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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1422080
This article is part of the Research Topic Approaches to improve the performance of virtual screening: scoring functions, structural filtration, prediction of physicochemical properties/pharmacological activity View all articles
Identification of high-affinity Monoamine oxidase B inhibitors for Depression and Parkinson's Disease treatment: Bioinformatic approach of drug repurposing
Provisionally accepted- 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.
Keywords: monoamine oxidase B, drug repurposing, Virtual Screening, Molecular dynamic simulation (MD), molecular docking
Received: 23 Apr 2024; Accepted: 26 Aug 2024.
Copyright: © 2024 Shahwan, Prasad, Yadav, Khan and Shamsi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Anas Shamsi, Ajman University, Ajman, United Arab Emirates
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