In Silico Evaluation of Cyanobacteria-Derived Bioactive Compounds as Potential Monoamine Oxidase-B Inhibitors for Parkinson’s Disease: Molecular Docking and Molecular Dynamics Simulation Study

Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and impaired motor and non-motor functions. Current therapies provide symptomatic relief but do not prevent disease progression, highlighting the need for novel neuroprotective agents. Cyanobacteria-derived bioactive compounds possess diverse pharmacological properties, including antioxidant and anti-inflammatory activities, making them potential therapeutic candidates. This study aimed to identify potential monoamine oxidase B (MAO-B) targeting cyanobacterial compounds using computational approaches. Methods: Forty-five cyanobacterial bioactive compounds were screened from the literature and databases based on their antioxidant and anti-inflammatory properties. Molecular docking against MAO-B was performed using PyRx, and interactions were analyzed using BIOVIA Discovery Studio. The top-ranked compounds were evaluated through ADMET profiling and 100 ns molecular dynamics simulations using the CHARMM36 force field with Swiss-Param-based ligand parameterization. Results: Among the screened compounds, Scytonemin (−11.9 kcal/mol), Calothrixin B (−11.7 kcal/mol), and Zeaxanthin (−11.5 kcal/mol) demonstrated the predicted binding affinity toward MAO-B. ADMET analysis revealed distinct pharmacokinetic profiles among the selected compounds. ADMET analysis showed favorable GI absorption and BBB permeability for Calothrixin B, whereas Scytonemin and Zeaxanthin showed low GI absorption and no predicted BBB permeability. Molecular dynamics simulations indicated stable ligand–protein interactions throughout the simulation period. Conclusions: The integrative computational analysis identified Scytonemin, Calothrixin B, and Zeaxanthin as potential MAO-B-interacting candidates. Based on the combined docking, ADMET, and molecular dynamics profiles, Calothrixin B demonstrated the most favorable overall computational profile, followed by Scytonemin and Zeaxanthin, highlighting all three compounds as candidates for further investigation in MAO-B-targeted drug discovery. Further in vitro and in vivo studies are required to validate their MAO-B inhibitory, neuroprotective, and pharmacokinetic potential.