Synthesis and antitumor activity evaluation of N,N'-dibenzoyl-N,N'- Diethylurea against human breast cancer cell line (MCF-7)

Objective: To find new antitumor agents a serie of ring-substituted N,N'-Dibenzoyl-N,N'-Diethylureas (3a-d) were designed and synthesized. The study was conducted to synthesize N,N'-Dibenzoyl-N,N'-Diethylureas and examine their antitumor activity against human breast carcinoma cell line (MCF-7). Methods: The compounds were synthesized from reaction of N,N'-diethylurea with ring-substitued-benzoylureas. The molecular structures were confirmed by FTIR, ¹H-NMR, ¹³C-NMR and MS spectroscopy. Their antitumor activities were tested in vitro against human breast carcinoma cell line (MCF-7) using MTT assay. In silico molecular modeling was carried out through docking the compounds into binding site of ERK2 (PDB. 1TVO). Results: The tested compounds exhibited antitumor activity higher than reference drug hydroxyurea. One of them (3c) displayed the highest activity among the tested compounds with IC₅₀ 0.56 μM, twenty-fold more active than hydroxyurea (IC₅₀= 11.58 μM). This compound more fitting to the enzyme's binding site than hydroxyurea could explain its better inhibitory activity. Conclusion: Four ring-substituted N,N'-Dibenzoyl-N,N'-Diethylurea derivatives had been synthesized and one of them is highly potential as antitumor agents against human breast carcinoma cell line (MCF-7).