Abstract
This study emphasizes the explorations of binding of Prima-1MET with two targets, p53 a tumor suppressor protein, and tyrosine kinase of epidermal growth factor receptor. In silico investigations reveal that Prima-1MET showed robust binding with both targets. Molecular docking simulations demonstrated the binding affinity of Prima-1MET with p53 and tyrosine kinase was found to be −38.601 kJ/mol and −38.976 kJ/mol. In addition, the stability of Prima-1MET was explored by molecular dynamics simulation. Prima-1MET attains stability in the binding site of the respective protein till the simulation period is over. Moreover, the free binding energy ΔGbind was calculated by the molecular mechanics Poisson Boltzmann surface area method. The ΔGbind of Prima-1MET with tyrosine kinase was found to be −58.585 ± 0.327 kJ/mol and with p53 it was −35.910 ± 0.335 kJ/mol. Next, cytotoxicity of the Prima-1MET was evaluated using multiple cancer cell lines and the IC50 value were ranging between 4.5 and 30 μM. The cell death was identified by apoptosis assay. Further, the p53 and tyrosine kinase expression was monitored using immunofluorescence techniques, it was found Prima-1MET induces the expression of p53 protein and mimics the level of tyrosine kinase oncogenic target. Also, reactive oxygen species (ROS) and membrane potential activity of Prima-1MET was evaluated by using a lung cancer cell line. A significant decrease in intracellular ROS was observed and resulted in disruption of mitochondrial transmembrane potential. This study uncovers the underlying mechanism of Prima-1MET and could be helpful to design further leads against lung cancers.
Communicated by Ramaswamy H. Sarma
Disclosure statement
All authors have no conflict of interest and all data will be available on the authors’ request.
Authors’ contributions
RKM and SAM contributes to in silico, in vitro work and Draft preparations. SSA contributes to in vitro study, and editing. All author read and approve the final manuscript for publication.
Acknowledgments
All authors are thankful to Dr. Binata Nayak, Professor, School of Life Sciences, Sambalpur University for critical revisions, editing, constructive suggestions and provide laboratory facilities to conduct the present study. SAM wishes to acknowledge Dr. Ibrahim Khalifa, Behna University, Egypt for providing access to MOE tools.