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Identification of Novel Arachidonic Acid 15-Lipoxygenase Inhibitors Based on the Bayesian Classifier Model and Computer-Aided High-Throughput Virtual Screening
Ferroptosis is an iron-dependent lipid peroxidative form of cell death that is distinct from apoptosis and necrosis. ALOX15, also known as arachidonic acid 15-lipoxygenase, promotes ferroptosis by converting intracellular unsaturated lipids into oxidized lipid intermediates and is an important ferro...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695033/ https://www.ncbi.nlm.nih.gov/pubmed/36422570 http://dx.doi.org/10.3390/ph15111440 |
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author | Liao, Yinglin Cao, Peng Luo, Lianxiang |
author_facet | Liao, Yinglin Cao, Peng Luo, Lianxiang |
author_sort | Liao, Yinglin |
collection | PubMed |
description | Ferroptosis is an iron-dependent lipid peroxidative form of cell death that is distinct from apoptosis and necrosis. ALOX15, also known as arachidonic acid 15-lipoxygenase, promotes ferroptosis by converting intracellular unsaturated lipids into oxidized lipid intermediates and is an important ferroptosis target. In this study, a naive Bayesian machine learning classifier with a structure-based, high-throughput screening approach and a molecular docking program were combined to screen for three compounds with excellent target-binding potential. In the absorption, distribution, metabolism, excretion, and toxicity characterization, three candidate molecules were predicted to exhibit drug-like properties. The subsequent molecular dynamics simulations confirmed their stable binding to the targets. The findings indicated that the compounds exhibited excellent potential ALOX15 inhibitor capacity, thereby providing novel candidates for the treatment of inflammatory ischemia-related diseases caused by ferroptosis. |
format | Online Article Text |
id | pubmed-9695033 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96950332022-11-26 Identification of Novel Arachidonic Acid 15-Lipoxygenase Inhibitors Based on the Bayesian Classifier Model and Computer-Aided High-Throughput Virtual Screening Liao, Yinglin Cao, Peng Luo, Lianxiang Pharmaceuticals (Basel) Article Ferroptosis is an iron-dependent lipid peroxidative form of cell death that is distinct from apoptosis and necrosis. ALOX15, also known as arachidonic acid 15-lipoxygenase, promotes ferroptosis by converting intracellular unsaturated lipids into oxidized lipid intermediates and is an important ferroptosis target. In this study, a naive Bayesian machine learning classifier with a structure-based, high-throughput screening approach and a molecular docking program were combined to screen for three compounds with excellent target-binding potential. In the absorption, distribution, metabolism, excretion, and toxicity characterization, three candidate molecules were predicted to exhibit drug-like properties. The subsequent molecular dynamics simulations confirmed their stable binding to the targets. The findings indicated that the compounds exhibited excellent potential ALOX15 inhibitor capacity, thereby providing novel candidates for the treatment of inflammatory ischemia-related diseases caused by ferroptosis. MDPI 2022-11-20 /pmc/articles/PMC9695033/ /pubmed/36422570 http://dx.doi.org/10.3390/ph15111440 Text en © 2022 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 Liao, Yinglin Cao, Peng Luo, Lianxiang Identification of Novel Arachidonic Acid 15-Lipoxygenase Inhibitors Based on the Bayesian Classifier Model and Computer-Aided High-Throughput Virtual Screening |
title | Identification of Novel Arachidonic Acid 15-Lipoxygenase Inhibitors Based on the Bayesian Classifier Model and Computer-Aided High-Throughput Virtual Screening |
title_full | Identification of Novel Arachidonic Acid 15-Lipoxygenase Inhibitors Based on the Bayesian Classifier Model and Computer-Aided High-Throughput Virtual Screening |
title_fullStr | Identification of Novel Arachidonic Acid 15-Lipoxygenase Inhibitors Based on the Bayesian Classifier Model and Computer-Aided High-Throughput Virtual Screening |
title_full_unstemmed | Identification of Novel Arachidonic Acid 15-Lipoxygenase Inhibitors Based on the Bayesian Classifier Model and Computer-Aided High-Throughput Virtual Screening |
title_short | Identification of Novel Arachidonic Acid 15-Lipoxygenase Inhibitors Based on the Bayesian Classifier Model and Computer-Aided High-Throughput Virtual Screening |
title_sort | identification of novel arachidonic acid 15-lipoxygenase inhibitors based on the bayesian classifier model and computer-aided high-throughput virtual screening |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695033/ https://www.ncbi.nlm.nih.gov/pubmed/36422570 http://dx.doi.org/10.3390/ph15111440 |
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