Molecular docking, ADMET and molecular dynamics simulation revealed metralindole as a multitargeted inhibitor for division kinases

Abstract

Abstract Lung cancer is the most common type of cancer in the world, and alone, in 2020, almost 2.21 million new cases were diagnosed, with 1.80 million deaths, and are increasing daily. Non-small cell lung (NSCLC) is the primary type of lung cancer, predominantly forms around 80% of cases compared to small cell carcinoma, and about 75% of patients are already in an advanced state when diagnosed. Despite notable advances in early diagnosis and treatment, the five-year survival rate for NSCLC is not encouraging. Therefore, it is crucial to investigate the molecular causes of non-small cell lung cancer to create more efficient therapeutic approaches. Lung cancer showed a more significant and persistent binding affinity and energy landscape with the target CDK2 staurosporine and FGF receptor-1. In this study, we have picked two essential target proteins, human cyclin-dependent kinase-2 and Human Protein Kinase CK2 Holoenzyme and screened the entire prepared DrugBank prepared library of 1,55,888 compounds and identified 2-(2-methyl-5-nitroimidazole-1-yl) ethanol (Metralindole) as a major inhibitor. Metralindole has displayed high docking scores of -5.159 Kcal/mol and -5.99 Kcal/mol with good hydrogen bonding and other bonding topologies such as van der Waals force, and ADMET results shown excellent bioavailability, outstanding solubility, no side effects, and toxicity. The molecular dynamics simulation for 100ns in a water medium confirmed the compound's stability and interaction pattern with the lowest deviation and fluctuations. Our in-silico study suggests Metralindole, an experimental compound, can effectively cure lung cancer. Further, the experimental validation of the compound is a must before any prescription.