Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 772
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Nat Microbiol ; 4(10): 1706-1715, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31332382

RESUMO

In the surface ocean, phytoplankton transform inorganic substrates into organic matter that fuels the activity of heterotrophic microorganisms, creating intricate metabolic networks that determine the extent of carbon recycling and storage in the ocean. Yet, the diversity of organic molecules and interacting organisms has hindered detection of specific relationships that mediate this large flux of energy and matter. Here, we show that a tightly coupled microbial network based on organic sulfur compounds (sulfonates) exists among key lineages of eukaryotic phytoplankton producers and heterotrophic bacterial consumers in the North Pacific Subtropical Gyre. We find that cultured eukaryotic phytoplankton taxa produce sulfonates, often at millimolar internal concentrations. These same phytoplankton-derived sulfonates support growth requirements of an open-ocean isolate of the SAR11 clade, the most abundant group of marine heterotrophic bacteria. Expression of putative sulfonate biosynthesis genes and sulfonate abundances in natural plankton communities over the diel cycle link sulfonate production to light availability. Contemporaneous expression of sulfonate catabolism genes in heterotrophic bacteria highlights active cycling of sulfonates in situ. Our study provides evidence that sulfonates serve as an ecologically important currency for nutrient and energy exchange between microbial autotrophs and heterotrophs, highlighting the importance of organic sulfur compounds in regulating ecosystem function.


Assuntos
Bactérias/metabolismo , Eucariotos/metabolismo , Consórcios Microbianos , Fitoplâncton/metabolismo , Água do Mar/microbiologia , Ácidos Sulfônicos/metabolismo , Processos Autotróficos , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Ritmo Circadiano , Eucariotos/classificação , Eucariotos/genética , Eucariotos/isolamento & purificação , Processos Heterotróficos , Luz , Redes e Vias Metabólicas/genética , Oceano Pacífico , Fitoplâncton/classificação , Fitoplâncton/genética , Água do Mar/química , Ácidos Sulfônicos/química
2.
Int J Med Microbiol ; 309(7): 151324, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31278055

RESUMO

The MmcO protein of Mycobacterium tuberculosis is a membrane-associated multicopper oxidase. Its natural substrate(s) and its role in pathogenesis are not well characterized. A recent report proposes that MmcO contributes to copper resistance in M. tuberculosis during infection. We have expressed and reconstituted the active enzyme from inclusion bodies in E. coli. MmcO exhibits maximal activity against the experimental substrate 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) or ABTS, at pH 4. The enzyme also exhibits ferroxidase activity at pH 4. Most notable was the finding that MmcO is able to scavenge the reactive oxygen species (ROS) generated by the xanthine/xanthine oxidase enzyme system. This ROS scavenging activity of MmcO was also evident against ROS generated by THP-1 cells. We propose that MmcO protects M. tuberculosis during infection against ROS attack in addition to providing copper resistance to the pathogen.


Assuntos
Proteínas de Bactérias/metabolismo , Ceruloplasmina/metabolismo , Cobre/metabolismo , Mycobacterium tuberculosis/enzimologia , Oxirredutases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sequência de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/isolamento & purificação , Benzotiazóis/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Mycobacterium tuberculosis/genética , Oxirredutases/química , Oxirredutases/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Ácidos Sulfônicos/metabolismo , Células THP-1
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 219: 358-366, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31055242

RESUMO

Caffeic acid (CA) is a plant metabolite acting as a carcinogenic inhibitor, and exhibits a high antioxidant effect and some antimicrobial activity. Besides, this compound can be useful in the prevention of heart diseases and atherosclerosis, among others. The present study aims to determine the in vitro antioxidant activity of CA in order to increase the frequency of its use and reliability in the prevention of damage caused by free radicals and other reactive species. The tests performed were as follows: Radical anion superoxide capture; crocin bleaching assay; capturing ability of hypochlorous acid; H2O2 capture; capturing capacity of the ABTS•+/DPPH•; and SOD-like activity. The values of the CA antioxidant activity were very close to the values of standards in all tests. Besides, CA presented an antioxidant activity greater than that of ascorbic acid and trolox, and its advantages include higher stability than ascorbic acid and extraction from natural sources, as opposed to trolox.


Assuntos
Antioxidantes/farmacologia , Ácidos Cafeicos/farmacologia , Ácido Ascórbico/farmacologia , Benzotiazóis/metabolismo , Compostos de Bifenilo/metabolismo , Cromanos/farmacologia , Radicais Livres/metabolismo , Peróxido de Hidrogênio/metabolismo , Ácido Hipocloroso/metabolismo , Picratos/metabolismo , Ácidos Sulfônicos/metabolismo , Superóxidos/metabolismo
4.
J Pharmacol Exp Ther ; 369(3): 389-405, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30918069

RESUMO

Lithocholic acid (LCA) is a bile acid associated with adverse effects, including cholestasis, and it exists in vivo mainly as conjugates known as glyco-LCA (GLCA) and tauro-LCA (TLCA). Tamoxifen has been linked to the development of cholestasis, and it inhibits sulfotransferase 2A1 (SULT2A1)-catalyzed dehydroepiandrosterone (DHEA) sulfonation. The present study was done to characterize the sulfonation of LCA, GLCA, and TLCA and to investigate whether triphenylethylene (clomifene, tamoxifen, toremifene, ospemifene, droloxifene), benzothiophene (raloxifene, arzoxifene), tetrahydronaphthalene (lasofoxifene, nafoxidine), indole (bazedoxifene), and benzopyran (acolbifene) classes of selective estrogen receptor modulator (SERM) inhibit LCA, GLCA, and TLCA sulfonation. Human recombinant SULT2A1, but not SULT2B1b or SULT1E1, catalyzed LCA, GLCA, and TLCA sulfonation, whereas each of these enzymes catalyzed DHEA sulfonation. LCA, GLCA, and TLCA sulfonation is catalyzed by human liver cytosol, and SULT2A1 followed the substrate inhibition model with comparable apparent K m values (≤1 µM). Each of the SERMs inhibited LCA, GLCA, and TLCA sulfonation with varying potency and mode of enzyme inhibition. The potency and extent of inhibition of LCA sulfonation were attenuated or increased by structural modifications to toremifene, bazedoxifene, and lasofoxifene. The inhibitory effect of raloxifene, bazedoxifene, and acolbifene on LCA sulfonation was also observed in HepG2 human hepatocellular carcinoma cells. Overall, among the SERMs investigated, bazedoxifene and raloxifene were the most effective inhibitors of LCA, GLCA, and TLCA sulfonation. These findings provide insight into the structural features of specific SERMs that contribute to their inhibition of SULT2A1-catalyzed LCA sulfonation. Inhibition of LCA, GLCA, and TLCA detoxification by a SERM may provide a biochemical basis for adverse effects associated with a SERM.


Assuntos
Biocatálise/efeitos dos fármacos , Ácido Litocólico/análogos & derivados , Moduladores Seletivos de Receptor Estrogênico/química , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Ácidos Sulfônicos/metabolismo , Sulfotransferases/metabolismo , Ácido Taurolitocólico/metabolismo , Citosol/efeitos dos fármacos , Citosol/metabolismo , Células Hep G2 , Humanos , Cinética , Ácido Litocólico/metabolismo , Fígado/citologia , Oxirredução , Moduladores Seletivos de Receptor Estrogênico/metabolismo , Sulfotransferases/antagonistas & inibidores
5.
Int J Mol Sci ; 20(4)2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30781644

RESUMO

Oxidative stress is the main pathogenesis of diabetic microangiopathy, which can cause microvascular endothelial cell damage and destroy vascular barrier. In this study, it is found that carnosol protects human microvascular endothelial cells (HMVEC) through antioxidative mechanisms. First, we measured the antioxidant activity of carnosol. We showed that carnosol pretreatment suppressed tert-butyl hydroperoxide (t-BHP)-induced cell viability, affected the production of lactate dehydrogenase (LDH) as well as reactive oxygen species (ROS), and increased the produce of nitric oxide (NO). Additionally, carnosol promotes the protein expression of vascular endothelial cadherin (VE-cadherin) to keep the integrity of intercellular junctions, which indicated that it protected microvascular barrier in oxidative stress. Meanwhile, we investigated that carnosol can interrupt Nrf2-Keap1 protein-protein interaction and stimulated antioxidant-responsive element (ARE)-driven luciferase activity in vitro. Mechanistically, we showed that carnosol promotes the expression of heme oxygenase 1(HO-1) and nuclear factor-erythroid 2 related factor 2(Nrf2). It can also promote the expression of endothelial nitric oxide synthase (eNOS). Collectively, our data support the notion that carnosol is a protective agent in HMVECs and has the potential for therapeutic use in the treatments of microvascular endothelial cell injury.


Assuntos
Abietanos/farmacologia , Antioxidantes/farmacologia , Células Endoteliais/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Abietanos/química , Antígenos CD/metabolismo , Benzotiazóis/metabolismo , Caderinas/metabolismo , Linhagem Celular , Citoproteção/efeitos dos fármacos , Citoproteção/genética , Células Endoteliais/efeitos dos fármacos , Depuradores de Radicais Livres/metabolismo , Humanos , Microvasos/patologia , Simulação de Acoplamento Molecular , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ácidos Sulfônicos/metabolismo , terc-Butil Hidroperóxido
6.
BMC Complement Altern Med ; 19(1): 30, 2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30691451

RESUMO

BACKGROUND: Exposure of skin to urban air pollutants is closely related to skin aging and inflammatory responses such as wrinkles formation, pigmentation spot, atopic dermatitis, and acne. Thus, a great deal of interest has been focused on the development of natural resources that can provide a protective effect to skin from pollutants. METHODS: The antioxidative activity of Camellia japonica flower extract (CJFE) was evaluated by 1,2-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) assay, and the inhibitory effect of CJFE by urban air pollutants-induced reactive oxygen species (ROS) production was determined in cultured normal human dermal fibroblasts (NHDFs). We additionally investigated the protective effects of CJFE against urban air pollutant using in vitro and ex vivo model. RESULTS: CJFE with high phenolic concentration showed antioxidative activity on scavenging capacity of 1,2-diphenyl-2-picrylhydrazyl (DPPH) radicals and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) radical cation in a concentration dependent manner. CJFE inhibited urban air pollutants-induced ROS generation, matrixmetalloproteinase-1 (MMP-1) production and a xenobiotic response element (XRE)-luciferase activity indicating the aryl hydrocarbon receptor (AhR) transactivation. In addition, CJFE showed an excellent protective activity against pollutants-induced deteriorating effect in ex vivo model. CJFE reduced the level of pollutants-induced malondialdehyde (MDA), lipid peroxidation marker, inhibited MMP-1 expression and increased collagen synthesis. It also reduced the cell numbers with pyknotic nuclei (mainly occurring in apoptosis) and detachment of dermo-epidermal junction (DEJ) induced by pollutants. CONCLUSIONS: Apparently, it is proposed that CJFE can be used as a protective material against pollutant-induced skin damages.


Assuntos
Poluentes Atmosféricos/toxicidade , Camellia/química , Flores/química , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Benzotiazóis/metabolismo , Compostos de Bifenilo/metabolismo , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Humanos , Oxirredução/efeitos dos fármacos , Picratos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ácidos Sulfônicos/metabolismo
7.
Colloids Surf B Biointerfaces ; 175: 671-679, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30590328

RESUMO

In this research we report the biological synthesis of electrically conducting polymer - Polypyrrole (Ppy). Cell-assisted enzymatic polymerization/oligomerization of Ppy was achieved using whole cell culture and cell-free crude enzyme extract from two white-rot fungal cultures. The selected fungal strains belong to Trametes spp., known laccase producers, commonly applied in bioremediation and bioelectrochemical fields. The biocatalytic reaction was initiated in situ through the copper-containing enzymes biosynthesized within the cell cultures under submerged aerobe cultivation conditions. The procedure was inspired by successful reports of laccase-catalyzed pyrrole polymerization. The usage of whole culture and/or crude enzyme extract has the advantage of overcoming enzyme purification and minimizing the liability of enzyme inactivation through improved stability of enzymes in their natural environment. Spectral and electrochemical techniques (UV-vis spectroscopy, infrared spectroscopy; cyclic voltammetry (CV)) and pH measurements provided insight into the evolution of pyrrole polymerization/oligomerization and the electrochemical features of the final product. Microscopy techniques (optical microscopy and scanning electron microscopy (SEM)) were primary tools for visualization of the formed Ppy particles. The relevance of our research is twofold: Ppy prepared in crude enzyme extract results in enzyme encapsulated within Ppy and/or Ppy-modified fungal cells can be formed when polymerization occurs in whole cell culture. The route of biocatalysis can be chosen according to the desired bioelectrochemical application. The reported study focuses on the improvement of charge transfer through the fungal cell membrane and/or cell wall by modification of the fungal cells with conducting polymer - polypyrrole.


Assuntos
Proteínas Fúngicas/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Polímeros/metabolismo , Pirróis/metabolismo , Trametes/metabolismo , Benzotiazóis/metabolismo , Benzotiazóis/farmacologia , Biocatálise , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Meios de Cultura/química , Meios de Cultura/farmacologia , Condutividade Elétrica , Técnicas Eletroquímicas , Fermentação/efeitos dos fármacos , Guaiacol/metabolismo , Guaiacol/farmacologia , Hidrazonas/metabolismo , Hidrazonas/farmacologia , Concentração de Íons de Hidrogênio , Polímeros/química , Pirróis/química , Ácidos Sulfônicos/metabolismo , Ácidos Sulfônicos/farmacologia , Trametes/efeitos dos fármacos
8.
Spectrochim Acta A Mol Biomol Spectrosc ; 208: 243-254, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30342339

RESUMO

Due to the high sensitivity to alterations in microenvironment polarity of macromolecules, pyrene and its derivatives have long been applied in biosciences. Human serum albumin (HSA), besides its numerous physiological functions, is the main responsible by transport of endogenous and exogenous compounds in the circulatory system. Here, a comprehensive study was carry out to understand the interaction between HSA and the pyrene derivative 1-pyrenesulfonic acid (PMS), which showed a singular behaviour when bound to this protein. The complexation of PMS with HSA was studied by steady state, time-resolved and anisotropy fluorescence, induction of circular dichroism (ICD) and molecular docking. The fluorescence quenching of PMS by HSA was abnormal, being stronger at lower concentration of the quencher. Similar behaviour was obtained by measuring the ICD signal and fluorescence lifetime of PMS complexed in HSA. The displacement of PMS by site-specific drugs showed that this probe occupied both sites, but with higher affinity for site II. The movement of PMS between these main binding sites was responsible by the abnormal effect. Using the holo (PDB: ID 1A06) and apo (PDB: ID 1E7A) HSA structures, the experimental results were corroborated by molecular docking simulation. The abnormal spectroscopic behaviour of PMS is related to its binding in different regions in the protein. The movement of PMS into the protein can be traced by alteration in the spectroscopic signals. These findings bring a new point of view about the use of fluorescence quenching to characterize the interaction between albumin and ligands.


Assuntos
Conalbumina/metabolismo , Pirenos/metabolismo , Soroalbumina Bovina/metabolismo , Albumina Sérica Humana/metabolismo , Ácidos Sulfônicos/metabolismo , Animais , Anisotropia , Sítios de Ligação , Bovinos , Dicroísmo Circular , Fluorescência , Humanos , Simulação de Acoplamento Molecular , Pirenos/química , Ácidos Sulfônicos/química , Termodinâmica , Fatores de Tempo , Triptofano/análogos & derivados , Triptofano/química
9.
Sci Total Environ ; 654: 19-27, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30428410

RESUMO

Organic compounds could be taken up by plants via different pathways, depending on chemical properties and biological species, which is important for the risk assessment and risk control. To investigate the transport pathways of perfluoroalkyl acids (PFAAs) by wheat (Triticum acstivnm L.), the uptake of five perfluoroalkyl carboxylic acids (PFCAs): TFA (C2), PFPrA (C3), PFBA (C4), PFHxA (C6), PFOA (C8), and a perfluoroalkyl sulfonic acid: PFOS (C8)) were studied using hydroponic experiments. Various inhibitors including a metabolic inhibitor (Na3VO4), two anion channel blockers (9-AC, DIDS), and two aquaporin inhibitors (AgNO3, glycerol) were examined. The wheat root and shoot showed different concentration trends with the carbon chain length of PFAAs. The uptake of TFA was inhibited by Na3VO4 and 9-AC whereas PFPrA was inhibited by Na3VO4, AgNO3 and 9-AC. For the other four PFAAs, only Na3VO4 was effective. These results together with the result of concentration-dependent uptake, which followed the Michaelis-Menten model, indicate that the uptake of PFAAs by wheat is mainly an energy-dependent active process mediated by carriers. For the ultra-short chain PFCAs (C2 and C3), aquaporins and anion channels may also be involved. A competition between TFA and PFPrA was determined during the plant uptake but no competition was observed between these two shorter chain analogues with other analogues, neither between PFBA and PFHxA, PFBA and PFBS, PFOA and PFOS.


Assuntos
Fluorcarbonetos/metabolismo , Plântula/metabolismo , Poluentes do Solo/metabolismo , Triticum/metabolismo , Poluentes Químicos da Água/metabolismo , Ácidos Carboxílicos/análise , Ácidos Carboxílicos/metabolismo , Relação Dose-Resposta a Droga , Fluorcarbonetos/análise , Plântula/crescimento & desenvolvimento , Poluentes do Solo/análise , Ácidos Sulfônicos/análise , Ácidos Sulfônicos/metabolismo , Fatores de Tempo , Triticum/crescimento & desenvolvimento , Poluentes Químicos da Água/análise
10.
Sci Total Environ ; 650(Pt 2): 2697-2704, 2019 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-30296776

RESUMO

In this study, eggs from free-range and barn chickens in farms around a fluorochemical facility were collected to assess the distribution profiles of perfluoroalkyl acids (PFAAs), including isomers of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonate (PFHxS), in egg yolk and albumen. The results revealed that the concentrations of PFAAs in yolks were significantly higher than those in albumen. All 17 PFAAs examined could be detected in yolks, showing decreasing concentrations with increasing distance from the fluorochemical facility. The three predominant compounds in yolks were perfluorobutanoic acid (PFBA, mean concentration 81.4 ng/g ww), PFOS (28.0 ng/g ww), and PFOA (4.83 ng/g ww), and this result is consistent with the product structure of the facility. Moreover, n-PFOA, n-PFOS, and n-PFHxS were the dominant contaminants in yolk, with mean concentrations of 4.75, 25.7, and 4.29 ng/g ww, respectively. In albumen, PFBA was still the predominant PFAA congener (mean concentration = 3.93 ng/g ww), followed by PFOA. Docking analysis indicated that the PFAAs presented higher binding abilities with the low density lipoprotein, high density lipoprotein, and vitellin proteins in yolk than that with ovalbumin albumen proteins, which might be the main factor influencing the possible difference in distributions of PFAAs in yolk and albumen.


Assuntos
Ácidos Alcanossulfônicos/metabolismo , Caprilatos/metabolismo , Clara de Ovo/química , Gema de Ovo/química , Exposição Ambiental , Poluentes Ambientais/metabolismo , Fluorcarbonetos/metabolismo , Ácidos Sulfônicos/metabolismo , Animais , Galinhas , China , Monitoramento Ambiental
11.
Molecules ; 24(1)2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30577525

RESUMO

Inflammation is a complex phenomenon that results as a healing response of organisms to different factors, exerting immune signaling, excessive free radical activity and tissue destruction. Lipoxygenases and their metabolites e.g., LTB4, are associated with allergy, cell differentiation and carcinogenesis. Lipoxygenase 12/15 has been characterized as a mucosal-specific inhibitor of IgA and a contributor to the development of allergic sensitization and airway inflammation. Development of drugs that interfere with the formation or effects of these metabolites would be important for the treatment of various diseases like asthma, psoriasis, ulcerative colitis, rheumatoid arthritis, atherosclerosis, cancer and blood vessel disorders. In this study we extended our previous research synthesizing a series of multi-target cinnamic acids from the corresponding aldehydes with suitable 4-OH/Br substituted phenyl acetic acid by Knoevenagel condensation. The final products 1i, 3i, 3ii, 4i, 6i, 6ii, and 7i were obtained in high yields (52⁻98%) Their structures were verified spectrometrically, while their experimentally lipophilicity was determined as RM values. The novel derivatives were evaluated for their antioxidant activity using DPPH, hydroxyl radical, superoxide anion and ABTS+•, anti-lipid peroxidation and soybean lipoxygenase inhibition assays. The compounds presented medium interaction with DPPH (30⁻48% at 100 µM). In contrast all the synthesized derivatives strongly scavenge OH radicals (72⁻100% at 100 µM), ABTS+• (24⁻83% at 100 µM) and presented remarkable inhibition (87⁻100% at 100 µM) in linoleic acid peroxidation (AAPH). The topological polar surface of the compounds seems to govern the superoxide anion scavenging activity. Molecular docking studies were carried out on cinnamic acid derivative 3i and found to be in accordance with experimental biological results. All acids presented interesting lipoxygenase inhibition (IC50 = 7.4⁻100 µM) with compound 3i being the most potent LOX inhibitor with IC50 = 7.4 µM combining antioxidant activities. The antioxidant results support the LOX inhibitory activities. The recorded in vitro results highlight compound 3i as a lead compound for the design of new potent lipoxygenase inhibitors for the treatment of asthma, psoriasis, ulcerative colitis, rheumatoid arthritis, atherosclerosis, cancer and blood vessel disorders.


Assuntos
Cinamatos/farmacologia , Benzotiazóis/química , Benzotiazóis/metabolismo , Compostos de Bifenilo/química , Compostos de Bifenilo/metabolismo , Radical Hidroxila/química , Radical Hidroxila/metabolismo , Inflamação/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Lipoxigenase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Picratos/química , Picratos/metabolismo , Ácidos Sulfônicos/química , Ácidos Sulfônicos/metabolismo
12.
Inorg Chem ; 57(23): 14471-14475, 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30450898

RESUMO

ABTS (2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid) oxidation to form its radical cation in the presence of H2O2 is frequently used as a test for determining the peroxidase activity of enzyme mimics. Detailed studies using salen-type Mn(III) complexes show that photochemical processes involving H2O2, ABTS, and the complex itself can lead to erroneous results. The capability of the complexes to act as •OH scavengers can be also relevant when the mechanism of their biological activity is considered.


Assuntos
Benzotiazóis/química , Complexos de Coordenação/química , Peroxidase/metabolismo , Processos Fotoquímicos , Ácidos Sulfônicos/química , Benzotiazóis/metabolismo , Complexos de Coordenação/metabolismo , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Estrutura Molecular , Peroxidase/química , Espectrofotometria Ultravioleta , Ácidos Sulfônicos/metabolismo
13.
Free Radic Res ; 52(10): 1140-1157, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30422019

RESUMO

Inflammation is a protective immune response against invading pathogens, however, dysregulated inflammation is detrimental. As the complex inflammatory response involves multiple mediators, including the involvement of reactive oxygen species, concomitantly targeting proinflammatory and antioxidant check-points may be a more rational strategy. We report the synthesis and anti-inflammatory/antioxidant activity of a novel indanedione derivative DMFO. DMFO scavenged reactive oxygen species (ROS) in in-vitro radical scavenging assays and in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. In acute models of inflammation (carrageenan-induced inflammation in rat paw and air pouch), DMFO effectively reduced paw oedema and leucocyte infiltration with an activity comparable to diclofenac. DMFO stabilised mast cells (MCs) in in-vitro A23187 and compound 48/80-induced assays. Additionally, DMFO stabilised MCs in an antigen (ovalbumin)-induced MC degranulation model in-vivo, without affecting serum IgE levels. In a model of chronic immune-mediated inflammation, Freund's adjuvant-induced arthritis, DMFO reduced arthritic score and contralateral paw oedema, and increased the pain threshold with an efficacy comparable to diclofenac but without being ulcerogenic. Additionally, DMFO significantly reduced serum TNFα levels. Mechanistic studies revealed that DMFO reduced proinflammatory genes (IL1ß, TNFα, IL6) and protein levels (COX2, MCP1), with a concurrent increase in antioxidant genes (NQO1, haem oxygenase 1 (HO-1), Glo1, Nrf2) and protein (HO-1) in LPS-stimulated macrophages. Importantly, the anti-inflammatory/antioxidant effect on gene expression was absent in primary macrophages isolated from Nrf2 KO mice suggesting an Nrf2-targeted activity, which was subsequently confirmed using siRNA transfection studies in RAW macrophages. Therefore, DMFO is a novel, orally-active, safe (even at 2 g/kg p.o.), a small molecule which targets Nrf2 in ameliorating inflammation.


Assuntos
Antioxidantes/metabolismo , Indanos/farmacologia , Inflamação/tratamento farmacológico , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Benzotiazóis/antagonistas & inibidores , Benzotiazóis/metabolismo , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/metabolismo , Carragenina , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Edema/induzido quimicamente , Edema/tratamento farmacológico , Indanos/síntese química , Indanos/química , Inflamação/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Mastócitos , Camundongos , Camundongos Knockout , Fator 2 Relacionado a NF-E2/deficiência , Fator 2 Relacionado a NF-E2/metabolismo , Picratos/antagonistas & inibidores , Picratos/metabolismo , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Ácidos Sulfônicos/antagonistas & inibidores , Ácidos Sulfônicos/metabolismo
14.
Future Med Chem ; 10(19): 2345-2367, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30273014

RESUMO

Protein tyrosine phosphatase1B (PTP1B), a significant negative regulator in insulin and leptin signaling pathways, has emerged as a promising drug target for Type II diabetes mellitus and obesity. Numerous potent PTP1B inhibitors have been discovered within both academia and pharmaceutical industry. However, nearly all medicinal chemistry efforts have been severely hindered because a vast majority of them demonstrate poor membrane permeability and low-selectivity, especially over T-cell protein tyrosine phosphatase (TCPTP). To search the rules about the selectivity over TCPTP and membrane permeability of PTP1B inhibitors, based on the PTP1B/inhibitor crystal complexes, the development PTP1B inhibitors defined as AB, AC, ABC and ADC types have been concluded in the review.


Assuntos
Inibidores Enzimáticos/química , Simulação de Acoplamento Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Ácido Benzoico/química , Ácido Benzoico/metabolismo , Sítios de Ligação , Desenho de Fármacos , Inibidores Enzimáticos/metabolismo , Humanos , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Relação Estrutura-Atividade , Ácidos Sulfônicos/química , Ácidos Sulfônicos/metabolismo , Tiofenos/química , Tiofenos/metabolismo
15.
Enzyme Microb Technol ; 119: 17-23, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30243382

RESUMO

The degradation of lignin has attracted much attention since it represents approximately 30% of all non-fossil carbon sources and constitutes a sustainable bio-resource for fuels and aromatic derivatives. Here we investigated the degradation of lignin by laccase-catalysed reactions using 2,2'-Azino-bis(3-ethybenzothiazoline-6-sulfonic acid) (ABTS) as a mediator coupled with the carbon material graphene. Results indicated that there was a significant, two-fold, increase in the catalytic activity of lignin degradation in laccase-ABTS systems in the presence of graphene. Analysis suggested that the enhancement of lignin degradation could be attributed to graphene acting as an electron transfer conductor, thereby accelerating electron transfer, which facilitated the formation of intermediate oxidation states of ABTS and rendered the reactions between lignin and ABTS intermediates more efficient. This study could promote the development of novel enzymatic lignin degradation systems coupled with the carbon-based material graphene.


Assuntos
Benzotiazóis/química , Elétrons , Grafite/química , Lacase/metabolismo , Lignina/química , Ácidos Sulfônicos/química , Trametes/enzimologia , Benzotiazóis/metabolismo , Catálise , Transporte de Elétrons , Grafite/metabolismo , Indicadores e Reagentes/química , Indicadores e Reagentes/metabolismo , Lacase/química , Lacase/genética , Lignina/metabolismo , Oxirredução , Ácidos Sulfônicos/metabolismo
16.
Colloids Surf B Biointerfaces ; 171: 668-674, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30107340

RESUMO

Polyetheretherketone (PEEK) is ideal for dental and orthopedic applications because its mechanical properties are similar to cortical bones. However, its inherent inert ability hinders its clinical applications. In this work, bone morphogenetic protein-2 (BMP-2) was immobilized onto the sulfonated PEEK (SPEEK) using lyophilization technology. The surface morphologies of the samples were analyzed by field-emission scanning electron microscopy (FE-SEM), and the chemical compositions were analyzed by energy-dispersive X-ray spectrometry (EDS). The release content of BMP-2 of the samples immersed in the PBS (pH = 7.4) was detected by a human BMP-2 ELISA kit. The results indicated that controllable and durable BMP-2 release was accomplished due to the three-dimensional (3D) network of sulfonated PEEK. The in vitro cellular experiments showed that the BMP-2-immobilized samples significantly enhanced the initial adhesion and spreading of rat bone mesenchymal stem cells (rBMSCs). Moreover, the collagen secretion, extracellular matrix mineralization and ALP activity were also improved. Thus, the BMP-2-immobilized samples greatly promoted the osteogenic differentiation of rBMSCs, which revealed that BMP-2 immobilization paves the way for the use of PEEK in clinical applications.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Cetonas/farmacologia , Osteogênese/efeitos dos fármacos , Polietilenoglicóis/farmacologia , Ácidos Sulfônicos/farmacologia , Animais , Proteína Morfogenética Óssea 2/química , Adesão Celular/efeitos dos fármacos , Humanos , Cetonas/química , Cetonas/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Tamanho da Partícula , Polietilenoglicóis/química , Polietilenoglicóis/metabolismo , Porosidade , Ratos , Ácidos Sulfônicos/química , Ácidos Sulfônicos/metabolismo , Propriedades de Superfície
17.
Chemosphere ; 211: 294-301, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30077109

RESUMO

The inhibitory effect of thiourea (TUA), ammonium thiosulfate (TSA) and amidosulfonic acid (ASA) on the reactivity of fly ash air was investigated using a thermobalance at different heating rates (5, 10 and 20 K min-1). A model fly ash (activated carbon + 50 wt% CuCl2·2H2O, pyrolyzed at 700 °C and washed) was used as carbonaceous material. Adding CuCl2·2H2O to the activated carbon led to an increased rate of decomposition with the air's oxygen. TUA and TSA behaved in a similar way, accelerating the decomposition of the model fly ash. ASA also accelerated the decomposition but to a lower extent. We postulate that the increase in decomposition rate is caused by a reaction between carbonaceous material and N and S-containing compounds. The formation of nitrogenated and sulphured compounds was confirmed by TG-MS. A kinetic model based on a single reaction of order 0.6 showed very good correlations with all the heating rates tested in oxidant atmosphere.


Assuntos
Cinza de Carvão/análise , Incineração/métodos , Ácidos Sulfônicos/química , Tiossulfatos/química , Tioureia/química , Cinza de Carvão/química , Material Particulado , Ácidos Sulfônicos/metabolismo , Tiossulfatos/metabolismo , Tioureia/metabolismo
18.
Int J Antimicrob Agents ; 52(5): 622-628, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30063998

RESUMO

Vector-borne diseases cause more than 1 million deaths annually. The research into new medicines is urgent, especially as there is currently no specific treatment. In this study, the authors have selected 64 endemic plants from the Mascarene Islands based on their endemism, their medicinal use and their registration in the French Pharmacopeia to evaluate the antiplasmodial, anti-chikungunya and antioxidant activities. The list of these 64 plants including their local name, population, data of collection and voucher number are available in the Supporting Information. Forty active extracts were identified from the 38 species: 22 responded positively to the antiplasmodial activity, 8 to the anti-chikungunya activity and 8 to the antioxidant activity. Six plants demonstrated high antiplasmodial activity (concentration inhibiting 50% of parasitic growth (IC50) <5 µg/mL): Casearia coriaceae, Monimia rotundifolia, Poupartia borbonica, Psiadia retusa, Vernonia fimbrillifera and Zanthoxylum heterophyllum; and five showed high anti-chikungunya activity (IC50<20 µg/mL): Aphloia theiformis, Stillingia lineata, Croton mauritianus, Indigofera ammoxylum, and Securinega durissima. Eight plants displayed an important antioxidant activity, with values of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP) or oxygen Radical Absorbance Capacity (ORAC) >2000 µM of Trolox equivalent per mg/mL of extract: Bertiera borbonica, Erythroxylon laurifolium, Erythroxylon sideroxyloides, I. ammoxylum, P. borbonica, Scolopia heterophylla, Sophora denudata, and Terminalia bentzoe. Some data obtained tend to corroborate the reported traditional use of the plant, such as Z. heterophyllum (antiplasmodial), A. theiformis (anti-chikungunya), and E. laurifolium (antioxidant).


Assuntos
Antimaláricos/isolamento & purificação , Antioxidantes/isolamento & purificação , Antivirais/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Plantas/química , Antimaláricos/farmacologia , Antioxidantes/farmacologia , Antivirais/farmacologia , Benzotiazóis/metabolismo , Vírus Chikungunya/efeitos dos fármacos , Compostos Férricos/metabolismo , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Oxirredução , Capacidade de Absorbância de Radicais de Oxigênio , Testes de Sensibilidade Parasitária , Extratos Vegetais/farmacologia , Plasmodium/efeitos dos fármacos , Reunião , Ácidos Sulfônicos/metabolismo
19.
Ecotoxicol Environ Saf ; 161: 669-675, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29935431

RESUMO

Perfluorooctane sulfonamide (FOSA) is an important perfluorooctane sulfonate (PFOS) precursor used for commercial applications. In order to investigate the transformation and responses of selected antioxidant and degradation enzymes of FOSA in the plants, in vivo exposure of soybean (Glycine max L. Merrill) and pumpkin (Cucurbita maxima L.) were conducted in the solution-plant microcosms. FOSA was readily taken up by soybean and pumpkin roots and translocated to shoots, and metabolized to PFOS, perfluorohexane sulfonate (PFHxS) and perfluorobutane sulfonate (PFBS). Although morphological and biomass effects were not visible, significant changes in oxidative stress response were observed except for thiobarbituric acid reactive substances (TBARS). Superoxide dismutase (SOD) and peroxidase (POD) activities were significantly increased by 19.2-30.8% and 19.2-20.7% in soybean (8-12 d) respectively, and increased by 39.2-92.8% and 21.1-37.6% in pumpkin (3-12 d) respectively, suggesting an activation of the antioxidant defense system in the plants exposed to FOSA. Glutathione-S-transferase (GST) activities were decreased in soybean (2-12 d) with 9.0-36.1% inhibition and increased in pumpkin (3-12 d) with 22.5-47.3% activation respectively; cytochrome P450 (CYP450) activities were increased markedly in soybean and pumpkin with 13.2-53.6% and 26.7-50.2% activation respectively, giving indirect evidences on the involvement of CYP450 and GST in degradation of FOSA in plants.


Assuntos
Cucurbita/metabolismo , Poluentes Ambientais/farmacocinética , Fluorcarbonetos/farmacocinética , Soja/metabolismo , Sulfonamidas/farmacocinética , Ácidos Alcanossulfônicos/metabolismo , Antioxidantes , Biotransformação , Cucurbita/enzimologia , Fluorcarbonetos/metabolismo , Hidroponia , Estresse Oxidativo , Soja/enzimologia , Ácidos Sulfônicos/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
20.
Sci Rep ; 8(1): 9529, 2018 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-29934537

RESUMO

The thermal inactivation kinetics of enzymes, including polyphenol oxidase (PPO) and peroxidase (POD), in chicory (Cichorium intybus L.) leaves were evaluated. In addition, the influences of different drying techniques (shade drying, hot air drying and freeze drying) on the phenolic profiles and antioxidant activities of chicory leaves were determined. The antioxidant activities of chicory leaves were evaluated on the basis of their 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, reducing power, and 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity. The results showed that the activation energy for PPO and POD inactivation were 123.00 kJ/mol and 78.99 kJ/mol, respectively. Preliminary treatment with hot water for 3 min at 90 °C was beneficial for preserving the phenolics present in fresh leaves. Hot air drying was better for the phenolics preservation. The hot air-dried and freeze-dried leaves possessed good antioxidant activities. The leaves with higher phenolics contents had better antioxidant activities, which indicated that the preservation of the phenolics was important for maintaining the antioxidant activity of chicory leaves.


Assuntos
Antioxidantes/metabolismo , Chicória/metabolismo , Liofilização/métodos , Temperatura Alta , Fenóis/metabolismo , Folhas de Planta/metabolismo , Benzotiazóis/metabolismo , Compostos de Bifenilo/metabolismo , Catecol Oxidase/metabolismo , Chicória/enzimologia , Ativação Enzimática , Cinética , Peroxidases/metabolismo , Picratos/metabolismo , Folhas de Planta/enzimologia , Ácidos Sulfônicos/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA