A series of rhodanine derivatives was synthesized in the Knoevenagel condensation of rhodanine and different aldehydes using choline chloride:urea (1:2) deep eutectic solvent. This environmentally friendly and catalyst free approach was very effective in the condensation of rhodanine with commercially available aldehydes, as well as the ones synthesized in our laboratory. All rhodanine derivatives were subjected to 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging activity investigation and quantitative structure-activity relationship (QSAR) studies were performed to elucidate their structure-activity relationship. The best multiple linear QSAR model demonstrate a stability in the internal validation and Y-randomization (R² = 0.81; F = 24.225; Q²_loo = 0.72; R²_Yscr = 0.148). Sphericity of the molecule, ratio of symmetric atoms enhanced atomic mass along the principle axes in regard to total number of atoms in molecule, and 3D distribution of the atoms higher electronegativity (O, N, and S) in molecules are important characteristic for antioxidant ability of rhodanine derivatives. Molecular docking studies were carried out in order to explain in silico antioxidant studies, a specific protein tyrosine kinase (2HCK). The binding interactions of the most active compound have shown strong hydrogen bonding and van der Waals interactions with the target protein.

Deep eutectic solvents, as green and environmentally friendly media, were utilized in the synthesis of novel coumarinyl Schiff bases. Novel derivatives were synthesized from 2-((4-methyl-2-oxo-2H-chromen-7-yl)oxy)acetohydrazide and corresponding aldehyde in choline chloride:malonic acid (1:1) based deep eutectic solvent. In these reactions, deep eutectic solvent acted as a solvent and catalyst as well. Novel Schiff bases were synthesized in high yields (65–75%) with no need for further purification, and their structures were confirmed by mass spectra, ¹H and ¹³C NMR. Furthermore, their antioxidant activity was determined and compared to antioxidant activity of previously synthesized derivatives, thus investigating their structure–activity relationship utilizing quantitative structure-activity relationship QSAR studies. Calculation of molecular descriptors has been performed by DRAGON software. The best QSAR model (R_tr = 0.636; R_ext = 0.709) obtained with three descriptors (MATS3m, Mor22u, Hy) implies that the pairs of atoms higher mass at the path length 3, three-dimensional arrangement of atoms at scattering parameter s = 21 Å⁻¹, and higher number of hydrophilic groups (-OH, -NH) enhanced antioxidant activity. Electrostatic potential surface of the most active compounds showed possible regions for donation of electrons to 1,1-diphenyl-2-picryhydrazyl (DPPH) radicals.

A series of fluorinated 4,5-dihydro-1H-pyrazole derivatives were synthesized in the reaction of corresponding acetophenone and different aldehydes followed by the second step synthesis of desired compounds from synthesized chalcone, hydrazine hydrate, and formic acid. Structures of all compounds were confirmed by both ¹H and ¹³C NMR and mass spectrometry. Antibacterial properties of compounds were tested on four bacterial strains, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Staphylococcus aureus. Among synthesized compounds, the strongest inhibitor of monophenolase activity of mushroom tyrosinase (32.07 ± 3.39%) was found to be 5-(2-chlorophenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehyde. The PASS program has predicted the highest probable activity for the phosphodiesterase inhibition. To shed light on molecular interactions between the synthesized compounds and phosphodiesterase, all compounds were docked into the active binding site. The obtained results showed that the compound with the dimethoxyphenyl ring could be potent as an inhibitor of phosphodiesterase, which interacts in PDE5 catalytic domain of the enzyme. Key interactions are bidentate hydrogen bond (H-bond) with the side-chain of Gln817 and van der Waals interactions of the dimethoxyphenyl ring and pyrazole ring with hydrophobic clamp, which contains residuals, Val782, Phe820, and Tyr612. Interactions are similar to the binding mode of the inhibitor sildenafil, the first oral medicine for the treatment of male erectile dysfunction.