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Data-Driven Approaches Used for Compound Library Design for the Treatment of Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disease in older individuals worldwide. Pharmacological treatment for such a disease consists of drugs such as monoamine oxidase B (MAO-B) inhibitors to increase dopamine concentration in the brain. However, such drugs have adverse...

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Autores principales: Barrera-Vazquez, Oscar, Santiago-de-la-Cruz, Jose Alberto, Rivero-Segura, Nadia Alejandra, Estrella-Parra, Edgar Antonio, Morales-Paoli, Genaro Salvador, Flores-Soto, Edgar, Gomez-Verjan, Juan Carlos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9867512/
https://www.ncbi.nlm.nih.gov/pubmed/36674652
http://dx.doi.org/10.3390/ijms24021134
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author Barrera-Vazquez, Oscar
Santiago-de-la-Cruz, Jose Alberto
Rivero-Segura, Nadia Alejandra
Estrella-Parra, Edgar Antonio
Morales-Paoli, Genaro Salvador
Flores-Soto, Edgar
Gomez-Verjan, Juan Carlos
author_facet Barrera-Vazquez, Oscar
Santiago-de-la-Cruz, Jose Alberto
Rivero-Segura, Nadia Alejandra
Estrella-Parra, Edgar Antonio
Morales-Paoli, Genaro Salvador
Flores-Soto, Edgar
Gomez-Verjan, Juan Carlos
author_sort Barrera-Vazquez, Oscar
collection PubMed
description Parkinson’s disease (PD) is the second most common neurodegenerative disease in older individuals worldwide. Pharmacological treatment for such a disease consists of drugs such as monoamine oxidase B (MAO-B) inhibitors to increase dopamine concentration in the brain. However, such drugs have adverse reactions that limit their use for extended periods; thus, the design of less toxic and more efficient compounds may be explored. In this context, cheminformatics and computational chemistry have recently contributed to developing new drugs and the search for new therapeutic targets. Therefore, through a data-driven approach, we used cheminformatic tools to find and optimize novel compounds with pharmacological activity against MAO-B for treating PD. First, we retrieved from the literature 3316 original articles published between 2015–2021 that experimentally tested 215 natural compounds against PD. From such compounds, we built a pharmacological network that showed rosmarinic acid, chrysin, naringenin, and cordycepin as the most connected nodes of the network. From such compounds, we performed fingerprinting analysis and developed evolutionary libraries to obtain novel derived structures. We filtered these compounds through a docking test against MAO-B and obtained five derived compounds with higher affinity and lead likeness potential. Then we evaluated its antioxidant and pharmacokinetic potential through a docking analysis (NADPH oxidase and CYP450) and physiologically-based pharmacokinetic (PBPK modeling). Interestingly, only one compound showed dual activity (antioxidant and MAO-B inhibitors) and pharmacokinetic potential to be considered a possible candidate for PD treatment and further experimental analysis.
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spelling pubmed-98675122023-01-22 Data-Driven Approaches Used for Compound Library Design for the Treatment of Parkinson’s Disease Barrera-Vazquez, Oscar Santiago-de-la-Cruz, Jose Alberto Rivero-Segura, Nadia Alejandra Estrella-Parra, Edgar Antonio Morales-Paoli, Genaro Salvador Flores-Soto, Edgar Gomez-Verjan, Juan Carlos Int J Mol Sci Article Parkinson’s disease (PD) is the second most common neurodegenerative disease in older individuals worldwide. Pharmacological treatment for such a disease consists of drugs such as monoamine oxidase B (MAO-B) inhibitors to increase dopamine concentration in the brain. However, such drugs have adverse reactions that limit their use for extended periods; thus, the design of less toxic and more efficient compounds may be explored. In this context, cheminformatics and computational chemistry have recently contributed to developing new drugs and the search for new therapeutic targets. Therefore, through a data-driven approach, we used cheminformatic tools to find and optimize novel compounds with pharmacological activity against MAO-B for treating PD. First, we retrieved from the literature 3316 original articles published between 2015–2021 that experimentally tested 215 natural compounds against PD. From such compounds, we built a pharmacological network that showed rosmarinic acid, chrysin, naringenin, and cordycepin as the most connected nodes of the network. From such compounds, we performed fingerprinting analysis and developed evolutionary libraries to obtain novel derived structures. We filtered these compounds through a docking test against MAO-B and obtained five derived compounds with higher affinity and lead likeness potential. Then we evaluated its antioxidant and pharmacokinetic potential through a docking analysis (NADPH oxidase and CYP450) and physiologically-based pharmacokinetic (PBPK modeling). Interestingly, only one compound showed dual activity (antioxidant and MAO-B inhibitors) and pharmacokinetic potential to be considered a possible candidate for PD treatment and further experimental analysis. MDPI 2023-01-06 /pmc/articles/PMC9867512/ /pubmed/36674652 http://dx.doi.org/10.3390/ijms24021134 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Barrera-Vazquez, Oscar
Santiago-de-la-Cruz, Jose Alberto
Rivero-Segura, Nadia Alejandra
Estrella-Parra, Edgar Antonio
Morales-Paoli, Genaro Salvador
Flores-Soto, Edgar
Gomez-Verjan, Juan Carlos
Data-Driven Approaches Used for Compound Library Design for the Treatment of Parkinson’s Disease
title Data-Driven Approaches Used for Compound Library Design for the Treatment of Parkinson’s Disease
title_full Data-Driven Approaches Used for Compound Library Design for the Treatment of Parkinson’s Disease
title_fullStr Data-Driven Approaches Used for Compound Library Design for the Treatment of Parkinson’s Disease
title_full_unstemmed Data-Driven Approaches Used for Compound Library Design for the Treatment of Parkinson’s Disease
title_short Data-Driven Approaches Used for Compound Library Design for the Treatment of Parkinson’s Disease
title_sort data-driven approaches used for compound library design for the treatment of parkinson’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9867512/
https://www.ncbi.nlm.nih.gov/pubmed/36674652
http://dx.doi.org/10.3390/ijms24021134
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