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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.

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.

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;9999:1–4. © 2017 SETAC

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.