Identification of a Prenyl Chalcone as a Competitive Lipoxygenase Inhibitor: Screening, Biochemical Evaluation and Molecular Modeling Studies
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3390/molecules26082205 http://hdl.handle.net/11449/207682 |
Resumo: | Cyclooxygenase (COX) and lipoxygenase (LOX) are key targets for the development of new anti-inflammatory agents. LOX, which is involved in the biosynthesis of mediators in inflammation and allergic reactions, was selected for a biochemical screening campaign to identify LOX inhibitors by employing the main natural product library of Brazilian biodiversity. Two prenyl chalcones were identified as potent inhibitors of LOX-1 in the screening. The most active compound, (E)-2-O-farnesyl chalcone, decreased the rate of oxygen consumption to an extent similar to that of the positive control, nordihydroguaiaretic acid. Additionally, studies on the mechanism of the action indicated that (E)-2-O-farnesyl chalcone is a competitive LOX-1 inhibitor. Molecular modeling studies indicated the importance of the prenyl moieties for the binding of the inhibitors to the LOX binding site, which is related to their pharmacological properties. |
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Identification of a Prenyl Chalcone as a Competitive Lipoxygenase Inhibitor: Screening, Biochemical Evaluation and Molecular Modeling StudieschalconesdockinginflammationNuBBE databaseCyclooxygenase (COX) and lipoxygenase (LOX) are key targets for the development of new anti-inflammatory agents. LOX, which is involved in the biosynthesis of mediators in inflammation and allergic reactions, was selected for a biochemical screening campaign to identify LOX inhibitors by employing the main natural product library of Brazilian biodiversity. Two prenyl chalcones were identified as potent inhibitors of LOX-1 in the screening. The most active compound, (E)-2-O-farnesyl chalcone, decreased the rate of oxygen consumption to an extent similar to that of the positive control, nordihydroguaiaretic acid. Additionally, studies on the mechanism of the action indicated that (E)-2-O-farnesyl chalcone is a competitive LOX-1 inhibitor. Molecular modeling studies indicated the importance of the prenyl moieties for the binding of the inhibitors to the LOX binding site, which is related to their pharmacological properties.Fundação AraucáriaFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Laboratório de Fitoquímica e Biomoléculas (LabFitoBio) Departamento de Química Universidade Estadual de Londrina (UEL)Núcleo de Bioensaios Biossíntese e Ecofisiologia de Produtos Naturais (NuBBE) Departamento de Química Orgânica Instituto de Química Universidade Estadual Paulista (UNESP)Laboratório de Química Medicinal e Computacional (LQMC) Centro de Pesquisa e Inovação em Biodiversidade e Fármacos (CIBFar) Instituto de Física de São Carlos Universidade de São Paulo (USP)Departamento de Química Faculdade de Ciências Universidade Estadual Paulista (UNESP)Instituto de Biociências Letras e Ciências Exatas Universidade Estadual Paulista (UNESP)Núcleo de Bioensaios Biossíntese e Ecofisiologia de Produtos Naturais (NuBBE) Departamento de Química Orgânica Instituto de Química Universidade Estadual Paulista (UNESP)Departamento de Química Faculdade de Ciências Universidade Estadual Paulista (UNESP)Instituto de Biociências Letras e Ciências Exatas Universidade Estadual Paulista (UNESP)FAPESP: 2010/01506-7, 2013/07600-3, 2014/50926-0CNPq: 2014/465637-0, 429073/2016-0Universidade Estadual de Londrina (UEL)Universidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Zeraik, Maria Luiza [UNESP]Pauli, IvaniDutra, Luiz A. [UNESP]Cruz, Raquel S. [UNESP]Valli, Marilia [UNESP]Paracatu, Luana C. [UNESP]de Faria, Carolina M Q G [UNESP]Ximenes, Valdecir F. [UNESP]Regasini, Luis O. [UNESP]Andricopulo, Adriano D.Bolzani, Vanderlan S. [UNESP]2021-06-25T10:59:13Z2021-06-25T10:59:13Z2021-04-12info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/molecules26082205Molecules (Basel, Switzerland), v. 26, n. 8, 2021.1420-3049http://hdl.handle.net/11449/20768210.3390/molecules260822052-s2.0-85105159530Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengMolecules (Basel, Switzerland)info:eu-repo/semantics/openAccess2021-10-23T17:45:52Zoai:repositorio.unesp.br:11449/207682Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T14:48:13.914946Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Identification of a Prenyl Chalcone as a Competitive Lipoxygenase Inhibitor: Screening, Biochemical Evaluation and Molecular Modeling Studies |
title |
Identification of a Prenyl Chalcone as a Competitive Lipoxygenase Inhibitor: Screening, Biochemical Evaluation and Molecular Modeling Studies |
spellingShingle |
Identification of a Prenyl Chalcone as a Competitive Lipoxygenase Inhibitor: Screening, Biochemical Evaluation and Molecular Modeling Studies Zeraik, Maria Luiza [UNESP] chalcones docking inflammation NuBBE database |
title_short |
Identification of a Prenyl Chalcone as a Competitive Lipoxygenase Inhibitor: Screening, Biochemical Evaluation and Molecular Modeling Studies |
title_full |
Identification of a Prenyl Chalcone as a Competitive Lipoxygenase Inhibitor: Screening, Biochemical Evaluation and Molecular Modeling Studies |
title_fullStr |
Identification of a Prenyl Chalcone as a Competitive Lipoxygenase Inhibitor: Screening, Biochemical Evaluation and Molecular Modeling Studies |
title_full_unstemmed |
Identification of a Prenyl Chalcone as a Competitive Lipoxygenase Inhibitor: Screening, Biochemical Evaluation and Molecular Modeling Studies |
title_sort |
Identification of a Prenyl Chalcone as a Competitive Lipoxygenase Inhibitor: Screening, Biochemical Evaluation and Molecular Modeling Studies |
author |
Zeraik, Maria Luiza [UNESP] |
author_facet |
Zeraik, Maria Luiza [UNESP] Pauli, Ivani Dutra, Luiz A. [UNESP] Cruz, Raquel S. [UNESP] Valli, Marilia [UNESP] Paracatu, Luana C. [UNESP] de Faria, Carolina M Q G [UNESP] Ximenes, Valdecir F. [UNESP] Regasini, Luis O. [UNESP] Andricopulo, Adriano D. Bolzani, Vanderlan S. [UNESP] |
author_role |
author |
author2 |
Pauli, Ivani Dutra, Luiz A. [UNESP] Cruz, Raquel S. [UNESP] Valli, Marilia [UNESP] Paracatu, Luana C. [UNESP] de Faria, Carolina M Q G [UNESP] Ximenes, Valdecir F. [UNESP] Regasini, Luis O. [UNESP] Andricopulo, Adriano D. Bolzani, Vanderlan S. [UNESP] |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual de Londrina (UEL) Universidade Estadual Paulista (Unesp) Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Zeraik, Maria Luiza [UNESP] Pauli, Ivani Dutra, Luiz A. [UNESP] Cruz, Raquel S. [UNESP] Valli, Marilia [UNESP] Paracatu, Luana C. [UNESP] de Faria, Carolina M Q G [UNESP] Ximenes, Valdecir F. [UNESP] Regasini, Luis O. [UNESP] Andricopulo, Adriano D. Bolzani, Vanderlan S. [UNESP] |
dc.subject.por.fl_str_mv |
chalcones docking inflammation NuBBE database |
topic |
chalcones docking inflammation NuBBE database |
description |
Cyclooxygenase (COX) and lipoxygenase (LOX) are key targets for the development of new anti-inflammatory agents. LOX, which is involved in the biosynthesis of mediators in inflammation and allergic reactions, was selected for a biochemical screening campaign to identify LOX inhibitors by employing the main natural product library of Brazilian biodiversity. Two prenyl chalcones were identified as potent inhibitors of LOX-1 in the screening. The most active compound, (E)-2-O-farnesyl chalcone, decreased the rate of oxygen consumption to an extent similar to that of the positive control, nordihydroguaiaretic acid. Additionally, studies on the mechanism of the action indicated that (E)-2-O-farnesyl chalcone is a competitive LOX-1 inhibitor. Molecular modeling studies indicated the importance of the prenyl moieties for the binding of the inhibitors to the LOX binding site, which is related to their pharmacological properties. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-06-25T10:59:13Z 2021-06-25T10:59:13Z 2021-04-12 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3390/molecules26082205 Molecules (Basel, Switzerland), v. 26, n. 8, 2021. 1420-3049 http://hdl.handle.net/11449/207682 10.3390/molecules26082205 2-s2.0-85105159530 |
url |
http://dx.doi.org/10.3390/molecules26082205 http://hdl.handle.net/11449/207682 |
identifier_str_mv |
Molecules (Basel, Switzerland), v. 26, n. 8, 2021. 1420-3049 10.3390/molecules26082205 2-s2.0-85105159530 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Molecules (Basel, Switzerland) |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1808128420477927424 |