Aim: The main goal of this study was to synthesize new derivatives of 4-amino-3-chloro benzoate ester, including 1,3,4-oxadiazole derivatives (), benzohydrazone derivatives (), and hydrazine-1-carbothioamide derivatives () that target epidermal growth factor receptor (EGFR) tyrosine kinase.
Materials & Methods: The new derivatives were characterized using various spectroscopic techniques. Docking studies were used to investigate the binding patterns to EGFR, and the anti-proliferative properties were tested in vitro.
Results: In silico analysis showed that the hydrazine-1-carbothioamide derivatives () had the best matching pattern with EGFR pharmacophoric queries compared to erlotinib, exhibited a favorable safety profile, and showed the best stability among the tested compounds. Compound induced cytotoxicity in the three cancer cell lines tested (A549, HepG2, and HCT-116), by targeting EGFR and activating caspase 3 and caspase 8, therefore, inducing the extrinsic apoptotic pathway.
Conclusion: The results of this study show that compound is a promising cytotoxic compound that inhibits the tyrosine kinase activity of EGFR.
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