Although COVID-19 is not a pandemic anymore, the virus frequently mutates, resulting in new strains and presenting global public health challenges. The lack of oral antiviral drugs makes it difficult to treat him, which makes the creation of broadly acting antivirals necessary to fight current and next epidemics of viruses. Using the molecular docking approach, 118 compounds derived from marine organisms and 92 previously synthesized compounds were screened to assess their binding affinity for the main protease and papain-like protease enzymes of SARS-CoV-2. The best candidates from the xanthene, benzoxazole, and coumarin classes were identified. Marine-derived compounds showed slightly better potential as enzyme inhibitors, though the binding affinities of synthesized compounds were similar, with the best candidates displaying affinity values between 0.2 and 0.4 mM. Xanthenes, among both marine origin and synthesized compounds, emerged as the most promising scaffolds for further research as inhibitors. The papain-like protease was found to be more druggable than the main protease. Additionally, all top candidates met the criteria for various drug-likeness properties, indicating good oral bioavailability and low risk of adverse effects. This research provides valuable insights into the comparative affinities of marine origin and synthesized compounds from the xanthene, coumarin, and benzoxazole classes, highlighting promising candidates for further in vitro and in vivo studies.

The pyrimidine heterocycle plays an important role in anticancer research. In particular, the pyrimidine derivative families of uracil show promise as structural scaffolds relevant to cervical cancer. This group of chemicals lacks data-driven machine learning quantitative structure-activity relationships (QSARs) that allow for generalization and predictive capabilities in the search for new active compounds. To achieve this, a dataset of pyrimidine and uracil compounds from ChEMBL were collected and curated. A workflow was developed for data-driven machine learning QSAR using an intuitive dataset design and forwards selection of molecular descriptors. The model was thoroughly externally validated against available data. Blind validation was also performed by synthesis and antiproliferative evaluation of new synthesized uracil-based and pyrimidine derivatives. The most active compound among new synthesized derivatives, 2,4,5-trisubstituted pyrimidine was predicted with the QSAR model with differences of 0.02 compared to experimentally tested activity.

Solvent and substitution effects on the UV/Vis spectroscopic and fluorescence behaviour of seven synthesized 3-substituted 4-hydroxycoumarin derivatives were tested. The tested compounds were dissolved in ethyl acetate, acetonitrile, and dimethyl sulfoxide. Absorption and emission spectra were recorded in the range of 200–800 nm. All tested 4-hydroxycoumarin derivatives showed good absorption in a wide range of 200–550 nm, depending on the properties of the substituents on the benzene ring of the cinnamoyl moiety and the type of solvent. In comparison to the unsubstituted analogue, compounds with an electron-donating group exhibited bathochromically shifted UV/Vis absorption and emission spectra. The highest fluorescence quantum yield was observed for compounds with dimethylamino and acetamido groups as substituents at the benzene ring. Considering that both substitution and solvent affect the absorption and emission spectra of the tested compounds, it can be concluded that judiciously selecting these parameters can improve their absorption and fluorescence properties, making them suitable for various analytical uses.

Xanthene derivatives are an important class of heterocyclic compounds with a wide spectrum of pharmacological activities. In our previous investigations, we found the good antiproliferative activity of two xanthene derivatives, with minimal toxicity investigated by in vitro tests. In this study, we tested the interaction of compound 1 (powerful potent antiproliferative compound) with calf thymus DNA (CT-DNA) under physiological conditions by spectrophotometric titration. The probable prediction of binding and the type of interaction forces involved in the arrangement between xanthene derivatives and CT-DNA were explored also through molecular docking studies. The results indicated that compound 1 interacts with CT-DNA by grove binding. The binding constant was found to be 2.5 ∙ 10 4 M −1 indicating the non-covalent binding of compound 1 to CT-DNA. Docking study results proposed possible binding modes, with binding energies of −9.39 and −8.65 kcal mol −1 for compounds 1 and 2, respectively, which supported previously obtained in vitro results for antiproliferative activity. In addition to experimental investigation, density functional theory (DFT) calculation with B3LYP/6-31G*, B3LYP/6-31G**, and B3LYP/6-31+G* levels of theories was performed on compounds 1 and 2 to obtain optimised geometry, spectroscopic and electronic properties. These studies could help in understanding the mechanisms of toxicity, resistance, side effects of xanthene derivatives, and their binding action mechanism to DNA

Amaranthaceae Juss. family encompasses many edible plants with prominent biological activity. This investigation tested the bioactive properties of ethanolic and methanolic extract of three well-known species: spinach (Spinacia oleracea L.), chard (Beta vulgaris L. subsp. vulgaris), and orache (Atriplex hortensis L.) through the determination of total phenolic and flavonoid content, antioxidant activity, and antibacterial properties. The particular goal was to evaluate the antibiofilm potential of extracts and to demarcate concentration-depending changes in the biofilm-forming category of included bacterial strains. The mass of the chard and orache methanolic extracts gained by maceration are lower in comparison to the mass of ethanolic extracts obtained by the Soxhlet method. In the case of spinach, the results are the opposite. All extracts have an antiradical activity that can be attributed to the established amounts of phenols and flavonoids. Total phenolics in dry leaves ranged from 0.09 to 0.44 mg GAE/g dw, and total flavonoids from 0.42 to 1.9 mg RTE/g dw. All investigated extracts performed inhibitory potential in terms of bacterial growth, while there was no bactericidal effect observed. Values of the minimum inhibitory concentration ranged from 125 µg/ml to 500 µg/ml. Overall results suggested orache extracts as the strongest inhibitory agents. Antibiofilm assays showed that examined extracts of spinach, chard, and orache caused changes in the biofilm-forming capacity of investigated bacterial pathogens. Fluctuations in observed biofilm-forming categories after application of extracts were concentration-dependent.

The content of micro- and macroelements in dry wild and edible Morchella esculenta and Lactarius piperatus mushrooms collected in Bosnia and Herzegovina was determined using the ICP-OES (inductively coupled plasma optical emission spectrom- etry) technique. The contents of microelements in M. esculenta and L. piperatus expressed in mg kg −1 DW (dry weight) were as follows: Co 0.08 and 0.28, Cu 37.35 and 27.66, Fe 174.29 and 28.11, Mn 21.26 and 19.31, Se 0.46 and 0.52, Zn 122.84 and 45.06, Al 27.80 and 24.80, Cr 0.83 and 1.06, Ni 0.99 and 0.96, As 0.32 and 0.09, Cd 0.48 and 0.13, and Pb 0.61 and 0.12, respectively, while the contents of macroelements were: K 26989.48 and 36117.20, Na 70.85 and 28.60, Ca 643.48 and 271.93, Mg 684.16 and 840.64, S 2329.33 and 610.42, and P 10339.35 and 5107.63, respectively. In this study, the potential health risks of heavy metals were assessed, and target hazard quotient (THQ) for As, Cd, Pb, Cu, Zn, Ni, and Cr in the tested mushrooms was lower than the safe level. Edible wild mushrooms M. esculenta and L. piperatus , according to this study, could be used in human nutrition due to their favourable characteristics. Based on the accumulations of heavy metals in the tested mushrooms, it was shown that the collection surfaces are environmentally acceptable. Mushrooms collected from this area are generally safe to eat and pose no health risks to humans.

: The objective of this study was to test the inhibitory effect of five newly synthesized arylmethylene-bis(3-hydroxy- 5,5 -dimethylcyclohex-2-en-1- one) derivatives. The structural characterization and stereochemistry of synthesized compounds were deduced from analyses of experimental FT- IR, 1 H, 13 C NMR spectra and theoretical methodology of DFT study based on the global chemical reactivity indices calculated using the 6- 31G** level of theory. the stability of the newly synthesized compounds, the reactivity descriptors obtained at B3LYP level ( E gap , dipole moment, μ , η , ω ) were computed. The docking study and the selected quantum chemical descriptors computed for compounds 1 −5 exhibit a good agreement. The strongest inhibitors showed 25 to 30 % inhi bition of tyrosinase activity. Results were supported by docking studies of the binding of the strongest inhibitors to the enzyme. The results suggest that tetraketones of this type, due to their tyrosinas e inhibitory effect, represent potential agents in the treatment of various types of melanomas and skin hyperpigmentation. 189.42 3´), 190.75 - C -1´). Anal. Calcd. mass fractions of elements, w / %, for C 23 H 26 Br 2 O 4 ( M r = 524.02) are: C = 52.49, H = 4.98; found: C = 52.75, H = 5.02.

The aim of the present study is to improve the solubility and antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin by formulating its inclusion complexes with 2-hydroxypropyl-β-cyclodextrin in solution and in solid state. The phase solubility study was used to investigate the interactions between 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and 2-hydroxypropyl-β-cyclodextrin and to estimate the molar ratio between them. The structural characterization of binary systems (prepared by physical mixing, kneading and solvent evaporation methods) was analysed using the FTIR-ATM spectroscopy. The antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and inclusion complexes prepared by solvent evaporation method was tested by the diffusion and dilution methods on various strains of microorganisms. The results of phase solubility studies showed that 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin formed the inclusion complexes with 2-hydroxypropyl-β-cyclodextrin of AP type. The solubility of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin was increased 64.05-fold with 50% w/w of 2-hydroxypropyl-β-cyclodextrin at 37 o C. The inclusion complexes in solid state, prepared by the solvent evaporation method, showed higher solubility in purified water and in phosphate buffer solutions in comparison with 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin alone. The inclusion complexes prepared by solvent evaporation method showed higher activity on Bacillus subtilis and Staphylococcus aureus compared to uncomplexed 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin due to improved aqueous solubility, thus increasing the amount of available 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin that crosses the bacterial membrane.

The content of macro- and microelements in dry samples of mushrooms of the species Macrolepiota procera, Boletus edulis and Cantharellus cibarius, collected at different areas in Bosnia and Herzegovina, was determined using the ICP-OES method (inductively coupled plasma optical emission spectrometry). Of the macroelements, K is the most represented, followed by S, P, Mg, and the least represented Ca and Na. Zn is the most represented of the essential microelements, followed by Fe, Se, Cu, Mn and Co. Al is the most abundant of the other trace elements followed by Ni and Cr. Of the toxic metals, the most represented is Cd, followed by Pb and As. There are differences in the concentration of micro- and macroelements in the mushrooms analysed, depending on the area from which they were collected because natural geology and geochemistry influence the content of macro- and microelements in wild edible mushrooms. The results show that the analysed mushrooms can be considered a good source of essential elements. The study also assessed potential health risks of heavy metals and the target hazard quotient (THQ) for As, Cd, Pb, Cu, Zn, Ni and Cr in the analysed mushrooms was lower than the safe level. The carcinogenic risk index revealed that Cd and Ni are the most prevalent pollutants in the mushrooms studied.  

Efforts to reduce air pollution in developing countries may require increased use of biomass fuels. Even biomass fuels are a sustainable alternative to fossil fuels there is limited quantitative information concerning heavy metal content in their ashes. Therefore, this study focuses on the determination of the heavy metal concentrations in wood pellet ash obtained from the combustion of 10 pellet brans from Bosnia and Herzegovina and Italy, the effects of adding the ashes to soils, and the assessment of health risk assessment. Ash content was determined by gravimetric method. The amount and composition of ash remaining after combustion of wood pellets varies considerably according to the type of biomass and wood from which the pellet is made. Samples were prepared by wet digestion using HNO3, and heavy metals are determined by atomic absorption spectroscopy-flame and graphite furnace. The results showed that the lowest concentration in ashes was obtained for Co 0.01 mg kg−1 and the highest for Fe 571.63 mg kg−1. The Hazard Index (HI), calculated for non-cancerous substances for children was 2.23E−01, and the total Risk index was 4.54E−05. As for adults, HI was 1.51E−02, while the Risk index value was 3.21E−06. Human health risk calculated through HI and Risk index for children and adults associated with analyzed pellets is not of significant concern. The calculated enrichment factor and metal pollution index for wood pellet ashes indicate the risk of soil contamination with heavy metals. From this point of view, analyzed samples of ashes could be a serious contaminant of soil, so further monitoring is required.

The kinetics of passive transport of ketoprofen and metformin, as model substances for high and low permeability, respectively, across the artificial membrane under the influence of the pH of donor solution was investigated. There was an upward trend in the apparent permeation coefficient (Papp) of ketoprofen with the decrease in pH to a value close to pKa. At the pH value below pKa the permeation coefficient had lower value, due to the higher retention of ketoprofen in the artificial membrane. Metformin is a low permeable compound, and the highest permeation values were recorded at pH 7.4. Two dissociation constants determine that metformin at physiological pH exists as a hydrophilic cationic molecule, i.e. predominantly in ionized form. At pH values below 2.8, metformin mainly exists in diprotonated form, and it was, thus, very poorly permeable. The highest retention, i.e. affinity of both ketoprofen and metformin to the membrane, was at the lowest pH values, which is explained by different mechanisms. At higher pH values of donor compartment the substances showed significantly less affinity to the membrane. The obtained values of apparent permeation coefficients at studied pH values showed good correlation with the obtained experimental values by other in vitro methods.