2-Aryladenine Derivatives as a Potent Scaffold for Adenosine Receptor Antagonists: The 6-Morpholino Derivatives.

A set of 2-aryl-9-H or methyl-6-morpholinopurine derivatives were synthesized and assayed through radioligand binding tests at human A1, A2A, A2B, and A3 adenosine receptor subtypes. Eleven purines showed potent antagonism at A1, A3, dual A1/A2A, A1/A2B, or A1/A3 adenosine receptors. Additionally, three compounds showed high affinity without selectivity for any specific adenosine receptor. The structure-activity relationships were made for this group of new compounds. The 9-methylpurine derivatives were generally less potent but more selective, and the 9H-purine derivatives were more potent but less selective. These compounds can be an important source of new biochemical tools and/or pharmacological drugs.

Discovery of 2,9-diaryl-6-carbamoylpurines as a novel class of antitubercular agents.

A series of novel 9-alkyl/aryl-2-aryl-6-carbamoylpurines were synthesized, and their activity against Mycobacterium tuberculosis strain H37Rv was assessed. The SAR analysis on the first set of derivatives, with an alkyl or aryl unit at N-9 and a phenolic unit at C-2, showed that the activity depends on the purine ring substituents at N-9 and C-2. A phenyl group at N-9 combined with a 3-hydroxyphenyl or 4-hydroxyphenyl at C-2 improve the activity. The most active compound of this set has a phenyl group at N-9 and a 4-hydroxyphenyl group at C-2, displaying an IC90 = 1.2 µg/mL and a selectivity index higher than 25.5. This compound served as a Hit to design the second set of derivatives. A phenyl group at N-9 was maintained, and the group at C-2 was diversified. The SAR analysis showed that the aryl unit at C-2 must have an oxygen or nitrogen atom bonded in the para position. A proton, a small alkyl or a substituted aryl group may also be bonded to the oxygen. The compound with the 4-methoxyphenyl group at C-2, 1Bd, exhibits the highest activity with an IC90 < 0.19 µg/mL. This compound is highly potent against M. tuberculosis strain H37Rv and non-toxic for VERO mammalian cells with an SI > 153.8. Compound 1Bd was also non-cytotoxic against primary macrophage cultures at IC90, 2xIC90, and 10xIC90 and significantly reduced the bacterial load in M. tuberculosis-infected macrophages at the same concentrations. Compound 1Bd showed a favorable pharmacokinetic profile when administered orally, with major lung and liver accumulation. In vivo antimycobacterial efficacy of 1Bd was tested at 25 mg/kg. At the tested regimen, a decrease in bacterial burden was observed in the liver. Optimization of the treatment regimen should be performed to fully potentiate the in vivo efficacy of our lead molecule, particularly in the lung, the main target organ of M. tuberculosis.

Analysis of selective fluorescence for the characterization of microplastic fibers: Use of a Nile Red-based analytical method to compare between natural and synthetic fibers.

The scientific community has been focusing on studying and understanding the extent of damage caused by microplastics (MPs) to flora, fauna, and humans, including the environmental and health risks associated with them. MPs with different morphologies have been described in different environments, with fibers being the most common type regardless of the environment. Various methods have been used to analyze MPs. Analytical methodologies such as visual inspection, spectroscopic methods, and others currently used to study MPs are time-consuming, and only subjective results are obtained when these methods are used for sample analysis. Researchers have used various dyes, such as Nile Red (NR), a selective fluorescent stain, to differentiate the polymers from the other sample components and address these problems. Using such dyes helps distinguish polymer particles from other contaminants present in the samples. We aimed to study the analytical process, morphology, and wettability of synthetic (such as polyethylene and polypropylene) and natural (such as linen and cotton) fibers using NR to characterize the fibers. The fibers were fragmented manually, and the samples were prepared using a cryomicrotome. The prepared samples were subjected to different NR incubation times of 30 min, 24 h, and 168 h, and characterized under ultraviolet light using optical microscopy. We investigated the effect of NR on different fibers, and the samples selection using the fluorescence properties generated when the fibers adsorbed the NR dye. The wettabilities of the samples indicated that polyethylene and polypropylene were hydrophobic, while linen and cotton were hydrophilic. Both synthetic and natural fibers exhibited fluorescence properties in the presence of NR. This increased the complexity of executing the MP characterization process, indicating that combined methodologies and optical and chemical identification processes should be used to characterize plastic specimens efficiently. We summarize and discuss the results and findings and provide recommendations for future laboratory research on microplastic fibers focusing on (I) microplastic selection, (II) stain preparation, and (III) microplastic characterization.

Regioselective Synthesis of 2-Aryl-5-cyano-1-(2-hydroxyaryl)-1H-imidazole-4-carboxamides Self-Assisted by a 2-Hydroxyaryl Group.

The reactivity of the diaminomaleonitrile-based imines containing hydroxyphenyl substituents with diverse aromatic aldehydes has been explored for the synthesis of novel highly substituted nitrogen heterocycles, which are considered privileged scaffolds in drug discovery. We report here a simple and efficient method for the regiocontrolled synthesis of a variety of 2-aryl-5-cyano-1-(2-hydroxyaryl)-1H-imidazole-4-carboxamides from 2-hydroxybenzylidene imines and aromatic aldehydes. Computational studies on the reaction path revealed that the regioselectivity of the reaction toward the formation of imidazole derivatives instead of 1,2-dihydropyrazines, most likely via a diaza-Cope rearrangement, is driven by the 2-hydroxyaryl group in the scaffold. The latter group promotes the intramolecular abstraction and protonation process in the cycloadduct intermediate, triggering the evolution of the reaction toward the formation of imidazole derivatives.

2-Aryladenine derivatives as a potent scaffold for A1, A3 and dual A1/A3 adenosine receptor antagonists: Synthesis and structure-activity relationships.

From a collection containing more than 1500 academic compounds, in silico screening identified a hit for the human A1 adenosine receptor containing a new purine scaffold. To study the structure activity relationships of this new chemical series for adenosine receptors, a library of 24 purines was synthesized and tested in radioligand binding assays at human A1, A2A, A2B and A3 adenosine receptor subtypes. Fourteen molecules showed potent antagonism at A1, A3 or dual A1/A3 adenosine receptors. This purine scaffold is an important source for novel biochemical tools and/or therapeutic drugs.

Therapeutic education, the premise of adherence to the type 2 diabetes therapeutic regimen

BACKGROUND: type 2 diabetes mellitus includes changes in lifestyle in its etiology of prevention, but the evidence is clear -even when people know what to do and what they want to do, they simply do not adopt adherence behaviors. Structured education will allow improving not only metabolic control, but also the adjustment process to a new situation of disease, as well as to develop the patient's skills in order to make him the key manager of his illness. OBJECTIVES: To determine patients' adherence to prescribed therapeutic regimens. MATERIAL AND METHODS: Quantitative, cross-sectional, non-experimental, descriptive, correlational study, with a sample of 102 people with type 2 diabetes, aged between 40 and 85 years old, mostly male (51.96%). The evaluation protocol included social-demographic and clinical questionnaire, Diabetes Self-care Scale and a questionnaire on Diabetes' knowledge. We also used HbA1c in order to directly assess adherence. RESULTS: It appears that there is no statistically significant correlation between socio-demographic variables such as gender and age and adherence. Variables, such as blood glucose monitoring, specific diet compliance and knowledge, reveal a statistically significant effect on adherence (P < .05). CONCLUSION: The evidence is clear on the urgent need to recognize the importance of measuring patient adherence to a diabetes treatment plan for the maintenance of glycaemic control. We suggest the reinforcement of educational programs in people with type 2 diabetes so as to improve adherence to self-care

No disponible

Synthesis and radical scavenging activity of phenol-imidazole conjugates.

Novel hydroxylated benzylideneamino imidazole derivatives were synthesized and their radical scavenging activity was assessed against DPPH and hydroxyl radicals. In the DPPH assay, most of the synthesized compounds showed an IC50 in the range 3.2µM⩽IC50⩽8.4µM, lower than the reference compound trolox (IC50=9.5µM) or the parent aldehydes (5.4µM⩽IC50⩽11.6µM). The activity depends mainly on the phenolic subunit (number and position of the hydroxyl groups) and the extent of conjugation with the imidazole ring. In the deoxyribose assay, all the compounds, including parent imidazoles and aldehydes, showed high activity against the hydroxyl radical and the ability to chelate iron ions. At 5µM concentration, the compounds protected the deoxyribose from degradation by hydroxyl radical between 62% and 38%.

Fatores predisponentes e medidas preventivas aos acidentes com materiais perfurocortantes: revisão integrativa / Predisposing factors and preventive measures for accidents with sharp materials: integrative review

Objetivos: identificar os fatores predisponentes à ocorrência de acidentes com materiais perfurocortantesentre profissionais de enfermagem e mostrar as medidas preventivas para a sua redução. Método: revisãointegrativa, com levantamento de artigos de 2005 e 2012 na base de dados LILACS e na biblioteca virtualSCIELO, com a questão de pesquisa > Para coleta de dados foi usado um questionário e aamostra foi composta de 12 artigos. Para a apreciação, a análise de conteúdo foi utilizada. Resultados: apósa análise emergiram as seguintes categorias > e >. Conclusão: a notificação dos acidentes e a identificação dos fatores predisponentespossibilitarão a elaboração de estratégias de intervenção baseadas na realidade de cada instituição de saúde.

Um estudo sobre tempo e espaço na prática pedagógica de educadoras de educação infantil

Este trabalho teve por objetivo apresentar um estudo sobre tempo e espaço na prática pedagógica de educadoras da Educação Infantil. Pretendeu-se compreender como tempo e espaço são vividos e se desvelam na prática pedagógica dessas educadoras. Considerando que os atributos espaciais e temporais -- construídos socialmente e essenciais para o estabelecimento de relações com o mundo – são fatores importantes de nossas experiências e ferramentas fundamentais para sistematizar nossa relação com a realidade externa, buscou-se um embasamento teórico capaz de trazer à luz as concepções de tempo e espaço e a relação destas noções com a prática pedagógica. No intuito de entender a dinâmica em que o fenômeno se constituía e compreender a vivência de tempo e espaço, a abordagem fenomenológica foi escolhida. Este método, de natureza descritiva, supõe a exclusão de pressupostos a respeito daquilo que se vai estudar e aponta para a descrição do fenômeno tal como ele vai sendo apresentado à experiência de quem o vê. Propõe, também, a busca dos elementos constitutivos do fenômeno observado, excluindo elementos causais e focalizando as constâncias. A pesquisa foi realizada em uma creche, da periferia de São Paulo, administrada pela Associação de Moradores do bairro e conveniada à Prefeitura Municipal. Quatro educadoras foram observadas – das turmas B2, de crianças de 1 ano e 6 meses a 1 ano e 11 meses; do G2, de 2 anos a 2 anos e 11 meses; do G3, de 3 anos a 3 anos e 11 meses; e do G4, 4 anos a 4 anos e 11 meses -- duas destas educadoras foram entrevistadas, assim como a Coordenadora Pedagógica. Os dados coletados foram organizados em constelações, analisados e, concluímos que para estas educadoras, o tempo e o espaço vividos apontaram para um reconhecimento de objetos e de si mesmas no mundo como uma limitação de linguagem, de experiências e de exploração de possibilidades (AU)