Design and Synthesis of Novel Pyrazole-Based 1,2,3-Triazole Hybrids with Potent Cytotoxic Activity as Selective EGFR Kinase Inhibitors

Abstract

A series of novel pyrazole-based 1,2,3-triazole hybrids 7a–7h were synthesized and tested for in vitro cytotoxicity against MCF-7, IMR-32, HeLa, and HER293 cell lines. The compounds 1-(4-methylphenyl)-3-phenyl-1H-pyrazole-4-carbaldehyde O-[(1-phenyl-1H-1,2,3-triazol-5-yl)methyl]oxime (7a), 1-(4-bromo­phenyl)-3-phenyl-1H-pyrazole-4-carbaldehyde O-[(1-phenyl-1H-1,2,3-triazol-5-yl)methyl]oxime (7e), and 1-(4-nitrophenyl)-3-phenyl-1H-pyrazole-4-carbaldehyde O-[(1-phenyl-1H-1,2,3-triazol-5-yl)methyl]oxime (7g) displayed potential cytotoxic activity against the tested cell lines. The in silico molecular docking study of pyrazole-based 1,2,3-triazole hybrids 7a–7h on the EGFR receptor revealed that compounds 7a, 7e, and 7g strongly bind to the protein, and the calculated binding energies were in excellent agreement with the corresponding IC₅₀ values.