Molecular docking analysis of mefluhybenamine with lung cancer targets.

Abstract

Lung cancer is the most prevalent type of cancer worldwide, with 2.21 million cases and 1.80 million fatalities in 2020. The main factor influencing lung cancer is smoking, and the most common form of lung cancer, non-small cell lung cancer (NSCLC), accounts for around 80% of instances compared to small cell carcinoma, and about 75% of patients are already in an advanced stage when they are detected. Despite significant early detection and therapy improvements, the five-year survival rate for NSCLC is not encouraging. Therefore, it is essential to look into the molecular origins of non-small cell lung cancer to develop more effective therapeutic strategies-the binding affinities and energy landscape with the proteins. Cyclin Dependent kinase 2 (CDK2) and Insulin-like Growth Factor 1 Receptor (IGF1) were more substantial and sustained in lung cancer that was chosen as the two primary target proteins in this. We screened the entire Drug Bank-prepared library of 1,55,888 compounds and found (2R,3R)-7-(Methylsulfonyl)-3-(2,4,5-trifluorophenyl) -1,2,3,4-tetrahydropyrido[1,2-a] benzimidazol-2-aminium (Mefluhybenamine) to be a significant inhibitor. Mefluhybenamine showed strong hydrogen bonding and other bonding topologies, such as van der Waals force, in its high docking scores of -6.168 Kcal/mol and -5.26 Kcal/mol, and ADMET results showed excellent bioavailability, remarkable solubility, no side effects, and toxicity. The molecular dynamicsimulation confirmed the compound's stability and interaction pattern for 100 ns in an SPC water medium with the slightest deviation and fluctuation. Data shows that Mefluhybenamine is a potential candidate. However, validation of the compound is essential.