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https://www.readbyqxmd.com/read/26390117/preparation-of-halogenated-fluorescent-diaminophenazine-building-blocks
#1
Matthieu Koepf, Shin Hee Lee, Bradley J Brennan, Dalvin D Méndez-Hernández, Victor S Batista, Gary W Brudvig, Robert H Crabtree
A short, convenient, and scalable protocol for the one-pot synthesis of a series of fluorescent 7,8-dihalo-2,3-diaminophenazines is introduced. The synthetic route is based on the oxidative condensation of 4,5-dihalo-1,2-diaminobenzenes in aqueous conditions. The resulting diaminophenazines could be attractive intermediates for the preparation of polyfunctional phenazines and extended polyheteroacenes. We find that the undesired hydroxylation byproducts, typically obtained in aqueous conditions, are completely suppressed by addition of a stoichiometric amount of acetone during the oxidation step allowing for selective formation of 7,8-dihalo-2,2-dimethyl-2,3-dihydro-1H-imidazo[4,5-b]phenazine derivatives with good to excellent yields...
October 16, 2015: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/26386191/toxicokinetics-and-toxicity-of-atorvastatin-in-dogs
#2
C E Herron, C C Brueckner, J P Chism, D C Kemp, J S Prescott, G A Smith, D H Melich, N Oleas, J W Polli
HMG-CoA reductase inhibitors (e.g., statins) are an important clinical option to lower cholesterol and treat co-morbidities. Atorvastatin is the most prescribed statin and has obtained generic status. We recently had a clinical development program evaluating a combination of atorvastatin with a GPR119 agonist as a treatment for dyslipidemia, where toxicological evaluations in dogs were completed. There were several challenges related to selecting doses for atorvastatin, including understanding the dose-exposure relationship from different drug forms used by the innovator in their general toxicology studies, bioanalytical assays that did not separate and quantify parent from metabolites, and high variability in the systemic exposures following oral dosing...
November 15, 2015: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/26361012/evolutionary-comparisons-predict-that-dimerization-of-human-cytochrome-p450-aromatase-increases-its-enzymatic-activity-and-efficiency
#3
COMPARATIVE STUDY
Lisandra L Martin, Jessica K Holien, Dario Mizrachi, C Jo Corbin, Alan J Conley, Michael W Parker, Raymond J Rodgers
Estrogen is an essential vertebrate hormone synthesized from androgens involving multiple hydroxylations, catalyzed by cytochrome P450 aromatase (P450arom or CYP19) enzymes. Despite their importance, very few comparative studies have been conducted on vertebrate and/or mammalian P450arom enzymes, either structurally or functionally. Here we directly compared the human (h-) and porcine gonadal (p(g)-) P450arom, as p(g)-P450arom has very low catalytic efficiency, with a ten-fold higher affinity (Km) for a substrate (androstenedione) and ten-fold reduction in turnover (Vmax)...
November 2015: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/26352800/structures-of-pseudomonas-aeruginosa-lpxa-reveal-the-basis-for-its-substrate-selectivity
#4
Emmanuel W Smith, XiuJun Zhang, Cyrus Behzadi, Logan D Andrews, Frederick Cohen, Yu Chen
In Gram-negative bacteria, the first step of lipid A biosynthesis is catalyzed by UDP-N-acetylglucosamine acyltransferase (LpxA) through the transfer of a R-3-hydroxyacyl chain from the acyl carrier protein (ACP) to the 3-hydroxyl group of UDP-GlcNAc. Previous studies suggest that LpxA is a critical determinant of the acyl chain length found in lipid A, which varies among species of bacteria. In Escherichia coli and Leptospira interrogans, LpxA prefers to incorporate longer R-3-hydroxyacyl chains (C14 and C12, respectively), whereas in Pseudomonas aeruginosa, the enzyme is selective for R-3-hydroxydecanoyl, a 10-hydrocarbon long acyl chain...
September 29, 2015: Biochemistry
https://www.readbyqxmd.com/read/26342264/insights-into-solar-photo-fenton-reaction-parameters-in-the-oxidation-of-a-sanitary-landfill-leachate-at-lab-scale
#5
Tânia F C V Silva, Rui Ferreira, Petrick A Soares, Diego R Manenti, Amélia Fonseca, Isabel Saraiva, Rui A R Boaventura, Vítor J P Vilar
This work evaluates the effect of the main photo-Fenton (PF) reaction variables on the treatment of a sanitary landfill leachate collected at the outlet of a leachate treatment plant, which includes aerated lagooning followed by aerated activated sludge and a final coagulation-flocculation step. The PF experiments were performed in a lab-scale compound parabolic collector (CPC) photoreactor using artificial solar radiation. The photocatalytic reaction rate was determined while varying the total dissolved iron concentration (20-100 mg Fe(2+)/L), solution pH (2...
December 1, 2015: Journal of Environmental Management
https://www.readbyqxmd.com/read/26327384/the-catalytic-mechanism-and-unique-low-ph-optimum-of-caldicellulosiruptor-bescii-family-3-pectate-lyase
#6
Markus Alahuhta, Larry E Taylor, Roman Brunecky, Deanne W Sammond, William Michener, Michael W W Adams, Michael E Himmel, Yannick J Bomble, Vladimir Lunin
The unique active site of the Caldicellulosiruptor bescii family 3 pectate lyase (PL3) enzyme has been thoroughly characterized using a series of point mutations, X-ray crystallography, pK(a) calculations and biochemical assays. The X-ray structures of seven PL3 active-site mutants, five of them in complex with intact trigalacturonic acid, were solved and characterized structurally, biochemically and computationally. The results confirmed that Lys108 is the catalytic base, but there is no clear candidate for the catalytic acid...
September 2015: Acta Crystallographica. Section D, Biological Crystallography
https://www.readbyqxmd.com/read/26321196/role-of-drug-metabolism-in-the-cytotoxicity-and-clinical-efficacy-of-anthracyclines
#7
REVIEW
Derek W Edwardson, Rashmi Narendrula, Simon Chewchuk, Kyle Mispel-Beyer, Jonathan P J Mapletoft, Amadeo M Parissenti
Many clinical studies involving anti-tumor agents neglect to consider how these agents are metabolized within the host and whether the creation of specific metabolites alters drug therapeutic properties or toxic side effects. However, this is not the case for the anthracycline class of chemotherapy drugs. This review describes the various enzymes involved in the one electron (semi-quinone) or two electron (hydroxylation) reduction of anthracyclines, or in their reductive deglycosidation into deoxyaglycones...
2015: Current Drug Metabolism
https://www.readbyqxmd.com/read/26309284/noctilisin-a-venom-glycopeptide-of-sirex-noctilio-hymenoptera-siricidae-causes-needle-wilt-and-defense-gene-responses-in-pines
#8
J Michael Bordeaux, W Walter Lorenz, Darryl Johnson, Majors J Badgett, John Glushka, Ronald Orlando, Jeffrey F D Dean
During oviposition, female Sirex noctilio (F.) (Siricidae) woodwasps inject their conifer hosts with a venom gland secretion. The secretion induces a variety of host physiological changes that facilitate subsequent lethal infection by a symbiotic fungus. A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants...
October 1, 2014: Journal of Economic Entomology
https://www.readbyqxmd.com/read/26299827/discovery-of-5-substituted-tetrahydronaphthalen-2yl-methyl-with-n-phenyl-n-piperidin-4-yl-propionamide-derivatives-as-potent-opioid-receptor-ligands
#9
Srinivas Deekonda, Lauren Wugalter, Vinod Kulkarni, David Rankin, Tally M Largent-Milnes, Peg Davis, Neemah M Bassirirad, Josephine Lai, Todd W Vanderah, Frank Porreca, Victor J Hruby
A new series of novel opioid ligands have been designed and synthesized based on the 4-anilidopiperidine scaffold containing a 5-substituted tetrahydronaphthalen-2yl)methyl group with different N-phenyl-N-(piperidin-4-yl)propionamide derivatives to study the biological effects of these substituents on μ and δ opioid receptor interactions. Recently our group reported novel 4-anilidopiperidine analogues, in which several aromatic ring-contained amino acids were conjugated with N-phenyl-N-(piperidin-4-yl)propionamide and examined their biological activities at the μ and δ opioid receptors...
September 15, 2015: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/26267117/oxygen-18-kinetic-isotope-effects-of-nonheme-iron-enzymes-hepd-and-mpns-support-iron-iii-superoxide-as-the-hydrogen-abstraction-species
#10
Hui Zhu, Spencer C Peck, Florence Bonnot, Wilfred A van der Donk, Judith P Klinman
Nonheme iron oxygenases that carry out four-electron oxidations of substrate have been proposed to employ iron(III) superoxide species to initiate this reaction [Paria, S.; Que, L.; Paine, T. K. Angew. Chem. Int. Ed. 2011, 50, 11129]. Here we report experimental evidence in support of this proposal. (18)O KIEs were measured for two recently discovered mononuclear nonheme iron oxygenases: hydroxyethylphosphonate dioxygenase (HEPD) and methylphosphonate synthase (MPnS). Competitive (18)O KIEs measured with deuterated substrates are larger than those measured with unlabeled substrates, which indicates that C-H cleavage must occur before an irreversible reductive step at molecular oxygen...
August 26, 2015: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/26266701/in-situ-atr-ftir-study-of-h2o-and-d2o-adsorption-on-tio2-under-uv-irradiation
#11
Hamza Belhadj, Amer Hakki, Peter K J Robertson, Detlef W Bahnemann
The adsorption of water and deuterium oxide on TiO2 surfaces was investigated in the dark as well as under UV(A) irradiation using in situ ATR-FTIR spectroscopy under oxygen and oxygen free conditions. Adsorption of H2O-D2O mixtures revealed an isotopic exchange reaction occurring onto the surface of TiO2 in the dark. Under UV(A) irradiation, the amount of both OH and OD groups was found to be increased by the presence of molecular oxygen. Furthermore, the photocatalytic formation of hydroperoxide under oxygenated condition has been recorded utilizing Attenuated Total Reflection Fourier Transformed Infrared (ATR-FTIR) spectroscopy which appeared as new band at 3483 cm(-1)...
September 21, 2015: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/26266610/water-on-the-mgo-001-surface-surface-reconstruction-and-ion-solvation
#12
Milan Ončák, Radosław Włodarczyk, Joachim Sauer
The interaction of water with the MgO(001) surface under ambient conditions is investigated by density functional theory combined with statistical thermodynamics. For water loadings of more than one monolayer, we show that the standard structure model, a fully hydroxylated surface, needs to be revised. Reconstructed surfaces, involving hydrated/hydroxylated Mg(2+) ions above the surface, are more stable. These findings provide a consistent picture for surface hydroxylation between low and high water coverage that is in agreement with available XPS data...
June 18, 2015: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/26264479/protective-effects-of-epigallocatechin-3-gallate-against-acetaminophen-induced-liver-injury-in-rats
#13
Hsien-Tsung Yao, Yu-Chi Yang, Chen-Hui Chang, Hui-Ting Yang, Mei-Chin Yin
(-)-Epigallocatechin-3-gallate (EGCG) is the most abundant catechin with various biological activities found in tea. In this study, the effects of EGCG on the metabolism and toxicity of acetaminophen in rat liver were investigated. Male Sprague-Dawley rats were fed a controlled diet without or with EGCG (0.54 %, w/w) for 1 week and were then intraperitoneally injected with acetaminophen (1 g/kg body weight) and killed after 12 h. Concentrations of acetaminophen and its conjugates in plasma and liver were then determined...
September 2015: BioMedicine
https://www.readbyqxmd.com/read/26262600/tissue-distribution-excretion-and-the-metabolic-pathway-of-2-2-4-4-5-penta-chlorinated-diphenylsulfide-cdps-99-in-icr-mice
#14
Xiaolan Zeng, Xuesheng Zhang, Li Qin, Zunyao Wang
The tissue distribution, excretion, and metabolic pathway of 2,2',4,4',5-penta-chlorinated diphenylsulfide (CDPS-99) in ICR mice were investigated after oral perfusion at 10mg/kg body weight (b.w.). Biological samples were extracted and separated and, for the first time, were determined by a novel, sensitive, and specific GC-MS method under the full scan and selected ion monitoring (SIM) modes. The results showed that the concentrations of CDPS-99 in the liver, kidneys, and serum reached a maximum after a one-day exposure and that the CDPS-99 concentration in the liver was the highest (3...
September 15, 2015: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/26259765/effect-of-dietary-vanadium-and-vitamin-c-on-egg-quality-and-antioxidant-status-in-laying-hens
#15
J P Wang, K R He, X M Ding, Y H Luo, S P Bai, Q F Zeng, Z W Su, Y Xuan, K Y Zhang
This study assessed the effect of dietary vanadium (V) and vitamin C (VC) on production performance, egg quality and antioxidant status in laying hens. A total of 360 laying hens (31-week-old) were randomly allotted into a 3 × 3 factorial arrangement treatments (four replicates and 10 chicks per replicate) with three levels of dietary V (0, 5 and 10 mg/kg) and three levels of vitamin C (0, 50 and 100 mg/kg) for 12 weeks. The effect of V and VC did not alter egg production, egg weight, average daily feed intake and feed conversion ratio during 1-12 week...
June 2016: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/26248410/-effects-of-hydroxyl-acetylated-curcumin-induced-sonodynamic-therapy-on-viability-apoptosis-and-necrosis-of-thp-1-macrophages
#16
Li-ming Yang, Hui-juan Liang, Cheng-hai Peng, Jia-li Cheng, Huan Wang, Ld-qing Weng, Zhi-tao Li, Ye Tian
OBJECTIVE: We aim to investigate the sonodynamic effect induced by hydroxyl acetylated curcumin (HAC) on THP-1 macrophages. METHODS: THP-1 derived macrophages (1 x 10(5) per milliliter) were cultured with HAC at a concentration of 5 µg/mL for 4 h and then exposed to pulse ultrasound treatment (0.5 W/cm2) for 5 min. Six hours later, cell viability analysis was performed with CCK-8 assay, apoptosis and necrosis analysis were detected with Annexin V/PI staining by flow cytometery...
March 2015: Chinese Journal of Applied Physiology
https://www.readbyqxmd.com/read/26246720/optimization-of-ultrasonic-assisted-extraction-of-antioxidant-compounds-from-guava-psidium-guajava-l-leaves-using-response-surface-methodology
#17
Fansheng Kong, Shujuan Yu, Zeng Feng, Xinlan Wu
OBJECTIVE: To optimization of extraction of antioxidant compounds from guava (Psidium guajava L.) leaves and showed that the guava leaves are the potential source of antioxidant compounds. MATERIALS AND METHODS: The bioactive polysaccharide compounds of guava leaves (P. guajava L.) were obtained using ultrasonic-assisted extraction. Extraction was carried out according to Box-Behnken central composite design, and independent variables were temperature (20-60°C), time (20-40 min) and power (200-350 W)...
July 2015: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/26243287/amycolatopsis-stemonae-sp-nov-isolated-from-thai-medicinal-plant
#18
Nattaporn Klykleung, Somboon Tanasupawat, Pattama Pittayakhajonwut, Moriya Ohkuma, Takuji Kudo
A novel actinomycete, strain ST1-08T, was isolated from stem of Stemona sp. in Thailand. The taxonomic position of this isolate was determined by using polyphasic approach. Strain ST1-08T contained meso-diaminopimelic acid in cell wall peptidoglycan and contained arabinose and galactose as the diagnostic sugars of the whole cell hydrolysate that were typical properties of the members in the genus Amycolatopsis. It grew at 15-40 oC, pH 6-9 and on 5 % (w/v) NaCl. Gelatin liquefaction, starch hydrolysis and skim milk peptonization were positive...
August 4, 2015: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/26232674/determinants-of-disinfectant-pretreatment-efficacy-for-nitrosamine-control-in-chloraminated-drinking-water
#19
Daniel L McCurry, Stuart W Krasner, Urs von Gunten, William A Mitch
Utilities using chloramines need strategies to mitigate nitrosamine formation to meet potential future nitrosamine regulations. The ability to reduce NDMA formation under typical post-chloramination conditions of pretreatment with ultraviolet light from a low pressure mercury lamp (LPUV), free chlorine (HOCl), ozone (O3), and UV light from a medium pressure mercury lamp (MPUV) were compared at exposures relevant to drinking water treatment. The order of efficacy after application to waters impacted by upstream wastewater discharges was O3 > HOCl ≈ MPUV > LPUV...
November 1, 2015: Water Research
https://www.readbyqxmd.com/read/26220399/hydroxyproline-ring-pucker-causes-frustration-of-helix-parameters-in-the-collagen-triple-helix
#20
W Ying Chow, Dominique Bihan, Chris J Forman, David A Slatter, David G Reid, David J Wales, Richard W Farndale, Melinda J Duer
Collagens, the most abundant proteins in mammals, are defined by their triple-helical structures and distinctive Gly-Xaa-Yaa repeating sequence, where Xaa is often proline and Yaa, hydroxyproline (Hyp/O). It is known that hydroxyproline in the Yaa position stabilises the triple helix, and that lack of proline hydroxylation in vivo leads to dysfunctional collagen extracellular matrix assembly, due to a range of factors such as a change in hydration properties. In addition, we note that in model peptides, when Yaa is unmodified proline, the Xaa proline has a strong propensity to adopt an endo ring conformation, whilst when Yaa is hydroxyproline, the Xaa proline adopts a range of endo and exo conformations...
2015: Scientific Reports
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