Síntesis y estructura de espiro [pirrolidin-2,4'-piperidinas]

RESUMENSe estudió la formación de r,2',5'-trimetilespiro[pirrolidin-2,4'-piperidinasJ a partir de sus correspondientes l,2,5-trimetil-4-alil-4-aminopiperidinas en condiciones de la reacción de aminomercuración. Los productos formados se aislaron por cromatografía en columna sobre alúmina (ALO,) y sus estructuras se establecieron por medio del análisis espectroscópico ( IR, RMN 'H y espectrometría de masas). _________________________________________________________________________________ ABSTRACTThe synthesis of 1,2,5-trimethylspiro[piper¡dine-4,2'-pirrolidines] from their respectives 1,2,5-trimethyl-4-allyl-4-aminopipcridines were carried out under the conditions of amino-mercuration reaction. The obtained producís were isoiated by column chromatography on alumine (ALO,) and their structures were determinated by spectroscopic analysis( IR, 'H NMR and mass spectrometry)

A pesquisa-ação como ferramenta para informação sobre agrotóxicos: o caso de trabalhadores rurais da Zona da Mata, Rondônia, Brasil

A região da Zona da Mata em Rondônia, Brasil, destaca-se pela grande produção de grãos e cereais, e também tem sido evidenciada pela utilização de grande quantidade e variedade de agrotóxicos por trabalhadores rurais locais. Considerando tal cenário, uma série de atividades foi planejada em municípios da Zona da Mata, no âmbito de uma pesquisa-ação, com o propósito de informar os trabalhadores rurais quanto aos riscos da má utilização de agrotóxicos e incentivar mudanças de rotina e a busca de informações técnicas. A pesquisa-ação foi desenvolvida em duas etapas. A primeira consistiu em eventos de integração entre trabalhadores rurais, órgãos públicos e o pesquisador; a segunda parte, realizada doze meses depois, consistiu da avaliação do impacto das atividades da primeira etapa na rotina de utilização de agrotóxicos.  Os achados revelaram que a maioria dos técnicos dos órgãos públicos (87,5%) e dos trabalhadores rurais (70,0%) entrevistados afirmou ter havido um aumento das consultas à assistência técnica. Quanto à utilização de agrotóxicos, 76,2% dos entrevistados relataram ter reduzido a quantidade utilizada ou ter processado a troca do agrotóxico utilizado por outros de menor toxicidade humana. É interessante observar que de acordo com 75,0% dos produtores rurais, houve um aumento na produtividade da lavoura. Dessa forma, atividades utilizando a pesquisa-ação podem constituir-se em ferramenta útil para promoção da saúde e divulgação de noções de segurança na utilização de agrotóxicos.

α-Amylase inhibitors : a review of raw material and isolated compounds from plant source

ABSTRACTInhibition of α-amylase, enzyme that plays a role in digestion of starch and glycogen, is considered a strategy for the treatment of disorders in carbohydrate uptake, such as diabetes and obesity, as well as, dental caries and periodontal diseases. Plants are an important source of chemical constituents with potential for inhibition of α-amylase and can be used as therapeutic or functional food sources. A review about crude extracts and isolated compounds from plant source that have been tested for α-amylase inhibitory activity has been done. The analysis of the results shows a variety of crude extracts that present α-amylase inhibitory activity and some of them had relevant activity when compared with controls used in the studies. Amongst the phyto-constituents that have been investigated, flavonoids are one of them that demonstrated the highest inhibitory activities with the potential of inhibition related to number of hydroxyl groups in the molecule of the compound. Several phyto-constituents and plant species as α-amylase inhibitors are being reported in this article. Majority of studies have focused on the anti-amylase phenolic compounds

Preparation of modified clay with cetylpyridinium chloride and evaluation of their interaction with PVC

Foi preparada uma argila modificada com cloreto de cetilpiridíneo a partir da argila sódica por troca de cátions em solução. Foi avaliada a quantidade de agente de modificação em relação à argila sódica e o tempo reacional. Os materiais obtidos foram caracterizados por difração de raio X (XRD), análise termogravimétrica (TGA) e ressonância magnética nuclear (RMN) de baixo campo. Após a caracterização foi confirmada a modificação da argila e, também, foi verificado que o produto obtido pode ser empregado na preparação de nanocompósitos de PVC, considerando que o início da degradação do material preparado ocorreu em temperatura superior às comumente utilizadas no processamento do polímero. A adição da argila modificada apresentou uma dispersão adequada no PVC e manteve o início da degradação do material em temperatura compatível com o processamento do polímero, gerando um nanocompósito com parte esfoliada e intercalada. _________________________________________________________________________________ ABSTRACTA modified silicate with cetylpyridinium was prepared from sodium clay with cation exchange in solution. The amount of modification agent for clay and the reaction time were evaluated. The materials produced were characterized using X ray diffraction (XRD), termogravimetric analysis (TGA) and low field nuclear magnetic resonance (NMR). The formation of new organic clay was confirmed, which was introduced in PVC for the formation of nanocomposites. The beginning of degradation of the new clay occurred at temperatures higher than commonly used in the processing of PVC. The nanocomposites were partially exfoliated and partially intercalated

Plants from Brazilian cerrado with potent tyrosinase inhibitory activity

The increased amount of melanin leads to skin disorders such as age spots, freckles, melasma and malignant melanoma. Tyrosinase is known to be the key enzyme in melanin production. Plants and their extracts are inexpensive and rich resources of active compounds that can be utilized to inhibit tyrosinase as well as can be used for the treatment of dermatological disorders associated with melanin hyperpigmentation. Using in vitro tyrosinase inhibitory activity assay, extracts from 13 plant species from Brazilian Cerrado were evaluated. The results showed that Pouteria torta and Eugenia dysenterica extracts presented potent in vitro tyrosinase inhibition compared to positive control kojic acid. Ethanol extract of Eugenia dysenterica leaves showed significant (p<0.05) tyrosinase inhibitory activity exhibiting the IC50 value of 11.88 µg/mL, compared to kojic acid (IC50 value of 13.14 µg/mL). Pouteria torta aqueous extract leaves also showed significant inhibitory activity with IC50 value of 30.01 µg/mL. These results indicate that Pouteria torta and Eugenia dysenterica extracts and their isolated constituents are promising agents for skin-whitening or antimelanogenesis formulations

Seasonal monitoring of the antioxidant activity of Erythroxylum suberosum A. St.-Hil. leaves: Correlation with hyperoside and isoquercitrin contents

373-382This study evaluated the seasonal effects of two flavonoids on antioxidant activity and chromatographic profiles by thin layer chromatography and high-performance liquid chromatography (HPLC) in Erythroxylum suberosum A. St.-Hil, a species used by the Brazilian indigenous community. These variables were observed from August 2013 to May 2014 in correlation with climatic variables, such as temperature, rainfall index and global radiation. The chromatographic profiles were found to be similar in the aqueous and ethanol extracts, and flavonoid hyperoside and isoquercitrin were identified and quantified. In the inhibition of the DPPH• radical, the most active was the aqueous extract from the 2nd collection (IC50: 4.45 μg/mL). For the phosphomolybdenum complex reduction method, the ethanol extract from the 1st collection was the most active (206.39 μg/mL equivalent ascorbic acid). Regarding the environmental correlations, it was observed that a higher global radiation index had a strong influence on the concentrations of hyperoside and contributed to the antioxidant activity. On the other hand, higher temperatures contributed to a higher isoquercitrin content in the aqueous extracts. These results indicate that August is the best month for the collection of Erythroxylum suberosum A. St.-Hil. leaves which have the highest isoquercitrin and hyperoside content and, thus, a high antioxidant activity

Determination of harpagoside in Harpagophytum procumbens DC tablet’s using analytical method by High Performance Liquid Chromatography

The species Harpagophytum procumbens DC. is popularly known as devil’s claw and is widely used because of its anti-inflammatory properties that are attributed to an iridoid glycoside, the harpagoside. This medicinal plant is part of the Brazilian List of Essential Medicines, that is, it was selected and standardized for the resolution of diseases in the Brazilian public health system, SUS, and can be found in several brands. Due to the importance of quality monitoring, the objective of this study was to create and validate a method for identification and quantification of harpagoside in tablets of the devil’s claw, as well as to evaluate the content of this iridoid glycoside in three commercially available brands in Brasília, DF, Brazil. The evaluated parameters in the validation by high performance liquid chromatography (HPLC) were linearity, limits of detection and quantification, precision, selectivity, accuracy and robustness, as required by the Brazilian regulation. The developed and validated method proved satisfactory for the quality control of commercial products that present in this composition the medicinal plant. All the devil’s claw brands presented divergences regarding the quality that can interfere with therapeutics and with safety and efficacy

Thyroid hormone response element organization dictates the composition of active receptor

Thyroid hormone (triiodothyronine, T3) is known to activate transcription by binding heterodimers of thyroid hormone receptors (TRs) and retinoid X receptors (RXRs). RXR-TRs bind to T3 response elements (TREs) composed of direct repeats of the sequence AGGTCA spaced by four nucleotides (DR-4). In other TREs, however, the half-sites can be arranged as inverted palindromes and palindromes (Pal). Here we show that TR homodimers and monomers activate transcription from representative TREs with alternate half-site placements. TRβ activates transcription more efficiently than TRα at an inverted palindrome (F2), and this correlates with preferential TRβ homodimer formation at F2 in vitro. Furthermore, reconstruction of TR transcription complexes in yeast indicates that TRβ homodimers are active at F2, whereas RXR-TRs are active at DR-4 and Pal. Finally, analysis of TRβ mutations that block homodimer and/or heterodimer formation reveal TRE-selective requirements for these surfaces in mammalian cells, which suggest that TRβ homodimers are active at F2, RXR-TRs at DR-4, and TR monomers at Pal. TRβ requires higher levels of hormone for activation at F2 than other TREs, and this differential effect is abolished by a dimer surface mutation suggesting that it is related to composition of the TR·TRE complex. We propose that interactions of particular TR oligomers with different elements play unappreciated roles in TRE-selective actions of liganded TRs in vivo

Determination of rosmarinic acid in Cordia verbenacea by liquid chromatography : applicability in seasonal study

Neste estudo, uma técnica de cromatografia líquida de alta resolução em fase reversa (CLAE-FR) para a determinação de ácido rosmarínico em Cordia verbenacea foi desenvolvida e validada. A análise de regressão foi avaliada, com observação de uma boa linearidade (r = 0,9997). Os valores obtidos para a precisão e exatidão estão de acordo com as diretrizes do ICH e com a legislação brasileira. Os valores de repetibilidade e precisão intermediária foram 2,79% e 4,76%, respectivamente. Os limites de detecção e de quantificação de ácido rosmarínico foram de 1,92 µg/mL e 5,81 µg/mL, respectivamente. Os resultados mostraram que o método desenvolvido é uma técnica por CLAE-FR de confiança para a determinação de ácido rosmarínico em tintura de C. verbenacea. Além disso, essa metodologia foi aplicada em estudo sazonal, que revela uma correlação positiva relativamente forte entre o período de chuvas e o teor de ácido rosmarínico.In this study, a reverse phase-high performance liquid chromatography (RP-HPLC) technique for determination of rosmarinic acid in the Cordia verbenacea was developed and validated. A regression analysis was performed, with the observation of good linearity (r =0.999949). The values obtained for precision and accuracy determination are in agreement with ICH guidelines and the Brazilian legislation. The values of repeatability and intermediate precision were 2.79% and 4.76%, respectively. The detection and the quantitation limits of the rosmarinic acid were 1.92 µg/mL and 5.81 µg/mL, respectively. The results demonstrated that the developed method is a reliable RP-HPLC technique for the determination of rosmarinic acid in C. verbenacea tincture. In addition, this methodology was applied at a seasonal study indicating relatively strong positive correlation between the rain period and the rosmarinic acid content

In vitro effects of European and Latin-American medicinal plants in CYP3A4 gene expression, glutathione levels, and P-glycoprotein activity

Many medicinal plants species from European -such as Artemisia absinthium, Equisetum arvense, Lamium album, Malva sylvestris, Morus nigra, Passiflora incarnata, Frangula purshiana, and Salix alba- as well as Latin American traditions -such as Libidibia ferrea, Bidens pilosa, Casearia sylvestris, Costus spicatus, Monteverdia ilicifolia, Persea americana, Schinus terebinthifolia, Solidago chilensis, Syzygium cumini, Handroanthus impetiginosus, and Vernonanthura phosphorica- are shortlisted by the Brazilian National Health System for future clinical use. However, they lack many data on their action upon some key ADME targets. In this study, we assess non-toxic concentrations (up to100 μg/ml) of their infusions for in vitro ability to modulate CYP3A4 mRNA gene expression and intracellular glutathione levels in HepG2 cells, as well as P-glycoprotein (P-gp) activity in vincristine-resistant Caco-2 cells (Caco-2 VCR). We further investigated the activation of human pregnane X receptor (hPXR) in transiently co-transfected HeLa cells and the inhibition of Gamma-glutamyl transferase (GGT) in HepG2 cells. Our results demonstrate L. ferrea, C. sylvestris, M. ilicifolia, P. americana, S. terebinthifolia, S. cumini, V. phosphorica, E. arvense, P. incarnata, F. purshiana, and S. alba can significantly increase CYP3A4 mRNA gene expression in HepG2 cells. Only F. purshiana shown to do so likely via hPXR activation. P-gp activity was affected by L. ferrea, F. purshiana, S. terebinthifolia, and S. cumini. Total intracellular glutathione levels were significantly depleted by exposure to all extracts except S. alba and S. cumini This was accompanied by a lower GGT activity in the case of C. spicatus, P. americana, S. alba, and S. terebinthifolia, whilst L. ferrea, P. incarnata and F. purshiana increased it. Surprisingly, S. cumini aqueous extract drastically decreased GGT activity (−48%, p < 0.01). In conclusion, this preclinical study shows that the administration of some of these herbal medicines causes in vitro disturbances to key drug metabolism mechanisms. We recommend active pharmacovigilance for Libidibia ferrea (Mart.) L. P. Queiroz, Frangula purshiana Cooper, Schinus terebinthifolia Raddi, and Salix alba L. which were able to alter all targets in our preclinical study