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.

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

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.

Two tetraketone derivatives, one previously reported and one novel, were synthesized, whose structures have been confirmed by elemental analyses, NMR, HPLC-MS, and IR spectroscopy. The crystal structures of synthesized tetraketones were determined using X-ray single-crystal diffraction. To analyze the molecular geometry and compare with experimentally obtained X-ray crystal data of synthesized compounds 1 (2,2'-((4-nitrophenyl)methylene)bis(5,5-dimethylcyclohexane-1,3-dione)) and 2 (2,2'-((4-hydroxy-3-methoxy-5-nitrophenyl)methylene)bis(5,5-dimethylcyclohexane-1,3-dione)), DFT calculations were performed with the standard 6-31G*(d), 6-31G**, and 6-31+G* basis sets. The calculated HOMO-LUMO energy gap for compound 1 was 4.60 eV and this value indicated that compound 1 is chemically more stable compared to compound 2 whose energy gap was 3.73 eV. Both compounds' calculated bond lengths and bond angles were in very good accordance to experimental values determined by X-ray single-crystal diffraction.

: 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.

Using X-ray single crystal diffraction, the crystal structures of biologically active benzoxazole derivatives were determined. DFT calculation was performed with standard 6-31G*(d), 6-31G** and 6-31+G* basis set to analyze the molecular geometry and compare with experimentally obtained X-ray crystal data of compounds. The calculated HOMO-LUMO energy gap in compound 2 (2-(2-hydroxynaphtalen-1-yl)-4-methyl-7-isopropyl-1,3-benzoxazol-5-ol) is 3.80 eV and this small gap value indicates that compound 2 is chemically more reactive compared to compounds 1 (4-methyl-2-phenyl-7-isopropyl-1,3-benzoxazol-5-ol) and 3 (2-(4-chlorophenyl)-4-methyl-7-isopropyl-1,3-benzoxazol-5-ol). The crystal structures are stabilized by both intra- and intermolecular hydrogen bonds in which an intermolecular O-H⋅⋅⋅N hydrogen bond generates N3 and O7 chain motif in compounds 1, 2, and 3, respectively. The calculated bond lengths and bond angles of all three compounds are remarkably close to the experimental values obtained by X-ray single crystal diffraction.

Metal chelators can be potentially employed in the treatment of various diseases, ranging from metal overload to neoplastic conditions. Some xanthene derivatives were previously reported to complex metals. Thus, in a search for a novel iron or copper chelator, a series of 9-(substituted phenyl)-2,6,7-trihydroxy-xanthene-3-ones was tested using a competitive spectrophotometric approach. The most promising compound was evaluated in biological models (breast adenocarcinoma cell lines and erythrocytes). In general, substitution of the benzene ring in position 9 had a relatively low effect on the chelation. Only the trifluoromethyl substitution resulted in stronger chelation, probably via a positive effect on solvation. All compounds chelated iron, but their copper-chelating effect was only minimal, since it was no longer observed under highly competitive conditions. Interestingly, all compounds reduced both iron and copper. Additional experiments showed that the trifluoromethyl derivative protected erythrocytes and even cancer cells against excess copper. In summary, the tested compounds are iron chelators, which are also capable of reducing iron/copper, but the copper-reducing effect is not associated with increased copper toxicity.