Bis-(N-aminoethylethanolamine)-Copper(II) nanocatalysis (AEEA-Cu(II)-NPs) meditated to synthesis a series of 2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide derivatives: Characterization of theoretical, computational and evaluation of molecular docking, and cytotoxicity activities

In this work, bis-(N-aminoethylethanolamine)-Copper (II) nano (AEEA-Cu(II)-NPs) catalysis was synthesized and used as a catalyst in Biginelli reactions. Synthesized nanocatalysis was characterized by UV, FT-IR, XRD, SEM, and particle size distribution analysis. The title compounds of thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide derivatives (1a-1o) were synthesized via Biginelli method, the reaction was carry out via AEEA-Cu(II)-NPs catalysis. Synthesized compounds (1a-1o) were characterized by FT-IR, 1H NMR, 13C NMR, mass spectrometry, and elemental analysis. The spectral data of compound 1a was confirmed by the comparison of both experimental and theoretical values. GC-EI-MS analysis of the characteristic protonation pathways for GC-EI-MS fragmentation of synthetic 2-thioxo-pyrimidine-5-carboxamide derivatives is reported. Computing methods of compound 1a was studied such as optimize the geometry, frontier molecular orbital analysis (HOMO-LUMO), and molecular electrostatic potential (MESP). In cytotoxicity screening, compounds were tested against. Cell lines 2HepG2 (liver), MCF-7 (breast), and HeLa (cervical) cancer cell lines. Molecular docking was used to determine the inter and intramolecular interactions. In order to determine the most effective pyrimidine derivatives (1f and 1 g) for the protein 4FM9, and Autodock Vina 1.1.2 software was used in conjunction with the binding mode of fluorouracil as a reference compound. The compounds 1f and 1g were extremely effective against HepG2 cells compared to fluorouracil. During docking studies, 1f showed a higher attraction for the 4FM9 protein (−6.5 kcal/mol) than fluorouracil (−5.4 kcal/mol). The compounds 1f, and 1g showed impressive inhibitory properties in cytotoxic screening as compared to the reference compound. Due to the docking studies and cytotoxicity screening results, the new compounds look promising as therapeutic agents.