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Herein, we report a KIO3-catalyzed oxidative coupling of thiols to their corresponding disulfides in water, in a short time and at ambient temperature. The reaction has a broad scope and exhibits good functional group tolerance, resulting in the desired products in excellent yields. This approach allows the reuse of the reaction system in multiple cycles and scale-up. Furthermore, the current protocol demonstrates compatibility for in situ generation of disulfides and post application in C(sp2)-H bond sulfenylation.
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A versatile synthesis strategy for fluorescent 3-halo-4H-chromen-4-one derivatives is reported. The method involves the oxidative α-halogenation of enaminones performed by an efficient and sustainable oxidation system. The use of Oxone® in combination with KCl, KBr, or KI enables the preparation of 3-chloro-, 3-bromo-, or 3-iodo-4H-chromen-4-one in good to excellent yields, with great functional group tolerance where the protocol is amenable to gram-scale synthesis. The analysis of the photophysical properties of the presented 4H-chromen-4-one showed absorption in the UV region and fluorescence emission in the violet-to-cyan region with a relatively large Stokes shift. In solution, all compounds present a dual fluorescence emission, regardless of the solvent, assigned to a partially aromatised intramolecular charge transfer mechanism, considering the presence of a pseudo-aromatic ring in the chromone scaffold and the absence of the influence of substituent electronic features in optical behaviour.
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This work presents the design, synthesis, and MAO-B inhibitor activity of a series of chalcogenyl-2,3-dihydrobenzofurans derivatives. Using solvent- and metal-free methodology, a series of chalcogen-containing dihydrobenzofurans 7-9 was obtained with yields ranging from 40% to 99%, using an I2 /DMSO catalytic system. All compounds were fully structurally characterized using 1 H and 13 C NMR analysis, and the unprecedented compounds were additionally analyzed using high-resolution mass spectrometry (HRMS). In addition, the mechanistic proposal that iodide is the most likely species to act in the transfer of protons along the reaction path was studied through theoretical calculations. Finally, the compounds 7b-e, 8a-e, and 9a showed great promise as inhibitors against MAO-B activity.
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In this paper, we report an eco-friendly approach for the C(sp2)-H bond selenylation of imidazopyridines and other N-heteroarenes as well as simple arenes at ambient temperature. This new protocol consists of the reaction between (N-hetero)-arenes and the diorganyl-diselenides and trichloroisocyanuric acid (TCCA)-ethanol reagent system. In a short reaction time, the desired selenylated products were obtained regioselectively in good yields, with tolerance for a wide range of functional groups.
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COVID-19 has caused many deaths since the first outbreak in 2019. The burden on healthcare systems around the world has been reduced by the success of vaccines. However, population adherence and the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are still challenging tasks to be affronted. In addition, the newly approved drug presents some limitations in terms of side effects and drug interference, highlighting the importance of searching for new antiviral agents against SARS-CoV-2. The SARS-CoV-2 main protease (Mpr o ) represents a versatile target to search for new drug candidates due to its essential role in proteolytic activities responsible for the virus replication. In this work, a series of 190 compounds, composed of 27 natural ones and 163 synthetic compounds, were screened in vitro for their inhibitory effects against SARS-CoV-2 Mpro . Twenty-five compounds inhibited Mpro with inhibitory constant values (Ki ) between 23.2 and 241 µM. Among them, a thiosemicarbazone derivative was the most active compound. Molecular docking studies using Protein Data Bank ID 5RG1, 5RG2, and 5RG3 crystal structures of Mpro revealed important interactions identified as hydrophobic, hydrogen bonding and steric interactions with amino acid residues in the active site cavity. Overall, our findings indicate the described thiosemicarbazones as good candidates to be further explored to develop antiviral leads against SARS-CoV-2. Moreover, the studies showed the importance of careful evaluation of test results to detect and exclude false-positive findings.
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COVID-19 , SARS-CoV-2 , Humanos , Simulação de Acoplamento Molecular , Inibidores de Proteases/farmacologia , Inibidores de Proteases/química , Relação Estrutura-Atividade , Antivirais/farmacologia , Antivirais/química , Simulação de Dinâmica MolecularRESUMO
We report an electrochemical oxidative intramolecular cyclization reaction between 2-alkynylphenol derivatives and different diselenides species to generate a wide variety of substituted-benzo[b]furans. Driven by the galvanostatic electrolysis assembled in an undivided cell, it provided efficient transformation into oxidant-, base-, and metal-free conditions in an open system at room temperature. With satisfactory functional group compatibility, the products were obtained in good to excellent yields.
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BACKGROUND: COVID-19 is still causing long-term health consequences, mass deaths, and collapsing healthcare systems around the world. There are no efficient drugs for its treatment. However, previous studies revealed that SARS-CoV-2 and SARS-CoV have 96% and 86.5% similarities in cysteine proteases (3CLpro) and papain-like protease (PLpro) sequences, respectively. This resemblance could be important in the search for drug candidates with antiviral effects against SARS-CoV-2. OBJECTIVE: This paper is a compilation of natural products that inhibit SARS-CoV 3CLpro and PLpro and, concomitantly, reduce inflammation and/or modulate the immune system as a perspective strategy for COVID-19 drug discovery. It also presents in silico studies performed on these selected natural products using SARS-CoV-2 3CLpro and PLpro as targets to propose a list of hit compounds. METHODS: The plant metabolites were selected in the literature based on their biological activities on SARS-CoV proteins, inflammatory mediators, and immune response. The consensus docking analysis was performed using four different packages. RESULTS: Seventy-nine compounds reported in the literature with inhibitory effects on SARS-CoV proteins were reported as anti-inflammatory agents. Fourteen of them showed immunomodulatory effects in previous studies. Five and six of these compounds showed significant in silico consensus as drug candidates that can inhibit PLpro and 3CLpro, respectively. Our findings corroborated recent results reported on anti-SARS-CoV-2 in the literature. CONCLUSION: This study revealed that amentoflavone, rubranoside B, savinin, psoralidin, hirsutenone, and papyriflavonol A are good drug candidates for the search of antibiotics against COVID-19.
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Produtos Biológicos , Tratamento Farmacológico da COVID-19 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Descoberta de Drogas , Humanos , Imunidade , Simulação de Acoplamento Molecular , Inibidores de Proteases/farmacologia , Inibidores de Proteases/uso terapêutico , SARS-CoV-2RESUMO
Herein, we report the preparation of CuO@ borophosphate nanoparticles (CuOnano@glass) and their wide catalytic applications. The glass annealing, under a controlled atmosphere, enables the growth of copper nanoparticles on the glass surface (not within) by an uncommon bottom-up process. Following the thermal annealing of metallic nanoparticles under air atmosphere, supported copper oxide nanoparticles CuONPs on the glass surface can be obtained. The approach enables the glass matrix to be explored as a precursor and a route for the synthesis of supported copper-based nanoparticles in a solvent-free process without immobilization steps or stabilizing agents. In order to demonstrate the wide synthetic utility of this CuONPs glass-based catalyst, one-pot three-component domino reactions were performed under an air atmosphere, affording the desired selenylated oxadiazoles in good to excellent yields. We also extended the application of these new materials as a glass-based catalyst in the phenol hydroxylation and the reduction of 4-nitrophenol.
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Indoles are an important nucleus of N-heterocycles found in many natural products, active pharmaceuticals, and functional materials. In addition, indoles have various reactive positions, each one with a different reactivity, which may be susceptible to different reactions. This characteristic makes them important substrates for further transformations. This paper deals with the methodologies published in the last ten years, which used metal-free conditions to prepare indoles starting from alkynes and nitrogen compounds.
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The easy preparation and functionalization of pyrazoles associated with their innumerable biological properties have made this class of N-heterocycles very attractive for the development of new synthetic routes and applications. The cyclization reactions of alkynes and nitrogen compounds represent a powerful tool for the preparation of pyrazoles. This Review covers the recent advances in the preparation of pyrazoles by reacting alkynes and nitrogen compounds under transition-metal-catalyzed or metal-free conditions.
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Diabetes is a metabolic disease characterized by hyperglycemia because of insulin resistance and/or insufficient insulin release. The most common diabetic brain complications include cognitive decline and depression. The present study investigated whether the 4-4'-dichlorodiphenyl diselenide (p-ClPhSe)2 is effective against memory impairment induced by diabetes in mice and the role of hippocampal BDNF/TrkB signaling in this effect. Male adult Swiss mice received an injection of streptozotocin (STZ) (200â¯mg/kg, i.p.) to induce diabetes. The results revealed that STZ injection in mice resulted in resilience (glycemia <200â¯mg/dl) or diabetes (glycemia ≥200â¯mg/dl). The vehicle-control group received citrate buffer (5â¯ml/kg). The animals were subchronically treated with (p-ClPhSe)2 (1 or 5â¯mg/kg, i.g.) for 7â¯days. Mice performed a battery of well-validated behavior tests designated to evaluate memory, object recognition (ORT), object location (OLT), and Morris water maze (MWM). The hippocampal protein contents of the BDNF/TrkB pathway were determined in the samples of experimental groups. Fluoro Jade C (FJC) was used for staining degenerating neurons. The STZ administration resulted in memory impairment that was demonstrated in the mouse ORT, OLT, and MWM tests. The molecular findings indicate an increase in hippocampal protein levels of proBDNF and TrKB but a decrease in those of mBDNF and pCREB in diabetic mice. The number of FJC-positive cells was increased in the hippocampus of diabetic mice. (p-ClPhSe)2 at the dose of 5â¯mg/kg modulated the hippocampal BDNF/TrkB pathway, reduced FJC-positive cells and reversed memory impairment induced by STZ in mice. These findings demonstrate the effectiveness of (p-ClPhSe)2 against memory impairment caused by diabetes in mice. (p-ClPhSe)2 modulated the hippocampal BDNF/TrkB signaling pathway in diabetic mice.
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Fator Neurotrófico Derivado do Encéfalo/metabolismo , Diabetes Mellitus Experimental/metabolismo , Hipocampo/metabolismo , Glicoproteínas de Membrana/metabolismo , Transtornos da Memória/prevenção & controle , Compostos Organosselênicos/farmacologia , Receptor trkB/metabolismo , Animais , Escala de Avaliação Comportamental/estatística & dados numéricos , Contagem de Células/estatística & dados numéricos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Diabetes Mellitus Experimental/complicações , Relação Dose-Resposta a Droga , Fluoresceínas/metabolismo , Masculino , Transtornos da Memória/complicações , Camundongos , Fosforilação , Transdução de Sinais/efeitos dos fármacos , EstreptozocinaRESUMO
This study aimed to evaluate the antimicrobial activity of 2-phenylethynyl-butyltellurium (PEBT) in Escherichia coli and the relation to its pro-oxidant effect. For this, we carried out disk diffusion test, minimum inhibitory concentration (MIC) assay, and survival curve analysis. We also measured the level of extracellular reactive oxygen species (ROS), activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and level of non-protein thiols (NPSH). PEBT at 1.28 and 0.128 mg/disk exhibited antimicrobial capability in the disk diffusion test, with an MIC value of 1.92 mg/ml, whereas PEBT at 0.96, 1.92, and 3.84mg/ml inhibited bacterial growth after a 9-h exposure. PEBT at 3.84, 1.92, and 0.96 mg/ml increased extracellular ROS production, decreased the intracellular NPSH level, and reduced the SOD and CAT activities. Glutathione or ascorbic acid in the medium protected the bacterial cells from the antimicrobial effect of PEBT. In conclusion, PEBT exhibited antimicrobial activity against E. coli, involving the generation of ROS, oxidation of NPSH, and reduction of the antioxidant defenses in the bacterial cells.
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Anti-Infecciosos/farmacologia , Escherichia coli/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Ácido Ascórbico/metabolismo , Catalase/metabolismo , Escherichia coli/crescimento & desenvolvimento , Glutationa/metabolismo , Testes de Sensibilidade Microbiana , Compostos Organometálicos/química , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , TelúrioRESUMO
Obesity is a chronic and complex medical condition characterized by excessive fat accumulation and its complications include metabolic syndrome, diabetes and chronic inflammation. The aim of this study was to expand the knowledge about p-chloro-diphenyl diselenide (p-ClPhSe)2 effects on enzymes and proteins involved in the metabolism of lipids and carbohydrates in a model of neuroendocrine obesity induced by MSG. Male Wistar rats were treated during the first ten postnatal days with MSG (4â¯g/kg, s.c.) and received (p-ClPhSe)2 (10â¯mg/kg, i.g.) from 90th to 97th postnatal day. The hypothalamic function, insulin resistance and other biochemical parameters were determined in the rat blood, liver and skeletal muscle. The MSG administration induced hypothalamic neurotoxicity accompanied by metabolic disorders, including obesity, a transient insulin resistance, and metabolic alterations, demonstrated in the blood, liver and skeletal muscle, and lipotoxicity, characterized in the liver and skeletal muscle. The metabolic disorders in the liver and skeletal muscle were accompanied by the decrease in AMPK phosphorylation and activation of Akt. (p-ClPhSe)2 restored most of metabolic parameters altered by MSG administration in rats. The hypothalamic neurotoxicity induced by MSG was accompanied by metabolic disorders in rats, which were regulated by (p-ClPhSe)2.
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Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Compostos Organosselênicos/uso terapêutico , Glutamato de Sódio/administração & dosagem , Alanina Transaminase/sangue , Animais , Animais Recém-Nascidos , Aspartato Aminotransferases/sangue , Colesterol/sangue , Creatinina/sangue , Modelos Animais de Doenças , Comportamento Alimentar/efeitos dos fármacos , Teste de Tolerância a Glucose , Glucose-6-Fosfatase/metabolismo , Hemoglobinas Glicadas/metabolismo , Homeostase , Hipotálamo/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Glicogênio Hepático/metabolismo , Masculino , Doenças Metabólicas/induzido quimicamente , Músculo Esquelético/metabolismo , Obesidade/induzido quimicamente , Compostos Organosselênicos/farmacologia , Ratos Wistar , Triglicerídeos/sangue , Triglicerídeos/metabolismoRESUMO
Chronic stress or chronically high levels of glucocorticoids can result in memory impairment. This study aimed to investigate if 4,4'-dichloro-diphenyl diselenide (p-ClPhSe)2 reverses memory impairment-related to stress caused by corticosterone administration in mice and its possible mechanism of action. Swiss mice received corticosterone (20µg/ml) in their drinking water during four weeks. In the last week, the animals were treated with (p-ClPhSe)2 (1 or 5mg/kg) by the intragastric route (i.g.) once a day for 7days. The cognitive performance of mice was assessed through the object recognition test (ORT), the object location test (OLT) and the step-down passive avoidance test (SDPA), some of predictive tests of memory. Biochemical parameters were determined and locomotor activity of mouse was performed to gain insight in (p-ClPhSe)2 toxicity. The findings demonstrated that treatment with (p-ClPhSe)2 in both doses was effective in reversing memory deficits in the ORT, the OLT and the SDPA caused by corticosterone exposure in mice. Treatment with (p-ClPhSe)2 at both doses reversed the increase in the [(3)H] glutamate uptake by hippocampal slices of mice treated with corticosterone. By contrast, [(3)H] glutamate uptake by brain cortical slices was not altered in mice exposed to corticosterone. The Na(+)K(+)ATPase activity was not altered in hippocampus and cerebral cortices of mice treated with corticosterone. There was no sign of toxicity in mice treated with (p-ClPhSe)2. This organoselenium compound reversed memory impairment-related to stress caused by corticosterone and modulated hippocampal [(3)H]glutamate uptake in mice.
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Anti-Inflamatórios/toxicidade , Antidepressivos/uso terapêutico , Corticosterona/toxicidade , Ácido Glutâmico/metabolismo , Transtornos da Memória , Compostos Organosselênicos/uso terapêutico , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Comportamento Exploratório/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Locomoção/efeitos dos fármacos , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/patologia , Camundongos , Distribuição Aleatória , Tempo de Reação/efeitos dos fármacos , Reconhecimento Psicológico/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/metabolismo , Trítio/metabolismoRESUMO
Depression is a disorder with symptoms manifested at the psychological, behavioral and physiological levels. Monosodium glutamate (MSG) is the most widely used additive in the food industry; however, some adverse effects induced by this additive have been demonstrated in experimental animals and humans, including functional and behavioral alterations. The aim of this study was to investigate the possible antidepressant-like effect of diphenyl diselenide (PhSe)2, an organoselenium compound with pharmacological properties already documented, in the depressive-like behavior induced by MSG in rats. Male and female newborn Wistar rats were divided in control and MSG groups, which received, respectively, a daily subcutaneous injection of saline (0.9%) or MSG (4g/kg/day) from the 1st to 5th postnatal day. At 60th day of life, animals received (PhSe)2 (10mg/kg, intragastrically) 25min before spontaneous locomotor and forced swimming tests (FST). The cerebral cortices of rats were removed to determine [(3)H] serotonin (5-HT) uptake and Na(+), K(+)-ATPase activity. A single administration of (PhSe)2 was effective against locomotor hyperactivity caused by MSG in rats. (PhSe)2 treatment protected against the increase in the immobility time and a decrease in the latency for the first episode of immobility in the FST induced by MSG. Furthermore, (PhSe)2 reduced the [(3)H] 5-HT uptake and restored Na(+), K(+)-ATPase activity altered by MSG. In the present study a single administration of (PhSe)2 elicited an antidepressant-like effect and decrease the synaptosomal [(3)H] 5-HT uptake and an increase in the Na(+), K(+)-ATPase activity in MSG-treated rats.
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Antidepressivos/farmacologia , Derivados de Benzeno/farmacologia , Transtorno Depressivo/tratamento farmacológico , Compostos Organosselênicos/farmacologia , Serotonina/metabolismo , Glutamato de Sódio/toxicidade , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Animais Recém-Nascidos , Antidepressivos/química , Derivados de Benzeno/química , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Transtorno Depressivo/fisiopatologia , Modelos Animais de Doenças , Feminino , Masculino , Estrutura Molecular , Atividade Motora/efeitos dos fármacos , Compostos Organosselênicos/química , Ratos WistarRESUMO
Preliminary findings suggest that food intake reduction induced by p-chloro-diphenyl diselenide [(p-ClPhSe)2] in rats is mediated by a satiating action; however, additional experiments are necessary to clarify its actions. The purpose of this study was to investigate the effects of diets supplemented with (p-ClPhSe)2 on feeding behavior of rats as well as the (p-ClPhSe)2 effectiveness in producing aversive reactions or specific flavor. The results demonstrated that behavioral satiety sequence (BSS) was preserved in animals exposed to (p-ClPhSe)2-supplemented diets (0.01 and 0.1%) and associated with a shift of the onset of resting to the left indicating a satiating action at the first contact. In addition, the frequency, the mean duration and the mean size of meals were decreased in rats exposed to a 0.1% (p-ClPhSe)2 diet. Alternatively, a second contact with a 0.01% (p-ClPhSe)2 diet caused disruption of BSS and pronounced changes in the meal pattern, suggesting that it produces aversiveness. In fact, rats developed a significant taste aversion to the saccharin solution after receiving the administration of (p-ClPhSe)2 (1 and 10mg/kg; i.p.). Lastly, a diet containing 0.1% of (p-ClPhSe)2 seems to alter the palatability of food given that rats had a preference for the control diet. The findings of the present study suggest that (p-ClPhSe)2 reduced the food intake of rats by inducing a satiating action at the first contact, but it also produced aversive reactions when rats were re-exposed to it. A specific flavor seems also to contribute to (p-ClPhSe)2 suppressant effects on feeding.
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Dieta , Suplementos Nutricionais , Comportamento Alimentar , Compostos Organosselênicos/administração & dosagem , Tecido Adiposo , Animais , Aprendizagem da Esquiva , Peso Corporal , Comportamento de Escolha , Condicionamento Psicológico , Comportamento Alimentar/fisiologia , Masculino , Atividade Motora , Ratos Wistar , Saciação/fisiologia , Percepção Gustatória , Fatores de TempoRESUMO
RATIONALE: The searching for safe and effective antiobesity drugs has been the subject of intense research. Previous studies have shown several pharmacological applications of organoselenium compounds; however, their possible anorectic-like actions have not been investigated. OBJECTIVE: This study aims to investigate the effects of (PhSe)2 and (p-ClPhSe)2 on feeding behavior of rats and their potential as weight-reducing agents. METHODS: The effects of intraperitoneal administration of diselenides were investigated through the microstructural pattern of feeding behavior, behavioral satiety sequence (BSS), hypothalamic serotonin (5-HT) uptake, body weight, and epididymal fat content of male rats. RESULTS: Our findings demonstrated that food intake of fasted rats was reduced by both diselenides (1 and 10 mg/kg). Diphenyl diselenide [(PhSe)2] (1 mg/kg) and p-chloro-diphenyl diselenide [(p-ClPhSe)2] (10 mg/kg) decreased the frequency, mean duration, and mean size of meals compared with the control treatment. The BSS structure was preserved when organoselenium compounds (1 mg/kg) were administered, and it was associated to a displacement to the left when the resting period started indicating a satiating action. Inhibition of 5-HT uptake in the hypothalamus (â¼20 %) was also found in rats treated with low doses of (PhSe)2 and (p-ClPhSe)2 (1 mg/kg). Treatments with a high dose of both diselenides (10 mg/kg) carried out for 7 days induced weight loss and epididymal fat reduction in sated rats. CONCLUSION: This study suggests that diselenides caused a satiating action in rats that could be partially explained by the inhibition of hypothalamic 5-HT uptake. These organoselenium compounds were potential weight-reducing agents when repeatedly administered.
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Derivados de Benzeno/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Compostos Organosselênicos/farmacologia , Resposta de Saciedade/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Relação Dose-Resposta a Droga , Comportamento Alimentar/fisiologia , Masculino , Ratos , Ratos Wistar , Resposta de Saciedade/fisiologiaRESUMO
Anxiety is a serious disorder with symptoms manifested at the psychological, behavioral, and physiological levels, accompanied by alterations in the serotonergic system and monoaminergic signaling. In this study, the anxiolytic-like effect of 2-phenylethynyl butyltellurium (PEBT), in three well-consolidated anxiety mouse models (light-dark test, novelty suppressed-feeding, elevated plus-maze), was investigated. The involvement of the serotonergic system, synaptosomal [(3)H] serotonin (5-HT) uptake and monoamine oxidase (MAO A and B) activities on cerebral cortices of mice, was examined. Mice received PEBT (1mg/kg, by intragastric route, i.g.) or canola oil (10 ml/kg, i.g.) 30 min before behavioral tests. The results showed that PEBT was effective in increasing the time spent by mice in the illuminated side on the light-dark box and in the open arms on the elevated plus-maze. PEBT decreased the latency to begin eating on the novelty suppressed-feeding test, indicating an anxiolytic-like effect of PEBT. Furthermore, PEBT reduced [(3)H] 5-HT uptake and selectively inhibited MAO-A activity in cerebral cortex, suggesting the involvement of the serotonergic system in the mechanism of action of this tellurium compound.
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Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Serotonina/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Monoaminoxidase/metabolismoRESUMO
Organotellurium compounds are known for their toxicological effects. These effects may be associated with the chemical structure of these compounds and the oxidation state of the tellurium atom. In this context, 2-phenylethynyl-butyltellurium (PEBT) inhibits the activity of the sulfhydryl enzyme, δ-aminolevulinate dehydratase. The present study investigated on the importance of the tellurium atom in the PEBT ability to oxidize mono- and dithiols of low molecular weight and sulfhydryl enzymes in vitro. PEBT, at high micromolar concentrations, oxidized dithiothreitol (DTT) and inhibited cerebral Na(+), K(+)-ATPase activity, but did not alter the lactate dehydrogenase activity. The inhibition of cerebral Na(+), K(+)-ATPase activity was completely restored by DTT. By contrast, 2-phenylethynyl-butyl, a molecule without the tellurium atom, neither oxidized DTT nor altered the Na(+), K(+)-ATPase activity. In conclusion, the tellurium atom of PEBT is crucial for the catalytic oxidation of sulfhydryl groups from thiols of low molecular weight and from Na(+), K(+)-ATPase.
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Inibidores Enzimáticos/farmacologia , Compostos Organometálicos/farmacologia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Telúrio/química , Animais , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Masculino , Estrutura Molecular , Compostos Organometálicos/química , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/metabolismo , Relação Estrutura-Atividade , Telúrio/farmacologiaRESUMO
Taking into account the memory-enhancing properties of 2-phenylethynyl-butyltellurium (PEBT) and the constant search for drugs that improve cognitive performance, the present study was designed to investigate the effect of PEBT on cognitive impairment induced by scopolamine in mice. PEBT (10 mg/kg, gavage) was administered to mice 1 h before the probe trial in the Morris water maze task. Memory impairment was induced by scopolamine (1 mg/kg, intraperitoneally) 30 min before the probe trial. PEBT significantly ameliorated the scopolamine-induced impairment of long-term memory, as indicated by a decrease in escape latency and an increase in the number of crossings of the platform location when compared with the amnesic mice. To evaluate the effect of PEBT on different phases of memory (acquisition, consolidation, and retrieval) impaired by scopolamine, the step-down inhibitory avoidance task was used. Scopolamine was administered 30 min before training (acquisition), test (retrieval), or immediately after training (consolidation). PEBT, administered 30 min before scopolamine, increased step-down latency in memory-impaired mice, improving the consolidation and retrieval stages, but not acquisition. No significant alterations in locomotor or exploratory behaviors were found in animals treated with PEBT and/or scopolamine. PEBT improved memory deficits during consolidation and retrieval induced by scopolamine.