New Antiproliferative Pyrazole/Quinoline Hybrids: Design, Synthesis, and Biological Evaluation as EGFR Inhibitors

A series of new pyrazole/quinoline hybrids 11a-n was constructed and synthesized as prospective antiproliferative agents. The antiproliferative activities of the newly synthesized hybrids were assessed against a panel of four human cancer cells: HT-29, A-549, Panc-1, and MCF-7. Hybrids 11c, 11d, 11h, 11i, and 11k demonstrated remarkable antiproliferative activity, with IC₅₀ ranging from 36 to 61 nM, compared to erlotinib, which had IC₅₀ ranging from 30 to 40 nM. Hybrid 11i was the most potent EGFR inhibitor with an IC₅₀ of 87 nM and exhibited comparable EGFR inhibition to that of erlotinib (IC₅₀ = 80 nM). Molecular docking study results in the EGFR active site agreed with the EGFR inhibitory activity results.