Designing of benzothiazole derivatives as promising EGFR tyrosine kinase inhibitors: a pharmacoinformatics study.

Benzothiazole derivatives represent an important class of therapeutic chemical agents and are widely used for interesting biological activities and therapeutic functions including anticancer, antitumor and antimicrobial. In this study, we have performed similarity/substructure-based search of eMolecule database to find out promising benzothiazole derivatives as EGFR tyrosine kinase inhibitors. Several screening criteria that included molecular docking, pharmacokinetics and synthetic accessibility were used on initially derived about 7000 molecules consisting of benzothiazole as major component. Finally, four molecules were found to be promising EGFR tyrosine kinase inhibitors. The best docked pose of each molecule was considered for binding interactions followed by molecular dynamics (MD) and binding energy calculation. Molecular docking clearly showed the final proposed derivatives potential to form a number of binding interactions. MD simulation trajectories undoubtedly indicated that the EGFR protein becomes stable when proposed derivatives bind to the receptor cavity. Strong binding affinity was found for all molecules toward the EGFR which was substantiated by the binding energy calculation using the MM-PBSA approach. Therefore, proposed benzothiazole derivatives may be promising EGFR tyrosine kinase inhibitors for potential application as cancer therapy. Communicated by Ramaswamy H. Sarma.