Design, Synthesis, Biological Evaluation, and Molecular Docking of Novel Thiazolyl–Pyrazoline Derivatives as Potential EGFR Inhibitors

ABSTRACT

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 ¹ H NMR, ¹³ C 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 (IC ₅₀  = 1.09 ± 0.8, 2.33 ± 0.84, and 2.11 ± 0.26 μM, respectively), A549 (IC ₅₀  = 2.06 ± 0.16, 2.81 ± 0.16, and 2.76 ± 0.42 μM, respectively), and HeLa cells (IC ₅₀  = 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.