Molecular docking and dynamic simulation study to explore quercetin as a multi-potent candidate against gliomas

Purpose: To search for novel gliomas targets and their inhibitors using a molecular docking approach. Methods: Quercetin multi-targeting potential was investigated against some of the emerging gliomas targets such as epidermal growth factor receptor (EGFR), ephrin type-A receptor 2 (EphA2), nicotinamide phosphoribosyltransferase (NMRPTase) and plasminogen activator inhibitor-1 (PAI-1). Crucial biochemical interaction of quercetin with these targets were analyzed using molecular docking study. Results: Quercetin interacted strongly via hydrogen bonding with important active sites consisting of amino acid residues of EphA2 and PAI-1, and showed binding energy of -7.44 and -7.38 kcal/mol, respectively. Some crucial active site amino acids involved in the interaction of known EphA2 and PAI-1 inhibitors (Alw-II-41-27 and ACT001) were common in quercetin interactions as well, and both inhibitors as well as quercetin did not violate Lipinski rules. Importantly, the quercetin-EphA2 and quercetin-PAI-1 complexes were stable as minimal fluctuations within the permissible limit were observed during a 20 ns trajectory performed on desmond simulation platform. Conclusion: Despite the fact that quercetin has been studied extensively against various cancer pathways, its transformation from a long-time bench candidate into bedside medications still needs further exploration. Nevertheless, the present predictive biochemical interaction analysis against emerging glioma targets might pave way for the design of novel therapeutic agents based on quercetin scaffolds.