In silico screening of anti-Parkinsonian multi-target drugs from natural compounds
Alice Nunes Silva Itturriet, Rafaella Sinnott Dias, Frederico Schmitt Kremer
Abstract
Parkinson’s disease (PD), a neurodegenerative condition, manifests with tremors, muscle rigidity, and movement difficulties, primarily in individuals over 60 years old. The exact cause is unknown, but it involves the gradual loss of dopamine-producing neurons in the brain. Current treatments include medications like levodopa and dopaminergic agonists, as well as therapies such as physiotherapy and deep brain stimulation surgery. However, the main challenge of PD lies in managing the disease progression and its adverse effects over time. To address the therapeutic bottleneck of the disease, in silico strategies, such as quantitative structure-activity relationships (QSAR) and molecular docking, are particularly effective. In this study, we employed in silico techniques to identify natural compounds with multi target potential for the treatment of PD. The core computational methodologies employed included molecular docking, which predicted the binding affinities of compounds to key PD-related protein targets, followed by molecular dynamics (MD) simulations to assess the stability of these protein-ligand complexes over time. Crucially, the analysis incorporated comprehensive ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) prediction to evaluate the drug-likeness and pharmacokinetic profiles of potential candidates, with a particular emphasis on their predicted blood-brain barrier permeability, a critical factor for central nervous system (CNS) drugs. The investigation successfully identified several natural compounds with significant potential, notably Luteolin, which exhibited strong predicted multi-target activities. These activities include potent inhibition of Monoamine Oxidase-B (MAO-B), a well-established target for symptomatic relief in PD, alongside predicted antioxidant and anti-inflammatory properties, addressing the neurodegenerative aspects of the disease. Despite promising in silico results, we emphasize the need for experimental validation, such as in vitro and in vivo studies to confirm binding, assess neuroprotective effects, and analyze ADMET properties, advancing these compounds as potential treatments for Parkinson’s disease.
Keywords
References
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Submitted date:
12/03/2024
Accepted date:
07/07/2025
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