In silico study was performed to twelve 1,5-benzothiazepine chalcone derivatives with the protein target from the crystallographic structure modeling of the enzyme tyrosine kinase. The objective of this study is to execute and to estimate the biological activity of chalcone-based 1,5-benzothiazepine derivatives as potential inhibitors for breast cancer MCF7. To get insight into potential anticancer activities, molecular docking, molecular dynamic and ADME prediction were performed. Docking results reported that compound MA9 with binding free energy of -11.2 kcal / mol can interact through hydrogen bonds with amino acids Cys788 on 1T46 protein active site. In addition, the lowest binding free energy conformation indicated its stability during molecular dynamic simulation. MA9 is also shown to have drug likeness properties based on ADME prediction. In order to evaluate the modeling outcomes, MTT assay were performed for some of the most and least promising benzologs (i.e., MA1, MA6, MA8 and MA9). As expected, compound MA9 with the best calculated anticancer properties revealed the best inhibition against MCF7cell line in vitro. Thus, this compound was chosen as the reference for the next stage in the drug design.

Combination of similarity searching with docking and molecular dynamic simulations were performed. In this study, chalcone-based 1,5-benzothiazepine compound (i.e. MA9) was used as parent compound, since it exhibits potential enhancement and improvement of biological activity over doxorubicin (i.e. the common agent for cancer treatment). The main aim of this study was to explore a new potential inhibitor against breast cancer from a large database. To study this effect, several computational approaches were applied. Initially, seven compounds were observed according to the Euclidean distance and Tanimoto coefficient. Parent compound and all these seven compounds were docked into 1T46 protein active site. Docking results reported that ZINC4377306 and ZINC4377309 have exhibited binding free energy of -6.75 and -6.49 kcal/mol, respectively. In addition, they showed the binding interaction through hydrogen bond, van der Waals and other interactions with the notable residues around the active site. Both compounds were stable during the molecular dynamic simulation. Thus, ZINC4377306 and ZINC4377309 can be used as new potential agents against breast cancer as an early stage in drug discovery process.