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

Abstract

In here, two new Schiff base molecules (3 and 4) were synthesized from the condensation reaction of 1-amino-5benzoyl-4-phenylpyrimidine-2(1H)-one (1) and 1-amino-5-(4methylbenzoyl)-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 P2 1 /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.

Synthesis and Therapeutic Potential of selected Schiff Bases: In vitro Antibacterial, Antioxidant, Antidiabetic, and Computational Studies

“…Molecular docking is a computational tool described to enhance compound-protein binding interactions, a mimic of drug-target interactions with applications in drug design and the pharmaceutical industry. [64][65][66][67] A preliminary step to molecular docking is energy minimization, and the minimization energies of all compounds considered in this study with other molecular parameters are presented in Table 6.…”

A review on pyrimidine‐based derivatives: Synthesis and their biological application

“…It is a building block for nucleic acids, DNA, RNA, forming the fundamental basis of the genetic code and ensuring the transmission of genetic information [24,25]. Pyrimidines are common structural motifs in nature and can be found in many different types of molecules, such as antibiotics, vitamins, alkaloids, and nucleotides (Figure 2) [26][27][28]. The diverse biological activities of numerous substituted pyrimidines further emphasize the importance of the marked pyrimidine medications [10,29].…”

“…The diverse biological activities of numerous substituted pyrimidines further emphasize the importance of the marked pyrimidine medications [10,29]. However, due to its incorporation in a various F I G U R E 2 Chart of the pyrimidine incorporated natural products (source of pyrimidine shown in parenthesis) [26][27][28] bioactive chemical compounds, pyrimidine has diversified into a substantial heterocyclic system during many years of active research.…”

“…Chart of the pyrimidine incorporated natural products (source of pyrimidine shown in parenthesis) [26–28]…”