Design, Synthesis, Biological Evaluation, and Molecular Docking of Novel Thiazolyl-Pyrazoline Derivatives as...

A novel series of thiazolyl-pyrazoline derivatives (MAP-1 to MAP-20) was designed and synthesized as potential epidermal growth factor receptor (EGFR) inhibitors. The structures of all compounds were confirmed by ¹H NMR, ¹³C NMR, and HRMS analyses. The synthesized derivatives were evaluated for in vitro anticancer activity using the MTT assay against MCF-7 (breast), A549 (lung), HeLa (cervical), and non-tumorigenic MCF-10A cell lines. Among the tested compounds, MAP-13, MAP-15, and MAP-19 exhibited potent cytotoxic activity against MCF-7 (IC₅₀ = 1.09 ± 0.8, 2.33 ± 0.84, and 2.11 ± 0.26 μM, respectively), A549 (IC₅₀ = 2.06 ± 0.16, 2.81 ± 0.16, and 2.76 ± 0.42 μM, respectively), and HeLa cells (IC₅₀ = 1.18 ± 0.9, 2.27 ± 0.18, and 2.15 ± 0.36 μM, respectively), with improved selectivity over normal MCF-10A cells. Molecular docking studies against EGFR (PDB ID: 4I23) revealed strong binding affinities, with docking scores of -8.67, -9.31, and -9.00 kcal/mol for MAP-13, MAP-15, and MAP-19, respectively. Key interactions within the ATP-binding pocket suggested stable ligand-receptor complex formation. In silico ADMET profiling confirmed acceptable drug-likeness and pharmacokinetic properties for the lead compounds. These findings indicate that thiazolyl-pyrazoline hybrids represent promising scaffolds for the development of selective EGFR-targeted anticancer agents.