Synthesis, molecular docking, ADMET evaluation and in vitro cytotoxic activity evaluation on RD and L20B cell lines of 3-substituted 5,5-diphenylimidazolidine-2,4-dione derivatives.

Hydantoins comprise an important class of compounds which have long attracted attention due to their remarkable biological and pharmacological properties including antitumor and antiviral activities. As a continuation of our studies on hydantoins derivatives we report the successful synthesis of hydantoins derivatives. These synthesized compounds were evaluated for their cytotoxic activity against Vero cells L20B (African green monkey kidney cell line) and Human Rhabdomyosarcoma RD cell lines using methotrexate drug (MTX) as a reference drug in cytotoxic activity studies. The percentage of the cell line viability was carried out by using Trypan blue dye exclusion method. The tested compounds showed equipotent cytotoxicity effect against Vero cells (L20B) and a moderate effect against Human Rhabdomyosarcoma (RD) cell lines. These results exhibited better activity for 4a-b compounds than the reference drug methotrexate (MTX). Molecular docking studies indicated that the synthesized compounds are suitable inhibitors of humain dihydrofolate reductase (DHFR) enzyme, which may explain the high antiproliferative activity.Communicated by Ramaswamy H. Sarma.

LC-MS profile, in vitro acetylcholinesterase inhibitory, antibacterial and hemostatic properties of Ranunculus bullatus extract.

The ethanol extract from aerial parts of Ranunculus were investigated for its chemical composition by LC-ESI-MS/MS technique, which allowed to identify a series of glycosylated flavonoids and one phenolic acid. RBEE extract showed acetyl-cholinesterase inhibition higher than the reference compound Galantamine at a concentrationof 200 µg/mL. A moderate antibacterial activity of the extract was also obtained against Staphylococcus aureus ATCC43300, Citrobacter freundii ATCC8090, and Proteus vulgaris ATCC29905 at a concentration 100 µg. Additionally, a good reduction in plasma coagulation time at 200 µL was also observed for RBEE.

Crystal structure and Hirshfeld surface analysis of 2-oxo-2-phenyl-ethyl 3-nitroso-2-phenyl-imidazo[1,2-a]pyridine-8-carboxyl-ate.

The title compound, C22H15N3O4, is built up from a central imidazo[1,2-a]pyridine ring system connected to a nitroso group, a phenyl ring and a 2-oxo-2-phenyl-ethyl acetate group. The imidazo[1,2-a] pyridine ring system is almost planar (r.m.s. deviation = 0.017 Å) and forms dihedral angles of 22.74 (5) and 45.37 (5)°, respectively, with the phenyl ring and the 2-oxo-2-phenyl-ethyl acetate group. In the crystal, the mol-ecules are linked into chains parallel to the b axis by C-H⋯O hydrogen bonds, generating R 2 1 (5) and R 4 4 (28) graph-set motifs. The chains are further linked into a three-dimensional network by C-H⋯π and π-stacking inter-actions. The inter-molecular inter-actions were investigated using Hirshfeld surface analysis and two-dimensional fingerprint plots, revealing that the most important contributions for the crystal packing are from H⋯H (36.2%), H⋯C/C⋯H (20.5%), H⋯O/O⋯H (20.0%), C⋯O/O⋯C (6.5%), C⋯N/N⋯C (6.2%), H⋯N/N⋯H (4.5%) and C⋯C (4.3%) inter-actions.

Crystal structure and Hirshfeld surface analysis of 6-((E)-2-{4-[2-(4-chloro-phen-yl)-2-oxoeth-oxy]phen-yl}ethen-yl)-4,5-di-hydro-pyridazin-3(2H)-one.

The pyridazine ring in the title compound, C20H17ClN2O3, adopts a screw-boat conformation. The whole mol-ecule is flattened, the dihedral angles subtended by the least-squares plane of the central aromatic ring with those of the terminal benzene and pyridazine rings being 15.18 (19) and 11.23 (19)°, respectively. In the crystal, the mol-ecules are linked by pairs of N-H⋯O bonds into centrosymmetric dimers and by C-H⋯π contacts into columns. The results of the Hirshfeld surface analysis show that the most prominent inter-actions are H⋯H, accounting for 36.5% of overall crystal packing, and H⋯O/O⋯H (18.6% contribution) contacts.

Crystal structure and Hirshfeld surface analysis of 4-(2,6-di-chloro-benz-yl)-6-[(E)-2-phenyl-ethen-yl]pyridazin-3(2H)-one.

The title pyridazinone derivative, C19H14Cl2N2O, an important pharmacophore with a wide variety of biological applications is not planar, the chloro-phenyl and pyridazinone rings being almost perpendicular, subtending a dihedral angle of 85.73 (11)°. The phenyl ring of the styryl group is coplanar with the pyridazinone ring [1.47 (12)°]. In the crystal, N-H⋯O hydrogen bonds form inversion dimers with an R 2 2(8) ring motif and C-H⋯Cl hydrogen bonds also occur. The roles of the inter-molecular inter-actions in the crystal packing were clarified using Hirshfeld surface analysis, and two-dimensional fingerprint plots indicate that the most important contributions to the crystal packing are from H⋯H (37.9%), C⋯H/H⋯C (18.7%), Cl⋯H/ H⋯Cl (16.4%) and Cl⋯C/C⋯Cl (6.7%) contacts.

Crystal structure, Hirshfeld surface analysis, DFT and mol-ecular docking investigation of 2-(2-oxo-1,3-oxazolidin-3-yl)ethyl 2-[2-(2-oxo-1,3-oxazolidin-3-yl)eth-oxy]quinoline-4-carboxyl-ate.

In the mol-ecular structure of the title compound, C20H21N3O7, the quinoline ring system is slightly bent, with a dihedral angle between the phenyl and the pyridine rings of 3.47 (7)°. In the crystal, corrugated layers of mol-ecules extending along the ab plane are generated by C-H⋯O hydrogen bonds. The inter-molecular inter-actions were qu-anti-fied by Hirshfeld surface analysis and two-dimensional fingerprint plots. The most significant contributions to the crystal packing are from H⋯H (42.3%), H⋯O/O⋯H (34.5%) and H⋯C/ C⋯H (17.6%) contacts. Mol-ecular orbital calculations providing electron-density plots of the HOMO and LUMO as well as mol-ecular electrostatic potentials (MEP) were computed, both with the DFT/B3LYP/6-311 G++(d,p) basis set. A mol-ecular docking study between the title mol-ecule and the COVID-19 main protease (PDB ID: 6LU7) was performed, showing that it is a good agent because of its affinity and ability to adhere to the active sites of the protein.