Molecular Docking & MD Simulation Studies to Design Benzothiazole-Thiazole Hybrids as Potent p56lck Inhibitors for the Treatment of Cancer

The p56lck enzyme is mainly known for its important role in T cells. Immense effort has been put into developing p56lck inhibitors for diseases such as cancer, osteoporosis, and many others. Various studies on benzothiazole derivatives are of great interest because of their potent antitumor activity, and they act by binding to the ATP binding site of protein kinase. The protein kinase ATP binding site provided a great opportunity to develop newer analogs for protein kinase inhibitors. In the present investigation, we carried out ADMET molecular docking and Molecular Dynamic Simulation to know the structural requirements for inhibition of the p56lck enzyme. A docking study was performed on 51 analogs of benzothiazole and MD Simulation on three selected molecules. A molecular docking study on designed molecules and some standard molecules gives information on binding patterns like hing region, Allosteric site, and activation loop. ADMET study results allowed us to determine the selectivity of substitution and to know whether molecules obey Lipinski’s rule of five or not. Compound 1 was identified as a competitive inhibitor of p56lck by Molecular docking and MD Simulation. The benzothiazole-thiazole hybrids revealed structural features required to inhibit p56lck.