Human leukotriene A4 hydrolase enzyme (LTA4H) catalyses the biotransformation of the inactive precursor leukotriene A4 (LTA4) to the bioactive Leukotriene B4 (LTB4), which causes many inflammatory responses in the human body. Therefore, the selective inhibition of this enzyme becomes a useful strategy for the treatment of several illnesses such as asthma, allergic rhinitis, cardiovascular diseases, and cancer. Herein we report a 3D-QSAR/ /CoMFA and CoMSIA study on a series of 47 benzimidazoles, benzoxazoles, benzothiazoles and thiazolopyridines reported as potent LTA4H inhibitors. Good statistical parameters were obtained for the best model (q2 = 0.568, r2 ncv = 0.891 and r2 test = 0.851). A new series of 10 compounds capable of inhibiting leukotriene A4 hydrolase with high potency was presented. All designed inhibitors showed low IC50 in nano- and sub-nanomolar ranges, when they were evaluated in 3D-QSAR models. Subsequently, the designed molecules, as well as the least and most active compounds were subjected to docking and molecular dynamics studies into LTA4H. In conclusion, we summarised a thorough structure?activity relationship (SAR) of LTA4H inhibitors of heterocyclic structure. These models can be used for the rational proposal of new inhibitors.

Defining the interaction of newly synthesized compounds with plasma proteins is an important step in the drug development process. Chromatographic techniques can be successfully used in predicting the biopharmaceutical and pharmacokinetic properties of newly synthesized compounds. The aim of this study is to investigate and isolate the most important molecular properties that affect the interaction of 20 newly synthesized chalcones and commercial compounds (lopinavir, ritonavir, darunavir and ivermectin) with human serum albumin (HSA). The retention behaviour of the selected compounds was tested on a CHIRALPAK?HSA column. A mixture of phosphate buffer (pH 7.0) and isopropanol (80:20 volume ratio) was used as the mobile phase, and the support vector method was used to form the quantitative structure retention relationship (QSRR) model. Based on the obtained values of retention parameters, it was observed that halogenated derivatives show the strongest, and methylated chalcone derivatives the weakest interaction with HSA. By correlating the retention and physicochemical properties of the tested compounds, it was shown that the structural (SDSCH) and electronic properties (MAXQ, EEM_F1) groups have the greatest influence on the retention behaviour and the interaction of the tested compounds with HSA. The obtained QSRR model can be applied in the prediction of the retention characteristics of new, structurally related chalcone derivatives on HSA stationary phase.

The absence of designated remedies for coronavirus disease 19 (Covid-19) and the lack of treatment protocols drove scientists to propose new small molecules and to attempt to repurpose existing drugs against various targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in order to bring forward efficient solutions. The main protease (Mpro) is one of the most promising drug targets due to its crucial role in fighting viral replication. Several antiviral drugs have been used in an attempt to overcome the pandemic, such as hydroxychloroquine (HCQ). Despite its perceived positive outcomes in the beginning of the disease, HCQ was associated with several drawbacks, such as insolubility, toxicity, and cardiac adverse effects. Therefore, in the present study, a structure-based virtual screening approach was performed to identify structurally modified ligands of the chloroquinoline (CQ) scaffold with good solubility, absorption, and permeation aimed at eventually suggesting a more dependable alternative. PDB ID:7BRP Mpro was chosen as the most reliable receptor after cross-docking calculation using 30 crystal structures. Then, a SiteMap analysis was performed and a total of 231,456 structurally modified compounds of the CQ scaffold were suggested. After Lipinski criteria filtration, 64,312 molecules were docked and their MM-GBSA free binding energy were calculated. Next, ADME descriptors were calculated, and 12 molecules with ADME properties better than that of HCQ were identified. The resulting molecules were subjected to molecular dynamics (MD) simulation for 100 ns. The results of the study indicate that 3 molecules (CQ_22; CQ_2 and CQ_5) show better interactions and stability with the Mpro receptor. Binding interaction analysis indicates that GLU143, THR26, and HIS41 amino acids are potential binding hot-spot residues for the remaining 3 ligands.

Bisphenol A (BPA) is a monomer commonly used in the production of epoxy resins, plastic bottles and dental filling materials. Due to its chemical structure, BPA and its derivates show activity similar to the endocrine horm-ones. It can bind to estrogen receptors and cause neurological disturbances, even at low doses. Therefore, it is important to determine BPA and its deri-vatives quickly and sensitively at low concentrations. In this study, a single amperometric tyrosinase enzyme biosensor was designed for the determination of the amount of BPA, bisphenol F (BPF) and bisphenol S (BPS) monomers. Tyrosinase was immobilized onto a modified carbon paste electrode by cross- -linking with glutaraldehyde. The amount of BPA (BPS and BPF) was deter-mined directly on the reduction of quinone compound released as a result of the enzymatic reaction at ?0.15V. Km(app) value of the designed biosensor for BPA was found 0.00067 ?M, the linear operating range was 0.001?0.005 ?M (a) and 0.03?0.1 ?M (b) and the lower detection limit was found 1 nM for each mono-mer. It is clear that designed biosensor enable the fast, efficient and precise determination of BPA and its derivatives released from materials used in dental materials.

After sample processing for RNA and DNA analysis, the leftover protein pellets are usually discarded due to the limited efficiency of pellet reconstitution/solubilisation. As the pelleted proteins are tightly packed, they are most often solubilised using chaotropic agents (e.g., guanidine hydrochloride or urea), detergents (e.g., SDS), salts (NaCl) or basic buffer (Tris). The aim of this study was to define and optimise the procedure for the efficient extraction of proteins from human peripheral blood mononuclear cells (PBMCs), obtained by a single blood draw and lysed in TRIzol reagent, by varying experimental conditions in terms of protein precipitation solvent (isopropanol or acetone), washing (with or without guanidine hydrochloride) and solubilisation solution (containing SDS, NaCl, urea and/or Tris). We evaluated the efficacy of the final, optimised protocol to solubilise both small cytoplasmic and larger transmembrane proteins, and the compatibility with methods employed for the subsequent analysis of protein posttranslational modifications, such as glycosylation. The optimised protocol for the extraction and isolation of post-TRIzol leftover proteins from PBMCs can be defined as follows: protein precipitation from the organic phase with ice-cold acetone, pellet washing with absolute ethanol and solubilisation in 1 % SDS, employing 20 min heating at 50?C and vortexing.

Electrophoretic deposition (EPD) occurs as a cataphoretic deposition ? the coating is deposited on the cathode, and anaphoretic deposition ? the coating is deposited on the anode. The primary purpose of EPD is to obtain compact and uniform organic/inorganic coatings of the desired thickness and adhesion on metal surfaces by applying an electric field to the particles of coating precursor. EPD basic principles for coatings deposition concerning fundamental explanations and considerations of practical parameters of the process are presented. Cataphoretic deposition has become popular because it can apply organic coatings to complex structures that are otherwise very difficult to coat. These coatings were found to improve the characteristics of the substrate, such as biocompatibility, appearance and resistance to the corrosion processes. The key EPD parameters are composition, pH value and viscosity of deposition medium, as well as zeta potential of the particles, electric field strength, etc. A special survey is given to the process of anaphoretic deposition, which is relatively new, and its advantages over cataphoretic deposition are discussed. Through the process of joint anaphoresis/substrate anodization process, the surface of the substrate is simultaneously anodized and modified by incorporation of the foreign particles into the anodic layer. The coatings of mixed composition of better adhesion and corrosion resistance with respect to cataphoretically- deposited coatings are obtained as result.

The electrical conductivity of LiCl-GdCl3 molten systems with the gadolinium chloride additions ranging from 0 to 23 mol% was measured depending on both the temperature and concentration of GdCl3. The molar electrical conductivity of the molten GdCl3-LiCl system is calculated taking into account the assumption of additivity of the molar volume of the mixture. The obtained temperature dependencies can be approximated by Arrhenius-type equation. The effective activation energy Ea increased with the GdCl3 content. The liquidus temperatures of the studied systems were determined by differential scanning calorimetry. The high-temperature Raman spectra of LiCl-GdCl3 chloride melts were recorded. In addition, the electrical conductivity of 0.77LiCl-0.23GdCl3 molten system with 1 mol% of Gd2O3 was measured. The investigation demonstrates that the addition of gadolinium oxide results in a decrease of the electrical conductivity of the chloride molten system and growth of its liquidus temperature

Lignite and coal waste used as feed fuels in thermal power plants (TPPs) and semi-industrial fluidized bed boiler (FBB), as well as their representative fly ashes (FAs), were examined. Fly ashes were compared employing anions and cations content in correspondent water extracts, trace elements and polycyclic aromatic hydrocarbon concentrations, as well as health risk assessments of substances known to be of concern for public health. Fluoride and sulfate contents in water extracted FAs are far below the legislation limits for waste, classifying all investigated FAs as non-hazardous. Among investigated trace elements, Cd content is the lowest, while Mn content is the highest. The highest enrichment ratios are noticed for As, Pb, Hg, Cu, V and Cr. The results indicate that total PAHs content is elevated in FA from the combustion of coal waste (AFB), with fluoranthene prevailing. The cancer risk of As and the non-cancer risk of As and Ni in some FAs surpass their respective permissible limits. The incremental lifetime cancer risk of an adult population indicates a potential PAHs risk in AFB, whereas all other fly ashes are within safe limits.

The coating of aluminum nitride powder has a great importance industrially and environmentally. AlN can be rapidly hydrolyzed to aluminum hydroxide and ammonia in the atmosphere or water media. To prevent the hydrolysis of AlN, the inorganic or organic based coatings are used frequently. For the first time, this study describes the phosphate esters as organophosphate coating used for the inhibition of hydrolysis reaction of AlN in its water suspension. Phenyl phosphate showed the best inhibition against AlN hydrolysis with an easy application technique and at low concentration of 0.005 M. AlN coating efficiency was proved by spectroscopic and imaging methods. It was concluded that the coating acquired the protective properties of phenyl phosphate through its water repellence.

The influence of sulfate-reducing bacteria Desulfovibrio desulfuricans on stainless steel SS 202 corrosion in neutral media was studied in detail using weight loss and electrochemical routes. The bacterial activity resulted in material loss with an average rate of 0.015 mm/year. The scanning electron microscopy (SEM) analysis showed a significant increase in the sessile bacterial population with the immersion period. Use of 500 ppm palash (Butea monosperma) leaf extract (PLE) reduced the average corrosion rate to 0.002 mm/year. SEM analysis showed a very thin external film formation in the presence of the inhibitor. The X-ray photoelectron spectroscopy studies confirmed the presence of corrosion products such as Fe2O3 and FeS. The gas chromatography?mass spectrometry studies showed the dominant percentage of various terpenoids along with vitamin E as the main components of the PLE. Electrochemical analysis showed the existence of a diffusion barrier. The resistance offered by the diffusion barrier is high in the inhibited sample when compared to uninhibited samples.