In silico Molecular Docking, Molecular Dynamic Simulation and ADME Study of New (2-Methyl Benzimidazole-1-yl)-N- Derivatives with Potential Anti-proliferative Activity

ABSTRACT Although there has been great progress in the development of anticancer medications, numerous obstacles remain, including drug resistance, poor effectiveness, and excessive toxicity, which have all profoundly impacted the daily lives of cancer patients. Because of this, finding highly selective, effective, and non-toxic anticancer drugs is a major challenge in current cancer research. We present an in silico evaluation of a new series of 2-methylbenzimidazole derivatives to determine the anti-proliferative effect in the epidermal growth factor receptor (EGFR) active sites. Our six compounds docked with the EGFR crystal structure (protein data bank code: 4HJO) to determine their binding affinity to active sites. One of these compounds showed a high score (75.5) and two compounds had as binding energy as the gold standard drug erlotinib. The molecular dynamic simulation study revealed that compound 1 had good alignment with the EGFR receptor according to Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF) data. After analyzing the ADME study of virtually active compounds, they achieved Lipinski's rules, and other pharmacokinetic properties. Lastly, these compounds can function as precursors for the development of novel anti-proliferative drug.