Chalcones and their B-aryl analogues as myeloperoxidase inhibitors: In silico, in vitro and ex vivo investigations
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/10.1016/j.bioorg.2021.104773 http://hdl.handle.net/11449/207465 |
Resumo: | In the present study, a series of chalcones and their B-aryl analogues were prepared and evaluate as inhibitors of myeloperoxidase (MPO) chlorinating activity, using in vitro and ex vivo assays. Among these, B-thiophenyl chalcone (analogue 9) demonstrated inhibition of in vitro and ex vivo MPO chlorinating activity, exhibiting IC50 value of 0.53 and 19.2 µM, respectively. Potent ex vivo MPO inhibitors 5, 8 and 9 were not toxic to human neutrophils at 50 µM, as well as displayed weak 2,2-diphenyl-1-pycrylhydrazyl radical (DPPH•) and hypochlorous acid (HOCl) scavenger abilities. Docking simulations indicated binding mode of MPO inhibitors, evidencing hydrogen bonds between the amino group at 4′position (ring A) of chalcones with Gln91, Asp94, and Hys95 MPO residues. In this regard, the efficacy and low toxicity promoted aminochalcones and arylic analogues to the rank of hit compounds in the search for new non-steroidal anti-inflammatory compounds. |
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Chalcones and their B-aryl analogues as myeloperoxidase inhibitors: In silico, in vitro and ex vivo investigationsChalconeIn silicoIn vitroMyeloperoxidase (MPO)Structure-activity relationship (SAR)In the present study, a series of chalcones and their B-aryl analogues were prepared and evaluate as inhibitors of myeloperoxidase (MPO) chlorinating activity, using in vitro and ex vivo assays. Among these, B-thiophenyl chalcone (analogue 9) demonstrated inhibition of in vitro and ex vivo MPO chlorinating activity, exhibiting IC50 value of 0.53 and 19.2 µM, respectively. Potent ex vivo MPO inhibitors 5, 8 and 9 were not toxic to human neutrophils at 50 µM, as well as displayed weak 2,2-diphenyl-1-pycrylhydrazyl radical (DPPH•) and hypochlorous acid (HOCl) scavenger abilities. Docking simulations indicated binding mode of MPO inhibitors, evidencing hydrogen bonds between the amino group at 4′position (ring A) of chalcones with Gln91, Asp94, and Hys95 MPO residues. In this regard, the efficacy and low toxicity promoted aminochalcones and arylic analogues to the rank of hit compounds in the search for new non-steroidal anti-inflammatory compounds.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Institute of Biosciences Humanities and Exact Sciences São Paulo State University (UNESP)Department of Chemistry Faculty of Sciences São Paulo State University (UNESP)Physics Institute of São Carlos University of São PauloDepartment of Organic Chemistry Institute of Chemistry São Paulo State UniversityDepartment of Chemistry State University of Londrina (UEL)Institute of Biosciences Humanities and Exact Sciences São Paulo State University (UNESP)Department of Chemistry Faculty of Sciences São Paulo State University (UNESP)Department of Organic Chemistry Institute of Chemistry São Paulo State UniversityUniversidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Universidade Estadual de Londrina (UEL)Santos, Mariana Bastos dos [UNESP]Carvalho Marques, Beatriz [UNESP]Miranda Ayusso, Gabriela [UNESP]Rocha Garcia, Mayara Aparecida [UNESP]Chiquetto Paracatu, Luana [UNESP]Pauli, IvaniSilva Bolzani, Vanderlan [UNESP]Defini Andricopulo, AdrianoFarias Ximenes, Valdecir [UNESP]Zeraik, Maria LuizaRegasini, Luis Octavio [UNESP]2021-06-25T10:55:34Z2021-06-25T10:55:34Z2021-05-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.bioorg.2021.104773Bioorganic Chemistry, v. 110.1090-21200045-2068http://hdl.handle.net/11449/20746510.1016/j.bioorg.2021.1047732-s2.0-85102643721Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBioorganic Chemistryinfo:eu-repo/semantics/openAccess2021-10-23T17:16:58Zoai:repositorio.unesp.br:11449/207465Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T17:16:58Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Chalcones and their B-aryl analogues as myeloperoxidase inhibitors: In silico, in vitro and ex vivo investigations |
title |
Chalcones and their B-aryl analogues as myeloperoxidase inhibitors: In silico, in vitro and ex vivo investigations |
spellingShingle |
Chalcones and their B-aryl analogues as myeloperoxidase inhibitors: In silico, in vitro and ex vivo investigations Santos, Mariana Bastos dos [UNESP] Chalcone In silico In vitro Myeloperoxidase (MPO) Structure-activity relationship (SAR) |
title_short |
Chalcones and their B-aryl analogues as myeloperoxidase inhibitors: In silico, in vitro and ex vivo investigations |
title_full |
Chalcones and their B-aryl analogues as myeloperoxidase inhibitors: In silico, in vitro and ex vivo investigations |
title_fullStr |
Chalcones and their B-aryl analogues as myeloperoxidase inhibitors: In silico, in vitro and ex vivo investigations |
title_full_unstemmed |
Chalcones and their B-aryl analogues as myeloperoxidase inhibitors: In silico, in vitro and ex vivo investigations |
title_sort |
Chalcones and their B-aryl analogues as myeloperoxidase inhibitors: In silico, in vitro and ex vivo investigations |
author |
Santos, Mariana Bastos dos [UNESP] |
author_facet |
Santos, Mariana Bastos dos [UNESP] Carvalho Marques, Beatriz [UNESP] Miranda Ayusso, Gabriela [UNESP] Rocha Garcia, Mayara Aparecida [UNESP] Chiquetto Paracatu, Luana [UNESP] Pauli, Ivani Silva Bolzani, Vanderlan [UNESP] Defini Andricopulo, Adriano Farias Ximenes, Valdecir [UNESP] Zeraik, Maria Luiza Regasini, Luis Octavio [UNESP] |
author_role |
author |
author2 |
Carvalho Marques, Beatriz [UNESP] Miranda Ayusso, Gabriela [UNESP] Rocha Garcia, Mayara Aparecida [UNESP] Chiquetto Paracatu, Luana [UNESP] Pauli, Ivani Silva Bolzani, Vanderlan [UNESP] Defini Andricopulo, Adriano Farias Ximenes, Valdecir [UNESP] Zeraik, Maria Luiza Regasini, Luis Octavio [UNESP] |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade de São Paulo (USP) Universidade Estadual de Londrina (UEL) |
dc.contributor.author.fl_str_mv |
Santos, Mariana Bastos dos [UNESP] Carvalho Marques, Beatriz [UNESP] Miranda Ayusso, Gabriela [UNESP] Rocha Garcia, Mayara Aparecida [UNESP] Chiquetto Paracatu, Luana [UNESP] Pauli, Ivani Silva Bolzani, Vanderlan [UNESP] Defini Andricopulo, Adriano Farias Ximenes, Valdecir [UNESP] Zeraik, Maria Luiza Regasini, Luis Octavio [UNESP] |
dc.subject.por.fl_str_mv |
Chalcone In silico In vitro Myeloperoxidase (MPO) Structure-activity relationship (SAR) |
topic |
Chalcone In silico In vitro Myeloperoxidase (MPO) Structure-activity relationship (SAR) |
description |
In the present study, a series of chalcones and their B-aryl analogues were prepared and evaluate as inhibitors of myeloperoxidase (MPO) chlorinating activity, using in vitro and ex vivo assays. Among these, B-thiophenyl chalcone (analogue 9) demonstrated inhibition of in vitro and ex vivo MPO chlorinating activity, exhibiting IC50 value of 0.53 and 19.2 µM, respectively. Potent ex vivo MPO inhibitors 5, 8 and 9 were not toxic to human neutrophils at 50 µM, as well as displayed weak 2,2-diphenyl-1-pycrylhydrazyl radical (DPPH•) and hypochlorous acid (HOCl) scavenger abilities. Docking simulations indicated binding mode of MPO inhibitors, evidencing hydrogen bonds between the amino group at 4′position (ring A) of chalcones with Gln91, Asp94, and Hys95 MPO residues. In this regard, the efficacy and low toxicity promoted aminochalcones and arylic analogues to the rank of hit compounds in the search for new non-steroidal anti-inflammatory compounds. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-06-25T10:55:34Z 2021-06-25T10:55:34Z 2021-05-01 |
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/10.1016/j.bioorg.2021.104773 Bioorganic Chemistry, v. 110. 1090-2120 0045-2068 http://hdl.handle.net/11449/207465 10.1016/j.bioorg.2021.104773 2-s2.0-85102643721 |
url |
http://dx.doi.org/10.1016/j.bioorg.2021.104773 http://hdl.handle.net/11449/207465 |
identifier_str_mv |
Bioorganic Chemistry, v. 110. 1090-2120 0045-2068 10.1016/j.bioorg.2021.104773 2-s2.0-85102643721 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Bioorganic Chemistry |
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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1803046491636367360 |