Structure-based multitargeted docking screening, pharmacokinetics, DFT, and dynamics simulation studies reveal mitoglitazone as a potent inhibitor of cellular survival and stress response proteins of lung cancer

In this study, we have performed multitargeted molecular docking studies of Drug Bank compounds with HTVS, SP and XP algorithms followed by MM\GBSA against the four proteins of lung cancer cellular survival and stress responses, which revealed Mitoglitazone as a multitargeted inhibitor with a docking and MM\GBSA score ranging from  − 5.784 to − 7.739 kcal/mol and − 25.81 to − 47.65kcal/mol, respectively. Moreover, we performed pharmacokinetics studies and QM-based DFT analysis, showing suitable candidate and interaction pattern analysis revealed the most count of interacting residues was 4GLY, 5PHE, 6A SP, 6GLU, 6LYS, and 6THR. Further, the results were validated with SPC water model-based MD simulation for 100ns in neutralised condition, showing the cumulative deviation and fluctuation <  2Å with many intermolecular interactions. The whole analysis has suggested that Mitoglitazone can be used as a multitargeted inhibitor against lung cancer—however, experimental studies are needed before human use.
Source: Medical Oncology - Category: Cancer & Oncology Source Type: research