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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...

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Detalles Bibliográficos
Autores principales: Liao, Yinglin, Cao, Peng, Luo, Lianxiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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