In Silico and In Vitro Studies of Novel Azomethines on DNA Repair Genes in Gastric Cell Lines.

We herein report the determination of the cytotoxic activity and expression profiles of some DNA repair genes of newly synthesized azomethines in the gastric cancer cell line (AGS). The studied novel compounds were synthesized by a condensation reaction and received compounds were characterized by 1H and 13C NMR spectroscopy methods. Furthermore, they were applied to the AGS cell line at eight different concentrations (0.1-50 µg/mL). Anticancer activities were determined using the MTT method. Expression levels of ATR, ERCC1, TOP2A, and ABCB1 genes were determined by the RT-PCR method. Biochemical parameters were also examined. The interaction of proteins with other proteins was investigated with the String v11 program. The IC50 values of compounds 1, 2, and 3 obtained after 72 h were 23.10, 8.93, and 1.58 µg/mL, respectively. The results demonstrate that the cytotoxic activity of compound 3 on AGS cancer cells is higher in comparison with other molecules. It was determined that the expression levels of ATR, TOP2A, and ABCB1 genes in compounds 1, 2, and 3 were decreased compared to the control group. In addition, it was determined that ERCC1 gene expression increased in compound 3, decreased in compound 2, and remained unchanged in compound 1 (p < 0.001). In AGS gastric cancer cells, a 64% decrease was detected for GST levels in compound 1, while a 38% decrease in GSH levels in compound 2. In addition, compounds 1-3 were examined at the molecular level with computational techniques and the docking studies revealed 4LN0 as a target protein.

Synthesis, nanostructuring and in silico studies of a new imine bond containing a macroheterocycle as a promising PBP-2a non-ß-lactam inhibitor.

This study is devoted to the synthesis of a 40-membered macroheterocycle with its further nanostructuring by magnetite nanoparticles. The mentioned macroheterocycle was synthesized by the [2+2] cyclocondensation of the oxygen-containing diamine with an aromatic dialdehyde in a non-catalytic medium and with no work-up procedure. The structure of the obtained macroheterocycle was studied by 1H and 13C nuclear magnetic resonance spectroscopy and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Furthermore, the nanosupramolecular complex of macroheterocycles with magnetite nanoparticles was obtained and investigated by Fourier-transform infrared and ultraviolet-visible spectroscopy methods. Shifts in the infrared spectra of the nanosupramolecular complex indicate the interaction through metal-aromatic ring non-covalent bonding. The shift is also observed for the C-O-C stretching band of ether bonds. The loading rate of macroheterocycles on magnetite nanoparticles was 18.6%. The morphology of the ensemble was studied by transmission electron microscopy, which confirmed the synthesis of nanospherical particles with a diameter range of 10-20 nm. Powder X-ray diffraction analysis showed patterns of cubic Fe3O4 nanoparticles with a crystallite size equal to 9.1 nm. The macroheterocycle and its nanosupramolecular complex were tested against Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. The results have shown that the created complex has shown 64 times better activity against Staphylococcus aureus in comparison with the individual macroheterocycle and 32 times better activity in comparison with the pristine antibiotic Ampicillin as a control. In addition, computational analysis of the macroheterocycle was performed at the B3LYP/6-31G level in water. Molecular docking analyses for the macroheterocycle revealed Penicillin-binding protein PBP2a (5M18) from the transpeptidase family as a target protein in Staphylococcus aureus.

Synthesis, crystal structure and antibacterial studies of dihydropyrimidines and their regioselectively oxidized products.

The syntheses and investigations of new biologically active derivatives of dihydropyrimidines by Biginelli reaction in the presence of copper triflate are reported. Due to the fact that salicylaldehyde and its derivatives under Biginelli reaction conditions can lead to the formation of 2 types of dihydropyrimidines, the influence of copper triflate on product formation was also investigated. In addition to this, regioselective oxidation of dihydropyrimidines was performed in the presence of cerium ammonium nitrate and novel oxidized dihydropyrimidines were obtained. Single crystals of some of them were obtained and as a result, the structures of them were investigated by X-ray diffraction method, which allows determining the presence of hydrogen bonds in their structures. In addition to this, the presence of hydrogen bonds in their structures affects the formation of the corresponding tautomer during oxidizing of dihydropyrimidines. Since dihydropyrimidines are claimed to be biologically active compounds, activities of the synthesized compounds were studied against Acinetobacter baumanii, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus bacteria.

Correction: Synthesis, crystal structure and antibacterial studies of dihydropyrimidines and their regioselectively oxidized products.

[This corrects the article DOI: 10.1039/D0RA10255E.].