Target-based Virtual Screening of Natural Compounds as Promising Anti-Parkinson’s Agents

Background: Parkinson's disease (PD), the second most common neurodegenerative disease among the elderly, is caused by the death of dopaminergic neurons, resulting in dopamine depletion. Monoamine oxidase B (MAO-B) is an important enzyme in PD because it degrades dopamine. Dopamine levels can be elevated by inhibiting MAO-B, especially in the early stages of the disease.Methods: This study involves virtual screening (docking) of ZINC database natural compounds (N = 200) against MAO-B, followed by ADME and drug-likeness analysis of the top hits.Results: ZINC899884, ZINC4098705, ZINC14764165, and ZINC18847036 compounds exhibited strong binding to MAO-B and interacted with key MAO-B residues. The Cys172, Ile198, Phe168, Ile199, Leu171, Gln206, Gly58, Tyr326, Leu328, Phe343, Tyr398, Ser59, Tyr60, Gly434, and Tyr435 residues of MAO-B were important in binding with these compounds. In addition, these compounds, like the control Rasagiline, interact with MAO-B via several common residues. Furthermore, ADME and drug-like prediction resulted in promising results, indicating that these compounds have a high gastrointestinal absorption property.Conclusion: ZINC899884, ZINC4098705, ZINC14764165, and ZINC18847036 can be used as MAO-B inhibitors for PD. However, experimental validation is required to optimize them as MAO-B inhibitors.Keywords: Drug-likeness; Monoamine oxidase B; Natural compounds; Neurodegenerative disease; Parkinson’s disease