Novel pyrimidine-triazole conjugates for targeted inhibition of EGFR: synthesis and biological evaluation

To design, synthesize, and evaluate novel pyrimidine-triazole derivatives as epidermal growth factor receptor (EGFR) inhibitors for anticancer activity.

Ten derivatives (SM-1A to SM-1J) were synthesized and assessed for cytotoxicity against A549 lung cancer cell line also performed EGFR inhibition assay. Molecular docking was performed on the ATP binding pocket of EGFR (PDB: 1XKK).

Compounds SM-1F and SM-1 G exhibited good cytotoxic activity (IC₅₀ = 0.5 and 0.7 µM) than standard drug erlotinib (IC₅₀ = of 0.9 µM). Compound SM-1F showed a good binding score -8.93 kcal/mol and interactions with amino acid residues THR 854, THR 790, CYS 775, and PHE856.

The results showed SM-1F may be used as a lead compound for further development of novel EGFR inhibitors.