Molecular docking investigating methotrexate as a potential target for addressing cardiovascular disease risk associated with cancer.

Abstract

e24000 Background: Cardiovascular Disease (CVD) and Cancer are recognized as the leading cause of mortality worldwide, and adult cancer survivors have a 42% increased risk of CVD in comparison to individuals without cancer. The Advanced Glycation End Products receptor (RAGE) interactions play a crucial role in the atherogenic pathogenesis associated with CVD. Prior studies suggest that anticancer drugs including Methotrexate (MTX) and Niraparib, have potential to prevent and treat atherosclerosis. Computational molecular docking was performed with four anticancer drugs and RAGE to identify potential drug targets for preventing atherosclerosis associated with increased CVD risk for patients with or recovering from Cancer. Methods: The molecular docking modeling and analysis was performed using AutoDock Tool 4.2 version software to model the binding interaction between RAGE and each of the four anticancer drugs studied: MTX, Niraparib, Abemaciclib, and Saracatinib. Quinolinic Acid (QA), a known extracellular ligand of RAGE was the positive control for the docking study. The binding affinity and docking conformation of each receptor-drug interaction was modelled. Results: Among the four docking interactions, MTX had the strongest binding interaction with RAGE as demonstrated by the lowest binding energy and mean binding energy calculated, -7.59 kcal/mol, in comparison to the binding affinity of QA. Saracatinib had the weakest binding interaction with RAGE with a binding affinity of -2.74 kcal/mol. Conclusions: The molecular docking findings show that among the anticancer drug interactions studied, MTX had the strongest binding interaction with RAGE. This suggests that MTX may potentially reduce the progression of atherosclerosis and CVD risk among cancer survivors by inhibiting RAGE.