AIMS

This study aimed to synthesize novel chalcone-urea derivatives and evaluate their anticancer potential through antiproliferative, apoptotic, and epidermal growth factor receptor (EGFR) inhibitory activities, supported by molecular modeling.

MATERIALS & METHODS: Thirty-three chalcone-urea derivatives were synthesized in two series: pyrrole-chalcone ureas (-) and thiophene-chalcone ureas (-). Compounds were characterized using H NMR, C NMR, and mass spectrometry. Their antiproliferative effects were assessed against renal adenocarcinoma (769P), lung carcinoma (A549), colorectal adenocarcinoma (HT-29), and healthy kidney (HEK-293) cell lines. Selected compounds were further evaluated for EGFR inhibition, apoptotic activity, and cell cycle arrest. Molecular docking was performed to predict binding interactions with wild-type human EGFR.

RESULTS

Compounds , , and (pyrrole series) showed strong cytotoxicity against A549 and HT-29, while , , and (thiophene series) were effective on 769P. Compound exhibited the highest EGFR inhibition (IC₅₀ = 1 nM), potent apoptotic induction, and cell cycle arrest at the S phase in A549 cells. Docking studies confirmed favorable binding of , , and within the EGFR active site.

CONCLUSIONS

Several chalcone-urea derivatives demonstrated potent anticancer properties, with compound 5c emerging as a promising EGFR inhibitor with strong cytotoxic and pro-apoptotic effects.