Design, Synthesis, Cytotoxic Activity, and In Silico Studies of New Schiff Bases Including Pyrimidine Core

In here, two new Schiff base molecules (3 and 4) were synthesized from the condensation reaction of 1-amino-5-benzoyl-4-phenylpyrimidine-2(1H)-one (1) and 1-amino-5-(4-methylbenzoyl)-4-p-tolylpyrimidin-2(1H)-one (2) with 4-bromobenzaldehyde. These molecules were completely characterized by IR, NMR, and HR-MS. Moreover, molecule 4 was determined by single crystal x-ray diffraction (SC-XRD) patterns. The crystallographic analysis revealed that molecule 4 crystallizes in the monoclinic system, space group P21/c. The molecules were screened in colon, lung and liver cell lines. The results showed that molecule 4 had cytotoxic activity in all screened cancer cell lines. Molecular docking studies of molecules 3 and 4, which were synthesized experimentally and whose cytotoxic activities were examined, were carried out with in silico approaches. Binding parameter values and active binding sites were determined by interacting the compounds with EGFR (PDB ID : 1M17) and VEGFR-2 (PDB ID : 4ASD) crystal structures, respectively, in molecular docking. In addition, the theoretical pharmacokinetic properties of compounds 3 and 4 were evaluated using ADME analysis. © 2023 Wiley-VCH GmbH.