The Experts below are selected from a list of 2976 Experts worldwide ranked by ideXlab platform
Paul R Thompson - One of the best experts on this subject based on the ideXlab platform.
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Development of a Suicide Inhibition-Based Protein Labeling Strategy for Nicotinamide N-Methyltransferase
ACS Chemical Biology, 2019Co-Authors: Santanu Mondal, Ari J. Salinger, Walter Fast, Eranthie Weerapana, Li Zheng, Paul R ThompsonAbstract:Nicotinamide N-methyltransferase (NNMT) catalyzes the S-adenosyl-l-methionine-dependent methylation of nicotinamide to form N-methylnicotinamide. This enzyme detoxifies xenobiotics and regulates NAD+ biosynthesis. Additionally, NNMT is overexpressed in various cancers. Herein, we describe the first NNMT-targeted suicide substrates. These compounds, which include 4-Chloropyridine and 4-chloronicotinamide, exploit the broad substrate scope of NNMT; methylation of the pyridine nitrogen enhances the electrophilicity of the C4 position, thereby promoting an aromatic nucleophilic substitution by C159, a noncatalytic cysteine. On the basis of this activity, we developed a suicide inhibition-based protein labeling strategy using an alkyne-substituted 4-Chloropyridine that selectively labels NNMT in vitro and in cells. In total, this study describes the first NNMT-directed activity-based probes.
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Development of a Suicide Inhibition-Based Protein Labeling Strategy for Nicotinamide N‑Methyltransferase
2019Co-Authors: Sudeshna Sen, Ari J. Salinger, Walter Fast, Eranthie Weerapana, Santanu Mondal, Li Zheng, Paul R ThompsonAbstract:Nicotinamide N-methyltransferase (NNMT) catalyzes the S-adenosyl-l-methionine-dependent methylation of nicotinamide to form N-methylnicotinamide. This enzyme detoxifies xenobiotics and regulates NAD+ biosynthesis. Additionally, NNMT is overexpressed in various cancers. Herein, we describe the first NNMT-targeted suicide substrates. These compounds, which include 4-Chloropyridine and 4-chloronicotinamide, exploit the broad substrate scope of NNMT; methylation of the pyridine nitrogen enhances the electrophilicity of the C4 position, thereby promoting an aromatic nucleophilic substitution by C159, a noncatalytic cysteine. On the basis of this activity, we developed a suicide inhibition-based protein labeling strategy using an alkyne-substituted 4-Chloropyridine that selectively labels NNMT in vitro and in cells. In total, this study describes the first NNMT-directed activity-based probes
Francisco J. Urbano - One of the best experts on this subject based on the ideXlab platform.
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A comparative study of photocatalytic degradation of 3-Chloropyridine under UV and solar light by homogeneous (photo-Fenton) and heterogeneous (TiO2) photocatalysis
Applied Catalysis B: Environmental, 2012Co-Authors: M.c. Ortega-liébana, Alberto Marinas, José M. Marinas, Elena Sánchez-lópez, Jesús Hidalgo-carrillo, Francisco J. UrbanoAbstract:Abstract Photocatalytic degradation of 3-Chloropyridine in the homogeneous (photo-Fenton) and heterogeneous (TiO 2 ) phase was studied using both UV and sun light. Complete mineralization was achieved in both cases though times required in photo-Fenton process were ca. 5 times shorter under our experimental conditions. Results found at lab scale (solar simulator) were successfully extrapolated to a larger scale (30 L) thus evidencing the validity of the method for treatment of waters polluted with this kind of chemical. Toxicity tests ( Vibrio fischeri ) showed that some intermediates more toxic than 3-Chloropyridine were formed as reaction proceeded.
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Titania nano-photocatalysts synthesized by ultrasound and microwave methodologies: Application in depuration of water from 3-Chloropyridine
Journal of Molecular Catalysis A-chemical, 2010Co-Authors: Juan Carlos Colmenares, María A. Aramendía, Alberto Marinas, José M. Marinas, Francisco J. UrbanoAbstract:Abstract The effect of aging the gel under ultrasonic (us) and microwave (mw) irradiation on the characteristics of the synthesized solids was studied. Sonication ensured the obtention of pure anatase nanoparticles in high crystalline state and generally led to obtain a high surface area and more active photocatalyst. Catalysts were characterized by a wide range of physical techniques (ICP-MS, N 2 isotherms, XRD, UV–vis and TEM). The total degradation of 3-Chloropyridine was studied under titania-based photocatalysts, this degradation followed a zero-order kinetics respect to 3-Chloropyridine. In our conditions, 100 ppm of 3-Chloropyridine was degraded completely within ca. 8 h of UV-radiation (365 nm wavelength) on bare-titania systems. Some reactions intermediates were identified by SPME-GC–MS and a plausible mineralization route was suggested implying two parallel routes with hydroxylation and ring opening prior to or after the release of chloride ions. The modification of titania surface with metals (Fe, Pt, Pd) was detrimental for photocatalysis.
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Individual and competitive liquid-phase hydrodechlorination of chlorinated pyridines over alkali-modified Pd/ZrO2
Applied Catalysis B-environmental, 2007Co-Authors: José María Armingol Moreno, María A. Aramendía, Alberto Marinas, José M. Marinas, Francisco J. UrbanoAbstract:Individual and competitive liquid-phase hydrodechlorination of chlorinated pyridines has been studied over alkali-modified zirconia-supported palladium catalysts. All experiments proceed without catalyst deactivation as a result of the interaction of the reaction products (HCl and pyridine) forming pyridinium chloride, thus avoiding the detrimental effect of HCl on palladium particles. Individual experiments indicate a different behaviour for 2-Chloropyridine and 3-Chloropyridine. Catalyst modification with alkali metals improves the catalytic activity for 3-Chloropyridine but not for 2-Chloropyridine hydrodechlorination. 2,3-DiChloropyridine hydrodechlorination yields lower reaction rates than 2- or 3-Chloropyridine. Moreover, no partially chlorinated compounds were detected. Competitive hydrodechlorination of equimolecular mixtures of 2-and 3-Chloropyridine allow us to obtain both the reactivity and adsorption coefficient of 3-Chloropyridine with respect to 2-Chloropyridine. Again, in competitive hydrodehalogenation, 3-Chloropyridine reacts faster than 2-Chloropyridine for all catalysts. However, results indicate that the alkali-modified catalysts adsorb preferably 2-Chloropyridine instead of 3-Chloropyridine. Moreover, competitive hydrodehalogenation carried out for the couples 3-Chloropyridine/chlorobenzene, 2-chloropiridine/chlorobenzene and 2,3-diChloropyridine/chlorobenzene revealed that chlorinated pyridines are reduced to the detriment of chlorobenzene due to the preferential adsorption of chlorinated pyridines against chlorobenzene. All data support a reaction mechanism based on an electrophilic attack to the carbon bearing the chlorine atoms.
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Hydrodechlorination of 3-Chloropyridine and chlorobenzene in methanol solution over alkali-modified zirconia-supported palladium catalysts
Applied Catalysis B-environmental, 2005Co-Authors: José María Armingol Moreno, María A. Aramendía, Alberto Marinas, José M. Marinas, Francisco J. UrbanoAbstract:Abstract The liquid-phase hydrodechlorination of 3-Chloropyridine and chlorobenzene has been studied over alkali-modified zirconia-supported palladium catalysts. The modification of the ZrO 2 with alkali metal carbonates improves the catalytic activity of the final palladium catalyst. Therefore, the larger the ionic radii (Li + + + ), the greater the catalytic activity (TOF) of the palladium catalyst. For 3-Chloropyridine, hydrodechlorination proceeds without catalyst deactivation. This is explained as the result of the interaction of reaction products (pyridine and HCl) forming pyridinium chloride, thus avoiding the detrimental effect of HCl on the palladium particles. Catalytic hydrodechlorination of chlorobenzene over Pd catalysts exhibits an initial catalytic activity (TOF) much lower than that of 3-Chloropyridine and the Pd catalysts deactivate as the reaction proceeds. Finally, chlorobenzene hydrodehalogenation has also been carried out in the presence of an equimolecular amount of pyridine resulting in a decrease in the initial reaction rate on the one hand, but also in an increase in final conversion on the other.
Fabrice Cottet - One of the best experts on this subject based on the ideXlab platform.
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Silyl‐Mediated Halogen/Halogen Displacement in Pyridines and Other Heterocycles
European Journal of Organic Chemistry, 2002Co-Authors: Manfred Schlosser, Fabrice CottetAbstract:Heating with bromotrimethylsilane converts 2-Chloropyridine into 2-bromopyridine and 2-chloro-6-methylpyridine into 2-bromo-6-methylpyridine. Both 2-Chloropyridines and 2-bromopyridines give the corresponding iodo compd. when treated with in situ generated iodotrimethylsilane. Although 3- and 4-Chloropyridine are completely inert, 2,4-diChloropyridine undergoes the halogen/halogen exchange simultaneously at the 2- and 4-position. Halogen displacement takes place exclusively at the 2-position with 2,3-diChloropyridine and 2,5-diChloropyridine. In agreement with the intermediacy of N-trimethylsilylpyridinium salts as a prerequisite for the occurrence of halogen exchange, neither 2-fluoropyridine and 2-fluoro-6-methylpyridine nor any 2,6-dihalopyridine reacts. Finally, bromine/chlorine and iodine/chlorine substitution can also be accomplished with 2- or 4-chloroquinoline, 1-chloroisoquinoline, 2-chloropyrimidine, chloropyrazine, and 2,3-dichloroquinoxaline as substrates. [on SciFinder (R)]
Santanu Mondal - One of the best experts on this subject based on the ideXlab platform.
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Development of a Suicide Inhibition-Based Protein Labeling Strategy for Nicotinamide N-Methyltransferase
ACS Chemical Biology, 2019Co-Authors: Santanu Mondal, Ari J. Salinger, Walter Fast, Eranthie Weerapana, Li Zheng, Paul R ThompsonAbstract:Nicotinamide N-methyltransferase (NNMT) catalyzes the S-adenosyl-l-methionine-dependent methylation of nicotinamide to form N-methylnicotinamide. This enzyme detoxifies xenobiotics and regulates NAD+ biosynthesis. Additionally, NNMT is overexpressed in various cancers. Herein, we describe the first NNMT-targeted suicide substrates. These compounds, which include 4-Chloropyridine and 4-chloronicotinamide, exploit the broad substrate scope of NNMT; methylation of the pyridine nitrogen enhances the electrophilicity of the C4 position, thereby promoting an aromatic nucleophilic substitution by C159, a noncatalytic cysteine. On the basis of this activity, we developed a suicide inhibition-based protein labeling strategy using an alkyne-substituted 4-Chloropyridine that selectively labels NNMT in vitro and in cells. In total, this study describes the first NNMT-directed activity-based probes.
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Development of a Suicide Inhibition-Based Protein Labeling Strategy for Nicotinamide N‑Methyltransferase
2019Co-Authors: Sudeshna Sen, Ari J. Salinger, Walter Fast, Eranthie Weerapana, Santanu Mondal, Li Zheng, Paul R ThompsonAbstract:Nicotinamide N-methyltransferase (NNMT) catalyzes the S-adenosyl-l-methionine-dependent methylation of nicotinamide to form N-methylnicotinamide. This enzyme detoxifies xenobiotics and regulates NAD+ biosynthesis. Additionally, NNMT is overexpressed in various cancers. Herein, we describe the first NNMT-targeted suicide substrates. These compounds, which include 4-Chloropyridine and 4-chloronicotinamide, exploit the broad substrate scope of NNMT; methylation of the pyridine nitrogen enhances the electrophilicity of the C4 position, thereby promoting an aromatic nucleophilic substitution by C159, a noncatalytic cysteine. On the basis of this activity, we developed a suicide inhibition-based protein labeling strategy using an alkyne-substituted 4-Chloropyridine that selectively labels NNMT in vitro and in cells. In total, this study describes the first NNMT-directed activity-based probes
J.h. Koziorowska - One of the best experts on this subject based on the ideXlab platform.
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Protective role of reactive oxygen species scavengers against toxicity of 3-Chloropyridine and 2-Chloropyridine N-oxide.
Toxicology in Vitro, 1996Co-Authors: E.l. Anuszewska, J.h. KoziorowskaAbstract:Abstract The nature of biological effects of substituted pyridines and their N -oxides is a matter for discussion. Our previous study demostrated that 3-Chloropyridine is cytotoxic and clastogenic. No cytotoxic activity was observed with 2-Chloropyridine tested in the same dose range. In this study experiments were performed to assess cytotoxicity and clastogenicity of 2-Chloropyridine N -oxide and 3-Chloropyridine N -oxide. In the dose range from 800 to 3200 μg 2-Chloropyridine/ml, N -oxide showed a dose-dependent cytotoxicity and clastogenicity. In the same dose range, 3-Chloropyridine N -oxide was found to be non-cytotoxic and non-clastogenic. The nature of the effects induced by 3-Chloropyridine and 2-Chloropyridine N -oxide was analysed on the basis of possible protection by scavengers of reactive oxygen species. The cytotoxicity of both compounds was effectively suppressed by catalase and hydroxyl radicals scavengers. Pretreatment of V 3 cells with dimethyl sulfoxide or catalase provided protection against the ability of both compounds to induce chromosomal aberrations. From the data of this study we conclude that cytotoxicity and clastogenicity of 3-Chloropyridine and 2-Chloropyridine N -oxide are linked to the generation of reactive oxygen species.
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Role of pyridine N-oxide in the cytotoxicity and genotoxicity of Chloropyridines
Toxicology in Vitro, 1995Co-Authors: E.l. Anuszewska, J.h. KoziorowskaAbstract:Abstract During metabolic processes, substituted pyridines may undergo N-oxidation and decomposition. It is a matter of discussion whether these processes influence the reactivity of this class of compounds. To elucidate this problem, the cytotoxicity and clastogenicity of two selected Chloropyridines on cultured V3 cells was assessed in the absence and in the presence of pyridine N-oxide. For this purpose two cytotoxicity assays in parallel with chromosomal analysis were performed. In the dose range from 400 to 3200 μg/ml, 3-Chloropyridine showed a dose-dependent cytotoxicity and clastogenicity towards V3 cells, whereas in the same dose range 2-Chloropyridine was found to be non-cytotoxic and non-clastogenic. Pyridine N-oxide (200 μg/ml) showed protective effects against 3-Chloropyridine-induced cytotoxicity and clastogenicity. Under analogous experimental conditions cytotoxic and clastogenic effects were induced by 2-Chloropyridine. From these studies it appears that the expression of toxicity by halogenated pyridines differing in the position of the halogen moiety may be influenced in different ways by the potential metabolite.