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1.
Sci Rep ; 11(1): 24121, 2021 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-34916536

RESUMO

A novel synthetic compound from the 2-benzoyl-6-benzylidenecyclohexanone analogue, namely 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol (BBHC), showed pronounced nitric oxide inhibition in IFN-γ/LPS-induced RAW 264.7 cells. Based on this previous finding, our present study aimed to investigate the antinociceptive effects of BBHC via chemical and thermal stimuli in vivo. The investigation of the antinociceptive activity of BBHC (0.1, 0.3, 1.0 and 3.0 mg/kg, i.p.) was initiated with 3 preliminary screening tests, then BBHC was subjected to investigate its possible involvement with excitatory neurotransmitters and opioid receptors. The potential acute toxicity of BBHC administration was also studied. Administration of BBHC significantly inhibited acetic acid-induced abdominal constrictions, formalin-induced paw licking activity and developed notable increment in the latency time. BBHC's ability to suppress capsaicin- and glutamate-induced paw licking activities, as well as to antagonise the effect of naloxone, had indicated the possible involvement of its antinociception with TRPV1, glutamate and opioid receptors, respectively. The antinociceptive activities of BBHC was not related to any sedative action and no evidence of acute toxic effect was detected. The present study showed that BBHC possessed significant peripheral and central antinociceptive activities via chemical- and thermal-induced nociceptive murine models without any locomotor alteration and acute toxicity.


Assuntos
Analgésicos , Dor/tratamento farmacológico , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Compostos de Benzil/farmacologia , Compostos de Benzil/uso terapêutico , Compostos de Bromo/farmacologia , Compostos de Bromo/uso terapêutico , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Glutamatos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Neurotransmissores , Óxido Nítrico/antagonistas & inibidores , Células RAW 264.7 , Receptores Opioides , Canais de Cátion TRPV
2.
Bioconjug Chem ; 32(7): 1214-1222, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-33724798

RESUMO

Positron Emission Tomography (PET) imaging with antibody-based contrast agents frequently uses the radioisotopes [64Cu]Cu2+ and [89Zr]Zr4+. The macrobicyclic chelator commonly known as sarcophagine (sar) is ideal for labeling receptor-targeted biomolecules with [64Cu]Cu2+. The siderophore chelator, desferrioxamine-B (dfo), has been widely used to incorporate [89Zr]Zr4+ into antibodies. Here, we describe new bifunctional chelators of sar and dfo: these chelators have been functionalized with dibromomaleimides (dbm), that enable site-specific and highly stable attachment of molecular cargoes to reduced, solvent-accessible, interstrand native disulfide groups. The new sar-dbm and dfo-dbm derivatives can be easily conjugated with the IgG antibody trastuzumab via reaction with reduced interstrand disulfide groups to give site-specifically modified dithiomaleamic acid (dtm) conjugates, sar-dtm-trastuzumab and dfo-dtm-trastuzumab, in which interstrand disulfides are rebridged covalently with a small molecule linker. Both sar- and dfo-dtm-trastuzumab conjugates have been radiolabeled with [64Cu]Cu2+ and [89Zr]Zr4+, respectively, in near quantitative radiochemical yield (>99%). Serum stability studies, in vivo PET imaging, and biodistribution analyses using these radiolabeled immunoconjugates demonstrate that both [64Cu]Cu-sar-dtm-trastuzumab and [89Zr]Zr-dfo-dtm-trastuzumab possess high stability in biological milieu. Dibromomaleimide technology can be easily applied to enable stable, site-specific attachment of radiolabeled chelators, such as sar and dfo, to native interstrand disulfide regions of antibodies, enabling tracking of antibodies with PET imaging.


Assuntos
Compostos de Bromo/química , Quelantes/farmacologia , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos/química , Animais , Humanos
3.
ACS Appl Mater Interfaces ; 13(4): 5602-5613, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33496182

RESUMO

Respiration monitoring and human sweat sensing have promising application prospects in personal healthcare data collection, disease diagnostics, and the effective prevention of human-to-human transmission of fatal viruses. Here, we have introduced a unique respiration monitoring and touchless sensing system based on a CsPb2Br5/BaTiO3 humidity-sensing layer operated by water-induced interfacial polarization and prepared using a facile aerosol deposition process. Based on the relationship between sensing ability and layer thickness, the sensing device with a 1.0 µm thick layer was found to exhibit optimal sensing performance, a result of its ideal microstructure. This sensor also exhibits the highest electrical signal variation at 0.5 kHz due to a substantial polarizability difference between high and low humidity. As a result, the CsPb2Br5/BaTiO3 sensing device shows the best signal variation of all types of breath-monitoring devices reported to date when used to monitor sudden changes in respiratory rates in diverse situations. Furthermore, the sensor can effectively detect sweat evaporation when placed 1 cm from the skin, including subtle changes in capacitance caused by finger area and motion, skin moisture, and contact time. This ultrasensitive sensor, with its fast response, provides a potential new sensing platform for the long-term daily monitoring of respiration and sweat evaporation.


Assuntos
Compostos de Bário/química , Técnicas Biossensoriais/instrumentação , Compostos de Bromo/química , Respiração , Suor/química , Titânio/química , Testes Respiratórios/instrumentação , Césio/química , Desenho de Equipamento , Humanos , Umidade , Chumbo/química , Monitorização Fisiológica/instrumentação , Nanocompostos/química
4.
Int J Nanomedicine ; 15: 6225-6237, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884271

RESUMO

BACKGROUND: The realization of multifunction in one bulk material is fascinating for developing a new generation of devices. Quaternary phosphorus salts were seldom utilized as templates in haloargentate systems, and the hybridization of alkyl(triphenyl)phosphonium with halometallate will be a good strategy for the development of multifunctional material, especially for biological material. METHODS: Under the template of (triphenyl)phosphonium-based quaternary phosphorus salts with different spacer lengths (n=2, 3, 4), three bromoargentate hybrids were constructed via the solution method, ie, (1,2-DBTPP)(Ag2Br4) (1), {(1,3-DBTPP)2(Ag7Br11)]∙CH3CN∙H2O} n (2), and {[(1,4-DBTPP)(Ag5Br7)](CH3CN)2∙H2O} n (3) (1,2-DBTPP2+=ethane-1,2-diylbis (triphenyl)phosphonium, 1,3-DBTPP2+=propane-1,3-diylbis (triphenyl)phosphonium, 1,4-DBTPP2+=butane-1,4-diylbis (triphenyl)phosphonium)). RESULTS: The (Ag7Br11) n 4n- chain in 2 is a new type of 1-D bromoargentate chain constructed from cubane-like Ag4Br4 nodes, AgBr4 tetrahedrons and AgBr3 triangles. Interestingly, by elongating spacer n from 2 to 4, argentophilicity interactions are weakened, and the hydrogen bonds are strengthened. Consequently, their water stabilities and photocurrents are improved, in which the Ag-4d/Br-4p to π* anti-bonding orbital of the quaternary phosphorus transfer is facilitated. Furthermore, the greenish blue emissions can be detected. Finally, high inhabitation rates against Streptococcus mutans and Candida albicans can be observed in 2 and 3. CONCLUSION: In all experiments, by elongating the spacer lengths of quaternary phosphorus salts, multifunctions were integrated in the quaternary phosphorus/bromoargentate hybrids, including greenish blue luminescence, repeatable photocurrent responses and durable antimicrobial activities with enhanced water stability. This work could provide a theoretical guide for the design of new biologically multifunctional materials.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Compostos de Bromo/química , Ácidos Graxos/química , Fósforo/química , Anti-Infecciosos/farmacocinética , Compostos de Bromo/farmacologia , Candida albicans/efeitos dos fármacos , Cristalografia por Raios X , Estabilidade de Medicamentos , Ácidos Graxos/farmacologia , Luminescência , Testes de Sensibilidade Microbiana , Estrutura Molecular , Processos Fotoquímicos , Streptococcus mutans/efeitos dos fármacos , Água/química
5.
Angew Chem Int Ed Engl ; 58(50): 18235-18239, 2019 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-31595619

RESUMO

Reported here is a simple and practical functionalization of primary sulfonamides, by means of a pyrylium salt (Pyry-BF4 ), with nucleophiles. This simple reagent activates the poorly nucleophilic NH2 group in a sulfonamide, enabling the formation of one of the best electrophiles in organic synthesis: a sulfonyl chloride. Because of the variety of primary sulfonamides in pharmaceutical contexts, special attention has been focused on the direct conversion of densely functionalized primary sulfonamides by a late-stage formation of the corresponding sulfonyl chloride. A variety of nucleophiles could be engaged in this transformation, thus permitting the synthesis of complex sulfonamides, sulfonates, sulfides, sulfonyl fluorides, and sulfonic acids. The mild reaction conditions and the high selectivity of Pyry-BF4 towards NH2 groups permit the formation of sulfonyl chlorides in a late-stage fashion, tolerating a preponderance of sensitive functionalities.


Assuntos
Compostos de Bromo/química , Compostos de Flúor/química , Ácidos Sulfínicos/química , Sulfonamidas/síntese química , Cloreto de Magnésio/química , Estrutura Molecular
6.
Bioresour Technol ; 283: 28-35, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30897390

RESUMO

In this study, a 200-day deca-brominated diphenyl ether (deca-BDE) degradation activity experiment was carried out, using consumer-use curtain material as the substrate. During the degradation process, polybrominated diphenyl ether (PBDE) products with fewer bromine atoms were gradually generated by the debromination of deca-BDE. The influences of temperature, initial substrate dosing mass, and pH were also investigated. Interestingly, thermophilic conditions proved more beneficial for deca-BDE degradation than mesophilic conditions. The results also demonstrate that the debromination rate increased with the initial deca-BDE dosing mass, and that pH 7 was the most suitable for the reaction.


Assuntos
Compostos de Bromo/metabolismo , Éteres Difenil Halogenados/metabolismo , Anaerobiose , Bifenil Polibromatos/metabolismo , Temperatura
7.
Ecotoxicol Environ Saf ; 165: 343-348, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30212735

RESUMO

Polybrominated diphenyl ethers (PBDEs) in the feather and muscle of common kestrels (Falco tinnunculus), eagle owls (Bubo bubo) and little owls (Athene noctua) collected from Beijing, China were investigated. The concentrations of ∑23PBDEs in the muscle and feather of all the birds of prey ranged from 46 to 7.77 × 104 ng/g lipid weight (lw; median 241 ng/g lw) and 1.50-191 ng/g dry weight (dw; median 21.1 ng/g dw), respectively. Higher brominated congeners, e.g., BDE-209, -153, -207 and -196 were the dominant congeners in both feather and muscle. However, the concentrations of lower brominated congeners in feather were significantly correlated with those in muscle (p < 0.05), which suggested that feather could efficiently reflect lower brominated BDEs in the internal tissue of birds of prey. The calculated hazard quotients (HQs) > 10 in common kestrel and little owl suggested that the high levels of PBDEs posed potentially high risk to some birds of prey living in Beijing area.


Assuntos
Falconiformes , Plumas/química , Éteres Difenil Halogenados/análise , Músculo Esquelético/química , Estrigiformes , Animais , Pequim , Compostos de Bromo/análise , Monitoramento Ambiental
8.
Environ Sci Technol ; 52(15): 8764-8773, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-29984988

RESUMO

Long-term exposure to toxic chemicals often has deleterious effects on aquatic organisms. In order to support appropriate environmental management of chemicals, a mathematical model was developed to characterize the effects of chemicals on multigenerational population dynamics in aquatic animals. To parametrize the model, we conducted a multigenerational laboratory toxicity test in zebrafish ( Danio rerio) exposed to 2-bromo-4,6-dinitroaniline (BDNA). Long-term exposure to BDNA considerably reduced the fecundity of adult zebrafish (F0 and F1) and caused deformities in the offspring (F2). Life history data, including changes in fecundity and population growth, were then integrated into the model to predict population dynamics of zebrafish exposed to two novel brominated flame retardants, bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) and 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB). The model predicted that the fecundity of adult zebrafish would be significantly impaired after exposure to 90.36 µM TBPH and 99.16 µM TBB. Thus, prolonged exposure to such levels over multiple generations could result in population extinction within 20 years. Our results provide an intensive temporal perspective to investigate a keystone that connects with individual response to chemicals, population dynamics, and ultimately ecosystem influences.


Assuntos
Compostos de Bromo , Retardadores de Chama , Animais , Demografia , Ecossistema , Peixe-Zebra
9.
Molecules ; 23(6)2018 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-29799497

RESUMO

In this work, feasible mechanisms and pathways of the C2H5O2 + BrO reaction in the atmosphere were investigated using quantum chemistry methods, i.e., QCISD(T)/6-311++G(2df,2p)//B3LYP/6-311++G(2df,2p) levels of theory. Our result indicates that the title reaction occurs on both the singlet and triplet potential energy surfaces (PESs). Kinetically, singlet C2H5O3Br and C2H5O2BrO were dominant products under the atmospheric conditions below 300 K. CH3CHO2 + HOBr, CH3CHO + HOBrO, and CH3CHO + HBrO2 are feasible to a certain extent thermodynamically. Because of high energy barriers, all products formed on the triplet PES are negligible. Moreover, time-dependent density functional theory (TDDFT) calculation implies that C2H5O3Br and C2H5O2BrO will photolyze under the sunlight.


Assuntos
Atmosfera/química , Compostos de Bromo/química , Etilenoglicol/química , Óxidos/química , Cinética , Fotólise , Teoria Quântica , Luz Solar , Termodinâmica
10.
Molecules ; 22(12)2017 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-29206144

RESUMO

MP2/aug-cc-pVTZ calculations were performed for complexes of BrF3 and BrF5 acting as Lewis acids through the bromine centre, with species playing a role of Lewis base: dihydrogen, acetylene, ethylene, and benzene. The molecular hydrogen donates electrons by its σ-bond, while in remaining moieties-in complexes of hydrocarbons; such an electron transfer follows from π-electrons. The complexes are linked by a kind of the halogen bond that is analyzed for the first time in this study, i.e., it is the link between the multivalent halogen and π or σ-electrons. The nature of such a halogen bond is discussed, as well as various dependencies and correlations are presented. Different approaches are applied here, the Quantum Theory of Atoms in Molecules, Natural Bond Orbital method, the decomposition of the energy of interaction, the analysis of electrostatic potentials, etc.


Assuntos
Compostos de Bromo/química , Elétrons , Compostos de Flúor/química , Ácidos de Lewis/química , Bases de Lewis/química , Acetileno/química , Benzeno/química , Etilenos/química , Hidrogênio/química , Ligação de Hidrogênio , Teoria Quântica , Eletricidade Estática , Termodinâmica
11.
J Am Chem Soc ; 139(38): 13562-13569, 2017 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-28858493

RESUMO

Herein, we report that under mild solvolytic conditions, enantioenriched bromochlorides can be ionized, stereospecifically cyclized to an array of complex bromocyclic scaffolds, or intermolecularly trapped by exogenous nucleophiles. Mechanistic investigations support an ionic mechanism wherein the bromochloride serves as an enantioenriched bromonium surrogate. Several natural product-relevant motifs are accessed in enantioenriched form for the first time with high levels of stereocontrol, and this technology is applied to the scalable synthesis of a polycyclic brominated natural product. Arrays of nucleophiles including olefins, alkynes, heterocycles, and epoxides are competent traps in the bromonium-induced cyclizations, leading to the formation of enantioenriched mono-, bi-, and tricyclic products. This strategy is further amenable to intermolecular coupling between cinnamyl bromochlorides and a diverse set of commercially available nucleophiles. Collectively, this work demonstrates that enantioenriched bromonium chlorides are configurationally stable under solvolytic conditions in the presence of a variety of functional groups.


Assuntos
Compostos de Bromo/química , Cloretos/química , Solventes/química , Ácidos Heterocíclicos/química , Alcenos/química , Alcinos/química , Produtos Biológicos/química , Ciclização , Compostos de Epóxi/química , Íons
12.
Environ Sci Technol ; 51(18): 10718-10728, 2017 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-28806069

RESUMO

This work demonstrated that bromophenols (BrPs) could be readily oxidized by peroxydisulfate (PDS) activated by a commercial carbon nanotube (CNT), while furfuryl alcohol (a chemical probe for singlet oxygen (1O2)) was quite refractory. Results obtained by radical quenching experiments, electron paramagnetic resonance spectroscopy, and Fourier transform infrared spectroscopy further confirmed the involvement of nonradical PDS-CNT complexes rather than 1O2. Bicarbonate and chloride ion exhibited negligible impacts on BrPs degradation by the PDS/CNT system, while a significant inhibitory effect was observed for natural organic matter. The oxidation of BrPs was influenced by solution pH with maximum rates occurring at neutral pH. Linear free energy relationships (LFERs) were established between the observed pseudo-first-order oxidation rates of various substituted phenols and the classical descriptor variables (i.e., Hammett constant σ+, and half-wave oxidation potential E1/2). Products analyses by liquid chromatography tandem mass spectrometry clearly showed the formation of hydroxylated polybrominated diphenyl ethers and hydroxylated polybrominated biphenyls on CNT surface. Their formation pathway possibly involved the generation of bromophenoxyl radicals from BrPs one-electron oxidation and their subsequent coupling reactions. These results suggest that the novel nonradical PDS/CNT oxidation technology is a good alternative for selectively eliminating BrPs with alleviating toxic byproducts in treated water effluent.


Assuntos
Compostos de Bromo/química , Nanotubos de Carbono , Fenóis/química , Cinética , Oxirredução , Bifenil Polibromatos , Purificação da Água
13.
Anal Bioanal Chem ; 409(22): 5307-5317, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28741109

RESUMO

Commonly, analytical methods measuring brominated flame retardants (BFRs) of different chemical polarities in human serum are labor consuming and tedious. Our study used acidified diatomaceous earth as solid-phase extraction (SPE) adsorbent and defatting material to simultaneously determine the most abundant BFRs and their metabolites with different polarities in human serum samples. The analytes include three types of commercial BFRs, tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCD) isomers, and polybrominated biphenyl ethers (PBDEs), and dominant hydroxylated BDE (OH-PBDE) and methoxylated BDE (MeO-PBDE) metabolites of PBDEs. The sample eluents were sequentially analyzed for PBDEs and MeO-BDEs on online gel permeation chromatography/gas chromatography-electron capture-negative ionization mass spectrometry (online GPC GC-ECNI-MS) and for TBBPA, HBCD, and OH-BDEs on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Method recoveries were 67-134% with a relative standard deviation (RSD) of less than 20%. Method detection limits (MDLs) were 0.30-4.20 pg/mL fresh weight (f.w.) for all analytes, except for BDE-209 of 16 pg/mL f.w. The methodology was also applied in a pilot study, which analyzed ten real samples from healthy donors in China, and the majority of target analytes were detected with a detection rate of more than 80%. To our knowledge, it is the first time for us in effectively determining BFRs of most types in one aliquot of human serum samples. This new analytical method is more specific, sensitive, accurate, and time saving for routine biomonitoring of these BFRs and for integrated assessment of health risk of BFR exposure.


Assuntos
Análise Química do Sangue/métodos , Retardadores de Chama/análise , Éteres Difenil Halogenados/sangue , Compostos de Bromo/análise , Éteres Difenil Halogenados/metabolismo , Humanos , Limite de Detecção , Controle de Qualidade , Extração em Fase Sólida , Fatores de Tempo
14.
J Am Soc Mass Spectrom ; 28(10): 2022-2038, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28653243

RESUMO

The chemical cross-linking/mass spectrometry (MS) approach is gaining increasing importance as an alternative method for studying protein conformation and for deciphering protein interaction networks. This study is part of our ongoing efforts to develop innovative cross-linking principles for a facile and efficient assignment of cross-linked products. We evaluate two homobifunctional, amine-reactive, and MS-cleavable cross-linkers regarding their potential for automated analysis of cross-linked products. We introduce the bromine phenylurea (BrPU) linker that possesses a unique structure yielding a distinctive fragmentation pattern on collisional activation. Moreover, BrPU delivers the characteristic bromine isotope pattern and mass defect for all cross-linker-decorated fragments. We compare the fragmentation behavior of the BrPU linker with that of our previously described MS-cleavable TEMPO-Bz linker (which consists of a 2,2,6,6-tetramethylpiperidine-1-oxy moiety connected to a benzyl group) that was developed to perform free-radical-initiated peptide sequencing. Comparative collisional activation experiments (collision-induced dissociation and higher-energy collision-induced dissociation) with both cross-linkers were conducted in negative electrospray ionization mode with an Orbitrap Fusion mass spectrometer using five model peptides. As hypothesized in a previous study, the presence of a cross-linked N-terminal aspartic acid residue seems to be the prerequisite for the loss of an intact peptide from the cross-linked products. As the BrPU linker combines a characteristic mass shift with an isotope signature, it presents a more favorable combination for automated assignment of cross-linked products compared with the TEMPO-Bz linker. ᅟ.


Assuntos
Reagentes de Ligações Cruzadas/química , Peptídeos/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Angiotensina II/química , Compostos de Bromo/química , Óxidos N-Cíclicos/química , Radicais Livres/química , Conformação Proteica , Espectrometria de Massas por Ionização por Electrospray/instrumentação , Espectrometria de Massas em Tandem/métodos
15.
Environ Sci Technol ; 51(10): 5464-5472, 2017 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-28440636

RESUMO

Photochemical halogenation of dissolved organic matter (DOM) may represent an important abiotic process for the formation of natural organobromine compounds (OBCs) and natural organoiodine compounds (OICs) within surface waters. Here we report the enhanced formation of OBCs and OICs by photohalogenating DOM in freshwater and seawater, as well as the noticeable difference in the distribution and composition pattern of newly formed OBCs and OICs. By using negative ion electrospray ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry, various OBCs and OICs were identified during the photohalogenation processes in sunlit waters. The respective number of OBCs and OICs formed in artificial seawater (ASW) under light radiation was higher than that in artificial freshwater (AFW), suggesting a possible role of the mixed reactive halogen species. OBCs were formed mainly via substitution reactions and addition reactions accompanied by other reactions and distributed into three classes: unsaturated hydrocarbons with relatively low oxygen content, unsaturated aliphatic compounds, and saturated fatty acids and carbohydrates with relatively high hydrogen content. Unlike the OBCs, OICs were located primarily in the region of carboxylic-rich alicyclic molecules composed of esterified phenolic, carboxylated, and fused alicyclic structures and were generated mainly through electrophilic substitution of the aromatic proton. Our findings call for further investigation on the exact structure and toxicity of the OBCs and OICs generated in the natural environment.


Assuntos
Compostos de Bromo/química , Compostos de Iodo/química , Espectrometria de Massas , Água do Mar/química , Água Doce , Halogenação , Espectrometria de Massas por Ionização por Electrospray
16.
Acta Pol Pharm ; 74(2): 401-404, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29624245

RESUMO

Three new methods were developed for the quantitative determination of mesalazine in the form of the pure substance or in the form of suppositories and tablets - accordingly: bromatometric, diazotization and visible light spectrophotometry method. Optimizing the time and the temperature of the bromination reaction (50°C, 50 min) 4-amino-2,3,5,6-tetrabromophenol was obtained. The results obtained were reproducible, accurate and precise. Developed methods were compared to the pharmacopoeial approach - alkalimetry in an aqueous medium. The validation parameters of all methods were comparable. Developed methods for quantification of mesalazine are a viable alternative to other more expensive approaches.


Assuntos
Anti-Inflamatórios não Esteroides/análise , Compostos de Bromo/análise , Compostos de Diazônio/análise , Mesalamina/análise , Espectrofotometria/métodos , Anti-Inflamatórios não Esteroides/química , Compostos de Bromo/química , Química Farmacêutica , Compostos de Diazônio/química , Composição de Medicamentos , Cinética , Mesalamina/química , Reprodutibilidade dos Testes , Supositórios , Comprimidos , Temperatura
17.
Biochemistry ; 55(27): 3727-34, 2016 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-27332697

RESUMO

The histone acetyltransferase (HAT) enzymes p300 and CBP are closely related paralogs that serve as transcriptional coactivators and have been found to be dysregulated in cancer and other diseases. p300/CBP is a multidomain protein and possesses a highly conserved bromodomain that has been shown to bind acetylated Lys residues in both proteins and various small molecules, including I-CBP112 and CBP30. Here we show that the ligand I-CBP112 can stimulate nucleosome acetylation up to 3-fold while CBP30 does not. Activation of p300/CBP by I-CBP112 is not observed with the isolated histone H3 substrate but requires a nucleosome substrate. I-CBP112 does not impact nucleosome acetylation by the isolated p300 HAT domain, and the effects of I-CBP112 on p300/CBP can be neutralized by CBP30, suggesting that I-CBP112 likely allosterically activates p300/CBP through bromodomain interactions. Using mass spectrometry and Western blots, we have found that I-CBP112 particularly stimulates acetylation of Lys18 of histone H3 (H3K18) in nucleosomes, an established in vivo site of p300/CBP. In addition, we show that I-CBP112 enhances H3K18 acetylation in acute leukemia and prostate cancer cells in a concentration range commensurate with its antiproliferative effects. Our findings extend the known pharmacology of bromodomain ligands in the regulation of p300/CBP and suggest a novel approach to modulating histone acetylation in cancer.


Assuntos
Compostos de Bromo/farmacologia , Proteína p300 Associada a E1A/metabolismo , Leucemia/patologia , Nucleossomos/metabolismo , Neoplasias da Próstata/patologia , Fatores de Transcrição de p300-CBP/metabolismo , Acetilação , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Histonas/metabolismo , Humanos , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Masculino , Modelos Moleculares , Mutagênese Sítio-Dirigida , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Ligação Proteica , Conformação Proteica , Células Tumorais Cultivadas
18.
Environ Sci Technol ; 50(1): 321-30, 2016 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-26618527

RESUMO

Previously unreported natural and synthetic organo-bromine compounds (NSOBCs) have been found to contribute more than 99% of total organic bromine (TOB) in environmental matrices. We recently developed a novel untargeted method (data-independent precursor isolation and characteristic fragment, DIPIC-Frag) and identified ∼2000 NSOBCs in two sediments from Lake Michigan. In this study, this method was used to investigate the distributions of these NSOBCs in 23 surficial samples and 24 segments of a sediment core from Lake Michigan. NSOBCs were detected in all 23 surficial samples and exhibited 10- to 100-fold variations in peak abundance among locations. The pattern of distributions of NSOBCs was correlated with depth of the water column (r(2) = 0.61, p < 0.001). Hierarchical cluster analysis showed that sediments in close proximity exhibited similar profiles of NSOBCs. Distributions of NSOBCs in 24 segments of a sediment core dated from 1766 to 2008 were investigated, and samples from similar depths exhibited similar profiles of NSOBCs. NSOBCs were grouped into four clusters (soft-cluster analysis) with different temporal trends of abundances. 515 and 768 of the NSOBCs were grouped into cluster 1 and cluster 3 with increasing temporal trends, especially since 1950, indicating that abundances of these compounds might have been affected by human activities.


Assuntos
Compostos de Bromo/análise , Sedimentos Geológicos/química , Éteres Difenil Halogenados/análise , Hidrocarbonetos Bromados/análise , Lagos/química , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Michigan
19.
Pest Manag Sci ; 72(1): 57-66, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25754847

RESUMO

BACKGROUND: Restrictions on soil fumigants are prompting the development of new compounds for controlling nematodes, other soilborne pathogens and weeds. We evaluated the nematicidal activity of five bromine compounds against Meloidogyne javanica in vitro, and tested the two most effective ones against Pratylenchus penetrans and Xiphinema index in vitro and in soil. RESULTS: Only allyl bromide and dibromo(nitro)methane showed nematicidal activity against M. javanica juveniles in vitro at <320 mg L(-1) . Allyl bromide killed M. javanica and P. penetrans at 20 mg L(-1), and X. index at 10 mg L(-1), whereas 320 mg dibromo(nitro)methane L(-1) was required to kill P. penetrans. Allyl bromide also showed higher nematicidal activity than dibromo(nitro)methane against M. javanica and P. penetrans in soil. Allyl bromide at 40 and 20 mg L(-1) soil eliminated root galls and nematode eggs on tomato roots grown in M. javanica-inoculated loess and sandy soils respectively, showing higher nematicidal activity than 1,3-dichloropropene. No P. penetrans were recovered from soil treated with 80 mg allyl bromide L(-1) soil or 320 mg dibromo(nitro)methane L(-1) soil. CONCLUSION: Allyl bromide showed high nematicidal activity against all three nematode species, and nematicidal activity of dibromo(nitro)methane was discovered. These compounds could serve as new fumigation nematicides, pending further experiments.


Assuntos
Antinematódeos , Compostos de Bromo , Nematoides , Doenças das Plantas/prevenção & controle , Animais , Doenças das Plantas/parasitologia , Tylenchoidea
20.
J Phys Chem A ; 119(19): 4618-32, 2015 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-25768043

RESUMO

Over the last two decades it has emerged that measured hydroxyl radical levels in the upper troposphere are often underestimated by models, leading to the assertion that there are missing sources. Here we report laboratory studies of the kinetics and products of the reaction between CH3O2 and BrO radicals that shows that this could be an important new source of hydroxyl radicals:BrO + CH3O2 → products (1). The temperature dependent value in Arrhenius form of k(T) is k1 = (2.42­0.72+1.02) × 10­14 exp[(1617 ± 94)/T] cm3 molecule­1 s­1. In addition, CH2OO and HOBr are believed to be the major products. Global model results suggest that the decomposition of H2COO to form OH could lead to an enhancement in OH of up to 20% in mid-latitudes in the upper troposphere and in the lower stratosphere enhancements in OH of 2­9% are inferred from model integrations. In addition, reaction 1 aids conversion of BrO to HOBr and slows polar ozone loss in the lower stratosphere.


Assuntos
Atmosfera/química , Compostos de Bromo/química , Radical Hidroxila/química , Metano/química , Peróxidos/química , Simulação por Computador , Cinética , Análise dos Mínimos Quadrados , Modelos Lineares , Metano/análogos & derivados , Modelos Químicos , Temperatura
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