology information. PMID:27347635

  19. 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.

  20. 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.

  1. Behind the Label "Alcoholic."

    ERIC Educational Resources Information Center

    Wright, Deborah M.

    1989-01-01

    Relates individual's personal story of her childhood influenced by her parent's alcoholism, her own alcoholism as a young adult, and her experiences with counseling. Asks others not to reject her because of the label "alcoholic." (ABL)

  2. 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

  3. 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.

  4. Purification from Fusobacterium mortiferum ATCC 25557 of a 6-phosphoryl-O-alpha-D-glucopyranosyl:6-phosphoglucohydrolase that hydrolyzes maltose 6-phosphate and related phospho-alpha-D-glucosides.

    PubMed Central

    Thompson, J; Gentry-Weeks, C R; Nguyen, N Y; Folk, J E; Robrish, S A

    1995-01-01

    6-Phosphoryl-O-alpha-D-glucopyranosyl:6-phosphoglucohydrolase (6-phospho-alpha-glucosidase) has been purified from Fusobacterium mortiferum ATCC 25557. p-Nitrophenyl-alpha-D-glucopyranoside 6-phosphate (pNP alpha Glc6P) served as the chromogenic substrate for detection and assay of enzyme activity. The O2-sensitive, metal-dependent phospho-alpha-glucosidase was stabilized during purification by inclusion of dithiothreitol and Mn2+ ion in chromatography buffers. Various 6-phosphoryl-O-alpha-linked glucosides, including maltose 6-phosphate, pNP alpha Glc6P, trehalose 6-phosphate, and sucrose 6-phosphate, were hydrolyzed by the enzyme to yield D-glucose 6-phosphate and aglycone moieties in a 1:1 molar ratio. 6-Phospho-alpha-glucosidase (M(r) of approximately 49,000; pI of approximately 4.9) is activated by Fe2+, Mn2+, Co2+, and Ni2+, and the maximum rate of pNP alpha Glc6P hydrolysis occurs at 40 degrees C within the pH range 7.0 to 7.5. The sequence of the first 32 amino acids of 6-phospho-alpha-glucosidase exhibits 67% identity (90% similarity) to that deduced for the N terminus of a putative phospho-beta-glucosidase (designated ORF f212) encoded by glvG in Escherichia coli. Western blots involving highly specific polyclonal antibody against 6-phospho-alpha-glucosidase and spectrophotometric analyses with pNP alpha Glc6P revealed only low levels of the enzyme in glucose-, mannose-, or fructose-grown cells of F. mortiferum. Synthesis of 6-phospho-alpha-glucosidase increased dramatically during growth of the organism on alpha-glucosides, such as maltose, alpha-methylglucoside, trehalose, turanose, and palatinose. PMID:7730284

  5. Routing and Label Space Reduction in Label Switching Networks

    NASA Astrophysics Data System (ADS)

    Solano, Fernando; Caro, Luis Fernando; Stidsen, Thomas; Papadimitriou, Dimitri

    This chapter is devoted to the analysis and modeling of some problems related to the optimal usage of the label space in label switching networks. Label space problems concerning three different technologies and architectures - namely Multi-protocol Label Switching (MPLS), Ethernet VLAN-Label Switching (ELS) and All-Optical Label Switching (AOLS) - are discussed in this chapter. Each of these cases yields to different constraints of the general label space reduction problem. We propose a generic optimization model and, then, we describe some adaptations aiming at modeling each particular case. Simulation results are briefly discussed at the end of this chapter.

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. In vitro antibacterial, antifungal and cytotoxic activities of some triazole Schiff bases and their oxovanadium(IV) complexes.

    PubMed

    Sumrra, Sajjad H; Chohan, Zahid H

    2013-12-01

    The condensation reaction of 3,5-diamino-1,2,4-triazole with methoxy-, chloro-, bromo-, iodo- and nitro-substituted 2-hydroxybenzaldehydes formed triazole Schiff bases (L(1))-(L(6)). The synthesized ligands have been characterized through physical, spectral and analytical data. Furthermore, the reaction of synthesized Schiff bases with the oxovanadium(IV) sulphate in (1:2) (metal:ligand) molar ratio afforded the oxovanadium(IV) complexes (1)-(6). All the complexes were non-electrolytic and showed a square-pyramidal geometry. The synthesized compounds have been screened for in-vitro antibacterial, antifungal and brine shrimp bioassay. The bioactivity data showed the complexes to be more active than the original Schiff bases.

  11. 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.

  12. Assessing molecular docking tools for relative biological activity prediction: a case study of triazole HIV-1 NNRTIs.

    PubMed

    Frączek, Tomasz; Siwek, Agata; Paneth, Piotr

    2013-12-23

    Molecular docking is a technique widely used in drug design. Many studies exist regarding the general accuracy of various docking programs, but case studies for a given group of related compounds are rare. In order to facilitate identification of novel triazole HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs), several docking and scoring programs were evaluated for their ability to predict relative biological activity of 111 known 1,2,4-triazole and 76 other azole type NNRTIs. Glide, FlexX, Molegro Virtual Docker, AutoDock Vina, and Hyde were used. Different protocols, settings, scoring functions, and interaction terms were analyzed. We have found that the programs performance was dependent on the data set, indicating the importance of choosing good quality target data for any comparative study. The results suggest that after optimization and proper validation, some of the molecular docking programs can help in predicting relative biological activity of azole NNRTIs. PMID:24266618

  13. A Library of 1,4-Disubstituted 1,2,3-Triazole Analogs of Oxazolidinone RNA-Binding Agents

    PubMed Central

    Acquaah-Harrison, George; Zhou, Shu; Hines, Jennifer V.; Bergmeier, Stephen C.

    2010-01-01

    The design and synthesis of small molecules that target RNA is immensely important in antibacterial therapy. We had previously reported on the RNA binding of a series of 4,5-disubstituted 2-oxazolidinones that bind to a highly conserved bulge region of bacterial RNA. This biological target T box antitermination system, which is found mainly in Gram-positive bacteria, regulates the expression of several amino acid related genes. In an effort to amplify our library, we have prepared a library of 1,4-disubstituted 1,2,3-triazole analogs that entails an isosteric replacement of the oxazolidinone nucleus. The synthesis of the new analogs was enhanced via copper(I) catalysis of an azide and alkyne cycloaddition reaction. A total of 108 1,4-disubstituted 1,2,3-triazole compounds have been prepared. All compounds were evaluated as RNA binding agents. PMID:20557032

  14. Studies toward the synthesis of linear triazole linked pseudo oligosaccharides and the use of ferrocene as analytical probe.

    PubMed

    Schmidt, Magnus S; Götz, Kathrin H; Koch, Wolfgang; Grimm, Tanja; Ringwald, Markus

    2016-04-29

    Three different building blocks have been synthesised and used for the synthesis of linear triazole linked pseudo oligosaccharides with copper(I)-catalysed cycloaddition (CuAAC). Ethynylferrocene has been used as analytical probe to improve the UV/Vis properties and HPLC methods have been used and optimised for the analysis of the pseudo oligosaccharides. The smallest ones have been isolated and characterised by analytical HPLC, NMR, ESI-MS and elemental analysis.

  15. [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

  16. Inhibition of Acinetobacter baumannii, Staphylococcus aureus and Pseudomonas aeruginosa biofilm formation with a class of TAGE-triazole conjugates.

    PubMed

    Huigens, Robert W; Rogers, Steven A; Steinhauer, Andrew T; Melander, Christian

    2009-02-21

    A chemically diverse library of TAGE-triazole conjugates was synthesized utilizing click chemistry on the TAGE scaffold. This library of small molecules was screened for anti-biofilm activity and found to possess the ability of inhibiting biofilm formation against Acinetobacter baumannii, Staphylococcus aureus and Pseudomonas aeruginosa. One such compound in this library demonstrated the most potent inhibitory effect against Staphylococcus aureus biofilm formation that has been displayed by any 2-aminoimidazole derivative. PMID:19194596

  17. Copper(I)-Catalyzed Cycloaddition of Bismuth(III) Acetylides with Organic Azides: Synthesis of Stable Triazole Anion Equivalents

    PubMed Central

    Worrell, Brady T.; Ellery, Shelby P.

    2014-01-01

    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, bench-stable 5-bismuth triazolides. This uniquely reactive intermediates can be further functionalized under extremely mild conditions to give fully substituted 1,2,3-triazoles. PMID:24130150

  18. 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

  19. 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- ...

  20. Synthesis and Biological Evaluation of Triazole-Containing N-Acyl Homoserine Lactones as Quorum Sensing Modulators

    PubMed Central

    Stacy, Danielle M.; Le Quement, Sebastian T.; Hansen, Casper L.; Clausen, Janie W.; Tolker-Nielsen, Tim; Brummond, Jacob W.; Givskov, Michael; Nielsen, Thomas E.; Blackwell, Helen E.

    2013-01-01

    Many bacterial species are capable of assessing their local population densities through a cell-cell signaling mechanism termed quorum sensing (QS). This intercellular communication process is mediated by small molecule or peptide ligands and their cognate protein receptors. Numerous pathogens use QS to initiate virulence once they achieve a threshold cell number on a host. Consequently, approaches to intercept QS have attracted considerable attention as potential anti-infective therapies. Our interest in the development of small molecule tools to modulate QS pathways motivated us to evaluate triazole-containing analogs of natural N-acyl L-homoserine lactone (AHL) signals as non-native QS agonists and antagonists in Gram-negative bacteria. We synthesized 72 triazole derivatives of five broad structure types in high yields and purities using efficient Cu(I)-catalyzed azide-alkyne couplings. These compounds were evaluated for their ability to activate or inhibit two QS receptors from two prevalent pathogens – LasR from Pseudomonas aeruginosa and AbaR from Acinetobacter baumannii – using bacterial reporter strains. Several triazole derivatives were identified that were capable of strongly modulating the activity of LasR and AbaR. These compounds represent a new and synthetically accessible class of AHL analogs, and could find utility as chemical tools to study QS and its role in bacterial virulence. PMID:23258305

  1. Prediction of electronically nonadiabatic decomposition mechanisms of isolated gas phase nitrogen-rich energetic salt: Guanidium-triazolate

    NASA Astrophysics Data System (ADS)

    Ghosh, Jayanta; Bhattacharya, Atanu

    2016-01-01

    Electronically nonadiabatic decomposition pathways of guanidium triazolate are explored theoretically. Nonadiabatically coupled potential energy surfaces are explored at the complete active space self-consistent field (CASSCF) level of theory. For better estimation of energies complete active space second order perturbation theories (CASPT2 and CASMP2) are also employed. Density functional theory (DFT) with B3LYP functional and MP2 level of theory are used to explore subsequent ground state decomposition pathways. In comparison with all possible stable decomposition products (such as, N2, NH3, HNC, HCN, NH2CN and CH3NC), only NH3 (with NH2CN) and N2 are predicted to be energetically most accessible initial decomposition products. Furthermore, different conical intersections between the S1 and S0 surfaces, which are computed at the CASSCF(14,10)/6-31G(d) level of theory, are found to play an essential role in the excited state deactivation process of guanidium triazolate. This is the first report on the electronically nonadiabatic decomposition mechanisms of isolated guanidium triazolate salt.

  2. 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

  3. Crystal structure of bis­(1-benzyl-1H-1,2,4-triazole) perchloric acid monosolvate

    PubMed Central

    Qin, Yong-Qi; Xue, Jin-hui; Qiao, Yuan-Biao; Zhang, Zi-Feng

    2014-01-01

    The title compound, 2C9H9N3·HClO4, was prepared by reaction of 1-benzyl-1H-1,2,4-triazole and HClO4 in ethanol at room temperature. The asymmetric unit consists of two mol­ecules of 1-benzyl-1H-1,2,4-triazole and one of HClO4 mol­ecule. The benzene and triazole rings make dihedral angles of 85.45 (8) and 84.76 (8)° in the two mol­ecules. The H-atom position of the perchloric acid mol­ecule is split over two O atoms (real peaks on difference map), with site-occupation factors of 0.5. These H atoms form two classical hydrogen bonds [2.546 (5) and 2.620 (4) Å] with the same N atoms in both mol­ecules. Five inter­molecular non-classical C—H⋯O inter­actions, with C⋯O distances in the range 3.147 (5)–3.483 (5) Å, are found in the crystal structure. PMID:25553052

  4. Interactions of peptide triazole thiols with Env gp120 induce irreversible breakdown and inactivation of HIV-1 virions

    PubMed Central

    2013-01-01

    Background We examined the underlying mechanism of action of the peptide triazole thiol, KR13 that has been shown previously to specifically bind gp120, block cell receptor site interactions and potently inhibit HIV-1 infectivity. Results KR13, the sulfhydryl blocked KR13b and its parent non-sulfhydryl peptide triazole, HNG156, induced gp120 shedding but only KR13 induced p24 capsid protein release. The resulting virion post virolysis had an altered morphology, contained no gp120, but retained gp41 that bound to neutralizing gp41 antibodies. Remarkably, HIV-1 p24 release by KR13 was inhibited by enfuvirtide, which blocks formation of the gp41 6-helix bundle during membrane fusion, while no inhibition of p24 release occurred for enfuvirtide-resistant virus. KR13 thus appears to induce structural changes in gp41 normally associated with membrane fusion and cell entry. The HIV-1 p24 release induced by KR13 was observed in several clades of HIV-1 as well as in fully infectious HIV-1 virions. Conclusions The antiviral activity of KR13 and its ability to inactivate virions prior to target cell engagement suggest that peptide triazole thiols could be highly effective in inhibiting HIV transmission across mucosal barriers and provide a novel probe to understand biochemical signals within envelope that are involved in membrane fusion. PMID:24330857

  5. One-pot sequential alkynylation and cycloaddition: regioselective construction and biological evaluation of novel benzoxazole-triazole derivatives.

    PubMed

    Srivastava, Ananya; Aggarwal, Leena; Jain, Nidhi

    2015-01-12

    Individually, benzoxazole and triazole moieties are of significant biological interest owing to their importance in drugs and pharmaceuticals. To assess their combined biological impact when woven into one molecule, we designed a novel, regioselective, multicomponent, one-pot (MCOP) approach for the construction of benzoxazole-linked triazoles. The synthesis has been achieved in two sequential steps involving copper-catalyzed alkynylation of benzoxazole followed by a 1,3-dipolar cycloaddition reaction. By combination of these two bioactive units into one core, a series of new benzoxazole-triazole scaffolds has been synthesized and subjected to in vitro antibacterial and anticancer evaluation. Tests against clinical isolates of Staphylococcus aureus and Escherichia coli showed potent Gram-negative activity for compounds 4{1,1,1}, 4{1,1,4}, and 4{1,2,1}. The cytotoxicity of the synthesized library was determined against three cancer cell lines: HeLa, SKBr3, and Hep G2. Compound 4{2,2,2} showed significant cytotoxicity against all the cell lines. These preliminary bioassay evaluations strongly suggest the promise and scope of these novel molecules as therapeutic agents in medical science.

  6. 3-Benzyl-4-ethyl-1H-1,2,4-triazole-5(4H)-thione

    PubMed Central

    Karczmarzyk, Zbigniew; Pitucha, Monika; Wysocki, Waldemar; Pachuta-Stec, Anna; Stańczuk, Andrzej

    2013-01-01

    The title compound, C11H13N3S, exists in the 5-thioxo tautomeric form. The benzene ring exhibits disorder with a refined ratio of 0.77 (2):0.23 (2) for components A and B with a common bridgehead C atom. The 1,2,4-triazole ring is essentially planar, with a maximum deviation of 0.002 (3) Å for the benzyl-substituted C atom, and forms dihedral angles of 88.94 (18) and 86.56 (49)° with the benzene rings of components A and B, respectively. The angle between the plane of the ethyl chain and the mean plane of 1,2,4-triazole ring is 88.55 (15)° and this conformation is stabilized by an intra­molecular C—H⋯S contact. In the crystal, pairs of N—H⋯S hydrogen bonds link mol­ecules into inversion dimers. π–π inter­actions are observed between the triazole and benzene rings, with centroid–centroid separations of 3.547 (4) and 3.544 (12) Å for components A and B, and slippages of 0.49 (6) and 0.58 (15) Å, respectively. PMID:23424446

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. Reply to the comment of S. Rayne on "QSAR model reproducibility and applicability: A case study of rate constants of hydroxyl radical reaction models applied to polybrominated diphenyl ethers and (benzo-)triazoles".

    PubMed

    Gramatica, Paola; Kovarich, Simona; Roy, Partha Pratim

    2013-07-30

    We appreciate the interest of Dr. Rayne on our article and we completely agree that the dataset of (benzo-)triazoles, which were screened by the hydroxyl radical reaction quantitative structure-activity relationship (QSAR) model, was not only composed of benzo-triazoles but also included some simpler triazoles (without the condensed benzene ring), such as the chemicals listed by Dr. Rayne, as well as some related heterocycles (also few not aromatic). We want to clarify that in this article (as well as in other articles in which the same dataset was screened), for conciseness, the abbreviations (B)TAZs and BTAZs were used as general (and certainly too simplified) notations meaning an extended dataset of benzo-triazoles, triazoles, and related compounds.

  14. 1,2,3-Triazole-based analogue of benznidazole displays remarkable activity against Trypanosoma cruzi.

    PubMed

    de Andrade, Peterson; Galo, Oswaldo A; Carvalho, Marcelo R; Lopes, Carla D; Carneiro, Zumira A; Sesti-Costa, Renata; de Melo, Eduardo Borges; Silva, João S; Carvalho, Ivone

    2015-11-01

    The current treatment of Chagas disease is based on the use of two drugs, nifurtimox and benznidazole, which present limited efficacy in the chronic stage of the disease and toxic side effects. Although some progress has been made in the development of new drugs to treat this disease, the discovery of novel compounds is urgently required. In this work we report the synthesis and biological evaluation of 1,2,3-triazole-based analogues of benznidazole. A small series of 27 compounds was successfully synthesized via microwave-assisted copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) from N-benzyl-2-azidoacetamide (1) and a set of commercial terminal alkynes. Analogues 24 (IC50 40 μM) and 28 (IC50 50 μM) showed comparable activities to benznidazole (IC50 34 μM) against trypomastigote form and analogue 15 (IC50 7 μM) was found to be the most active. Regarding the cytotoxicity assessment of the series, most compounds were not cytotoxic. This work shows that the designed strategy is efficiently capable of generating novel benzindazole analogues and reveals one analogue is more active than benznidazole. PMID:26476667

  15. 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

  16. A triazole derivative elicits autophagic clearance of polyglutamine aggregation in neuronal cells

    PubMed Central

    Hsieh, Chang Heng; Lee, Li-Ching; Leong, Wai-Yin; Yang, Tsai-Chen; Yao, Ching-Fa; Fang, Kang

    2016-01-01

    Trinucleotide CAG repeat expansion in the coding region of genes has a propensity to form polyglutamine (polyQ) aggregates that contribute to neuronal disorders. Strategies in elevating autophagy to disintegrate the insoluble aggregates without injuring cells have become a major goal for therapy. In this work, a triazole derivative, OC-13, was found accelerating autophagic clearance of polyQ aggregation in human neuroblastoma cells following induction of the enhanced green fluorescence-conjugated chimeric protein that enclosed 79 polyQ repeats (Q79-EGFP). OC-13 accelerated autophagy development and removed nuclear Q79-EGFP aggregates. The increase of Beclin-1, turnover of LC3-I to LC3-II and degradation of p62 supported autophagy activation. Pretreatment of autophagy inhibitor, bafilomycin A1, not only suppressed autophagolysome fusion, but also impeded aggregate eradication. The study also showed that c-Jun N-terminal kinase/Beclin-1 pathway was activated during OC-13 treatment and c-Jun N-terminal kinase inhibitor impaired autophagy and final breakdown. Autophagic clearance of the insoluble aggregates demonstrated the feasibility of OC-13 in alleviating neuronal disorders because of expanded glutamine stretches.

  17. Stealth lipoplex decorated with triazole-tethered galactosyl moieties: a strong hepatotropic gene vector.

    PubMed

    Govender, Dhineshree; Islam, Rafique Ul; De Koning, Charles B; van Otterlo, Willem A L; Arbuthnot, Patrick; Ariatti, Mario; Singh, Moganavelli

    2015-03-01

    Mono-antennary galacto derivatives of cholesterol are being actively developed to direct lipoplexes to the asialoglycoprotein receptor (ASGP-R) on hepatocytes. Here we report on a novel ASGP-R ligand cholest-5-en-3-yl [1-(β-D-galactopyranosyl)-1H-1,2,3-triazol-4-yl]methylcarbamate (4), assembled by a copper(I)-catalyzed azide-alkyne cycloaddition (click chemistry), and compare it with cholest-5-en-3-yl-β-D-galactopyranoside (2) and cholest-5-en-3-yl [1-(β-D-galactopyranosyl-1'-oxy)phen-4-yl]carbamate (3), in liposome formulations with or without 5 mol% distearoylphosphatidylethanolamine poly(ethylene glycol)2000, intended for DNA delivery to ASGP-R-positive hepatocyte-derived HepG2 cells and the ASGP-R-negative embryo kidney cell line HEK293. Transfection levels attained with lipoplex 4 were 100 and 300% greater than those for lipoplexes 2 and 3 respectively in HepG2 cells, while competition assays reduced transfection levels by up to 98%. Transfection activities achieved in HEK293 cells were up to three orders of magnitude lower. Therefore, 4 is representative of a new class of promising hepatotropic ligands for gene delivery.

  18. Nav1.1 modulation by a novel triazole compound attenuates epileptic seizures in rodents.

    PubMed

    Gilchrist, John; Dutton, Stacey; Diaz-Bustamante, Marcelo; McPherson, Annie; Olivares, Nicolas; Kalia, Jeet; Escayg, Andrew; Bosmans, Frank

    2014-05-16

    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

  19. 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

  20. 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

  1. Ion pair recognition receptor based on an unsymmetrically 1,1'-disubstituted ferrocene-triazole derivative.

    PubMed

    Otón, Francisco; González, María del Carmen; Espinosa, Arturo; Ramírez de Arellano, Carmen; Tárraga, Alberto; Molina, Pedro

    2012-11-16

    The ferrocene-triazole derivative 4, available from 1,1'-bis(diazido)ferrocene by sequential functionalization through click-type chemistry and the Staudinger reaction, is elaborated as a lab-on-a-molecule for the selective sensing of HP(2)O(7)(3-) and Hg(2+). Receptor 4 behaves as a ratiometric fluorescent probe for HP(2)O(7)(3-) with a good selectivity over other anions, whereas in the presence of Hg(2+) it modifies the fluorescent emission of the pyrene unit, acting as a selective on-off fluorescent sensor for Hg(2+) with a low detection limit. The most salient feature of compound 4 is its behavior as an excellent electrooptical ion pair recognition receptor able to simultaneously recognize Pb(2+) cations in the presence of HP(2)O(7)(3-) anion through multichannel perturbations of the redox potential of the ferrocene unit, the emission spectrum, and a noticeable color change from yellow to green.

  2. Synthesis, structural charaterization, and electrochemical and optical properties of ferrocene-triazole-pyridine triads.

    PubMed

    Romero, Tomás; Orenes, Raúl A; Espinosa, Arturo; Tárraga, Alberto; Molina, Pedro

    2011-09-01

    The synthesis and electrochemical, optical, and cation-sensing properties of the ferrocene-triazole-pyridine triads 3 and 5 are presented. Azidoferrocene 1 and 1,1'-diazidoferrocene 4 underwent the "click" reaction with 2-ethynylpyridine to give the triads 3 and 5 in 81% and 68% yield, respectively. Electrochemical studies carried out in CH(3)CN in the presence of increasing amounts of Zn(2+), Ni(2+), Cd(2+), Hg(2+), and Pb(2+) metal cations, showed that the wave corresponding to the ferrocene/ferrocenium redox couple is anodically shifted by 70-130 mV for triad 3 and 167-214 mV for triad 5. The maximum shift of the ferrocene oxidation wave was found for 5 in the presence of Zn(2+). In addition, the low-energy band of the absorption spectra of 3 and 5 are red-shifted (Δλ = 5-10 nm) upon complexation with these metal cations. The crystal structures of compounds 3 and 5 and the complex [3(2)·Zn](2+) have been determined by single-crystal X-ray methods. (1)H NMR studies as well as density functional theory calculations have been carried out to get information about the binding sites that are involved in the complexation process.

  3. 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

  4. Solution-Phase Parallel Synthesis of Acyclic Nucleoside Libraries of Purine, Pyrimidine, and Triazole Acetamides

    PubMed Central

    2015-01-01

    Molecular diversity plays a pivotal role in modern drug discovery against phenotypic or enzyme-based targets using high throughput screening technology. Under the auspices of the Pilot Scale Library Program of the NIH Roadmap Initiative, we produced and report herein a diverse library of 181 purine, pyrimidine, and 1,2,4-triazole-N-acetamide analogues which were prepared in a parallel high throughput solution-phase reaction format. A set of assorted amines were reacted with several nucleic acid N-acetic acids utilizing HATU as the coupling reagent to produce diverse acyclic nucleoside N-acetamide analogues. These reactions were performed using 24 well reaction blocks and an automatic reagent-dispensing platform under inert atmosphere. The targeted compounds were purified on an automated purification system using solid sample loading prepacked cartridges and prepacked silica gel columns. All compounds were characterized by NMR and HRMS, and were analyzed for purity by HPLC before submission to the Molecular Libraries Small Molecule Repository (MLSMR) at NIH. Initial screening through the Molecular Libraries Probe Production Centers Network (MLPCN) program, indicates that several analogues showed diverse and interesting biological activities. PMID:24933643

  5. 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

  6. 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.

  7. 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

  8. Nanostructured Samarium Doped Fluorapatites and Their Catalytic Activity towards Synthesis of 1,2,4-Triazoles.

    PubMed

    Gangu, Kranthi Kumar; Maddila, Suresh; Maddila, Surya Narayana; Jonnalagadda, Sreekantha B

    2016-01-01

    An investigation was conducted into the influence of the amino acids as organic modifiers in the facile synthesis of metal incorporated fluorapatites (FAp) and their properties. The nanostructured Sm doped fluorapatites (Sm-FAp) were prepared by a co-precipitation method using four different amino acids, namely glutamic acid, aspartic acid, glycine and histidine. The materials were characterized by various techniques including X-ray diffraction (XRD), Fourier transform infra-red spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), high resolution transmission electron microscopy (HR-TEM), N₂-adsorption/desorption isotherm, temperature programmed desorption (TPD) and fluorescence spectrophotometry. Under similar conditions, Sm-FAp prepared using different amino acids exhibited distinctly different morphological structures, surface area and pore properties. Their activity as catalysts was assessed and Sm-FAp/Glycine displayed excellent efficiency in the synthesis of 1,2,4-triazole catalyzing the reaction between 2-nitrobenzaldehyde and thiosemicarbazide with exceptional selectivity and 98% yield in a short time interval (10 min). The study provides an insight into the role of organic modifiers as controllers of nucleation, growth and aggregation which significantly influence the nature and activity of the catalytic sites on Sm-FAp. Sm-FAp could also have potential as photoactive material. PMID:27669208

  9. 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

  10. 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:27397939

  11. Treatment of recurrent malignant gliomas with 13-cis-retinoic acid naphthalene triazole.

    PubMed

    Jia, Pi-Feng; Gu, Wei-Ting; Zhang, Wei-Feng; Li, Feng

    2015-05-01

    Glioblastoma multiforme and anaplastic astrocytoma are challenges to clinical biologists at present. The patients with glioblastoma have median survival of less than 12 months, despite advances in radiotherapeutical, chemotherapeutical and conventional surgical modalities. Retinoic acids are known to effect in vitro proliferation, differentiation, and apoptosis in colon, prostate, lung, and leukemia cancers. Retinoids are known to have anti-proliferation, anti-migration, and anti-invasive activity against human malignant gliomas, suggesting that retinoids are suitable anticancer agents to inhibit progression of tumors. Recurrent malignant cerebral gliomas have been treated with ATRA and 13-cis RA. However, the side effects associated with the use of high doses of retinoic acid demand for some more potent derivative free from such effects. The present clinical trials are undertaken to investigate the clinical safety and possible efficacy of administering retinoic acid naphthalene triazole (RANT) to patients with recurrent malignant gliomas. The toxicities observed in the patients during RANT treatment were mild. These preliminary results suggest that RANT is more potent compared to RA against recurrent malignant gliomas.

  12. 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.

  13. A triazole derivative elicits autophagic clearance of polyglutamine aggregation in neuronal cells

    PubMed Central

    Hsieh, Chang Heng; Lee, Li-Ching; Leong, Wai-Yin; Yang, Tsai-Chen; Yao, Ching-Fa; Fang, Kang

    2016-01-01

    Trinucleotide CAG repeat expansion in the coding region of genes has a propensity to form polyglutamine (polyQ) aggregates that contribute to neuronal disorders. Strategies in elevating autophagy to disintegrate the insoluble aggregates without injuring cells have become a major goal for therapy. In this work, a triazole derivative, OC-13, was found accelerating autophagic clearance of polyQ aggregation in human neuroblastoma cells following induction of the enhanced green fluorescence-conjugated chimeric protein that enclosed 79 polyQ repeats (Q79-EGFP). OC-13 accelerated autophagy development and removed nuclear Q79-EGFP aggregates. The increase of Beclin-1, turnover of LC3-I to LC3-II and degradation of p62 supported autophagy activation. Pretreatment of autophagy inhibitor, bafilomycin A1, not only suppressed autophagolysome fusion, but also impeded aggregate eradication. The study also showed that c-Jun N-terminal kinase/Beclin-1 pathway was activated during OC-13 treatment and c-Jun N-terminal kinase inhibitor impaired autophagy and final breakdown. Autophagic clearance of the insoluble aggregates demonstrated the feasibility of OC-13 in alleviating neuronal disorders because of expanded glutamine stretches. PMID:27695292

  14. 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.

  15. 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.

  16. 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 " ...

  17. 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.

  18. 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

  19. 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

  20. Synthesis of some new 1,2,4-triazole derivatives starting from 3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol with anti-lipase and anti-urease activities.

    PubMed

    Bekircan, Olcay; Menteşe, Emre; Ulker, Serdar; Kucuk, Cagatay

    2014-06-01

    In the present study, starting compound 4 was prepared by deamination of compound 2 in the presence of hypophosphorous acid and sodium nitrite. Treatment of compound 4 with ethyl bromoacetate produced ethyl[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetate (5), which was converted to the hydrazide derivative (6) by treatment with hydrazine hydrate. The reaction of compound 6 with aromatic aldehydes resulted in the formation of arylidene hydrazides (7). Treatment of 6 with CS2 in the presence of potassium hydroxide (KOH), followed by cyclization with hydrazine hydrate, afforded 4-amino-5-{[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]methyl}-2,4-dihydro-3H-1,2,4-triazole-3-thione (9). The condensation of 9 with appropriate aldehydes gave Schiff bases (10), which were converted into Mannich bases (11) in the presence of formaldehyde. All the synthesized compounds were screened for their anti-lipase and anti-urease activities. Compounds 7b, 7d, 11b, 11c, and 11d showed moderate-to-good lipase inhibitory effects compared to orlistat. Compounds 7b and 7d exhibited better anti-lipase activity. Furthermore, among the compounds tested, 11a and 11d were found to show high inhibitory effect against urease with IC50 values of 12.39 ± 0.35 and 16.12 ± 1.06 µg/mL, respectively. Compound 11c showed moderate inhibitory activity. The Mannich base containing compound 11 may be a source of good leads for the synthesis of lipase and urease dual inhibitors.

  1. 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

  2. 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

  3. Efficient method for iodine radioisotope labeling of cyclooctyne-containing molecules using strain-promoted copper-free click reaction.

    PubMed

    Jeon, Jongho; Kang, Jung Ae; Shim, Ha Eun; Nam, You Ree; Yoon, Seonhye; Kim, Hye Rim; Lee, Dong Eun; Park, Sang Hyun

    2015-07-01

    Herein we report an efficient method for iodine radioisotope labeling of cyclooctyne-containing molecules using copper-free click reaction. For this study, radioiodination using the tin precursor 2 was carried out at room temperature to give (125)I-labeled azide ([(125)I]1) with high radiochemical yield (85%) and excellent radiochemical purity. Dibenzocyclooctyne (DBCO) containing cRGD peptide and gold nanoparticle were labeled with [(125)I]1 at 37°C for 30min to give triazoles with good radiochemical yields (67-95%). We next carried out tissue biodistribution study of [(125)I]1 in normal ICR mice to investigate the level of organ accumulation which needs to be considered for pre-targeted in vivo imaging. Large amount of [(125)I]1 distributed rapidly in liver and kidney from bloodstream and underwent rapid renal and hepatobiliary clearance. Moreover [(125)I]1 was found to be highly stable (>92%) in mouse serum for 24h. Therefore [(125)I]1 could be used as a potentially useful radiotracer for pre-targeted imaging. Those results clearly indicated that the present radiolabeling method using copper free click reaction would be quite useful for both in vitro and in vivo labeling of DBCO group containing molecules with iodine radioisotopes. PMID:25960325

  4. 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

  5. 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

  6. Synthesis and explosive properties of copper(II) chlorate(VII) coordination polymer with 4-amino-1,2,4-triazole bridging ligand.

    PubMed

    Cudziło, Stanisław; Nita, Marcin

    2010-05-15

    Copper(II) chlorate(VII) coordination polymer with 4-amino-1,2,4-triazole as bridging ligand was prepared and characterized by elemental analysis, IR spectra and TG/DTA analyses. Sensitivity and detonator tests were also preformed. The compound has a 1D chain structure in which Cu(II) ions are linked by triple triazole N1,N2 bridges. It is a detonat with performance close to that of lead azide, but at the same time it shows moderate sensitivity to thermal (explosively decomposes above 250 degrees C) and mechanical stimuli (sensitivity to friction 10N).

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 1H-1,2,3-triazole tethered isatin-ferrocene conjugates: Synthesis and in vitro antimalarial evaluation.

    PubMed

    Kumar, Kewal; Pradines, Bruno; Madamet, Marilyn; Amalvict, Rémy; Benoit, Nicolas; Kumar, Vipan

    2014-11-24

    1H-1,2,3-triazole tethered isatin-ferrocene conjugates were synthesized and evaluated for their antiplasmodial activities against chloroquine-susceptible (3D7) and chloroquine-resistant (W2) strains of Plasmodium falciparum. The conjugates 5f and 5h with an optimum combination of electron-withdrawing halogen substituent at C-5 position of isatin ring and a propyl chain, introduced as linker, proved to be most potent and non-cytotoxic among the series with IC50 values of 3.76 and 4.58 μM against 3D7 and W2 strains, respectively.

  15. Design and synthesis of novel 1,2,3-triazole-pyrimidine-urea hybrids as potential anticancer agents.

    PubMed

    Ma, Li-Ying; Wang, Bo; Pang, Lu-Ping; Zhang, Miao; Wang, Sai-Qi; Zheng, Yi-Chao; Shao, Kun-Peng; Xue, Deng-Qi; Liu, Hong-Min

    2015-03-01

    A series of novel 1,2,3-triazole-pyrimidine-urea hybrids were designed, synthesized and evaluated for anticancer activity against four selected cancer cell lines (MGC-803, EC-109, MCF-7 and B16-F10). Majority of the synthesized compounds exhibited moderate to potent activity against all the cancer cell lines assayed. Particularly, compounds 26, 30 and 38 exhibited excellent growth inhibition against B16-F10 with IC50 values of 32nM, 35nM and 42nM, respectively. Flow cytometry analysis demonstrated that compound 26 induced the cellular apoptosis in a concentration-dependent manner.

  16. Multicomponent click synthesis of new 1,2,3-triazole derivatives of pyrimidine nucleobases: promising acidic corrosion inhibitors for steel.

    PubMed

    González-Olvera, Rodrigo; Espinoza-Vázquez, Araceli; Negrón-Silva, Guillermo E; Palomar-Pardavé, Manuel E; Romero-Romo, Mario A; Santillan, Rosa

    2013-12-06

    A series of new mono-1,2,3-triazole derivatives of pyrimidine nucleobases were synthesized by one-pot copper(I)-catalyzed 1,3-dipolar cycloaddition reactions between N-1-propargyluracil and thymine, sodium azide and several benzyl halides. The desired heterocyclic compounds were obtained in good yields and characterized by NMR, IR, and high resolution mass spectrometry. These compounds were investigated as corrosion inhibitors for steel in 1 M HCl solution, using electrochemical impedance spectroscopy (EIS) technique. The results indicate that these heterocyclic compounds are promising acidic corrosion inhibitors for steel.

  17. 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

  18. HIV-1 Env gp120 Structural Determinants for Peptide Triazole Dual Receptor Site Antagonism

    PubMed Central

    Tuzer, Ferit; Madani, Navid; Kamanna, Kantharaju; Zentner, Isaac; LaLonde, Judith; Holmes, Andrew; Upton, Elizabeth; Rajagopal, Srivats; McFadden, Karyn; Contarino, Mark; Sodroski, Joseph; Chaiken, Irwin

    2013-01-01

    Despite advances in HIV therapy, viral resistance and side-effects with current drug regimens require targeting new components of the virus. Dual antagonist peptide triazoles (PT) are a novel class of HIV-1 inhibitors that specifically target the gp120 component of the viral spike and inhibit its interaction with both of its cell surface protein ligands, namely the initial receptor CD4 and the co-receptor (CCR5/CXCR4), thus preventing viral entry. Following an initial survey of 19 gp120 alanine mutants by ELISA, we screened 11 mutants for their importance in binding to, and inhibition by the PT KR21 using surface plasmon resonance. Key mutants were purified and tested for their effects on the peptide’s affinity and its ability to inhibit binding of CD4 and the co-receptor surrogate mAb 17b. Effects of the mutations on KR21 viral neutralization were measured by single-round cell infection assays. Two mutations, D474A and T257A, caused large-scale loss of KR21 binding, as well as losses in both CD4/17b and viral inhibition by KR21. A set of other Ala mutants revealed more moderate losses in direct binding affinity and inhibition sensitivity to KR21. The cluster of sensitive residues defines a PT functional epitope. This site is in a conserved region of gp120 that overlaps the CD4 binding site and is distant from the co-receptor/17b binding site, suggesting an allosteric mode of inhibition for the latter. The arrangement and sequence conservation of the residues in the functional epitope explain the breadth of antiviral activity, and improve the potential for rational inhibitor development. PMID:23011758

  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.

  20. Design, synthesis and biological evaluation of mannosyl triazoles as FimH antagonists.

    PubMed

    Schwardt, Oliver; Rabbani, Said; Hartmann, Margrit; Abgottspon, Daniela; Wittwer, Matthias; Kleeb, Simon; Zalewski, Adam; Smieško, Martin; Cutting, Brian; Ernst, Beat

    2011-11-01

    Urinary tract infection (UTI) caused by uropathogenic Escherichia coli (UPEC) is one of the most prevalent infectious diseases. Particularly affected are women, who have a 40-50% risk to experience at least one symptomatic UTI episode at some time during their life. In the initial step of the infection, the lectin FimH, located at the tip of bacterial pili, interacts with the high-mannosylated uroplakin Ia glycoprotein on the urinary bladder mucosa. This interaction is critical for the ability of UPEC to colonize and invade the bladder epithelium. X-ray structures of FimH co-crystallized with two different ligands, the physiological binding epitope oligomannose-3 and the antagonist biphenyl α-D-mannoside 4a revealed different binding modes, an in-docking-mode and an out-docking-mode, respectively. To accomplish the in-docking-mode, that is the docking mode where the ligand is hosted by the so-called tyrosine gate, FimH antagonists with increased flexibility were designed and synthesized. All derivatives 5-8 showed nanomolar affinities, but only one representative, the 4-pyridiyl derivative 5j, was as potent as the reference compound n-heptyl α-D-mannoside (1b). Furthermore, a loss of affinity was observed for C-glycosides and derivatives where the triazole aglycone is directly N-linked to the anomeric center. A conformational analysis by NMR revealed that the triazolyl-methyl-C-mannosides 8 adopt an unusual (1)C(4) chair conformation, explaining the comparably lower affinity of these compounds. Furthermore, to address the druglikeness of this new class of FimH antagonists, selected pharmacokinetic parameters, which are critical for oral bioavailability (lipophilicity, solubility, and membrane permeation), were determined. PMID:21962988

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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

    2016-06-20

    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.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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

  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. 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

  2. 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...

  3. Synthesis and evaluation of new Hsp90 inhibitors based on a 1,4,5-trisubstituted 1,2,3-triazole scaffold.

    PubMed

    Taddei, Maurizio; Ferrini, Serena; Giannotti, Luca; Corsi, Massimo; Manetti, Fabrizio; Giannini, Giuseppe; Vesci, Loredana; Milazzo, Ferdinando M; Alloatti, Domenico; Guglielmi, Mario B; Castorina, Massimo; Cervoni, Maria L; Barbarino, Marcella; Foderà, Rosanna; Carollo, Valeria; Pisano, Claudio; Armaroli, Silvia; Cabri, Walter

    2014-03-27

    Ruthenium catalyzed 1,3-cycloaddition (click chemistry) of an azido moiety installed on dihydroxycumene scaffold with differently substituted aryl propiolates gave a new family of 1,4,5-trisubstituted triazole carboxylic acid derivatives that showed high affinity toward Hsp90 associated with cell proliferation inhibition, both in nanomolar range. The 1,5 arrangement of the resorcinol, the aryl moieties, and the presence of an alkyl (secondary) amide in position 4 of the triazole ring were essential to get high activity. Docking simulations suggested that the triazoles penetrate the Hsp90 ATP binding site. Some 1,4,5-trisubstituted triazole carboxamides induced dramatic depletion of the examined client proteins and a very strong increase in the expression levels of the chaperone Hsp70. In vitro metabolic stability and in vivo preliminary studies on selected compounds have shown promising results comparable to the potent Hsp90 inhibitor NVP-AUY922. One of them, (compound 18, SST0287CL1) was selected for further investigation as the most promising drug candidate. PMID:24588105

  4. 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

  5. Bis[3-(5-nitroimino-1,2,4-triazolate)]-based energetic salts: synthesis and promising properties of a new family of high-density insensitive materials.

    PubMed

    Wang, Ruihu; Xu, Hongyan; Guo, Yong; Sa, Rongjian; Shreeve, Jean'ne M

    2010-09-01

    Bis[3-(5-nitroimino-1,2,4-triazolate)]-based energetic salts were synthesized in a simple, straightforward manner. They exhibit low solubility in available solvents, high hydrolytic stability, excellent thermal stability, high density, positive heat of formation, low shock sensitivity, and excellent detonation properties. The physical and energetic properties of some salts are similar and even superior to those of RDX.

  6. Ethyl 1-(2,6-difluoro­benz­yl)-1H-1,2,3-triazole-4-carboxyl­ate

    PubMed Central

    Jia, Jing; Lu, Dingqiang

    2011-01-01

    In the title compound, C12H11F2N3O2, the dihedral angle between the triazole and phenyl rings is 73.74 (9)°. In the crystal, mol­ecules are linked into chains along [010] via weak C—H⋯O and C—H⋯N hydrogen bonds. PMID:21522638

  7. The 1,2,3-triazole derivative KP-A021 suppresses osteoclast differentiation and function by inhibiting RANKL-mediated MEK-ERK signaling pathway.

    PubMed

    Ihn, Hye Jung; Lee, Doohyun; Lee, Taeho; Shin, Hong-In; Bae, Yong Chul; Kim, Sang-Hyun; Park, Eui Kyun

    2015-12-01

    The triazole family of compounds has been implicated in modulating various biological processes such as inflammation, tumorigenesis, and infection. To our knowledge, this is the first study to demonstrate the effects of 1,2,3-triazole substituted biarylacrylonitrile compounds, including KP-A021, on the differentiation and function of osteoclasts. KP-A021 and its triazole derivatives, at a concentration that does not cause a cytotoxic response in bone marrow macrophages (BMMs), significantly inhibited osteoclast differentiation induced by receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) as assessed by tartrate-resistant acid phosphatase (TRAP) staining. KP-A021 also dramatically inhibited the expression of marker genes associated with osteoclast differentiation, such as TRAP, cathepsin K (Cat K), dendritic cell-specific transmembrane protein (DC-STAMP), and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1). Furthermore, KP-A021 inhibited actin ring formation in osteoclasts as well as resorption pit formation induced by osteoclasts. Analysis of the signaling pathway for KP-A021 indicated that this triazole compound inhibited the RANKL-induced activation of extracellular signal-regulated kinase (ERK) and its upstream signaling molecule, mitogen-activated protein kinase kinase1/2 (MEK1/2). Taken together, these results demonstrate that KP-A021 has an inhibitory effect on the differentiation and function of osteoclasts via modulation of the RANKL-induced activation of the MEK-ERK pathway.

  8. Design, synthesis and molecular docking studies of novel N-benzenesulfonyl-1,2,3,4-tetrahydroisoquinoline-based triazoles with potential anticancer activity.

    PubMed

    Pingaew, Ratchanok; Mandi, Prasit; Nantasenamat, Chanin; Prachayasittikul, Supaluk; Ruchirawat, Somsak; Prachayasittikul, Virapong

    2014-06-23

    A novel series of N-benzenesulfonyl-1,2,3,4-tetrahydroisoquinolines (14-33) containing triazole moiety were designed and synthesized through rational cycloadditions using the modified Pictet-Spengler reaction and the Click chemistry. Antiproliferative activity against four cancer cell lines (e.g., HuCCA-1, HepG2, A549 and MOLT-3) revealed that many substituted triazole analogs of benzoates (20, 29) and benzaldehydes (30, 32) exhibited anticancer activity against all of the tested cancer cell lines in which the ester analog 20 was shown to be the most potent compound against HuCCA-1 (IC50 = 0.63 μM) and A549 (IC50 = 0.57 μM) cell lines. Triazoles bearing phenyl (15, 24), tolyl (26, 27), acetophenone (19), benzoate (20, 29), benzaldehyde (21, 30) and naphthalenyl (25) substituents showed stronger anticancer activity against HepG2 cells than that of the etoposide. Interestingly, the p-tolyl analog (27) displayed the most potent inhibitory activity (IC50 = 0.56 μM) against HepG2 cells without affecting normal cells. Of the investigated tetrahydroisoquinoline-triazoles, the promising compounds 20 and 27 were selected for molecular docking against AKR1C3, which was identified to be a plausible target site. PMID:24836071

  9. 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…

  10. 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

  11. Principles of protein labeling techniques.

    PubMed

    Obermaier, Christian; Griebel, Anja; Westermeier, Reiner

    2015-01-01

    Protein labeling methods prior to separation and analysis have become indispensable approaches for proteomic profiling. Basically, three different types of tags are employed: stable isotopes, mass tags, and fluorophores. While proteins labeled with stable isotopes and mass tags are measured and differentiated by mass spectrometry, fluorescent labels are detected with fluorescence imagers. The major purposes for protein labeling are monitoring of biological processes, reliable quantification of compounds and specific detection of protein modifications and isoforms in multiplexed samples, enhancement of detection sensitivity, and simplification of detection workflows. Proteins can be labeled during cell growth by incorporation of amino acids containing different isotopes, or in biological fluids, cells or tissue samples by attaching specific groups to the ε-amino group of lysine, the N-terminus, or the cysteine residues. The principles and the modifications of the different labeling approaches on the protein level are described; benefits and shortcomings of the methods are discussed.

  12. 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

  13. Appliance energy labeling takes effect

    SciTech Connect

    Not Available

    1980-06-01

    Consumers buying household appliances will be helped by energy-efficiency labels and minimum efficiency standards required for refrigerators and refrigerator/freezers, freezers, dishwashers, water heaters, clothes washers, room air conditioners, and furnaces. The ENERGYGUIDE labels must be displayed in the store and in catalogs. Two voluntary efficiency programs were combined in the Energy Policy and Conservation Act (EPCA) requiring labels by 1980. Shoppers may compare the efficiencies of appliances and compute the actual cost differential over the lifetime of the equipment. Manufacturers have responded with more-efficient models, but the impact of efficient appliances on energy consumption will be small. A sample label with the required information is illustrated. (DCK)

  14. 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.

  15. 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.

  16. 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

  17. Labeled Cocaine Analogs

    SciTech Connect

    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.

  18. 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)...

  19. 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...

  20. 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...

  1. 76 FR 75809 - Prior Label Approval System: Generic Label Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-05

    ... poultry products will take effect January 1, 2012 (75 FR 82148, Dec. 29, 2010). These mandatory features... limited types of labels (e.g., labels for raw, single ingredient meat and poultry products) (48 FR 11410... Agency. On March 25, 1992, FSIS published an Advance Notice of Proposed Rulemaking (ANPRM) (57 FR...

  2. 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…

  3. 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 ...

  4. 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

  5. 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...

  6. 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...

  7. 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...

  8. 21 CFR 610.60 - Container label.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Container label. 610.60 Section 610.60 Food and... GENERAL BIOLOGICAL PRODUCTS STANDARDS Labeling Standards § 610.60 Container label. (a) Full label. The following items shall appear on the label affixed to each container of a product capable of bearing a...

  9. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Labels. 460.12 Section 460.12 Commercial Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels...

  10. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Labels. 460.12 Section 460.12 Commercial Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels...

  11. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Labels. 460.12 Section 460.12 Commercial Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels...

  12. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Labels. 460.12 Section 460.12 Commercial Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels...

  13. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 1 2013-01-01 2013-01-01 false Labels. 460.12 Section 460.12 Commercial Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels...

  14. 21 CFR 201.71 - Magnesium labeling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 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...

  15. 21 CFR 201.71 - Magnesium labeling.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 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...

  16. 21 CFR 201.71 - Magnesium labeling.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 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. 9 CFR 317.4 - Labeling approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... labeling of such final labeling has been submitted for approval to the Food Labeling Division, Regulatory... Secretary upon request. (b) The Food Labeling Division shall permit submission for approval of only sketch... Food Labeling Division, Regulatory Programs, Food Safety and Inspection Service, U.S. Department...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 21 CFR 201.64 - Sodium labeling.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... contains sodium bicarbonate, sodium phosphate, or sodium biphosphate as an active ingredient for oral... 21 Food and Drugs 4 2010-04-01 2010-04-01 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. Labeled Cocaine Analogs

    SciTech Connect

    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.

  5. 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.

  6. 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.

  7. Regioselective Synthesis of a Family of β‐Lactams Bearing a Triazole Moiety as Potential Apoptosis Inhibitors

    PubMed Central

    Garrido, Maria; Corredor, Miriam; Orzáez, Mar; Alfonso, Ignacio

    2016-01-01

    Abstract Apoptosis is a biological process important to several human diseases; it is strongly regulated through protein–protein interactions and complex formation. We previously reported the synthesis of apoptosis inhibitors bearing an exocyclic triazole amide isoster by using an Ugi four‐component coupling reaction (Ugi‐4CC), followed by a base‐promoted intramolecular cyclization. Depending on the substitution patterns and the reaction conditions, this cyclization forms the six‐ or four‐membered ring. Two compounds bearing the β‐lactam scaffold turned out to be the most potent inhibitors. This encouraged us to optimize the modulation of the cyclization, and prepare a library of 15 β‐lactams with total regioselectivity. Moreover, we aimed to improve the bioavailability of these compounds through the introduction of diversity at different substitution positions. The activity of these compounds as apoptosis inhibitors in cellular extracts has been evaluated, showing an increase in their potency. PMID:27777842

  8. Synthesis and aromatase inhibitory evaluation of 4-N-nitrophenyl substituted amino-4H-1,2,4-triazole derivatives.

    PubMed

    Song, Zhidan; Liu, Yanchun; Dai, Zhoutong; Liu, Wei; Zhao, Kai; Zhang, Tongcun; Hu, Yanying; Zhang, Xiuli; Dai, Yujie

    2016-10-01

    In this paper, 13 4-N-nitrophenyl substituted amino-4H-1,2,4-triazole derivatives were synthesized and their aromatase inhibitory activities were measured. The results show that the substitution of the groups on benzyl group can further improve their bioactivity and the compound with Cl on the para position of benzyl has the highest bioactivity (IC50=9.02nM). A QSAR model was constructed from the 13 compounds with genetic function approximation using DS 2.1 package. This model can explain 90.09% of the variance (R(2)Adj), while it can predict 84.95% of the variance (R(2)cv) with the confidence interval of 95%. PMID:27567077

  9. 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.

  10. Design, synthesis and anticancer activity of matrine-1H-1,2,3-triazole-chalcone conjugates.

    PubMed

    Zhao, Lihui; Mao, Lina; Hong, Ge; Yang, Xiaojiao; Liu, Tianjun

    2015-06-15

    A series of novel matrine-1H-1,2,3-triazole-chalcone conjugates was synthesized and their anticancer activity against A549, Bel-7402, Hela, and MCF-7 cancer cells was evaluated. Most of the conjugates displayed higher potency than their components. Compounds 6h and 6i exhibited more potent anticancer activity than 5-fluorouracil against the four tested human cancer cell lines and lower cytotoxicity to NIH3T3 normal cells. Flow cytometry tests demonstrated that compound 6h could induce apoptosis of A549 cells in a concentration-dependent manner. Moreover, 6h could efficiently suppress human tumor growth in mouse xenograft model without causing obvious toxicities.

  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.

  13. A structurally flexible triazolate-based metal-organic framework featuring coordinatively unsaturated copper(i) sites.

    PubMed

    Schmieder, P; Denysenko, D; Grzywa, M; Magdysyuk, O; Volkmer, D

    2016-09-21

    The novel metal-organic framework CFA-8 (Coordination Framework Augsburg University-8), [Cu2(tqpt)], containing the organic linker H2-tqpt {H2-tqpt = 6,6,14,14-tetramethyl-6,14-dihydroquinoxalino[2,3-b]phenazinebis-triazole}, has been synthesized. Reaction of H2-tqpt and anhydrous CuCl2 in N,N-dimethylacetamide (DMA) yields CFA-8 as orange crystals with lenticular shape. This framework shows a reversible breathing effect and is robust upon solvent removal. It has been characterized by single-crystal and powder X-ray diffraction, TGA, IR spectroscopy and gas sorption measurements. CO adsorption isotherms show that Cu(i) sites in this framework are able to bind carbon monoxide forming a weak complex which has been additionally characterized by IR spectroscopy and synchrotron powder X-ray diffraction measurements. PMID:27513160

  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. 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

  17. The effect of some triazole derivatives as inhibitors for the corrosion of mild steel in 1 M hydrochloric acid

    NASA Astrophysics Data System (ADS)

    Zhang, Shengtao; Tao, Zhihua; Li, Weihua; Hou, Baorong

    2009-05-01

    Corrosion inhibition by some new triazole derivatives on mild steel in 1 M hydrochloric acid solutions has been investigated by weight loss test, electrochemical measurement, scanning electronic microscope analysis and quantum chemical calculations. The results indicate that these compounds act as mixed-type inhibitors retarding the anodic and cathodic corrosion reactions and do not change the mechanism of either hydrogen evolution reaction or mild steel dissolution. The studied compounds following the Langmuir adsorption isotherm, and the thermodynamic parameters were determined and discussed. The effect of molecular structure on the inhibition efficiency has been investigated by ab initio quantum chemical calculations. The electronic properties such as highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO) energy levels, energy gap (LUMO-HOMO), dipole moment and molecular orbital densities were calculated.

  18. 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

  19. 21 CFR 1302.04 - Location and size of symbol on label and labeling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Location and size of symbol on label and labeling. 1302.04 Section 1302.04 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE LABELING... and labeling. The symbol shall be prominently located on the label or the labeling of the...

  20. 21 CFR 1302.04 - Location and size of symbol on label and labeling.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Location and size of symbol on label and labeling. 1302.04 Section 1302.04 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE LABELING... and labeling. The symbol shall be prominently located on the label or the labeling of the...

  1. Synthesis and promising properties of a new family of high-density energetic salts of 5-nitro-3-trinitromethyl-1H-1,2,4-triazole and 5,5'-bis(trinitromethyl)-3,3'-azo-1H-1,2,4-triazole.

    PubMed

    Thottempudi, Venugopal; Shreeve, Jean'ne M

    2011-12-14

    Salts of trinitromethyl-substituted triazoles, 5-nitro-3-trinitromethyl-1H-1,2,4-triazole and 5,5'-bis(trinitromethyl)-3,3'-azo-1H-1,2,4-triazole (5), form a new class of highly dense energetic materials. Single-crystal X-ray structuring supports the formation of the cocrystal of 5 with 3,5-diamino-1,2,4-triazole, which was found to be remarkably less impact-sensitive than the azo precursor. The compounds were fully characterized using IR and multinuclear NMR spectroscopy, elemental analysis, and differential scanning calorimetry. Based on heats of formation calculated with Gaussian 03 and combined with experimentally determined densities, detonation properties of the energetic materials obtained with the EXPLO5 program identify them as potentially explosive compounds. They exhibit high density, moderate to good thermal stability, acceptable oxygen balance, reasonable heat of formation, and excellent detonation properties, which in some cases are superior to those of 1,3,5,-trinitrotriazacyclohexane (RDX).

  2. Homosexual Labeling by University Youths

    ERIC Educational Resources Information Center

    Nyberg, Kenneth L.; Alston, Jon P.

    1977-01-01

    Details the responses of young, urban, college-educated people on their attitudes toward homosexuals, specifically focusing on issues of public identification and negative labeling as it effects homosexual persons and their behaviors. (Author/RK)

  3. 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, ...

  4. 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 ...

  5. 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 ...

  6. Electrothermal branding for embryo labeling.

    PubMed

    Wang, L; Beebe, D J; Williams, A R; Easley, K D

    1997-11-01

    A novel embryo labeling technique based on electrothermal branding is developed. Two types of micro branding irons are fabricated and tested. One utilizes 25 microns tungsten wire as the heating element. The other utilizes surface micromachining techniques to fabricate polysilicon branding irons. The thermal behavior of the branding irons and the heat distributions in the embryos are analytically modeled. Micron-scale labels on unfertilized bovine embryos are achieved.

  7. 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.

  8. Microwave assistant synthesis, antifungal activity and DFT theoretical study of some novel 1,2,4-triazole derivatives containing pyridine moiety.

    PubMed

    Sun, Guo-Xiang; Yang, Ming-Yan; Shi, Yan-Xia; Sun, Zhao-Hui; Liu, Xing-Hai; Wu, Hong-Ke; Li, Bao-Ju; Zhang, Yong-Gang

    2014-01-01

    In order to investigate the biological activity of novel 1,2,4-triazole compounds, seventeen novel 1,2,4-triazole derivatives containing pyridine moiety were synthesized under microwave assistant condition by multi-step reactions. The structures were characterized by 1H NMR, MS and elemental analyses. The target compounds were evaluated for their fungicidal activities against Stemphylium lycopersici (Enjoji) Yamamoto, Fusarium oxysporum. sp. cucumebrium, and Botrytis cinerea in vivo, and the results indicated that some of the title compounds displayed excellent fungicidal activities. Theoretical calculation of the title compound was carried out with B3LYP/6-31G (d,p). The full geometry optimization was carried out using 6-31G (d,p) basis set, and the frontier orbital energy, atomic net charges were discussed, and the structure-activity relationship was also studied. PMID:24815069

  9. Studies on Absorption and Emission Characteristics of Inclusion Complexes of Some 4-Arylidenamino-5-phenyl-4H-1, 2, 4-triazole-3-thiols.

    PubMed

    Panda, Sunakar; Nayak, Sashikanta

    2016-03-01

    The inclusion complexes of a series of 4-arylidenamino-5-phenyl-4H-1, 2, 4-triazole-3-thiols have been prepared with β-cyclodextrin. The compounds and their inclusion complexes have been characterized by studying their physical and spectral properties. The thermodynamic stability constant and free energy of activation have been determined to know the stability of inclusion complexes and type of host-guest relation. Finally, absorption, excitation and emission spectra of the compounds (4-arylidenamino-5-phenyl-4H-1, 2, 4-triazole-3-thiols) and their inclusion complexes have been taken. It is found that inclusion complex formation brings about a drastic change in absorption and fluorescence characteristic (both excitation and emission spectra) of newly synthesized compounds.

  10. Synthesis, Characterization and Antibacterial Activity of some Novel Thiosemicarbazides, 1,2,4-Triazol-3-thiols and their S-substituted Derivatives

    PubMed Central

    Kalhor, Mehdi; Shabani, Mahboobeh; Nikokar, Iraj; Reyhaneh Banisaeed, Seyedeh

    2015-01-01

    The thiosemicarbazides 3a-c were appeared by reaction of the corresponding substituted hydrazides 1a-c with allylisothiocyanate 2. Synthesis of some novel 1,2,4-triazole-thiols 4a-c bearing a pyridyl unit using 1-(x-picolinoyl)-4-allyl-thiosemicarbazides (x = 2,3,4) in an alkaline solution, is reported. Also, the S-alkylation of triazole derivatives 5-7a-c is described. The structure of the synthesized compounds resulted from the IR, 1H and -13C NMR spectroscopy and elemental analysis data. The antibacterial studies to all of the synthesized compounds against B. cereus, E. coli, P. aeroginosa, S. aureus and E. faecalis as MIC values are reported. Some of these compounds such as 7a, 4a and 3a exhibited a good to significant antibacterial activity. PMID:25561913

  11. Rhenium and technetium tricarbonyl complexes of 1,4-Substituted pyridyl-1,2,3-triazole bidentate 'click' ligands conjugated to a targeting RGD peptide.

    PubMed

    Connell, Timothy U; Hayne, David J; Ackermann, Uwe; Tochon-Danguy, Henri J; White, Jonathan M; Donnelly, Paul S

    2014-04-01

    New 1,4-substituted pyridyl-1,2,3-triazole ligands with pendent phenyl isothiocyanate functional groups linked to the heterocycle through a short methylene or longer polyethylene glycol spacers were prepared and conjugated to a peptide containing the arginine-glycine-aspartic acid peptide motif. Rhenium and technetium carbonyl complexes, [M(CO)3 L(x) (py)](+) (where M = Re(I) or (99m) Tc(I) ; L(x)  = 1,4-substituted pyridyl-1,2,3-triazole ligands and py = pyridine) were prepared. One rhenium complex has been characterized by X-ray crystallography, and the luminescent properties of [M(CO)3 L(x) (py)](+) are reported.

  12. Synthesis, characterization and antimicrobial evaluation of some new schiff, mannich and acetylenic Mannich bases incorporating a 1,2,4-triazole nucleus.

    PubMed

    Aouad, Mohamed R

    2014-01-01

    A series of Schiff and Mannich bases derived from 4-amino-5-(3-fluoro-phenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione were synthesized. The alkylation of 4-phenyl-5-(3-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione with propargyl bromide afforded the corresponding thiopropargylated derivative which upon treatment with the appropriate secondary amines in the presence of CuCl2 furnished the desired acetylenic Mannich bases. The synthesized compounds were characterized on the basis of their spectral (IR, 1H- and 13C-NMR) data and evaluated for their biological activities. Some of the compounds were found to exhibit significant antimicrobial activity.

  13. 4-Amino-3-(o-tolyl­oxymeth­yl)-1H-1,2,4-triazole-5(4H)-thione

    PubMed Central

    Fun, Hoong-Kun; Liew, Wei-Ching; Vijesh, A. M.; Padaki, Mahesh; Isloor, Arun M.

    2009-01-01

    The asymmetric unit of the title compound, C10H12N4OS, contains two independent mol­ecules, A and B, which differ significantly in the relative orientations of the benzene and triazole rings. The dihedral angle between the above two rings is 6.94 (5)° in mol­ecule A and 77.60 (5)° in mol­ecule B. In the crystal, mol­ecules are linked into a three-dimensional network by N—H⋯S, N—H⋯O, N—H⋯N and C—H⋯S hydrogen bonds and π–π inter­actions between the benzene and triazole rings [centroid–centroid distance = 3.5311 (6) Å] are also present. PMID:21583598

  14. Synthesis and biological evaluation of (4H-1,2,4-triazol-4-yl)isoquinoline derivatives as selective glycine transporter 1 inhibitors.

    PubMed

    Sugane, Takashi; Tobe, Takahiko; Hamaguchi, Wataru; Shimada, Itsuro; Maeno, Kyoichi; Miyata, Junji; Suzuki, Takeshi; Kimizuka, Tetsuya; Morita, Takuma; Sakamoto, Shuichi; Tsukamoto, Shin-ichi

    2012-01-01

    To identify novel glycine transporter 1(GlyT1) inhibitors with greater selectivity relative to GlyT2 and improved aqueous solubility, we synthesized a series of 4H-1,2,4-triazole derivatives with heteroaromatic rings at the 4-position and investigated their structure-activity relationships. Replacement of the 2-fluorophenyl group of lead compound 5 with various aromatic groups led to the identification of 5-(3-biphenyl-4-yl-5-ethyl-4H-1,2,4-triazol-4-yl)isoquinoline (15) with 38-fold selectivity between GlyT1 and GlyT2. 15 also showed improved aqueous solubility and in vivo efficacy on (+)-HA966-induced hyperlocomotion in mice over the lead compound.

  15. New 1,2,4-triazole-based azo-azomethine dyes. Part II: synthesis, characterization, electrochemical properties and computational studies.

    PubMed

    Khanmohammadi, Hamid; Erfantalab, Malihe; Bayat, Atena; Babaei, Ali; Sohrabi, Masoud

    2012-11-01

    A new series of monoiminated 1,2,4-triazole-based azo-azomethine dyes have been synthesized via condensation reaction of 4-amino-3-methyl-5-mercapto-1,2,4-triazole with various substituted azo-coupled salicylaldehyde. The dyes have been characterized by using FT-IR, UV-Vis and (1)H NMR spectroscopic methods as well as elemental analysis. The electrochemical behavior of the dyes has been investigated by cyclic voltammetry in DMSO at five different scan rates. Solvatochromic behavior of the dyes has been also investigated in four organic solvents with different polarities. Furthermore, the (1)H chemical shielding of the dyes were studied by the gauge independent atomic orbital (GIAO) method at the level of density functional theory (DFT). PMID:22902931

  16. Preparation and characterization of glycidyl methacrylate grafted 4-amino-1,2,4-triazole modified nonwoven fiber adsorbent for environmental application

    NASA Astrophysics Data System (ADS)

    Kavaklı, Cengiz; Akkaş Kavaklı, Pınar; Güven, Olgun

    2014-01-01

    A novel 4-amino-1,2,4-triazole (ATZ) containing nonwoven fiber was prepared by means of radiation induced graft polymerization. For this purpose, glycidyl methacrylate (GMA) was grafted onto polyethylene coated polypropylene nonwoven fibers (NWF) in emulsion medium by using radiation induced graft polymerization. Grafting conditions were optimized and epoxy groups of grafted GMA were then modified with ATZ. Optimum conditions for modification were conducted in different solvents i.e. water and dioxane/water mixture at different amino triazole concentrations (5%, 10%, 20% (w/w)). Maximum modification was obtained in 10% (w/w) ATZ solution in dioxane/water mixture as a solvent at 80 °C. Prepared nonwoven fibers were characterized by FTIR and thermal analysis techniques.

  17. Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

    PubMed Central

    Ötvös, Sándor B; Georgiádes, Ádám; Mándity, István M; Kiss, Lóránd

    2013-01-01

    Summary The preparation of novel multi-substituted 1,2,3-triazole-modified β-aminocyclohexanecarboxylic acid derivatives in a simple and efficient continuous-flow procedure is reported. The 1,3-dipolar cycloaddition reactions were performed with copper powder as a readily accessible Cu(I) source. Initially, high reaction rates were achieved under high-pressure/high-temperature conditions. Subsequently, the reaction temperature was lowered to room temperature by the joint use of both basic and acidic additives to improve the safety of the synthesis, as azides were to be handled as unstable reactants. Scale-up experiments were also performed, which led to the achievement of gram-scale production in a safe and straightforward way. The obtained 1,2,3-triazole-substituted β-aminocyclohexanecarboxylates can be regarded as interesting precursors for drugs with possible biological effects. PMID:23946850

  18. Biodegradation of IMX-101 explosive formulation constituents: 2,4-dinitroanisole (DNAN), 3-nitro-1,2,4-triazol-5-one (NTO), and nitroguanidine.

    PubMed

    Richard, Thomas; Weidhaas, Jennifer

    2014-09-15

    Defense agencies are increasingly using insensitive munitions (IM) in place of explosives such as 2,4,6-trinitrotoluene. In this study simultaneous aerobic degradation of the IMX-101 formulation constituents 2,4-dinitroanisole (DNAN), 3-nitro-1,2,4-triazol-5-one (NTO), and nitroguanidine (NQ) was observed and degradation products were examined. Degradation products over four days of incubation included: nitrourea, 1,2-dihydro-3H-1,2,4-triazol-3-one, and 2,4-dinitrophenol. The enrichment culture maximum specific growth rate of 0.12h(-1) and half saturation constant of 288 mg L(-1) during degradation of IMX-101 as a sole nitrogen source suggest that enrichment culture growth kinetics may closely relate to those of other explosive and nitroaromatic compounds.

  19. New 1,2,4-triazole-based azo-azomethine dyes. Part II: Synthesis, characterization, electrochemical properties and computational studies

    NASA Astrophysics Data System (ADS)

    Khanmohammadi, Hamid; Erfantalab, Malihe; Bayat, Atena; Babaei, Ali; Sohrabi, Masoud

    2012-11-01

    A new series of monoiminated 1,2,4-triazole-based azo-azomethine dyes have been synthesized via condensation reaction of 4-amino-3-methyl-5-mercapto-1,2,4-triazole with various substituted azo-coupled salicylaldehyde. The dyes have been characterized by using FT-IR, UV-Vis and 1H NMR spectroscopic methods as well as elemental analysis. The electrochemical behavior of the dyes has been investigated by cyclic voltammetry in DMSO at five different scan rates. Solvatochromic behavior of the dyes has been also investigated in four organic solvents with different polarities. Furthermore, the 1H chemical shielding of the dyes were studied by the gauge independent atomic orbital (GIAO) method at the level of density functional theory (DFT).

  20. Design, Synthesis and Structure-Activity Relationships of Novel Chalcone-1,2,3-triazole-azole Derivates as Antiproliferative Agents.

    PubMed

    Zhang, Sai-Yang; Fu, Dong-Jun; Yue, Xiao-Xin; Liu, Ying-Chao; Song, Jian; Sun, Hui-Hui; Liu, Hong-Min; Zhang, Yan-Bing

    2016-01-01

    A series of novel chalcone-1,2,3-triazole-azole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (SK-N-SH, EC-109 and MGC-803). Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Particularly, compound I-21 showed the most excellent antiproliferative activity with an IC50 value of 1.52 μM against SK-N-SH cancer cells. Further mechanism studies revealed that compound I-21 induced morphological changes of SK-N-SH cancer cells possibly by inducing apoptosis. Novel chalcone-1,2,3-triazole-azole derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating neuroblastoma. PMID:27213317

  1. Design, Synthesis and Structure-Activity Relationships of Novel Chalcone-1,2,3-triazole-azole Derivates as Antiproliferative Agents.

    PubMed

    Zhang, Sai-Yang; Fu, Dong-Jun; Yue, Xiao-Xin; Liu, Ying-Chao; Song, Jian; Sun, Hui-Hui; Liu, Hong-Min; Zhang, Yan-Bing

    2016-05-19

    A series of novel chalcone-1,2,3-triazole-azole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (SK-N-SH, EC-109 and MGC-803). Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Particularly, compound I-21 showed the most excellent antiproliferative activity with an IC50 value of 1.52 μM against SK-N-SH cancer cells. Further mechanism studies revealed that compound I-21 induced morphological changes of SK-N-SH cancer cells possibly by inducing apoptosis. Novel chalcone-1,2,3-triazole-azole derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating neuroblastoma.

  2. The 1,2,3-triazole derivative KP-A021 suppresses osteoclast differentiation and function by inhibiting RANKL-mediated MEK-ERK signaling pathway

    PubMed Central

    Ihn, Hye Jung; Lee, Doohyun; Lee, Taeho; Shin, Hong-In; Bae, Yong Chul; Kim, Sang-Hyun

    2015-01-01

    The triazole family of compounds has been implicated in modulating various biological processes such as inflammation, tumorigenesis, and infection. To our knowledge, this is the first study to demonstrate the effects of 1,2,3-triazole substituted biarylacrylonitrile compounds, including KP-A021, on the differentiation and function of osteoclasts. KP-A021 and its triazole derivatives, at a concentration that does not cause a cytotoxic response in bone marrow macrophages (BMMs), significantly inhibited osteoclast differentiation induced by receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) as assessed by tartrate-resistant acid phosphatase (TRAP) staining. KP-A021 also dramatically inhibited the expression of marker genes associated with osteoclast differentiation, such as TRAP, cathepsin K (Cat K), dendritic cell-specific transmembrane protein (DC-STAMP), and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1). Furthermore, KP-A021 inhibited actin ring formation in osteoclasts as well as resorption pit formation induced by osteoclasts. Analysis of the signaling pathway for KP-A021 indicated that this triazole compound inhibited the RANKL-induced activation of extracellular signal-regulated kinase (ERK) and its upstream signaling molecule, mitogen-activated protein kinase kinase1/2 (MEK1/2). Taken together, these results demonstrate that KP-A021 has an inhibitory effect on the differentiation and function of osteoclasts via modulation of the RANKL-induced activation of the MEK-ERK pathway. PMID:25769316

  3. Optimization of the anti-cancer activity of phosphatidylinositol-3 kinase pathway inhibitor PITENIN-1: switching a thiourea with 1,2,3-triazole

    PubMed Central

    Kommagalla, Yadagiri; Cornea, Sinziana; Riehle, Robert; Torchilin, Vladimir; Degterev, Alexei; Ramana, Chepuri V.

    2014-01-01

    We previously reported encouraging in vitro and in vivoanti-cancer activity of N-((3-chloro-2-hydroxy-5-nitrophenyl)carbamothioyl)benzamide (termed PITENIN-1). In the current work, we describe the structure-activity relationship study of PIT-1 series, based on the replacement of central thiourea unit with a 1,2,3-triazole, which leads to increased liver microsomal stability, drug likeness and toxicity towards cancer cells. PMID:25505943

  4. Synthesis and biological evaluation of 3-biphenyl-4-yl-4-phenyl-4H-1,2,4-triazoles as novel glycine transporter 1 inhibitors.

    PubMed

    Sugane, Takashi; Tobe, Takahiko; Hamaguchi, Wataru; Shimada, Itsuro; Maeno, Kyoichi; Miyata, Junji; Suzuki, Takeshi; Kimizuka, Tetsuya; Kohara, Atsuyuki; Morita, Takuma; Doihara, Hitoshi; Saita, Kyouko; Aota, Masaki; Furutani, Masako; Shimada, Yoshiaki; Hamada, Noritaka; Sakamoto, Shuichi; Tsukamoto, Shin-ichi

    2011-01-13

    We describe the preparation and evaluation of a novel series of glycine transporter 1 (GlyT1) inhibitors derived from a high-throughput screening hit. The SAR studies resulted in the discovery of 3-biphenyl-4-yl-4-(2-fluorophenyl)-5-isopropyl-4H-1,2,4-triazole (6p). A pharmacokinetic study was also conducted and revealed that 6p had excellent oral bioavailability and ameliorated learning impairment in passive avoidance tasks in mice.

  5. 3-Methyl­sulfanyl-5-phenyl-4H-1,2,4-triazol-4-amine–water (6/1)

    PubMed Central

    Wu, Deng-Ze; Liu, Miao-Chang; Wu, Hua-Yue; Huang, Xiao-Bo; Li, Jian-Jun

    2009-01-01

    In the title compound, 6C9H10N4S·H2O, the dihedral angle between the five-membered triazole ring and the phenyl ring is 44.33 (16)°. The solvent water molecule is disordered about a special position with symmetry and its occupancy cannot be greater than 0.1667. The crystal structure is stabilized by inter­molecular N—H⋯N and C–H⋯N hydrogen bonds. PMID:21582420

  6. One pot Click chemistry: A three component reaction for the synthesis of 2-mercaptobenzimidazole linked coumarinyl triazoles as anti-tubercular agents.

    PubMed

    Anand, Ashish; Kulkarni, Manohar V; Joshi, Shrinivas D; Dixit, Sheshagiri R

    2016-10-01

    2-Propargylthiobenzimidazole 1, 4-bromomethyl coumarins/1-aza-coumarins 2/3 and sodium azide have been reacted in one pot under Click chemistry conditions to give exclusively 1,4-disubstituted triazoles 5a-n. Anti-tubercular assays against M. tuberculosis (H37Rv) coupled with in silico molecular docking studies indicated that dimethyl substituents 5c and 5d showed promising activity with higher C-score values. PMID:27595420

  7. Prevalence and mechanism of triazole resistance in Aspergillus fumigatus in a referral chest hospital in Delhi, India and an update of the situation in Asia

    PubMed Central

    Chowdhary, Anuradha; Sharma, Cheshta; Kathuria, Shallu; Hagen, Ferry; Meis, Jacques F.

    2015-01-01

    Aspergillus fumigatus causes varied clinical syndromes ranging from colonization to deep infections. The mainstay of therapy of Aspergillus diseases is triazoles but several studies globally highlighted variable prevalence of triazole resistance, which hampers the management of aspergillosis. We studied the prevalence of resistance in clinical A. fumigatus isolates during 4 years in a referral Chest Hospital in Delhi, India and reviewed the scenario in Asia and the Middle East. Aspergillus species (n = 2117) were screened with selective plates for azole resistance. The isolates included 45.4% A. flavus, followed by 32.4% A. fumigatus, 15.6% Aspergillus species and 6.6% A. terreus. Azole resistance was found in only 12 (1.7%) A. fumigatus isolates. These triazole resistant A. fumigatus (TRAF) isolates were subjected to (a) calmodulin and β tubulin gene sequencing (b) in vitro antifungal susceptibility testing against triazoles using CLSI M38-A2 (c) sequencing of cyp51A gene and real-time PCR assay for detection of mutations and (d) microsatellite typing of the resistant isolates. TRAF harbored TR34/L98H mutation in 10 (83.3%) isolates with a pan-azole resistant phenotype. Among the remaining two TRAF isolates, one had G54E and the other had three non-synonymous point mutations. The majority of patients were diagnosed as invasive aspergillosis followed by allergic bronchopulmonary aspergillosis and chronic pulmonary aspergillosis. The Indian TR34/L98H isolates had a unique genotype and were distinct from the Chinese, Middle East, and European TR34/L98H strains. This resistance mechanism has been linked to the use of fungicide azoles in agricultural practices in Europe as it has been mainly reported from azole naïve patients. Reports published from Asia demonstrate the same environmental resistance mechanism in A. fumigatus isolates from two highly populated countries in Asia, i.e., China and India and also from the neighboring Middle East. PMID:26005442

  8. One pot Click chemistry: A three component reaction for the synthesis of 2-mercaptobenzimidazole linked coumarinyl triazoles as anti-tubercular agents.

    PubMed

    Anand, Ashish; Kulkarni, Manohar V; Joshi, Shrinivas D; Dixit, Sheshagiri R

    2016-10-01

    2-Propargylthiobenzimidazole 1, 4-bromomethyl coumarins/1-aza-coumarins 2/3 and sodium azide have been reacted in one pot under Click chemistry conditions to give exclusively 1,4-disubstituted triazoles 5a-n. Anti-tubercular assays against M. tuberculosis (H37Rv) coupled with in silico molecular docking studies indicated that dimethyl substituents 5c and 5d showed promising activity with higher C-score values.

  9. Synthesis of α-amino ketones from terminal alkynes via rhodium-catalyzed denitrogenative hydration of N-sulfonyl-1,2,3-triazoles.

    PubMed

    Miura, Tomoya; Biyajima, Tsuneaki; Fujii, Tetsuji; Murakami, Masahiro

    2012-01-11

    N-Sulfonyl-1,2,3-triazoles react with water in the presence of a rhodium catalyst to produce α-amino ketones in high yield. An intermediary α-imino rhodium(II) carbenoid undergoes insertion into the O-H bond of water. This transformation formally achieves 1,2-aminohydroxylation of terminal alkynes in a regioselective fashion when combined with the copper(I)-catalyzed 1,3-dipolar cycloaddition with N-sulfonyl azides. PMID:22129424

  10. One-dimensional coordination polymers generated from a new triazole bridging ligand and HgX2 (X = Cl, Br and I): characterization and luminescent properties.

    PubMed

    Qin, Na; Zhao, Chao-Wei; Ma, Jian-Ping; Liu, Qi-Kui; Dong, Yu-Bin

    2012-06-01

    The new 4-amino-1,2,4-triazole asymmetric bridging ligand 4-amino-5-(pyridin-3-yl)-3-[4-(pyridin-4-yl)phenyl]-4H-1,2,4-triazole (L) has been used to generate three novel isomorphic one-dimensional coordination polymers, viz. catena-poly[[tris[dichloridomercury(II)]-bis{μ(3)-4-amino-5-(pyridin-3-yl)-3-[4-(pyridin-4-yl)phenyl]-4H-1,2,4-triazole}] acetonitrile monosolvate], {[Hg(3)Cl(6)(C(18)H(14)N(6))(2)]·CH(3)CN}(n), (I), and the bromido, {[Hg(3)Br(6)(C(18)H(14)N(6))(2)]·CH(3)CN}(n), (II), and iodido, {[Hg(3)I(6)(C(18)H(14)N(6))(2)]·CH(3)CN}(n), (III), analogs. The asymmetric ligand acts as a tridentate ligand to coordinate the three different Hg(II) centers (two of which are symmetry-related). Two ligands and two symmetry-related Hg(II) centers form centrosymmetric rectangular units which are linked into one-dimensional chains via the other unique Hg atoms, which sit on mirror planes. The chains are elaborated into a three-dimensional structure via interchain hydrogen bonds. The acetonitrile solvent molecules are located in ellipsoidal cavities. The luminescent character of these three coordination complexes was investigated in the solid state.

  11. Synthesis, properties and surface self-assembly of a pentanuclear cluster based on the new π-conjugated TTF-triazole ligand

    PubMed Central

    Cui, Long; Geng, Yan-Fang; Leong, Chanel F.; Ma, Qian; D’Alessandro, Deanna M.; Deng, Ke; Zeng, Qing-Dao; Zuo, Jing-Lin

    2016-01-01

    The new π-extended redox-active ligand with both TTF and triazole units, 6-(4,5-bis(propylthio)-1,3-dithiol-2-ylidene)-1H-[1,3]dithiolo[4′,5′:4,5]benzo [1,2-d] [1–3]triazole, has been successfully prepared. Based on the versatile ligand and Cu(tta)2 precursors (tta− = 4,4,4-trifluoro-1-(thiophen-2-yl)butane-1,3-dione), a TTF-based pentanuclear CuII cluster (Cu5(tta)4(TTFN3)6) is synthesized and structurally characterized. Their absorption and electrochemical properties are investigated. Antiferromagnetic couplings are operative between metal ion centers bridged by triazoles in the complex. The self-assembled structure of the cluster complex on a highly oriented pyrolytic graphite (HOPG) surface was observed using scanning tunneling microscopy and density functional theory (DFT) calculations have been performed to provide insight into the formation mechanism. The introduction of the redox-active TTF unit into the cluster complexes with interesting magnetic properties renders them promising candidates for new multifunctional materials. PMID:27150720

  12. Heterometallic [MnPtn(L)2n](x+) Macrocycles from Dichloromethane-Derived Bis-2-pyridyl-1,2,3-triazole Ligands.

    PubMed

    Preston, Dan; Tucker, Robert A J; Garden, Anna L; Crowley, James D

    2016-09-01

    There is continued interest in the assembly of heterometallic metallosupramolecular assemblies due to the potential for new structural types and/or interesting chemical and physical properties. Two novel methylene-linked bis-2-pyridyl-1,2,3-triazole ligands (1a, 1b) were synthesized through CuAAC "click" chemistry between dichloromethane (DCM), sodium azide, and the appropriate ethynylpyridine, giving the shortest possible "regular" bis-pyridyl-1,2,3-triazole. The first example of bis-coordination of two 2-pyridyl-1,2,3-triazoles (Rpytri) around one Pt(II) center is reported, giving exclusive formation of head-to-tail [Pt(Rpytri)2](2+) complexes with vacant binding sites suitable for complexation with other metals and the formation of heterometallic assemblies. The concentration-dependent formation of an equilibrium mixture of a heterometallic [Pd2Pt2(L)4](8+) [4 + 4] square and [Pd3Pt3(L)6](12+) [6 + 6] hexagon was observed, and at lower concentrations ([reactants] = 1.5 mM) hexamer formation was negligible. The [Pt(L)2](2+) building block could also be utilized in the synthesis of a concentration-independent [Cu2Pt2(L)4](6+) metallomacrocyle. These compounds were characterized with (1)H, (13)C, and (1)H DOSY NMR spectroscopies, elemental analysis, mass spectrometry, and in some cases X-ray crystallography. PMID:27537620

  13. Synthesis, properties and surface self-assembly of a pentanuclear cluster based on the new π-conjugated TTF-triazole ligand

    NASA Astrophysics Data System (ADS)

    Cui, Long; Geng, Yan-Fang; Leong, Chanel F.; Ma, Qian; D'Alessandro, Deanna M.; Deng, Ke; Zeng, Qing-Dao; Zuo, Jing-Lin

    2016-05-01

    The new π-extended redox-active ligand with both TTF and triazole units, 6-(4,5-bis(propylthio)-1,3-dithiol-2-ylidene)-1H-[1,3]dithiolo[4‧,5‧:4,5]benzo [1,2-d] [1-3]triazole, has been successfully prepared. Based on the versatile ligand and Cu(tta)2 precursors (tta- = 4,4,4-trifluoro-1-(thiophen-2-yl)butane-1,3-dione), a TTF-based pentanuclear CuII cluster (Cu5(tta)4(TTFN3)6) is synthesized and structurally characterized. Their absorption and electrochemical properties are investigated. Antiferromagnetic couplings are operative between metal ion centers bridged by triazoles in the complex. The self-assembled structure of the cluster complex on a highly oriented pyrolytic graphite (HOPG) surface was observed using scanning tunneling microscopy and density functional theory (DFT) calculations have been performed to provide insight into the formation mechanism. The introduction of the redox-active TTF unit into the cluster complexes with interesting magnetic properties renders them promising candidates for new multifunctional materials.

  14. Energetic Salts Based on 3,5-Bis(dinitromethyl)-1,2,4-triazole Monoanion and Dianion: Controllable Preparation, Characterization, and High Performance.

    PubMed

    Zhang, Jiaheng; Dharavath, Srinivas; Mitchell, Lauren A; Parrish, Damon A; Shreeve, Jean'ne M

    2016-06-22

    Molecular modification of known explosives is considered to be an efficient route to design new energetic materials. A new family of energetic salts based on the 3,5-bis(dinitromethyl)-1,2,4-triazole monoanion and dianion were controllably synthesized by using 1-diamino-2,2-dinitroethene as a precursor. X-ray structure determination of monohydrazinium 3,5-bis(dinitromethyl)-1,2,4-triazolate (5) and monoammonium (6) and diammonium 3,5-bis(dinitromethyl)-1,2,4-triazolate hydrate (8·H2O) further confirmed the structures of these anions. In addition, as supported by X-ray data, in the monoanion system, the roving proton on the ring nitrogen rather than on the gem-dinitro carbon results in extensive hydrogen-bonding interactions and higher packing coefficients. Interestingly, 5 and 6 possess the highest calculated crystal densities, 1.965 and 1.957 g cm(-3) at 150 K, for hydrazinium and ammonium energetic salts, respectively. Energetic evaluation indicates that 5 (detonation velocity vD = 9086 m s(-1); detonation pressure P = 38.7 GPa) and 6 (vD, 9271 m s(-1); P = 41.0 GPa) exhibit great detonation properties, superior to those of current highly explosive benchmarks, such as 1,3,5-trinitroperhydro-1,3,5-triazine (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX). PMID:27267735

  15. Synthesis, spectral characterization and biological activity of zinc(II) complexes with 3-substituted phenyl-4-amino-5-hydrazino-1, 2, 4-triazole Schiff bases

    NASA Astrophysics Data System (ADS)

    Singh, A. K.; Pandey, O. P.; Sengupta, S. K.

    New Zn(II) complexes have been synthesized by the reactions of zinc(II) acetate with Schiff bases derived from 3-substituted phenyl-4-amino-5-hydrazino-1, 2, 4-triazole and benzaldehyde, 2-hydroxyacetophenone or 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 [ZnL(H 2O) 2], [ZnL'(OAc) 2(H 2O) 2] (L = dianionic Schiff bases derived from 3-(substituted phenyl)-4-amino-5-hydrazino-1, 2, 4-triazole and 2-hydroxyacetophenone or indoline-2,3-dione; L' = neutral Schiff bases derived from 3-(substituted phenyl)-4-amino-5-hydrazino-1, 2, 4-triazole and benzaldehyde) and they were characterized by FT-IR, 1H NMR, 13C NMR and FAB mass. All these Schiff bases and their complexes have also been screened for their antibacterial activities against Bacillus subtilis, Escherichia coli and antifungal activities against Colletotrichum falcatum, Aspergillus niger, Fusarium oxysporium and Carvularia pallescence by petriplates methods.

  16. Biotransformation and Degradation of the Insensitive Munitions Compound, 3-Nitro-1,2,4-triazol-5-one, by Soil Bacterial Communities.

    PubMed

    Krzmarzick, Mark J; Khatiwada, Raju; Olivares, Christopher I; Abrell, Leif; Sierra-Alvarez, Reyes; Chorover, Jon; Field, James A

    2015-05-01

    Insensitive munitions (IM) are a new class of explosives that are increasingly being adopted by the military. The ability of soil microbial communities to degrade IMs is relatively unknown. In this study, microbial communities from a wide range of soils were tested in microcosms for their ability to degrade the IM, 3-nitro-1,2,4-triazol-5-one (NTO). All seven soil inocula tested were able to readily reduce NTO to 3-amino-1,2,4-triazol-5-one (ATO) via 3-hydroxyamino-1,2,4-triazol-5-one (HTO), under anaerobic conditions with H2 as an electron donor. Numerous other electron donors were shown to be suitable for NTO-reducing bacteria. The addition of a small amount of yeast extract (10 mg/L) was critical to diminish lag times and increased the biotransformation rate of NTO in nearly all cases indicating yeast extract provided important nutrients for NTO-reducing bacteria. The main biotransformation product, ATO, was degradable only in aerobic conditions, as evidenced by a rise in the inorganic nitrogen species nitrite and nitrate, indicative of nitrogen-mineralization. NTO was nonbiodegradable in aerobic microcosms with all soil inocula. PMID:25839647

  17. Biotransformation and Degradation of the Insensitive Munitions Compound, 3-Nitro-1,2,4-triazol-5-one, by Soil Bacterial Communities.

    PubMed

    Krzmarzick, Mark J; Khatiwada, Raju; Olivares, Christopher I; Abrell, Leif; Sierra-Alvarez, Reyes; Chorover, Jon; Field, James A

    2015-05-01

    Insensitive munitions (IM) are a new class of explosives that are increasingly being adopted by the military. The ability of soil microbial communities to degrade IMs is relatively unknown. In this study, microbial communities from a wide range of soils were tested in microcosms for their ability to degrade the IM, 3-nitro-1,2,4-triazol-5-one (NTO). All seven soil inocula tested were able to readily reduce NTO to 3-amino-1,2,4-triazol-5-one (ATO) via 3-hydroxyamino-1,2,4-triazol-5-one (HTO), under anaerobic conditions with H2 as an electron donor. Numerous other electron donors were shown to be suitable for NTO-reducing bacteria. The addition of a small amount of yeast extract (10 mg/L) was critical to diminish lag times and increased the biotransformation rate of NTO in nearly all cases indicating yeast extract provided important nutrients for NTO-reducing bacteria. The main biotransformation product, ATO, was degradable only in aerobic conditions, as evidenced by a rise in the inorganic nitrogen species nitrite and nitrate, indicative of nitrogen-mineralization. NTO was nonbiodegradable in aerobic microcosms with all soil inocula.

  18. Pharmacophore Elucidation and Molecular Docking Studies on 5-Phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic Acid Derivatives as COX-2 Inhibitors

    PubMed Central

    Lindner, Marc; Sippl, Wolfgang; Radwan, Awwad A.

    2010-01-01

    A set of 5-phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic acid derivatives (16–32) showing anti-inflammatory activity was analyzed using a three-dimensional qualitative structure-selectivity relationship (3D QSSR) method. The CatalystHipHop approach was used to generate a pharmacophore model for cyclooxygenase-2 (COX-2) inhibitors based on a training set of 15 active inhibitors (1–15). The degree of fitting of the test set compounds (16–32) to the generated hypothetical model revealed a qualitative measure of the more or less selective COX-2 inhibition of these compounds. The results indicate that most derivatives (16, 18, 20–25, and 30–32) are able to effectively satisfy the proposed pharmacophore geometry using energy accessible conformers (Econf < 20 kcal/mol). In addition, the triazole derivatives (16–32) were docked into COX-1 and COX-2 X-ray structures, using the program GOLD. Based on the docking results it is suggested that several of these novel triazole derivatives are active COX inhibitors with a significant preference for COX-2. In principle, this work presents an interesting, comprehensive approach to theoretically predict the mode of action of compounds that showed anti-inflammatory activity in an in vivo model. PMID:21179343

  19. Carbon Dioxide Capture by a Metal-Organic Framework with Nitrogen-Rich Channels Based on Rationally Designed Triazole-Functionalized Tetraacid Organic Linker.

    PubMed

    Seth, Saona; Savitha, Govardhan; Moorthy, Jarugu Narasimha

    2015-07-20

    A semirigid tetraacid linker H4L functionalized with 1,2,3-triazole was rationally designed and synthesized to access nitrogen-rich MOFs for selective adsorption of CO2. The cadmium MOF, that is, Cd-L, obtained by the reaction of H4L with Cd(NO3)2, is found to be a 3D porous framework structure that is robust to desolvation. Crystal structure analysis reveals channels that are decorated by the triazole moieties of L. Gas adsorption studies show that Cd-L MOF permits remarkable CO2 uptake to the extent of 99 and 1000 cc/g at 1 and 30 bar, respectively, at 0 °C. While literature survey reveals that MIL-112, constructed from a 1,2,3-triazole functionalized linker, exhibits no porosity to gas adsorption due to structural flexibility, the results with Cd-L MOF described herein emphasize how rigidification of the organic linker improves gas uptake properties of the resultant MOF. PMID:26146942

  20. Energetic Salts Based on 3,5-Bis(dinitromethyl)-1,2,4-triazole Monoanion and Dianion: Controllable Preparation, Characterization, and High Performance.

    PubMed

    Zhang, Jiaheng; Dharavath, Srinivas; Mitchell, Lauren A; Parrish, Damon A; Shreeve, Jean'ne M

    2016-06-22

    Molecular modification of known explosives is considered to be an efficient route to design new energetic materials. A new family of energetic salts based on the 3,5-bis(dinitromethyl)-1,2,4-triazole monoanion and dianion were controllably synthesized by using 1-diamino-2,2-dinitroethene as a precursor. X-ray structure determination of monohydrazinium 3,5-bis(dinitromethyl)-1,2,4-triazolate (5) and monoammonium (6) and diammonium 3,5-bis(dinitromethyl)-1,2,4-triazolate hydrate (8·H2O) further confirmed the structures of these anions. In addition, as supported by X-ray data, in the monoanion system, the roving proton on the ring nitrogen rather than on the gem-dinitro carbon results in extensive hydrogen-bonding interactions and higher packing coefficients. Interestingly, 5 and 6 possess the highest calculated crystal densities, 1.965 and 1.957 g cm(-3) at 150 K, for hydrazinium and ammonium energetic salts, respectively. Energetic evaluation indicates that 5 (detonation velocity vD = 9086 m s(-1); detonation pressure P = 38.7 GPa) and 6 (vD, 9271 m s(-1); P = 41.0 GPa) exhibit great detonation properties, superior to those of current highly explosive benchmarks, such as 1,3,5-trinitroperhydro-1,3,5-triazine (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX).

  1. 21 CFR 610.60 - Container label.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Container label. 610.60 Section 610.60 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS GENERAL BIOLOGICAL PRODUCTS STANDARDS Labeling Standards § 610.60 Container label. (a) Full label....

  2. 21 CFR 225.180 - Labeling.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Labeling. 225.180 Section 225.180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR MEDICATED FEEDS Labeling § 225.180 Labeling. Labels shall...

  3. 21 CFR 225.180 - Labeling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Labeling. 225.180 Section 225.180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR MEDICATED FEEDS Labeling § 225.180 Labeling. Labels shall...

  4. 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...

  5. 40 CFR 211.108 - Sample label.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 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...

  6. 40 CFR 211.108 - Sample label.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 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...

  7. 40 CFR 211.108 - Sample label.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true 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...

  8. 9 CFR 381.132 - Labeling approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... been submitted for approval to the Food Labeling Division, Regulatory Programs, Food Safety and... request. (b) The Food Labeling Division shall permit submission for approval of only sketch labeling, as... Labeling Division, Regulatory Programs, Food Safety and Inspection Service, U.S. Department of...

  9. 9 CFR 381.132 - Labeling approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... product unless the sketch labeling of such final labeling has been submitted for approval to the Food Labeling Division, Regulatory Programs, Food Safety and Inspection Service, and approved by such division... authorized representative of the Secretary upon request. (b) The Food Labeling Division shall...

  10. 9 CFR 381.132 - Labeling approval.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... been submitted for approval to the Food Labeling Division, Regulatory Programs, Food Safety and... request. (b) The Food Labeling Division shall permit submission for approval of only sketch labeling, as... Labeling Division, Regulatory Programs, Food Safety and Inspection Service, U.S. Department of...

  11. 9 CFR 381.132 - Labeling approval.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... been submitted for approval to the Food Labeling Division, Regulatory Programs, Food Safety and... request. (b) The Food Labeling Division shall permit submission for approval of only sketch labeling, as... Labeling Division, Regulatory Programs, Food Safety and Inspection Service, U.S. Department of...

  12. 9 CFR 381.132 - Labeling approval.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... been submitted for approval to the Food Labeling Division, Regulatory Programs, Food Safety and... request. (b) The Food Labeling Division shall permit submission for approval of only sketch labeling, as... Labeling Division, Regulatory Programs, Food Safety and Inspection Service, U.S. Department of...

  13. 40 CFR 211.108 - Sample label.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 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...

  14. 21 CFR 895.25 - Labeling.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... eliminated by labeling or a change in labeling, or change in advertising if the device is a restricted device... person(s) responsible for the labeling or advertising of the device specifying: (1) The deception or risk... labeling, or change in advertising if the device is a restricted device, necessary to correct the...

  15. 16 CFR 309.17 - Labels.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... edges of the label. If you wish to change the format of this single component label, you must petition... no closer than 3/16″ (.48 cm) from the side edges of the label. If you wish to change the format of.... All labels must be capable of withstanding extremes of weather conditions for a period of at least...

  16. 16 CFR 309.17 - Labels.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... edges of the label. If you wish to change the format of this single component label, you must petition... no closer than 3/16″ (.48 cm) from the side edges of the label. If you wish to change the format of.... All labels must be capable of withstanding extremes of weather conditions for a period of at least...

  17. 16 CFR 309.17 - Labels.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... edges of the label. If you wish to change the format of this single component label, you must petition... no closer than 3/16″ (.48 cm) from the side edges of the label. If you wish to change the format of.... All labels must be capable of withstanding extremes of weather conditions for a period of at least...

  18. Exploring the Potential of (99m)Tc(CO)3-Labeled Triazolyl Peptides for Tumor Diagnosis.

    PubMed

    Gaonkar, Raghuvir H; Ganguly, Soumya; Baishya, Rinku; Dewanjee, Saikat; Sinha, Samarendu; Gupta, Amit; Ganguly, Shantanu; Debnath, Mita C

    2016-04-01

    In recent years the authors have reported on (99m)Tc(CO)3-labeled peptides that serve as carriers for biomolecules or radiopharmaceuticals to the tumors. In continuation of that work they report the synthesis of a pentapeptide (Met-Phe-Phe-Gly-His; pep-1), a hexapeptide (Met-Phe-Phe-Asp-Gly-His; pep-2), and a tetrapeptide (Asp-Gly-Arg-His; pep-3) and the attachment of 3-amino-1,2,4-triazole to the β carboxylic function of the aspartic acid unit of pep-2 and pep-3. The pharmacophores were radiolabeled in high yields with [(99m)Tc(CO)3(H2O)3](+) metal aqua ion, characterized for their stability in serum and saline, as well as in His solution, and found to be substantially stable. B16F10 cell line binding studies showed favorable uptake and internalization. In vivo behavior of the radiolabeled triazolyl peptides was assessed in mice bearing induced tumor. The (99m)Tc(CO)3-triazolyl pep-3 demonstrated rapid urinary clearance and comparatively better tumor uptake. Imaging studies showed visualization of the tumor using (99m)Tc(CO)3-triazolyl pep-3, but due to high abdominal background, low delineation occurred. Based on the results further experiments will be carried out for targeting tumor with triazolyl peptides. PMID:27093344

  19. Optimal policy for labeling training samples

    NASA Astrophysics Data System (ADS)

    Lipsky, Lester; Lopresti, Daniel; Nagy, George

    2013-01-01

    Confirming the labels of automatically classified patterns is generally faster than entering new labels or correcting incorrect labels. Most labels assigned by a classifier, even if trained only on relatively few pre-labeled patterns, are correct. Therefore the overall cost of human labeling can be decreased by interspersing labeling and classification. Given a parameterized model of the error rate as an inverse power law function of the size of the training set, the optimal splits can be computed rapidly. Projected savings in operator time are over 60% for a range of empirical error functions for hand-printed digit classification with ten different classifiers.

  20. 21 CFR 201.70 - Calcium labeling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... product is more than 3.2 grams: “Ask a doctor before use if you have 1 kidney stones a calcium-restricted... 21 Food and Drugs 4 2012-04-01 2012-04-01 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...

  1. 21 CFR 201.70 - Calcium labeling.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... product is more than 3.2 grams: “Ask a doctor before use if you have 1 kidney stones a calcium-restricted... 21 Food and Drugs 4 2013-04-01 2013-04-01 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...

  2. 21 CFR 201.70 - Calcium labeling.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... product is more than 3.2 grams: “Ask a doctor before use if you have 1 kidney stones a calcium-restricted... 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...

  3. 21 CFR 201.70 - Calcium labeling.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... product is more than 3.2 grams: “Ask a doctor before use if you have 1 kidney stones a calcium-restricted... 21 Food and Drugs 4 2014-04-01 2014-04-01 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...

  4. 21 CFR 201.70 - Calcium labeling.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... product is more than 3.2 grams: “Ask a doctor before use if you have 1 kidney stones a calcium-restricted... 21 Food and Drugs 4 2011-04-01 2011-04-01 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...

  5. Nutrition Labeling Using a Computer Program

    NASA Astrophysics Data System (ADS)

    Metzger, Lloyd E.

    The 1990 Nutrition Labeling and Education Act mandated nutritional labeling of most foods. As a result, a large portion of food analysis is performed for nutritional labeling purposes. A food labeling guide and links to the complete nutritional labeling regulations are available online at http://vm.cfsan.fda.gov/˜dms/flg-toc.html. However, interpretation of these regulations and the appropriate usage of rounding rules, available nutrient content claims, reference amounts, and serving size can be difficult.

  6. 49 CFR 172.430 - POISON label.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false POISON label. 172.430 Section 172.430... SECURITY PLANS Labeling § 172.430 POISON label. (a) Except for size and color, the POISON label must be as follows: EC02MR91.029 (b) In addition to complying with § 172.407, the background on the POISON label...

  7. 49 CFR 172.430 - POISON label.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false POISON label. 172.430 Section 172.430... SECURITY PLANS Labeling § 172.430 POISON label. (a) Except for size and color, the POISON label must be as follows: EC02MR91.029 (b) In addition to complying with § 172.407, the background on the POISON label...

  8. 49 CFR 172.430 - POISON label.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false POISON label. 172.430 Section 172.430... SECURITY PLANS Labeling § 172.430 POISON label. (a) Except for size and color, the POISON label must be as follows: EC02MR91.029 (b) In addition to complying with § 172.407, the background on the POISON label...

  9. 49 CFR 172.430 - POISON label.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false POISON label. 172.430 Section 172.430... SECURITY PLANS Labeling § 172.430 POISON label. (a) Except for size and color, the POISON label must be as follows: EC02MR91.029 (b) In addition to complying with § 172.407, the background on the POISON label...

  10. 49 CFR 172.430 - POISON label.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false POISON label. 172.430 Section 172.430... SECURITY PLANS Labeling § 172.430 POISON label. (a) Except for size and color, the POISON label must be as follows: EC02MR91.029 (b) In addition to complying with § 172.407, the background on the POISON label...

  11. Conformational behavior and tautomer selective photochemistry in low temperature matrices: the case of 5-(1H-tetrazol-1-yl)-1,2,4-triazole.

    PubMed

    Pagacz-Kostrzewa, M; Reva, I D; Bronisz, R; Giuliano, B M; Fausto, R; Wierzejewska, M

    2011-06-01

    The conformational properties and the photolysis behavior of one of the simplest N-C bonded bicyclic azoles, 5-(1H-tetrazol-1-yl)-1,2,4-triazole (T), were studied in argon and xenon matrices by infrared spectroscopy. Analysis of the experimental results was supported by extensive theoretical calculations carried out at the B3LYP/6-311++G(2d,2p) level of approximation. Out of the eight T minima located on the potential energy surface, the three most stable species were detected in low temperature matrices, namely, 5-(1H-tetrazol-1-yl)-1H-1,2,4-triazole (T1) and two conformers of 5-(1H-tetrazol-1-yl)-2H-1,2,4-triazole (T2a and T2b). With increase of the substrate temperature either during deposition of the matrices or during annealing the T2b → T2a conversion took place, in agreement with the predicted low energy barrier for this transformation (5.38 kJ mol(-1)). Both broad band and narrow band laser UV irradiations of T isolated in Xe and Ar matrices induce unimolecular decomposition involving cleavage of the tetrazole ring of T1 and T2a (T2b) that leads to the production of 1H-1,2,4-triazol-5-yl carbodiimide (P1) and 1H-1,2,4-triazol-3-yl carbodiimide (P2), respectively. When the laser is used, in addition to the main P1 and P2 photoproducts, several minor products could be successfully identified in the matrices: N-cyanocarbodiimide HNCNCN (detected for the first time) associated with nitrilimine HNNCH and HCN. An interesting phenomenon of tautomer-selective photochemistry was observed for the matrix-isolated compound. It could be explained by the different LUMO-HOMO energy gaps estimated for T1, T2a, and T2b, connected with different threshold energies necessary to start the photolysis of T1 and T2a (T2b).

  12. Metrics for Labeled Markov Systems

    NASA Technical Reports Server (NTRS)

    Desharnais, Josee; Jagadeesan, Radha; Gupta, Vineet; Panangaden, Prakash

    1999-01-01

    Partial Labeled Markov Chains are simultaneously generalizations of process algebra and of traditional Markov chains. They provide a foundation for interacting discrete probabilistic systems, the interaction being synchronization on labels as in process algebra. Existing notions of process equivalence are too sensitive to the exact probabilities of various transitions. This paper addresses contextual reasoning principles for reasoning about more robust notions of "approximate" equivalence between concurrent interacting probabilistic systems. The present results indicate that:We develop a family of metrics between partial labeled Markov chains to formalize the notion of distance between processes. We show that processes at distance zero are bisimilar. We describe a decision procedure to compute the distance between two processes. We show that reasoning about approximate equivalence can be done compositionally by showing that process combinators do not increase distance. We introduce an asymptotic metric to capture asymptotic properties of Markov chains; and show that parallel composition does not increase asymptotic distance.

  13. Positron emitter labeled enzyme inhibitors

    SciTech Connect

    Fowler, J.S.; MacGregor, R.R.; Wolf, A.P.; Langstrom, B.

    1990-04-03

    This invention involves a new strategy for imaging and mapping enzyme activity in the living human and animal body using positron emitter-labeled suicide enzyme inactivators or inhibitors which become covalently bound to the enzyme as a result of enzymatic catalysis. Two such suicide inactivators for monoamine oxidase have been labeled with carbon-11 and used to map the enzyme subtypes in the living human and animal body using PET. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography.

  14. Positron emitter labeled enzyme inhibitors

    DOEpatents

    Fowler, J.S.; MacGregor, R.R.; Wolf, A.P.

    1987-05-22

    This invention involved a new strategy for imaging and mapping enzyme activity in the living human and animal body using positron emitter-labeled suicide enzyme inactivators or inhibitors which become covalently bound to the enzyme as a result of enzymatic catalysis. Two such suicide in activators for monoamine oxidase have been labeled with carbon-11 and used to map the enzyme subtypes in the living human and animal body using PET. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography. 2 figs.

  15. Positron emitter labeled enzyme inhibitors

    DOEpatents

    Fowler, Joanna S.; MacGregor, Robert R.; Wolf, Alfred P.; Langstrom, Bengt

    1990-01-01

    This invention involves a new strategy for imaging and mapping enzyme activity in the living human and animal body using positron emitter-labeled suicide enzyme inactivators or inhibitors which become covalently bound to the enzyme as a result of enzymatic catalysis. Two such suicide inactivators for monoamine oxidase have been labeled with carbon-11 and used to map the enzyme subtypes in the living human and animal body using PET. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography.

  16. Denture labeling: A new approach.

    PubMed

    Bansal, Pardeep K; Sharma, Akshey; Bhanot, Rajesh

    2011-04-01

    The need for denture labeling is important for forensic and social reasons in case patients need to be identified individually. The importance of denture marking has long been acknowledged by the dental profession. Over the years, various denture marking systems have been reported in the literature, but none till date fulfills all the prescribed ADA specifications. A simple, easy, inexpensive procedure for marking accurate identification marks on dentures with a lead foil is described here. The label caring the patient information is incorporated in the acrylic resin during the denture processing.

  17. Synthetic mucin fragments. Benzyl O-(2-acetamido-2-deoxy-alpha-D-glucopyranosyl)-(1----3)-O-beta-D- galactopyranosyl-(1----3)-O-[(2-acetamido-2-deoxy-beta-D-glucopyran osy l)- (1----6)]-2-acetamido-2-deoxy-alpha-D-galactopyranoside and benzyl O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1----3)-O-beta-D- galactopyranosyl-(1----3)-O-[beta-D-galactopyranosyl-(1----6)]-2-ac eta mido- 2-deoxy-alpha-D-galactopyranoside.

    PubMed

    Thomas, R L; Abbas, S A; Matta, K L

    1988-12-01

    Treatment of benzyl 2-acetamido-2-deoxy-alpha-D-galactopyranoside with 4-methoxybenzaldehyde dimethyl acetal in N,N-dimethylformamide in the presence of 4-toluenesulfonic acid afforded the 4,6-O-(4-methoxybenzylidene) acetal, which was glycosylated with 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide (1). Reductive ring-opening of the acetal group provided a 6-O-(4-methoxybenzyl) derivative (4) which was glycosylated with 1, followed by removal of the 4-methoxybenzyl ether group, to give benzyl 2-acetamido-2-deoxy-3,4-di-O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyran osyl)- alpha-D-galactopyranoside (7). The disaccharide diol 5, obtained from 4, and benzyl O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl-(1----3) -O- (2,4,6-tri-O-acetyl-beta-D-galactopyranosyl)-(1----3)-2-acetamido-2-deox y- alpha-D-galactopyranoside (11) were similarly glycosylated with 1 to afford a trisaccharide derivative 9 and a tetrasaccharide derivative 14, respectively. Diol 11 was also condensed with 2-methyl-(3,4,6-tri-O-acetyl-1,2-di-deoxy-alpha-D-glucopyrano)-[2, 1-d]-2- oxazoline to give a tetrasaccharide derivative 16. O-Deacetylation of trisaccharides 7 and 9, and tetrasaccharides 14 and 16 furnished trisaccharides 8 and 10, and the title tetrasaccharides 15 and 17, respectively. The structures of compounds 8, 10, 15, and 17 were established by 13C-n.m.r. spectroscopy.

  18. 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

  19. Rock Music Gets a Label.

    ERIC Educational Resources Information Center

    Cutietta, Robert

    1986-01-01

    A group called Parents Music Resource Center (PMRC) has captured the media spotlight with a proposal to have warning labels placed on music albums containing sexually explicit or violent lyrics. Major record companies have agreed to a version of the PMRC's demands for a one-year trial period, beginning in 1986. (RM)

  20. Nutrition Marketing on Food Labels

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutrition marketing may influence purchasing behavior and thereby be a factor in the obesity epidemic. Very little peer-reviewed research has been published which investigates the relationship between nutrition marketing on food labels and consumer behavior. The purpose of this paper was to give an ...

  1. Revisiting Labels: "Hearing" or Not?

    ERIC Educational Resources Information Center

    Rhoades, Ellen A.

    2010-01-01

    This position paper briefly presents evidence-based findings pertaining to the language of labels for people with hearing loss that relate to stigma, expectation levels, stereotypes, and self-fulfilling prophecies. These constructs are important for auditory-based practitioners, administrators, policymakers, students, families, and persons with…

  2. Psychological effectiveness of carbon labelling

    NASA Astrophysics Data System (ADS)

    Beattie, Geoffrey

    2012-04-01

    Despite the decision by supermarket-giant Tesco to delay its plan to add carbon-footprint information onto all of its 70,000 products, carbon labelling, if carefully designed, could yet change consumer behaviour. However, it requires a new type of thinking about consumers and much additional work.

  3. The Labelling Approach to Deviance.

    ERIC Educational Resources Information Center

    Rains, Prudence M.; Kitsuse, John L.; Duster, Troy; Freidson, Eliot

    2003-01-01

    This reprint of one chapter from the 1975 text, "Issues in the Classification of Children" by Nicholas Hobbs and others, addresses the theoretical, methodological, and empirical issues involved in the "labeling" approach to the sociology of deviance. It examines the social process of classification, the use of classification in social agencies,…

  4. Synthesis and Antitumor Activity of 1,5-Disubstituted 1,2,4-Triazoles as Cis-Restricted Combretastatin Analogues

    PubMed Central

    Romagnoli, Romeo; Baraldi, Pier Giovanni; Cruz-Lopez, Olga; Lopez Cara, Carlota; Carrion, Maria Dora; Brancale, Andrea; Hamel, Ernest; Chen, Longchuan; Bortolozzi, Roberta; Basso, Giuseppe; Viola, Giampietro

    2010-01-01

    A series of 1-aryl-5-(3′,4′,5′-trimethoxyphenyl) derivatives and their related 1-(3′,4′,5′-trimethoxyphenyl)-5-aryl-1,2,4-triazoles, designed as cis-restricted combretastatin analogues, were synthesized and evaluated for antiproliferative activity, inhibitory effects on tubulin polymerization, cell cycle effects, and apoptosis induction. Their activity was greater than, or comparable with, that of the reference compound CA-4. Flow cytometry studies showed that HeLa and Jurkat cells treated with the most active compounds 4l and 4o were arrested in the G2/M phase of the cell cycle in a concentration dependent manner. This effect was accompanied by apoptosis of the cells, mitochondrial depolarization, generation of reactive oxygen species, activation of caspase-3, and PARP cleavage. Compound 4l was also shown to have potential antivascular activity, since it induced endothelial cell shape change in vitro and disrupted the sprouting of endothelial cells in the chick aortic ring assay. PMID:20420439

  5. In-vitro activity of the new triazole D0870 compared with amphotericin B and itraconazole against Aspergillus spp.

    PubMed

    Moore, C B; Law, D; Denning, D W

    1993-12-01

    The in-vitro activity of D0870, a new triazole, was compared with amphotericin B (AMP B) and itraconazole (ITZ) against 40 Aspergillus isolates, which included 25 isolates of Aspergillus fumigatus, using a broth macro-dilution method at 37 degrees C. Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) (killing of > or = 98%) were measured. For 40 isolates, geometric mean (GM) MIC values and ranges were D0870 10.55 and 2-32, ITZ 2.26 and 0.5-64, AMP B 2.42 and 1-64 mg/L. Differences in susceptibilities between species were apparent with Aspergillus flavus (n = 5) being the most susceptible to D0870 (GM 2.64, range 2-8 mg/L). MFC values were within one dilution of the MIC value for 90% of isolates (D0870 and ITZ) and 95% of isolates (AMP B). In reproducibility studies, seven, eight and four of eight isolates retested gave MIC results within one dilution for D0870, AMP B, and ITZ, respectively. Therefore, in-vitro mould testing with D0870 is feasible and reproducible with clear MIC and MFC end-points. D0870 is active against most Aspergillus spp., but at higher concentrations than either ITZ or AMP B. PMID:8144422

  6. Spin density in a triazole-nitronyl-nitroxide radical presenting linear ferromagnetic interactions: role of hydrogen bonding

    NASA Astrophysics Data System (ADS)

    Gillon, Béatrice; Aebersold, Michael A.; Kahn, Olivier; Pardi, Luca; Delley, Bernard

    1999-11-01

    The compound 2-{3-[4-methyl-1,2,4-triazolyl]}-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide, abbreviated as Metrz-Nit, crystallizes in the non-centrosymmetric space group P2 12 12 1. The investigation of the magnetic properties has revealed the occurrence of intermolecular ferromagnetic interactions. The crystal structure has been refined by neutron diffraction at 11 K. The spin density distribution has been determined from polarized neutron diffraction experiments carried out at 1.5 K under a magnetic field of 5 T. As expected, the main contributions of the spin distribution have been observed in the 2p π orbitals of the nitrogen and oxygen atoms of the two NO groups, and a significant negative spin population has been detected on the sp 2 carbon atom of the nitronyl nitroxide moiety. The spin distribution is slightly dissymmetrical, so that the sp 3 carbon atoms in α-position of the nitro nitrogen atoms carry spin populations of opposite signs. Concerning the triazole ring, the main spin population, of negative sign, has been found on the nitrogen atom occupying the 3-position. The carbon atom of the methyl group attached to the 4-position has been also found to carry a significant negative spin population. The spin populations on the hydrogen atoms have been determined. These experimental data have been compared to the results of LSD calculations performed on an isolated molecule. The role of intermolecular interactions in the spin distribution has been discussed.

  7. Incorporation of Bulky and Cationic Cyclam-Triazole Moieties into Marimastat Can Generate Potent MMP Inhibitory Activity without Inducing Cytotoxicity

    PubMed Central

    Yu, Mingfeng; Lim, Ngee H; Ellis, Samantha; Nagase, Hideaki; Triccas, James A; Rutledge, Peter J; Todd, Matthew H

    2013-01-01

    The synthesis and matrix metalloproteinase (MMP) inhibitory activity of a cyclam–marimastat conjugate and its metal complexes are described. The conjugate, synthesized with a copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (“click” reaction), contains two zinc-binding groups (ZBGs). The metal complexation behavior with copper(II) and zinc(II) was investigated using UV/Vis spectrophotometry and 1H NMR spectroscopy, respectively, demonstrating that the first equivalent of the metal ion was chelated by the cyclam-triazole moiety rather than the hydroxamic acid site. Thus, the corresponding mononuclear metal–cyclam complexes were successfully prepared with one equivalent of the metal salt. Both the cyclam–marimastat conjugate and its metal complexes exhibited slightly reduced potency against MMP-1, but essentially identical inhibitory activity against MMP-3. The conjugate and its metal complexes displayed little or no cytotoxicity, further supporting their potential suitability for imaging MMP localization and activity. To the best of our knowledge, this is the first report that describes the incorporation of metal complexes into an MMP inhibitor without influencing the preexisting ZBG, and the first report of the evaluation of structures containing more than one ZBG as MMP inhibitors. PMID:24551546

  8. Evaluation of CADASTER QSAR models for the aquatic toxicity of (benzo)triazoles and prioritisation by consensus prediction.

    PubMed

    Cassani, Stefano; Kovarich, Simona; Papa, Ester; Roy, Partha Pratim; Rahmberg, Magnus; Nilsson, Sara; Sahlin, Ullrika; Jeliazkova, Nina; Kochev, Nikolay; Pukalov, Ognyan; Tetko, Igor; Brandmaier, Stefan; Durjava, Mojca Kos; Kolar, Boris; Peijnenburg, Willie; Gramatica, Paola

    2013-03-01

    QSAR regression models of the toxicity of triazoles and benzotriazoles ([B]TAZs) to an alga (Pseudokirchneriella subcapitata), Daphnia magna and a fish (Onchorhynchus mykiss), were developed by five partners in the FP7-EU Project, CADASTER. The models were developed by different methods - Ordinary Least Squares (OLS), Partial Least Squares (PLS), Bayesian regularised regression and Associative Neural Network (ASNN) - by using various molecular descriptors (DRAGON, PaDEL-Descriptor and QSPR-THESAURUS web). In addition, different procedures were used for variable selection, validation and applicability domain inspection. The predictions of the models developed, as well as those obtained in a consensus approach by averaging the data predicted from each model, were compared with the results of experimental tests that were performed by two CADASTER partners. The individual and consensus models were able to correctly predict the toxicity classes of the chemicals tested in the CADASTER project, confirming the utility of the QSAR approach. The models were also used for the prediction of aquatic toxicity of over 300 (B)TAZs, many of which are included in the REACH pre-registration list, and were without experimental data. This highlights the importance of QSAR models for the screening and prioritisation of untested chemicals, in order to reduce and focus experimental testing.

  9. Spirooxindole-derived morpholine-fused-1,2,3-triazoles: Design, synthesis, cytotoxicity and apoptosis inducing studies.

    PubMed

    Senwar, Kishna Ram; Sharma, Pankaj; Reddy, T Srinivasa; Jeengar, Manish Kumar; Nayak, V Lakshma; Naidu, V G M; Kamal, Ahmed; Shankaraiah, Nagula

    2015-09-18

    A series of new spirooxindole-derived morpholine-fused-1,2,3-triazole derivatives has been synthesized from isatin spiro-epoxides. The protocol involves regiospecific isatin-epoxide ring opening with azide nucleophile followed by sequential O-propargylation, and intramolecular 1,3-dipolar cycloaddition reaction. These compounds have been evaluated for their antiproliferative activity against selected human tumor cell lines of lung (A549), breast (MCF-7), cervical (HeLa), and prostate (DU-145). Among the tested compounds, 6i, 6n and 6p showed potent growth inhibition against A549 cell line with IC50 values in the range of 1.87-4.36 μM, which are comparable to reference standards doxorubicin and 5-flourouracil. The compounds 6i and 6p treated A549 cells displayed typical apoptotic morphological features such as cell shrinkage, nuclear condensation, fragmentation, and decreased migration potential. Flow-cytometry analysis revealed that the compounds arrested the cells in G2/M phase of cell cycle. Hoechst and acridine orange/ethidium bromide staining studies also showed that the cell proliferation was inhibited through induction of apoptosis. Moreover, the compounds treatment led to collapse of the mitochondrial membrane potential (DΨm) and increased levels of reactive oxygen species (ROS) were noted in A549 cells. PMID:26301558

  10. Removal of ethylenthiourea and 1,2,4-triazole pesticide metabolites from water by adsorption in commercial activated carbons.

    PubMed

    Amorim, Camila C; Bottrel, Sue Ellen C; Costa, Elizângela P; Teixeira, Ana Paula C; Leão, Mônica M D

    2013-01-01

    This study evaluated the adsorption capacity of ethylenthiourea (ETU) and 1H-1,2,4-triazole (1,2,4-T) for two commercial activated carbons: charcoal-powdered activated carbon (CPAC) and bovine bone-powdered activated carbon (BPAC). The tests were conducted at a bench scale, with ETU and 1,2,4-T diluted in water, for isotherm and adsorption kinetic studies. The removal of the compounds was accompanied by a total organic carbon (TOC) analysis and ultraviolet (UV) reduction analysis. The coals were characterized by their surface area using nitrogen adsorption/desorption, by a scanning electron microscopy and energy-dispersive X-ray spectroscopy (SEM/EDS) and by a zero charge point analysis (pHpcz). The results showed that adsorption kinetics followed a pseudo-second-order model for both coals, and the adsorption isotherms for CPAC and BPAC were adjusted to the Langmuir and Freundlich isotherms, respectively. The CPAC removed approximately 77% of the ETU and 76% of the 1,2,4-T. The BPAC was ineffective at removing the contaminants. PMID:23356339

  11. From BACE1 Inhibitor to Multifunctionality of Tryptoline and Tryptamine Triazole Derivatives for Alzheimer’s Disease

    PubMed Central

    Jiaranaikulwanitch, Jutamas; Govitrapong, Piyarat; Fokin, Valery V.; Vajragupta, Opa

    2013-01-01

    Efforts to discover new drugs for Alzheimer’s disease emphasizing multiple targets was conducted seeking to inhibit amyloid oligomer formation and to prevent radical formation. The tryptoline and tryptamine cores of BACE1 inhibitors previously identified by virtual screening were modified in silico for additional modes of action. These core structures were readily linked to different side chains using 1,2,3-triazole rings as bridges by copper catalyzed azide-alkyne cycloaddition reactions. Three compounds among the sixteen designed compounds exerted multifunctional activities including β-secretase inhibitory action, anti-amyloid aggregation, metal chelating and antioxidant effects at micromolar levels. The neuroprotective effects of the multifunctional compounds 6h, 12c and 12h on Aβ1–42 induced neuronal cell death at 1 μM were significantly greater than those of the potent single target compound, BACE1 inhibitor IV and were comparable to curcumin. The observed synergistic effect resulting from the reduction of the Aβ1–42 neurotoxicity cascade substantiates the validity of our multifunctional strategy in drug discovery for Alzheimer’s disease. PMID:22781443

  12. Breakpoints for antifungal agents: an update from EUCAST focussing on echinocandins against Candida spp. and triazoles against Aspergillus spp.

    PubMed

    Arendrup, Maiken C; Cuenca-Estrella, Manuel; Lass-Flörl, Cornelia; Hope, William W

    2013-12-01

    Candida and Aspergillus infections have emerged as significant pathogens in recent decades. During this same time, broad spectrum triazole and echinocandin antifungal agents have been developed and increasingly used. One consequence of widespread use is leading to the emergence of mutants with acquired resistance mutations. Therefore, accurate susceptibility testing and appropriate clinical breakpoints for the interpretation of susceptibility results have become increasingly important. Here we review the underlying methodology by which breakpoints have been selected by EUCAST (European Committee on Antimicrobial Susceptibility Testing). Five parameters are evaluated: dosing regimens used; EUCAST MIC distributions from multiple laboratories, species and compound specific epidemiological cut off values (upper MIC limits of wild type isolates or ECOFFs), pharmacokinetic/pharmacodynamic relationships and targets associated with outcome and finally clinical data by species and MIC when available. The general principles are reviewed followed by a detailed review of the individual aspects for Candida species and the three echinocandins and for Aspergillus and the three mould-active azoles. This review provides an update of the subcommittee on antifungal susceptibility testing (AFST) of the EUCAST methodology and summarises the current EUCAST breakpoints for Candida and Aspergillus. Recommendations about applicability of antifungal susceptibility testing in the routine setting are also included. PMID:24618110

  13. Cryptic and rare Aspergillus species in Brazil: prevalence in clinical samples and in vitro susceptibility to triazoles.

    PubMed

    Negri, C E; Gonçalves, S S; Xafranski, H; Bergamasco, M D; Aquino, V R; Castro, P T O; Colombo, A L

    2014-10-01

    Aspergillus spp. are among the most common causes of opportunistic invasive fungal infections in tertiary care hospitals. Little is known about the prevalence and in vitro susceptibility of Aspergillus species in Latin America, because there are few medical centers able to perform accurate identification at the species level. The purpose of this study was to analyze the distribution of cryptic and rare Aspergillus species among clinical samples from 133 patients with suspected aspergillosis admitted in 12 medical centers in Brazil and to analyze the in vitro activity of different antifungal drugs. The identification of Aspergillus species was performed based on a polyphasic approach, as well as sequencing analysis of the internal transcribed spacer (ITS) region, calmodulin, and β-tubulin genes and phylogenetic analysis when necessary. The in vitro susceptibility tests with voriconazole, posaconazole, and itraconazole were performed according to the CLSI M38-A2 document (2008). We demonstrated a high prevalence of cryptic species causing human infection. Only three isolates, representing the species Aspergillus thermomutatus, A. ochraceus, and A. calidoustus, showed less in vitro susceptibility to at least one of the triazoles tested. Accurate identifications of Aspergillus at the species level and with in vitro susceptibility tests are important because some species may present unique resistance patterns against specific antifungal drugs.

  14. Synthesis, spectral, antitumor and antimicrobial studies on Cu(II) complexes of purine and triazole Schiff base derivatives

    NASA Astrophysics Data System (ADS)

    Amer, Said; El-Wakiel, Nadia; El-Ghamry, Hoda

    2013-10-01

    A series of copper (II) complexes of Schiff bases derived from 7H-2,6-diaminopurine and 4H-3,5-diamino-1,2,4-triazole with 2-pyridinecarbaldehyde, salicylaldehyde, 2,4-dihydroxybenzaldehyde and 2-hydroxy-1-naphthaldehyde have been prepared. The donor atoms and the possible geometry of the complexes were investigated by means of elemental and thermal analyses, molar conductance, magnetic moment, UV-Vis, IR, ESR and mass spectra. The ligands behaved as tetradentate, coordinating through the nitrogen atom of the azomethine group and the nearest nitrogen atom to it or oxygen atom of α-hydroxyl group. The results of simultaneous DTA & TGA analyses of the complexes showed the final degradation product for these complexes is CuO. The spectral studies confirmed a four coordinate environment around the metal ion. The obtained results were supported by 3D molecular modeling of complexes using molecular mechanics (MM+) and semiempirical molecular orbital calculations (PM3). These complexes were also tested for their in vitro antimicrobial activities against some bacterial and fungal strains. Complex 2 was investigated for its cyctotoxic effect against human breast cancer (MCF7), liver carcinoma (HEPG2) and colon carcinoma cell lines (HCT116). This compound exhibited a moderate activity against the tested cell lines with IC50 of 10.3, 9.8 and 8.7 μg/ml against MCF7, HCT116 and HEPG2, respectively.

  15. Synthesis of Triazole-Linked Analogues of c-di-GMP and Their Interactions with Diguanylate Cyclase.

    PubMed

    Fernicola, Silvia; Torquati, Ilaria; Paiardini, Alessandro; Giardina, Giorgio; Rampioni, Giordano; Messina, Marco; Leoni, Livia; Del Bello, Fabio; Petrelli, Riccardo; Rinaldo, Serena; Cappellacci, Loredana; Cutruzzolà, Francesca

    2015-10-22

    Cyclic di-GMP (c-di-GMP) is a widespread second messenger that plays a key role in bacterial biofilm formation. The compound's ability to assume multiple conformations allows it to interact with a diverse set of target macromolecules. Here, we analyzed the binding mode of c-di-GMP to the allosteric inhibitory site (I-site) of diguanylate cyclases (DGCs) and compared it to the conformation adopted in the catalytic site of the EAL phosphodiesterases (PDEs). An array of novel molecules has been designed and synthesized by simplifying the native c-di-GMP structure and replacing the charged phosphodiester backbone with an isosteric nonhydrolyzable 1,2,3-triazole moiety. We developed the first neutral small molecule able to selectively target DGCs discriminating between the I-site of DGCs and the active site of PDEs; this molecule represents a novel tool for mechanistic studies, particularly on those proteins bearing both DGC and PDE modules, and for future optimization studies to target DGCs in vivo.

  16. Inhibition of M. tuberculosis β-ketoacyl CoA reductase FabG4 (Rv0242c) by triazole linked polyphenol-aminobenzene hybrids: comparison with the corresponding gallate counterparts.

    PubMed

    Banerjee, Deb Ranjan; Senapati, Kalyan; Biswas, Rupam; Das, Amit K; Basak, Amit

    2015-03-15

    Herein we report six novel triazole linked polyphenol-aminobenzene hybrids (3-8) as inhibitors of Mycobacterium tuberculosis FabG4 (Rv0242c), a less explored β-ketoacyl CoA reductase that has immense potential to be the future anti-tuberculosis drug target due to its possible involvement in drug resistance and latent infection. Novel triazole linked polyphenol-aminobenzene hybrids have been synthesized, characterized and evaluated for their inhibitory activity against FabG4. All of them inhibit FabG4 at low micromolar concentrations. In silico docking study has been carried out to explain the experimental findings. A comparative study of these new inhibitors with previously reported gallate counterparts leads to structure-activity relations (SAR) of substituent linked to N-1 of triazole ring.

  17. Azide-alkyne cycloaddition en route towards 1H-1,2,3-triazole-tethered β-lactam-ferrocene and β-lactam-ferrocenylchalcone conjugates: synthesis and in vitro anti-tubercular evaluation.

    PubMed

    Kumar, Kewal; Carrère-Kremer, Séverine; Kremer, Laurent; Guérardel, Yann; Biot, Christophe; Kumar, Vipan

    2013-02-01

    A diverse range of triazoles were prepared following well established, Cu-mediated azide-alkyne cycloaddition reactions with the aim of probing the anti-tubercular structure-activity relationships (SAR) within the β-lactam-ferrocene-triazole conjugate family. The anti-tubercular evaluation studies of the synthesized conjugates revealed that none of the scaffolds exhibited any activity that restricted mycobacterial growth even at high doses. The introduction of various substituents onto the N-1 of the β-lactam ring, introducing mono- or di-ferrocenylchalcone substituents at the C-3 position as well as introducing a spacer of varying chain length failed to produce any significant enhancement in the activity profiles. The described protocol was a successful attempt on the inclusion of a ferrocene nucleus in the β-lactam family tethered via triazole linkers having metabolic stability and physicochemical favourability.

  18. Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction

    PubMed Central

    Reddy, Tummala R.K.; Li, Chan; Guo, Xiaoxia; Fischer, Peter M.; Dekker, Lodewijk V.

    2014-01-01

    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

  19. Synthesis and biological evaluation of 1-(6-methylpyridin-2-yl)-5-(quinoxalin-6-yl)-1,2,3-triazoles as transforming growth factor-β type 1 receptor kinase inhibitors.

    PubMed

    Li, Fei; Park, Yunjeong; Hah, Jung-Mi; Ryu, Jae-Sang

    2013-02-15

    A series of 1-(6-methylpyridin-2-yl)-5-(quinoxalin-6-yl)-1,2,3-triazoles has been synthesized and evaluated for their ALK5 inhibitory activity. The 1-(6-methylpyridin-2-yl)-1,2,3-triazoles were assembled by Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition. Following this, quinoxaline was introduced through Pd-catalyzed direct arylation. The synthesized 1-(6-methylpyridin-2-yl)-5-(quinoxalin-6-yl)-1,2,3-triazoles revealed significant selectivity differences with respect to p38α MAP kinase. In particular, 12k showed 80.8% ALK5 inhibitory activity at a concentration of 10 μM and IC(50) value of 4.69 μM, but did not show p38α MAP kinase inhibitory activity (-1.94% inhibition at a concentration of 10 μM).

  20. 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

  1. 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

  2. The labeling debate in the United States.

    PubMed

    Marchant, Gary E; Cardineau, Guy A

    2013-01-01

    The mandatory labeling of genetically modified (GM) food has become the predominant policy issue concerning biotechnology in the United States. The controversy over GM labeling is being debated at several different levels and branches of government. At the federal level, the Food and Drug Administration, which has primary jurisdiction over food safety and labeling, has steadfastly refused to require labeling of GM foods since 1992 based on its conclusion that GM foods as a category present no unique or higher risks than other foods. Proposed legislation has been repeatedly introduced in the US. Congress over the years to mandate GM labeling, but has made very little progress. With federal labeling requirements apparently stalled, the main activity has switched to the state level, where numerous individual states are considering mandatory GM labeling, either through legislation or proposition. The debate over GM labeling, at both the federal and state levels, has focused on five issues: (1) public opinion; (2) the legality of labeling requirements; (3) the risks and benefits of GM foods; (4) the costs and burdens of GM labeling; and (5) consumer choice. While the pro-labeling forces argue that all of these factors weigh in favor of mandatory GM labeling, a more careful evaluation of the evidence finds that all five factors weigh decisively against mandatory GM labeling requirements.

  3. 21 CFR 211.125 - Labeling issuance.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... identity and conformity to the labeling specified in the master or batch production records. (c) Procedures... discrepancies shall be investigated in accordance with § 211.192. Labeling reconciliation is waived for cut...

  4. 21 CFR 211.125 - Labeling issuance.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... identity and conformity to the labeling specified in the master or batch production records. (c) Procedures... discrepancies shall be investigated in accordance with § 211.192. Labeling reconciliation is waived for cut...

  5. 21 CFR 211.125 - Labeling issuance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... identity and conformity to the labeling specified in the master or batch production records. (c) Procedures... discrepancies shall be investigated in accordance with § 211.192. Labeling reconciliation is waived for cut...

  6. 21 CFR 211.125 - Labeling issuance.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... identity and conformity to the labeling specified in the master or batch production records. (c) Procedures... discrepancies shall be investigated in accordance with § 211.192. Labeling reconciliation is waived for cut...

  7. 21 CFR 211.125 - Labeling issuance.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... identity and conformity to the labeling specified in the master or batch production records. (c) Procedures... discrepancies shall be investigated in accordance with § 211.192. Labeling reconciliation is waived for cut...

  8. 40 CFR 205.158 - Labeling requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Motorcycles § 205.158 Labeling requirements. (a)(1) The... information: (i) The label heading: Motorcycle Noise Emission Control Information; (ii) The statement: This ___ (model year) ___ (model specific code) motorcycle, ___ (serial number), meets EPA noise...

  9. 40 CFR 1033.135 - Labeling.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... THAT IT IS REMANUFACTURED, EXCEPT AS ALLOWED BY 40 CFR 1033.750.” (3) Label diesel-fueled locomotives... locomotives certified for use with both LSD and ULSD. (c) Engine labels. (1) For engines not...

  10. 21 CFR 640.84 - Labeling.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Albumin (Human) § 640.84 Labeling. In addition to the labeling... percent albumin is administered to a patient with marked dehydration; (d) The protein...

  11. 21 CFR 640.84 - Labeling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Albumin (Human) § 640.84 Labeling. In addition to the labeling... percent albumin is administered to a patient with marked dehydration; (d) The protein...

  12. 21 CFR 640.84 - Labeling.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Albumin (Human) § 640.84 Labeling. In addition to the labeling... percent albumin is administered to a patient with marked dehydration; (d) The protein...

  13. 21 CFR 640.84 - Labeling.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Albumin (Human) § 640.84 Labeling. In addition to the labeling... percent albumin is administered to a patient with marked dehydration; (d) The protein...

  14. 21 CFR 640.84 - Labeling.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Albumin (Human) § 640.84 Labeling. In addition to the labeling... percent albumin is administered to a patient with marked dehydration; (d) The protein...

  15. 21 CFR 640.94 - Labeling.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Plasma Protein Fraction (Human) § 640.94 Labeling. In addition... package labels shall contain the following information: (a) The osmotic equivalent in terms of plasma,...

  16. 21 CFR 640.94 - Labeling.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Plasma Protein Fraction (Human) § 640.94 Labeling. In addition... package labels shall contain the following information: (a) The osmotic equivalent in terms of plasma,...

  17. 21 CFR 640.94 - Labeling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Plasma Protein Fraction (Human) § 640.94 Labeling. In addition... package labels shall contain the following information: (a) The osmotic equivalent in terms of plasma,...

  18. 21 CFR 640.94 - Labeling.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Plasma Protein Fraction (Human) § 640.94 Labeling. In addition... package labels shall contain the following information: (a) The osmotic equivalent in terms of plasma,...

  19. 21 CFR 640.94 - Labeling.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Plasma Protein Fraction (Human) § 640.94 Labeling. In addition... package labels shall contain the following information: (a) The osmotic equivalent in terms of plasma,...

  20. 27 CFR 19.437 - Labels.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... affix a label showing the following information: (1) The proprietor's name and plant number; (2) The... paragraph (a) of this section is not required when the sample container bears a label approved under part...