A Novel Short-Step Synthesis of New Xanthenedione Derivatives from the Cyclization of 3-Cinnamoyl-2-styrylchromones

Novel (E)-3-aryl-4-benzylidene-8-hydroxy-3,4-dihydro-1 H-xanthene-1,9(2H)-diones are prepared by the cyclization of (E,E)-3-cinnamoyl-5-hydroxy-2-styrylchromones efficiently catalyzed with boron tribromide. The (E,E)-3-cinnamoyl-5-hydroxy-2-styrylchromones are obtained from the Baker–Venkataraman rearrangement of (E,E)-2-acetyl-1,3-phenylene bis(3-phenylacrylate), which is greatly improved under microwave irradiation.

Xanthenedione derivatives, new promising antioxidant and acetylcholinesterase inhibitor agents

Natural and synthetic xanthone derivatives are well-known for their ability to act as antioxidants and/or enzyme inhibitors. This paper aims to present a successful synthetic methodology towards xanthenedione derivatives and the study of their aromatization to xanthones. Additionally their ability to reduce Fe(III), to scavenge DPPH radicals and to inhibit AChE was evaluated. The results demonstrated that xanthenedione derivative 5e, bearing a catechol unit, showed higher reduction capacity than BHT and similar to quercetin, strong DPPH scavenging activity (EC50 = 3.79 ± 0.06 μM) and it was also showed to be a potent AChEI (IC50 = 31.0 ± 0.09 μM) when compared to galantamine (IC50 = 211.8 ± 9.5 μM).

Solid-phase microextraction for determination of 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone in water

Solid-phase microextraction, using on-line bis(trimethylsilyl)trifluoroacetamide derivatisation, gas chromatography, and mass spectrometry, was evaluated in the quantification of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in water samples. Fibres encompassing a wide range of polarities were used with headspace and direct immersion sampling. For the immersion procedure, various parameters affecting MX extraction, including pH, salinity, temperature, and extraction time were evaluated. The optimised method (polyacrylate fibre; 20% Na2SO4; pH 2.0; 60 min; 20 °C) was applied for reservoir chlorinated water samples-either natural or spiked with MX (50 ng L-1 and 100 ng L-1). The recovery of MX ranged from 44 to 72%. Quantification of MX in water samples was done using external standard and the selected ion monitoring mode. Correlation coefficient (0.98%), relative standard deviation (5%), limit of detection (30 ng L-1) and limit of quantification (50 ng L-1) were obtained from calibration curve.

Biotransformation of sucrose into 5-hydroxy-2-hydroxymethyl-γ-pirone by Aspergillus flavus

Foram investigadas a hidrólise da sacarose e a preferência pela glicose frente à frutose no processo de produção do 5-hidroxi-2-hidroximetil-γ-pirona (HHMP) na presença de Aspergillus flavus IOC 3974 cultivado em meio líquido Czapeck. Quantidades de 0,5g de pelletes foram utilizadas como inóculo. Doze frascos cônicos de 250 ml contendo 100 ml de meio de cultura com diferentes concentrações de sacarose foram utilizados. Os microrganismos foram cultivados a 120 rpm e 28"C por 16 dias sem ajuste do pH. O maior rendimento do HHMP foi 26g l^-1 em 120g l^-1 de sacarose. Nestas condições, A. flavus, foi capaz de produzir uma invertase possibilitando a hidrólise de 65% da concentração total de sacarose em 24 horas, conjuntamente com a produção de uma isomerase que foi capaz de converter a frutose em glicose. Este trabalho está focalizado preferencialmente no consumo da glicose frente à frutose por A. flavus e na estratégia de produção do HHMP.

Fragm. lat. I 75 - Psalterium (Ps 4,2 - 7,3; 10,5 - 14,2)

Trägerband: 'Ad Repositorium sub Litt. <...> Lin. 1 Num. 7'; Vorbesitzer: Karmeliterkloster Frankfurt am Main

3-Hydroxy-4, 5-dimethyl-2 (5 H)-furanone levels in fortified Madeira wines: Relationship to sugar content

The maturation of Madeira wines usually involves exposure to relatively high temperatures and humidity levels >70%, which affect the aroma and flavor composition and lead to the formation of the typical and characteristic bouquet of these wines. To estimate the levels of sotolon [3-hydroxy4,5-dimethyl-2(5 H )-furanone] and their behavior over time, 86 aged Madeira wines samples (1-25 years old), with different sugar concentrations, respectively, 90 g L-1 for Boal, 110 g L-1 for Malvazia, 25 g L -1 for Sercial, and 65 g L-1 for Verdelho varieties, were analyzed. Isolation was performed by liquid-liquid extraction with dichloromethane followed by chromatographic analysis by GC-MS. The reproducibility of the method was found to be 4.9%. The detection and quantification limits were 1.2 and 2.0 µgL-1, respectively. The levels of sotolon found ranged from not detected to 2000 µgL-1 for wines between 1 and 25 years old. It was observed that during aging, the concentration of sotolon increased with time in a linear fashion ( r ) 0.917). The highest concentration of sotolon was found in wines with the highest residual sugar contents, considering the same time of storage. The results show that there is a strong correlation between sotolon and sugar derivatives: furfural, 5-methylfurfural, 5-hydroxymethylfurfural, and 5-ethoxymethylfurfural. These compounds are also well correlated with wine aging. These findings indicate that the kinetics of sotolon formation is closely related with residual sugar contents, suggesting that this molecule may come from a component like sugar.

In Vitro and in Vivo Assays of 3,5-Disubstituted-Tetrahydro-2H-1,3,5-Thiadiazin-2-Thione Derivatives against Trypanosoma cruzi

Cytotoxicity assays of 24 new 3,5-disubstituted-tetrahydro-2H-1,3,5-thiadiazin-2-thione derivatives were performed. The 17 compounds with higher anti-epimastigote activity and lower cytotoxicity were, thereafter, screened against amastigote of Trypanosoma cruzi. Out of these 17 derivatives S-2d was selected to be assayed in vivo, because of its remarkable trypanocidal properties. To determine toxicity against J774 macrophages, a method based on quantification of cell damage, after 24 h, was used. Cell respiration, an indicator of cell viability, was assessed by the reduction of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] to formazan. Anti-amastigote activity was estimated after 48 h by microscopic counts of May Grünwald-Giemsa-stained monolayers. Nifurtimox and benznidazole were used as reference drugs. For the in vivo experiences, mice were infected with 10(4) blood trypomastigotes and then treated during 15 days with S-2d or nifurtimox by oral route. All of the compounds were highly toxic at 100 µg/ml for macrophages and a few of them maintained this cytotoxicity even at 10 µg/ml. Of the derivatives assayed against amastigotes 3k and S-2d showed an interesting activity, that was held even at 1µg/ml. It is demonstrated that the high anti-epimastigote activity previously reported is mainly due to the non-specific toxicity of these compounds. In vivo assays assessed a reduction of parasitemia after administration of S-2d to infected mice.

Inhibition of NF-kB activation and cytokines production in THP-1 monocytes by 2-styrylchromones

Nuclear factor kappa B (NF-kB) is one of the most important transcription factors whose modulation triggers a cascade of signaling events, namely the expression of many cytokines, enzymes, chemokines, and adhesion molecules, some of which being potential key targets for intervention in the treatment of inflammatory conditions. The 2-styrylchromones (2-SC) designation represents a well-recognized group of natural and synthetic chromones, vinylogues of flavones (2-phenylchromones). Several 2-SC were recently tested for their anti-inflammatory potential, regarding the arachidonic acid metabolic cascade, showing some motivating results. In addition, several flavones with structural similarities to 2-SC have shown NF-kB inhibitory properties. Hence, the aim of the present work was to continue the investigation on the interference of 2-SC in inflammatory pathways. Herein we report their effects on lipopolysaccharide (LPS)-induced NF-kB activation and consequent production of proinflammatory cytokines/chemokine, using a human monocytic cell line (THP-1). From the twelve 2-SC tested, three of them were able to significantly inhibit the NF-kB activation and to reduce the production of the proinflammatory cytokines/chemokine. The compound 3',4',5-trihydroxy-2- styrylchromone stood up as the most active in both assays, being a promising candidate for an anti-inflammatory drug.

Ação do metabólito secundário 5-hidroxi-2-hidroximetil gama-pirona isolado de fungos do gênero Aspergillus sobre monócitos humanos in vitro

O 5-hidroxi-2-hidroximetil-gama-pirona (HMP) é um metabólito secundário sintetizado por algumas espécies de fungos dos gêneros Aspergillus, Penicillium Acetobac-ter. O HMP tem várias aplicações, sendo utilizado como antioxidante, inibidor da tirosinase, agente protetor contra a radiação e antitumoral. Recentemente, foi também demonstrado que esse metabólito atua como ativador de macrófagos. No entanto, o efeito do HMP em mo-nócitos humanos é desconhecido. Assim, o objetivo deste estudo foi avaliar os efeitos de HMP sobre a viabilidade e diferenciação celular de monócitos do sangue humano in vi-tro. Leucócitos humanos do sangue periférico foram obtidos a partir de bolsas de san-gue doadas pela Fundação Centro de Hemoterapia e Hematologia do Pará (HEMOPA). O isolamento das células foi realizado por meio de gradiente de densidade com Histopaque ®1077. Os monócitos foram tratados durante 24, 48 e 72 horas com 50 e 100 μg / mL de HMP. A análise ultraestrutural dos monócitos tratados revelou que essas células apresen-tam maior espraiamento, elevado número de projeções citoplasmáticas e vacúolos, caracterís-ticas que são frequentemente observadas em células ativadas. A análise da expressão da proteína de superfície específica para macrófago (F4/80) por imunofluorescência, de-monstrou que os monócitos humanos tratados com 50 e 100 μg / mL de HMP por 48 e 72 horas, mostrou um padrão de expressão semelhante ao verificado em macrófagos humanos originados de monócitos tratados com o M-CFS. Os testes de viabilidade utilizados (Método thiazolyl blue, Potencial de membrana mitocondrial, Vermelho Neutro e Azul de Tripan) mostraram que o HMP não tem nenhum efeito citotóxico em monócitos humanos quando tra-tados com 50 e 100 μg/ mL do bioproduto. Estes resultados demonstram um novo papel pa-ra HMP como um agente imunomodulador, induzindo a diferenciação de monócitos em macrófagos.