Antiparkinsonian Potential of Natural Products: Molecular Docking, Prediction of Pharmacokinetic and Toxicological Properties

Background: Parkinson's disease (PD) is a neurodegenerative pathology common in the elderly, and it may be related to several factors, such as excessive and continuous use of drugs, alcoholism, and cerebral ischemia, among others. Emphasizing that there is still no cure for PD, current pharmacological treatment aims to restore reduced dopaminergic activity in the central nervous system and manage symptoms. However, due to the different side effects caused by antiparkinsonian drugs, their use is recommended just when symptoms considerably impair professional performance or the patient's daily tasks. Therefore, studies for developing new drugs have been conducted, and natural products are gaining importance due to the possibility of discovering new bioactive molecules. In this sense, this research aimed to perform the in silico study of molecules of natural origin for treating PD. Methods: A search for molecules from medicinal plants was carried out; they underwent a pharmacokinetic and toxicological prediction with a subsequent molecular docking study coupled with the MAO-B enzyme and the dopamine receptor 2. Results: The ginsenosides compounds present an unfavorable pharmacokinetic pattern, which can be explained by their molecular mass, while the other molecules present average patterns, with the exception of kavains, which obtained very satisfactory results. When it comes to toxicity, the molecules curcumin, dihydrokavain, vitexin, kavain and tetrahydrocurcumin did not exhibit any toxic alert. As for the molecular docking study, the compound curcumin stood out with many interactions at many amino acid residues relevant to antiparkinsonian activity, both in the MAO-B enzyme and in the D2 receptor. Conclusion: Of 25 molecules of natural products, 3 are good candidates for studies of oral drugs, owing to their excellent pharmacokinetic profile and low probability of being toxic. The curcumin molecule has great notoriety, as it obtained relevant interactions with the two proteins studied in molecular docking, especially in the MAO-B enzyme.