Moyad Shahwan ¹ Pratibha Prasad ¹ Dharmendra K. Yadav ² Mohd S. Khan ³ Anas Shamsi ^1*

• ¹ Ajman University, Ajman, United Arab Emirates
• ² Gachon University, Seongnam, Gyeonggi, Republic of Korea
• ³ King Saud University, Riyadh, Riyadh, Saudi Arabia

Depression and Parkinson's disease (PD) are devastating neurological disorders that require the development of novel therapeutic interventions. Drug repurposing target predefined pharmacological targets is a widely use approach in modern drug discovery. Monoamine oxidase B (MAO-B) is a critical protein implicated in these conditions. In this study, we undertook a systematic exploration of repurposed drugs as potential inhibitors of MAO-B. Exploring a library of 3648 commercially available drug molecules, we conducted virtual screening using a molecular docking approach to target the MAO-B binding pocket. Two promising drug molecules, Brexpiprazole and Trifluperidol, were identified based on their exceptional binding potential and drug profiling. Subsequently, all-atom molecular dynamics (MD) simulations were performed on the MAO-B-ligand complexes for a trajectory of 300 nanoseconds (ns). Simulation results demonstrated that the binding of Brexpiprazole and Trifluperidol induced only minor structural alterations in MAO-B and showed significant stabilization throughout the simulation trajectory. Overall, the finding suggests that Brexpiprazole and Trifluperidol exhibit strong potential as repurposed inhibitors of MAO-B that might be explored further in experimental investigations for the development of targeted therapies for depression and PD.