Computational Insights Into Alpha-Synuclein Interactions: Exploring Therapeutic Avenues for Parkinson's Disease

This research assesses the ADME (Absorption, Distribution, Metabolism, and Excretion) characteristics andmolecular docking interactions of five phytochemicals—Apigenin, Luteolin, Quercetin, Bacoside A, andBacoside B—with alpha-synuclein (PDB ID: 8A9L), a critical protein implicated in the pathogenesis ofParkinson's disease (PD). Parkinson's disease is an age-related progressive neurodegenerative disorder that ischaracterized by motor dysfunction and the deposition of alpha-synuclein aggregates within the brain. ADMEprofiling showed that flavonoids (Apigenin, Luteolin, and Quercetin) have good drug-likeness, excellentgastrointestinal absorption, and good oral bioavailability, hence can be used for oral delivery. On the contrary,Bacoside A and B showed poor pharmacokinetic features such as high molecular weight and numerousviolations of drug-likeness parameters. Molecular docking analyses revealed similar binding affinities of allthe compounds with alpha-synuclein, although Bacoside A and B were slightly better binders (docking scores-6.6 and -6.7 kcal/mol, respectively) than the flavonoids. The poor pharmacokinetics and bioavailability renderthe Bacosides poor candidates as drugs. Hence, the flavonoids become interesting leads for further studies ondeveloping therapeutic agents against Parkinson's disease.