Docking and Antiproliferative Effect of 4-T-Butylbenzoyl-3-Allylthiourea on MCF-7 Breast Cancer Cells With/Without Her-2 Overexpression

Abstract

Breast cancer is currently one of the most common causes of death in women all over the world, with 30 percent cases caused by overexpression of HER-2 and poor prognosis. HER-2 plays an important role in cell proliferation, thereby, making it a promising strategy in the treatment of breast cancer. This research, therefore, uses 4-t-butylbenzoyl-3-allylthiourea a category of the thiourea group which acts as a needed pharmacophore for cytotoxic activity. Its aim is to dock and investigate the antiproliferative effect of 4-t-butylbenzoyl-3-allylthiourea on MCF-7/HER-2 and MCF-7 parented breast cancer cells. Virtual screening was conducted by docking the interaction study of the compounds into the binding site of EGFR and/or HER-2, with PBD code: 1M17 and 3PP0 to predict their affinity. Furthermore, it enabled the extraction of RS -91.0665 kcal/mol value on the EGFR receptor (1M17.pdb) and RS -91.0365 kcal/mol value on the HER-2 receptor (3PP0.pdb). The Anti-proliferative effect of the compound on MCF-7 and MCF-7/HER-2 cell line was observed by MTT assay, while 4-t-butylbenzoyl-3-allylthiourea exhibited its effect on MCF-7/HER-2 cells using IC50 values of 0.15±6.48 mM higher than MCF-7 cells with IC50 values of 0.26±2.48 mM. In conclusion, 4-t-butylbenzoyl-3-allylthiourea is potentially developed as an anti-breast cancer agent with overexpression of HER-2.

Keywords: 4-t-butylbenzoyl-3-allylthiourea, MCF-7, MCF-7/HER-2, docking, antiproliferative