New Biginelli derivatives with trifluoro extension as inhibitors of epidermal growth factor receptor tyrosine kinase: molecular docking study in comparison with monastrol

New tetrahydropyrimidone derivatives with structural modifications of anti-cancer drug, monastrol, were synthesized, and molecular docking study of the interaction with epidermal growth factor receptor tyrosine kinase (EGFR-TK) was performed. The substituted aromatic part was derived from benzaldehyde derivatives having hydroxy, methoxy and fluoro substituents at 3,4,5 positions. Structural modifications in monastrol with conversion of methyl group to trifluoromethyl fraction and the sulphur atom in place of oxygen atom are the core of synthesis in this paper. Structural and bonding features of newly synthesized compounds are reported along with molecular docking study with EGFR-TK in comparison to monastrol. Target compounds were synthesized using p- toluenesulfonic acid as catalyst. Synthesized compounds show improved binding affinity as compared to monastrol in docking study. ADMET study of all the compounds shows high GI absorption. Single-crystal X-ray study of four derivatives with superposition of the crystal structures is also reported in the study.