Structure-activity relationships of hypervalent organochalcogenanes as inhibitors of cysteine cathepsins V and S

A new series of organotelluranes were synthesized and investigated, and the structure-activity relationships in cysteine proteases inhibition were determinated. It was possible to identify the relevance of structural components linked to the reactivity of these compounds as inhibitors. for example, dibromo-organotelluranes showed to be more reactive than dichloro-organotelluranes towards cysteine cathepsins V and S. Besides, no remarkable enantio-selectivity was verified. in general the achiral organotelluranes were more reactive than the chiral congeners against cysteine cathepsins V and S. A reactivity order for organochalcogenanes and cysteine cathepsins was proposed after the comparison of the inhibitory potencies of organotelluranes with the related organoselenanes. (C) 2011 Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Biofis, Escola Paulista Med, BR-04044200 São Paulo, BrazilUniv São Paulo, Inst Quim, BR-05508900 São Paulo, BrazilUniv British Columbia, Dept Dent, Fac Dent, Vancouver, BC V6T 1Z3, CanadaUniv British Columbia, UBC Ctr Blood Res, Fac Dent, Vancouver, BC V6T 1Z3, CanadaUniv Fed ABC, CCNH, BR-09210580 Santo Andre, SP, BrazilUniversidade Federal de São Paulo, Dept Biofis, Escola Paulista Med, BR-04044200 São Paulo, BrazilWeb of Scienc

Enzymatic kinetic resolution of (RS)-1-(Phenyl)ethanols by Burkholderia cepacia lipase immobilized on magnetic nanoparticles

Lipase from Burkholderia cepacia immobilized on superparamagnetic nanoparticles using adsorption and chemisorption methodologies was efficiently applied as recyclable biocatalyst in the enzymatic kinetic resolution of (RS)-1-(phenyl)ethanols via transesterification reactions. (R)-Esters and the remaining (S)-alcohols were obtained with excellent enantiomeric excess (> 99%), which corresponds to a perfect process of enzymatic kinetic resolution (conversion 50%, E > 200). The transesterification reactions catalysed with B. cepacia lipase immobilized by the glutaraldehyde method showed the best results in terms of reusability, preserving the enzyme activity (conversion 50%, E > 200) for at least 8 successive cycles.A lipase proveniente da Burkholderia cepacia imobilizada em nanopartículas superparamagnéticas usando diferentes metodologias de imobilização (adsorção e quimiosorção) foi eficientemente aplicada como biocatalisador reciclável na resolução cinética de (RS)-1-(fenil)etanols através de reações de transesterificação. Os (R)-ésteres e os (S)-alcoóis foram obtidos com excelente excesso enantiomérico (> 99%), o que corresponde a um perfeito processo de resolução cinética enzimática (conversão 50%, E > 200). As reações de transesterificação catalisadas pela lipase de B. cepacia imobilizada pela metodologia com glutaraldeído apresentaram os melhores resultados em termos de conversão após 8 ciclos de reação.FAPESPCNPqPETROBRA

Bioreduction of substituted a-tetralones promoted by Daucus carota root

The bioreduction of a series of substituted a-tetralones, carried out using Daucus carota root (carrot), afforded the corresponding homochiral a-tetralols in variable conversions (9 to 90%) and excellent enantiomeric excesses. Two of the assayed a-tetralones were resistant to the bioreduction conditions. The absolute configurations of four a-tetralols were assigned as being (S), by comparison to the (S)-enantiomers obtained by kinetic resolution promoted by CALB-catalysed acetylation. Additionally, the new 5-methoxy-6-methyl-1-tetralone was synthesized in seven steps from 3-methylsalicylic acid.FAPESPCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)CNP

Interventions for physical activity promotion applied to the primary healthcare settings for people living in regions of low socioeconomic level: study protocol for a non-randomized controlled trial.

BACKGROUND: Regular physical activity practice has been widely recommended for promoting health, but the physical activity levels remain low in the population. Therefore, the study of interventions to promote physical activity is essential. OBJECTIVE: To present the methodology of two physical activity interventions from the "Ambiente Ativo" ("Active Environment") project. METHODS: 12-month non-randomized controlled intervention trial. 157 healthy and physically inactive individuals were selected: health education (n = 54) supervised exercise (n = 54) and control (n = 49). Intervention based on health education: a multidisciplinary team of health professionals organized the intervention in group discussions, phone calls, SMS and educational material. Intervention based on supervised exercise program: consisted of offering an exercise program in groups supervised by physical education professionals involving strength, endurance and flexibility exercises. The physical activity level was assessed by the International Physical Activity Questionnaire (long version), physical activities recalls, pedometers and accelerometers over a seven-day period. RESULT: This study described two different proposals for promoting physical activity that were applied to adults attended through the public healthcare settings. The participants were living in a region of low socioeconomic level, while respecting the characteristics and organization of the system and its professionals, and also adapting the interventions to the realities of the individuals attended. CONCLUSION: Both interventions are applicable in regions of low socioeconomic level, while respecting the social and economic characteristics of each region. TRIAL REGISTRATION: ClinicalTrials.gov NCT01852981

Chemoenzymatic synthesis of organoselenium(IV) compounds and their evaluation as cysteine protease inhibitors

A series of organoselenium dihalides (organoselenanes) was synthesized from organoselenides using a chemoenzymatic approach. The organoselenanes have variations in their stereochemistry and in the halogen atom bonded to the selenium atom. Because of the unique selenium-thiol chemistry displayed by several organoselenium compounds, the organoselenanes were evaluated as new potential inhibitors of cysteine proteases (cathepsins S and V). By the analysis of the second-order rate constants of the inhibition of cathepsin S and V, it was possible to conclude that organoselenanes inhibited the cathepsin S faster than cathepsin V. It was observed higher inhibitory potencies for the dibromo organoselenanes derivatives than the dichloro analogues. In addition, the present data suggest the use of hypervalent selenium compounds as novel motifs for cysteine proteases inhibitors.Uma série de organosselenanas foi sintetizada utilizando-se uma metodologia quimio-enzimática. Estas organosselenanas apresentam variações na estereoquímica e no halogênio ligado ao átomo de selênio. Devido à reação característica envolvendo compostos de selênio e tióis, estas organosselenanas foram avaliadas como inibidores de cisteíno proteases (catepsinas V e S). As constantes de inibição de segunda-ordem mostraram que a catepsina S é inibida mais rapidamente do que a catepsina V. Pode-se observar que as organosselenanas dibromadas são inibidores mais potentes do que as dicloradas. Desta forma, os resultados obtidos mostram que compostos hipervalentes de selênio podem ser aplicados como inibidores de cisteíno proteases

Effect of pH Variation on Synthesis and Photocatalytic Activity of Bi2Fe4O9

The Pechini synthesis method, presents chemical homogeneity as its main advantage, enabling the desired phase to be obtained. This synthesis usually occurs at pH 7. In this study, Bi2Fe4O9 was synthesized using the Pechini method at different pHs (pH= 3, 5, 7, 8, 10 and 12) to verify if the pH conditions can influence in its photocatalytic activity. The materials obtained at different conditions were characterized by using X rays diffraction (XRD), UV/Vis diffuse reflectance and scanning electron microscopy by field emission (MEV/FEG).It was possible to synthesize the material under conditions already mentioned, but it was not observed significant differences in the chemical structure of the obtained materials from the characterization techniques. However, they presented a small variation in the band gap values, morphological aspects and photocatalytic activities. All the materials proved to be a good semiconductor, maintaining high degradation rates. The photocatalyst synthesized at pH 3 (BFO - 1) presented a degradation rate of approximately 95% for the group chromophore and 93% for the aromatic group of the structure of the tartrazine yellow dye, proving to be a promising photocatalyst for industrial applications. This result is particularly important because BFO – 1 showed higher catalyst activity since the chromophore of the aromatic group was degraded. The highlights of this study is the synthesis of Bi2Fe4O9 performed at pH=3, since it reduces the quantity of reagents comparing to the conventional Pechini method and presented high photocatalytic activity. DOI: http://dx.doi.org/10.17807/orbital.v13i2.148

Screening of Microorganisms Producing Cold-Active Oxidoreductases to Be Applied in Enantioselective Alcohol Oxidation. An Antarctic Survey

Several microorganisms were isolated from soil/sediment samples of Antarctic Peninsula. The enrichment technique using (RS)-1-(phenyl)ethanol as a carbon source allowed us to isolate 232 psychrophile/psychrotroph microorganisms. We also evaluated the enzyme activity (oxidoreductases) for enantioselective oxidation reactions, by using derivatives of (RS)-1-(phenyl)ethanol as substrates. Among the studied microorganisms, 15 psychrophile/psychrotroph strains contain oxidoreductases that catalyze the (S)-enantiomer oxidation from racemic alcohols to their corresponding ketones. Among the identified microorganisms, Flavobacterium sp. and Arthrobacter sp. showed excellent enzymatic activity. These new bacteria strains were selected for optimization study, in which the (RS)-1-(4-methyl-phenyl)ethanol oxidation was evaluated in several reaction conditions. From these studies, it was observed that Flavobacterium sp. has an excellent enzymatic activity at 10 °C and Arthrobacter sp. at 15 and 25 °C. We have also determined the growth curves of these bacteria, and both strains showed optimum growth at 25 °C, indicating that these bacteria are psychrotroph

Stock de carbono en especies arbóreas del espinal entrerriano

El objetivo fue estimar el stock de carbono (C) en la biomasa arbórea de los bosques nativos del Espinal y valorar el servicio ecosistémico que prestan como secuestradores de C ante escenarios de cambio climático. El estudio se desarrolló en el área de bosques nativos de Entre Ríos. Se cuantificó la biomasa arbórea aérea y la fracción de C por componente (fuste, ramas ≥5cm de diámetro y <5cm) de las especies dominantes (Prosopis affinis, Vachellia caven y P.nigra). Se obtuvieron para cada especie, modelos alométricos de alta precisión y factores de expansión de la biomasa, que constituyen herramientas de utilidad para estimar el C almacenado en estos ecosistemas. Los bosques nativos del Espinal entrerriano almacenan en promedio en su biomasa arbórea aérea, un stock de 43,99±10,43 tC/ha, que representan 161,44 t CO2/ha capturados de la atmósfera. Se estimó una tasa promedio de captura y fijación de C de 0,75±0,17 tC/ha/año. Este valor indica que en promedio, 1 ha de bosque nativo secuestra 2,75 t CO2/año. La información generada permite valorar el servicio ambiental que brindan los bosques nativos del Espinal entrerriano como sumidero de C en un escenario de cambio climático, siendo prioritaria su protección contra la deforestación y degradación.Fil: Sione, Silvana Maria Jose. Provincia de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Universidad Autónoma de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción; Argentina. Universidad Nacional de Entre Ríos. Facultad de Ciencias Agropecuarias; ArgentinaFil: Ledesma, Silvia Gabriela. Universidad Nacional de Entre Ríos. Facultad de Ciencias Agropecuarias. Departamento de Ciencias de la Tierra; ArgentinaFil: Rosenberger, Leandro Javier. Universidad Nacional de Entre Ríos. Facultad de Ciencias Agropecuarias; ArgentinaFil: Oszust, José Daniel. Universidad Nacional de Entre Ríos. Facultad de Ciencias Agropecuarias. Departamento de Ciencias de la Tierra; ArgentinaFil: Maciel, Gabriel Omar. Universidad Nacional de Entre Ríos. Facultad de Ciencias Agropecuarias; ArgentinaFil: Wilson, Marcelo Germán. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Entre Ríos. Estación Experimental Agropecuaria Paraná; ArgentinaFil: Andrade Castañeda, H.. Universidad del Tolima; ColombiaFil: Sasal, Maria Carolina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Entre Ríos. Estación Experimental Agropecuaria Paraná; Argentin

Exposure of cultured fibroblasts to the peptide PR-11 for the identification of induced proteome alterations and discovery of novel potential ligands.

The PR-11 peptide corresponds to the N-terminal and active region of the endogenously synthesized PR-39 molecule, of porcine origin. It is known to possess various biological effects including antimicrobial properties, angiogenic and anti-inflammatory activities. Apart from its reported activity as a proteasome inhibitor, a more comprehensive understanding of its function, at the molecular level, is still lacking. In this study, we used a label-free shotgun strategy to evaluate the proteomic alterations caused by exposure of cultured fibroblasts to the peptide PR-11. This approach revealed that more than half of the identified moleculeswere related to signalling, transcription and translation. Proteins directly associated to regulation of angiogenesis and interaction with the hypoxia-inducible factor 1-? (HIF-1?) were significantly altered. In addition, at least three differentially expressed molecules of the NF-?B pathway were detected, suggesting an anti-inflammatory property of PR-11. At last, we demonstrated novel potential ligands of PR-11, through its immobilization for affinity chromatography. Among the elutedmolecules, gC1qR, a known complement receptor, appearedmarkedly enriched. This provided preliminary evidence of a PR-11 ligand possibly involved in the internalization of this peptide. Altogether, our findings contributed to a better understanding of the cellular pathways affected by PR-39 derived molecules