Iboga Inspired N-Indolylethyl-Substituted Isoquinuclidines as a Bioactive Scaffold: Chemoenzymatic Synthesis and Characterization as GDNF Releasers and Antitrypanosoma Agents

The first stage of the drug discovery process involves the identification of small compounds with biological activity. Iboga alkaloids are monoterpene indole alkaloids (MIAs) containing a fused isoquinuclidine-tetrahydroazepine ring. Both the natural products and the iboga-inspired synthetic analogs have shown a wide variety of biological activities. Herein, we describe the chemoenzymatic preparation of a small library of novel N-indolylethyl-substituted isoquinuclidines as iboga-inspired compounds, using toluene as a starting material and an imine Diels–Alder reaction as the key step in the synthesis. The new iboga series was investigated for its potential to promote the release of glial cell line-derived neurotrophic factor (GDNF) by C6 glioma cells, and to inhibit the growth of infective trypanosomes. GDNF is a neurotrophic factor widely recognized by its crucial role in development, survival, maintenance, and protection of dopaminergic neuronal circuitries affected in several neurological and psychiatric pathologies. Four compounds of the series showed promising activity as GDNF releasers, and a leading structure (compound 11) was identified for further studies. The same four compounds impaired the growth of bloodstream Trypanosoma brucei brucei (EC₅₀ 1–8 μM) and two of them (compounds 6 and 14) showed a good selectivity index.     

Chondroitin Sulfate Protects the Liver in an Experimental Model of Extra-Hepatic Cholestasis Induced by Common Bile Duct Ligation

During liver fibrogenesis, there is an imbalance between regeneration and wound healing. The current treatment is the withdrawal of the causing agent; thus, investigation of new and effective treatments is important. Studies have highlighted the action of chondroitin sulfate (CS) in different cells; thus, our aim was to analyze its effect on an experimental model of bile duct ligation (BDL). Adult Wistar rats were subjected to BDL and treated with CS for 7, 14, 21, or 28 days intraperitoneally. We performed histomorphometric analyses on Picrosirius-stained liver sections. Cell death was analyzed according to caspase-3 and cathepsin B activity and using a TUNEL assay. Regeneration was evaluated using PCNA immunohistochemistry. BDL led to increased collagen content with corresponding decreased liver parenchyma. CS treatment reduced total collagen and increased parenchyma content after 21 and 28 days. The treatment also promoted changes in the hepatic collagen type III/I ratio. Furthermore, it was observed that CS treatment reduced caspase-3 activity and the percentage of TUNEL-positive cells after 14 days and cathepsin B activity only after 28 days. The regeneration increased after 14, 21, and 28 days of CS treatment. In conclusion, our study showed a promising hepatoprotective action of CS in fibrogenesis induced by BDL.     

K-line X-ray fluorescence from highly charged iron ions under dense astrophysical plasma conditions

In the present work, we report an investigation of plasma environment effects on the atomic parameters associated with the K-vacancy states in highly charged iron ions within the astrophysical context of accretion disks around black holes. More particularly, the sensitivity of K-line X-ray fluorescence parameters (wavelengths, radiative transition probabilities, and Auger rates) in Fe XVII–Fe XXV ions has been estimated for plasma conditions characterized by an electron temperature ranging from 10⁵ to 10⁷ K and an electron density ranging from 10¹⁸ to 10²² cm⁻³. In order to do this, relativistic multiconfiguration Dirac-Fock atomic structure calculations have been carried out by considering a time averaged Debye-Hückel potential for both the electron–nucleus and electron–electron interactions.     

Simulation of the ion beam-plasma interaction processes for point-like ions in doped DT plasmas

The purpose of this work is to study the interaction between an ion beam and a doped deuterium-tritium (DT) plasma in a fast ignition nuclear fusion context. In order to analyze the influence of the dopants in the interaction process, we present a physical model to carry out spatial-temporal simulations of the stopping of an ion beam interacting with a doped plasma target, the plasma heating processes, and the formation of the ignition regions. We perform a set of numerical experiments where different concentrations of dopants are added to a fully ionized DT plasma. These simulations allow us to characterize the increase in the stopping power and the maximum temperatures achieved with the presence of impurities, as well as the reduction of the heated and ignition regions. This reduction in the ignition region indicates difficulties for the formation of an efficient hot spot when there are dopants in the DT plasma.     

N,N′‐Bis(2‐tosyl­amino­benzyl­idene)‐1,2‐ethanedi­amine

The structure of the title compound, C₃₀H₃₀N₄O₄S₂, is highly conditioned in the solid state by two strong N—H?N interactions. The values of the distances between the aminic N atoms [5.865 (3) Å] and the iminic N atoms [2.930 (4) Å], in conjunction with the long distance between the S atoms of the two tosyl groups [7.673 (1) Å], suggest that when the molecule acts as a ligand it will provide a single cavity for N₄ coordination to the metal centre.     

Discriminating Bacterial Infection from Other Causes of Fever Using Body Temperature Entropy Analysis

Body temperature is usually employed in clinical practice by strict binary thresholding, aiming to classify patients as having fever or not. In the last years, other approaches based on the continuous analysis of body temperature time series have emerged. These are not only based on absolute thresholds but also on patterns and temporal dynamics of these time series, thus providing promising tools for early diagnosis. The present study applies three time series entropy calculation methods (Slope Entropy, Approximate Entropy, and Sample Entropy) to body temperature records of patients with bacterial infections and other causes of fever in search of possible differences that could be exploited for automatic classification. In the comparative analysis, Slope Entropy proved to be a stable and robust method that could bring higher sensitivity to the realm of entropy tools applied in this context of clinical thermometry. This method was able to find statistically significant differences between the two classes analyzed in all experiments, with sensitivity and specificity above 70% in most cases.     

Seasonal Variability of a Caryophyllane Chemotype Essential Oil of Eugenia patrisii Vahl Occurring in the Brazilian Amazon

Eugenia patrisii Vahl is a native and non-endemic myrtaceous species of the Brazilian Amazon. Due to few botanical and phytochemical reports of this species, the objective of the present work was to evaluate the seasonal variability of their leaf essential oils, performed by GC and GC-MS and chemometric analysis. The results indicated that the variation in oil yields (0.7 ± 0.1%) could be correlated with climatic conditions and rainy (R) and dry seasons (D). (E)-caryophyllene (R = 17.1% ± 16.0, D = 20.2% ± 17.7) and caryophyllene oxide (R = 30.1% ± 18.4, D = 14.1% ± 19.3) are the major constituents and did not display significant differences between the two seasons. However, statistically, a potential correlation between the main constituents of E. patrisii essential oil and the climatic parameters is possible. It was observed that the higher temperature and insolation rates and the lower humidity rate, which are characteristics of the dry season, lead to an increase in the (E)-caryophyllene contents, while lower temperature and insolation and higher humidity, which occur in the rainy season, lead to an increase in the caryophyllene oxide content. The knowledge of variations in the E. patrisii essential oil composition could help choose the best plant chemical profile for medicinal purposes.     

Crosslinked penicillin acylase aggregates for synthesis of β-lactam antibiotics in organic medium

Crosslinked enzyme aggregates (CLEAs) of a partially purified penicillin acylase from a recombinant Escherichia coli strain have been produced as a novel type of biocatalysts well endowed to perform in organic media. Different protein precipitants were studied and glutaraldehyde was used as the crosslinking agent. Precipitation curves were obtained for all precipitants to determine the concentrations at which all the protein precipitated out of the solution. The effect of the glutaraldehyde-to-protein ratio was studied with respect to process recovery and the specific activity and stability of the biocatalyst. Recovery of penicillin acylase activity was moderately high, about 50%; major losses of enzyme activity were produced at the precipitation step. Specific activities of all CLEAs were very high, which is one of the advantages of using nonsupported biocatalysts. Ammonium sulfate and tert-butyl alcohol were the best precipitants at a glutaraldehyde-protein mass ratio of 2 and were selected to perform the kinetically controlled synthesis of ampicillin in 60% (v/v) ethylene glycol medium. At comparable conversion yields, volumetric and specific antibiotic productivity were much higher for CLEAs than for carrier-bound penicillin acylases.     

Modelling of optical absorption of silver NP’s produced by UV radiation embedded in mesostructured silica films

Hexagonal mesostructured films containing silver ions were obtained by sol–gel method. Brij 58 was used to produce channels into the film, which house these ions. The films were exposure to UV radiation to produced silver metallic nanoparticles. The presence of the metallic nanoparticles was determined by infrared spectroscopy and optical absorption. Besides, these nanoparticles and core–shell structures of silver–silver oxide nanoparticles were identified by high-resolution transmission electronic microscopy. From these measurements, the obtained size range for silver nanoparticles was 6.1 nm. The absorption spectrum located at 440 nm was modelled and well fitted with the Gans theory considering refractive index higher than the one coming from host matrix. This index is explained because the silver oxide shell modifies the local surrounding medium of the metallic nanoparticles.     

Attenuation of the depolarizing field in a thin film model relaxor

The behavior of the polarization in a microscopic statistical model for a thin film relaxor placed between two metallic electrodes is studied by numerical simulations. Depolarization fields different from zero, due to a non-perfect compensation of surface charges at the metallic electrodes, are taken into account. Different thicknesses and different values of the compositional charge disorder density for the relaxor are considered. Depolarization field is found to be extremely attenuated for large values of the number density of charge carriers in the relaxor. In such a case, field attenuation allows for the existence of a homogeneous ferroelectric ground state.