The Potency of 4-Methyl-3-Benzoyl Allylthiourea as Anti-Breast Cancer: Molecular Dynamic Simulation, Cytotoxic Activity and its Selectivity Index

Breast cancer is currently one of the most common causes of death in women all over the world. In breast cancer, the proliferation and invasiveness of cancer cells are primarily regulated by hormone receptor-mediated signalling, including estrogen, progesterone, and human epidermal growth factor receptors. The study aims to conduct an in silico investigation using molecular docking and molecular dynamic simulation, as well as to determine the cytotoxicity activity and selectivity index (SI) of 4-methyl-3-benzoyl allylthiourea as an anti-breast cancer agent. Molecular docking was conducted by using the MOE 2022 program to predict the anticancer with three targeted proteins: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2). Molecular dynamics simulation was performed by AMBER 20 to investigate the binding affinity of 4-methyl-3-benzoyl allylthiourea on the selected targets with RMSD, RMSF, and MM-GBSA parameters. The cytotoxic activity was performed using the MTT method against T47D and MCF7/HER2 breast cancer cells. The selectivity of the compound was tested by the same method on normal Vero. Results showed the highest binding affinity of 4-methyl-3-benzoyl allylthiourea to ER, followed by PR and HER2 receptors with S scores of -6.287, -7.127, and -6.855 kcal/mol, respectively. The molecular dynamics simulation showed that interaction between 4-methyl-3-benzoyl allylthiourea and 1E3K is predicted to be the most stable conformation than other receptors. The cytotoxicity test resulted in IC50 in T47D and MCF7/HER2 cells of 296 and 134 µM, respectively. The SI values of 4-methyl-3-benzoyl allylthiourea for T47D and MCF7/HER2 are 2 and 4, respectively. In conclusion, 4-methyl-3-benzoyl allylthiourea has high potential as an anti-breast cancer candidate that acts on the ER, PR, and HER2 receptors. Therefore, it is very promising for further development.