Saturated Iso-Type Fatty Acids from the Marine Bacterium Mesoflavibacter zeaxanthinifaciens with Anti-Trypanosomal Potential.

Chagas disease is a Neglected Tropical Disease with limited and ineffective therapy. In a search for new anti-trypanosomal compounds, we investigated the potential of the metabolites from the bacteria living in the corals and sediments of the southeastern Brazilian coast. Three corals, Tubastraea coccinea, Mussismilia hispida, Madracis decactis, and sediments yielded 11 bacterial strains that were fully identified by MALDI-ToF/MS or gene sequencing, resulting in six genera-Vibrio, Shewanella, Mesoflavibacter, Halomonas, Bacillus, and Alteromonas. To conduct this study, EtOAc extracts were prepared and tested against Trypanosoma cruzi. The crude extracts showed IC50 values ranging from 15 to 51 µg/mL against the trypomastigotes. The bacterium Mesoflavibacter zeaxanthinifaciens was selected for fractionation, resulting in an active fraction (FII) with IC50 values of 17.7 µg/mL and 23.8 µg/mL against the trypomastigotes and amastigotes, respectively, with neither mammalian cytotoxicity nor hemolytic activity. Using an NMR and ESI-HRMS analysis, the FII revealed the presence of unsaturated iso-type fatty acids. Its lethal action was investigated, leading to a protein spectral profile of the parasite altered after treatment. The FII also induced a rapid permeabilization of the plasma membrane of the parasite, leading to cell death. These findings demonstrate that these unsaturated iso-type fatty acids are possible new hits against T. cruzi.

A new reduced chalcone-derivative affects the membrane permeability and electric potential of multidrug-resistant Enterococcusfaecalis.

The emergence and spread of multidrug-resistant (MDR) enterococci and other Gram-positive bacteria represents a severe problem due to the lack of effective therapeutic alternatives. Natural products have long been an important source of new antibacterial scaffolds and can play a key role in the current antibiotic crisis. Enterococci are predominantly non-pathogenic gastrointestinal commensal bacteria, but among them, Enterococcus faecalis and Enterococcus faecium represent the species that account for most clinically relevant infections. The emergence of MDR enterococci has reduced the available antibiotic treatment options and highlights the need to develop new antimicrobial compounds. In the search for new hit compounds against MDR Enterococcus spp., natural-derived compounds represent inspiring scaffolds for drug design studies. In this work, the antimicrobial activity of a fully synthetic chalcone derivative (r4MB) was determined on a clinical panel of 34 MDR Gram-positive bacteria, mostly constituted by E. faecalis and E. faecium, along with Staphylococcus spp., amongst others. Compound r4MB showed activity against 100% of the tested strains, with the minimum inhibitory concentration (MIC) in the range of 5-20 µM. The lethal action of the compound was evaluated using different fluorescent-based assays. The compound showed a time-dependent permeabilisation of the membrane of a vancomycin-resistant E. faecalis, detected by the fluorescent probe SYTOX Green, and digital fluorescent microscopy corroborated the spectrofluorimetric analysis within 6 min of incubation. Flow cytometry analysis of the membrane electric potential demonstrated a significant depolarization, confirming the target of the compound towards the bacterial membrane. No cytotoxic haemolysis was observed with mammalian erythrocytes, and a 99% cytotoxic concentration of 118 µM on NCTC cells demonstrated a promising antimicrobial selectivity. In silico studies using SwissADME and ADMETLabs servers suggest that compound r4MB displayed adequate ADME properties, with no alerts for pan-assay interference compounds (PAINS). Future hit-to-lead optimization of this chalcone derivative can contribute to developing a more potent derivative against infections caused by MDR enterococci.

Avaliação de resíduos de agrotóxicos em amostras de farinha de trigo por espectrometria de massas / Evaluation of pesticide residues in wheat flour by mass spectrometry

Os cereais são uma importante fonte alimentícia e econômica, dentre eles se destaca o trigo e sua farinha. Durante o cultivo, visando o controle de pragas, frequentemente são utilizados os agrotóxicos, porém seu uso abusivo pode acarretar danos à saúde humana e ao meio ambiente. O trabalho teve como objetivo avaliar a presença de resíduos de agrotóxicos em amostras de farinha de trigo comercializadas no estado de São Paulo, utilizando o método QuEChERS (Rápido, Fácil, Barato, Efetivo, Robusto e Seguro) modificado, seguido de análise por CG-EM/EM e CLUE-EMAR para identificação e quantificação. No total, 124 ingredientes ativos (i.a.) estavam dentro dos critérios de aceitação para linearidade, limites de detecção e quantificação, exatidão e precisão (intervalo de confiança de 95%; k = 2). Os resultados de 25 amostras indicaram a presença de bifentrina, fenitrotiona, clorpirifós, deltametrina, lambda-cialotrina e pirimifós-metílico em farinha de trigo comum e os quatro últimos i.a. também foram detectados em farinha de trigo orgânica. O pirimifósmetílico foi detectado em 92% das amostras. Os i.a. encontrados nas amostras estavam abaixo do Limite Máximo de Resíduos (LMR) estabelecidos pela Agência Nacional de Vigilância Sanitária (Anvisa) para farinha de trigo e as amostras foram consideradas próprias para o consumo (AU).

Cereals are an important economic factor and food source, which wheat and its flour stand out. Pesticides are often employed to control harmful organisms, but their abusive use can cause damage to human health and the environment. This study aimed to evaluate the presence of pesticide residues in wheat flour samples commercialized in the state of São Paulo ­ Brazil, using the modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method, followed by GC-MS/MS and UHPLC-HRMS analysis for identification and quantification. Thus, 124 active ingredients (a.i.) were within acceptable criteria for linearity, limits of detection and quantification, accuracy (trueness), and precision (95% confidence level; k = 2). The results for 25 wheat flour samples showed the presence of bifenthrin, fenitrothion, chlorpyrifos, deltamethrin, lambda-cyhalothrin, and pirimiphos-methyl, and the last four a.i. were also detected in organic wheat flour. Pirimiphos-methyl was detected in 92% of all samples. All compounds were found below the Maximum Residue Levels (MRL) established by Brazilian Health Regulatory Agency (Anvisa) for wheat flour and the samples were considered suitable for consumption (AU).

Persistence of indoor permethrin and estimation of dermal and non-dietary exposure.

Pesticides applied indoors may persist longer than they would in outdoor environments, making people more vulnerable to the risk of exposure. Permethrin is a pyrethroid insecticide used in agricultural, residential, and public health sites, and is commonly detected in indoor environments. The objectives of this study were to evaluate the persistence of permethrin indoors and to estimate the levels of possible dermal and non-dietary exposure to this insecticide. Permethrin was applied on aluminum foil and kept in a glass chamber and a test house for 112 days; its concentration was measured at application and after 28, 56, and 112 days. Permethrin persisted for the entire 112 days in concentrations equal to a maximum of 89.6% of the initial concentration. We observed low levels of human dermal and non-dietary exposure to permethrin.

Pyrethroid concentrations and persistence following indoor application.

Residential indoor environments are potential sources of exposure to pyrethroids, which have low acute toxicity to humans but are allergenic and suspected endocrine disruptors. The present study evaluated the persistence of the pyrethroids cypermethrin and beta-cyfluthrin on indoor surfaces and in house dust. Cypermethrin and beta-cyfluthrin were applied and maintained on aluminum foils and in dust samples for 112 d under controlled conditions and for 12 mo in a test house; periodically, they were quantified by high-performance liquid chromatography. Cypermethrin and beta-cyfluthrin concentrations showed decreases of 10.1% and 7.7% on aluminum foils, and 12.7% and 16.4% in dust, respectively, at 112 d under controlled conditions. In the test house, cypermethrin and beta-cyfluthrin concentrations decreased by 40.3% and 60.2% on aluminum foils, and 29.6% and 56.2% in dust at the end of the study. The results show the considerable persistence of cypermethrin and beta-cyfluthrin indoors and indicate the risk of exposure to these products. Environ Toxicol Chem 2017;36:2895-2898. © 2017 SETAC.