In vitro and ex vivo activity of an Azadirachta indica A.Juss. seed kernel extract on early sporogonic development of Plasmodium in comparison with azadirachtin A, its most abundant constituent.

PubMed

Dahiya, Nisha; Chianese, Giuseppina; Abay, Solomon Mequanente; Taglialatela-Scafati, Orazio; Esposito, Fulvio; Lupidi, Giulio; Bramucci, Massimo; Quassinti, Luana; Christophides, George; Habluetzel, Annette; Lucantoni, Leonardo

2016-12-15

NeemAzal ® (NA) is a quantified extract from seed kernels of neem, Azadirachta indica A.Juss. (Meliaceae), with a wide spectrum of biological properties, classically ascribed to its limonoid content. NA contains several azadirachtins (A to L), azadirachtin A (AzaA) being its main constituent. AzaA has been shown to inhibit microgamete formation of the rodent malaria parasite Plasmodium berghei, and NA was found to completely inhibit the transmission of Plasmodium berghei to Anopheles stephensi mosquitoes when administered to gametocytemic mice at a corresponding AzaA dose of 50mg/kg before exposure to mosquitoes. The present study was aimed at i) assessing the pharmacodynamics and duration of action of NA and AzaA against P. berghei exflagellation in systemic circulation in mice and ii) elucidating the transmission blocking activity (TBA) of the main NA constituents. The NA and AzaA pharmacodynamics on exflagellation were assessed through ex vivo exflagellation assays, while TBA of NA constituents was evaluated through in vitro ookinete development assay. Pharmacodynamics experiments: Peripheral blood from P. berghei infected BALB/c mice with circulating mature gametocytes, were treated i.p. with 50mg/kg and 100mg/kg pure AzaA and with NeemAzal ® (Trifolio-M GmbH) at the corresponding AzaA concentrations. The effect magnitude and duration of action of compounds was estimated by counting exflagellation centers, formed by microgametocytes in process of releasing flagellated gametes, at various time points after treatment in ex vivo exflagellation tests. Ookinete Development Assay: The direct effects of NeemAzal ® and AzaA on ookinete development were measured by fluorescence microscopy after incubation of gametocytemic blood with various concentrations of test substances in microplates for 24h. The exflagellation tests revealed an half-life of NA anti-plasmodial compounds of up to 7h at a NA dose corresponding to 100mg/kg equivalent dose of AzaA. The ookinete development assay showed an increased activity of NA against early sporogonic stages compared to that of AzaA. The IC 50 value determined for NA was 6.8µg/ml (CI 95 : 5.95-7.86), about half of the AzaA IC 50 (12.4µg/ml; CI 95 : 11.0-14.04). The stronger activity of NA, when compared to AzaA, could not be explained by an additive or synergistic effect by other azadirachtins (B, D and I) present in NA. In fact, the addition of these compounds at 50µM concentration to AzaA did not evidence any decrease of the IC 50 against early sporogonic stages to that obtained with AzaA alone. It is likely that other non-limonoid compounds present in NA may contribute to AzaA activity and enhanced pharmacodynamics against exflagellation both in vitro and in vivo. Copyright © 2016. Published by Elsevier GmbH.

Materials based on cellulose fabric and PVC with porous structures formed by jointed aza- and oxa-aza-crown macromolecules

NASA Astrophysics Data System (ADS)

Fridman, A. Ya.; Tsivadze, A. Yu.; Morozova, E. M.; Sokolova, N. P.; Shiryaev, A. A.; Petukhova, G. A.; Voloshchuk, A. M.; Bardyshev, I. I.; Gorbunov, A. M.; Polyakova, I. Ya.; Novikov, A. K.; Titova, V. N.; Yavich, A. A.; Petrova, N. V.

2016-12-01

A material with porous structures formed by jointed aza- and oxa-aza-crowns with peripheral OHgroups is synthesized on the basis of cellulose fabric and PVC transformed into hydroxyethylcyclam. Mesopores are mainly observed on the fiber surface. The specific surface of the material is 6 m2/g; the volume of free space is 0.112 cm3/g. Assuming the internal pores have a disk-like shape, their width is estimated at 2 nm. The material sorbs vapors of aliphatic and aromatic hydrocarbons, alcohols, aldehydes, ketones, amines, amides, nitriles, and sulfoxides. It also swells to a limited degree in organic solvents. When sulfuric acid or sodium hydroxide is sorbed in the pores, compounds of them with H+- and OH--conducting systems of hydrogen bonds are formed.

Azadirachtin, a neem-derived biopesticide, impairs behavioral and hematological parameters in carp (Cyprinus carpio).

PubMed

Murussi, Camila R; Menezes, Charlene C; Nunes, Mauro E M; Araújo, Maria do Carmo S; Quadros, Vanessa A; Rosemberg, Denis B; Loro, Vania L

2016-11-01

Azadirachtin (Aza) is a promisor biopesticide used in organic production and aquaculture. Although this compound is apparently safe, there is evidence that it may have deleterious effects on fish. Behavioral and hematological tests are grouped into a set of parameters that may predict potential toxicity of chemical compounds. Here, we investigate the effects of Aza, in the commercial formulation Neenmax ™ , on carp (Cyprinus carpio) by defining LC 50 (96 h), and testing behavioral and hematological parameters. In our study, LC 50 was estimated at 80 μL/L. We exposed carp to Aza at 20, 40, and 60 μL/L, values based on 25, 50, and 75% of LC 50 , respectively. At 60 μL/L, Aza promoted significant changes in several parameters, increasing the distance traveled and absolute turn angle. In addition, the same concentration decreased the time spent immobile and the number of immobile episodes. Hematological parameters, such as hematocrit, hemoglobin, hematimetrics index, and red cell distribution, were decreased at 60 μL/L Aza exposure. In conclusion, our study demonstrates that 60 μL/L Aza altered locomotor activity, motor pattern, and hematological parameters, suggesting potential toxicity to carp after acute exposure. In addition, this is the first report that evaluates the actions of a chemical contaminant using automated behavioral tracking of carp, which may be a useful tool for assessing the potential toxicity of biopesticides in conjunction with hematological tests. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1381-1388, 2016. © 2015 Wiley Periodicals, Inc.

Theoretical study of the alkaline hydrolysis of an aza-β-lactam derivative of clavulanic acid

NASA Astrophysics Data System (ADS)

Garcías, Rafael C.; Coll, Miguel; Donoso, Josefa; Muñoz, Francisco

2003-04-01

DFT calculations based on the hybrid functional B3LYP/6-31+G * were used to study the alkaline hydrolysis of an aza-clavulanic acid, which results from the substitution of the carbon atom at position 6 in clavulanic acid by a nitrogen atom. The presence of the nitrogen atom endows the compound with special properties; in fact, once formed, the tetrahedral intermediate can evolve with cleavage of the N 4-C 7 or N 6-C 7 bond, which obviously leads to different reaction products. These differential bond cleavages may play a central role in the inactivation of β-lactamases, so the compound may be a powerful inactivator of these enzymes.

Synthesis of Novel Aza-aromatic Curcuminoids with Improved Biological Activities towards Various Cancer Cell Lines.

PubMed

Theppawong, Atiruj; Van de Walle, Tim; Grootaert, Charlotte; Bultinck, Margot; Desmet, Tom; Van Camp, John; D'hooghe, Matthias

2018-05-01

Curcumin, a natural compound extracted from the rhizomes of Curcuma longa , displays pronounced anticancer properties but lacks good bioavailability and stability. In a previous study, we initiated structure modification of the curcumin scaffold by imination of the labile β-diketone moiety to produce novel β-enaminone derivatives. These compounds showed promising properties for elaborate follow-up studies. In this work, we focused on another class of nitrogen-containing curcuminoids with a similar objective: to address the bioavailability and stability issues and to improve the biological activity of curcumin. This paper thus reports on the synthesis of new pyridine-, indole-, and pyrrole-based curcumin analogues (aza-aromatic curcuminoids) and discusses their water solubility, antioxidant activity, and antiproliferative properties. In addition, multivariate statistics, including hierarchical clustering analysis and principal component analysis, were performed on a broad set of nitrogen-containing curcuminoids. Compared to their respective mother structures, that is, curcumin and bisdemethoxycurcumin, all compounds, and especially the pyridin-3-yl β-enaminone analogues, showed better water solubility profiles. Interestingly, the pyridine-, indole-, and pyrrole-based curcumin derivatives demonstrated improved biological effects in terms of mitochondrial activity impairment and protein content, in addition to comparable or decreased antioxidant properties. Overall, the biologically active N -alkyl β-enaminone aza-aromatic curcuminoids were shown to offer a desirable balance between good solubility and significant bioactivity.

Synthesis and blood pressure lowering activity of benzylic ethers of 2-diethylaminoethanol and a related diamine.

PubMed

El-Antably, S M; Soine, T O; Shaath, N A; Gupta, P K

1975-08-01

Based upon the unpublished finding that 3'-hydroxy-4'-(beta-diethylaminoethoxy)-3',4'-dihydroseselin possessed a potent blood pressure lowering effect in the cat at a dose of 1 mg/kg, the present study examined the activities of several related compounds. These compounds were derived by dissection of the parent compound to give four benzylic ethers of 2-diethylaminoethanol and a diamine, derived by replacing the ether oxygen of the parent compound with an N--CH3 function. The simplest compounds were the benzyl and 2,6-dimethoxybenzyl ethers of the aminoalcohol. Closely related to the benzyl compound was a congener with a hydroxymethyl group on the benzylic carbon. The beta-diethylaminoethyl ether of 4-chromanol was the most complex of the ethers. The blood pressure measurements were carried out on male cats and compared to papaverine hydrochloride as a standard. In all cases, the most potent blood pressure lowering activity resided in the parent compound, which was not greatly superior to the diamine but substantially more active than the other compounds.

RUNX3 is involved in caspase-3-dependent apoptosis induced by a combination of 5-aza-CdR and TSA in leukaemia cell lines.

PubMed

Zhai, Feng-Xian; Liu, Xiang-Fu; Fan, Rui-Fang; Long, Zi-Jie; Fang, Zhi-Gang; Lu, Ying; Zheng, Yong-Jiang; Lin, Dong-Jun

2012-03-01

Epigenetic therapy has had a significant impact on the management of haematologic malignancies. The aim of this study was to assess whether 5-aza-CdR and TSA inhibit the growth of leukaemia cells and induce caspase-3-dependent apoptosis by upregulating RUNX3 expression. K562 and Reh cells were treated with 5-aza-CdR, TSA or both compounds. RT-PCR and Western blot analyses were used to examine the expression of RUNX3 at the mRNA and protein levels, respectively. Immunofluorescence microscopy was used to detect the cellular location of RUNX3. Additionally, after K562 cells were transfected with RUNX3, apoptosis and proliferation were studied using Annexin V staining and MTT assays. The expression of RUNX3 in leukaemia cell lines was markedly less than that in the controls. Demethylating drug 5-aza-CdR could induce RUNX3 expression, but the combination of TSA and 5-aza-CdR had a greater effect than did treatment with a single compound. The combination of 5-aza-CdR and TSA induced the translocation of RUNX3 from the cytoplasm into the nucleus. TSA enhanced apoptosis induced by 5-aza-CdR, and Annexin V and Hoechst 33258 staining showed that the combination induced apoptosis but not necrosis. Furthermore, apoptosis was dependent on the caspase-3 pathway. RUNX3 overexpression in K562 cells led to growth inhibition and apoptosis and potentiated the effects of 5-aza-CdR induction. RUNX3 plays an important role in leukaemia cellular functions, and the induction of RUNX3-mediated effects may contribute to the therapeutic value of combination TSA and 5-aza-CdR treatment.

Biodegradable polymer based encapsulation of neem oil nanoemulsion for controlled release of Aza-A.

PubMed

Jerobin, Jayakumar; Sureshkumar, R S; Anjali, C H; Mukherjee, Amitava; Chandrasekaran, Natarajan

2012-11-06

Azadirachtin a biological compound found in neem have medicinal and pesticidal properties. The present work reports on the encapsulation of neem oil nanoemulsion using sodium alginate (Na-Alg) by cross linking with glutaraldehyde. Starch and polyethylene glycol (PEG) were used as coating agents for smooth surface of beads. The SEM images showed beads exhibited nearly spherical shape. Swelling of the polymeric beads reduced with coating which in turn decreased the rate of release of Aza-A. Starch coated encapsulation of neem oil nanoemulsion was found to be effective when compared to PEG coated encapsulation of neem oil nanoemulsion. The release rate of neem Aza-A from the beads into an aqueous environment was analyzed by UV-visible spectrophotometer (214 nm). The encapsulated neem oil nanoemulsion have the potential for controlled release of Aza-A. Neem oil nanoemulsion encapsulated beads coated with PEG was found to be toxic in lymphocyte cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

Synthesis of Aromatic Aza-metallapentalenes from Metallabenzene via Sequential Ring Contraction/Annulation

NASA Astrophysics Data System (ADS)

Wang, Tongdao; Han, Feifei; Huang, Haiping; Li, Jinhua; Zhang, Hong; Zhu, Jun; Lin, Zhenyang; Xia, Haiping

2015-04-01

The concept of aromaticity has long played an important role in chemistry and continues to fascinate both experimentalists and theoreticians. Among the archetypal aromatic compounds, heteroaromatics are particularly attractive. Recently, substitution of a transition-metal fragment for a carbon atom in the anti-aromatic hydrocarbon pentalene has led to the new heteroaromatic osmapentalenes. However, construction of the aza-homolog of osmapentalenes cannot be accomplished by a similar synthetic manipulation. Here, we report the synthesis of aza-osmapentalenes by sequential ring contraction/annulation reactions of osmabenzenes via osmapentafulvenes. Nuclear magnetic resonance spectra, X-ray crystallographic analysis, and DFT calculations all suggest that these aza-osmapentalenes exhibit aromatic character. Thus, the stepwise transformation of metallabenzenes to metallapentafulvenes and then aza-metallapentalenes provides an efficient and facile synthetic route to these bicyclic heteroaromatics.

Methods for the synthesis of aza(deaza)xanthines as a basis of biologically active compounds

NASA Astrophysics Data System (ADS)

Babkov, D. A.; Geisman, A. N.; Khandazhinskaya, A. L.; Novikov, M. S.

2016-03-01

The review covers methods for the synthesis of aza(deaza)xanthines, i.e., fused pyrrolo-, pyrazolo- and triazolopyrimidine heterocyclic systems, which are common core structures of various biologically active compounds. The extensive range of modern synthetic approaches is organized according to target structures and starting building blocks. The presented material is intended to benefit broad audience of specialists in the fields of organic, medicinal and pharmaceutical chemistry. The bibliography includes 195 references.

A fluorescent combinatorial logic gate with Na+, H+-enabled OR and H+-driven low-medium-high ternary logic functions.

PubMed

Spiteri, Jasmine M A; Mallia, Carl J; Scerri, Glenn J; Magri, David C

2017-12-06

A novel fluorescent molecular logic gate with a 'fluorophore-spacer 1 -receptor 1 -spacer 2 -receptor 2 ' format is demonstrated in 1 : 1 (v/v) methanol/water. The molecule consists of an anthracene fluorophore, and tertiary alkyl amine and N-(2-methoxyphenyl)aza-15-crown-5 ether receptors. In the presence of threshold concentrations of H + and Na + , the molecule switches 'on' as an AND logic gate with a fluorescence quantum yield of 0.21 with proton and sodium binding constants of log β H+ = 9.0 and log β Na+ = 3.2, respectively. At higher proton levels, protonation also occurs at the anilinic nitrogen atom ether with a log β H+ = 4.2, which allows for Na + , H + -enabled OR (OR + AND circuit) and H + -driven ternary logic functions. The reported molecule is compared and contrasted to classic anthracene-based Na + and H + logic gates. We propose that such logic-based molecules could be useful tools for probing the vicinity of Na + , H + antiporters in biological systems.

Radionuclide-binding compound, a radionuclide delivery system, a method of making a radium complexing compound, a method of extracting a radionuclide, and a method of delivering a radionuclide

DOEpatents

Fisher, Darrell R.; Wai, Chien M.; Chen, Xiaoyuan

2000-01-01

The invention pertains to compounds which specifically bind radionuclides, and to methods of making radionuclide complexing compounds. In one aspect, the invention includes a radionuclide delivery system comprising: a) a calix[n]arene-crown-[m]-ether compound, wherein n is an integer greater than 3, and wherein m is an integer greater than 3, the calix[n]arene-crown-[m]-ether compound comprising at least two ionizable groups; and b) an antibody attached to the calix[n]arene-crown-[m]-ether compound. In another aspect, the invention includes a method of making a radium complexing compound, comprising: a) providing a calix[n]arene compound, wherein n is an integer greater than 3, the calix[n]arene compound comprising n phenolic hydroxyl groups; b) providing a crown ether precursor, the crown ether precursor comprising a pair of tosylated ends; c) reacting the pair of tosylated ends with a pair of the phenolic hydroxyl groups to convert said pair of phenolic hydroxyl groups to ether linkages, the ether linkages connecting the crown ether precursor to the calix[n]arene to form a calix[n]arene-crown-[m]-ether compound, wherein m is an integer greater than 3; d) converting remaining phenolic hydroxyl groups to esters; e) converting the esters to acids, the acids being proximate a crown-[m]-ether portion of the calix[n]arene-crown-[m]-ether compound; and f) providing a Ra.sup.2+ ion within the crown-[m]-ether portion of the calix[n]arene-crown-[m]-ether compound.

New insights into the causes of human illness due to consumption of azaspiracid contaminated shellfish

PubMed Central

Chevallier, O. P.; Graham, S. F.; Alonso, E.; Duffy, C.; Silke, J.; Campbell, K.; Botana, L. M.; Elliott, C. T.

2015-01-01

Azaspiracid (AZA) poisoning was unknown until 1995 when shellfish harvested in Ireland caused illness manifesting by vomiting and diarrhoea. Further in vivo/vitro studies showed neurotoxicity linked with AZA exposure. However, the biological target of the toxin which will help explain such potent neurological activity is still unknown. A region of Irish coastline was selected and shellfish were sampled and tested for AZA using mass spectrometry. An outbreak was identified in 2010 and samples collected before and after the contamination episode were compared for their metabolite profile using high resolution mass spectrometry. Twenty eight ions were identified at higher concentration in the contaminated samples. Stringent bioinformatic analysis revealed putative identifications for seven compounds including, glutarylcarnitine, a glutaric acid metabolite. Glutaric acid, the parent compound linked with human neurological manifestations was subjected to toxicological investigations but was found to have no specific effect on the sodium channel (as was the case with AZA). However in combination, glutaric acid (1mM) and azaspiracid (50nM) inhibited the activity of the sodium channel by over 50%. Glutaric acid was subsequently detected in all shellfish employed in the study. For the first time a viable mechanism for how AZA manifests itself as a toxin is presented. PMID:25928256

4-Functionalized 1,3-diarylpyrazoles bearing 6-aminosulfonylbenzothiazole moiety as potent inhibitors of carbonic anhydrase isoforms hCA I, II, IX and XII.

PubMed

SitaRam; Ceruso, Mariangela; Khloya, Poonam; Supuran, Claudiu T; Sharma, Pawan K

2014-12-15

A series of 24 novel heterocyclic compounds-functionalized at position 4 with aldehyde (5a-5f), carboxylic acid (6a-6f), nitrile (7a-7f) and oxime (8a-8f) functional groups-bearing 6-aminosulfonybenzothiazole moiety at position 1 of pyrazole has been synthesized and investigated for the inhibition of four isoforms of the α-class carbonic anhydrases (CAs, EC 4.2.1.1), comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (transmembrane, tumor associated isozymes). Against the human isozyme hCA I, compounds 6a-6f showed medium-weak inhibitory potential with Ki values in the range of 157-690nM with 6a showing better potential than the standard drug acetazolamide (AZA). Against hCA II, all the compounds showed excellent to moderate inhibition with Ki values of compounds 5a, 5d, 5f, 6a-6f, 8d and 8f lower than 12nM (Ki of AZA). Against hCA IX, all the compounds showed moderate inhibition with the exception of 6e which showed nearly 9 fold a better profile compared to AZA, whereas against hCA XII, four compounds 6e, 7a, 7b and 7d showed Ki in the same order as that of AZA. Carboxylic acid 6e was found to be an excellent inhibitor of both hCA IX and XII, with Ki values of 2.8nM and 5.5nM, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

Heteropoly acid-catalyzed microwave-assisted three-component aza-Diels-Alder cyclizations: diastereoselective synthesis of potential drug candidates for Alzheimer's disease.

PubMed

Borkin, Dmitry; Morzhina, Elena; Datta, Silpi; Rudnitskaya, Aleksandra; Sood, Abha; Török, Marianna; Török, Béla

2011-03-07

A highly diastereoselective microwave-assisted three component synthesis of azabicyclo[2.2.2]octan-5-ones by a silicotungstic acid-catalyzed aza-Diels-Alder cyclization is described. The one-pot process involves the formation of the in situ generated Schiff base and its immediate cyclization with cyclohex-2-enone. The short reaction times, good yields and excellent diastereoselectivity make this annulation a practical and environmentally attractive method for the synthesis of the target compounds. Preliminary assays were carried out to determine the activity of the products in AChE as well as in amyloid β fibrillogenesis inhibition.

Determination of 6-mercaptopurine and azathioprine in plasma by high-performance liquid chromatography.

PubMed

Ding, T L; Benet, L Z

1979-07-21

Using 1-ml plasma samples, levels of 6-mercaptopurine (6MP) as low as 5 ng/ml and azathioprine (AZA) as low as 40 ng/ml can be detected using a high-performance liquid chromatography reversed-phase column procedure following extraction. Both compounds were stable in frozen plasma for seven weeks. AZA stability in blood was temperature dependent; the half-lives of AZA breakdown to 6MP at 37 degrees were 28 and 46 min in blood drawn from two rhesus monkeys. Plasma levels of 6MP were measured in a rhesus monkey following 6MP (1.47 mg/kg) and AZA (3 mg/kg) intravenous administration. 6MP levels were also measured in three renal transplant patients on daily 50- and 100-mg AZA doses. Peak levels (45-75 ng/ml) were reached within an hour and 6MP levels were detected for up to 7 h.

POSSIBLE MECHANISMS OF THYROID HORMONE DISRUPTION IN MICE BY BDE 47, A MAJOR POLYBROMINATED DIPHENYL ETHER CONGENER

EPA Science Inventory

ABSTRACT Polybromindated diphenyl ethers (PBDEs) are a class of polyhalogenated aromatic compounds commercially used as fire retardants in consumer products. These compounds have been shown to decrease thyroid hormone concentrations in rodents after acute exposures. Based on t...

Optimization of three- and four-component reactions for polysubstituted piperidines: application to the synthesis and preliminary biological screening of a prototype library.

PubMed

Ulaczyk-Lesanko, Agnieszka; Pelletier, Eric; Lee, Maria; Prinz, Heino; Waldmann, Herbert; Hall, Dennis G

2007-01-01

Several solid- and solution-phase strategies were evaluated for the preparation of libraries of polysubstituted piperidines of type 7 using the tandem aza[4+2]cycloaddition/allylboration multicomponent reaction between 1-aza-4-boronobutadienes, maleimides, and aldehydes. A novel four-component variant of this chemistry was developed in solution phase, and it circumvents the need for pre-forming the azabutadiene component. A parallel synthesis coupled with compound purification by HPLC with mass-based fraction collection allowed the preparation of a library of 944 polysubstituted piperidines in a high degree of purity suitable for biological screening. A representative subset of 244 compounds was screened against a panel of phosphatase enzymes, and despite the modest levels of activity obtained, this study demonstrated that piperidines of type 7 display the right physical properties (e.g., solubility) to be assayed effectively in high-throughput enzymatic tests.

Azelaic acid was sensitizing effect in the chemotherapeutic treatment of several melanoma cell lines.

PubMed

Rodriguez-Vicente, J; Vicente-Ortega, V; Canteras-Jordana

1996-12-01

Chemotherapy for melanoma results in low response and must be reinforced with sensitizer compounds. We believed that azelaic acid (AZA) could modulate melanomas' resistance to antineoplastics. Therefore we tried to compare in vitro treatment with antineoplastics alone versus AZA treatment followed by antineoplastics. We carried out MTT assays to evaluate the cytotoxicity of melphalan, lomustine (CCNU), fotemustine, and 4-Hydroxyanisole (4-HA) on three melanoma lines (B16F10, SK-MEL-28, and SK-MEL-1), and the modulating effect of pretreatment with AZA (1 mM). AZA showed a dose-dependent antineoplastic activity on the three lines. Melphalan was the most active drug followed by CCNU, fotemustine, and 4-HA. The most sensitive line was B16F10 and the least sensitive was SK-meL-1. Previous treatment with AZA of B16F10 reinforced the effect of melphalan (2.5 times), CCNU (10 times), and fotemustine (14 times); whereas for SK-MEL-28 and SK-MEL-1, only the cytotoxicity of CCNU and fotemustine increased. An antagonist effect was produced by 4-HA on all three lines. We concluded that AZA enhances in vitro cytotoxicity of CCNU and fotemustine.

Organocatalytic aza-Michael/retro-aza-Michael reaction: pronounced chirality amplification in aza-Michael reaction and racemization via retro-aza-Michael reaction.

PubMed

Cai, Yong-Feng; Li, Li; Luo, Meng-Xian; Yang, Ke-Fang; Lai, Guo-Qiao; Jiang, Jian-Xiong; Xu, Li-Wen

2011-05-01

A detailed experimental investigation of an aza-Michael reaction of aniline and chalcone is presented. A series of Cinchona alkaloid-derived organocatalysts with different functional groups were prepared and used in the aza-Michael and retro-aza-Michael reaction. There was an interesting finding that a complete reversal of stereoselectivity when a benzoyl group was introduced to the cinchonine and cinchonidine. The chirality amplification vs. time proceeds in the quinine-derived organocatalyst containing silicon-based bulky group, QN-TBS, -catalyzed aza-Michael reaction under solvent-free conditions. In addition, we have demonstrated for the first time that racemization was occurred in suitable solvents under mild conditions due to retro-aza-Michael reaction of the Michael adduct of aniline with chalcone. These indicate the equilibrium of retro-aza-Michael reaction and aza-Michael reaction produce the happening of chirality amplification in aza-Michael reaction and racemization via retro-aza-Michael reaction under different conditions, which would be beneficial to the development of novel chiral catalysts for the aza-Michael reactions. Copyright © 2011 Wiley-Liss, Inc.

Halogen atom effect on the photophysical properties of substituted aza-BODIPY derivatives.

PubMed

De Simone, B C; Mazzone, G; Pirillo, J; Russo, N; Sicilia, E

2017-01-18

The influence of halogen atom substitution (Br and I), in different amounts and positions in an aza-BODIPY skeleton, on the photophysical properties of some aza-BODIPY derivatives has been investigated by using density functional theory and its time-dependent extension. The heavy atom effect on excitation energies, singlet-triplet energy gaps and spin-orbit matrix elements has been considered. The maximum absorption within the therapeutic window has been confirmed for all the aza-BODIPY derivatives. The feasible intersystem spin crossing pathways for the population of the lowest triplet state, that will depend on the values of the spin-orbit matrix elements, the energy gap as well as the orbital composition of the involved states have been found to most likely involve the S 1 and T 1 or T 2 states. The outcomes of computations support the potential therapeutic use of these compounds as photosensitizers in photodynamic therapy.

2,4-Bis(3-methoxy-phen-yl)-3-aza-bicyclo-[3.3.1]nonan-9-one.

PubMed

Parthiban, P; Ramkumar, V; Jeong, Yeon Tae

2009-12-04

In the crystal structure, the title compound, C(22)H(25)NO(3), exists in a twin-chair conformation with equatorial orientations of the meta-methoxy-phenyl groups on both sides of the secondary amino group. The title compound is a positional isomer of 2,4-bis-(2-methoxy-phen-yl)-3-aza-bicyclo-[3.3.1]nonan-9-one and 2,4-bis-(4-methoxy-phen-yl)-3-aza-bicyclo-[3.3.1]nonan-9-one, which both also exhibit twin-chair conformations with equatorial dispositions of the anisyl rings on both sides of the secondary amino group. In the title compound, the meta-methoxy-phenyl rings are orientated at an angle of 25.02 (3)° with respect to each other, whereas in the ortho and para isomers, the anisyl rings are orientated at dihedral angles of 33.86 (3) and 37.43 (4)°, respectively. The crystal packing is dominated by van der Waals inter-actions and by an inter-molecular N-H⋯O hydrogen bond, whereas in the ortho isomer, an inter-molecular N-H⋯π inter-action (H⋯Cg = 2.75 Å) is found.

Some actions of substituted choline phenyl ethers, particularly of choline 2:6-xylyl ether

PubMed Central

Edge, N. D.; Mason, D. F. J.; Wyllie, J. H.

1957-01-01

Marked nicotine-like stimulant properties are possessed by choline phenyl ether and choline o-tolyl ether, and to a decreasing extent by choline 2:6-xylyl ether and choline 2:4:6-mesityl ether. The compounds all show neuromuscular blocking properties, which are of short duration and pass from mainly decamethonium-like to mainly curare-like as more methyl groups are added to the phenyl nucleus. This series of compounds also possesses muscarinic, weak anti-adrenaline and vasodilator properties, as well as long-lasting local anaesthetic effects in the two compounds tested by intradermal injection. PMID:13460236

Self-assembled nanostructures of linear arylacetylenes and their aza-substituted analogues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Jia-Ju; Department of Physics and Materials Science and Centre of Super Diamond and Advanced Films; Yang, Xiong-Bo

2016-06-15

A series of linear phenylene ethynylene molecules have been synthesized, and aza-substitution has been used as a strategy to fine-tune the properties of the molecules. All the compounds exhibited pure blue emission both in solution and solid state, and fluorescence quantum yields as high as 0.66, 0.63 and 0.82 were found in chloroform solutions. The well-defined nanostructures such as quasi-cubes, cubes and rods were fabricated by self-assembly method from these compounds. The photophysical properties and aggregation behavior of self-assembled structures were analyzed in detail. The morphology as well as photophysical properties of these nanostructures have been tuned with selective requirements.

Synthesis and antibacterial activity of bis-[2-hydroxy-3-(1,7,8,9,10-pentamethyl-3,5-dioxo-4-aza-tricyclo[5.2.1.0(2,6)]dec-8-en-4-yloxy)-propyl]-dimethyl-ammonium chloride.

PubMed

Struga, Marta; Kossakowski, Jerzy; Stefańska, Joanna; Zimniak, Andrzej; Koziol, Anna E

2008-06-01

A new quaternary ammonium compound, bis-[2-hydroxy-3-(1,7,8,9,10-pentamethyl-3,5-dioxo-4-aza-tricyclo[5.2.1.0(2,6)]dec-8-en-4-yloxy)-propyl]-dimethyl-ammonium chloride (4), was synthesized. The compound was investigated for antibacterial activity, including Gram-positive cocci and Gram-negative rods, and antifungal activity. Compound 4 showed significant inhibition against Staphylococcus aureus. Research was carried out over 4 standard strains and 40 hospital strains. Elementary analysis and/or MS, (1)H NMR and (13)C NMR spectra confirmed the identity of the products. The molecular structure of 3 was determined by an X-ray analysis.

Microsphere-Based Immunoassay for the Detection of Azaspiracids

PubMed Central

Rodríguez, Laura P.; Vilariño, Natalia; Louzao, M. Carmen; Dickerson, Tobin J.; Nicolaou, K. C.; Frederick, Michael O.; Botana, Luis M.

2014-01-01

Azaspiracids (AZAs) are a group of lipophilic toxins discovered in mussels from Ireland in 1995 following a human poisoning incident. Nowadays the regulatory limit for AZAs in many countries is set at 160 Fg of azaspiracid equivalents per kg of shellfish meat. In this work a microsphere-based immunoassay has been developed for the detection of AZAs using a Luminex system. This method is based on the competition between AZA-2 immobilized onto the surface of microspheres and free AZAs for the interaction with a monoclonal anti-azaspiracid antibody (mAb 8F4). In this inhibition immunoassay the amount of mAb 8F4 bound to AZA-2-microspheres was quantified using a phycoerythrin-labeled anti-mouse antibody, and the fluorescence was measured with a Luminex analyzer. Simple acetate/methanol or methanol extractions yielded final extracts with no matrix interferences and adequate recovery rates of 86.5% and 75.8%, respectively. In summary, this work presents, a sensitive and easily performed screening method capable of detecting AZAs at concentrations below the range of the European regulatory limit using a microsphere/flow cytometry system. PMID:24215909

AzaHx, a novel fluorescent, DNA minor groove and G·C recognition element: Synthesis and DNA binding properties of a p-anisyl-4-aza-benzimidazole-pyrrole-imidazole (azaHx-PI) polyamide.

PubMed

Satam, Vijay; Babu, Balaji; Patil, Pravin; Brien, Kimberly A; Olson, Kevin; Savagian, Mia; Lee, Megan; Mepham, Andrew; Jobe, Laura Beth; Bingham, John P; Pett, Luke; Wang, Shuo; Ferrara, Maddi; Bruce, Chrystal D; Wilson, W David; Lee, Moses; Hartley, John A; Kiakos, Konstantinos

2015-09-01

The design, synthesis, and DNA binding properties of azaHx-PI or p-anisyl-4-aza-benzimidazole-pyrrole-imidazole (5) are described. AzaHx, 2-(p-anisyl)-4-aza-benzimidazole-5-carboxamide, is a novel, fluorescent DNA recognition element, derived from Hoechst 33258 to recognize G·C base pairs. Supported by theoretical data, the results from DNase I footprinting, CD, ΔT(M), and SPR studies provided evidence that an azaHx/IP pairing, formed from antiparallel stacking of two azaHx-PI molecules in a side-by-side manner in the minor groove, selectively recognized a C-G doublet. AzaHx-PI was found to target 5'-ACGCGT-3', the Mlu1 Cell Cycle Box (MCB) promoter sequence with specificity and significant affinity (K(eq) 4.0±0.2×10(7) M(-1)). Copyright © 2015 Elsevier Ltd. All rights reserved.

Antimicrobial and cytotoxic constituents from leaves of Sapium baccatum.

PubMed

Ahmed, Yunus; Sohrab, Md Hossain; Al-Reza, Sharif M; Tareq, Faqir Shahidulla; Hasan, Choudhury M; Sattar, M A

2010-02-01

Six compounds, namely, Lupeol (1), Betulin (2), beta-Taraxerol (3), Taraxerone (4), Stigmasterol (5) and beta-Sitosterol (6) were isolated from the petroleum ether extract of the leaves of Sapium baccatum based on spectroscopic evidence. Lupeol (1), Betulin (2) and Stigmasterol (5) were isolated for the first time from this plant. The cytotoxic potential of the different solvent extracts (methanol, petroleum ether, carbon-tetrachloride and dichloromethane); six column fractions (F-4, F-7, F-10, F-12, F-18 and F-22) of petroleum ether extract and three pure compounds 1, 4 and 6 were determined by using brine shrimp lethality bioassay. The LC50 of all the tested samples were showed to be lethal to brine shrimp nauplii. However, petroleum ether, carbon-tetrachloride extract, column fractions F-4 and F-18 of petroleum ether extract and pure compound 6 showed quite potent activity in brine shrimp lethality bioassay with LC50 1.33, 1.35, 1.40, 1.58 and 1.58 microg/ml, respectively. These result suggested that they might be contain antitumor or pesticidal activity. Further, the methanol extract and four column fractions (F-7, F-12, F-18 and F-22) of petroleum ether showed significant activity against the tested microorganisms. Copyright 2009 Elsevier Ltd. All rights reserved.

Nephrotoxicity of Epigenetic Inhibitors Used for the Treatment of Cancer

PubMed Central

Scholpa, N.E.; Kolli, R.T.; Moore, M.; Arnold, R.D.; Glenn, T.C.; Cummings, B.S.

2016-01-01

This study determined the anti-neoplastic activity and nephrotoxicity of epigenetic inhibitors in vitro. The therapeutic efficacy of epigenetic inhibitors was determined in human prostate cancer cells (PC-3 and LNCaP) using the DNA methyltransferase inhibitor 5-azacytidine (5-Aza) and the histone deacetylase inhibitor trichostatin A (TSA). Cells were also treated with carbamazepine (CBZ), an anti-convulsant with histone deacetylase inhibitor-like properties. 5-Aza, TSA or CBZ alone did not decrease MTT staining in PC-3 or LNCaP cells after 48 hr. In contrast, docetaxel, a frontline chemotherapeutic induced concentration-dependent decreases in MTT staining. Pretreatment with 5-Aza or TSA increased docetaxel-induced cytotoxicity in LNCaP cells, but not PC-3 cells. TSA pretreatment also increased cisplatin-induced toxicity in LNCaP cells. Carfilzomib (CFZ), a protease inhibitor approved for the treatment of multiple myeloma had minimal effect on LNCaP cell viability, but reduced MTT staining 50% in PC-3 cells compared to control, and pretreatment with 5-Aza further enhanced toxicity. Treatment of normal rat kidney (NRK) and human embryonic kidney 293 (HEK293) cells with the same concentrations of epigenetic inhibitors used in prostate cancer cells significantly decreased MTT staining in all cell lines after 48 hr. Interestingly, we found that the toxicity of epigenetic inhibitors to kidney cells was dependent on both the compound and the stage of cell growth. The effect of 5-Aza and TSA on DNA methyltransferase and histone deacetylase activity, respectively, was confirmed by assessing the methylation and acetylation of the CDK inhibitor p21. Collectively, these data show that combinatorial treatment with epigenetic inhibitors alters the efficacy of chemotherapeutics in cancer cells in a compound- and cell-specific manner; however, this treatment also has the potential to induce nephrotoxic cell injury. PMID:27543423

Comparative study of sister chromatid exchange induction and antitumor effects by homo-aza-steroidal esters of [p-[bis(2-chloroethyl)amino]phenyl]butyric acid.

PubMed

Camoutsis, C; Catsoulacos, D; Karayiann, V; Papageorgiou, A; Mourelatos, D; Mioglou, E; Kritsi, Z; Nikolaropoulos, S

2001-01-01

The present work was undertaken in order to test the hypothesis that the Sister Chromatid Exchange (SCE) assay in vitro can be used for the prediction of in vivo tumor response to newly synthesized potential chemotherapeutics. The effect of three homo-aza-steroidal esters containing the -CONH- in the steroidal nucleus, 1, 2, and 3 on SCE rates and on cell kinetics in cultured human lymphocytes was studied. The antitumor activity of these compounds was tested on leukemia P388- and leukemia L1210-bearing mice. The three substances induced statistically significant enhancement of SCEs and of cell division delays. Compounds 1 and 3 were identified, on a molar basis, as more effective inducers of SCEs and of cell division delays compared with compound 2. Compounds 1 and 3 had upon both experimental tumors better therapeutic effects compared with compound 2 at equitoxic doses. Therefore, the order of the antitumor effectiveness of the three compounds coincided with the order of the cytogenetic effects they induced.

A phosphine mediated sequential annulation process of 2-tosylaminochalcones with MBH carbonates to construct functionalized aza-benzobicyclo[4.3.0] derivatives.

PubMed

Zhang, Qinglong; Zhu, Yannan; Jin, Hongxing; Huang, You

2017-04-04

A novel phosphine mediated sequential annulation process to construct functionalized aza-benzobicyclo[4.3.0] derivatives has been developed involving a one-pot sequential catalytic and stoichiometric process, which generates a series of benzobicyclo[4.3.0] compounds containing one quaternary center with up to 94% yield and 20 : 1 dr value. In this reaction, MBH carbonates act as 1,2,3-C 3 synthons.

Evaluation of the first cytostatically active 1-aza-9-oxafluorenes as novel selective CDK1 inhibitors with P-glycoprotein modulating properties.

PubMed

Brachwitz, Kristin; Voigt, Burkhardt; Meijer, Laurent; Lozach, Olivier; Schächtele, Christoph; Molnár, Josef; Hilgeroth, Andreas

2003-02-27

The first series of synthetic 1-aza-9-oxafluorenes with cytostatic activities in the micromolar range was evaluated as cyclin-dependent kinase (CDK1) inhibitors. Activity was found to be selective in comparison to the inhibition of other kinases within the CDK family. Compounds were shown to inhibit the membrane-efflux pump P-glycoprotein responsible for multidrug resistance in cancer cells. First structure-activity relationships are discussed.

Palladium-Catalyzed Formal Cross-Coupling of Diaryl Ethers with Amines: Slicing the 4-O-5 Linkage in Lignin Models.

PubMed

Zeng, Huiying; Cao, Dawei; Qiu, Zihang; Li, Chao-Jun

2018-03-26

Lignin is the second most abundant organic matter on Earth, and is an underutilized renewable source for valuable aromatic chemicals. For future sustainable production of aromatic compounds, it is highly desirable to convert lignin into value-added platform chemicals instead of using fossil-based resources. Lignins are aromatic polymers linked by three types of ether bonds (α-O-4, β-O-4, and 4-O-5 linkages) and other C-C bonds. Among the ether bonds, the bond dissociation energy of the 4-O-5 linkage is the highest and the most challenging to cleave. To date, 4-O-5 ether linkage model compounds have been cleaved to obtain phenol, cyclohexane, cyclohexanone, and cyclohexanol. The first example of direct formal cross-coupling of diaryl ether 4-O-5 linkage models with amines is reported, in which dual C(Ar)-O bond cleavages form valuable nitrogen-containing derivatives. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Isostrychnine synthesis mediated by hypervalent iodine reagent.

PubMed

Jacquemot, Guillaume; Maertens, Gaëtan; Canesi, Sylvain

2015-05-18

Althought there are several reported synthetic routes to strychnine, one of the most widely recognized alkaloids, we report an unexplored route with an oxidative dearomatizing process mediated by hypervalent iodine as the key step. The new syntheses of isostrychnine and strychnine have been achieved from an readily available phenol in nine and ten steps. In addition to the key step, these syntheses involve an aza Michael-ether-enol tandem transformation, two heck type cyclizations, a reductive isomerization, and a double reductive amination in cascade leading to the alkaloid main core. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Wholly Aromatic Ether-imides. Potential Materials for n-Type Semiconductors

NASA Technical Reports Server (NTRS)

Dingemans, Theo J.; St.Clair, Terry L.; Samulski, Edward T.; Bushnell, Dennis M. (Technical Monitor)

2002-01-01

We report on the synthesis and characterization of a novel series low-molar-mass ether-imide rod-shaped model compounds. All ether-imides were obtained by terminating the appropriate rigid core dianhydride, i.e. pyromellitic dianhydride (PMDA), 1,4,5,8-naphthalenetetracarboxylic dianhydride (NDA), 3,3',4,4'-biphenyltetracarboxylic dianhydride (BPDA), and 3,3,4,4'-oxydiphthalic dianhydride (ODPA) with three flexible aryl-ether tails of different chain length. The mono-functional aryl-ether amines, i.e. 4-(3-phenoxy-phenoxy)-phenylamine (2) and 4-(3-phenoxy-3-phenoxy-phenoxy)-phenylamine (4), were synthesized using standard fluoro-displacement and Ullmann condensation techniques. The corresponding ether-imide model compounds were obtained in high yields using a one-step solution imidization procedure. Increasing the number of meta-substituted aryl-ether units reduces the melt transition temperatures and at the same time it increases the solubility of the model compounds. Most model compounds are crystalline solids and form isotropic melts upon heating. 2,7-Bis-(-4-phenoxy-phenyl)-benzo[Imn][3,8]phenanthroline1,3,6,8-tetraone (NDA-n0), however, displays a smectic A (SA) when cooled from the isotropic phase, followed by what appears to be either a highly ordered smectic phase or a, columnar phase. This is the first example, known to date, in which a mesophase is detected in a wholly aromatic ether-imide compound. For all compounds we present spectroscopic data and X-ray diffraction data. Cyclic voltammetry was used to determine the redox behavior and pertinent energy levels of the model compounds.

In vivo cardiomyocyte response to YTX- and AZA-1-induced damage: autophagy versus apoptosis.

PubMed

Ferreiro, Sara F; Vilariño, Natalia; Carrera, Cristina; Louzao, M Carmen; Santamarina, Germán; Cantalapiedra, Antonio G; Cifuentes, J Manuel; Crespo, Andrés; Botana, Luis M

2017-04-01

Yessotoxins (YTX) and azaspiracids (AZAs) are marine toxins produced by phytoplanktonic dinoflagellates that get accumulated in filter feeding shellfish and finally reach human consumers through the food web. Both toxin classes are worldwide distributed, and food safety authorities have regulated their content in shellfish in many countries. Recently, YTXs and AZAs have been described as compounds with subacute cardiotoxic potential in rats owed to alterations of the cardiovascular function and ultrastructural heart damage. These molecules are also well known in vitro inducers of cell death. The aim of this study was to explore the presence of cardiomyocyte death after repeated subacute exposure of rats to AZA-1 and YTX for 15 days. Because autophagy and apoptosis are often found in dying cardiomyocytes, several autophagic and apoptotic markers were determined by western blot in heart tissues of these rats. The results showed that hearts from YTX-treated rats presented increased levels of the autophagic markers microtubule-associated protein light chain 3-II (LC3-II) and beclin-1, nevertheless AZA-1-treated hearts evidenced increased levels of the apoptosis markers cleaved caspase-3 and -8, cleaved PARP and Fas ligand. Therefore, while YTX-induced damage to the heart triggers autophagic processes, apoptosis activation occurs in the case of AZA-1. For the first time, activation of cell death signals in cardiomyocytes is demonstrated for these toxins with in vivo experiments, which may be related to alterations of the cardiovascular function.

Radiation-resistant, amorphous, all-aromatic poly(arylene ether sulfones) - Synthesis, physical behavior, and degradation characteristics

NASA Technical Reports Server (NTRS)

Lewis, D. A.; O'Donnell, James H.; Hedrick, J. L.; Ward, T. C.; Mcgrath, J. E.

1989-01-01

The effects of Co-60 gamma radiation on a series of poly(arylene ether sulfones) prepared by nucleophilic activated aromatic substitution are investigated experimentally. The preparation of the test compounds is described, and the test results are presented in extensive tables and graphs. Radiation-induced degradation, as measured by SO2 production, was found to be lowest in compounds based on biphenol rather than bisphenol A; these findings were also well correlated with ultimate-tensile-strain measurements.

New prodrugs of two pyrimidine acyclic nucleoside phosphonates: Synthesis and antiviral activity.

PubMed

Krečmerová, Marcela; Dračínský, Martin; Snoeck, Robert; Balzarini, Jan; Pomeisl, Karel; Andrei, Graciela

2017-09-01

New 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy]pyrimidine (PMEO-DAPy) and 1-[2-(phosphonomethoxy)ethyl]-5-azacytosine (PME-5-azaC) prodrugs were prepared with a pro-moiety consisting of carbonyloxymethyl esters (POM, POC), alkoxyalkyl esters, amino acid phosphoramidates and/or tyrosine. The activity of the prodrugs was evaluated in vitro against different virus families. None of the synthesized prodrugs demonstrated activity against RNA viruses but some of them proved active against herpesviruses [including herpes simplex virus (HSV), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV)]. The bis(POC) and the bis(amino acid) phosphoramidate prodrugs of PMEO-DAPy inhibited herpesvirus replication at lower doses than the parent compound although the selectivity against HSV and VZV was only slightly improved compared to PMEO-DAPy. The mono-octadecyl ester of PME-5-azaC emerged as the most potent and selective PME-5-azaC prodrug against HSV, VZV and HCMV with EC 50 's of 0.15-1.12µM while PME-5-azaC only had marginal anti-herpesvirus activity. Although the bis(hexadecylamido-l-tyrosyl) and the bis(POM) esters of PME-5-azaC were also very potent anti-herpesvirus drugs, these were less selective than the mono-octadecyl ester prodrug. Copyright © 2017 Elsevier Ltd. All rights reserved.

Arabidopsis ENHANCED DISEASE SUSCEPTIBILITY1 promotes systemic acquired resistance via azelaic acid and its precursor 9-oxo nonanoic acid.

PubMed

Wittek, Finni; Hoffmann, Thomas; Kanawati, Basem; Bichlmeier, Marlies; Knappe, Claudia; Wenig, Marion; Schmitt-Kopplin, Philippe; Parker, Jane E; Schwab, Wilfried; Vlot, A Corina

2014-11-01

Systemic acquired resistance (SAR) is a form of inducible disease resistance that depends on salicylic acid and its upstream regulator ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1). Although local Arabidopsis thaliana defence responses activated by the Pseudomonas syringae effector protein AvrRpm1 are intact in eds1 mutant plants, SAR signal generation is abolished. Here, the SAR-specific phenotype of the eds1 mutant is utilized to identify metabolites that contribute to SAR. To this end, SAR bioassay-assisted fractionation of extracts from the wild type compared with eds1 mutant plants that conditionally express AvrRpm1 was performed. Using high-performance liquid chromatography followed by mass spectrometry, systemic immunity was associated with the accumulation of 60 metabolites, including the putative SAR signal azelaic acid (AzA) and its precursors 9-hydroperoxy octadecadienoic acid (9-HPOD) and 9-oxo nonanoic acid (ONA). Exogenous ONA induced SAR in systemic untreated leaves when applied at a 4-fold lower concentration than AzA. The data suggest that in planta oxidation of ONA to AzA might be partially responsible for this response and provide further evidence that AzA mobilizes Arabidopsis immunity in a concentration-dependent manner. The AzA fragmentation product pimelic acid did not induce SAR. The results link the C9 lipid peroxidation products ONA and AzA with systemic rather than local resistance and suggest that EDS1 directly or indirectly promotes the accumulation of ONA, AzA, or one or more of their common precursors possibly by activating one or more pathways that either result in the release of these compounds from galactolipids or promote lipid peroxidation. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Arabidopsis ENHANCED DISEASE SUSCEPTIBILITY1 promotes systemic acquired resistance via azelaic acid and its precursor 9-oxo nonanoic acid

PubMed Central

Wittek, Finni; Hoffmann, Thomas; Kanawati, Basem; Bichlmeier, Marlies; Knappe, Claudia; Wenig, Marion; Schmitt-Kopplin, Philippe; Parker, Jane E.; Schwab, Wilfried; Vlot, A. Corina

2014-01-01

Systemic acquired resistance (SAR) is a form of inducible disease resistance that depends on salicylic acid and its upstream regulator ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1). Although local Arabidopsis thaliana defence responses activated by the Pseudomonas syringae effector protein AvrRpm1 are intact in eds1 mutant plants, SAR signal generation is abolished. Here, the SAR-specific phenotype of the eds1 mutant is utilized to identify metabolites that contribute to SAR. To this end, SAR bioassay-assisted fractionation of extracts from the wild type compared with eds1 mutant plants that conditionally express AvrRpm1 was performed. Using high-performance liquid chromatography followed by mass spectrometry, systemic immunity was associated with the accumulation of 60 metabolites, including the putative SAR signal azelaic acid (AzA) and its precursors 9-hydroperoxy octadecadienoic acid (9-HPOD) and 9-oxo nonanoic acid (ONA). Exogenous ONA induced SAR in systemic untreated leaves when applied at a 4-fold lower concentration than AzA. The data suggest that in planta oxidation of ONA to AzA might be partially responsible for this response and provide further evidence that AzA mobilizes Arabidopsis immunity in a concentration-dependent manner. The AzA fragmentation product pimelic acid did not induce SAR. The results link the C9 lipid peroxidation products ONA and AzA with systemic rather than local resistance and suggest that EDS1 directly or indirectly promotes the accumulation of ONA, AzA, or one or more of their common precursors possibly by activating one or more pathways that either result in the release of these compounds from galactolipids or promote lipid peroxidation. PMID:25114016

Molecular structure impacts on secondary organic aerosol formation from glycol ethers

NASA Astrophysics Data System (ADS)

Li, Lijie; Cocker, David R.

2018-05-01

Glycol ethers, a class of widely used solvents in consumer products, are often considered exempt as volatile organic compounds based on their vapor pressure or boiling points by regulatory agencies. However, recent studies found that glycol ethers volatilize at ambient conditions nearly as rapidly as the traditional high-volatility solvents indicating the potential of glycol ethers to form secondary organic aerosol (SOA). This is the first work on SOA formation from glycol ethers. The impact of molecular structure, specifically -OH, on SOA formation from glycol ethers and related ethers are investigated in the work. Ethers with and without -OH, with methyl group hindrance on -OH and with -OH at different location are studied in the presence of NOX and under "NOX free" conditions. Photooxidation experiments under different oxidation conditions confirm that the processing of ethers is a combination of carbonyl formation, cyclization and fragmentation. Bulk SOA chemical composition analysis and oxidation products identified in both gas and particle phase suggests that the presence and location of -OH in the carbon bond of ethers determine the occurrence of cyclization mechanism during ether oxidation. The cyclization is proposed as a critical SOA formation mechanism to prevent the formation of volatile compounds from fragmentation during the oxidation of ethers. Glycol ethers with -CH2-O-CH2CH2OH structure is found to readily form cyclization products, especially with the presence of NOx, which is more relevant to urban atmospheric conditions than without NOx. Glycol ethers are evaluated as dominating SOA precursors among all ethers studied. It is estimated that the contribution of glycol ethers to anthropogenic SOA is roughly 1% of the current organic aerosol from mobile sources. The contribution of glycol ethers to anthropogenic SOA is roughly 1% of the current organic aerosol from mobile sources and will play a more important role in future anthropogenic SOA formation.

Comparative study of the affinity and metabolism of type I and type II binding quinoline carboxamide analogs by cytochrome P450 3A4

PubMed Central

Dahal, Upendra P.; Joswig-Jones, Carolyn; Jones, Jeffrey P.

2011-01-01

Compounds that coordinate to the heme-iron of cytochrome P450 (CYP) enzymes are assumed to increase metabolic stability. However, recently we observed that the type II binding quinoline carboxamide (QCA) compounds were metabolically less stable. To test if the higher intrinsic clearance of type II binding compounds relative to type I binding compounds is general for other metabolic transformations, we synthesized a library of QCA compounds that could undergo N-dealkylation, O-dealkylation, benzylic hydroxylation and aromatic hydroxylation. The results demonstrated that type II binding QCA analogs were metabolically less stable (2 to 12 fold) at sub-saturating concentration compared to type I binding counterparts for all the transformations. When the rates of different metabolic transformations between type I and type II binding compounds were compared, they were found to be in the order of N-demethylation>benzylic hydroxylation> O-demethylation> aromatic hydroxylation. Finally, for the QCA analogs with aza-heteroaromatic rings, we did not detect metabolism in aza-aromatic rings (pyridine, pyrazine, pyrimidine) indicating electronegativity of the nitrogen can change regioselectivity in CYP metabolism. PMID:22087535

Titanium isopropoxide as efficient catalyst for the aza-Baylis-Hillman reaction. Selective formation of alpha-methylene-beta-amino acid derivatives.

PubMed

Balan, Daniela; Adolfsson, Hans

2002-04-05

The direct formation of alpha-methylene-beta-amino acid derivatives is achieved using the aza version of the Baylis-Hillman protocol. The products are readily formed in a three-component one-pot reaction between arylaldehydes, sulfonamides, and alpha,beta-unsaturated carbonyl compounds. The reaction is efficiently catalyzed by titanium isopropoxide and 2-hydroxyquinuclidine in the presence of molecular sieves. The protocol allows for structural variation of the substrates, tolerating electron-poor and electron-rich arylaldehydes and various Michael acceptors.

Biodegradation of bis(1-chloro-2-propyl) ether via initial ether scission and subsequent dehalogenation by Rhodococcus sp. strain DTB.

PubMed

Moreno Horn, Marcus; Garbe, Leif-Alexander; Tressl, Roland; Adrian, Lorenz; Görisch, Helmut

2003-04-01

Rhodococcus sp. strain DTB (DSM 44534) grows on bis(1-chloro-2-propyl) ether (DDE) as sole source of carbon and energy. The non-chlorinated diisopropyl ether and bis(1-hydroxy-2-propyl) ether, however, did not serve as substrates. In ether degradation experiments with dense cell suspensions, 1-chloro-2-propanol and chloroacetone were formed, which indicated that scission of the ether bond is the first step while dehalogenation of the chlorinated C(3)-compounds occurs at a later stage of the degradation pathway. Inhibition of ether scission by methimazole suggested that the first step in degradation is catalyzed by a flavin-dependent enzyme activity. The non-chlorinated compounds 1,2-propanediol, hydroxyacetone, lactate, pyruvate, 1-propanol, propanal, and propionate also supported growth, which suggested that the intermediates 1,2-propanediol and hydroxyacetone are converted to pyruvate or to propionate, which can be channeled into the citric acid cycle by a number of routes. Total release of chloride and growth-yield experiments with DDE and non-chlorinated C(3)-compounds suggested complete biodegradation of the chlorinated ether.

Alkyl substituted cyclic ethers in 2,300 M yr old Transvaal algal stromatolite

NASA Technical Reports Server (NTRS)

Zumberge, J. E.; Nagy, B.

1975-01-01

Two cyclic ethers have been identified for the first time from insoluble polymer-like kerogen in a Precambrian rock by ozonolysis, gas chromatography, and mass spectrometry. The ethers are 2-n-propyl-3-methyltetrahydrofuran and 2-n-propyltetrahydropyran. These compounds could prove to be the oldest indigenous biochemical fossils. The sample was obtained 750 m stratigraphically above the base of the Transvaal Sequence from an outcrop approximately 315 km north-east of Johannesburg, South Africa.

Obligate methylotrophy: evaluation of dimethyl ether as a C1 compound.

PubMed Central

Meyers, A J

1982-01-01

The suitability of dimethyl ether as a C1 compound was examined with the obligate methylobacterium Methylococcus capsulatus (Texas). The ether did not support growth and was not formed during growth on methane; it was an inhibitor of growth and oxidation of methane and a poor oxidation substrate for cell suspensions. NADH stimulation of methane, but not dimethyl ether, oxidation occurred in cell extracts. PMID:6802804

Synthesis and Antifungal in Vitro Evaluation of Pyrazolo[3,4-b]pyridines Derivatives Obtained by Aza-Diels-Alder Reaction and Microwave Irradiation.

PubMed

Quiroga, Jairo; Villarreal, Yazmín; Gálvez, Jaime; Ortíz, Alejandro; Insuasty, Braulio; Abonia, Rodrigo; Raimondi, Marcela; Zacchino, Susana

2017-02-01

A series of pyrazolo[3,4-b]pyridines were prepared by a microwave-assisted aza-Diels-Alder reaction between pyrazolylformimidamides 1 and β-nitrostyrenes 2 in toluene as the solvent. This procedure provides a simple one-step and environmentally friendly methodology with good yields for the synthesis of these compounds. All compounds were tested for antifungal activity against two clinically important fungi Candida albicans and Cryptococcus neoformans. Within the compounds of the series bearing a -CH 3 group on the carbon C-3 of the azole ring (3a-e), the compound without a substituent on the p'-phenyl ring (3a), showed the best activity against both fungi, followed by the p'-Br-phenyl (3c). Within the compounds of the series bearing a tert-butyl group in the carbon C-3 of the azole ring (3f-j), the non-substituted p'-compound (3f) was the most active one, followed by (3h) (p'-Br substituted) that showed the best activity against both fungi. The remaining compounds of this sub-series (3g, i, j) showed similar moderate activities. The antifungal activity of the compounds of the series was found to be correlated with a higher log P and a lower dipole moment in the more active compounds.

Synthesis of Triazole Derivatives of Levoglucosenone As Promising Anticancer Agents: Effective Exploration of the Chemical Space through retro-aza-Michael//aza-Michael Isomerizations.

PubMed

Tsai, Yi-Hsuan; Borini Etichetti, Carla M; Di Benedetto, Carolina; Girardini, Javier E; Martins, Felipe Terra; Spanevello, Rolando A; Suárez, Alejandra G; Sarotti, Ariel M

2018-04-06

The design and synthesis of biomass-derived triazoles and the in vitro evaluation as potential anticancer agents are described. The discovery of base-catalyzed retro-aza-Michael//aza-Michael isomerizations allowed the exploration of the chemical space by affording novel types of triazoles, difficult to obtain otherwise. Following this strategy, 2,4-disubstituted 1,2,3-triazoles could be efficiently obtained from the corresponding 1,4-disubstituted analogues.

LC-MS-MS aboard ship: tandem mass spectrometry in the search for phycotoxins and novel toxigenic plankton from the North Sea.

PubMed

Krock, Bernd; Tillmann, Urban; John, Uwe; Cembella, Allan

2008-11-01

Phycotoxins produced by various species of toxigenic microalgae occurring in the plankton are a global threat to the security of seafood resources and the health of humans and coastal marine ecosystems. This has necessitated the development and application of advanced methods in liquid chromatography coupled to mass spectrometry (LC-MS) for monitoring of these compounds, particularly in plankton and shellfish. Most such chemical analyses are conducted in land-based laboratories on stored samples, and thus much information on the near real-time biogeographical distribution and dynamics of phycotoxins in the plankton is unavailable. To resolve this problem, we conducted ship-board analysis of a broad spectrum of phycotoxins collected directly from the water column on an oceanographic cruise along the North Sea coast of Scotland, Norway, and Denmark. We equipped the ship with a triple-quadrupole linear ion-trap hybrid LC-MS-MS system for detection and quantitative analysis of toxins, such as domoic acid, gymnodimine, spirolides, dinophysistoxins, okadaic acid, pectenotoxins, yessotoxins, and azaspiracids (AZAs). We focused particular attention on the detection of AZAs, a group of potent nitrogenous polyether toxins, because the culprit species associated with the occurrence of these toxins in shellfish has been controversial. Marine toxins were analyzed directly from size-fractionated plankton net tows (20 microm mesh size) and Niskin bottle samples from discrete depths, after rapid methanolic extraction but without any further clean-up. Almost all expected phycotoxins were detected in North Sea plankton samples, with domoic acid and 20-methylspirolide G being most abundant. Although AZA was the least abundant of these toxins, the high sensitivity of the LC-MS-MS enabled detailed quantification, indicating that the highest amounts of AZA-1 were present in the southern Skagerrak in the 3-20 microm size-fraction. The direct on-board toxin measurements enabled isolation of plankton from stations with high AZA-1 levels and from the most suspicious size-fraction, i.e. most likely to contain the AZA-producer. A large number (>100) of crude cultures were established by serial dilution and later screened for the presence of AZAs after several weeks growth. From one crude culture containing AZA, a small dinoflagellate was subsequently isolated and brought into pure culture. We have thus proved that even sophisticated mass spectrometers can be operated in ship laboratories without any limitation caused by vibrations of the ship's engine or by wave movement during heavy seas at wind forces up to nine Beaufort. On-board LC-MS-MS is a valuable method for near real-time analysis of phycotoxins in plankton for studies on bloom dynamics and the fate of toxins in the food web, and for characterization and isolation of putatively toxigenic organisms.

5-Azacytidine combined with 2,4-D improves somatic embryogenesis of Acca sellowiana (O. Berg) Burret by means of changes in global DNA methylation levels.

PubMed

Fraga, Hugo P F; Vieira, Leila N; Caprestano, Clarissa A; Steinmacher, Douglas A; Micke, Gustavo A; Spudeit, Daniel A; Pescador, Rosete; Guerra, Miguel P

2012-12-01

DNA methylation is an epigenetic regulatory mechanism of gene expression which can be associated with developmental phases and in vitro morphogenetic competence in plants. The present work evaluated the effects of 5-azacytidine (AzaC) and 2,4-dichlorophenoxyacetic acid (2,4-D) on Acca sellowiana somatic embryogenesis (SE) and global DNA methylation levels by high-performance liquid chromatography mass spectrometry (HPLC/MS/MS). 2,4-D-free treatments revealed no somatic embryo formation in both accessions tested. Treatments supplemented with 2,4-D pulse plus AzaC in the culture medium resulted in increased embryo formation. In AzaC-free treatment, HPLC/MS/MS analysis showed a gradual increase in methylation levels in cultures of both accessions tested during SE induction. Treatment with AzaC and 2,4-D-free resulted in a marked decrease in methylation for both accessions, ranging from 37.6 to 20.8 %. In treatment with 2,4-D and AzaC combined, the 85 accession showed increasing global methylation levels. Otherwise, the 101X458 accession, in the same treatment, showed a decrease between 10 and 20 days, followed by an increase after 30 days (39.5, 36.2 and 41.6 %). These results indicate that 2,4-D pulse combined with AzaC improves SE induction. However, the conversion phase showed that although positively influencing SE induction, AzaC had a dysregulatory effect on the stage of autotrophic plant formation, resulting in significantly lower conversion rates. The results suggest that DNA methylation dramatically influences SE in Acca sellowiana, and global DNA methylation dynamics are related to morphogenetic response. 5-Azacytidine combined with 2,4-D increases the number of Acca sellowiana somatic embryos. Global DNA methylation is directly affected by these compounds.

Acid-catalyzed rearrangements of flavans to novelbenzofuran derivatives

Treesearch

Richard W. Hemingway; Weiling Peng; Anthony H. Conner; Petrus J. Steynberg; Jan P. Steynberg

1998-01-01

The objective of this work was to define reactions that occur when proanthocyanidins and their derivatives are reacted in the presence of acid catalysts. Pure compounds (either as the free phenols, the methyl ether, or the methyl ether-acetate derivatives) were isolated by a variety of chromatographic methods. Proof of their structure was based mainly on 2D-NMR, as...

Design and synthesis of aryl ether and sulfone hydroxamic acids as potent histone deacetylase (HDAC) inhibitors.

PubMed

Pabba, Chittari; Gregg, Brian T; Kitchen, Douglas B; Chen, Zhen Jia; Judkins, Angela

2011-01-01

A series of novel hydroxamic acid based histone deacetylases (HDAC) inhibitors with aryl ether and aryl sulfone residues at the terminus of a substituted, unsaturated 5-carbon spacer moiety have been synthesized for the first time and evaluated. Compounds with meta- and para-substitution on the aryl ring of ether hydroxamic acids 19c, 20c, 19e, 19f and 19g are potent HDAC inhibitors with activities at low nanomolar levels. Copyright © 2010 Elsevier Ltd. All rights reserved.

Temperature dependences of the retention indices of mono- and polyethylene glycol acetals and ethers on stationary phase DB-1 and enthalpies of their sorption from the gas phase

NASA Astrophysics Data System (ADS)

Zhabina, A. A.; Krasnykh, E. L.

2017-12-01

Gas chromatography is used to study the sorption characteristics and retention of a series of mono-, di-, and triethylene glycol ethers on nonpolar phase DB-1 in the temperature range of 70-180°C. Temperature dependences of the retention indices of the compounds are obtained and their linear character in the investigated range of temperatures is demonstrated. The enthalpies of sorption of the investigated compounds are calculated and analyzed, based on the temperature dependences of the retention factors.

2-[(2-Hy­droxy-4-meth­oxy­benzyl­idene)aza­nium­yl]benzoate monohydrate

PubMed Central

Hang, Zhi-Xi; Dong, Bo; Wang, Xing-Wen

2010-01-01

In the title compound, C15H13NO4·H2O, the Schiff base exists in a zwitterionic form and a bifurcated intra­molecular N—H⋯(O,O) hydrogen bond generates two S(6) rings. The dihedral angle between the two benzene rings is 25.8 (2)°. The crystal structure is stabilized by inter­molecular O—H⋯O hydrogen bonds. PMID:21587989

DFT study on the adsorption of diethyl, ethyl methyl, and dimethyl ethers on the surface of gallium doped graphene

NASA Astrophysics Data System (ADS)

Shokuhi Rad, Ali; Sani, Emad; Binaeian, Ehsan; Peyravi, Majid; Jahanshahi, Mohsen

2017-04-01

In this study, we used density functional theory (DFT) to search on the adsorption properties of three important compounds of ether family; diethyl ether (DEE), ethyl methyl ether (EME), and dimethyl ether (DME) on the surface of Gallium doped graphene (GaG). We used three functionals (B3LYP, wb97xd, and MPW1PW91) for optimization and calculation of adsorption energy. After fully optimization, we scrutinized on the charge allocations on the adsorbed ethers as well as GaG (at the area of interaction) based on natural bond orbitals (NBO). Besides, we have calculated the amount of charge transfer upon adsorption of each analyte. We revel that GaG is an ideal adsorbent for chemisorption of all above-mentioned ethers. There is a little difference between the values of adsorption; -123.5, -120, and -118.3 kJ/mol (based on wb97xd) for DEE, EME, and DME, respectively. We found significant changes in the electronic structure of both adsorbent and adsorbate upon adsorption. Moreover, results of charge analyses confirm GaG is a p-type semiconductor.

AZA-MS: a novel multiparameter mass spectrometry method to determine the intracellular dynamics of azacitidine therapy in vivo

PubMed Central

Unnikrishnan, A; Vo, A N Q; Pickford, R; Raftery, M J; Nunez, A C; Verma, A; Hesson, L B; Pimanda, J E

2018-01-01

The cytidine analogue, 5-azacytidine (AZA; 5-AZA-cR), is the primary treatment for myelodysplastic syndrome and chronic myelomonocytic leukaemia. However, only ~50% of treated patients will respond to AZA and the drivers of AZA resistance in vivo are poorly understood. To better understand the intracellular dynamics of AZA upon therapy and decipher the molecular basis for AZA resistance, we have developed a novel, multiparameter, quantitative mass spectrometry method (AZA-MS). Using AZA-MS, we have accurately quantified the abundance of the ribonucleoside (5-AZA-cR) and deoxyribonucleoside (5-AZA-CdR) forms of AZA in RNA, DNA and the cytoplasm within the same sample using nanogram quantities of input material. We report that although AZA induces DNA demethylation in a dose-dependent manner, it has no corresponding effect on RNA methylation. By applying AZA-MS to primary bone marrow samples from patients undergoing AZA therapy, we have identified that responders accumulate more 5-AZA-CdR in their DNA compared with nonresponders. AZA resistance was not a result of impaired AZA metabolism or intracellular accumulation. Furthermore, AZA-MS has helped to uncover different modes of AZA resistance. Whereas some nonresponders fail to incorporate sufficient 5-AZA-CdR into DNA, others incorporate 5-AZA-CdR and effect DNA demethylation like AZA responders, but show no clinical benefit. PMID:29249821

Property-Guided Synthesis of Aza-Tricyclic Indolines: Development of Gold Catalysis En Route.

PubMed

Barbour, Patrick M; Wang, Wei; Chang, Le; Pickard, Kasey L; Rais, Rana; Slusher, Barbara S; Wang, Xiang

2016-04-28

Antibiotic resistance is a worldwide public health threat that needs to be addressed by improved antibiotic stewardship and continuing development of new chemical entities to treat resistant bacterial infections. Compounds that work alongside known antibiotics as combination therapies offer an efficient and sustainable approach to counteract antibiotic resistance in bacteria. Guided by property-based analysis, a series of aza-tricyclic indolines (ATIs) were synthesized to optimize their physiochemical properties as novel combination therapies with β-lactams to treat methicillin-resistant S. aureus (MRSA) infections. A novel and highly efficient gold-catalyzed tandem cyclization was developed to facilitate the synthesis of these ATIs. One guanidine-containing ATI was discovered to possess both improved anti-MRSA activity and lower mammalian toxicity both in vitro and in vivo. In addition, it also showed significantly enhanced aqueous solubility and metabolic stability. These results indicated that the ATIs are a novel class of anti-MRSA agents suitable for further evaluations as adjuvant therapy in animal model studies.

Organic non-aqueous cation-based redox flow batteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Lu; Huang, Jinhua; Burrell, Anthony

The present invention provides a non-aqueous redox flow battery comprising a negative electrode immersed in a non-aqueous liquid negative electrolyte, a positive electrode immersed in a non-aqueous liquid positive electrolyte, and a cation-permeable separator (e.g., a porous membrane, film, sheet, or panel) between the negative electrolyte from the positive electrolyte. During charging and discharging, the electrolytes are circulated over their respective electrodes. The electrolytes each comprise an electrolyte salt (e.g., a lithium or sodium salt), a transition-metal free redox reactant, and optionally an electrochemically stable organic solvent. Each redox reactant is selected from an organic compound comprising a conjugated unsaturatedmore » moiety, a boron cluster compound, and a combination thereof. The organic redox reactant of the positive electrolyte comprises a tetrafluorohydroquinone ether compound or a tetrafluorocatechol ether compound.« less

α-Imino Esters in Organic Synthesis: Recent Advances.

PubMed

Eftekhari-Sis, Bagher; Zirak, Maryam

2017-06-28

α-Imino esters are useful precursors for the synthesis of a variety of types of natural and unnatural α-amino acid derivatives, with a wide range of biological activities. Due to the adjacent ester group, α-imino esters are more reactive relative to other types of imines and undergo different kinds of reactions, including organometallics addition, metal catalyzed vinylation and alkynylation, aza-Henry, aza-Morita-Baylis-Hillman, imino-ene, Mannich-type, and cycloaddition reactions, as well as hydrogenation and reduction. This review discusses the mechanism, scope, and applications of the reactions of α-imino esters and related compounds in organic synthesis, covering the literature from the last 12 years.

Characterization of isolated 1-aza-adamantan-4-one (C9H13NO) from microwave, millimeter-wave and infrared spectroscopy supported by electronic structure calculations

NASA Astrophysics Data System (ADS)

Pirali, O.; Goubet, M.; Boudon, V.; D'Accolti, L.; Fusco, C.; Annese, C.

2017-08-01

We have synthesized 1-aza-adamantan-4-one (C9H13NO) starting from commercial 1,4-cyclohexanedionemonoethylene acetal and tosylmethylisocianide, following a procedure already described in the literature. The high degree of sample purity was demonstrated by gas chromatography and mass spectrometric measurements and its structure evidenced by 1H and 13C NMR spectroscopy. Among numerous interests in physical chemistry, this target molecule is of high relevance for mechanistic evaluation and the synthesis of novel pharmaceutical compounds. We present a thorough spectroscopic study of this molecule by gas phase vibrational and rotational spectroscopy. Accurate vibrational frequencies have been determined from infrared and far-infrared spectra. The pure rotational spectrum of the molecule has been recorded both by cavity-based Fourier transform microwave spectroscopy in the 2-20 GHz region by supersonically expanding the vapor pressure of the warm sample and by room-temperature absorption spectroscopy in the 140-220 GHz range. Accurate sets of rotational and centrifugal distortion parameters of 1-aza-adamantan-4-one in its ground state and in five vibrationally excited states have been derived from these measurements and compared to accurate quantum chemical calculations. The hyperfine parameters have been discussed in terms of molecular structure around the nitrogen quadrupole nucleus.

[Study on the constituents of petroleum ether fraction of Buxus microphylla].

PubMed

Dai, Zhi-Kai; Liang, Jun; Su, Xiao-Jian; Xu, Qing; Zhang, Hui-Qin

2009-07-01

To study the chemical constituents from the petroleum ether fraction of Buxus microphylla. The petroleum ether fraction of Buxus microphylla was isolated and identified by silica gel column chromatography. And the anticancer activity of different chemical constituents was measured by MTT reduction test. Eight compounds were isolated and identified as lupeol (1), butulin (3), beta-sitosterol (4), stigmasterol (5), dibutyl phthalate (6), 3beta, 30-dihydroxy-lup-20 (29) ene (7), daucosterol (8). Compound 7 inhibited KB cells' proliferation in a dose-dependent manner. Compounds 2 - 5, 7, 8 are isolated from this genus for the first time. Compound 7 has certainly anticancer effects.

Routes to ultra-pure alkyls of indium and gallium and their adducts with ethers, phosphines and amines

NASA Astrophysics Data System (ADS)

Jones, Anthony C.; Holliday, A. Kenneth; Cole-Hamilton, David J.; Ahmad, M. Munir; Gerrard, Neil D.

1984-09-01

Electrolysis of tetrahydrofuran (thf) solutions of dimethylmagnesium containing tetraethylammonium percholrate using a gallium anode gives [Me 3Ga·thf], but higher yields of both [Me 3Ga·thf] and [Me 3In·thf] are obtained on electrolysis of thf solutions of Grignard reagents with sacrificial metal anodes in the absence of a carrying electrolyte. The thf adducts can be converted into adducts with other Lewis bases, [ Me3M· L], M = Ga or In, L = PMe 3, PEt 3, NEt 3, by simple base exchange reactions. Base-free trimethylgallium can be prepared from: (i) reaction of methyl iodide with the intermetallic compound [Mg 5Ga 2] in a high boiling ether; (ii) electrolysis of Grignard reagents in high boiling ethers using sacrificial gallium anodes; (iii) reactions of GaCl 3 with Grignard reagents in high boiling ethers or (iv) ether exchange reaction between [Me 3Ga·OEt 2] and high boiling ethers. All of these reactions lead to adducts between trimethylgallium and the high boiling ether which, on heating, decompose to give base-free trimethylgallium. [Me 3Ga·OEt 2] can be prepared from reaction of Grignard reagents with gallium trichloride in diethylether or from electrolysis of Grignard reagents in diethyl ether using a sacrificial gallium anode. Similar reactions using an indium anode lead to [Me 3In·OEt 2] from which base-free trimethylindium can be liberated using known chemistry. The use of alkyls prepared in this way for vapour phase epitaxy as well as the purity of the alkyls are discussed.

Synthesis and structure-activity relationship of dicationic diaryl ethers as novel potent anti-MRSA and anti-VRE agents.

PubMed

Hu, Laixing; Kully, Maureen L; Boykin, David W; Abood, Norman

2009-08-15

A series of dicationic diaryl ethers have been synthesized and evaluated for in vitro antibacterial activities, including drug resistant bacterial strains. Most of these compounds have shown potent antibacterial activities. Several compounds, such as piperidinyl and thiomorpholinyl compounds 9e and 9l, improved the antimicrobial selectivity and kept potent anti-MRSA and anti-VRE activity. The most potent bis-indole diphenyl ether 19 exhibited anti-MRSA MIC value of 0.06 microg/mL and enhanced antimicrobial selectivity.

Atmospheric degradation of 2-chloroethyl vinyl ether, allyl ether and allyl ethyl ether: Kinetics with OH radicals and UV photochemistry.

PubMed

Antiñolo, M; Ocaña, A J; Aranguren, J P; Lane, S I; Albaladejo, J; Jiménez, E

2017-08-01

Unsaturated ethers are oxygenated volatile organic compounds (OVOCs) emitted by anthropogenic sources. Potential removal processes in the troposphere are initiated by hydroxyl (OH) radicals and photochemistry. In this work, we report for the first time the rate coefficients of the gas-phase reaction with OH radicals (k OH ) of 2-chloroethyl vinyl ether (2ClEVE), allyl ether (AE), and allyl ethyl ether (AEE) as a function of temperature in the 263-358 K range, measured by the pulsed laser photolysis-laser induced fluorescence technique. No pressure dependence of k OH was observed in the 50-500 Torr range in He as bath gas, while a slightly negative T-dependence was observed. The temperature dependent expressions for the rate coefficients determined in this work are: The estimated atmospheric lifetimes (τ OH ) assuming k OH at 288 K were 3, 2, and 4 h for 2ClEVE, AE and AEE, respectively. The kinetic results are discussed in terms of the chemical structure of the unsaturated ethers by comparison with similar compounds. We also report ultraviolet (UV) and infrared (IR) absorption cross sections (σ λ and σ(ν˜), respectively). We estimate the photolysis rate coefficients in the solar UV actinic region to be less than 10 -7 s -1 , implying that these compounds are not removed from the atmosphere by this process. In addition, from σ(ν˜) and τ OH , the global warming potential of each unsaturated ether was calculated to be almost zero. A discussion on the atmospheric implications of the titled compounds is presented. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hydrosilylation induced by N→Si intramolecular coordination: spontaneous transformation of organosilanes into 1-aza-silole-type molecules in the absence of a catalyst.

PubMed

Novák, Miroslav; Dostál, Libor; Alonso, Mercedes; De Proft, Frank; Růžička, Aleš; Lyčka, Antonín; Jambor, Roman

2014-02-24

Our attempts to synthesize the N→Si intramolecularly coordinated organosilanes Ph2 L(1) SiH (1 a), PhL(1) SiH2 (2 a), Ph2 L(2) SiH (3 a), and PhL(2) SiH2 (4 a) containing a CH=N imine group (in which L(1) is the C,N-chelating ligand {2-[CH=N(C6 H3 -2,6-iPr2)]C6 H4}(-) and L(2) is {2-[CH=N(tBu)]C6 H4}(-)) yielded 1-[2,6-bis(diisopropyl)phenyl]-2,2-diphenyl-1-aza-silole (1), 1-[2,6-bis(diisopropyl)phenyl]-2-phenyl-2-hydrido-1-aza-silole (2), 1-tert-butyl-2,2-diphenyl-1-aza-silole (3), and 1-tert-butyl-2-phenyl-2-hydrido-1-aza-silole (4), respectively. Isolated organosilicon amides 1-4 are an outcome of the spontaneous hydrosilylation of the CH=N imine moiety induced by N→Si intramolecular coordination. Compounds 1-4 were characterized by NMR spectroscopy and X-ray diffraction analysis. The geometries of organosilanes 1 a-4 a and their corresponding hydrosilylated products 1-4 were optimized and fully characterized at the B3LYP/6-31++G(d,p) level of theory. The molecular structure determination of 1-3 suggested the presence of a Si-N double bond. Natural bond orbital (NBO) analysis, however, shows a very strong donor-acceptor interaction between the lone pair of the nitrogen atom and the formal empty p orbital on the silicon and therefore, the calculations show that the Si-N bond is highly polarized pointing to a predominantly zwitterionic Si(+) N(-) bond in 1-4. Since compounds 1-4 are hydrosilylated products of 1 a-4 a, the free energies (ΔG298), enthalpies (ΔH298), and entropies (ΔH298) were computed for the hydrosilylation reaction of 1 a-4 a with both B3LYP and B3LYP-D methods. On the basis of the very negative ΔG298 values, the hydrosilylation reaction is highly exergonic and compounds 1 a-4 a are spontaneously transformed into 1-4 in the absence of a catalyst. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rational design of a low molecular weight, stable, potent, and long-lasting GPR103 aza-β3-pseudopeptide agonist.

PubMed

Neveu, Cindy; Lefranc, Benjamin; Tasseau, Olivier; Do-Rego, Jean-Claude; Bourmaud, Adèle; Chan, Philippe; Bauchat, Patrick; Le Marec, Olivier; Chuquet, Julien; Guilhaudis, Laure; Boutin, Jean A; Ségalas-Milazzo, Isabelle; Costentin, Jean; Vaudry, Hubert; Baudy-Floc'h, Michèle; Vaudry, David; Leprince, Jérôme

2012-09-13

26RFa, a novel RFamide neuropeptide, is the endogenous ligand of the former orphan receptor GPR103. Intracerebroventricular injection of 26RFa and its C-terminal heptapeptide, 26RFa((20-26)), stimulates food intake in rodents. To develop potent, stable ligands of GPR103 with low molecular weight, we have designed a series of aza-β(3)-containing 26RFa((20-26)) analogues for their propensity to establish intramolecular hydrogen bonds, and we have evaluated their ability to increase [Ca(2+)](i) in GPR103-transfected cells. We have identified a compound, [Cmpi(21),aza-β(3)-Hht(23)]26RFa((21-26)), which was 8-fold more potent than 26RFa((20-26)) in mobilizing [Ca(2+)](i). This pseudopeptide was more stable in serum than 26RFa((20-26)) and exerted a longer lasting orexigenic effect in mice. This study constitutes an important step toward the development of 26RFa analogues that could prove useful for the treatment of feeding disorders.

CO-OCCURRENCE OF METHYL- TERT-BUTYL ETHER (MTBE) AND BTEX COMPOUNDS AT MARINAS IN A LARGE RESEVOIR

EPA Science Inventory

Methyl tert-butyl ether (MTBE) is released into the environment as one of some gasoline components, not as a pure compound. BTEX compounds (benzene, tolune, ethylbenzene, and xylenes) are major volatile constituents found in gasoline and are water soluble and mobile. This study...

GC/GCMS analysis of the petroleum ether and dichloromethane extracts of Moringa oleifera roots

PubMed Central

Faizi, Shaheen; Sumbul, Saima; Versiani, Muhammed Ali; Saleem, Rubeena; Sana, Aisha; Siddiqui, Hira

2014-01-01

Objective To explore the phytochemical constituents from petroleum ether and dichloromethane extracts of Moringa oleifera (M. oleifera) roots using GC/GC-MS. Methods A total of 5.11 kg fresh and undried crushed root of M. oleifera were cut into small pieces and extracted with petroleum ether and dichloromethane (20 L each) at room temperature for 2 d. The concentrated extracts were subjected to their GC-MS analysis. Results The GC-MS analysis of the petroleum ether and dichloromethane extracts of M. oleifera roots, which showed promising biological activities, has resulted in the identification 102 compounds. These constituents belong to 15 classes of compounds including hydrocarbons, fatty acids, esters, alcohols, isothiocyanate, thiocyanate, pyrazine, aromatics, alkamides, cyanides, steroids, halocompounds, urea and N-hydroxyimine derivatives, unsaturated alkenamides, alkyne and indole. GC/GC-MS studies on petroleum ether extract of the roots revealed that it contained 39 compounds, belonging to nine classes. Cyclooctasulfur S8 has been isolated as a pure compound from the extract. The major compounds identified from petroleum ether extract were trans-13-docosene (37.9%), nonacosane (32.6%), cycloartenol (28.6%) nonadecanoic acid (13.9%) and cyclooctasulfur S8 (13.9%). Dichloromethane extract of the roots was composed of 63 compounds of which nasimizinol (58.8%) along with oleic acid (46.5%), N-benzyl-N-(7-cyanato heptanamide (38.3%), N-benzyl-N-(1-chlorononyl) amide (30.3%), bis [3-benzyl prop-2-ene]-1-one (19.5%) and N, N-dibenzyl-2-ene pent 1, 5-diamide (11.6%) were the main constituents. Conclusions This study helps to predict the formula and structure of active molecules which can be used as drugs. This result also enhances the traditional usage of M. oleifera which possesses a number of bioactive compounds. PMID:25183335

Stable divalent germanium, tin and lead amino(ether)-phenolate monomeric complexes: structural features, inclusion heterobimetallic complexes, and ROP catalysis.

PubMed

Wang, Lingfang; Roşca, Sorin-Claudiu; Poirier, Valentin; Sinbandhit, Sourisak; Dorcet, Vincent; Roisnel, Thierry; Carpentier, Jean-François; Sarazin, Yann

2014-03-21

Stable germanium(II) and lead(II) amido complexes {LO(i)}M(N(SiMe3)2) (M = Ge(II), Pb(II)) bearing amino(ether)phenolate ligands are readily available using the proteo-ligands {LO(i)}H of general formula 2-CH2NR2-4,6-tBu2-C6H2OH (i = 1, NR2 = N((CH2)2OCH3)2; i = 2, NR2 = NEt2; i = 3, NR2 = aza-15-crown-5) and M(N(SiMe3)2)2 precursors. The molecular structures of these germylenes and plumbylenes, as well as those of {LO(3)}GeCl, {LO(3)}SnCl and of the congeneric {LO(4)}Sn(II)(N(SiMe3)2) where NR2 = aza-12-crown-4, have been determined crystallographically. All complexes are monomeric, with 3-coordinate metal centres. The phenolate systematically acts as a N^O(phenolate) bidentate ligand, with no interactions between the metal and the O(side-arm) atoms in these cases (for {LO(1)}(-), {LO(3)}(-) and {LO(4)}(-)) where they could potentially arise. For each family, the lone pair of electrons essentially features ns(2) character, and there is little, if any, hybridization of the valence orbitals. Heterobimetallic complexes {LO(3)}M(N(SiMe3)2)·LiOTf, where the Li(+) cation sits inside the tethered crown-ether, were prepared by reaction of {LO(3)}M(N(SiMe3)2) and LiOTf (M = Ge(II), Sn(II)). The inclusion of Li(+) (featuring a close contact with the triflate anion) in the macrocycle bears no influence on the coordination sphere of the divalent tetrel element. In association with iPrOH, the amido germylenes, stannylenes and plumbylenes catalyse the controlled polymerisation of L- and racemic lactide. The activity increases linearly according to Ge(II) ≪ Sn(II) ≪ Pb(II). The simple germylenes generate very sluggish catalysts, but the activity is significantly boosted if the heterobimetallic complex {LO(3)}Ge(N(SiMe3)2)·LiOTf is used instead. On the other hand, with 10-25 equiv. of iPrOH, the plumbylenes afford highly active binary catalysts, converting 1000 or 5000 equiv. of monomer at 60 °C within 3 or 45 min, respectively, in a controlled fashion.

Azelaic acid reduced senescence-like phenotype in photo-irradiated human dermal fibroblasts: possible implication of PPARγ.

PubMed

Briganti, Stefania; Flori, Enrica; Mastrofrancesco, Arianna; Kovacs, Daniela; Camera, Emanuela; Ludovici, Matteo; Cardinali, Giorgia; Picardo, Mauro

2013-01-01

Azelaic acid (AzA) has been used for the treatment for inflammatory skin diseases, such as acne and rosacea. Interestingly, an improvement in skin texture has been observed after long-time treatment with AzA. We previously unrevealed that anti-inflammatory activity of AzA involves a specific activation of PPARγ, a nuclear receptor that plays a relevant role in inflammation and even in ageing processes. As rosacea has been considered as a photo-aggravated disease, we investigated the ability of AzA to counteract stress-induced premature cell senescence (SIPS). We employed a SIPS model based on single exposure of human dermal fibroblasts (HDFs) to UVA and 8-methoxypsoralen (PUVA), previously reported to activate a senescence-like phenotype, including long-term growth arrest, flattened morphology and increased synthesis of matrix metalloproteinases (MMPs) and senescence-associated β-galactosidase (SA-β-gal). We found that PUVA-treated HDFs grown in the presence of AzA maintained their morphology and reduced MMP-1 release and SA-β-galactosidase-positive cells. Moreover, AzA induced a reduction in ROS generation, an up-modulation of antioxidant enzymes and a decrease in cell membrane lipid damages in PUVA-treated HDFs. Further evidences of AzA anti-senescence effect were repression of p53 and p21, increase in type I pro-collagen and abrogation of the enhanced expression of growth factors, such as HGF and SCF. Interestingly, PUVA-SIPS showed a decreased activation of PPARγ and AzA counteracted this effect, suggesting that AzA effect involves PPARγ modulation. All together these data showed that AzA interferes with PUVA-induced senescence-like phenotype and its ability to activate PPAR-γ provides relevant insights into the anti-senescence mechanism. © 2013 John Wiley & Sons A/S.

Cathelicidin, kallikrein 5, and serine protease activity is inhibited during treatment of rosacea with azelaic acid 15% gel

PubMed Central

Coda, Alvin B.; Hata, Tissa; Miller, Jeremiah; Audish, David; Kotol, Paul; Two, Aimee; Shafiq, Faiza; Yamasaki, Kenshi; Harper, Julie C.; Del Rosso, James Q.; Gallo, Richard L.

2014-01-01

Background Excess cathelicidin and kallikrein 5 (KLK5) have been hypothesized to play a role in the pathophysiology of rosacea. Objective We sought to evaluate the effects of azelaic acid (AzA) on these elements of the innate immune system. Methods Gene expression and protease activity were measured in laboratory models and patients with rosacea during a 16-week multicenter, prospective, open-label study of 15% AzA gel. Results AzA directly inhibited KLK5 in cultured keratinocytes and gene expression of KLK5, Toll-like receptor-2, and cathelicidin in mouse skin. Patients with rosacea showed reduction in cathelicidin and KLK5 messenger RNA after treatment with AzA gel. Subjects without rosacea had lower serine protease activity (SPA) than patients with rosacea. Distinct subsets of patients with rosacea who had high and low baseline SPA were identified, and patients with high baseline exhibited a statistically significant reduction of SPA with 15% AzA gel treatment. Limitations Study size was insufficient to predict clinical efficacy based on the innate immune response to AzA. Conclusions These results show that cathelicidin and KLK5 decrease in association with AZA exposure. Our observations suggest a new mechanism of action for AzA and that SPA may be a useful biomarker for disease activity. PMID:23871720

Incombustible resin composition

NASA Technical Reports Server (NTRS)

Akima, T.

1982-01-01

Incombustible resin compositions composed of aromatic compounds were obtained through (1) combustion polymer material and (2) bisphenol A or halogenated bisphenol A and bisphenol A diglycidl ether or halogenated bisphenol A diglycidyl ether. The aromatic compound is an adduct of bifunctional phenols and bifunctional epoxy resins.

[Chalcones from Bauhinia glauca subsp. pernervosa].

PubMed

Wu, Zengbao; Wang, Bin; Zhao, Yuying; Yang, Xiuwei; Liang, Hong

2009-07-01

To study the chemical constituents of Bauhinia glauca subsp. pernervosa. The coulis of B. glauca subsp. pernervosa were extracted with 95% EtOH at room temperature. The compounds were isolated and separated by chromatographic techniques, and structures were identified by spectroscopic methods. Seven chalcones were isolated and identified: butein-4-methyl ether (1), isoliquiritigenin (2), butein (3), isoliquiritigenin-2'-methyl ether (4), 2',4'-dihydroxychalcone (5), isoliquiritigenin-4-methyl ether (6), 4-hydroxy-2',4'-dimethoxychalcone (7). Compounds 1, 3, and 7 were isolated from the genus Bauhinia for the first time, the other compounds were obtained from this plant for the first time.

2[prime] and 3[prime] Carboranyl uridines and their diethyl ether adducts

DOEpatents

Soloway, A.H.; Barth, R.F.; Anisuzzaman, A.K.; Alam, F.; Tjarks, W.

1992-12-15

A process is described for preparing carboranyl uridine nucleoside compounds and their diethyl ether adducts, which exhibit a tenfold increase in boron content over prior art boron containing nucleoside compounds. The carboranyl uridine nucleoside compounds exhibit enhanced lipophilicity and hydrophilic properties adequate to enable solvation in aqueous media for subsequent incorporation of the compounds in methods for boron neutron capture therapy in mammalian tumor cells. No Drawings

2' and 3' Carboranyl uridines and their diethyl ether adducts

DOEpatents

Soloway, Albert H.; Barth, Rolf F.; Anisuzzaman, Abul K.; Alam, Fazlul; Tjarks, Werner

1992-01-01

There is disclosed a process for preparing carboranyl uridine nucleoside compounds and their diethyl ether adducts, which exhibit a tenfold increase in boron content over prior art boron containing nucleoside compounds. Said carboranyl uridine nucleoside compounds exhibit enhanced lipophilicity and hydrophilic properties adequate to enable solvation in aqueous media for subsequent incorporation of said compounds in methods for boron neutron capture therapy in mammalian tumor cells.

Formation of Azaspiracids-3, -4, -6, and -9 via decarboxylation of carboxyazaspiracid metabolites from shellfish.

PubMed

McCarron, Pearse; Kilcoyne, Jane; Miles, Christopher O; Hess, Philipp

2009-01-14

The azaspiracid (AZA) class of phycotoxins has been responsible for extended closures of shellfisheries in various locations around Europe, where levels of AZA1-3 are regulated in shellfish. Since their discovery in 1995, AZAs have been the focus of much research, resulting in the discovery of numerous analogues. During studies of procedures for processing of AZA-contaminated mussels ( Mytilus edulis ), an unusual phenomenon was observed involving AZA3. In uncooked tissues, AZA3 levels would increase significantly when heated for short periods of time in the absence of water loss. A similar increase in AZA3 concentrations occurred during storage of shellfish tissue reference materials for several months at temperatures as low as 4 degrees C. Concentrations of AZA1 and AZA2 did not change during these experiments. Several possible explanations were investigated, including an AZA3-specific matrix effect upon heating of tissues, release of AZA3 from the matrix, and formation of AZA3 from a precursor. Preliminary experiments indicated that toxin conversion was responsible, and more detailed studies focused on this possibility. LC-MS analysis of heating trials, deuterium labeling experiments, and kinetic studies demonstrated that a carboxylated AZA analogue, AZA17, undergoes rapid decarboxylation when heated to produce AZA3. Heat-induced decarboxylation of AZA19, AZA21, and AZA23 to form AZA6, AZA4, and AZA9, respectively, was also demonstrated. This finding is of great significance in terms of procedures used in the processing of shellfish for regulatory analysis, and it exemplifies the role that chemical analysis can play in understanding the contribution of metabolic processes to the toxin profiles observed in shellfish samples.

Maleate/vinyl ether UV-cured coatings: Effects of composition on curing and properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noren, G.K.

1996-10-01

The effect of the composition of the maleate polyester and the vinyl ether terminated compound on their UV-curing and properties has been investigated. Linear unsaturated polyester resins based on maleic anhydride and 1,5-pentane diol were synthesized. The molecular weight of the unsaturated polyesters was varied by changing the ratio of maleic anhydride to 1,5-pentane diol and the double bond equivalent weight was varied by replacing maleic anhydride with succinic anhydride. Coating formulations containing these unsaturated polyesters, triethylene glycol divinyl ether and a free radical photoinitiator were crosslinked in the presence of UV light. The coatings were very brittle, exhibiting tensilemore » strengths in the range of 1.5-4.0 MPa and elongations of only 3-7%. Diethyl maleate and isobutyl vinyl ether were effective diluents for reducing viscosity but reduced the cure speed. A vinyl ether urethane oligomer was synthesized and enhanced the flexibility and toughness of the coatings when substituted for triethylene glycol divinyl ether.« less

Synthesis and electronic factors in thermal cyclodimerization of functionalized aromatic trifluorovinyl ethers.

PubMed

Spraul, Bryan K; Suresh, S; Jin, Jianyong; Smith, Dennis W

2006-05-31

A series of 19 p-substituted aromatic trifluorovinyl ether compounds were prepared from versatile intermediate p-Br-C(6)H(4)-O-CF=CF(2) and underwent thermal radical mediated cyclodimerization to new difunctional compounds containing the 1,2-disubstituted perfluorocyclobutyl (PFCB) linkage. The synthetic scope demonstrates the functional group transformation tolerance of the fluorovinyl ether, and the dimers are useful as monomers for traditional step-growth polymerization methods. (19)F NMR spectra confirmed that p-substitution affects the trifluorovinyl ether group chemical shifts. The first kinetic studies and substituent effects on thermal cyclodimerization were performed, and the results indicated that electron-withdrawing groups slow the rate of cyclodimerization. The data were further analyzed using the Hammett equation, and reaction constants (rho) of -0.46 at 120 degrees C and -0.59 at 130 degrees C were calculated. This study presents the first liner free energy relationship reported for the cyclodimerization of aromatic trifluorovinyl ethers to PFCB compounds.

The Discovery of Crown Ethers

NASA Astrophysics Data System (ADS)

Pedersen, Charles J.

1988-07-01

The discovery of the crown ethers stemmed from efforts to control the catalytic activity of vanadium and copper by complexation with multidentate ligands. The first crown ether, 2,3,11,12-dibenzo-1,4,7,10,13,16-hexaoxacyclo-octadeca-2,11-diene, was obtained in 0.4% yield during an attempt to prepare a phenolic ligand from catechol and bis(2-chloroethyl)ether. This compound, which complexed with the sodium cation, was the first compound known to display such activity and became known as dibenzo-18-crown-6, an 18-atom heterocycle containing 6 oxygen atoms. Some 60 related compounds were made involving heterocyclic rings containing 12 to 60 atoms including 4 and 10 oxygen atoms. There are optimum polyether ring sizes for the different alkali metal cations: 15 to 18 for sodium, 18 for potassium, and 18 to 21 for cesium. Complexes having polyether to cation ratios of 1:1, 3:2, and 2:1 were prepared. Solubilization of inorganic salts in aprotic solvents, especially by saturated crown ethers, was demonstrated.

Steroid catechol degradation: disecoandrostane intermediates accumulated by Pseudomonas transposon mutant strains.

PubMed

Leppik, R A

1989-07-01

Eleven transposon mutant strains affected in bile acid catabolism were each found to form yellow, muconic-like intermediates from bile acids. To characterize these unstable intermediates, media from the growth of one of these mutants with deoxycholic acid was treated with ammonia, then the crude product was methylated with diazomethane. Four compounds were subsequently isolated; spectral evidence suggested that they were methyl 12 alpha-hydroxy-3-oxo-23,24-dinorchola-1,4-dien-22-oate, methyl 4-aza-12 beta-hydroxy-9(10)-secoandrosta-1,3,5-triene-9,17-dione-3-carboxyl ate, 4-aza-9 alpha, 12 beta-dihydroxy-9(10)-secoandrosta-1,3,5-trien-17-one-3- methyl carboxylate and 4 alpha-[3'-propionic acid]-5-amino-7 beta-hydroxy-7 alpha beta-methyl- 3a alpha, 4,7,7a-tetrahydro-1-indanone-delta-lactam. It is proposed that the mutants are blocked in the utilization of such muconic-like compounds as the 3,12 beta-dihydroxy-5,9,17-trioxo-4(5),9(10)- disecoandrostal (10),2-dien-4-oic acid formed from deoxycholic acid. A further mutant was examined, which converted deoxycholic acid to 12 alpha-hydroxyandrosta-1,4-dien-3,17-dione, but accumulated yellow products from steroids which lacked a 12 alpha-hydroxy function, such as chenodeoxycholic acid. The products from the latter acid were treated as above; spectral evidence suggested that the two compounds isolated were methyl 4-aza-7-hydroxy-9(10)-secoandrosta-1,3,5- triene-9,17-dione-3-carboxylate and 4 alpha-[1'alpha-hydroxy-3'-propionic acid]-5-amino-7a beta-methyl-3a alpha,4,7,7a-tetrahydro-1-indanone-delta-lactam.

Signals of Systemic Immunity in Plants: Progress and Open Questions

PubMed Central

Ádám, Attila L.; Nagy, Zoltán Á.; Kátay, György; Mergenthaler, Emese; Viczián, Orsolya

2018-01-01

Systemic acquired resistance (SAR) is a defence mechanism that induces protection against a wide range of pathogens in distant, pathogen-free parts of plants after a primary inoculation. Multiple mobile compounds were identified as putative SAR signals or important factors for influencing movement of SAR signalling elements in Arabidopsis and tobacco. These include compounds with very different chemical structures like lipid transfer protein DIR1 (DEFECTIVE IN INDUCED RESISTANCE1), methyl salicylate (MeSA), dehydroabietinal (DA), azelaic acid (AzA), glycerol-3-phosphate dependent factor (G3P) and the lysine catabolite pipecolic acid (Pip). Genetic studies with different SAR-deficient mutants and silenced lines support the idea that some of these compounds (MeSA, DIR1 and G3P) are activated only when SAR is induced in darkness. In addition, although AzA doubled in phloem exudate of tobacco mosaic virus (TMV) infected tobacco leaves, external AzA treatment could not induce resistance neither to viral nor bacterial pathogens, independent of light conditions. Besides light intensity and timing of light exposition after primary inoculation, spectral distribution of light could also influence the SAR induction capacity. Recent data indicated that TMV and CMV (cucumber mosaic virus) infection in tobacco, like bacteria in Arabidopsis, caused massive accumulation of Pip. Treatment of tobacco leaves with Pip in the light, caused a drastic and significant local and systemic decrease in lesion size of TMV infection. Moreover, two very recent papers, added in proof, demonstrated the role of FMO1 (FLAVIN-DEPENDENT-MONOOXYGENASE1) in conversion of Pip to N-hydroxypipecolic acid (NHP). NHP systemically accumulates after microbial attack and acts as a potent inducer of plant immunity to bacterial and oomycete pathogens in Arabidopsis. These results argue for the pivotal role of Pip and NHP as an important signal compound of SAR response in different plants against different pathogens. PMID:29642641

Formulation Studies of InhA inhibitors and Combination therapy to improve efficacy against Mycobacterium tuberculosis

PubMed Central

Knudson, Susan E.; Cummings, Jason E.; Bommineni, Gopal R.; Pan, Pan; Tonge, Peter J.; Slayden, Richard A.

2016-01-01

Summary Previously, structure-based drug design was used to develop substituted diphenyl ethers with potency against the Mycobacterium tuberculosis (Mtb) enoyl-ACP reductase (InhA), however, the highly lipophilic centroid compound, SB-PT004, lacked sufficient efficacy in the acute murine Mtb infection model. A next generation series of compounds were designed with improved specificity, potency against InhA, and reduced cytotoxicity in vitro, but these compounds also had limited solubility. Accordingly, solubility and pharmacokinetics studies were performed to develop formulations for this class and other experimental drug candidates with high logP values often encountered in drug discovery. Lead diphenyl ethers were formulated in co-solvent and Self-Dispersing Lipid Formulations (SDLFs) and evaluated in a rapid murine Mtb infection model that assesses dissemination to and bacterial burden in the spleen. In vitro synergy studies were performed with the lead diphenyl ether compounds, SB-PT070 and SB-PT091, and rifampin (RIF), which demonstrated an additive effect, and that guided the in vivo studies. Combinatorial therapy in vivo studies with these compounds delivered in our Self-Micro Emulsifying Drug Delivery System (SMEDDS) resulted in an additional 1.4 log10 CFU reduction in the spleen of animals co-treated with SB-PT091 and RIF and an additional 1.7 log10 reduction in the spleen with animals treated with both SB-PT070 and RIF. PMID:27865404

Analogues of 2-aminopyridine-based selective inhibitors of neuronal nitric oxide synthase with increased bioavailability

PubMed Central

Lawton, Graham R.; Ranaivo, Hantamalala Ralay; Chico, Laura K.; Ji, Haitao; Xue, Fengtian; Martásek, Pavel; Roman, Linda J.; Watterson, D. Martin; Silverman, Richard B.

2009-01-01

Overproduction of nitric oxide by neuronal nitric oxide synthase (nNOS) has been linked to several neurodegenerative diseases. We have recently designed potent and isoform selective inhibitors of nNOS, but the lead compound contains several basic functional groups. A large number of charges and hydrogen bond donors can impede the ability of molecules to cross the blood brain barrier and thereby limit the effectiveness of potential neurological therapeutics. Replacement of secondary amines in our lead compound with neutral ether and amide groups was made to increase bioavailability and to determine if the potency and selectivity of the inhibitor would be impacted. An ether analogue has been identified that retains a similar potency and selectivity to that of the lead compound, and shows increased ability to penetrate the blood brain barrier. PMID:19268602

"Crown Ether" Synthesis: An Organic Laboratory Experiment.

ERIC Educational Resources Information Center

Field, Kurt W.; And Others

1979-01-01

This experiment is designed to acquaint the student with a macromolecular synthesis of a crown ether type compound. The starting materials are readily available and the product, a cyclic polyether, belongs to a class of compounds that has aroused the interest of chemist and biologist alike. (Author/BB)

AFOSR Technical Report Summaries, April-June 1986,

DTIC Science & Technology

1986-06-01

C1HARGE DENSITY. ELECTRODES. INTERrACIAL TENSION. PRESSURE, SIIRFACE PROPERTIES. CORROSION INHIBITION, MOLECULES, ORGANIC COMPOUNDS . SORPTION . FILMS... Perfluorinated derivatives of hydrocarbon Compounds usually ewhibit different propeties than their hydrocarbon analogues. The perfluoro crown ether-s are m.arkedly...Binary Hydrocarbon Mixtures, AD-A166 130 Materials for Emergency Repair AD-A167 094 of Runways. -BROMINE COMPOUNDS AD-Ai64 225 tCHEMICAL LASERS Analysis of

Thiophenyl ether disiloxanes and trisiloxanes useful as lubricant fluids

NASA Technical Reports Server (NTRS)

Bilow, N.; Akawie, R. I. (Inventor)

1974-01-01

The characteristics of organosilicon compounds for lubrication under extreme conditions are discussed. The substances considered are thiophenyl ether disiloxanes and trisiloxanes. These substances have low pour points and a high degree of radiation resistance. Substitution of sulfur for the phenoxy group oxygen of either siloxane compounds has been found to result in a marked improvement in lubricity. The chemical formulas of the organic compounds are presented.

Decreased expression of connective tissue growth factor in non-small cell lung cancer is associated with clinicopathological variables and can be restored by epigenetic modifiers.

PubMed

Drzewiecka, Hanna; Gałęcki, Bartłomiej; Jarmołowska-Jurczyszyn, Donata; Kluk, Andrzej; Dyszkiewicz, Wojciech; Jagodziński, Paweł P

2016-09-01

Recent studies indicated undisputed contribution of connective tissue growth factor (CTGF) in the development of many cancers, including non-small cell lung cancer (NSCLC). However, the functional role and regulation of CTGF expression during tumorigenesis remain elusive. Our goal was to determine CTGF transcript and protein levels in tumoral and matched control tissues from 98 NSCLC patients, to correlate the results with clinicopathological features and to investigate whether the CTGF expression can be epigenetically regulated in NSCLC. We used quantitative PCR, Western blotting and immunohistochemistry to evaluate CTGF expression in lung cancerous and histopathologically unchanged tissues. We tested the impact of 5-Aza-2'-deoxycytidine (5-dAzaC) and trichostatin A (TSA) on CTGF transcript and protein levels in NSCLC cells (A549, Calu-1). DNA methylation status of the CTGF regulatory region was evaluated by bisulfite sequencing. The influence of 5-dAzaC and TSA on NSCLC cells viability and proliferation was monitored by the trypan blue assay. We found significantly decreased levels of CTGF mRNA and protein (both p < 0.0000001) in cancerous tissues of NSCLC patients. Down-regulation of CTGF occurred regardless of gender in all histological subtypes of NSCLC. Moreover, we showed that 5-dAzaC and TSA were able to restore CTGF mRNA and protein contents in NSCLC cells. However, no methylation within CTGF regulatory region was detected. Both compounds significantly reduced NSCLC cells proliferation. Decreased expression of CTGF is a common feature in NSCLC; however, it can be restored by the chromatin-modifying agents such as 5-dAzaC or TSA and consequently restrain cancer development.

Analytical results from ground-water sampling using a direct-push technique at the Dover National Test Site, Dover Air Force Base, Delaware, June-July 2001

USGS Publications Warehouse

Guertal, William R.; Stewart, Marie; Barbaro, Jeffrey R.; McHale, Timthoy J.

2004-01-01

A joint study by the Dover National Test Site and the U.S. Geological Survey was conducted from June 27 through July 18, 2001 to determine the spatial distribution of the gasoline oxygenate additive methyl tert-butyl ether and selected water-quality constituents in the surficial aquifer underlying the Dover National Test Site at Dover Air Force Base, Delaware. The study was conducted to support a planned enhanced bio-remediation demonstration and to assist the Dover National Test Site in identifying possible locations for future methyl tert-butyl ether remediation demonstrations. This report presents the analytical results from ground-water samples collected during the direct-push ground-water sampling study. A direct-push drill rig was used to quickly collect 115 ground-water samples over a large area at varying depths. The ground-water samples and associated quality-control samples were analyzed for volatile organic compounds and methyl tert-butyl ether by the Dover National Test Site analytical laboratory. Volatile organic compounds were above the method reporting limits in 59 of the 115 ground-water samples. The concentrations ranged from below detection limits to maximum values of 12.4 micrograms per liter of cis-1,2-dichloroethene, 1.14 micrograms per liter of trichloroethene, 2.65 micrograms per liter of tetrachloroethene, 1,070 micrograms per liter of methyl tert-butyl ether, 4.36 micrograms per liter of benzene, and 1.8 micrograms per liter of toluene. Vinyl chloride, ethylbenzene, p,m-xylene, and o-xylene were not detected in any of the samples collected during this investigation. Methyl tert-butyl ether was detected in 47 of the 115 ground-water samples. The highest methyl tert-butyl ether concentrations were found in the surficial aquifer from -4.6 to 6.4 feet mean sea level, however, methyl tert-butyl ether was detected as deep as -9.5 feet mean sea level. Increased methane concentrations and decreased dissolved oxygen concentrations were found in samples that contained methyl tert-butyl ether.

Oxidative Stress Mechanisms Do Not Discriminate between Genotoxic and Nongenotoxic Liver Carcinogens.

PubMed

Deferme, Lize; Wolters, Jarno; Claessen, Sandra; Briedé, Jacco; Kleinjans, Jos

2015-08-17

It is widely accepted that in chemical carcinogenesis different modes-of-action exist, e.g., genotoxic (GTX) versus nongenotoxic (NGTX) carcinogenesis. In this context, it has been suggested that oxidative stress response pathways are typical for NGTX carcinogenesis. To evaluate this, we examined oxidative stress-related changes in gene expression, cell cycle distribution, and (oxidative) DNA damage in human hepatoma cells (HepG2) exposed to GTX-, NGTX-, and noncarcinogens, at multiple time points (4-8-24-48-72 h). Two GTX (azathriopine (AZA) and furan) and two NGTX (tetradecanoyl-phorbol-acetate, (TPA) and tetrachloroethylene (TCE)) carcinogens as well as two noncarcinogens (diazinon (DZN, d-mannitol (Dman)) were selected, while per class one compound was deemed to induce oxidative stress and the other not. Oxidative stressors AZA, TPA, and DZN induced a 10-fold higher number of gene expression changes over time compared to those of furan, TCE, or Dman treatment. Genes commonly expressed among AZA, TPA, and DZN were specifically involved in oxidative stress, DNA damage, and immune responses. However, differences in gene expression between GTX and NGTX carcinogens did not correlate to oxidative stress or DNA damage but could instead be assigned to compound-specific characteristics. This conclusion was underlined by results from functional readouts on ROS formation and (oxidative) DNA damage. Therefore, oxidative stress may represent the underlying cause for increased risk of liver toxicity and even carcinogenesis; however, it does not discriminate between GTX and NGTX carcinogens.

Neurotoxic effects of gasoline and gasoline constituents.

PubMed Central

Burbacher, T M

1993-01-01

This overview was developed as part of a symposium on noncancer end points of gasoline and key gasoline components. The specific components included are methyl tertiary butyl ether, ethyl tertiary butyl ether, tertiary amyl methyl ether, butadiene, benzene, xylene, toluene, methyl alcohol, and ethyl alcohol. The overview focuses on neurotoxic effects related to chronic low-level exposures. A few general conclusions and recommendations can be made based on the results of the studies to date. a) All the compounds reviewed are neuroactive and, as such, should be examined for their neurotoxicity. b) For most of the compounds, there is a substantial margin of safety between the current permissible exposure levels and levels that would be expected to cause overt signs of neurotoxicity in humans. This is not the case for xylene, toluene, and methanol, however, where neurologic effects are observed at or below the current Threshold Limit Value. c) For most of the compounds, the relationship between chronic low-level exposure and subtle neurotoxic effects has not been studied. Studies therefore should focus on examining the dose-response relationship between chronic low-level exposure and subtle changes in central nervous system function. PMID:8020437

Triclosan and Hydroxylated Polybrominated Diphenyl Ethers in Lake and Esturaine Sediments

NASA Astrophysics Data System (ADS)

Arnold, W. A.; Kerrigan, J. F.; McNeill, K.; Erickson, P. R.; Grandbois, M.

2014-12-01

Halogenated diphenyl ethers are a class of emerging contaminants that includes the antibacterial compound triclosan and the flame retardant polybrominated diphenyl ethers (PBDEs). Both triclosan and hydroxylated polybrominated diphenyl ethers (OH-BDEs) are known to form dioxins when exposed to sunlight in aqueous solution. Thus, it is important to understand the sources and presence of these compounds in the environment, especially because OH-BDEs are breakdown products of PBDEs and also naturally produced compounds. In this work, the levels of OH-BDEs were determined in lake sediments from Minnesota and esturaine sediments from San Francisco Bay. Both surface sediments over a broad spatial area and sediment cores were collected and analyzed. Triclosan was used as a marker of wastewater as a source of the targeted emerging contaminants. The relationship between triclosan and OH-BDE levels provides insight into the importance of natural and anthropogenic influences on the levels of OH-BDEs.

Perfluorinated compounds and polybrominated diphenyl ethers in great blue heron eggs from Indiana Dunes National Lakeshore, Indiana

USGS Publications Warehouse

Custer, T.W.; Kannan, K.; Tao, L.; Saxena, A.R.; Route, B.

2009-01-01

In 2007 archived great blue heron (Ardea herodias) eggs collected from Indiana Dunes National Lakeshore, IN, (Indiana Dunes) in 1993 were analyzed for 11 perfluorinated compounds (PFCs) and 7 polybrominated diphenyl ethers (PBDEs). Concentrations of perfluorooctane sulfonate, the major contributor to total PFC concentrations, were below the toxicity thresholds estimated for bobwhite quail (Colinus virginianus) and mallards (Anas platyrhynchos), but within the toxicity threshold estimated for white leghorn chickens (Gallus domesticus). The ranking of PBDE congener concentrations by percent concentration (PBDE-47 > -99 > -100 > -153 > -154 > -28 > -183) was consistent with the Penta-PBDE formulation. Total PBDE concentrations in great blue heron eggs from Indiana Dunes were elevated and probably reflect local contamination from highly urbanized and industrialized inputs into Lake Michigan. Polybrominated diphenyl ether concentrations were within levels associated with altered reproductive behavior in other avian species and based on trends in other Great Lakes birds are probably higher today.

Antifouling phenyl ethers and other compounds from the invertebrates and their symbiotic fungi collected from the South China Sea.

PubMed

Wang, Chao-Yi; Wang, Kai-Ling; Qian, Pei-Yuan; Xu, Ying; Chen, Min; Zheng, Juan-Juan; Liu, Min; Shao, Chang-Lun; Wang, Chang-Yun

2016-12-01

Marine organism-derived secondary metabolites are promising potential sources for discovering environmentally safe antifouling agents. In present study, 55 marine secondary metabolites and their synthesized derivatives were tested and evaluated for their antifouling activities and security. These compounds include 44 natural products isolated from marine invertebrates and their symbiotic microorganisms collected from the South China Sea and 11 structural modified products derived from the isolated compounds. The natural secondary metabolites, covering phenyl ether derivatives, terpenoids, 9, 11-secosteroids, anthraquinones, alkaloids, nucleoside derivatives and peptides, were isolated from two corals, one sponge and five symbiotic fungi. All of the isolated and synthesized compounds were tested for their antifouling activities against the cyprids of barnacle Balanus (Amphibalanus) amphitrite Darwin. Noticeably, five phenyl ether derivatives (9, 11, 13-15) exhibited potent anti-larval settlement activity with the EC 50 values lower than 3.05 μM and the LC 50 /EC 50 ratios higher than 15. The study of structure-activity relationship (SAR) revealed that the introduction of acetoxy groups and bromine atoms to phenyl ether derivatives could significantly improve their antifouling activities. This is the first report on the SAR of phenyl ether derivatives on antifouling activity against barnacle B. amphitrite. The polybrominated diphenyl ether derivative, 2, 4, 6, 2', 4', 6'-hexabromo-diorcinol (13), which displayed excellent antifouling activity, was considered as a promising candidate of environmentally friendly antifouling agents.

Single-crystal-to-single-crystal transformation and solvochromic luminescence of a dinuclear gold(I)-(aza-[18]crown-6)dithiocarbamate compound.

PubMed

Tzeng, Biing-Chiau; Chao, An

2015-01-26

The treatment of [AuCl(SMe2 )] with an equimolar amount of NaO5 NCS2 (O5 NCS2 =(aza-[18]crown-6)dithiocarbamate) in CH3 CN gave [Au2 (O5 NCS2 )2 ]⋅2 CH3 CN (2⋅2 CH3 CN), and its crystal structure displays a dinuclear gold(I)-azacrown ether ring and an intermolecular gold(I)⋅⋅⋅gold(I) contact of 2.8355(3) Å in crystal lattices. It is noted that two other single crystals of 2⋅tert-butylbenzene⋅H2 O and 2⋅0.5 m-xylene can be successfully obtained from a single-crystal-to-single-crystal (SCSC) transformation process by immersing single crystals of 2⋅2 CH3 CN in the respective solvents, and both also show intermolecular gold(I)⋅⋅⋅gold(I) contacts of 2.9420(5) and 2.890(2)-2.902(2) Å, respectively. Significantly, the emissions of all three 2⋅solvates are well correlated with their respective intermolecular gold(I)⋅⋅⋅gold(I) contacts, where such contacts increase with 2⋅2 CH3 CN (2.8355(3) Å)<2⋅0.5 m-xylene (2.890(2)-2.902(2) Å)<2⋅tert-butylbenzene⋅H2 O (2.9420(5) Å), and their emission energies increase with 2⋅2 CH3 CN (602 nm)<2⋅0.5 m-xylene (583 nm)<2⋅tert-butylbenzene⋅H2 O (546 nm) as well. In this regard, we further examine the solvochromic luminescence for some other aromatics, and finally their emissions are within 546-602 nm. Obviously, the above results are mostly ascribed to the occurrence of intermolecular gold(I)⋅⋅⋅gold(I) contacts in 2⋅solvates, which are induced by the presence of various solvates in the solid state, as a key role to be responsible for their solvochromic luminescence. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cathelicidin, kallikrein 5, and serine protease activity is inhibited during treatment of rosacea with azelaic acid 15% gel.

PubMed

Coda, Alvin B; Hata, Tissa; Miller, Jeremiah; Audish, David; Kotol, Paul; Two, Aimee; Shafiq, Faiza; Yamasaki, Kenshi; Harper, Julie C; Del Rosso, James Q; Gallo, Richard L

2013-10-01

Excess cathelicidin and kallikrein 5 (KLK5) have been hypothesized to play a role in the pathophysiology of rosacea. We sought to evaluate the effects of azelaic acid (AzA) on these elements of the innate immune system. Gene expression and protease activity were measured in laboratory models and patients with rosacea during a 16-week multicenter, prospective, open-label study of 15% AzA gel. AzA directly inhibited KLK5 in cultured keratinocytes and gene expression of KLK5, Toll-like receptor-2, and cathelicidin in mouse skin. Patients with rosacea showed reduction in cathelicidin and KLK5 messenger RNA after treatment with AzA gel. Subjects without rosacea had lower serine protease activity (SPA) than patients with rosacea. Distinct subsets of patients with rosacea who had high and low baseline SPA were identified, and patients with high baseline exhibited a statistically significant reduction of SPA with 15% AzA gel treatment. Study size was insufficient to predict clinical efficacy based on the innate immune response to AzA. These results show that cathelicidin and KLK5 decrease in association with AZA exposure. Our observations suggest a new mechanism of action for AzA and that SPA may be a useful biomarker for disease activity. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Clinical Value of Mercaptopurine After Failing Azathioprine Therapy in Patients With Inflammatory Bowel Disease.

PubMed

Meijer, Berrie; Seinen, Margien L; Leijte, Niek N W; Mulder, Chris J J; van Bodegraven, Adriaan A; de Boer, Nanne K H

2016-08-01

Thiopurines have been widely accepted as immunosuppressive therapy in inflammatory bowel disease. However, many patients have to discontinue thiopurines due to intolerance or ineffectiveness. A therapeutically beneficial effect of switching from azathioprine (AZA) to mercaptopurine (MP) after developing adverse events (AEs) has been reported. The authors assessed the clinical value of MP therapy after AZA discontinuation due to intolerance and, secondary, due to ineffectiveness. In this retrospective single-center study, the authors analyzed data from patients in whom AZA therapy had failed and who were subsequently treated with MP. Thirty-eight patients initiated MP therapy after intolerance to AZA. Intolerance reoccurred in 22 (58%) patients and the remaining 16 (42%) tolerated MP. In 18 out of 48 patients (38%), the AEs that led to discontinuation of MP were similar to those of AZA. A longer duration of prior AZA use was more common in patients who were subsequently tolerant for MP (5.3 versus 1.2 months; P = 0.04). Twenty-two patients discontinued AZA due to ineffectiveness. Eight (36%) patients had clinical benefit from a switch to MP. Six out of these 8 (75%) patients used allopurinol alongside MP, due to ineffectiveness based on a skewed thiopurine metabolism. Patients were more likely to have clinical benefit if the interval between both thiopurines was longer (4.4 versus 0.01 months; P < 0.05). The authors showed that a noteworthy number of patients benefitted therapeutically from a switch from AZA to MP when failing due to intolerance or ineffectiveness; however, the percentage was lower than previously reported in literature.

Preparation of highly fluorinated diols containing ether linkages.

NASA Technical Reports Server (NTRS)

Rochow, S. E.; Stump, E. C., Jr.

1970-01-01

Hydroxy-terminated perfluoroethers and polyurethane resins derived from ethers have outstanding chemical resistance and good thermal properties. They can be used as potting compounds, coatings, and seals. The hydroxy-terminated ethers serve as intermediates in the synthesis of highly fluorinated elastomers and adhesives.

40 CFR Table 37 to Subpart G of... - Default Biorates for List 1 Compounds

Code of Federal Regulations, 2010 CFR

2010-07-01

... DIMethyl sulfate 0.178 Dinitrophenol 2,4 0.620 Dinitrotoluene(2,4) 0.784 Dioxane(1,4) 0.393 Ethylene glycol dimethyl ether 0.364 Ethylene glycol monomethyl ether acetate 0.159 Ethylene glycol monobutyl ether acetate...

Atom-type-based AI topological descriptors: application in structure-boiling point correlations of oxo organic compounds.

PubMed

Ren, Biye

2003-01-01

Structure-boiling point relationships are studied for a series of oxo organic compounds by means of multiple linear regression (MLR) analysis. Excellent MLR models based on the recently introduced Xu index and the atom-type-based AI indices are obtained for the two subsets containing respectively 77 ethers and 107 carbonyl compounds and a combined set of 184 oxo compounds. The best models are tested using the leave-one-out cross-validation and an external test set, respectively. The MLR model produces a correlation coefficient of r = 0.9977 and a standard error of s = 3.99 degrees C for the training set of 184 compounds, and r(cv) = 0.9974 and s(cv) = 4.16 degrees C for the cross-validation set, and r(pred) = 0.9949 and s(pred) = 4.38 degrees C for the prediction set of 21 compounds. For the two subsets containing respectively 77 ethers and 107 carbonyl compounds, the quality of the models is further improved. The standard errors are reduced to 3.30 and 3.02 degrees C, respectively. Furthermore, the results obtained from this study indicate that the boiling points of the studied oxo compound dominantly depend on molecular size and also depend on individual atom types, especially oxygen heteroatoms in molecules due to strong polar interactions between molecules. These excellent structure-boiling point models not only provide profound insights into the role of structural features in a molecule but also illustrate the usefulness of these indices in QSPR/QSAR modeling of complex compounds.

Comparative toxicity of two azadirachtin-based neem pesticides to Daphnia pulex.

PubMed

Goktepe, Ipek; Plhak, Leslie C

2002-01-01

Azadirachtin (AZA)-based pesticides (Neemix and Bioneem) demonstrated toxicity in 48-h nonrenewal toxicity assays using Daphnia pulex at levels that were comparable with several organophosphate pesticides. The median lethal concentration (LC50) values for the two neem pesticides were found to be 0.028 and 0.033 microl/ml, respectively. The LC50 value for nonformulated (95% pure) AZA was determined to be 0.382 microg AZA/ml. Neemix and Bioneem were exposed to air and northern sky daylight in a light box at 24 and 37 degrees C for 1, 3, 6, and 9 d. Standard 48-h acute toxicity tests were used to determine the effect of aging in these dry environmental conditions. Neemix and Bioneem were also fractionated into volatile and nonvolatile fractions, and the toxicity of each was tested. Compared with Neemix, Bioneem remained toxic longer when exposed to light and air at 37 degrees C, indicating that this pesticide may be less prone to environmental degradation. When fractionated, the nonvolatile fractions for both pesticides exhibited significantly lower LC50 values than the full formulations. These results suggest that, depending on the application rate and environmental fate, AZA-based pesticides may have direct adverse effects on aquatic organisms and that the toxicity and stability of formulated pesticides depend on factors other than only the AZA concentration.

Poly(arylene ether)s That Resist Atomic Oxygen

NASA Technical Reports Server (NTRS)

Connell, John W.; Hergenrother, Paul; Smith, Joseph G., Jr.

1994-01-01

Novel poly(arylene ether)s containing phosphine oxide (PAEPO's) made via aromatic nucleophilic displacement reactions of activated aromatic dihalides (or, in some cases, activated aromatic dinitro compounds) with new bisphenol monomers containing phosphine oxide. Exhibited favorable combination of physical and mechanical properties and resistance to monatomic oxygen in oxygen plasma environment. Useful as adhesives, coatings, films, membranes, moldings, and composite matrices.

meso-Dihydroguaiaretic acid derivatives with antibacterial and antimycobacterial activity.

PubMed

Reyes-Melo, Karen; García, Abraham; Romo-Mancillas, Antonio; Garza-González, Elvira; Rivas-Galindo, Verónica M; Miranda, Luis D; Vargas-Villarreal, Javier; Favela-Hernández, Juan Manuel J; Camacho-Corona, María Del Rayo

2017-10-15

Thirty-three meso-dihydroguaiaretic acid (meso-DGA) derivatives bearing esters, ethers, and amino-ethers were synthesized. All derivatives were tested against twelve drug-resistant clinical isolates of Gram-positive and Gram-negative bacteria, including sensitive (H37Rv) and multidrug-resistant Mycobacterium tuberculosis strains. Among the tested compounds, four esters (7, 11, 13, and 17), one ether (23), and three amino-ethers (30, 31, and 33) exhibited moderate activity against methicillin-resistant Staphylococcus aureus, whereas 30 and 31 showed better results than levofloxacin against vancomycin-resistant Enterococcus faecium. Additionally, nineteen meso-DGA derivatives displayed moderate to potent activity against M. tuberculosis H37Rv with minimum inhibitory concentration (MIC) values ranging from 3.125 to 50µg/mL. Seven meso-DGA derivatives bearing amino-ethers (26-31 and 33) exhibited the lowest MICs against M. tuberculosis H37Rv and G122 strains, with 31 being as potent as ethambutol (MICs of 3.125 and 6.25µg/mL). The presence of positively charged group precursors possessing steric and hydrophobic features (e.g. N-ethylpiperidine moieties in meso-31) resulted essential to significantly increase the antimycobacterial properties of parent meso-DGA as supported by the R-group pharmacophoric and field-based QSAR analyses. To investigate the safety profile of the antimycobacterial compounds, cytotoxicity on Vero cells was determined. The amino-ether 31 exhibited a selectivity index value of 23, which indicate it was more toxic to M. tuberculosis than to mammalian cells. Therefore, 31 can be considered as a promising antitubercular agent for further studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

40 CFR Table 36 to Subpart G of... - Compound Lists Used for Compliance Demonstrations for Enhanced Biological Treatment Processes...

Code of Federal Regulations, 2010 CFR

2010-07-01

.... Ethylene Glycol MonobutylEther Acetate Chloroprene. Ethylene Glycol MonomethylEther Acetate Cumene (isopropylbenzene). Ethylene Glycol Dimethyl Ether Dibromoethane 1,2. Hexachlorobenzene Dichlorobenzene 1,4.... Ethylbenzene. Ethylene Oxide. Ethylene Dibromide. Hexachlorobutadiene. Hexachloroethane. Hexane-n. Methyl...

Formulation studies of InhA inhibitors and combination therapy to improve efficacy against Mycobacterium tuberculosis.

PubMed

Knudson, Susan E; Cummings, Jason E; Bommineni, Gopal R; Pan, Pan; Tonge, Peter J; Slayden, Richard A

2016-12-01

Previously, structure-based drug design was used to develop substituted diphenyl ethers with potency against the Mycobacterium tuberculosis (Mtb) enoyl-ACP reductase (InhA), however, the highly lipophilic centroid compound, SB-PT004, lacked sufficient efficacy in the acute murine Mtb infection model. A next generation series of compounds were designed with improved specificity, potency against InhA, and reduced cytotoxicity in vitro, but these compounds also had limited solubility. Accordingly, solubility and pharmacokinetics studies were performed to develop formulations for this class and other experimental drug candidates with high logP values often encountered in drug discovery. Lead diphenyl ethers were formulated in co-solvent and Self-Dispersing Lipid Formulations (SDLFs) and evaluated in a rapid murine Mtb infection model that assesses dissemination to and bacterial burden in the spleen. In vitro synergy studies were performed with the lead diphenyl ether compounds, SB-PT070 and SB-PT091, and rifampin (RIF), which demonstrated an additive effect, and that guided the in vivo studies. Combinatorial therapy in vivo studies with these compounds delivered in our Self-Micro Emulsifying Drug Delivery System (SMEDDS) resulted in an additional 1.4 log 10  CFU reduction in the spleen of animals co-treated with SB-PT091 and RIF and an additional 1.7 log 10 reduction in the spleen with animals treated with both SB-PT070 and RIF. Copyright © 2016 Elsevier Ltd. All rights reserved.

Berberine and coptisine free bases

NASA Astrophysics Data System (ADS)

Dostál, Jiří; Man, Stanislav; Sečkářová, Pavlína; Hulová, Dagmar; Nečas, Marek; Potáček, Milan; Toušek, Jaromír.; Dommisse, Roger; Van Dongen, Walter; Marek, Radek

2004-01-01

The free bases of protoberberine alkaloids berberine and coptisine and related compounds have been examined. The 1H and 13C NMR data of 8-hydroxy-7,8-dihydroberberine (2a), 8-hydroxy-7,8-dihydrocoptisine (2b), bis(7,8-dihydroberberin-8-yl) ether (3a), 8-oxoberberine (5a), and 8-oxocoptisine (5b) as well as X-ray data of compounds 2a, 5a, and 5b are reported and discussed.

Enzymatic Incorporation of Modified Purine Nucleotides in DNA.

PubMed

Abu El Asrar, Rania; Margamuljana, Lia; Abramov, Mikhail; Bande, Omprakash; Agnello, Stefano; Jang, Miyeon; Herdewijn, Piet

2017-12-14

A series of nucleotide analogues, with a hypoxanthine base moiety (8-aminohypoxanthine, 1-methyl-8-aminohypoxanthine, and 8-oxohypoxanthine), together with 5-methylisocytosine were tested as potential pairing partners of N 8 -glycosylated nucleotides with an 8-azaguanine or 8-aza-9-deazaguanine base moiety by using DNA polymerases (incorporation studies). The best results were obtained with the 5-methylisocytosine nucleotide followed by the 1-methyl-8-aminohypoxanthine nucleotide. The experiments demonstrated that small differences in the structure (8-azaguanine versus 8-aza-9-deazaguanine) might lead to significant differences in recognition efficiency and selectivity, base pairing by Hoogsteen recognition at the polymerase level is possible, 8-aza-9-deazaguanine represents a self-complementary base pair, and a correlation exists between in vitro incorporation studies and in vivo recognition by natural bases in Escherichia coli, but this recognition is not absolute (exceptions were observed). © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design and synthesis of (aza)indolyl maleimide-based covalent inhibitors of glycogen synthase kinase 3β.

PubMed

Yang, Zhimin; Liu, Hui; Pan, Botao; He, Fengli; Pan, Zhengying

2018-05-21

As an important kinase in multiple signal transduction pathways, GSK-3β has been an attractive target for chemical probe discovery and drug development. Compared to numerous reversible inhibitors that have been developed, covalent inhibitors of GSK-3β are noticeably lacking. Here, we report the discovery of a series of covalent GSK-3β inhibitors by optimizing both non-covalent interactions and reactive groups. Among these covalent inhibitors, compound 38b with a mild α-fluoromethyl amide reactive group emerges as a selective and covalent inhibitor against GSK-3β, effectively inhibits the phosphorylation of glycogen synthase and tau protein, and increases β-catenin's levels in living cells. In addition, compound 38b is highly permeable and not a substrate of P-glycoprotein.

Development of an ELISA for the Detection of Azaspiracids.

PubMed

Samdal, Ingunn A; Løvberg, Kjersti E; Briggs, Lyn R; Kilcoyne, Jane; Xu, Jianyan; Forsyth, Craig J; Miles, Christopher O

2015-09-09

Azaspiracids (AZAs) are a group of biotoxins that cause food poisoning in humans. These toxins are produced by small marine dinoflagellates such as Azadinium spinosum and accumulate in shellfish. Ovine polyclonal antibodies were produced and used to develop an ELISA for quantitating AZAs in shellfish, algal cells, and culture supernatants. Immunizing antigens were prepared from synthetic fragments of the constant region of AZAs, while plate coating antigen was prepared from AZA-1. The ELISA provides a sensitive and rapid analytical method for screening large numbers of samples. It has a working range of 0.45-8.6 ng/mL and a limit of quantitation for total AZAs in whole shellfish at 57 μg/kg, well below the maximum permitted level set by the European Commission. The ELISA has good cross-reactivity to AZA-1-10, -33, and -34 and 37-epi-AZA-1. Naturally contaminated Irish mussels gave similar results whether they were cooked or uncooked, indicating that the ELISA also detects 22-carboxy-AZA metabolites (e.g., AZA-17 and AZA-19). ELISA results showed excellent correlation with LC-MS/MS analysis, both for mussel extract spiked with AZA-1 and for naturally contaminated Irish mussels. The assay is therefore well suited to screening for AZAs in shellfish samples intended for human consumption, as well as for studies on AZA metabolism.

Potential for mcl-PHA production from nonanoic and azelaic acids.

PubMed

Gillis, James; Ko, Kenton; Ramsay, Juliana A; Ramsay, Bruce A

2018-01-01

Greater than 65% of canola and high-oleic soy oil fatty acids is oleic acid, which is readily converted to nonanoic (NA) and azelaic (AzA) acids by ozonolysis. NA is an excellent substrate for medium-chain-length polyhydroxyalkanoate (mcl-PHA) production but AzA has few uses. Pseudomonas citronellolis DSM 50332 and Pseudomonas fluorescens ATCC 17400, both able to produce mcl-PHA from fatty acids and to grow on AzA as the sole source of carbon and energy, were assessed for the accumulation of mcl-PHA from AzA and NA. In N-limited shake flasks using NA, P. citronellolis produced 32% of its dry biomass as mcl-PHA containing 78% 3-hydroxynonanoate with 22% 3-hydroxyheptanoate. Pseudomonas fluorescens produced only 2% PHA. N-limited P. citronellolis on AzA produced 20% dry weight PHA containing 75% 3-hydroxydecanoate and 25% 3-hydroxyoctanoate, indicative of de novo synthesis. Although selective pressure, including β-oxidation inhibition, under well-controlled (chemostat) conditions was applied to P. citronellolis, no side-chain carboxyl groups were detected. It was concluded that one or more of FabG and PhaJ or the PHA synthase cannot catalyze reactions involving ω-carboxy substrates. However, a process based on oleic acid could be established if Pseudomonas putida was engineered to grow on AzA.

Absorption and Effect of Azaspiracid-1 Over the Human Intestinal Barrier.

PubMed

Abal, Paula; Louzao, M Carmen; Fraga, María; Vilariño, Natalia; Ferreiro, Sara; Vieytes, Mercedes R; Botana, Luis M

2017-01-01

Azaspiracids (AZAs) are marine biotoxins produced by the dinoflagellates genera Azadinium and Amphidoma. These toxins cause azaspiracid poisoning (AZP), characterized by severe gastrointestinal illness in humans after the consumption of bivalve molluscs contaminated with AZAs. The main aim of the present study was to examine the consequences of human exposure to AZA1 by the study of absorption and effects of the toxin on Caco-2 cells, a reliable model of the human intestine. The ability of AZA1 to cross the human intestinal epithelium has been evaluated by the Caco-2 transepithelial permeability assay. The toxin has been detected and quantified using a microsphere-based immunoassay. Cell alterations and ultrastructural effects has been observed with confocal and transmission electron microscopy Results: AZA1 was absorbed by Caco-2 cells in a dose-dependent way without affecting cell viability. However, modifications on occludin distribution detected by confocal microscopy imaging indicated a possible monolayer integrity disruption. Nevertheless, transmission electron microscopy imaging revealed ultrastructural damages at the nucleus and mitochondria with autophagosomes in the cytoplasm, however, tight junctions and microvilli remained unaffected. After the ingestion of molluscs with the AZA1, the toxin will be transported through the human intestinal barrier to blood causing damage on epithelial cells. © 2017 The Author(s). Published by S. Karger AG, Basel.

Oxidation mechanism of diethyl ether: a complex process for a simple molecule.

PubMed

Di Tommaso, Stefania; Rotureau, Patricia; Crescenzi, Orlando; Adamo, Carlo

2011-08-28

A large number of organic compounds, such as ethers, spontaneously form unstable peroxides through a self-propagating process of autoxidation (peroxidation). Although the hazards of organic peroxides are well known, the oxidation mechanisms of peroxidizable compounds like ethers reported in the literature are vague and often based on old experiments, carried out in very different conditions (e.g. atmospheric, combustion). With the aim to (partially) fill the lack of information, in this paper we present an extensive Density Functional Theory (DFT) study of autoxidation reaction of diethyl ether (DEE), a chemical that is largely used as solvent in laboratories, and which is considered to be responsible for various accidents. The aim of the work is to investigate the most probable reaction paths involved in the autoxidation process and to identify all potential hazardous intermediates, such as peroxides. Beyond the determination of a complex oxidation mechanism for such a simple molecule, our results suggest that the two main reaction channels open in solution are the direct decomposition (β-scission) of DEE radical issued of the initiation step and the isomerization of the peroxy radical formed upon oxygen attack (DEEOO˙). A simple kinetic evaluation of these two competing reaction channels hints that radical isomerization may play an unexpectedly important role in the global DEE oxidation process. Finally industrial hazards could be related to the hydroperoxide formation and accumulation during the chain propagation step. The resulting information may contribute to the understanding of the accidental risks associated with the use of diethyl ether.

Biocidal Properties of Anti-Icing Additives for Aircraft Fuels

PubMed Central

Neihof, R. A.; Bailey, C. A.

1978-01-01

The biocidal and biostatic activities of seven glycol monoalkyl ether compounds were evaluated as part of an effort to find an improved anti-icing additive for jet aircraft fuel. Typical fuel contaminants, Cladosporium resinae, Gliomastix sp., Candida sp., Pseudomonas aeruginosa, and a mixed culture containing sulfate-reducing bacteria were used as assay organisms. Studies were carried out over 3 to 4 months in two-phase systems containing jet fuel and aqueous media. Diethylene glycol monomethyl ether, triethylene glycol monomethyl ether, triethylene glycol monoethyl ether, and 2-methoxyethanol were generally biocidal in aqueous concentrations of 10 to 17% for all organisms except Gliomastix, which required 25% or more. 2-Ethoxyethanol, 2-propoxyethanol, and 2-butoxyethanol were biocidal at progressively lower concentrations down to 1 to 2% for 2-butoxyethanol. The enhanced antimicrobial activity of these three compounds was attributed to cytoplasmic membrane damage because of the correlation between surface tension measurements and lytic activity with P. aeruginosa cells. The mechanism of action of the less active compounds appeared to be due to osmotic (dehydrating) effects. When all requirements are taken into account, diethylene glycol monomethyl ether appears to be the most promising replacement for the currently used additive, 2-methoxyethanol. PMID:646356

Three new diphenyl ether derivatives from the fermentation products of an endophytic fungus Phomopsis fukushii.

PubMed

Gao, Yu-Hong; Zheng, Rui; Li, Jing; Kong, Wei-Song; Liu, Xin; Ye, Lin; Mi, Qi-Li; Kong, Wei-Song; Zhou, Min; Yang, Guang-Yu; Hu, Qiu-Fen; Du, Gang; Yang, Hai-Ying; Li, Xue-Mei

2018-01-17

Three new diphenyl ethers (1-3), together with four known isopentylated diphenyl ethers derivatives (4-7), were isolated from the fermentation products of an endophytic fungus Phomopsis fukushii. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1-3 were evaluated for their anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity. The results revealed that compounds 1 and 2 showed strong inhibitions with inhibition zone diameters (IZD) of 20.2 ± 2.5 mm and 17.9 ± 2.2 mm, respectively. Compound 3 also showed good inhibition with IZD 15.2 ± 1.8 mm. The IZD data of compound 1 is close to that of positive control with IZD 21.9 ± 2.1 mm.

Arylglycerol-γ-Formyl Ester as an Aromatic Ring Cleavage Product of Nonphenolic β-O-4 Lignin Substructure Model Compounds Degraded by Coriolus versicolor†

PubMed Central

Kawai, Shingo; Umezawa, Toshiaki; Higuchi, Takayoshi

1985-01-01

4-Ethoxy-3-methoxyphenylglycerol-γ-formyl ester (compound IV) was identified as a degradation product of both 4-ethoxy-3-methoxyphenylglycerol-β-syringaldehyde ether (compound I) and 4-ethoxy-3-methoxyphenylglycerol-β-2,6-dimethoxyphenyl ether (compound II) by a ligninolytic culture of Coriolus versicolor. An isotopic experiment with a 13C-labeled compound (compound II′) indicated that the formyl group of compound IV was derived from the β-phenoxyl group of β-O-4 dimer as an aromatic ring cleavage fragment. However, compound IV was not formed from 4-ethoxy-3-methoxyphenylglycerol-β-guaiacyl ether (compound III). γ-Formyl arylglycerol (compound IV) could be a precursor of 4-ethoxy-3-methoxyphenylglycerol (compound VI), because 3-(4-ethoxy-3-methoxyphenyl)-1-formyloxy propane (compound VII) was cleaved to give 3-(4-ethoxy-3-methoxyphenyl)-1-propanol (compound VIII) by C. versicolor. 4-Ethoxy-3-methoxyphenylglycerol-β,γ-cyclic carbonate (compound V), previously found as a degradation product of compound III by Phanerochaete chrysosporium (T. Umezawa, and T. Higuchi, FEBS Lett., 25:123-126, 1985), was also identified from the cultures with compound I, II, and III and degraded to give the arylglycerol (compound VI). An isotopic experiment with 13C-labeled compounds II′ and III′ indicated that the carbonate carbon of compound V was derived from the β-phenoxyl groups of β-O-4 substructure. PMID:16346950

O-methylation of natural phenolic compounds based on green chemistry using dimethyl carbonate

NASA Astrophysics Data System (ADS)

Prakoso, N. I.; Pangestu, P. H.; Wahyuningsih, T. D.

2016-02-01

The alkyl aryl ether compounds, of which methyl eugenol and veratraldehyde are the simplest intermediates can be synthesized by reacting eugenol and vanillin with the green reagent dimethyl carbonate (DMC). The reaction was carried out under mild of temperature and pressure. Excellent yields and selective products were obtained (95-96%) after a few hours. In the end of the reaction, the catalysts (base and Phase Transfer Catalyst) can be recovered and regenerated.

Recent Advanced in Rare Earth Chemistry: IREC (International Rare Earth Conference) 85 Held at Zurich (Switzerland) on 4-8 Mar 85.

DTIC Science & Technology

1985-06-04

compounds were employed since 1979. The polyfunc- studied using time-resolved spectro- tlonal ligands (L) included crown ethers scopy, and the...structure of rare earth * Aqueous complexes with cyclic poly - compounds (for example Cs3Ln2X9), was ethers crown ethers , Alstad, Univer- presented by A...Approved for public release; distribution unlimited U.S. Office of Naval Research, London ag - ’ 3 k) I 5.’ - ~1 I 9 ’<I. A -i I. 4. -A kA IS7 ASS

Sorbents based on asbestos with a layer of an hydroxyethylcyclam derivative of PVC containing aquacomplexes of sulfuric acid or sodium hydroxide with aza-crown groups

NASA Astrophysics Data System (ADS)

Tsivadze, A. Yu.; Fridman, A. Ya.; Morozova, E. M.; Sokolova, N. P.; Voloshchuk, A. M.; Petukhova, G. A.; Bardyshev, I. I.; Gorbunov, A. M.; Polyakova, I. Ya.; Titova, V. N.; Yavich, A. A.; Novikov, A. K.; Petrova, N. V.

2016-07-01

Aquacomplexes of sulfuric acid and sodium hydroxide with aza-crown groups are synthesized in cavities of a sorbent from the porous layer of a PVC cyclam-derivative grafted onto fibers of asbestos fabric. The structure of sorbents with complexes is studied and their adsorption characteristics are determined. It is shown that the affinity of the developed surface toward ethanol, benzene, and hexane depends on the nature of complexes in the pore walls, and the volume of cavities formed as a result of the pores on the developed asbestos surface being coated with networks of aza-crown groups is larger than that of cavities with walls of aza-crown groups in the layers of a PVC cyclam derivative. Indicators of H+- and OH--conductivity of sorbents with complexes as electrochemical bridges are determined. It is shown that the major part of H+- and OH--ions moves through complexes with aza-crown groups in the region of cavities formed of pores on the surface of asbestos.

Value-added organonitrogen chemicals evolution from the pyrolysis of chitin and chitosan.

PubMed

Liu, Chao; Zhang, Huiyan; Xiao, Rui; Wu, Shubin

2017-01-20

Thermogravimetric characteristics of chitin and chitosan and their potentials to produce value-added organonitrogen chemicals were separately evaluated via TG/DSC-FTIR and Py-GC/MS. Results shown that chitin had the better thermal stability and higher activation energy than chitosan because of the abundant acetamido group. Furthermore, the dominated volatilization in active pyrolysis of chitin contributed to its endothermic property, whereas the charring in chitosan led to the exothermal. During fast pyrolysis, the acetamido group in chitin and chitosan was converted into acetic acid or acetamide. Typical products from chitosan pyrolysis were aza-heterocyclic chemicals, i.e. pyridines, pyrazines, and pyrroles, with the total selectivity of 50.50% at 600°C. Herein, selectivity of pyrazine compounds was up to 22.99%. These aza-heterocyclic chemicals came from the nucleophilic addition reaction of primary amine and carbonyl. However, main reaction during chitin pyrolysis was ring-opening degradation, which led to the formation of acetamido chemicals, especially acetamido acetaldehyde with the highest selectivity of 27.27% at 450°C. In summary, chitosan had the potential to produce aza-heterocyclic chemicals, and chitin to acetamido chemicals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Observation of the Strong Electronic Coupling in Near-Infrared-Absorbing Tetraferrocene aza-Dipyrromethene and aza-BODIPY with Direct Ferrocene-α- and Ferrocene-β-Pyrrole Bonds: Toward Molecular Machinery with Four-Bit Information Storage Capacity.

PubMed

Zatsikha, Yuriy V; Holstrom, Cole D; Chanawanno, Kullapa; Osinski, Allen J; Ziegler, Christopher J; Nemykin, Victor N

2017-01-17

The 1,3,7,9-tetraferrocenylazadipyrromethene (3) and the corresponding 1,3,5,7-tetraferrocene aza-BODIPY (4) were prepared via three and four synthetic steps, respectively, starting from ferrocenecarbaldehyde using the chalcone-type synthetic methodology. The novel tetra-iron compounds have ferrocene groups directly attached to both the α- and the β-pyrrolic positions, and the shortest Fe-Fe distance determined by X-ray crystallography for 3 was found to be ∼6.98 Å. These new compounds were characterized by UV-vis, nuclear magnetic resonance, and high-resolution electrospray ionization mass spectrometry methods, while metal-metal couplings in these systems were probed by electro- and spectroelectrochemistry, chemical oxidations, and Mössbauer spectroscopy. Electrochemical data are suggestive of the well-separated stepwise oxidations of all four ferrocene groups in 3 and 4, while spectroelectrochemical and chemical oxidation experiments allowed for characterization of the mixed-valence forms in the target compounds. Intervalence charge-transfer band analyses indicate that the mixed-valence [3] + and [4] + complexes belong to the weakly coupled class II systems in the Robin-Day classification. This interpretation was further supported by Mössbauer spectroscopy in which two individual doublets for Fe(II) and Fe(III) centers were observed in room-temperature experiments for the mixed-valence [3] n+ and [4] n+ species (n = 1-3). The electronic structure, redox properties, and UV-vis spectra of new systems were correlated with Density Functional Theory (DFT) and time-dependent DFT calculations (TDDFT), which are suggestive of a ferrocene-centered highest occupied molecular orbital and chromophore-centered lowest unoccupied molecular orbital in 3 and 4 as well as predominant spin localization at the ferrocene fragment attached to the α-pyrrolic positions in [3] + and [4] + .

Ether-based nonflammable electrolyte for room temperature sodium battery

NASA Astrophysics Data System (ADS)

Feng, Jinkui; Zhang, Zhen; Li, Lifei; Yang, Jian; Xiong, Shenglin; Qian, Yitai

2015-06-01

Safety problem is one of the key points that hinder the development of room temperature sodium batteries. In this paper, four well-known nonflammable organic compounds, Trimethyl Phosphate (TMP), Tri(2,2,2-trifluoroethyl) phosphite (TFEP), Dimethyl Methylphosphonate (DMMP), Methyl nonafluorobuyl Ether (MFE), are investigated as nonflammable solvents in sodium batteries for the first time. Among them, MFE is stable towards sodium metal at room temperature. The electrochemical properties and electrode compatibility of MFE based electrolyte are investigated. Both Prussian blue cathode and carbon nanotube anode show good electrochemical performance retention in this electrolyte. The results suggest that MFE is a promising option as nonflammable electrolyte additive for sodium batteries.

Spectral luminescent and generation properties of new active media in the blue region of the spectrum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gruzinskii, V.V.; Degtyarenko, K.M.; Kopylova, T.N.

A series of organic luminophores based on benzene, diphenyl, diphenyl ether, diphenylmethane and diphenylene oxide (4,4'-distyryldiphenyl ether and 3,6-distyryldiphenylene oxide were obtained for the first time) were synthesized by a new method, and new patterns of change in their spectral-luminscent properties, depending on the structure of the molecules, were found. The generation of emission obtained for the new compounds in vapors and in solutions is fairly efficient, especially in the case of 4,4'-di(phenylethynyl)diphenyl.

RhII -Catalyzed β-C(sp2 )-H Alkylation of Enol Ethers, Enamides and Enecarbamates with α-Diazo Dicarbonyl Compounds.

PubMed

McLarney, Brett D; Cavitt, Marchello A; Donnell, Theodore M; Musaev, Djamaladdin G; France, Stefan

2017-01-23

A Rh II -catalyzed method for intermolecular alkylation of the β-C(sp 2 )-H bond of enol ethers, enamides, and enecarbamates with α-diazo-1,3-dicarbonyl compounds is reported. The products are formed in up to 99 % yield and can be readily derivatized under a variety of conditions. By utilizing a combination of experimental and computational studies, the presumptive addition-elimination reaction mechanism was investigated and found to proceed under thermodynamic control at higher temperature. The acquired fundamental knowledge was translated into a strategic reaction design and yielded the first example of the β-C-H functionalizations of acyclic enol ethers using α-diazo-1,3-dicarbonyl compounds. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

New polyarylene ethers

NASA Technical Reports Server (NTRS)

Hergenrother, P. M.; Havens, S. J.; Jensen, B. J.

1986-01-01

A series of new polyarylene ethers (PAEs) were prepared from the reaction of activated dihalo compounds with various bisphenols. Measured number average molecular weights for the PAEs ranged from 13,500 to 39,400 g/mole, and glass transition temperatures varied from 152 to 280 C. Ethynyl-terminated polyarylene ethers (ETPAEs) were also prepared by endcapping hydroxy-terminated polyarylene ethers with 4-ethynylbenzoyl chloride. Structure/property relationships for the PAEs, and the advantages offered by the ETPAEs, are discussed.

A 150-year record of polycyclic aromatic compound (PAC) deposition from high Andean Cajas National Park, southern Ecuador.

PubMed

Bandowe, Benjamin A Musa; Fränkl, Lea; Grosjean, Martin; Tylmann, Wojciech; Mosquera, Pablo V; Hampel, Henrietta; Schneider, Tobias

2018-04-15

The temporal profiles of polycyclic aromatic compounds (PACs) in lake sediments reflect past changes in emissions, transport and deposition of these pollutants and, thus, record natural and anthropogenic processes. We document fluxes of PACs [(polycyclic aromatic hydrocarbons (PAHs), oxygenated PAHs (OPAHs) and azaarenes (AZAs)] deposited in two tropical high-altitude lakes in the Cajas National Park (Ecuadorian Andes, 2°50'S, 79°10'W). In remote and high elevation Laguna Fondococha (4130m a.s.l.), the temporal fluxes of OPAHs and AZAs were similar to those of PAHs suggesting similar sources. A significant increase of PAC deposition after the 1950s reflects Ecuador's economic development. PAH fluxes were relatively low (∑27PAHs (without retene and perylene): 0.86-11.21ngcm -2 yr -1 ) with a composition pattern typical for long-range atmospheric transport (high 9-fluorenone/fluorene ratios) and biomass burning (30% low molecular weight PAHs). PAHs diagnostic of high temperature combustion (industry, traffic) make up 20-25% of total PAHs. Perylene concentrations increase linearly with increasing sediment depth suggesting diagenetic in-situ production. At lower elevations (Laguna Llaviucu, 3140m a.s.l.) and closer to urban areas, PAC fluxes in the past decades were 4-5 times higher than in the remote high-elevation lake. Laguna Llaviucu also showed higher concentrations of high molecular weight pyrogenic PAHs and a greater diversity of AZAs. Individual OPAHs and AZAs reflect mainly combustion activities. In Laguna Llaviucu, which is at a lower elevation (3140m a.s.l.) and closer to the city, molecular ratios suggest short-range atmospheric transport and deposition of PACs. A very foggy climate (170 rainy days per year) with the precipitation maximum at 3500m removes PACs very efficiently (by wet deposition) from the atmosphere at very short distances from emission sources. This partly explains why L. Llaviucu shows higher fluxes of PACs than the higher elevation L. Fondococha. This study presents the first historical record of organic pollutants from environmental archives in Ecuador. Copyright © 2017 Elsevier B.V. All rights reserved.

Similar, but different: structurally related azelaic acid and hexanoic acid trigger differential metabolomic and transcriptomic responses in tobacco cells.

PubMed

Djami-Tchatchou, Arnaud T; Ncube, Efficient N; Steenkamp, Paul A; Dubery, Ian A

2017-11-29

Plants respond to various stress stimuli by activating an enhanced broad-spectrum defensive ability. The development of novel resistance inducers represents an attractive, alternative crop protection strategy. In this regard, hexanoic acid (Hxa, a chemical elicitor) and azelaic acid (Aza, a natural signaling compound) have been proposed as inducers of plant defense, by means of a priming mechanism. Here, we investigated both the mode of action and the complementarity of Aza and Hxa as priming agents in Nicotiana tabacum cells in support of enhanced defense. Metabolomic analyses identified signatory biomarkers involved in the establishment of a pre-conditioned state following Aza and Hxa treatment. Both inducers affected the metabolomes in a similar manner and generated common biomarkers: caffeoylputrescine glycoside, cis-5-caffeoylquinic acid, feruloylglycoside, feruloyl-3-methoxytyramine glycoside and feruloyl-3-methoxytyramine conjugate. Subsequently, quantitative real time-PCR was used to investigate the expression of inducible defense response genes: phenylalanine ammonia lyase, hydroxycinnamoyl CoA quinate transferase and hydroxycinnamoyl transferase to monitor activation of the early phenylpropanoid pathway and chlorogenic acids metabolism, while ethylene response element-binding protein, small sar1 GTPase, heat shock protein 90, RAR1, SGT1, non-expressor of PR genes 1 and thioredoxin were analyzed to report on signal transduction events. Pathogenesis-related protein 1a and defensin were quantified to investigate the activation of defenses regulated by salicylic acid and jasmonic acid respectively. The qPCR results revealed differential expression kinetics and, in general (except for NPR1, Thionin and PR1a), the relative gene expression ratios observed in the Hxa-treated cells were significantly greater than the expression observed in the cells treated with Aza. The results indicate that Aza and Hxa have a similar priming effect through activation of genes involved in the establishment of systemic acquired resistance, associated with enhanced synthesis of hydroxycinnamic acids and related conjugates.

Growth inhibition and ultrastructural alterations induced by Delta24(25)-sterol methyltransferase inhibitors in Candida spp. isolates, including non-albicans organisms.

PubMed

Ishida, Kelly; Rodrigues, Juliany Cola Fernandes; Ribeiro, Marcos Dornelas; Vila, Taíssa Vieira Machado; de Souza, Wanderley; Urbina, Julio A; Nakamura, Celso Vataru; Rozental, Sonia

2009-04-20

Although Candida species are commensal microorganisms, they can cause many invasive fungal infections. In addition, antifungal resistance can contribute to failure of treatment.The purpose of this study was to evaluate the antifungal activity of inhibitors of Delta24(25)-sterol methyltransferase (24-SMTI), 20-piperidin-2-yl-5alpha-pregnan-3beta-20(R)-diol (AZA), and 24(R,S),25-epiminolanosterol (EIL), against clinical isolates of Candida spp., analysing the ultrastructural changes. AZA and EIL were found to be potent growth inhibitors of Candida spp. isolates. The median MIC50 was 0.5 microg.ml-1 for AZA and 2 microg.ml-1 for EIL, and the MIC90 was 2 microg.ml-1 for both compounds. All strains used in this study were susceptible to amphotericin B; however, some isolates were fluconazole- and itraconazole-resistant. Most of the azole-resistant isolates were Candida non-albicans (CNA) species, but several of them, such as C. guilliermondii, C. zeylanoides, and C. lipolytica, were susceptible to 24-SMTI, indicating a lack of cross-resistance. Reference strain C. krusei (ATCC 6258, FLC-resistant) was consistently susceptible to AZA, although not to EIL. The fungicidal activity of 24-SMTI was particularly high against CNA isolates. Treatment with sub-inhibitory concentrations of AZA and EIL induced several ultrastructural alterations, including changes in the cell-wall shape and thickness, a pronounced disconnection between the cell wall and cytoplasm with an electron-lucent zone between them, mitochondrial swelling, and the presence of electron-dense vacuoles. Fluorescence microscopy analyses indicated an accumulation of lipid bodies and alterations in the cell cycle of the yeasts. The selectivity of 24-SMTI for fungal cells versus mammalian cells was assessed by the sulforhodamine B viability assay. Taken together, these results suggest that inhibition of 24-SMT may be a novel approach to control Candida spp. infections, including those caused by azole-resistant strains.

Growth inhibition and ultrastructural alterations induced by Δ24(25)-sterol methyltransferase inhibitors in Candida spp. isolates, including non-albicans organisms

PubMed Central

2009-01-01

Background Although Candida species are commensal microorganisms, they can cause many invasive fungal infections. In addition, antifungal resistance can contribute to failure of treatment. The purpose of this study was to evaluate the antifungal activity of inhibitors of Δ24(25)-sterol methyltransferase (24-SMTI), 20-piperidin-2-yl-5α-pregnan-3β-20(R)-diol (AZA), and 24(R,S),25-epiminolanosterol (EIL), against clinical isolates of Candida spp., analysing the ultrastructural changes. Results AZA and EIL were found to be potent growth inhibitors of Candida spp. isolates. The median MIC50 was 0.5 μg.ml-1 for AZA and 2 μg.ml-1 for EIL, and the MIC90 was 2 μg.ml-1 for both compounds. All strains used in this study were susceptible to amphotericin B; however, some isolates were fluconazole- and itraconazole-resistant. Most of the azole-resistant isolates were Candida non-albicans (CNA) species, but several of them, such as C. guilliermondii, C. zeylanoides, and C. lipolytica, were susceptible to 24-SMTI, indicating a lack of cross-resistance. Reference strain C. krusei (ATCC 6258, FLC-resistant) was consistently susceptible to AZA, although not to EIL. The fungicidal activity of 24-SMTI was particularly high against CNA isolates. Treatment with sub-inhibitory concentrations of AZA and EIL induced several ultrastructural alterations, including changes in the cell-wall shape and thickness, a pronounced disconnection between the cell wall and cytoplasm with an electron-lucent zone between them, mitochondrial swelling, and the presence of electron-dense vacuoles. Fluorescence microscopy analyses indicated an accumulation of lipid bodies and alterations in the cell cycle of the yeasts. The selectivity of 24-SMTI for fungal cells versus mammalian cells was assessed by the sulforhodamine B viability assay. Conclusion Taken together, these results suggest that inhibition of 24-SMT may be a novel approach to control Candida spp. infections, including those caused by azole-resistant strains. PMID:19379501

In Vitro Enzymatic Depolymerization of Lignin with Release of Syringyl, Guaiacyl, and Tricin Units

PubMed Central

Gall, Daniel L.; Kontur, Wayne S.; Lan, Wu; Kim, Hoon; Li, Yanding; Ralph, John

2017-01-01

ABSTRACT New environmentally sound technologies are needed to derive valuable compounds from renewable resources. Lignin, an abundant polymer in terrestrial plants comprised predominantly of guaiacyl and syringyl monoaromatic phenylpropanoid units, is a potential natural source of aromatic compounds. In addition, the plant secondary metabolite tricin is a recently discovered and moderately abundant flavonoid in grasses. The most prevalent interunit linkage between guaiacyl, syringyl, and tricin units is the β-ether linkage. Previous studies have shown that bacterial β-etherase pathway enzymes catalyze glutathione-dependent cleavage of β-ether bonds in dimeric β-ether lignin model compounds. To date, however, it remains unclear whether the known β-etherase enzymes are active on lignin polymers. Here we report on enzymes that catalyze β-ether cleavage from bona fide lignin, under conditions that recycle the cosubstrates NAD+ and glutathione. Guaiacyl, syringyl, and tricin derivatives were identified as reaction products when different model compounds or lignin fractions were used as substrates. These results demonstrate an in vitro enzymatic system that can recycle cosubstrates while releasing aromatic monomers from model compounds as well as natural and engineered lignin oligomers. These findings can improve the ability to produce valuable aromatic compounds from a renewable resource like lignin. IMPORTANCE Many bacteria are predicted to contain enzymes that could convert renewable carbon sources into substitutes for compounds that are derived from petroleum. The β-etherase pathway present in sphingomonad bacteria could cleave the abundant β–O–4-aryl ether bonds in plant lignin, releasing a biobased source of aromatic compounds for the chemical industry. However, the activity of these enzymes on the complex aromatic oligomers found in plant lignin is unknown. Here we demonstrate biodegradation of lignin polymers using a minimal set of β-etherase pathway enzymes, the ability to recycle needed cofactors (glutathione and NAD+) in vitro, and the release of guaiacyl, syringyl, and tricin as depolymerized products from lignin. These observations provide critical evidence for the use and future optimization of these bacterial β-etherase pathway enzymes for industrial-level biotechnological applications designed to derive high-value monomeric aromatic compounds from lignin. PMID:29180366

Propenyl ether monomers for photopolymerization

DOEpatents

Crivello, J.V.

1996-10-22

Propenyl ether monomers of formula A(OCH{double_bond}CHCH{sub 3}){sub n} wherein n is an integer from one to six and A is selected from cyclic ethers, polyether and alkanes are disclosed. The monomers are readily polymerized in the presence of cationic photoinitiators, when exposed to actinic radiation, to form poly(propenyl ethers) that are useful for coatings, sealants, varnishes and adhesives. Compositions for preparing polymeric coatings comprising the compounds of the above formula together with particular cationic photoinitiators are also disclosed, as are processes for making the monomers from allyl halides and readily available alcohols. The process involves rearranging the resulting allyl ethers to propenyl ethers.

Propenyl ether monomers for photopolymerization

DOEpatents

Crivello, James V.

1996-01-01

Propenyl ether monomers of formula V A(OCH.dbd.CHCH.sub.3).sub.n wherein n is an integer from one to six and A is selected from cyclic ethers, polyether and alkanes are disclosed. The monomers are readily polymerized in the presence of cationic photoinitiators, when exposed to actinic radiation, to form poly(propenyl ethers) that are useful for coatings, sealants, varnishes and adhesives. Compositions for preparing polymeric coatings comprising the compounds of formula V together with particular cationic photoinitiators are also disclosed, as are processes for making the monomers from allyl halides and readily available alcohols. The process involves rearranging the resulting allyl ethers to propenyl ethers.

Process for making propenyl ethers and photopolymerizable compositions containing them

DOEpatents

Crivello, James V.

1996-01-01

Propenyl ether monomers of formula V A(OCH.dbd.CHCH.sub.3).sub.n wherein n is an integer from one to six and A is selected from cyclic ethers, polyether and alkanes are disclosed. The monomers are readily polymerized in the presence of cationic photoinitiators, when exposed to actinic radiation, to form poly(propenyl ethers) that are useful for coatings, sealants, varnishes and adhesives. Compositions for preparing polymeric coatings comprising the compounds of formula V together with particular cationic photoinitiators are also disclosed, as are processes for making the monomers from allyl halides and readily available alcohols. The process involves rearranging the resulting allyl ethers to propenyl ethers.

Antitumor evaluation and 3D-QSAR studies of a new series of the spiropyrroloquinoline isoindolinone/aza-isoindolinone derivatives by comparative molecular field analysis (CoMFA).

PubMed

Sadeghzadeh, Masoud; Salahinejad, Maryam; Zarezadeh, Nahid; Ghandi, Mehdi; Baghery, Maryam Keshavarz

2017-11-01

In current study, antitumor activity of two series of the newly synthesized spiropyrroloquinoline isoindolinone and spiropyrroloquinoline aza-isoindolinone scaffolds was evaluated against three human breast normal and cancer cell lines (MCF-10A, MCF-7 and SK-BR-3) and compared with cytotoxicity values of doxorubicin and colchicine as the standard drugs. It was found that several compounds were endowed with cytotoxicity in the low micromolar range. Among these two series, compounds 6i, 6j, 6k and 7l, 7m, 7n, 7o containing 3-ethyl-1H-indole moiety were found to be highly effective against both cancer cell lines ranging from [Formula: see text] to [Formula: see text] in comparison with the corresponding analogs. Compared with human cancer cells, the most potent compounds did not show high cytotoxicity against human breast normal MCF-10A cells. Generally, most of the evaluated compounds 6a-l and 7a-o series showed more antitumor activity against SK-BR-3 than MCF-7 cells. Moreover, comparative molecular field analysis (CoMFA) as a popular tools of three-dimensional quantitative structure-activity relationship (3D-QSAR) studies was carried out on 27 spiropyrroloquinolineisoindolinone and spiropyrroloquinolineaza-isoindolinone derivatives with antitumor activity against on SK-BR-3 cells. The obtained CoMFA models showed statistically excellent performance, which also possessed good predictive ability for an external test set. The results confirm the important effect of molecular steric and electrostatic interactions of these compounds on in vitro cytotoxicity against SK-BR-3.

Phytochemical Characterization of an Adaptogenic Preparation from Rhodiola heterodonta

PubMed Central

Grace, Mary H.; Yousef, Gad G.; Kurmukov, Anvar G.; Raskin, Ilya; Lila, Mary Ann

2013-01-01

The phytochemical constituents of a biologically active, standardized, 80% ethanol extract of Rhodiola heterodonta were characterized. The extract was fractionated over a Sephadex LH-20 column to afford two main fractions representing two classes of secondary metabolites: phenylethanoids and proanthocyanidins. This fractionation facilitated the identification and quantification of individual compounds in the fractions and sub-fractions using HPLC, and LC-MS. The major compounds in the phenylethanoid fraction were heterodontoside, tyrosol methyl ether, salidroside, viridoside, mongrhoside, tyrosol, and the cyanogenic glucoside rhodiocyanoside A. These seven compounds comprised 17.4% of the EtOH extract. Proanthocyanidins ranged from oligomers to polymers based on epigallocatechin and gallate units. The main identified oligomeric compounds in the proanthocyanidin fraction were epigallocatechin gallate, epigallocatechin-epigallocatechin-3-O-gallate and 3-O-galloylepigallocatechin-epigallocatechin-3-O-gallate, which constituted 1.75% of the ethanol extract. Tyrosol methyl ether, mongrhoside, and the two proanthocyanidin dimers were reported for the first time from this species in this study. Intraperitoneal injection of the 80% ethanol extract increased survival time of mice under hypoxia by 192%, as an indication of adaptogenic activity. PMID:19768982

Identification of a xanthine oxidase-inhibitory component from Sophora flavescens using NMR-based metabolomics.

PubMed

Suzuki, Ryuichiro; Hasuike, Yuka; Hirabayashi, Moeka; Fukuda, Tatsuo; Okada, Yoshihito; Shirataki, Yoshiaki

2013-10-01

We demonstrate that NMR-based metabolomics studies can be used to identify xanthine oxidase-inhibitory compounds in the diethyl ether soluble fraction prepared from a methanolic extract of Sophora flavescens. Loading plot analysis, accompanied by direct comparison of 1H NMR spectraexhibiting characteristic signals, identified compounds exhibiting inhibitory activity. NMR analysis indicated that these characteristic signals were attributed to flavanones such as sophoraflavanone G and kurarinone. Sophoraflavanone G showed inhibitory activity towards xanthine oxidase in an in vitro assay.

Current use of pharmacogenetic testing: a national survey of thiopurine methyltransferase testing prior to azathioprine prescription.

PubMed

Fargher, E A; Tricker, K; Newman, W; Elliott, R; Roberts, S A; Shaffer, J L; Bruce, I; Payne, K

2007-04-01

Azathioprine is an immunosuppressant prescribed for the treatment of inflammatory conditions and after organ transplantation. Risk of neutropaenia has limited the effective use of azathioprine (AZA) and driven requirements for careful monitoring and blood tests. Thiopurine methyltransferase (TPMT) is a genetically moderated key enzyme involved in the metabolism of AZA that can be used to stratify individuals into different levels of risk of developing neutropaenia. Two techniques can be used to measure TPMT status: enzyme-level testing (phenotype testing) and DNA based testing (genotype testing). To identify the current uptake of TPMT enzyme-level testing, TPMT genotype testing, and, the role of guidelines; to inform the prescribing and monitoring of AZA. A survey was mailed to a consultant dermatologist, gastroenterologist, and rheumatologist at every NHS Hospital Trust in England. The survey comprised mainly closed questions exploring: use of AZA and monitoring; use of TPMT enzyme-level testing and genotype testing; and, the role of guidelines to guide prescribing practice. A 70% (n=287) response rate was obtained. The majority of respondents reported prescribing AZA (99%, n=283). Prescribing and monitoring patterns differed between individual respondents and between the three disciplines. TPMT enzyme-level testing was reportedly used by 67% (n=189) of respondents, but this differed by discipline (dermatologists 94%, gastroenterologists 60%, rheumatologists 47%). In 91% of cases enzyme-level testing was carried out prior to prescribing AZA. Genotype testing is not typically available to NHS clinicians but 15 clinicians (six dermatologists, six gastroenterologists, three rheumatologists) reported using it. Most consultants (82%) reported using guidelines to inform their AZA prescribing and monitoring (dermatologists 81%, gastroenterologists 75%, rheumatologists 94%). Two-thirds of the consultants surveyed in England are using TPMT enzyme-level testing, prior to AZA treatment. Uptake differs between specialities. High uptake of TPMT enzyme-level testing by dermatologists, compared with gastroenterologists and rheumatologists, may reflect national guidelines advocating its use prior to AZA. Uptake of enzyme-level testing may alter in other specialties as other guidelines are developed.

Spontaneous Generation of Chirality in Simple Diaryl Ethers.

PubMed

Lennartson, Anders; Hedström, Anna; Håkansson, Mikael

2015-07-01

We studied the spontaneous formation of chiral crystals of four diaryl ethers, 3-phenoxybenzaldehyde, 1; 1,3-dimethyl-2-phenoxybenzene, 2; di(4-aminophenyl) ether, 3; and di(p-tolyl) ether, 4. Compounds 1, 3, and 4 form conformationally chiral molecules in the solid state, while the chirality of 2 arises from the formation of supramolecular helices. Compound 1 is a liquid at ambient temperature, but 2-4 are crystalline, and solid-state CD-spectroscopy showed that they could be obtained as optically active bulk samples. It should be noted that the optical activity arise upon crystallization, and no optically active precursors were used. Indeed, even commercial samples of 3 and 4 were found to be optically active, giving evidence for the ease at which total spontaneous resolution may occur in certain systems. © 2015 Wiley Periodicals, Inc.

Physicochemical properties of selected polybrominated diphenyl ethers and extension of the UNIFAC model to brominated aromatic compounds.

PubMed

Kuramochi, Hidetoshi; Maeda, Kouji; Kawamoto, Katsuya

2007-04-01

The aqueous solubilities (S(w)) at various temperatures from 283 K to 308 K and 1-octanol/water partition coefficients (K(ow)) for four polybrominated diphenyl ethers (PBDEs: 4,4'-dibromodiphenyl ether (BDE-15), 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), and 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153)) were measured by the generator column method. The S(w) and K(ow) data revealed the effect of bromine substitution and basic structure on S(w) and K(ow). To estimate the infinite dilution activity coefficients (gamma(i)(w,infinity)) of the PBDEs in water from the S(w) data, enthalpies of fusion and melting points for those compounds were measured with a differential scanning calorimeter. Henry's Law constants (H(w)) of the PBDEs were derived from the determined gamma(i)(w,infinity) and literature vapor pressure data. Some physicochemical characteristics of PBDEs were also suggested by comparing the present property data with that of polychlorinated dibenzo-p-dioxins, brominated phenols and brominated benzenes in past studies. Furthermore, in order to represent different phase equilibria including solubility and partition equilibrium for other brominated aromatic compounds using the UNIFAC model, a pair of UNIFAC group interaction parameters between the bromine and water group were determined from the S(w) and K(ow) data of PBDEs and brominated benzenes. The ability of the determined parameters to represent both properties of brominated aromatics was evaluated.

Comparative Environmental Performance of Two-Diesel-Fuel Oxygenates: Dibutyl Maleate (DBM) and Triproplyene Glycol Monomethyl Ether (TGME)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Layton, D.W.; Marchetti, A.A.

2001-10-01

Many studies have shown that the addition of oxygen bearing compounds to diesel fuel can significantly reduce particulate emissions. To assist in the evaluation of the environmental performance of diesel-fuel oxygenates, we have implemented a suite of diagnostic models for simulating the transport of compounds released to air, water, and soils/groundwater as well as regional landscapes. As a means of studying the comparative performance of DBM and TGME, we conducted a series of simulations for selected environmental media. Benzene and methyl tertiary butyl ether (MTBE) were also addressed because they represent benchmark fuel-related compounds that have been the subject ofmore » extensive environmental measurements and modeling. The simulations showed that DBM and TGME are less mobile in soil because of reduced vapor-phase transport and increased retention on soil particles. The key distinction between these two oxygenates is that DBM is predicted to have a greater potential than TGME for aerobic biodegradation, based on chemical structure.« less

The synthesis of highly functionalised pyridines using Ghosez-type reactions of dihydropyrazoles.

PubMed

Catti, Federica; Kiuru, Paula S; Slawin, Alexandra M Z; Westwood, Nicholas J

2008-09-29

The aza-Diels-Alder reaction of αβ-unsaturated hydrazones is a general methodology that has been applied both to the synthesis of natural products and in the development of multicomponent reactions. Trends have emerged as to the effect of substituents on the efficiency of this reaction with substituents at the C2 and C4-positions of the aza-diene in general suppressing the reaction. Here we report that 4,5-dihydropyrazoles can function as substrates in this process despite the presence of substituents at both of these positions. A one pot, four chemical step sequence carried out under standard thermal or microwave conditions results in the formation of the corresponding pyridine-containing compounds. The scope of the reaction is explored and additional insights into the proposed mechanism of this reaction are provided.

Cooked carrot volatiles. AEDA and odor activity comparisons. Identification of linden ether as an important aroma component.

PubMed

Buttery, Ron G; Takeoka, Gary R

2013-09-25

MS with GC-RI evidence was found for the presence of linden ether in cooked carrot (Daucus carota). Evaluation of the GC effluent from cooked carrot volatiles using aroma extract dilution analysis (AEDA) found linden ether with the highest flavor dilution (FD) factor. Others with 10-fold lower FD factors were β-ionone, eugenol, the previously unidentified β-damascenone, (E)-2-nonenal, octanal (+ myrcene), and heptanal. All other previously identified volatiles showed lower FD factors. Odor thresholds, concentrations, and odor activity values of previously identified compounds are reviewed. This indicated that at least 20 compounds occur in cooked carrots above their odor thresholds (in water). Compounds showing the highest odor activity values included β-damascenone, (E)-2-nonenal, (E,E)-2,4-decadienal, β-ionone, octanal, (E)-2-decenal, eugenol, and p-vinylguaiacol.

A Visible Light Initiating System for Free Radical Promoted Cationic Polymerization

DTIC Science & Technology

1994-02-02

identify the end groups in the polymer of cyclohexene oxide. N,N-Dimethylnaphthyl amine (DNA), a compound with high fluorescence quantum yield, was used...candidates to be polymerized via a cationic mechanism include cyclic ethers, cyclic formals and acetals, vinyl ethers, and epoxy compounds . Of these...reported sensitizer, bears two dimethylamino groups, is direct evidence that an aromatic amine can be present in a cationically photopolymerizable system

Functional Group Analysis.

ERIC Educational Resources Information Center

Smith, Walter T., Jr.; Patterson, John M.

1984-01-01

Literature on analytical methods related to the functional groups of 17 chemical compounds is reviewed. These compounds include acids, acid azides, alcohols, aldehydes, ketones, amino acids, aromatic hydrocarbons, carbodiimides, carbohydrates, ethers, nitro compounds, nitrosamines, organometallic compounds, peroxides, phenols, silicon compounds,…

DIETARY INTAKE OF PBDES BASED ON CONSUMPTION OF CATFISH IN SOUTHERN MISSISSIPPI

EPA Science Inventory

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in a wide variety of consumer products. Concerns surrounding these compounds are primarily due to their ubiquitous presence in the environment as well as human tissues, coupled with evidence indicating the poten...

Repellent activity of estrogenic compounds toward zoospores of the phytopathogenic fungus Aphanomyces cochlioides.

PubMed

Islam, M T; Tahara, S

2001-01-01

Screening chemical compounds, we found that a xenoestrogen, bisphenol A, showed potent repellent activity against the zoospores of Aphanomyces cochlioides. Based on this finding, we tested a number of androgenic and estrogenic compounds (e.g. testosterone, progesterone, estradiols, diethylstilbestrol, estrone, estriol, pregnenolone, dienestrol etc.) on the motility behavior of A. cochlioides zoospores. Interestingly, most of the estrogenic compounds exhibited potent repellent activity (1 microg/ml or less by the "particle method") toward the motile zoospores of A. cochlioides. We derivatized some of the estrogens and discussed the relationship between the structure of active molecules and their repellent activity. Apparently, aromatization of the A ring with a free hydroxyl group at C-3 position of a steroidal structure is necessary for higher repellent activity. Interestingly, methylation of diethylstilbestrol (DES) yielded completely different activity i.e. both mono- and di-methyl ethers of DES showed attractant activity. Moreover, the attracted zoospores were encysted and then germinated in the presence of di-methyl ether of DES. The potential usefulness of this repellent test is discussed for the detection of estrogenic activity of naturally occurring compounds, and the possible role of phytoestrogens in host/parasite interactions. So far, this will be the first report of repellent activity of estrogenic compounds toward trivial fungal zoospores.

Process for making propenyl ethers and photopolymerizable compositions containing them

DOEpatents

Crivello, J.V.

1996-01-23

Propenyl ether monomers of formula A(OCH{double_bond}CHCH{sub 3}){sub n} (V) wherein n is an integer from one to six and A is selected from cyclic ethers, polyether, and alkanes are disclosed. The monomers are readily polymerized in the presence of cationic photoinitiators, when exposed to actinic radiation, to form poly(propenyl ethers) that are useful for coatings, sealants, varnishes and adhesives. Compositions for preparing polymeric coatings comprising the compounds of formula V together with particular cationic photoinitiators are also disclosed, as are processes for making the monomers from allyl halides and readily available alcohols. The process involves rearranging the resulting allyl ethers to propenyl ethers.

Utility of charge-transfer complexation for the assessment of macrocyclic polyethers: Spectroscopic, thermal and surface morphology characteristics of two highly crown ethers complexed with acido acceptors

NASA Astrophysics Data System (ADS)

Refat, Moamen S.; Adam, Abdel Majid A.; Saad, Hosam A.

2015-04-01

The study of the complexing ability of macrocyclic compounds to organic and inorganic substances is of great interest. The aim of this work is to provide basic data that can be used to the assessment of macrocyclic crown ethers quantitatively based on charge-transfer (CT) complexation. This goal was achieved by preparing CT complexes of two interesting mixed nitrogen-oxygen crown ethers with acido acceptors (chloranilic and picric acid), which were fully structurally characterized. The crown ethers are 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane (HDHC) and 1,4,10-trioxa-7,13-diaza-cyclopentadecane (TDPD). The obtained complexes were structurally characterized via elemental analysis, IR, Raman, 1H NMR, and UV-visible spectroscopy. Thermal properties of these complexes were also studied, and their kinetic thermodynamic parameters were calculated. Furthermore, the microstructure properties of these complexes have also been investigated using X-ray diffraction (XRD) and scanning electron microscope (SEM).

Reduced sensitizing capacity of epoxy resin systems: a structure-activity relationship study.

PubMed

Niklasson, Ida B; Broo, Kerstin; Jonsson, Charlotte; Luthman, Kristina; Karlberg, Ann-Therese

2009-11-01

Epoxy resins can be prepared from numerous chemical compositions. Until recently, alternatives to epoxy resins based on diglycidyl ethers of bisphenol A (DGEBA) or bisphenol F (DGEBF) monomers have not received commercial interest, but are presently doing so, as epoxy resins with various properties are desired. Epoxy resin systems are known to cause allergic contact dermatitis because of contents of uncured monomers, reactive diluents, and hardeners. Reactive diluents, for example, glycidyl ethers, which also contain epoxide moieties, are added to reduce viscosity and improve polymerization. We have investigated the contact allergenic properties of a series of six analogues to phenyl glycidyl ether (PGE), all with similar basic structures but with varying carbon chain lengths and degrees of saturation. The chemical reactivity of the compounds in the test series toward the hexapeptide H-Pro-His-Cys-Lys-Arg-Met-OH was investigated. All epoxides were shown to bind covalently to both cysteine and proline residues. The percent depletion of nonreacted peptide was also studied resulting in 88% depletion when using PGE and 46% when using butyl glycidyl ether (5) at the same time point, thus revealing a large difference between the fastest and the slowest reacting epoxide. The skin sensitization potencies of the epoxides using the murine local lymph node assay (LLNA) were evaluated in relation to the observed physicochemical and reactivity properties. To enable determination of statistical significance between structurally closely related compounds, a nonpooled LLNA was performed. It was found that the compounds investigated ranged from strong to weak sensitizers, congruent with the reactivity data, indicating that even small changes in chemical structure result in significant differences in sensitizing capacity.

Room temperature rechargeable magnesium batteries with sulfur-containing composite cathodes prepared from elemental sulfur and bis(alkenyl) compound having a cyclic or linear ether unit

NASA Astrophysics Data System (ADS)

Itaoka, Kanae; Kim, In-Tae; Yamabuki, Kazuhiro; Yoshimoto, Nobuko; Tsutsumi, Hiromori

2015-11-01

Room temperature rechargeable magnesium (Mg) batteries are constructed from Mg as a negative material, sulfur (S)-containing composite prepared from elemental sulfur and the bis(alkenyl) compound having a crown ether unit (BUMB18C6) or linear ether unit (UOEE) as a positive material and the simple electrolyte (0.7 mol dm-3 Mg[N(SO2CF3)2]2-triglyme (G3) solution). The reaction between molten S and the bis(alkenyl) compound (BUMB18C6 or UOEE) provides the sulfur-containing composite, S-BUMB18C6 or S-UOEE. Both of the sulfur-containing composites are electrochemically active in the Mg salt-based electrolyte, acetonitrile- or G3- Mg[N(SO2CF3)2]2 electrolyte. The first discharge capacity of the test cells with the sulfur-containing composite is 460 Ah kg-1 (per the weight of sulfur in the composite) with the S-BUMB18C6 electrode and 495 Ah kg-1 with the S-UOEE electrode. According to the continuous charge-discharge cycle tests (at 10th cycle), the discharge capacity of the test cell with the S-BUMB18C6 electrode (68.1 Ah kg-1) is higher than that with the S-UOEE electrode (0.18 Ah kg-1). The crown ether units in the S-BUMB18C6 composite may create ion-conducting paths in the cathode, prevent rise in the internal resistance of the cathode, and provide better cycle performance of the test cells with the S-BUMB18C6 composite electrode than that with the S-UOEE electrode.

Multi-parameter optimization of aza-follow-ups to BI 207524, a thumb pocket 1 HCV NS5B polymerase inhibitor. Part 2: Impact of lipophilicity on promiscuity and in vivo toxicity.

PubMed

Beaulieu, Pierre L; Bolger, Gordon; Deon, Dan; Duplessis, Martin; Fazal, Gulrez; Gagnon, Alexandre; Garneau, Michel; LaPlante, Steven; Stammers, Timothy; Kukolj, George; Duan, Jianmin

2015-03-01

We describe our efforts to identify analogs of thumb pocket 1 HCV NS5B inhibitor 1 (aza-analog of BI 207524) with improved plasma to liver partitioning and a predicted human half-life consistent with achieving a strong antiviral effect at a reasonable dose in HCV-infected patients. Compounds 3 and 7 were identified that met these criteria but exhibited off-target promiscuity in an in vitro pharmacology screen and in vivo toxicity in rats. High lipophilicity in this class was found to correlate with increased probability for promiscuous behavior and toxicity. The synthesis of an 8×11 matrix of analogs allowed the identification of C3, an inhibitor that displayed comparable potency to 1, improved partitioning to the liver and reduced lipophilicity. Although C3 displayed reduced propensity for in vitro off-target inhibition and the toxicity profile in rats was improved, the predicted human half-life of this compound was short, resulting in unacceptable dosing requirements to maintain a strong antiviral effect in patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

[The Study of Decitabine Effect on the Endometrial Carcinoma Xenografted in Nude Mice.

PubMed

Li, Ran-Hong; Wang, Xue-Ping; Liu, Hui

2016-11-01

To explore the effect of the demethylation drug 5-Aza-CdR on endometrial carcinoma xenografted in nude mice. Randomly assigned the mice into decitabine (AZA),cisplatin (DDP),medroxyprogesterone acetate (MPA),AZA+DDP,AZA+MPA,DDP+MPA and model groups (three in each group) after building the models of xenografted tumor by transplanting the HEC-1B cells on nude mice,and dealt them respectively with corresponding drugs (1 μg/g,single or combination) in the experiment groups and normal saline in model group (injected per 3 d,8 injections in total).Then the tumor inhibitory rates in different groups were calculated.The methylation and protein expression of RASSF1A gene was estimated by methylation specific PCR (MSP) and Western blot respectively,and apoptosis situation of carcinoma cell was estimated by tunel. Inhibitory rate in AZA+DDP group was the highest,and the lowest was AZA group. RASSF1A gene promoter region methylation levels of AZA,AZA+DDP and AZA+MPA groups significantly reduced and showed obvious demethylation stripes while other groups mainly showed the methylation stripes.The differences of RASSF1A protein expression between AZA,AZA+DDP and AZA+MPA groups were not statistical significant ( P >0.05),but the three were higher than model group ( P <0.05);there was no statistically significant difference respectively in the DDP,MPA,DDP+ MPA groups compared with that of model group ( P >0.05).In the comparison of apoptosis index,model group was the lowest,followed by the three single medicine groups,and the highest was three combination groups ( P <0.05). Demethylation drug 5-Aza-CdR in endometrial cancer treatment has a great potential clinical application value by reversing the abnormal methylation of RASSF1A gene,restoring biological functions of RASSF1A protein and strengthening the efficacy of DDP and MPA.

Efficacy of topical azelaic acid (AzA) gel 15% plus oral doxycycline 40 mg versus metronidazole gel 1% plus oral doxycycline 40 mg in mild-to-moderate papulopustular rosacea.

PubMed

Del Rosso, James Q; Bruce, Suzanne; Jarratt, Michael; Menter, Alan; Staedtler, Gerald

2010-06-01

Rosacea is a leading reason why people seek the care of a dermatologist, accounting for nearly 7 million office visits annually. Pharmacologic treatments include both topical and oral medications, which are increasingly being used in combination, especially at the outset of therapy. This exploratory study assesses the safety, effectiveness and speed of onset of two common topical agents for the treatment of rosacea--azelaic acid gel (AzA) 15% and metronidazole gel 1%--used in conjunction with anti-inflammatory dose doxycycline (40 mg once daily). Men and women (n = 207) with mild-to-moderate papulopustular rosacea were enrolled and randomized to receive either AzA gel 15% twice daily plus doxycycline 40 mg once daily (AzA group) or metronidazole gel 1% once daily plus doxycycline 40 mg once daily (Metro group) for 12 weeks. Both regimens were safe, efficacious and well tolerated. Efficacy parameters revealed a possible trend toward greater and earlier benefit with the AzA-based regimen than with the metronidazole-based regimen. These findings warrant further investigation in a sufficiently powered study.

Structure activity relationship of C-2 ether substituted 1,5-naphthyridine analogs of oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents (Part-5).

PubMed

Singh, Sheo B; Kaelin, David E; Meinke, Peter T; Wu, Jin; Miesel, Lynn; Tan, Christopher M; Olsen, David B; Lagrutta, Armando; Fukuda, Hideyuki; Kishii, Ryuta; Takei, Masaya; Takeuchi, Tomoko; Takano, Hisashi; Ohata, Kohei; Kurasaki, Haruaki; Nishimura, Akinori; Shibata, Takeshi; Fukuda, Yasumichi

2015-09-01

Oxabicyclooctane linked novel bacterial topoisomerase inhibitors (NBTIs) are new class of recently reported broad-spectrum antibacterial agents. They target bacterial DNA gyrase and topoisomerase IV and bind to a site different than quinolones. They show no cross-resistance to known antibiotics and provide opportunity to combat drug-resistant bacteria. A structure activity relationship of the C-2 substituted ether analogs of 1,5-naphthyridine oxabicyclooctane-linked NBTIs are described. Synthesis and antibacterial activities of a total of 63 analogs have been summarized representing alkyl, cyclo alkyl, fluoro alkyl, hydroxy alkyl, amino alkyl, and carboxyl alkyl ethers. All compounds were tested against three key strains each of Gram-positive and Gram-negative bacteria as well as for hERG binding activities. Many key compounds were also tested for the functional hERG activity. Six compounds were evaluated for efficacy in a murine bacteremia model of Staphylococcus aureus infection. Significant tolerance for the ether substitution (including polar groups such as amino and carboxyl) at C-2 was observed for S. aureus activity however the same was not true for Enterococcus faecium and Gram-negative strains. Reduced clogD generally showed reduced hERG activity and improved in vivo efficacy but was generally associated with decreased overall potency. One of the best compounds was hydroxy propyl ether (16), which mainly retained the potency, spectrum and in vivo efficacy of AM8085 associated with the decreased hERG activity and improved physical property. Copyright © 2015 Elsevier Ltd. All rights reserved.

A new route to synthesize aryl acetates from carbonylation of aryl methyl ethers

PubMed Central

Yang, Youdi; Li, Shaopeng; Han, Buxing

2018-01-01

Ether bond activation is very interesting because the synthesis of many valuable compounds involves conversion of ethers. Moreover, C–O bond cleavage is also very important for the transformation of biomass, especially lignin, which abundantly contains ether bonds. Developing efficient methods to activate aromatic ether bonds has attracted much attention. However, this is a challenge because of the inertness of aryl ether bonds. We proposed a new route to activate aryl methyl ether bonds and synthesize aryl acetates by carbonylation of aryl methyl ethers. The reaction could proceed over RhCl3 in the presence of LiI and LiBF4, and moderate to high yields of aryl acetates could be obtained from transformation of various aryl methyl ethers with different substituents. It was found that LiBF4 could assist LiI to cleave aryl methyl ether bonds effectively. The reaction mechanism was proposed by a combination of experimental and theoretical studies. PMID:29795781

Antioxidant and antiapoptotic effects of green tea polyphenols against azathioprine-induced liver injury in rats.

PubMed

El-Beshbishy, Hesham A; Tork, Ola M; El-Bab, Mohamed F; Autifi, Mohamed A

2011-04-01

Green tea polyphenols (GTP) is considered to have protective effects against several diseases. The hepatotoxicity of azathioprine (AZA) has been reported and was found to be associated with oxidative damage. This study was conducted to evaluate the role of GTP to protect against AZA-induced liver injury in rats. AZA was administered i.p. in a single dose (50mgkg(-1)) to adult male rats. AZA-intoxicated rats were orally administered GTP (either 100mgkg(-1)day(-1) or 300mgkg(-1)day(-1), for 21 consecutive days, started 7 days prior AZA injection). AZA administration to rats resulted in significant elevation of serum transaminases (sALT and sAST), alkaline phosphatase (sALP), depletion of hepatic reduced glutathione (GSH), catalase (CAT) and glutathione peroxidase (GPx), accumulation of oxidized glutathione (GSSG), elevation of lipid peroxides (LPO) expressed as malondialdehyde (MDA), reduction of the hepatic total antioxidant activity (TAA), decrease serum total proteins and elevation of liver protein carbonyl content. Significant rises in liver tumor necrosis factor-alpha (TNF-α) and caspase-3 levels were noticed in AZA-intoxicated rats. Treatment of the AZA-intoxicated rats with GTP significantly prevented the elevations of sALT, sAST and sALP, inhibited depletion of hepatic GSH, GPx, CAT and GSSG and inhibited MDA accumulation. Furthermore, GTP had normalized serum total proteins and hepatic TAA, CAT, TNF-α and caspase-3 levels of AZA-intoxicated rats. In addition, GTP prevented the AZA-induced apoptosis and liver injury as indicated by the liver histopathological analysis. The linear regression analysis showed significant correlation in either AZA-GTP100 or AZA-GTP300 groups between TNF-α and each of serum ALT, AST, ALP and total proteins and liver TAA, GPX, CAT, GSH, GSSG, MDA and caspase-3 levels. However, liver TNF-α produced non-significant correlation with the serum total proteins in both AZA-GTP100 and AZA-GTP300 groups. In conclusion, our data indicate that GTP protects against AZA-induced liver injury in rats through antioxidant, anti-inflammatory and antiapoptotic mechanisms. However, further merit investigations are needed to verify these results and to assess the efficacy of GTP therapy to counteract the liver injury and oxidative stress status. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Copper-catalyzed oxidative C-O bond formation of 2-acyl phenols and 1,3-dicarbonyl compounds with ethers: direct access to phenol esters and enol esters.

PubMed

Park, Jihye; Han, Sang Hoon; Sharma, Satyasheel; Han, Sangil; Shin, Youngmi; Mishra, Neeraj Kumar; Kwak, Jong Hwan; Lee, Cheong Hoon; Lee, Jeongmi; Kim, In Su

2014-05-16

A copper-catalyzed oxidative coupling of 2-carbonyl-substituted phenols and 1,3-dicarbonyl compounds with a wide range of dibenzyl or dialkyl ethers is described. This protocol provides an efficient preparation of phenol esters and enol esters in good yields with high chemoselectivity. This method represents an alternative protocol for classical esterification reactions.

A PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODEL FOR DEVELOPMENTAL EXPOSURE TO PBDE-47 IN RODENTS

EPA Science Inventory

Polybrominated diphenyl ethers (PBDEs) are used commercially as additive flame retardants and have been shown to transfer into environmental compartments where they have the potential to bioaccumulate in wildlife and in people. These compounds have been detected in blood and oth...

Removing Biostatic Agents From Fermentation Solutions

NASA Technical Reports Server (NTRS)

Du Fresne, E. R.

1984-01-01

Liquid carbon dioxide inexpensive solvent. Inexpensive process proposed for removing such poisons as furfural and related compounds from fermentation baths of biomass hydrolysates. New process based on use of liquid carbon dioxide as extraction solvent. Liquid CO2 preferable to such other liquid solvents as ether or methylene chloride.

Radiolabeled cholesteryl ethers: A need to analyze for biological stability before use.

PubMed

Manual Kollareth, Denny Joseph; Chang, Chuchun L; Hansen, Inge H; Deckelbaum, Richard J

2018-03-01

Radiolabeled cholesteryl ethers are widely used as non-metabolizable tracers for lipoproteins and lipid emulsions in a variety of in vitro and in vivo experiments. Since cholesteryl ethers do not leave cells after uptake and are not hydrolyzed by mammalian cellular enzymes, these compounds can act as markers for cumulative cell uptakes of labeled particles. We have employed [ 3 H]cholesteryl oleoyl ether to study the uptake and distribution of triglyceride-rich emulsion particles on animal models. However, questionable unexpected results compelled us to analyze the stability of these ethers. We tested the stability of two commercially available radiolabeled cholesteryl ethers - [ 3 H]cholesteryl oleoyl ether and [ 3 H]cholesteryl hexadecyl ether from different suppliers, employing in vitro , in vivo and chemical model systems. Our results show that, among the two cholesteryl ethers tested, one ether was hydrolyzed to free cholesterol in vitro , in vivo and chemically under alkaline hydrolyzing agent. Free cholesterol, unlike cholesteryl ether, can then re-enter the circulation leading to confounding results. The other ether was not hydrolyzed to free cholesterol and remained as a stable ether. Hence, radiolabeled cholesteryl ethers should be analyzed for biological stability before utilizing them for in vitro or in vivo experiments.

Azaspiracid Shellfish Poisoning: A Review on the Chemistry, Ecology, and Toxicology with an Emphasis on Human Health Impacts

PubMed Central

Twiner, Michael J.; Rehmann, Nils; Hess, Philipp; Doucette, Gregory J.

2008-01-01

Azaspiracids (AZA) are polyether marine toxins that accumulate in various shellfish species and have been associated with severe gastrointestinal human intoxications since 1995. This toxin class has since been reported from several countries, including Morocco and much of western Europe. A regulatory limit of 160 μg AZA/kg whole shellfish flesh was established by the EU in order to protect human health; however, in some cases, AZA concentrations far exceed the action level. Herein we discuss recent advances on the chemistry of various AZA analogs, review the ecology of AZAs, including the putative progenitor algal species, collectively interpret the in vitro and in vivo data on the toxicology of AZAs relating to human health issues, and outline the European legislature associated with AZAs. PMID:18728760

Biodegradation of coal-related model compounds. [C. versicolor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campbell, J.A.; Stewart, D.L.; McCulloch, M.

1988-01-01

The details of the specific reactions of lignin biodegradation, and the biochemistry involved, have been primarily based on the use of low molecular weight compounds representing specific substructures rather than the complex, polymeric lignin material. The authors have studied the reactions of model compounds having coal-related functionalities (ester linkages, ether linkages, PAH) with the intact organisms, cell-free filtrate, and cell-free enzyme of C. versicolor to better understand the process of biosolubilization. Many of the degradation products have been identified by gas chromatography/mass spectrometry (GC/MS). Results are discussed.

5-AZA-2'-DEOXYCYTIDINE-INDUCED DYSMORPHOGENESIS IN THE RAT

EPA Science Inventory

5-AZA-2'-deoxycytidine-induced dysmorphogenesis in the rat.

Branch S, Chernoff N, Brownie C, Francis BM.

Department of Toxicology, North Carolina State University, Raleigh, North Carolina 27695, USA. S_Branch@ncsu.edu

5-aza-2'-deoxycytidine (d-AZA) causes tem...

POLYBROMINATED DIPHENYL ETHERS (PBDES) CONTAMINATION OF UNITED STATES FOOD

EPA Science Inventory

Elevated levels of polybrominated diphenyl ethers (PBDEs), a type of brominated flame retardant, were recently detected in United States (U.S.) nursing mothers' milk. These halogenated compounds chemically and toxicologically resemble others such as polychlorinated biphenyls (PC...

Preparation, Fabrication, and Evaluation of Advanced Polymeric and Composite Materials

NASA Technical Reports Server (NTRS)

Orwoll, Robert A.

1997-01-01

The thesis titles are given below: physical and mechanical behavior of amorphous poly(arylene ether-co-imidasole)s and poly(arylene ether-co-imidasole) modification epoxies; the requirements of patentability as applied to the chemical arts; fabrication of thermoplastic polymer composite ribbon; blend of reactive diluents with phenylethynyl-terminated arylene ether oligomers; the synthesis, characterization, and application of ether-containing polyimides; the synthesis of reflective and electrically conductive polyimide films via an in-situ self-metalization procedure using silver (I) complexes; the thermal cure of phenylethynyl terminated polyimides and selected model compounds; and the synthesis, characterization, and molecular modeling of cyclic arylene ether oligomers.

Synergic effects in the extraction of paracetamol from aqueous NaCl solution by the binary mixtures of diethyl ether and low molecular weight primary alcohols

NASA Astrophysics Data System (ADS)

Nikolić, G. M.; Živković, J. V.; Atanasković, D. S.; Nikolić, M. G.

2013-12-01

Liquid-liquid extraction of paracetamol from aqueous NaCl solutions was performed with diethyl ether, 1-propanol, 1-butanol, isobutanol, 1-pentanol, and binary mixtures diethyl ether/1-propanol, diethyl ether/1-butanol, and diethyl ether/isobutanol. Among the pure solvents investigated in this study best extraction efficacy was obtained with 1-butanol. Synergic effects in the extraction with binary mixtures was investigated and compared with some other systems used for the extraction of poorly extractable compounds. Results obtained in this study may be of both fundamental and practical importance.

Comparative effects of sodium channel blockers in short term rat whole embryo culture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nilsson, Mats F, E-mail: Mats.Nilsson@farmbio.uu.se; Sköld, Anna-Carin; Ericson, Ann-Christin

2013-10-15

This study was undertaken to examine the effect on the rat embryonic heart of two experimental drugs (AZA and AZB) which are known to block the sodium channel Nav1.5, the hERG potassium channel and the L-type calcium channel. The sodium channel blockers bupivacaine, lidocaine, and the L-type calcium channel blocker nifedipine were used as reference substances. The experimental model was the gestational day (GD) 13 rat embryo cultured in vitro. In this model the embryonic heart activity can be directly observed, recorded and analyzed using computer assisted image analysis as it responds to the addition of test drugs. The effectmore » on the heart was studied for a range of concentrations and for a duration up to 3 h. The results showed that AZA and AZB caused a concentration-dependent bradycardia of the embryonic heart and at high concentrations heart block. These effects were reversible on washout. In terms of potency to cause bradycardia the compounds were ranked AZB > bupivacaine > AZA > lidocaine > nifedipine. Comparison with results from previous studies with more specific ion channel blockers suggests that the primary effect of AZA and AZB was sodium channel blockage. The study shows that the short-term rat whole embryo culture (WEC) is a suitable system to detect substances hazardous to the embryonic heart. - Highlights: • Study of the effect of sodium channel blocking drugs on embryonic heart function • We used a modified method rat whole embryo culture with image analysis. • The drugs tested caused a concentration dependent bradycardia and heart block. • The effect of drugs acting on multiple ion channels is difficult to predict. • This method may be used to detect cardiotoxicity in prenatal development.« less

Substrate-derived triazolo- and azapeptides as inhibitors of cathepsins K and S.

PubMed

Galibert, Matthieu; Wartenberg, Mylène; Lecaille, Fabien; Saidi, Ahlame; Mavel, Sylvie; Joulin-Giet, Alix; Korkmaz, Brice; Brömme, Dieter; Aucagne, Vincent; Delmas, Agnès F; Lalmanach, Gilles

2018-01-20

Cathepsin (Cat) K is a critical bone-resorbing protease and is a relevant target for the treatment of osteoporosis and bone metastasis, while CatS is an attractive target for drugs in autoimmune diseases (e.g. rheumatoid arthritis), emphysema or neuropathic pain. Despite major achievements, current pharmacological inhibitors are still lacking in safety and may have damaging side effects. A promising strategy for developing safer reversible and competitive inhibitors as new lead compounds could be to insert non-cleavable bonds at the scissile P1-P1' position of selective substrates of CatS and CatK. Accordingly, we introduced a 1,4-disubstituted 1,2,3-triazole heterocycle that mimics most of the features of a trans-amide bond, or we incorporated a semicarbazide bond (azaGly residue) by replacing the α-carbon of the glycyl residue at P1 by a nitrogen atom. AzaGly-containing peptidomimetics inhibited powerfully their respective target proteases in the nM range, while triazolopeptides were weaker inhibitors (Ki in the μM range). The selectivity of the azaGly CatS inhibitor (1b) was confirmed by using spleen lysates from wild-type vs CatS-deficient mice. Alternatively, the azaGly bradykinin-derived CatK inhibitor (2b) potently inhibited CatK (Ki = 9 nM) and impaired its kininase activity in vitro. Molecular modeling studies support that the semicarbazide bond of 2b is more favorable than the 1,2,3-triazole linkage of the bradykinin-derived pseudopeptide 2a to preserve an effective affinity towards CatK, its protease target. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Enhanced cytogenetic and antineoplastic effects by the combined action of two esteric steroidal derivatives of nitrogen mustards.

PubMed

Papageorgiou, A; Nikolaropoulos, S S; Arsenou, E S; Karaberis, E; Mourelatos, D; Kotsis, A; Chryssogelou, E

1999-01-01

The authors studied the effect of two modified steroids containing different proportions (%) of alkylating agents alone or in combination on sister chromatid exchange (SCE) rates and on human lymphocyte proliferation kinetics. The antitumor activity of these compounds was tested on leukemia P388- and leukemia L1210-bearing mice. The two chemicals in mixtures enhance SCE induction and antitumor activity in a synergistic manner. The homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenyl acetic acid was found to be more effective than the homo-aza-steroidal ester of o-bis(2-chloroethyl)aminobenzoic acid in causing cytogenetic damage and antineoplastic activity. A correlation was observed between the magnitude of the SCE response and the depression of the cell proliferation index. The order of the antitumor effectiveness of the five different treatments tested coincided with the order of the cytogenetic effects they induced.

Fairy Chemicals, 2-Azahypoxanthine and 2-Aza-8-oxohypoxanthine, Regulate Carotenoid Accumulation in Citrus Juice Sacs in Vitro.

PubMed

Ma, Gang; Zhang, Lancui; Yamawaki, Kazuki; Yahata, Masaki; Choi, Jae-Hoon; Kawagishi, Hirokazu; Kato, Masaya

2015-08-19

"Fairy chemicals", 2-azahypoxanthine (AHX) and 2-aza-8-oxohypoxanthine (AOH), are two novel plant-growth regulating compounds isolated from a fairy ring forming fungus, Lepista sordida. In the present study, the effects of AHX and AOH on the accumulation of carotenoids and expression of genes related to carotenoid metabolism were investigated in the juice sacs of Satsuma mandarin (Citrus unshiu Marc.) in vitro. The results showed that AHX and AOH regulated carotenoid metabolism in the citrus juice sacs. Carotenoid accumulation was induced by AHX in the second week and by AOH in the fourth week. In the meanwhile, the modification of carotenoid accumulation by the AHX and AOH treatments was highly regulated at the transcriptional level. The results presented herein provide new information on the functions of AHX and AOH in plants and contribute to elucidating the mechanisms by which AHX and AOH stimulate plant growth.

Nature-inspired indolyl-2-azabicyclo[2.2.2]oct-7-ene derivatives as promising agents for the attenuation of withdrawal symptoms: synthesis of 20-desethyl-20-hydroxymethyl-11-demethoxyibogaine.

PubMed

Passarella, D; Barilli, A; Efange, S M N; Elisabetsky, E; Leal, M B; Lesma, G; Linck, V M; Mash, D C; Martinelli, M; Peretto, I; Silvani, A; Danieli, B

2006-07-10

Microwave assisted Diels-Alder cycloaddition of 5-Br-N-benzylpyridinone (2) with methyl acrylate is described to gain an easy access to 7-bromo-2-benzyl-3-oxo-2-aza-5 or 6-carbomethoxy bicyclo[2.2.2]oct-7-enes (3)-(6). The preparation of the ibogaine analogue 20-desethyl-(20-endo)-hydroxymethyl-11-demethoxyibogaine (17) is described by stereoselective hydrogenation of the C(7)-C(8) double bond. Biological evaluation showed an interesting in vitro binding profile toward dopamine transporter, serotonin transporter and opioid receptor systems accompanied by an antiwithdrawal effect in mice for hydroxymethyl 7-indolyl-2-aza-bicyclo[2.2.2]oct-2-ene (14). The simplification of the ibogaine structure appears as a promising approach toward the design of compounds that could reduce the withdrawal symptoms.

Method for determination of methyl tert-butyl ether and its degradation products in water

USGS Publications Warehouse

Church, C.D.; Isabelle, L.M.; Pankow, J.F.; Rose, D.L.; Tratnyek, P.G.

1997-01-01

An analytical method is described that can detect the major alkyl ether compounds that are used as gasoline oxygenates (methyl tert-butyl ether, MTBE; ethyl tert-butyl ether, ETBE; and tert-amyl methyl ether, TAME) and their most characteristic degradation products (tert-butyl alcohol, TBA; tert-butyl formate, TBF; and tert-amyl alcohol, TAA) in water at sub-ppb concentrations. The new method involves gas chromatography (GC) with direct aqueous injection (DAI) onto a polar column via a splitless injector, coupled with detection by mass spectrometry (MS). DAI-GC/MS gives excellent agreement with conventional purge-and-trap methods for MTBE over a wide range of environmentally relevant concentrations. The new method can also give simultaneous identification of polar compounds that might occur as degradation products of gasoline oxygenates, such as TBA, TBF, TAA, methyl acetate, and acetone. When the method was applied to effluent from a column microcosm prepared with core material from an urban site in New Jersey, conversion of MTBE to TBA was observed after a lag period of 35 days. However, to date, analyses of water samples from six field sites using the DAI-GC/MS method have not produced evidence for the expected products of in situ degradation of MTBE.An analytical method is described that can detect the major alkyl ether compounds that are used as gasoline oxygenates (methyl tert-butyl ether, MTBE; ethyl tert-butyl ether, ETBE; and tert-amyl methyl ether, TAME) and their most characteristic degradation products (tert-butyl alcohol, TBA; tert-butyl formate, TBF; and tert-amyl alcohol, TAA) in water at sub-ppb concentrations. The new method involves gas chromatography (GC) with direct aqueous injection (DAI) onto a polar column via a splitless injector, coupled with detection by mass spectrometry (MS). DAI-GC/MS gives excellent agreement with conventional purge-and-trap methods for MTBE over a wide range of environmentally relevant concentrations. The new method can also give simultaneous identification of polar compounds that might occur as degradation products of gasoline oxygenates, such as TBA, TBF, TAA, methyl acetate, and acetone. When the method was applied to effluent from a column microcosm prepared with core material from an urban site in New Jersey, conversion of MTBE to TBA was observed after a lag period of 35 days. However, to date, analyses of water samples from six field sites using the DAI-GC/MS method have not produced evidence for the expected products of in situ degradation of MTBE.

Anti-Helicobacter pylori activity of bioactive components isolated from Hericium erinaceus.

PubMed

Liu, Jian-Hui; Li, Liang; Shang, Xiao-Dong; Zhang, Jun-Ling; Tan, Qi

2016-05-13

The fungus Hericium erinaceus (Bull.) Pers is used in Chinese traditional medicine to treat symptoms related to gastric ulcers. Different extracts from the fungus were assessed for anti-Helicobacter pylori activity to investigate the antibacterial activity of the ethanol extracts from H. erinaceus and verify the traditional indication of use. The fruiting bodies of H. erinaceus were concentrated with ethanol by HPD-100 macroporous resin and the whole extract was partitioned by petroleum ether and chloroform to afford fractions with using a silica gel column. Several pure compounds of petroleum ether extracts were obtained and analyzed using nuclear magnetic resonance (NMR). The activity of the extracts and fractions towards H. pylori was assessed by the microdilution assay and by the disk diffusion assay in vitro. From the most active fraction, two pure compounds were isolated and identified as the main components with anti-H. pylori activity from the fungus H. erinaceus. The cytotoxicity of these two compounds against the human erythroleu-kemia cell line K562 was also evaluated. The crude ethanol extracts from the fungus H. erinaceus were inhibitory to H. pylori. The petroleum ether extracts (PE1s, PE2s) and the chloroform extracts (TEs) demonstrated strong inhibition to H. pylori. The inhibition of H. pylori was observed through an agar dilution test with minimal inhibition concentration (MIC) values from 400μg/mL to 12.5µg/mL. Two pure compounds, 1-(5-chloro-2-hydroxyphenyl)-3-methyl-1-butanone and 2,5-bis(methoxycarbonyl)terephthalic acid were isolated from the petroleum ether fractions and identified using (1)H NMR and (13)C NMR spectra analysis. The MIC value for 1-(5-chloro-2-hydroxyphenyl)-3-methyl-1-butanone was 12.5-50µg/mL and the MIC value for 2,5-bis(methoxycarbonyl)terephthalic acid was 6.25-25µg/mL. Both two compounds showed weak cytotoxicity against K562 with IC50<200mM. This study revealed that the extracts from petroleum ether contribute to the anti-H. pylori activity. The compounds obtained from petroleum ether extracts, 1-(5-chloro-2-hydroxyphenyl)-3-methyl-1-butanone and 2,5-bis(methoxycarbonyl)terephthalic acid, inhibit the growth of H. pylori. Copyright © 2016. Published by Elsevier Ireland Ltd.

[Study on Chemical Constituents of Petroleum Ether Fraction from Rubus alceaefolius].

PubMed

Chen, Pan; Fang, Zhi-jian; Yan, Han-jing; Zhou, Hong-bo; Mei, Quan-xi

2015-01-01

To investigate the chemical constituents of Rubus alceaefolius. Nine compounds were isolated and purified from the petroleum ether extract of 95% alcohol extract of Rubus alceaefolius by repeated column chromatography on silica, Sephadex LH-20 and structurally identified by spectral analysis. The compounds were identified as chrysophanol(1), physcion (2), β-sitosterol(3), 3-oxotirucalla-7, 24-dien-21-oic acid(4), myricadiol(5), 19-α-hydroxy-3-acetyl-ursolic acid(6), N-benzoylphenylalaninyl-N-benzoylphenylalaninate(7), aurantiamide acetate(8) and euscaphic acid(9). Compounds land 4~8 are isolated from this plant for the first time, and compounds 4 - 8 are found in plants of Rubus genus for the first time.

Has there been a change in the natural history of Crohn's disease? Surgical rates and medical management in a population-based inception cohort from Western Hungary between 1977-2009.

PubMed

Lakatos, Peter Laszlo; Golovics, Petra Anna; David, Gyula; Pandur, Tunde; Erdelyi, Zsuzsanna; Horvath, Agnes; Mester, Gabor; Balogh, Mihaly; Szipocs, Istvan; Molnar, Csaba; Komaromi, Erzsebet; Veres, Gabor; Lovasz, Barbara Dorottya; Szathmari, Miklos; Kiss, Lajos S; Lakatos, Laszlo

2012-04-01

Medical therapy for Crohn's disease (CD) has changed significantly over the past 20 years with increasing use of immunosuppressives. In contrast, surgery rates are still high and there is little evidence that disease outcomes for CD have changed over the past decades. The objective of this study was to analyze the evolution of the surgical rates and medical therapy in the population-based Veszprem province database. Data of 506 incident CD patients were analyzed (age at diagnosis: 31.5 years, s.d. 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. The study population was divided into three groups by the year of diagnosis (cohort A: 1977-1989, cohort B: 1990-1998 and cohort C: 1999-2008). Overall, azathioprine (AZA), systemic steroid, and biological (only available after 1998) exposure was 45.8, 68.6, and 9.5%, respectively. The 1- and 5-year probability of AZA use were 3.2 and 6.2% in cohort A, 11.4 and 29.9% in cohort B, and 34.8 and 46.2% in cohort C. In a multivariate Cox-regression analysis, decade of diagnosis (P < 0.001, hazard ratio (HR)(cohorts B-C): 2.88-6.53), age at onset (P = 0.008, HR: 1.76), disease behavior at diagnosis (P < 0.001, HR(complicated): 1.76-2.07), and need for systemic steroids (P < 0.001, HR: 2.71) were significantly associated with the time to initiation of AZA therapy. Early AZA use was significantly associated with the time to intestinal surgery in CD patients; in a multivariate Cox analysis (HR: 0.43, 95% confidence interval (CI): 0.28-0.65) and after matching on propensity scores for AZA use (HR: 0.42, 95% CI: 0.26-0.67). This population-based inception cohort has shown that the recent reduction in surgical rates was independently associated with increased and earlier AZA use.

THE RELATION OF CHEMICAL STRUCTURE IN CATECHOL COMPOUNDS AND DERIVATIVES TO POISON IVY HYPERSENSITIVENESS IN MAN AS SHOWN BY THE PATCH TEST

PubMed Central

Keil, Harry; Wasserman, David; Dawson, Charles R.

1944-01-01

1. Additional evidence is presented in support of the view which postulates a close chemical and biologic relation between the active ingredients in poison ivy and Japan lac. 2. Biologic evidence, based on the use of the patch test in man, is presented in support of the view that the active ingredient in poison ivy is a catechol derivative with a long, unsaturated side-chain in the 3-position. 3. Of the catechol compounds and derivatives studied, group reactions in patients sensitive to poison ivy leaves or extract were exhibited by the following compounds: 3-pentadecyl catechol (100 per cent of 21 cases), 4-pentadecyl catechol (38 per cent of 21 cases), "urushiol" dimethyl ether (33 per cent of 33 cases), 3-pentadecenyl-1'-veratrole (21 per cent of 14 cases), 3-methyl catechol (14 per cent of 21 cases), and hydrourushiol dimethyl ether (10 per cent of 20 cases). It has been found that 3-geranyl catechol shows a practically constant group reactivity in persons sensitive to poison ivy. 4. The uniformly positive group reaction to 3-pentadecyl catechol is notable since this substance possesses a saturated side-chain, whereas the active ingredient in poison ivy is known to have an unsaturated side-chain. 5. The group reactivity was not restricted to the 3-position, for in some instances 4-pentadecyl catechol also gave group reactions which, however, were less intense and less frequent than those shown by 3-pentadecyl catechol. This indicates that in some cases a long side-chain in the 4 position may be effective in producing group specific reactions. 6. Only an occasional person showed sensitiveness to 3-methyl catechol (short side-chain), and in one instance the group reactivity appeared to be specific for the 3-position. 7. The position of the side-chain in the catechol configuration has some bearing on the degree and incidence of group reactions in persons hypersensitive to poison ivy. 8. Evidence is presented to indicate that the introduction of double bonds in the alkyl side-chain increases the incidence and intensity of group reactions. 9. Methylating the hydroxyl groups in the catechol configuration diminishes strongly the incidence of group reactivity but does not eliminate it entirely in persons hypersensitive to poison ivy. Thus, "urushiol" dimethyl ether (3-pentadecadienyl veratrole) gave group reactions in 33 per cent of 33 persons. 10. Methylating the hydroxyl groups as well as saturating the double bonds in the alkyl side-chain still further diminishes the group reactions but an occasional person hypersensitive to poison ivy may still show positive reaction to such a substance as 3-pentadecyl veratrole (hydrourushiol dimethyl ether). In this respect our results are not in full agreement with those recorded by Toyama who stated that hydrourushiol dimethyl ether is entirely harmless. 11. The significance of the group reactivity displayed by certain veratrole compounds is discussed, and several possible explanations of their behavior are advanced. 12. The group reactions discussed in this paper relate only to various catechol and veratrole compounds. Preliminary studies by us indicate that this sensitiveness extends to other phenolic derivatives. 13. Among the veratrole compounds showing positive reactions, the order of frequency and intensity was: (1) "urushiol" dimethyl ether (average of two double bonds); (2) S-pentadecenyl-1'-veratrole (one double bond); (3) hydrourushiol dimethyl ether (saturated side-chain). It may be noted that 4-pentadecyl veratrole was inactive. PMID:19871415

THE RELATION OF CHEMICAL STRUCTURE IN CATECHOL COMPOUNDS AND DERIVATIVES TO POISON IVY HYPERSENSITIVENESS IN MAN AS SHOWN BY THE PATCH TEST.

PubMed

Keil, H; Wasserman, D; Dawson, C R

1944-10-01

1. Additional evidence is presented in support of the view which postulates a close chemical and biologic relation between the active ingredients in poison ivy and Japan lac. 2. Biologic evidence, based on the use of the patch test in man, is presented in support of the view that the active ingredient in poison ivy is a catechol derivative with a long, unsaturated side-chain in the 3-position. 3. Of the catechol compounds and derivatives studied, group reactions in patients sensitive to poison ivy leaves or extract were exhibited by the following compounds: 3-pentadecyl catechol (100 per cent of 21 cases), 4-pentadecyl catechol (38 per cent of 21 cases), "urushiol" dimethyl ether (33 per cent of 33 cases), 3-pentadecenyl-1'-veratrole (21 per cent of 14 cases), 3-methyl catechol (14 per cent of 21 cases), and hydrourushiol dimethyl ether (10 per cent of 20 cases). It has been found that 3-geranyl catechol shows a practically constant group reactivity in persons sensitive to poison ivy. 4. The uniformly positive group reaction to 3-pentadecyl catechol is notable since this substance possesses a saturated side-chain, whereas the active ingredient in poison ivy is known to have an unsaturated side-chain. 5. The group reactivity was not restricted to the 3-position, for in some instances 4-pentadecyl catechol also gave group reactions which, however, were less intense and less frequent than those shown by 3-pentadecyl catechol. This indicates that in some cases a long side-chain in the 4 position may be effective in producing group specific reactions. 6. Only an occasional person showed sensitiveness to 3-methyl catechol (short side-chain), and in one instance the group reactivity appeared to be specific for the 3-position. 7. The position of the side-chain in the catechol configuration has some bearing on the degree and incidence of group reactions in persons hypersensitive to poison ivy. 8. Evidence is presented to indicate that the introduction of double bonds in the alkyl side-chain increases the incidence and intensity of group reactions. 9. Methylating the hydroxyl groups in the catechol configuration diminishes strongly the incidence of group reactivity but does not eliminate it entirely in persons hypersensitive to poison ivy. Thus, "urushiol" dimethyl ether (3-pentadecadienyl veratrole) gave group reactions in 33 per cent of 33 persons. 10. Methylating the hydroxyl groups as well as saturating the double bonds in the alkyl side-chain still further diminishes the group reactions but an occasional person hypersensitive to poison ivy may still show positive reaction to such a substance as 3-pentadecyl veratrole (hydrourushiol dimethyl ether). In this respect our results are not in full agreement with those recorded by Toyama who stated that hydrourushiol dimethyl ether is entirely harmless. 11. The significance of the group reactivity displayed by certain veratrole compounds is discussed, and several possible explanations of their behavior are advanced. 12. The group reactions discussed in this paper relate only to various catechol and veratrole compounds. Preliminary studies by us indicate that this sensitiveness extends to other phenolic derivatives. 13. Among the veratrole compounds showing positive reactions, the order of frequency and intensity was: (1) "urushiol" dimethyl ether (average of two double bonds); (2) S-pentadecenyl-1'-veratrole (one double bond); (3) hydrourushiol dimethyl ether (saturated side-chain). It may be noted that 4-pentadecyl veratrole was inactive.

Eco-friendly synthesis, physicochemical studies, biological assay and molecular docking of steroidal oxime-ethers

PubMed Central

Alam, Mahboob; Lee, Dong-Ung

2015-01-01

The aim of this study was to report the synthesis of biologically active compounds; 7-(2′-aminoethoxyimino)-cholest-5-ene (4), a steroidal oxime-ether and its derivatives (5, 6) via a facile microwave assisted solvent free reaction methodology. This new synthetic, eco-friendly, sustainable protocol resulted in a remarkable improvement in the synthetic efficiency (85-93 % yield) and high purity using basic alumina. The synthesized compounds were screened for their antibacterial against six bacterial strains by disc diffusion method and antioxidant potential by DPPH assay. The binding capabilities of a compound 6 exhibiting good antibacterial potential were assessed on the basis of molecular docking studies and four types of three-dimensional molecular field descriptors. Moreover the structure-antimicrobial activity relationships were studied using some physicochemical and quantum-chemical parameters with GAMESS interface as well as WebMO Job Manager by using the basic level of theory. Hence, this synthetic approach is believed to provide a better scope for the synthesis of steroidal oxime-ether analogues and will be a more practical alternative to the presently existing procedures. Moreover, detailed in silico docking studies suggested the plausible mechanism of steroidal oxime-ethers as effective antimicrobial agents. PMID:27330525

Using aggregated, de-identified electronic health record data for multivariate pharmacosurveillance: a case study of azathioprine.

PubMed

Patel, Vishal N; Kaelber, David C

2014-12-01

To demonstrate the use of aggregated and de-identified electronic health record (EHR) data for multivariate post-marketing pharmacosurveillance in a case study of azathioprine (AZA). Using aggregated, standardized, normalized, and de-identified, population-level data from the Explore platform (Explorys, Inc.) we searched over 10 million individuals, of which 14,580 were prescribed AZA based on RxNorm drug orders. Based on logical observation identifiers names and codes (LOINC) and vital sign data, we examined the following side effects: anemia, cell lysis, fever, hepatotoxicity, hypertension, nephrotoxicity, neutropenia, and neutrophilia. Patients prescribed AZA were compared to patients prescribed one of 11 other anti-rheumatologic drugs to determine the relative risk of side effect pairs. Compared to AZA case report trends, hepatotoxicity (marked by elevated transaminases or elevated bilirubin) did not occur as an isolated event more frequently in patients prescribed AZA than other anti-rheumatic agents. While neutropenia occurred in 24% of patients (RR 1.15, 95% CI 1.07-1.23), neutrophilia was also frequent (45%) and increased in patients prescribed AZA (RR 1.28, 95% CI 1.22-1.34). After constructing a pairwise side effect network, neutropenia had no dependencies. A reduced risk of neutropenia was found in patients with co-existing elevations in total bilirubin or liver transaminases, supporting classic clinical knowledge that agranulocytosis is a largely unpredictable phenomenon. Rounding errors propagated in the statistically de-identified datasets for cohorts as small as 40 patients only contributed marginally to the calculated risk. Our work demonstrates that aggregated, standardized, normalized and de-identified population level EHR data can provide both sufficient insight and statistical power to detect potential patterns of medication side effect associations, serving as a multivariate and generalizable approach to post-marketing drug surveillance. Copyright © 2013 Elsevier Inc. All rights reserved.

5-AZA-2'-DEOXYCYTIDINE INDUCED CYTOTOXICITY AND LONG BONE REDUCTION DEFECTS IN THE MURINE LIMB

EPA Science Inventory

The antineoplastic drug 5-aza-2'-deoxycytidine (dAZA) is a DNA hypomethylating agent that can be used to induce hind limb phocomelia in the offspring of CD-1 Swiss Webster mice. Previously, our laboratory investigated the possibility that dAZA induced alterations in gene express...

The use of monitoring data in EU chemicals management--experiences and considerations from the German environmental specimen bank.

PubMed

Koschorreck, Jan; Heiss, Christiane; Wellmitz, Jörg; Fliedner, Annette; Rüdel, Heinz

2015-02-01

Since the 1970s, environmental specimen banks (ESB) have emerged in many countries. Their highly standardised sampling and archiving strategies make them a valuable tool in tracing time trends and spatial distributions of chemicals in ecosystem compartments. The present article intends to highlight the potential of ESBs for regulatory agencies in the European Union (EU). The arguments are supported by examples of retrospective monitoring studies conducted under the programme of the German ESB. These studies have evaluated the success of regulatory and industry provisions for substances of concern (i.e. PCB, polybrominated diphenyl ethers, perfluorinated compounds, alkylphenol compounds, organotin compounds, triclosan/methyl-triclosan, musk fragrances). Time trend studies revealed for example that levels of organotin compounds in marine biota from German coastal waters decreased significantly after the EU had decided on a total ban of organotin-based antifoulings in 2003. Similarly, concentrations of commercially relevant congeners of polybrominated diphenyl ethers decreased in herring gull eggs from the North Sea only after an EU-wide ban in 2004. The data presented demonstrate the usefulness of ESB samples for (retrospective) time trend monitoring and underline the benefit of a more intensive cooperation between chemicals management and specimen banking.

Effect of ionization and vehicle on skin absorption and penetration of azelaic acid.

PubMed

Li, Nan; Wu, Xiaohong; Jia, Weibu; Zhang, Michelle C; Tan, Fengping; Zhang, Jerry

2012-08-01

The aim of this study is to investigate the effect of ionization and vehicle of topical formulations on skin absorption and penetration of azelaic acid (AZA). In vitro transport of AZA was determined for two topical formulations containing AZA with pH values of 3.9 and 4.9, respectively. FINACEA(®) (15% AZA gel), a US Food and Drug Administration approved drug for treatment of acne and rosacea, was also used for comparison. Release profile and flux of AZA were determined in an in vitro hairless mouse skin model using Franz Diffusion Cell. The data have shown that a higher concentration of AZA is retained in the epidermis/dermis layer and the whole skin for the formulation with pH = 4.9 as compared to that with pH = 3.9 at an active loading level of 2.82 mg/cm(2). In addition, the flux of ionized species of AZA in the pH 4.9 formulation (128.4 ± 35.9 μg/cm(2)/h) is approximately five-fold greater than that in the pH 3.9 formulation (27.7 ± 4.0 μg/cm(2)/h). The results suggest that the ionized AZA penetrates through the skin and accounts for majority of the total flux. This study has demonstrated that the penetration and absorption of AZA show a strong pH- and vehicle-dependency. Solubilization is the rate-limiting step in percutaneous absorption of AZA.

A new cytotoxic flavonoid from the fruit of Sinopodophyllum hexandrum.

PubMed

Kong, Yue; Xiao, Jun-Jun; Meng, Shu-Cong; Dong, Xiao-Min; Ge, Yue-Wei; Wang, Ru-Feng; Shang, Ming-Ying; Cai, Shao-Qing

2010-07-01

Constituents of the fruit of Sinopodophyllum hexandrum (Royle) Ying (Sinopodophylli Fructus) were investigated. A new flavonoid, 8,2'-diprenylquercetin 3-methyl ether along with 9 known compounds were isolated and identified. Among them, the new compound 8,2'-diprenylquercetin 3-methyl ether exhibited cytotoxic activities against MDA-231 and T47D breast cancer cell lines, quercetin, kaempferol and rutin were isolated from Sinopodophylli Fructus for the first time. Copyright 2009 Elsevier B.V. All rights reserved.

Sunlight decreased genotoxicity of azadirachtin on root tip cells of Allium cepa and Eucrosia bicolor.

PubMed

Kwankua, W; Sengsai, S; Kuleung, C; Euawong, N

2010-07-01

Utilization of neem plant (Azadirachta indica A. Juss) extract for pest control in agriculture has raised concerns over contamination by the residues to the environment. Such residues, particularly azadirachtin (Aza), may cause deleterious effect to non-target organisms. This investigation was conducted to find out if Aza could be inactivated through exposures to sunlight. Activity of Aza was assessed as its ability to cause cytotoxic and genotoxic effects in the forms of nuclei abnormality and chromosome aberration as measured by mitotic index (MI) and mitotic aberration (MA). Varying concentrations of Aza were tested on Allium cepa and Eucrosia bicolor. It was found that the MI of all root tip meristematic cells of A. cepa and E. bicolor treated with 0.00005%, 0.00010%, 0.00015%, and 0.00020% (w/v) Aza-containing neem extract for 24h, were significantly lower than the controls. Complementary to the lower levels of MI, the Aza-treated groups showed higher MA levels in all cases investigated. Furthermore, the decreasing levels of MI and the increasing levels of MA related well with the increasing concentration of Aza. Microscopic examination of root tip meristematic cells revealed that the anomaly found most often were mitotic disturbances and chromosomal bridges. Exposures of 0.00020% (w/v) Aza to sunlight for 3 days and 7 days decreased Aza ability to induce cytotoxicity and genotoxicity, both in terms of MI and MA, to root tip meristematic cells in A. cepa and E. bicolor. Photodegradation of Aza upon exposure to direct sunlight was confirmed by HPLC. The study implicates that Aza would unlikely cause long term deleterious effects to the environment since it would be inactivated by sunlight. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Genetic evaluation of the Association of Zoos and Aquariums Matschie's tree kangaroo (Dendrolagus matschiei) captive breeding program.

PubMed

McGreevy, Thomas J; Dabek, Lisa; Husband, Thomas P

2011-01-01

Matschie's tree kangaroo (Dendrolagus matschiei) is an endangered species that has been bred in captivity since the 1970s. In 1992, the Tree Kangaroo Species Survival Plan(®) (TKSSP) was established to coordinate the captive management of Association of Zoos and Aquariums (AZA) D. matschiei. The TKSSP makes annual breeding recommendations primarily based on the mean kinship (MK) strategy. Captive breeding programs often use the MK strategy to preserve genetic diversity in small populations-to avoid the negative consequences of inbreeding and retain their adaptive potential. The ability of a captive breeding program to retain the population's genetic diversity over time can be evaluated by comparing the genetic diversity of the captive population to wild populations. We analyzed DNA extracted from blood and fecal samples from AZA (n = 71), captive (n = 28), and wild (n = 22) D. matschiei using eight microsatellite markers and sequenced the partial mitochondrial DNA control region gene. AZA D. matschiei had a similar expected heterozygosity (H(e) = 0.595 ± 0.184) compared with wild D. matschiei (H(e) = 0.628 ± 0.143), but they had different allelic frequencies (F(ST) = 0.126; P < 0.001). AZA D. matschiei haplotype diversity was almost two times lower than wild D. matschiei Ĥ = 0.740 ± 0.063. These data will assist management of AZA D. matschiei and serve as a baseline for AZA and wild D. matschiei genetic diversity values that could be used to monitor future changes in their genetic diversity. © 2010 Wiley Periodicals, Inc.

Extraction and GC determination of volatile aroma compounds from extracts of three plant species of the Apiaceae family

NASA Astrophysics Data System (ADS)

Stan, M.; Soran, M. L.; Varodi, C.; Lung, I.; Copolovici, L.; MǎruÅ£oiu, C.

2013-11-01

Parsley (Petroselinum crispum), dill (Anethum graveolens) and celery (Apium graveolens), three aromatic plants belonging to the Apiaceae (Umbelliferae) botanical family, were selected as sources of essential or volatile oils. Essential oils are composed of a large diversity of volatile aroma compounds. Plant-derived essential oils and extracts have long been used as natural agents in food preservation, pharmaceuticals and medicinal therapies. In the present study, the plant extracts from leaves of parsley, dill and celery, were obtained by maceration, ultrasound-assisted extraction and microwave-assisted extraction. All extractions were performed at 30°C, using different solvents (ethanol, diethyl ether, n-hexane) and solvent mixtures (1:1, v/v). The most effective solvent system for the extraction of volatile aroma compounds was diethyl ether - n-hexane (1:1, v/v). Extraction efficiency and determination of aroma volatiles were performed by GC-FID and GC-MS, respectively. The major volatile compounds present in plant extracts were myristicin, α-phellandrene, β-phellandrene, 1,3,8-p-menthatriene, apiol, dill ether and allyl phenoxyacetate.

Roles of molecular hydrogen and a hydrogen donor solvent in the cracking of moal model compounds with dispersed catalysts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Toshimitsu; Ikenaga, Na-oki; Sakota, Takahiro

1994-12-31

It is of great importance to evaluate quantitative hydrogen transfer process by using coal model compounds with a hydrogen-donor solvent. Cronauer el al. showed that in the cracking of benzyl phenyl ether the hydrogen required to stabilize free radicals comes from a donor solvent or intramolecular rearrangement and not from gaseous hydrogen in the absence of a catalyst. Korobkov et al. and Schlosberg et al. showed that the thermolysis of benzyl phenyl ether and dibenzyl ether were accomplished by intramolecular rearrangements. Yokokawa et al. reported that tetralin retarded the catalyzed hydrocracking of coal model compounds containing C-C and C-O bonds.more » However, few studies dealt with quantitative discussion in the hydrogen transfer process from a hydrogen-donor solvent or molecular hydrogen to free radicals derived from a model compound except a series of studies by Nicole and co-workers. On the other hand, it is well known that the amount of naphthalene produced from tetralin decreases after the liquefaction of coal in tetralin with catalyst as compared to the liquefaction in the absence of catalysts. To account for this, two mechanisms are proposed. One is that the catalyst hydrogenates naphthalene produced from tetralin, and the other is that the catalyst promotes the direct hydrogen transfer from molecular hydrogen to free radicals. The purpose of this work is to elucidate the role of catalyst and tetralin by means of the quantitative treatment of the hydrogen transfer reaction stabilizing thermally decomposed free radicals. Cracking of benzyl phenyl ether (BPE), dibenzyl ether (DBE), 1,2-diphenylethane, and 1,3-diphenylpropane was studied in tetralin in the presence of highly disposed catalyst.« less

Hydroxylated near-infrared BODIPY fluorophores as intracellular pH sensors

PubMed Central

Salim, Mohamed M.; Owens, Eric A.; Gao, Tielong; Lee, Jeong Heon; Hyun, Hoon; Choi, Hak Soo; Henary, Maged

2015-01-01

In this study, a series of new, highly sensitive BF2-chelated tetraarylazadipyrromethane dyes are synthesized and analyzed to be suitable as on/off photo-induced electron transfer modulated fluorescent sensors for determination of intracellular pH. The ethanolic solutions of the new indicators feature absorption maxima in the range of 696–700 nm and a fluorescence emission maximum at 720 nm. Molar absorptivity and fluorescence quantum yield data were determined for the studied set of aza-BODIPY indicators. These indicators have high molar absorption coefficients of ~80 000 M−1 cm−1 and quantum yields (up to 18%). Corresponding pKa values of indicators are determined from absorbance and fluorescence measurements and range from 9.1 to 10.8, depending on the selective positioning of electron-donating functionalities. The excellent photostability of the aza-BODIPY indicators makes them particularly suitable for long duration measurements. The in vitro cellular staining of living tissues in PC3 cells based on the isosbestic point at pH 7.8 and pH 9.3 has been employed which shows an increase in fluorescence intensity at 800 nm with increase in pH for certain compounds and fluorescence intensity decreases at 700 nm. Therefore, the new indicators are suitable for exploitation and adaptation in a diverse range of analytical applications. PMID:25105177

Analysis of neem oils by LC-MS and degradation kinetics of azadirachtin-A in a controlled environment. Characterization of degradation products by HPLC-MS-MS.

PubMed

Barrek, Sami; Paisse, Olivier; Grenier-Loustalot, Marie-Florence

2004-02-01

Since it was first isolated, the oil extracted from seeds of neem (Azadirachtin indica A juss) has been extensively studied in terms of its efficacy as an insecticide. Several industrial formulations are produced as emulsifiable solutions containing a stated titer of the active ingredient azadirachtin-A (AZ-A). The work reported here is the characterization of a formulation of this insecticide marketed under the name of Neem-azal T/S and kinetic studies of the major active ingredient of this formulation. We initially performed liquid-liquid extraction to isolate the neem oil from other ingredients in the commercial mixture. This was followed by a purification using flash chromatography and semi-preparative chromatography, leading to (13)C NMR identification of structures such as azadirachtin-A, azadirachtin-B, and azadirachtin-H. The neem extract was also characterized by HPLC-MS using two ionization sources, APCI (atmospheric pressure chemical ionization) and ESI (electrospray ionization) in positive and negative ion modes of detection. This led to the identification of other compounds present in the extract-azadirachtin-D, azadirachtin-I, deacetylnimbin, deacetylsalannin, nimbin, and salannin. The comparative study of data gathered by use of the two ionization sources is discussed and shows that the ESI source enables the largest number of structures to be identified. In a second part, kinetic changes in the main product (AZ-A) were studied under precise conditions of pH (2, 4, 6, and 8), temperature (40 to 70 degrees C), and light (UV, dark room and in daylight). This enabled us to determine the degradation kinetics of the product (AZ-A) over time. The activation energy of the molecule (75+/-9 kJ mol(-1)) was determined by examining thermal stability in the range 40 to 70 degrees C. The degradation products of this compound were identified by use of HPLC-MS and HPLC-MS-MS. The results enabled proposal of a chemical degradation reaction route for AZ-A under different conditions of pH and temperature. The data show that at room temperature and pH between 4 and 5 the product degrades into two preferential forms that are hydrolyzed to a single product over time and as a function of pH change.

Bioactive Lignans from Zanthoxylum alatum Roxb. stem bark with cytotoxic potential.

PubMed

Mukhija, Minky; Lal Dhar, Kanaya; Nath Kalia, Ajudhia

2014-02-27

Zanthoxylum alatum is used in traditional medicinal systems for number of disorders like cholera, diabetes, cough, diarrhea, fever, headache, microbial infections, toothache, inflammation and cancer. The aim of the present study was to evaluate Zanthoxylum alatum stem bark for its cytotoxic potential and to isolate the bioactive constituents. Cytotoxicity of the different extracts and isolated compounds was studied on lung carcinoma cell line (A549) and pancreatic carcinoma cell line (MIA-PaCa) using MTT assay. Isolation of compounds from most active extract (petroleum ether) was done on silica gel column. Structure elucidation was done by using various spectrophotometric techniques like UV, IR, (1)H NMR, (13)C NMR and mass spectroscopy. The type of cell death caused by most active compound C was explored by fluorescence microscopy using the acridine orange/ethidium bromide method. Petroleum ether extract of plant has shown significant cytotoxic potential. Three lignans sesamin (A), kobusin (B), and 4'O demethyl magnolin (C) has been isolated. All lignans showed cytotoxic activities in different ranges. Compound C was the novel bioactive compound from a plant source and found to be most active. In apoptosis study, treatment caused typical apoptotic morphological changes. It enhances the apoptosis at IC50 dose (21.72 µg/mL) however showing necrotic cell death at higher dose after 24h on MIA-PaCa cell lines. Petroleum ether extract (60-80 °C) of Zanthoxylum alatum has cytotoxic potential. The lignans isolated from the petroleum ether extract were responsible for the cytotoxic potential of the extract. 4'O demethyl magnolin was novel compound from Zanthoxylum alatum. Hence the Zanthoxylum alatum can be further explored for the development of anticancer drug. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Saccharin Aza Bioisosteres-Synthesis and Preclinical Property Comparisons.

PubMed

Chen, Yantao; Aurell, Carl-Johan; Pettersen, Anna; Lewis, Richard J; Hayes, Martin A; Lepistö, Matti; Jonson, Anna C; Leek, Hanna; Thunberg, Linda

2017-06-08

Saccharin is a well-known scaffold in drug discovery. Herein, we report the synthesis and preclinical property comparisons of three bioisosteres of saccharin: aza-pseudosaccharins (cluster B ), and two new types of aza-saccharins (clusters C and D ). We demonstrate a convenient protocol to selectively synthesize products in cluster C or D when primary amines are used. Preclinical characterization of selected matched-pair products is reported. Through comparison of two diastereomers, we highlight how stereochemistry affects the preclinical properties. Given that saccharin-based derivatives are widely used in many chemistry fields, we foresee that structures exemplified by clusters C and D offer new opportunities for novel drug design, creating a chiral center on the sulfur atom and the option of substitution at two different nitrogens.

POLYBROMINATED DIPHENYL ETHERS IN SOUTHERN MISSISSIPPI CATFISH

EPA Science Inventory

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in a wide variety of consumer products. Concerns surrounding these compounds are primarily due do their ubiquitous presence in the environment as well as in human tissue, such as milk, coupled with evidence indi...

Biodegradation of coal-related model compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campbell, J.A.; Stewart, D.L.; McCulloch, M.

1988-06-01

We have studied the reactions of model compounds having coal-related functionalities (ester linkages, ether linkages, PAH) with the intact organism, cell-free filtrate, and cell-free enzyme of C. versicolor to better understand the process of biosolubilization. Many of the degradation products have been identified by gas chromatography/mass spectroscopy (GC/MS). Results indicate that the two compounds tested with the intact fungal organism were completely degraded. Complete degradation refers to no recovery of model compound. We can probably assume that the other two would also be totally degraded, since we have not yet found a simple compound that will survive long-term exposure tomore » the intact fungus. The ease of degradation with the cell-free filtrate appears to be in the order: phenylbenzoate > benzylbenzoate > benzyl ether > methoxybenzophenone. Esters and ethers that are activated by aromatic rings appear to be susceptible to the fungal extract; however, aromatic ketones are not affected by the extract. From the limited results we have obtained from the isolated enzyme, it appears that the activity may parallel the cell-free filtrate. When the cell-free extract was tested with the model compounds indole, dibenzothiophene, and bibenzyl, no degradation with the enzyme was noted: however, exposure of these compounds to the intact organism resulted in complete degradation. Analysis of the controls indicated no degradation. 8 refs., 1 fig., 1 tab.« less

Eunicellin-based diterpenoids from the Formosan soft coral Klyxum molle with inhibitory activity on superoxide generation and elastase release by neutrophils.

PubMed

Lin, Ming-Chang; Chen, Bo-Wei; Huang, Chiung-Yao; Dai, Chang-Feng; Hwang, Tsong-Long; Sheu, Jyh-Horng

2013-09-27

Eleven new eunicellin-based diterpenoids possessing a cladiellane skeleton with a C-2, C-9 ether bridge, klymollins I-S (1-11), have been isolated from the EtOAc extract of the soft coral Klyxum molle from Taiwan waters. The structures of compounds 1-11 were elucidated by extensive spectroscopic analysis, including 2D NMR spectroscopy (COSY, HSQC, HMBC, and NOESY). Compound 5 exhibited cytotoxicity toward several cancer cell lines. Compound 5 is the first eunicellin-based metabolite bearing a phenyl group and displays significant inhibition of both superoxide anion generation and elastase release in N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced human neutrophils.

Early pregnancy azathioprine use and pregnancy outcomes.

PubMed

Cleary, Brian J; Källén, Bengt

2009-07-01

Azathioprine (AZA) is used during pregnancy by women with inflammatory bowel disease (IBD), other autoimmune disorders, malignancy, and organ transplantation. Previous studies have demonstrated potential risks. The Swedish Medical Birth Register was used to identify 476 women who reported the use of AZA in early pregnancy. The effect of AZA exposure on pregnancy outcomes was studied after adjustment for maternal characteristics that could act as confounders. The most common indication for AZA use was IBD. The rate of congenital malformations was 6.2% in the AZA group and 4.7% among all infants born (adjusted OR: 1.41, 95% CI: 0.98-2.04). An association between early pregnancy AZA exposure and ventricular/atrial septal defects was found (adjusted OR: 3.18, 95% CI: 1.45-6.04). Exposed infants were also more likely to be preterm, to weigh <2500 gm, and to be small for gestational age compared to all infants born. This effect remained for preterm birth and low birth weight when infants of women with IBD but without AZA exposure were used as a comparison group. A trend toward an increased risk of congenital malformations was found among infants of women with IBD using AZA compared to women with IBD not using AZA (adjusted OR: 1.42, 95% CI: 0.93-2.18). Infants exposed to AZA in early pregnancy may be at a moderately increased risk of congenital malformations, specifically ventricular/atrial septal defects. There is also an increased risk of growth restriction and preterm delivery. These associations may be confounded by the severity of maternal illness.

In vitro chronic effects on hERG channel caused by the marine biotoxin Azaspiracid-2

PubMed Central

Ferreiro, Sara F.; Vilariño, Natalia; Louzao, M.Carmen; Nicolaou, K. C.; Frederick, Michael O.; Botana, Luis M.

2014-01-01

Azaspiracids (AZAs) are marine biotoxins produced by the dinoflagellate Azadinium spinosum that accumulate in many shellfish species. Azaspiracid poisoning caused by AZA-contaminated seafood consumption is primarily manifested by diarrhea in humans. To protect human health, AZA-1, AZA-2 and AZA-3 content in seafood has been regulated by food safety authorities in many countries. Recently AZAs have been reported as a low/moderate hERG channel blockers. Furthermore AZA-2 has been related to arrhythmia appearance in rats, suggesting potential heart toxicity. In this study AZA-2 in vitro effects on hERG channel after chronic exposure are analyzed to further explore potential cardiotoxicity. The amount of hERG channel in the plasma membrane, hERG channel trafficking and hERG currents were evaluated up to 12 h of toxin exposure. In these conditions AZA-2 caused an increase of hERG levels in the plasma membrane, probably related to hERG retrograde trafficking impairment. Although this alteration did not translate into an increase of hERG channel-related current, more studies will be necessary to understand its mechanism and to know what consequences could have in vivo. These findings suggest that azaspiracids might have chronic cardiotoxicity related to hERG channel trafficking and they should not be overlooked when evaluating the threat to human health. PMID:25286396

Determinants of orofacial clefting II: Effects of 5-Aza-2'-deoxycytidine on gene methylation during development of the first branchial arch.

PubMed

Seelan, Ratnam S; Mukhopadhyay, Partha; Warner, Dennis R; Smolenkova, Irina A; Pisano, M Michele; Greene, Robert M

2017-01-01

Defects in development of the secondary palate, which arise from the embryonic first branchial arch (1-BA), can cause cleft palate (CP). Administration of 5-Aza-2'-deoxycytidine (AzaD), a demethylating agent, to pregnant mice on gestational day 9.5 resulted in complete penetrance of CP in fetuses. Several genes critical for normal palatogenesis were found to be upregulated in 1-BA, 12h after AzaD exposure. MethylCap-Seq (MCS) analysis identified several differentially methylated regions (DMRs) in DNA extracted from AzaD-exposed 1-BAs. Hypomethylated DMRs did not correlate with the upregulation of genes in AzaD-exposed 1-BAs. However, most DMRs were associated with endogenous retroviral elements. Expression analyses suggested that interferon signaling was activated in AzaD-exposed 1-BAs. Our data, thus, suggest that a 12-h in utero AzaD exposure demethylates and activates endogenous retroviral elements in the 1-BA, thereby triggering an interferon-mediated response. This may result in the dysregulation of key signaling pathways during palatogenesis, causing CP. Copyright © 2016 Elsevier Inc. All rights reserved.

A new cytotoxic sterol methoxymethyl ether from a deep water marine sponge Scleritoderma sp. cf. paccardi.

PubMed

Gunasekera, S P; Kelly-Borges, M; Longley, R E

1996-02-01

24(R)-Methyl-5 alpha-cholest-7-enyl 3 beta-methoxymethyl ether (1), a new sterol ether, has been isolated from a deep-water marine sponge Scleritoderma sp. cf. paccardi. Compound 1 exhibited in vitro cytotoxicity against the cultured murine P-388 tumor cell line with an IC50 of 2.3 micrograms/mL. The isolation and structure elucidation of 1 by NMR spectroscopy is described.

Quercetin-3-methyl ether inhibits lapatinib-sensitive and -resistant breast cancer cell growth by inducing G2/M arrest and apoptosis

PubMed Central

Li, Jixia; Zhu, Feng; Lubet, Ronald A.; De Luca, Antonella; Grubbs, Clinton; Ericson, Marna E.; D’Alessio, Amelia; Normano, Nicola; Dong, Zigang; Bode, Ann M.

2012-01-01

Lapatinib, an oral, small-molecule, reversible inhibitor of both EGFR and HER2, is highly active in HER2 positive breast cancer as a single agent and in combination with other therapeutics. However, resistance against lapatinib is an unresolved problem in clinical oncology. Recently, interest in the use of natural compounds to prevent or treat cancers has gained increasing interest because of presumed low toxicity. Quercetin-3-methyl ether, a naturally occurring compound present in various plants, has potent anticancer activity. Here, we found that quercetin-3-methyl ether caused in a significant growth inhibition of lapatinib-sensitive and -resistant breast cancer cells. Western blot data showed that quercetin-3-methyl ether had no effect on Akt or ERKs signaling in resistant cells. However, quercetin-3-methyl ether caused a pronounced G2/M block mainly through the Chk1-Cdc25c-cyclin B1/Cdk1 pathway in lapatinib-sensitive and -resistant cells. In contrast, lapatinib produced an accumulation of cells in the G1 phase mediated through cyclin D1, but only in lapatinib-sensitive cells. Moreover, quercetin-3-methyl ether induced significant apoptosis, accompanied with increased levels of cleaved caspase 3, caspase 7 and poly (ADP-ribose) polymerase (PARP) in both cell lines. Overall, these results suggested that quercetin-3-methyl ether might be a novel and promising therapeutic agent in lapatinib-sensitive or -resistant breast cancer patients. PMID:22086611

Investigation of Reagent Gases for the Positive Chemical Ionization of Select Polybrominated Diphenyl Ethers

EPA Science Inventory

Polybrominated diphenyl ethers (PBDEs) fall into the class of compounds known as brominated flame retardants and their incorporation in a multitude of products is responsible for saving numerous lives. However, toxicology studies have alerted researchers to the potential adverse...

Biomedical potentials of crown ethers: prospective antitumor agents.

PubMed

Kralj, Marijeta; Tusek-Bozić, Ljerka; Frkanec, Leo

2008-10-01

Crown ethers are of enormous interest and importance in chemistry, biochemistry, materials science, catalysis, separation, transport and encapsulated processes, as well as in the design and synthesis of various synthetic systems with specific properties, diverse capabilities, and programmable functions. Classical crown ethers are macrocyclic polyethers that contain 3-20 oxygen atoms separated from each other by two or more carbon atoms. They are exceptionally versatile in selectively binding a range of metal ions and a variety of organic neutral and ionic species. Crown ethers are currently being studied and used in a variety of applications beyond their traditional place in chemistry. This review presents additional applications and the ever-increasing biomedical potentials of these intriguing compounds, with particular emphasis on the prospects of their relevance as anticancer agents. We believe that further research in this direction should be encouraged, as crown compounds could either induce toxicities that are different from those of conventional antitumor drugs, or complement drugs in current use, thereby providing a valuable adjunct to therapy.

PHYSIOLOGICALLY-BASED PHARMACOKINETIC ( PBPK ) MODEL FOR METHYL TERTIARY BUTYL ETHER ( MTBE ): A REVIEW OF EXISTING MODELS

EPA Science Inventory

MTBE is a volatile organic compound used as an oxygenate additive to gasoline, added to comply with the 1990 Clean Air Act. Previous PBPK models for MTBE were reviewed and incorporated into the Exposure Related Dose Estimating Model (ERDEM) software. This model also included an e...

Multiple QSAR models, pharmacophore pattern and molecular docking analysis for anticancer activity of α, β-unsaturated carbonyl-based compounds, oxime and oxime ether analogues

NASA Astrophysics Data System (ADS)

Masand, Vijay H.; El-Sayed, Nahed N. E.; Bambole, Mukesh U.; Quazi, Syed A.

2018-04-01

Multiple discrete quantitative structure-activity relationships (QSARs) models were constructed for the anticancer activity of α, β-unsaturated carbonyl-based compounds, oxime and oxime ether analogues with a variety of substituents like sbnd Br, sbnd OH, -OMe, etc. at different positions. A big pool of descriptors was considered for QSAR model building. Genetic algorithm (GA), available in QSARINS-Chem, was executed to choose optimum number and set of descriptors to create the multi-linear regression equations for a dataset of sixty-nine compounds. The newly developed five parametric models were subjected to exhaustive internal and external validation along with Y-scrambling using QSARINS-Chem, according to the OECD principles for QSAR model validation. The models were built using easily interpretable descriptors and accepted after confirming statistically robustness with high external predictive ability. The five parametric models were found to have R2 = 0.80 to 0.86, R2ex = 0.75 to 0.84, and CCCex = 0.85 to 0.90. The models indicate that frequency of nitrogen and oxygen atoms separated by five bonds from each other and internal electronic environment of the molecule have correlation with the anticancer activity.

CSA/AZA, in the absence of prednisone, improves linear growth in renal transplanted children.

PubMed

David-Neto, E; Nahas, W; Sampaio, E C; Ianhez, L E; Sabbaga, E; Arap, S

1992-01-01

We compared the results of 44 renal transplants in children, of whom 24 were treated with CSA/AZA and 20 with prednisone in combination with AZA and/or CSA. There were no differences in age distribution or mean ages at transplant between the two treatment groups. The CSA/AZA group had a longer follow-up (29 +/- 33 vs 17 +/- 18 months). At the last follow-up, five children in the CSA/AZA and none in the prednisone group had lost their grafts. Serum creatinine increased in both groups from 0.7 +/- 0.1 mg/dl and 0.9 +/- 0.1 mg/dl at the end of the first month to 1.1 +/- 0.2 mg/dl in the 36th month (CSA/AZA group) (P < 0.0001) and to 1.5 +/- 0.6 mg/dl in the 18th month (prednisone group) (P < 0.05), respectively. Total cholesterol level was 189 +/- 52 mg/dl and 178 +/- 60 mg/dl and LDL level was 117 +/- 48 mg/dl and 115 +/- 51 mg/dl for the prednisone and CSA/AZA groups, respectively. HDL was greater in the CSA/AZA group (50 +/- 10 vs 41 +/- 10 mg/dl) (P < 0.03), and VLDL was greater in the prednisone group (31 +/- 13 vs 22 +/- 8 mg/dl) (P < 0.05). Serum triglyceride was greater in the prednisone group (174 +/- 93 vs 112 +/- 50 mg/dl) (P < 0.03). The standard deviation score for height of the children in the prednisone group did not change (-2.4 +/- 1.4 vs -2.1 +/- 1.4 SDS), whereas the SDS height score for the CSA/AZA children increased from -3.1 +/- 1.7 to -2.6 +/- 1.5, -1.9 +/- 1.4 and -1.7 +/- 1.4, at 12, 24 and 36 months, respectively (P < 0.001). CSA/AZA is a good immunosuppressive regime for the first renal transplant in children, but only 75% tolerated AZA/CSA without same damage to their grafts.

Synthesis of phenanthridine derivatives by microwave-mediated cyclization of o-furyl(allylamino)arenes.

PubMed

Read, Matthew Lovell; Gundersen, Lise-Lotte

2013-02-01

A novel and efficient synthesis of phenanthridines and aza analogues is reported. The key step is a microwave-mediated intramolecular Diels-Alder cyclization of o-furyl(allylamino)arenes. In the presence of a catalytic amount of acid, the DA-adduct reacts further to give the dihydrophenanthridines, which easily can be oxidized to fully aromatic compounds by air in the presence of UV light or by DDQ.

Prolonged Administration of Azacitidine With or Without Entinostat for Myelodysplastic Syndrome and Acute Myeloid Leukemia With Myelodysplasia-Related Changes: Results of the US Leukemia Intergroup Trial E1905

PubMed Central

Prebet, Thomas; Sun, Zhuoxin; Figueroa, Maria E.; Ketterling, Rhett; Melnick, Ari; Greenberg, Peter L.; Herman, James; Juckett, Mark; Smith, Mitchell R.; Malick, Lisa; Paietta, Elisabeth; Czader, Magdalena; Litzow, Mark; Gabrilove, Janice; Erba, Harry P.; Gore, Steven D.; Tallman, Martin S.

2014-01-01

Purpose Although azacitidine (AZA) improves survival in patients with high-risk myelodysplastic syndrome, the overall response remains approximately 50%. Entinostat is a histone deacetylase inhibitor that has been combined with AZA with significant clinical activity in a previous phase I dose finding study. Design Open label phase II randomized trial comparing AZA 50 mg/m2/d given for 10 days ± entinostat 4 mg/m2/d day 3 and day 10. All subtypes of myelodysplasia, chronic myelomonocytic leukemia, and acute myeloid leukemia with myelodysplasia-related changes were eligible for the study. The primary objective was the rate of hematologic normalization (HN; complete remission + partial remission + trilineage hematological improvement). Results One hundred forty-nine patients were analyzed, including 97 patients with myelodysplastic syndrome and 52 patients with acute myeloid leukemia. In the AZA group, 32% (95% CI, 22% to 44%) experienced HN and 27% (95% CI, 17% to 39%) in the AZA + entinostat group. Both arms exceeded the HN rate of historical control (Cancer and Leukemia Group B 9221 trial), but only the AZA group fulfilled the primary objective of the study. Rates of overall hematologic response were 46% and 44%, respectively. Median overall survivals were 18 months for the AZA group and 13 months for the AZA + entinostat group. The combination arm led to less demethylation compared with the monotherapy arm, suggesting pharmacodynamic antagonism. Conclusion Addition of entinostat to AZA did not increase clinical response as defined by the protocol and was associated with pharmacodynamic antagonism. However, the prolonged administration of AZA by itself seems to increase HN rate compared with standard dosing and warrants additional investigation. PMID:24663049

Prolonged administration of azacitidine with or without entinostat for myelodysplastic syndrome and acute myeloid leukemia with myelodysplasia-related changes: results of the US Leukemia Intergroup trial E1905.

PubMed

Prebet, Thomas; Sun, Zhuoxin; Figueroa, Maria E; Ketterling, Rhett; Melnick, Ari; Greenberg, Peter L; Herman, James; Juckett, Mark; Smith, Mitchell R; Malick, Lisa; Paietta, Elisabeth; Czader, Magdalena; Litzow, Mark; Gabrilove, Janice; Erba, Harry P; Gore, Steven D; Tallman, Martin S

2014-04-20

Although azacitidine (AZA) improves survival in patients with high-risk myelodysplastic syndrome, the overall response remains approximately 50%. Entinostat is a histone deacetylase inhibitor that has been combined with AZA with significant clinical activity in a previous phase I dose finding study. Open label phase II randomized trial comparing AZA 50 mg/m(2)/d given for 10 days ± entinostat 4 mg/m(2)/d day 3 and day 10. All subtypes of myelodysplasia, chronic myelomonocytic leukemia, and acute myeloid leukemia with myelodysplasia-related changes were eligible for the study. The primary objective was the rate of hematologic normalization (HN; complete remission + partial remission + trilineage hematological improvement). One hundred forty-nine patients were analyzed, including 97 patients with myelodysplastic syndrome and 52 patients with acute myeloid leukemia. In the AZA group, 32% (95% CI, 22% to 44%) experienced HN and 27% (95% CI, 17% to 39%) in the AZA + entinostat group. Both arms exceeded the HN rate of historical control (Cancer and Leukemia Group B 9221 trial), but only the AZA group fulfilled the primary objective of the study. Rates of overall hematologic response were 46% and 44%, respectively. Median overall survivals were 18 months for the AZA group and 13 months for the AZA + entinostat group. The combination arm led to less demethylation compared with the monotherapy arm, suggesting pharmacodynamic antagonism. Addition of entinostat to AZA did not increase clinical response as defined by the protocol and was associated with pharmacodynamic antagonism. However, the prolonged administration of AZA by itself seems to increase HN rate compared with standard dosing and warrants additional investigation.

AVOIDING HYDROLYSIS OF FUEL ETHER OXYGENATES DURING STATIC HEADSPACE ANALYSIS

EPA Science Inventory

A headspace autosampler, gas chromatograph and ion trap mass spectrometer (headspace GC/MS) were used for trace analysis of fuel oxygenates and related compounds and aromatics in water. A method has been developed for determination of methyl tert-butyl ether (MTBE), ethyl tert-b...

Electrochemical systems and methods using metal halide to form products

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albrecht, Thomas A.; Solas, Dennis; Leclerc, Margarete K.

There are provided electrochemical methods and systems to form one or more organic compounds or enantiomers thereof selected from the group consisting of substituted or unsubstituted dioxane, substituted or unsubstituted dioxolane, dichloroethylether, dichloromethyl methyl ether, dichloroethyl methyl ether, chloroform, carbon tetrachloride, phosgene, and combinations thereof.

Polymer blend compositions and methods of preparation

DOEpatents

Naskar, Amit K.

2016-09-27

A polymer blend material comprising: (i) a first polymer containing hydrogen bond donating groups having at least one hydrogen atom bound to a heteroatom selected from oxygen, nitrogen, and sulfur, or an anionic version of said first polymer wherein at least a portion of hydrogen atoms bound to a heteroatom is absent and replaced with at least one electron pair; (ii) a second polymer containing hydrogen bond accepting groups selected from nitrile, halogen, and ether functional groups; and (iii) at least one modifying agent selected from carbon particles, ether-containing polymers, and Lewis acid compounds; wherein, if said second polymer contains ether functional groups, then said at least one modifying agent is selected from carbon particles and Lewis acid compounds. Methods for producing the polymer blend, molded forms thereof, and articles thereof, are also described.

Epigenetic therapy of cancer with 5-aza-2'-deoxycytidine (decitabine).

PubMed

Momparler, Richard L

2005-10-01

Epigenetic events, such as aberrant DNA methylation, have been demonstrated to silence the expression of many genes that suppress malignancy. Since the event is reversible, it is an interesting target for intervention with specific inhibitors of DNA methylation, such as 5-aza-2'-deoxycytidine (5-AZA-CdR, decitabine). 5-AZA-CdR is a prodrug that requires activation via phosphorylation by deoxcytidine kinase. The nucleotide analog is incorporated into DNA, where it produces an irreversible inactivation of DNA methyltransferase. 5-AZA-CdR is an S-phase-specific agent. The demethylation of DNA by this analog in neoplastic cells can lead to the reactivation of silent tumor-suppressor genes, induction of differentiation or senescence, growth inhibition, and loss of clonogenicity. 5-AZA-CdR was demonstrated to be a potent antineoplastic agent against leukemia and tumors in animal models. Preliminary clinical trials of 5-AZA-CdR using different dose-schedules have shown interesting antineoplastic activity in patients with leukemia, myelodysplastic syndrome (MDS), and non-small cell lung cancer (NSCLC). Pharmacokinetic studies have shown that 5-AZA-CdR has a short in vivo half-life of 15 to 25 minutes. The major toxicity produced by this analog is granulocytopenia. To exploit the full chemotherapeutic potential of 5-AZA-CdR for the treatment of cancer, its optimal dose-schedule has to be found. This will require a good understanding of the pharmacology of this analog and its action on both normal and neoplastic cells.

Production and Isolation of Azaspiracid-1 and -2 from Azadinium spinosum Culture in Pilot Scale Photobioreactors

PubMed Central

Jauffrais, Thierry; Kilcoyne, Jane; Séchet, Véronique; Herrenknecht, Christine; Truquet, Philippe; Hervé, Fabienne; Bérard, Jean Baptiste; Nulty, Cíara; Taylor, Sarah; Tillmann, Urban; Miles, Christopher O.; Hess, Philipp

2012-01-01

Azaspiracid (AZA) poisoning has been reported following consumption of contaminated shellfish, and is of human health concern. Hence, it is important to have sustainable amounts of the causative toxins available for toxicological studies and for instrument calibration in monitoring programs, without having to rely on natural toxin events. Continuous pilot scale culturing was carried out to evaluate the feasibility of AZA production using Azadinium spinosum cultures. Algae were harvested using tangential flow filtration or continuous centrifugation. AZAs were extracted using solid phase extraction (SPE) procedures, and subsequently purified. When coupling two stirred photobioreactors in series, cell concentrations reached 190,000 and 210,000 cell·mL−1 at steady state in bioreactors 1 and 2, respectively. The AZA cell quota decreased as the dilution rate increased from 0.15 to 0.3 day−1, with optimum toxin production at 0.25 day−1. After optimization, SPE procedures allowed for the recovery of 79 ± 9% of AZAs. The preparative isolation procedure previously developed for shellfish was optimized for algal extracts, such that only four steps were necessary to obtain purified AZA1 and -2. A purification efficiency of more than 70% was achieved, and isolation from 1200 L of culture yielded 9.3 mg of AZA1 and 2.2 mg of AZA2 of >95% purity. This work demonstrated the feasibility of sustainably producing AZA1 and -2 from A. spinosum cultures. PMID:22822378

Sensitive multiresidue method by HS-SPME/GC-MS for 10 volatile organic compounds in urine matrix: a new tool for biomonitoring studies on children.

PubMed

Antonucci, Arianna; Vitali, Matteo; Avino, Pasquale; Manigrasso, Maurizio; Protano, Carmela

2016-08-01

A HS-SPME method coupled with GC-MS analysis has been developed for simultaneously measuring the concentration of 10 volatile organic compounds (VOCs) (benzene, toluene, ethylbenzene, o-, m-, and p-xylene, methyl tert-butyl ether, ethyl tert-butyl ether, 2-methyl-2-butyl methyl ether, and diisopropyl ether) in urine matrix as a biomonitoring tool for populations at low levels of exposure to such VOCs. These compounds, potentially toxic for human health, are common contaminants of both outdoor and indoor air, as they are released by autovehicular traffic; some of them are also present in environmental tobacco smoke (ETS). Thus, the exposure to these pollutants cannot be neglected and should be assessed. The low limits of detection and quantification (LODs and LOQs <6.5 and 7.5 ng L(-1), respectively) and the high reproducibility (CVs <4 %) make the developed method suited for biomonitoring populations exposed at low levels such as children. Further, the method is cost-effective and low in time-consumption; therefore, it is useful for investigating large populations. It has been applied to children exposed to traffic pollution and/or ETS; the relevant results are reported, and the relevant implications are discussed.

Headspace Solid-Phase Microextraction and Ultrasonic Extraction with the Solvent Sequences in Chemical Profiling of Allium ursinum L. Honey.

PubMed

Jerković, Igor; Kuś, Piotr M

2017-11-06

A volatile profile of ramson (wild garlic, Allium ursinum L.) honey was investigated by headspace solid-phase microextraction (HS-SPME) and ultrasonic solvent extraction (USE) followed by gas chromatography and mass spectrometry (GC-FID/GC-MS) analyses. The headspace was dominated by linalool derivatives: cis - and trans -linalool oxides (25.3%; 9.2%), hotrienol (12.7%), and linalool (5.8%). Besides direct extraction with dichloromethane and pentane/diethyl ether mixture (1:2, v / v ), two solvent sequences (I: pentane → diethyl ether; II: pentane → pentane/diethyl ether (1:2, v / v ) → dichloromethane) were applied. Striking differences were noted among the obtained chemical profiles. The extracts with diethyl ether contained hydroquinone (25.8-36.8%) and 4-hydroxybenzoic acid (11.6-16.6%) as the major compounds, while ( E )-4-(r-1',t-2',c-4'-trihydroxy-2',6',6'-trimethylcyclohexyl)but-3-en-2-one predominated in dichloromethane extracts (18.3-49.1%). Therefore, combination of different solvents was crucial for the comprehensive investigation of volatile organic compounds in this honey type. This particular magastigmane was previously reported only in thymus honey and hydroquinone in vipers bugloss honey, while a combination of the mentioned predominant compounds is unique for A. ursinum honey.

Synthesis, Characterization, and Cross-Linking Strategy of a Quercetin-Based Epoxidized Monomer as a Naturally-Derived Replacement for BPA in Epoxy Resins.

PubMed

Kristufek, Samantha L; Yang, Guozhen; Link, Lauren A; Rohde, Brian J; Robertson, Megan L; Wooley, Karen L

2016-08-23

The natural polyphenolic compound quercetin was functionalized and cross-linked to afford a robust epoxy network. Quercetin was selectively methylated and functionalized with glycidyl ether moieties using a microwave-assisted reaction on a gram scale to afford the desired monomer (Q). This quercetin-derived monomer was treated with nadic methyl anhydride (NMA) to obtain a cross-linked network (Q-NMA). The thermal and mechanical properties of this naturally derived network were compared to those of a conventional diglycidyl ether bisphenol A-derived counterpart (DGEBA-NMA). Q-NMA had similar thermal properties [i.e., glass transition (Tg ) and decomposition (Td ) temperatures] and comparable mechanical properties (i.e., Young's Modulus, storage modulus) to that of DGEBA-NMA. However, it had a lower tensile strength and higher flexural modulus at elevated temperatures. The application of naturally derived, sustainable compounds for the replacement of commercially available petrochemical-based epoxies is of great interest to reduce the environmental impact of these materials. Q-NMA is an attractive candidate for the replacement of bisphenol A-based epoxies in various specialty engineering applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Epigenetic modifiers reduce inflammation and modulate macrophage phenotype during endotoxemia-induced acute lung injury

PubMed Central

Thangavel, Jayakumar; Samanta, Saheli; Rajasingh, Sheeja; Barani, Bahar; Xuan, Yu-Ting; Dawn, Buddhadeb; Rajasingh, Johnson

2015-01-01

ABSTRACT Acute lung injury (ALI) during sepsis is characterized by bilateral alveolar infiltrates, lung edema and respiratory failure. Here, we examined the efficacy the DNA methyl transferase (DNMT) inhibitor 5-Aza 2-deoxycytidine (Aza), the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA), as well as the combination therapy of Aza and TSA (Aza+TSA) provides in the protection of ALI. In LPS-induced mouse ALI, post-treatment with a single dose of Aza+TSA showed substantial attenuation of adverse lung histopathological changes and inflammation. Importantly, these protective effects were due to substantial macrophage phenotypic changes observed in LPS-stimulated macrophages treated with Aza+TSA as compared with untreated LPS-induced macrophages or LPS-stimulated macrophages treated with either drug alone. Further, we observed significantly lower levels of pro-inflammatory molecules and higher levels of anti-inflammatory molecules in LPS-induced macrophages treated with Aza+TSA than in LPS-induced macrophages treated with either drug alone. The protection was ascribed to dual effects by an inhibition of MAPK–HuR–TNF and activation of STAT3–Bcl2 pathways. Combinatorial treatment with Aza+TSA reduces inflammation and promotes an anti-inflammatory M2 macrophage phenotype in ALI, and has a therapeutic potential for patients with sepsis. PMID:26116574

Metabolism of Some Anionic Tallow-based Detergents by Sewage Microorganisms1

PubMed Central

Cordon, Theone C.; Maurer, Elmer W.; Nuñez-Ponzoa, M. V.; Stirton, A. J.

1968-01-01

A method in which the test detergent was the sole source of carbon was used to study the metabolism of several tallow-based detergents. These were tallow alcohol sulfates, long-chain ether alcohol sulfates, and esters of α-sulfo fatty acids. Sodium p-(1-methylundecyl)benzenesulfonate (LAS) was used as a reference material. The alcohol sulfates were the most rapidly and completely metabolized (96 to 99%), and one ether alcohol sulfate was 94% degraded. The other compounds were metabolized to the extent of 61 to 87%; LAS was 80% degraded. Except for the alcohol sulfates, loss of methylene blue activity (MBAS) occurred long before the chemical oxygen demand (COD) values had reached a minimum; with the alcohol sulfates, MBAS and COD decreased simultaneously. PMID:5636472

Determinants of orofacial clefting I: Effects of 5-Aza-2'-deoxycytidine on cellular processes and gene expression during development of the first branchial arch.

PubMed

Mukhopadhyay, Partha; Seelan, Ratnam S; Rezzoug, Francine; Warner, Dennis R; Smolenkova, Irina A; Brock, Guy; Pisano, M Michele; Greene, Robert M

2017-01-01

In this study, we identify gene targets and cellular events mediating the teratogenic action(s) of 5-Aza-2'-deoxycytidine (AzaD), an inhibitor of DNA methylation, on secondary palate development. Exposure of pregnant mice (on gestation day (GD) 9.5) to AzaD for 12h resulted in the complete penetrance of cleft palate (CP) in fetuses. Analysis of cells of the embryonic first branchial arch (1-BA), in fetuses exposed to AzaD, revealed: 1) significant alteration in expression of genes encoding several morphogenetic factors, cell cycle inhibitors and regulators of apoptosis; 2) a decrease in cell proliferation; and, 3) an increase in apoptosis. Pyrosequencing of selected genes, displaying pronounced differential expression in AzaD-exposed 1-BAs, failed to reveal significant alterations in CpG methylation levels in their putative promoters or gene bodies. CpG methylation analysis suggested that the effects of AzaD on gene expression were likely indirect. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthesis of Enantiopure Alicyclic Ethers and Their Activity on the Chemosensory Organ of the Ectoparasite of Honey Bees, Varroa destructor.

PubMed

Pinnelli, Govardhana R; Singh, Nitin K; Soroker, Victoria; Plettner, Erika

2016-11-16

The preparation of enantiopure conformationally restricted alicyclic ethers and their inhibitory activities on the chemosensory organ of the Varroa destructor, a parasite of honey bees, are reported in this article. We tested the effect of enantiopure ethers of cis-5-(2'-hydroxyethyl)cyclopent-2-en-1-ol on the Varroa chemosensory organ by electrophysiology, for their ability to inhibit the responses to two honey bee-produced odors that are important for the mite to locate its host: nurse bee head space odor and (E)-β-ocimene, a honey bee brood pheromone. Previous work with the racemic compounds showed that they suppress the mite's olfactory response to its bee host, which led to incorrect host choice. Based on a structure-activity relationship, we predicted that the two most active compounds-cis-1-butoxy-5-(2'-methoxyethyl)cyclopent-2-ene, cy{4,1}, and (cis-1-ethoxy-5-(2'ethoxyethyl)cyclopent-2-ene, cy{2,2}-could have opposite active enantiomers. Here we studied the enantiomers of both ethers, whose preparation involved enzymatic resolution of racemic diol cis-5-(2'-hydroxyethyl)cyclopent-2-en-1-ol using Lipase AK with vinyl acetate. The racemic diol was prepared from commercially available 2,5-norbornadiene. We observed that the responses of the chemosensory organ to honey bee head space volatiles were significantly decreased by both enantiomers of cy{4,1} and cy{2,2}, but that responses to (E)-β-ocimene were decreased significantly only by (+)-cy{4,1} (1R,5S) and (-)-cy{2,2} (1S,5R) and not by their respective enantiomers. The importance of this result is that the racemates could be used to inhibit olfactory detection of bee odors by mites, without a loss in activity relative to the more expensive enantiopure compounds.

A Divergent Mechanistic Course of Pd(0)-Catalyzed Aza-Claisen Rearrangement and Aza-Rautenstrauch-Type Cyclization of N-Allyl-Ynamides

PubMed Central

DeKorver, Kyle A.; Hsung, Richard P.; Lohse, Andrew G.; Zhang, Yu

2010-01-01

A fascinating mechanistic study of ynamido-palladium-π-allyl complexes is described that features isolation of a unique silyl-ketenimine via aza-Claisen rearrangement, which can be accompanied by an unusual thermal N-to-C 1,3-Ts shift in the formation of tertiary nitriles, and a novel cyclopentenimine formation via a palladium catalyzed aza-Rautenstrauch-type cyclization pathway. PMID:20337418

Azelaic Acid Exerts Antileukemic Activity in Acute Myeloid Leukemia

PubMed Central

Pan, Yunbao; Liu, Dong; Wei, Yongchang; Su, Dan; Lu, Chenyang; Hu, Yanchao; Zhou, Fuling

2017-01-01

Acute myeloid leukemia (AML) is an acute leukemia common in most adults; its prevalence intensifies with age. The overall survival of AML is very poor because of therapeutic resistance. Azelaic acid (AZA) is non-toxic, non-teratogenic, and non-mutagenic and its antitumor effect on various tumor cells is well established; Nonetheless, its therapeutic effects in AML cells are largely unknown. In this study, it was shown that AZA significantly inhibits the cell viability and induces apoptosis in AML cells in a dose-dependent manner. Additionally, AZA suppressed the expression of phosphorylated Akt, Jab1 and Trx, and this suppression was enhanced by treatment with Jab1 siRNA. Furthermore, AZA sensitized AML cells to Ara-c chemotherapy. The suppressive effect of AZA on tumor growth was examined in vivo by subcutaneously inoculated AML cells in a tumor model using nude mice. These findings indicate that AZA is useful as an effective ingredient in antineoplastic activity. PMID:28659796

Azelaic Acid Exerts Antileukemic Activity in Acute Myeloid Leukemia.

PubMed

Pan, Yunbao; Liu, Dong; Wei, Yongchang; Su, Dan; Lu, Chenyang; Hu, Yanchao; Zhou, Fuling

2017-01-01

Acute myeloid leukemia (AML) is an acute leukemia common in most adults; its prevalence intensifies with age. The overall survival of AML is very poor because of therapeutic resistance. Azelaic acid (AZA) is non-toxic, non-teratogenic, and non-mutagenic and its antitumor effect on various tumor cells is well established; Nonetheless, its therapeutic effects in AML cells are largely unknown. In this study, it was shown that AZA significantly inhibits the cell viability and induces apoptosis in AML cells in a dose-dependent manner. Additionally, AZA suppressed the expression of phosphorylated Akt, Jab1 and Trx, and this suppression was enhanced by treatment with Jab1 siRNA. Furthermore, AZA sensitized AML cells to Ara-c chemotherapy. The suppressive effect of AZA on tumor growth was examined in vivo by subcutaneously inoculated AML cells in a tumor model using nude mice. These findings indicate that AZA is useful as an effective ingredient in antineoplastic activity.

Anaerobic biodegradability of alkylphenols and fuel oxygenates in the presence of alternative electron acceptors.

PubMed

Puig-Grajales, L; Tan, N G; van der Zee, F; Razo-Flores, E; Field, J A

2000-11-01

Alkylphenols and fuel oxygenates are important environmental pollutants produced by the petrochemical industry. A batch biodegradability test was conducted with selected ortho-substituted alkylphenols (2-cresol, 2,6-dimethylphenol and 2-ethylphenol), fuel oxygenates (methyl tert-butyl ether, ethyl tert-butyl ether and tert-amylmethyl ether) and tert-butyl alcohol (TBA) as model compounds. The ortho-substituted alkylphenols were not biodegraded after 100 days of incubation under methanogenic, sulfate-, or nitrate-reducing conditions. However, biodegradation of 2-cresol and 2-ethylphenol (150 mg l(-1)) was observed in the presence of Mn (IV) as electron acceptor. The biodegradation of these two compounds took place in less than 15 days and more than 90% removal was observed for both compounds. Mineralization was indicated since no UV-absorbing metabolites accumulated after 23 days of incubation. These alkylphenols were also slowly chemically oxidized by Mn (IV). No biodegradation of fuel oxygenates or TBA (1 g l(-1)) was observed after 80 or more days of incubation under methanogenic, Fe (III)-, or Mn (IV)-reducing conditions, suggesting that these compounds are recalcitrant under anaerobic conditions. The fuel oxygenates caused no toxicity towards acetoclastic methanogens activity in anaerobic granular sludge.

hERGCentral: a large database to store, retrieve, and analyze compound-human Ether-à-go-go related gene channel interactions to facilitate cardiotoxicity assessment in drug development.

PubMed

Du, Fang; Yu, Haibo; Zou, Beiyan; Babcock, Joseph; Long, Shunyou; Li, Min

2011-12-01

The unintended and often promiscous inhibition of the cardiac human Ether-à-go-go related gene (hERG) potassium channel is a common cause for either delay or removal of therapeutic compounds from development and withdrawal of marketed drugs. The clinical manifestion is prolongation of the duration between QRS complex and T-wave measured by surface electrocardiogram (ECG)-hence Long QT Syndrome. There are several useful online resources documenting hERG inhibition by known drugs and bioactives. However, their utilities remain somewhat limited because they are biased toward well-studied compounds and their number of data points tends to be much smaller than many commercial compound libraries. The hERGCentral ( www.hergcentral.org ) is mainly based on experimental data obtained from a primary screen by electrophysiology against more than 300,000 structurally diverse compounds. The system is aimed to display and combine three resources: primary electrophysiological data, literature, as well as online reports and chemical library collections. Currently, hERGCentral has annotated datasets of more than 300,000 compounds including structures and chemophysiological properties of compounds, raw traces, and biophysical properties. The system enables a variety of query formats, including searches for hERG effects according to either chemical structure or properties, and alternatively according to the specific biophysical properties of current changes caused by a compound. Therefore, the hERGCentral, as a unique and evolving resource, will facilitate investigation of chemically induced hERG inhibition and therefore drug development. © MARY ANN LIEBERT, INC.

hERGCentral: A Large Database to Store, Retrieve, and Analyze Compound-Human Ether-à-go-go Related Gene Channel Interactions to Facilitate Cardiotoxicity Assessment in Drug Development

PubMed Central

Du, Fang; Yu, Haibo; Zou, Beiyan; Babcock, Joseph; Long, Shunyou

2011-01-01

Abstract The unintended and often promiscous inhibition of the cardiac human Ether-à-go-go related gene (hERG) potassium channel is a common cause for either delay or removal of therapeutic compounds from development and withdrawal of marketed drugs. The clinical manifestion is prolongation of the duration between QRS complex and T-wave measured by surface electrocardiogram (ECG)—hence Long QT Syndrome. There are several useful online resources documenting hERG inhibition by known drugs and bioactives. However, their utilities remain somewhat limited because they are biased toward well-studied compounds and their number of data points tends to be much smaller than many commercial compound libraries. The hERGCentral (www.hergcentral.org) is mainly based on experimental data obtained from a primary screen by electrophysiology against more than 300,000 structurally diverse compounds. The system is aimed to display and combine three resources: primary electrophysiological data, literature, as well as online reports and chemical library collections. Currently, hERGCentral has annotated datasets of more than 300,000 compounds including structures and chemophysiological properties of compounds, raw traces, and biophysical properties. The system enables a variety of query formats, including searches for hERG effects according to either chemical structure or properties, and alternatively according to the specific biophysical properties of current changes caused by a compound. Therefore, the hERGCentral, as a unique and evolving resource, will facilitate investigation of chemically induced hERG inhibition and therefore drug development. PMID:22149888

Synthesis and in vitro activity of dicationic indolyl diphenyl ethers as novel potent antibiotic agents against drug-resistant bacteria.

PubMed

Chen, Xiaofang; Hu, Xinxin; Wu, Yanbin; Liu, Yonghua; Bian, Cong; Nie, Tongying; You, Xuefu; Hu, Laixing

2017-02-15

A series of 4,4'-bis-[2-(6-N-substituted-amidino)indolyl] diphenyl ether have been synthesized and tested for their in vitro antibacterial activity including a range of Gram-positive and Gram-negative pathogens and cytotoxicity. Most of these compounds have mainly shown anti-Gram positive bacteria activities especially against drug resistant bacterial strains MRSA, MRSE and VRE. The anti-MRSA and anti-MRSE activities of compound 7a and 7j were more potent than that of the lead compound 2, levofloxacin and vancomycin. Interestingly, 7j had greatly improved anti negative bacterial activity, especially for the producing NDM-1 Klebsiella pneumonia strain and less toxic than that of the lead compound 2. Copyright © 2017 Elsevier Ltd. All rights reserved.

Isolation and characterization of an ether-type polyurethane-degrading micro-organism and analysis of degradation mechanism by Alternaria sp.

PubMed

Matsumiya, Y; Murata, N; Tanabe, E; Kubota, K; Kubo, M

2010-06-01

To degrade ether-type polyurethane (ether-PUR), ether-PUR-degrading micro-organism was isolated. Moreover, ether-PUR-degrading mechanisms were analysed using model compounds of ether-PUR. A fungus designated as strain PURDK2, capable of changing the configuration of ether-PUR, has been isolated. This isolated fungus was identified as Alternaria sp. Using a scanning electron microscope, the grid structure of ether-PUR was shown to be melted and disrupted by the fungus. The degradation of ether-PUR by the fungus was analysed, and the ether-PUR was degraded by the fungus by about 27.5%. To analyse the urethane-bond degradation by the fungus, a degraded product of ethylphenylcarbamate was analysed using GC/MS. Aniline and ethanol were detected by degradation with the supernatant, indicating that the fungus secreted urethane-bond-degrading enzyme(s). PURDK2 also degraded urea bonds when diphenylmethane-4,4'-dibutylurea was used as a substrate. The enzyme(s) from PURDK2 degraded urethane and urea bonds to convert the high molecular weight structure of ether-PUR to small molecules; and then the fungus seems to use the small molecules as an energy source. Ether-PUR-degrading fungus, strain PURDK2, was isolated, and the urethane- and urea-bonds-degrading enzymes from strain PURDK2 could contribute to the material recycling of ether-PUR.

The atmosphere can be a source of certain water soluble volatile organic compounds in urban streams

USGS Publications Warehouse

Kenner, Scott J.; Bender, David A.; Zogorski, John S.; ,; James F. Pankow,

2014-01-01

Surface water and air volatile organic compound (VOC) data from 10 U.S. Geological Survey monitoring sites were used to evaluate the potential for direct transport of VOCs from the atmosphere to urban streams. Analytical results of 87 VOC compounds were screened by evaluating the occurrence and detection levels in both water and air, and equilibrium concentrations in water (Cws) based on the measured air concentrations. Four compounds (acetone, methyl tertiary butyl ether, toluene, and m- & p-xylene) were detected in more than 20% of water samples, in more than 10% of air samples, and more than 10% of detections in air were greater than long-term method detection levels (LTMDL) in water. Benzene was detected in more than 20% of water samples and in more than 10% of air samples. Two percent of benzene detections in air were greater than one-half the LTMDL in water. Six compounds (chloroform, p-isopropyltoluene, methylene chloride, perchloroethene, 1,1,1-trichloroethane, and trichloroethene) were detected in more than 20% of water samples and in more than 10% of air samples. Five VOCs, toluene, m- & p-xylene, methyl tert-butyl ether (MTBE), acetone, and benzene were identified as having sufficiently high concentrations in the atmosphere to be a source to urban streams. MTBE, acetone, and benzene exhibited behavior that was consistent with equilibrium concentrations in the atmosphere.

A randomized investigator-blind parallel-group study to assess efficacy and safety of azelaic acid 15% gel vs. adapalene 0.1% gel in the treatment and maintenance treatment of female adult acne.

PubMed

Thielitz, A; Lux, A; Wiede, A; Kropf, S; Papakonstantinou, E; Gollnick, H

2015-04-01

Growing numbers of post-adolescent females are suffering from treatment-resistant or relapsing adult acne forms, therefore requiring the definition of safe and effective treatment options for this burdening disease. To assess the efficacy of azelaic acid 15% gel (AzA) vs. no treatment during maintenance therapy of female adult acne and to compare its efficacy and safety vs. adapalene 0.1% gel (AD) during a 9-month period (3-month treatment and 6-month maintenance treatment). A total of 55 women between 18 and 45 years with adult acne were included in this investigator-blind trial and randomized into three groups receiving AzA gel b.i.d. for 9 months (AzA9M, n = 17) or AzA gel b.i.d. for 3 months followed by a 6-month observational phase (AzA3M, n = 19) or AD gel once daily for 9 months (AD9M, n = 19). Parameters of efficacy, safety and patient-related factors were analysed. The reduction in lesion counts, severity and Dermatology Life Quality Index score was significant (P < 0.05) and comparable between groups during the treatment phase, while dryness and scaling were significantly lower (P < 0.05) in group AzA9M vs. AD9M. During maintenance, AzA9M was superior to AzA3M in the control of inflammatory lesions (P = 0.008) and total lesions (P = 0.014) at week 24. From week 12 to week 36, a mild relative increase in inflammatory lesions could be observed in all groups. In AzA3M, this increase exceeded that of AzA9M by 23.1% (P = 0.109), while the difference of total lesions diverged to 30.8% (P = 0.038). No significant differences could be detected between AzA9M and AD9M. Group AzA9M was non-inferior to AD9M (non-inferiority margin of 50% for the confidence limit for the relative effect) in the control of inflammatory acne lesions. AzA15% gel is a safe and effective treatment and maintenance treatment of female adult acne with non-inferior efficacy to AD 0.1% gel in the control of inflammatory acne. © 2014 European Academy of Dermatology and Venereology.

A General Asymmetric Formal Synthesis of Aza-Baylis-Hillman Type Products under Bifunctional Catalysis.

PubMed

Frías, María; Carrasco, Ana Cristina; Fraile, Alberto; Alemán, José

2018-03-02

A new organocatalytic strategy for the synthesis of enantioenriched aza-Baylis-Hillman type products via a frustrated vinylogous reaction is presented. This process proceeds under mild conditions with good yields, completed Z/E selectivity and excellent enantioselectivities. Moreover, easy derivatizations of the final products led to important building blocks of organic synthesis such as 1,3-aminoalcohols and Lewis base catalysts. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phenyl ethers from cultured lichen mycobionts of Graphis scripta var. serpentina and G. rikuzensis.

PubMed

Takenaka, Yukiko; Tanahashi, Takao; Nagakura, Naotaka; Hamada, Nobuo

2003-07-01

Spore-derived mycobionts of the lichen Graphis scripta var. serpentina and G. rikuzensis were cultivated on a malt-yeast extract medium supplemented with 10% sucrose and their metabolites were investigated. 3,3'-Dihydroxy-5,5'-dimethyldiphenyl ether was isolated from the cultures of the mycobionts of G. scripta var. serpentina, while a new phenyl ether, rikuzenol, along with two known diphenyl ethers, violaceol-I and violaceol-II, were isolated from those of G. rikuzensis. The structure of the new compound was determined by spectroscopic methods. Violaceol-I was chemically synthesized and interconversion between violaceol-I and violaceol-II was proven.

Versatility of azelaic acid 15% gel in treatment of inflammatory acne vulgaris.

PubMed

Thiboutot, Diane

2008-01-01

Azelaic acid (AzA) 15% gel is approved for the treatment of rosacea in the US, but also has approval for the treatment of acne vulgaris in many European countries where it has demonstrated success. Two randomized, multicenter, controlled clinical trials compared the effects of AzA 15% gel with those of topical benzoyl peroxide 5% or topical clindamycin 1%, all using a twice-daily dosing regimen. The primary endpoint in the intent-to-treat analysis was a reduction in inflammatory papules and pustules. AzA 15% gel resulted in a 70% to 71% median reduction of facial papules and pustules compared with a 77% reduction with benzoyl peroxide 5% gel and a 63% reduction with clindamycin. AzA 15% gel was well-tolerated. In addition, a 1-year European observational study conducted by dermatologists in private practice evaluated the safety and efficacy of AzA 15% gel used as monotherapy or in combination with other agents in more than 1200 patients with acne. Most physicians (81.9%) described an improvement in patients' symptoms after an average of 34.6 days, and 93.9% of physicians reported patient improvement after an average of 73.1 days. Both physicians and patients assessed AzA 15% gel to be effective with 74% of patients being "very satisfied" at the end of therapy. AzA 15% gel was considered "well-tolerated" or "very well-tolerated" by 95.7% of patients. The majority of patients were more satisfied with AzA than with previous therapies. AzA 15% gel represents a new therapeutic option for the treatment of acne vulgaris.

Kinetic Resolution of α-Hydroxy-Substituted Oxime Ethers by Enantioselective Cu-H-Catalyzed Si-O Coupling.

PubMed

Dong, Xichang; Kita, Yuji; Oestreich, Martin

2018-04-12

A catalyst-controlled enantioselective alcohol silylation by Cu-H-catalyzed dehydrogenative Si-O coupling of hydroxy groups α to an oxime ether and simple hydrosilanes is reported. The selectivity factors reached in this kinetic resolution are generally high (s≈50), and these reactions thereby provide reliable access to highly enantioenriched α-hydroxy-substituted oxime ethers. The synthetic usefulness of these compounds is also demonstrated. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Emodin enhances the demethylation by 5-Aza-CdR of pancreatic cancer cell tumor-suppressor genes P16, RASSF1A and ppENK.

PubMed

Pan, Feng-Ping; Zhou, Hong-Kun; Bu, He-Qi; Chen, Zi-Qiang; Zhang, Hao; Xu, Lu-Ping; Tang, Jian; Yu, Qing-Jiang; Chu, Yong-Quan; Pan, Jie; Fei, Yong; Lin, Sheng-Zhang; Liu, Dian-Lei; Chen, Liang

2016-04-01

5-Aza-2'-deoxycytidine (5-Aza-CdR) is currently acknowledged as a demethylation drug, and causes a certain degree of demethylation in a variety of cancer cells, including pancreatic cancer cells. Emodin, a traditional Chinese medicine (TCM), is an effective monomer extracted from rhubarb and has been reported to exhibit antitumor activity in different manners in pancreatic cancer. In the present study, we examined whether emodin caused demethylation and increased the demethylation of three tumor-suppressor genes P16, RASSF1A and ppENK with a high degree of methylation in pancreatic cancer when combined with 5-Aza-CdR. Our research showed that emodin inhibited the growth of pancreatic cancer Panc-1 cells in a dose- and time-dependent manner. Dot-blot results showed that emodin combined with 5-Aza-CdR significantly suppressed the expression of genome 5mC in PANC-1 cells. In order to verify the effect of methylation, methylation-specific PCR (MSP) and bisulfite genomic sequencing PCR (BSP) combined with TA were selected for the cloning and sequencing. Results of MSP and BSP confirmed that emodin caused faint demethylation, and 5-Aza-CdR had a certain degree of demethylation. When emodin was combined with 5-Aza-CdR, the demethylation was more significant. At the same time, fluorescent quantitative PCR and western blot analysis results confirmed that when emodin was combined with 5-Aza-CdR, the expression levels of P16, RASSF1A and ppENK were increased more significantly compared to either treatment alone. In contrast, the expression levels of DNA methyltransferase 1 (DNMT1) and DNMT3a were more significantly reduced with the combination treatment than the control or either agent alone, further proving that emodin in combination with 5-Aza-CdR enhanced the demethylation effect of 5-Aza-CdR by reducing the expression of methyltransferases. In conclusion, the present study confirmed that emodin in combination with 5-Aza-CdR enhanced the demethylation by 5-Aza-CdR of tumor-suppressor genes p16, RASSF1A and ppENK by reducing the expression of methyltransferases DNMT1 and DNMT3a.

Emodin enhances the demethylation by 5-Aza-CdR of pancreatic cancer cell tumor-suppressor genes P16, RASSF1A and ppENK

PubMed Central

PAN, FENG-PING; ZHOU, HONG-KUN; BU, HE-QI; CHEN, ZI-QIANG; ZHANG, HAO; XU, LU-PING; TANG, JIAN; YU, QING-JIANG; CHU, YONG-QUAN; PAN, JIE; FEI, YONG; LIN, SHENG-ZHANG; LIU, DIAN-LEI; CHEN, LIANG

2016-01-01

5-Aza-2′-deoxycytidine (5-Aza-CdR) is currently acknowledged as a demethylation drug, and causes a certain degree of demethylation in a variety of cancer cells, including pancreatic cancer cells. Emodin, a traditional Chinese medicine (TCM), is an effective monomer extracted from rhubarb and has been reported to exhibit antitumor activity in different manners in pancreatic cancer. In the present study, we examined whether emodin caused demethylation and increased the demethylation of three tumor-suppressor genes P16, RASSF1A and ppENK with a high degree of methylation in pancreatic cancer when combined with 5-Aza-CdR. Our research showed that emodin inhibited the growth of pancreatic cancer Panc-1 cells in a dose- and time-dependent manner. Dot-blot results showed that emodin combined with 5-Aza-CdR significantly suppressed the expression of genome 5mC in PANC-1 cells. In order to verify the effect of methylation, methylation-specific PCR (MSP) and bisulfite genomic sequencing PCR (BSP) combined with TA were selected for the cloning and sequencing. Results of MSP and BSP confirmed that emodin caused faint demethylation, and 5-Aza-CdR had a certain degree of demethylation. When emodin was combined with 5-Aza-CdR, the demethylation was more significant. At the same time, fluorescent quantitative PCR and western blot analysis results confirmed that when emodin was combined with 5-Aza-CdR, the expression levels of P16, RASSF1A and ppENK were increased more significantly compared to either treatment alone. In contrast, the expression levels of DNA methyltransferase 1 (DNMT1) and DNMT3a were more significantly reduced with the combination treatment than the control or either agent alone, further proving that emodin in combination with 5-Aza-CdR enhanced the demethylation effect of 5-Aza-CdR by reducing the expression of meth-yltransferases. In conclusion, the present study confirmed that emodin in combination with 5-Aza-CdR enhanced the demethylation by 5-Aza-CdR of tumor-suppressor genes p16, RASSF1A and ppENK by reducing the expression of methyltransferases DNMT1 and DNMT3a. PMID:26782786

[5-aza-2'-deoxycytidine-induced inhibition of CDH13 expression and its inhibitory effect on methylation status in human colon cancer cells in vitro and on growth of xenograft in nude mice].

PubMed

Ren, Jian-zhen; Huo, Ji-rong

2012-01-01

To determine the inhibitory effect of 5-aza-2'-deoxycytidine (5-Aza-CdR) on the growth of human colon carcinoma cells and xenografts in nude mice, to observe its effect on CDH13 gene expression and methylation in the xenografts, and to explore the possible mechanisms. Human colon carcinoma cell line HCT116 cells were treated with 5-Aza-CdR, and the cell morphology was observe by phase contrast microscopy. The cell growth was assessed by MTT assay. A tumor-bearing mouse model was generated by subcutaneous inoculation of human colon carcinoma HCT116 cells into nude mice. The tumor growth in the nude mice was observed, the CDH13 gene expression and its methylation status in the tumors were detected using methylation specific PCR (MSP), RT-PCR, Western blotting and immunohistochemistry. After treatment with 5-Aza-CdR, the inhibition rate of the growth of cultured HCT116 cells was increased as the concentration was increasing. The growth of the xenografts in nude mice was significantly inhibited, and the methylated CDH13 gene was reactivated. After 4 weeks of 5-Aza-CdR treatment, no significant difference was found between the body weights of nude mice in the 5-Aza-CdR group [(18.06 ± 1.29) g] and control group [(17.07 ± 0.84) g], (P > 0.10), and the average volume of xenografts of the 5-Aza-CdR group was (907.00 ± 87.29) mm(3), significantly smaller than the (1370.93 ± 130.20) mm(3) in the control group (P < 0.005). No expression of CDH13 gene was found in the control group. The expression of CDH13 gene in the 5-Aza-CdR group was increased along with the increasing concentration of 5-Aza-CdR. 5-Aza-CdR inhibits the growth of human colon cancer cells in culture and in nude mice, and induces the cancer cells to re-express CDH13 in nude mice. Its mechanism may be that demethylation of the methylated CDH13 promoter induced by 5-Aza-CdR restores CDH13 expression and thus inhibits the tumor growth in nude mice.

Vapor intrusion risk of fuel ether oxygenates methyl tert-butyl ether (MTBE), tert-amyl methyl ether (TAME) and ethyl tert-butyl ether (ETBE): A modeling study.

PubMed

Ma, Jie; Xiong, Desen; Li, Haiyan; Ding, Yi; Xia, Xiangcheng; Yang, Yongqi

2017-06-15

Vapor intrusion of synthetic fuel additives represents a critical yet still neglected problem at sites contaminated by petroleum fuel releases. This study used an advanced numerical model to investigate the vapor intrusion potential of fuel ether oxygenates methyl tert-butyl ether (MTBE), tert-amyl methyl ether (TAME), and ethyl tert-butyl ether (ETBE). Simulated indoor air concentration of these compounds can exceed USEPA indoor air screening level for MTBE (110μg/m 3 ). Our results also reveal that MTBE has much higher chance to cause vapor intrusion problems than TAME and ETBE. This study supports the statements made by USEPA in the Petroleum Vapor Intrusion (PVI) Guidance that the vertical screening criteria for petroleum hydrocarbons may not provide sufficient protectiveness for fuel additives, and ether oxygenates in particular. In addition to adverse impacts on human health, ether oxygenate vapor intrusion may also cause aesthetic problems (i.e., odour and flavour). Overall, this study points out that ether oxygenates can cause vapor intrusion problems. We recommend that USEPA consider including the field measurement data of synthetic fuel additives in the existing PVI database and possibly revising the PVI Guidance as necessary. Copyright © 2017 Elsevier B.V. All rights reserved.

Phytochemical comparison between Pet ether and ethanolic extracts of Bacopa monnieri, Evolvulus alsinoides and Tinospora cordifolia.

PubMed

Gupta, Avneet; Raj, Hem; Sharma, Bhartendu; Upmanyu, Neeraj

2014-04-01

Bacopa monnieri, Evolvulus alsinoides and Tinospora cordifolia are established ayurvedic herbs having neuropharmacological effect. In present study is aimed to Phytochemical Comparison between Pet ether and Ethanolic extracts of Bacopa monnieri (BME), Evolvulus alsinoides (EAE) and Tinospora cordifolia (TCE). To identify the presence (+) or absence (-) of different phytoconstituents in Pet ether and Ethanolic extracts of BME, EAE and TCE by using various phytochemical testing methods. Phytochemical investigation showed the presence of various phytochemical constituents in Pet ether and Ethanolic extracts of BME, EAE and TCE. When comparison between Pet ether and Ethanolic extracts of BME, EAE and TCE; Ethanolic extracts of these plants showed more phytoconstituents as compared to Pet ether extracts of these plants. From present investigation, it can be concluded that phytochemical comparison is subsequently momentous and useful in finding chemical constituents in the plant substances that may lead to their quantitative evaluation and also pharmacologically active chemical compounds.

Alteration of runt-related transcription factor 3 gene expression and biologic behavior of esophageal carcinoma TE-1 cells after 5-azacytidine intervention.

PubMed

Wang, Shuai; Liu, Hong; Akhtar, Javed; Chen, Hua-Xia; Wang, Zhou

2013-01-01

5-Azacytidine (5-azaC) was originally identified as an anticancer drug (NSC102876) which can cause hypomethylation of tumor suppressor genes. To assess its effects on runt-related transcription factor 3 (RUNX3), expression levels and the promoter methylation status of the RUNX3 gene were assessed. We also investigated alteration of biologic behavior of esophageal carcinoma TE-1 cells. MTT assays showed 5-azaC inhibited the proliferation of TE-1 cells in a time and dose-dependent way. Although other genes could be demethylated after 5-azaC intervention, we focused on RUNX3 gene in this study. The expression level of RUNX3 mRNA increased significantly in TE-1 cells after treatment with 5-azaC at hypotoxic levels. RT-PCR showed 5-azaC at 50 μM had the highest RUNX3-induction activity. Methylation-specific PCR indicated that 5-azaC induced RUNX3 expression through demethylation. Migration and invasion of TE-1 cells were inhibited by 5-azaC, along with growth of Eca109 xenografts in nude mice. In conclusion, we demonstrate that the RUNX3 gene can be reactivated by the demethylation reagent 5-azaC, which inhibits the proliferation, migration and invasion of esophageal carcinoma TE-1 cells.

4-Aza-1-azoniabicyclo­[2.2.2]octa­ne–2-amino­benzoate–2-amino­benzoic acid (1/1/1)

PubMed Central

Arman, Hadi D.; Kaulgud, Trupta; Tiekink, Edward R. T.

2011-01-01

A 4-aza-1-azoniabicyclo­[2.2.2]octane cation, a 2-amino­benzoate anion and a neutral 2-amino­benzoic acid mol­ecule comprise the asymmetric unit of the title compound, C6H13N2 +·C7H6NO2 −·C7H7NO2. An intra­molecular N—H⋯O hydrogen bond occurs in the anion and in the neutral 2-amino­benzoic acid mol­ecule. The cation provides a charge-assisted N—H⋯O hydrogen bond to the anion, and the 2-amino­benzoic acid mol­ecule forms an O—H⋯N hydrogen bond to the unprotonated amino N atom in the cation. In this way, a three-component aggregate is formed. These are connected into a three-dimensional network by amino–carboxyl­ate N—H⋯O hydrogen bonds. N—H⋯N hydrogen bonds are also observed. PMID:22219964

Chemical defence in mussels: antifouling effect of crude extracts of the periostracum of the blue mussel Mytilus edulis.

PubMed

Bers, A Valeria; D'Souza, Fraddry; Klijnstra, Job W; Willemsen, Peter R; Wahl, Martin

2006-01-01

Shells of the blue mussel Mytilus edulis remain free of fouling organisms as long as they possess an intact periostracum, and a multiple antifouling defence that comprises a ripple-like microtopography and the production of chemical antifouling compounds has been suggested previously. This study investigates the chemical defence strategy of blue mussels for the first time. Six crude extracts of the periostracum of intact shells were made using solvents of increasing polarity. These extracts were tested against common fouling organisms in laboratory based bioassays. Non-polar and moderately polar fractions showed the highest activities: the diethyl ether fraction strongly inhibited attachment of Balanus amphitrite cyprids and the marine bacteria Cobetia marina and Marinobacter hydrocarbonoclasticus. Attachment of the benthic diatom Amphora coffeaeformis was significantly reduced by the dichloromethane extract, whereas both ethyl acetate and diethyl ether fractions slowed diatom growth. These results provide the first evidence of surface bound compounds that may moderate surface colonisation.

Perfluorinated Compounds and Polybrominated Diphenyl Ethers in Great Blue Heron Eggs from Three Colonies on the Mississippi River, Minnesota

USGS Publications Warehouse

Custer, T.W.; Kannan, K.; Tao, L.; Yun, S.-H.; Trowbridge, A.

2010-01-01

Archived Great Blue Heron (Ardea herodias) eggs (N = 16) collected in 1993 from three colonies on the Mississippi River in Minnesota were analyzed in 2007 for perfluorinated compounds (PFCs) and polybrominated diphenyl ethers (PBDEs). One of the three colonies, Pig's Eye, was located near a presumed source of PFCs. Based on a multivariate analysis, the pattern of nine PFC concentrations differed significantly between Pig's Eye and the upriver (P = 0.002) and downriver (P = 0.02) colonies; but not between the upriver and downriver colonies (P = 0.25). Mean concentrations of perfluorooctane sulfonate (PFOS), a major PFC compound, were significantly higher at the Pig's Eye colony (geometric mean = 940 ng/g wet weight) than at upriver (60 ng/g wet weight) and downriver (131 ng/g wet weight) colonies. Perfluorooctane sulfonate concentrations from the Pig's Eye colony are among the highest reported in bird eggs. Concentrations of PFOS in Great Blue Heron eggs from Pig's Eye were well below the toxicity thresholds estimated for Bobwhite Quail (Colinus virginianus) and Mallards (Anas platyrhynchos), but within the toxicity threshold estimated for White Leghorn Chickens (Gallus domesticus). The pattern of six PBDE congener concentrations did not differ among the three colonies (P = 0.08). Total PBDE concentrations, however, were significantly greater (P = 0.03) at Pig's Eye (geometric mean = 142 ng/g wet weight) than the upriver colony (13 ng/g wet weight). Polybrominated diphenyl ether concentrations in two of six Great Blue Heron eggs from the Pig's Eye colony were within levels associated with altered reproductive behavior in American Kestrels (Falco sparverius).

The antimicrobial efficacy and structure activity relationship of novel carbohydrate fatty acid derivatives against Listeria spp. and food spoilage microorganisms.

PubMed

Nobmann, Patricia; Smith, Aoife; Dunne, Julie; Henehan, Gary; Bourke, Paula

2009-01-15

Novel mono-substituted carbohydrate fatty acid (CFA) esters and ethers were investigated for their antibacterial activity against a range of pathogenic and spoilage bacteria focussing on Listeria monocytogenes. Carbohydrate derivatives with structural differences enable comparative studies on the structure/activity relationship for antimicrobial efficacy and mechanism of action. The antimicrobial efficacy of the synthesized compounds was compared with commercially available compounds such as monolaurin and monocaprylin, as well as the pure free fatty acids, lauric acid and caprylic acid, which have proven antimicrobial activity. Compound efficacy was compared using an absorbance based broth microdilution assay to determine the minimum inhibitory concentration (MIC), increase in lag phase and decrease in maximum growth rate. Among the carbohydrate derivatives synthesized, lauric ether of methyl alpha-d-glucopyranoside and lauric ester of methyl alpha-d-mannopyranoside showed the highest growth-inhibitory effect with MIC values of 0.04 mM, comparable to monolaurin. CFA derivatives were generally more active against Gram positive bacteria than Gram negative bacteria. The analysis of both ester and ether fatty acid derivatives of the same carbohydrate, in tandem with alpha and beta configuration of the carbohydrate moiety suggest that the carbohydrate moiety is involved in the antimicrobial activity of the fatty acid derivatives and that the nature of the bond also has a significant effect on efficacy, which requires further investigation. This class of CFA derivatives has great potential for developing antibacterial agents relevant to the food industry, particularly for control of Listeria or other Gram-positive pathogens.

Furfuryl ethyl ether: important aging flavor and a new marker for the storage conditions of beer.

PubMed

Vanderhaegen, Bart; Neven, Hedwig; Daenen, Luk; Verstrepen, Kevin J; Verachtert, Hubert; Derdelinckx, Guy

2004-03-24

Recently, it was reported that furfuryl ethyl ether is an important flavor compound indicative of beer storage and aging conditions. A study of the reaction mechanism indicates that furfuryl ethyl ether is most likely formed by protonation of furfuryl alcohol or furfuryl acetate followed by S(N)2-substitution of the leaving group by the nucleophilic ethanol. For the reaction in beer, a pseudo-first-order reaction kinetics was derived. A close correlation was found between the values predicted by the kinetic model and the actual furfuryl ethyl ether concentration evolution during storage of beer. Furthermore, 10 commercial beers of different types, aged during 4 years in natural conditions, were analyzed, and it was found that the furfuryl ethyl ether flavor threshold was largely exceeded in each type of beer. In these natural aging conditions, lower pH, darker color, and higher alcohol content were factors that enhanced furfuryl ethyl ether formation. On the other hand, sulfite clearly reduced furfuryl ethyl ether formation. All results show that the furfuryl ethyl ether concentration is an excellent time-temperature integrator for beer storage.

Azelaic acid 15% gel once daily versus twice daily in papulopustular rosacea.

PubMed

Thiboutot, Diane M; Fleischer, Alan B; Del Rosso, James Q; Graupe, Klaus

2008-06-01

Twice-daily azelaic acid (AzA) is the conventional regimen for papulopustular rosacea, but once-daily AzA may be equally effective, with greater convenience and dosing flexibility. In order to test this hypothesis, an exploratory study was conducted. The evaluable efficacy population of this 12-week double-blind, parallel-group study included 72 patients and the population that was used to report safety results included 92 patients. Baseline characteristics were comparable between the once-daily and twice-daily study groups. Evaluations were performed at baseline and at weeks 4, 8, and 12. No significant difference was found between the once-daily and twice-daily groups at the end of study therapy in mean investigator global assessment (IGA) scores, treatment success, or treatment response. The mean number of inflammatory lesions, the intensity of erythema intensity, and the intensity of telangiectasia at treatment end were likewise not significantly different (P>.205 for all). More than 90% of subjects in each group rated cosmetic acceptability of this AzA gel as satisfactory or better. Based on these findings and those of prior studies, once-daily AzA 15% gel can therefore be utilized as a safe, effective, and economical dosing option for the treatment of mild-to-moderate papulopustular rosacea. Once-daily dosing of AzA 15% gel was well accepted by patients and can offer considerable dosing flexibility and convenience for the patient as well as for the dermatologist.

Acidolysis small molecular phenolic ether used as accelerator in photosensitive diazonaphthaquinone systems

NASA Astrophysics Data System (ADS)

Zhou, Haihua; Zou, Yingquan

2006-03-01

The photosensitive compounds in the photosensitive coatings of positive PS plates are the diazonaphthaquinone derivatives. Some acidolysis small molecular phenolic ethers, which were synthesized by some special polyhydroxyl phenols with vinyl ethyl ether, are added in the positive diazonaphthaquinone photosensitive composition to improve its sensitivity, composed with photo-acid-generators. The effects to the photosensitivity, anti-alkali property, anti-isopropyl alcohol property, dot resolution and line resolution of the coatings are studied with different additive percent of the special phenolic ethers. In the conventional photosensitive diazonaphthaquinone systems for positive PS plates, the photosensitivity is improved without negative effects to resolution, anti-alkali and anti-isopropyl alcohol properties when added about 5% of the special acidolysis phenolic ethers, EAAE or DPHE, composed with photo-acid-generators.

2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor

PubMed Central

Hanuš, Lumír; Abu-Lafi, Saleh; Fride, Ester; Breuer, Aviva; Vogel, Zvi; Shalev, Deborah E.; Kustanovich, Irina; Mechoulam, Raphael

2001-01-01

Two types of endogenous cannabinoid-receptor agonists have been identified thus far. They are the ethanolamides of polyunsaturated fatty acids—arachidonoyl ethanolamide (anandamide) is the best known compound in the amide series—and 2-arachidonoyl glycerol, the only known endocannabinoid in the ester series. We report now an example of a third, ether-type endocannabinoid, 2-arachidonyl glyceryl ether (noladin ether), isolated from porcine brain. The structure of noladin ether was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and was confirmed by comparison with a synthetic sample. It binds to the CB1 cannabinoid receptor (Ki = 21.2 ± 0.5 nM) and causes sedation, hypothermia, intestinal immobility, and mild antinociception in mice. It binds weakly to the CB2 receptor (Ki > 3 μM). PMID:11259648

Design, synthesis, and structure-activity relationships of 3,4-dihydropyridopyrimidin-2(1H)-one derivatives as a novel class of sodium/calcium exchanger inhibitor.

PubMed

Hasegawa, Hirohiko; Muraoka, Masami; Ohmori, Mikiko; Matsui, Kazuki; Kojima, Atsuyuki

2005-10-01

Design, synthesis, and structure-activity relationships for 3,4-dihydropyridopyrimidin-2(1H)-one derivatives, which are aza-3,4-dihydro-2(1H)-quinazolinone derivatives, as the sodium/calcium (Na+/Ca2+) exchanger inhibitors are discussed. These studies based on 3,4-dihydro-2(1H)-quinazolinone derivatives led to the discovery of a structurally novel and potent Na+/Ca2+ exchanger inhibitor, 3,4-dihydropyridopyrimidin-2(1H)-one derivative (26), with an IC30 value of 0.02 microM. Compound 26 directly inhibited the Na+-dependent Ca2+ influx via the Na+/Ca2+ exchanger after Na+-free treatment in cardiomyocytes.

Synthetic Analogs of Phospholipid Metabolites as Antimalarials.

DTIC Science & Technology

1979-07-01

phosphatidic acid analogs containing ether and phosphonate groups; completely non-hydrolyzable lecithin analogs containing phosphinate and ether groups...The phosphatidic acid and lecithin target compounds were successfully synthesized and submitted, together with a number of intermediates. A model of a... Phosphatidic acid analogs ......................... 5 Z.Z Lecithin Analogs .................................. 6 2.3 Analogs of Cytidine Diphosphate

Chemical Aspects of General Anesthesia: Part 1. From Ether to Halothane

ERIC Educational Resources Information Center

Brunsvold, Robert; Ostercamp, Daryl L.

2006-01-01

The history and evolution of general anesthesia, which invokes a variety of drugs, each compound having a specific purpose from muscle relaxation to unconsciousness is discussed. Some of the popular anesthetics discussed are ether, chloroform, halocarbons, gaseous nitrous oxide, halothane, and mixture of 70% nitrous oxide and 30% oxygen.

Polybrominated diphenyl ethers from the marine organisms Lendenfeldia dendyi and Sinularia dura with anti-MRSa activity

USDA-ARS?s Scientific Manuscript database

Bioassay-guided fractionation of the marine sponge Lendenfeldia dendyi and the soft coral Sinularia dura resulted in the isolation of five polybrominated diphenyl ethers (1-5). The structures of the isolated compounds were determined using spectroscopic methods(lD and 2D NMR) and HRMS analyses. The ...

Larvicidal Activity of Centaurea bruguierana ssp. belangerana Against Anopheles stephensi Larvae.

PubMed

Khanavi, Mahnaz; Rajabi, Afsaneh; Behzad, Masoud; Hadjiakhoondi, Abbas; Vatandoost, Hassan; Abaee, Mohammad Reza

2011-01-01

In this study, the total 80% of MeOH extract and also petroleum ether, CHCl3, EtOAc, n-BuOH, and the remaining MeOH fractions obtained by solvent-solvent fractionation of the whole flowering samples of Centaurea bruguierana (DC.) Hand.-Mzt. ssp. belangerana (DC.) Bornm. (Asteraceae), namely "Baad-Avard", collected from Borazjan in Bushehr Province (Bushehr, Iran) were investigated for larvicidal activity against malaria vector, Anopheles stephensi Liston, according to WHO methods. The mortality rate of total extract and petroleum ether fraction in concentration of 40 ppm were 28% and 86% respectively and the other fractions were inactive. The probit regression analysis for the dose-response to petroleum ether fraction treatment of larvae exhibited the LC50 and LC90 values of 15.7 ppm and 48.3 ppm, respectively. As results showed, the larvicidal activity of the petroleum ether fraction would be due to the nonpolar compounds in the plant which further isolation and purification would obtain the more active compounds in lower concentrations useful for preparation of biological insecticides.

Larvicidal Activity of Centaurea bruguierana ssp. belangerana Against Anopheles stephensi Larvae

PubMed Central

Khanavi, Mahnaz; Rajabi, Afsaneh; Behzad, Masoud; Hadjiakhoondi, Abbas; Vatandoost, Hassan; Abaee, Mohammad Reza

2011-01-01

In this study, the total 80% of MeOH extract and also petroleum ether, CHCl3, EtOAc, n-BuOH, and the remaining MeOH fractions obtained by solvent-solvent fractionation of the whole flowering samples of Centaurea bruguierana (DC.) Hand.-Mzt. ssp. belangerana (DC.) Bornm. (Asteraceae), namely “Baad-Avard”, collected from Borazjan in Bushehr Province (Bushehr, Iran) were investigated for larvicidal activity against malaria vector, Anopheles stephensi Liston, according to WHO methods. The mortality rate of total extract and petroleum ether fraction in concentration of 40 ppm were 28% and 86% respectively and the other fractions were inactive. The probit regression analysis for the dose-response to petroleum ether fraction treatment of larvae exhibited the LC50 and LC90 values of 15.7 ppm and 48.3 ppm, respectively. As results showed, the larvicidal activity of the petroleum ether fraction would be due to the nonpolar compounds in the plant which further isolation and purification would obtain the more active compounds in lower concentrations useful for preparation of biological insecticides. PMID:24250419

Bioactivities and chemical constituents of a Vietnamese medicinal plant Che Vang, Jasminum subtriplinerve Blume (Oleaceae).

PubMed

Ngan, Dai Hue; Hoai, Ho Thi Cam; Huong, Le Mai; Hansen, Poul Erik; Vang, Ole

2008-01-01

Five crude extracts were made from leaves and stems of Jasminum subtriplinerve Blume (Oleaceae) and investigated for antimicrobial, antioxidant and cytotoxic activities. The extractions were done with petroleum ether, ethyl acetate, ethanol, methanol or water. All extracts exhibited anti-bacterial activity except the water fraction. On the other hand, all extracts exhibit antioxidant activity except the petroleum ether fraction using the DPPH radical scavenging assay. Only the petroleum ether fraction showed a cytotoxicity activity against tested cell-lines, Hep-G2 and RD with IC(50) values of 19.2 and 20 microg mL(-1), respectively. From the petroleum ether and ethyl acetate extracts, two triterpenes namely 3beta-acetyl-oleanolic acid and lup-20-en-3beta-ol and a sterol, stigmast-5-en-3beta-ol were isolated. The structure of those compounds were elucidated by spectrometric methods IR, MS, 1D-NMR, 2D-NMR and simulated ACD/NMR spectra. The data presented here indicate that J. subtriplinerve do contain compounds with interesting biological activity.

Cross-dehydrogenative coupling and oxidative-amination reactions of ethers and alcohols with aromatics and heteroaromatics

PubMed Central

Vuram, Prasanna K.

2017-01-01

Cross-dehydrogenative coupling (CDC) is a process in which, typically, a C–C bond is formed at the expense of two C–H bonds, either catalyzed by metals or other organic compounds, or via uncatalyzed processes. In this perspective, we present various modes of C–H bond-activation at sp3 centers adjacent to ether oxygen atoms, followed by C–C bond formation with aromatic systems as well as with heteroaromatic systems. C–N bond-formation with NH-containing heteroaromatics, leading to hemiaminal ethers, is also an event that can occur analogously to C–C bond formation, but at the expense of C–H and N–H bonds. A large variety of hemiaminal ether-forming reactions have recently appeared in the literature and this perspective also includes this complementary chemistry. In addition, the participation of C–H bonds in alcohols in such processes is also described. Facile access to a wide range of compounds can be attained through these processes, rendering such reactions useful for synthetic applications via Csp3 bond activations. PMID:28970941

Bis(amino)cyclopropenylidene (BAC) catalyzed aza-benzoin reaction.

PubMed

Wilde, Myron M D; Gravel, Michel

2014-10-17

A bis(amino)cyclopropenylidene (BAC) catalyzed aza-benzoin reaction between aldehydes and phosphinoyl imines has been developed. The reaction is general with a wide range of aromatic aldehydes and aromatic imines. The reaction displays excellent chemoselectivity favoring aza-benzoin products over homobenzoin products.

Biodegradation of potential diesel oxygenate additives: dibutyl maleate (DBM), and tripropylene glycol methyl ether (TGME).

PubMed

Marchetti, Alfredo A; Knize, Mark G; Chiarappa-Zucca, Marina L; Pletcher, Ronald J; Layton, David W

2003-08-01

The addition of oxygen-bearing compounds to diesel fuel considerably reduces particulate emissions. TGME and DBM have been identified as possible diesel additives based on their physicochemical characteristics and performance in engine tests. Although these compounds will reduce particulate emissions, their potential environmental impacts are unknown. As a means of characterizing their persistence in environmental media such as soil and groundwater, we conducted a series of biodegradation tests of DBM and TGME. Benzene and methyl tertiary butyl ether (MTBE) were also tested as reference compounds. Primary degradation of DBM fully occurred within 3 days, while TGME presented a lag phase of approximately 8 days and was not completely degraded by day 28. Benzene primary degradation occurred completely by day 3 and MTBE did not degrade at all. The total mineralized fractions of DBM and TGME achieved constant values as a function of time of approximately 65% and approximately 40%, respectively. Transport predictions show that, released to the environment, DBM and TGME would concentrate mostly in soils and waters with minimal impact to air. From an environmental standpoint, these results combined with the transport predictions indicate that DBM is a better choice than TGME as a diesel additive.

Unusually Strong Binding to the DNA Minor Groove by a Highly Twisted Benzimidazole-Diphenylether: Induced Fit and Bound Water†

PubMed Central

Tanious, Farial A.; Laine, William; Peixoto, Paul; Bailly, Christian; Goodwin, Kristie D.; Lewis, Mark A.; Long, Eric C.; Georgiadis, Millie M.; Tidwell, Richard R.; Wilson, W. David

2008-01-01

RT29 is a dicationic diamidine derivative that does not obey the classical “rules” for shape and functional group placement that are expected to result in strong binding and specific recognition of the DNA minor groove. The compound contains a benzimidazole-diphenyl ether core that is flanked by the amidine cations. The diphenyl ether is highly twisted and gives the entire compound too much curvature to fit well to the shape of the minor groove. DNaseI footprinting, fluorescence intercalator displacement studies and circular dichroism spectra, however, indicate that the compound is an AT specific minor groove binding agent. Even more surprisingly, quantitative biosensor-surface plasmon resonance and isothermal titration calorimetric results indicate that the compound binds with exceptional strength to certain AT sequences in DNA with a large negative enthalpy of binding. Crystallographic results for the DNA complex of RT29 compared to calculated results for the free compound show that the compound undergoes significant conformational changes to enhance its minor groove interactions. In addition, a water molecule is incorporated directly into the complex to complete the compound-DNA interface and it forms an essential link between the compound and base pair edges at the floor of the minor groove. The calculated ΔCp value for complex formation is substantially less than the experimentally observed value in support of water being an intrinsic part of the complex with a major contribution to the ΔCp value. Both the induced fit conformational changes of the compound and the bound water are essential for strong binding to DNA by RT29. PMID:17506529

Inhibitors of the tick-borne, hemorrhagic fever-associated flaviviruses.

PubMed

Flint, Mike; McMullan, Laura K; Dodd, Kimberly A; Bird, Brian H; Khristova, Marina L; Nichol, Stuart T; Spiropoulou, Christina F

2014-06-01

No antiviral therapies are available for the tick-borne flaviviruses associated with hemorrhagic fevers: Kyasanur Forest disease virus (KFDV), both classical and the Alkhurma hemorrhagic fever virus (AHFV) subtype, and Omsk hemorrhagic fever virus (OHFV). We tested compounds reported to have antiviral activity against members of the Flaviviridae family for their ability to inhibit AHFV replication. 6-Azauridine (6-azaU), 2'-C-methylcytidine (2'-CMC), and interferon alpha 2a (IFN-α2a) inhibited the replication of AHFV and also KFDV, OHFV, and Powassan virus. The combination of IFN-α2a and 2'-CMC exerted an additive antiviral effect on AHFV, and the combination of IFN-α2a and 6-azaU was moderately synergistic. The combination of 2'-CMC and 6-azaU was complex, being strongly synergistic but with a moderate level of antagonism. The antiviral activity of 6-azaU was reduced by the addition of cytidine but not guanosine, suggesting that it acted by inhibiting pyrimidine biosynthesis. To investigate the mechanism of action of 2'-CMC, AHFV variants with reduced susceptibility to 2'-CMC were selected. We used a replicon system to assess the substitutions present in the selected AHFV population. A double NS5 mutant, S603T/C666S, and a triple mutant, S603T/C666S/M644V, were more resistant to 2'-CMC than the wild-type replicon. The S603T/C666S mutant had a reduced level of replication which was increased when M644V was also present, although the replication of this triple mutant was still below that of the wild type. The S603 and C666 residues were predicted to lie in the active site of the AHFV NS5 polymerase, implicating the catalytic center of the enzyme as the binding site for 2'-CMC. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Inhibitors of the Tick-Borne, Hemorrhagic Fever-Associated Flaviviruses

PubMed Central

Flint, Mike; McMullan, Laura K.; Dodd, Kimberly A.; Bird, Brian H.; Khristova, Marina L.; Nichol, Stuart T.

2014-01-01

No antiviral therapies are available for the tick-borne flaviviruses associated with hemorrhagic fevers: Kyasanur Forest disease virus (KFDV), both classical and the Alkhurma hemorrhagic fever virus (AHFV) subtype, and Omsk hemorrhagic fever virus (OHFV). We tested compounds reported to have antiviral activity against members of the Flaviviridae family for their ability to inhibit AHFV replication. 6-Azauridine (6-azaU), 2′-C-methylcytidine (2′-CMC), and interferon alpha 2a (IFN-α2a) inhibited the replication of AHFV and also KFDV, OHFV, and Powassan virus. The combination of IFN-α2a and 2′-CMC exerted an additive antiviral effect on AHFV, and the combination of IFN-α2a and 6-azaU was moderately synergistic. The combination of 2′-CMC and 6-azaU was complex, being strongly synergistic but with a moderate level of antagonism. The antiviral activity of 6-azaU was reduced by the addition of cytidine but not guanosine, suggesting that it acted by inhibiting pyrimidine biosynthesis. To investigate the mechanism of action of 2′-CMC, AHFV variants with reduced susceptibility to 2′-CMC were selected. We used a replicon system to assess the substitutions present in the selected AHFV population. A double NS5 mutant, S603T/C666S, and a triple mutant, S603T/C666S/M644V, were more resistant to 2′-CMC than the wild-type replicon. The S603T/C666S mutant had a reduced level of replication which was increased when M644V was also present, although the replication of this triple mutant was still below that of the wild type. The S603 and C666 residues were predicted to lie in the active site of the AHFV NS5 polymerase, implicating the catalytic center of the enzyme as the binding site for 2′-CMC. PMID:24663025

Enhancing the Bioconversion of Azelaic Acid to Its Derivatives by Response Surface Methodology.

PubMed

Khairudin, Nurshafira; Basri, Mahiran; Fard Masoumi, Hamid Reza; Samson, Shazwani; Ashari, Siti Efliza

2018-02-13

Azelaic acid (AzA) and its derivatives have been known to be effective in the treatment of acne and various cutaneous hyperpigmentary disorders. The esterification of azelaic acid with lauryl alcohol (LA) to produce dilaurylazelate using immobilized lipase B from Candida antarctica (Novozym 435) is reported. Response surface methodology was selected to optimize the reaction conditions. A well-fitting quadratic polynomial regression model for the acid conversion was established with regards to several parameters, including reaction time and temperature, enzyme amount, and substrate molar ratios. The regression equation obtained by the central composite design of RSM predicted that the optimal reaction conditions included a reaction time of 360 min, 0.14 g of enzyme, a reaction temperature of 46 °C, and a molar ratio of substrates of 1:4.1. The results from the model were in good agreement with the experimental data and were within the experimental range (R² of 0.9732).The inhibition zone can be seen at dilaurylazelate ester with diameter 9.0±0.1 mm activities against Staphylococcus epidermidis S273. The normal fibroblasts cell line (3T3) was used to assess the cytotoxicity activity of AzA and AzA derivative, which is dilaurylazelate ester. The comparison of the IC 50 (50% inhibition of cell viability) value for AzA and AzA derivative was demonstrated. The IC 50 value for AzA was 85.28 μg/mL, whereas the IC 50 value for AzA derivative was more than 100 μg/mL. The 3T3 cell was still able to survive without any sign of toxicity from the AzA derivative; thus, it was proven to be non-toxic in this MTT assay when compared with AzA.

Distribution of methyl tert-butyl ether (MTBE) and selected water-quality constituents in the surficial aquifer at the Dover National Test Site, Dover Air Force Base, Delaware, 2001

USGS Publications Warehouse

Stewart, Marie; Guertal, William R.; Barbaro, Jeffrey R.; McHale, Timothy J.

2004-01-01

A joint study by the Dover National Test Site, Dover Air Force Base, Delaware, and the U.S. Geological Survey was conducted from June 27 through July 18, 2001, to determine the spatial distribution of the gasoline oxygenate additive methyl tert-butyl ether and selected water-quality constituents in the surficial aquifer underlying the Dover National Test Site. This report provides a summary assessment of the distribution of methyl tert-butyl ether and a preliminary screening of selected constituents that may affect natural attenuation and remediation demonstrations at the Dover National Test Site. The information gathered during this study is designed to assist potential remedial investigators who are considering conducting a methyl tert-butyl ether remedial demonstration at the test site. In addition, the study supported a planned enhanced bioremediation demonstration and assisted the Dover National Test Site in identifying possible locations for future methyl tert-butyl ether remediation demonstrations. A direct-push drill rig was used to collect a total of 147 ground-water samples (115 VOC samples and 32 quality-assurance samples) at varying depths. Volatile organic compounds were above the method reporting limits in 59 of the 115 ground-water samples. The concentrations ranged from below detection limits to maximum values of 12.4 micrograms per liter of cis-1,2-dichloro-ethene, 1.14 micrograms per liter of trichloro-ethene, 2.65 micrograms per liter of tetrachloro-ethene, 1,070 micrograms per liter of methyl tert-butyl ether, 4.36 micrograms per liter of benzene, and 1.8 micrograms per liter of toluene. Vinyl chloride, ethylbenzene, p,m-xylene, and o-xylene were not detected in any of the samples collected during this investigation. Methyl tert-butyl ether was detected in 47 of the 115 ground-water samples. The highest concentrations of methyl tert-butyl ether were detected in the surficial aquifer from ?4.6 to 6.4 feet mean sea level; however, methyl tert-butyl ether was detected as deep as ?9.5 feet mean sea level. Increased methane concentrations and decreased dissolved oxygen concentrations that were found in association with the ground-water samples that contained methyl tert-butyl ether are preliminary indicators that will assist in determining if natural attenuation of methyl tert-butyl ether is occurring in the surficial aquifer. A full assessment of natural attenuation of methyl tert-butyl ether at the site is beyond the scope of this study, but the data collected during the study will be useful in selecting appropriate remedial methyl tert-butyl ether demonstrations.

Examination of the potential for adaptive chirality of the nitrogen chiral center in aza-aspartame.

PubMed

Bouayad-Gervais, Samir H; Lubell, William D

2013-11-28

The potential for dynamic chirality of an azapeptide nitrogen was examined by substitution of nitrogen for the α-carbon of the aspartate residue in the sweetener S,S-aspartame. Considering that S,S- and R,S-aspartame possess sweet and bitter tastes, respectively, a bitter-sweet taste of aza-aspartame 9 could be indicative of a low isomerization barrier for nitrogen chirality inter-conversion. Aza-aspartame 9 was synthesized by a combination of hydrazine and peptide chemistry. Crystallization of 9 indicated a R,S-configuration in the solid state; however, the aza-residue chiral center was considerably flattened relative to its natural amino acid counterpart. On tasting, the authors considered aza-aspartame 9 to be slightly bitter or tasteless. The lack of bitter sweet taste of aza-aspartame 9 may be due to flattening from sp2 hybridization in the urea as well as a high barrier for sp3 nitrogen inter-conversion, both of which may interfere with recognition by taste receptors.

HPLC-UV Method for the Identification and Screening of Hydroquinone, Ethers of Hydroquinone and Corticosteroids Possibly Used as Skin-Whitening Agents in Illicit Cosmetic Products.

PubMed

Gimeno, Pascal; Maggio, Annie-Françoise; Bancilhon, Marjorie; Lassu, Nelly; Gornes, Hervé; Brenier, Charlotte; Lempereur, Laurent

2016-03-01

Corticosteroids, hydroquinone and its ethers are regulated in cosmetics by the Regulation 1223/2009. As corticosteroids are forbidden to be used in cosmetics and cannot be present as contaminants or impurities, an identification of one of these illicit compounds deliberately introduced in these types of cosmetics is enough for market survey control. In order to quickly identify skin-whitening agents present in illegal cosmetics, this article proposes an HPLC-UV method for the identification and screening of hydroquinone, 3 ethers of hydroquinone and 39 corticosteroids that may be found in skin-whitening products. Two elution gradients were developed to separate all compounds. The main solvent gradient (A) allows the separation of 39 compounds among the 43 compounds considered in 50 min. Limits of detection on skin-whitening cosmetics are given. For compounds not separated, a complementary gradient elution (B) using the same solvents is proposed. Between 2004 and 2009, a market survey on "skin-whitening cosmetic" was performed on 150 samples and highlights that more than half of the products tested do not comply with the Cosmetic Regulation 1223/2009 (amending the Council Directive 76/768/EEC). © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Somatic mutation dynamics in MDS patients treated with azacitidine indicate clonal selection in patients-responders

PubMed Central

Polgarova, Kamila; Vargova, Karina; Kulvait, Vojtech; Dusilkova, Nina; Minarik, Lubomir; Zemanova, Zuzana; Pesta, Michal; Jonasova, Anna; Stopka, Tomas

2017-01-01

Azacitidine (AZA) for higher risk MDS patients is a standard therapy with limited durability. To monitor mutation dynamics during AZA therapy we utilized massive parallel sequencing of 54 genes previously associated with MDS/AML pathogenesis. Serial sampling before and during AZA therapy of 38 patients (reaching median overall survival 24 months (Mo) with 60% clinical responses) identified 116 somatic pathogenic variants with allele frequency (VAF) exceeding 5%. High accuracy of data was achieved via duplicate libraries from myeloid cells and T-cell controls. We observed that nearly half of the variants were stable while other variants were highly dynamic. Patients with marked decrease of allelic burden upon AZA therapy achieved clinical responses. In contrast, early-progressing patients on AZA displayed minimal changes of the mutation pattern. We modeled the VAF dynamics on AZA and utilized a joint model for the overall survival and response duration. While the presence of certain variants associated with clinical outcomes, such as the mutations of CDKN2A were adverse predictors while KDM6A mutations yield lower risk of dying, the data also indicate that allelic burden volatility represents additional important prognostic variable. In addition, preceding 5q- syndrome represents strong positive predictor of longer overall survival and response duration in high risk MDS patients treated with AZA. In conclusion, variants dynamics detected via serial sampling represents another parameter to consider when evaluating AZA efficacy and predicting outcome. PMID:29340104

Epigenetic regulation of the circadian clock: role of 5-aza-2′-deoxycytidine

PubMed Central

Tomita, Tatsunosuke; Kurita, Ryoji

2017-01-01

We have been investigating transcriptional regulation of the BMAL1 gene, a critical component of the mammalian clock system including DNA methylation. Here, a more detailed analysis of the regulation of DNA methylation of BMAL1 proceeded in RPMI8402 lymphoma cells. We found that CpG islands in the BMAL1 and the PER2 promoters were hyper- and hypomethylated, respectively and that 5-aza-2′-deoxycytidine (aza-dC) not only enhanced PER2 gene expression but also PER2 oscillation within 24 h in RPMI8402 cells. That is, such hypermethylation of CpG islands in the BMAL1 promoter restricted PER2 expression which was recovered by aza-dC within 1 day in these cells. These results suggest that the circadian clock system can be recovered through BMAL1 expression induced by aza-dC within a day. The RPIB9 promoter of RPMI8402 cells, which is a methylation hotspot in lymphoblastic leukemia, was also hypermethylated and aza-dC gradually recovered RPIB9 expression in 3 days. In addition, methylation-specific PCR revealed a different degree of aza-dC-induced methylation release between BMAL1 and RPIB9. These results suggest that the aza-dC-induced recovery of gene expression from DNA methylation is dependent on a gene, for example the rapid response to demethylation by the circadian system, and thus, is of importance to clinical strategies for treating cancer. PMID:28487473

An Efficient Synthesis of de novo Imidates via Aza-Claisen Rearrangements of N-Allyl Ynamides

PubMed Central

DeKorver, Kyle A.; North, Troy D.; Hsung, Richard P.

2010-01-01

A novel thermal 3-aza-Claisen rearrangement of N-allyl ynamides for the synthesis of α-allyl imidates is described. Also, a sequential aza-Claisen, Pd-catalyzed Overman rearrangement is described for the synthesis of azapine-2-ones. PMID:21278848

Genotoxic and mutagenic properties of Bauhinia platypetala extract, a traditional Brazilian medicinal plant.

PubMed

Santos, Francisco José Borges Dos; Moura, Dinara Jaqueline; Péres, Valéria Flores; Sperotto, Angelo Regis de Moura; Caramão, Elina Bastos; Cavalcante, Ana Amélia de Carvalho Melo; Saffi, Jenifer

2012-12-18

Bauhinia platypetala Burch. is a traditionally used Brazilian medicinal plant, although no evidence in the literature substantiates the safety of its use. The aim of this study was to investigate the safety of the ethanolic extract and the ethereal fraction of B. platypetala leaves. The identification of chemical compounds from the B. platypetala ethanolic extract and its ethereal fraction was performed by GC/MS and ESI-MS/MS. The plant's toxicological, cytotoxic, mutagenic and genotoxic properties were determined in Saccharomyces cerevisiae strains and V79 cell culture by survival assays and comet assay. The major compound identified in the B. platypetala ethanolic extract is palmitic acid, kaempferitirin and quercitrin, while the B. platypetala ethereal fraction was found to be rich in phytol, gamma-sitosterol and vitamin E. Moreover, the results indicated that the B. platypetala ethanolic extract has an anti-oxidative effect against H(2)O(2) in yeast. In addition, the B. platypetala ethanolic extract did not induce mutagenic effects on the S. cerevisiae N123 strain, but the ethereal fraction of B. platypetala at higher concentrations (250-500 μg/mL) induced cytotoxicity and mutagenicity. A slight cytotoxic effect was observed in mammalian V79 cells; however, both the B. platypetala ethanolic extract and its ethereal fraction were able to induce DNA strand breaks in V79 cells, as detected by the alkaline comet assay. The B. platypetala ethanolic extract has antioxidant action and showed absence of mutagenic effects in yeast S. cerevisiae. On the other hand B. platypetala ethereal fraction is mutagenic and does not show antioxidant activity in yeast. In mammalian cells B. platypetala ethanolic extract and it's ethereal fraction induce cyotoxic and genotoxic action. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Thrust Evaluation of an Arcjet Thruster Using Dimethyl Ether as a Propellant

NASA Astrophysics Data System (ADS)

Kakami, Akira; Beppu, Shinji; Maiguma, Muneyuki; Tachibana, Takeshi

This paper describes the performance of an arcjet thruster using dimethyl ether (DME) as a propellant. DME, an ether compound, has adequate characteristics for space propulsion systems; DME is storable in a liquid state without a high pressure or cryogenic device and requires no sophisticated temperature management. DME is gasified and liquefied simply by adjusting temperature, whereas hydrazine, a conventional propellant, requires an iridium-based particulate catalyst for its gasification. In this study, thrust of the designed kW-class DME arcjet thruster is measured with a torsional thrust stand. Thrust measurements show that thrust is increased with propellant mass flow rate, and that thrust using DME propellant is higher than when using nitrogen. The prototype DME arcjet thruster yields a specific impulse of 330 s, a thruster efficiency of 0.14, and a thrust of 0.19 N at 60-mg/s DME mass flow rate at 25-A discharge current. The corresponding discharge power and specific power are 2.3 kW and 39 MJ/kg.

Diphenyl ethers from a marine-derived isolate of Aspergillus sp. CUGB-F046.

PubMed

Xu, Xiuli; Yang, Haijin; Xu, Huitao; Yin, Liyuan; Chen, Zhengkun; Shen, Huihui

2018-04-01

One new diphenyl ether, diorcinol K (1), along with three known compounds, diorcinols D (2), F (3) and I (4) were isolated from the fermentation media of a marine-derived fungus Aspergillus sp. CUGB-F046 which was isolated from a sediment sample collected from the Bohai Sea, China. Their structures were elucidated by detailed spectroscopic methods. Compounds 1, 2 and 4 displayed significant antibacterial activities against Staphylococcus aureus and methicillin-resistant S. aureus with MIC values of 3.125, 6.25 and 6.25 μg/mL, respectively.

Convenient Route to Di- and Triorganosilyl Ethyl Ethers and the Corresponding Di- and Triorganosilanes

DTIC Science & Technology

1993-11-22

example R2 R’SiH. Early reports indicated that formation of R3SiCI or R2SiCI 2 compounds by the addition of organolithium or Grignard reagents to...corresponding Grignard reagents are far less effective for the substiution reactions. 7 3 Table I. Conversion of (CH3 CH20) 4Si to Organosilyl Ethyl Ethers (X...ABSTRACT (Maximum 200 words) Tetraethoxysilane was treated with alkyl- and aryllithium reagents for the preparation of organosilyl ethyl ethers of the

HIGH LEVELS OF MONOAROMATIC COMPOUNDS LIMIT THE USE OF SOLID-PHASE MICROEXTRACTION OF METHYL TERTIARY BUTYL ETHER AND TERTIARY BUTYL ALCOHOL

EPA Science Inventory

Recently, two papers reported the use of solid-phase microextraction (SPME) with polydimethylsiloxane(PDMS)/Carboxen fibers to determine trace levels of methyl tertiary butyl ether (MTBE) and tertiary butyl alcohol (tBA) in water. Attempts were made to apply this technique to th...

High-Performance Synthetic Fibers for Composites

DTIC Science & Technology

1992-04-01

under evaluation today include polyether ether ketone , polyamide, 23 polyamideimide, polyimide, polysulfone, and polyphenylene sulfide. Epoxy resins...shrinkage under intense neutron radiation . This attribute, together with other properties of high-temperature strength, toughness, and low nuclear...and (2) liquid or solid resins cross-linked with other esters in chopped-fiber and mineral-filled molding compounds. Polyether ether ketone (PEEK) A

Partition coefficients of some purine derivatives and its application to pharmacokinetics.

PubMed

Chrzanowska, M; Sobiak, J; Kuehn, M; Dorawa, E; Hermann, T

2009-12-01

Metazathioprine (MAZA), a methylated derivative of azathioprine (AZA), demonstrated the greatest values of apparent and specific partition coefficients in n-octanol/phosphate buffer at pH 5.7 and pH 7.4 among purine derivatives such as 6-mercaptopurine (6-MP), 6-thioguanine (6-TG) and AZA. Introduction of a methyl group into the imidazole ring of AZA increases lipophilic properties of MAZA compared to AZA. Mass balance of purine derivatives in n-octanol and in phosphate buffer indicated their chemical stability in those media.

Evaluation of a gas chromatography method for azelaic acid determination in selected biological samples

PubMed Central

Garelnabi, Mahdi; Litvinov, Dmitry; Parthasarathy, Sampath

2010-01-01

Background: Azelaic acid (AzA) is the best known dicarboxilic acid to have pharmaceutical benefits and clinical applications and also to be associated with some diseases pathophysiology. Materials and Methods: We extracted and methylesterified AzA and determined its concentration in human plasma obtained from healthy individuals and also in mice fed AzA containing diet for three months. Results: AzA was detected in Gas Chromatography (GC) and confirmed by Liquid chromatography mass spectrometry (LCMS), and gas chromatography mass spectrometry (GCMC). Our results have shown that AzA can be determined efficiently in selected biological samples by GC method with 1nM limit of detection (LoD) and the limit of quantification (LoQ); was established at 50nM. Analytical Sensitivity as assayed by hexane demonstrated an analytical sensitivity at 0.050nM. The method has demonstrated 8-10% CV batch repeatability across the sample types and 13-18.9% CV for the Within-Lab Precision analysis. The method has shown that AzA can efficiently be recovered from various sample preparation including liver tissue homogenate (95%) and human plasma (97%). Conclusions: Because of its simplicity and lower limit of quantification, the present method provides a useful tool for determining AzA in various biological sample preparations. PMID:22558586

Evaluation of a gas chromatography method for azelaic acid determination in selected biological samples.

PubMed

Garelnabi, Mahdi; Litvinov, Dmitry; Parthasarathy, Sampath

2010-09-01

Azelaic acid (AzA) is the best known dicarboxilic acid to have pharmaceutical benefits and clinical applications and also to be associated with some diseases pathophysiology. We extracted and methylesterified AzA and determined its concentration in human plasma obtained from healthy individuals and also in mice fed AzA containing diet for three months. AzA was detected in Gas Chromatography (GC) and confirmed by Liquid chromatography mass spectrometry (LCMS), and gas chromatography mass spectrometry (GCMC). Our results have shown that AzA can be determined efficiently in selected biological samples by GC method with 1nM limit of detection (LoD) and the limit of quantification (LoQ); was established at 50nM. Analytical Sensitivity as assayed by hexane demonstrated an analytical sensitivity at 0.050nM. The method has demonstrated 8-10% CV batch repeatability across the sample types and 13-18.9% CV for the Within-Lab Precision analysis. The method has shown that AzA can efficiently be recovered from various sample preparation including liver tissue homogenate (95%) and human plasma (97%). Because of its simplicity and lower limit of quantification, the present method provides a useful tool for determining AzA in various biological sample preparations.

Azathioprine-induced Acute Pancreatitis in Patients with Inflammatory Bowel Diseases—A Prospective Study on Incidence and Severity

PubMed Central

Mohl, Wolfgang; Bokemeyer, Bernd; Bündgens, Burkhard; Büning, Jürgen; Miehlke, Stephan; Hüppe, Dietrich; Maaser, Christian; Klugmann, Tobias; Kruis, Wolfgang; Siegmund, Britta; Helwig, Ulf; Weismüller, Joseph; Drabik, Attyla; Stallmach, Andreas

2016-01-01

Background and Aims: Azathioprine [AZA] is recommended for maintenance of steroid-free remission in inflammatory bowel disease IBD. The aim of this study has been to establish the incidence and severity of AZA-induced pancreatitis, an idiosyncratic and major side effect, and to identify specific risk factors. Methods: We studied 510 IBD patients [338 Crohn’s disease, 157 ulcerative colitis, 15 indeterminate colitis] with initiation of AZA treatment in a prospective multicentre registry study. Acute pancreatitis was diagnosed in accordance with international guidelines. Results: AZA was continued by 324 [63.5%] and stopped by 186 [36.5%] patients. The most common cause of discontinuation was nausea [12.2%]. AZA-induced pancreatitis occurred in 37 patients [7.3%]. Of these: 43% were hospitalised with a median inpatient time period of 5 days; 10% had peripancreatic fluid collections; 24% had vomiting; and 14% had fever. No patient had to undergo nonsurgical or surgical interventions. Smoking was the strongest risk factor for AZA-induced acute pancreatitis [p < 0.0002] in univariate and multivariate analyses. Conclusions: AZA-induced acute pancreatitis is a common adverse event in IBD patients, but in this study had a mild course in all patients. Smoking is the most important risk factor. PMID:26468141

Outcome of High-Risk Myelodysplastic Syndrome After Azacitidine Treatment Failure

PubMed Central

Prébet, Thomas; Gore, Steven D.; Esterni, Benjamin; Gardin, Claude; Itzykson, Raphael; Thepot, Sylvain; Dreyfus, François; Rauzy, Odile Beyne; Recher, Christian; Adès, Lionel; Quesnel, Bruno; Beach, C.L.; Fenaux, Pierre; Vey, Norbert

2011-01-01

Purpose Azacitidine (AZA) is the current standard of care for high-risk (ie, International Prognostic Scoring System high or intermediate 2) myelodysplastic syndrome (MDS), but most patients will experience primary or secondary treatment failure. The outcome of these patients has not yet been described. Patients and Methods Overall, 435 patients with high-risk MDS and former refractory anemia with excess blasts in transformation (RAEB-T) were evaluated for outcome after AZA failure. The cohort of patients included four data sets (ie, AZA001, J9950, and J0443 trials and the French compassionate use program). Results The median follow-up after AZA failure was 15 months. The median overall survival was 5.6 months, and the 2-year survival probability was 15%. Increasing age, male sex, high-risk cytogenetics, higher bone marrow blast count, and the absence of prior hematologic response to AZA were associated with significantly worse survival in multivariate analysis. Data on treatment administered after AZA failure were available for 270 patients. Allogeneic stem-cell transplantation and investigational agents were associated with a better outcome when compared with conventional clinical care. Conclusion Outcome after AZA failure is poor. Our results should serve as a basis for designing second-line clinical trials in this population. PMID:21788559

Synthetic versatility of 2-substituted-6-methyl 2,3-dihydropyridinones in the synthesis of polyfunctional piperidine-based compounds and related β amino acid derivatives.

PubMed

Yang, Yang; Hardman, Clayton

2017-10-18

Chiral 2-substituted-6-methyl 2,3-dihydropyidinones 9, which can be facilely obtained from an asymmetric vinylogous Mannich reaction (VMR) with 1,3-bis-trimethysily enol ether, were used as versatile intermediates in constructing chiral polyfunctional piperidine-based compounds. The 6-methyl group of such compounds can be conveniently functionalized via alkylation and acylation reactions to provide efficient entries to the synthesis of a variety of chiral multi-substituted piperidine-based compounds. Further elaboration of the corresponding intermediates also provided access to polyfunctional indolizidine-based compounds. These methods were showcased in an asymmetric synthesis of 2,6-di-substituted piperidine compound 13, reported as the key intermediate in the synthesis of (+)-calvine and a natural alkaloid (-)-indolizidine 209D. Furthermore, selective C5 iodination of compound 9 enabled the installation of additional functional groups at this position. Finally, we demonstrated that the oxidative cleavage of 2-substituted-6-methyl-2,3-dihydropyidinones is a practical and efficient method for the enantioselective synthesis of β-amino acids, which can undergo further intra-molecular cyclization to give the corresponding chiral four-membered β-lactam derivatives.

Perianal disease, small bowel disease, smoking, prior steroid or early azathioprine/biological therapy are predictors of disease behavior change in patients with Crohn's disease.

PubMed

Lakatos, Peter Laszlo; Czegledi, Zsofia; Szamosi, Tamas; Banai, Janos; David, Gyula; Zsigmond, Ferenc; Pandur, Tunde; Erdelyi, Zsuzsanna; Gemela, Orsolya; Papp, Janos; Lakatos, Laszlo

2009-07-28

To assess the combined effect of disease phenotype, smoking and medical therapy [steroid, azathioprine (AZA), AZA/biological therapy] on the probability of disease behavior change in a Caucasian cohort of patients with Crohn's disease (CD). Three hundred and forty well-characterized, unrelated, consecutive CD patients were analyzed (M/F: 155/185, duration: 9.4 +/- 7.5 years) with a complete clinical follow-up. Medical records including disease phenotype according to the Montreal classification, extraintestinal manifestations, use of medications and surgical events were analyzed retrospectively. Patients were interviewed on their smoking habits at the time of diagnosis and during the regular follow-up visits. A change in disease behavior was observed in 30.8% of patients with an initially non-stricturing, non-penetrating disease behavior after a mean disease duration of 9.0 +/- 7.2 years. In a logistic regression analysis corrected for disease duration, perianal disease, smoking, steroid use, early AZA or AZA/biological therapy use were independent predictors of disease behavior change. In a subsequent Kaplan-Meier survival analysis and a proportional Cox regression analysis, disease location (P = 0.001), presence of perianal disease (P < 0.001), prior steroid use (P = 0.006), early AZA (P = 0.005) or AZA/biological therapy (P = 0.002), or smoking (P = 0.032) were independent predictors of disease behavior change. Our data suggest that perianal disease, small bowel disease, smoking, prior steroid use, early AZA or AZA/biological therapy are all predictors of disease behavior change in CD patients.

Toxicokinetics of ethers used as fuel oxygenates.

PubMed

Dekant, W; Bernauer, U; Rosner, E; Amberg, A

2001-10-15

The toxicokinetics and biotransformation of methyl-tert.butyl ether (MTBE), ethyl-tert.butyl ether (ETBE) and tert.amyl-methyl ether (TAME) in rats and humans are summarized. These ethers are used as gasoline additives in large amounts, and thus, a considerable potential for human exposure exists. After inhalation exposure MTBE, ETBE and TAME are rapidly taken up by both rats and humans; after termination of exposure, clearance by exhalation and biotransformation to urinary metabolites is rapid in rats. In humans, clearance by exhalation is slower in comparison to rats. Biotransformation of MTBE and ETBE is both qualitatively and quantitatively similar in humans and rats after inhalation exposure under identical conditions. The extent of biotransformation of TAME is also quantitatively similar in rats and humans; the metabolic pathways, however, are different. The results suggest that reactive and potentially toxic metabolites are not formed during biotransformation of these ethers and that toxic effects of these compounds initiated by covalent binding to cellular macromolecules are unlikely.

Comparison of interferon beta products and azathioprine in the treatment of relapsing-remitting multiple sclerosis.

PubMed

Etemadifar, M; Janghorbani, M; Shaygannejad, V

2007-12-01

We compared the relative efficacy of interferon beta (IFNbeta) products and azathioprine (AZA) in the treatment of relapsing- remitting multiple sclerosis (RRMS). Ninety-four previously untreated patients of short duration with RRMS were randomly allocated to the two treatment groups. The first group received IFNbeta products (Betaferon,Avonex or Rebif); the second group received AZA for 12 months. Response to treatment was assessed at 3, 6, and 12 months after starting therapy. The mean number of relapse during one year of the study was lower in the AZA group than in the IFNbeta products group (0.28 vs. 0.64, P < 0.05). After 12 months, 57.4% of patients receiving IFNbeta products remained relapse free compared with 76.6% of those given AZA. The Expanded Disability Status Scale (EDSS) decreased by 0.30 units in IFNbeta-treated patients (P < 0.05) and 0.46 in AZAtreated patients (P < 0.001). Treatment with IFNbeta products and AZA significantly reduces the relapse rate and EDSS score in patients with RRMS, while AZA is more effective than the IFNbeta formulations.

Contact allergy to reactive diluents and related aliphatic epoxy resins.

PubMed

Aalto-Korte, Kristiina; Kuuliala, Outi; Henriks-Eckerman, Maj-Len; Suuronen, Katri

2015-06-01

Diglycidyl ether of bisphenol A resin (DGEBA-R) is the most common sensitizer in epoxy systems, but a minority of patients also develop contact allergy to reactive diluents. To analyse the frequency and clinical relevance of allergic reactions to different epoxy reactive diluents and related aliphatic epoxy resins. Test files (January 1991 to June 2014) were screened, and the clinical records of patients with allergic reactions were analysed for occupation, concomitant allergic reactions, and exposure. A total of 67 patients reacted to at least one of the compounds. The largest numbers of allergic reactions were to phenyl glycidyl ether (PGE; n = 41), 1,4-butanediol diglycidyl ether (BDDGE; n = 34), and p-tert-butylphenyl glycidyl ether (PTBPGE; n = 19). Ten of the patients did not have contact allergy to DGEBA-R. The reactions of 5 of these were related to the use of BDDGE-containing products. We found no significant exposure to PGE or PTBPGE in patients sensitized to them, but some of the patients had used cresyl glycidyl ether-containing products. Allergic reactions to reactive diluents and related aliphatic epoxy resins usually occurred together with reactions to DGEBA-R. BDDGE was the clinically most significant compound, and was the sole cause of occupational allergic contact dermatitis in 3 patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Crown ethers in graphene

DOE PAGES

Guo, Junjie; Lee, Jaekwang; Contescu, Cristian I.; ...

2014-11-13

Crown ethers, introduced by Pedersen1, are at their most basic level neutral rings constructed of oxygen atoms linked by two- or three-carbon chains. They have attracted special attention for their ability to selectively incorporate various atoms2 or molecules within the cavity formed by the ring3-6. This property has led to the use of crown ethers and their compounds in a wide range of chemical and biological applications7,8. However, crown ethers are typically highly flexible, frustrating efforts to rigidify them for many uses that demand higher binding affinity and selectivity9,10. In this Letter, we report atomic-resolution images of the same basicmore » structures of the original crown ethers embedded in graphene. This arrangement constrains the crown ethers to be rigid and planar and thus uniquely suited for the many applications that crown ethers are known for. First-principles calculations show that the close similarity of the structures seen in graphene with those of crown ether molecules also extends to their selectivity towards specific metal cations depending on the ring size. Atoms (or molecules) incorporated within the crown ethers in graphene offer a simple environment that can be easily and systematically probed and modeled. Thus, we expect that this discovery will introduce a new wave of investigations and applications of chemically functionalized graphene.« less

Crown Ether Complexes of Alkali-Metal Chlorides from SO2.

PubMed

Reuter, Kirsten; Rudel, Stefan S; Buchner, Magnus R; Kraus, Florian; von Hänisch, Carsten

2017-07-18

The structures of alkali-metal chloride SO 2 solvates (Li-Cs) in conjunction with 12-crown-4 or 1,2-disila-12-crown-4 show strong discrepancies, despite the structural similarity of the ligands. Both types of crown ethers form 1:1 complexes with LiCl to give [Li(1,2-disila-12-crown-4)(SO 2 Cl)] (1) and [Li(12-crown-4)Cl]⋅4 SO 2 (2). However, 1,2-disila-12-crown-4 proved unable to coordinate cations too large for the cavity diameter, for example, by the formation of sandwich-type complexes. As a result, 12-crown-4 reacts exclusively with the heavier alkali-metal chlorides NaCl, KCl and RbCl. Compounds [Na(12-crown-4) 2 ]Cl⋅4 SO 2 (3) and [M(12-crown-4) 2 (SO 2 )]Cl⋅4 SO 2 (4: M=K; 5: M=Rb) all showed S-coordination to the chloride ions through four SO 2 molecules. Compounds 4 and 5 additionally exhibit the first crystallographically confirmed non-bridging O,O'-coordination mode of SO 2 . Unexpectedly, the disila-crown ether supports the dissolution of RbCl and CsCl in the solvent and gives the homoleptic SO 2 -solvated alkali-metal chlorides [MCl⋅3 SO 2 ] (6: M=Rb; 7: M=Cs), which incorporate bridging μ-O,O'-coordinating moieties and the unprecedented side-on O,O'-coordination mode. All compounds were characterised by single-crystal X-ray diffraction. The crown ether complexes were additionally studied by using NMR spectroscopy, and the presence of SO 2 at ambient temperature was revealed by IR spectroscopy of the neat compounds. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A comparative study on cytogenetic and antineoplastic effects induced by two modified steroidal alkylating agents.

PubMed

Papageorgiou, A; Tsavdaridis, D; Geromichalos, G D; Camoutsis, C; Karaberis, E; Mourelatos, D; Chrysogelou, E; Houvartas, S; Kotsis, A

2001-01-01

We investigated the effects of two newly synthesized steroidal derivatives of nitrogen mustard on sister chromatid exchange rates and on human lymphocyte proliferation kinetics. The compound 33-hydroxy-5alpha,22alpha-spirostan- 12-one-p-(N,N-bis(2-chloroethyl)amino)phenylacetate(1) was, on a molar basis, less effective in inducing sister chromatid exchange and suppressing cell proliferation rate indices than compound 3beta-hydroxy-12alpha-aza-C-homo-5alpha,22alpha-spirostan-12-one-p-(N,N-bis(2-chloroethyl)amino)phenylacetate(2). A correlation was observed between the magnitude of the sister chromatid exchange response and the depression of cell proliferation index. We also studied the effects of the aforementioned compounds on Lewis lung carcinoma. The order of the percent inhibition of tumor growth achieved by the compounds coincides with the order of the cytogenetic effects they induce.

Effect of ultraviolet light absorbers on photostabilization of azadirachtin-A in solution (part: II).

PubMed

Deota, P T; Upadhyay, P R; Valodkar, V B

2003-01-01

The effect of photostabilization of azadirachtin-A (Aza-A) was examined in solutions when exposed to UV radiation, in the presence of four structurally different UV absorbers namely, p-aminobenzoic acid, 2,4-dihydroxybenzophenone, 4,4'-dihydroxybenzophenone and phenyl salicylate. The percentages of Aza-A recovered from the solutions after 6 h exposed to UV radiation in the presence and absence of UV absorbers indicated that the order of stabilization of Aza-A by these absorbers was similar to that obtained in the solid phase experiments in accordance with our previous observations. It is observed that the addition of phenyl salicylate in Aza-A (in 1:1 mole ratio) provides the excellent photostabilization of Aza-A molecule in solid phase as well as in solution among the four absorbers studied.

Impact of a heteroatom in a structure-activity relationship study on analogues of phenyl glycidyl ether (PGE) from epoxy resin systems.

PubMed

Niklasson, Ida B; Delaine, Tamara; Luthman, Kristina; Karlberg, Ann-Therese

2011-04-18

Epoxy resins are among the most common causes of occupational contact dermatitis. They are normally used in so-called epoxy resin systems (ERS). These commercial products are combinations of epoxy resins, curing agents, modifiers, and reactive diluents. The most frequently used resins are diglycidyl ethers based on bisphenol A (DGEBA) and bisphenol F (DGEBF). In this study, we have investigated the contact allergenic properties of a series of analogues to the reactive diluent phenyl glycidyl ether (PGE), all with similar basic structures but with varying heteroatoms or with no heteroatom present. The chemical reactivity of the compounds in the test series toward the hexapeptide H-Pro-His-Cys-Lys-Arg-Met-OH was investigated. All epoxides were shown to bind covalently to both cysteine and proline residues. The percent depletion of nonreacted peptide was also studied resulting in ca. 60% depletion when using either PGE, phenyl 2,3-epoxypropyl sulfide (2), or N-(2,3-epoxypropyl)aniline (3), and only 15% when using 1,2-epoxy-4-phenylbutane (4) at the same time point. The skin sensitization potencies of the epoxides using the murine local lymph node assay (LLNA) were evaluated in relation to the observed physicochemical and reactivity properties. To enable determination of statistical significance between structurally closely related compounds, a nonpooled LLNA was performed. It was found that all investigated compounds containing a heteroatom in the α-position to the epoxide were strong sensitizers, congruent with the reactivity data, indicating that the impact of a heteroatom is crucial for the sensitizing capacity for this type of epoxides.

DNA-hypomethylating agent, 5'-azacytidine, induces cyclooxygenase-2 expression via the PI3-kinase/Akt and extracellular signal-regulated kinase-1/2 pathways in human HT1080 fibrosarcoma cells.

PubMed

Yu, Seon-Mi; Kim, Song-Ja

2015-10-01

The cytosine analogue 5'-azacytidine (5'-aza) induces DNA hypomethylation by inhibiting DNA methyltransferase. In clinical trials, 5'-aza is widely used in epigenetic anticancer treatments. Accumulated evidence shows that cyclooxygenase-2 (COX-2) is overexpressed in various cancers, indicating that it may play a critical role in carcinogenesis. However, few studies have been performed to explore the molecular mechanism underlying the increased COX-2 expression. Therefore, we tested the hypothesis that 5'-aza regulates COX-2 expression and prostaglandin E2 (PGE2) production. The human fibrosarcoma cell line HT1080, was treated with various concentrations of 5'-aza for different time periods. Protein expressions of COX-2, DNA (cytosine-5)-methyltransferase 1 (DNMT1), pAkt, Akt, extracellular signal-regulated kinase (ERK), and phosphorylated ERK (pERK) were determined using western blot analysis, and COX-2 mRNA expression was determined using RT-PCR. PGE2 production was evaluated using the PGE2 assay kit. The localization and expression of COX-2 were determined using immunofluorescence staining. Treatment with 5'-aza induces protein and mRNA expression of COX-2. We also observed that 5'-aza-induced COX-2 expression and PGE2 production were inhibited by S-adenosylmethionine (SAM), a methyl donor. Treatment with 5'-aza phosphorylates PI3-kinase/Akt and ERK-1/2; inhibition of these pathways by LY294002, an inhibitor of PI3-kinase/Akt, or PD98059, an inhibitor of ERK-1/2, respectively, prevents 5'-aza-induced COX-2 expression and PGE2 production. Overall, these observations indicate that the hypomethylating agent 5'-aza modulates COX-2 expression via the PI3-kinase/Akt and ERK-1/2 pathways in human HT1080 fibrosarcoma cells.

Enantioselective organocatalytic one-pot amination/aza-Michael/aldol condensation reaction sequence: synthesis of 3-pyrrolines with a quaternary stereocenter.

PubMed

Desmarchelier, Alaric; Coeffard, Vincent; Moreau, Xavier; Greck, Christine

2012-10-08

Primary amine-catalyzed direct conversion of α,α-disubstituted aldehydes into 3-pyrrolines with a quaternary stereocenter is reported. The one-pot enantioselective sequence is based on a α-amination, an aza-Michael addition of hydrazine, an aldol condensation dehydratation and proceeds with good yields and excellent levels of enantioselectivity. Synthetically attractive applications including the formation of aziridinopyrrolidine or epoxypyrrolidine derivatives with good yields and selectivities are also described. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Oxidative cleavage of non-phenolic β-O-4 lignin model dimers by an extracellular aromatic peroxygenase

Treesearch

Matthias Kinne; Marzena Poraj-Kobielska; Rene Ullrich; Paula Nousiainen; Jussi Sipilä; Katrin Scheibner; Kenneth E. Hammel; Martin Hofrichter

2011-01-01

The extracellular aromatic peroxygenase of the agaric fungus Agrocybe aegerita catalyzed the H2O2-dependent cleavage of non-phenolic arylgiycerol-ß-aryl ethers (ß-O-4 ethers). For instance 1-(3,4-dimethoxyphenyl)-2-(2-methoxy-phenoxy)propane-1,3-diol, a recalcitrant dimeric lignin model compound that represents the major...

Metabolism of dibenzo-p-dioxin by Sphingomonas sp. strain RW1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wittich, R.M.; Wilkes, H.; Sinnwell, V.

In the course of screening for dibenzo-p-dioxin-utilizing bacteria, a Sphingomonas sp. strain was isolated from enrichment cultures inoculated with water samples from the river Elbe. The isolate grew with both the biaryl ethers dibenzo-p-dioxin and dibenzofuran (DF) as the sole sources of carbon and energy, showing doubling times of about 8 and 5 h, respectively. Biodegradation of the two aromatic compounds initially proceeded after an oxygenolytic attack at the angular position adjacent to the ether bridge, producing 2,2{prime},3-trihydroxydiphenyl ether or 2,2{prime},3-trihydroxybiphenyl from the initially formed dihydrodiols, which represent extremely unstable hemiacetals. Results obtained from determinations of enzyme activities and oxygenmore » consumption suggest meta cleavage of the trihydroxy compounds. During dibenzofuran degradation, hydrolysis of 2-hydroxy-6-oxo-6-(2-hydroxyphenyl)-hexa-2,4-dienoate yielded salicylate, which was branched into the catechol meta cleavage pathway and the gentisate pathway. Catechol obtained from the product of meta ring fission of 2,2{prime},3-trihydroxydiphenyl ether was both ortho and meta cleaved by Sphingomonas sp. strain RW1 when this organism was grown with dibenzo-p-dioxin.« less

[Effects of 5-aza-2-deoxycytidine on methylation status of RECK gene and cancer cell invasion in tongue cancer SCC-4 cells].

PubMed

Jiang, Xv

2014-10-01

To investigate the effects of 5-aza-2-deoxycytidine on methylation status and invasion ability of RECK gene in tongue cancer SCC-4 cells. Tongue cancer cell line SCC-4 cells were treated with 5-aza-dC at different concentrations for 72 h. Methylation status of RECK gene of SCC-4 cells was detected by methylation specific PCR (MSP), the expression of RECK gene mRNA was detected by real-time quantitative PCR. The expression of RECK protein was detected by Western blot, and the invasion ability of SCC-4 cell was examined by Transwell assay. SPSS13.0 software package was used for statistical analysis. RECK gene of SCC-4 cells was in high methylation status in untreated group, abnormal methylation was effectively reversed by 5-aza-dC treatment. After treatment with different concentration of 5-aza-dC for 72 h, relative mRNA expression level increased gradually (P<0.05). The relative expression level of RECK protein in 5-aza-dC treated group was significantly higher than that in the control group,the invasion ability of SCC-4 cell was decreased gradually. 5-aza-dC treatment for tongue cancer SCC-4 cells can successfully reverse high methylation status of RECK gene and restore the expression of RECK gene mRNA and protein, and reduced the invasion ability.

Polarity dependent photoisomerization of ether substituted azodyes: Synthesis and photoswitching behavior.

PubMed

Gan, Siew Mei; Pearl, Zynia Fernandes; Yuvaraj, A R; Lutfor, M R; Gurumurthy, Hegde

2015-10-05

Two new ether substituted azodyes were synthesized and characterized by different spectral analysis such as (1)H NMR, (13)C NMR, FTIR and UV/Vis. Synthesized compounds were used to study the photoisomerization phenomenon by using UV-Vis spectro-photometer. Interesting polarity dependent effect is observed for the first time on these materials. Trans-cis (E-Z) and cis-trans (Z-E) conversion occurred within 41 s and 445 min, respectively for both the compounds in solutions. Polarizing optical microscopy studies revealed that there is no liquid crystal phase for both the compounds. The dramatic variation in the optical property is speculated to be the polarity of the chemical species. These derivatives are useful to fabricate optical data storage devices. Copyright © 2015 Elsevier B.V. All rights reserved.

Radiation polymerisable compositions containing 3-sorboyloxy-2-hydroxypropyl groups

DOE Office of Scientific and Technical Information (OSTI.GOV)

Green, G.E.

1976-02-03

Compounds having at least three 3-sorboyloxy-2-hydroxypropyl groups directly attached to ether oxygen atoms are polymerised by exposure to actinic radiation, preferably in the presence of a sensitizer such as Michler's ketone or benzoin. The compounds may be obtained by the reaction either of sorbic acid with a substance having at least three glycidyl ether groups or of glycidyl sorbate with a substance having at least three phenolic or alcoholic hydroxyl groups: if desired, not all of the glycidyl groups may be consumed, so that, after actinically induced polymerisation, the epoxide-containing polymer may be cross-linked by reaction with a curing agentmore » for epoxide resins. The compounds are useful in making printed circuits or printing plates for offset printing.« less

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.

Synthesis and biological evaluation of arctigenin ester and ether derivatives as activators of AMPK.

PubMed

Shen, Sida; Zhuang, Jingjing; Chen, Yijia; Lei, Min; Chen, Jing; Shen, Xu; Hu, Lihong

2013-07-01

A series of new arctigenin and 9-deoxy-arctigenin derivatives bearing different ester and ether side chains at the phenolic hydroxyl positions are designed, synthesized, and evaluated for activating AMPK potency in L6 myoblasts. Initial biological evaluation indicates that some alkyl ester and phenethyl ether arctigenin derivatives display potential activities in AMPK phosphorylation improvement. Further structure-activity relationship analysis shows that arctigenin ester derivatives 3a, 3h and 9-deoxy-arctigenin phenethyl ether derivatives 6a, 6c, 6d activate AMPK more potently than arctigenin. Moreover, the 2-(3,4-dimethoxyphenyl)ethyl ether moiety of 6c has been demonstrated as a potential functional group to improve the effect of AMPK phosphorylation. The structural optimization of arctigenin leads to the identification of 6c as a promising lead compound that exhibits excellent activity in AMPK activation. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Research in Energetic Compounds.

DTIC Science & Technology

1980-03-01

SECURITY CLASSIFICATION OF THIS PAGE(When Data Entered) ,2 ABSTRACT (cont’d.) chloroperbenzoic acid gave 3-nitrooxetane. Fluoronitromalonate esters were...tetrahydropyranyl ethers. Base hydrolysis of the ester groups followed by acid hydrolysis of the tetrahydropyranyl groups gave 2-fluo- ro-2-nitroethanol...of 3-allyloxyoxetane.3 Treatment of allyl alcohol with 0.25 equivalunt of t-butyl h-pochlorite and a catalytic amount of p-toluenesulfonic acid was

Acute Neurobehavorial Toxicity of Flame Retardant Replacement Compounds in Zebrafish Larvae

EPA Science Inventory

As polybrominated diphenyl ethers (PBDEs) are phased out, numerous compounds areemerging as potential replacement flame retardants for use in consumer and electronicproducts. Little is known, however, about the neurobehavioral toxicity of thesereplacements. This study evaluated t...

Gas Phase Ion-Molecule Chemistry of Carbon, Nitrogen and Oxygen Compounds.

DTIC Science & Technology

1985-01-29

silyl anions aza allyl anion) phosphide anion sulfides) Reactivity; nitrite estersj electron affinityMechanism’, sulfur dioxidej. (cont’d) M L..J A6*rAcr...use of silane chemistry to attack a problem of fundamental importance to all organic chemistry, the relative acidity of the alkanes.20 While it is well...alkane lost are a measure of the relative acidity of RH. For example, because ethane is lost less easily than methane, we believe that the ethyl anion

Calculation of the physicochemical properties of thienopyridines by the Pariser-Parr-Pople (PPP) method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vysotskii, Yu.B.; Zemskaya, E.A.; Zemskii, B.P.

1987-10-01

The dipole moments, diamagnetic susceptibilities, chemical shifts of the /sup 1/H, /sup 13/C, and /sup 14/N nuclei, and the energies of the lowest singlet-singlet transitions of aza-substituted thiophenes and benzo(b)thiophenes were calculated within the framework of the bonded variant of perturbation theory by the Pariser-Parr-Pople (PPP) method. A scale of aromatic character of the investigated class of compounds is given on the basis of the current distributions found.

Cesium cation templated selective synthesis of a "cone-shaped" sugar macrotricyclic cryptand: A dual anion-cation molecular recognition of potassium tartrate.

PubMed

Porwanski, S; Moretti, F; Dumarcay-Charbonnier, F; Marsura, A

2016-05-01

Cesium templated Staudinger-aza-Wittig tandem reaction (S.A.W.) has been used in the synthesis of a bis-diazacrown-bis-cellobiosyl-tetra-ureido cryptand. A novel macrotricyclic compound having a "cone-shaped" configuration was selectively obtained. Additionally, first results on potential recognition properties of the cryptand are also given. Copyright © 2015 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

Characterization and relevance of physicochemical interactions among components of a novel multiparticulate formulation for colonic delivery.

PubMed

Singh, Brahma N; Kim, Kwon H

2007-08-16

The primary objective of this study was to investigate potential interactions among a model drug (azathioprine; AZA), polymers and a divalent metal ion, which were utilized in the development of a novel multiparticulate formulation for colonic delivery. The approach involved preparation of beads by ionotropic gelation of deacylated gellan gum (DGG) in the presence of Ca(2+) ions, followed by coating with Eudragit S-100. Various possible physicochemical interactions among formulation components were characterized by DSC, FT-IR, XRPD, (1)H-NMR, and an isothermal stress test. Results of isothermal stress testing indicated that there was no significant interaction of AZA with DGG and Eudragit S-100. However, results of DSC and XRPD studies suggested that there could be interactions between AZA and DGG, and ionotropic gelation can affect the physical state of AZA, which may have implications for drug release characteristics and, physical and chemical stability. The results of FT-IR studies were suggestive of interactions of DGG with AZA and Eudragit S-100, and provided evidence for interactions of AZA and DGG with Ca(2+) ions. The electrostatic interaction of DGG with Ca(2+) was also supported by results of DSC studies while that between AZA and Ca(2+) was confirmed by (1)H-NMR studies. This study, to our knowledge, is first reported investigation in which the unique thermal property of gellan gum gels, and possible interactions between a drug and counter ions of an ionotropic agent have been demonstrated through bead characterization studies. The formation of AZA-Ca(2+) complex could have an impact on drug release kinetics, product stability and clinical efficacy for treatment of inflammatory bowel diseases or other diseases, which merit further investigation.

A new member of the 4-methylideneimidazole-5-one–containing aminomutase family from the enediyne kedarcidin biosynthetic pathway

PubMed Central

Huang, Sheng-Xiong; Lohman, Jeremy R.; Huang, Tingting; Shen, Ben

2013-01-01

4-Methylideneimidazole-5-one (MIO)-containing aminomutases catalyze the conversion of l-α-amino acids to β-amino acids with either an (R) or an (S) configuration. l-Phenylalanine and l-tyrosine are the only two natural substrates identified to date. The enediyne chromophore of the chromoprotein antitumor antibiotic kedarcidin (KED) harbors an (R)-2-aza-3-chloro-β-tyrosine moiety reminiscent of the (S)-3-chloro-5-hydroxy-β-tyrosine moiety of the C-1027 enediyne chromophore, the biosynthesis of which uncovered the first known MIO-containing aminomutase, SgcC4. Comparative analysis of the KED and C-1027 biosynthetic gene clusters inspired the proposal for (R)-2-aza-3-chloro-β-tyrosine biosynthesis starting from 2-aza-l-tyrosine, featuring KedY4 as a putative MIO-containing aminomutase. Here we report the biochemical characterization of KedY4, confirming its proposed role in KED biosynthesis. KedY4 is an MIO-containing aminomutase that stereospecifically catalyzes the conversion of 2-aza-l-tyrosine to (R)-2-aza-β-tyrosine, exhibiting no detectable activity toward 2-aza-l-phenylalanine or l-tyrosine as an alternative substrate. In contrast, SgcC4, which stereospecifically catalyzes the conversion of l-tyrosine to (S)-β-tyrosine in C-1027 biosynthesis, exhibits minimal activity with 2-aza-l-tyrosine as an alternative substrate but generating (S)-2-aza-β-tyrosine, a product with the opposite stereochemistry of KedY4. This report of KedY4 broadens the scope of known substrates for the MIO-containing aminomutase family, and comparative studies of KedY4 and SgcC4 provide an outstanding opportunity to examine how MIO-containing aminomutases control substrate specificity and product enantioselectivity. PMID:23633564

Folic Acid and Grape Seed Extract Prevent Azathioprine-induced Fetal Malformations and Renal Toxicity in Rats.

PubMed

El-Ashmawy, Ibrahim M; Bayad, Aida E

2016-12-01

Azathioprine (AZA) is an important drug commonly used in the therapy of the autoimmune system disorders. It induces many hazard effects that restrict its use. The present study was designed to investigate the influence of AZA on the fetal development and renal function and its co-administration with either folic acid (FA) or grape seed extract (GSE). The effects of administration of GSE or FA on AZA toxicity by gavage simultaneously for 4 weeks were studied by determining the changes in kidney histology, the glutathione level (GSH), and lipid per oxidation content as malondialdehyde in the kidney tissue. Additionally, their effects on the fetal development were investigated. Azathioprine induced a renal damage as indicated from the pronounced changes in histological structure, a significant increase in serum urea and creatinine, and malondialdehyde content in the kidney tissue. Meanwhile, the GSH activity was significantly decreased. Co-treatment with GSE significantly minimized the previously mentioned hazard effects of AZA by ameliorating the antioxidant activity. At this point, FA induced a nonsignificant protective activity. The results also revealed that administration of FA or GSE at 6th to 15th day of gestation did not altered fetal development. While, AZA administration clearly disturbed fetal development as indicated from a significant decrease in fetal weights. Furthermore, co-administration of both drugs significantly minimized similarly the hazards of AZA on the fetal development. It may be concluded that GSE and FA are a useful remedies. Maternal administrations of either both are protective agents against AZA-induced fetal malformations. Grape seed extract was more active than FA in potentiating the antioxidative defenses for controlling AZA-induced oxidative renal damages. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Gene expression profile of high-fat diet-fed C57BL/6J mice: in search of potential role of azelaic acid.

PubMed

Muthulakshmi, Shanmugam; Chakrabarti, Alok K; Mukherjee, Sanjay

2015-03-01

High-fat diet (HFD) elevates circulatory fatty acids and influences glucose and fat metabolism. Azelaic acid (AzA), a naturally occurring α,ω-dicarboxylic acid in wheat, rye, barley, oat seeds and sorghum, has been reported to exert antidiabetic effects in HFD-induced type 2 diabetes mellitus (T2DM) C57BL/6J mice. The present study was undertaken to identify the genes that are differentially modulated by treatment with AzA in HFD-fed mice. Mice were fed HFD for 10 weeks and subjected to intragastric administration of 80 mg/kg body weight (BW) of AzA daily along with HFD from 11 to 15 weeks. Lipid profile, adipokines and cytokines were examined in the plasma/liver of mice. Whole genome profiling was performed in the liver of mice using microarray and validated by qRT-PCR, Western blot and immunohistochemical analyses. HFD intake resulted in significantly elevated lipids (except high-density lipoproteins), resistin, tumour necrosis factor alpha and interleukin-6 with marked reduction in adiponectin. Administration of AzA to HFD-fed mice significantly restored the lipids, adipokines and cytokines to near normal. Transcript profiling revealed that HFD intake activated the genes involved in stress response, cell cycle regulation and apoptosis. Treatment with AzA caused increased expression of genes involved in reactive oxygen species (ROS) scavenging, receptor-mediated signalling, transcription, protein modification and insulin signal transduction. AzA activates insulin signal molecules leading to insulin sensitivity. The ability of AzA to modulate the expression of these genes supports the notion that AzA is a promising drug candidate for the treatment of insulin resistance associated with T2DM.

Coordinate regulation of microenvironmental stimuli and role of methylation in bone metastasis from breast carcinoma.

PubMed

Matteucci, Emanuela; Maroni, Paola; Disanza, Andrea; Bendinelli, Paola; Desiderio, Maria Alfonsina

2016-01-01

The pathogenesis of bone metastasis is unclear, and much focus in metastatic biology and therapy relays on epigenetic alterations. Since DNA-methyltransferase blockade with 5-aza-2'-deoxycytidine (dAza) counteracts tumour growth, here we utilized dAza to clarify whether molecular events undergoing epigenetic control were critical for bone metastatization. In particular, we investigated the patterns of secreted-protein acidic and rich in cysteine (SPARC) and of Endothelin 1, affected by DNA methyltransferases in tumours, with the hypothesis that in bone metastasis a coordinate function of SPARC and Endothelin 1, if any occurs, was orchestrated by DNA methylation. To this purpose, we prepared a xenograft model with the clone 1833, derived from human-MDA-MB231 cells, and dAza administration slowed-down metastasis outgrowth. This seemed consequent to the reductions of SPARC and Endothelin 1 at invasive front and in the bone marrow, mostly due to loss of Twist. In the metastasis bulk Snail, partly reduced by dAza, might sustain Endothelin 1-SPARC cooperativity. Both SPARC and Endothelin 1 underwent post-translational control by miRNAs, a molecular mechanism that might explain the in vivo data. Ectopic miR29a reduced SPARC expression also under long-term dAza exposure, while Endothelin 1 down-regulation occurred in the presence of endogenous-miR98 expression. Notably, dAza effects differed depending on in vivo and in vitro conditions. In 1833 cells exposed to 30-days dAza, SPARC-protein level was practically unaffected, while Endothelin 1 induction depended on the 3'-UTR functionality. The blockade of methyltransferases leading to SPARC reduction in vivo, might represent a promising strategy to hamper early steps of the metastatic process affecting the osteogenic niche. Copyright © 2015 Elsevier B.V. All rights reserved.

Perianal disease, small bowel disease, smoking, prior steroid or early azathioprine/biological therapy are predictors of disease behavior change in patients with Crohn’s disease

PubMed Central

Lakatos, Peter Laszlo; Czegledi, Zsofia; Szamosi, Tamas; Banai, Janos; David, Gyula; Zsigmond, Ferenc; Pandur, Tunde; Erdelyi, Zsuzsanna; Gemela, Orsolya; Papp, Janos; Lakatos, Laszlo

2009-01-01

AIM: To assess the combined effect of disease phenotype, smoking and medical therapy [steroid, azathioprine (AZA), AZA/biological therapy] on the probability of disease behavior change in a Caucasian cohort of patients with Crohn’s disease (CD). METHODS: Three hundred and forty well-characterized, unrelated, consecutive CD patients were analyzed (M/F: 155/185, duration: 9.4 ± 7.5 years) with a complete clinical follow-up. Medical records including disease phenotype according to the Montreal classification, extraintestinal manifestations, use of medications and surgical events were analyzed retrospectively. Patients were interviewed on their smoking habits at the time of diagnosis and during the regular follow-up visits. RESULTS: A change in disease behavior was observed in 30.8% of patients with an initially non-stricturing, non-penetrating disease behavior after a mean disease duration of 9.0 ± 7.2 years. In a logistic regression analysis corrected for disease duration, perianal disease, smoking, steroid use, early AZA or AZA/biological therapy use were independent predictors of disease behavior change. In a subsequent Kaplan-Meier survival analysis and a proportional Cox regression analysis, disease location (P = 0.001), presence of perianal disease (P < 0.001), prior steroid use (P = 0.006), early AZA (P = 0.005) or AZA/biological therapy (P = 0.002), or smoking (P = 0.032) were independent predictors of disease behavior change. CONCLUSION: Our data suggest that perianal disease, small bowel disease, smoking, prior steroid use, early AZA or AZA/biological therapy are all predictors of disease behavior change in CD patients. PMID:19630105

A new member of the 4-methylideneimidazole-5-one-containing aminomutase family from the enediyne kedarcidin biosynthetic pathway.

PubMed

Huang, Sheng-Xiong; Lohman, Jeremy R; Huang, Tingting; Shen, Ben

2013-05-14

4-Methylideneimidazole-5-one (MIO)-containing aminomutases catalyze the conversion of L-α-amino acids to β-amino acids with either an (R) or an (S) configuration. L-phenylalanine and L-tyrosine are the only two natural substrates identified to date. The enediyne chromophore of the chromoprotein antitumor antibiotic kedarcidin (KED) harbors an (R)-2-aza-3-chloro-β-tyrosine moiety reminiscent of the (S)-3-chloro-5-hydroxy-β-tyrosine moiety of the C-1027 enediyne chromophore, the biosynthesis of which uncovered the first known MIO-containing aminomutase, SgcC4. Comparative analysis of the KED and C-1027 biosynthetic gene clusters inspired the proposal for (R)-2-aza-3-chloro-β-tyrosine biosynthesis starting from 2-aza-L-tyrosine, featuring KedY4 as a putative MIO-containing aminomutase. Here we report the biochemical characterization of KedY4, confirming its proposed role in KED biosynthesis. KedY4 is an MIO-containing aminomutase that stereospecifically catalyzes the conversion of 2-aza-L-tyrosine to (R)-2-aza-β-tyrosine, exhibiting no detectable activity toward 2-aza-L-phenylalanine or L-tyrosine as an alternative substrate. In contrast, SgcC4, which stereospecifically catalyzes the conversion of L-tyrosine to (S)-β-tyrosine in C-1027 biosynthesis, exhibits minimal activity with 2-aza-L-tyrosine as an alternative substrate but generating (S)-2-aza-β-tyrosine, a product with the opposite stereochemistry of KedY4. This report of KedY4 broadens the scope of known substrates for the MIO-containing aminomutase family, and comparative studies of KedY4 and SgcC4 provide an outstanding opportunity to examine how MIO-containing aminomutases control substrate specificity and product enantioselectivity.

Sinopestalotiollides A-D, cytotoxic diphenyl ether derivatives from plant endophytic fungus Pestalotiopsis palmarum.

PubMed

Xiao, Jian; Hu, Jia-Yao; Sun, Hao-Dong; Zhao, Xiang; Zhong, Wan-Tong; Duan, Dong-Zhu; Wang, Le; Wang, Xiao-Ling

2017-11-28

Four new diphenyl ether derivatives, sinopestalotiollides A-D (1-4), one new natural α-pyrone product (11), as well as twelve known compounds (5-1 7), were obtained from the ethyl acetate extract of the endophytic fungus Pestalotiopsis palmarum isolated from the leaves of medicinal plant Sinomenium acutum (Thunb.) Rehd et Wils. The structures were elucidated by HR-ESI-MS and NMR spectrometry data. Bioassay experiments revealed that compounds 1-4 and 11 exhibited strong to weak cytotoxicities against three human tumor cell lines Hela, HCT116 and A549. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis and antiviral activity of certain second generation methylenecyclopropane nucleosides

PubMed Central

Williams, John D.; Khan, Atiyya R.; Harden, Emma A.; Hartline, Caroll B.; Jefferson, Geraldine M.; Keith, Kathy A.; Prichard, Mark N.; Zemlicka, Jiri; Peet, Norton P.; Bowlin, Terry L.

2012-01-01

A second-generation series of substituted methylenecyclopropane nucleosides (MCPNs) has been synthesized and evaluated for antiviral activity against a panel of human herpesviruses, and for cytotoxicity. Although alkylated 2,6-diaminopurine analogs showed little antiviral activity, the compounds containing ether and thioether substituents at the 6-position of the purine did demonstrate potent and selective antiviral activity against several different human herpesviruses. In the 6-alkoxy series, antiviral activity depended on the length of the ether carbon chain, with the optimum chain length being about four carbon units long. For the corresponding thioethers, compounds containing secondary thioethers were more potent than those with primary thioethers. PMID:22607883

Role of the catechol group in the antioxidant and neuroprotective effects of virgin olive oil components in rat brain.

PubMed

De La Cruz, J P; Ruiz-Moreno, M I; Guerrero, A; López-Villodres, J A; Reyes, J J; Espartero, J L; Labajos, M T; González-Correa, J A

2015-05-01

The aim of the present study was to determine the role of the catechol group in the antioxidant and neuroprotective effects of minor components of virgin olive oil in rat brain tissue. Hydroxytyrosol ethyl ether (HT, 2 OH), tyrosol ethyl ether (Ty, 1 OH) and 3,4-di-ortho-methylidene-hydroxytyrosol ethyl ether (MET, no OH) were compared. Oxidative stress was induced with ferrous salts (lipid peroxidation induction), diethylmaleate (depletion of glutathione) and hypoxia-reoxygenation in brain slices. Lipid peroxidation was inhibited in direct proportion to the number of OH groups: HT>Ty>MET. Exposure to HT led to partial recovery of the glutathione system after chemical inhibition or hypoxia-reoxygenation. All three compounds inhibited cell death in hypoxia-reoxygenation experiments (HT≥Ty>MET). Peroxynitrite formation (3-nitrotyrosine) and inflammatory mediators (prostaglandin E2 and interleukin 1ß) were inhibited by all three compounds. In conclusion, the presence of OH groups in the molecule of these phenolic compounds from virgin olive oil is a determinant factor in their antioxidant effect in brain tissue, but this antioxidant effect is not the only explanation for their neuroprotective effect. Copyright © 2015. Published by Elsevier Inc.

Superacid Catalyzed Coal Conversion Chemistry. 1st and 2nd Quarterly Technical Progress Reports, September 1, 1983-March 30, 1984.

DOE R&D Accomplishments Database

Olah, G. A.

1984-01-01

In our laboratories we have previously developed a mild coal conversion process. This involves the use of a superacid system consisting of HF and BF{sub 3} in presence of hydrogen and/or a hydrogen donor solvent. In order to understand the chemistry involved in the process of depolymerization of coal by the HF:BF{sub 3}:H{sub 2} system we are carrying out a systematic study of a number of coal model compounds. The model compounds selected for present study have two benzene rings connected with various bridging units such as alkylidene, ether, sulfide etc. From studies so far carried out it appears that high pyridine extractibilities achieved by treating coal at temperature below 100 degrees C results from the cleavage of bridges such as present in bibenzyl, diphenyl methane, dibenzyl ether, dibenzyl sulfide etc. On the other hand the increased cyclohexane extractibility and distillability observed at relatively higher temperatures and hydrogen pressures reflects the hydrogenation and cleavage of the aromatic backbone in coal structure similar to what is seen in the conversion of model compounds such as biphenyl, diphenyl ether, diphenyl sulfide, anthracene, etc.

Four new sesquiterpenes from the rhizomes of Curcuma phaeocaulis and their iNOS inhibitory activities.

PubMed

Ma, Jiang-Hao; Wang, Ying; Liu, Yue; Gao, Su-Yu; Ding, Li-Qin; Zhao, Feng; Chen, Li-Xia; Qiu, Feng

2015-05-01

Three new guaiane-type sesquiterpenes named phaeocaulisins K-M (1-3), and one germacrane-type sesquiterpenoid with new ring system of 1,5- and 1,8-ether groups named phagermadiol (4), were isolated from rhizomes of Curcuma phaeocaulis. Their structures were established based on extensive spectroscopic analysis. Compound 1, the first example of norsesquiterpene with tropone backbone, and compound 3 with a novel 1,2-dioxolane sesquiterpene alcohol were isolated from the genus Curcuma. All of the isolated compounds were tested for inhibitory activity against lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 macrophages. Compound 3 inhibited NO production with IC50 value of 6.05 ± 0.43 μM. The plausible biosynthetic pathway for compounds 3 and 4 in C. phaeocaulis was also discussed.

Antibacterial activity of berberine-NorA pump inhibitor hybrids with a methylene ether linking group.

PubMed

Samosorn, Siritron; Tanwirat, Bongkot; Muhamad, Nussara; Casadei, Gabriele; Tomkiewicz, Danuta; Lewis, Kim; Suksamrarn, Apichart; Prammananan, Therdsak; Gornall, Karina C; Beck, Jennifer L; Bremner, John B

2009-06-01

Conjugation of the NorA substrate berberine and the NorA inhibitor 5-nitro-2-phenyl-1H-indole via a methylene ether linking group gave the 13-substituted berberine-NorA inhibitor hybrid, 3. A series of simpler arylmethyl ether hybrid structures were also synthesized. The hybrid 3 showed excellent antibacterial activity (MIC Staphylococcus aureus, 1.7 microM), which was over 382-fold more active than the parent antibacterial berberine, against this bacterium. This compound was also shown to block the NorA efflux pump in S. aureus.

Uptake and efflux of rhenium in cells exposed to rhenium diseleno-ether and tissue distribution of rhenium and selenium after rhenium diseleno-ether treatment in mice.

PubMed

Collery, Philippe; Bastian, Gérard; Santoni, François; Mohsen, Ahmed; Wei, Ming; Collery, Thomas; Tomas, Alain; Desmaele, Didier; D'Angelo, Jean

2014-04-01

We proposed a new water-soluble rhenium diseleno-ether compound (with one atom of Re and two atoms of Se) and investigated the uptake of Re into the nucleus of malignant cells in culture exposed to the compound for 48 h and its efflux from the nucleus after a post-exposure period of 48 h, as DNA is the main target of Re. We also studied the distribution of both Re and Se in the main organs after an oral administration of 10 or 40 mg/kg Re diseleno-ether to mice for four weeks, five days-a-week. Re and Se concentrations were assayed by inductively coupled plasma mass spectrometry (ICP-MS). Statistical analysis was performed using the Wilcoxon signed-rank test, comparing two related groups. We observed that Re was well incorporated into the nucleus of malignant cells in the most sensitive cells MCF-7, derived from human breast cancer, and that there was no efflux of Re. In contrast, in MCF-7 resistant cells (MCF-7 Mdr and MCF-7 R), A549 and HeLa cells, there was significant efflux of Re from the nucleus after the wash-out period. In mice, an important and dose-dependent uptake of both Re and Se was observed in the liver, with lower concentrations in kidneys. The lowest concentrations were observed in blood, lung, spleen and bones. There was a significant increase of Re concentrations in the blood, liver and kidney in mice treated with Re diseleno-ether at the dose of 40 mg/kg/24 h versus those treated at the dose of 10 mg/kg/24 h. There was a significant increase of Se concentrations in all tissues with the dose of Re diseleno-ether of 10 mg/kg/24 h versus controls, and a significant increase in the liver in mice treated with dose of Re diseleno-ether of 40 mg/kg/24h versus those treated with 10 mg/kg/24 h. We are the first to demonstrate that a compound combining Re and Se in a single molecule, is able to deliver Re and Se to the organism via an oral route, for cancer treatment.

Novel indole sulfides as potent HIV-1 NNRTIs.

PubMed

Brigg, Siobhan; Pribut, Nicole; Basson, Adriaan E; Avgenikos, Moscos; Venter, Reinhardt; Blackie, Margaret A; van Otterlo, Willem A L; Pelly, Stephen C

2016-03-15

In a previous communication we described a series of indole based NNRTIs which were potent inhibitors of HIV replication, both for the wild type and K103N strains of the virus. However, the methyl ether functionality on these compounds, which was crucial for potency, was susceptible to acid promoted indole assisted SN1 substitution. This particular problem did not bode well for an orally bioavailable drug. Here we describe bioisosteric replacement of this problematic functional group, leading to a series of compounds which are potent inhibitors of HIV replication, and are acid stable. Copyright © 2016 Elsevier Ltd. All rights reserved.

The discovery of tropane-derived CCR5 receptor antagonists.

PubMed

Armour, Duncan R; de Groot, Marcel J; Price, David A; Stammen, Blanda L C; Wood, Anthony; Perros, Manos; Burt, Catherine

2006-04-01

The development of compound 1, a piperidine-based CCR5 receptor antagonist with Type I CYP2D6 inhibition, into the tropane-derived analogue 5, is described. This compound, which is devoid of CYP2D6 liabilities, is a highly potent ligand for the CCR5 receptor and has broad-spectrum activity against a range of clinically relevant HIV isolates. The identification of human ether a-go-go-related gene channel inhibition within this series is described and the potential for QTc interval prolongation discussed. Furthermore, structure activity relationship (SAR) around the piperidine moiety is also described.

β-Sitosterol and flavonoids isolated from Bauhinia malabarica found during screening for Wnt signaling inhibitory activity.

PubMed

Park, Hyun Young; Toume, Kazufumi; Arai, Midori A; Koyano, Takashi; Kowithayakorn, Thaworn; Ishibashi, Masami

2014-01-01

Screening with a cell-based luciferase assay was conducted to identify bioactive natural products which inhibit Wnt signaling activity-guided separation of an MeOH extract of Bauhinia malabarica (Caesalpiniaceae) leaves yielded five compounds, which were identified as β-sitosterol (1), quercetin (2), 6,8-C-dimethyl kaempferol-3-O-rhamnopyranoside (3), hyperin (4), and 6,8-C-dimethyl kaempferol-3-methyl ether (5). The tested compounds 1, 3, and 5 exhibited Wnt signaling inhibitory activity, with IC50 values of 0.77, 0.74, and 16.6 μM, respectively.

On the temperature dependence of flammability limits of gases.

PubMed

Kondo, Shigeo; Takizawa, Kenji; Takahashi, Akifumi; Tokuhashi, Kazuaki

2011-03-15

Flammability limits of several combustible gases were measured at temperatures from 5 to 100 °C in a 12-l spherical flask basically following ASHRAE method. The measurements were done for methane, propane, isobutane, ethylene, propylene, dimethyl ether, methyl formate, 1,1-difluoroethane, ammonia, and carbon monoxide. As the temperature rises, the lower flammability limits are gradually shifted down and the upper limits are shifted up. Both the limits shift almost linearly to temperature within the range examined. The linear temperature dependence of the lower flammability limits is explained well using a limiting flame temperature concept at the lower concentration limit (LFL)--'White's rule'. The geometric mean of the flammability limits has been found to be relatively constant for many compounds over the temperature range studied (5-100 °C). Based on this fact, the temperature dependence of the upper flammability limit (UFL) can be predicted reasonably using the temperature coefficient calculated for the LFL. However, some compounds such as ethylene and dimethyl ether, in particular, have a more complex temperature dependence. Copyright © 2011 Elsevier B.V. All rights reserved.

Probability Based hERG Blocker Classifiers.

PubMed

Wang, Zhi; Mussa, Hamse Y; Lowe, Robert; Glen, Robert C; Yan, Aixia

2012-09-01

The US Food and Drug Administration (FDA) require in vitro human ether-a-go-go related (hERG) ion channel affinity tests for all drug candidates prior to clinical trials. In this study, probabilistic-based methods were employed to develop prediction models on hERG inhibition prediction, which are different from traditional QSAR models that are mainly based on supervised 'hard point' (HP) classification approaches giving 'yes/no' answers. The obtained models can 'ascertain' whether or not a given set of compounds can block hERG ion channels. The results presented indicate that the proposed probabilistic-based method can be a valuable tool for ranking compounds with respect to their potential cardio-toxicity and will be promising for other toxic property predictions. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and biological investigation of PIM mimics carrying biotin or a fluorescent label for cellular imaging.

PubMed

Front, Sophie; Bourigault, Marie-Laure; Rose, Stéphanie; Noria, Ségueni; Quesniaux, Valérie F J; Martin, Olivier R

2013-01-16

Phosphatidyl inositol mannosides (PIMs) are constituents of the mycobacterial cell wall; these glycolipids are known to exhibit potent inhibitory activity toward the LPS-induced production of cytokines by macrophages, and therefore have potential as anti-inflammatory agents. Recently, heterocyclic analogues of PIMs in which the inositol is replaced by a piperidine (aza-PIM mimics) or a tetrahydropyran moiety (oxa-PIM mimics) have been prepared by short synthetic sequences and shown to retain the biological activity of the parent PIM structures. In this investigation, the aza-PIM analogue was used as a convenient scaffold to link biotin or a fluorescent label (tetramethyl-rhodamine) by way of an aminocaproyl spacer, with the goal of using these conjugates for intracellular localization and for the study of the mechanism of their antiinflammatory action. The synthesis of these compounds is reported, as well as the evaluation of their activities as inhibitors of LPS-induced cytokine production by macrophages (TNFα, IL12p40); preliminary investigations by FACS and confocal microscopy indicated that PIM-biotin conjugate binds to macrophage membranes with rapid kinetics.

[Manuel Azaña and psychology].

PubMed

Bandrés, Javier; Llavona, Rafael

2010-08-01

Manuel Azaña (1880-1940) was President of the II Spanish Republic and one of the most influential intellectuals of the Republican culture. His doctoral thesis addressed some of the social psychology problems of his time regarding the issue of the legal responsibility of the masses. Azaña also showed interest in psychology during his time as a grantee in Paris and he became a close friend of two of the most influential Spanish psychologists: Luis Simarro y Gonzalo Rodríguez Lafora. Azaña's biography reflects the rise of Spanish psychologists of the early 20th century and their tragic dispersion at the end of the Spanish Civil War.

Effect of some ultraviolet light absorbers on photo-stabilization of azadirachtin-A.

PubMed

Deota, P T; Upadhyay, P R; Patel, K B; Mehta, K J; Varshney, A K; Mehta, M H

2002-10-01

The effect of photo-stabilization of Azadirachtin-A (Aza-A) was examined when exposed to sunlight and ultraviolet light in the presence of four structurally different ultraviolet stabilizers namely 4-aminobenzoic acid, 2,4-dihydroxybenzophenone, 4,4'-dihydroxybenzophenone and phenyl salicylate. The percentages of Aza-A recovered at different time intervals from slides exposed to different light conditions with and without UV stabilizers as well as kinetic studies indicated that the addition of phenyl salicylate in methanolic solution of Aza-A (in 1:1 mole ratio) provides the best photo-stabilization of Aza-A molecule among the four UV stabilizers studied.

Quick and simple sample treatment for multiresidue analysis of bisphenols, bisphenol diglycidyl ethers and their derivatives in canned food prior to liquid chromatography and fluorescence detection.

PubMed

Alabi, A; Caballero-Casero, N; Rubio, S

2014-04-04

We report herein a multiresidue method for canned food determination of 12 bisphenols [bisphenol A (BPA), bisphenol B (BPB), bisphenol F (BPF), bisphenol E (BPE)], bisphenol diglycidyl ethers [bisphenol F diglycidyl ether (BFDGE), bisphenol A diglycidyl ether (BADGE)] and their derivatives [BADGE·2H2O, BADGE·H2O, BADGE·HCl·H2O, BADGE·HCl, BADGE·2HCl and BFDGE·2HCl]. The method was based on the microextraction of the target contaminants in 200mg food sample with 600 μL of a supramolecular solvent made up of inverse aggregates of tetradecanol, followed by analysis of the extract by liquid chromatography/fluorescence detection using external calibration. Chromatographic separation of all target compounds, including the ortho-ortho, ortho-para and para-para isomers of BFDGE and BFDGE·2HCl, was achieved with baseline separation (Resolution ≥ 1.52). No concentration of the extracts was required, the microextraction took about 30 min and several samples could be simultaneous treated. Method validation was carried out according to the recommendations of the European Commission Decision 2002/657/EC. Quantitation limits for the different analytes ranged between 0.9 and 3.5 μg kg(-1). Repeatability and reproducibility, expressed as relative standard deviation, were in the ranges 1.8-6.8% and 4.4-8.1%. The method was applied to the analysis of the target compounds in different food categories including vegetables, legumes, fruits, fish and seafood, meat product and grain. Recoveries in samples were within the range 80-110%. Only BPF and BPE were undetected in the canned food analyzed. The concentration found for the rest of bisphenols, diglycidyl ethers and derivatives was in the range 7.1-959 μg kg(-1). The study of the isomeric distribution of BFDGE and BFDGE·2HCl in food showed that they are preferentially present as one of the isomeric forms, that highlighting for further studies. The analytical and operational characteristics of this multiresidue method make it suitable for monitoring programs intended for the assessment of human exposure to bisphenols, diglycidyl ethers and derivatives from diet. Copyright © 2014 Elsevier B.V. All rights reserved.

5-Azacytidine mediated reactivation of silenced transgenes in potato (Solanum tuberosum) at the whole plant level.

PubMed

Tyč, Dimitrij; Nocarová, Eva; Sikorová, Lenka; Fischer, Lukáš

2017-08-01

Transient 5-azacytidine treatment of leaf explants from potato plants with transcriptionally silenced transgenes allows de novo regeneration of plants with restored transgene expression at the whole plant level. Transgenes introduced into plant genomes frequently become silenced either at the transcriptional or the posttranscriptional level. Transcriptional silencing is usually associated with DNA methylation in the promoter region. Treatments with inhibitors of maintenance DNA methylation were previously shown to allow reactivation of transcriptionally silenced transgenes in single cells or tissues, but not at the whole plant level. Here we analyzed the effect of DNA methylation inhibitor 5-azacytidine (AzaC) on the expression of two silenced reporter genes encoding green fluorescent protein (GFP) and neomycin phosphotransferase (NPTII) in potato plants. Whereas no obvious reactivation was observed in AzaC-treated stem cuttings, transient treatment of leaf segments with 10 μM AzaC and subsequent de novo regeneration of shoots on the selective medium with kanamycin resulted in the production of whole plants with clearly reactivated expression of previously silenced transgenes. Reactivation of nptII expression was accompanied by a decrease in cytosine methylation in the promoter region of the gene. Using the plants with reactivated GFP expression, we found that re-silencing of this transgene can be accidentally triggered by de novo regeneration. Thus, testing the incidence of transgene silencing during de novo regeneration could be a suitable procedure for negative selection of transgenic lines (insertion events) which have an inclination to be silenced. Based on our analysis of non-specific inhibitory effects of AzaC on growth of potato shoots in vitro, we estimated that AzaC half-life in the culture media is approximately 2 days.

Alterations of immune response of non-small cell lung cancer with Azacytidine

PubMed Central

Easwaran, Hariharan; Mohammad, Helai P.; Vendetti, Frank; VanCriekinge, Wim; DeMeyer, Tim; Du, Zhengzong; Parsana, Princy; Rodgers, Kristen; Yen, Ray-Whay; Zahnow, Cynthia A.; Taube, Janis M.; Brahmer, Julie R.; Tykodi, Scott S.; Easton, Keith; Carvajal, Richard D.; Jones, Peter A.; Laird, Peter W.; Weisenberger, Daniel J.; Tsai, Salina; Juergens, Rosalyn A.; Topalian, Suzanne L.; Rudin, Charles M.; Brock, Malcolm V.; Pardoll, Drew; Baylin, Stephen B.

2013-01-01

Innovative therapies are needed for advanced Non-Small Cell Lung Cancer (NSCLC). We have undertaken a genomics based, hypothesis driving, approach to query an emerging potential that epigenetic therapy may sensitize to immune checkpoint therapy targeting PD-L1/PD-1 interaction. NSCLC cell lines were treated with the DNA hypomethylating agent azacytidine (AZA – Vidaza) and genes and pathways altered were mapped by genome-wide expression and DNA methylation analyses. AZA-induced pathways were analyzed in The Cancer Genome Atlas (TCGA) project by mapping the derived gene signatures in hundreds of lung adeno (LUAD) and squamous cell carcinoma (LUSC) samples. AZA up-regulates genes and pathways related to both innate and adaptive immunity and genes related to immune evasion in a several NSCLC lines. DNA hypermethylation and low expression of IRF7, an interferon transcription factor, tracks with this signature particularly in LUSC. In concert with these events, AZA up-regulates PD-L1 transcripts and protein, a key ligand-mediator of immune tolerance. Analysis of TCGA samples demonstrates that a significant proportion of primary NSCLC have low expression of AZA-induced immune genes, including PD-L1. We hypothesize that epigenetic therapy combined with blockade of immune checkpoints – in particular the PD-1/PD-L1 pathway – may augment response of NSCLC by shifting the balance between immune activation and immune inhibition, particularly in a subset of NSCLC with low expression of these pathways. Our studies define a biomarker strategy for response in a recently initiated trial to examine the potential of epigenetic therapy to sensitize patients with NSCLC to PD-1 immune checkpoint blockade. PMID:24162015

Combined epigenetic and differentiation-based treatment inhibits neuroblastoma tumor growth and links HIF2α to tumor suppression

PubMed Central

Westerlund, Isabelle; Shi, Yao; Toskas, Konstantinos; Fell, Stuart M.; Li, Shuijie; Surova, Olga; Södersten, Erik; Kogner, Per; Nyman, Ulrika; Schlisio, Susanne; Holmberg, Johan

2017-01-01

Neuroblastoma is a pediatric cancer characterized by variable outcomes ranging from spontaneous regression to life-threatening progression. High-risk neuroblastoma patients receive myeloablative chemotherapy with hematopoietic stem-cell transplant followed by adjuvant retinoid differentiation treatment. However, the overall survival remains low; hence, there is an urgent need for alternative therapeutic approaches. One feature of high-risk neuroblastoma is the high level of DNA methylation of putative tumor suppressors. Combining the reversibility of DNA methylation with the differentiation-promoting activity of retinoic acid (RA) could provide an alternative strategy to treat high-risk neuroblastoma. Here we show that treatment with the DNA-demethylating drug 5-Aza-deoxycytidine (AZA) restores high-risk neuroblastoma sensitivity to RA. Combined systemic distribution of AZA and RA impedes tumor growth and prolongs survival. Genome-wide analysis of treated tumors reveals that this combined treatment rapidly induces a HIF2α-associated hypoxia-like transcriptional response followed by an increase in neuronal gene expression and a decrease in cell-cycle gene expression. A small-molecule inhibitor of HIF2α activity diminishes the tumor response to AZA+RA treatment, indicating that the increase in HIF2α levels is a key component in tumor response to AZA+RA. The link between increased HIF2α levels and inhibited tumor growth is reflected in large neuroblastoma patient datasets. Therein, high levels of HIF2α, but not HIF1α, significantly correlate with expression of neuronal differentiation genes and better prognosis but negatively correlate with key features of high-risk tumors, such as MYCN amplification. Thus, contrary to previous studies, our findings indicate an unanticipated tumor-suppressive role for HIF2α in neuroblastoma. PMID:28696319

Combined epigenetic and differentiation-based treatment inhibits neuroblastoma tumor growth and links HIF2α to tumor suppression.

PubMed

Westerlund, Isabelle; Shi, Yao; Toskas, Konstantinos; Fell, Stuart M; Li, Shuijie; Surova, Olga; Södersten, Erik; Kogner, Per; Nyman, Ulrika; Schlisio, Susanne; Holmberg, Johan

2017-07-25

Neuroblastoma is a pediatric cancer characterized by variable outcomes ranging from spontaneous regression to life-threatening progression. High-risk neuroblastoma patients receive myeloablative chemotherapy with hematopoietic stem-cell transplant followed by adjuvant retinoid differentiation treatment. However, the overall survival remains low; hence, there is an urgent need for alternative therapeutic approaches. One feature of high-risk neuroblastoma is the high level of DNA methylation of putative tumor suppressors. Combining the reversibility of DNA methylation with the differentiation-promoting activity of retinoic acid (RA) could provide an alternative strategy to treat high-risk neuroblastoma. Here we show that treatment with the DNA-demethylating drug 5-Aza-deoxycytidine (AZA) restores high-risk neuroblastoma sensitivity to RA. Combined systemic distribution of AZA and RA impedes tumor growth and prolongs survival. Genome-wide analysis of treated tumors reveals that this combined treatment rapidly induces a HIF2α-associated hypoxia-like transcriptional response followed by an increase in neuronal gene expression and a decrease in cell-cycle gene expression. A small-molecule inhibitor of HIF2α activity diminishes the tumor response to AZA+RA treatment, indicating that the increase in HIF2α levels is a key component in tumor response to AZA+RA. The link between increased HIF2α levels and inhibited tumor growth is reflected in large neuroblastoma patient datasets. Therein, high levels of HIF2α, but not HIF1α, significantly correlate with expression of neuronal differentiation genes and better prognosis but negatively correlate with key features of high-risk tumors, such as MYCN amplification. Thus, contrary to previous studies, our findings indicate an unanticipated tumor-suppressive role for HIF2α in neuroblastoma.

Discovery of potent and selective acetylcholinesterase (AChE) inhibitors: acacetin 7-O-methyl ether Mannich base derivatives synthesised from easy access natural product naringin.

PubMed

Liu, Hao-Ran; Men, Xue; Gao, Xiao-Hui; Liu, Lin-Bo; Fan, Hao-Qun; Xia, Xin-Hua; Wang, Qiu-An

2018-03-01

Naringin, as a component universal existing in the peel of some fruits or medicinal plants, was usually selected as the material to synthesise bioactive derivates since it was easy to gain with low cost. In present investigation, eight new acacetin-7-O-methyl ether Mannich base derivatives (1-8) were synthesised from naringin. The bioactivity evaluation revealed that most of them exhibited moderate or potent acetylcholinesterase (AChE) inhibitory activity. Among them, compound 7 (IC 50 for AChE = 0.82 ± 0.08 μmol•L -1 , IC 50 for BuChE = 46.30 ± 3.26 μmol•L -1 ) showed a potent activity and high selectivity compared with the positive control Rivastigmine (IC 50 for AChE = 10.54 ± 0.86 μmol•L -1 , IC 50 for BuChE = 0.26 ± 0.08 μmol•L -1 ). The kinetic study suggested that compound 7 bind to AChE with mix-type inhibitory profile. Molecular docking study revealed that compound 7 could combine both catalytic active site (CAS) and peripheral active site (PAS) of AChE with four points (Trp84, Trp279, Tyr70 and Phe330), while it could bind with BuChE via only His 20.

Biomimetics for Treating Biofilm-Embedded Infections

DTIC Science & Technology

2012-12-17

ethers and benzimidazoles . Among all three series, PMX519 series is the most studied. Several arylamides, hybrid arylurea/ethers and... benzimidazoles have improved activity/safety profiles relative to PMX519. Eight compounds were efficacious against S. aureus in vivo. The activity against Gram... benzimidazole PMX1405 was identified and proved to be active against E.coli in vivo. Arylamide 519 series. The arylamide series have been

Isolation and identification of the antibacterial active compound from petroleum ether extract of neem oil.

PubMed

Zhang, Yu-Qun; Xu, Jiao; Yin, Zhong-Qiong; Jia, Ren-Yong; Lu, Yang; Yang, Fan; Du, Yong-Hua; Zou, Ping; Lv, Cheng; Hu, Ting-Xiu; Liu, Shu-Liang; Shu, Gang; Yi, Geng

2010-10-01

From a petroleum ether extract of neem oil (Azadirachta indica A. Juss) the new tetrahydrofuranyl diester 1 was isolated as an anti-bacterial constituent. 1 showed significant activities against three standard bacterial strains, including Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922 and Salmonella enteritidis CMCC (B) 50041. Copyright © 2010 Elsevier B.V. All rights reserved.

Purifying contaminated water

DOEpatents

Daughton, Christian G.

1983-01-01

Process for removing biorefractory compounds from contaminated water (e.g., oil shale retort waste-water) by contacting same with fragmented raw oil shale. Biorefractory removal is enhanced by preactivating the oil shale with at least one member of the group of carboxylic, acids, alcohols, aldehydes, ketones, ethers, amines, amides, sulfoxides, mixed ether-esters and nitriles. Further purification is obtained by stripping, followed by biodegradation and removal of the cells.

Antiknock evaluation of hydrocarbons and ethers as aviation fuel components

NASA Technical Reports Server (NTRS)

Barnett, Henry C

1950-01-01

The results of a NACA investigation conducted over a period of several years to evaluate the anti-knock characteristics of organic compounds are summarized. Included are data for 18 branched paraffins and olefins, 27 aromatics, and 22 ethers. The factors of performance investigated were blending characteristics, temperature sensitivity, lead response, and relation between molecular structure and antiknock ratings. Four engines were used.

Crown ether stereoisomerism: Implications in metal ion extraction and ionic liquid design

NASA Astrophysics Data System (ADS)

Pawlak, Alan J.

Since their discovery more than four decades ago, crown ethers (CEs) have been the subject of intense investigation in a number of fields. Although many of the structural features that govern the behavior of these compounds have been thoroughly explored, the effect of their stereochemistry has received relatively little attention. In the present work, crown ether stereochemistry is shown to have important implications in both the design of ternary (i.e., three-component) ionic liquids (TILs) and metal ion extraction. Specifically, as a first step toward the development of guidelines for the rational design of ternary ionic liquids employing crown ethers as the neutral extractant, a systematic examination of the effect of crown ether stereochemistry (employing dicyclohexano-18-crown-6 (DCH18C6) as a representative crown compound), along with ring size, the nature and number of donor atoms, and the presence of functional groups, on the thermal properties (i.e., melting point or glass transition; decomposition or evaporation) of these compounds was carried out. Stereochemistry was found to have no appreciable impact on the onset temperature for mass loss. Rather, molecular weight and aromaticity were found to be more influential. Stereochemistry was, however, found to significantly affect the melting point of a TIL prepared from it; while the metal-CE formation constant, which varies with stereoisomer was observed to determine the onset temperature for mass loss of the TIL. To explore the implications of crown ether stereoisomerism in metal ion extraction, the formation constants for alkaline earth cation complexes with the isomers of DCH18C6 and selected stereoisomers of di-tert-butylcyclohexano-18-crown-6 (DtBuCH18C6) were measured. These values were found to vary inversely with the ligand strain (i.e., reorganizational) energy for the isomer, as determined by molecular mechanics calculations. Using this relationship (along with additional identification methods), three isomers of DtBuCH18C6, which were separated by preparative LC, were definitively identified. Three additional isomers were partially identified.

Synthesis and foaming properties of new anionic surfactants based on a renewable building block: sodium dodecyl isosorbide sulfates.

PubMed

Lavergne, Aurélie; Zhu, Ying; Pizzino, Aldo; Molinier, Valérie; Aubry, Jean-Marie

2011-08-15

Two agro-based anionic surfactants containing an isosorbide moiety have been synthesized and their amphiphilic properties evaluated. Since isosorbide is now considered as an important platform chemical of the starch industry, these compounds could represent bio-sourced alternatives to the alkyl ether sulfates (notably lauryl ether sulfate, LES) that are based on petroleum-derived ethylene oxides. As isosorbide is an asymmetric diol, two isomers can be prepared (2-O-dodecyl isosorbide sulfate and 5-O-dodecyl isosorbide sulfate) that show significantly different aqueous properties as regards to their Krafft temperatures and critical micellar concentrations. 5-O-dodecyl isosorbide sulfate is the most soluble and the most efficient surfactant. It possesses a much lower critical micelle concentration (cmc) than sodium dodecyl sulfate, SDS, leading to comparable foaming properties with a three times lower concentration. Its behavior compares well with the one of pure diethoxylated dodecyl sulfate that has also been prepared and evaluated in this work. Copyright © 2011 Elsevier Inc. All rights reserved.

Molecular determinants of the olfactory receptor Olfr544 activation by azelaic acid.

PubMed

Thach, Trung Thanh; Hong, Yu-Jung; Lee, Sangho; Lee, Sung-Joon

2017-04-01

The mouse olfactory receptor Olfr544 is expressed in several non-olfactory tissues and has been suggested as a functional receptor regulating different signaling pathways. However, the molecular interaction between Olfr544 and its natural ligand, azelaic acid (AzA), remains poorly characterized, primarily due to difficulties in the heterologous expression of the receptor protein on the cell membrane and lack of entire protein structure. In this report, we describe the molecular determinants of Olfr544 activation by AzA. N-terminal lucy-flag-rho tag ensured the heterologous expression of Olfr544 on the Hana3A cell surface. Molecular modeling and docking combined with mutational analysis identified amino acid residues in the Olfr544 for the interaction with AzA. Our data demonstrated that the Y109 residue in transmembrane helix 3 forms a hydrogen bond with AzA, which is crucial for the receptor-ligand interaction and activation. Y109 is required for the Olfr544 activation by AzA which, in turn, stimulates the Olfr544-dependent CREB-PGC-1α signaling axis and is followed by the induction of mitochondrial biogenesis in Olfr544 wild-type transfected Hana3A cells, but not in mock or Y109A mutant transfected cells. Collectively, these data indicated that a hydrogen bond between Y109 residue and AzA is a major determinant of the Olfr544-AzA interaction and activation. Copyright © 2017 Elsevier Inc. All rights reserved.

The early epigenetic response to ozone: impacts on DNA ...

EPA Pesticide Factsheets

Epigenetics have been increasingly recognized as a mechanism linking environment and gene expression. Despite awareness of the role of DNA methylation and hydroxymethylation as potential drivers of the response to air pollutants, very little work has been performed investigating the direct epigenetic effects following exposure to ambient air pollution. Thus the purpose of this study was to investigate the early epigenetic response to ozone in comparison to the epigenetic modifier 5-aza-2'-deoxycytidine (5-Aza) in rats. 12 week old, male Long-Evans rats (n=16) were exposed to 4 hours of whole-body 1.0 ppm ozone or air and immediately euthanized. A subset of animals were additionally treated with 5-Aza (n=16) to serve as an epigenetic control to ozone exposure. Neither 5-Aza nor ozone by itself induced changes to the global methylome or hydroxmethylome of the lung measured by ELISA. Despite this finding, ozone exposure induced a significant increase in the activity of the DNA methyltransferase enzymes in the lung which was reversed with 5-Aza treatment. Interestingly, a significant interaction between 5-Aza treatment and ozone exposure was found in a large array of data. The interaction between 5-Aza and ozone produced indicators of pulmonary edema and elevated lung damage. Along with these adverse changes, expression of major epigenetic enzymes (Tet 1-3, Dnmt3 a-b) were found to be perturbed in both the lung and hepatic tissues. While ozone exposure appears to in

Subacute Cardiovascular Toxicity of the Marine Phycotoxin Azaspiracid-1 in Rats

PubMed Central

Vilariño, Natalia; Carrera, Cristina; Louzao, M. Carmen; Cantalapiedra, Antonio G.; Santamarina, Germán; Cifuentes, J. Manuel; Vieira, Andrés C.; Botana, Luis M.

2016-01-01

Azaspiracids (AZAs) are marine toxins produced by Azadinium spinosum that get accumulated in filter feeding shellfish through the food-web. The first intoxication was described in The Netherlands in 1990, and since then several episodes have been reported worldwide. Azaspiracid-1, AZA-2, and AZA-3 presence in shellfish is regulated by food safety authorities of several countries to protect human health. Azaspiracids have been related to widespread organ damage, tumorogenic properties and acute heart rhythm alterations in vivo but the mechanism of action remains unknown. Azaspiracid toxicity kinetics in vivo and in vitro suggests accumulative effects. We studied subacute cardiotoxicity in vivo after repeated exposure to AZA-1 by evaluation of the ECG, arterial blood pressure, plasmatic heart damage biomarkers, and myocardium structure and ultrastructure. Our results showed that four administrations of AZA-1 along 15 days caused functional signs of heart failure and structural heart alterations in rats at doses ranging from 1 to 55 µg/kg. Azaspiracid-1 altered arterial blood pressure, tissue inhibitors of metalloproteinase-1 plasma levels, heart collagen deposition, and ultrastructure of the myocardium. Overall, these data indicate that repeated exposure to low amounts of AZA-1 causes cardiotoxicity, at doses that do not induce signs of other organic system toxicity. Remarkably, human exposure to AZAs considering current regulatory limits of these toxins may be dangerously close to clearly cardiotoxic doses in rats. These findings should be considered when human risk is estimated particularly in high cardiovascular risk subpopulations. PMID:26865666

The action of ether and methoxyflurane on synaptic transmission in isolated preparations of the mammalian cortex.

PubMed Central

Richards, C D; Russell, W J; Smaje, J C

1975-01-01

1. The actions of ether and methoxyflurane on the evoked potentials of in vitro preparations of the guinea-pig olfactory cortex were studied. Following stimulation of the lateral olfactory tract (l.o.t.) evoked potentials could be recorded from the cortical surface; these potentials consisted of an initial wave (the compound action potential of the l.o.t.) followed by a negative field potential which was associated with the synchronous excitation of many superficial excitatory synapses (population e.p.s.p.). Superimposed on the population e.p.s.p. was a number of positive peaks. These positive peaks reflect the synchronous discharge of many neurones and so have been called population spikes. 2. When ether or methoxyflurane was added to the gas stream that superfused the surface of the preparations, the population e.p.s.p.s. and population spikes were depressed at lower concentrations than those required to depress the compound action potential of the afferent fibres. 3. The evoked activity of individual cells in the cortex was depressed by ether and methoxyflurane. However, five of the twelve cells tested in ether showed an increase in their evoked activity at concentrations below 4-5%, but at higher concentrations these cells also became depressed. 4. Both ether and methoxyflurane depressed the sensitivity of cortical neurones to iontophoretically applied L-glutamate and may similarly depress the sensitivity of the post-synaptic membrane to the released transmitter substance. 5. Neither anaesthetic appeared to increase the threshold depolarization required for nerve impulse generation. Thus, the decrease of the discharge of the post-synaptic cells was primarily caused by a depression of chemical transmission. 6. Ether caused some cells in the cortex to alter their normal pattern of synaptically evoked discharge and both anaesthetics induced similar changes during excitation by glutamate. PMID:168356

Metabolism of nitrodiphenyl ether herbicides by dioxin-degrading bacterium Sphingomonas wittichii RW1.

PubMed

Keum, Young Soo; Lee, Young Ju; Kim, Jeong-Han

2008-10-08

Nitrodiphenyl ether herbicides, including chlomethoxyfen, nitrofen, and oxyfluorfen are potent herbicides. Some metabolites and parent compounds are considered as possible mutagens and endocrine disruptors. Both properties pose serious hygienic and environmental risks. Sphingomonas wittichii RW1 is a well-known degrader of polychlorinated dibenzo- p-dioxins, dibenzofurans, and diphenyl ethers. However, no detailed research of its metabolic activity has been performed against pesticides with a diphenyl ether scaffold. In this study, we report S. wittichii RW1 as a very potent diphenyl ether herbicide-metabolizing bacterium with broad substrate specificity. The structures of metabolites were determined by instrumental analysis and synthetic standards. Most pesticides were rapidly removed from the culture medium in the order of nitrofen > oxyfluorfen > chlomethoxyfen. In general, herbicides were degraded through the initial reduction and N-acetylation of nitro groups, followed by ether bond cleavage. Relatively low concentrations of phenolic and catecholic metabolites throughout the study suggested that these metabolites were rapidly metabolized and incorporated into primary metabolism. These results indicate that strain RW1 has very versatile metabolic activities over a wide range of environmental contaminants.

Pyrolysis reaction networks for lignin model compounds: unraveling thermal deconstruction of β-O-4 and α-O-4 compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Yong S.; Singh, Rahul; Zhang, Jing

2016-01-01

Although lignin is one of the main components of biomass, its pyrolysis chemistry is not well understood due to complex heterogeneity. To gain insights into this chemistry, the pyrolysis of seven lignin model compounds (five ..beta..-O-4 and two ..alpha..-O-4 linked molecules) was investigated in a micropyrolyzer connected to GC-MS/FID. According to quantitative product mole balance for the reaction networks, concerted retro-ene fragmentation and homolytic dissociation were strongly suggested as the initial reaction step for ..beta..-O-4 compounds and ..alpha..-O-4 compounds, respectively. The difference in reaction pathway between compounds with different linkages was believed to result from thermodynamics of the radical initiation.more » The rate constants for the different reaction pathways were predicted from ab initio density functional theory calculations and pre-exponential literature values. The computational findings were consistent with the experiment results, further supporting the different pyrolysis mechanisms for the ..beta..-ether linked and ..alpha..-ether linked compounds. A combination of the two pathways from the dimeric model compounds was able to describe qualitatively the pyrolysis of a trimeric lignin model compound containing both ..beta..-O-4 and ..alpha..-O-4 linkages.« less

Production of Jet Fuel-Range Hydrocarbons from Hydrodeoxygenation of Lignin over Super Lewis Acid Combined with Metal Catalysts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Hongliang; Wang, Huamin; Kuhn, Eric

Super Lewis acids containing the triflate anion (e.g. Hf(OTf)4, Ln(OTf)3, Al(OTf)3) and noble metal catalysts (e.g. Ru/C, Ru/Al2O3) formed efficient catalytic systems to generate saturated hydrocarbons from lignin in high yields. In such catalytic systems, the metal triflates mediated rapid ether bond cleavage via selective bonding to etheric oxygens while the noble metal catalysed subsequent hydrodeoxygenation (HDO) reactions. Near theoretical yields of hydrocarbons were produced from lignin model compounds by the combined catalysis of Hf(OTf)4 and ruthenium-based catalysts. When a technical lignin derived from a pilot-scale biorefinery was used, more than 30 wt% of the hydrocarbons produced with this catalyticmore » system were cyclohexane and alkylcyclohexanes in the jet fuel range. Super Lewis acids are postulated to strongly interact with lignin substrates via protonating hydroxyls and ether linkages, forming intermediate species that enhance hydrogenation catalysis by supported noble metal catalysts. Meanwhile, the hydrogenation of aromatic rings by the noble metal catalysts can promote oxygenation reactions catalysed by super Lewis acids.« less

Induction of mutagenesis and transformation in BALB/c-3T3 clone A31-1 cells by diverse chemical carcinogens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lubet, R.A.; Kouri, R.E.; Curren, R.A.

1990-01-01

BALB/c-3T3 cells were employed to examine the genotoxic potential of a variety of known chemical carcinogens. BALB/c-3T3 cells displayed a dose-dependent transformation response to a variety of carcinogens (polycyclic hydrocarbons, methylating agents, ethylating agents, aflatoxin B{sub 1} (AFT{sub 1}), and 4-nitroquinoline-N-oxide (4-NQO)). When the ability of these compounds to induce mutagenesis to resistance to the cardiac glycoside ouabain (OUA{sup R}) was examined, the authors found the short chain alkylating agents to be particularly effective mutagens, causing biologic effects at doses below those necessary to induce a transformation response. In contrast, the polycyclic hydrocarbons which were potent transforming agents were weaker,more » albeit significant, mutagens for the OUA{sup R} locus in this system, while AFB{sub 1} was quite weak. Further studies were performed with 5-azacytidine (5-AZA) and the nongenotoxic carcinogen cinnamyl anthranilate (CIN). 5-AZA was a potent transforming agent, but failed to cause mutagenesis. CIN similarly caused in vitro transformation. When a series of eight structurally diverse compounds were examined in both the BALB/c-3T3 and C3H10T1/2 mouse fibroblast transformation systems, the BALB/c-3T3 system was shown to be sensitive to a wide variety of potential carcinogens, whereas the C3H10T1/2 system proved routinely sensitive only to the polycyclic hydrocarbons.« less

Computational Study of the Aza-Michael Addition of the Flavonoid (+)-Taxifolin in the Inhibition of β-Amyloid Fibril Aggregation.

PubMed

Ginex, Tiziana; Trius, Marta; Luque, F Javier

2018-04-17

Inhibition of abnormal protein self-aggregation is an attractive strategy against amyloidogenic diseases, but has found limited success due to the complexity of protein self-assembly, the absence of fully reproducible aggregation assays, and the scarce knowledge of the inhibition mechanisms by small molecules. In this context, catechol-containing compounds may lead to covalent adducts with amyloid fibrils that interfere with the aggregation process. In particular, the covalent adduct formed between the oxidized form of (+)-taxifolin and an β-amyloid (Aβ42) suggests the involvement of a specific recognition motif that enables the chemical reaction with Aβ42. In this study, we have examined the mechanisms implicated in the aza-Michael addition of the o-quinone species of (+)-taxifolin with Aβ42 fibrils. The results support the binding of (+)-taxifolin to the hydrophobic groove delimited by the edges defined by Lys16 and Glu22 residues in the fibril. The chemical reaction proceeds through the nucleophilic attack of the deprotonated amino group of a Lys16 residue in a process activated by the interaction between the o-quinone ring with a vicinal Lys16 residue, as well as by a water-assisted proton transfer, which is the rate-limiting step of the reaction. This specific inhibition mechanism, which may explain the enhanced anti-aggregating activity of oxidized flavonoids compared to fresh compounds, holds promise for developing disease-modifying therapies. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Separation of mutagenic components in synthetic crudes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guerin, M. R.; Ho, C. H.; Clark, B. R.

1978-01-01

Mutagenic, basic constituents of a synthetic coal oil and a shale oil were isolated from the crude mixtures. In arriving at an efficient isolation procedure, several liquid chromatographic packing-eluent combinations were tried and the fractions bioassayed to determine the distributions of the mutagenic components. The most effective separation was achieved using a sequential elution scheme with first an alumina-benzene combination followed by a Sephadex LH-20 gel-isopropanol-acetone system. About 75 to 80% of an ether soluble base is eluted with benzene through alumina (activity I). Analysis of this fraction has revealed a wide range of alkyl substituted quinolines and pyridines. Materialmore » remaining on the alumina column was eluted with ethanol, dried and placed on the Sephadex column. Isopropanol (approximately 250 ml) and acetone (approximately 600 ml) were used in that order to elute the material quantitatively. About 12% of the ether-soluble base is eluted with the isopropanol while the rest (approximately 10%) is eluted with the acetone. Additional alkyl pyridine compounds are eluted with isopropanol while the acetone fractions are predominantly multi-ring nitrogen heterocyclic compounds, according to mass spectral analyses. Bioassay data show excellent isolation of the mutagenic activities into the acetone fractions. Negligible activity is found in the sum of the other (90% wt) fractions.« less

Part 3. a novel stereocontrolled, in situ, solution- and solid-phase, Aza Michael approach for high-throughput generation of tetrahydroaminoquinoline-derived natural-product-like architectures.

PubMed

Prakesch, Michael; Srivastava, Stuti; Leek, Donald M; Arya, Prabhat

2006-01-01

With the goal of rapidly accessing tetrahydroquinoline-based natural-product-like polycyclic architectures, herein, we report an unprecedented, in situ, stereocontrolled Aza Michael approach in solution and on the solid phase. The mild reaction conditions required to reach the desired target are highly attractive for the use of this method in library generation. To our knowledge, this approach has not been used before, and it opens a novel route leading to a wide variety of tetrahydroquinoline-derived bridged tricyclic derivatives.

Identification of marine neuroactive molecules in behaviour-based screens in the larval zebrafish.

PubMed

Long, Si-Mei; Liang, Feng-Yin; Wu, Qi; Lu, Xi-Lin; Yao, Xiao-Li; Li, Shi-Chang; Li, Jing; Su, Huanxing; Pang, Ji-Yan; Pei, Zhong

2014-05-30

High-throughput behavior-based screen in zebrafish is a powerful approach for the discovery of novel neuroactive small molecules for treatment of nervous system diseases such as epilepsy. To identify neuroactive small molecules, we first screened 36 compounds (1-36) derived from marine natural products xyloketals and marine isoprenyl phenyl ether obtained from the mangrove fungus. Compound 1 demonstrated the most potent inhibition on the locomotor activity in larval zebrafish. Compounds 37-42 were further synthesized and their potential anti-epilepsy action was then examined in a PTZ-induced epilepsy model in zebrafish. Compound 1 and compounds 39, 40 and 41 could significantly attenuate PTZ-induced locomotor hyperactivity and elevation of c-fos mRNA in larval zebrafish. Compound 40 showed the most potent inhibitory action against PTZ-induced hyperactivity. The structure-activity analysis showed that the OH group at 12-position played a critical role and the substituents at the 13-position were well tolerated in the inhibitory activity of xyloketal derivatives. Thus, these derivatives may provide some novel drug candidates for the treatment of epilepsy.

Self-association of short-chain nonionic amphiphiles in binary and ternary systems: comparison between the cleavable ethylene glycol monobutyrate and its ether counterparts.

PubMed

Zhu, Ying; Fournial, Anne-Gaëlle; Molinier, Valérie; Azaroual, Nathalie; Vermeersch, Gaston; Aubry, Jean-Marie

2009-01-20

In the context of environmental concerns for the production of surface active species, the introduction of a carbonyl function into the skeleton of ethyleneglycol-derived solvo-surfactants is a way to access cleavable compounds with presumed enhanced biodegradability. Ethylene glycol monobutyrate (C(3)COE(1)) was synthesized and compared to its ether counterparts, ethylene glycol monopropyl (C(3)E(1)) and monobutyl ethers (C(4)E(1)), to assess the effect of the insertion of a carbonyl function in the skeleton of short-chain ethoxylated amphiphilic compounds. In aqueous solutions, the ester has intermediate behavior between that of the two ethers with regard to surface tension, solubilization of Me-naphtalene in water, and self-diffusion by PGSE NMR. In ternary systems, C(3)COE(1) and C(3)E(1) have the same optimal oil (EACN = 2.8), which is much more polar than that of C(4)E(1) (EACN = 8.5). With regard to the ability to form structured systems, the behavior in water does not differ significantly for the three compounds, and the transition between nonassociating solvents and amphiphilic solvents, sometimes called solvo-surfactants, is gradual. In ternary systems, however, only C(4)E(1) and C(3)COE(1) form a third phase near the optimal formulation, which tends to show that C(3)COE(1) possesses the minimum amphiphilicity to get a structuration. Self-diffusion NMR studies of the one-phase domains do not, however, allow us to distinguish between different degrees of organization in the three systems.

Purifying contaminated water. [DOE patent application

DOEpatents

Daughton, C.G.

1981-10-27

Process is presented for removing biorefactory compounds from contaminated water (e.g., oil shale retort waste-water) by contacting same with fragmented raw oil shale. Biorefractory removal is enhanced by preactivating the oil shale with at least one member of the group of carboxylic acids, alcohols, aldehydes, ketones, ethers, amines, amides, sulfoxides, mixed ether-esters and nitriles. Further purification is obtained by stripping, followed by biodegradation and removal of the cells.

New Coumarinyl Ethers in Daphne oleoides Schreb. Collected from Sardinia Island.

PubMed

Venditti, Alessandro; Sanna, Cinzia; Lorenzetti, Lorenzo M; Ballero, Mauro; Bianco, Armandodoriano

2017-06-01

The phytochemical analysis of the ethanolic extract obtained from D. oleoides collected from Sardinia Island allowed the isolation of several new constituents for the species (3, 8, and 9) together with two new coumarinyl ethers (1 and 2) besides the chemotaxonomic markers of the Daphne genus (4 - 7 and 10) which are also known to possess interesting biological activities. The structure of the new compounds were elucidated by extensive spectroscopic and spectrometric analyses. The identification of these compounds gives an experimental evidence of the variability in the secondary metabolites pattern owned by populations growing in restricted area in respect to populations not confined by geographical barrier. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Identification of Novel Perfluoroalkyl Ether Carboxylic Acids (PFECAs) and Sulfonic Acids (PFESAs) in Natural Waters Using Accurate Mass Time-of-Flight Mass Spectrometry (TOFMS).

PubMed

Strynar, Mark; Dagnino, Sonia; McMahen, Rebecca; Liang, Shuang; Lindstrom, Andrew; Andersen, Erik; McMillan, Larry; Thurman, Michael; Ferrer, Imma; Ball, Carol

2015-10-06

Recent scientific scrutiny and concerns over exposure, toxicity, and risk have led to international regulatory efforts resulting in the reduction or elimination of certain perfluorinated compounds from various products and waste streams. Some manufacturers have started producing shorter chain per- and polyfluorinated compounds to try to reduce the potential for bioaccumulation in humans and wildlife. Some of these new compounds contain central ether oxygens or other minor modifications of traditional perfluorinated structures. At present, there has been very limited information published on these "replacement chemistries" in the peer-reviewed literature. In this study we used a time-of-flight mass spectrometry detector (LC-ESI-TOFMS) to identify fluorinated compounds in natural waters collected from locations with historical perfluorinated compound contamination. Our workflow for discovery of chemicals included sequential sampling of surface water for identification of potential sources, nontargeted TOFMS analysis, molecular feature extraction (MFE) of samples, and evaluation of features unique to the sample with source inputs. Specifically, compounds were tentatively identified by (1) accurate mass determination of parent and/or related adducts and fragments from in-source collision-induced dissociation (CID), (2) in-depth evaluation of in-source adducts formed during analysis, and (3) confirmation with authentic standards when available. We observed groups of compounds in homologous series that differed by multiples of CF2 (m/z 49.9968) or CF2O (m/z 65.9917). Compounds in each series were chromatographically separated and had comparable fragments and adducts produced during analysis. We detected 12 novel perfluoroalkyl ether carboxylic and sulfonic acids in surface water in North Carolina, USA using this approach. A key piece of evidence was the discovery of accurate mass in-source n-mer formation (H(+) and Na(+)) differing by m/z 21.9819, corresponding to the mass difference between the protonated and sodiated dimers.

RECOVERY OF URANIUM FROM PITCHBLENDE

DOEpatents

Ruehle, A.E.

1958-06-24

The decontamination of uranium from molybdenum is described. When acid solutions containing uranyl nitrate are contacted with ether for the purpose of extracting the uranium values, complex molybdenum compounds are coextracted with the uranium and also again back-extracted from the ether with the uranium. This invention provides a process for extracting uranium in which coextraction of molybdenum is avoided. It has been found that polyhydric alcohols form complexes with molybdenum which are preferentially water-soluble are taken up by the ether extractant to only a very minor degree. The preferred embodiment of the process uses mannitol, sorbitol or a mixture of the two as the complexing agent.

Synthesis of aza-fused polycyclic quinolines through copper-catalyzed cascade reactions.

PubMed

Cai, Qian; Li, Zhengqiu; Wei, Jiajia; Fu, Liangbin; Ha, Chengyong; Pei, Duanqing; Ding, Ke

2010-04-02

A new and efficient method for the synthesis of aza-fused polycyclic quinolines (e.g., benzimidazo[1,2-a]quinolines) is described. This protocol includes an intermolecular condensation followed by a copper-catalyzed intramolecular C-N coupling reaction. The method is applied to a wide range of 2-iodo, 2-bromo, and 2-chloro aryl aldehyde substrates to yield the aza-fused polycyclic quinolines in good yields.

Antineoplastic activity of the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine in anaplastic large cell lymphoma

PubMed Central

Hassler, Melanie R.; Klisaroska, Aleksandra; Kollmann, Karoline; Steiner, Irene; Bilban, Martin; Schiefer, Ana-Iris; Sexl, Veronika; Egger, Gerda

2012-01-01

DNA methylation is an epigenetic mechanism establishing long-term gene silencing during development and cell commitment, which is maintained in subsequent cell generations. Aberrant DNA methylation is found at gene promoters in most cancers and can lead to silencing of tumor suppressor genes. The DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-aza-CdR) is able to reactivate genes silenced by DNA methylation and has been shown to be a very potent epigenetic drug in several hematological malignancies. In this report, we demonstrate that 5-aza-CdR exhibits high antineoplastic activity against anaplastic large cell lymphoma (ALCL), a rare CD30 positive non-Hodgkin lymphoma of T-cell origin. Low dose treatment of ALCL cell lines and xenografted tumors causes apoptosis and cell cycle arrest in vitro and in vivo. This is also reflected in genome-wide expression analyses, where genes related to apoptosis and cell death are amongst the most affected targets of 5-aza-CdR. Furthermore, we observed demethylation and re-expression of p16INK4A after drug administration and senescence associated β-galactosidase activity. Thus, our data provide evidence that 5-aza-CdR is highly efficient against ALCL and warrants further clinical evaluation for future therapeutic use. PMID:22687603

Azathioprine Intolerance in Japanese Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis

PubMed Central

Morishita, Michiko; Watanabe, Haruki; Yan, Minglu; Zeggar, Sonia; Hiramatsu, Sumie; Ohashi, Keiji; Miyawaki, Yoshia; Katsuyama, Eri; Katsuyama, Takayuki; Takano Narazaki, Mariko; Toyota Tatebe, Noriko; Sunahori Watanabe, Katsue; Kawabata, Tomoko; Sada, Ken-Ei; Wada, Jun

2017-01-01

Objective To assess the safety of azathioprine (AZA) in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods We retrospectively enrolled 67 consecutive AAV patients who had initiated AZA treatment from January 2006 to August 2014 at Okayama University Hospital. We evaluated the development of severe adverse events (AEs), AZA discontinuation due to total AEs (severe AEs included) within 1 year, and AZA-associated risk factors. Results The patients' median age was 70 years old. Forty-nine women and 18 men participated at the initiation of the study. Fifty-eight (87%) patients experienced AEs, and 36 experienced severe AEs (21 hepatic and 11 cytopenic severe AEs). Thirty-one (46%) patients discontinued treatment because of AEs. Abnormal hepatic laboratory test results at the treatment initiation were more frequent in patients with hepatic severe AEs and were associated with treatment discontinuation. The leukocyte and neutrophil counts at the treatment initiation were lower in the patients who discontinued treatment because of cytopenic AEs than in those who continued treatment. Only two patients experienced flare-ups during treatment. Conclusion The AE-associated AZA discontinuation rate in Japanese AAV patients was relatively high. AZA use warrants caution in patients with abnormal hepatic laboratory test results or low leukocyte or neutrophil counts. PMID:28674351

Enhanced differentiation of mesenchymal stromal cells by three-dimensional culture and azacitidine

PubMed Central

Bae, Yoo-Jin; Kwon, Yong-Rim; Kim, Hye Joung; Lee, Seok

2017-01-01

Background Mesenchymal stromal cells (MSCs) are useful for cell therapy because of their potential for multilineage differentiation. However, MSCs that are expanded in traditional two-dimensional (2D) culture systems eventually lose their differentiation abilities. Therefore, we investigated whether azacitidine (AZA) supplementation and three-dimensional culture (3D) could improve the differentiation properties of MSCs. Methods 2D- or 3D-cultured MSCs which were prepared according to the conventional or hanging-drop culture method respectively, were treated with or without AZA (1 µM for 72 h), and their osteogenic and adipogenic differentiation potential were determined and compared. Results AZA treatment did not affect the cell apoptosis or viability in both 2D- and 3D-cultured MSCs. However, compared to conventionally cultured 2D-MSCs, AZA-treated 2D-MSCs showed marginally increased differentiation abilities. In contrast, 3D-MSCs showed significantly increased osteogenic and adipogenic differentiation ability. When 3D culture was performed in the presence of AZA, the osteogenic differentiation ability was further increased, whereas adipogenic differentiation was not affected. Conclusion 3D culture efficiently promoted the multilineage differentiation of MSCs, and in combination with AZA, it could help MSCs to acquire greater osteogenic differentiation ability. This optimized culture method can enhance the therapeutic potential of MSCs. PMID:28401097

Azadirachtin(A) distinctively modulates subdomain 2 of actin - novel mechanism to induce depolymerization revealed by molecular dynamics study.

PubMed

Pravin Kumar, R; Roopa, L; Sudheer Mohammed, M M; Kulkarni, Naveen

2016-12-01

Azadirachtin(A) (AZA), a potential insecticide from neem, binds to actin and induces depolymerization in Drosophila. AZA binds to the pocket same as that of Latrunculin A (LAT), but LAT inhibits actin polymerization by stiffening the actin structure and affects the ADP-ATP exchange. The mechanism by which AZA induces actin depolymerization is not clearly understood. Therefore, different computational experiments were conducted to delineate the precise mechanism of AZA-induced actin depolymerization. Molecular dynamics studies showed that AZA strongly interacted with subdomain 2 and destabilized the interactions between subdomain 2 of one actin and subdomains 1 and 4 of the adjacent actin, causing the separation of actin subunits. The separation was observed between subdomain 3 of subunit n and subdomain 4 of subunit n + 2. However, the specific triggering point for the separation of the subunits was the destabilization of direct interactions between subdomain 2 of subunit n (Arg39, Val45, Gly46 and Arg62) and subdomain 4 of subunit n + 2 (Asp286, Ile287, Asp288, Ile289, Asp244 and Lys291). These results reveal a unique mechanism of an actin filament modulator that induces depolymerization. This mechanism of AZA can be used to design similar molecules against mammalian actins for cancer therapy.

Insights into the Competing Mechanisms and Origin of Enantioselectivity for N-Heterocyclic Carbene-Catalyzed Reaction of Aldehyde with Enamide

NASA Astrophysics Data System (ADS)

Qiao, Yan; Chen, Xinhuan; Wei, Donghui; Chang, Junbiao

2016-12-01

Hydroacylation reactions and aza-benzoin reactions have attracted considerable attention from experimental chemists. Recently, Wang et al. reported an interesting reaction of N-heterocyclic carbene (NHC)-catalyzed addition of aldehyde to enamide, in which both hydroacylation and aza-benzoin reactions may be involved. Thus, understanding the competing relationship between them is of great interest. Now, density functional theory (DFT) investigation was performed to elucidate this issue. Our results reveal that enamide can tautomerize to its imine isomer with the assistance of HCO3-. The addition of NHC to aldehydes formed Breslow intermediate, which can go through cross-coupling with enamide via hydroacylation reaction or its imine isomer via aza-benzoin reaction. The aza-benzoin reaction requires relatively lower free energy barrier than the hydroacylation reaction. The more polar characteristic of C=N group in the imine isomers, and the more advantageous stereoelectronic effect in the carbon-carbon bond forming transition states in aza-benzoin pathway were identified to determine that the imine isomer can react with the Breslow intermediate more easily. Furthermore, the origin of enantioselectivities for the reaction was explored and reasonably explained by structural analyses on key transition states. The work should provide valuable insights for rational design of switchable NHC-catalyzed hydroacylation and aza-benzoin reactions with high stereoselectivity.

[The Role of 5-Aza-CdR on Methylation of Promoter in RASSF1A Gene in Endometrial Carcinoma].

PubMed

Huang, Li-ping; Chen, Chen; Wang, Xue-ping; Liu, Hui

2015-05-01

To explore the effect of demethylating drug 5-Aza-2'-deoxycytidine (5-Aza-CdR) on methtylation status of the Ras-association domain familylA gene (RASSF1A) in human endometrial carcinoma. Randomly'assign the human endometrial carcinoma cell line HEC-1-B into groups and use demethylating drug 5-Aza-CdR of different concentration to treat them. Then Methylation-specific polymerase chain reaction (MSP), real-time PCR, Western blot, TUNEL technology were used to analyze methylation status of RASSF1A promoter CpG islands, RASSF1A mRNA expression, RASSF1A protein expression and apoptosis of HEC-1-B cell. High DNA methylation in RASSF1A gene promoter region, low RASSF1A mRNA level and protein expression and out of control of human endometrial carcinoma cell HEC-1-B apoptosis were observed. 5-Aza-CdR of different concentration could reverse RASSF1A gene's methylation status, recover the expression of mRNA and protein, and control the growth of HEC-1-B by inducing apoptosis. Aberrant methylation of RASSF1A in endometrial cancer as a therapeutic target, demethylating agent 5-Aza-CdR could be an effective way of gene therapy.

Antifungal activity against plant pathogens of metabolites from the endophytic fungus Cladosporium cladosporioides

USDA-ARS?s Scientific Manuscript database

Bioassay-guided fractionation of Cladosporium cladosporioides crude extracts led to the isolation of four compounds, including cladosporin (1), isocladosporin (2), 5'-hydroxyasperentin (3), cladosporin-8-methyl ether (4). The compound 6, 5'-diacetyl cladosporin (5) was synthesized by acetylation of ...

Economic impact of combination therapy with infliximab plus azathioprine for drug-refractory Crohn's disease: a cost-effectiveness analysis.

PubMed

Saito, Shota; Shimizu, Utako; Nan, Zhang; Mandai, Nozomu; Yokoyama, Junji; Terajima, Kenshi; Akazawa, Kouhei

2013-03-01

Combination therapy with infliximab (IFX) and azathioprine (AZA) is significantly more effective for treatment of active Crohn's disease (CD) than IFX monotherapy. However, AZA is associated with an increased risk of lymphoma in patients with inflammatory bowel disease. To evaluate the cost-effectiveness of combination therapy with IFX plus AZA for drug-refractory CD. A decision analysis model is constructed to compare, over a time horizon of 1year, the cost-effectiveness of combination therapy with IFX plus AZA and that of IFX monotherapy for CD patients refractory to conventional non-anti-TNF-α therapy. The treatment efficacy, adverse effects, quality-of-life scores, and treatment costs are derived from published data. One-way and probabilistic sensitivity analyses are performed to estimate the uncertainty in the results. The incremental cost-effectiveness ratio (ICER) of combination therapy with IFX plus AZA is 24,917 GBP/QALY when compared with IFX monotherapy. The sensitivity analyses reveal that the utility score of nonresponding active disease has the strongest influence on the cost-effectiveness, with ICERs ranging from 17,147 to 45,564 GBP/QALY. Assuming that policy makers are willing to pay 30,000 GBP/QALY, the probability that combination therapy with IFX plus AZA is cost-effective is 0.750. Combination therapy with IFX plus AZA appears to be a cost-effective treatment for drug-refractory CD when compared with IFX monotherapy. Furthermore, the additional lymphoma risk of combination therapy has little significance on its cost-effectiveness. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Febuxostat as a novel option to optimize thiopurines' metabolism in patients with inadequate metabolite levels.

PubMed

Doré, Maxime; Frenette, Anne Julie; Mansour, Anne-Marie; Troyanov, Yves; Bégin, Josiane

2014-05-01

To report the use of febuxostat in order to potentiate thiopurines' metabolism in a patient on azathioprine (AZA) therapy with low metabolite 6-thioguanine nucleotides (6-TGN) levels and elevated metabolite 6-methylmercaptopurine (6-MMP) levels. A 44-year-old woman with a history of anti-signal recognition particle necrotizing myopathy was treated with AZA-allopurinol combination therapy. When she developed an atypical drug-induced hypersensitivity syndrome, allopurinol was replaced by the new xanthine oxidase (XO) inhibitor febuxostat, at a daily dose of 40 mg. Febuxostat-AZA combination was successful with 6-TGN reaching therapeutic levels while 6-MMP levels remained low. After 5 months, she developed similar manifestations that she had presented on AZA-allopurinol combination. Febuxostat and AZA were then stopped. AZA and 6-MP are both inactive pro-drugs that undergo a complex metabolic transformation leading to active 6-TGN and potentially hepatotoxic 6-MMP. Some patients with unfavorable thiopurine metabolism might benefit from addition of XO inhibitor allopurinol in order to potentiate 6-TGN and reduce 6-MMP levels. It is likely that febuxostat, via its XO inhibition, would exhibit the same effect on thiopurines' metabolism. It has been shown that low dose of febuxostat was able to prevent hypermethylation and to potentiate 6-TGN levels in an AZA-treated patient. Thus, febuxostat could be useful in optimizing thiopurines' metabolism, but more data are needed before this practice can be recommended. The mechanisms by which febuxostat optimizes thiopurines' metabolism remain to be confirmed. Also, the optimal dose of febuxostat for this use remains to be determined.

Field efficacy of azadirachtin-A, tetrahydroazadirachtin-A, NeemAzal and endosulfan against key pests of okra (Abelmoschus esculentus).

PubMed

Dhingra, Swaran; Walia, Suresh; Kumar, Jitendra; Singh, Shivendra; Singh, Gyanendra; Parmar, Balraj S

2008-11-01

BACKGROUND Unlike synthetic pesticides, azadirachtin-based neem pesticides are environmentally friendly and are well known for their diverse pest control properties. Their use is, however, limited by the instability of azadirachtin, necessitating application at short intervals. The efficacy of relatively stable tetrahydroazadirachtin-A, therefore, needed to be established under field conditions. Azadirachtin-A (Aza-A), its stable derivative tetrahydroazadirachtin-A (THA) and other neem pesticides have been evaluated for their field efficacy against major insect pests of okra, Abelmoschus esculentus (L.) Moench., during summer (kharif) 2003 and 2004. The optimum doses of Aza-A and THA against the fruit borer, Earias vittella F., were also established. Reductions in population of whitefly, Bemisia tabaci (Genn.), and leafhopper (jassid), Amrasca biguttulla biguttulla Ishida, after application of THA or endosulfan was evident up to 10 days after treatment (DAT), whereas with Aza-A and NeemAzal (NZ) the effect was observed up to 7 DAT only. Endosulfan and THA also caused higher reduction in the larvae of shoot and fruit borer E. vittella and E. insulana Boisd., and recorded the highest yields of 4600 and 4180 kg ha(-1). The efficacy of THA (0.05 g L(-1) emulsion) was comparable with that of 0.5 g L(-1) endosulfan emulsion in reducing fruit borer infestation, the reduction over the control being 86.0 and 87.3%, 84.9 and 94.1% and 90.2 and 92.6% at first, second and third picking. THA 0.02 g L(-1) and Aza-A 0.05 g L(-1) were on a par. Laboratory-made neem oil emulsifiable concentrate was the least effective, but was superior to untreated check. Three consecutive sprays of THA, a neem-based biopesticide, and endosulfan have been found to be superior in controlling field pests of okra to Aza-A and NZ, which were on a par. THA thus holds potential as a component of pest management strategies against okra pests. Copyright (c) 2008 Society of Chemical Industry.

Comparison of the anti-cancer effect of Disulfiram and 5-Aza-CdR on pancreatic cancer cell line PANC-1.

PubMed

Dastjerdi, Mehdi Nikbakht; Babazadeh, Zahra; Salehi, Mansour; Hashemibeni, Batool; Kazemi, Mohammad

2014-01-01

Pancreatic cancer has poor prognosis by surgical and chemotherapy when it is diagnosed, so other anti-cancerous assistant therapeutic drugs are suggested e.g. epigenetic reversal of tumor-suppressor genes on promoter hypermethylation. 5-Aza-CdR is a nucleoside analog of DNMTi but it has long-term cytotoxicity effects. This study compares the anticancer effect of 5-Aza-CdR and Disulfiram potencies on PANC-1 cell line and up-regulation of p21. PANC-1 cell line was cultured in DMEM high glucose and treated by 5-Aza-CdR with 5 and 10 μM concentration for four days and 13 μM DSF (Diulfiram) for 24 hours. MS-PCR and RT-PCR were carried out to detect the methylation pattern and estimate the mRNA expression of RASSF1A and p21 in PANC-1. MS-PCR demonstrated partial unmethylation after treatment with 5-Aza-CdR while there was no unmethylated band after DSF treatment. RT-PCR showed significant differences between re-expression of RASSF1A before and after treatment with 10 μM 5-Aza-CdR (P < 0.01) but not after treatment with 13 μM DSF (P > 0.05). The significant correlation was observed between RASSF1A re-expression and p21 up-regulation before and after treatment with 10 μM 5-Aza-CdR (P < 0.01) but not after treatment with 13 μM DSF (P > 0.05), while p21 up-regulation was significantly higher after DSF treatment (P < 0.01). Our findings indicated that 5-Aza-CdR induces the re-expression of RASSF1A and p21 up-regulation in PANC-1. DSF showed no epigenetic reversion while it affected p21 up-regulation.

Down-regulation of p16 and MGMT promotes the anti-proliferative and pro-apoptotic effects of 5-Aza-dC and radiation on cervical cancer cells.

PubMed

Chen, Guan-di; Qian, De-Ying; Li, Zhi-Gang; Fan, Ge-Ying; You, Ke-Li; Wu, Yi-Long

2017-12-01

Cervical cancer is one of the most common malignancies of the female reproductive system. Therefore, it is critical to investigate the molecular mechanisms involved in the development and progression of cervical cancer. In this study, we stimulated cervical cancer cells with 5-aza-2'-deoxycytidine (5-Aza-dC) and found that this treatment inhibited cell proliferation and induced apoptosis; additionally, methylation of p16 and O-6-methylguanine-DNA methyltransferase (MGMT) was reversed, although their expression was suppressed. 5-Aza-dC inhibited E6 and E7 expression and up-regulated p53, p21, and Rb expression. Cells transfected with siRNAs targeting p16 and MGMT as well as cells stimulated with 5-Aza-dC were arrested in S phase, and the expression of p53, p21, and Rb was up-regulated more significantly. However, when cells were stimulated with 5-Aza-dC after transfection with siRNAs targeting p16 and MGMT, proliferation decreased significantly, and the percentage of cells in the sub-G1 peak and in S phase was significantly increased, suggesting a marked increase in apoptosis. But E6 and E7 overexpression could rescue the observed effects in proliferation. Furthermore, X-ray radiation caused cells to arrest in G2/M phase, but cells transfected with p16- and MGMT-targeted siRNAs followed by X-ray radiation exhibited a significant decrease in proliferation and were shifted toward the sub-G1 peak, also indicating enhanced apoptosis. In addition, the effects of 5-Aza-dC and X-ray radiation were most pronounced when MGMT expression was down-regulated. Therefore, down-regulation of p16 and MGMT expression enhances the anti-proliferative effects of 5-Aza-dC and X-ray radiation. This discovery may provide novel ideas for the treatment of cervical cancer. Copyright © 2017 John Wiley & Sons, Ltd.

Efficacy of azelaic acid on hepatic key enzymes of carbohydrate metabolism in high fat diet induced type 2 diabetic mice.

PubMed

Muthulakshmi, Shanmugam; Saravanan, Ramalingam

2013-06-01

Azelaic acid (AzA), a C9 linear α,ω-dicarboxylic acid, is found in whole grains namely wheat, rye, barley, oat seeds and sorghum. The study was performed to investigate whether AzA exerts beneficial effect on hepatic key enzymes of carbohydrate metabolism in high fat diet (HFD) induced type 2 diabetic C57BL/6J mice. C57BL/6J mice were fed high fat diet for 10 weeks and subjected to intragastric administration of various doses (20 mg, 40 mg and 80 mg/kg BW) of AzA daily for the subsequent 5 weeks. Rosiglitazone (RSG) was used as reference drug. Body weight, food intake, plasma glucose, plasma insulin, blood haemoglobin (Hb), blood glycosylated haemoglobin (HbA1c), liver glycolytic enzyme (hexokinase), hepatic shunt enzyme (glucose-6-phosphate dehydrogenase), gluconeogenic enzymes(glucose-6-phosphatase and fructose-1,6-bisphosphatase), liver glycogen, plasma and liver triglycerides were examined in mice fed with normal standard diet (NC), high fat diet (HFD), HFD with AzA (HFD + AzA) and HFD with rosiglitazone (HFD + RSG). Among the three doses, 80 mg/kg BW of AzA was able to positively regulate plasma glucose, insulin, blood HbA1c and haemoglobin levels by significantly increasing the activity of hexokinase and glucose-6-phosphate dehydrogenase and significantly decreasing the activity of glucose-6-phosphatase and fructose-1,6-bisphosphatase thereby increasing the glycogen content in the liver. From this study, we put forward that AzA could significantly restore the levels of plasma glucose, insulin, HbA1c, Hb, liver glycogen and carbohydrate metabolic key enzymes to near normal in diabetic mice and hence, AzA may be useful as a biomaterial in the development of therapeutic agents against high fat diet induced T2DM. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

INSECTICIDAL AND OXIDATIVE EFFECTS OF AZADIRACHTIN ON THE MODEL ORGANISM Galleria mellonella L. (LEPIDOPTERA: PYRALIDAE).

PubMed

Dere, Beyza; Altuntaş, Hülya; Nurullahoğlu, Z Ulya

2015-07-01

The insecticidal effects, specifically, changes in hemolymph total protein and malondialdehyde (MDA) levels, and antioxidant enzyme activities of azadirachtin (AZA) given to the wax moth, Galleria mellonella L. (Lepidoptera: Pyralidae) larvae via force feeding were investigated. Bioassays showed that the LD50 and LD99 (lethal dose) values of AZA were 2.1 and 4.6 μg/larva, respectively. Experimental analyses were performed with five doses of AZA (0.5, 1, 1.5, 2, and 3 μg/larva). Total protein level in larval hemolymph increased at all AZA doses at 24 h whereas a considerable decrease was observed at 2 and 3 μg/larva doses, and only an increase displayed at 1.5 μg/larva at 72 h. The level of MDA increased at 2 and 3 μg/larva doses at 24 h compared with controls. This trend was also observed at 1.5, 2, and 3 μg/larva doses at 72 h and MDA levels were lower when compared with those of 24 h at all doses except for 1.5 μg/larva dose. Catalase activity decreased at 1, 1.5, and 2 μg/larva doses at 24 h whereas increased at all doses except for 0.5 μg/larva at 72 h compared with controls. AZA led to a decline in superoxide dismutase activity at all experimental doses at 24 and 72 h except for 3 μg/larva doses at 72 h. An increase in glutathione-S-transferase (GST) activity was evident at all AZA doses at 24 h. AZA displayed 68% decline in GST activity at 72 h post treatments when compared to 24 h. Consequently, We infer that the toxicity of AZA extends beyond its known actions in molting processes to redox homeostasis. © 2015 Wiley Periodicals, Inc.

AzaSite® inhibits Staphylococcus aureus and coagulase-negative Staphylococcus biofilm formation in vitro.

PubMed

Wu, Eric C; Kowalski, Regis P; Romanowski, Eric G; Mah, Francis S; Gordon, Y Jerold; Shanks, Robert M Q

2010-12-01

The aim of this study was to analyze the effect of azithromycin (AZM) 1% ophthalmic solution in DuraSite® (AzaSite®) on biofilm formation by Staphylococcus aureus and coagulase-negative staphylococci in vitro. Susceptible and resistant clinical strains (n = 8) of S. aureus and coagulase-negative staphylococci were challenged with serial dilutions of AzaSite® and its components: AZM, benzalkonium chloride (BAK), and the DuraSite drug delivery vehicle. After 20 h of incubation, bacterial growth was quantified using a spectrophotometer (A = 600 nm). Plates were stained with crystal violet and biofilm formation was quantified spectrophotometrically at A = 590 nm. AzaSite® and AZM inhibited bacterial growth (P < 0.05) and biofilm formation (P < 0.05) in AZM-susceptible strains at all studied dilutions. AZM-resistant strains treated with AzaSite® exhibited a significant reduction in biofilm formation (P < 0.05) at subinhibitory concentrations (1.25%-5%). AZM had no effect on bacterial growth in resistant strains but conferred a small reduction in biofilm formation at concentrations from 1.25 to 10 mg/mL in most strains. DuraSite® inhibited biofilm formation at concentrations between 10% and 2.5% in all studied strains (P < 0.05), without affecting bacterial growth. BAK inhibited bacterial growth and biofilm formation in all strains between concentrations of 0.042 and 0.375 mg/mL (P < 0.05). AzaSite®, AZM, or BAK prevented biofilm formation by inhibiting growth of AZM-susceptible strains. AzaSite®, AZM, and DuraSite® also reduced biofilm formation at subinhibitory concentrations for growth. Our data indicate that AZM has a moderate inhibitory effect on biofilm formation, whereas DuraSite® appears to play a greater role in the inhibition of staphylococcal biofilm formation by AzaSite®.

A multicenter study of topical azelaic acid 15% gel in combination with oral doxycycline as initial therapy and azelaic acid 15% gel as maintenance monotherapy.

PubMed

Thiboutot, Diane M; Fleischer, Alan B; Del Rosso, James Q; Rich, Phoebe

2009-07-01

This two-phase, multicenter study was undertaken to examine the safety and efficacy of combination therapy with oral doxycycline and topical azelaic acid (AzA) 15% gel in moderate-to-severe papulopustular rosacea and to determine the effect of subsequent maintenance monotherapy with AzA 15% gel alone. In the initial open-label, non-randomized phase of the study, subjects (n=172) received topical AzA 15% gel and oral doxycycline (100 mg), both twice daily, for < or = 12 weeks. In the second, double-blind study phase, subjects who had initially undergone at least four weeks of combination treatment in phase 1 and who achieved > or = 75% inflammatory lesion count reduction (n=136) were randomized to receive either AzA 15% gel or its vehicle twice daily for an additional 24 weeks. Assessments of efficacy were obtained at four-week intervals throughout both phases of the study and included change in inflammatory lesion count, investigator global assessment (IGA) of rosacea severity, and separate assessments of erythema and telangiectasia severity. At the last visit for each phase of the study, the investigator and participant each rated overall improvement, with the participant rating cosmetic acceptability and the investigator rating treatment as "success" or "failure" based on IGA score. During the second phase of the trial, the rate of relapse -- defined as either a 50% deterioration in the lesion count improvement from phase 1, an increase in erythema intolerable to the subject or maintenance therapy failure as judged by the investigator and/or the subject -- was obtained. Safety assessments were conducted for both phases of the study and included analysis of adverse events (AEs) and a rating of cutaneous tolerability by the subject. By week 12 of the open-label phase of the study, 81.4% of subjects had reached a 75% or greater reduction in inflammatory lesion count, and 64% of patients achieved treatment success. During the second study phase (maintenance phase), AzA 15% gel consistently provided a better maintenance response than vehicle, with maintenance of remission in 75% of patients over the six-month duration of the maintenance phase. Additionally AzA 15% gel showed a statistically significantly lower deterioration in absolute inflammatory lesion counts than did vehicle after 8, 16, 20 and 24 weeks of maintenance therapy. No serious treatment-related AEs were encountered in the study, and 98.5% of subjects were satisfied with the local tolerability of both AzA gel and vehicle.

Synthesis and amphiphilic properties of decanoyl esters of tri- and tetraethylene glycol.

PubMed

Zhu, Ying; Molinier, Valérie; Queste, Sébastien; Aubry, Jean-Marie

2007-08-15

Well-defined decanoyl triethylene glycol ester and decanoyl tetraethylene glycol ester were synthesized and compared to their ether counterparts (C(10)E(4) and C(10)E(3)). Their physicochemical properties i.e. critical micelle concentrations (CMC), cloud points, and equilibrium surface tensions were determined. Binary water-surfactant phase behavior was also studied by polarized optical microscopy. The stability of the ester bond was determined by investigating alkaline hydrolysis of the compounds. It was found that CMC, cloud point and equilibrium surface tension are roughly the same for corresponding ethers and esters. In the binary diagram, the esters form only lamellar phases, the area of which is smaller than that of the ether counterparts. These different behaviors can be related to the modification of the molecular conformation induced by the replacement of the ether group by the ester group.

Polybrominated diphenyl ethers and their methoxylated analogs in mullet (Mugil cephalus) and sea bass (Dicentrarchus labrax) from Bizerte Lagoon, Tunisia.

PubMed

Ben Ameur, Walid; Ben Hassine, Sihem; Eljarrat, Ethel; El Megdiche, Yassine; Trabelsi, Souad; Hammami, Bèchir; Barceló, Damià; Driss, Mohamed Ridha

2011-12-01

Concentrations of ten polybrominated diphenyl ethers (PBDEs) and eight methoxylated polybrominated diphenyl ethers (MeO-PBDEs) in mullet (Mugil cephalus) and sea bass (Dicentrarchus labrax) collected from the Bizerte Lagoon and the Mediterranean Sea were investigated. To the best of our knowledge, this is the first report of these compounds in marine fishes from Tunisia. The PBDE mean concentrations in fish from Bizerte Lagoon were 45.3 and 96.2 ng g(-1) lw respectively in mullet and sea bass, while the concentrations of these compounds in mullet and sea bass from Mediterranean Sea were 7.80 and 27.9 ng g(-1) lw respectively. MeO-PBDE concentrations in mullet and sea bass from Bizerte Lagoon ranged from 6.46 to 286 ng g(-1) lw and from 49.4 to 798 ng g(-1) lw respectively, while the concentrations of these compounds in mullet and sea bass from Mediterranean Sea ranged from 190 to 401 ng g(-1) lw and from 353 to 578 ng g(-1) lw respectively. The total PBDEs and total MeO-PBDEs concentration in fish from Bizerte Lagoon were similar or slightly lower than those reported for other species from other locations around the world. Copyright © 2011 Elsevier Ltd. All rights reserved.

Meroterpenoid and diphenyl ether derivatives from Penicillium sp. MA-37, a fungus isolated from marine mangrove rhizospheric soil.

PubMed

Zhang, Yi; Li, Xiao-Ming; Shang, Zhuo; Li, Chun-Shun; Ji, Nai-Yun; Wang, Bin-Gui

2012-11-26

Penicillium sp. MA-37, which was obtained from the rhizospheric soil of the mangrove plant Bruguiera gymnorrhiza, exhibited different chemical profiles in static and shaken fermentation modes. Three new meroterpenoid derivatives, 4,25-dehydrominiolutelide B (1), 4,25-dehydro-22-deoxyminiolutelide B (2), and isominiolutelide A (3), together with three known ones were characterized from its static fermentation, while three new diphenyl ether derivatives, namely, Δ(1('),3('))-1'-dehydroxypenicillide (4), 7-O-acetylsecopenicillide C (5), and hydroxytenellic acid B (6), along with five related metabolites were isolated from the shaken culture. The structures of these compounds were elucidated on the basis of spectroscopic analysis, and the structure of compound 2 was confirmed by X-ray crystallographic analysis. The absolute configurations of 1-3 and 6 were determined by ECD and modified Mosher's method, respectively. All isolated compounds were evaluated for brine shrimp lethality and antibacterial activity.

Occurrence of MTBE and other gasoline oxygenates in CWS source waters

USGS Publications Warehouse

Carter, Janet M.; Grady, Stephen J.; Delzer, Gregory C.; Koch, Bart; Zogorski, John S.

2006-01-01

Results from two national surveys indicate that the gasoline oxygenate methyl tertiary butyl ether (MTBE) is one of the most frequently detected volatile organic compounds in source waters used by community water systems in the United States. Three other ether oxygenates were detected infrequently but almost always co-occurred with MTBE. A random sampling of source waters across the United States found MTBE in almost 9% of samples. In geographic areas with high MTBE use, the compound was detected in 23% of source water samples. Although MTBE concentrations were low (<1 µg/L) in most samples, some concentrations equaled or exceeded the drinking water advisory of 20 µg/L set by the US Environmental Protection Agency. The frequent detection of even low concentrations of MTBE demonstrates the vulnerability of US source waters to anthropogenic compounds, indicating a need to include MTBE in monitoring programs to track the trend of contamination.

Synthesis of Substituted 2,3,5,6-tetraarylbenzo(1,2-b:5,4-b')difurans

NASA Technical Reports Server (NTRS)

Abdul-Aziz, Mahmoud; Auping, Judith V.; Meador, Michael A.

1995-01-01

A series of substituted 2,3,5,6-tetraarylbenzo(l,2-b:5,4-b')difurans 1 was synthesized. This synthesis is based upon the photocyclization of 2,5-dibenzoylresorcinol dibenzyl ethers to the corresponding tetrahydrobenzo(1,2-b:5,4-b')difurans. Treatment of the photoproducts with methanesulfonyl chloride in pyridine afforded 1 in overall yields ranging from 30-72%. A number of these compounds have high fluorescence quantum yields (of phi(sub f) = 0.76-0.90), and their fluorescence spectra exhibit large solvatochromic shifts. These compounds may be suitable for use as fluorescent probes.

Development of many-body polarizable force fields for Li-battery components: 1. Ether, alkane, and carbonate-based solvents.

PubMed

Borodin, Oleg; Smith, Grant D

2006-03-30

Classical many-body polarizable force fields were developed for n-alkanes, perflouroalkanes, polyethers, ketones, and linear and cyclic carbonates on the basis of quantum chemistry dimer energies of model compounds and empirical thermodynamic liquid-state properties. The dependence of the electron correlation contribution to the dimer binding energy on basis-set size and level of theory was investigated as a function of molecular separation for a number of alkane, ether, and ketone dimers. Molecular dynamics (MD) simulations of the force fields accurately predicted structural, dynamic, and transport properties of liquids and unentangled polymer melts. On average, gas-phase dimer binding energies predicted with the force field were between those from MP2/aug-cc-pvDz and MP2/aug-cc-pvTz quantum chemistry calculations.

Regioselective and stereospecific deuteration of bioactive aza compounds by the use of ruthenium nanoparticles.

PubMed

Pieters, Grégory; Taglang, Céline; Bonnefille, Eric; Gutmann, Torsten; Puente, Céline; Berthet, Jean-Claude; Dugave, Christophe; Chaudret, Bruno; Rousseau, Bernard

2014-01-03

An efficient H/D exchange method allowing the deuteration of pyridines, quinolines, indoles, and alkyl amines with D2 in the presence of Ru@PVP nanoparticles is described. By a general and simple procedure involving mild reaction conditions and simple filtration to recover the labeled product, the isotopic labeling of 22 compounds proceeded in good yield with high chemo- and regioselectivity. The viability of this procedure was demonstrated by the labeling of eight biologically active compounds. Remarkably, enantiomeric purity was conserved in the labeled compounds, even though labeling took place in the vicinity of the stereogenic center. The level of isotopic enrichment observed is suitable for metabolomic studies in most cases. This approach is also perfectly adapted to tritium labeling because it uses a gas as an isotopic source. Besides these applications to molecules of biological interest, this study reveals a rich and underestimated chemistry on the surface of ruthenium nanoparticles. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of Perfluorinated Ethers by Solution Phase Direct Fluorination: An Adaptation of the La-Mar Technique

DTIC Science & Technology

1990-08-22

Six of the 3 perfluorinated ethers prepared have been previously synthesized by other methods: perfluoro -5,5-bis(ethoxy- f methyl) -3,7-dioxanonane...from partially fluorinated starting material [34]. Third, as with perfluoroalkanes and simple perfluoroethers , Clark’s experimental results indicated 3...a highly branched perfluoroether ) by direct fluorination 3 in solution. Second, since some of these perfluorinated compounds had been previously

Crystal structure of cis-di­chlorido­(1,4,8,11-tetra­aza­cyclo­tetra­decane-κ4 N)chromium(III) (oxalato-κ2 O 1,O 2)(1,4,8,11-tetra­aza­cyclo­tetra­decane-κ4 N)chromium(III) bis(perchlorate) from synchrotron data

PubMed Central

Moon, Dohyun; Choi, Jong-Ha

2016-01-01

In the asymmetric unit of the title compound, [CrCl2(C10H24N4)][Cr(C2O4)(C10H24N4)](ClO4)2 (C10H24N4 = 1,4,8,11-tetra­aza­cyclo­tetra­decane, cyclam; C2O4 = oxalate, ox), there are two independent halves of the [CrCl2(cyclam)]+ and [Cr(ox)(cyclam)]+ cations, and one perchlorate anion. In the complex cations, which are completed by application of twofold rotation symmetry, the CrIII ions are coordinated by the four N atoms of a cyclam ligand, and by two chloride ions or one oxalate bidentate ligand in a cis arrangement, displaying an overall distorted octa­hedral coordination environment. The Cr—N(cyclam) bond lengths are in the range of 2.075 (5) to 2.096 (4) Å while the Cr—Cl and Cr—O(ox) bond lengths are 2.3358 (14) and 1.956 (4) Å, respectively. Both cyclam moieties adopt the cis-V conformation. The slightly distorted tetra­hedral ClO4 − anion remains outside the coordination sphere. The supra­molecular architecture includes N—H⋯O and N—H⋯Cl hydrogen bonding between cyclam NH donor groups, O atoms of the oxalate ligand or ClO4 − anions and one Cl ligand as acceptors, leading to a three-dimensional network structure. PMID:27746932

The historical significance of anaesthesia events at Pearl Harbor.

PubMed

Crowhurst, Ja

2014-07-01

Up to the end of World War II, less than 10% of the general anaesthetics administered was with intravenous barbiturates. The remaining 90% of anaesthetics given in the USA were with diethyl ether. In the United Kingdom and elsewhere, chloroform was also popular. Diethyl ether administration was a relatively safe and simple procedure, often delegated to nurses or junior doctors with little or no specific training in anaesthesia. During the Japanese attack on the US bases at Pearl Harbor, with reduced stocks of diethyl ether available, intravenous Sodium Pentothal(®), a most 'sophisticated and complex' drug, was used with devastating effects in many of those hypovolaemic, anaemic and septic patients. The hazards of spinal anaesthesia too were realised very quickly. These effects were compounded by the dearth of trained anaesthetists. This paper presents the significance of the anaesthesia tragedies at Pearl Harbor, and the discovery in the next few years of many other superior drugs that caused medical and other health professionals to realise that anaesthesia needed to be a specialist medical discipline in its own right. Specialist recognition, aided by the foundation of the National Health Service in the UK, the establishment of Faculties of Anaesthesia and appropriate training in pharmacology, physiology and other sciences soon followed. Modern anaesthesiology, as we understand it today, was born and a century or more of ether anaesthesia finally ceased.

The combination effect of sodium butyrate and 5-Aza-2'-deoxycytidine on radiosensitivity in RKO colorectal cancer and MCF-7 breast cancer cell lines.

PubMed

Cho, Hang Joo; Kim, Sin Young; Kim, Kee Hwan; Kang, Won Kyung; Kim, Ji Il; Oh, Seong Tack; Kim, Jeong Soo; An, Chang Hyeok

2009-05-21

The overall level of chromatin compaction is an important mechanism of radiosensitivity, and modification of DNA methylation and histone deacetylation may increase radiosensitivity by altering chromatin compaction. In this study, we investigated the effect of a demethylating agent, a histone deacetylase(HDAC) inhibitor, and the two agents combined on radiosensitivity in human colon and breast cancer cell lines. In this study, we used RKO colorectal cancer cell line and MCF-7 breast cancer cell lines and normal colon cell lines. On each of the cell lines, we used three different agents: the HDAC inhibitor sodium butyrate(SB), the demethylating agent 5-Aza-2'-deoxycytidine(5-aza-DC), and radiation. We then estimated the percentage of the cell survival using the XTT method and experimented to determine if there was an augmentation in the therapeutic effect by using different combinations of the two or three of the treatment methods. After treatment of each cell lines with 5-aza-DC, SB and 6 grays of radiation, we observed that the survival fraction was lower after the treatment with 5-aza-DC or SB than with radiation alone in RKO and MCF-7 cell lines(p < 0.001). The survival fraction was lowest when the two agents, 5-aza-DC and SB were combined with radiation in both RKO and MCF-cell lines. In conclusion, 5-aza-DC and SB can enhance radiosensitivity in both MCF-7 and RKO cell lines. The combination effect of a demethylating agent and an HDAC inhibitor is more effective than that of single agent treatment in both breast and colon cancer cell lines.

5-azacytidine promotes microspore embryogenesis initiation by decreasing global DNA methylation, but prevents subsequent embryo development in rapeseed and barley

PubMed Central

Solís, María-Teresa; El-Tantawy, Ahmed-Abdalla; Cano, Vanesa; Risueño, María C.; Testillano, Pilar S.

2015-01-01

Microspores are reprogrammed by stress in vitro toward embryogenesis. This process is an important tool in breeding to obtain double-haploid plants. DNA methylation is a major epigenetic modification that changes in differentiation and proliferation. We have shown changes in global DNA methylation during microspore reprogramming. 5-Azacytidine (AzaC) cannot be methylated and leads to DNA hypomethylation. AzaC is a useful demethylating agent to study DNA dynamics, with a potential application in microspore embryogenesis. This work analyzes the effects of short and long AzaC treatments on microspore embryogenesis initiation and progression in two species, the dicot Brassica napus and the monocot Hordeum vulgare. This involved the quantitative analyses of proembryo and embryo production, the quantification of DNA methylation, 5-methyl-deoxy-cytidine (5mdC) immunofluorescence and confocal microscopy, and the analysis of chromatin organization (condensation/decondensation) by light and electron microscopy. Four days of AzaC treatments (2.5 μM) increased embryo induction, response associated with a decrease of DNA methylation, modified 5mdC, and heterochromatin patterns compared to untreated embryos. By contrast, longer AzaC treatments diminished embryo production. Similar effects were found in both species, indicating that DNA demethylation promotes microspore reprogramming, totipotency acquisition, and embryogenesis initiation, while embryo differentiation requires de novo DNA methylation and is prevented by AzaC. This suggests a role for DNA methylation in the repression of microspore reprogramming and possibly totipotency acquisition. Results provide new insights into the role of epigenetic modifications in microspore embryogenesis and suggest a potential benefit of inhibitors, such as AzaC, to improve the process efficiency in biotechnology and breeding programs. PMID:26161085

In vitro toxicities of experimental jet fuel system ice-inhibiting agents.

PubMed

Geiss, K T; Frazier, J M

2001-07-02

One research emphasis within the Department of Defense has been to seek the replacement of operational compounds with alternatives that pose less potential risk to human and ecological systems. Alternatives to glycol ethers, such as diethylene glycol monomethyl ether (M-DE), were investigated for use as jet fuel system ice-inhibiting agents (FSIIs). This group of chemicals includes three derivatives of 1,3-dioxolane-4-methanol (M-1, M-2, and M-3) and a 1,3-dioxane (M-27). In addition, M-DE was evaluated as a reference compound. Our approach was to implement an in vitro test battery based on primary rat hepatocyte cultures to perform initial toxicity evaluations. Hepatocytes were exposed to experimental chemicals (0, 0.001, 0.01, 0.1, 1, 10 mM dosages) for periods up to 24 h. Samples were assayed for lactate dehydrogenase (LDH) release, MTT dye reduction activity, glutathione level, and rate of protein synthesis as indicators of toxicity. Of the compounds tested, M-1, especially at the 10-mM dose, appeared to be more potent than the other chemicals, as measured by these toxicity assays. M-DE, the current FSII, elicited little response in the toxicity assays. Although some variations in toxicity were observed at the 10-mM dose, the in vitro toxicities of the chemicals tested (except for M-1) were not considerably greater than that of M-DE.

The rationale for advancing the formulation of azelaic acid vehicles.

PubMed

Draelos, Zoe Diana

2006-02-01

When first approved in December 2002, 15% azelaic acid (AzA) gel represented a significant advance over the available 20% AzA cream. Although a smaller amount of AzA was present in the new formulation, the gel medium provided a highly effective system for delivering the active ingredient, thus providing more effective treatment. This article explores the nature of these 2 vehicles and highlights the importance of the formulation in which dermatologic drugs are delivered.

Unveiling the water-associated conformational mobility in the active site of ascorbate peroxidase.

PubMed

Chao, Wei-Chih; Lin, Li-Ju; Lu, Jyh-Feng; Wang, Jinn-Shyan; Lin, Tzu-Chieh; Chen, Yi-Han; Chen, Yi-Ting; Yang, Hsiao-Ching; Chou, Pi-Tai

2018-03-01

We carried out comprehensive spectroscopic studies of wild type and mutants of ascorbate peroxidase (APX) to gain understanding of the conformational mobility of the active site. In this approach, three unnatural tryptophans were applied to replace the distal tryptophan (W41) in an aim to probe polarity/water environment near the edge of the heme-containing active site. 7-azatryptophan ((7-aza)Trp) is sensitive to environment polarity, while 2,7-azatryptophan ((2,7-aza)Trp) and 2,6-diazatryptophan ((2,6-aza)Trp) undergo excited-state water-catalyzed double and triple proton transfer, respectively, and are sensitive to the water network. The combination of their absorption, emission bands and the associated relaxation dynamics of these fluorescence probes, together with the Soret-band difference absorption and resonance Raman spectroscopy, lead us to unveil the water associated conformational mobility in the active site of APX. The results are suggestive of the existence of equilibrium between two different environments surrounding W41 in APX, i.e., the water-rich and water-scant forms with distinct fluorescence relaxation. Our results thus demonstrate for the first time the power of integrating multiple sensors (7-aza)Trp, (2,7-aza)Trp and (2,6-aza)Trp in probing the water environment of a specifically targeted Trp in proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

The efficacy of low dose azathioprine/6-mercaptopurine in patients with inflammatory bowel disease.

PubMed

Kim, Dong Uk; Kim, Young-Ho; Kim, Beom Jin; Chang, Dong Kyung; Son, Hee Jung; Rhee, Poong-Lyul; Kim, Jae J; Rhee, Jong Chul

2009-01-01

Azathioprine (AZA) and 6-mercaptopurine (6-MP) have been widely used in patients with ulcerative colitis (UC) and Crohn's disease (CD). However, some patients cannot tolerate standard doses (2-2.5 mg/kg for AZA or 1-1.5 mg/kg for 6-MP) due to side effects such as leukopenialneutropenia. The aim of this study was to evaluate the efficacy of low dose AZA/6-MP compared to the standard dose. From 1995 to 2005, 122 patients with UC or CD treated with AZA/6-MP at Samsung Medical Center in Korea were enrolled. We divided these patients into 2 groups (standard dose group versus low dose group) according to the maintenance dose. Among the 122 patients, 17 received the standard dose and 105 received a low dose. The mean maintenance doses were 2.25 mg/kg for the standard dose group and 1.35mg/kg for the low dose group. The clinical outcomes of remission induction, maintenance of remission and relapse rate showed no significant difference in comparisons between these two groups. Low dose AZA/6-MP was as effective as the standard dose for remission induction and maintenance of remission in patients with UC and CD. For patients that develop leukopenia/neutropenia during dose escalation, maintenance therapy with low dose AZA/6-MP should be considered.

Local myogenic pulp-derived cell injection enhances craniofacial muscle regeneration in vivo.

PubMed

Jung, J E; Song, M J; Shin, S; Choi, Y J; Kim, K H; Chung, C J

2017-02-01

To enhance myogenic differentiation in pulp cells isolated from extracted premolars by epigenetic modification using a DNA demethylation agent, 5-aza-2'-deoxycytidine (5-Aza), and to evaluate the potent stimulatory effect of 5-Aza-treated pulp cell injection for craniofacial muscle regeneration in vivo. Pulp cells were isolated from premolars extracted for orthodontic purposes from four adults (age range, 18-22.1 years). Levels of myogenic differentiation and functional contraction response in vitro were compared between pulp cells with or without pre-treatment of 5-Aza. Changes in muscle regeneration in response to green fluorescent protein (GFP)-labelled myogenic pulp cell injection in vivo were evaluated using a cardiotoxin (CTX)-induced muscle injury model of the gastrocnemius as well as the masseter muscle in mice. Pre-treatment of 5-Aza in pulp cells stimulated myotube formation, myogenic differentiation in terms of desmin and myogenin expression, and the level of collagen gel contraction. The local injection of 5-Aza pre-treated myogenic pulp cells was engrafted into the host tissue and indicated signs of enhanced muscle regeneration in both the gastrocnemius and the masseter muscles. The epigenetic modification of pulp cells from extracted premolars and the local injection of myogenic pulp cells may stimulate craniofacial muscles regeneration in vivo. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Insights into the Competing Mechanisms and Origin of Enantioselectivity for N-Heterocyclic Carbene-Catalyzed Reaction of Aldehyde with Enamide

PubMed Central

Qiao, Yan; Chen, Xinhuan; Wei, Donghui; Chang, Junbiao

2016-01-01

Hydroacylation reactions and aza-benzoin reactions have attracted considerable attention from experimental chemists. Recently, Wang et al. reported an interesting reaction of N-heterocyclic carbene (NHC)-catalyzed addition of aldehyde to enamide, in which both hydroacylation and aza-benzoin reactions may be involved. Thus, understanding the competing relationship between them is of great interest. Now, density functional theory (DFT) investigation was performed to elucidate this issue. Our results reveal that enamide can tautomerize to its imine isomer with the assistance of HCO3−. The addition of NHC to aldehydes formed Breslow intermediate, which can go through cross-coupling with enamide via hydroacylation reaction or its imine isomer via aza-benzoin reaction. The aza-benzoin reaction requires relatively lower free energy barrier than the hydroacylation reaction. The more polar characteristic of C=N group in the imine isomers, and the more advantageous stereoelectronic effect in the carbon-carbon bond forming transition states in aza-benzoin pathway were identified to determine that the imine isomer can react with the Breslow intermediate more easily. Furthermore, the origin of enantioselectivities for the reaction was explored and reasonably explained by structural analyses on key transition states. The work should provide valuable insights for rational design of switchable NHC-catalyzed hydroacylation and aza-benzoin reactions with high stereoselectivity. PMID:27905524

DIPPR Project 871 For 1995 - Thermodynamic Properties and Ideal-Gas Enthalpies of Formation for Methyl Benzoate, Ethyl Benzoate, (R)-(+)-Limonene, Tert-Amyl Methyl Ether, Trans-Crotonaldehyde, and

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steele, W.V.

2002-07-01

Ideal-gas enthalpies of formation of methyl benzoate, ethyl benzoate, (R)-(+)-limonene, tert-amyl methyl ether, trans-crotonaldehyde, and diethylene glycol are reported. The standard energy of combustion and hence standard enthalpy of formation of each compound in the liquid phase has been measured using an oxygen rotating-bomb calorimeter without rotation. Vapor pressures were measured to a pressure limit of 270 kPa or the lower decomposition point for each of the six compounds using a twin ebulliometric apparatus. Liquid-phase densities along the saturation line were measured for each compound over a range of temperature (ambient to a maximum of 548 K). A differential scanningmore » calorimeter was used to measure two-phase (liquid + vapor) heat capacities for each compound in the temperature region ambient to the critical temperature or lower decomposition point. For methyl benzoate and tert-amyl methyl ether, critical temperatures and critical densities were determined from the DSC results and corresponding critical pressures derived from the fitting procedures. Fitting procedures were used to derive critical temperatures, critical pressures, and critical densities for each of the remaining compounds. The results of the measurements were combined to derive a series of thermophysical properties including critical temperature, critical density, critical pressure, acentric factor, enthalpies of vaporization (restricted to within {+-}50 K of the temperature region of the experimentally determined vapor pressures), and heat capacities along the saturation line. Wagner-type vapor-pressure equations were derived for each compound. All measured and derived values were compared with those obtained in a search of the literature. Recommended critical parameters are listed for each of the compounds studied. Group-additivity parameters, useful in the application of the Benson gas-phase group-contribution correlations, were derived.« less

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

PubMed Central

Sallio, Romain; Lebrun, Stéphane; Capet, Frédéric; Agbossou-Niedercorn, Francine

2018-01-01

A new asymmetric organocatalyzed intramolecular aza-Michael reaction by means of both a chiral auxiliary and a catalyst for stereocontrol is reported for the synthesis of optically active isoindolinones. A selected cinchoninium salt was used as phase-transfer catalyst in combination with a chiral nucleophile, a Michael acceptor and a base to provide 3-substituted isoindolinones in good yields and diastereomeric excesses. This methodology was applied to the asymmetric synthesis of a new pazinaclone analogue which is of interest in the field of benzodiazepine-receptor agonists. PMID:29623121

Synthesis, characterization and electrochemical properties of 5-aza[5]helicene-CH2O-CO-MWCNTs nanocomposite

NASA Astrophysics Data System (ADS)

Fontana, F.; Melone, F.; Iannazzo, D.; Leonardi, S. G.; Neri, G.

2017-03-01

In this study, we report the preparation of a novel nanocomposite, 5-aza[5]helicene-CH2O-CO-MWCNTs, obtained by grafting the 5-aza[5]helicene moiety on the surface of multi-walled carbon nanotubes (MWCNTs). Thermogravimetry (TGA), Fourier transform-infrared spectroscopy (FTIR), ultraviolet (UV), and photoluminescence (PL) measurements provided evidence that the organic moiety is covalently grafted to the MWCNTs. The 5-aza[5]helicene-CH2O-CO-MWCNTs nanocomposite was utilized to fabricate modified commercial screen-printed carbon electrodes. Its electrochemical behavior was studied in neutral buffer solution in the presence of ferricyanide and hydroquinone (HQ). Finally, the electrochemical sensing of epinephrine in the presence of ascorbic acid by using the linear sweep voltammetry (LSV) technique was investigated. Results have demonstrated the enhanced electrocatalytic activity and excellent ability of the 5-aza[5]helicene-CH2O-CO-MWCNTs-modified electrode in the separation between the anodic peaks of epinephrine (EP) and ascorbic acid (AA), even in the presence of a high amount of AA, with a detection limit (S/N = 3) of 5 μmol l-1.

Synthesis of Polyheterocyclic Pyrrolo[3,4-b]pyridin-5-ones via a One-Pot (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization/SN2) Process. A Suitable Alternative towards Novel Aza-Analogues of Falipamil.

PubMed

Zamudio-Medina, Angel; García-González, Ailyn N; Herrera-Carrillo, Genesis K; Zárate-Zárate, Daniel; Benavides-Macías, Adriana; Tamariz, Joaquín; Ibarra, Ilich A; Islas-Jácome, Alejandro; González-Zamora, Eduardo

2018-03-27

We describe the one-pot synthesis of twenty polyheterocyclic pyrrolo[3,4- b ]pyridin-5-ones via a cascade process (Ugi-3CR/aza Diels-Alder/ N -acylation/aromatization) in 20 to 95% overall yields, as well as four pharmacologically promising analogues via an improved cascade process (Ugi-3CR/aza Diels-Alder/ N -acylation/aromatization/S N 2): two piperazine-linked pyrrolo[3,4- b ]pyridin-5-ones in 33 and 34%, and a couple of Falipamil aza-analogues in 30 and 35% overall yields. It is worth highlighting the good substrate scope found, because final products are furnished with alkyl, aryl, and heterocyclic substituents. The use of chain-ring tautomerizable isocyanides (as key reagents for the Ugi-type three component reaction) allowed for a rapid and efficient assembly of the polysubstituted oxindoles, which were used in situ toward the complex products, conferring features like robustness, sustainability, and the one-pot approach to this synthetic methodology.

Anti-inflammatory, gastroprotective, and cytotoxic effects of Sideritis scardica extracts.

PubMed

Tadić, Vanja M; Jeremic, Ivica; Dobric, Silva; Isakovic, Aleksandra; Markovic, Ivanka; Trajkovic, Vladimir; Bojovic, Dragica; Arsic, Ivana

2012-03-01

Sideritis scardica Griseb. (ironwort, mountain tea), an endemic plant of the Balkan Peninsula, has been used in traditional medicine in the treatment of gastrointestinal complaints, inflammation, and rheumatic disorders. This study aimed to evaluate its gastroprotective and anti-inflammatory activities. Besides, continuously increasing interest in assessing the role of the plant active constituents preventing the risk of cancer was a reason to make a detailed examination of the investigated ethanol, diethyl ether, ethyl acetate, and N-butanol extracts regarding cytotoxicity. Oral administration of the investigated extracts caused a dose-dependent anti-inflammatory effect in a model of carrageenan-induced rat paw edema. Gastroprotective activity of the extracts was investigated using an ethanol-induced acute stress ulcer in rats. The cytotoxic activity of plant extracts was assessed on PBMC, B16, and HL-60 cells and compared to the cytotoxicity of phenolic compounds identified in extracts. Apoptotic and necrotic cell death were analyzed by double staining with fluoresceinisothiocyanate (FITC)-conjugated annexin V and PI. The developed HPLC method enabled qualitative fingerprint analysis of phenolic compounds in the investigated extracts. Compared to the effect of the positive control, the anti-inflammatory drug indomethacine (4 mg/kg), which produced a 50 % decrease in inflammation, diethyl ether and N-butanol extracts exhibited about the same effect in doses of 200 and 100 mg/kg (53.6 and 48.7 %; 48.4 and 49.9 %, respectively). All investigated extracts produced dose-dependent gastroprotective activity with the efficacy comparable to that of the reference drug ranitidine. The diethyl ether extract showed significant dose-dependent cytotoxicity on B16 cells and HL-60 cells, decreasing cell growth to 51.3 % and 77.5 % of control, respectively, when used at 100 µg/mL. It seems that phenolic compounds (apigenin, luteolin, and their corresponding glycosides) are responsible for the diethyl ether extract cytotoxic effect. It also appears that induction of oxidative stress might be involved in its cytotoxicity, since B16 and HL-60 cells increased their ROS production in response to treatment with diethyl ether extract. Neither of the tested extracts nor any phenolic compounds showed significant cytotoxic effect to human PBMC. These results demonstrated the potent anti-inflammatory and gastroprotective activities, as well as the promising cytotoxicity. © Georg Thieme Verlag KG Stuttgart · New York.

Application of a source apportionment model in consideration of volatile organic compounds in an urban stream

USGS Publications Warehouse

Asher, W.E.; Luo, W.; Campo, K.W.; Bender, D.A.; Robinson, K.W.; Zogorski, J.S.; Pankow, J.F.

2007-01-01

Position-dependent concentrations of trichloroethylene and methyl-tert-butyl ether are considered for a 2.81-km section of the Aberjona River in Massachusetts, USA. This river flows through Woburn and Winchester (Massachusetts, USA), an area that is highly urbanized, has a long history of industrial activities dating to the early 1800s, and has gained national attention because of contamination from chlorinated solvent compounds in Woburn wells G and H. The river study section is in Winchester and begins approximately five stream kilometers downstream from the Woburn wells superfund site. Approximately 300 toxic release sites are documented in the watershed upstream from the terminus of the study section. The inflow to the river study section is considered one source of contamination. Other sources are the atmosphere, a tributary flow, and groundwater flows entering the river; the latter are categorized according to stream zone (1, 2, 3, etc.). Loss processes considered include outflows to groundwater and water-to-atmosphere transfer of volatile compounds. For both trichloroethylene and methyl-rerf-butyl ether, degradation is neglected over the timescale of interest. Source apportionment fractions with assigned values ??inflow, ??1, ??2, ??3, etc. are tracked by a source apportionment model. The strengths of the groundwater and tributary sources serve as fitting parameters when minimizing a reduced least squares statistic between water concentrations measured during a synoptic study in July 2001 versus predictions from the model. The model fits provide strong evidence of substantial unknown groundwater sources of trichloroethylene and methyl-tert-butyl ether amounting to tens of grams per day of trichloroethylene and methyl-tert-butyl ether in the river along the study section. Modeling in a source apportionment manner can be useful to water quality managers allocating limited resources for remediation and source control. ?? 2007 SETAC.

Isolation and Identification of Active Compounds from Papaya Plants and Activities as Antimicrobial

NASA Astrophysics Data System (ADS)

Prasetya, A. T.; Mursiti, S.; Maryan, S.; Jati, N. K.

2018-04-01

Extraction and isolation of papaya seeds and leaves (Carica papaya L) has been performed using n-hexane and ethanol solvents. Further isolation of the extract obtained using ethyl acetate and diethyl ether solvents. The result of the phytochemical test of papaya extract obtained by mixture of an active compound of flavonoids, alkaloids, tannins, steroids, and saponins. Ethyl acetate isolates containing only flavonoids and diethyl ether isolates contain only alkaloids. Extracts and isolates from papaya plants had gram-positive antibacterial activity greater than the gram-negative bacteria, but both did not have antifungal activity. Papaya extracts have greater antibacterial activity than flavonoid isolates and alkaloid isolates. Strong antibacterial inhibitory sequences are extracts of papaya plants, flavonoid isolates, and alkaloid isolates.

Preliminary report of clinical application of hematoporphyrin monomethyl ether in photodynamic therapy for alimentary cancers

NASA Astrophysics Data System (ADS)

Gu, Ying; Li, Junheng; Xu, De-Yu; Zhang, Zi-Qi; Huang, Yingcai; Wang, Kai

1995-03-01

A new sensitizer, hematoporphyrin monomethyl ether (HMME), purified by the Second Military Medical University was used with a gold vapor laser for PDT in 8 cases of alimentary cancers. The results showed that 2 cases of early stage gastric cancer and 1 case of rectal polyps with malignancy revealed CR, SR was obtained in 1 case of esophageal cancer and 4 others were MR. No sunburn occurred within the 8 patients who received 12 doses of HMME at 5 mg/kg 2 - 3 hours prior to laser treatment and who were kept away from sun light only 6 hours. Hematoporphyrin monomethyl ether is an effective single compound and safer for PDT.

Update 2014: advances to optimize 6-mercaptopurine and azathioprine to reduce toxicity and improve efficacy in the management of IBD.

PubMed

Amin, Jaimin; Huang, Brian; Yoon, Jessica; Shih, David Q

2015-02-01

The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine (AZA), remain as a mainstay therapy in inflammatory bowel disease (IBD). Differences in metabolism of these drugs lead to individual variation in thiopurine metabolite levels that can determine its therapeutic efficacy and development of adverse reactions. In this update, we will review thiopurine metabolic pathway along with the up-to-date approaches in administering thiopurine medications based on the current literature. A search of the PubMed database by 2 independent reviewers identifying 98 articles evaluating thiopurine metabolism and IBD management. Monitoring thiopurine metabolites can assist physicians in optimizing 6-MP and AZA therapy in treating patients with IBD. Of the dosing strategies reviewed, we found evidence for monitoring thiopurine metabolite level, use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of AZA or 6-MP to optimize thiopurine therapy and minimize adverse effects in IBD. Based on the currently available literature, various dosing strategies to improve therapeutic response and reduce adverse reactions can be considered, including use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of thiopurine.

Synthetic bioactive novel ether based Schiff bases and their copper(II) complexes

NASA Astrophysics Data System (ADS)

Shabbir, Muhammad; Akhter, Zareen; Ismail, Hammad; Mirza, Bushra

2017-10-01

Novel ether based Schiff bases (HL1- HL4) were synthesized from 5-chloro-2-hydroxy benzaldehyde and primary amines (1-amino-4-phenoxybenzene, 4-(4-aminophenyloxy) biphenyl, 1-(4-aminophenoxy) naphthalene and 2-(4-aminophenoxy) naphthalene). From these Schiff bases copper(II) complexes (Cu(L1)2-Cu(L4)2)) were synthesized and characterized by elemental analysis and spectroscopic (FTIR, NMR) techniques. The synthesized Schiff bases and copper(II) complexes were further assessed for various biological studies. In brine shrimp assay the copper(II) complexes revealed 4-fold higher activity (LD50 3.8 μg/ml) as compared with simple ligands (LD50 12.4 μg/ml). Similar findings were observed in potato disc antitumor assay with higher activities for copper(II) complexes (IC50 range 20.4-24.1 μg/ml) than ligands (IC50 range 40.5-48.3 μg/ml). DPPH assay was performed to determine the antioxidant potential of the compounds. Significant antioxidant activity was shown by the copper(II) complexes whereas simple ligands have shown no activity. In DNA protection assay significant protection behavior was exhibited by simple ligand molecules while copper(II) complexes showed neutral behavior (neither protective nor damaging).

Molecular Signatures of Methanogens in Cultures and Environmental Samples

NASA Astrophysics Data System (ADS)

Summons, R. E.; Embaye, T.; Jahnke, L. L.; Baumgartner, M.

2002-12-01

The core lipids of methanogens comprise C20 and C40 isoprenoid chains, linked through ether bonds to glycerol. Additional structural diversity is encoded into the polar head groups that are attached to the glycerol ether cores. These compounds are potentially very useful as taxonomic markers in microbial mats and other environmental samples while the nature of the hydrocarbon chains provide a means to identify methanogenic inputs to ancient sediments. The structural diversity of methanogen polar lipids is most valuable when it can be directly correlated to 16S rRNA phylogeny. On the other hand, this diversity can also leads to analytical challenges because there is no single approach that works for all structural types. While some intact methanogen lipids have been identified using mass spectrometry and NMR spectroscopy, the most common means of analysing the lipid cores involves cleavage of the ether bonds using HI and subsequent reduction of the alkyl iodides to hydrocarbons with LiAlH4. One class of methanogenic lipids, the 3?-hydroxyarchaeols, escaped detection for some years because strong acid treatments in the analysis protocols destroyed hydroxyl-containing isoprenoid chains. We have been systematically re-examining the lipids of methanogens, using milder procedures involving weak acid hydrolysis of polar head groups, derivatisation to form trimethylsilyl ethers and analysis by GC-MS. As well as archaeol, sn-2- and sn-3-hydroxyarchaeol, we have tentatively identified a dihydroxyarchaeol in several Methanococcus sp. For Methanococcus thermolithotrophicus an analysis of the total lipid extracts using BBr3 as an ether cleavage reagent followed by LiBEt3H, reduction revealed a very complex mixture consisting of phytane, phytenes, biphytane, biphytenes and a suite of related alcohols. The latter compounds were analysed by GC-MS as their trimethylsilyl ethers and found to comprise a mixture tentatively identified as phytan-N-ol and biphytan-N-ol where N= 3 or 7 or 11 or 15. Apart from phytan-3-ol, these compounds appear to have been overlooked in previous analyses of methanogen lipids. Methanopyrus kandleri, a hyperthermophile that is distinguished from other methanogens by some unusual biochemical features, is also differentiated by having biphytanyl chains with cyclopentane rings. This is a structural feature more commonly found in the Crenarchaeota. We are applying this biomarker methodology to environmental samples in studies of the spatial distribution of methanogenesis relative to other physiologies.

Combination of three metals for the treatment of cancer: gallium, rhenium and platinum. 1. Determination of the optimal schedule of treatment.

PubMed

Collery, Philippe; Mohsen, Ahmed; Kermagoret, Anthony; D'Angelo, Jean; Morgant, Georges; Desmaele, Didier; Tomas, Alain; Collery, Thomas; Wei, Ming; Badawi, Abdelfattah

2012-07-01

Platinum is well known for its anticancer activity, firstly used as cis-diaminedichloroplatinum (II) (CDDP), with a wide range of activity. Its main mechanism of action involves its binding to DNA. Gallium, another metal, has also demonstrated apoptotic effects on malignant cells, but through interaction with targets other than DNA, such as the membrane, cytoskeleton and proteasome, and on enzyme activities. An antitumor synergism between CDDP and both gallium and rhenium compounds has been demonstrated. For these reasons, we proposed to combine these three metals and to determine at which doses each compound could be administered without major toxicity. CDDP, tetrakis(1-octanol) tris(5-aminosalicylate)gallium(III), and a diseleno-ether rhenium(I) complex were used in this experimental study in breast cancer MCF-7 tumor-bearing mice. CDDP was administered intraperitoneally (i.p.) twice a week at the dose of 3 mg/kg. Tetrakis(1-octanol) tris(5-aminosalicylate) gallium (III) and rhenium(I) diseleno-ether complexes were administered orally, daily, five days a week for three weeks, at doses ranging from 20 to 100 mg/kg for the gallium compound and from 10 to 50 mg/kg for the rhenium compound. Doses of 10 mg/kg of rhenium(I) diseleno-ether, and 100 mg/kg of the salicylate gallium compound, in combination with CDDP induced a significant decrease of 50% of the tumor volume, by comparison with the control group. In contrast, the decrease of the tumor volume in mice treated by CDDP alone was less than 25%. Changes in the sequence of administration of the three metals will be discussed to improve the therapeutic index.

Sorption and biodegradation of organic micropollutants during river bank filtration: a laboratory column study.

PubMed

Bertelkamp, C; Reungoat, J; Cornelissen, E R; Singhal, N; Reynisson, J; Cabo, A J; van der Hoek, J P; Verliefde, A R D

2014-04-01

This study investigated sorption and biodegradation behaviour of 14 organic micropollutants (OMP) in soil columns representative of the first metre (oxic conditions) of the river bank filtration (RBF) process. Breakthrough curves were modelled to differentiate between OMP sorption and biodegradation. The main objective of this study was to investigate if the OMP biodegradation rate could be related to the physico-chemical properties (charge, hydrophobicity and molecular weight) or functional groups of the OMPs. Although trends were observed between charge or hydrophobicity and the biodegradation rate for charged compounds, a statistically significant linear relationship for the complete OMP mixture could not be obtained using these physico-chemical properties. However, a statistically significant relationship was obtained between biological degradation rates and the OMP functional groups. The presence of ethers and carbonyl groups will increase biodegradability, while the presence of amines, ring structures, aliphatic ethers and sulphur will decrease biodegradability. This predictive model based on functional groups can be used by drinking water companies to make a first estimate whether a newly detected compound will be biodegraded during the first metre of RBF or that additional treatment is required. In addition, the influence of active and inactive biomass (biosorption), sand grains and the water matrix on OMP sorption was found to be negligible under the conditions investigated in this study. Retardation factors for most compounds were close to 1, indicating mobile behaviour of these compounds during soil passage. Adaptation of the biomass towards the dosed OMPs was not observed for a 6 month period, implying that new developed RBF sites might not be able to biodegrade compounds such as atrazine and sulfamethoxazole in the first few months of operation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bacterial Utilization of Ether Glycols

PubMed Central

Fincher, Edward L.; Payne, W. J.

1962-01-01

A soil bacterium capable of using oligo- and polyethylene glycols and ether alcohols as sole sources of carbon for aerobic growth was isolated. The effects of substituent groups added to the ether bonds on the acceptability of the compounds as substrates were studied. Mechanisms for the incorporation of two-carbon compounds were demonstrated by the observation that acetate, glyoxylate, ethylene glycol, and a number of the tricarboxylic acid cycle intermediates served as growth substrates in minimal media. The rate of oxidation of the short-chained ethylene glycols by adapted resting cells varied directly with increasing numbers of two-carbon units in the chains from one to four. The amount of oxygen consumed per carbon atom of oligo- and polyethylene glycols was 100% of theoretical, but only 67% of theoretical for ethylene glycol. Resting cells oxidized oligo- and polyethylene glycols with 2 to 600 two-carbon units in the chains. Longer chained polyethylene glycols (up to 6,000) were oxidized at a very slow rate by these cells. Dehydrogenation of triethylene glycol by adapted cells was observed, coupling the reaction with methylene blue reduction. PMID:13945208

Conformational Study of Dibenzyl Ether

NASA Astrophysics Data System (ADS)

Hernandez-Castillo, Alicia O.; Abeysekera, Chamara; Hewett, Daniel M.; Zwier, Timothy S.

2017-06-01

Understanding the initial stages of polycyclic aromatic hydrocarbon (PAH) aggregation, the onset of soot formation, is an important goal on the pathway to cleaner combustion processes. PAHs with short alkyl chains, present in fuel-rich combustion environments, can undergo reactions that will chemically link aromatic rings together. One such example of a linked diaryl compound is dibenzyl ether, C_{6}H_{5}-CH_{2}-O-CH_{2}-C_{6}H_{5}. The -CH_{2}-O-CH_{2}- linkage has a length and flexibility well-suited to forming a π-stacked conformation between the two phenyl rings. In this talk, we will explore the single-conformation spectroscopy of dibenzyl ether under jet-cooled conditions in the gas phase. Laser-induced fluorescence, chirped pulse Fourier transform microwave (8-18 GHz region), and single-conformation infrared spectroscopy in the alkyl CH stretch region were all carried out on the molecule, thereby interrogating its full array of electronic, vibrational and rotational degrees of freedom. This work is the first step in a broader study to determine the extent of π-stacking in linked aryl compounds as a function of linkage and PAH size.

Antifungal activity from polar and non-polar extracts of some Chenopodiaceae wild species growing in Tunisia.

PubMed

Boughalleb, N; Trabelsi, L; Harzallah-Skhiri, F

2009-01-01

Nine plants belonging to Chenopodiaceae family were collected around salt marshes near Monastir, located in the east Mediterranean coast of Tunisia. They were tested for their antifungal activities against six plant pathogenic fungi: Botrytis cinerea, Fusarium oxysporum f. sp. niveum, F. solani f. sp. cucurbitae, Phytophthora cactorum, Rhizoctonia solani and Nattrassia mangiferae. Data of this study showed that the highest inhibition of Botrytis cinerea growth was observed with the petroleum ether extract of Atriplex inflata fruits (F) (24.5 mm). The in vitro growth of F. oxysporum f. sp. niveum was reduced only with A. inflata whole plant (WP) petroleum ether extract (32.3 mm). The most important inhibition zones were obtained against F. solani f. sp. cucurbitae with Atriplex semibaccata methanol and acetone extracts (34.7 and 31.0 mm, respectively). This work revealed that fungitoxic compounds were probably present in the petroleum ether extract obtained from A. portulacoides (WP), since it has suppressed the growth of F. s. cucurbitae. Our investigation proved that many Chenopodiaceae species adapted to saline soils may contain phytochemical compounds with fungicidal properties.

Alkali metal cation complexation by 1,3-alternate, mono-ionisable calix[4]arene-benzocrown-6 compounds

DOE PAGES

Surowiec, Malgorzata A.; Custelcean, Radu; Surowiec, Kazimierz; ...

2014-04-23

Alkali metal cation extraction behavior for two series of 1,3-alternate, mono-ionizable calix[4]arene-benzocrown-6 compounds is examined. In Series 1, the proton-ionizable group is a substituent on the benzo group of the polyether ring that directs it away from the crown ether cavity. In Series 2, the proton-ionizable group is attached to one para position in the calixarene framework, thus positioning it over the crown ether ring. Competitive solvent extraction of alkali metal cations from aqueous solutions into chloroform shows high Cs+ efficiency and selectivity. Single-species extraction pH profiles of Cs+ for Series 1 and 2 ligands with the same proton-ionizable groupmore » are very similar. Thus, association of Cs+ with the calixcrown ring is more important than the the proton-ionizable group’s position in relation to the crown ether cavity. Solid-state structures are presented for two unionized ligands from Series 2, as is a crystal containing two different ionized ligand–Cs+ complexes.« less

[Chemical constituents of Swertia macrosperma].

PubMed

Wang, Hongling; Geng, Changan; Zhang, Xuemei; Ma, Yunbao; Jiang, Zhiyong; Chen, Jijun

2010-12-01

To study the chemical constituents of Swertia macrosperma. The air-dried whole plants of Swertia macrosperma were extracted with boiling water. The extract was concentrated to a small amount of volume and extracted with petroleum ether, EtOAc and n-BuOH, successively. The compounds were isolated and purified by column chromatography from the EtOAc fraction, and identified based on spectral analyses (MS, 1H-NMR, 13C-NMR). Thirteen compounds were isolated from S. macrosperma, and were characterized as norbellidifolin (1), 1-hydroxy-3,7, 8-trimethoxy-xanthone (2), norswertianolin (3), swertianolin (4), 1,3,7,8-tetrahydroxyxanthone-8-O-beta-D-glucopyranoside (5), swertiamatin (6), decentapicrin (7), coniferl aldehyde (8), sinapaldehyde (9), balanophonin (10), together with beta-sitosterol, daucosterol, and oleanolic acid . Compounds 2, 4-10 were obtained from Swertia macrosperma for the first time.

Tautomerism provides a molecular explanation for the mutagenic properties of the anti-HIV nucleoside 5-aza-5,6-dihydro-2'-deoxycytidine.

PubMed

Li, Deyu; Fedeles, Bogdan I; Singh, Vipender; Peng, Chunte Sam; Silvestre, Katherine J; Simi, Allison K; Simpson, Jeffrey H; Tokmakoff, Andrei; Essigmann, John M

2014-08-12

Viral lethal mutagenesis is a strategy whereby the innate immune system or mutagenic pool nucleotides increase the error rate of viral replication above the error catastrophe limit. Lethal mutagenesis has been proposed as a mechanism for several antiviral compounds, including the drug candidate 5-aza-5,6-dihydro-2'-deoxycytidine (KP1212), which causes A-to-G and G-to-A mutations in the HIV genome, both in tissue culture and in HIV positive patients undergoing KP1212 monotherapy. This work explored the molecular mechanism(s) underlying the mutagenicity of KP1212, and specifically whether tautomerism, a previously proposed hypothesis, could explain the biological consequences of this nucleoside analog. Establishing tautomerism of nucleic acid bases under physiological conditions has been challenging because of the lack of sensitive methods. This study investigated tautomerism using an array of spectroscopic, theoretical, and chemical biology approaches. Variable temperature NMR and 2D infrared spectroscopic methods demonstrated that KP1212 existed as a broad ensemble of interconverting tautomers, among which enolic forms dominated. The mutagenic properties of KP1212 were determined empirically by in vitro and in vivo replication of a single-stranded vector containing a single KP1212. It was found that KP1212 paired with both A (10%) and G (90%), which is in accord with clinical observations. Moreover, this mutation frequency is sufficient for pushing a viral population over its error catastrophe limit, as observed before in cell culture studies. Finally, a model is proposed that correlates the mutagenicity of KP1212 with its tautomeric distribution in solution.

Geissoschizine methyl ether N-oxide, a new alkaloid with antiacetylcholinesterase activity from Uncaria rhynchophylla.

PubMed

Jiang, Wei-Wei; Su, Jia; Wu, Xing-De; He, Juan; Peng, Li-Yan; Cheng, Xiao; Zhao, Qin-Shi

2015-01-01

Geissoschizine methyl ether N-oxide, a new oxindole alkaloid, along with 14 known alkaloids, was isolated from the aerial part of Uncaria rhynchophylla. Their structures were identified by comprehensive spectral methods, including 2D NMR experiments, and confirmed by comparing with the literature data. In vitro acetylcholinesterase (AChE) inhibitory activity assay showed that the new compound exhibited anti-AChE activity with IC₅₀ value of 23.4 μM.

Modifying effects of 5-azacytidine on metal-containing proteins profile in Guerin carcinoma with different sensitivity to cytostatics.

PubMed

Chekhun, V F; Lozovska, Y V; Naleskina, L A; Borikun, T V; Burlaka, A P; Todor, I N; Demash, D V; Yalovenko, T M; Zadvornyi, T V; Pavlova, A O; Storchay, D M; Lukianova, N Yu

2016-12-01

To assess the influence of the treatment with 5-azacytidine (5-aza) on the profile of metal-containing proteins and factors of their regulation in Guerin carcinoma cells in vivo. The study was conducted on Wistar rats transplanted with wild-type Guerin carcinoma (Guerin/WT) and its strains resistant to cisplatin (Guerin/CP) or doxorubicin (Guerin/Dox). Animals were distributed in 6 groups treated with 5-aza and control animals without treatment. 5-Aza was injected by i.v. route (1 injection in 4 days at a dose of 2 mg/kg starting from the 4 th day after tumor transplantation, 4 injections in total). Ferritin levels in blood serum and tumor tissue were measured by ELISA, transferrin and free iron complexes - by low-temperature EPR, miRNA-200b, -133a and -320a levels and promoter methylation - by real-time quantitative reverse transcription polymerase chain reaction. The study has shown that 5-aza treatment caused demethylation of promoter regions of fth1 and tfr1 genes in all studied Guerin carcinoma strains. 5-Aza treatment resulted in a significant decrease of ferritin levels in tumor tissue (by 32.1% in Guerin/WT strain, by 29.8% in Guerin/Dox and by 69.1% in Guerin/CP). These events were accompanied by 3.5-fold and 2-fold increase of free iron complexes levels in tumor tissue of doxorubicin and cisplatin resistant strains, respectively. Also, 5-aza treatment resulted in significantly elevated levels of miR-200b, -133a, 320a expression in tumor tissue. After 5-aza treatment, ferritin levels in blood serum of animals with Guerin/Dox were increased by 23.9%, while in Guerin/Wt and Guerin/CP they were decreased by 17 and 16%, respectively. Alterations of epigenetic regulation upon in vivo treatment with 5-aza change the levels of metal-containing proteins due to DNA demethylation and altered miRNA expression profiles in Guerin carcinoma cells.

Flavonoids and stilbenoids from Derris eriocarpa.

PubMed

Zhang, Hong-Xia; Lunga, Paul-Keilah; Li, Zhi-Jian; Dai, Qin; Du, Zhi-Zhi

2014-06-01

One new resveratrol analogue, 1-(3',4',5'-trimethoxyphenyl)-2-methoxy-2-(4″-methoxyphenyl)-ethane-1-ol (1), and two new prenylisoflavones, 4'-hydroxy-5,7-dimethoxy-6-(3-methyl-2-butenyl)-isoflavone (2), and derrubon 5-methyl ether (3), together with 17 known compounds including one new natural product, 5,7-dihydroxy-3-[4'-O-(3-methyl-2-butenyl)-phenyl]-isoflavone (4), were isolated from the stems of ethnomedicinal plant Derris eriocarpa How. (Leguminosae). Their structures were elucidated based on chemical evidence and spectroscopic techniques including two-dimensional NMR methods. All compounds are reported from this species for the first time. Antimicrobial activities of the new compounds were evaluated. Compound 2 exhibited good inhibitory activities against Candida guilliermondii, C. albicans and Microsporium gypseum with the minimal inhibitory concentration (MIC) values of 12.5 μg/ml. Copyright © 2014 Elsevier B.V. All rights reserved.

Three-dimensional collagenous niche and azacytidine selectively promote time-dependent cardiomyogenesis from human bone marrow-derived MSC spheroids.

PubMed

Joshi, Jyotsna; Mahajan, Gautam; Kothapalli, Chandrasekhar R

2018-04-17

Endogenous adult cardiac regenerative machinery is not capable of replacing the lost cells following myocardial infarction, often leading to permanent alterations in structure-function-mechanical properties. Regenerative therapies based on delivering autologous stem cells within an appropriate 3D milieu could meet such demand, by enabling homing and directed differentiation of the transplanted cells into lost specialized cell populations. Since type I collagen is the predominant cardiac tissue matrix protein, we here optimized the 3D niche which could promote time-dependent evolution of cardiomyogenesis from human bone marrow-derived mesenchymal stem cells (BM-MSC). 3D collagen gel physical and mechanical characteristics were assessed using SEM and AFM, respectively, while the standalone and combined effects of collagen concentration, culture duration, and 5-azacytidine (aza) dose on the phenotype and genotype of MSC spheroids were quantified using immunofluorescence labeling and RT-PCR analysis. Increasing collagen concentration led to a significant increase in Young's modulus (p < 0.01) but simultaneous decrease in the mean pore size, resulting in stiffer gels. Spheroid formation significantly modulated MSC differentiation and genotype, mostly due to better cell-cell interactions. Among the aza dosages tested, 10 μM appears to be optimal, while 3 mg/ml gels resulted in significantly lower cell viability compared to 1 or 2 mg/ml gels. Stiffer gels (2 and 3 mg/ml) and exposure to 10 μM aza upregulated early and late cardiac marker expressions in a time-dependent fashion. On the other hand, cell-cell signaling within the MSC spheroids seem to have a strong role in influencing mature cardiac markers expression, since neither aza nor gel stiffness seem to significantly improve their expression. Western blot analysis suggested that canonical Wnt/β-catenin signaling pathway might be primarily mediating the observed benefits of aza on cardiac differentiation of MSC spheroids. In conclusion, 2 mg/ml collagen and 10 μM aza appears to offer optimal 3D microenvironment in terms of cell viability and time-dependent evolution of cardiomyogenesis from human BM-MSCs, with significant applications in cardiac tissue engineering and stem cell transplantation for regenerating lost cardiac tissue. © 2018 Wiley Periodicals, Inc.

Drug May Help Prevent Resistance to Toxin-Based Leukemia Therapy

Cancer.gov

Adding the drug 5-AZA to moxetumomab pasudotox, a toxin-based cancer drug, may improve its efficacy in acute lymphoblastic leukemia (ALL). As this Cancer Currents blog post explains, in mice, both drugs were more effective than moxetumomab alone.

CHLORINATED SOLVENT PLUME CONTROL

EPA Science Inventory

This lecture will cover recent success in controlling and assessing the treatment of shallow ground water plumes of chlorinated solvents, other halogenated organic compounds, and methyl tert-butyl ether (MTBE).

ON EXTRACELLULAR AND INTRACELLULAR VENOM ACTIVATORS OF THE BLOOD, WITH ESPECIAL REFERENCE TO LECITHIN AND FATTY ACIDS AND THEIR COMPOUNDS.

PubMed

Noguchi, H

1907-07-17

In normal serums of the majority of mammalian and avian blood there exists certain substances capable of activating venom haemolysin. They are extractable from serum by means of ether, and are capable of conferring upon the originally non-activating serum a power to activate venom, when mixed with the latter. The ethereal extract consists of fatty acids, neutral fats and possibly also some ether soluble organic soaps. The fatty acids and soaps, especially of the oleinic series, acquire certain characteristics of complements in general, when they are mixed with serum. They are inactive without the venom in the mixture; they are inactivable with calcium chloride; they exhibit a tendency to go off in activity with age; they are inactive or only weakly active at 0 degrees C., and they are extractable by ether. In testing the serum from which the ether soluble substances are removed, it is found that no venom activating property is left. Warm alcoholic extraction of such serum yields, however, a large quantity of lecithin. In the case of non-activating serums no venom activating fats appear in the ethereal extract. Lecithin exists in such serum in no less quantity than in the activating kind. The addition of oleinic acid or its soluble soaps to a non-activating serum, in a ratio which corresponds to the percentage of fatty acids or soaps contained in some of the easily activating serums, will make the serum highly active in regard to venom. In normal serum of dog there exists, besides the group of activators already mentioned, another kind of venom activators which has been identified as a lecithin compound acting in the manner of free lecithin. A very sharp differentiation of the haemolysis produced by this activator and by the other groups of activators is obtained by means of calcium chloride, which is powerless against lecithin or lecithin compounds, but effective in removing the action of the latter. This lecithin containing proteid can be precipitated by half saturation with ammonium sulphate, but is perfectly soluble in water, and is not coagulated in neutral alkaline salt solutions upon boiling. Alcohol precipitates a proteid-like coagulum and extracts lecithin from it; ether does not extract lecithin from this compound. Non-activating serums do not contain any such lecithin compound. Lecithin contained in other serum proteids, mainly as lecithalbumin, and perhaps as contained in globulin, is not able to activate venom. This is true of all the serums with which I worked; it matters not whether these fractions (obtained with ammonium sulphate) belong to the most activating serum (dog) or to the non-activating serum (ox). The non-coagulable portion of all heated serum contains a venom activator of the nature of lecithin. This activator is contained in a non-coagulable proteid described by Howell which is identical with Chabrie's albumon. As there is no ether-extractable lecithin in this portion of the serum, the activating property of heated serum must be due to this proteid compound of lecithin. That this lecithin proteid does not pre-exist in normal serum but is produced by the action of high temperature is true of all serums except that of the dog. In venom activation we know now that lecithin becomes reactive with venom when it is transformed from other proteid compounds into the non-coagulable form, the albumon. Howell's view of the non-existence of the non-coagulable proteid in normal serum seems to receive a biological support from venom haemolysis. Ovovitellin derived from hen's egg is one of the best venom activators of the lecithin proteid type. The cause of venom susceptibility of various kinds of blood corpuscles does not depend upon the existence of lecithin in the corpuscles, but solely upon the amount of fatty acids, and perhaps, also, soaps and fats, contained in the corpuscles. The protection which calcium chloride gives against venom haemolysis is proof of the absence of lecithin activation. From the stroma of susceptible corpuscles fatty acids or some fats can be extracted with ether. After ethereal extraction the stroma becomes non-activating, while the extract contains fatty acids and some soaps or fats, which when added to venom-resistant corpuscles render the latter vulnerable to venom. The corpuscular solution of non-activating corpuscles does not contain enough fatty acids. The larger the amount of fatty acids and soaps in the corpuscles, the easier the cells undergo venom haemolysis. Lecithin exists in the strorna of all kinds of corpuscles, but in a form unavailable for venom activation. The somatic cytolytic processes caused by venom requires intracellular complements. The experiments performed on the cells of liver, kidney, testis and brain of the guinea-pig and rat indicate that the substances which act as complements are inactivable by calcium chloride.

Production of Jet Fuel-Range Hydrocarbons from Hydrodeoxygenation of Lignin over Super Lewis Acid Combined with Metal Catalysts

DOE PAGES

Wang, Hongliang; Wang, Huamin; Kuhn, Eric; ...

2017-11-14

Super Lewis acids containing the triflate anion [e.g., Hf(OTf) 4, Ln(OTf) 3, In(OTf) 3, Al(OTf) 3] and noble metal catalysts (e.g., Ru/C, Ru/Al2O 3) formed efficient catalytic systems to generate saturated hydrocarbons from lignin in high yields. In such catalytic systems, the metal triflates mediated rapid ether bond cleavage through selective bonding to etheric oxygens while the noble metal catalyzed subsequent hydrodeoxygenation (HDO) reactions. Near theoretical yields of hydrocarbons were produced from lignin model compounds by the combined catalysis of Hf(OTf)4 and ruthenium-based catalysts. When a technical lignin derived from a pilot-scale biorefinery was used, more than 30 wt %more » of the hydrocarbons produced with this catalytic system were cyclohexane and alkylcyclohexanes in the jet fuel range. Super Lewis acids are postulated to strongly interact with lignin substrates by protonating hydroxyl groups and ether linkages, forming intermediate species that enhance hydrogenation catalysis by supported noble metal catalysts. Meanwhile, the hydrogenation of aromatic rings by the noble metal catalysts can promote oxygenation reactions catalyzed by super Lewis acids.« less

Production of Jet Fuel-Range Hydrocarbons from Hydrodeoxygenation of Lignin over Super Lewis Acid Combined with Metal Catalysts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Hongliang; Wang, Huamin; Kuhn, Eric

Super Lewis acids containing the triflate anion [e.g., Hf(OTf) 4, Ln(OTf) 3, In(OTf) 3, Al(OTf) 3] and noble metal catalysts (e.g., Ru/C, Ru/Al2O 3) formed efficient catalytic systems to generate saturated hydrocarbons from lignin in high yields. In such catalytic systems, the metal triflates mediated rapid ether bond cleavage through selective bonding to etheric oxygens while the noble metal catalyzed subsequent hydrodeoxygenation (HDO) reactions. Near theoretical yields of hydrocarbons were produced from lignin model compounds by the combined catalysis of Hf(OTf)4 and ruthenium-based catalysts. When a technical lignin derived from a pilot-scale biorefinery was used, more than 30 wt %more » of the hydrocarbons produced with this catalytic system were cyclohexane and alkylcyclohexanes in the jet fuel range. Super Lewis acids are postulated to strongly interact with lignin substrates by protonating hydroxyl groups and ether linkages, forming intermediate species that enhance hydrogenation catalysis by supported noble metal catalysts. Meanwhile, the hydrogenation of aromatic rings by the noble metal catalysts can promote oxygenation reactions catalyzed by super Lewis acids.« less

Production of Jet Fuel-Range Hydrocarbons from Hydrodeoxygenation of Lignin over Super Lewis Acid Combined with Metal Catalysts.

PubMed

Wang, Hongliang; Wang, Huamin; Kuhn, Eric; Tucker, Melvin P; Yang, Bin

2018-01-10

Super Lewis acids containing the triflate anion [e.g., Hf(OTf) 4 , Ln(OTf) 3 , In(OTf) 3 , Al(OTf) 3 ] and noble metal catalysts (e.g., Ru/C, Ru/Al 2 O 3 ) formed efficient catalytic systems to generate saturated hydrocarbons from lignin in high yields. In such catalytic systems, the metal triflates mediated rapid ether bond cleavage through selective bonding to etheric oxygens while the noble metal catalyzed subsequent hydrodeoxygenation (HDO) reactions. Near theoretical yields of hydrocarbons were produced from lignin model compounds by the combined catalysis of Hf(OTf) 4 and ruthenium-based catalysts. When a technical lignin derived from a pilot-scale biorefinery was used, more than 30 wt % of the hydrocarbons produced with this catalytic system were cyclohexane and alkylcyclohexanes in the jet fuel range. Super Lewis acids are postulated to strongly interact with lignin substrates by protonating hydroxyl groups and ether linkages, forming intermediate species that enhance hydrogenation catalysis by supported noble metal catalysts. Meanwhile, the hydrogenation of aromatic rings by the noble metal catalysts can promote deoxygenation reactions catalyzed by super Lewis acids. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Spectroscopic and molecular modeling approaches to investigate the interaction of bisphenol A, bisphenol F and their diglycidyl ethers with PPARα.

PubMed

Zhang, Jie; Zhang, Tiehua; Guan, Tianzhu; Ruan, Ping; Ren, Dayong; Dai, Weichang; Yu, Hansong; Li, Tiezhu

2017-08-01

A fluorescence polarization (FP) assay for the simultaneous determination of bisphenol A (BPA), bisphenol F (BPF), bisphenol A diglycidyl ether (BADGE) and bisphenol F diglycidyl ether (BFDGE) was developed. The method was based on the competition between bisphenols (BPs) and fluorescein-labeled dexamethasone derivative (Dex-fl) for mouse peroxisome proliferator-activated receptor α ligand binding domain (mPPARα-LBD). A recombinant soluble protein derivative mPPARα-LBD* was prepared, then in vitro binding of 4 BPs to mPPARα-LBD* was investigated. Fluorescence polarization assay showed that these compounds exhibited different binding potencies with mPPARα-LBD*. Additionally, molecular dynamics simulations were performed to further understand the mechanism of BPs binding affinity for mPPARα-LBD*. Docking results elucidated that the driving forces for the binding of BPs to mPPARα-LBD* were predominantly dependent on hydrophobic and hydrogen-bonding interactions. Comparison of the calculated binding energies vs. experimental binding affinities yielded a good correlation (R 2  = 0.7258). The proposed method has potential for multi-residue detection of BPA, BPF, BADGE, and BFDGE. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sesquiterpene amino ether and cytotoxic phenols from Dendrobium wardianum Warner.

PubMed

Zhang, Cong; Liu, Shou-Jin; Yang, Liu; Yuan, Ming-Yan; Li, Jin-Yu; Hou, Bo; Li, Hong-Mei; Yang, Xing-Zhi; Ding, Chang-Chun; Hu, Jiang-Miao

2017-10-01

A new bibenzyl derivative, dendrocandin V (1) and a new sesquiterpene amino ether, wardianumine A (2), together with eleven known compounds, including phenanthrenes (denbinobin (3), 9,10-dihydro-denbinobin (4), mostatin (5), loddigesiinols A (6)), bibenzyls (moscatilin (7), 5-hydroxy-3,4'-dimethoxybibenzyl (8), 3,4-dihydroxy-5,4'-dimethoxy bibenzyl (9), dendrocandin A (10), gigantol (11), dendrocandin U (12)) and an alkaloids (dihydroshihunine, 13) were isolated from the EtOH extraction of stems of Dendrobium wardianum Warner. Isolation of the new compound 2 indicated that N,N-dimethylethanolamine as the key adduction in the synthesis of dendroxine and its analogs in Dendrobium species. The hypothetical biosynthetic pathway of 2 was then postulated. Inspired by literature and traditional usage of the herbal medicine, some compounds were sent for cytotoxic activity and the results indicated that compounds 1, 3, 4, 5 showed cytotoxic activities against five human cancer cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW-480) with IC50 from 2.33-38.48μM. Among those compounds, 3 and 4 showed cell line selectivity with strong activity comparable to DDP. Copyright © 2017. Published by Elsevier B.V.

Voltammetric studies of Azathioprine on the surface of graphite electrode modified with graphene nanosheets decorated with Ag nanoparticles.

PubMed

Asadian, Elham; Iraji Zad, Azam; Shahrokhian, Saeed

2016-01-01

By using graphene nanosheets decorated with Ag nanoparticles (AgNPs-G) as an effective approach for the surface modification of pyrolytic graphite electrode (PGE), a sensing platform was fabricated for the sensitive voltammetric determination of Azathioprine (Aza). The prepared AgNPs-G nanosheets were characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), UV-vis and Raman spectroscopy techniques. The electrochemical behavior of Aza was investigated by means of cyclic voltammetry. Comparing to the bare PGE, a remarkable enhancement was observed in the response characteristics of Aza on the surface of the modified electrode (AgNPs-G/PGE) as well as a noticeable decrease in its reduction overpotential. These results can be attributed to the incredible enlargement in the microscopic surface area of the electrode due to the presence of graphene nanosheets together with strong adsorption of Aza on its surface. The effect of experimental parameters such as accumulation time, the amount of modifier suspension and pH of the supporting electrolyte were also optimized toward obtaining the maximum sensitivity. Under the optimum conditions, the calibration curve studies demonstrated that the peak current increased linearly with Aza concentrations in the range of 7 × 10(-7) to 1 × 10(-4)mol L(-1) with the detection limit of 68 nM. Further experiments revealed that the modified electrode can be successfully applied for the accurate determination of Aza in pharmaceutical preparations. Copyright © 2015 Elsevier B.V. All rights reserved.

Combinatorial Therapy with Acetylation and Methylation Modifiers Attenuates Lung Vascular Hyperpermeability in Endotoxemia-Induced Mouse Inflammatory Lung Injury

PubMed Central

Thangavel, Jayakumar; Malik, Asrar B.; Elias, Harold K.; Rajasingh, Sheeja; Simpson, Andrew D.; Sundivakkam, Premanand K.; Vogel, Stephen M.; Xuan, Yu-Ting; Dawn, Buddhadeb; Rajasingh, Johnson

2015-01-01

Impairment of tissue fluid homeostasis and migration of inflammatory cells across the vascular endothelial barrier are crucial factors in the pathogenesis of acute lung injury (ALI). The goal for treatment of ALI is to target pathways that lead to profound dysregulation of the lung endothelial barrier. Although studies have shown that chemical epigenetic modifiers can limit lung inflammation in experimental ALI models, studies to date have not examined efficacy of a combination of DNA methyl transferase inhibitor 5-Aza 2-deoxycytidine and histone deacetylase inhibitor trichostatin A (herein referred to as Aza+TSA) after endotoxemia-induced mouse lung injury. We tested the hypothesis that treatment with Aza+TSA after lipopolysaccharide induction of ALI through epigenetic modification of lung endothelial cells prevents inflammatory lung injury. Combinatorial treatment with Aza+TSA mitigated the increased endothelial permeability response after lipopolysaccharide challenge. In addition, we observed reduced lung inflammation and lung injury. Aza+TSA also significantly reduced mortality in the ALI model. The protection was ascribed to inhibition of the eNOS-Cav1-MLC2 signaling pathway and enhanced acetylation of histone markers on the vascular endothelial-cadherin promoter. In summary, these data show for the first time the efficacy of combinatorial Aza+TSA therapy in preventing ALI in lipopolysaccharide-induced endotoxemia and raise the possibility of an essential role of DNA methyl transferase and histone deacetylase in the mechanism of ALI. PMID:24929240

Novel crosslinked membranes based on sulfonated poly(ether ether ketone) for direct methanol fuel cells.

PubMed

Zhu, Yuanqin; Zieren, Shelley; Manthiram, Arumugam

2011-07-14

Novel covalently crosslinked membranes based on sulfonated poly(ether ether ketone) and carboxylated polysulfone exhibit much lower methanol crossover and better performance in direct methanol fuel cells at 65 °C in 1 and 2 M methanol solutions compared to Nafion 115 membranes.

Chemical constituents and anti-inflammatory activities of Maqian (Zanthoxylum myriacanthum var. pubescens) bark extracts

PubMed Central

Zhang, Huan-li; Gan, Xiao-qing; Fan, Qing-fei; Yang, Jing-jing; Zhang, Ping; Hu, Hua-bin; Song, Qi-shi

2017-01-01

In this study, 44 compounds in the petroleum ether extract of Maqian (Zanthoxylum myriacanthum var. pubescens) bark, a traditional Dai herbal medicine, were identified by GC-MS. Major components included 3(2H)-benzofuranone, asarinin and (dimethoxymethyl)-3-methoxy-benzene. A total of 18 compounds were isolated from the ethyl acetate extracts of Maqian bark by column chromatography and identified by chemical and spectral analyses. Rhoifoline B, zanthoxyline dimethoxy derivative, N-nortidine, nitidine, decarine are the major alkaloids. Both the petroleum ether and ethyl acetate extracts showed significant inhibition on NO production, which imply anti-inflammatory activity, in lipopolysaccharide-induced RAW 264.7 cells without cell toxicity. Decarine is the major anti-inflammatory constituent with NO IC50 values of 48.43 μM on RAW264.7 cells. The petroleum ether extract, the ethyl acetate extract and decarine showed anti-inflammatory activities through inhibiting TNF-α and IL-1β production in lipopolysaccharide-stimulated THP-1 cells without cell toxicity too. Decarine showed anti-inflammatory activity on human colon cells by reducing IL-6 and IL-8 production in TNF-α+IL-1β-induced Caco-2 cells. These results support the use of Maqian bark as a remedy for enteritis and colitis recorded by Dai medicine in China, and elucidate the major pharmacological compounds in Maqian bark. PMID:28383530

Novel fluorogenic probe for fluoride ion based on the fluoride-induced cleavage of tert-butyldimethylsilyl ether

NASA Astrophysics Data System (ADS)

Yang, Xiao-Feng

2007-06-01

A highly sensitive and selective fluorogenic probe for fluoride ion, 4-methylumbelliferyl tert-butyldimethylsilyl ether (4-MUTBS), was designed and synthesized. 4-MUTBS was a weakly fluorescent compound and was synthesized via the one-step reaction of 4-MU with tert-butyldimethylsilyl chloride. Upon incubation with fluoride ion in acetone-water solution (7:3, v/v), the Si-O bond of 4-MUTBS was cleaved and highly fluorescent 4-methylumbelliferone (4-MU) was released, hence leading to the fluorescence increase of the reaction solution. The fluorescence increase is linearly with fluoride concentration in the range 50-8000 nmol l -1 with a detection limit of 19 nmol l -1 (3 σ). Because of the high affinity of silicon toward fluoride ion, the proposed probe shows excellent selectivity toward fluoride ion over other anions. The method has been successfully applied to the fluoride determination in toothpaste and tap water samples.

Cage-like bifunctional chelators, copper-64 radiopharmaceuticals and PET imaging using the same

DOEpatents

Conti, Peter S.; Cai, Hancheng; Li, Zibo; Liu, Shuanglong

2016-08-02

Disclosed is a class of versatile Sarcophagine based bifunctional chelators (BFCs) containing a hexa-aza cage for labeling with metals having either imaging, therapeutic or contrast applications radiolabeling and one or more linkers (A) and (B). The compounds have the general formula ##STR00001## where A is a functional group selected from group consisting of an amine, a carboxylic acid, an ester, a carbonyl, a thiol, an azide and an alkene, and B is a functional group selected from the group consisting of hydrogen, an amine, a carboxylic acid, and ester, a carbonyl, a thiol, an azide and an alkene. Also disclosed are conjugate of the BFC and a targeting moiety, which may be a peptide or antibody. Also disclosed are metal complexes of the BFC/targeting moiety conjugates that are useful as radiopharmaceuticals, imaging agents or contrast agents.

Exothermic or Endothermic Decomposition of Disubstituted Tetrazoles Tuned by Substitution Fashion and Substituents.

PubMed

Jia, Yu-Hui; Yang, Kai-Xiang; Chen, Shi-Lu; Huang, Mu-Hua

2018-01-11

Nitrogen-rich compounds such as tetrazoles are widely used as candidates in gas-generating agents. However, the details of the differentiation of the two isomers of disubstituted tetrazoles are rarely studied, which is very important information for designing advanced materials based on tetrazoles. In this article, pairs of 2,5- and 1,5-disubstituted tetrazoles were carefully designed and prepared for study on their thermal decomposition behavior. Also, the substitution fashion of 2,5- and 1,5- and the substituents at C-5 position were found to affect the endothermic or exothermic properties. This is for the first time to the best of our knowledge that the thermal decomposition properties of different tetrazoles could be tuned by substitution ways and substitute groups, which could be used as a useful platform to design advanced materials for temperature-dependent rockets. The aza-Claisen rearrangement was proposed to understand the endothermic decomposition behavior.

Bioconversion of AHX to AOH by resting cells of Burkholderia contaminans CH-1.

PubMed

Choi, Jae-Hoon; Kikuchi, Ayaka; Pumkaeo, Panyapon; Hirai, Hirofumi; Tokuyama, Shinji; Kawagishi, Hirokazu

2016-10-01

Fairy rings are zones of stimulated grass growth owing to the interaction between a fungus and a plant. We previously reported the discovery of two novel plant-growth regulating compounds related to forming fairy rings, 2-azahypoxanthine (AHX) and 2-aza-8-oxohypoxanthine (AOH). In this study, a bacterial strain CH-1 was isolated from an airborne-contaminated nutrient medium containing AHX. The strain converted AHX to AOH and identified as Burkholderia contaminans based on the gene sequence of its 16S rDNA. The quantitative production of AOH by resting cells of the strain was achieved. Among seven Burkholderia species, two bacteria and two yeasts tested, B. contaminans CH-1 showed the highest rate of conversion of AHX to AOH. By batch system, up to 10.6 mmol AHX was converted to AOH using the resting cells. The yield of this process reached at 91%.

Epothilones as lead structures for the synthesis-based discovery of new chemotypes for microtubule stabilization.

PubMed

Feyen, Fabian; Cachoux, Frédéric; Gertsch, Jürg; Wartmann, Markus; Altmann, Karl-Heinz

2008-01-01

Epothilones are macrocyclic bacterial natural products with potent microtubule-stabilizing and antiproliferative activity. They have served as successful lead structures for the development of several clinical candidates for anticancer therapy. However, the structural diversity of this group of clinical compounds is rather limited, as their structures show little divergence from the original natural product leads. Our own research has explored the question of whether epothilones can serve as a basis for the development of new structural scaffolds, or chemotypes, for microtubule stabilization that might serve as a basis for the discovery of new generations of anticancer drugs. We have elaborated a series of epothilone-derived macrolactones whose overall structural features significantly deviate from those of the natural epothilone scaffold and thus define new structural families of microtubule-stabilizing agents. Key elements of our hypermodification strategy are the change of the natural epoxide geometry from cis to trans, the incorporation of a conformationally constrained side chain, the removal of the C3-hydroxyl group, and the replacement of C12 with nitrogen. So far, this approach has yielded analogs 30 and 40 that are the most advanced, the most rigorously modified, structures, both of which are potent antiproliferative agents with low nanomolar activity against several human cancer cell lines in vitro. The synthesis was achieved through a macrolactone-based strategy or a high-yielding RCM reaction. The 12-aza-epothilone ("azathilone" 40) may be considered a "non-natural" natural product that still retains most of the overall structural characteristics of a true natural product but is structurally unique, because it lies outside of the general scope of Nature's biosynthetic machinery for polyketide synthesis. Like natural epothilones, both 30 and 40 promote tubulin polymerization in vitro and at the cellular level induce cell cycle arrest in mitosis. These facts indicate that cancer cell growth inhibition by these compounds is based on the same mechanistic underpinnings as those for natural epothilones. Interestingly, the 9,10-dehydro analog of 40 is significantly less active than the saturated parent compound, which is contrary to observations for natural epothilones B or D. This may point to differences in the bioactive conformations of N-acyl-12-aza-epothilones like 40 and natural epothilones. In light of their distinct structural features, combined with an epothilone-like (and taxol-like) in vitro biological profile, 30 and 40 can be considered as representative examples of new chemotypes for microtubule stabilization. As such, they may offer the same potential for pharmacological differentiation from the original epothilone leads as various newly discovered microtubule-stabilizing natural products with macrolactone structures, such as laulimalide, peloruside, or dictyostatin.

Mono- and Dialkyl Glycerol Ether Lipids in Anaerobic Bacteria: Biosynthetic Insights from the Mesophilic Sulfate Reducer Desulfatibacillum alkenivorans PF2803T

PubMed Central

Mollex, Damien; Vinçon-Laugier, Arnauld; Hakil, Florence; Pacton, Muriel; Cravo-Laureau, Cristiana

2015-01-01

Bacterial glycerol ether lipids (alkylglycerols) have received increasing attention during the last decades, notably due to their potential role in cell resistance or adaptation to adverse environmental conditions. Major uncertainties remain, however, regarding the origin, biosynthesis, and modes of formation of these uncommon bacterial lipids. We report here the preponderance of monoalkyl- and dialkylglycerols (1-O-alkyl-, 2-O-alkyl-, and 1,2-O-dialkylglycerols) among the hydrolyzed lipids of the marine mesophilic sulfate-reducing proteobacterium Desulfatibacillum alkenivorans PF2803T grown on n-alkenes (pentadec-1-ene or hexadec-1-ene) as the sole carbon and energy source. Alkylglycerols account for one-third to two-thirds of the total cellular lipids (alkylglycerols plus acylglycerols), depending on the growth substrate, with dialkylglycerols contributing to one-fifth to two-fifths of the total ether lipids. The carbon chain distribution of the lipids of D. alkenivorans also depends on that of the substrate, but the chain length and methyl-branching patterns of fatty acids and monoalkyl- and dialkylglycerols are systematically congruent, supporting the idea of a biosynthetic link between the three classes of compounds. Vinyl ethers (1-alken-1′-yl-glycerols, known as plasmalogens) are not detected among the lipids of strain PF2803T. Cultures grown on different (per)deuterated n-alkene, n-alkanol, and n-fatty acid substrates further demonstrate that saturated alkylglycerols are not formed via the reduction of hypothetic alken-1′-yl intermediates. Our results support an unprecedented biosynthetic pathway to monoalkyl/monoacyl- and dialkylglycerols in anaerobic bacteria and suggest that n-alkyl compounds present in the environment can serve as the substrates for supplying the building blocks of ether phospholipids of heterotrophic bacteria. PMID:25724965

Oligoethylene Glycol-substituted Aza-BODIPY Dyes As Red Emitting ER-Probes

PubMed Central

Kamkaew, Anyanee; Thavornpradit, Sopida; Puangsamlee, Thamon; Xin, Dongyue; Wanichacheva, Nantanit; Burgess, Kevin

2015-01-01

This study features aza-BODIPY (BF2-chelated azadipyrromethene) dyes with two aromatic substituents linked by oligoethylene glycol fragments to increase hydrophilicity of aza-BODIPY for applications in intracellular imaging. To prepare these, two chalcones were attached α,ω onto oligoethylene glycol fragments, then reacted with nitromethane anion. Conjugate addition products from this reaction were then subjected to typical conditions for synthesis of aza-BODIPY dyes (NH4OAc, nBuOH, 120 °C); formation of boracycles in this reaction was concomitant with creation of macrocycles containing the oligoethylene glycol fragments. Similar dyes with acyclic oligoelythene glycol substituents in the same position were used to compare the efficiencies of the intra- and inter-molecular aza-BODIPY forming reactions, and the characteristics of the products. All the fluors with oligoethylene glycol fragments, ie cyclic or acyclic, localized in the endoplasmic reticulum of a fibroblast cell line (WEHI-13VAR), the human pancreatic cancer cell line (PANC-1, rough ER predominates) and human liver cancer cell line (HepG2, smooth ER prevalent). These fluors are potentially useful for near IR (λmax emis at 730 nm) ER staining probes. PMID:26138325

Structural analysis by reductive cleavage with LiAlH4 of an allyl ether choline-phospholipid, archaetidylcholine, from the hyperthermophilic methanoarchaeon Methanopyrus kandleri

PubMed Central

Nishihara, Masateru; Morii, Hiroyuki; Matsuno, Koji; Ohga, Mami; Stetter, Karl O.; Koga, Yosuke

2002-01-01

A choline-containing phospholipid (PL-4) in Methanopyrus kandleri cells was identified as archaetidylcholine, which has been described by Sprott et al. (1997). The PL-4 consisted of a variety of molecular species differing in hydrocarbon composition. Most of the PL-4 was acid-labile because of its allyl ether bond. The identity of PL-4 was confirmed by thin-layer chromatography (TLC) followed by positive staining with Dragendorff-reagent and fast-atom bombardment–mass spectrometry. A new method of LiAlH4 hydrogenolysis was developed to cleave allyl ether bonds and recover the corresponding hydrocarbons. We confirmed the validity of the LiAlH4 method in a study of the model compound synthetic unsaturated archaetidic acid (2,3-di-O-geranylgeranyl-sn-glycerol-1-phosphate). Saturated ether bonds were not cleaved by the LiAlH4 method. The hydrocarbons formed following LiAlH4 hydrogenolysis of PL-4 were identified by gas–liquid chromatography and mass spectrometry. Four kinds of hydrocarbons with one to four double bonds were detected: 47% of the hydrocarbons had four double bonds; 11% had three double bonds; 14% had two double bonds; 7% had one double bond; and 6% were saturated species. The molecular species composition of PL-4 was also estimated based on acid lability: 77% of the molecular species had two acid-labile hydrocarbons; 11% had one acid-labile and one acid-stable hydrocarbon; and 11% had two acid-stable hydrocarbons. To our knowledge, this is the first report of a specific chemical degradation method for the structural analysis of allyl ether phospholipid in archaea. PMID:15803650

Deriving Biomonitoring Equivalents for selected E- and P-series glycol ethers for public health risk assessment.

PubMed

Poet, Torka; Ball, Nicholas; Hays, Sean M

2016-01-01

Glycol ethers are a widely used class of solvents that may lead to both workplace and general population exposures. Biomonitoring studies are available that have quantified glycol ethers or their metabolites in blood and/or urine amongst exposed populations. These biomonitoring levels indicate exposures to the glycol ethers, but do not by themselves indicate a health hazard risk. Biomonitoring Equivalents (BEs) have been created to provide the ability to interpret human biomonitoring data in a public health risk context. The BE is defined as the concentration of a chemical or metabolite in a biological fluid (blood or urine) that is consistent with exposures at a regulatory derived safe exposure limit, such as a tolerable daily intake (TDI). In this exercise, we derived BEs for general population exposures for selected E- and P-series glycol ethers based on their respective derived no effect levels (DNELs). Selected DNELs have been derived as part of respective Registration, Evaluation, Authorisation and Regulation of Chemicals (REACh) regulation dossiers in the EU. The BEs derived here are unique in the sense that they are the first BEs derived for urinary excretion of compounds following inhalation exposures. The urinary mass excretion fractions (Fue) of the acetic acid metabolites for the E-series GEs range from approximately 0.2 to 0.7. The Fues for the excretion of the parent P-series GEs range from approximately 0.1 to 0.2, with the exception of propylene glycol methyl ether and its acetate (Fue = 0.004). Despite the narrow range of Fues, the BEs exhibit a larger range, resulting from the larger range in DNELs across GEs. The BEs derived here can be used to interpret human biomonitoring data for inhalation exposures to GEs amongst the general population. Copyright © 2015 Elsevier GmbH. All rights reserved.

Preparation of Radiochemical-Labeled Compounds for the U.S. Army Drug Development Program

DTIC Science & Technology

1992-04-20

hydrochloric acid , b) extraction with ether, c) basification with potassium carbonate, d extraction with ether. 2. The crude product was isolated by...Chloride Fisher A-575 880667 Nethylene Chloride Fisher D-37 913251 Alumina, basic Act.I Woelm B 1385 Ethylene Natheson 08227 Hydrochloric Acid Fisher A...4-14C]WR-242511) and [!6- 14C]ertelinic acid were coupleted. A total of 31 m~i of (414 ]WR-238605 was prepared with specific activity of 21 mCi

Ionic complexation of N 2O 4 by 18-crown-6

NASA Astrophysics Data System (ADS)

Ricard, S.; Audet, P.; Savoie, R.

1988-08-01

An ionic complex has been obtained from N 2O 4 in the presence of the macrocyclic ether 18-crown-6. This crystalline compound has been shown from its Raman spectrum to have the formula NO +·crown·H(NO 3) 2-, with the nitrosonium ion closely associated with the crown ether rather than with the hydrogen dinitrate accompanying ion. This adduct decomposes readily in moist air to give the known complex (HNO 3·H 2O) 2·crown.

Should we test TPMT enzyme levels before starting azathioprine?

PubMed

Richard, Vijay Samuel; Al-Ismail, Deana; Salamat, Ahmed

2007-08-01

Thiopurine methyltransferase (TPMT) is the main enzyme responsible for inactivating toxic products of azathioprine (AZA) metabolism. Patients with homozygous deficiency of this enzyme have no enzyme activity and ideally should not be given AZA. Patients with heterozygous deficiency have 50% of enzyme activity and have been shown to respond well and tolerate half a standard dose. We describe a patient with homozygous deficiency of TPMT who developed life threatening neutropenic sepsis, and advocate that all patients should be tested for TPMT activity prior to starting AZA therapy.

Insecticidal and genotoxic potential of two semi-synthetic derivatives of dillapiole for the control of Aedes (Stegomyia) aegypti (Diptera: Culicidae).

PubMed

Domingos, Pedro Rauel Cândido; da Silva Pinto, Ana Cristina; dos Santos, Joselita Maria Mendes; Rafael, Míriam Silva

2014-09-15

The effects of two semi-synthetic dillapiole derivatives, ethyl-ether dillapiole and n-butyl ether dillapiole, on eggs and larvae of Aedes aegypti were studied in view of the need for expansion and renovation of strategic action to control this mosquito - the vector of Dengue virus -, which currently shows a high resistance to chemical insecticides. Eggs and third-instar larvae of A. aegypti that had been exposed to different concentrations of these two compounds showed toxicity and susceptibility, with 100% mortality. Classical cytogenetic assays showed genotoxicity caused by the two compounds in A. aegypti from the cumulative effect of nuclear abnormalities, indicating that these derivatives may be potential alternatives to control A. aegypti. Copyright © 2014 Elsevier B.V. All rights reserved.

THE NATURE OF SERUM ANTITRYPSIN

PubMed Central

Jobling, James W.; Petersen, William

1914-01-01

1. The ferment-inhibiting action of the serum is due to the presence of compounds of the unsaturated fatty acids. 2. These fatty acid compounds may be removed from the serum by means of chloroform or ether. 3. Soaps prepared by saponifying the chloroform or ether extracts inhibit the action of trypsin. 4. The anti-enzyme action of the serum can be removed by filtering acid serum through kaolin, and can in part be restored by extracting the kaolin. 5. The decrease in strength of anti-enzyme in old sera is probably due to the action of the serum lipase. 6. Iodin, potassium iodide, or hydrogen peroxide remove the inhibiting action of the serum. 7. Soaps of the unsaturated fatty acids lose their ferment-inhibiting action when heated with serum at 70° C. PMID:19867786

Inhibition of DNA methyltransferase induces G2 cell cycle arrest and apoptosis in human colorectal cancer cells via inhibition of JAK2/STAT3/STAT5 signalling.

PubMed

Xiong, Hua; Chen, Zhao-Fei; Liang, Qin-Chuan; Du, Wan; Chen, Hui-Min; Su, Wen-Yu; Chen, Guo-Qiang; Han, Ze-Guang; Fang, Jing-Yuan

2009-09-01

DNA methyltransferase inhibitors (MTIs) have recently emerged as promising chemotherapeutic or preventive agents for cancer, despite their poorly characterized mechanisms of action. The present study shows that DNA methylation is integral to the regulation of SH2-containing protein tyrosine phosphatase 1 (SHP1) expression, but not for regulation of suppressors of cytokine signalling (SOCS)1 or SOCS3 in colorectal cancer (CRC) cells. SHP1 expression correlates with down-regulation of Janus kinase/signal transducers and activators of transcription (JAK2/STAT3/STAT5) signalling, which is mediated in part by tyrosine dephosphorylation events and modulation of the proteasome pathway. Up-regulation of SHP1 expression was achieved using a DNA MTI, 5-aza-2'-deoxycytidine (5-aza-dc), which also generated significant down-regulation of JAK2/STAT3/STAT5 signalling. We demonstrate that 5-aza-dc suppresses growth of CRC cells, and induces G2 cell cycle arrest and apoptosis through regulation of downstream targets of JAK2/STAT3/STAT5 signalling including Bcl-2, p16(ink4a), p21(waf1/cip1) and p27(kip1). Although 5-aza-dc did not significantly inhibit cell invasion, 5-aza-dc did down-regulate expression of focal adhesion kinase and vascular endothelial growth factor in CRC cells. Our results demonstrate that 5-aza-dc can induce SHP1 expression and inhibit JAK2/STAT3/STAT5 signalling. This study represents the first evidence towards establishing a mechanistic link between inhibition of JAK2/STAT3/STAT5 signalling and the anticancer action of 5-aza-dc in CRC cells that may lead to the use of MTIs as a therapeutic intervention for human colorectal cancer.

Intrauterine stress induces bone loss in adult offspring of C3H/HeJ mice having high bone mass phenotype but not C57BL/6J mice with low bone mass phenotype.

PubMed

Raygorodskaya, M; Gabet, Y; Shochat, C; Kobyliansky, E; Torchinsky, A; Karasik, D

2016-06-01

In this study we examined to what extent and how genetics may modify osteoporosis risk arising due to environmental stresses which act during the antenatal period of life and have the potential to induce bone loss in adulthood. C57Bl/6J (C57) and C3H/HeJ (C3H) mice were used as a model system. The mice were exposed to a single injection of 5-aza-2'-deoxycytidine (5-AZA) on day 10 of pregnancy and the structure and bone mineral density (BMD) of the femur and 3rd lumbar vertebra of 3- and 6-month-old male and female offspring were evaluated by micro-computed tomography (μCT). Besides, we also attempted to evaluate whether 5-AZA affects the expression of some osteogenic genes in the embryonic limb buds. The main observation of this study is that 5-AZA-induced loss of bone quality was registered in 6-mo-old C3H offspring but not in their C57 counterparts. We also observed that C57 and C3H embryos may differ in their response to 5-AZA-induced detrimental stimuli: whereas 5-AZA treated C3H embryos exhibited a decreased expression of Col1a1, C57 embryos exhibit a decreased expression of Sox9. Overall, our study, by thorough characterization of bone homeostasis in 3- and 6-month-old offspring of 5-AZA-exposed C57 and C3H mice, allows hypothesizing that the adaptive response to antenatal insults may be stronger in offspring inherently exhibiting a low bone mass phenotype than in offspring inherently exhibiting a high bone mass phenotype. Copyright © 2016 Elsevier Inc. All rights reserved.

Simultaneous quantitative determination of 5-aza-2′-deoxycytidine genomic incorporation and DNA demethylation by liquid chromatography tandem mass spectrometry as exposure-response measures of nucleoside analog DNA methyltransferase inhibitors

PubMed Central

Anders, Nicole M.; Liu, Jianyong; Wanjiku, Teresia; Giovinazzo, Hugh; Zhou, Jianya; Vaghasia, Ajay; Nelson, William G.; Yegnasubramanian, Srinivasan; Rudek, Michelle A.

2016-01-01

The epigenetic and anti-cancer activities of the nucleoside analog DNA methyltransferase (DNMT) inhibitors decitabine (5-aza-2′-deoxycytidine, DAC), azacitidine, and guadecitabine are thought to require cellular uptake, metabolism to 5-aza-2′-deoxycytidine triphosphate, and incorporation into DNA. This genomic incorporation can then lead to trapping and degradation of DNMT enzymes, and ultimately, passive loss of DNA methylation. To facilitate measurement of critical exposure-response relationships of nucleoside analog DNMT inhibitors, a sensitive and reliable method was developed to simultaneously quantitate 5-aza-2′-deoxycytidine genomic incorporation and genomic 5-methylcytosine content using LC-MS/MS. Genomic DNA was extracted and digested into single nucleosides. Chromatographic separation was achieved with a Thermo Hyperpcarb porous graphite column (100 mm × 2.1 mm, 5μm) and isocratic elution with a 10 mM ammonium acetate:acetonitrile with 0.1% formic acid (70:30, v/v) mobile phase over a 5 minute total analytical run time. An AB Sciex 5500 triple quadrupole mass spectrometer operated in positive electrospray ionization mode was used for the detection of 5-aza-2′-deoxycytidine, 2′-deoxycytidine, and 5-methyl-2′-deoxycytidine. The assay range was 2 – 400 ng/mL for 5-aza-2′-deoxycytidine, 50 – 10,000 ng/mL for 2′-deoxycytidine, and was 5 – 1,000 ng/mL for 5-methyl-2′-deoxycytidine. The assay proved to be accurate (93.0–102.2%) and precise (CV ≤ 6.3%) across all analytes. All analytes exhibited long-term frozen digest matrix stability at −70°C for at least 117 days. The method was applied for the measurement of genomic 5-aza-2′-deoxycytidine and 5-methyl-2′-deoxycytidine content following exposure of in vitro cell culture and in vivo animal models to decitabine. PMID:27082761

Sensitization to reactive diluents and hardeners in epoxy resin systems. IVDK data 2002-2011. Part II: concomitant reactions.

PubMed

Geier, Johannes; Lessmann, Holger; Hillen, Uwe; Skudlik, Christoph; Jappe, Uta

2016-02-01

Beside the basic resins, reactive diluents and hardeners are important sensitizers in epoxy resin systems (ERSs). Because of chemical similarities, immunological cross-reactivity may occur. To analyse concomitant reactivity among reactive diluents and hardeners in the patients concerned, as one integral part of a research project on the sensitizing capacity of ERSs (FP-0324). A retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2002-2011, was performed. There was close concomitant reactivity to 1,6-hexanediol diglycidyl ether and 1,4-butanediol diglycidyl ether (1,4-BDDGE), and to phenyl glycidyl ether (PGE) and cresyl glycidyl ether (CGE), whereas reactions to p-tert-butylphenyl glycidyl ether occurred more independently from those to PGE and CGE. Concomitant reactions to butyl glycidyl ether and 1,4-BDDGE may point to a common allergenic compound derived from the metabolism of 1,4-BDDGE. Among the structurally more diverse group of hardeners, there was no evidence of immunological cross-reactions. More detailed knowledge of cross-reactivity among ERS components facilitates the interpretation of patch test results and will allow safer ERSs to be composed in the future. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Synthesis, Luminescent Properties of aza-Boron-Diquinomethene Difluoride Complexes and Their Application for Fluorescent Security Inks.

PubMed

Gu, Long; Liu, Rui; Shi, Hong; Wang, Qiang; Song, Guangliang; Zhu, Xiaolin; Yuan, Shidong; Zhu, Hongjun

2016-03-01

Two aza-boron-diquinomethene (aza-BODIQU) complexes bearing phenyl and carbazyl substituents were synthesized and characterized. Their photophysical properties were investigated systematically via spectroscopic and theoretical methods. Both complexes exhibit strong (1)π-π* transition absorptions (λ(abs) = 400-540 nm) and intense fluorescent emissions (λ(em) = 440-600 nm, Φ(PL) = 0.93 and 0.78) in CH2Cl2 solution and in solid state at room temperature. Compared to the complex with phenyl groups, the complex bearing carbazyl groups shows significant bathochromic shift in both absorption and emission. This could be attributed to the larger π-electron conjugation of the carbazole unit and intramolecular charge transfer feature from carbazole to aza-BODIQU component. In addition, the complexes exhibit intense photoluminescence and good stability on antacid, anti-alkali and stability in printing ink samples, which makes them potential dopants for the application of fluorescent security inks.

From a marine neuropeptide to antimicrobial pseudopeptides containing aza-β(3)-amino acids: structure and activity

PubMed Central

Laurencin, Mathieu; Legrand, Baptiste; Duval, Emilie; Henry, Joël; Baudy-Floc'H, Michèle; Zatylny-Gaudin, Céline; Bondon, Arnaud

2012-01-01

Incorporation of aza-β3-amino acids into endogenous neuropeptide from mollusks (ALSGDAFLRF-NH2) with weak antimicrobial activities allows us to design new AMPs sequences. We find that, depending on the nature of the substitution, these could result either in inactive pseudopeptides or in a drastic enhancement of the antimicrobial activity without high cytotoxicity resulted. Structural studies perform by NMR and circular dichroism on the pseudopeptides show the impact of aza-β3-amino acids on the peptide structures. We obtain the first three-dimensional structures of pseudopeptides containing aza-β3-amino acids in aqueous micellar SDS and demonstrate that hydrazino turn can be formed in aqueous solution. Overall, these results demonstrate the ability to modulate AMPs activities through structural modifications induced by the nature and the position of these amino acid analogs in the peptide sequences. PMID:22320306

1-(4,5-Dinitro-10-aza­tricyclo­[6.3.1.02,7]dodeca-2,4,6-trien-10-yl)-2,2,2-trifluoro­ethanone

PubMed Central

Xu, Hao; Quan, Ji-Cai; Xu, Jian; Chen, Jing; Wang, Jin-Tang

2008-01-01

In the title compound, C13H10F3N3O5, a derivative of andrographolide, the five-membered ring adopts an envelope conformation, while the non-planar six-membered ring has a chair conformation. An intra­molecular C—H⋯F hydrogen bond results in the formation of a non-planar six-membered ring adopting a twisted conformation. In the crystal structure, inter­molecular C—H⋯O hydrogen bonds link the mol­ecules into centrosymmetric dimers. PMID:21581393

Microbial degradation of decabromodiphenyl ether (DBDE) in soil slurry microcosms.

PubMed

Chou, Hsi-Ling; Hwa, Mei-Yin; Lee, Yao-Chuan; Chang, Yu-Jie; Chang, Yi-Tang

2016-03-01

Decabromodiphenyl ether (DBDE), which has been identified as an endocrine disrupting compound, is used as brominated flame retardant, and this can result in serious bioaccumulation within ecological systems. The objective of this study was to explore DBDE bioremediation (25 mg/kg) using laboratory scale soil slurry microcosms. It was found that effective biodegradation of DBDE occurred in all microcosms. Various biometabolites were identified, namely polybrominated diphenyl ethers congeners and hydroxylated brominated diphenyl ether. Reductive debrominated products such as tri-BDE to hepta-BDE congeners were also detected, and their total concentrations ranged from 77.83 to 91.07 ng/g. The mechanism of DBDE biodegradation in soil slurry microcosms is proposed to consist of a series of biological reactions involving hydroxylation and debromination. Catechol 2,3-oxygenase genes, which are able to bring about meta-cleavage at specific unbrominated locations in carbon backbones, were identified as present during the DBDE biodegradation. No obvious effect on the ecological functional potential based on community-level physiological profiling was observed during DBDE biodegradation, and one major facultative Pseudomonas sp. (99 % similarity) was identified in the various soil slurry microcosms. These findings provide an important basis that should help environmental engineers to design future DBDE bioremediation systems that use a practical microcosm system. A bacterial-mixed culture can be selected as part of the bioaugmentation process for in situ DBDE bioremediation. A soil/water microcosm system can be successfully applied to carry out ex situ DBDE bioremediation.

Ionization of EPA Contaminants in Direct and Dopant-Assisted Atmospheric Pressure Photoionization and Atmospheric Pressure Laser Ionization

NASA Astrophysics Data System (ADS)

Kauppila, Tiina J.; Kersten, Hendrik; Benter, Thorsten

2015-06-01

Seventy-seven EPA priority environmental pollutants were analyzed using gas chromatography-mass spectrometry (GC-MS) equipped with an optimized atmospheric pressure photoionization (APPI) and an atmospheric pressure laser ionization (APLI) interface with and without dopants. The analyzed compounds included e.g., polycyclic aromatic hydrocarbons (PAHs), nitro compounds, halogenated compounds, aromatic compounds with phenolic, acidic, alcohol, and amino groups, phthalate and adipatic esters, and aliphatic ethers. Toluene, anisole, chlorobenzene, and acetone were tested as dopants. The widest range of analytes was ionized using direct APPI (66/77 compounds). The introduction of dopants decreased the amount of compounds ionized in APPI (e.g., 54/77 with toluene), but in many cases the ionization efficiency increased. While in direct APPI the formation of molecular ions via photoionization was the main ionization reaction, dopant-assisted (DA) APPI promoted ionization reactions, such as charge exchange and proton transfer. Direct APLI ionized a much smaller amount of compounds than APPI (41/77 compounds), showing selectivity towards compounds with low ionization energies (IEs) and long-lived resonantly excited intermediate states. DA-APLI, however, was able to ionize a higher amount of compounds (e.g. 51/77 with toluene), as the ionization took place entirely through dopant-assisted ion/molecule reactions similar to those in DA-APPI. Best ionization efficiency in APPI and APLI (both direct and DA) was obtained for PAHs and aromatics with O- and N-functionalities, whereas nitro compounds and aliphatic ethers were the most difficult to ionize. Halogenated aromatics and esters were (mainly) ionized in APPI, but not in APLI.

Epigenetic modulation of AR gene expression in prostate cancer DU145 cells with the combination of sodium butyrate and 5'-Aza-2'-deoxycytidine.

PubMed

Fialova, Barbora; Luzna, Petra; Gursky, Jan; Langova, Katerina; Kolar, Zdenek; Trtkova, Katerina Smesny

2016-10-01

The androgen receptor (AR) plays an essential role in the development and progression of prostate cancer. Castration-resistant prostate cancer (CRPC) is a consequence of androgen deprivation therapy. Unchecked CRPC followed by metastasis is lethal. Some CRPCs show decreased AR gene expression due to epigenetic mechanisms such as DNA methylation and histone deacetylation. The aim of this study was to epigenetically modulate the methylated state of the AR gene leading to targeted demethylation and AR gene expression in androgen-independent human prostate cancer DU145 cell line, representing the CRPC model with very low or undetectable AR levels. The cell treatment was based on single and combined applications of two epigenetic inhibitors, sodium butyrate (NaB) as histone deacetylases inhibitor and 5'-Aza-2'-deoxycytidine (Aza-dC) as DNA methyltransferases inhibitor. We found that the Aza-dC in combination with NaB may help reduce the toxicity of higher NaB concentrations in cancer cells. In normal RWPE-1 cells and even stronger in cancer DU145 cells, the combined treatment induced both AR gene expression on the mRNA level and increased histone H4 acetylation in AR gene promoter. Also activation and maintenance of G2/M cell cycle arrest and better survival in normal RWPE-1 cells compared to cancer DU145 cells were observed after the treatments. These results imply the selective toxicity effect of both inhibitors used and their potentially more effective combined use in the epigenetic therapy of prostate cancer patients.

Patient-reported outcomes of azelaic acid foam 15% for patients with papulopustular rosacea: secondary efficacy results from a randomized, controlled, double-blind, phase 3 trial.

PubMed

Tyring, Stephen; Solomon, James A; Staedtler, Gerald; Lott, Jason P; Nkulikiyinka, Richard; Shakery, Kaweh

2016-10-01

Patient-reported treatment outcomes are important for evaluating the impact of drug therapies on patient experience. A randomized, double-blind, vehicle-controlled, parallel-group, multicenter, phase 3 study was conducted in 961 participants to assess patient perception of efficacy, utility, and effect on quality of life (QOL) of an azelaic acid (AzA) 15% foam formulation for the treatment of papulopustular rosacea (PPR). Secondary end points included patient-reported global assessment of treatment response, global assessment of tolerability, and opinion on cosmetic acceptability and practicability of product use. Quality of life assessments included the Dermatology Quality of Life Index (DLQI) and Rosacea Quality of Life Index (RosaQOL). Self-reported global assessment of treatment response favored AzA foam over vehicle foam (P<.001), with 57.2% of the AzA foam group reporting excellent or good improvement versus 44.7% in the vehicle foam group. Tolerability was rated excellent or good in 67.8% of the AzA foam group versus 78.2% of the vehicle foam group. Mean overall DLQI scores at end of treatment (EoT) were improved (P=.018) in favor of the AzA foam group compared with the vehicle foam group. Both treatment groups showed improvements in RosaQOL. Treatment with AzA foam was associated with improved QOL and meaningful reductions in the patient-perceived burden of PPR, which correlates with earlier reported primary end points of this study and supports the inclusion of patient perspectives in studies evaluating the effects of topical dermatologic treatments.

Integrated data analysis identifies potential inducers and pathways during the endothelial differentiation of bone-marrow stromal cells by DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine.

PubMed

Xu, Rui; Chen, Wenbin; Zhang, Zhifen; Qiu, Yang; Wang, Yong; Zhang, Bingchang; Lu, Wei

2018-05-30

Bone-Marrow Stromal Cells (BMSCs)-derived vascular endothelial cells (VECs) is regarded as an important therapeutic strategy for spinal cord injury, disc degeneration, cerebral ischemic disease and diabetes. The change in DNA methylation level is essential for stem cell differentiation. However, the DNA methylation related mechanisms underlying the endothelial differentiation of BMSCs are not well understood. In this study, DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC) significantly elevated the endothelial markers expression (CD31/PECAM1, CD105/ENG, eNOS and VE-cadherin), as well as promoted the capacity of angiogenesis on Matrigel. The result of Alexa 488-Ac-LDL uptake assay indicated that the differentiation ratio of BMSCs into VECs was 68.7% in 5-azaz-dC induced differentiation. And then we screened differentiation inducers with altered expression patterns and DNA methylation levels in four important families (VEGF, ANG, FGF and ETS). By integrating these data, five endothelial differentiation inducers (VEGFA, ANGPT2, FGF2, FGF9 and ETS1) which were directly upregulated by 5-aza-dC and five indirect factors (FGF1, FGF3, ETS2, ETV1 and ETV4) were identified. These data suggested that 5-aza-dC is an excellent chemical molecule for BMSCs differentiation into functional VECs and also provided essential clues for DNA methylation related signaling during 5-aza-dC induced endothelial differentiation of BMSCs. Copyright © 2018 Elsevier B.V. All rights reserved.

Occurrence of phthalate diesters (phthalates), p-hydroxybenzoic acid esters (parabens), bisphenol A diglycidyl ether (BADGE) and their derivatives in indoor dust from Vietnam: Implications for exposure.

PubMed

Tran, Tri Manh; Minh, Tu Binh; Kumosani, Taha A; Kannan, Kurunthachalam

2016-02-01

Phthalate diesters (phthalates), esters of p-hydroxybenzoic acid (parabens), and bisphenol A diglycidyl ether (BADGE) are used in personal care products, food packages, household products, or pharmaceuticals. These compounds possess endocrine-disrupting potentials and have been reported to occur in the environment. Nevertheless, no previous studies have reported the occurrence of these compounds in indoor dust from Vietnam. In this study, nine phthalates, six parabens, and four BADGEs were determined in indoor dust samples collected from Hanoi, Hatinh, Hungyen, and Thaibinh, in Vietnam. Total concentrations of phthalates, parabens, and BADGEs in indoor dust ranged from 3440 to 106,000 ng/g (median: 22,600 ng/g), 40-840 ng/g (median: 123 ng/g), and 23 to 1750 ng/g (median: 184 ng/g), respectively. Based on the measured median concentration of phthalates, parabens, and BADGEs in indoor dust, we estimated human exposure doses to these compounds through indoor dust ingestion for various age groups. The exposure doses to phthalates, parabens, and BADGEs decreased with age and ranged from 19.4 to 90.4 ng/kg-bw/d, 0.113-0.528 ng/kg-bw/d, and 0.158-0.736 ng/kg-bw/d, respectively. This is the first study on the occurrence and human exposure of phthalates, parabens, and BADGEs in indoor dust from Vietnam. Copyright © 2015 Elsevier Ltd. All rights reserved.

MUTYH mediates the toxicity of combined DNA 6-thioguanine and UVA radiation.

PubMed

Grasso, Francesca; Ruggieri, Vitalba; De Luca, Gabriele; Leopardi, Paola; Mancuso, Maria Teresa; Casorelli, Ida; Pichierri, Pietro; Karran, Peter; Bignami, Margherita

2015-04-10

The therapeutic thiopurines, including the immunosuppressant azathioprine (Aza) cause the accumulation of the UVA photosensitizer 6-thioguanine (6-TG) in the DNA of the patients' cells. DNA 6-TG and UVA are synergistically cytotoxic and their interaction causes oxidative damage. The MUTYH DNA glycosylase participates in the base excision repair of oxidized DNA bases. Using Mutyh-nullmouse fibroblasts (MEFs) we examined whether MUTYH provides protection against the lethal effects of combined DNA 6-TG/UVA. Surprisingly, Mutyh-null MEFs were more resistant than wild-type MEFs, despite accumulating higher levels of DNA 8-oxo-7,8-dihydroguanine (8-oxoG).Their enhanced 6-TG/UVA resistance reflected the absence of the MUTYH protein and MEFs expressing enzymatically-dead human variants were as sensitive as wild-type cells. Consistent with their enhanced resistance, Mutyh-null cells sustained fewer DNA strand breaks and lower levels of chromosomal damage after 6-TG/UVA. Although 6-TG/UVA treatment caused early checkpoint activation irrespective of the MUTYH status, Mutyh-null cells failed to arrest in S-phase at late time points. MUTYH-dependent toxicity was also apparent in vivo. Mutyh-/- mice survived better than wild-type during a 12-month chronicexposure to Aza/UVA treatments that significantly increased levels of skin DNA 8-oxoG. Two squamous cell skin carcinomas arose in Aza/UVA treated Mutyh-/- mice whereas similarly treated wild-type animals remained tumor-free.

Investigation on modes of toxic action to rats based on aliphatic and aromatic compounds and comparison with fish toxicity based on exposure routes.

PubMed

He, Jia; Li, Jin J; Wen, Yang; Tai, Hong W; Yu, Yang; Qin, Wei C; Su, Li M; Zhao, Yuan H

2015-06-01

The modes of toxic action (MOAs) play an important role in the assessment of the ecotoxicity of organic pollutants. However, few studies have been reported on the MOAs in rat toxicity. In this paper, the toxic contributions of functional groups in 1255 aromatic compounds were calculated from regression and were then compared with the toxic contributions in aliphatic compounds. The results show that some functional groups have same toxic contributions both in aromatic and aliphatic compounds, but some have not. To investigate the MOAs in rat toxicity, the distribution of toxic ratio (TR) was examined for well-known baseline and less inert compounds and thresholds of log TR=0.3 and 0.5 were used to classify baseline, less inert and reactive compounds. The results showed that some compounds identified as baseline compounds in fish toxicity were also classified as baseline compounds in rat toxicity. Except for phenols and anilines which were identified as less inert compounds in fish toxicity, aromatic compounds with functional groups such as ether, nitrile, nitrophenol, isocyanatoe and chloro were identified as less inert chemicals in rat toxicity. Reactive compounds identified in fish toxicity exhibit greater toxicity to rats. These compounds can undergo nucleophilic substitution, acylation and Schiff base formation with biological macromolecules. The critical body residues (CBRs) calculated from absorption and bioconcentration show that log 1/CBRs in rat toxicity are not equal to that in fish for some compounds. It suggests that the exposure route can affect the identification of MOAs between these two species for these compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

SEPARATION OF INORGANIC SALTS FROM ORGANIC SOLUTIONS

DOEpatents

Katzin, L.I.; Sullivan, J.C.

1958-06-24

A process is described for recovering the nitrates of uranium and plutonium from solution in oxygen-containing organic solvents such as ketones or ethers. The solution of such salts dissolved in an oxygen-containing organic compound is contacted with an ion exchange resin whereby sorption of the entire salt on the resin takes place and then the salt-depleted liquid and the resin are separated from each other. The reaction seems to be based on an anion formation of the entire salt by complexing with the anion of the resin. Strong base or quaternary ammonium type resins can be used successfully in this process.

Synthesis, fluorescence properties and the promising cytotoxicity of pyrene-derived aminophosphonates.

PubMed

Lewkowski, Jarosław; Rodriguez Moya, Maria; Wrona-Piotrowicz, Anna; Zakrzewski, Janusz; Kontek, Renata; Gajek, Gabriela

2016-01-01

A large series of variously substituted amino(pyren-1-yl)methylphosphonic acid derivatives was synthesized using a modified aza-Pudovik reaction in 20-97% yields. The fluorescence properties of the obtained compounds were investigated revealing that N-alkylamino(pyren-1-yl)methylphosphonic derivatives are stronger emissive compounds than the corresponding N-aryl derivatives. N-Benzylamino(pyren-1-yl)methylphosphonic acid displayed strong fluorescence (ΦF = 0.68) in phosphate-buffered saline (PBS). The influence of a series of derivatives on two colon cancer cell lines HT29 and HCT116 was also investigated. The most promising results were obtained for N-(4-methoxyphenyl)amino(pyren-1-yl)methylphosphonate, which was found to be cytotoxic for the HCT116 cancer cell line (IC50 = 20.8 μM), simultaneously showing weak toxicity towards normal lymphocytes (IC50 = 230.8 µM).

Food risk assessment for perfluoroalkyl acids and brominated flame retardants in the French population: results from the second French total diet study.

PubMed

Rivière, G; Sirot, V; Tard, A; Jean, J; Marchand, P; Veyrand, B; Le Bizec, B; Leblanc, J C

2014-09-01

To determine the exposure of the French population to toxic compounds contaminating the food chain, a total diet study was performed in France between 2007 and 2009. This study was designed to reflect the consumption habits of the French population and covered the most important foods in terms of consumption, selected nutrients and contribution to contamination. Based on French consumption data, the present study reports the dietary exposure to perfluoroalkyl acids (16 congeners) and brominated flame retardants (polybrominated diphenyl ethers, hexabromocyclododecane and polybrominated biphenyls). Comparison of the calculated dietary exposures with the generally accepted health-based guidance values revealed that most compounds do not pose any risk. There are however knowledge gaps for some congeners in these large chemical classes. Copyright © 2014 Elsevier B.V. All rights reserved.

Anti-knock quality of sugar derived levulinic esters and cyclic ethers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian, Miao; McCormick, Robert L.; Luecke, Jon

Here, the objective of this paper is to investigate the anti-knock quality of sugar-derived levulinic esters (methyl levulinate (ML) and ethyl levulinate (EL)) and cyclic ethers (furfuryl ethyl ether (FEE) and ethyl tetrahydrofurfuryl ether (ETE)). To this end, combustion experiments were carried out in both an engine and a constant volume autoignition device. The results from both apparati demonstrate that ML, EL and FEE have superior anti-knock quality than the reference Euro95 gasoline. ETE, conversely, performed markedly worse than the reference fuel on both setups and might therefore be a more appropriate fuel for compression ignition engines. The main reasonmore » of the distinctions in anti-knock quality can be found in the molecular structure of the neat biofuels. ML and EL are levulinic esters, with a ketone (C=O) functionality and an ester (C(=O)-O) group on the carbon chain. They can readily produce stable intermediates during the auto-ignition process, thereby slowing down the overall reaction rate. The unsaturated cyclic ether (FEE) has very strong ring C-H bonds. However, the saturated cyclic ether (ETE) has weak ring C-H bonds, which facilitate more readily ring opening reactions. Long side chains on the cyclic ethers further accelerate the reaction rate. Importantly for future research, our results suggest that IQT and engine experiments are interchangeable setups with respect to qualitative anti-knock quality evaluation of novel compounds.« less

Anti-knock quality of sugar derived levulinic esters and cyclic ethers

DOE PAGES

Tian, Miao; McCormick, Robert L.; Luecke, Jon; ...

2017-04-22

Here, the objective of this paper is to investigate the anti-knock quality of sugar-derived levulinic esters (methyl levulinate (ML) and ethyl levulinate (EL)) and cyclic ethers (furfuryl ethyl ether (FEE) and ethyl tetrahydrofurfuryl ether (ETE)). To this end, combustion experiments were carried out in both an engine and a constant volume autoignition device. The results from both apparati demonstrate that ML, EL and FEE have superior anti-knock quality than the reference Euro95 gasoline. ETE, conversely, performed markedly worse than the reference fuel on both setups and might therefore be a more appropriate fuel for compression ignition engines. The main reasonmore » of the distinctions in anti-knock quality can be found in the molecular structure of the neat biofuels. ML and EL are levulinic esters, with a ketone (C=O) functionality and an ester (C(=O)-O) group on the carbon chain. They can readily produce stable intermediates during the auto-ignition process, thereby slowing down the overall reaction rate. The unsaturated cyclic ether (FEE) has very strong ring C-H bonds. However, the saturated cyclic ether (ETE) has weak ring C-H bonds, which facilitate more readily ring opening reactions. Long side chains on the cyclic ethers further accelerate the reaction rate. Importantly for future research, our results suggest that IQT and engine experiments are interchangeable setups with respect to qualitative anti-knock quality evaluation of novel compounds.« less

EPR, UV-vis, magnetic, spectral studies and electrochemical behaviour of mononuclear transition metal complexes derived from novel hexa-aza-macrotricyclic ligand

NASA Astrophysics Data System (ADS)

Chandra, Sulekh; Gupta, Nidhi; Gupta, Rachna; Bawa, Sukhwant Singh

2005-11-01

Aza-macrocyclic complexes have gained importance because of their pharmacological properties [N.K. Singh, Srivastava, Trans. Met. Chem. 25 (2000) 133]. Hexa-aza-macrocyles containing glutarimide efficiently coordinate as hexa-dentate ligand, to give complexes of Cu(II) possessing tetragonal structure and Mn(II), Co(II) and Ni(II) metal ions that are essentially octahedral. Spectroscopic, and chemical characterizations of these systems are presented in this article. For Ni(II) complexes results on electron transfer processes measured by cyclic voltammetry and colourimetry have been studied.

2-Chloro-2,2-difluoroacetophenone: a non-ODS-based difluorocarbene precursor and its use in the difluoromethylation of phenol derivatives.

PubMed

Zhang, Laijun; Zheng, Ji; Hu, Jinbo

2006-12-22

A novel and non-ODS-based (ODS = ozone-depleting substance) preparation of 2-chloro-2,2-difluoroacetophenone (1) was achieved in high yield by using 2,2,2-trifluoroacetophenone as the starting material. Compound 1 was found to act as a good difluorocarbene reagent, which readily reacts with a variety of structurally diverse phenol derivatives 4 in the presence of potassium hydroxide or potassium carbonate to produce aryl difluoromethyl ethers 5 in good yields. This new and easy-to-handle synthetic methodology offers an environmentally friendly alternative to other Freon- or Halon-based difluoromethylating approaches.

A phase 3 randomized, double-blind, vehicle-controlled trial of azelaic acid foam 15% in the treatment of papulopustular rosacea.

PubMed

Draelos, Zoe Diana; Elewski, Boni E; Harper, Julie C; Sand, Meike; Staedtler, Gerald; Nkulikiyinka, Richard; Shakery, Kaweh

2015-07-01

Rosacea is a chronic relapsing skin disorder primarily affecting the face. Although its etiology is not well defined, rosacea is associated with immune dysregulation and inflammation potentiated by external factors. These manifestations lead to skin sensitivity and impaired quality of life. Azelaic acid (AzA) is approved for the treatment of rosacea in a 15% gel formulation. This phase 3 study evaluated the efficacy and safety of AzA in a 15% foam formulation for the treatment of papulopustular rosacea (PPR). Coprimary efficacy end points were treatment success according to investigator global assessment (IGA) and the nominal change in inflammatory lesion count (ILC) from baseline to the end of treatment (EoT). Adverse events (AEs) were evaluated as a measure of safety. The IGA success rate at EoT was significantly greater in the AzA foam group versus vehicle (P<.001; Cochran-Mantel-Haenszel test). Likewise, nominal ILC change at EoT in the AzA foam group showed a significantly greater decrease versus vehicle (P<.001; F test). Drug-related AEs were mainly mild to moderate, cutaneous, and local. Overall, the study results support the efficacy and safety of twice-daily AzA foam 15% in patients with PPR.

A single day of 5-azacytidine exposure during development induces neurodegeneration in neonatal mice and neurobehavioral deficits in adult mice.

PubMed

Subbanna, Shivakumar; Nagre, Nagaraja N; Shivakumar, Madhu; Basavarajappa, Balapal S

2016-12-01

The present study was undertaken to evaluate the immediate and long-term effects of a single-day exposure to 5-Azacytidine (5-AzaC), a DNA methyltransferase inhibitor, on neurobehavioral abnormalities in mice. Our findings suggest that the 5-AzaC treatment significantly inhibited DNA methylation, impaired extracellular signal-regulated kinase (ERK1/2) activation and reduced expression of the activity-regulated cytoskeleton-associated protein (Arc). These events lead to the activation of caspase-3 (a marker for neurodegeneration) in several brain regions, including the hippocampus and cortex, two brain areas that are essential for memory formation and memory storage, respectively. 5-AzaC treatment of P7 mice induced significant deficits in spatial memory, social recognition, and object memory in adult mice and deficits in long-term potentiation (LTP) in adult hippocampal slices. Together, these data demonstrate that the inhibition of DNA methylation by 5-AzaC treatment in P7 mice causes neurodegeneration and impairs ERK1/2 activation and Arc protein expression in neonatal mice and induces behavioral abnormalities in adult mice. DNA methylation-mediated mechanisms appear to be necessary for the proper maturation of synaptic circuits during development, and disruption of this process by 5-AzaC could lead to abnormal cognitive function. Published by Elsevier Inc.

AID downregulation is a novel function of the DNMT inhibitor 5-aza-deoxycytidine

PubMed Central

Tsai, Chiou-Tsun; Yang, Pei-Ming; Chern, Ting-Rong; Chuang, Shu-Hui; Lin, Jung-Hsin; Klemm, Lars; Müschen, Markus; Chen, Ching-Chow

2014-01-01

Activation-induced cytidine deaminase (AID) was originally identified as an inducer of somatic hypermutation (SHM) and class switch recombination (CSR) in immunoglobulin genes. However, AID can also cause mutations in host genes and contribute to cancer progression and drug resistance. In this study, molecular docking showed the interaction of free 5-aza-CdR and Zebularine (Zeb) with AID. However, only 5-aza-CdR-incorporated ssDNA bound to the active site of AID and inhibited AID expression through proteasomal degradation. 5-aza-CdR demonstrated cytotoxicity against AID-positive and -negative hematopoietic cancer cells. In contrast, Zeb exhibited a cytotoxic effect only in AID-negative cells due to its inability to inhibit AID expression. This differential effect might be due to the DNMT1 stabilization induced by AID, thus restricting the ability of Zeb to deplete DNMT1 and induce tumor suppressor genes (TSGs), such as p21, in AID-positive cells. Moreover, the in vivo anticancer effect of 5-aza-CdR but not Zeb in AID-positive hematopoietic cancer cells was demonstrated. The study not only displays the association of AID and DNMT1 and identifies a novel biological function of AID, but also provides novel information regarding the use of DNMT inhibitors to treat AID-positive hematopoietic cancers. PMID:24457556

Rumex acetosa Y chromosomes: constitutive or facultative heterochromatin?

PubMed

Mosiołek, Magdalena; Pasierbek, Paweł; Malarz, Janusz; Moś, Maria; Joachimiak, Andrzej J

2005-01-01

Condensed Y chromosomes in Rumex acetosa L. root-tip nuclei were studied using 5-azaC treatment and immunohistochemical detection of methylated histones. Although Y chromosomes were decondensed within root meristem in vivo, they became condensed and heteropycnotic in roots cultured in vitro. 5-azacytidine (5-azaC) treatment of cultured roots caused transitional dispersion of their Y chromosome bodies, but 7 days after removal of the drug from the culture medium, Y heterochromatin recondensed and again became visible. The response of Rumex sex chromatin to 5-azaC was compared with that of condensed segments of pericentromeric heterochromatin in Rhoeo spathacea (Sw.) Steam roots. It was shown that Rhoeo chromocentres, composed of AT-rich constitutive heterochromatin, did not undergo decondensation after 5-azaC treatment. The Y-bodies observed within male nuclei of R. acetosa were globally enriched with H3 histone, demethylated at lysine 4 and methylated at lysine 9. This is the first report of histone tail-modification in condensed sex chromatin in plants. Our results suggest that the interphase condensation of Y chromosomes in Rumex is facultative rather than constitutive. Furthermore, the observed response of Y-bodies to 5-azaC may result indirectly from demethylation and the subsequent altered expression of unknown genes controlling tissue-specific Y-inactivation as opposed to the global demethylation of Y-chromosome DNA.

Radiation Stability of Benzyl Tributyl Ammonium Chloride towards Technetium-99 Extraction - 13016

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paviet-Hartmann, Patricia; Horkley, Jared; Campbell, Keri

2013-07-01

A closed nuclear fuel cycle combining new separation technologies along with generation III and generation IV reactors is a promising way to achieve a sustainable energy supply. But it is important to keep in mind that future recycling processes of used nuclear fuel (UNF) must minimize wastes, improve partitioning processes, and integrate waste considerations into processes. New separation processes are being developed worldwide to complement the actual industrialized PUREX process which selectively separates U(VI) and Pu(IV) from the raffinate. As an example, the UREX process has been developed in the United States to co-extract hexavalent uranium (U) and hepta-valent technetiummore » (Tc) by tri-n-butyl phosphate (TBP). Tc-99 is recognized to be one of the most abundant, long-lived radio-toxic isotopes in UNF (half-life, t{sub 1/2} = 2.13 x 10{sup 5} years), and as such, is targeted in UNF separation strategies for isolation and encapsulation in solid waste-forms for final disposal in a nuclear waste repository. Immobilization of Tc-99 by a durable solid waste-form is a challenge, and its fate in new advanced technology processes is of importance. It is essential to be able to quantify and locate 1) its occurrence in any new developed flowsheets, 2) its chemical form in the individual phases of a process, 3) its potential quantitative transfer in any waste streams, and consequently, 4) its quantitative separation for either potential transmutation to Ru-100 or isolation and encapsulation in solid waste-forms for ultimate disposal. In addition, as a result of an U(VI)-Tc(VII) co-extraction in a UREX-based process, Tc(VII) could be found in low level waste (LLW) streams. There is a need for the development of new extraction systems that would selectively extract Tc-99 from LLW streams and concentrate it for feed into high level waste (HLW) for either Tc-99 immobilization in metallic waste-forms (Tc-Zr alloys), and/or borosilicate-based waste glass. Studies have been launched to investigate the suitability of new macro-compounds such as crown-ethers, aza-crown ethers, quaternary ammonium salts, and resorcin-arenes for the selective extraction of Tc-99 from nitric acid solutions. The selectivity of the ligand is important in evaluating potential separation processes and also the radiation stability of the molecule is essential for minimization of waste and radiolysis products. In this paper, we are reporting the extraction of TcO{sub 4}{sup -} by benzyl tributyl ammonium chloride (BTBA). Experimental efforts were focused on determining the best extraction conditions by varying the ligand's matrix conditions and concentration, as well as varying the organic phase composition (i.e. diluent variation). Furthermore, the ligand has been investigated for radiation stability. The ?-irradiation was performed on the neat organic phases containing the ligand at different absorbed doses to a maximum of 200 kGy using an external Co-60 source. Post-irradiation solvent extraction measurements will be discussed. (authors)« less

Ultra-trace determination of Persistent Organic Pollutants in Arctic ice using stir bar sorptive extraction and gas chromatography coupled to mass spectrometry.

PubMed

Lacorte, S; Quintana, J; Tauler, R; Ventura, F; Tovar-Sánchez, A; Duarte, C M

2009-12-04

This study presents the optimization and application of an analytical method based on the use of stir bar sorptive extraction (SBSE) gas chromatography coupled to mass spectrometry (GC-MS) for the ultra-trace analysis of POPs (Persistent Organic Pollutants) in Arctic ice. In a first step, the mass-spectrometry conditions were optimized to quantify 48 compounds (polycyclic aromatic hydrocarbons, brominated diphenyl ethers, chlorinated biphenyls, and organochlorinated pesticides) at the low pg/L level. In a second step, the performance of this analytical method was evaluated to determine POPs in Arctic cores collected during an oceanographic campaign. Using a calibration range from 1 to 1800 pg/L and by adjusting acquisition parameters, limits of detection at the 0.1-99 and 102-891 pg/L for organohalogenated compounds and polycyclic aromatic hydrocarbons, respectively, were obtained by extracting 200 mL of unfiltered ice water. alpha-hexachlorocyclohexane, DDTs, chlorinated biphenyl congeners 28, 101 and 118 and brominated diphenyl ethers congeners 47 and 99 were detected in ice cores at levels between 0.5 to 258 pg/L. We emphasise the advantages and disadvantages of in situ SBSE in comparison with traditional extraction techniques used to analyze POPs in ice.

[Chemical constituents of Halenia elliptica].

PubMed

Wang, Hongling; Chen, Hao; Geng, Chang'an; Zhang, Xuemei; Ma, Yunbao; Jiang, Zhiyong; Chen, Jijun

2011-06-01

To study the chemical constituents of Halenia elliptica. The air-dried whole plants of Halenia elliptica were extracted with 90% EtOH. The EtOH extract was condensed to a small amount of volume and extracted with petroleum ether, EtOAc and n-BuOH, successively. The compounds were isolated and purified by column chromatography from the EtOAc fraction, and identified based on spectral analyses (MS, 1H-NMR, 13C-NMR). 12 compounds were isolated from H. elliptica, and characterized as 8-hydroxy-2-methylchromone (1), 5-methoxy-2-methylchromone (2), 7-epi-vogeloside (3), coniferl aldehyde (4), sinapaldehyde (5), norbellidifolin (6), 1-hydroxyl-2,3,4,6-tetramethoxyxanthone (7), 1-hydroxyl-2,3,4,7-tetramethoxyxanthone (8), 1-hydroxyl-2,3,5-trimethoxyxanthone (9), together with azelaic acid, beta-sitosterol, and oleanolic acid. Compounds 1, 2 were new natural compounds and compounds 3-6, 10 were obtained from H. elliptica for the first time and compound 6 showed inhibitory activities against HBsAg and HBeAg secretion with IC50 value of 0.77 and < 0.62 mmol x L(-1), respectively.

Caco-2 Permeability Studies and In Vitro hERG Liability Assessment of Tryptanthrin and Indolinone.

PubMed

Jähne, Evelyn A; Eigenmann, Daniela E; Moradi-Afrapoli, Fahimeh; Verjee, Sheela; Butterweck, Veronika; Hebeisen, Simon; Hettich, Timm; Schlotterbeck, Götz; Smieško, Martin; Hamburger, Matthias; Oufir, Mouhssin

2016-08-01

Tryptanthrin and (E,Z)-3-(4-hydroxy-3,5-dimethoxybenzylidene)indolinone (indolinone) were recently isolated from Isatis tinctoria as potent anti-inflammatory and antiallergic alkaloids, and shown to inhibit COX-2, 5-LOX catalyzed leukotriene synthesis, and mast cell degranulation at low µM to nM concentrations. To assess their suitability for oral administration, we screened the compounds in an in vitro intestinal permeability assay using human colonic adenocarcinoma cells. For exact quantification of the compounds, validated UPLC-MS/MS methods were used. Tryptanthrin displayed high permeability (apparent permeability coefficient > 32.0 × 10(-6) cm/s) across the cell monolayer. The efflux ratio below 2 (< 1.12) and unchanged apparent permeability coefficient values in the presence of the P-glycoprotein inhibitor verapamil (50 µM) indicated that tryptanthrin was not involved in P-glycoprotein interactions. For indolinone, a low recovery was found in the human colon adenocarcinoma cell assay. High-resolution mass spectrometry pointed to extensive phase II metabolism of indolinone (sulfation and glucuronidation). Possible cardiotoxic liability of the compounds was assessed in vitro by measurement of an inhibitory effect on human ether-a-go-go-related gene tail currents in stably transfected HEK 293 cells using the patch clamp technique. Low human ether-a-go-go-related gene inhibition was found for tryptanthrin (IC50 > 10 µM) and indolinone (IC50 of 24.96 µM). The analysis of compounds using various in silico methods confirmed favorable pharmacokinetic properties, as well as a slight inhibition of the human ether-a-go-go-related gene potassium channel at micromolar concentrations. Georg Thieme Verlag KG Stuttgart · New York.

Anaerobic degradation of veratrylglycerol-beta-guaiacyl ether and guaiacoxyacetic acid by mixed rumen bacteria.

PubMed Central

Chen, W; Supanwong, K; Ohmiya, K; Shimizu, S; Kawakami, H

1985-01-01

Veratrylglycerol-beta-guaiacyl ether (0.2 g/liter), a lignin model compound, was found to be degraded by mixed rumen bacteria in a yeast extract medium under strictly anaerobic conditions to the extent of 19% within 24 h. Guaiacoxyacetic acid, 2-(o-methoxyphenoxy)ethanol, vanillic acid, and vanillin were detected as degradation products of veratrylglycerol-beta-guaiacyl ether by thin-layer chromatography, gas chromatography, and gas chromatography-mass spectrometry. Guaiacoxyacetic acid (0.25 g/liter), when added into the medium as a substrate, was entirely degraded within 36 h, resulting in the formation of phenoxyacetic acid, guaiacol, and phenol. These results suggest that the beta-arylether bond, an important intermonomer linkage in lignin, can be cleaved completely by these rumen anaerobes. PMID:3841472

A Facile and Efficient Synthesis of Diaryl Amines or Ethers under Microwave Irradiation at Presence of KF/Al2O3 without Solvent and Their Anti-Fungal Biological Activities against Six Phytopathogens

PubMed Central

Huang, Liang-Zhu; Han, Pan; Li, You-Qiang; Xu, Ying-Meng; Zhang, Tao; Du, Zhen-Ting

2013-01-01

A series of diaryl amines, ethers and thioethers were synthesized under microwave irradiation efficiently at presence of KF/Al2O3 in 83%–96% yields without any solvent. The salient characters of this method lie in short reaction time, high yields, general applicability to substrates and simple workup procedure. At the same time, their antifungal biological activities against six phytopathogen were evaluated. Most of the compounds (3b, 3c, 3g–o) are more potent than thiophannate-methyl against to Magnaporthe oryzae. This implies that diaryl amine or ether moiety may be helpful in finding a fungicide against Magnaporthe oryzae. PMID:24036444

Nitrile functionalized halloysite nanotubes/poly(arylene ether nitrile) nanocomposites: Interface control, characterization, and improved properties

NASA Astrophysics Data System (ADS)

Wan, Xinyi; Zhan, Yingqing; Zeng, Guangyong; He, Yi

2017-01-01

To develop high-performance halloysite nanotube (HNT)-based nanocomposites, the two key issues need to be considered: precise interface control and the dispersal of HNTs. This study presents an efficient way to functionalize halloysite nanotubes with 3-aminophenoxy-phthalonitrile, followed by compounding with poly(arylene ether nitrile) (PEN), to prepare functional nanocomposite films. The surface functionalization of HNTs was characterized and confirmed by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). Compared with neat PEN, the tensile strength and modulus of the resulting PEN nanocomposites with 3 wt% functionalized HNTs were found to increase by 25.7% and 20.7%, respectively. The good dispersion and high capacitance of the dielectric layer resulted in PEN/HNTs nancomposites with enhanced dielectric permittivity and relatively low dielectric loss. Moreover, the addition of functional HNTs greatly improved the thermal stability of PEN, which could be further enhanced through the chemical cross-linking reaction between the functional HNTs and the PEN matrix. This work provides a new path toward obtaining advanced polymer-based nanocomposites with functional properties.

The 5-HT(4) agonists cisapride, mosapride, and CJ-033466, a Novel potent compound, exhibit different human ether-a-go-go-related gene (hERG)-blocking activities.

PubMed

Toga, Tetsuo; Kohmura, Yumi; Kawatsu, Ryoichi

2007-10-01

The blocking effect of three 5-HT(4) agonists, cisapride, mosapride, and the newly discovered CJ-033466 on the human ether-a-go-go-related gene (hERG) channel was studied using a whole cell patch-clamp technique in HEK293 cells. Cisapride was found to be the most potent of the hERG blockers. CJ-033466 had the widest safety margin between its hERG blocking activity and 5-HT(4) agonism among the tested compounds. This suggests a lower clinical risk of cardiac arrhythmia in CJ-033466 compared with the other 2 agonists. Therefore, CJ-033466 has the potential to be a drug with higher therapeutic efficacy and less cardiac risk than both cisapride and mosapride.

Tribromophenoxy flame retardants in the Great Lakes atmosphere.

PubMed

Ma, Yuning; Venier, Marta; Hites, Ronald A

2012-12-18

The 2,4,6-tribromophenoxy moiety is a common structural feature of several brominated flame retardants, and we have previously reported on the environmental concentrations of one such compound, 1,2-bis(2,4,6-tribromophenoxy) ethane (TBE). Here we report the atmospheric concentrations of TBE and three other tribromophenoxy compounds: allyl 2,4,6-tribromophenyl ether (ATE), 2-bromoallyl 2,4,6-tribromophenyl ether (BATE), and 2,3-dibromopropyl 2,4,6-tribromophenyl ether (DPTE). The samples were collected at five sites near the shores of the Great Lakes during the period 2008-2009, inclusive. Of these four compounds, TBE and ATE are currently used as flame retardants, and DPTE was formerly used as a flame retardant until its production ceased in the mid-1980s. The total concentrations of ATE, BATE, and DPTE were ∼2 pg/m³ in the cities of Chicago and Cleveland and 0.1-0.4 pg/m³ at the rural and remote sites. The concentrations of TBE were ∼1 pg/m³ in these cities and 0.2-0.8 pg/m³ at the rural and remote sites. In both cases, this was a very significant urban effect. The concentrations of ATE, BATE, and DPTE did not change significantly over the two-year study, but the concentrations of TBE decreased by about a factor of 2 during this time. This temporal change was statistically significant but not strong compared to the urban effect.

Theoretical study of chromophores for biological sensing: Understanding the mechanism of rhodol based multi-chromophoric systems

NASA Astrophysics Data System (ADS)

Rivera-Jacquez, Hector J.; Masunov, Artëm E.

2018-06-01

Development of two-photon fluorescent probes can aid in visualizing the cellular environment. Multi-chromophore systems display complex manifolds of electronic transitions, enabling their use for optical sensing applications. Time-Dependent Density Functional Theory (TDDFT) methods allow for accurate predictions of the optical properties. These properties are related to the electronic transitions in the molecules, which include two-photon absorption cross-sections. Here we use TDDFT to understand the mechanism of aza-crown based fluorescent probes for metals sensing applications. Our findings suggest changes in local excitation in the rhodol chromophore between unbound form and when bound to the metal analyte. These changes are caused by a charge transfer from the aza-crown group and pyrazol units toward the rhodol unit. Understanding this mechanism leads to an optimized design with higher two-photon excited fluorescence to be used in medical applications.

Theoretical study of chromophores for biological sensing: Understanding the mechanism of rhodol based multi-chromophoric systems.

PubMed

Rivera-Jacquez, Hector J; Masunov, Artëm E

2018-06-05

Development of two-photon fluorescent probes can aid in visualizing the cellular environment. Multi-chromophore systems display complex manifolds of electronic transitions, enabling their use for optical sensing applications. Time-Dependent Density Functional Theory (TDDFT) methods allow for accurate predictions of the optical properties. These properties are related to the electronic transitions in the molecules, which include two-photon absorption cross-sections. Here we use TDDFT to understand the mechanism of aza-crown based fluorescent probes for metals sensing applications. Our findings suggest changes in local excitation in the rhodol chromophore between unbound form and when bound to the metal analyte. These changes are caused by a charge transfer from the aza-crown group and pyrazol units toward the rhodol unit. Understanding this mechanism leads to an optimized design with higher two-photon excited fluorescence to be used in medical applications. Copyright © 2018 Elsevier B.V. All rights reserved.

Tautomerism provides a molecular explanation for the mutagenic properties of the anti-HIV nucleoside 5-aza-5,6-dihydro-2′-deoxycytidine

PubMed Central

Li, Deyu; Fedeles, Bogdan I.; Singh, Vipender; Peng, Chunte Sam; Silvestre, Katherine J.; Simi, Allison K.; Simpson, Jeffrey H.; Tokmakoff, Andrei; Essigmann, John M.

2014-01-01

Viral lethal mutagenesis is a strategy whereby the innate immune system or mutagenic pool nucleotides increase the error rate of viral replication above the error catastrophe limit. Lethal mutagenesis has been proposed as a mechanism for several antiviral compounds, including the drug candidate 5-aza-5,6-dihydro-2′-deoxycytidine (KP1212), which causes A-to-G and G-to-A mutations in the HIV genome, both in tissue culture and in HIV positive patients undergoing KP1212 monotherapy. This work explored the molecular mechanism(s) underlying the mutagenicity of KP1212, and specifically whether tautomerism, a previously proposed hypothesis, could explain the biological consequences of this nucleoside analog. Establishing tautomerism of nucleic acid bases under physiological conditions has been challenging because of the lack of sensitive methods. This study investigated tautomerism using an array of spectroscopic, theoretical, and chemical biology approaches. Variable temperature NMR and 2D infrared spectroscopic methods demonstrated that KP1212 existed as a broad ensemble of interconverting tautomers, among which enolic forms dominated. The mutagenic properties of KP1212 were determined empirically by in vitro and in vivo replication of a single-stranded vector containing a single KP1212. It was found that KP1212 paired with both A (10%) and G (90%), which is in accord with clinical observations. Moreover, this mutation frequency is sufficient for pushing a viral population over its error catastrophe limit, as observed before in cell culture studies. Finally, a model is proposed that correlates the mutagenicity of KP1212 with its tautomeric distribution in solution. PMID:25071207

6-Methylsulfinylhexyl isothiocyanate and its homologues as food-originated compounds with antibacterial activity against Escherichia coli and Staphylococcus aureus.

PubMed

Ono, H; Tesaki, S; Tanabe, S; Watanabe, M

1998-02-01

Cruciferae plants, banana and coriander each showed antibacterial activity. The highest activity among the food-stuffs tested was found in the stems of wasabi. An ethereal extract from wasabi stems had potent antibacterial activity and we isolated the active compound from the extract. Instrumental analysis identified the compound as 6-methylsulfinylhexyl isothiocyanate. Some homologues of 6-methylsulfinylhexyl isothiocyanate were also active against Escherichia coli and Staphylococcus aureus.

Thiopurine Drugs Azathioprine and 6-Mercaptopurine Inhibit Mycobacterium paratuberculosis Growth In Vitro▿

PubMed Central

Shin, Sung Jae; Collins, Michael T.

2008-01-01

The in vitro susceptibility of human- and bovine-origin Mycobacterium paratuberculosis to the thioupurine drugs 6-mercaptopurine (6-MP) and azathioprine (AZA) was established using conventional plate counting methods and the MGIT 960 ParaTB culture system. Both 6-MP and AZA had antibacterial activity against M. paratuberculosis; isolates from Crohn's disease patients tended to be more susceptible than were bovine-origin isolates. Isolates of Mycobacterium avium, used as controls, were generally resistant to both AZA and 6-MP, even at high concentrations (≥64.0 μg/ml). Among rapidly growing mycobacteria, Mycobacterium phlei was susceptible to 6-MP and AZA whereas Mycobacterium smegmatis strains were not. AZA and 6-MP limited the growth of, but did not kill, M. paratuberculosis in a dose-dependent manner. Anti-inflammatory drugs in the sulfonamide family (sulfapyridine, sulfasalazine, and 5-aminosalycilic acid [mesalamine]) had little or no antibacterial activity against M. paratuberculosis. The conventional antibiotics azithromycin and ciprofloxacin, used as control drugs, were bactericidal for M. paratuberculosis, exerting their killing effects on the organism relatively quickly. Simultaneous exposure of M. paratuberculosis to 6-MP and ciprofloxacin resulted in significantly higher CFU than use of ciprofloxacin alone. These data may partially explain the paradoxical response of Crohn's disease patients infected with M. paratuberculosis to treatment with immunosuppressive thiopurine drugs, i.e., they do not worsen with anti-inflammatory treatment as would be expected with a microbiological etiologic pathogen. These findings also should influence the design of therapeutic trials to evaluate antibiotic treatments of Crohn's disease: AZA drugs may confound interpretation of data on therapeutic responses for both antibiotic-treated and control groups. PMID:18070971

Developmental ethanol exposure impairs locomotor movement in Japanese medaka (Oryzias latipes) larvae targeting epigenome.

PubMed

Dasmahapatra, Asok K; Carty, Dennis R; Khan, Ikhlas A

2017-11-01

Evidence indicated ethanol exposure during development disrupts brain functions that induces fetal alcohol spectrum disorder (FASD) phenotypes with behavioral abnormalities. We aimed to investigate whether prenatal ethanol exposure has any potential impact on behavior of a FASD fish model. Fertilized Japanese medaka (Oryzias latipes) eggs were exposed to 100-300 mM ethanol or 2 mM 5-azacytidine (5-azaC), 0-2 day post fertilization (dpf), in embryo-rearing medium (ERM). Survived embryos were maintained in clean ERM and used either for gene expression analysis on 2- and 6-dpf or allowed to hatch for behavioral study. Photomotor response of 3-4 day post hatch larvae were tracked for 3 h with light-dark transitions. It was observed that larval swimming was phototactic; enhanced in presence of light, declined in dark. Phototactic response was also observed in larvae prenatally exposed to ethanol or 5-azaC; however, the total distance swum by these larvae compared to controls declined. Further analysis indicated that, in light phases, total swimming activity and average swimming speed were reduced in larvae prenatally exposed to ethanol (300 mM) or 5-azaC. Expression analysis of baz1a and baz2a in embryos indicated developmental regulation. Ethanol (100-300 mM) or 5-azaC (2 mM) were able to modulate downregulation of both baz1a and baz2a mRNAs only in 6 dpf embryos of 300 mM ethanol and 5-azaC (2 mM) groups. These studies indicated that prenatal exposure to ethanol or 5-azaC was able to disrupt movements and thus swimming behavior in FASD phenotypes probably due to delayed remodeling of genome and epigenome. Published by Elsevier Ltd.

Selective inhibition of esophageal cancer cells by combination of HDAC inhibitors and Azacytidine

PubMed Central

Ahrens, Theresa D; Timme, Sylvia; Hoeppner, Jens; Ostendorp, Jenny; Hembach, Sina; Follo, Marie; Hopt, Ulrich T; Werner, Martin; Busch, Hauke; Boerries, Melanie; Lassmann, Silke

2015-01-01

Esophageal cancers are highly aggressive tumors with poor prognosis despite some recent advances in surgical and radiochemotherapy treatment options. This study addressed the feasibility of drugs targeting epigenetic modifiers in esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) cells. We tested inhibition of histone deacetylases (HDACs) by SAHA, MS-275, and FK228, inhibition of DNA methyltransferases by Azacytidine (AZA) and Decitabine (DAC), and the effect of combination treatment using both types of drugs. The drug targets, HDAC1/2/3 and DNMT1, were expressed in normal esophageal epithelium and tumor cells of ESCC or EAC tissue specimens, as well as in non-neoplastic esophageal epithelial (Het-1A), ESCC (OE21, Kyse-270, Kyse-410), and EAC (OE33, SK-GT-4) cell lines. In vitro, HDAC activity, histone acetylation, and p21 expression were similarly affected in non-neoplastic, ESCC, and EAC cell lines post inhibitor treatment. Combined MS-275/AZA treatment, however, selectively targeted esophageal cancer cell lines by inducing DNA damage, cell viability loss, and apoptosis, and by decreasing cell migration. Non-neoplastic Het-1A cells were protected against HDACi (MS-275)/AZA treatment. RNA transcriptome analyses post MS-275 and/or AZA treatment identified novel regulated candidate genes (up: BCL6, Hes2; down: FAIM, MLKL), which were specifically associated with the treatment responses of esophageal cancer cells. In summary, combined HDACi/AZA treatment is efficient and selective for the targeting of esophageal cancer cells, despite similar target expression of normal and esophageal cancer epithelium, in vitro and in human esophageal carcinomas. The precise mechanisms of action of treatment responses involve novel candidate genes regulated by HDACi/AZA in esophageal cancer cells. Together, targeting of epigenetic modifiers in esophageal cancers may represent a potential future therapeutic approach. PMID:25923331

Acute exposure to the biopesticide azadirachtin affects parameters in the gills of common carp (Cyprinus carpio).

PubMed

Murussi, Camila R; Costa, Maiara D; Leitemperger, Jossiele W; Flores-Lopes, Fábio; Menezes, Charlene C; Loebens, Luisa; de Avila, Luis Antonio; Rizzetti, Tiele M; Adaime, Martha B; Zanella, Renato; Loro, Vania L

2016-02-01

The biopesticide, azadirachtin (Aza) is less hazardous to the environment, but may cause several toxic effects in aquatic organisms. The Cyprinus carpio (n=12, for all concentrations) after 10days of acclimation under controlled conditions, were exposed at 20, 40, and 60μL/L of Aza during 96h. After this period, fish were anesthetized and euthanized then mucus layer and gills collected. In this study, the effects of exposure to different Aza concentrations were analysed through a set of biomarkers: Na(+)/K(+-)ATPase, lipid peroxidation (TBARS), protein carbonyl (PC), superoxide dismutase (SOD), glutathione-S-transferase (GST), catalase (CAT), glutathione peroxidase (GPx), non-protein thiols (NPSH), ascorbic acid (AsA) and histological parameters and, yet, protein and glucose concentration in the surface area of mucous layer. Na(+)K(+-)ATPase was inhibited at 40 and 60μL/L compared to control. TBARS decreased at 40μL/L compared to control. PC, SOD and GST increased at 60μL/L in comparison to control. CAT increased at 20 and 60μL/L, and GPx increased in all Aza concentrations compared to control. NPSH decreased and AsA increased in all concentrations in comparison to control. Histological analyses demonstrated an increase in the intensity of the damage with increasing Aza concentration. Alterations in histological examination were elevation and hypertrophy of the epithelial cells of the secondary filament, hypertrophy and hyperplasia of the mucous and chlorate cells and lamellar aneurism. Glucose and protein concentrations in mucus layer increased at 60μL/L compared to control. In general, we suggest that 60μL/L Aza concentration affected several parameters causing disruptions carp metabolism. Copyright © 2015 Elsevier Inc. All rights reserved.

Research on DNA methylation of human osteosarcoma cell MGMT and its relationship with cell resistance to alkylating agents.

PubMed

Guo, Jun; Cui, Qiu; Jiang, WeiHao; Liu, Cheng; Li, DingFeng; Zeng, Yanjun

2013-08-01

The objective of this study was to explore the O(6)-methylguanine-DNA methyltransferase (MGMT) gene methylation status and its protein expression, as well as the effects of demethylating agent 5-Aza-2'-deoxycytidine (5-Aza-CdR) on MGMT gene expression and its resistance to alkylating agents, and to elucidate MGMT expression mechanism and significance in osteosarcoma. The human osteosarcoma cell lines Saos-2 and MG-63 were collected and treated with 5-Aza-CdR for 6 days. The cells not treated with 5-Aza-CdR were set as a negative control. The genomic DNA was extracted from the Saos-2 and MG-63 cells using methylation-specific PCR to detect the promoter CpG island methylation status of the MGMT gene. Cell sensitivity to alkylating agents before and after drug administration was detected by the MTT method. The variation in MGMT gene mRNA and protein was detected by reverse transcription PCR (RT-PCR) and Western blotting. The MGMT promoter gene of normal Saos-2 cells was methylated, with reduced MGMT mRNA and protein expression; the MGMT mRNA and protein expression of Saos-2 cells treated with 5-Aza-CdR was obviously enhanced, and its sensitivity to alkylating agents was reversed. Meanwhile, with promoter CpG island unmethylation of the MGMT gene, MGMT protein was expressed in the normal MG-63 cells and the MG-63 cells treated with 5-Aza-CdR, and both showed resistance to alkylating agents. The methylation status of the MGMT gene promoter in human osteosarcoma cells reflected the cells' ability to induce MGMT protein expression and can be used as a molecular marker to project the sensitivity of cancer tissues to alkylating agent drugs.

Chemical constituents of Piper betle Linn. (Piperaceae) roots.

PubMed

Ghosh, K; Bhattacharya, T K

2005-08-31

Column chromatography of the alcoholic extract of Piper betle roots furnished aristololactam A-II and a new phenyl propene, characterized as 4-allyl resorcinol, while the petroleum-ether extract yielded a diketosteroid, viz. stigmast-4-en-3,6-dione. All these compounds were characterized by spectroscopic means. Isolation of these compounds from this source is being reported here for the first time.