Synthesis and anticancer evaluation of N-benzoyl-N'-phenyltiourea derivatives against human breast cancer cells (T47D)

New anti-breast cancer compounds have been found and may prove to have stronger activity. To predict the activities of N-benzoyl-N'-phenylthiourea (BPTU) derivatives, namely N-(3-chloro)benzoyl-N'-phenylthiourea (3-Cl-BPTU) and N-(3,4-dichloro)benzoyl-N'-phenylthiourea (3,4-2Cl-BPTU) with Sirtuin-1 receptor (PDB code: 4I5I), molecular docking was conducted at the beginning of this study. The compounds were then synthesized from benzoyl chloride derivatives and N-phenylthiourea. Molecular structure was confirmed using FTIR, ¹H NMR, ¹³C NMR and Mass Spectra, while the anticancer activity was tested in vitro against human breast cancer cells (T47D) using MTT assay. The results indicated that the anti-cancer activities of the test compounds were better than those of the hydroxyurea as the reference compound, evidenced by the Rerank Score (RS). Furthermore, cytotoxic effect of 3-Cl-BPTU (IC₅₀: 0.43 mM) and 3,4-dichloro-BPTU (IC₅₀: 0.85 mM) showed better result compared with hydroxyurea (IC₅₀: 4.58 mM). Therefore, we concluded that these compounds could possess termendous potential as the candidate for a new anticancer drug.     

Synthesis of N-(phenylcarbamothioyl)-benzamide derivatives and their cytotoxic activity against MCF-7 cells

Cancer is one of the leading causes of death both in developing countries and across the globe. In Indonesia, cancer ranks as the fifth primary cause of death following heart disease, stroke, respiratory tract and diarrhea. Therefore, studies on thiourea derivative compounds as anticancer agents have been profoundly conducted but still require further continuous development. In the present study, we aimed tosynthesize new anticancer compounds of N-(phenylcarbamothioyl)-benzamide derivatives, namely N-(phenylcarbamothioyl)-4-bromobenzamide and N-(phenylcarbamothioyl)-4-fluorobenzamide compounds and assess their activities against MCF-7 breast cancer cells. The initial step was to predict the drug-receptor activity through docking between the tested compounds using epidermal growth factor receptor (EGFR) (PDB code: 1M17). The compounds were futher synthesized from the reactions between benzoyl chloride derivatives and N-phenylthiourea. The structures of the new compounds were identifiedusing FTIR, ¹H NMR, ¹³C NMR and mass spectra. The cytotoxic activities (IC₅₀) to breast cancer cells of MCF-7 N-(phenylcarbamothioyl)-4-bromobenzamide compound and N-(phenylcarbamothioyl)-4-fluorobenzamide were 0.27 mM and 0.31 mM, respectively. These two new compounds had better cytotoxic activities than those of the currenthydroxyurea-based anticancer drugs (the reference compound) with an IC₅₀ value of 9.76 mM. Furthermore, these two newcompounds were not toxic to Vero normal cells. Therefore, they possessedtremendous potentials as the candidates for new drugs against breastcancer.