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

ABSTRACT 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 IC 50 ranging from 36 to 61 nM, compared to erlotinib, which had IC 50 ranging from 30 to 40 nM. Hybrid 11i was the most potent EGFR inhibitor with an IC 50 of 87 nM and exhibited comparable EGFR inhibition to that of erlotinib (IC 50 = 80 nM). Molecular docking study results in the EGFR active site agreed with the EGFR inhibitory activity results.