2-Bromo-1,4-naphthoquinone: a potentially improved substitute of menadione in Apatone͐2; therapy

Apatone͐2;, a combination of menadione (2-methyl-1,4-naphthoquinone, VK3) and ascorbic acid (vitamin C, VC) is a new strategy for cancer treatment. Part of its effect on tumor cells is related to the cellular pro-oxidative imbalance provoked by the generation of hydrogen peroxide (H2O2) through naphthoquinone redox cycling. In this study, we attempted to find new naphthoquinone derivatives that would increase the efficiency of H2O2 production, thereby potentially increasing its efficacy for cancer treatment. The presence of an electron-withdrawing group in the naphthoquinone moiety had a direct effect on the efficiency of H2O2 production. The compound 2-bromo-1,4-naphthoquinone (BrQ), in which the bromine atom substituted the methyl group in VK3, was approximately 10- and 19-fold more efficient than VK3 in terms of oxygen consumption and H2O2 production, respectively. The ratio [H2O2]produced / [naphthoquinone]consumed was 68 ± 11 and 5.8 ± 0.2 (µM/µM) for BrQ and VK3, respectively, indicating a higher efficacy of BrQ as a catalyst for the autoxidation of ascorbic acid. Both VK3 and BrQ reacted with glutathione (GSH), but BrQ was the more effective substrate. Part of GSH was incorporated into the naphthoquinone, producing a nucleophilic substitution product (Q-SG). The depletion of BrQ by GSH did not prevent its redox capacity since Q-SG was also able to catalyze the production of reactive oxygen species. VK3/VC has already been submitted to clinical trials for the treatment of prostate cancer and has demonstrated promising results. However, replacement of VK3 with BrQ will open new lines of investigation regarding this approach to cancer treatment.

In vitro activity of thienyl-2-nitropropene compounds against Trypanosoma cruzi

The in vitro activity of four 2-nitropropene derivatives, 1-(3-benzothienyl)-2-nitropropene (N1), 1-(3-thienyl)-2-nitropropene (N2), 1-(5-bromo-2-thienyl)-2-nitropropene (N3) and 1-(4-bromo-2-thienyl)-2-nitropropene (N4), were tested against cultures of the parasite Trypanosoma cruzi. Cytotoxicity studies were performed using Vero cells. The blood trypomastigotes, amastigotes and epimastigotes showed differential degrees of sensitivity towards the four tested compounds; the highest activity against the epimastigotes and blood tripomastigotes was exhibited by N1, followed by N3, N4 and finally N2. In contrast, whereas the compounds N1, N3 and N4 exerted similar magnitudes of activity against amastigotes, N2 was found to be a much less potent compound. According to our results, the compound N1 had the highest level of activity (IC50: 0.6 μM) against epimastigotes.

Métodos sintéticos para preparação de 2,2'-bipiridinas substituídas

The 2,2'-bipyridine has been entitled as the most widely used ligand. Nowadays there is a large variety of known molecules comprising at least two 2,2'-bipyridine units and the number of applications in many areas such as catalysis, new materials, optoeletronics and electrochemistry have increased very much in the past decades. Nevertheless, there is no article that gives an overview of the main synthetic methods for obtaining the substituted 2,2'-bipyridines, generally non available. This article presents a synthetic discussion about the three different methods (coupling reaction, ciclo-functionalization and functionalization of the heteroaromatic rings of 2,2'-bipyridine) for preparing these heterocyclic compounds and also provides a practical and fundamental guide, for obtaining more than eighty different symmetric and unsymmetrical substituted 2,2'-bipyridines, shown in a table with the corresponding references.

Urinary 2,5-hexanedione in workers exposed to n-hexane: influence of the sample treatment

The aim of the present study was to determine 2,5-hexanedione (2,5-HD), a metabolite of n-hexane, by gas chromatography/flame ionization detection in 31 workers exposed to n-hexane after two types of sample pretreatment, i.e., with (total 2,5-HD) and without (free 2,5-HD) acid hydrolysis. The mean urinary 2,5-HD was 0.52 mg/L (free) and 2.88 mg/L (total), this difference being significant (Student t-test, p < 0.05). The differences in the results according to the sample treatment support the need to modify the current Brazilian legislation, which proposes the analysis of 2,5-HD without indicating whether it is the free or total metabolite.

Síntese de 2-iodobenzamidas e 3-(iodoacetamido)benzamidas ligadas à D-galactose e suas reações de carbociclização radicalar mediadas por hidreto de tri-n-butilestanho

Starting from methyl 6-O-allyl-4-azido-2,3-di-O-benzyl-4-deoxy-α-D-galactopyranoside, four new derivatives containing 2-iodobenzamido and 3-(iodoacetamido)benzamido groups were synthesized. These four compounds were submitted to tri-n-butyltin hydride mediated radical cyclization reactions, resulting in two macrolactams from 11- and 15-endo aryl radical cyclization. The corresponding four hydrogenolysis products were also obtained. The structures of the new compounds were elucidated by ¹H and 13C NMR spectroscopy, DEPT, COSY, HMQC and HMBC experiments.

MÉTODO ALTERNATIVO PARA A SÍNTESE E MECANISMO DE 2-(1,3-DITIANO-2-ILIDENO)-ACETONITRILA

We report an alternative method for the synthesis of 2-(1,3-dithian-2-ylidene)-acetonitrile using 3-(4-chlorophenyl)-3-oxopropanenitrile and carbon disulfide as starting materials. The methanolysis of the intermediate 3-(4-chlorophenyl)-2-(1,3-dithian-2-ylidene)-3-oxopropanenitrile occurs via three possible intermediates, leading to the formation of the product at a 75% overall yield. Molecular modeling simulation of the reaction pathway using B3LYP 6-311G++(2df,2p) justified the proposed reaction mechanism.

Spectrophotometric determination of arsenic in soil samples using 2-(5-bromo-2-pyridylazo)-5-di-ethylaminophenol (Br-PADAP)

In this paper, a new, simple and sensitive method for arsenic determination in soil is proposed. This is based on the reduction of silver (I) and iron (III) ions by arsine followed by a complexation reaction of iron (II) with the spectrophotometric reagent Br-PADAP 2-(5-bromo-2-pyridylazo)-5-di-ethylaminophenol. Arsenic determination with a Sandell's sensitivity of 3.1 10-4 cm-2, linear range from 0.1 µg ml-1 to 2.0 µg ml-1 (r560 = 0.9995), molar absorptivity of 2.45 10(5) l mol-1 cm-1 and a concentration detection limit of 1.4 ng ml-1 (3s) were obtained using a 10 ml sample volume. Selectivity was increased with the use of EDTA as a masking agent. The proposed method was applied for arsenic determination in the presence of several ions amounts in digested soil samples. The results revealed that antimony (III), mercury (II), germanium (IV), platinum (IV) interferes at all analyzed proportions. The interferences can be easily removed by the use of EDTA. Precision and accuracy obtained were satisfactory with a R.S.D. < 5 %. Recovery of arsenic in soil samples varied from 95.55 to 102.70 % with a mean of 99.63 %. These results demonstrated that the proposed method is applicable for arsenic analysis in different soil samples.

Synthesis and characterization of solid 2-methoxycinnamylidenepyruvic acid

The 2-methoxycinnamylidenepyruvic acid (2-MeO-HCP) was synthesized and characterized for nuclear magnetic resonance (¹H and 13C NMR), mass spectrometry (MS), Infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The application of DSC for purity determination is well documented in literature and is used in the analysis of pure organic compounds. The molecular geometry and vibrational frequencies of 2-MeO-HCP have been calculated.

Classificação BI-RADS™: categorização de 4.968 mamografias

Seguindo o modelo adotado pelo Colégio Americano de Radiologia, utilizamos o método BI-RADS™ (Breast Imaging Reporting and Data System) numa análise regional retrospectiva de 4.968 mamogramas, para categorizar e avaliar a freqüência dos achados mamográficos, distribuindo-os nos diferentes grupos desta classificação. Das 4.968 mamografias foram laudadas 44,4% (n = 2.208) como negativas, 46,3% (n = 2.305) como achados mamográficos benignos, 7,5% (n = 374) como achados mamográficos provavelmente benignos, 0,98% (n = 49) como achados mamográficos suspeitos e 0,72% (n = 36) como achados mamográficos altamente suspeitos. O estudo também demonstra a importância da uniformização do laudo mamográfico, através da aplicação da classificação BI-RADS™, sobretudo como preditor de malignidade, bem como na avaliação da conduta a ser seguida.

Specific fluorogenic substrates for neprilysin (neutral endopeptidase, EC 3.4.24.11) which are highly resistant to serine- and metalloproteases

Two intramolecularly quenched fluorogenic peptides containing o-aminobenzoyl (Abz) and ethylenediamine 2,4-dinitrophenyl (EDDnp) groups at amino- and carboxyl-terminal amino acid residues, Abz-DArg-Arg-Leu-EDDnp (Abz-DRRL-EDDnp) and Abz-DArg-Arg-Phe-EDDnp (Abz-DRRF-EDDnp), were selectively hydrolyzed by neutral endopeptidase (NEP, enkephalinase, neprilysin, EC 3.4.24.11) at the Arg-Leu and Arg-Phe bonds, respectively. The kinetic parameters for the NEP-catalyzed hydrolysis of Abz-DRRL-EDDnp and Abz-DRRF-EDDnp were Km = 2.8 µM, kcat = 5.3 min-1, kcat/Km = 2 min-1 µM-1 and Km = 5.0 µM, kcat = 7.0 min-1, kcat/Km = 1.4 min-1 µM-1, respectively. The high specificity of these substrates was demonstrated by their resistance to hydrolysis by metalloproteases [thermolysin (EC 3.4.24.2), angiotensin-converting enzyme (ACE; EC 3.4.24.15)], serineproteases [trypsin (EC 3.4.21.4), a-chymotrypsin (EC 3.4.21.1)] and proteases present in tissue homogenates from kidney, lung, brain and testis. The blocked amino- and carboxyl-terminal amino acids protected these substrates against the action of aminopeptidases, carboxypeptidases and ACE. Furthermore, DR amino acids ensured total protection of Abz-DRRL-EDDnp and Abz-DRRF-EDDnp against the action of thermolysin and trypsin. Leu-EDDnp and Phe-EDDnp were resistant to hydrolysis by a-chymotrypsin. The high specifity of these substrates suggests their use for specific NEP assays in crude enzyme preparations

In vitro antimicrobial activity of a new series of 1,4-naphthoquinones

The antibacterial activity of a series of 1,4-naphthoquinones was demonstrated. Disk diffusion tests were carried out against several Gram-positive and Gram-negative bacteria. The compound 5-amino-8-hydroxy-1,4-naphthoquinone was the most effective, presenting inhibition zones measuring 20 mm against staphylococci, streptococci and bacilli at 50 µg/ml. Methicillin-resistant Staphylococcus aureus and several clinical isolates of this bacterium were also inhibited. Naphthazarin, 5-acetamido-8-hydroxy-1,4-naphthoquinone, and 2,3-diamino-1,4-naphthoquinone were the next most active compounds. The minimal inhibitory concentration of the active compounds was determined against S. aureus, ranging from 30 to 125 µg/ml. All compounds presented a minimal bactericidal concentration higher than 500 µg/ml, indicating that their effect was bacteriostatic. The EC50, defined as the drug concentration that produces 50% of maximal effect, was 8 µg/ml for 5-amino-8-hydroxy-1,4-naphthoquinone against S. aureus, S. intermedius, and S. epidermidis. These results indicate an effective in vitro activity of 5-amino-8-hydroxy-1,4-naphthoquinone and encourage further studies for its application in antibiotic therapy.

Eficiência de trifloxysulfuron-sodium no controle de Cyperus rotundus L. na cultura da cana-de-açúcar

O objetivo foi avaliar a eficiência de trifloxysulfuron-sodium isolado, em mistura, ou em aplicação sequencial a outros herbicidas no controle de Cyperus rotundus L. na cultura da cana-de-açúcar. O estudo foi realizado em área de produção comercial do cultivar RB 72-454 na Usina Paraíso e em casa de vegetação da Universidade Estadual do Norte Fluminense Darcy Ribeiro, em Campos dos Goytacazes, Rio de Janeiro. As parcelas no campo foram submetidas a nove tratamentos: 2,4-D; trifloxysulfuron-sodium + ametryn; trifloxysulturon-sodium; 2,4-D + 2,4-D (20 dias após a primeira aplicação -DAP); 2,4-D + trifloxysulfuron-sodium + ametryn (20 DAP); 2,4-D + trifloxysulfuron-sodium (20 DAP); halosulfuron (20 DAP) e testemunha com e sem capina. Em casa de vegetação avaliou-se a viabilidade dos bulbos de C. rotundus em função dos tratamentos utilizados no experimento instalado em campo. Os resultados indicaram que o trifloxysulfuron-sodium isolado ou em mistura com ametryn, em aplicação sequencial ao 2,4-D, foi excelente no controle de C. rotundus. Esse herbicida e o halosulfuron, aplicados isoladamente, reduziram a capacidade de reinfestação da espécie daninha em razão da redução de sua propagação e do seu crescimento.

Efeito de substratos e boro no enraizamento de estacas de pitaya

A pitaya é uma espécie vegetal trepadeira e frutífera, pertencente à família das cactáceas e que vem se destacando no mercado de frutas exóticas no Brasil. Objetivou-se avaliar diferentes substratos no enraizamento de cladódios com a base imersa e não-imersa em solução com ácido bórico, na formação e no desenvolvimento inicial de raízes, visando à obtenção de mudas mais vigorosas, de melhor qualidade e com maiores chances de sobrevivência. O experimento foi conduzido sob ripado no Departamento de Produção Vegetal, setor de Horticultura da Faculdade de Ciências Agronômicas no campus de Botucatu, UNESP, São Paulo. O delineamento experimental foi o inteiramente casualizado em esquema fatorial 4 x 2 (substratos x boro), com quatro repetições. Após 60 dias da instalação do experimento foram avaliados: massa de matérias fresca e seca da parte aérea, massa de matérias fresca e seca das raízes e comprimento da maior raiz. O crescimento e desenvolvimento radicular inicial de estacas são influenciados pelo tipo de substrato e pelo uso do micronutriente boro. A mistura areia + esterco proporciona maior acúmulo de fitomassa na parte aérea e no sistema radicular de pitaya vermelha. Dentre os substratos trabalhados, o mais indicado para a produção de mudas mais vigorosas e de boa qualidade é o preparado à base de mistura de areia + esterco bovino curtido.

Influência da presença da bordadura e dos níveis de água na evaporação obtida em minievaporímetros

Este trabalho objetivou avaliar a influência de bordadura com água e diferentes profundidades do nível de água dentro do evaporatório dos minievaporímetros UFV-1 e UFV-2 sobre a evaporação. Para analisar o efeito da bordadura e das profundidades dos níveis de água iguais a 30, 45, 60 e 75 mm da borda nos minievaporímetros, o experimento foi montado em esquema fatorial 4 x 2 (quatro níveis de água e dois tipos de minievaporímetros), no delineamento inteiramente casualizado, com três repetições. De acordo com os resultados, a bordadura com água reduziu a evaporação no minievaporímetro UFV-2 em 1,10 mm d-1, em média, nas diferentes profundidades dos níveis de água estudados, comparativamente ao minievaporímetro UFV-1. À medida que se aumentou a profundidade do nível de água no evaporatório dos dois tipos de minievaporímetros, a evaporação diminuiu e se aproximou do valor obtido no tanque Classe A. O aumento na profundidade dos níveis de água nos minievaporímetros UFV-1 e UFV-2 de 30 para 75 mm reduziu a evaporação de 5,45 para 4,9 mm d-1 e de 4,29 para 3,81 mm d-1, respectivamente.

Produção da bananeira 'Prata anã'(AAB) em função de diferentes doses e fontes de potássio

Dentre os nutrientes exigidos pela bananeira, o K é o que mais influencia na produção desta cultura. Este trabalho teve por objetivos comparar os efeitos de duas fontes de K (cloreto de potássio e sulfato de potássio) sobre a produção, bem como estimar as doses de K para obter a máxima eficiência física (MEF) e econômica (MEE) e determinar o nível crítico de K na folha da bananeira 'Prata anã' (AAB) irrigada, cultivada na região semiárida do norte de Minas Gerais, Brasil. O experimento foi realizado em Latossolo Vermelho-Amarelo (LVA), textura média. Os tratamentos foram originados do fatorial (4 x 2), sendo quatro doses de K (0, 400, 800 e 1200 kg /ha ano de K2O) e duas fontes de K (KCl e K2SO4), gerando oito tratamentos, que foram distribuídos em blocos ao acaso, com quatro repetições. Não houve diferenças entre os efeitos do KCl e K2SO4 sobre a produção da bananeira. A análise econômica demonstrou que o KCl apresentou maior viabilidade para ser utilizado como fonte de K. As doses estimadas para a MEF nos 2º e 3º ciclos de produção, utilizando-se o KCl, foram de 827 e 835 kg ha-1 ano-1 de K2O, respectivamente. Já para a MEE, as doses foram de 157 e 670 kg/ha ano de K2O, respectivamente. Os níveis críticos foliares de K, obtidos nos 2º e 3º ciclos de produção, foram de 2,85 dag kg-1 para a MEF e, para a MEE, de 2,41 e 2,80 dag kg-1, respectivamente.