Abstract
A green, simple and efficient protocol for the synthesis of the two new barbituric acid derivatives: 4 and 5 is described. One pot fashion of 2 mol of barbituric acid derivatives with 3-fiuorobenzaldehyde in green solvent (H2O) providing compound 4. Reaction of equimolar of barbituric acid derivatives, dimedone and 4-(trifluoromethyl)benzaldehyde gave compound 5. Using the density functional theory at the B3LYP level and 6-311G(d,p) as basis set, the molecular structures of the studied compounds were optimized. The minimum energy structures have geometrical parameters correlated well with the experimental data. 4 has two barbituric acid moieties more deviated from the planarity than the barbiturate ring in 5. The latter exists in the enol form and it is stabilized by strong intramolecular hydrogen bonding interactions. The NBO analysis revealed the presence of significant pi-pi* intramolecular charge transfer in this ring, while this effect is absent in 4. The electronic spectra of the studied compounds were investigated experimentally and theoretically using the TD-DFT method. The compound which has one more conjugated ring (5) has one more band at longer wavelength of 318 nm (calc. 313.5 nm) which is assigned to H -> L (93%) excitation. The anti-oxidant activity as reactive oxygen scavenger was examined in this research. The NO and DPPH radical scavenger assays were carried out. The results clearly demonstrated that compounds 4 and 5 possess a significant effect as reactive oxygen scavenger compared with the standard drugs. The ligand efficiency (LE) metrics as LE value and ligand lipophilic efficiency (LLE) were calculated and they showed that compound 4 has better character as drug likeness candidate rather than compound 5. The docking study of the compounds showed that compound 4 docked with the receptor (PDB ID: 3JSW) through lipophilic-lipophilic interaction. Interestingly, compound 5 represent dissimilarity from compound 4. (C) 2018 Elsevier B.V. All rights reserved.