This study employs structure-based in silico methodologies, including molecular docking and molecular dynamics (MD) simulations, to screen approximately 2500 FDA-approved drugs against the glyoxalase I enzyme. A two-step molecular docking approach was implemented, initially utilizing iGemdock software to screen the drugs, from which the top 20 compounds were selected for further analysis. Subsequent molecular docking in Autodock Vina, comparing scores with that of S-p-bromobenzyl-glutathione, a known enzyme inhibitor, identified 6 ligands for MD simulations. Results from the MD simulations highlight Trilaciclib and Olmesartan as potential glyoxalase I inhibitors. Furthermore, molecular docking indicated that these two drugs also exhibit potency as inhibitors of glyoxalase II. This suggests potential applications of Trilaciclib and Olmesartan as drugs for diseases modulated by the inhibition of the glyoxalase system.
