Activity of Fluorine‐Containing Analogues of WC‐9 and Structurally Related Analogues against Two Intracellular Parasites: Trypanosoma cruzi and Toxoplasma gondii

Two obligate intracellular parasites, Trypanosoma cruzi, the agent of Chagas disease, and Toxoplasma gondii, an agent of toxoplasmosis, upregulate the mevalonate pathway of their host cells upon infection, which suggests that this host pathway could be a potential drug target. In this work, a number of compounds structurally related to WC‐9 (4‐phenoxyphenoxyethyl thiocyanate), a known squalene synthase inhibitor, were designed, synthesized, and evaluated for their effect on T. cruzi and T. gondii growth in tissue culture cells. Two fluorine‐containing derivatives, the 3‐(3‐fluorophenoxy)‐ and 3‐(4‐fluorophenoxy)phenoxyethyl thiocyanates, exhibited half‐maximal effective concentration (EC₅₀) values of 1.6 and 4.9 μm , respectively, against tachyzoites of T. gondii, whereas they showed similar potency to WC‐9 against intracellular T. cruzi (EC₅₀ values of 5.4 and 5.7 μm , respectively). In addition, 2‐[3‐ (phenoxy)phenoxyethylthio]ethyl‐1,1‐bisphosphonate, which is a hybrid inhibitor containing 3‐phenoxyphenoxy and bisphosphonate groups, has activity against T. gondii proliferation at sub‐micromolar levels (EC₅₀=0.7 μm ), which suggests a combined inhibitory effect of the two functional groups.     

N‐Benzyl‐4‐((heteroaryl)methyl)benzamides: A New Class of Direct NADH‐Dependent 2‐trans Enoyl–Acyl Carrier Protein Reductase (InhA) Inhibitors with Antitubercular Activity

Isoniazid (INH) remains one of the cornerstones of antitubercular chemotherapy for drug‐sensitive strains of M. tuberculosis bacteria. However, the increasing prevalence of multidrug‐resistant (MDR) and extensively drug‐resistant (XDR) strains containing mutations in the KatG enzyme, which is responsible for the activation of INH into its antitubercular form, have rendered this drug of little or no use in many cases of drug‐resistant tuberculosis. Presented herein is a novel family of antitubercular direct NADH‐dependent 2‐trans enoyl–acyl carrier protein reductase (InhA) inhibitors based on an N‐benzyl‐4‐((heteroaryl)methyl)benzamide template; unlike INH, these do not require prior activation by KatG. Given their direct InhA target engagement, these compounds should be able to circumvent KatG‐related resistance in the clinic. The lead molecules were shown to be potent inhibitors of InhA and showed activity against M. tuberculosis bacteria. This new family of inhibitors was found to be chemically tractable, as exemplified by the facile synthesis of analogues and the establishment of structure–activity relationships. Furthermore, a co‐crystal structure of the initial hit with the enzyme is disclosed, providing valuable information toward the design of new InhA inhibitors for the treatment of MDR/XDR tuberculosis.     

The Use of Reverse Osmosis in the Removal of PAHs from Municipal Landfill Leachate

Polycyclic aromatic hydrocarbons (PAHs) are relatively well-known organic pollutants and due to their carcinogenic and mutagenic properties their presence in the environment still attracts a lot of attention.

According to literature reports and own research, PAHs presence in wastewaters is common. It was confirmed that PAHs are the components of municipal landfill leachate. Membrane techniques are one of the most interesting ways of removing PAHs from leachate.

The purpose of this article is to monitor PAHs concentration changes during the membrane (reverse osmosis - RO) leachate treatment processes. In the first stage of testing leachates were filtrated on the sand bed (pre-filtration). After the pre-filtration they were directed to the membrane module for the main filtration.

Sixteen PAHs listed by EPA were analyzed. The results with information on PAHs concentration in leachate samples were presented using HPLC with fluorescence detection (FLD). The changes in PAHs concentration were determined in leachate samples before and after pre-filtration as well as after RO. The decrease of PAHs concentration in the samples was observed after these processes. The total concentration of 16 PAHs in raw municipal landfill leachates amounted to 23.64–26.95 μg/L. The research confirmed the high efficiency in removal of PAHs while using a reverse osmosis (59–72%). Including the pre-filtration, the overall level of removed PAHs reached 81–86%. The average PAHs concentration after pre-filtration and RO was in the 4.46–4.99 μg/L range. The municipal landfill leachate with a high concentration of PAHs should be cleaned before it is discharged into the environment.     

Theoretical and empirical assessment of evaluation methods of the electric charge transference in welding with covered electrodes

The present work is based on an assessment of experimentally obtained results from the application of different methods of evaluation, reported in the specialised literature, of the electrical charge transference stability in the arc. A simple factorial design, taking the welding current as independent variable, was applied to the process with an AWS A5.1 E6013 electrode. The welds were carried out in the flat position by a gravity device. It was possible to obtain criteria to classify the electrical charge transference stability of the process by digital signal processing and a statistical technique. The outcome was based on visual inspection and morphologic studies. It was concluded that amongst the considered parameters, the average value of the arc conductivity during reignition peaks and the quantity of reignition peaks are the more representative indices, both from statistics and from phenomenological points of view. This finding is validated by the fact that the bead morphology and the stability analysis of the electrical charge transference process coincides with the fact that the 160 A (for 4 mm-diameter electrodes) is the most stable regime.     

Selecting the Pre-Hydrolysis Conditions for Eucalyptus Wood in A Fractional Exploitation Biorefining Scheme

The operating conditions for the autohydrolysis of eucalyptus wood were optimized with a view to maximizing hemicellulose extraction while preserving the integrity of glucan. The influence of the operating conditions used in the soda–anthraquinone pulping of the solid phase resulting from the autohydrolysis process was examined. Autohydrolysis of the raw material at a liquid/solid ratio of 8 kg water/kg material at 180°C for 30 min was found to provide a commercially useful liquid phase containing most of the starting hemicellulose. The autohydrolysis treatment allowed the subsequent production of soda–anthraquinone cellulose pulp and paper with properties as good as or even better than those obtained without the pretreatment.     

Polymeric Nanoparticle-Based Photodynamic Therapy for Chronic Periodontitis in Vivo

Antimicrobial photodynamic therapy (aPDT) is increasingly being explored for treatment of periodontitis. Here, we investigated the effect of aPDT on human dental plaque bacteria in suspensions and biofilms in vitro using methylene blue (MB)-loaded poly(lactic-co-glycolic) (PLGA) nanoparticles (MB-NP) and red light at 660 nm. The effect of MB-NP-based aPDT was also evaluated in a clinical pilot study with 10 adult human subjects with chronic periodontitis. Dental plaque samples from human subjects were exposed to aPDT—in planktonic and biofilm phases—with MB or MB-NP (25 µg/mL) at 20 J/cm² in vitro. Patients were treated either with ultrasonic scaling and scaling and root planing (US + SRP) or ultrasonic scaling + SRP + aPDT with MB-NP (25 µg/mL and 20 J/cm²) in a split-mouth design. In biofilms, MB-NP eliminated approximately 25% more bacteria than free MB. The clinical study demonstrated the safety of aPDT. Both groups showed similar improvements of clinical parameters one month following treatments. However, at three months ultrasonic SRP + aPDT showed a greater effect (28.82%) on gingival bleeding index (GBI) compared to ultrasonic SRP. The utilization of PLGA nanoparticles encapsulated with MB may be a promising adjunct in antimicrobial periodontal treatment.     

The Impact of Polyoxyethylene Sorbitan Surfactants in the Microstructure and Rheological Behaviour of Emulsions Made With Melted Fat From Cupuassu (<Emphasis Type="Italic">Theobroma grandiflorum</Emphasis>)

Cupuassu fat is a good candidate for partial substitution of cocoa butter in many products, including emulsions. However, for such use it is necessary to know the characteristics of the products prepared with cupuassu fat. Therefore, the main goal of this work is to characterize emulsions prepared with cupuassu fat using the surfactants Tween^® 60, Tween^® 80 and Tween^® 85 as emulsifiers. The emulsions were prepared at 43 °C with addition of 0.5 or 1.5 % (w/v) of surfactant and compared with an emulsion without surfactant. All emulsions were analysed by conductivity, stability, pH, optical microscopy, rheology and oxidative stability. It was verified that the emulsions prepared with Tween^® 60 and Tween^® 80 have higher stability, smaller droplet size and higher apparent viscosity. Also, these properties are positively influenced by the concentration of the surfactant. On the other hand, emulsions prepared with Tween 85 or without surfactant reached unsatisfactory results. The rheological behaviour of the emulsions was adequately described by both Herschel-Bulkley and Mizhari-Berki models revealing pseudoplastic character. These emulsions also present strong gel behaviour, with storage modulus higher than loss modulus. In conclusion, cupuassu fat can be used as oil phase for emulsions products and this characterization helps to understand their behaviour in order to increase their use in food industry.