PEG‐400 Mediated Synthesis of Benzo[ d ]Imidazo[2,1‐ b ]Thiazoles as Bioactive Scaffolds: Antibreast Cancer Potential, EGFR Inhibition, Antioxidant Study, Molecular Docking, and DFT Insights

Abstract This study reports the synthesis and biological evaluation of benzo[ d ]imidazo[2,1‐ b ]thiazole derivatives, emphasizing green chemistry and bioactivity. PEG‐400 was identified as the optimal solvent for synthesizing derivatives 5(a–o) , offering high yields and a sustainable, versatile approach. Structural confirmation via FT‐IR, 1 H NMR, and 13 C NMR analysis demonstrated successful functional group incorporation, aligning with the proposed frameworks. Anticancer evaluation against MCF‐7 breast cancer cells revealed significant structure‐activity relationships. Compound 5a , featuring a methoxy group at R 2 and bromine at R 1 , exhibited the highest cytotoxicity (IC 50  = 10.78 ± 0.892 µM). Conversely, compounds with electron‐withdrawing groups, such as bromine at both R1 and R2 (5b), showed reduced activity (IC 50  = 29.7 ± 2.73 µM). Molecular docking against EGFR tyrosine kinase validated these results, with 5a demonstrating superior binding interactions (docking score: −6.7 kcal/mol). Antioxidant activity, assessed via DPPH assay, highlighted the influence of substituents. Compound 5l , with a 7‐fluoro and 2‐bromophenyl group, achieved the highest inhibition (80.20%, IC 50  = 0.1090 µM). DFT studies on 5a revealed optimized geometry, strong conjugation, and significant electronic stability. HOMO‐LUMO analysis and molecular electrostatic potential (MESP) maps underscored its enhanced reactivity and potential for anticancer applications.